Uri Ladabaum

All Publications

• Multiomic analysis of familial adenomatous polyposis reveals molecular pathways associated with early tumorigenesis. Nature cancer Esplin, E. D., Hanson, C., Wu, S., Horning, A. M., Barapour, N., Nevins, S. A., Jiang, L., Contrepois, K., Lee, H., Guha, T. K., Hu, Z., Laquindanum, R., Mills, M. A., Chaib, H., Chiu, R., Jian, R., Chan, J., Ellenberger, M., Becker, W. R., Bahmani, B., Khan, A., Michael, B., Weimer, A. K., Esplin, D. G., Shen, J., Lancaster, S., Monte, E., Karathanos, T. V., Ladabaum, U., Longacre, T. A., Kundaje, A., Curtis, C., Greenleaf, W. J., Ford, J. M., Snyder, M. P. 2024

  Abstract

  Familial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP. Transcriptomic, proteomic, metabolomic and lipidomic analyses revealed a dynamic choreography of thousands of molecular and cellular events that occur during precancerous transitions toward cancer formation. These involve processes such as cell proliferation, immune response, metabolic alterations (including amino acids and lipids), hormones and extracellular matrix proteins. Interestingly, activation of the arachidonic acid pathway was found to occur early in hyperplasia; this pathway is targeted by aspirin and other nonsteroidal anti-inflammatory drugs, a preventative treatment under investigation in persons with FAP. Overall, our results reveal key genomic, cellular and molecular events during the earliest steps in CRC formation and potential mechanisms of pharmaceutical prophylaxis.

  View details for DOI 10.1038/s43018-024-00831-z

  View details for PubMedID 39478120

  View details for PubMedCentralID 2706149

• Global loss of promoter-enhancer connectivity and rebalancing of gene expression during early colorectal cancer carcinogenesis. Nature cancer Zhu, Y., Lee, H., White, S., Weimer, A. K., Monte, E., Horning, A., Nevins, S. A., Esplin, E. D., Paul, K., Krieger, G., Shipony, Z., Chiu, R., Laquindanum, R., Karathanos, T. V., Chua, M. W., Mills, M., Ladabaum, U., Longacre, T., Shen, J., Jaimovich, A., Lipson, D., Kundaje, A., Greenleaf, W. J., Curtis, C., Ford, J. M., Snyder, M. P. 2024

  Abstract

  Although three-dimensional (3D) genome architecture is crucial for gene regulation, its role in disease remains elusive. We traced the evolution and malignant transformation of colorectal cancer (CRC) by generating high-resolution chromatin conformation maps of 33 colon samples spanning different stages of early neoplastic growth in persons with familial adenomatous polyposis (FAP). Our analysis revealed a substantial progressive loss of genome-wide cis-regulatory connectivity at early malignancy stages, correlating with nonlinear gene regulation effects. Genes with high promoter-enhancer (P-E) connectivity in unaffected mucosa were not linked to elevated baseline expression but tended to be upregulated in advanced stages. Inhibiting highly connected promoters preferentially represses gene expression in CRC cells compared to normal colonic epithelial cells. Our results suggest a two-phase model whereby neoplastic transformation reduces P-E connectivity from a redundant state to a rate-limiting one for transcriptional levels, highlighting the intricate interplay between 3D genome architecture and gene regulation during early CRC progression.

  View details for DOI 10.1038/s43018-024-00823-z

  View details for PubMedID 39478119

  View details for PubMedCentralID 7541718

• Projected Impact and Cost-Effectiveness of Novel Molecular Blood-Based or Stool-Based Screening Tests for Colorectal Cancer. Annals of internal medicine Ladabaum, U., Mannalithara, A., Schoen, R. E., Dominitz, J. A., Lieberman, D. 2024

  Abstract

  Cell-free DNA blood tests (cf-bDNA) and next-generation stool tests could change colorectal cancer (CRC) screening.To estimate the clinical and economic impacts of novel CRC screening tests.Cost-effectiveness analysis using MOSAIC (Model of Screening and Surveillance for Colorectal Cancer).Published data.Average-risk persons.Ages 45 to 100 years.Health sector.Novel versus established CRC screening tests.Incidence and mortality of CRC, quality-adjusted life-years (QALYs), costs.For colonoscopy every 10 years, annual fecal immunochemical test (FIT), and triennial next-generation multitarget stool DNA, FIT-RNA, cf-bDNA (Guardant Shield), or cf-bDNA (Freenome), the relative rates (RRs) and 95% uncertainty intervals (UIs) versus no screening for CRC incidence were 0.21 (0.19 to 0.22), 0.29 (0.27 to 0.31), 0.33 (0.32 to 0.36), 0.32 (0.30 to 0.34), 0.58 (0.55 to 0.61) and 0.58 (0.55 to 0.60), respectively; the RRs for CRC death were 0.19 (0.17 to 0.20), 0.25 (0.23 to 0.27), 0.28 (0.27 to 0.30), 0.28 (0.26 to 0.30), 0.44 (0.42 to 0.47), and 0.46 (0.44 to 0.49), respectively. The cf-bDNA test (Shield; list price $1495) cost $89 600 ($74 800 to $102 300) per QALY gained versus no screening; alternatives were less costly and more effective.Incremental costs exceeded incremental benefits when novel test intervals were shortened to 2 or 1 years. The cf-bDNA test matched FIT's impact on CRC mortality at 1.35 (1.30 to 1.40)-fold FIT's uptake rate, assuming equal colonoscopy follow-up. If persons who accept colonoscopy or stool tests shifted to cf-bDNA, CRC deaths increased. This adverse effect was overcome if every 3 such substitutions were counterbalanced by cf-bDNA uptake by 2 or more persons refusing alternatives, assuming equal colonoscopy follow-up.Longitudinal test-specific participation patterns are unknown.First-generation cf-bDNA tests may deliver net benefit or harm, depending on the balance between achieving screening in persons who decline alternatives versus substituting cf-bDNA for more effective alternatives.The Gorrindo Family Fund.

  View details for DOI 10.7326/ANNALS-24-00910

  View details for PubMedID 39467291

• Global Progression Rates of Precursor Lesions for Gastric Cancer: A Systematic Review and Meta-Analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Hahn, A. I., Mülder, D. T., Huang, R. J., Zhou, M. J., Blake, B., Omofuma, O., Murphy, J. D., Gutiérrez-Torres, D. S., Zauber, A. G., O'Mahony, J. F., Camargo, M. C., Ladabaum, U., Yeh, J. M., Hur, C., Lansdorp-Vogelaar, I., Meester, R., Laszkowska, M. 2024

  Abstract

  Whether gastric cancer (GC) precursor lesions progress to invasive cancer at similar rates globally remains unknown. We conducted a systematic review and meta-analysis to determine the progression of precursor lesions to GC in countries with low versus medium/high incidence.We searched relevant databases for studies reporting the progression of endoscopically confirmed precursor lesions to GC. Studies were stratified by low (<6 per 100,000) or medium/high (≥6 per 100,000) GC incidence countries. Random-effects models were used to estimate the progression rates of atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia to GC per 1,000 person-years.Among the 5,829 studies identified, 44 met our inclusion criteria. The global pooled estimates of the progression rate per 1,000 person-years were 2.09 (95% CI 1.46-2.99), 2.89 (2.03-4.11) and 10.09 (5.23-19.49) for AG, IM, and dysplasia respectively. The estimated progression rates per 1,000 person-years for low versus medium/high GC incidence countries, respectively, were 0.97 (0.86-1.10) vs. 2.47 (1.70-2.99) for AG (p<0.01); 2.37 (1.43-3.92) vs. 3.47 (2.13-5.65) for IM (p=0.29); and 5.51 (2.92-10.39) vs. 14.80 (5.87-37.28) for dysplasia (p=0.08). There were no differences for progression of AG between groups when high quality studies were compared.Similar progression rates of IM and dysplasia were observed among low and medium/high GC incidence countries. This suggests that the potential benefits of surveillance for these lesions in low-risk regions may be comparable to those of population-wide interventions in high-risk regions. Further prospective studies are needed to confirm these findings and inform global screening and surveillance guidelines.

  View details for DOI 10.1016/j.cgh.2024.09.003

  View details for PubMedID 39362617

• Impact of the serrated pathway on the simulated comparative effectiveness of colorectal cancer screening tests. JNCI cancer spectrum Meester, R. G., Ladabaum, U. 2024

  Abstract

  BACKGROUND: Colorectal cancers (CRCs) arise from adenomas, which can produce fecal occult blood and can be detected endoscopically, or sessile serrated lesions (SSLs), which rarely bleed and may be more challenging to detect. Models informing CRC screening policy should reflect both pathways, accounting for uncertainty.METHODS: Novel decision-analytic model of the adenoma and serrated pathways for CRC (ANSER) to compare current and emerging screening strategies, accounting for differential test sensitivities for adenomas and SSLs, and uncertainty. Strategies included colonoscopy every 10years, stool-DNA/FIT (sDNA-FIT) every 1-3years, or fecal immunochemical testing (FIT) every year from age 45-75years. Outcomes included CRC cases and deaths, cost-effectiveness (cost/quality-adjusted life-year (QALY) gained), and burden-benefit (colonoscopies/life-year gained), with 95% uncertainty intervals (95%UIs).RESULTS: ANSER predicted 62.5 (95%UI, 58.8-66.3) lifetime CRC cases and 24.1 (95%UI, 22.5-25.7) CRC deaths/1,000 45-year-olds without screening, and 78-87% CRC mortality reductions with screening. The tests' outcome distributions overlapped for QALYs gained but separated for required colonoscopies and costs. All strategies cost <$100,000/QALY gained vs no screening. Colonoscopy was the most effective and cost-effective, costing $9,300/life-year gained (95%UI, $500-21,900) vs FIT. sDNA-FIT cost >$500,000/QALY gained vs FIT. As more CRCs arose from SSLs, colonoscopy remained preferred based on clinical benefit and cost-effectiveness, but cost-effectiveness improved for a next-generation sDNA-FIT.CONCLUSION: When the serrated pathway is considered, modeling suggests colonoscopy is cost-effective vs FIT. In contrast, modeling suggests sDNA-FIT is not cost-effective vs FIT despite its greater sensitivity for SSLs, even if a substantial minority of CRCs arise from SSLs.FUNDING: Dutch Research Council (NWO).

  View details for DOI 10.1093/jncics/pkae077

  View details for PubMedID 39240660

• Reply to Aziz et al. Gastroenterology Ladabaum, U., Mannalithara, A., Schoen, R. E., Dominitz, J. A., Lieberman, D. 2024

  View details for DOI 10.1053/j.gastro.2024.08.027

  View details for PubMedID 39209125

• Quality Indicators for Colonoscopy. The American journal of gastroenterology Rex, D. K., Anderson, J. C., Butterly, L. F., Day, L. W., Dominitz, J. A., Kaltenbach, T., Ladabaum, U., Levin, T. R., Shaukat, A., Achkar, J. P., Farraye, F. A., Kane, S. V., Shaheen, N. J. 2024

  View details for DOI 10.14309/ajg.0000000000002972

  View details for PubMedID 39167112

• Will computer-aided detection of polyps decrease colorectal cancer incidence and mortality? Endoscopy Ladabaum, U. 2024

  View details for DOI 10.1055/a-2371-1556

  View details for PubMedID 39111736

• Generation of two induced pluripotent stem cell lines from patients with Li-Fraumeni Syndrome carrying TP53 mutation. Stem cell research Sun, J., Ren, L., Canel Rivero, G., Xu, L., Ladabaum, U., C Wu, J. 2024; 81: 103527

  Abstract

  Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited genetic disorder that greatly increases the risk of developing several types of cancer, including young children and young adults. LFS is primarily caused by specific mutations in the tumor suppressor gene TP53. In this study, we successfully generated two human induced pluripotent stem cell (iPSC) lines derived from patients diagnosed with LFS, each carrying a distinct heterozygous mutation in the TP53 gene. These LFS patient-derived iPSC lines exhibited robust expression of key pluripotency markers, demonstrated the capacity to differentiate into all three germ layers (endoderm, mesoderm, and ectoderm), and maintained a normal karyotype. The establishment of these iPSC lines provides a valuable tool for modeling LFS in vitro, enabling researchers to investigate the underlying pathological mechanisms associated with the disease across various cell types and tissues.

  View details for DOI 10.1016/j.scr.2024.103527

  View details for PubMedID 39133963

• Quality indicators for colonoscopy. Gastrointestinal endoscopy Rex, D. K., Anderson, J. C., Butterly, L. F., Day, L. W., Dominitz, J. A., Kaltenbach, T., Ladabaum, U., Levin, T. R., Shaukat, A., Achkar, J., Farraye, F. A., Kane, S. V., Shaheen, N. J. 2024

  View details for DOI 10.1016/j.gie.2024.04.2905

  View details for PubMedID 39177519

• RISK FACTORS FOR METACHRONOUS COLORECTAL CANCER OR ADVANCED LESIONS AFTER ENDOSCOPIC RESECTION OF SERRATED POLYPS: A SYSTEMATIC REVIEW AND META-ANALYSIS. Gastrointestinal endoscopy Baile-Maxía, S., Mangas-Sanjuán, C., Ladabaum, U., Ardila, C. S., Sala-Miquel, N., Hassan, C., Rutter, M. D., Bretthauer, M., Zapater, P., Jover, R. 2024

  Abstract

  Serrated polyps (SPs) are precursors to 15-20% of colorectal cancers (CRCs). However, there are uncertainties regarding which SPs require surveillance and at what intervals, with recommendations adapted from those for adenomas in the absence of solid evidence. Our aim was to assess which SP risk characteristics relate to a higher risk of metachronous CRC or advanced polyps.We systematically searched PubMed, EMBASE, and Cochrane for cohort, case-control studies, and clinical trials from inception to Dec 31, 2023, for CRC or advanced polyps [advanced adenoma (AA) or advanced SP] incidence at surveillance stratified by baseline SP size, dysplasia, location, and multiplicity. We defined advanced SPs as those >10mm or with dysplasia. CRC and advanced polyp incidence per 1,000 person-years (p-y) were estimated. We performed a meta-analysis by calculating pooled relative risks (RR) using a random-effects model.5,903 studies were reviewed and 14 included, with 493,949 patients (mean age 59·5 years, 55% men). Mean follow-up was 4·9 years. CRC incidence per 1,000 p-y was 2·09 (95%CI 1·29-2·90) for advanced SP, 1·52 (0·78-2·25) for SP>10mm, 5·86 (2·16-9·56) for SP with dysplasia, 1·18 (0·77-1·60) for proximal SP, 0·52 (0·08-1·12) for >3SP, 0·50 (0·35-0·66) for non-advanced SP, and 0·44 (0·41-0·46) for normal colonoscopy. Metachronous CRC risk was higher in advanced SP vs non-advanced SP (RR 1·84, 95%CI 1·11-3·04), and vs normal colonoscopy (RR 2·92, 2·26-3·77); in SP>10mm vs <10mm (RR 2·61, 1·43-4·77), and vs normal colonoscopy (RR 3·52, 2·17-5·69); and in SP with dysplasia vs normal colonoscopy (RR 2·71, 2·00-3·67). No increase in CRC or advanced polyp risk was found in patients with proximal vs distal SP, nor in >3SP vs 1-2SP.CRC risk is significantly higher in patients with baseline advanced SP after 4·9 years of follow-up, with risk magnitudes similar to those described for AA, supporting the current recommendation for 3-year surveillance in patients with advanced SP.

  View details for DOI 10.1016/j.gie.2024.05.021

  View details for PubMedID 38851458

• Of Humans and Machines in Endoscopy: Flying Solo, Instrument-Aided, or on Autopilot? Gastroenterology Ladabaum, U. 2024

  View details for DOI 10.1053/j.gastro.2024.03.032

  View details for PubMedID 38548191

• Comparative Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening With Blood-Based Biomarkers (Liquid Biopsy) vs Fecal Tests or Colonoscopy. Gastroenterology Ladabaum, U., Mannalithara, A., Weng, Y., Schoen, R. E., Dominitz, J. A., Desai, M., Lieberman, D. 2024

  Abstract

  Colorectal cancer (CRC) screening is highly effective but underused. Blood-based biomarkers (eg, liquid biopsy) could improve screening participation.Using our established Markov model, screening every 3 years with a blood-based test that meets minimum Centers for Medicare & Medicaid Services' thresholds (CMSmin) (CRC sensitivity 74%, specificity 90%) was compared with established alternatives. Test attributes were varied in sensitivity analyses.CMSmin reduced CRC incidence by 40% and CRC mortality by 52% vs no screening. These reductions were less profound than the 68%-79% and 73%-81%, respectively, achieved with multi-target stool DNA (Cologuard; Exact Sciences) every 3 years, annual fecal immunochemical testing (FIT), or colonoscopy every 10 years. Assuming the same cost as multi-target stool DNA, CMSmin cost $28,500/quality-adjusted life-year gained vs no screening, but FIT, colonoscopy, and multi-target stool DNA were less costly and more effective. CMSmin would match FIT's clinical outcomes if it achieved 1.4- to 1.8-fold FIT's participation rate. Advanced precancerous lesion (APL) sensitivity was a key determinant of a test's effectiveness. A paradigm-changing blood-based test (sensitivity >90% for CRC and 80% for APL; 90% specificity; cost ≤$120-$140) would be cost-effective vs FIT at comparable participation.CMSmin could contribute to CRC control by achieving screening in those who will not use established methods. Substituting blood-based testing for established effective CRC screening methods will require higher CRC and APL sensitivities that deliver programmatic benefits matching those of FIT. High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers. APL detection should not be penalized by a definition of test specificity that focuses on CRC only.

  View details for DOI 10.1053/j.gastro.2024.03.011

  View details for PubMedID 38552670

• Prevalence of Gastric Precursor Lesions in Countries with Differential Gastric Cancer Burden: A Systematic Review & Meta-Analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Mülder, D. T., Hahn, A. I., Huang, R. J., Zhou, M. J., Blake, B., Omofuma, O., Murphy, J. D., Gutiérrez-Torres, D. S., Zauber, A. G., O'Mahony, J. F., Camargo, M. C., Ladabaum, U., Yeh, J. M., Hur, C., Lansdorp-Vogelaar, I., Meester, R., Laszkowska, M. 2024

  Abstract

  The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions.We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high-GC incidence. Since IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori (H.pylori) infection, symptomatology, and period (<2000, 2000-2010, and >2010).Among the 582 articles which underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2% and 2.0%, based on 126 studies that reported the prevalence of less advanced precursors regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high- and medium- compared to low-GC incidence countries (p<0.01). Prevalence of AG and IM was significantly higher among H.pylori-infected individuals (p<0.01), but not statistically different between symptomatic and asymptomatic individuals (p>0.17). All precursors demonstrated a secular decrease in prevalence over time.Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H.pylori infection. Given the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies.

  View details for DOI 10.1016/j.cgh.2024.02.023

  View details for PubMedID 38438000

• Colorectal cancer screening at age 45 years in Israel: Cost-effectiveness and global implications. Cancer Half, E. E., Levi, Z., Mannalithara, A., Leshno, M., Ben-Aharon, I., Abu-Freha, N., Silverman, B., Ladabaum, U. 2024

  Abstract

  Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions.A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated.FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years.Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.

  View details for DOI 10.1002/cncr.35097

  View details for PubMedID 38180788

• Artificial intelligence-assisted colonoscopy in real-world clinical practice: A systematic review and meta-analysis. Clinical and translational gastroenterology Wei, M. T., Fay, S., Yung, D., Ladabaum, U., Kopylov, U. 2023

  Abstract

  BACKGROUND: Artificial intelligence (AI) could minimize the operator-dependent variation in colonoscopy quality. Computer-aided detection (CADe) has improved adenoma detection rate (ADR) and adenomas per colonoscopy (APC) in randomized controlled trials (RCTs). There is a need to assess the impact of CADe in real-world settings.METHODS: We searched MEDLINE, EMBASE, and Web of Science for non-randomized, real-world studies of CADe in colonoscopy. Random-effects meta-analyses were performed to examine the effect of CADe on ADR and APC. The study is registered under PROSPERO (CRD42023424037). There was no funding for this study.RESULTS: Twelve of 1,314 studies met inclusion criteria. Overall, ADR was statistically significantly higher with vs. without CADe (36.3% vs. 35.8%, risk ratio [RR] 1.13, 95% CI 1.01-1.28). This difference remained significant in subgroup analyses evaluating 6 prospective (37.3% vs 35.2%, RR 1.15, 95% CI 1.01-1.32) but not 6 retrospective (35.7% vs 36.2%, RR 1.12, 95% CI 0.92-1.36) studies. Among 6 studies with APC data, APC rate ratio with vs. without CADe was 1.12 (95% CI 0.95-1.33). In 4 studies with GI Genius (Medtronic), there was no difference in ADR with vs. without CADe (RR 0.96, 95% CI 0.85-1.07).CONCLUSIONS: ADR, but not APC, was slightly higher with vs. without CADe among all available real-world studies. This difference was attributed to the results of prospective but not retrospective studies. The discrepancies between these findings vs. those of RCTs call for future research on the true impact of current AI technology on colonoscopy quality, and the subtleties of human-AI interactions.

  View details for DOI 10.14309/ctg.0000000000000671

  View details for PubMedID 38146871

• NordICC's 10-year interim results are unexpected, and inconsistent with modeling predictions. Gastroenterology Ladabaum, U., Schoen, R. E., Meester, R. 2023

  View details for DOI 10.1053/j.gastro.2023.09.041

  View details for PubMedID 37783281

• The Time Has Come to Adopt the Sessile Serrated Lesion Detection Rate as a Quality Metric. The American journal of gastroenterology Ladabaum, U. 2023

  View details for DOI 10.14309/ajg.0000000000002466

  View details for PubMedID 37753926

• Does Screening Colonoscopy Have a Future in the United States? Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Rex, D. K., Ladabaum, U., Anderson, J. C., Shaukat, A., Butterly, L. F., Dominitz, J. A., Kaltenbach, T., Levin, T. R., Hassan, C. 2023

  View details for DOI 10.1016/j.cgh.2023.05.034

  View details for PubMedID 37536529

• Adherence to Recommendations for Repeat Surveillance After Publication of New Postpolypectomy Guidelines. Gastro hep advances Rosas, U. S., Pan, J. Y., Sundaram, V., Su, A., Fazal, M., Dinh, P., Ladabaum, U. 2023; 2 (1): 132-143

  Abstract

  The 2012 and 2020 US Multi-Society Task Force postpolypectomy guidelines have recommended progressively longer surveillance intervals for patients with low-risk adenomas (LRAs). These guidelines require data from past colonoscopies. We examined the impact of the 2012 guidelines for second surveillance on clinical practice, including the availability of prior colonoscopy data, with the aim of informing the implementation of the 2020 guidelines.We identified surveillance colonoscopies at Stanford Health Care and the Palo Alto Veterans Affairs Health Care System in 3 periods: preguideline (March-August 2012), postguideline (January-June 2013), and delayed postguideline (July-September 2017). We collected data on the most recent previous colonoscopy, findings at the study entry surveillance colonoscopy, and recommendations for subsequent surveillance.Among 977 patients, the most recent prior colonoscopy data were available in 78% of preguideline, 78% of postguideline, and 61% of delayed postguideline cases (P < .001). The fraction of surveillance colonoscopy reports that deferred recommendations awaiting pathology increased from 6% to 11% in preguideline and postguideline to 59% in delayed postguideline cases (P < .001). Overall adherence to guidelines for subsequent surveillance was similar in all 3 periods (54%-67%; P = .089). In the postguideline and delayed postguideline periods combined, a 10-year subsequent surveillance interval was recommended in 0 of 29 cases with LRA followed by normal surveillance colonoscopy.In patients undergoing surveillance, prior colonoscopy data were not always available and recommendations were often deferred awaiting pathology. Adherence to subsequent surveillance guidelines was suboptimal, especially for LRA followed by normal colonoscopy. Strategies addressing these gaps are needed to optimize implementation of the updated 2020 postpolypectomy guidelines.

  View details for DOI 10.1016/j.gastha.2022.07.014

  View details for PubMedID 39130145

  View details for PubMedCentralID PMC11307611

• An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles. Gut Bresalier, R. S., Senore, C., Young, G. P., Allison, J., Benamouzig, R., Benton, S., Bossuyt, P. M., Caro, L., Carvalho, B., Chiu, H. M., Coupé, V. M., de Klaver, W., de Klerk, C. M., Dekker, E., Dolwani, S., Fraser, C. G., Grady, W., Guittet, L., Gupta, S., Halloran, S. P., Haug, U., Hoff, G., Itzkowitz, S., Kortlever, T., Koulaouzidis, A., Ladabaum, U., Lauby-Secretan, B., Leja, M., Levin, B., Levin, T. R., Macrae, F., Meijer, G. A., Melson, J., O'Morain, C., Parry, S., Rabeneck, L., Ransohoff, D. F., Sáenz, R., Saito, H., Sanduleanu-Dascalescu, S., Schoen, R. E., Selby, K., Singh, H., Steele, R. J., Sung, J. J., Symonds, E. L., Winawer, S. J. 2023

  Abstract

  New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers.A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles.Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence.New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

  View details for DOI 10.1136/gutjnl-2023-329701

  View details for PubMedID 37463757

• Impact of race/ethnicity and socioeconomic status on incident and prevalent esophageal cancer in patients with Barrett's esophagus. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus Zhou, M. J., Ladabaum, U., Triadafilopoulos, G., Clarke, J. O. 2023

  Abstract

  The impact of race/ethnicity (RE) or socioeconomic status (SES) on progression from Barrett's esophagus (BE) to esophageal cancer (EC) is not well established. We aimed to evaluate the association between demographic factors and SES on EC diagnosis in an ethnically diverse BE cohort. Patients aged 18-63 with incident BE diagnosed in October 2015-March 2020 were identified in the Optum Clinformatics DataMart Database. Patients were followed until the diagnosis of prevalent EC <1year or incident EC ≥1year from BE diagnosis, or until the end of their continuous enrollment period. Cox proportional hazards analysis was used to determine associations between demographics, SES factors, BE risk factors, and EC. Demographics of the 12,693 patients included mean age of BE diagnosis 53.0 (SD 8.5) years, 56.4% male, 78.3% White/10.0% Hispanic/6.4% Black/3.0% Asian. The median follow-up was 26.8 (IQR 19.0-42.0) months. In total, 75 patients (0.59%) were diagnosed with EC (46 [0.36%] prevalent EC; 29 [0.23%] incident EC), and 74 patients (0.58%) developed high-grade dysplasia (HGD) (46 [0.36%] prevalent HGD; 28 [0.22%] incident HGD). Adjusted HR (95% CI) for prevalent EC comparing household net worth ≥$150,000 vs. <$150,000 was 0.57 (0.33-0.98). Adjusted HRs (95% CI) for prevalent and incident EC comparing non-White vs. White patients were 0.93 (0.47-1.85) and 0.97 (0.21-3.47), respectively. In summary,a lower SES, captured by the household net worth, was associated with prevalent EC. There was no significant difference in prevalent or incident EC among White vs. non-White patients. EC progression in BE may be similar among racial/ethnic groups, but SES disparities may impact BE outcomes.

  View details for DOI 10.1093/dote/doad044

  View details for PubMedID 37431107

• BELIEFS AND ATTITUDES ABOUT ARTIFICIAL INTELLIGENCE (AI) AMONG COLONOSCOPIST PARTICIPANTS IN A PRAGMATIC IMPLEMENTATION TRIAL OF COMPUTER-AIDED DETECTION (CADE) OF POLYPS THAT DID NOT REPLICATE THE POSITIVE RESULTS OF RANDOMIZED TRIALS Ladabaum, U., Mannalithara, A., Weng, Y., Shaw, B., Olsen, E., Watkins, K., Hoogerbrug, J., Bohn, R., Singer, S. MOSBY-ELSEVIER. 2023: AB763-AB764

  View details for Web of Science ID 001038022801598

• ENDOSCOPIST ADENOMA DETECTION RATE IS ASSOCIATED WITH DETECTION OF COLORECTAL CANCER AT COLONOSCOPY PERFORMED FOR SCREENING OR EVALUATION OF ABNORMAL STOOL TEST Dominitz, J., Holub, J., Issaka, R., Ko, C., Robertson, D., Ladabaum, U. MOSBY-ELSEVIER. 2023: AB239-AB240

  View details for Web of Science ID 001038022800373

• ENDOSCOPIST ADENOMA DETECTION RATE IS ASSOCIATED WITH DETECTION OF COLORECTAL CANCER AT COLONOSCOPY PERFORMED FOR SCREENING OR EVALUATION OF ABNORMAL STOOL TEST Dominitz, J., Holub, J., Issaka, R., Ko, C., Robertson, D., Ladabaum, U. MOSBY-ELSEVIER. 2023: AB137-AB138

  View details for Web of Science ID 001038022800209

• Colorectal cancer risk prediction to tailor screening: Will we embrace it or KISS it goodbye? Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Ladabaum, U., Ko, C. W. 2023

  View details for DOI 10.1016/j.cgh.2023.04.010

  View details for PubMedID 37100217

• Clinical implications of conflicting variant interpretations in the cancer genetics clinic. Genetics in medicine : official journal of the American College of Medical Genetics Zukin, E., Culver, J. O., Liu, Y., Yang, Y., Ricker, C. N., Hodan, R., Sturgeon, D., Kingham, K., Chun, N. M., Rowe-Teeter, C., Singh, K., Zell, J. A., Ladabaum, U., McDonnell, K. J., Ford, J. M., Parmigiani, G., Braun, D., Kurian, A. W., Gruber, S. B., Idos, G. E. 2023: 100837

  Abstract

  To describe the clinical impact of commercial laboratories issuing conflicting classifications of genetic variants.Results from 2,000 patients undergoing a multi-gene hereditary cancer panel by a single laboratory were analyzed. Clinically significant discrepancies between the lab provided test reports and other major commercial laboratories were identified, including differences between pathogenic/likely pathogenic (P/LP) and variant of uncertain significance (VUS) classifications, via review of ClinVar archives. For patients carrying a VUS, clinical documentation was assessed for evidence of provider awareness of the conflict.50/975 (5.1%) patients with non-negative results carried a variant with a clinically significant conflict, 19 with a P/LP variant reported in APC or MUTYH, and 31 with a VUS reported in CDKN2A, CHEK2, MLH1, MSH2, MUTYH, RAD51C, or TP53. Only 10/28 (36%) patients with a VUS with a clinically significant conflict had a documented discussion by a provider about the conflict. Discrepant counseling strategies were utilized for different patients with the same variant. Among patients with a CDKN2A variant or a monoallelic MUTYH variant, providers were significantly more likely to make recommendations based on the laboratory-reported classification.Our findings highlight the frequency of variant interpretation discrepancies and importance of clinician awareness. Guidance is needed on managing patients with discrepant variants to support accurate risk assessment.

  View details for DOI 10.1016/j.gim.2023.100837

  View details for PubMedID 37057674

• RISK FACTORS FOR METACHRONOUS COLORECTAL CANCER OR ADVANCED ADENOMAS AFTER ENDOSCOPIC RESECTION OF HIGH-RISK ADENOMAS. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Baile-Maxia, S., Mangas-Sanjuan, C., Ladabaum, U., Hassan, C., Rutter, M. D., Bretthauer, M., Medina-Prado, L., Sala-Miquel, N., Pomares, O. M., Zapater, P., Jover, R. 2022

  Abstract

  BACKGROUND AND AIMS: Among the characteristics of high-risk adenomas (HRA), some may predict a higher risk of metachronous advanced lesions. Our aim was to assess which HRA characteristics are associated with high risk of metachronous colorectal cancer (CRC) or advanced adenomas (AA).METHODS: We systematically searched Pubmed, EMBASE and Cochrane for cohort studies and clinical trials of CRC or AA incidence at surveillance stratified by baseline lesion size, histology, and multiplicity. We calculated pooled relative risks (RR) using a random-effects model. Heterogeneity was assessed with the I2 statistic.RESULTS: Fifty-five studies were included, with 936,540 patients. CRC incidence per 1,000 person-years was 2.6 (2.1-3.0) for adenomas ≥20mm, 2.7 (2.2-3.2) for high-grade dysplasia (HGD), 2.0 (1.8-2.3) for villous component, 0.8 (0.1-1.4) for ≥5 adenomas, 1.0 (0.7-1.2) for ≥3 adenomas. Metachronous CRC risk was higher in adenomas ≥20mm vs 10-19mm (RR 2.08, 95%CI 1.20-3.61), HGD vs low-grade dysplasia (RR 2.89, 95%CI 1.88-4.44), villous vs tubular (RR 1.75, 95%CI 1.33-2.31). No significant differences in CRC risk were found in ≥3 adenomas vs 1-2 (RR 1.24, 95%CI 0.84-1.83), nor in ≥5 adenomas vs 3-4 (RR 0.79, 95%CI 0.30-2.11). Compared to normal colonoscopy, RR for CRC risk was 2.61 (95%CI 2.06-3.32) for ≥10mm, 6.62 (95%CI 4.60-9.52) for HGD, 3.58 (95%CI 2.24-5.73) for villous component, 2.03 (95%CI 1.40-2.94) for ≥3 adenomas. Similar trends were seen for metachronous AA.CONCLUSION: Metachronous CRC risk is highest in patients with baseline adenomas with ≥20mm or HGD. Multiplicity does not seem to be associated with substantially higher CRC risk.

  View details for DOI 10.1016/j.cgh.2022.12.005

  View details for PubMedID 36549471

• Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology Ladabaum, U., Shepard, J., Weng, Y., Desai, M., Singer, S. J., Mannalithara, A. 2022

  View details for DOI 10.1053/j.gastro.2022.12.004

  View details for PubMedID 36528131

• Risk of Proximal Gastrointestinal Cancer after Positive Fecal Immunochemical Test. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Zhou, M. J., Singh, G., Hwang, J. H., Ladabaum, U. 2022

  View details for DOI 10.1016/j.cgh.2022.11.032

  View details for PubMedID 36464140

• COVID-19 PANDEMIC-RELATED COLORECTAL CANCER SCREENING DELAYS IMPACT UNSCREENED OLDER ADULTS THE MOST, BUT MITIGATION STRATEGIES EXIST. Gastroenterology Sinha, S., Li, Z., Bar-Mashiah, A., Ladabaum, U., Sharaf, R. N. 2022

  View details for DOI 10.1053/j.gastro.2022.08.035

  View details for PubMedID 36007579

• Cost-effectiveness of earlier or more intensive colorectal cancer screening in overweight and obese patients. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Yeoh, A., Mannalithara, A., Ladabaum, U. 2022

  Abstract

  Overweight and obese persons have elevated rates of colorectal cancer (CRC) but also higher competing mortality and healthcare spending. We examined the cost-effectiveness of intensified CRC screening in overweight and obese persons.We adapted our validated decision analytic model of CRC screening to compare screening starting at age 45 or 40 instead of 50, and/or shortening screening intervals, in women and men with body-mass-index (BMI) ranging from normal to grade III obesity. Strategies included colonoscopy every 10 (Colo10) or 5 years (Colo5), or annual FIT.Without screening, sex-specific total CRC deaths were similar for persons with overweight or obesity I-III, reflecting the counterbalancing of higher CRC risk by lower life-expectancy as BMI rises. For all BMI/sex groups, Colo10 starting at 45 or FIT starting at 40 were cost-effective at a threshold of $100,000/quality-adjusted life year (QALY) gained. Colo10 starting at 40 was cost-effective only for men with obesity II-III, at $93,300 and $80,400/QALY gained, respectively. Shifting Colo10 to earlier starting ages was always preferred over Colo5 starting at later ages. Results were robust in sensitivity analysis, including varying all-cause mortality, complication, and BMI-specific CRC risks.CRC screening starting at age 45 with colonoscopy, or 40 with FIT, appears cost-effective for women and men across the range of BMI. In men with obesity II-III, who have the highest CRC but also all-cause mortality risks, colonoscopy starting at 40 appears cost-effective. It remains to be decided whether BMI should be used as a single predictor or incorporated into a multivariable tool to tailor CRC screening.

  View details for DOI 10.1016/j.cgh.2022.07.028

  View details for PubMedID 35940514

• Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer. Nature genetics Becker, W. R., Nevins, S. A., Chen, D. C., Chiu, R., Horning, A. M., Guha, T. K., Laquindanum, R., Mills, M., Chaib, H., Ladabaum, U., Longacre, T., Shen, J., Esplin, E. D., Kundaje, A., Ford, J. M., Curtis, C., Snyder, M. P., Greenleaf, W. J. 2022

  Abstract

  To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.

  View details for DOI 10.1038/s41588-022-01088-x

  View details for PubMedID 35726067

• GA White Paper: Challenges and Gaps in Innovation for the Performance of Colonoscopy for Screening and Surveillance of Colorectal Cancer. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Komanduri, S., Dominitz, J. A., Rabeneck, L., Kahi, C., Ladabaum, U., Imperiale, T. F., Byrne, M. F., Lee, J. K., Lieberman, D., Wang, A. Y., Sultan, S., Shaukat, A., Pohl, H., Muthusamy, V. R. 2022

  Abstract

  In 2018 the American Gastroenterological Association's (AGA) Center for GI Innovation and Technology (CGIT) convened a consensus conference, entitled, "Colorectal Cancer Screening and Surveillance: Role of Emerging Technology and Innovation to Improve Outcomes." The conference participants, which included more than 60 experts in colorectal cancer (CRC), considered recent improvements in CRC screening rates and polyp detection, persistent barriers to colonoscopy uptake, and opportunities for performance improvement and innovation. This white paper originates from that conference. It aims to summarize current patient- and physician-centered gaps and challenges in colonoscopy, diagnostic and therapeutic challenges affecting colonoscopy uptake, and the potential use of emerging technologies and quality metrics to improve patient outcomes.

  View details for DOI 10.1016/j.cgh.2022.03.051

  View details for PubMedID 35688352

• Reducing the Burden of Colorectal Cancer: AGA Position Statements. Gastroenterology Lieberman, D., Ladabaum, U., Brill, J. V., May, F. P., Kim, L. S., Murphy, C., Wender, R., Teixeira, K. 2022

  View details for DOI 10.1053/j.gastro.2022.05.011

  View details for PubMedID 35715380

• Adenoma and Sessile Serrated Lesion Detection Rates at Screening Colonoscopy for Ages 45-49 Years vs. Older Ages Since the Introduction of New Colorectal Cancer Screening Guidelines. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Ladabaum, U., Shepard, J., Mannalithara, A. 2022

  Abstract

  BACKGROUND: All major U.S. guidelines now endorse average-risk colorectal cancer (CRC) screening at ages 45-49. Concerns exist that endoscopic capacity may be strained, that low-risk persons may self-select for screening, and that calculations of the adenoma detection rate (ADR) may be diluted. We analyzed age-specific screening colonoscopy volumes and lesion detection rates before vs. after the endorsement of CRC screening at ages 45-49.METHODS: We compared colonoscopy volumes and lesion detection rates in our healthcare system during Period I (October 2017-December 2018), before the first change in guidelines, vs. Period II (January 2019-August 2021), the era of new guidelines.RESULTS: The proportion of first-time screening colonoscopies performed in 45-49 year-olds increased from 3.5% to 11.6% (RR 3.36 [95% CI, 2.45-4.61]). The Period II detection rates for adenoma, advanced adenoma, sessile serrated lesion (SSL), advanced SSL, adenomas per colonoscopy (APC), and lesions per colonoscopy (LPC) were very similar for 45-49 year-olds (34.3%, 6.3%, 8.6%, 2.9%, 0.58, and 0.69) and 50-54 year-olds (38.2%, 5.8%, 9.4%, 3.0%, 0.63, and 0.76) at first-time screening, and for 60-64 year-olds at re-screening (33.4%, 6.1%, 7.2%, 2.3%, 0.61, and 0.70). All detection rates, APC and LPC increased from Period I to Period II (e.g. overall ADR 35.1% to 42.6%, p<0.0001), without any decreases among 45-49 year-olds.CONCLUSIONS: In our healthcare system, a lower CRC screening initiation age has modestly affected colonoscopy volume by age without compromising screening yield. Lesion detection rates, including for advanced adenomas, in average-risk 45-49 year-olds approximate those in 50-54 year-olds at first-time screening, and 60-64 year-olds at re-screening. National monitoring is needed to assess fully the impact of lowering the CRC screening initiation age.

  View details for DOI 10.1016/j.cgh.2022.04.037

  View details for PubMedID 35580769

• Fulfilling the promise of colorectal cancer screening. The lancet. Gastroenterology & hepatology Ladabaum, U. 2022

  View details for DOI 10.1016/S2468-1253(22)00121-2

  View details for PubMedID 35561738

• Somatic tumor testing implications for Lynch syndrome germline genetic testing. Cancer genetics Barrus, K., Purington, N., Chun, N., Ladabaum, U., Ford, J. M. 2022; 264-265: 16-22

  Abstract

  Clinicians involved in cancer treatment often utilize somatic tumor sequencing to help tailor chemotherapy and immunotherapy. However, somatic tumor sequencing can also identify patients at risk for germline pathogenic variants causing cancer predisposition syndromes like Lynch syndrome. The extent to which clinicians realize this implication of tumor sequencing is currently unclear. We performed a retrospective chart review of Stanford Health Care patients who had somatic variant(s) in the Lynch syndrome genes or microsatellite instability identified on tumor sequencing to determine the proportion of patients who were referred to genetics. Among 6,556 patients who had tumor testing, 90 (1.37%) had findings compatible with Lynch syndrome. Of the 62 patients who had not already seen genetics, 47/62 (75.8%) were not referred to genetics for germline testing. Additionally, 26/47 (55.3%) of these individuals had a tumor type within the Lynch syndrome spectrum. Of the 10 patients who did elect germline testing after tumor sequencing, 3/10 were positive for Lynch syndrome. Our study highlights the need for specific guidelines to inform clinician referral practices on germline follow-up of somatic tumor testing and demonstrates the importance of continued research on the relationship between somatic tumor variants and germline variants to inform such guidelines.

  View details for DOI 10.1016/j.cancergen.2022.02.010

  View details for PubMedID 35286930

• MITI minimum information guidelines for highly multiplexed tissue images. Nature methods Schapiro, D., Yapp, C., Sokolov, A., Reynolds, S. M., Chen, Y., Sudar, D., Xie, Y., Muhlich, J., Arias-Camison, R., Arena, S., Taylor, A. J., Nikolov, M., Tyler, M., Lin, J., Burlingame, E. A., Human Tumor Atlas Network, Chang, Y. H., Farhi, S. L., Thorsson, V., Venkatamohan, N., Drewes, J. L., Pe'er, D., Gutman, D. A., Herrmann, M. D., Gehlenborg, N., Bankhead, P., Roland, J. T., Herndon, J. M., Snyder, M. P., Angelo, M., Nolan, G., Swedlow, J. R., Schultz, N., Merrick, D. T., Mazzili, S. A., Cerami, E., Rodig, S. J., Santagata, S., Sorger, P. K., Abravanel, D. L., Achilefu, S., Ademuyiwa, F. O., Adey, A. C., Aft, R., Ahn, K. J., Alikarami, F., Alon, S., Ashenberg, O., Baker, E., Baker, G. J., Bandyopadhyay, S., Bayguinov, P., Beane, J., Becker, W., Bernt, K., Betts, C. B., Bletz, J., Blosser, T., Boire, A., Boland, G. M., Boyden, E. S., Bucher, E., Bueno, R., Cai, Q., Cambuli, F., Campbell, J., Cao, S., Caravan, W., Chaligne, R., Chan, J. M., Chasnoff, S., Chatterjee, D., Chen, A. A., Chen, C., Chen, C., Chen, B., Chen, F., Chen, S., Chheda, M. G., Chin, K., Cho, H., Chun, J., Cisneros, L., Coffey, R. J., Cohen, O., Colditz, G. A., Cole, K. A., Collins, N., Cotter, D., Coussens, L. M., Coy, S., Creason, A. L., Cui, Y., Zhou, D. C., Curtis, C., Davies, S. R., Bruijn, I., Delorey, T. M., Demir, E., Denardo, D., Diep, D., Ding, L., DiPersio, J., Dubinett, S. M., Eberlein, T. J., Eddy, J. A., Esplin, E. D., Factor, R. E., Fatahalian, K., Feiler, H. S., Fernandez, J., Fields, A., Fields, R. C., Fitzpatrick, J. A., Ford, J. M., Franklin, J., Fulton, B., Gaglia, G., Galdieri, L., Ganesh, K., Gao, J., Gaudio, B. L., Getz, G., Gibbs, D. L., Gillanders, W. E., Goecks, J., Goodwin, D., Gray, J. W., Greenleaf, W., Grimm, L. J., Gu, Q., Guerriero, J. L., Guha, T., Guimaraes, A. R., Gutierrez, B., Hacohen, N., Hanson, C. R., Harris, C. R., Hawkins, W. G., Heiser, C. N., Hoffer, J., Hollmann, T. J., Hsieh, J. J., Huang, J., Hunger, S. P., Hwang, E., Iacobuzio-Donahue, C., Iglesia, M. D., Islam, M., Izar, B., Jacobson, C. A., Janes, S., Jayasinghe, R. G., Jeudi, T., Johnson, B. E., Johnson, B. E., Ju, T., Kadara, H., Karnoub, E., Karpova, A., Khan, A., Kibbe, W., Kim, A. H., King, L. M., Kozlowski, E., Krishnamoorthy, P., Krueger, R., Kundaje, A., Ladabaum, U., Laquindanum, R., Lau, C., Lau, K. S., LeBoeuf, N. R., Lee, H., Lenburg, M., Leshchiner, I., Levy, R., Li, Y., Lian, C. G., Liang, W., Lim, K., Lin, Y., Liu, D., Liu, Q., Liu, R., Lo, J., Lo, P., Longabaugh, W. J., Longacre, T., Luckett, K., Ma, C., Maher, C., Maier, A., Makowski, D., Maley, C., Maliga, Z., Manoj, P., Maris, J. M., Markham, N., Marks, J. R., Martinez, D., Mashl, J., Masilionis, I., Massague, J., Mazurowski, M. A., McKinley, E. T., McMichael, J., Meyerson, M., Mills, G. B., Mitri, Z. I., Moorman, A., Mudd, J., Murphy, G. F., Deen, N. N., Navin, N. E., Nawy, T., Ness, R. M., Nevins, S., Nirmal, A. J., Novikov, E., Oh, S. T., Oldridge, D. A., Owzar, K., Pant, S. M., Park, W., Patti, G. J., Paul, K., Pelletier, R., Persson, D., Petty, C., Pfister, H., Polyak, K., Puram, S. V., Qiu, Q., Villalonga, A. Q., Ramirez, M. A., Rashid, R., Reeb, A. N., Reid, M. E., Remsik, J., Riesterer, J. L., Risom, T., Ritch, C. C., Rolong, A., Rudin, C. M., Ryser, M. D., Sato, K., Sears, C. L., Semenov, Y. R., Shen, J., Shoghi, K. I., Shrubsole, M. J., Shyr, Y., Sibley, A. B., Simmons, A. J., Sinha, A., Sivagnanam, S., Song, S., Southar-Smith, A., Spira, A. E., Cyr, J. S., Stefankiewicz, S., Storrs, E. P., Stover, E. H., Strand, S. H., Straub, C., Street, C., Su, T., Surrey, L. F., Suver, C., Tan, K., Terekhanova, N. V., Ternes, L., Thadi, A., Thomas, G., Tibshirani, R., Umeda, S., Uzun, Y., Vallius, T., Van Allen, E. R., Vandekar, S., Vega, P. N., Veis, D. J., Vennam, S., Verma, A., Vigneau, S., Wagle, N., Wahl, R., Walle, T., Wang, L., Warchol, S., Washington, M. K., Watson, C., Weimer, A. K., Wendl, M. C., West, R. B., White, S., Windon, A. L., Wu, H., Wu, C., Wu, Y., Wyczalkowski, M. A., Xu, J., Yao, L., Yu, W., Zhang, K., Zhu, X. 2022; 19 (3): 262-267

  View details for DOI 10.1038/s41592-022-01415-4

  View details for PubMedID 35277708

• Surgery for Hereditary Diffuse Gastric Cancer: Long-Term Outcomes. Cancers Forrester, J. D., Foster, D., Ford, J. M., Longacre, T. A., Ladabaum, U., Fry, S., Norton, J. A. 2022; 14 (3)

  Abstract

  Gastric cancer is inherited as an autosomal dominant condition in hereditary diffuse gastric cancer (HDGC). The gene associated with HDGC is an E-cadherin gene CDH1. At the time of initiation of this study, it was estimated that 70% of patients who inherited the CDH1 gene mutation would develop gastric cancer. We hypothesized that the rate of signet ring cell cancer in asymptomatic patients with CDH1 mutations may be higher than anticipated and that the surgery could be conducted with acceptable short-term and long-term complications suggesting that the quality of life with the surgery is acceptable.We prospectively studied the role of total gastrectomy in symptomatic and asymptomatic patients with CDH1 mutations. A total of 43 patients with mutations of the CDH1 gene were studied prospectively, including 8 with symptoms and 35 without symptoms. Total gastrectomy was recommended to each. Quality of life was assessed in patients who underwent prophylactic gastrectomy. Proportions are compared with Fisher's exact test.In total, 13 (30%) asymptomatic patients declined surgery. Total gastrectomy was performed in 8 symptomatic patients and 22 asymptomatic patients of whom only 3 asymptomatic patients (14%) had endoscopically proven signet ring cell cancer preoperatively, while 21 of 22 (95%) had it on final pathology (p = 0.05). Each asymptomatic patient was T1, N0, while seven out of eight symptomatic patients had T3-T4 tumors and six had positive lymph nodes. None had operative complications or operative death. The median follow-up was 7 years. Five (63%) symptomatic patients died, while only one (95%) prophylactic patient died of a non-gastric cancer- or surgery-related issue (p = 0.05). A total of 15 prophylactic patients had long-term follow-up. Each had significant weight loss (mean 23%) but all had a normal body mass index. In total, 40% had bile reflux gastritis controlled with sucralfate. Each returned to work and, if given the choice, said that they would undergo the surgery again.Total gastrectomy is indicated for patients who have an inherented CDH1 mutation. Endoscopic screening is not reliable for diagnosing signet ring cell stomach cancer. If patients wait for symptoms, they will have a more advanced disease and significantly reduced survival. Operative complications of prophylactic gastrectomy are minimal, and long-term quality of life is acceptable.

  View details for DOI 10.3390/cancers14030728

  View details for PubMedID 35158993

• Counting Advanced Pre-Cancerous Lesions as True Positives When Determining Colorectal Cancer Screening Test Specificity. Journal of the National Cancer Institute Ladabaum, U., Church, T. R., Feng, Z., Ransohoff, D. F., Schoen, R. E. 2022

  Abstract

  The landmark Centers for Medicare & Medicaid Services (CMS) Decision Memo on blood-based biomarkers to screen for colorectal cancer (CRC) sets thresholds of ≥ 74% for sensitivity and ≥90% for specificity for CRC. This approach does not consider detection of advanced precancerous lesions as true positives. We contrasted the impact of counting advanced precancerous lesions as true vs. false positives, and projected CRC outcomes under contrasting tests in a validated model. A test with the threshold performance set by CMS decreased CRC incidence by 30% and CRC mortality by 48% in 45-year-olds. If this test also detected advanced precancerous lesions with 30% sensitivity, CRC incidence decreased by 45% and mortality by 58%, but the test's CRC specificity of only 88% would not satisfy the CMS threshold. CMS should reconsider its definition of threshold specificity for CRC screening biomarkers. Future coverage determinations on biomarkers to screen for cancer should consider detection of relevant precursor lesions, and projected outcomes.

  View details for DOI 10.1093/jnci/djac027

  View details for PubMedID 35134969

• Potential effects of lowering colorectal cancer screening age to 45 years on colonoscopy demand, case mix and adenoma detection rate. Gastroenterology Crockett, S. D., Ladabaum, U. 2021

  View details for DOI 10.1053/j.gastro.2021.11.024

  View details for PubMedID 34838825

• Age-Specific Rates and Time-Courses of Gastrointestinal and Nongastrointestinal Complications Associated With Screening/Surveillance Colonoscopy. The American journal of gastroenterology Ladabaum, U., Mannalithara, A., Desai, M., Sehgal, M., Singh, G. 2021

  Abstract

  INTRODUCTION: The rates of serious cardiac, neurologic, and pulmonary events attributable to colonoscopy are poorly characterized, and background event rates are usually not accounted for.METHODS: We performed a multistate population-based study using changepoint analysis to determine the rates and timing of serious gastrointestinal and nongastrointestinal adverse events associated with screening/surveillance colonoscopy, including analyses by age (45 to <55, 55 to <65, 65 to <75, and ≥75 years). Among 4.5 million persons in the Ambulatory Surgery and Services Databases of California, Florida, and New York who underwent screening/surveillance colonoscopy in 2005-2015, we ascertained serious postcolonoscopy events in excess of background rates in Emergency Department (SEDD) and Inpatient Databases (SID).RESULTS: Most serious nongastrointestinal postcolonoscopy events were expected based on the background rate and not associated with colonoscopy itself. However, associated nongastrointestinal events predominated over gastrointestinal events at ages ≥65 years, including more myocardial infarctions plus ischemic strokes than perforations at ages ≥75 years (361 [95% confidence intervals {CI} 312-419] plus 1,279 [95% CI 1,182-1,384] vs 912 [95% CI 831-1,002] per million). At all ages, the observed-to-expected ratios for days 0-7, 0-30, and 0-60 after colonoscopy were substantially >1 for gastrointestinal bleeding and perforation, but minimally >1 for most nongastrointestinal complications. Risk periods ranged from 1 to 125 days depending on complication type and age. No excess postcolonoscopy in-hospital deaths were observed.DISCUSSION: Although crude counts substantially overestimate nongastrointestinal events associated with colonoscopy, nongastrointestinal complications exceed bleeding and perforation risk in older persons. The inability to ascertain modifications to antiplatelet therapy was a study limitation. Our results can inform benefit-to-risk determinations for preventive colonoscopy.

  View details for DOI 10.14309/ajg.0000000000001531

  View details for PubMedID 34693917

• The Stanford Colonoscopy Quality Assurance Program: Lessons from the intersection of quality improvement and clinical research. Gastroenterology Ladabaum, U. 2021

  View details for DOI 10.1053/j.gastro.2021.09.068

  View details for PubMedID 34653422

• Increased Colorectal Cancer Screening Sustained with Mailed Fecal Immunochemical Test Outreach. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Lee, B., Keyes, E., Rachocki, C., Grimes, B., Chen, E., Vittinghoff, E., Ladabaum, U., Somsouk, M. 2021

  Abstract

  BACKGROUND & AIMS: Reports of mailed fecal immunochemical test (FIT) outreach effectiveness over time are minimal. We aimed to better evaluate a mailed FIT program with longitudinal metrics.METHODS: A total of 10,771 patients aged 50-75 years not up-to-date (UTD) with colorectal cancer (CRC) screening were randomized to intervention or usual care. The intervention arm received an advanced notification call and informational postcard prior to a mailed FIT. Usual care was at the discretion of the primary care provider. Patients were followed for up to 2.5 years. The primary outcome was the difference in cumulative proportion of completed FIT screening between arms. Screening was further examined with the proportion of time UTD, consistency of adherence, and frequency of abnormal FIT.RESULTS: The cumulative proportion of FIT completion was higher in the outreach intervention (73.2% vs. 55.1%, p<0.001). The proportion of time covered by screening was higher in the intervention group (46.8% vs. 27.3%, Delta19.6%, 95% CI 18.2%-20.9%). Patients assigned to FIT outreach were more likely to consistently complete FITs (2 completed of 2 offered) (50.1% vs. 21.8%, p<0.001). However, for patients who did not complete the FIT during the first cycle, only 17.1% completed a FIT during the second outreach cycle. The number and overall proportion of abnormal FIT was significantly higher in the outreach intervention (6.9% Outreach vs. 4.1% Usual Care, p<0.01).CONCLUSIONS: Organized mailed FIT outreach significantly increased CRC screening over multiple years in this safety-net health system. While mailing was overall effective, the effect was modest in patients who did not complete FIT in first cycle of intervention. (ClincialTrials.gov, NCT02613260).

  View details for DOI 10.1016/j.cgh.2021.07.022

  View details for PubMedID 34280552

• Developing and Deploying an Automated Quality Reporting System in Your Practice: Learning From the Stanford Colonoscopy Quality Assurance Program. The American journal of gastroenterology Ladabaum, U., Shepard, J., Mannalithara, A. 2021; 116 (7): 1365-1370

  View details for DOI 10.14309/ajg.0000000000001265

  View details for PubMedID 34183571

• Doing our best to do no harm. Endoscopy Ladabaum, U. 2021; 53 (5): 509–10

  View details for DOI 10.1055/a-1290-7610

  View details for PubMedID 33887782

• Adenoma and Serrated Lesion Detection by Colonoscopy Indication: The ADR-ESS (ADR Extended to all Screening/Surveillance) Score. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Ladabaum, U., Shepard, J., Mannalithara, A. 2021

  Abstract

  BACKGROUND: The adenoma detection rate at screening (ADR) predicts interval colorectal cancer (CRC). Monitoring other lesion detection rates and colonoscopy indications has been proposed. We developed a comprehensive, automated colonoscopy audit program based on standardized clinical documentation, explored detection rates across indications, and developed the "Adenoma Detection Rate - Extended to all Screening / Surveillance" (ADR-ESS) score.METHODS: In a prospective cohort study, we calculated overall and advanced adenoma and sessile serrated lesion (SSL) detection rates among 15,253 colonoscopies by 35 endoscopists from 4 endoscopy units across all colonoscopy indications. We explored correlations between detection rates, and the precision and stability of ADR-ESS vs. ADR.RESULTS: The overall "Screening, first" ADR was 36.3% (95%CI 34.5-38.1%). The adenoma detection rate was lower for "Screening, not first" (RR 0.80 [95%CI 0.74-0.87]) and "Family history" (RR 0.84 [95%CI 0.74-0.96]), and higher for "Surveillance" (RR 1.22 [95%CI 1.15-1.31]) and "Follow-up, FIT" (RR 1.21 [95%CI 1.07-1.37]). For "Screening, first," the detection rates for advanced adenoma, SSL, and advanced SSL were 6.7% (95%CI 5.7-7.7%), 7.2% (95%CI 6.2-8.2%), and 2.6% (95%CI 2.0-3.2%), respectively. Adenoma and SSL detection were correlated (r=0.44, p=0.008). ADR-ESS had substantially narrower confidence intervals and less period-to-period variability than ADR, and was not improved by weighting for indication volume and correction for detection by indication.CONCLUSIONS: Comprehensive, automated colonoscopy audit based on standardized clinical documentation is feasible. Adenoma detection is a fair but imperfect proxy for SSL detection. ADR-ESS increases the precision of adenoma detection assessments and emphasizes quality across colonoscopy indications.

  View details for DOI 10.1016/j.cgh.2021.04.027

  View details for PubMedID 33895358

• Colorectal Cancer Incidence after Colonoscopy at Ages 45-49 or 50-54 Years. Gastroenterology Sehgal, M. n., Ladabaum, U. n., Mithal, A. n., Singh, H. n., Desai, M. n., Singh, G. n. 2021

  Abstract

  Colorectal cancer (CRC) incidence at ages <50 years is increasing, leading to proposals lower the CRC screening initiation age to 45 years. Data on the effectiveness of CRC screening at ages 45-49 years are lacking.We studied the association between undergoing colonoscopy at ages 45-49 or 50-54 years and CRC incidence in a retrospective population-based cohort study using Florida's linked Healthcare Cost and Utilization Project databases with mandated reporting from 2005-2017, and Cox models extended for time-varying exposure.Among 195,600 persons with and 2.6 million without exposure to colonoscopy at ages 45-49 years, 276 and 4,844 developed CRC, resulting in CRC incidence rates of 20.8 (95% confidence interval [CI], 18.5-23.4) and 30.6 (95% CI, 29.8-31.5) per 100,000 person-years, respectively. Among 660,248 persons with and 2.4 million without exposure to colonoscopy at ages 50-54 years, 798 and 6,757 developed CRC, resulting in CRC incidence rates of 19.0 (95% CI, 17.7-20.4) and 51.9 (95% CI, 50.7-53.1) per 100,000 person-years, respectively. The adjusted hazard ratios for incident CRC after undergoing compared with not undergoing colonoscopy were 0.50 (95% CI, 0.44-0.56) at ages 45-49 years and 0.32 (95% CI, 0.29-0.34) at ages 50-54 years. The results were similar for women and men (0.48 [95% CI, 0.40-0.57] and 0.52 [95% CI, 0.43-0.62] at ages 45-49 years, and 0.35 [95% CI 0.31-0.39] and 0.29 [95% CI 0.26-0.32] at ages 50-54 years, respectively).Colonoscopy at ages 45-49 years or 50-54 years was associated with substantial decreases in subsequent CRC incidence. These findings can inform screening guidelines.

  View details for DOI 10.1053/j.gastro.2021.02.015

  View details for PubMedID 33577872

• Hereditary inflammatory fibroid polyps caused by germline pathogenic variants in PDGFRA: Refining PDGFRA-mutation syndrome. Cancer genetics Hodan, R., Charville, G. W., Ladabaum, U. 2021; 256-257: 106-109

  Abstract

  A 35-year-old Filipino woman presented with epigastric pain and was found to have two large jejunal and ileal inflammatory fibroid polyps (IFPs) and dozens of subcentimeter small bowel submucosal nodules. Targeted exon sequencing of PDGFRA on the resected jejunum IFP identified a variant c.1664A>G that was subsequently confirmed in the germline. Family history was striking for three relatives with confirmed IFPs, including one with small bowel intussusception on five occasions. All relatives with IFPs were confirmed to have the same PDGFRA germline likely pathogenic variant, all were female, and all had IFPs by age 50 years that necessitated surgery. Two obligate carriers were reported to have had a similar phenotype while at least one obligate male carrier had no reported history of IFPs. This is the sixth reported family with a germline PDGFRA pathogenic variant and history of IFPs or gastrointestinal stromal tumor (GIST). This is the second report of the c.1664A>G likely pathogenic variant in a family that is unrelated to, and of different ethnic origin than, the first family. This second family exhibited a striking history of multiple IFPs without any reported GISTs, suggesting a possible genotype/phenotype association for this variant, and a possible female gender penetrance bias.

  View details for DOI 10.1016/j.cancergen.2021.05.003

  View details for PubMedID 34107389

• Subtle endoscopic manifestations of diffuse signet cell gastric adenocarcinoma in patients with CDH1 mutations. Gastrointestinal endoscopy Ladabaum, U., Ford, J. M., Poultsides, G., Norton, J. 2021

  View details for DOI 10.1016/j.gie.2021.08.006

  View details for PubMedID 34416278

• Life After May 25. Annals of internal medicine Ladabaum, U. 2020

  View details for DOI 10.7326/M20-4106

  View details for PubMedID 32744867

• Advanced Notification Calls Prior to Mailed Fecal Immunochemical Test in Previously Screened Patients: a Randomized Controlled Trial. Journal of general internal medicine Lee, B., Patel, S., Rachocki, C., Issaka, R., Vittinghoff, E., Shapiro, J. A., Ladabaum, U., Somsouk, M. 2020

  Abstract

  BACKGROUND: Phone calls as part of multimodal fecal immunochemical test (FIT) outreach are effective but resource-intensive. Previous studies of advanced notification calls before FIT mailing have not differentiated patients' prior screening status.OBJECTIVE: To determine the effectiveness of a phone call preceding mailing of a FIT kit on test completion rate for patients who have completed a prior FIT.DESIGN: Randomized controlled trial nested within a larger study. All patients were assigned to receive organized mailed FIT outreach in the larger study.PARTICIPANTS: Patients in a safety-net health setting ages 50-75 years old with a previously negative FIT.INTERVENTIONS: Patients were assigned to either receive an advanced notification phone call or no phone call preceding a mailed FIT kit. Both groups received an informational postcard prior to the mailed FIT.MAIN MEASURES: The primary outcome was FIT completion rate at 1 year. The secondary outcomes were FIT completion rates at 60, 90, and 180 days, rates stratified by demographic subgroups, and rates according to outcome of the phone call.KEY RESULTS: A total of 1645 patients were assigned to advanced notification calls and 1595 were assigned to no call preceding the FIT mailing. Although FIT completion rate was higher at day 60 (55.5% vs. 50.8%, p < 0.01), an advanced notification call did not significantly improve FIT completion at 1 year (70.9% vs. 69.9%, p = 0.52). Of the patients assigned to receive an advanced notification call, 90.5% were spoken with or left a voicemail; patients who were spoken with were more likely to complete a FIT at 1 year compared with patients who were only left a voicemail or could not be left a voicemail (79.9% vs. 69.2% vs. 49.6%, p < 0.01).CONCLUSIONS: Advanced notification phone calls prior to FIT mailing did not improve rates at 1 year for patients with a previously negative FIT.

  View details for DOI 10.1007/s11606-020-06009-4

  View details for PubMedID 32748345

• The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution. Cell Rozenblatt-Rosen, O., Regev, A., Oberdoerffer, P., Nawy, T., Hupalowska, A., Rood, J. E., Ashenberg, O., Cerami, E., Coffey, R. J., Demir, E., Ding, L., Esplin, E. D., Ford, J. M., Goecks, J., Ghosh, S., Gray, J. W., Guinney, J., Hanlon, S. E., Hughes, S. K., Hwang, E. S., Iacobuzio-Donahue, C. A., Jane-Valbuena, J., Johnson, B. E., Lau, K. S., Lively, T., Mazzilli, S. A., Pe'er, D., Santagata, S., Shalek, A. K., Schapiro, D., Snyder, M. P., Sorger, P. K., Spira, A. E., Srivastava, S., Tan, K., West, R. B., Williams, E. H., Human Tumor Atlas Network, Aberle, D., Achilefu, S. I., Ademuyiwa, F. O., Adey, A. C., Aft, R. L., Agarwal, R., Aguilar, R. A., Alikarami, F., Allaj, V., Amos, C., Anders, R. A., Angelo, M. R., Anton, K., Ashenberg, O., Aster, J. C., Babur, O., Bahmani, A., Balsubramani, A., Barrett, D., Beane, J., Bender, D. E., Bernt, K., Berry, L., Betts, C. B., Bletz, J., Blise, K., Boire, A., Boland, G., Borowsky, A., Bosse, K., Bott, M., Boyden, E., Brooks, J., Bueno, R., Burlingame, E. A., Cai, Q., Campbell, J., Caravan, W., Cerami, E., Chaib, H., Chan, J. M., Chang, Y. H., Chatterjee, D., Chaudhary, O., Chen, A. A., Chen, B., Chen, C., Chen, C., Chen, F., Chen, Y., Chheda, M. G., Chin, K., Chiu, R., Chu, S., Chuaqui, R., Chun, J., Cisneros, L., Coffey, R. J., Colditz, G. A., Cole, K., Collins, N., Contrepois, K., Coussens, L. M., Creason, A. L., Crichton, D., Curtis, C., Davidsen, T., Davies, S. R., de Bruijn, I., Dellostritto, L., De Marzo, A., Demir, E., DeNardo, D. G., Diep, D., Ding, L., Diskin, S., Doan, X., Drewes, J., Dubinett, S., Dyer, M., Egger, J., Eng, J., Engelhardt, B., Erwin, G., Esplin, E. D., Esserman, L., Felmeister, A., Feiler, H. S., Fields, R. C., Fisher, S., Flaherty, K., Flournoy, J., Ford, J. M., Fortunato, A., Frangieh, A., Frye, J. L., Fulton, R. S., Galipeau, D., Gan, S., Gao, J., Gao, L., Gao, P., Gao, V. R., Geiger, T., George, A., Getz, G., Ghosh, S., Giannakis, M., Gibbs, D. L., Gillanders, W. E., Goecks, J., Goedegebuure, S. P., Gould, A., Gowers, K., Gray, J. W., Greenleaf, W., Gresham, J., Guerriero, J. L., Guha, T. K., Guimaraes, A. R., Guinney, J., Gutman, D., Hacohen, N., Hanlon, S., Hansen, C. R., Harismendy, O., Harris, K. A., Hata, A., Hayashi, A., Heiser, C., Helvie, K., Herndon, J. M., Hirst, G., Hodi, F., Hollmann, T., Horning, A., Hsieh, J. J., Hughes, S., Huh, W. J., Hunger, S., Hwang, S. E., Iacobuzio-Donahue, C. A., Ijaz, H., Izar, B., Jacobson, C. A., Janes, S., Jane-Valbuena, J., Jayasinghe, R. G., Jiang, L., Johnson, B. E., Johnson, B., Ju, T., Kadara, H., Kaestner, K., Kagan, J., Kalinke, L., Keith, R., Khan, A., Kibbe, W., Kim, A. H., Kim, E., Kim, J., Kolodzie, A., Kopytra, M., Kotler, E., Krueger, R., Krysan, K., Kundaje, A., Ladabaum, U., Lake, B. B., Lam, H., Laquindanum, R., Lau, K. S., Laughney, A. M., Lee, H., Lenburg, M., Leonard, C., Leshchiner, I., Levy, R., Li, J., Lian, C. G., Lim, K., Lin, J., Lin, Y., Liu, Q., Liu, R., Lively, T., Longabaugh, W. J., Longacre, T., Ma, C. X., Macedonia, M. C., Madison, T., Maher, C. A., Maitra, A., Makinen, N., Makowski, D., Maley, C., Maliga, Z., Mallo, D., Maris, J., Markham, N., Marks, J., Martinez, D., Mashl, R. J., Masilionais, I., Mason, J., Massague, J., Massion, P., Mattar, M., Mazurchuk, R., Mazutis, L., Mazzilli, S. A., McKinley, E. T., McMichael, J. F., Merrick, D., Meyerson, M., Miessner, J. R., Mills, G. B., Mills, M., Mondal, S. B., Mori, M., Mori, Y., Moses, E., Mosse, Y., Muhlich, J. L., Murphy, G. F., Navin, N. E., Nawy, T., Nederlof, M., Ness, R., Nevins, S., Nikolov, M., Nirmal, A. J., Nolan, G., Novikov, E., Oberdoerffer, P., O'Connell, B., Offin, M., Oh, S. T., Olson, A., Ooms, A., Ossandon, M., Owzar, K., Parmar, S., Patel, T., Patti, G. J., Pe'er, D., Pe'er, I., Peng, T., Persson, D., Petty, M., Pfister, H., Polyak, K., Pourfarhangi, K., Puram, S. V., Qiu, Q., Quintanal-Villalonga, A., Raj, A., Ramirez-Solano, M., Rashid, R., Reeb, A. N., Regev, A., Reid, M., Resnick, A., Reynolds, S. M., Riesterer, J. L., Rodig, S., Roland, J. T., Rosenfield, S., Rotem, A., Roy, S., Rozenblatt-Rosen, O., Rudin, C. M., Ryser, M. D., Santagata, S., Santi-Vicini, M., Sato, K., Schapiro, D., Schrag, D., Schultz, N., Sears, C. L., Sears, R. C., Sen, S., Sen, T., Shalek, A., Sheng, J., Sheng, Q., Shoghi, K. I., Shrubsole, M. J., Shyr, Y., Sibley, A. B., Siex, K., Simmons, A. J., Singer, D. S., Sivagnanam, S., Slyper, M., Snyder, M. P., Sokolov, A., Song, S., Sorger, P. K., Southard-Smith, A., Spira, A., Srivastava, S., Stein, J., Storm, P., Stover, E., Strand, S. H., Su, T., Sudar, D., Sullivan, R., Surrey, L., Suva, M., Tan, K., Terekhanova, N. V., Ternes, L., Thammavong, L., Thibault, G., Thomas, G. V., Thorsson, V., Todres, E., Tran, L., Tyler, M., Uzun, Y., Vachani, A., Van Allen, E., Vandekar, S., Veis, D. J., Vigneau, S., Vossough, A., Waanders, A., Wagle, N., Wang, L., Wendl, M. C., West, R., Williams, E. H., Wu, C., Wu, H., Wu, H., Wyczalkowski, M. A., Xie, Y., Yang, X., Yapp, C., Yu, W., Yuan, Y., Zhang, D., Zhang, K., Zhang, M., Zhang, N., Zhang, Y., Zhao, Y., Zhou, D. C., Zhou, Z., Zhu, H., Zhu, Q., Zhu, X., Zhu, Y., Zhuang, X. 2020; 181 (2): 236–49

  Abstract

  Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.

  View details for DOI 10.1016/j.cell.2020.03.053

  View details for PubMedID 32302568

• Prevalence and Clinical Features of Sessile Serrated Polyps: A Systematic Review. Gastroenterology Meester, R. G., van Herk, M. M., Lansdorp-Vogelaar, I., Ladabaum, U. 2020

  Abstract

  BACKGROUND & AIMS: Sessile serrated polyps (SSPs) could account for a substantial proportion of colorectal cancers. We aimed to increase clarity on SSP prevalence and clinical features.METHODS: We performed a systematic review of Medline, Web of Science, Embase, and Cochrane databases for original studies published in English since 2000. We included studies of different populations (United States general or similar), interventions (colonoscopy, autopsy), comparisons (world regions, alternative polyp definitions, adenoma), outcomes (prevalence, clinical features), and study designs (cross-sectional). Random-effects regression was used for meta-analysis where possible.RESULTS: We identified 74 relevant colonoscopy studies. SSP prevalence varied by world region, from 2.6% in Asia (95% CI, 0-5.9%) to 10.5% in Australia (95% CI, 2.8%-18.2%). Prevalence values did not differ significantly between the United States and Europe (P=.51); the pooled prevalence was 4.6% (95% CI, 3.4%-5.8%), and SSPs accounted for 9.4% of polyps with malignant potential (95% CI, 6.6%-12.3%). Mean prevalence was higher when assessed through high-performance exams (9.1%; 95% CI, 4.0%-14.2%, P=.04) and with alternative definition of clinically relevant serrated polyps (12.3%; 95% CI, 9.3%-15.4%; P<.001). Increases in prevalence with age were not statistically significant, and prevalence did not differ significantly by sex. Compared with adenomas, a higher proportion of SSPs were solitary (69.0%; 95% CI, 45.9%-92.1%; P=.08), with diameters of 10 mm or more (19.3%; 95% CI, 12.4%-26.2%; P=.13), and were proximal (71.5%; 95% CI, 63.5%-79.5%; P=.009). Mean ages for detection of SSP without dysplasia, with any or low-grade dysplasia, and with high-grade dysplasia were 60.8 y, 65.6 y, and 70.2 y, respectively. The range for proportion of SSPs with dysplasia was 3.7%-42.9% across studies, possibly reflecting different study populations.CONCLUSIONS: In a systematic review, we found that sessile serrated polyps are relatively uncommon, compared with adenoma. More research is needed on appropriate diagnostic criteria, variations in detection, and long-term risk.

  View details for DOI 10.1053/j.gastro.2020.03.025

  View details for PubMedID 32199884

• AGA White Paper: Roadmap for the Future of Colorectal Cancer Screening in the United States. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Melson, J. E., Imperiale, T. F., Itzkowitz, S. H., Llor, X. n., Kochman, M. L., Grady, W. M., Schoen, R. E., Burke, C. n., Shaukat, A. n., Rabeneck, L. n., Ladabaum, U. n., Bresalier, R. n., Spiegel, B. n., Yee, J. n., Wang, T. n., Lieberman, D. n., Komanduri, S. n., Muthusamy, V. R., Dey, N. n. 2020

  View details for DOI 10.1016/j.cgh.2020.06.053

  View details for PubMedID 32634626

• Cost-Effectiveness of Current Colorectal Cancer Screening Tests. Gastrointestinal endoscopy clinics of North America Ladabaum, U. n. 2020; 30 (3): 479–97

  Abstract

  Cost-effectiveness analysis compares benefits and costs of different interventions to inform decision makers. Alternatives are compared based on an incremental cost-effectiveness ratio reported in terms of cost per quality-adjusted life-year gained. Multiple cost-effectiveness analyses of colorectal cancer (CRC) screening have been performed. Although regional epidemiology of CRC, relevant screening strategies, regional health system, and applicable medical costs in local currencies differ by country and region, several overarching points emerge from literature on cost-effectiveness of CRC screening. Cost-effectiveness analysis informs decisions in ongoing debates, including preferred age to begin average-risk CRC screening, and implementation of CRC screening tailored to predicted CRC risk.

  View details for DOI 10.1016/j.giec.2020.02.005

  View details for PubMedID 32439083

• Intensity of Surveillance for Patients With Colorectal Adenomas. Annals of internal medicine Meester, R. G., Lansdorp-Vogelaar, I. n., Winawer, S. J., Zauber, A. G., Knudsen, A. B., Ladabaum, U. n. 2020; 172 (6): 442

  View details for DOI 10.7326/L19-0829

  View details for PubMedID 32176909

• A nationwide analysis of readmission rates after colorectal cancer surgery in the US in the Era of the Affordable Care Act. American journal of surgery Kim, J. W., Mannalithara, A. n., Sehgal, M. n., Mithal, A. n., Singh, G. n., Ladabaum, U. n. 2020

  Abstract

  The Hospital Readmissions Reduction Program (HRRP), which was instituted in 2012, may have affected readmission rates for non-target conditions, including colorectal cancer (CRC). We aimed to analyze the nationwide all-cause 30-day readmission rate following CRC surgery in a US nationwide database.We queried the 2010-2015 Nationwide Readmissions Database to estimate readmission rates. All results were weighted for national estimates.Among 616,348 index cases, the overall 2010-2015 30-day readmission rate was 14.7% (95% confidence interval, 14.5%-14.9% [n = 90,555]), with a decreasing trend from 15.5% in 2010 and 2011 to 13.5% in 2015 (p-trend<0.001). Rectal resection, longer length of stay, non-invasive cancer, surgery at a metropolitan teaching hospital, non-routine discharge, elective admission, and higher Elixhauser comorbidity score were associated with subsequent readmission.In the US, 30-day readmission rates after CRC surgery showed a decreasing trend during 2010-2015, which could represent a spillover effect of the HRRP.

  View details for DOI 10.1016/j.amjsurg.2020.04.013

  View details for PubMedID 32362379

• Risk of ambulatory colonoscopy in patients with cirrhosis: a propensity-score matched cohort study. Endoscopy international open Huang, R. J., Banerjee, S. n., Friedland, S. n., Ladabaum, U. n. 2020; 8 (10): E1495–E1501

  Abstract

  Background and study aims  Patients with cirrhosis demonstrate alterations in physiology, hemodynamics, and immunity which may increase procedural risk. There exist sparse data regarding the safety of performing ambulatory colonoscopy in patients with cirrhosis. Patients and methods  From a population-based sample of three North American states (California, Florida, and New York), we collected data on 3,590 patients with cirrhosis who underwent ambulatory colonoscopy from 2009 to 2014. We created a control cohort propensity score-matched for cirrhotic severity who did not undergo colonoscopy (N = 3,590) in order to calculate the attributable risk for adverse events. The primary endpoint was the rate of unplanned hospital encounters (UHEs) within 14 days of colonoscopy (or from a synthetic index date for the control cohort). Predictors for UHE were assessed in multivariable regression. Results  The attributable risk for any UHE following colonoscopy was 3.1 % (confidence interval [CI] 2.1-4.1 %, P  < 0.001). There was increased risk for infection (0.9 %, CI 0.7-1.1 %), spontaneous bacterial peritonitis (0.1 %, CI 0.0-0.3 %), decompensation of ascites (0.3 %, CI 0.2-0.4 %), and cardiovascular event (0.4 %, CI 0.3-0.5 %). There was no increased attributable risk for gastrointestinal bleeding, perforation, or development of the hepatorenal syndrome. The presence of ascites at time of procedure was the only predictor for UHE in the fully-adjusted model (OR 2.6, CI 1.9-3.5, P  < 0.001). Conclusions  There is a moderate though detectable increase in risk for adverse event following ambulatory colonoscopy in patients with cirrhosis. The presence of ascites in particular portends higher risk. These data may guide clinicians when counseling patients with cirrhosis on the choice of colorectal cancer screening modality.

  View details for DOI 10.1055/a-1242-9958

  View details for PubMedID 33043119

  View details for PubMedCentralID PMC7541192

• Sessile serrated polyps and colorectal cancer mortality. The lancet. Gastroenterology & hepatology Meester, R. G., Ladabaum, U. n. 2020

  View details for DOI 10.1016/S2468-1253(20)30074-1

  View details for PubMedID 32192629

• Psychosocial outcomes following germline multigene panel testing in an ethnically and economically diverse cohort of patients. Cancer Culver, J. O., Ricker, C. N., Bonner, J. n., Kidd, J. n., Sturgeon, D. n., Hodan, R. n., Kingham, K. n., Lowstuter, K. n., Chun, N. M., Lebensohn, A. P., Rowe-Teeter, C. n., Levonian, P. n., Partynski, K. n., Lara-Otero, K. n., Hong, C. n., Morales Pichardo, J. n., Mills, M. A., Brown, K. n., Lerman, C. n., Ladabaum, U. n., McDonnell, K. J., Ford, J. M., Gruber, S. B., Kurian, A. W., Idos, G. E. 2020

  Abstract

  Little is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate-risk pathogenic variants (PVs).Study participants (N = 1264) were counseled and tested with a 25- or 28-gene panel and completed a 3-month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA).The mean age was 52 years, 80% were female, and 70% had cancer; 45% were non-Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non-English-speaking. The genetic test results were as follows: 7% had a high-risk PV, 6% had a moderate-risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of "never," "rarely," or only "sometimes" reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high- and moderate-risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High- and moderate-risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences.In a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds.Multigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate-risk pathogenic variants (mutations) and among carriers of variants of uncertain significance. This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% "never," "rarely," or only "sometimes" reacted negatively to results. Somewhat higher uncertainty and distress were identified among carriers of high- and moderate-risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

  View details for DOI 10.1002/cncr.33357

  View details for PubMedID 33320347

• Randomized Controlled Trial of Personalized Colorectal Cancer Risk Assessment vs Education to Promote Screening Uptake. The American journal of gastroenterology Yen, T. n., Qin, F. n., Sundaram, V. n., Asiimwe, E. n., Storage, T. n., Ladabaum, U. n. 2020

  Abstract

  Risk stratification has been proposed as a strategy to improve participation in colorectal cancer (CRC) screening, but evidence is lacking. We performed a randomized controlled trial of risk stratification using the National Cancer Institute's Colorectal Cancer Risk Assessment Tool (CCRAT) on screening intent and completion.A total of 230 primary care patients eligible for first-time CRC screening were randomized to risk assessment via CCRAT or education control. Follow-up of screening intent and completion was performed by record review and phone at 6 and 12 months. We analyzed change in intent after intervention, time to screening, overall screening completion rates, and screening completion by CCRAT risk score tertile.Of the patients, 61.7% of patients were aged <60 years, 58.7% female, and 94.3% with college or higher education. Time to screening did not differ between arms (hazard ratio 0.78 [95% confidence interval (CI) 0.52-1.18], P = 0.24). At 12 months, screening completion was 38.6% with CCRAT vs 44.0% with education (odds ratio [OR] 0.80 [95% CI 0.47-1.37], P = 0.41). Changes in screening intent did not differ between the risk assessment and education arms (precontemplation to contemplation: OR 1.52 [95% CI 0.81-2.86], P = 0.19; contemplation to precontemplation: OR 1.93 [95% CI 0.45-8.34], P = 0.38). There were higher screening completion rates at 12 months in the top CCRAT risk tertile (52.6%) vs the bottom (32.4%) and middle (31.6%) tertiles (P = 0.10).CCRAT risk assessment did not increase screening participation or intent. Risk stratification might motivate persons classified as higher CRC risk to complete screening, but unintentionally discourage screening among persons not identified as higher risk.

  View details for DOI 10.14309/ajg.0000000000000963

  View details for PubMedID 33009045

• What is Lynch-like Syndrome and How Should we Manage It? Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Ladabaum, U. 2019

  View details for DOI 10.1016/j.cgh.2019.08.009

  View details for PubMedID 31408703

• Cost-Effectiveness and National Effects of Initiating Colorectal Cancer Screening for Average-Risk Persons at Age 45 Years Instead of 50 Years GASTROENTEROLOGY Ladabaum, U., Mannalithara, A., Meester, R. S., Gupta, S., Schoen, R. E. 2019; 157 (1): 137–48

  View details for DOI 10.1053/j.gastro.2019.03.023

  View details for Web of Science ID 000471618100050

• Comparison of Universal Versus Age-Restricted Screening of Colorectal Tumors for Lynch Syndrome Using Mismatch Repair Immunohistochemistry: A Cohort Study. Annals of internal medicine Li, D., Hoodfar, E., Jiang, S., Udaltsova, N., Pham, N. P., Jodesty, Y., Armstrong, M. A., Hung, Y., Baker, R. J., Postlethwaite, D., Ladabaum, U., Levin, T. R., Corley, D. A., Bergoffen, J. 2019

  Abstract

  Background: Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied.Objective: To compare the performance of age-restricted and universal LS screening using reflex mismatch repair (MMR) immunohistochemistry (IHC) of CRC tumors.Design: Retrospective cohort study.Setting: A large, diverse, community-based health care system.Participants: 3891 persons with newly diagnosed CRC who had LS screening between 2011 and 2016.Measurements: Diagnostic yield of different LS screening strategies.Results: Sixty-three LS cases (diagnostic yield, 1.62%) were identified by universal screening, with only 5 (7.9%) detected after age 70 years and 1 (1.6%) detected after age 80 years. When all patients with CRC who had universal screening were used as the denominator, 58 LS cases (diagnostic yield, 1.49% [95% CI, 1.13% to 1.92%]) were identified in patients with CRC diagnosed at or before age 70 years, 60 LS cases (diagnostic yield, 1.54% [CI, 1.18% to 1.98%]) were identified in those with CRC diagnosed at or before age 75 years, and 62 LS cases (diagnostic yield, 1.59% [CI, 1.22% to 2.04%]) were identified in those with CRC diagnosed at or before age 80 years. Using 75 years as the upper age limit for screening missed 3 of 63 (4.8%) LS cases but resulted in 1053 (27.1%) fewer cases requiring tumor MMR IHC. Using 80 years as the upper age limit missed 1 of 63 (1.6%) LS cases and resulted in 668 (17.2%) fewer cases requiring tumor MMR IHC.Limitation: Persons who were eligible for but did not complete germline analysis were excluded from calculations of performance characteristics.Conclusion: The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed.Primary Funding Source: Kaiser Permanente Northern California Division of Research.

  View details for DOI 10.7326/M18-3316

  View details for PubMedID 31181578

• Preventive surgery after multiplex genetic panel testing (MGPT) Idos, G., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J., Kingham, K., Koff, R., Chun, N. M., Rowe-Teeter, C., Levonian, P., Hong, C., Mills, M., Ma, C., Lancaster, J. M., Brown, K., Kidd, J., McDonnell, K., Ladabaum, U., Ford, J. M., Gruber, S. B. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.1525

  View details for Web of Science ID 000487345804321

• Response. Gastrointestinal endoscopy Ertem, F. U., Ladabaum, U., Schoen, R. E. 2019; 89 (4): 896–97

  View details for DOI 10.1016/j.gie.2018.12.001

  View details for PubMedID 30902210

• How I do it: Does this cost-effectiveness analysis convince me about screening for Barrett's esophagus? Gastrointestinal endoscopy Ladabaum, U. 2019; 89 (4): 723–25

  View details for PubMedID 30902200

• Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk. JCO precision oncology Idos, G. E., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J. O., Kingham, K. E., Koff, R., Chun, N. M., Rowe-Teeter, C., Lebensohn, A. P., Levonian, P., Lowstuter, K., Partynski, K., Hong, C., Mills, M. A., Petrovchich, I., Ma, C. S., Hartman, A. R., Allen, B., Wenstrup, R. J., Lancaster, J. M., Brown, K., Kidd, J., Evans, B., Mukherjee, B., McDonnell, K. J., Ladabaum, U., Ford, J. M., Gruber, S. B. 2019; 3

  Abstract

  Multiplex gene panel testing (MGPT) allows for the simultaneous analysis of germline cancer susceptibility genes. This study describes the diagnostic yield and patient experiences of MGPT in diverse populations.This multicenter, prospective cohort study enrolled participants from three cancer genetics clinics-University of Southern California Norris Comprehensive Cancer Center, Los Angeles County and University of Southern California Medical Center, and Stanford Cancer Institute-who met testing guidelines or had a 2.5% or greater probability of a pathogenic variant (N = 2,000). All patients underwent 25- or 28-gene MGPT and results were compared with differential genetic diagnoses generated by pretest expert clinical assessment. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate).Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. A total of 242 participants (12%) carried one or more pathogenic variant (positive), 689 (34%) carried one or more variant of uncertain significance (VUS), and 1,069 (53%) carried no pathogenic variants or VUS (negative). More than one third of pathogenic variants (34%) were not included in the differential diagnosis. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Positive patients were twice as likely as negative/VUS patients (83% v 41%; P < .001) to encourage their relatives to be tested.In a racially/ethnically and socioeconomically diverse cohort, MGPT increased diagnostic yield. More than one third of identified pathogenic variants were not clinically anticipated. Patient regret and prophylactic surgery use were low, and patients appropriately encouraged relatives to be tested for clinically relevant results.

  View details for DOI 10.1200/PO.18.00217

  View details for PubMedID 34322651

  View details for PubMedCentralID PMC8260917

• Clinical and Economic Impact of Tailoring Screening to Predicted Colorectal Cancer Risk: A Decision Analytic Modeling Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Ladabaum, U. n., Mannalithara, A. n., Mitani, A. n., Desai, M. n. 2019

  Abstract

  Global increases in colorectal cancer (CRC) risk have spurred debate about optimal use of screening resources. We explored the potential clinical and economic impact of CRC screening tailored to predicted CRC risk.We compared screening tailored to predicted risk vs. uniform screening in a validated decision analytic model, considering the average risk population's actual CRC risk distribution, and a risk-prediction tool's discriminatory ability and cost. Low, moderate, and high risk tiers were identified as CRC risk after age 50 of <=3%, >3 to <12%, and >=12%, respectively, based on threshold analyses with willingness-to-pay <$50,000/quality-adjusted life-year (QALY) gained. Tailored colonoscopy (once at 60 for low risk, every 10 years for moderate risk, every 5 years for high risk) was compared to colonoscopy every 10 years for all. Tailored fecal immunochemical testing [FIT]/colonoscopy (annual FIT for low and moderate risk, colonoscopy every 5 years for high risk) was compared to annual FIT for all.Assuming no CRC risk misclassification or risk-prediction tool costs, tailored screening was preferred over uniform screening. Tailored colonoscopy was minimally less effective than uniform colonoscopy, but saved $90,200-$889,000/QALY; tailored FIT/colonoscopy yielded more QALYs/person than annual FIT at $10,600-$60,000/QALY gained. Relatively modest CRC risk misclassification rates or risk-prediction tool costs resulted in uniform screening as the preferred approach.Current risk-prediction tools may not yet be accurate enough to optimize CRC screening.Uniform screening is likely to be preferred over tailored screening if a risk-prediction tool is associated with even modest misclassification rates or costs.

  View details for DOI 10.1158/1055-9965.EPI-19-0949

  View details for PubMedID 31796524

• You Should Get Screened for Colon Cancer, Really. JAMA network open Ladabaum, U. n. 2019; 2 (8): e1910452

  View details for DOI 10.1001/jamanetworkopen.2019.10452

  View details for PubMedID 31469390

• The case for philanthropic investment to increase colorectal cancer screening rates: A novel paradigm to address a public health challenge. Cancer medicine Carmeli, A. n., Dranikoff, L. n., Kundu, A. n., Ladabaum, U. n. 2019

  Abstract

  Colorectal cancer (CRC) remains a leading cause of cancer-related death despite being highly preventable. Efforts to increase participation in CRC screening have not met national goals. We developed a novel approach: building a business case for philanthropic investment in CRC screening.A taskforce representing the public health community, professional societies, charitable foundations, academia, and industry was assembled to: (a) quantify the impact of improving CRC screening rates; (b) identify barriers to screening; (c) estimate the "activation cost" to overcome barriers and screen one additional person; (d) develop a holistic business case that is attractive to philanthropists; and (e) launch a demonstration project.We estimated that of 50 600 CRC deaths annually in the US, 55% occur in 50- to 85-year-olds and are potentially addressable by improvements in CRC screening. Barriers to screening were identified in all patient journey phases, including lack of awareness or insurance and logistical challenges in the pre-physician phase. The cost to activate one person to undergo screening was $25-175. This translated into a cost of $6000-36 000 per CRC death averted by philanthropic investment. Based on this work, the Colorectal Cancer Alliance launched the effort "March Forth" to prevent 100 000 CRC deaths in the US over 10 years, with the first pilot in Philadelphia.A holistic business plan can attract philanthropy to promote CRC screening. A simple message of "You can save a life from CRC with a $25 000 donation" can motivate demonstration projects in regions with high CRC rates and low screening participation.

  View details for DOI 10.1002/cam4.2745

  View details for PubMedID 31808317

• High-Intensity Versus Low-Intensity Surveillance for Patients With Colorectal Adenomas: A Cost-Effectiveness Analysis. Annals of internal medicine Meester, R. G., Lansdorp-Vogelaar, I. n., Winawer, S. J., Zauber, A. G., Knudsen, A. B., Ladabaum, U. n. 2019

  Abstract

  Surveillance of patients with colorectal adenomas has limited long-term evidence to support current practice.To compare the lifetime benefits and costs of high- versus low-intensity surveillance.Microsimulation model.U.S. cancer registry, cost data, and published literature.U.S. patients aged 50, 60, or 70 years with low-risk adenomas (LRAs) (1 to 2 small adenomas) or high-risk adenomas (HRAs) (3 to 10 small adenomas or ≥1 large adenoma) removed after screening with colonoscopy or fecal immunochemical testing (FIT).Lifetime.Societal.No further screening or surveillance, routine screening after 10 years, low-intensity surveillance (10 years after LRA removal and 5 years after HRA removal), and high-intensity surveillance (5 years after LRA removal and 3 years after HRA removal).Colorectal cancer (CRC) incidence and incremental cost-effectiveness.Without surveillance or screening, lifetime CRC incidence for patients aged 50 years was 10.9% after LRA removal and 17.2% after HRA removal at screening colonoscopy. Subsequent colonoscopic screening, low-intensity surveillance, or high-intensity surveillance decreased incidence by 39%, 46% to 48%, and 55% to 56%, respectively. Incidence of CRC and surveillance benefits were higher for adenomas detected at FIT screening and lower for older patients. High-intensity surveillance cost less than $30 000 per quality-adjusted life-year (QALY) gained compared with low-intensity surveillance.High-intensity surveillance cost less than $100 000 per QALY gained in most alternative scenarios for adenoma recurrence, CRC incidence, longevity, quality of life, screening ages, surveillance ages, test performance, disutilities, and cost.Few surveillance outcome data exist.The model suggests that high-intensity surveillance as recommended in the United States provides modest but clinically relevant benefits over low-intensity surveillance at acceptable cost.National Cancer Institute.

  View details for DOI 10.7326/M18-3633

  View details for PubMedID 31546257

• Strategies for Colorectal Cancer Screening. Gastroenterology Ladabaum, U. n., Dominitz, J. A., Kahi, C. n., Schoen, R. E. 2019

  Abstract

  The incidence of colorectal cancer (CRC) is increasing worldwide. CRC has high mortality when detected at advanced stages, yet it is also highly preventable. Given the difficulties in implementing major lifestyle changes or widespread primary prevention strategies to decrease CRC risk, screening is the most powerful public health tool to reduce mortality. Screening methods are effective but have limitations. Furthermore, many screen-eligible persons remain unscreened. We discuss established and emerging screening methods, and potential strategies to address current limitations in CRC screening. A quantum step in CRC prevention might come with the development of new screening strategies, but great gains can be made by deploying the available CRC screening modalities in ways that optimize outcomes while making judicious use of resources.

  View details for DOI 10.1053/j.gastro.2019.06.043

  View details for PubMedID 31394083

• Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk JCO Precision Oncology Idos, G. E., Kurian, A. W., Ricker, C., Sturgeon, D., Culver, J. O., Kingham, K. E., Koff, R., Chun, N. M., Rowe-Teeter, C., Lebensohn, A. P., Levonian, P., Lowstuter, K., Partynski, K., Hong, C., Mills, M. A., Petrovchich, I., Ma, C. S., Hartman, A., Allen, B., Wenstrup, R. J., Lancaster, J. M., Brown, K., Kidd, J., Evans, B., Mukherjee, B., et al 2019

  View details for DOI 10.1200/PO.18.00217

• Trends in Incidence and Stage at Diagnosis of Colorectal Cancer in Adults Aged 40 Through 49 Years, 1975-2015. JAMA Meester, R. G., Mannalithara, A. n., Lansdorp-Vogelaar, I. n., Ladabaum, U. n. 2019; 321 (19): 1933–34

  View details for DOI 10.1001/jama.2019.3076

  View details for PubMedID 31112249

• Reply to GASTRO-D-19-00808. Gastroenterology Ladabaum, U. n., Mannalithara, A. n., Meester, R. G., Gupta, S. n., Schoen, R. E. 2019

  View details for DOI 10.1053/j.gastro.2019.09.038

  View details for PubMedID 31589871

• Effectiveness and cost of organized outreach for colorectal cancer screening: A Randomized Controlled Trial. Journal of the National Cancer Institute Somsouk, M. n., Rachocki, C. n., Mannalithara, A. n., Garcia, D. n., Laleau, V. n., Grimes, B. n., Issaka, R. B., Chen, E. n., Vittinghoff, E. n., Shapiro, J. A., Ladabaum, U. n. 2019

  Abstract

  Colorectal cancer (CRC) screening remains underutilized especially in safety-net systems. The objective of this study was to determine the effectiveness, costs, and cost-effectiveness of organized outreach using fecal immunochemical tests (FIT) compared with usual care.Patients aged 50-75 years eligible for CRC screening from eight participating primary care safety-net clinics were randomized to outreach intervention with usual care versus usual care alone. The intervention included a mailed postcard and call, followed by a mailed FIT kit, and a reminder phone call if the FIT kit was not returned. The primary outcome was screening participation at one year and a microcosting analysis of the outreach activities with embedded long-term cost-effectiveness of outreach. All statistical tests were two-sided.5,386 patients were randomized to the intervention group and 5,434 to usual care. FIT screening was statistically significantly higher in the intervention group than in the control group (57.9% vs. 37.4%, P < 0.001; difference 20.5%, 95% CI 18.6-22.4%). In the intervention group, FIT completion rate was higher in patients who had previously completed a FIT versus those who had not (71.9% vs. 35.7%, P < 0.001). There was evidence of effect modification of the intervention by race/ethnicity, marital status, language, and clinic. Outreach cost approximately $23/patient and $112/additional patient screened. Projecting long-term outcomes, outreach was estimated to cost $9,200/quality-adjusted life-year gained vs. usual care.Population-based management with organized FIT outreach statistically significantly increased CRC screening and was cost-effective in a safety-net system. The sustainability of the program and any impact of economies of scale remains to be determined.

  View details for DOI 10.1093/jnci/djz110

  View details for PubMedID 31187126

• When Experts Fail: Use of a Short Turning Radius Colonoscope Facilitates Successful Completion of Colonoscopy in Patients with Bowel Fixity. Digestive diseases and sciences Girotra, M. n., Sethi, S. n., Barakat, M. T., Huang, R. J., Friedland, S. n., Ladabaum, U. n., Banerjee, S. n. 2019

  Abstract

  Rates of incomplete colonoscopy in non-expert settings range up to 13%. Expert colonoscopists can complete ~ 95% colonoscopies when other endoscopists fail; however, a small number remain incomplete even in expert hands, typically due to bowel fixity.Pentax Retroview™ (EC-3490TLi) is a new slim colonoscope with a short turning radius (STR) and greater tip deflection (210°), which allows easy maneuverability across sharply angulated/fixed colonic bends. We evaluated the utility of this colonoscope for completing colonoscopies that fail even in the hands of expert colonoscopists.Retrospective chart review was performed, and main outcomes measured included cecal intubation rate, lesions detected, dosage of sedation used, and complications.Using the STR colonoscope, complete colonoscopy to the cecum was possible in 34/37 patients (91.9%). No loss of lumen/blind advancement was necessary in any of the procedures. No adverse events occurred. Among the completed colonoscopies, 6/34 (17.6%) patients had adenomas, all proximal to the site of prior failure, including one advanced adenoma. All failures (n = 3, 8.1%) had a history of cancer surgeries, with peritoneal carcinomatosis/extensively fixed/frozen bowel (two patients) and an additional diverticular stricture with colo-vesical fistula (one patient).STR colonoscope facilitates completion of a high proportion (91.9%) of colonoscopies that previously failed in expert hands. Its STR allows easy maneuverability across segments of sharp angulation with bowel fixity without need for blind advancement. The use of this colonoscope led to the detection of adenomas in 17.6% of patients, all proximal to the site of prior failed colonoscopy.

  View details for DOI 10.1007/s10620-019-05882-2

  View details for PubMedID 31630343

• Moving From Current Guidelines To Personalized Colorectal Cancer Screening: Opportunities and Challenges. Gastroenterology Robertson, D. J., Ladabaum, U. 2018

  View details for PubMedID 30593801

• Contrasting Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening Under Commercial Insurance vs. Medicare AMERICAN JOURNAL OF GASTROENTEROLOGY Ladabaum, U., Mannalithara, A., Brill, J. V., Levin, Z., Bundorf, M. 2018; 113 (12): 1836–47

  View details for DOI 10.1038/s41395-018-0106-8

  View details for Web of Science ID 000458329000018

• Colorectal Cancer Knowledge, Risk Perception, and Screening Inclination Among Previously Unscreened Adults Yen, T., Asiimwe, E., Qin, F., Sundaram, V., Storage, T., Ladabaum, U. NATURE PUBLISHING GROUP. 2018: S163–S164

  View details for Web of Science ID 000464611000290

• Incidence of interval colorectal cancer attributable to an endoscopist in clinical practice GASTROINTESTINAL ENDOSCOPY Ertem, F. U., Ladabaum, U., Mehrotra, A., Tehranian, S., Shi, Z., Saul, M., Morris, M., Crockett, S. D., Schoen, R. E. 2018; 88 (4): 705-+

  Abstract

  Endoscopists who encounter an interval colorectal cancer (I-CRC) may be concerned about the implications because I-CRCs may represent a lapse in colonoscopy quality and a missed opportunity for prevention. We wanted to determine the I-CRC rate per colonoscopy examination and to examine the effect of colonoscopy volume and adenoma detection rate (ADR) on the number of I-CRCs attributable to an endoscopist.We determined the rate of I-CRC diagnosis per outpatient colonoscopy examination by measuring the incidence of CRC diagnosis in practice and by assessing, via literature review, the percentage of cancers that are interval. We also estimated the number of attributable I-CRCs as a function of ADR and colonoscopy volume.Among 93,562 colonoscopies performed in 2013 to 2015 by 120 physicians in 4 diverse U.S. medical centers, 526 CRCs were diagnosed (.6%). Of 149,556 CRCs in the published literature, 7958 were I-CRCs (5.25% ± .94%). With rates of .6% (CRC per colonoscopy) and 5.25% (I-CRC per CRC), the rate of I-CRC is 1 per 3174 colonoscopies (95% confidence interval, 1 per 2710 to 1 per 3875). An endoscopist at the median of outpatient colonoscopy volume (316/year) in the lowest ADR quintile of detection (7%-19%) would have an I-CRC attributed every 8.2 years, or 4.2 I-CRCs in a 35-year career, versus every 16.7 years, or 2.0 I-CRCs in a 35-year career, for an endoscopist in the highest ADR quintile (33%-52%).An average-volume endoscopist will have 2 to 4 attributable I-CRCs in a 35-year career, but the frequency will vary depending on colonoscopy volume and ADR.

  View details for DOI 10.1016/j.gie.2018.05.012

  View details for Web of Science ID 000444249600019

  View details for PubMedID 29803767

  View details for PubMedCentralID PMC6139042

• Potential Intended and Unintended Consequences of Recommending Initiation of Colorectal Cancer Screening at Age 45 Years GASTROENTEROLOGY Liang, P. S., Allison, J., Ladabaum, U., Martinez, M., Murphy, C. C., Schoen, R. E., Shaukat, A., Tinmouth, J., Gupta, S. 2018; 155 (4): 950–54

  View details for PubMedID 30138614

• Occult blood in faeces: a window into health beyond the colorectum? Gut Ladabaum, U. 2018

  View details for PubMedID 30012725

• Colonoscopy quality requisites for selecting surveillance intervals: A World Endoscopy Organization Delphi Recommendation. Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society Jover, R., Dekker, E., Schoen, R. E., Hassan, C., Pellise, M., Ladabaum, U., WEO Expert Working Group of Surveillance after colonic neoplasm 2018

  Abstract

  BACKGROUND AND AIMS: Different post-polypectomy guidelines underscore the need for high-quality baseline colonoscopy before appropriate surveillance recommendations can be made. Standards for colonoscopy practice have been advocated by gastrointestinal societies. Our aims were to define standards for the procedural practice of colonoscopy in this particular setting of surveillance and to generate a colonoscopy procedural quality checklist that could be implemented in clinical practice.METHODS: This study was based on the Delphi process methodology. The baseline questionnaire included 12 domains and 56 individual statements. A total of three rounds were carried out between September 2015 and March 2016 until consensus or lack of consensus was reached.RESULTS: In total, consensus was reached on 27 statements in nine domains. High levels of agreement and consensus were reached that: (i) colonoscopy should be considered complete only if the whole cecum has been inspected, including the ileocecal valve and the appendiceal orifice (agreement score 4.63; degree of consensus 82%); (ii) quality of the bowel preparation should always be reported (agreement score 4.9, degree of consensus 94%); and (iii) it is preferable to use a segmental validated scale (agreement score 4.36, degree of consensus 86%). Consensus was also reached regarding multiple statements related to documentation of polyps and their resection. Finally, a colonoscopy quality checklist was drafted.CONCLUSION: Consensus on different statements regarding quality of colonoscopy has been reached. Based on this consensus, we propose a colonoscopy quality checklist that would be helpful for post-polypectomy surveillance recommendations.

  View details for PubMedID 29971834

• Contrasting Effectiveness and Cost-Effectiveness of Colorectal Cancer Screening Under Commercial Insurance vs. Medicare. The American journal of gastroenterology Ladabaum, U., Mannalithara, A., Brill, J. V., Levin, Z., Bundorf, M. K. 2018

  Abstract

  OBJECTIVES: Most cost-effectiveness analyses of colorectal cancer (CRC) screening assume Medicare payment rates and a lifetime horizon. Our aims were to examine the implications of differential payment levels and time horizons for commercial insurers vs. Medicare on the cost-effectiveness of CRC screening.METHODS: We used our validated Markov cohort simulation of CRC screening in the average risk US population to examine CRC screening at ages 50-64 under commercial insurance, and at ages 65-80 under Medicare, using a health-care sector perspective. Model outcomes included discounted quality-adjusted life-years (QALYs) and costs per person, and incremental cost/QALY gained.RESULTS: Lifetime costs/person were 20-44% higher when assuming commercial payment rates rather than Medicare rates for people under 65. Most of the substantial clinical benefit of screening at ages 50-64 was realized at ages ≥65. For commercial payers with a time horizon of ages 50-64, fecal occult blood testing (FOBT) and fecal immunochemical testing (FIT) were cost-effective (<$61,000/QALY gained), but colonoscopy was costly (>$185,000/QALY gained). Medicare experienced substantial clinical benefits and cost-savings from screening done at ages <65, even if screening was not continued. Among those previously screened, continuing FOBT and FIT under Medicare was cost-saving and continuing colonoscopy was highly cost-effective (<$30,000/QALY gained), and initiating any screening in those previously unscreened was highly effective and cost-saving.CONCLUSIONS: Modeling suggests that CRC screening is highly cost-effective over a lifetime even when considering higher payment rates by commercial payers vs. Medicare. Screening may appear relatively costly for commercial payers if only a time horizon of ages 50-64 is considered, but it is predicted to yield substantial clinical and economic benefits that accrue primarily at ages ≥65 under Medicare.

  View details for PubMedID 29904156

• Trends in Cancer Survival by Health Insurance Status in California From 1997 to 2014 JAMA ONCOLOGY Ellis, L., Canchola, A. J., Spiegel, D., Ladabaum, U., Haile, R., Gomez, S. 2018; 4 (3): 317–23

  Abstract

  There have been substantial improvements in the early detection, treatment, and survival from cancer in the United States, but it is not clear to what extent patients with different types of health insurance have benefitted from these advancements.To examine trends in cancer survival by health insurance status from January 1997 to December 2014.California Cancer Registry (a statewide cancer surveillance system) data were used to estimate population-based survival by health insurance status in 3 calendar periods: January 1997 to December 2002, January 2003 to December 2008, and January 2009 to December 2014 with follow-up through 2014. Overall, 1 149 891 patients diagnosed with breast, prostate, colorectal, or lung cancer, or melanoma in California were included in the study.Five-year all-cause and cancer-specific survival probabilities by insurance category and calendar period for each cancer site and sex; hazard ratios (HRs) and 95% CIs for each insurance category (none, Medicare, other public) compared with private insurance in each calendar period.According to data from 1 149 891 patients diagnosed with breast, prostate, colorectal, or lung cancer, or melanoma gathered from the California Cancer Registry, improvements in survival were almost exclusively limited to patients with private or Medicare insurance. For patients with other public or no insurance, survival was largely unchanged or declined. Relative to privately insured patients, cancer-specific mortality was higher in uninsured patients for all cancers except prostate, and disparities were largest from 2009 to 2014 for breast (HR, 1.72; 95% CI, 1.45-2.03), lung (men: HR, 1.18; 95% CI, 1.06-1.31 and women: HR, 1.32; 95% CI, 1.15-1.50), and colorectal cancer (women: HR, 1.30; 95% CI, 1.05-1.62). Mortality was also higher for patients with other public insurance for all cancers except lung, and disparities were largest from 2009 to 2014 for breast (HR, 1.25; 95% CI, 1.17-1.34), prostate (HR, 1.17; 95% CI, 1.04-1.31), and colorectal cancer (men: HR, 1.16; 95% CI, 1.08-1.23 and women: HR, 1.11; 95% CI, 1.03-1.20).After accounting for patient and clinical characteristics, survival disparities for men with prostate cancer and women with lung or colorectal cancer increased significantly over time, reflecting a lack of improvement in survival for patients with other public or no insurance. To mitigate these growing disparities, all patients with cancer need access to health insurance that covers all the necessary elements of health care, from prevention and early detection to timely treatment according to clinical guidelines.

  View details for PubMedID 29192307

• Low Rates of Gastrointestinal and Non-Gastrointestinal Complications for Screening or Surveillance Colonoscopies in a Population-Based Study GASTROENTEROLOGY Wang, L., Mannalithara, A., Singh, G., Ladabaum, U. 2018; 154 (3): 540-+

  Abstract

  The full spectrum of serious non-gastrointestinal post-colonoscopy complications has not been well characterized. We analyzed rates of and factors associated with adverse post-colonoscopy gastrointestinal (GI) and non-gastrointestinal events (cardiovascular, pulmonary, or infectious) attributable to screening or surveillance colonoscopy (S-colo) and non-screening or non-surveillance colonoscopy (NS-colo).We performed a population-based study of colonoscopy complications using databases from California hospital-owned and nonhospital-owned ambulatory facilities, emergency departments, and hospitals from January 1, 2005 through December 31, 2011. We identified patients who underwent S-colo (1.58 million), NS-colo (1.22 million), or low-risk comparator procedures (joint injection, aspiration, lithotripsy; arthroscopy, carpal tunnel; or cataract; 2.02 million) in California's Ambulatory Services Databases. We identified patients who developed adverse events within 30 days, and factors associated with these events, through patient-level linkage to California's Emergency Department and Inpatient Databases.After S-colo, the numbers of lower GI bleeding, perforation, myocardial infarction, and ischemic stroke per 10,000-persons were 5.3 (95% confidence interval [CI], 4.8-5.9), 2.9 (95% CI, 2.5-3.3), 2.5 (95% CI, 2.1-2.9), and 4.7 (95% CI, 4.1-5.2) without biopsy or intervention; with biopsy or intervention, numbers per 10,000-persons were 36.4 (95% CI, 35.1-37.6), 6.3 (95% CI, 5.8-6.8), 4.2 (95% CI, 3.8-4.7), and 9.1 (95% CI, 8.5-9.7). Rates of dysrhythmia were higher. After NS-colo, event rates were substantially higher. Most serious complications led to hospitalization, and most GI complications occurred within 14 days of colonoscopy. Ranges of adjusted odds ratios for serious GI complications, myocardial infarction, ischemic stroke, and serious pulmonary events after S-colo vs comparator procedures were 2.18 (95% CI, 2.02-2.36) to 5.13 (95% CI, 4.81-5.47), 0.67 (95% CI, 0.56-0.81) to 0.99 (95% CI, 0.83-1.19), 0.66 (95% CI, 0.59-0.75) to 1.13 (95% CI, 0.99-1.29), and 0.64 (95% CI, 0.61-0.68) to 1.05 (95% CI, 0.98-1.11). Biopsy or intervention, comorbidity, black race, low income, public insurance, and NS-colo were associated with post-colonoscopy adverse events.In a population-based study in California, we found that following S-colo, rates of serious GI adverse events were low but clinically relevant, and that rates of myocardial infarction, stroke, and serious pulmonary events were no higher than after low-risk comparator procedures. Rates of myocardial infarction are similar to, but rates of stroke are higher than, those reported for the general population.

  View details for PubMedID 29031502

• Tumor Molecular Testing Guides Anti-PD-1 Therapy and Provides Evidence for Pathogenicity of Mismatch Repair Variants. The oncologist Patel, S. A., Longacre, T. A., Ladabaum, U. n., Lebensohn, A. n., Lin, A. Y., Haraldsdottir, S. n. 2018

  Abstract

  Lynch syndrome is characterized by germline abnormalities in mismatch repair (MMR) genes, leading to predisposition to multiple cancers [1]. A second hit to the unaffected allele is required for tumorigenesis. MMR proteins repair incorrectly paired nucleotides and prevent generation of insertions and deletions at microsatellites [2]. Aberrancies in these MMR proteins can be a result of germline mutations or somatic alterations. Defective MMR results in microsatellite instability (MSI) and a high mutational burden [3].The clinical implications of MSI are becoming readily apparent, as presence of MSI leads to the generation of neoantigens, stimulating tumor-associated lymphocytes [4,5]. This has led to the use of programmed cell death protein 1 blockade for MMR-deficient tumors [6]. The U.S. Food and Drug Administration recently approved pembrolizumab for any advanced solid tumor demonstrating MSI and nivolumab for metastatic MSI colorectal cancer. However, the clinical significance of numerous MMR gene variants remains uncertain. The International Society for Gastrointestinal Hereditary Tumors classification system categorizes 2,360 MMR variants, which can be used to gauge pathogenicity [7]. There are many variants of uncertain significance (VUS; or class 3) for which clinicians are unable to provide recommendations. In this study, we employed the combination of germline testing and tumor mutational assessment to help discern the clinical relevance of VUS and guide immunotherapeutic decisions.A clinical dilemma arises when genomic testing yields variants of uncertain significance (VUS).Germline VUS were identified in two patients with gastrointestinal malignancies, but only one patient had a second-hit mutation in a mismatch repair gene leading to mismatch repair deficiency that conferred response to immunotherapy.The combination of germline testing along with tumor mutational assessment can help discern the clinical relevance of VUS and can help guide therapeutic decision-making toward individualized patient care.

  View details for PubMedID 30072391

• Patient communication of cancer genetic test results in a diverse population. Translational behavioral medicine Ricker, C. N., Koff, R. B., Qu, C. n., Culver, J. n., Sturgeon, D. n., Kingham, K. E., Lowstuter, K. n., Chun, N. M., Rowe-Teeter, C. n., Lebensohn, A. n., Levonian, P. n., Partynski, K. n., Lara-Otero, K. n., Hong, C. n., Petrovchich, I. M., Mills, M. A., Hartman, A. R., Allen, B. n., Ladabaum, U. n., McDonnell, K. n., Ford, J. M., Gruber, S. B., Kurian, A. W., Idos, G. E. 2018; 8 (1): 85–94

  Abstract

  Research on the communication of genetic test results has focused predominately on non-Hispanic White (NHW) mutation-positive families with high-risk hereditary cancer conditions. Little is known about this process for racially and ethnically diverse individuals or for those with mutations in moderate risk genes. The communication behaviors of study participants who carry a gene mutation were analyzed 3 months after disclosure of genetic test results. Participants were queried about communication of their results, as part of a prospective study of multi-gene panel genetic testing. The responses of particpants who tested positive were analyzed by race/ethnicity and by level of cancer risk (high vs. moderate). Of the 216 mutation-positive study participants, 136 (63%) responded. Self-reported race/ethnicity was 46% NHW, 41% Hispanic, 10% Asian, and 2% Black. The majority (99.0%, n = 135) had shared their results with someone and 96% had told a family member (n = 130). Hispanic respondents were less likely to have told a healthcare provider about their results than NHW (29% vs. 68%, p < .0001). Asian respondents were less likely than NHW to encourage family members to undergo testing (OR = 0.1, p = .03); but Asian family members were more likely to undergo testing (OR = 8.0, p = .03). There were no differences in communication between those with a mutation in a high- or moderate-risk gene. Three months post genetic testing, communication of results was very high; 30% reported a family member underwent genetic testing. Further studies are needed to better understand the communication process in individuals from diverse racial/ethnic backgrounds.

  View details for PubMedID 29385580

• Racial and Ethnic Disparities in Cancer Survival: The Contribution of Tumor, Sociodemographic, Institutional, and Neighborhood Characteristics JOURNAL OF CLINICAL ONCOLOGY Ellis, L., Canchola, A. J., Spiegel, D., Ladabaum, U., Haile, R., Gomez, S. 2018; 36 (1): 25-+

  Abstract

  Purpose Racial/ethnic disparities in cancer survival in the United States are well documented, but the underlying causes are not well understood. We quantified the contribution of tumor, treatment, hospital, sociodemographic, and neighborhood factors to racial/ethnic survival disparities in California. Materials and Methods California Cancer Registry data were used to estimate population-based cancer-specific survival for patients diagnosed with breast, prostate, colorectal, or lung cancer between 2000 and 2013 for each racial/ethnic group (non-Hispanic black, Hispanic, Asian American and Pacific Islander, and separately each for Chinese, Japanese, and Filipino) compared with non-Hispanic whites. The percentage contribution of factors to overall racial/ethnic survival disparities was estimated from a sequence of multivariable Cox proportional hazards models. Results In baseline models, black patients had the lowest survival for all cancer sites, and Asian American and Pacific Islander patients had the highest, compared with whites. Mediation analyses suggested that stage at diagnosis had the greatest influence on overall racial/ethnic survival disparities accounting for 24% of disparities in breast cancer, 24% in prostate cancer, and 16% to 30% in colorectal cancer. Neighborhood socioeconomic status was an important factor in all cancers, but only for black and Hispanic patients. The influence of marital status on racial/ethnic disparities was stronger in men than in women. Adjustment for all covariables explained approximately half of the overall survival disparities in breast, prostate, and colorectal cancer, but it explained only 15% to 40% of disparities in lung cancer. Conclusion Overall reductions in racial/ethnic survival disparities were driven largely by reductions for black compared with white patients. Stage at diagnosis had the largest effect on racial/ethnic survival disparities, but earlier detection would not entirely eliminate them. The influences of neighborhood socioeconomic status and marital status suggest that social determinants, support mechanisms, and access to health care are important contributing factors.

  View details for PubMedID 29035642

  View details for PubMedCentralID PMC5756323

• Worldwide Practice Patterns in Lynch Syndrome Diagnosis and Management, Based on Data From the International Mismatch Repair Consortium. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Pan, J. Y., Haile, R. W., Templeton, A. n., Macrae, F. n., Qin, F. n., Sundaram, V. n., Ladabaum, U. n. 2018

  Abstract

  Families with a history of Lynch syndrome often do not adhere to guidelines for genetic testing and screening. We investigated practice patterns related to Lynch syndrome worldwide, to ascertain potential targets for research and public policy efforts METHODS: We collected data from the International Mismatch Repair Consortium [IMRC], which comprises major research and clinical groups engaged in the care of families with Lynch syndrome worldwide. IMRC institutions were invited to complete a questionnaire to characterize diagnoses of Lynch syndrome and management practice patterns.Fifty-five providers, representing 63 of 128 member institutions (49%) in 21 countries, completed the questionnaire. For case finding, 55% of respondents reported participating in routine widespread population tumor testing among persons with newly diagnosed Lynch syndrome-associated cancers, whereas 27% reported relying on clinical criteria with selective tumor and/or germline analyses. Most respondents (64%) reported using multi-gene panels for germline analysis, and only 28% reported testing tumors for biallelic mutations for cases where suspected pathogenic mutations were not confirmed by germline analysis. Respondents reported relying upon passive dissemination of information to at-risk family members, and there was variation in follow through of genetic testing recommendations. Reported risk management practices varied-nearly all programs (98%) recommended colonoscopy every 1-2 years, but only 35% recommended chemoprevention with aspirin.There is widespread heterogeneity in management practices for Lynch syndrome worldwide among IMRC member institutions. This may reflect the rapid pace of emerging technology, regional differences in resources, and the lack of definitive data for many clinical questions. Future efforts should focus on the large numbers of high-risk patients without access to state of the art Lynch syndrome management.

  View details for PubMedID 29702294

• Low Prevalence of Criteria for Early Screening in Young-Onset Colorectal Cancer AMERICAN JOURNAL OF PREVENTIVE MEDICINE Chen, F. W., Sundaram, V., Chew, T. A., Ladabaum, U. 2017; 53 (6): 933–34

  View details for PubMedID 29051017

  View details for PubMedCentralID PMC5873286

• Using Social Media to Characterize Public Sentiment Toward Medical Interventions Commonly Used for Cancer Screening: An Observational Study. Journal of medical Internet research Metwally, O., Blumberg, S., Ladabaum, U., Sinha, S. R. 2017; 19 (6)

  Abstract

  Although cancer screening reduces morbidity and mortality, millions of people worldwide remain unscreened. Social media provide a unique platform to understand public sentiment toward tools that are commonly used for cancer screening.The objective of our study was to examine public sentiment toward colonoscopy, mammography, and Pap smear and how this sentiment spreads by analyzing discourse on Twitter.In this observational study, we classified 32,847 tweets (online postings on Twitter) related to colonoscopy, mammography, or Pap smears using a naive Bayes algorithm as containing positive, negative, or neutral sentiment. Additionally, we characterized the spread of sentiment on Twitter using an established model to study contagion.Colonoscopy-related tweets were more likely to express negative than positive sentiment (negative to positive ratio 1.65, 95% CI 1.51-1.80, P<.001), in contrast to the more positive sentiment expressed regarding mammography (negative to positive ratio 0.43, 95% CI 0.39-0.47, P<.001). The proportions of negative versus positive tweets about Pap smear were not significantly different (negative to positive ratio 0.95, 95% CI 0.87-1.04, P=.18). Positive and negative tweets tended to share lexical features across screening modalities. Positive tweets expressed resonance with the benefits of early detection. Fear and pain were the principal lexical features seen in negative tweets. Negative sentiment for colonoscopy and mammography spread more than positive sentiment; no correlation with sentiment and spread was seen for Pap smear.Analysis of social media data provides a unique, quantitative framework to better understand the public's perception of medical interventions that are commonly used for cancer screening. Given the growing use of social media, public health interventions to improve cancer screening should use the health perceptions of the population as expressed in social network postings about tests that are frequently used for cancer screening, as well as other people they may influence with such postings.

  View details for DOI 10.2196/jmir.7485

  View details for PubMedID 28592395

• Advanced-Stage Colorectal Cancer in Persons Younger Than 50 Years Not Associated With Longer Duration of Symptoms or Time to Diagnosis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Chen, F. W., Sundaram, V., Chew, T. A., Ladabaum, U. 2017; 15 (5): 728-?

  Abstract

  The incidence of colorectal cancer (CRC) is increasing in the United States among adults younger than the age of 50 years. Studies of young-onset CRC have focused on outcomes and treatment patterns. We examined patient presentation, provider evaluation, and time to diagnosis, which can affect stage and prognosis.In a retrospective study, we collected data from patients with a diagnosis of colorectal adenocarcinoma, confirmed by pathologists, seen at the Stanford Cancer Institute from January 1, 2008, through December 31, 2014. We compared symptoms, clinical features, time to diagnosis, and cancer stage in patients with young-onset CRC (diagnosed at an age younger than 50 years; n = 253) with patients diagnosed with CRC at an age of 50 years or older (n = 232).A higher proportion of patients with young-onset CRC were diagnosed with advanced-stage tumors (72%) compared with older patients (63%) (P = .03). Larger proportions of patients with young-onset CRC also had a family history of CRC (25% vs 17% in older patients; P = .03), confirmed or probable hereditary cancer syndromes (7% vs 1% in older patients; P < .01), and left-sided disease (distal colon cancer in 41% vs 34% in older patients; P = .01; and rectal cancer in 40% vs 35% in older patients; P = .29). Patients with young-onset CRC had a significantly longer median time to diagnosis (128 vs 79 days for older patients; P < .05), symptom duration (60 vs 30 days for older patients; P < .01), and time of evaluation (31 vs 22 days; P < .05). In multivariable analyses, time to diagnosis was 1.4-fold longer for younger than for older patients (P < .01). Among younger patients, those with stage III or IV CRC had shorter durations of symptoms and evaluations than those with stage I or II CRC.In a retrospective analysis of patients with CRC, we found that greater proportions of patients younger than 50 years were diagnosed with advanced-stage tumors than older patients; this difference could not be explained simply by delays from symptom onset to diagnosis. Although tumor biology may be an important determinant of stage at diagnosis, clinicians should be aware of CRC alarm symptoms, family history, and genetic syndromes, to speed evaluation and diagnosis of younger patients and potentially improve outcomes. It remains to be determined whether subgroups of persons at risk for young-onset CRC who benefit from early screening can be identified.

  View details for DOI 10.1016/j.cgh.2016.10.038

  View details for Web of Science ID 000401101600021

  View details for PubMedCentralID PMC5401776

• The Case for a Multitarget Stool DNA Test: A Closer Look at the Cost Effectiveness Model Reply GASTROENTEROLOGY Ladabaum, U., Mannalithara, A. 2017; 152 (6): 1621-+

  View details for PubMedID 28376320

• Risk stratification of individuals with low-risk colorectal adenomas using clinical characteristics: a pooled analysis GUT Gupta, S., Jacobs, E. T., Baron, J. A., Lieberman, D. A., Murphy, G., Ladabaum, U., Cross, A. J., Jover, R., Liu, L., Martinez, M. E. 2017; 66 (3): 446-453

  Abstract

  For individuals with 1-2 small (<1 cm) low-risk colorectal adenomas, international guidelines range from no surveillance to offering surveillance colonoscopy in 5-10 years. We hypothesised that the risks for metachronous advanced neoplasia (AN) among patients with low-risk adenomas differ based on clinical factors distinct from those currently used.We pooled data from seven prospective studies to assess the risk of metachronous AN. Two groups with 1-2 small adenomas were defined based on guidelines from the UK (n=4516) or the European Union (EU)/US (n=2477).Absolute risk of metachronous AN ranged from a low of 2.9% to a high of 12.2%, depending on specific risk factor and guideline used. For the UK group, the highest absolute risks for metachronous AN were found among individuals with a history of prior polyp (12.2%), villous histology (12.2%), age ≥70 years (10.9%), high-grade dysplasia (10.9%), any proximal adenoma (10.2%), distal and proximal adenoma (10.8%) or two adenomas (10.1%). For the EU/US group, the highest absolute risks for metachronous AN were among individuals with a history of prior polyp (11.5%) or the presence of both proximal and distal adenomas (11.0%). In multivariate analyses, strong associations for increasing age and history of prior polyps and odds of metachronous AN were observed, whereas more modest associations were shown for baseline proximal adenomas and those with villous features.Risks of metachronous AN among individuals with 1-2 small adenomas vary according to readily available clinical characteristics. These characteristics may be considered for recommending colonoscopy surveillance and require further investigation.

  View details for DOI 10.1136/gutjnl-2015-310196

  View details for Web of Science ID 000394495800010

• Increased Post-procedural Non-Gastrointestinal Adverse Events After Outpatient Colonoscopy in High-Risk Patients. Clinical gastroenterology and hepatology Johnson, D. A., Lieberman, D., Inadomi, J. M., Ladabaum, U., Becker, R. C., Gross, S. A., Hood, K. L., Kushins, S., Pochapin, M., Robertson, D. J. 2016

  Abstract

  The incidence and predictors of non-gastrointestinal (GI) adverse events (AEs) after colonoscopy are not well-understood. We studied the effects of antithrombotic agents, cardiopulmonary comorbidities, and age on risk of non-GI AEs after colonoscopy.We performed a retrospective longitudinal analysis to assess the diagnosis, procedure, and prescription drug codes in a United States commercial claims database (March 2010-March 2012). Data from patients at increased risk (n = 82,025; defined as patients with pulmonary comorbidities or cardiovascular disease requiring antithrombotic medications) were compared with data from 398,663 average-risk patients. In a 1:1 matched analysis, 51,932 patients at increased risk, examined by colonoscopy, were compared with 51,932 matched (on the basis of age, sex, and comorbidities) patients at increased risk who did not undergo colonoscopy. We tracked cardiac, pulmonary, and neurovascular events 1-30 days after colonoscopy.Thirty days after outpatient colonoscopy, non-GI AEs were significantly higher in patients taking antithrombotic medications (7.3%; odds ratio [OR], 10.75; 95% confidence interval, 10.13-11.42) or those with pulmonary comorbidities (1.8%; OR, 2.44; 95% confidence interval, 2.27-2.62) vs average-risk patients (0.7%) and in patients 60-69 years old (OR, 2.21; 95% confidence interval, 2.01-2.42) or 70 years or older (OR, 6.45; 95% confidence interval, 5.89-7.06), compared with patients younger than 50 years. The 30-day incidence of non-GI AEs in patients at increased risk who underwent colonoscopy was also significantly higher than in matched patients at increased risk who did not undergo colonoscopy in the anticoagulant group (OR, 2.31; 95% confidence interval, 2.01-2.65) and in the chronic obstructive pulmonary disease group (OR, 1.33; 95% confidence interval, 1.13-1.56).Increased number of comorbidities and older age (older than 60 years) are associated with increased risk of non-GI AEs after colonoscopy. These findings indicate the importance of determining comorbid risk and evaluating antithrombotic management before colonoscopy.

  View details for DOI 10.1016/j.cgh.2016.12.015

  View details for PubMedID 28017846

• Adenoma miss rates associated with a 3-minute versus 6-minute colonoscopy withdrawal time: a prospective, randomized trial. Gastrointestinal endoscopy Kumar, S., Thosani, N., Ladabaum, U., Friedland, S., Chen, A. M., Kochar, R., Banerjee, S. 2016

  Abstract

  The 6-minute withdrawal time for colonoscopy, widely considered the standard of care, is controversial. The skill and technique of endoscopists may be as important as, or more important than, withdrawal time for adenoma detection. It is unclear whether a shorter withdrawal time with good technique yields an acceptable lesion detection rate. Our objective was to evaluate a 3-minute versus a 6-minute withdrawal time by using segmental tandem colonoscopy.We performed a prospective, randomized trial by using 4 expert endoscopists. Patients were randomized to a 3-minute or a 6-minute initial withdrawal, each followed by a tandem second 6-minute withdrawal. All polyps were removed. The primary outcomes were adenoma miss rates (AMRs), adenomas per colonoscopy (APC) rates, and adenoma detection rates (ADRs).A total of 99 and 101 patients were enrolled in the 3-minute and 6-minute withdrawal groups, respectively. The AMR was significantly higher in the 3-minute withdrawal group (48.0% vs 22.9%; P = .0001). After controlling for endoscopist, patient age and/or sex, Boston Bowel Preparation Scale score, and size and/or location and/or morphology of adenoma, the AMR remained significantly higher in the 3-minute withdrawal group (odds ratio, 2.78; 95% confidence interval, 1.35-5.15; P = .0001). The ADR was similar between both groups (39.2% vs 40.6%; P = .84). However, the mean APC rate was significantly lower in the 3-minute withdrawal group (0.55 vs 0.80; P = .0001).The AMR was significantly higher, and the APC rate was significantly lower in the 3-minute withdrawal group versus the 6-minute withdrawal group. Despite expert technique, a shorter withdrawal time is associated with an unacceptably high AMR and low APC rate. (Clinical trial registration number: NCT01802008.).

  View details for DOI 10.1016/j.gie.2016.11.030

  View details for PubMedID 27931951

• Screening for Colorectal Cancer and Evolving Issues for Physicians and Patients A Review JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Lieberman, D., Ladabaum, U., Cruz-Correa, M., Ginsburg, C., Inadomi, J. M., Kim, L. S., Giardiello, F. M., Wender, R. C. 2016; 316 (20): 2135-2145

  Abstract

  Colorectal cancer (CRC) is the second-leading cause of cancer death in the United States. Screening can reduce CRC mortality and incidence, and numerous screening options, although available, complicate informed decision making. This review provides evidence-based tools for primary care physicians to identify patients with higher-than-average-risk and engage patients in informed decision making about CRC screening options.Recently, the US Preventive Services Task Force recommended any of 8 CRC screening approaches for average-risk individuals, beginning at age 50 years. Only 2 methods have been shown in randomized clinical trials to reduce mortality: fecal occult blood testing and flexible sigmoidoscopy. Of the 8 programs, screenings using the fecal immunochemical test annually and colonoscopy every 10 years are now the most commonly used tests in the United States and among the most effective in reducing CRC mortality as determined by decision models. With the exception of primary screening using colonoscopy, all of the other screening approaches have multiple steps. Adherence to each phase of a multistep program is critical to achieving maximal effectiveness of the screening program. It is likely that each of the recommended programs can reduce CRC mortality, but other key outcomes may differ such as lifetime burden of colonoscopy, complications, patient acceptance, and cost. Decisions about the timing of screening cessation should be individualized.CRC screening is effective if patients adhere to the steps in each screening program. There is no evidence that one program is superior to another. Informed decision-making tools are provided to assist patients and clinicians with the goal of improving adherence to effective screening.

  View details for DOI 10.1001/jama.2016.17418

  View details for PubMedID 27893135

• Advanced-Stage Colorectal Cancer in Persons Younger Than 50 Years Not Associated With Longer Duration of Symptoms or Time to Diagnosis. Clinical gastroenterology and hepatology Chen, F. W., Sundaram, V., Chew, T. A., Ladabaum, U. 2016

  Abstract

  The incidence of colorectal cancer (CRC) is increasing in the United States among adults younger than the age of 50 years. Studies of young-onset CRC have focused on outcomes and treatment patterns. We examined patient presentation, provider evaluation, and time to diagnosis, which can affect stage and prognosis.In a retrospective study, we collected data from patients with a diagnosis of colorectal adenocarcinoma, confirmed by pathologists, seen at the Stanford Cancer Institute from January 1, 2008, through December 31, 2014. We compared symptoms, clinical features, time to diagnosis, and cancer stage in patients with young-onset CRC (diagnosed at an age younger than 50 years; n = 253) with patients diagnosed with CRC at an age of 50 years or older (n = 232).A higher proportion of patients with young-onset CRC were diagnosed with advanced-stage tumors (72%) compared with older patients (63%) (P = .03). Larger proportions of patients with young-onset CRC also had a family history of CRC (25% vs 17% in older patients; P = .03), confirmed or probable hereditary cancer syndromes (7% vs 1% in older patients; P < .01), and left-sided disease (distal colon cancer in 41% vs 34% in older patients; P = .01; and rectal cancer in 40% vs 35% in older patients; P = .29). Patients with young-onset CRC had a significantly longer median time to diagnosis (128 vs 79 days for older patients; P < .05), symptom duration (60 vs 30 days for older patients; P < .01), and time of evaluation (31 vs 22 days; P < .05). In multivariable analyses, time to diagnosis was 1.4-fold longer for younger than for older patients (P < .01). Among younger patients, those with stage III or IV CRC had shorter durations of symptoms and evaluations than those with stage I or II CRC.In a retrospective analysis of patients with CRC, we found that greater proportions of patients younger than 50 years were diagnosed with advanced-stage tumors than older patients; this difference could not be explained simply by delays from symptom onset to diagnosis. Although tumor biology may be an important determinant of stage at diagnosis, clinicians should be aware of CRC alarm symptoms, family history, and genetic syndromes, to speed evaluation and diagnosis of younger patients and potentially improve outcomes. It remains to be determined whether subgroups of persons at risk for young-onset CRC who benefit from early screening can be identified.

  View details for DOI 10.1016/j.cgh.2016.10.038

  View details for PubMedID 27856366

  View details for PubMedCentralID PMC5401776

• Predicting advanced neoplasia at colonoscopy in a diverse population with the National Cancer Institute colorectal cancer risk-assessment tool. Cancer Ladabaum, U., Patel, A., Mannalithara, A., Sundaram, V., Mitani, A., Desai, M. 2016; 122 (17): 2663-2670

  Abstract

  Tailoring screening to colorectal cancer (CRC) risk could improve screening effectiveness. Most CRCs arise from advanced neoplasia (AN) that dwells for years. To date, no available colorectal neoplasia risk score has been validated externally in a diverse population. The authors explored whether the National Cancer Institute (NCI) CRC risk-assessment tool, which was developed to predict future CRC risk, could predict current AN prevalence in a diverse population, thereby allowing its use in risk stratification for screening.This was a prospective examination of the relation between predicted 10-year CRC risk and the prevalence of AN, defined as advanced or multiple (≥3 adenomatous, ≥5 serrated) adenomatous or sessile serrated polyps, in individuals undergoing screening colonoscopy.Among 509 screenees (50% women; median age, 58 years; 61% white, 5% black, 10% Hispanic, and 24% Asian), 58 (11%) had AN. The prevalence of AN increased progressively from 6% in the lowest risk-score quintile to 17% in the highest risk-score quintile (P = .002). Risk-score distributions in individuals with versus without AN differed significantly (median, 1.38 [0.90-1.87] vs 1.02 [0.62-1.57], respectively; P = .003), with substantial overlap. The discriminatory accuracy of the tool was modest, with areas under the curve of 0.61 (95% confidence interval [CI], 0.54-0.69) overall, 0.59 (95% CI, 0.49-0.70) for women, and 0.63 (95% CI, 0.53-0.73) for men. The results did not change substantively when the analysis was restricted to adenomatous lesions or to screening procedures without any additional incidental indication.The NCI CRC risk-assessment tool displays modest discriminatory accuracy in predicting AN at screening colonoscopy in a diverse population. This tool may aid shared decision-making in clinical practice. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2663-2670. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30096

  View details for PubMedID 27219715

• Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state-of-the-science review. Cancer Lowery, J. T., Ahnen, D. J., Schroy, P. C., Hampel, H., Baxter, N., Boland, C. R., Burt, R. W., Butterly, L., Doerr, M., Doroshenk, M., Feero, W. G., Henrikson, N., Ladabaum, U., Lieberman, D., McFarland, E. G., Peterson, S. K., Raymond, M., Samadder, N. J., Syngal, S., Weber, T. K., Zauber, A. G., Smith, R. 2016; 122 (17): 2633-2645

  Abstract

  Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care. Existing data show that having 1 affected first-degree relative (FDR) increases the CRC risk 2-fold, and the risk increases with multiple affected FDRs and a younger age at diagnosis. There is variability in screening recommendations across consensus guidelines. Screening adherence is <50% and is lower in persons under the age of 50 years. A provider's recommendation, multiple affected relatives, and family encouragement facilitate screening; insufficient collection of FH, low knowledge of guidelines, and poor family communication are important barriers. Effective interventions incorporate strategies for overcoming barriers, but these have not been broadly tested in clinical settings. Four strategies for reducing CRC in persons with familial risk are suggested: 1) improving the collection and utilization of the FH of cancer, 2) establishing a consensus for screening guidelines by FH, 3) enhancing provider-patient knowledge of guidelines and communication about CRC risk, and 4) encouraging survivors to promote screening within their families and partnering with existing screening programs to expand their reach to high-risk groups. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2633-2645. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30080

  View details for PubMedID 27258162

• Comparative Effectiveness and Cost Effectiveness of a Multitarget Stool DNA Test to Screen for Colorectal Neoplasia. Gastroenterology Ladabaum, U., Mannalithara, A. 2016; 151 (3): 427-439 e6

  Abstract

  We developed a model to determine whether a multitarget stool DNA (MT-sDNA) test that detects colorectal cancer (CRC) and polyps with higher sensitivity and lower specificity, but at a higher cost, than the fecal immunochemical test (FIT) can be used in screening.We used a Markov model of average-risk CRC screening to compare the effectiveness and cost effectiveness of screening with the MT-sDNA test vs FIT or colonoscopy. We accounted for the complex longitudinal participation patterns observed in organized programs vs opportunistic screening, as well as organized programs' patient support costs and differential payment rates by commercial insurers vs Medicare.With optimal adherence, yearly FIT and colonoscopy every 10 years were dominant (more effective and less costly) than MT-sDNA every 3 years. Compared with successful organized FIT programs (50% consistent and 27% intermittent participation; patient support costs, $153/cycle), the patient support program for the MT-sDNA test would need 68% of subjects to participate consistently and 32% to participate intermittently every 3 years, or the MT-sDNA test would need to cost 60% less than in the base case ($260 commercial payment and $197 Medicare payment), for the MT-sDNA test to be preferred over FIT at a threshold of $100,000 per quality-adjusted life-year (QALY) gained. Compared with opportunistic yearly FIT screening (15% consistent and 30% intermittent participation), performing the MT-sDNA test every 3 years would cost less than $100,000 per QALY gained if the MT-sDNA test achieved a participation rate more than 1.7-fold that of FIT. The results were robust in sensitivity analyses. Assuming equal participation across strategies and a threshold of $100,000 per QALY gained, FIT was preferred in 99.3% of iterations in Monte Carlo simulation.In a Markov model, we found FIT and colonoscopy to be more effective and less costly than the MT-sDNA test when participation rates were equal for all strategies. For the MT-sDNA test to be cost effective, the patient support program included in its cost would need to achieve substantially higher participation rates than those of FIT, whether in organized programs or under the opportunistic screening setting that is more common in the United States than in the rest of the world.

  View details for DOI 10.1053/j.gastro.2016.06.003

  View details for PubMedID 27311556

• Risks and Predictors of Gastric Adenocarcinoma in Patients with Gastric Intestinal Metaplasia and Dysplasia: A Population-Based Study. American journal of gastroenterology Li, D., Bautista, M. C., Jiang, S., Daryani, P., Brackett, M., Armstrong, M. A., Hung, Y., Postlethwaite, D., Ladabaum, U. 2016; 111 (8): 1104-1113

  Abstract

  Gastric intestinal metaplasia and dysplasia are precursor lesions for adenocarcinoma. The risks of progression to malignancy from these lesions are not well characterized, particularly in the US populations.We identified 4,331 Kaiser Permanente Northern California members who were diagnosed with gastric intestinal metaplasia or dysplasia between 1997 and 2006 and followed them through December 2013. The incident rates of gastric adenocarcinoma, relative risks in comparison with the Kaiser Permanente general population, and predictors of progression to malignancy were investigated.Among 4,146 individuals with gastric intestinal metaplasia and 141 with low-grade dysplasia with 24,440 person-years follow-up, 17 and 6 cases of gastric adenocarcinoma were diagnosed, respectively, after 1 year from the index endoscopy. The incidence rate of gastric adenocarcinoma was 0.72/1,000 person-years in patients with intestinal metaplasia, with a relative risk of 2.56 (95% confidence interval (CI) 1.49-4.10) compared with the Kaiser Permanente member population, and 7.7/1,000 person-years for low-grade dysplasia, with a relative risk of 25.6 (95% CI, 9.4-55.7). The median time for gastric intestinal metaplasia to progress to adenocarcinoma was 6.1 years, and for low-grade dysplasia, 2.6 years. Hispanic race/ethnicity and history of dysplasia were associated with significantly higher risk of progression to gastric adenocarcinoma.Gastric intestinal metaplasia and dysplasia are significant predictors for gastric adenocarcinoma. The low risk for malignancy associated with intestinal metaplasia does not support routine endoscopic surveillance. However, surveillance should be considered in patients at higher risks, including those with suspicious endoscopic features, presence of dysplasia, and Hispanic race/ethnicity.

  View details for DOI 10.1038/ajg.2016.188

  View details for PubMedID 27185078

• Screening for Cancer Genetic Syndromes With a Simple Risk-Assessment Tool in a Community-Based Open-Access Colonoscopy Practice AMERICAN JOURNAL OF GASTROENTEROLOGY Gunaratnam, N. T., Akce, M., Al Natour, R., Bartley, A. N., Fioritto, A. F., Hanson, K., Ladabaum, U. 2016; 111 (5): 589-593

  View details for DOI 10.1038/ajg.2016.84

  View details for Web of Science ID 000377584000002

  View details for PubMedID 27021195

• Post-Polypectomy Surveillance That Would Please Goldilocks-Not Too Much, Not Too Little, but Just Right GASTROENTEROLOGY Ladabaum, U., Schoen, R. E. 2016; 150 (4): 791-796

  View details for DOI 10.1053/j.gastro.2016.01.033

  View details for Web of Science ID 000372730000008

  View details for PubMedID 26850494

• Feasibility and Usability Pilot Study of a Novel Irritable Bowel Syndrome Food and Gastrointestinal Symptom Journal Smartphone App CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY Zia, J., Schroeder, J., Munson, S., Fogarty, J., Nguyen, L., Barney, P., Heitkemper, M., Ladabaum, U. 2016; 7

  Abstract

  Seventy percent of patients with irritable bowel syndrome (IBS) identify certain foods as triggers for their symptom flare-ups. To help identify potential trigger foods, practitioners often rely on patient food and gastrointestinal (GI) symptom journaling. The aim of the study was to evaluate the feasibility and usability of a novel food and symptom journal app, specifically designed for patients with IBS. Secondary aims were to explore the effect of using the app on GI symptoms and to describe associations between diet and GI symptoms suggested by individual patient data.The feasibility and usability of the novel app was studied in 11 IBS patients (8 women), aged 21-65 years. Participants were asked to log GI symptoms (abdominal pain, bloating, diarrhea, constipation) using a 100-point color-graded sliding scale (green=none, red=severe) four times a day and to log every meal/snack they ate (at least three times a day) over a 2-week period. The app's feasibility as a data collection tool was evaluated by daily completion, compliance, data hoarding, and fatigability rates. Usability was evaluated with the System Usability Scale (SUS). To explore potential impact of using the app on bowel distress, we compared before and after intervention IBS-Symptom Severity Scale (IBS-SSS) scores. Meal entries were analyzed for nutrients using the Nutrition Data System for Research. Regression analyses were conducted for each participant journal to explore relationships between meal nutrients and subsequent GI symptoms.Daily average completion rates of the minimum requested entries for meal and GI symptoms were 112±47% and 78±44%, respectively. Average 24-h compliance rates were 90±19% and 94±12%, respectively. The SUS score was above average (mean 83, range 65-97.5; n=10). Most participants did not have a clinically significant decrease in IBS-SSS. At least one strong association (P≤0.05) between GI symptoms and a meal nutrient was found in 73% of participants. The mean number of associations was 2 (range 0-7; n=11). Patterns of associations differed between individual participants.Our app appeared to be a feasible and usable tool for IBS patients. Our findings are in line with anecdotes that most IBS patients have food triggers and that these vary by individual. Future studies can explore whether individualized dietary changes guided by an app can result in IBS symptom improvement.

  View details for DOI 10.1038/ctg.2016.9

  View details for PubMedID 26938478

• Economic evidence on identifying clinically actionable findings with whole-genome sequencing: a scoping review GENETICS IN MEDICINE Douglas, M. P., Ladabaum, U., Pletcher, M. J., Marshall, D. A., Phillips, K. A. 2016; 18 (2): 111-116

  Abstract

  The American College of Medical Genetics and Genomics (ACMG) recommends that mutations in 56 genes for 24 conditions are clinically actionable and should be reported as secondary findings after whole-genome sequencing (WGS). Our aim was to identify published economic evaluations of detecting mutations in these genes among the general population or among targeted/high-risk populations and conditions and identify gaps in knowledge. A targeted PubMed search from 1994 through November 2014 was performed, and we included original, English-language articles reporting cost-effectiveness or a cost-to-utility ratio or net benefits/benefit-cost focused on screening (not treatment) for conditions and genes listed by the ACMG. Articles were screened, classified as targeting a high-risk or general population, and abstracted by two reviewers. General population studies were evaluated for actual cost-effectiveness measures (e.g., incremental cost-effectiveness ratios (ICER)), whereas studies of targeted populations were evaluated for whether at least one scenario proposed was cost-effective (e.g., ICER of ≤$100,000 per life-year or quality-adjusted life-year gained). A total of 607 studies were identified, and 32 relevant studies were included. Identified studies addressed fewer than one-third (7 of 24; 29%) of the ACMG conditions. The cost-effectiveness of screening in the general population was examined for only 2 of 24 conditions (8%). The cost-effectiveness of most genetic findings that the ACMG recommends for return has not been evaluated in economic studies or in the context of screening in the general population. The individual studies do not directly address the cost-effectiveness of WGS.

  View details for DOI 10.1038/gim.2015.69

  View details for Web of Science ID 000369173600001

  View details for PubMedCentralID PMC4654986

• Economic evidence on identifying clinically actionable findings with whole-genome sequencing: a scoping review. Genetics in medicine : official journal of the American College of Medical Genetics Douglas, M. P., Ladabaum, U., Pletcher, M. J., Marshall, D. A., Phillips, K. A. 2016; 18 (2): 111-6

  Abstract

  The American College of Medical Genetics and Genomics (ACMG) recommends that mutations in 56 genes for 24 conditions are clinically actionable and should be reported as secondary findings after whole-genome sequencing (WGS). Our aim was to identify published economic evaluations of detecting mutations in these genes among the general population or among targeted/high-risk populations and conditions and identify gaps in knowledge. A targeted PubMed search from 1994 through November 2014 was performed, and we included original, English-language articles reporting cost-effectiveness or a cost-to-utility ratio or net benefits/benefit-cost focused on screening (not treatment) for conditions and genes listed by the ACMG. Articles were screened, classified as targeting a high-risk or general population, and abstracted by two reviewers. General population studies were evaluated for actual cost-effectiveness measures (e.g., incremental cost-effectiveness ratios (ICER)), whereas studies of targeted populations were evaluated for whether at least one scenario proposed was cost-effective (e.g., ICER of ≤$100,000 per life-year or quality-adjusted life-year gained). A total of 607 studies were identified, and 32 relevant studies were included. Identified studies addressed fewer than one-third (7 of 24; 29%) of the ACMG conditions. The cost-effectiveness of screening in the general population was examined for only 2 of 24 conditions (8%). The cost-effectiveness of most genetic findings that the ACMG recommends for return has not been evaluated in economic studies or in the context of screening in the general population. The individual studies do not directly address the cost-effectiveness of WGS.

  View details for DOI 10.1038/gim.2015.69

  View details for PubMedID 25996638

  View details for PubMedCentralID PMC4654986

• Where Do We Stand With Aspirin for the Prevention of Colorectal Cancer? The USPSTF Recommendations GASTROENTEROLOGY Chan, A. T., Ladabaum, U. 2016; 150 (1): 14-18

  View details for DOI 10.1053/j.gastro.2015.11.018

  View details for Web of Science ID 000366832800010

  View details for PubMedID 26602220

• American Gastroenterological Association Technical Review on the Diagnosis and Management of Lynch Syndrome. Gastroenterology Ladabaum, U., Ford, J. M., Martel, M., Barkun, A. N. 2015; 149 (3): 783-813 e20

  View details for DOI 10.1053/j.gastro.2015.07.037

  View details for PubMedID 26226576

• Value of Genetic Testing for Hereditary Colorectal Cancer in a Probability-Based US Online Sample MEDICAL DECISION MAKING Knight, S. J., Mohamed, A. F., Marshall, D. A., Ladabaum, U., Phillips, K. A., Walsh, J. M. 2015; 35 (6): 734-744

  View details for DOI 10.1177/0272989X14565820

  View details for Web of Science ID 000359427600007

• The reply. American journal of medicine Ladabaum, U., Mannalithara, A., Myer, P. A., Singh, G. 2015; 128 (5)

  View details for DOI 10.1016/j.amjmed.2015.01.011

  View details for PubMedID 25918926

• Cost-Effectiveness of Patient Navigation to Increase Adherence With Screening Colonoscopy Among Minority Individuals CANCER Ladabaum, U., Mannalithara, A., Jandorf, L., Itzkowitz, S. H. 2015; 121 (7): 1088-1097

  Abstract

  Colorectal cancer (CRC) screening is underused by minority populations, and patient navigation increases adherence with screening colonoscopy. In this study, the authors estimated the cost-effectiveness of navigation for screening colonoscopy from the perspective of a payer seeking to improve population health.A validated model of CRC screening was informed with inputs from navigation studies in New York City (population: 43% African American, 49% Hispanic, 4% white, 4% other; base-case screening: 40% without navigation, 65% with navigation; navigation costs: $29 per colonoscopy completer, $21 per noncompleter, $3 per non-navigated individual). Two analyses compared: 1) navigation versus no navigation for 1-time screening colonoscopy in unscreened individuals aged ≥50 years; and 2) programs of colonoscopy with versus without navigation versus fecal occult blood testing (FOBT) or fecal immunochemical testing (FIT) for individuals ages 50 to 80 years.In the base case: 1) 1-time navigation gained quality-adjusted life-years (QALYs) and decreased costs; 2) longitudinal navigation cost $9800 per QALY gained versus no navigation, and, assuming comparable uptake rates, it cost $118,700 per QALY gained versus FOBT but was less effective and more costly than FIT. The results were most dependent on screening participation rates and navigation costs: 1) assuming a 5% increase in screening uptake with navigation, and a navigation cost of $150 per completer, 1-time navigation cost $26,400 per QALY gained; and 2) longitudinal navigation with 75% colonoscopy uptake cost <$25,000 per QALY gained versus FIT when FIT uptake was <50%. Probabilistic sensitivity analyses did not alter the conclusions.Navigation for screening colonoscopy appears to be cost-effective, and 1-time navigation may be cost-saving. In emerging health care models that reward outcomes, payers should consider covering the costs of navigation for screening colonoscopy. Cancer 2015;121:1088-1097. © 2014 American Cancer Society.

  View details for DOI 10.1002/cncr.29162

  View details for Web of Science ID 000351615800018

  View details for PubMedID 25492455

• Key emerging themes for assessing the cost-effectiveness of reporting incidental findings GENETICS IN MEDICINE Phillips, K. A., Ladabaum, U., Pletcher, M. J., Marshall, D. A., Douglas, M. P. 2015; 17 (4): 314–15

  View details for PubMedID 25835195

  View details for PubMedCentralID PMC4395812

• Is the "$1000 Genome" really $1000? Understanding the full benefits and costs of genomic sequencing TECHNOLOGY AND HEALTH CARE Phillips, K. A., Pletcher, M. J., Ladabaum, U. 2015; 23 (3): 373-379

  View details for DOI 10.3233/THC-150900

  View details for Web of Science ID 000356500200016

  View details for PubMedID 25669213

  View details for PubMedCentralID PMC4527943

• Value of Genetic Testing for Hereditary Colorectal Cancer in a Probability-Based US Online Sample. Medical decision making : an international journal of the Society for Medical Decision Making Knight, S. J., Mohamed, A. F., Marshall, D. A., Ladabaum, U., Phillips, K. A., Walsh, J. M. 2015

  Abstract

  BACKGROUND: . While choices about genetic testing are increasingly common for patients and families, and public opinion surveys suggest public interest in genomics, it is not known how adults from the general population value genetic testing for heritable conditions. We sought to understand in a US sample the relative value of the characteristics of genetic tests to identify risk of hereditary colorectal cancer, among the first genomic applications with evidence to support its translation to clinical settings.METHODS: . A Web-enabled choice-format conjoint survey was conducted with adults age 50 years and older from a probability-based US panel. Participants were asked to make a series of choices between 2 hypothetical blood tests that differed in risk of false-negative test, privacy, and cost. Random parameters logit models were used to estimate preferences, the dollar value of genetic information, and intent to have genetic testing.RESULTS: . A total of 355 individuals completed choice-format questions. Cost and privacy were more highly valued than reducing the chance of a false-negative result. Most (97% [95% confidence interval (CI)], 95%-99%) would have genetic testing to reduce the risk of dying of colorectal cancer in the best scenario (no false negatives, results disclosed to primary care physician). Only 41% (95% CI, 25%-57%) would have genetic testing in the worst case (20% false negatives, results disclosed to insurance company).CONCLUSIONS: . Given the characteristics and levels included in the choice, if false-negative test results are unlikely and results are shared with a primary care physician, the majority would have genetic testing. As genomic services become widely available, primary care professionals will need to be increasingly knowledgeable about genetic testing decisions.

  View details for PubMedID 25589525

• The reply. American journal of medicine Ladabaum, U., Mannalithara, A., Myer, P. A., Singh, G. 2014; 127 (12)

  View details for DOI 10.1016/j.amjmed.2014.09.007

  View details for PubMedID 25481209

• Identifying Persons with Lynch Syndrome: Why and How? DIGESTIVE DISEASES AND SCIENCES Ladabaum, U. 2014; 59 (12): 2841–44

  View details for PubMedID 25344908

• Colorectal Cancer Mortality Among Hispanics in California: Differences by Neighborhood Socioeconomic Status and Nativity CANCER Tao, L., Ladabaum, U., Gomez, S. L., Cheng, I. 2014; 120 (22): 3510-3518

  Abstract

  Socioeconomic status (SES) plays an important role in colorectal cancer (CRC) mortality, although the independent and joint effects with nativity and neighborhood factors have yet to be evaluated.With nearly one-third of all US Hispanics residing in California, the authors obtained information from the California Cancer Registry to examine the associations between neighborhood SES and mortality in all 33,146 Hispanic individuals diagnosed with CRC from 1988 through 2010, with a particular focus on associations among US-born and foreign-born Hispanics. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CI) for overall and CRC-specific mortality.Hispanics residing in lower SES neighborhoods demonstrated a higher rate of overall and CRC-specific mortality than those residing in high SES neighborhoods (SES quintile 1[low] vs quintile 5 [high]: HR, 1.15 [95% CI, 1.05-1.26] and HR, 1.16 [95% CI, 1.03-1.30], respectively). Nativity modified the associations between SES and mortality (P for interaction, .02 for overall and P for interaction, .01 for CRC-specific mortality) such that the SES associations were observed only among US-born (P for trend < .01 for overall and CRC-specific mortality) but not among foreign-born Hispanics.Neighborhood SES demonstrates significant differential effects on overall and CRC-specific mortality between US-born and foreign-born Hispanics. Future efforts should investigate the underlying contextual and individual-level factors that could account for these differential associations by nativity.

  View details for DOI 10.1002/cncr.28837

  View details for Web of Science ID 000344650900013

  View details for PubMedCentralID PMC5736794

• Personalizing Colorectal Cancer Screening: A Systematic Review of Models to Predict Risk of Colorectal Neoplasia CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Ma, G. K., Ladabaum, U. 2014; 12 (10): 1624-U84

  Abstract

  A valid risk prediction model for colorectal neoplasia would allow patients to be screened for colorectal cancer (CRC) on the basis of risk. We performed a systematic review of studies reporting risk prediction models for colorectal neoplasia.We conducted a systematic search of MEDLINE, Scopus, and Cochrane Library databases from January 1990 through March 2013 and of references in identified studies. Case-control, cohort, and cross-sectional studies that developed or attempted to validate a model to predict risk of colorectal neoplasia were included. Two reviewers independently extracted data and assessed model quality. Model quality was considered to be good for studies that included external validation, fair for studies that included internal validation, and poor for studies with neither.Nine studies developed a new prediction model, and 2 tested existing models. The models varied with regard to population, predictors, risk tiers, outcomes (CRC or advanced neoplasia), and range of predicted risk. Several included age, sex, smoking, a measure of obesity, and/or family history of CRC among the predictors. Quality was good for 6 models, fair for 2 models, and poor for 1 model. The tier with the largest population fraction (low, intermediate, or high risk) depended on the model. For most models that defined risk tiers, the risk difference between the highest and lowest tier ranged from 2-fold to 4-fold. Two models reached the 0.70 threshold for the C statistic, typically considered to indicate good discriminatory power.Most current colorectal neoplasia risk prediction models have relatively weak discriminatory power and have not demonstrated generalizability. It remains to be determined how risk prediction models could inform CRC screening strategies.

  View details for DOI 10.1016/j.cgh.2014.01.042

  View details for Web of Science ID 000342625000012

  View details for PubMedID 24534546

• Response to Molakatalla and Kumar. American journal of gastroenterology Ladabaum, U., Clarke, C. A., Cheng, I., Gomez, S. L. 2014; 109 (10): 1687-?

  View details for DOI 10.1038/ajg.2014.259

  View details for PubMedID 25287095

• Colorectal testing utilization and payments in a large cohort of commercially insured US adults. American journal of gastroenterology Ladabaum, U., Levin, Z., Mannalithara, A., Brill, J. V., Bundorf, M. K. 2014; 109 (10): 1513-1525

  Abstract

  Screening decreases colorectal cancer (CRC) mortality. The national press has scrutinized colonoscopy charges. Little systematic evidence exists on colorectal testing and payments among commercially insured persons. Our aim was to characterize outpatient colorectal testing utilization and payments among commercially insured US adults.We conducted an observational cohort study of outpatient colorectal test utilization rates, indications, and payments among 21 million 18-64-year-old employees and dependants with noncapitated group health insurance provided by 160 self-insured employers in the 2009 Truven MarketScan Databases.Colonoscopy was the predominant colorectal test. Among 50-64-year olds, 12% underwent colonoscopy in 1 year. Most fecal tests and colonoscopies were associated with screening/surveillance indications. Testing rates were higher in women, and increased with age. Mean payments for fecal occult blood and immunochemical tests were $5 and $21, respectively. Colonoscopy payments varied between and within sites of service. Mean payments for diagnostic colonoscopy in an office, outpatient hospital facility, and ambulatory surgical center were $586 (s.d. $259), $1,400 (s.d. $681), and $1,074 (s.d. $549), respectively. Anesthesia and pathology services accompanied 35 and 52% of colonoscopies, with mean payments of $494 (s.d. $354) and $272 (s.d. $284), respectively. Mean payments for the most prevalent colonoscopy codes were 1.4- to 1.9-fold the average Medicare payments.Most outpatient colorectal testing among commercially insured adults was associated with screening or surveillance. Payments varied widely across sites of service, and payments for anesthesia and pathology services contributed substantially to total payments. Cost-effectiveness analyses of CRC screening have relied on Medicare payments as proxies for costs, but cost-effectiveness may differ when analyzed from the perspectives of Medicare or commercial insurers.

  View details for DOI 10.1038/ajg.2014.64

  View details for PubMedID 24980877

• Evaluating the utilization of educational materials in communicating about Lynch syndrome to at-risk relatives FAMILIAL CANCER Dilzell, K., Kingham, K., Ormond, K., Ladabaum, U. 2014; 13 (3): 381-389

  Abstract

  Facilitating family communication about Lynch syndrome is a public health priority since following appropriate screening guidelines can decrease morbidity and mortality. The aims of this study were to (1) ascertain what educational materials individuals with Lynch syndrome provide to at-risk relatives, and (2) identify relationships between receiving educational materials and pursuing clinical follow-up. Seventy-four participants, recruited from the Stanford Cancer Institute and a support group, completed an online questionnaire; 50 were first to be diagnosed with a Lynch syndrome mutation in their family (probands) and 24 were first or second-degree relatives. Probands reported informing 88 % (184/209) of first-degree relatives and 64 % (161/252) of second-degree relatives of the mutation. Probands shared their genetic counseling note with 53 % of relatives; other resources, including family letters, personal notes, testing laboratory information, online resources, support group information, and genetics referrals, were given to 33 % or fewer relatives. Probands reported that female relatives (p = 0.028) and first-degree relatives (p ≤ 0.001) were more likely to be given materials. Relatives who received an educational material were more likely to follow up with a clinician (74 vs 22 %, p ≤0.001) and attend a genetic counseling appointment (43 vs 16 %, p ≤ 0.001). First-degree relatives who received an educational material were more likely to have undergone genetic testing (51 vs 19 %, p = 0.012) and cancer screening (69 vs 29 %, p = 0.001). Facilitating information transmission in families with Lynch syndrome using educational materials may play a role in informed clinical decision-making and cascade screening of at-risk relatives.

  View details for DOI 10.1007/s10689-014-9720-9

  View details for Web of Science ID 000342176000007

  View details for PubMedID 24770865

• Obesity, Abdominal Obesity, Physical Activity, and Caloric Intake in US Adults: 1988 to 2010. American journal of medicine Ladabaum, U., Mannalithara, A., Myer, P. A., Singh, G. 2014; 127 (8): 717-727 e12

  Abstract

  Obesity and abdominal obesity are associated independently with morbidity and mortality. Physical activity attenuates these risks. We examined trends in obesity, abdominal obesity, physical activity, and caloric intake in US adults from 1988 to 2010.Univariate and multivariate analyses were performed using National Health and Nutrition Examination Survey data.Average body mass index (BMI) increased by 0.37% (95% confidence interval [CI], 0.30-0.44) per year in both women and men. Average waist circumference increased by 0.37% (95% CI, 0.30-0.43) and 0.27% (95% CI, 0.22-0.32) per year in women and men, respectively. The prevalence of obesity and abdominal obesity increased substantially, as did the prevalence of abdominal obesity among overweight adults. Younger women experienced the greatest increases. The proportion of adults who reported no leisure-time physical activity increased from 19.1% (95% CI, 17.3-21.0) to 51.7% (95% CI, 48.9-54.5) in women, and from 11.4% (95% CI, 10.0-12.8) to 43.5% (95% CI, 40.7-46.3) in men. Average daily caloric intake did not change significantly. BMI and waist circumference trends were associated with physical activity level but not caloric intake. The associated changes in adjusted BMIs were 8.3% (95% CI, 6.9-9.6) higher among women and 1.7% (95% CI, 0.68-2.8) higher among men with no leisure-time physical activity compared with those with an ideal level of leisure-time physical activity.Our analyses highlight important dimensions of the public health problem of obesity, including trends in younger women and in abdominal obesity, and lend support to the emphasis placed on physical activity by the Institute of Medicine.

  View details for DOI 10.1016/j.amjmed.2014.02.026

  View details for PubMedID 24631411

• Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment JOURNAL OF CLINICAL ONCOLOGY Kurian, A. W., Hare, E. E., Mills, M. A., Kingham, K. E., McPherson, L., Whittemore, A. S., McGuire, V., Ladabaum, U., Kobayashi, Y., Lincoln, S. E., Cargill, M., Ford, J. M. 2014; 32 (19): 2001-2009

  Abstract

  Multiple-gene sequencing is entering practice, but its clinical value is unknown. We evaluated the performance of a customized germline-DNA sequencing panel for cancer-risk assessment in a representative clinical sample.Patients referred for clinical BRCA1/2 testing from 2002 to 2012 were invited to donate a research blood sample. Samples were frozen at -80° C, and DNA was extracted from them after 1 to 10 years. The entire coding region, exon-intron boundaries, and all known pathogenic variants in other regions were sequenced for 42 genes that had cancer risk associations. Potentially actionable results were disclosed to participants.In total, 198 women participated in the study: 174 had breast cancer and 57 carried germline BRCA1/2 mutations. BRCA1/2 analysis was fully concordant with prior testing. Sixteen pathogenic variants were identified in ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4 among 141 women without BRCA1/2 mutations. Fourteen participants carried 15 pathogenic variants, warranting a possible change in care; they were invited for targeted screening recommendations, enabling early detection and removal of a tubular adenoma by colonoscopy. Participants carried an average of 2.1 variants of uncertain significance among 42 genes.Among women testing negative for BRCA1/2 mutations, multiple-gene sequencing identified 16 potentially pathogenic mutations in other genes (11.4%; 95% CI, 7.0% to 17.7%), of which 15 (10.6%; 95% CI, 6.5% to 16.9%) prompted consideration of a change in care, enabling early detection of a precancerous colon polyp. Additional studies are required to quantify the penetrance of identified mutations and determine clinical utility. However, these results suggest that multiple-gene sequencing may benefit appropriately selected patients.

  View details for DOI 10.1200/JCO.2013.53.6607

  View details for Web of Science ID 000337925500007

• Response:. Gastrointestinal endoscopy Kumar, S., Gunaratnam, N., Ladabaum, U. 2014; 79 (6): 1031-1032

  View details for DOI 10.1016/j.gie.2014.02.003

  View details for PubMedID 24856847

• Cost-effectiveness of colorectal cancer screening in Germany: current endoscopic and fecal testing strategies versus plasma methylated Septin 9 DNA. Endoscopy international open Ladabaum, U., Alvarez-Osorio, L., Rösch, T., Brueggenjuergen, B. 2014; 2 (2): E96-E104

  Abstract

  Colorectal cancer (CRC) screening strategies in Germany include guaiac-based fecal occult blood testing (gFOBT) starting at age 50 and a switch to colonoscopy at age 55 or continued gFOBT testing, but screening utilization is limited. Blood-based biomarkers, such as methylated Septin 9 DNA ( (m) SEPT9), may improve screening rates. We performed a cost-effectiveness analysis of current and emerging CRC screening strategies in Germany.Using a validated Markov model, we compared annual gFOBT for ages 50 through 54 followed by biennial testing until age 75 (FOBT) or by colonoscopy at ages 55 and 65 (FOBT/COLO 55,65), substitution of fecal immunochemical testing (FIT) for gFOBT (FIT, FIT/COLO 55,65), and annual or biennial plasma (m) SEPT9 testing. We also considered persons who utilize only colonoscopy and varied age at colonoscopy utilization.The current strategies were more effective and less costly than no screening. FIT was more effective and less costly than (m) SEPT9 testing. FIT/COLO 55,65 cost €12 200 per quality-adjusted life-years gained in comparison with FIT. (m) SEPT9-based screening was cost-effective in comparison with no screening but was dominated by other cost-saving strategies. Differential screening utilization and adherence greatly affected incremental results between strategies. In probabilistic analyses, FIT was preferred in 49 % and FIT/COLO 55,65 in 47 % of iterations.Currently available CRC screening strategies in Germany, including hybrid fecal testing/colonoscopy, are likely to be cost-saving. Current strategies appear superior to (m) SEPT9-based screening. The impact of blood-based biomarkers is likely to depend on utilization and adherence as much as on test performance characteristics and cost.

  View details for DOI 10.1055/s-0034-1377182

  View details for PubMedID 26135268

  View details for PubMedCentralID PMC4440365

• The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype. European journal of human genetics Kwok, C., Vogelaar, I. P., van Zelst-Stams, W. A., Mensenkamp, A. R., Ligtenberg, M. J., Rapkins, R. W., Ward, R. L., Chun, N., Ford, J. M., Ladabaum, U., McKinnon, W. C., Greenblatt, M. S., Hitchins, M. P. 2014; 22 (5): 617-624

  Abstract

  Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by predisposing to early-onset colorectal, endometrial and other cancers. An alternative but rare cause of Lynch syndrome is constitutional epimutation of MLH1, whereby promoter methylation and transcriptional silencing of one allele occurs throughout normal tissues. A dominantly transmitted constitutional MLH1 epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide variants, NM_000249.2: c.-27C>A and c.85G>T, in a Caucasian family with Lynch syndrome from Western Australia. Subsequently, a second seemingly unrelated Caucasian Australian case with the same MLH1 haplotype and concomitant epimutation was reported. We now describe three additional, ostensibly unrelated, cancer-affected families of European heritage with this MLH1 haplotype in association with constitutional epimutation, bringing the number of index cases reported to five. Array-based genotyping in four of these families revealed shared haplotypes between individual families that extended across ≤2.6-≤6.4 megabase regions of chromosome 3p, indicating common ancestry. A minimal ≤2.6 megabase founder haplotype common to all four families was identified, which encompassed MLH1 and additional flanking genes and segregated with the MLH1 epimutation in each family. Our findings indicate that the MLH1 c.-27C>A and c.85G>T variants are borne on a European ancestral haplotype and provide conclusive evidence for its pathogenicity via a mechanism of epigenetic silencing of MLH1 within normal tissues. Additional descendants bearing this founder haplotype may exist who are also at high risk of developing Lynch syndrome-related cancers.

  View details for DOI 10.1038/ejhg.2013.200

  View details for PubMedID 24084575

• Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Kurian, A. W., Hare, E. E., Mills, M. A., Kingham, K. E., McPherson, L., Whittemore, A. S., McGuire, V., Ladabaum, U., Kobayashi, Y., Lincoln, S. E., Cargill, M., Ford, J. M. 2014

  Abstract

  Multiple-gene sequencing is entering practice, but its clinical value is unknown. We evaluated the performance of a customized germline-DNA sequencing panel for cancer-risk assessment in a representative clinical sample.Patients referred for clinical BRCA1/2 testing from 2002 to 2012 were invited to donate a research blood sample. Samples were frozen at -80° C, and DNA was extracted from them after 1 to 10 years. The entire coding region, exon-intron boundaries, and all known pathogenic variants in other regions were sequenced for 42 genes that had cancer risk associations. Potentially actionable results were disclosed to participants.In total, 198 women participated in the study: 174 had breast cancer and 57 carried germline BRCA1/2 mutations. BRCA1/2 analysis was fully concordant with prior testing. Sixteen pathogenic variants were identified in ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4 among 141 women without BRCA1/2 mutations. Fourteen participants carried 15 pathogenic variants, warranting a possible change in care; they were invited for targeted screening recommendations, enabling early detection and removal of a tubular adenoma by colonoscopy. Participants carried an average of 2.1 variants of uncertain significance among 42 genes.Among women testing negative for BRCA1/2 mutations, multiple-gene sequencing identified 16 potentially pathogenic mutations in other genes (11.4%; 95% CI, 7.0% to 17.7%), of which 15 (10.6%; 95% CI, 6.5% to 16.9%) prompted consideration of a change in care, enabling early detection of a precancerous colon polyp. Additional studies are required to quantify the penetrance of identified mutations and determine clinical utility. However, these results suggest that multiple-gene sequencing may benefit appropriately selected patients.

  View details for DOI 10.1200/JCO.2013.53.6607

  View details for PubMedID 24733792

• Colorectal Cancer Incidence in Asian Populations in California: Effect of Nativity and Neighborhood-Level Factors AMERICAN JOURNAL OF GASTROENTEROLOGY Ladabaum, U., Clarke, C. A., Press, D. J., Mannalithara, A., Myer, P. A., Cheng, I., Gomez, S. L. 2014; 109 (4): 579-588

  Abstract

  Heritable and environmental factors may contribute to differences in colorectal cancer (CRC) incidence across populations. We capitalized on the resources of the California Cancer Registry (CCR) and California's diverse Asian population to perform a cohort study exploring the relationships between CRC incidence, nativity, and neighborhood-level factors across Asian subgroups.We identified CRC cases in the CCR from 1990 to 2004 and calculated age-adjusted CRC incidence rates for non-Hispanic Whites and US-born vs. foreign-born Asian ethnic subgroups, stratified by neighborhood socioeconomic status (SES) and "ethnic enclave." Trends were studied with joinpoint analysis.CRC incidence was lowest among foreign-born South Asians (22.0/100,000; 95% confidence interval (CI): 19.7-24.5/100,000) and highest among foreign-born Japanese (74.6/100,000; 95% CI: 70.1-79.2/100,000). Women in all Asian subgroups except Japanese, and men in all Asian subgroups except Japanese and US-born Chinese, had lower CRC incidence than non-Hispanic Whites. Among Chinese men and Filipino women and men, CRC incidence was lower among foreign-born than US-born persons; the opposite was observed for Japanese women and men. Among non-Hispanic Whites, but not most Asian subgroups, CRC incidence decreased over time. CRC incidence was inversely associated with neighborhood SES among non-Hispanic Whites, and level of ethnic enclave among Asians.CRC incidence rates differ substantially across Asian subgroups in California. The significant associations between CRC incidence and nativity and residence in an ethnic enclave suggest a substantial effect of acquired environmental factors. The absence of declines in CRC incidence rates among most Asians during our study period may point to disparities in screening compared with Whites.

  View details for DOI 10.1038/ajg.2013.488

  View details for Web of Science ID 000335450300016

  View details for PubMedID 24492754

• Locally advanced gastric cancer complicated by mesenteric invasion and intestinal malrotation. Digestive diseases and sciences Huang, R. J., Visser, B. C., Chen, A. M., Ladabaum, U. 2014; 59 (2): 267-269

  View details for DOI 10.1007/s10620-013-2869-5

  View details for PubMedID 24036993

• Optical biopsy of sessile serrated adenomas: do these lesions resemble hyperplastic polyps under narrow-band imaging? Gastrointestinal endoscopy Kumar, S., Fioritto, A., Mitani, A., Desai, M., Gunaratnam, N., Ladabaum, U. 2013; 78 (6): 902-909

  Abstract

  Serrated colorectal lesions include hyperplastic polyps (HPs) and sessile serrated adenomas (SSAs). Optical biopsy could misclassify SSAs as unimportant if they resemble HPs.To explore the narrow-band imaging (NBI) features of SSAs. We hypothesized that SSAs resemble HPs under NBI.Retrospective analysis of data from our prospective study of NBI in routine practice.Single specialty group.Patients undergoing colonoscopy.Colonoscopy.Polyp histology prediction by community gastroenterologists. Features of SSAs versus HPs and adenomas by using the Narrow-Band Imaging International Colorectal Endoscopic (NICE) Classification.Among 2388 lesions, 141 were diagnosed on pathology as SSAs, 465 as HPs, and 1546 as adenomas. Each individual NICE feature of HPs was found in 38% to 42% of SSAs, 66% to 67% of HPs, and 15% to 20% of adenomas (P < .001 for each). Each individual NICE feature of adenomas was found in 57% to 62% of SSAs, 33% to 34% of HPs, and 80% to 84% of adenomas (P < .001 for each). Compared with HPs, SSAs were less likely (odds ratio [OR] 0.74; 95% confidence interval [CI], 0.69-0.79) and adenomas were even less likely (OR 0.62; 95% CI, 0.59-0.64) to have all 3 NICE features of HPs. SSAs >5 mm were more likely than smaller SSAs to have all 3 NICE features of adenomas. SSA location did not predict NBI features. Analyses restricted to high-confidence lesions showed similar results.The endoscopists were not NBI experts.Community gastroenterologists observed a profile of NICE features among SSAs that was intermediate to the profiles observed for HPs and adenomas. These results require confirmation by NBI experts.

  View details for DOI 10.1016/j.gie.2013.06.004

  View details for PubMedID 23849819

• Endoscopic optical biopsy: when we look, what can we see? LANCET ONCOLOGY Ladabaum, U. 2013; 14 (13): 1253–54

  View details for PubMedID 24239211

• Uptake of Genetic Testing by Relatives of Lynch Syndrome Probands: A Systematic Review CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Sharaf, R. N., Myer, P., Stave, C. D., Diamond, L. C., Ladabaum, U. 2013; 11 (9): 1093-1100

  Abstract

  BACKGROUND: Screening of persons with newly diagnosed colorectal cancer (CRC) for Lynch syndrome can yield substantial benefits at acceptable costs, presuming sufficient uptake of genetic testing by first-degree relatives of Lynch syndrome probands. We performed a systematic review of the literature to determine the frequency of, and factors associated with, genetic testing of first-degree relatives of Lynch syndrome probands. METHODS: We searched 4 databases (CINAHL, PsycInfo, PUBMED, and SCOPUS) for articles published through May 2011 reporting uptake of genetic testing by relatives of Lynch syndrome probands. Two investigators independently screened articles to determine whether they met inclusion criteria; data were collected on populations, methodologies, and uptake of genetic testing. A narrative, qualitative systematic review was performed. RESULTS: We identified 1258 potentially relevant articles; 533 were fully reviewed and 8 were included in the final analysis. Of first-degree relatives of Lynch syndrome probands, 52% or less received genetic testing. For each proband, 4.6 or fewer relatives underwent genetic testing. Demographic factors (age <50 y, female sex, parenthood, level of education, employment, participation in medical studies), psychological factors (lack of depressive symptoms), and possibly family history (greater number of relatives with cancer) were associated with uptake of genetic testing. CONCLUSION: Based on a systematic review, genetic testing appears to be underutilized by first-degree relatives of patients with Lynch syndrome. The clinical benefit and economic feasibility of screening persons with CRC for Lynch syndrome depends on optimizing family-wide uptake of genetic testing. Future research and clinical efforts should focus on ways to overcome barriers to genetic testing.

  View details for DOI 10.1016/j.cgh.2013.04.044

  View details for Web of Science ID 000323816100012

• Clinical and economic burden of emergency department visits due to gastrointestinal diseases in the United States. American journal of gastroenterology Myer, P. A., Mannalithara, A., Singh, G., Singh, G., Pasricha, P. J., Ladabaum, U. 2013; 108 (9): 1496-1507

  Abstract

  OBJECTIVES:Gastrointestinal (GI) emergencies may cause substantial morbidity. Our aims were to characterize the national clinical and economic burden of GI visits to emergency departments (EDs) in the United States.METHODS:We performed an observational cross-sectional study using the 2007 Nationwide Emergency Department Sample, the largest US all-payer ED database, to identify the leading causes for ED visits due to GI diseases and their associated charges, stratified by age and sex. Logistic regression was used to analyze predictors of hospitalization after an ED visit.RESULTS:Of the 122 million ED visits in 2007, 15 million (12%) had a primary GI diagnosis. The leading primary GI diagnoses were abdominal pain (4.7 million visits), nausea and vomiting (1.6 million visits), and functional disorders of the digestive system (0.7 million visits). The leading diagnoses differed by age group. The fraction of ED visits resulting in hospitalization was 21.6% for primary GI diagnoses vs. 14.7% for non-GI visits. Women had more ED visits with a primary GI diagnosis than men (58.5 (95% CI 56.0-60.9) vs. 41.6 (95% CI 39.8-43.3) per 1000 persons), but lower rates of subsequent hospitalization (20.0% (95% CI 19.4-20.7%) vs. 24.0% (95% CI 23.3-24.6%)). There were no differences in hospitalization rates between sexes after adjustment by age, primary GI diagnosis, and Charlson Comorbidity Score. The total charges for ED visits with a primary GI diagnosis in 2007 were $27.9 billion.CONCLUSIONS:GI illnesses account for substantial clinical and economic burdens on US emergency medical services.Am J Gastroenterol advance online publication, 16 July 2013; doi:10.1038/ajg.2013.199.

  View details for DOI 10.1038/ajg.2013.199

  View details for PubMedID 23857475

• Colorectal Cancer Screening with Blood-Based Biomarkers: Cost-Effectiveness of Methylated Septin 9 DNA versus Current Strategies CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Ladabaum, U., Allen, J., Wandell, M., Ramsey, S. 2013; 22 (9): 1567-1576

  Abstract

  Background: Screening reduces colorectal cancer (CRC) mortality, but many persons remain unscreened. Screening with a blood test could improve screening rates. We estimated the comparative effectiveness and cost-effectiveness of CRC screening with emerging biomarkers, illustrated by a methylated Septin 9 DNA plasma assay (mSEPT9), vs. established strategies. Methods: We conducted a cost-utility analysis using a validated decision analytic model comparing mSEPT9, fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), sigmoidoscopy and colonoscopy, projecting benefits and costs over a lifetime. Results: In the base case, mSEPT9 decreased CRC incidence by 35-41% and CRC mortality by 53-61% at costs of $8,400-$11,500/quality-adjusted life year gained vs. no screening. All established screening strategies were more effective than mSEPT9. FIT was cost-saving, dominated mSEPT9, and was preferred among all the alternatives. Screening uptake and longitudinal adherence rates over time strongly influenced the comparisons between strategies. At the population level, mSEPT9 yielded incremental benefit at acceptable costs when it increased the fraction of the population screened more than it was substituted for other strategies. Conclusions: mSEPT9 appears to be effective and cost-effective compared with no screening. In order to be cost-effective compared with established strategies, mSEPT9 or blood-based biomarkers with similar test performance characteristics would need to achieve substantially higher uptake and adherence rates than the alternatives. It remains to be proven whether CRC screening with a blood test can improve screening uptake or long-term adherence compared with established strategies. Impact: Our study offer insights into the potential role of CRC screening with blood-based biomarkers.

  View details for DOI 10.1158/1055-9965.EPI-13-0204

  View details for Web of Science ID 000324674500010

  View details for PubMedID 23796793

• Uptake of genetic testing by relatives of lynch syndrome probands: a systematic review. Clinical gastroenterology and hepatology Sharaf, R. N., Myer, P., Stave, C. D., Diamond, L. C., Ladabaum, U. 2013; 11 (9): 1093-1100

  Abstract

  BACKGROUND: Screening of persons with newly diagnosed colorectal cancer (CRC) for Lynch syndrome can yield substantial benefits at acceptable costs, presuming sufficient uptake of genetic testing by first-degree relatives of Lynch syndrome probands. We performed a systematic review of the literature to determine the frequency of, and factors associated with, genetic testing of first-degree relatives of Lynch syndrome probands. METHODS: We searched 4 databases (CINAHL, PsycInfo, PUBMED, and SCOPUS) for articles published through May 2011 reporting uptake of genetic testing by relatives of Lynch syndrome probands. Two investigators independently screened articles to determine whether they met inclusion criteria; data were collected on populations, methodologies, and uptake of genetic testing. A narrative, qualitative systematic review was performed. RESULTS: We identified 1258 potentially relevant articles; 533 were fully reviewed and 8 were included in the final analysis. Of first-degree relatives of Lynch syndrome probands, 52% or less received genetic testing. For each proband, 4.6 or fewer relatives underwent genetic testing. Demographic factors (age <50 y, female sex, parenthood, level of education, employment, participation in medical studies), psychological factors (lack of depressive symptoms), and possibly family history (greater number of relatives with cancer) were associated with uptake of genetic testing. CONCLUSION: Based on a systematic review, genetic testing appears to be underutilized by first-degree relatives of patients with Lynch syndrome. The clinical benefit and economic feasibility of screening persons with CRC for Lynch syndrome depends on optimizing family-wide uptake of genetic testing. Future research and clinical efforts should focus on ways to overcome barriers to genetic testing.

  View details for DOI 10.1016/j.cgh.2013.04.044

  View details for PubMedID 23669308

• Health Benefits and Cost-effectiveness of a Hybrid Screening Strategy for Colorectal Cancer CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Tuan Dinh, T., Ladabaum, U., Alperin, P., Caldwell, C., Smith, R., Levin, T. R. 2013; 11 (9): 1158-1166

  Abstract

  BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines recommend screening schedules for each single type of test except for concurrent sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost-effectiveness of a hybrid screening strategy that was based on a fecal immunological test (FIT) and colonoscopy. METHODS: We conducted a cost-effectiveness analysis by using the Archimedes Model to evaluate the effects of different CRC screening strategies on health outcomes and costs related to CRC in a population that represents members of Kaiser Permanente Northern California. The Archimedes Model is a large-scale simulation of human physiology, diseases, interventions, and health care systems. The CRC submodel in the Archimedes Model was derived from public databases, published epidemiologic studies, and clinical trials. RESULTS: A hybrid screening strategy led to substantial reductions in CRC incidence and mortality, gains in quality-adjusted life years (QALYs), and reductions in costs, comparable with those of the best single-test strategies. Screening by annual FIT of patients 50-65 years old and then a single colonoscopy when they were 66 years old (FIT/COLOx1) reduced CRC incidence by 72% and gained 110 QALYs for every 1000 people during a period of 30 years, compared with no screening. Compared with annual FIT, FIT/COLOx1 gained 1400 QALYs/100,000 persons at an incremental cost of $9700/QALY gained and required 55% fewer FITs. Compared with FIT/COLOx1, colonoscopy at 10-year intervals gained 500 QALYs/100,000 at an incremental cost of $35,100/QALY gained but required 37% more colonoscopies. Over the ranges of parameters examined, the cost-effectiveness of hybrid screening strategies was slightly more sensitive to the adherence rate with colonoscopy than the adherence rate with yearly FIT. Uncertainties associated with estimates of FIT performance within a program setting and sensitivities for flat and right-sided lesions are expected to have significant impacts on the cost-effectiveness results. CONCLUSIONS: In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.

  View details for DOI 10.1016/j.cgh.2013.03.013

  View details for Web of Science ID 000323816100022

  View details for PubMedID 23542330

• Cost analysis of a patient navigation system to increase screening colonoscopy adherence among urban minorities CANCER Jandorf, L., Stossel, L. M., Cooperman, J. L., Zivin, J. G., Ladabaum, U., Hall, D., Thelemaque, L. D., Redd, W., Itzkowitz, S. H. 2013; 119 (3): 612-620

  Abstract

  Patient navigation (PN) is being used increasingly to help patients complete screening colonoscopy (SC) to prevent colorectal cancer. At their large, urban academic medical center with an open-access endoscopy system, the authors previously demonstrated that PN programs produced a colonoscopy completion rate of 78.5% in a cohort of 503 patients (predominantly African Americans and Latinos with public health insurance). Very little is known about the direct costs of implementing PN programs. The objective of the current study was to perform a detailed cost analysis of PN programs at the authors' institution from an institutional perspective.In 2 randomized controlled trials, average-risk patients who were referred for SC by primary care providers were recruited for PN between May 2008 and May 2010. Patients were randomized to 1 of 4 PN groups. The cost of PN and net income to the institution were determined in a cost analysis.Among 395 patients who completed colonoscopy, 53.4% underwent SC alone, 30.1% underwent colonoscopy with biopsy, and 16.5% underwent snare polypectomy. Accounting for the average contribution margins of each procedure type, the total revenue was $95,266.00. The total cost of PN was $14,027.30. Net income was $81,238.70. In a model sample of 1000 patients, net incomes for the institutional completion rate (approximately 80%), the historic PN program (approximately 65%), and the national average (approximately 50%) were compared. The current PN program generated additional net incomes of $35,035.50 and $44,956.00, respectively.PN among minority patients with mostly public health insurance generated additional income to the institution, mainly because of increased colonoscopy completion rates.

  View details for DOI 10.1002/cncr.27759

  View details for Web of Science ID 000313878500022

  View details for PubMedID 22833205

  View details for PubMedCentralID PMC3492525

• An Uncommon Complication of Percutaneous Endoscopic Gastrostomy Tubes CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Wong, R., Ladabaum, U. 2013; 11 (2): XXV-XXV

  View details for DOI 10.1016/j.cgh.2012.08.008

  View details for Web of Science ID 000314705400001

  View details for PubMedID 22902280

  View details for PubMedCentralID PMC3552138

• Preferences for outcomes associated with decisions to undergo or forgo genetic testing for Lynch syndrome CANCER Kuppermann, M., Wang, G., Wong, S., Blanco, A., Conrad, P., Nakagawa, S., Terdiman, J., Ladabaum, U. 2013; 119 (1): 215-225

  Abstract

  Current guidelines recommend offering genetic testing for Lynch syndrome to individuals whose tumors suggest this condition and to relatives of affected individuals. Little is known, however, regarding how patients view the prospect of such testing. In addition, data on preferences (utilities) for the potential outcomes of testing decisions for use in cost-effectiveness analyses are lacking.Time tradeoff utilities were elicited for 10 potential outcomes of Lynch syndrome testing decisions and 3 associated cancers from 70 participants, representing a range of knowledge about and experiences with Lynch syndrome.Highest mean utilities were assigned to scenarios in which only the assessor's sibling had Lynch-associated colorectal cancer (ranging from 0.669 ± 0.231 to 0.760 ± 0.220). Utilities assigned to scenarios in which the assessor had Lynch-associated colorectal cancer ranged from 0.605 ± 0.252 to 0.682 ± 0.246, whereas the lowest mean utilities were assigned to 2 of the general cancer states (0.601 ± 0.238 and 0.593 ± 0.272 for colorectal and ovarian cancer respectively). Only 43% of the sample assigned higher values to undergoing Lynch testing and receiving negative results versus forgoing Lynch testing, whereas 50% assigned higher values to undergoing rather than forgoing surgery to prevent a subsequent cancer.Genetic testing for Lynch syndrome, regardless of results, can have profound effects on quality of life; the utilities we collected can be used to incorporate these effects into cost-effectiveness analyses. Importantly, preferences for the potential outcomes of testing vary substantially, calling into question the extent to which patients would avail themselves of such testing if it were offered to them.

  View details for DOI 10.1002/cncr.27634

  View details for Web of Science ID 000312543000028

  View details for PubMedID 22786716

• Comparative Effectiveness and Cost-Effectiveness of Screening Colonoscopy vs. Sigmoidoscopy and Alternative Strategies AMERICAN JOURNAL OF GASTROENTEROLOGY Sharaf, R. N., Ladabaum, U. 2013; 108 (1): 120-132

  Abstract

  Fecal occult blood testing (FOBT) and sigmoidoscopy are proven to decrease colorectal cancer (CRC) incidence and mortality. Sigmoidoscopy's benefit is limited to the distal colon. Observational data are conflicting regarding the degree to which colonoscopy affords protection against proximal CRC. Our aim was to explore the comparative effectiveness and cost-effectiveness of colonoscopy vs. sigmoidoscopy and alternative CRC screening strategies in light of the latest published data.We performed a contemporary cost-utility analysis using a Markov model validated against data from randomized controlled trials of FOBT and sigmoidoscopy. Persons at average CRC risk within the general US population were modeled. Screening strategies included those recommended by the United States (US) Preventive Services Task Force, including colonoscopy every 10 years (COLO), flexible sigmoidoscopy every 5 years (FS), annual fecal occult blood testing, annual fecal immunochemical testing (FIT), and the combination FS/FIT. The main outcome measures were quality-adjusted life-years (QALYs) and costs.In the base case, FIT dominated other strategies. The advantage of FIT over FS and COLO was contingent on rates of uptake and adherence that are well above current US rates. Compared with FIT, FS and COLO both cost <$50,000/QALY gained when FIT per-cycle adherence was <50%. COLO cost $56,800/QALY gained vs. FS in the base case. COLO cost <$100,000/QALY gained vs. FS when COLO yielded a relative risk of proximal CRC of <0.5 vs. no screening. In probabilistic analyses, COLO was cost-effective vs. FS at a willingness-to-pay threshold of $100,000/QALY gained in 84% of iterations.Screening colonoscopy may be cost-effective compared with FIT and sigmoidoscopy, depending on the relative rates of screening uptake and adherence and the protective benefit of colonoscopy in the proximal colon. Colonoscopy's cost-effectiveness compared with sigmoidoscopy is contingent on the ability to deliver ~50% protection against CRC in the proximal colon.

  View details for DOI 10.1038/ajg.2012.380

  View details for Web of Science ID 000316186600017

  View details for PubMedID 23247579

• How to value technological innovation: a proposal for determining relative clinical value. Gastroenterology Ladabaum, U., Brill, J. V., Sonnenberg, A., Shaheen, N. J., Inadomi, J., Wilcox, C. M., Park, W. G., Hur, C., Pasricha, P. J. 2013; 144 (1): 5-8

  View details for DOI 10.1053/j.gastro.2012.11.006

  View details for PubMedID 23153872

• Real-Time Optical Biopsy of Colon Polyps With Narrow Band Imaging in Community Practice Does Not Yet Meet Key Thresholds for Clinical Decisions GASTROENTEROLOGY Ladabaum, U., Fioritto, A., Mitani, A., Desai, M., Kim, J. P., Rex, D. K., Imperiale, T., Gunaratnam, N. 2013; 144 (1): 81-91

  Abstract

  Accurate optical analysis of colorectal polyps (optical biopsy) could prevent unnecessary polypectomies or allow a "resect and discard" strategy with surveillance intervals determined based on the results of the optical biopsy; this could be less expensive than histopathologic analysis of polyps. We prospectively evaluated real-time optical biopsy analysis of polyps with narrow band imaging (NBI) by community-based gastroenterologists.We first analyzed a computerized module to train gastroenterologists (N = 13) in optical biopsy skills using photographs of polyps. Then we evaluated a practice-based learning program for these gastroenterologists (n = 12) that included real-time optical analysis of polyps in vivo, comparison of optical biopsy predictions to histopathologic analysis, and ongoing feedback on performance.Twelve of 13 subjects identified adenomas with >90% accuracy at the end of the computer study, and 3 of 12 subjects did so with accuracy ≥90% in the in vivo study. Learning curves showed considerable variation among batches of polyps. For diminutive rectosigmoid polyps assessed with high confidence at the end of the study, adenomas were identified with mean (95% confidence interval [CI]) accuracy, sensitivity, specificity, and negative predictive values of 81% (73%-89%), 85% (74%-96%), 78% (66%-92%), and 91% (86%-97%), respectively. The adjusted odds ratio for high confidence as a predictor of accuracy was 1.8 (95% CI, 1.3-2.5). The agreement between surveillance recommendations informed by high-confidence NBI analysis of diminutive polyps and results from histopathologic analysis of all polyps was 80% (95% CI, 77%-82%).In an evaluation of real-time optical biopsy analysis of polyps with NBI, only 25% of gastroenterologists assessed polyps with ≥90% accuracy. The negative predictive value for identification of adenomas, but not the surveillance interval agreement, met the American Society for Gastrointestinal Endoscopy-recommended thresholds for optical biopsy. Better results in community practice must be achieved before NBI-based optical biopsy methods can be used routinely to evaluate polyps; ClinicalTrials.gov number, NCT01638091.

  View details for DOI 10.1053/j.gastro.2012.09.054

  View details for Web of Science ID 000312965100029

  View details for PubMedID 23041328

• Proximal and Distal Colorectal Cancer Resection Rates in the United States Since Widespread Screening by Colonoscopy GASTROENTEROLOGY Myer, P. A., Mannalithara, A., Singh, G., Ladabaum, U. 2012; 143 (5): 1227-1236

  Abstract

  Screening decreases colorectal cancer (CRC) incidence and mortality. Colonoscopy has become the most common CRC screening test in the United States, but the degree to which it protects against CRC of the proximal colon is unclear. We examined US trends in rates of resection for proximal vs distal CRC, which reflect CRC incidence, in the context of national CRC screening data, before and since Medicare's 2001 decision to pay for screening colonoscopy.We used the Nationwide Inpatient Sample, the largest US all-payer inpatient database, to estimate age-adjusted rates of resection for distal and proximal CRC, from 1993 to 2009, in adults. Temporal trends were analyzed using Joinpoint regression analysis.The rate of resection for distal CRC decreased from 38.7 per 100,000 persons (95% confidence interval [CI], 35.4-42.0) to 23.2 per 100,000 persons (95% CI, 20.9-25.5) from 1993 to 2009, with annual decreases of 1.2% (95% CI, 0.1%-2.3%) from 1993 to 1999, followed by larger annual decreases of 3.8% (95% CI, 3.3%-4.3%) from 1999 to 2009 (P < .001). In contrast, the rate of resection for proximal CRC decreased from 30.0 per 100,000 persons (95% CI, 27.4-32.5) to 22.7 per 100,000 persons (95% CI, 20.6-24.7) from 1993 to 2009, but significant annual decreases of 3.1% (95% CI, 2.3%-4.0%) occurred only after 2002 (P < .001). Rates of resection for CRC decreased for adults ages 50 years and older, but increased for younger adults.These findings support the hypothesis that population-level decreases in rates of resection for distal CRC are associated with screening, in general, and that implementation of screening colonoscopy, specifically, might be an important factor that contributes to population-level decreases in rates of resection for proximal CRC.

  View details for DOI 10.1053/j.gastro.2012.07.107

  View details for Web of Science ID 000310459700035

  View details for PubMedID 22841786

• Lynch Syndrome in Patients With Colorectal Cancer Finding the Needle in the Haystack JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Ladabaum, U., Ford, J. M. 2012; 308 (15): 1581-1583

  View details for Web of Science ID 000309858100025

  View details for PubMedID 23073955

• Influence of Patient Preferences on the Cost-Effectiveness of Screening for Lynch Syndrome AMERICAN JOURNAL OF MANAGED CARE Wang, G., Kuppermann, M., Kim, B., Phillips, K. A., Ladabaum, U. 2012; 18 (5): E179-U2

  Abstract

  Patients and relatives have varying preferences for genetic testing and interventions related to hereditary cancer syndromes. We examined how the impact of these services on quality of life (QoL) affects the cost-effectiveness of screening for Lynch syndrome among probands newly diagnosed with colorectal cancer and their relatives.We constructed a state-transition model comparing screening strategies (clinical criteria, prediction algorithms, tumor testing, and upfront germline testing) with no screening to identify Lynch syndrome. The model incorporated individuals' health state utilities after screening, germline testing, and risk-reducing surgeries, with utilities persisting for 12 months in the base case. Outcomes consisted of quality-adjusted lifeyears (QALYs), costs, and cost per QALY gained. Sensitivity analyses assessed how the duration and magnitude of changes in QoL influenced results.Multiple screening strategies yielded gains in QALYs at acceptable costs compared with no screening. The preferred strategy-immunohistochemistry of tumors followed by BRAF mutation testing (IHC/BRAF)-cost $59,700 per QALY gained in the base case. The duration and magnitude of decreases in QoL after decisions related to germline testing and surgeries were key determinants of the cost-effectiveness of screening. IHC/BRAF cost >$100,000 per QALY gained when decrements to QoL persisted for 21 months.Screening for Lynch syndrome in the population is likely to yield long-term gains in life expectancy that outweigh any short-term decreases in QoL, at acceptable costs. Counseling for individuals should aim to mitigate potential negative impact of genetic testing and risk-reducing interventions on QoL.

  View details for Web of Science ID 000308443400008

  View details for PubMedID 22694112

• Influence of patient preferences on the cost-effectiveness of screening for lynch syndrome. Journal of oncology practice / American Society of Clinical Oncology Wang, G., Kuppermann, M., Kim, B., Phillips, K. A., Ladabaum, U. 2012; 8 (3): e24s-30s

  Abstract

  Patients and relatives have varying preferences for genetic testing and interventions related to hereditary cancer syndromes. We examined how the impact of these services on quality of life (QoL) affects the cost-effectiveness of screening for Lynch syndrome among probands newly diagnosed with colorectal cancer and their relatives.We constructed a state-transition model comparing screening strategies (clinical criteria, prediction algorithms, tumor testing, and upfront germline testing) with no screening to identify Lynch syndrome. The model incorporated individuals' health state utilities after screening, germline testing, and risk-reducing surgeries, with utilities persisting for 12 months in the base case. Outcomes consisted of quality-adjusted life-years (QALYs), costs, and cost per QALY gained. Sensitivity analyses assessed how the duration and magnitude of changes in QoL influenced results.Multiple screening strategies yielded gains in QALYs at acceptable costs compared with no screening. The preferred strategy-immunohistochemistry of tumors followed by BRAF mutation testing (IHC/BRAF)-cost $59,700 per QALY gained in the base case. The duration and magnitude of decreases in QoL after decisions related to germline testing and surgeries were key determinants of the cost-effectiveness of screening. IHC/BRAF cost > $100,000 per QALY gained when decrements to QoL persisted for 21 months.Screening for Lynch syndrome in the population is likely to yield long-term gains in life expectancy that outweigh any short-term decreases in QoL, at acceptable costs. Counseling for individuals should aim to mitigate potential negative impact of genetic testing and risk-reducing interventions on QoL.

  View details for DOI 10.1200/JOP.2011.000535

  View details for PubMedID 22942831

• Disparities in cancer screening in individuals with a family history of breast or colorectal cancer CANCER Ponce, N. A., Tsui, J., Knight, S. J., Afable-Munsuz, A., Ladabaum, U., Hiatt, R. A., Haas, J. S. 2012; 118 (6): 1656-1663

  Abstract

  Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. The authors evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population-based survey.By using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, screening was defined as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years.The authors found no significant BC screening disparities by race/ethnicity or income in the family history risk groups. Racial/ethnic disparities were more evident in CRC screening, and the Latino-white gap widened among individuals with family history risk. Among adults with a family history for CRC, the magnitude of the Latino-white difference in CRC screening (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.60) was more substantial than that for individuals with no family history (OR, 0.74; 95% CI, 0.59-0.92).Knowledge of their family history widened the Latino-white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their physicians about family history and cancer risk could reduce the substantial Latino-white screening disparity in Latinos most susceptible to CRC.

  View details for DOI 10.1002/cncr.26480

  View details for Web of Science ID 000300973000022

  View details for PubMedID 22009719

  View details for PubMedCentralID PMC3262934

• Preferences for Genetic Testing to Identify Hereditary Colorectal Cancer: Perspectives of High-Risk Patients, Community Members, and Clinicians JOURNAL OF CANCER EDUCATION Walsh, J., Arora, M., Hosenfeld, C., Ladabaum, U., Kuppermann, M., Knight, S. J. 2012; 27 (1): 112-119

  Abstract

  The aim of this study was to establish key characteristics that patients, consumers, and health professionals value regarding genetic testing (GT) and personalized medicine using the example of GT for hereditary Lynch syndrome. We conducted a series of focus groups with individuals recruited from a clinic that follows those at high risk for hereditary cancer, individuals recruited from the community, physicians, and genetic counselors. Participants were presented with clinical scenarios about Lynch syndrome testing and asked to identify characteristics that they perceived as important in making decisions about GT. Forty-two participants (19 community members, 8 high-risk and cancer patients, 3 genetic counselors, and 8 physicians) participated. Among community members and patients, the most frequently discussed considerations were the personal impact of GT and family impact, respectively. Among physicians, the most frequently discussed topic was the characteristics of genomic services (e.g., test invasiveness); among genetic counselors, the most frequently discussed topic was evidence and recommendations. A variety of test characteristics were important in decision making about GT. High-risk patients, community members, and health care providers had different priorities. Health care professionals should be aware of differences between their own considerations about GT and those that are important to patients.

  View details for DOI 10.1007/s13187-011-0286-z

  View details for Web of Science ID 000300490600019

  View details for PubMedID 22131063

• Cancer-Associated Aorto-Enteric Fistula DIGESTIVE DISEASES AND SCIENCES Singh, S., Ladabaum, U., Hovsepian, D. M., Triadafilopoulos, G. 2012; 57 (3): 625-629

  View details for DOI 10.1007/s10620-011-1945-y

  View details for Web of Science ID 000300578200005

  View details for PubMedID 22021052

• Diagnosis, Comorbidities, and Management of Irritable Bowel Syndrome in Patients in a Large Health Maintenance Organization CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Ladabaum, U., Boyd, E., Zhao, W. K., Mannalithara, A., Sharabidze, A., Singh, G., Chung, E., Levin, T. R. 2012; 10 (1): 37-45

  Abstract

  Irritable bowel syndrome (IBS) imposes significant clinical and economic burdens. We aimed to characterize practice patterns for patients with IBS in a large health maintenance organization, analyzing point of diagnosis, testing, comorbidities, and treatment.Members of Kaiser Permanente Northern California who were diagnosed with IBS were matched to controls by age, sex, and period of enrollment. We compared rates of testing, comorbidities, and interventions.From 1995-2005, IBS was diagnosed in 141,295 patients (mean age, 46 years; standard deviation, 17 years; 74% female). Internists made 68% of diagnoses, gastroenterologists 13%, and others 19%. Lower endoscopy did not usually precede IBS diagnosis. Patients with IBS were more likely than controls to have blood, stool, endoscopic, and radiologic tests and to undergo abdominal or pelvic operations (odds ratios, 1.5-10.7; all P < .0001). Only 2.7% were tested for celiac disease, and only 1.8% were eventually diagnosed with inflammatory bowel disease. Chronic pain syndromes, anxiety, and depression were more common among IBS patients than among controls (odds ratios, 2.7-4.6; all P < .0001). Many patients with IBS were treated with anxiolytics (61%) and antidepressants (55%). Endoscopic and radiologic testing was most strongly associated with having IBS diagnosed by a gastroenterologist. Psychotropic medication use was most strongly associated with female sex.In a large, managed care cohort, most diagnoses of IBS were made by generalists, often without endoscopic evaluation. Patients with IBS had consistently higher rates of testing, chronic pain syndromes, psychiatric comorbidity, and operations than controls. Most patients with IBS were treated with psychiatric medications.

  View details for DOI 10.1016/j.cgh.2011.08.015

  View details for Web of Science ID 000298812400015

  View details for PubMedID 21871250

  View details for PubMedCentralID PMC3242893

• Economic evaluation of targeted cancer interventions: Critical review and recommendations GENETICS IN MEDICINE Elkin, E. B., Marshall, D. A., Kulin, N. A., Ferrusi, I. L., Hassett, M. J., Ladabaum, U., Phillips, K. A. 2011; 13 (10): 853-860

  Abstract

  Scientific advances have improved our ability to target cancer interventions to individuals who will benefit most and spare the risks and costs to those who will derive little benefit or even be harmed. Several approaches are currently used for targeting interventions for cancer risk reduction, screening, and treatment, including risk prediction algorithms for identifying high-risk subgroups and diagnostic tests for tumor markers and germline genetic mutations. Economic evaluation can inform decisions about the use of targeted interventions, which may be more costly than traditional strategies. However, assessing the impact of a targeted intervention on costs and health outcomes requires explicit consideration of the method of targeting. In this study, we describe the importance of this principle by reviewing published cost-effectiveness analyses of targeted interventions in breast cancer. Few studies we identified explicitly evaluated the relationships among the method of targeting, the accuracy of the targeting test, and outcomes of the targeted intervention. Those that did found that characteristics of targeting tests had a substantial impact on outcomes. We posit that the method of targeting and the outcomes of a targeted intervention are inextricably linked and recommend that cost-effectiveness analyses of targeted interventions explicitly consider costs and outcomes of the method of targeting.

  View details for DOI 10.1097/GIM.0b013e31821f3e64

  View details for Web of Science ID 000295884200001

  View details for PubMedID 21637102

• Strategies to Identify the Lynch Syndrome Among Patients With Colorectal Cancer A Cost-Effectiveness Analysis ANNALS OF INTERNAL MEDICINE Ladabaum, U., Wang, G., Terdiman, J., Blanco, A., Kuppermann, M., Boland, C. R., Ford, J., Elkin, E., Phillips, K. A. 2011; 155 (2): 69-U50

  Abstract

  Testing has been advocated for all persons with newly diagnosed colorectal cancer to identify families with the Lynch syndrome, an autosomal dominant cancer-predisposition syndrome that is a paradigm for personalized medicine.To estimate the effectiveness and cost-effectiveness of strategies to identify the Lynch syndrome, with attention to sex, age at screening, and differential effects for probands and relatives.Markov model that incorporated risk for colorectal, endometrial, and ovarian cancers.Published literature.All persons with newly diagnosed colorectal cancer and their relatives.Lifetime.Third-party payer.Strategies based on clinical criteria, prediction algorithms, tumor testing, or up-front germline mutation testing, followed by tailored screening and risk-reducing surgery.Life-years, cancer cases and deaths, costs, and incremental cost-effectiveness ratios.The benefit of all strategies accrued primarily to relatives with a mutation associated with the Lynch syndrome, particularly women, whose life expectancy could increase by approximately 4 years with hysterectomy and salpingo-oophorectomy and adherence to colorectal cancer screening recommendations. At current rates of germline testing, screening, and prophylactic surgery, the strategies reduced deaths from colorectal cancer by 7% to 42% and deaths from endometrial and ovarian cancer by 1% to 6%. Among tumor-testing strategies, immunohistochemistry followed by BRAF mutation testing was preferred, with an incremental cost-effectiveness ratio of $36,200 per life-year gained.The number of relatives tested per proband was a critical determinant of both effectiveness and cost-effectiveness, with testing of 3 to 4 relatives required for most strategies to meet a threshold of $50,000 per life-year gained. Immunohistochemistry followed by BRAF mutation testing was preferred in 59% of iterations in probabilistic sensitivity analysis at a threshold of $100,000 per life-year gained. Screening for the Lynch syndrome with immunohistochemistry followed by BRAF mutation testing only up to age 70 years cost $44,000 per incremental life-year gained compared with screening only up to age 60 years, and screening without an upper age limit cost $88,700 per incremental life-year gained compared with screening only up to age 70 years.Other types of cancer, uncertain family pedigrees, and genetic variants of unknown significance were not considered.Widespread colorectal tumor testing to identify families with the Lynch syndrome could yield substantial benefits at acceptable costs, particularly for women with a mutation associated with the Lynch syndrome who begin regular screening and have risk-reducing surgery. The cost-effectiveness of such testing depends on the participation rate among relatives at risk for the Lynch syndrome.National Institutes of Health.

  View details for DOI 10.1059/0003-4819-155-2-201107190-00002

  View details for PubMedID 21768580

• The American Society for Gastrointestinal Endoscopy PIVI (Preservation and Incorporation of Valuable Endoscopic Innovations) on real-time endoscopic assessment of the histology of diminutive colorectal polyps GASTROINTESTINAL ENDOSCOPY Rex, D. K., Kahi, C., O'Brien, M., Levin, T. R., Pohl, H., Rastogi, A., Burgart, L., Imperiale, T., Ladabaum, U., Cohen, J., Lieberman, D. A. 2011; 73 (3): 419-422

  Abstract

  The PIVI (Preservation and Incorporation of Valuable endoscopic Innovations) initiative is an ASGE program whose objectives are to identify important clinical questions related to endoscopy and to establish a priori diagnostic and/or therapeutic thresholds for endoscopic technologies designed to resolve these clinical questions. Additionally, PIVIs may also outline the data and or the research study design required for proving an established threshold is met. Once endoscopic technologies meet an established PIVI threshold, those technologies are appropriate to incorporate into clinical practice presuming the appropriate training in that endoscopic technology has been achieved. The ASGE encourages and supports the appropriate use of technologies that meet its established PIVI thresholds. The PIVI initiative was developed primarily to direct endoscopic technology development toward resolving important clinical issues in endoscopy. The PIVI initiative is also designed to minimize the possibility that potentially valuable innovations are prematurely abandoned due to lack of utilization and to avoid widespread use of an endoscopic technology before clinical studies documenting their effectiveness have been performed. The following document, or PIVI, is one of a series of statements defining the diagnostic or therapeutic threshold that must be met for a technique or device to become considered appropriate for incorporation into clinical practice. It is also meant to serve as a guide for researchers or those seeking to develop technologies that are designed to improve digestive health outcomes. An ad hoc committee under the auspices of the existing ASGE Technology and Standards of Practice Committees Chairs develops PIVIs. An expert in the subject area chairs the PIVI, with additional committee members chosen for their individual expertise. In preparing this document, evidence-based methodology was employed, using a MEDLINE and PubMed literature search to identify pertinent clinical studies on the topic. PIVIs are ultimately submitted to the ASGE Governing Board for approval, as is done for all Technology and Standards of Practice documents. This document is provided solely for educational and informational purposes and to support incorporating these endoscopic technologies into clinical practice. It should not be construed as establishing a legal standard of care.

  View details for DOI 10.1016/j.gie.2011.01.023

  View details for Web of Science ID 000287903400001

  View details for PubMedID 21353837

• Cost-effectiveness of screening for recurrent hepatocellular carcinoma after liver transplantation CLINICAL TRANSPLANTATION Ladabaum, U., Cheng, S. L., Yao, F. Y., Roberts, J. P. 2011; 25 (2): 283-291

  Abstract

  The effectiveness of screening and treatment of recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT) remains undefined. Our aim was to evaluate the potential cost-effectiveness of screening for recurrent HCC after LT. We constructed a Markov model of the natural history after LT for HCC. We superimposed screening with computed tomography, alpha-fetoprotein, and chest X-ray every six months for 1-5 yr after LT, with resection for treatable recurrence. Screening only those whose explant pathology exceeded Milan Criteria (MC) for two yr cost $ 138,000/life-yr gained, and the incremental cost of screening all patients was $ 340,000/life-yr gained. Screening for longer than two yr incurred progressively higher incremental costs/life-yr gained. The most critical variable in sensitivity analyses was the survival benefit of finding a resectable recurrence. With the most favorable assumptions for a two-yr screening duration, screening those whose explant pathology exceeded MC cost $ 91,000/life-yr gained. In conclusion, screening for HCC recurrence after LT would probably yield most of its benefit in the first two yr, but at a relatively high cost/life-yr gained. Screening for two yr in only those whose explant pathology exceeds MC may be relatively cost-effective depending on the survival benefit of resection.

  View details for DOI 10.1111/j.1399-0012.2010.01212.x

  View details for Web of Science ID 000289153400030

  View details for PubMedID 20156221

• Cost-Effectiveness of Colorectal Cancer Screening in High-Risk Spanish Patients: Use of a Validated Model to Inform Public Policy CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Ladabaum, U., Ferrandez, A., Lanas, A. 2010; 19 (11): 2765-2776

  Abstract

  The European Community has made a commitment to colorectal cancer (CRC) screening, but regional considerations may affect the design of national screening programs. We developed a decision analytic model tailored to a pilot screening program for high-risk persons in Spain with the aim of informing public policy decisions.We constructed a decision analytic Markov model based on our validated model of CRC screening that reflected CRC epidemiology and costs in persons with first-degree relatives with CRC in Aragón, Spain, and superimposed colonoscopy every 5 or 10 years from ages 40 to 80 years. The pilot program's preliminary clinical results and our modeling results were presented to regional health authorities.In the model, without screening, 88 CRC cases occurred per 1,000 persons from age 40 to 85 years. In the base case, screening reduced this by 72% to 77% and gained 0.12 discounted life years per person. Screening every 10 years was cost saving, and screening every 5 years versus every 10 years cost 7,250 euros per life year gained. Based on these savings, 36 to 39 euros per person per year could go toward operating costs while maintaining a neutral budget. If screening costs doubled, screening remained highly cost-effective but no longer cost saving. These results contributed to the health authorities' decision to expand the pilot program to the entire region in 2009.Colonoscopic screening of first-degree relatives of persons with CRC may be cost saving in public systems like that of Spain. Decision analytic modeling tailored to regional considerations can inform public policy decisions.Tailored decision analytic modeling can inform regional policy decisions on cancer screening.

  View details for DOI 10.1158/1055-9965.EPI-10-0530

  View details for Web of Science ID 000283991600009

  View details for PubMedID 20810603

  View details for PubMedCentralID PMC3159034

• Rate and yield of repeat upper endoscopy in patients with dyspepsia WORLD JOURNAL OF GASTROENTEROLOGY Ladabaum, U., Dinh, V. 2010; 16 (20): 2520-2525

  Abstract

  To determine the rate and yield of repeat esophagogastroduodenoscopy (EGD) for dyspepsia in clinical practice, whether second opinions drive its use, and whether it is performed at the expense of colorectal cancer screening.We performed a retrospective cohort study of all patients who underwent repeat EGD for dyspepsia from 1996 to 2006 at the University of California, San Francisco endoscopy service.Of 24,780 EGDs, 5460 (22%) were performed for dyspepsia in 4873 patients. Of these, 451 patients (9.3%) underwent repeat EGD for dyspepsia at a median 1.7 (interquartile range, 0.8-3.1) years after initial EGD. Significant findings possibly related to dyspepsia were more likely at initial (29%) vs repeat EGD (18%) [odds ratio (OR), 1.45; 95% confidence interval (CI): 1.20-1.75, P < 0.0001], and at repeat EGD if the initial EGD had reported such findings (26%) than if it had not (14%) (OR, 1.32; 95% CI: 1.08-1.62, P = 0.0015). The same endoscopist performed the repeat and initial EGD in 77% of cases. Of patients aged 50 years or older, 286/311 (92%) underwent lower endoscopy.Repeat EGD for dyspepsia occurred at a low but substantial rate, with lower yield than initial EGD. Optimizing endoscopy use remains a public health priority.

  View details for DOI 10.3748/wjg.v16.i20.2520

  View details for Web of Science ID 000278196800009

  View details for PubMedID 20503451

  View details for PubMedCentralID PMC2877181

• Citalopram Provides Little or No Benefit in Nondepressed Patients With Irritable Bowel Syndrome CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Ladabaum, U., Sharabidze, A., Levin, T. R., Zhao, W. K., Chung, E., Bacchetti, P., Jin, C., Grimes, B., Pepin, C. J. 2010; 8 (1): 42-48

  Abstract

  Data on the benefit of selective serotonin reuptake inhibitors (SSRIs) in irritable bowel syndrome (IBS) are conflicting. The longitudinal relationship between clinical symptoms and sensitivity to barostat-mediated rectal distension in IBS remains unclear. We assessed the benefit of citalopram and explored the relationships between symptoms, quality of life (QOL), and rectal sensitivity to barostat distension in non-depressed IBS patients.Patients from primary, secondary, and tertiary care settings were randomly assigned to receive citalopram (20 mg/day for 4 weeks, then 40 mg/day for 4 weeks) or placebo in a study with double-masking and concealed allocation. Symptoms were assessed weekly, and IBS-QOL and rectal sensation by barostat were assessed at the beginning and end of the study.Patients receiving citalopram did not achieve a higher rate of adequate relief of IBS symptoms than patients receiving placebo (12/27 [44%] vs 15/27 [56%]; P = .59), regardless of IBS subtype. The odds ratio for weekly response with citalopram vs placebo was 0.80 (95% confidence interval, 0.61-1.04). Improvements in specific symptom and IBS-QOL scores were not superior for citalopram. Changes in IBS-QOL score and pressure eliciting pain showed a modest correlation (r = 0.33; 95% confidence interval, 0.03-0.57), but changes in symptoms and IBS-QOL scores or rectal sensitivity were not correlated substantially.Citalopram was not superior to placebo in treating non-depressed IBS patients. Changes in symptoms were not substantially correlated with changes in rectal sensation assessed by barostat. Any benefit of citalopram in non-depressed IBS patients is likely to be modest at best.

  View details for DOI 10.1016/j.cgh.2009.09.008

  View details for Web of Science ID 000277420800012

  View details for PubMedID 19765674

• Esophageal verrucous carcinoma arising from hyperkeratotic plaques associated with human papilloma virus type 51 DISEASES OF THE ESOPHAGUS Tonna, J., Palefsky, J. M., Rabban, J., Campos, G. M., Theodore, P., Ladabaum, U. 2010; 23 (5): E17-E20

  Abstract

  Esophageal verrucous carcinoma is a rare variant of esophageal squamous cell carcinoma. We report a case of esophageal verrucous carcinoma associated with human papilloma virus (HPV) type 51. The patient had long-standing dysphagia and odynophagia, and white esophageal plaques showing hyperkeratosis on biopsy. At repeat endoscopy, the esophagus was covered with verrucous white plaques and areas of nodular mucosa with white fronds, with a distal 10-cm smooth mass protruding into the lumen. Biopsies demonstrated an atypical squamoproliferative lesion but no frank malignancy. HPV type 51 DNA was detected in endoscopic biopsy specimens by polymerase chain reaction. Because the size of the lesion favored an underlying verrucous carcinoma, our patient underwent minimally invasive esophagectomy with gastric pull-up and cervical anastomosis. The pathologic diagnosis was a well-differentiated esophageal verrucous carcinoma. One year after esophagectomy, the patient feels well and is free of disease. Although HPV DNA was not detected in the cancer tissue obtained at surgery, our case suggests an association between HPV type 51 and esophageal verrucous carcinoma. The clinical evolution in this case highlights the importance of endoscopic surveillance in patients with exuberant esophageal hyperkeratosis, and of definitive surgical resection when malignancy is suspected even if frank malignancy is not demonstrated on superficial biopsies.

  View details for DOI 10.1111/j.1442-2050.2010.01087.x

  View details for Web of Science ID 000280125700001

  View details for PubMedID 20626449

• Cost Effectiveness of Ulcerative Colitis Surveillance in the Setting of 5-Aminosalicylates AMERICAN JOURNAL OF GASTROENTEROLOGY Rubenstein, J. H., Waljee, A. K., Jeter, J. M., Velayos, F. S., Ladabaum, U., Higgins, P. D. 2009; 104 (9): 2222-2232

  Abstract

  Colorectal cancer (CRC) is a feared complication of chronic ulcerative colitis (UC). Annual endoscopic surveillance is recommended for the detection of early neoplasia. 5-Aminosalicylates (5-ASAs) may prevent some UC-associated CRC. Therefore, in patients prescribed 5-ASAs for maintenance of remission, annual surveillance might be overly burdensome and inefficient. We aimed to determine the ideal frequency of surveillance in patients with UC maintained on 5-ASAs.We performed systematic reviews of the literature, and created a Markov computer model simulating a cohort of 35-year-old men with chronic UC, followed until the age of 90 years. Twenty-two strategies were modeled: natural history (no 5-ASA or surveillance), surveillance without 5-ASA at intervals of 1-10 years, 5-ASA plus surveillance every 1-10 years, and 5-ASA alone. The primary outcome was the ideal interval of surveillance in the setting of 5-ASA maintenance, assuming a third-party payer was willing to pay $100,000 for each quality-adjusted life-year (QALY) gained.In the natural history strategy, the CRC incidence was 30%. Without 5-ASA, annual surveillance was the ideal strategy, preventing 89% of CRC and costing $69,100 per QALY gained compared with surveillance every 2 years. 5-ASA alone prevented 49% of CRC. In the setting of 5-ASA, surveillance every 3 years was ideal, preventing 87% of CRC. 5-ASA with surveillance every 2 years cost an additional $147,500 per QALY gained, and 5-ASA with annual surveillance cost nearly $1 million additional per QALY gained compared with every 2 years. In Monte Carlo simulations, surveillance every 2 years or less often was ideal in 95% of simulations.If 5-ASA is efficacious chemoprevention for UC-associated CRC, endoscopic surveillance might be safely performed every 2 years or less often. Such practice could decrease burdens to patients and on endoscopic resources with a minimal decrease in quality-adjusted length of life, because 5-ASA with annual surveillance may cost nearly $1 million per additional QALY gained.

  View details for DOI 10.1038/ajg.2009.264

  View details for Web of Science ID 000270024800016

  View details for PubMedID 19491824

• Melanosis coli. Clinical gastroenterology and hepatology Li, D., Browne, L. W., Ladabaum, U. 2009; 7 (9): A20-?

  View details for DOI 10.1016/j.cgh.2008.11.030

  View details for PubMedID 19264571

• Addressing the Challenges of the Clinical Application of Pharmacogenetic Testing CLINICAL PHARMACOLOGY & THERAPEUTICS Ikediobi, O. N., Shin, J., Nussbaum, R. L., Phillips, K. A. 2009; 86 (1): 28-31

  Abstract

  Pharmacogenomics aims to use molecular genetic markers to predict treatment outcome. Indeed, within the past decade there has been a rapid emergence of pharmacogenetic tests to aid clinicians in predicting efficacy or toxicity for some drugs. Despite this major advance in therapeutic drug management, there remain challenges to the appropriate use of pharmacogenetic tests. We discuss UGT1A1 pharmacogenetic testing to illustrate the knowledge gaps impeding widespread use of pharmacogenetic tests in the clinical setting.

  View details for DOI 10.1038/clpt.2009.30

  View details for Web of Science ID 000267225200008

  View details for PubMedID 19536122

• Can calcium chemoprevention of adenoma recurrence substitute or serve as an adjunct for colonoscopic surveillance? INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE Shaukat, A., Parekh, M., Lipscomb, J., Ladabaum, U. 2009; 25 (2): 222-231

  Abstract

  The aim of this study was to examine the potential cost-effectiveness of calcium chemoprevention post-polypectomy as a substitute or adjunct for surveillance.We constructed a Markov model of post-polypectomy adenoma recurrence and colorectal cancer (CRC) development, calibrated to data from prospective chemoprevention trials of fiber, calcium, antioxidants, and aspirin. We modeled four scenarios for 50-year-old patients immediately after polypectomy: (i) natural history with no further intervention; (ii) elemental calcium 1,200 mg/day from age 50-80; (iii) surveillance colonoscopy from age 50-80 every 5 years, or 3 years for large adenoma; (iv) calcium + surveillance. Patients were followed up until age 100 or death.Calcium was cost-effective compared to natural history ($49,900/life-year gained). However, surveillance was significantly more effective than calcium (18.729 versus 18.654 life-years/patient; 76 percent versus 14 percent reduction in CRC incidence) at an incremental cost of $15,900/life-year gained. Calcium + surveillance yielded a very small benefit (0.0003 incremental life-years/patient) compared with surveillance alone, at a substantial incremental cost of $3,090,000/life-year gained.Post-polypectomy calcium chemoprevention is unlikely to be a reasonable substitute for surveillance. It may be cost-effective in patients unwilling or unable to undergo surveillance.

  View details for DOI 10.1017/S026646230909028X

  View details for Web of Science ID 000265300600013

  View details for PubMedID 19331713

• Cost-Effectiveness of 5-Aminosalicylic Acid Therapy for Maintenance of Remission in Ulcerative Colitis AMERICAN JOURNAL OF GASTROENTEROLOGY Yen, E. F., Kane, S. V., Ladabaum, U. 2008; 103 (12): 3094-3105

  Abstract

  Oral 5-aminosalicylic acid (5-ASA, mesalamine) is effective in inducing and maintaining remission in ulcerative colitis (UC). The relative benefits and costs of maintenance 5-ASA therapy are uncertain. Our aims were to evaluate this strategy's potential cost-effectiveness.We constructed a Markov model to compare two strategies over 2 yr: (a) no maintenance 5-ASA, with 5-ASA 4.8 g/day given for flares, (b) maintenance 5-ASA 2.4 g/day, escalated and maintained at 4.8 g/day after the first flare. In both arms, the failure to induce remission led to other treatments, as needed: prednisone, parenteral corticosteroids, cyclosporine, 6-mercaptopurine, infliximab, and colectomy.Without maintenance 5-ASA, the mean flares per person were 1.92, and the mean cost per person was $3,402. With maintenance 5-ASA providing a relative risk of flare of 0.7 at 5-ASA cost of $198/month, flares per person decreased to 1.38 at a cost of $8,810/flare prevented. Maintenance 5-ASA increased discounted quality-adjusted life-years per person (QALYs per person) from 1.75 to 1.77 at a discounted cost of $224,000/QALY gained. The results were most sensitive to the flare risk reduction and cost of 5-ASA, the utilities of being in remission without or with 5-ASA, and the colectomy rates. At $15/month (the cost of sulfasalazine), maintenance 5-ASA cost $640/flare prevented and $16,300/QALY gained.Maintenance 5-ASA therapy decreases UC flares, but its cost may be substantial, depending on society's willingness to pay. If sulfasalazine can be tolerated and yields comparable benefits, sulfasalazine maintenance therapy is likely to be cost-effective. The cost per QALY gained by 5-ASA maintenance is highly dependent on the quality of life while taking versus not taking maintenance 5-ASA, highlighting the importance of patients' preferences.

  View details for DOI 10.1111/j.1572-0241.2008.02130.x

  View details for Web of Science ID 000261361200022

  View details for PubMedID 18775007

• Colonoscopic treatment of acute diverticular hemorrhage using endoclips DIGESTIVE DISEASES AND SCIENCES Yen, E. F., Ladabaum, U., Muthusamy, V. R., Cello, J. P., Mcquaid, K. R., Shah, J. N. 2008; 53 (9): 2480-2485

  Abstract

  Although colonoscopy is used in the diagnostic evaluation of patients with diverticular hemorrhage, data on colonoscopic treatment outcomes are limited. We reviewed records of inpatients undergoing colonoscopy to identify patients that were colonoscopically diagnosed and treated for acute diverticular hemorrhage. Eleven patients with acute diverticular hemorrhage had active bleeding (n = 7) or non-bleeding visible vessel (n = 4) at colonoscopy. Endoclip treatment (preceded by epinephrine injection in 64%) achieved hemostasis in all patients without procedural complications. Patients were discharged within three days without evidence of early rebleeding. During a median follow-up of 15 months, late recurrent bleeding occurred in two patients (18.2%). Colonoscopic treatment of patients with acute diverticular hemorrhage using endoclips appears to be effective and safe, with high rates of immediate and long-term success. Colonoscopy should be considered in patients with suspected acute diverticular hemorrhage, as it may enable definitive therapy without the need for more invasive treatment.

  View details for DOI 10.1007/s10620-007-0151-4

  View details for Web of Science ID 000258601800026

  View details for PubMedID 18157637

• As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia ALIMENTARY PHARMACOLOGY & THERAPEUTICS Parekh, M., Fendrick, A. M., Ladabaum, U. 2008; 27 (8): 697-712

  Abstract

  Colorectal cancer screening and treatment are rapidly evolving. Aims To reappraise stool-based colorectal cancer screening in light of changing test performance characteristics, lower test cost and increasing colorectal cancer care costs.Using a Markov model, we compared faecal DNA testing every 3 years, annual faecal occult blood testing or immunochemical testing, and colonoscopy every 10 years.In the base case, faecal occult blood testing and faecal immunochemical testing gained life-years/person and cost less than no screening. Faecal DNA testing version 1.1 at $300 (the current PreGen Plus test) gained 5323 life-years/100 000 persons at $16 900/life-year gained and faecal DNA testing version 2 (enhanced test) gained 5795 life-years/100 000 persons at $15 700/life-year gained vs. no screening. In the base case and most sensitivity analyses, faecal occult blood testing and faecal immunochemical testing were preferred to faecal DNA testing. Faecal DNA testing version 2 cost $100 000/life-year gained vs. faecal immunochemical testing when per-cycle adherence with faecal immunochemical testing was 22%. Faecal immunochemical testing with excellent adherence was superior to colonoscopy every 10 years.As novel biological therapies increase colorectal cancer treatment costs, faecal occult blood testing and faecal immunochemical testing could become cost-saving. The cost-effectiveness of faecal DNA testing compared with no screening has improved, but faecal occult blood testing and faecal immunochemical testing are preferred to faecal DNA testing when patient adherence is high. Faecal immunochemical testing may be comparable to colonoscopy every 10 years in persons adhering to yearly testing.

  View details for DOI 10.1111/j.1365-2036.2008.03632.x

  View details for Web of Science ID 000254189000008

  View details for PubMedID 18248653

• When even people at high risk do not take up colorectal cancer screening GUT Ladabaum, U. 2007; 56 (12): 1648-1650

  View details for DOI 10.1136/gut.2007.125823

  View details for Web of Science ID 000250895100003

  View details for PubMedID 17998319

• Trends in colonoscopy for colorectal cancer screening MEDICAL CARE Phillips, K. A., Liang, S., Ladabaum, U., Haas, J., Kerlikowske, K., Lieberman, D., Hiatt, R., Nagamine, M., Van Bebber, S. L. 2007; 45 (2): 160-167

  Abstract

  A major health priority is to increase colorectal cancer screening, and colonoscopy has become an increasingly important method of screening. The Medicare program began coverage for colonoscopy for average risk individuals in 2001.We sought to examine whether overall colorectal cancer screening increased over time and whether these increases were a result of increased utilization of all methods or a result of greater use of colonoscopy but reduced use of other methods, whether the enactment of Medicare coverage was associated with an increase in colonoscopy among Medicare enrollees, and whether these trends equally affected subpopulations.We used nationally representative data from the 2000 and 2003 National Health Interview Surveys and analyzed data using used chi, difference-in-differences tests, and logistic regression analyses to examine whether screening rates differed between 2000 and 2003.The percentage of individuals being screened for colorectal cancer using any method increased modestly from 2000 to 2003 (3%), with increases a result of increased use of colonoscopy and a reduction in the use of other methods. Increases in colonoscopy use were significant among all populations except the insured, non-Medicare population with low incomes. Among Medicare enrollees with high/middle incomes, colonoscopy use increased 14% from 2000 to 2003 compared with an increase of only 7% among low-income groups, which was a significant difference (P < 0.01). Similarly, among insured, non-Medicare enrollees with high/middle incomes, colonoscopy use increased 11% from 2000 to 2003 compared with an increase of only 4% among low-income groups, which also was a significant difference (P < 0.01).Colorectal cancer screening utilization increased modestly from 2000 to 2003, with the increases that primarily were the result of increased colonoscopy use. Increases in colonoscopy use, however, were primarily among high/middle income groups. Although Medicare coverage may have indirectly facilitated the increase in colonoscopy, we could not determine that coverage directly increased screening rates. Screening rates remain modest and lower income individuals continue to be screened less. Topics for future research include approaches to facilitating screening among low-income individuals and evaluating the impact of policy coverage decisions.

  View details for Web of Science ID 000244351600009

  View details for PubMedID 17224779

• Gastric fundic distension activates fronto-limbic structures but not primary somatosensory cortex: A functional magnetic resonance imaging study NEUROIMAGE Ladabaum, U., Roberts, T. P., McGonigle, D. J. 2007; 34 (2): 724-732

  Abstract

  The brain representation of visceral stimulation bears important similarities to that of somatic stimulation. However, the role of the primary (S1) and secondary (S2) somatosensory cortices in mediating gastric sensation is uncertain.Eighteen healthy, right-handed volunteers (age 32 years+/-6.5 years; 14 men) underwent dynamic assessment of the relationship between sensation and fundic barostat distending pressure and volume, and then brain functional magnetic resonance imaging (fMRI) during noxious fundic distension. Cytoarchitectonic probability maps were used to examine in detail the null hypothesis that fundic distension did not produce significant activation of S1 or S2.Distending volume explained 74% of the variance in gastric sensation, compared to 64% with distending pressure. Incorporating distending volume into the regressor function for our fMRI analyses, we found that noxious fundic distension activated a widespread network of brain regions, including the pontine brainstem, thalami, cerebellum, insular cortex bilaterally, anterior and posterior cingulate cortex, right frontal lobe, and inferior parietal lobules. In detailed analyses, we found no evidence of activation of S1, but did find activation in one region of S2.Our findings suggest that an extensive, predominantly fronto-limbic network of brain regions, including the insular cortex, mediates perception of noxious gastric fundic distension in healthy humans, without significant participation by the primary somatosensory cortex. This and other recent studies lay the groundwork for investigations comparing brain processing of visceral stimuli between healthy volunteers and patients with functional dyspepsia.

  View details for DOI 10.1016/j.neuroimage.2006.07.033

  View details for Web of Science ID 000242901100022

  View details for PubMedID 17110130

• Rates and predictors of colorectal cancer screening. Preventing chronic disease Liang, S., Phillips, K. A., Nagamine, M., Ladabaum, U., Haas, J. S. 2006; 3 (4): A117-?

  Abstract

  Despite widespread recommendations for colorectal cancer screening, the U.S. screening rate is low. The objectives of this study were to describe the rates and predictors of colorectal cancer screening use by examining groups in two categories--1) those who have ever been screened and 2) those with up-to-date screening--and to assess whether trends and predictors change over time.We analyzed data from the 2000 and 2003 National Health Interview Surveys about the use of fecal occult blood tests, sigmoidoscopies, and colonoscopies for adults aged 50 years and older and without a history of colorectal cancer (N = 11,574 in 2000 and N = 11,779 in 2003).Rates in the 2000 study population of those who have ever been screened for colorectal cancer (53%) had increased in the 2003 study population (55%) as had the rates in the 2003 study population of those with up-to-date colorectal screening (53%) compared with the rates in the 2000 study population (38%). Among those who were ever screened, 76% were up-to-date with screening in 2003, compared with 68% in 2000. There was increased use of colonoscopies but decreased use of fecal occult blood tests and sigmoidoscopies. Individuals were more likely to be up-to-date with screening if they had higher income, higher education, insurance coverage, a usual source of care, and a dental visit in the last year than if these predictors were not evident. Since 2000, these predictors of colorectal cancer screening use have remained stable.Although there has been relatively limited success in increasing overall screening, it is encouraging that most people in the group of those who have ever been screened are up-to-date with colorectal cancer screening. Predictors for colorectal screening were stable over time despite changes in screening policies and rates. Further research is needed to uncover barriers to colorectal cancer screening.

  View details for PubMedID 16978492

• A patient with high risk of gastrointestinal bleeding requiring nonsteroidal anti-inflammatory drugs CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Wilcox, C. M., Ladabaum, U. 2006; 4 (9): 1090-1093

  View details for DOI 10.1016/j.cgh.2006.06.017

  View details for Web of Science ID 000240651100006

  View details for PubMedID 16890026

• Consensus development conference on the use of nonsteroidal anti-inflammatory agents, including cyclooxygenase-2 enzyme inhibitors and aspirin CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Wilcox, C. M., Allison, J., Benzuly, K., Borum, M., Cryer, B., Grosser, T., Hunt, R., Ladabaum, U., Lanas, A., Paulus, H., Regueiro, C., Sandler, R. S., Simon, L. 2006; 4 (9): 1082-1089

  View details for DOI 10.1016/j.cgh.2006.04.010

  View details for Web of Science ID 000240651100005

  View details for PubMedID 16877048

• Colorectal cancer screening - Differential costs for younger versus older Americans AMERICAN JOURNAL OF PREVENTIVE MEDICINE Ladabaum, U., Phillips, K. A. 2006; 30 (5): 378-384

  Abstract

  Colorectal cancer (CRC) incidence rises with age, and most CRC arises from adenomatous polyps. It was therefore hypothesized that increased use of CRC screening and polypectomy in younger persons might yield CRC-related savings later in life for payers such as Medicare.Using a decision analytic Markov model, the impact of increased CRC screening uptake on healthcare payers for younger Americans versus payers for older Americans, such as Medicare, was projected.As screening uptake increased, CRC incidence and mortality decreased, and annual costs related to CRC care and testing increased for younger persons, but decreased for older persons. Compared with current screening uptake of 40%, screening 75% of the U.S. population aged 50 to 80 increased annual costs related to CRC care and testing from 3.6 billion US dollars to 5.0 billion US dollars for 50- to 64-year-olds, but decreased annual costs from 5.9 billion US dollars to 5.6 billion US dollars for those aged 65 years and older. Sensitivity analyses suggest that future costs for other diseases could offset CRC care savings in older Americans that are attributable to screening. However, even without net cost savings for any age group, screening remained relatively cost-effective.Investments in screening and polypectomy in younger persons may decrease CRC-related costs, including screening and surveillance, for healthcare payers for older Americans, including Medicare. While these savings could potentially be offset by future health costs for other diseases, screening would still be cost-effective. Widespread CRC screening beginning at age 50 must remain a national priority.

  View details for DOI 10.1016/j.amepre.2005.12.010

  View details for Web of Science ID 000237018000003

  View details for PubMedID 16627125

• American gastroenterological association technical review on the evaluation of dyspepsia GASTROENTEROLOGY Allison, J. A., Inadomi, J. M., Ladabaum, U., McQuaid, K., Metz, D. 2005; 129 (5): 1756-1780

  View details for DOI 10.1053/j.gastro.2005.09.020

  View details for Web of Science ID 000233296000038

  View details for PubMedID 16285971

• Projected national impact of colorectal cancer screening on clinical and economic outcomes and health services demand Digestive Disease Week Meeting/105th Annual Meeting of the American-Gastroenterological-Association Ladabaum, U., Song, K. W B SAUNDERS CO-ELSEVIER INC. 2005: 1151–62

  Abstract

  Colorectal cancer (CRC) screening is effective and cost-effective, but the potential national impact of widespread screening is uncertain. It is controversial whether screening colonoscopy can be offered widely and how emerging tests may impact health services demand. Our aim was to produce integrated, comprehensive estimates of the impact of widespread screening on national clinical and economic outcomes and health services demand.We used a Markov model and census data to estimate the national consequences of screening 75% of the US population with conventional and emerging strategies.Screening decreased CRC incidence by 17%-54% to as few as 66,000 cases per year and CRC mortality by 28%-60% to as few as 23,000 deaths per year. With no screening, total annual national CRC-related expenditures were 8.4 US billion dollars. With screening, expenditures for CRC care decreased by 1.5-4.4 US billion dollars but total expenditures increased to 9.2-15.4 US billion dollars. Screening colonoscopy every 10 years required 8.1 million colonoscopies per year including surveillance, with other strategies requiring 17%-58% as many colonoscopies. With improved screening uptake, total colonoscopy demand increased in general, even assuming substantial use of virtual colonoscopy.Despite savings in CRC care, widespread screening is unlikely to be cost saving and may increase national expenditures by 0.8-2.8 US billion dollars per year with conventional tests. The current national endoscopic capacity, as recently estimated, may be adequate to support widespread use of screening colonoscopy in the steady state. The impact of emerging tests on colonoscopy demand will depend on the extent to which they replace screening colonoscopy or increase screening uptake in the population.

  View details for DOI 10.1053/j.gastro.2005.07.059

  View details for Web of Science ID 000232586000005

  View details for PubMedID 16230069

• Sedation for gastrointestinal endoscopy: New practices, new economics AMERICAN JOURNAL OF GASTROENTEROLOGY Aisenberg, J., Brill, J. V., Ladabaum, U., Cohen, L. B. 2005; 100 (5): 996-1000

  View details for Web of Science ID 000228489900002

  View details for PubMedID 15842568

• Obstipation as a paraneoplastic presentation of small cell lung cancer: case report and literature review NEUROGASTROENTEROLOGY AND MOTILITY Jun, S., Dimyan, M., Jones, K. D., Ladabaum, U. 2005; 17 (1): 16-22

  Abstract

  Paraneoplastic symptoms caused by abnormal gastrointestinal motility may be the initial manifestation of small cell lung cancer (SCLC). We report a case of a 63-year-old woman who presented with progressive constipation culminating in obstipation, and associated symptoms of more widespread dysmotility. A paraneoplastic syndrome was suspected. The only abnormality on chest computed tomography was a minimally enlarged paratracheal lymph node. Positron emission tomography demonstrated increased activity in the lymph node. The antinuclear neuronal antibody titer was elevated. Bronchoscopy with transtracheal biopsy confirmed the diagnosis of SCLC. One year after diagnosis, the patient had progressive symptoms of intestinal obstruction, and ultimately feculent vomiting. On abdominal radiography, colonic sitz markers ingested a year earlier were in virtually the same positions as after ingestion. Palliative colectomy with ileostomy was performed. The myenteric plexus in the terminal ileum and colon showed infiltration by a mixture of B-cell and T-cell lymphocytes and plasma cells, and no gross neuronal abnormalities. We review the clinical and pathologic features, clinical course, and management of paraneoplastic pseudoobstruction.

  View details for DOI 10.1111/j.1365-2982.2004.00608.x

  View details for Web of Science ID 000226572700004

  View details for PubMedID 15670259

• Cost-effectiveness of hepatocellular carcinoma surveillance in patients with hepatitis C virus-related cirrhosis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Patel, D., Terrault, N. A., Yao, F. Y., Bass, N. M., Ladabaum, U. 2005; 3 (1): 75-84

  Abstract

  HCV-related cirrhosis is a leading risk factor for hepatocellular carcinoma (HCC). Surveillance might detect HCC at a treatable stage. We estimated the clinical and economic consequences of a common HCC surveillance strategy in patients with HCV-related cirrhosis in the context of alternative HCC treatment strategies.With a Markov model, we examined surveillance with serum alpha-fetoprotein and ultrasound every 6 months in patients with compensated HCV-related cirrhosis from age 45-70 years or death, and HCC treatment with resection, cadaveric liver transplantation (CLT), or living donor liver transplantation (LDLT).Compared to natural history in the base case, surveillance with resection, listing for CLT, or LDLT increased life expectancy by 0.49, 2.58, and 3.81 quality-adjusted life-years (QALYs), respectively, all at costs less than 51,000 US dollars/QALY gained. The consequences of surveillance were most sensitive to the outcomes and costs of HCC treatments but not surveillance test performance characteristics or cost. Prioritizing CLT for patients with HCC over those with decompensated cirrhosis resulted in greater overall life expectancy with minimal increase in cost.Surveillance for HCC in patients with compensated HCV-related cirrhosis might gain QALYs at acceptable costs. The impact of surveillance depends most on the outcomes and costs of HCC treatments, rather than surveillance test characteristics. By increasing organ availability for timely definitive treatment, LDLT might achieve the greatest gain in life expectancy at acceptable costs. Prioritizing CLT for HCC might increase the population-wide benefits of CLT.

  View details for DOI 10.1053/S1542-3565(04)00443-4

  View details for Web of Science ID 000233980000012

  View details for PubMedID 15645408

• Colorectal Neoplasia Screening With Virtual Colonoscopy: When, at What Cost, and With What National Impact? CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Ladabaum, U., Song, K., Fendrick, A. M. 2004; 2 (7): 554-563

  Abstract

  When optimized, virtual colonoscopy may be highly sensitive for colorectal neoplasia. We evaluated the effectiveness and cost-effectiveness of virtual colonoscopy screening (VC) vs. colonoscopy screening (COLO) and the potential impact at the national level.Using a Markov model, we estimated the clinical and economic consequences of VC and COLO from ages 50 to 80 years. Using census data, we made projections to the national level.In the best case considered (95%, 94%, and 87% sensitivity for colorectal cancer [CRC], polyps > or =10 mm, and polyps <10 mm), VC was nearly as effective as COLO. However, if test costs were equal, total cost per person was 15% greater for VC than COLO, making COLO dominant. When test cost for VC was < or =60% of test cost for COLO, the small benefit of COLO vs. VC cost >200,000 US dollars/incremental life-year. The greater the likelihood of being referred for colonoscopy after VC, the greater the advantage of COLO. With 75% screening adherence in the United States, VC and COLO could decrease CRC incidence by 46%-54%, with COLO requiring 6.9 million colonoscopies/yr, and VC, 3.2 million colonoscopies/yr, plus 5.4 million virtual colonoscopies/yr with VC.Even if screening test sensitivities were similar, COLO is likely to be preferred over VC unless virtual colonoscopy costs significantly less than colonoscopy. VC may be most appropriate in persons unlikely to need colonoscopy, such as those at low CRC risk. If VC were substituted for COLO, the demand on resources would shift from endoscopic to radiologic services, but would not diminish.

  View details for DOI 10.1053/S1542-3565(04)00247-2

  View details for Web of Science ID 000208071900006

  View details for PubMedID 15224279

• Serological testing for coeliac disease in patients with symptoms of irritable bowel syndrome: a cost-effectiveness analysis ALIMENTARY PHARMACOLOGY & THERAPEUTICS Mein, S. M., Ladabaum, U. 2004; 19 (11): 1199-1210

  Abstract

  Patients diagnosed with irritable bowel syndrome may have coeliac disease.To evaluate the cost-effectiveness of coeliac disease testing in suspected irritable bowel syndrome.We used decision analysis to estimate the number of coeliac disease cases detected, quality-adjusted life-years gained, and costs resulting from testing suspected irritable bowel syndrome patients for tissue transglutaminase antibody or an antibody panel (tissue transglutaminase, gliadin, total immunoglobulin A). Positive tests prompted endoscopic biopsy. A gluten-free diet improved quality of life in coeliac disease.Assuming a coeliac disease prevalence of 3%, tissue transglutaminase detected 28 and the panel detected 29 of 30 coeliac disease cases among 1000 suspected irritable bowel syndrome patients. The cost/case detected was $4600 with tissue transglutaminase and $8800 with the panel. The cost/quality-adjusted life-year gained with tissue transglutaminase was $7400, and the incremental cost/quality-adjusted life-year gained for the panel vs. tissue transglutaminase was $287 000. Tissue transglutaminase cost under $100 000/quality-adjusted life-year gained at a coeliac disease prevalence >/=1.1%, assuming a modest utility gain of 0.005 with coeliac disease diagnosis.Testing for coeliac disease in patients with suspected irritable bowel syndrome is likely to be cost-effective even at a relatively low coeliac disease prevalence and with small improvements in quality of life with a gluten-free diet.

  View details for DOI 10.1111/j.1365-2036.2004.01958.x

  View details for Web of Science ID 000221532600008

  View details for PubMedID 15153173

• Fecal DNA testing compared with conventional colorectal cancer screening methods: A decision analysis Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy/Digestive Disease Week 2003 Song, K., Fendrick, A. M., Ladabaum, U. W B SAUNDERS CO-ELSEVIER INC. 2004: 1270–79

  Abstract

  Fecal DNA testing is an emerging tool to detect colorectal cancer (CRC). Our aims were to estimate the clinical and economic consequences of fecal DNA testing vs. conventional CRC screening.Using a Markov model, we estimated CRC incidence, CRC mortality, and discounted cost/life-year gained for screening by fecal DNA testing (F-DNA), fecal occult blood testing (FOBT) and/or sigmoidoscopy, or colonoscopy (COLO) in persons at average CRC risk from age 50 to 80 years.Compared with no screening, F-DNA at a screening interval of 5 years decreased CRC incidence by 35% and CRC mortality by 54% and gained 4560 life-years per 100,000 persons at USD $47,700/life-year gained in the base case. However, F-DNA gained fewer life-years and was more costly than conventional screening. The average number of colonoscopies per person was 3.8 with COLO and 0.8 with F-DNA. In most 1-way sensitivity analyses and Monte Carlo simulation iterations, F-DNA remained reasonably cost-effective compared with no screening, but COLO and FOBT dominated F-DNA. Assuming fecal DNA testing sensitivities of 65% for CRC and 40% for large polyp, and 95% specificity, a screening interval of 2 years and a test cost of USD $195 would be required to make F-DNA comparable with COLO.Fecal DNA testing every 5 years appears effective and cost-effective compared with no screening, but inferior to other strategies such as FOBT and COLO. Fecal DNA testing could decrease the national CRC burden if it could improve adherence with screening, particularly where the capacity to perform screening colonoscopy is limited.

  View details for DOI 10.1053/j.gastro.2004.02.016

  View details for Web of Science ID 000221217100008

  View details for PubMedID 15131787

• Potential cost-effectiveness of colorectal cancer chemoprevention with nonsteroidal anti-inflammatory drugs. Expert review of pharmacoeconomics & outcomes research Ladabaum, U. 2003; 3 (6): 757-771

  Abstract

  Colorectal cancer is the second leading cause of cancer-related death in the Western world. Screening for colorectal neoplasia, including the removal of adenomas, is highly effective and cost-effective in reducing colorectal cancer incidence and mortality. However, only a minority of the population is currently screened. Based on data from animal models, observational studies and randomized trials in humans, nonsteroidal anti-inflammatory drugs appear to have great promise as chemopreventive agents against colorectal cancer. The critical factors that will determine the roles of aspirin, other nonselective nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors in colorectal cancer chemoprevention include the magnitude of their protective effect, their risks, their costs, the treated population's characteristics, treatment adherence rates and how chemoprevention compares with established screening strategies.

  View details for DOI 10.1586/14737167.3.6.757

  View details for PubMedID 19807353

• Education does pay off: pneumococcal vaccine screening and administration in hospitalized adult patients with pneumonia. journal of the Louisiana State Medical Society Kruspe, R., Lillis, R., Daberkow, D. W., Blais, C. M., Wilbright, W., Gupta, S., Gould, C. A., Sun, T., Martinez, J. A., DeBoisblanc, B., Ladabaum, U., Sanders, C. V., Lopez, F. A. 2003; 155 (6): 325-331

  Abstract

  Streptococcus pneumoniae-associated infections are an important cause of hospitalization and mortality in high-risk and elderly patients. Even in the setting of appropriate therapy, the case fatality rate of invasive pneumococcal disease in the elderly may approach 40%. Since approximately 40,000 people die annually from pneumococcal-associated disease, it represents a substantial target for vaccine-preventable, bacterial fatalities. The 23-valent pneumococcal polysaccharide vaccine has proven consistently effective in preventing invasive pneumococcal disease. Despite its endorsement by numerous specialty societies, the pneumococcal vaccine is underutilized in the inpatient setting. In a recent report of quality indicators for Medicare beneficiaries, the percentage of Medicare beneficiaries in Louisiana admitted with pneumonia who were screened or received the pneumococcal vaccination prior to discharge was only 4%, the lowest percentage in the United States. The Louisiana State University-New Orleans Internal Medicine Department and its house staff embarked upon a retrospective study to determine its baseline pneumococcal vaccination or screening rates for all patients with pneumonia on its inpatient services at the The Medical Center of Louisiana in New Orleans from July 2000 through June 2001. From July 2001 through June 2002 an intensive educational intervention concentrating on the indications and benefits of pneumococcal vaccination was directed toward the Louisiana State University Internal Medicine house staff assigned to the inpatient service. Retrospective analysis for pneumococcal vaccine screening and administration of charts of all patients with pneumonia on the LSU Medicine service from July 2001 through June 2002 was performed in order to determine the effects of the intervention. Data from the pre-educational intervention period revealed a baseline pneumococcal vaccine screening or administration rate of 11% for all patients with pneumonia on the LSU Internal Medicine inpatient service. During the one-year intervention period, the pneumococcal vaccine screening or administration rate increased to 71%, a clinically and statistically significant increase (p-value < 0.0001). Data targeting patients 65 years of age and older revealed a baseline pneumococcal vaccine screening or administration rate of 10% for patients with pneumonia on the LSU Internal Medicine inpatient service which increased to 82% during the one year educational intervention (p-value < 0.0001). House officer scores (possible range 0-100) on a questionnaire assessing their understanding of the indications and benefits of pneumococcal vaccination were significantly higher after the educational intervention compared to before the intervention (means +/- standard deviations, 68 +/- 9 vs. 59 +/- 10, p < 0.0001). The findings from this study highlight the importance of education in increasing compliance with widely-accepted practice guidelines such as pneumococcal vaccine screening or administration in patients hospitalized with pneumonia.

  View details for PubMedID 14750752

• Potential effect of cyclooxygenase-2-specific inhibitors on the prevention of colorectal cancer: A cost-effectiveness analysis AMERICAN JOURNAL OF MEDICINE Ladabaum, U., Scheiman, J. A., Fendrick, A. M. 2003; 114 (7): 546-554

  Abstract

  To estimate the potential cost-effectiveness of colorectal cancer chemoprevention with cyclooxygenase-2-specific inhibitors (COX-2 inhibitors).Using a decision analytic Markov model, we estimated the discounted cost per life-year saved for three strategies: a COX-2 inhibitor alone; as an adjunct to colonoscopy every 10 years in persons at average risk of colorectal cancer; and as an adjunct to colonoscopy every 5 years in persons with first-degree relatives who had colorectal cancer.In the base case, the incremental cost per life-year saved with a COX-2 inhibitor alone compared with no screening was 233,300 dollars in persons at average risk of colorectal cancer and 56,700 dollars in persons with 2 first-degree relatives who had the disease. Chemoprevention was both less effective and more costly than screening. The incremental cost per life-year saved with a COX-2 inhibitor as an adjunct to screening was 823,800 dollars in persons at average risk and 404,700 dollars in persons with 2 first-degree relatives who had colorectal cancer. Combining a COX-2 inhibitor with less frequent screening was not as cost-effective as screening at currently recommended intervals. Cost-effectiveness estimates were highly sensitive to the cost of COX-2 inhibitors and their effect on the risk of cancer.Chemoprevention of colorectal cancer with COX-2 inhibitors is likely to incur substantially higher costs per life-year saved than are currently recommended screening strategies. COX-2 inhibitor use as an adjunct to screening may increase life expectancy, although at prohibitive costs, and is unlikely to result in less frequent screening.

  View details for DOI 10.1016/S0002-9343(03)00095-0

  View details for Web of Science ID 000182889900004

  View details for PubMedID 12753878

• Safety, efficacy and costs of pharmacotherapy for functional gastrointestinal disorders: the case of alosetron and its implications ALIMENTARY PHARMACOLOGY & THERAPEUTICS Ladabaum, U. 2003; 17 (8): 1021-1030

  Abstract

  Functional gastrointestinal disorders cause substantial morbidity, but not mortality. Alosetron may achieve 'adequate relief ' in diarrhoea-predominant irritable bowel syndrome, but may cause major complications, including death.To appraise, quantitatively, the trade-off between possible symptomatic improvement and serious complications in the treatment of functional gastrointestinal disorders.A decision analytical model was used to examine alosetron or standard treatment for 6 months in 45-year-old women with diarrhoea-predominant irritable bowel syndrome using the health care system's perspective.Assuming a 14% higher 'adequate relief' rate with alosetron compared to standard care, and a complication rate of four per 1000 persons in 6 months, alosetron gained 0.00081 quality-adjusted life-years (QALYs) per patient at a cost of 358,700 US dollars per QALY gained. Alosetron gained QALYs if 'adequate relief' increased the patients' utility by more than 0.01 in the base case. In probabilistic analysis, alosetron gained QALYs in 98.2% of iterations at a median cost of 212,600 US dollars per QALY (interquartile range, 138,000-338,900 US dollars per QALY). Results were highly sensitive to the utility gain with 'adequate relief' and alosetron's response and complication rates.Alosetron's benefit-to-risk profile appears to be favourable, but its cost per QALY gained may be substantial. Decision analyses on treatments for functional gastrointestinal disorders are likely to be highly sensitive to the utility estimates used. There is a pressing need for direct utility measurements in functional gastrointestinal disorders.

  View details for DOI 10.1046/j.0269-2813.2003.01545.x

  View details for Web of Science ID 000182119300006

  View details for PubMedID 12694084

• Helicobacter pylori test-and-treat intervention compared to usual care in primary care patients with suspected peptic ulcer disease in the United States AMERICAN JOURNAL OF GASTROENTEROLOGY Ladabaum, U., Fendrick, A. M., Glidden, D., Scheiman, J. M. 2002; 97 (12): 3007-3014

  Abstract

  [corrected] The Helicobacter pylori (H. pylori) "test-and-treat" strategy in uninvestigated dyspepsia is an effective alternative to prompt endoscopy. Our aims were to determine whether the combination of an educational session and availability of office-based H. pylori testing (test-and-treat intervention [TTI]) increases use of the test-and-treat strategy by primary care practitioners and whether it improves patient outcomes.We conducted a 1-yr prospective trial of patients with suspected peptic ulcer disease in six primary care centers, three with TTI and three designated as usual care controls (UCC).H. pylori testing was performed in 81% of 54 TTI patients and in 49% of 39 UCC patients (p = 0.004). TTI and UCC patients had similar gastroenterology referral rates (24% vs 33%, p = 0.33), endoscopy or upper GI radiography rates (30% vs 31%, p = 0.91), and primary care visits per patient (3.1 +/- 2.8 vs 3.1 +/- 2.6, p = 0.92). TTI patients were less likely than UCC patients to receive repeated antisecretory medication prescriptions (35% vs 66%, p = 0.003). Symptomatic status at 1 yr and satisfaction with medical care did not differ between groups. Median (and interquartile range) annualized disease-related expenditures per patient were $454 ($162-932) for TTI and $576 ($327-1,435) for UCC patients (p = 0.17).The combination of an educational session and availability of office-based H. pylori testing may increase acceptance of the test-and-treat strategy by primary care providers. It remains to be determined whether increased use of the test-and-treat strategy yields significant improvements in clinical and economic outcomes compared to usual care.

  View details for Web of Science ID 000179696000016

  View details for PubMedID 12492183

• The yield of lower endoscopy in patients with constipation: survey of a university hospital, a public county hospital, and a Veterans Administration medical center Annual Scientific Meeting of the American-College-of-Gastroenterology Pepin, C., Ladabaum, U. MOSBY-ELSEVIER. 2002: 325–32

  Abstract

  The role of endoscopy in the evaluation of constipation is controversial. The aim of this study was to clarify the yield of lower endoscopy in patients with constipation.Endoscopic databases from 3 diverse hospitals were searched for procedures with constipation as an indication. Detection of neoplasia was the main outcome of interest.Among 19,764 sigmoidoscopies or colonoscopies, constipation was a procedure indication for 563 patients (mean age 61 [16] years, 52% women); 58% had procedure indications in addition to constipation. Colorectal cancer was diagnosed in 8 (1.4%), adenomas in 82 (14.6%), and advanced lesions (cancer or adenoma with malignancy, high-grade dysplasia, villous features, or size > or = 10 mm) in 24 (4.3%). In the 358 patients who underwent colonoscopy, cancer was detected in 1.7%, adenomas in 19.6%, and advanced lesions in 5.9%. Two patients with cancer were less than 50 years of age. In as many as 6 patients with cancer, the tumor may have caused partial obstruction.The range of neoplasia in patients with constipation evaluated with lower endoscopy was comparable with what would be expected in asymptomatic subjects undergoing colorectal cancer screening. Although chronic constipation alone may not be an appropriate indication for lower endoscopy, age-appropriate colorectal cancer screening should be pursued when patients with constipation seek medical care.

  View details for DOI 10.1067/mge.2002.126882

  View details for Web of Science ID 000177775800001

  View details for PubMedID 12196767

• Effect of the selective serotonin reuptake inhibitor sertraline on gastric sensitivity and compliance in healthy humans NEUROGASTROENTEROLOGY AND MOTILITY Ladabaum, U., Glidden, D. 2002; 14 (4): 395-401

  Abstract

  Abstract Visceral hypersensitivity may contribute to symptoms in functional dyspepsia. Selective serotonin reuptake inhibitors (SSRIs) may be beneficial in functional gastrointestinal disorders. The aim of this study was to determine whether the SSRI sertraline affects gastric sensitivity and compliance in healthy humans. Ten healthy humans completed a 6-week randomized, double-blind, crossover trial of sertraline (50 mg day(-1)) vs. placebo. After each 2-week treatment, fullness, pain and nausea were rated at increasing gastric barostat distending pressures. Sensation thresholds above minimal distending pressure (MDP) were determined with a tracking method. Somatic sensory testing was performed by hand immersion in ice water. No differences were found between sertraline and placebo for symptoms as a function of distending pressure (fullness, P = 0.72; pain, P = 0.79; nausea, P = 0.41), gastric compliance (P = 0.15), median and interquartile range thresholds for first sensation [4.1 (3.5-5.7) vs. 6.2 (3.3-10.0) mmHg above MDP, P = 0.19] and pain [15.2 (8.3-21.0) vs. 15.3 (10.3-19.8) mmHg above MDP, P = 0.85], and median tolerance times for hand ice water immersion [27 (19-99) vs. 29 (20-180) s, P = 0.73]. In conclusion, sertraline had no effect on gastric sensitivity or compliance, or somatic pain tolerance in healthy humans. Studies are needed to assess the effects of SSRIs on visceral sensation and clinical symptoms in patients with functional dyspepsia.

  View details for Web of Science ID 000177851100009

  View details for PubMedID 12213107

• Reappraisal of non-invasive management strategies for uninvestigated dyspepsia: a cost-minimization analysis ALIMENTARY PHARMACOLOGY & THERAPEUTICS Ladabaum, U., Chey, W. D., Scheiman, J. M., Fendrick, A. M. 2002; 16 (8): 1491-1501

  Abstract

  The benefits of the Helicobacter pylori test-and-treat strategy are attributable largely to the cure of peptic ulcer disease while limiting the use of endoscopy.To reappraise the test-and-treat strategy and empirical proton pump inhibitor therapy for the management of uninvestigated dyspepsia in the light of the decreasing prevalence of H. pylori infection, peptic ulcer disease and peptic ulcer disease attributable to H. pylori.Using a decision analytical model, we estimated the cost per patient with uninvestigated dyspepsia managed with the test-and-treat strategy ($25/test; H.pylori treatment, $200) or proton pump inhibitor ($90/month). Endoscopy ($550) guided therapy for persistent or recurrent symptoms.In the base case (25%H. pylori prevalence, 20% likelihood of peptic ulcer disease, 75% of ulcers due to H.pylori), the cost per patient is $545 with the test-and-treat strategy and $529 with proton pump inhibitor, and both strategies yield similar clinical outcomes at 1 year. H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H.pylori are important determinants of the least costly strategy. At an H. pylori prevalence below 20%, proton pump inhibitor is consistently less costly than the test-and-treat strategy.As the H. pylori prevalence, the likelihood of peptic ulcer disease and the proportion of ulcers due to H. pylori decrease, empirical proton pump inhibitor becomes less costly than the test-and-treat strategy for the management of uninvestigated dyspepsia. Given the modest cost differential between the strategies, the test-and-treat strategy may be favoured if patients without peptic ulcer disease derive long-term benefit from H.pylori eradication.

  View details for Web of Science ID 000177505700011

  View details for PubMedID 12182749

• Positron emission tomography: the gastroenterologists's perspective GASTROINTESTINAL ENDOSCOPY Ladabaum, U. 2002; 55 (7): S64-S66

  View details for DOI 10.1067/mge.2002.124740

  View details for Web of Science ID 000176039300013

  View details for PubMedID 12024125

• Uninvestigated Dyspepsia. Current treatment options in gastroenterology Ladabaum, U., Chey, W. D. 2002; 5 (2): 125-131

  Abstract

  Dyspepsia, which is defined as pain or discomfort centered in the upper abdomen, is encountered frequently in primary care and subspecialty practice. Dyspepsia is a symptom complex caused by a heterogeneous group of disorders and diseases. A large fraction of patients with dyspepsia suffer from functional dyspepsia, in which no evidence of organic disease (typically on the basis of upper endoscopy) is found to explain persistent or recurrent symptoms. Initial management strategies for uninvestigated dyspepsia include empiric antisecretory therapy, the "test-and-treat" strategy for Helicobacter pylori, or prompt upper endoscopy. The cost-effectiveness of empiric therapy versus the test-and-treat strategy is dependent upon a number of variables including the prevalence of H. pylori infection, ulcer prevalence, and likelihood that an ulcer is due to H. pylori infection. As the prevalence of H. pylori infection falls and the likelihood of H. pylori negative ulcer increases, empiric antisecretory therapy will become more cost-effective. Upper endoscopy should be reserved for patients older than 45 to 50 years with symptom presentation and those with warning signs. Endoscopy also should be considered in those for whom empiric therapy or an attempt at the test-and-treat strategy fails. Common-sense dietary counseling can be helpful in patients with meal-related symptoms. Highly restrictive diets rarely improve symptoms and may be counterproductive if nutrition is compromised.

  View details for PubMedID 11879592

• Aspirin as an adjunct to screening for prevention of sporadic colorectal cancer - A cost-effectiveness analysis ANNALS OF INTERNAL MEDICINE Ladabaum, U., CHOPRA, C. L., Huang, G., Scheiman, J. M., Chernew, M. E., Fendrick, A. M. 2001; 135 (9): 769-781

  Abstract

  Aspirin may decrease colorectal cancer incidence, but its role as an adjunct to or substitute for screening has not been evaluated.To examine the potential cost-effectiveness of aspirin chemoprophylaxis in relation to screening.Markov model.Literature on colorectal cancer epidemiology, screening, costs, and aspirin chemoprevention (1980-1999).General U.S. population.50 to 80 years of age.Third-party payer.Aspirin therapy in patients screened with sigmoidoscopy every 5 years and fecal occult blood testing every year (FS/FOBT) or colonoscopy every 10 years (COLO).Discounted cost per life-year gained.When a 30% reduction in colorectal cancer risk was assumed, aspirin increased costs and decreased life-years because of related complications as an adjunct to FS/FOBT and cost $149 161 per life-year gained as an adjunct to COLO. In patients already taking aspirin, screening with FS/FOBT or COLO cost less than $31 000 per life-year gained.Cost-effectiveness estimates depended highly on the magnitude of colorectal cancer risk reduction with aspirin, aspirin-related complication rates, and the screening adherence rate in the population. However, when the model's inputs were varied over wide ranges, aspirin chemoprophylaxis remained generally non-cost-effective for patients who adhere to screening.In patients undergoing colorectal cancer screening, aspirin use should not be based on potential chemoprevention. Aspirin chemoprophylaxis alone cannot be considered a substitute for colorectal cancer screening. Public policy should focus on improving screening adherence, even in patients who are already taking aspirin.

  View details for Web of Science ID 000172013700002

  View details for PubMedID 11694102

• Outcomes of initial noninvasive Helicobacter pylori testing in US primary care patients with uninvestigated dyspepsia Digestive Diseases Week 99 Meeting Ladabaum, U., Fendrick, A. M., Scheiman, J. M. NATURE PUBLISHING GROUP. 2001: 2051–57

  Abstract

  Recent European trials demonstrate that testing and treatment for Helicobacter pylori (H. pylori) is an effective alternative to prompt endoscopy in uninvestigated dyspepsia. The eventual endoscopy rate after H. pylori testing, which is a key determinant of cost-effectiveness, is unknown in the United States. Our aim was to determine the endoscopy rate after H. pylori testing in primary care practice in the United States and to compare outcomes among seropositive and seronegative patients.We performed a retrospective review with mean 13 month follow-up of primary care patients with dyspeptic symptoms tested with office-based H. pylori serology.Of 268 adults tested (37+/-11 yr, 58% women), 57 (21%) were seropositive and 49/57 (86%) received eradication therapy. Endoscopy or contrast radiography was performed on 19% of seropositive and 19% of seronegative patients (p = 0.97). Annualized median disease-related expenditures were similar among seropositive and seronegative patients ($228 [$93-$654] vs $366 [$107-$1268], p = 0.19). However, aggregate expenditures were substantially lower than the cost of endoscopy alone ($816 [$296-$970]). On follow-up, seropositive and seronegative patients had similar numbers of primary care visits (2.9+/-3.2 vs 3.5+/-3.6, p = 0.23), prolonged antisecretory medication use (25 vs 33%, p = 0.27), and specialist referrals (23 vs 24%, p = 0.83).In a United States center, 81% of primary care patients tested for H. pylori did not undergo endoscopy, and patients incurred significantly lower median expenditures after noninvasive H. pylori testing than the cost of endoscopy alone. Seropositive and seronegative patients experienced comparable outcomes after H. pylori testing.

  View details for Web of Science ID 000169839600018

  View details for PubMedID 11467631

• Gastric distention correlates with activation of multiple cortical and subcortical regions GASTROENTEROLOGY Ladabaum, U., Minoshima, S., Hasler, W. L., Cross, D., Chey, W. D., Owyang, C. 2001; 120 (2): 369-376

  Abstract

  The pathophysiology of functional dyspepsia may involve abnormal processing of visceral stimuli at the level of the central nervous system. There is accumulating evidence that visceral and somatic pain processing in the brain share common neuronal substrates. However, the cerebral loci that process sensory information from the stomach are unknown. The aim of this study was to localize the human brain regions that are activated by gastric distention.Brain (15)O-water positron emission tomography was performed in 15 right-handed healthy volunteers during baseline and distal gastric distentions to 10 mm Hg, 20 mm Hg, threshold pain, and moderate pain. Pain, nausea, and bloating were rated during baseline and distentions (0-5 scale). Statistical subtraction analysis of brain images was performed between distentions and baseline.Symptoms increased with distending stimulus intensity (maximum pain, 2.1 +/- 0.4; nausea, 2.2 +/- 0.4; bloating, 3.7 +/- 0.2). Paralleling increases in distention stimulus and symptoms, progressive increases in activation (P < or = 0.05), were observed in the thalami, insula bilaterally, anterior cingulate cortex, caudate nuclei, brain stem periaqueductal gray matter, cerebellum, and occipital cortex.Symptomatic gastric distention activates structures implicated in somatic pain processing, supporting the notion of a common cerebral pain network.

  View details for Web of Science ID 000166705000009

  View details for PubMedID 11159877

• Effects of nutrients and serotonin 5-HT3 antagonism on symptoms evoked by distal gastric distension in humans AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Ladabaum, U., Brown, M. B., Pan, W. Q., Chung, O. Y., Hasler, W. L. 2001; 280 (2): G201-G208

  Abstract

  Distal gastric distension may contribute to meal-related dyspeptic symptoms. This study's aims were to determine the effects of distinct nutrient classes on symptoms induced by distal gastric distension and their dependence on 5-hydroxytryptamine(3) (5-HT3) receptors. Nine healthy subjects rated pain, nausea, and bloating induced by isobaric distal gastric distensions (6-24 mmHg) during duodenal lipid, carbohydrate, protein, or saline perfusion after treatment with placebo or the 5-HT3 receptor antagonist granisetron (10 microg/kg iv). Distensions produced greater pain, nausea, and bloating with lipid at 1.5 kcal/min compared with saline (P < or = 0.02), primarily because of greater distal gastric volumes at each distending pressure. In contrast, carbohydrate and protein had no significant effect. At 3 kcal/min, lipid increased symptoms through a volume-independent as well as a volume-dependent effect. Granisetron did not affect symptom perception or gastric pressure-volume relationships. In conclusion, isobaric distal gastric distension produces more intense symptoms during duodenal lipid compared with saline perfusion. Symptom perception during distal gastric distension is unaffected by 5-HT3 receptor antagonism.

  View details for Web of Science ID 000166346400005

  View details for PubMedID 11208541

• Pathobiology of visceral pain: Molecular mechanisms and therapeutic implications v. Central nervous system processing of somatic and visceral sensory signals AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Ladabaum, U., Minoshima, S., Owyang, C. 2000; 279 (1): G1-G6

  Abstract

  Somatic and visceral sensation, including pain perception, can be studied noninvasively in humans with functional brain imaging techniques. Positron emission tomography and functional magnetic resonance imaging have identified a series of cerebral regions involved in the processing of somatic pain, including the anterior cingulate, insular, prefrontal, inferior parietal, primary and secondary somatosensory, and primary motor and premotor cortices, the thalamus, hypothalamus, brain stem, and cerebellum. Experimental evidence supports possible specific roles for individual structures in processing the various dimensions of pain, such as encoding of affect in the anterior cingulate cortex. Visceral sensation has been examined in the setting of myocardial ischemia, distension of hollow viscera, and esophageal acidification. Although knowledge regarding somatic sensation is more extensive than the information available for visceral sensation, important similarities have emerged between cerebral representations of somatic and visceral pain.

  View details for Web of Science ID 000088144700001

  View details for PubMedID 10898740

• Images in clinical medicine. Barrett's esophagus with high-grade dysplasia. New England journal of medicine Ladabaum, U., Mcdonnell, W. M. 1999; 341 (19): 1439-?

  View details for PubMedID 10547407

• Barrett's esophagus with high-grade dysplasia NEW ENGLAND JOURNAL OF MEDICINE Ladabaum, U., Mcdonnell, W. M. 1999; 341 (19): 1439-1439

  View details for Web of Science ID 000083472100005

• Motility of the small intestine CURRENT OPINION IN GASTROENTEROLOGY Ladabaum, U., Hasler, W. L. 1999; 15 (2): 125-131

  Abstract

  Motility of the small intestine is controlled by myogenic, neural, and hormonal mechanisms and is modulated by external influences such as meals, central nervous system activation, and immune factors. Small-bowel dysmotility is recognized in a number of diseases, but its precise role in symptom generation remains unclear in many instances. We review publications that in the year under review added to the basic understanding of small-intestinal motility as well as its alteration in disease.

  View details for Web of Science ID 000080190500007

  View details for PubMedID 17023932

• Novel approaches to the treatment of nausea and vomiting DIGESTIVE DISEASES Ladabaum, U., Hasler, W. L. 1999; 17 (3): 125-132

  Abstract

  Nausea and vomiting are debilitating symptoms complicating many clinical conditions. Conventional antiemetic agents act as muscarinic, histamine, and dopamine receptor antagonists in the central nervous system. In a retrospective analysis, tricyclic antidepressant drugs demonstrated efficacy in long-term treatment of functional nausea. Some cases of vomiting result from impaired gastrointestinal motor activity. Agents which act on gastric serotonin (5-HT4), dopamine, and motilin receptors accelerate gastric emptying and relieve symptoms in gastroparesis. Recent investigations suggest that some patients with refractory gastroparesis may benefit from gastric electrical pacing. The treatment of acute chemotherapy-induced emesis was revolutionized by 5-HT3 receptor antagonists; however, these agents are less efficacious in delayed vomiting. Neurokinin (NK-1) receptor antagonists show promise in treating delayed chemotherapy-evoked emesis. Furthermore, animal studies indicate a broad spectrum of action for NK-1 antagonists in treating diverse causes of nausea and vomiting. The cyclic vomiting syndrome is characterized by discrete episodes of relentless vomiting separated by asymptomatic intervals and is associated with migraine headaches. Antimigraine therapies including the 5-HT1D receptor agonists sumatriptan reduce the severity of cyclic vomiting attacks. Investigations into these and other novel treatments may provide important advances in the care of difficult cases of nausea and vomiting resulting from disparate illnesses.

  View details for Web of Science ID 000084367500001

  View details for PubMedID 10697661

• Differential 5-HT3 mediation of human gastrocolonic response and colonic peristaltic reflex AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Bjornsson, E. S., Chey, W. D., Ladabaum, U., Woods, M. L., Hooper, F. G., Owyang, C., Hasler, W. L. 1998; 275 (3): G498-G505

  Abstract

  Colonic motor function is modulated by extended and local neural reflexes involving unknown mediators. To test the role of serotonin (5-HT3) pathways, increases in colonic tone during antral distension and duodenal lipid perfusion (gastrocolonic responses) and changes in orad and caudad colonic tone in response to local colonic distension (peristaltic reflex) were measured after double-blind granisetron (10 microg/kg) or placebo infusion in healthy human volunteers. Antral distension evoked increases in colonic tone, which were blunted by granisetron (P < 0.05) without effects on antral compliance. Intraduodenal lipid perfusion also evoked increased colonic tone, which was reduced by granisetron (P < 0.05). In contrast, orad colonic contractions and caudad relaxations and contractions during colonic distension were unaffected by granisetron. In conclusion, 5-HT3 receptor antagonism blunts both the mechano- and chemoreceptor components of the human gastrocolonic response without altering antral compliance. In contrast, 5-HT3 pathways play no role in the ascending or descending components of the colonic peristaltic reflex. These findings demonstrate different roles for 5-HT3 receptors in the control of colonic motor function by the proximal gastrointestinal tract and by local neural reflexes.

  View details for Web of Science ID 000075737700015

  View details for PubMedID 9724261

• Differential symptomatic and electrogastrographic effects of distal and proximal human gastric distension AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Ladabaum, U., Koshy, S. S., Woods, M. L., Hooper, F. G., Owyang, C., Hasler, W. L. 1998; 275 (3): G418-G424

  Abstract

  Nausea and gastric dysrhythmias occur in conditions associated with gastric distension. The roles of distal and proximal gastric mechanoreceptors in these responses are unexplored. Because antral distension induces vomiting in animals and antral and fundic vagal afferent discharges differ, we hypothesized that distal gastric distension in humans leads to greater symptomatic and dysrhythmic responses than proximal distension. Symptoms and electrogastrograms were recorded in healthy humans during distal and proximal gastric distension with a barostat. Distal but not proximal distension induced nausea and a 747 +/- 250% increase in dysrhythmic power (P < 0.05), responses not affected by granisetron, indomethacin, or atropine, agents that block dysrhythmias in other settings. In the distal stomach, bloating and pain developed at lower pressures (P < 0.05) not modified by granisetron, and compliance was significantly lower (P < 0.05). In conclusion, gastric mechanoreceptor activation in the less-compliant distal stomach produces nausea and dysrhythmias via non-5-hydroxytryptamine3 (5-HT3), non-prostaglandin-dependent, and noncholinergic pathways. Distal mechanoreceptor activation induces greater bloating and pain than proximal mechanoreceptor activation via 5-HT3-independent pathways.

  View details for Web of Science ID 000075737700006

  View details for PubMedID 9724252

• Potential population-wide impact of aspirin on colon cancer mortality GASTROENTEROLOGY Ladabaum, U., Sowers, M. 1998; 115 (2): 514-515

  View details for Web of Science ID 000075293400042

  View details for PubMedID 9758548