- Gastrointestinal cancer prevention and risk management
- Gastrointestinal cancer genetics
Medical Education:University of California at San Francisco School of Medicine (1991) CA
Residency:Stanford University Hospital -Clinical Excellence Research Center (1995) CA
Residency:Stanford University Hospital -Clinical Excellence Research Center (1994) CA
Internship:Stanford University Hospital -Clinical Excellence Research Center (1992) CA
A.B., University of California, Berkeley, Biochemistry (1987)
M.D., University of California, San Francisco, Medicine (1991)
M.S., University of Michigan, Ann Arbor, Clinical Research Design and Statistical Analysis (1999)
Residency, Stanford University Hospital - Internal Medicine, CA (1994)
Chief Residency, Stanford University Hospital - Internal Medicine, CA (1995)
Fellowship:University of Michigan Medical Center (1998) MI
Board Certification: Gastroenterology, American Board of Internal Medicine (1997)
Current Research and Scholarly Interests
Gastrointestinal cancer prevention and risk management. Risk stratification. Cost-effectiveness analysis. Health services research.
Postdoctoral Research Mentor
Adenoma miss rates associated with a 3-minute versus 6-minute colonoscopy withdrawal time: a prospective, randomized trial.
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
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
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
Comparative Effectiveness and Cost Effectiveness of a Multitarget Stool DNA Test to Screen for Colorectal Neoplasia.
2016; 151 (3): 427-439 e6
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
Predicting advanced neoplasia at colonoscopy in a diverse population with the National Cancer Institute colorectal cancer risk-assessment tool.
2016; 122 (17): 2663-2670
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.
2016; 122 (17): 2633-2645
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
Risks and Predictors of Gastric Adenocarcinoma in Patients with Gastric Intestinal Metaplasia and Dysplasia: A Population-Based Study.
American journal of gastroenterology
2016; 111 (8): 1104-1113
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
- Economic evidence on identifying clinically actionable findings with whole-genome sequencing: a scoping review GENETICS IN MEDICINE 2016; 18 (2): 111-116
- American Gastroenterological Association Technical Review on the Diagnosis and Management of Lynch Syndrome. Gastroenterology 2015; 149 (3): 783-813 e20
- Value of Genetic Testing for Hereditary Colorectal Cancer in a Probability-Based US Online Sample MEDICAL DECISION MAKING 2015; 35 (6): 734-744
- The reply. American journal of medicine 2015; 128 (5)
Cost-Effectiveness of Patient Navigation to Increase Adherence With Screening Colonoscopy Among Minority Individuals
2015; 121 (7): 1088-1097
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
- The reply. American journal of medicine 2014; 127 (12)
- Colorectal Cancer Mortality Among Hispanics in California: Differences by Neighborhood Socioeconomic Status and Nativity CANCER 2014; 120 (22): 3510-3518
Personalizing Colorectal Cancer Screening: A Systematic Review of Models to Predict Risk of Colorectal Neoplasia
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2014; 12 (10): 1624-U84
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
Colorectal testing utilization and payments in a large cohort of commercially insured US adults.
American journal of gastroenterology
2014; 109 (10): 1513-1525
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
2014; 13 (3): 381-389
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
2014; 127 (8): 717-727 e12
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
2014; 32 (19): 2001-2009
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 2014; 79 (6): 1031-1032
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
2014; 22 (5): 617-624
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
Colorectal Cancer Incidence in Asian Populations in California: Effect of Nativity and Neighborhood-Level Factors
AMERICAN JOURNAL OF GASTROENTEROLOGY
2014; 109 (4): 579-588
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 2014; 59 (2): 267-269
Optical biopsy of sessile serrated adenomas: do these lesions resemble hyperplastic polyps under narrow-band imaging?
2013; 78 (6): 902-909
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
Health Benefits and Cost-effectiveness of a Hybrid Screening Strategy for Colorectal Cancer
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2013; 11 (9): 1158-1166
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
Clinical and economic burden of emergency department visits due to gastrointestinal diseases in the United States.
American journal of gastroenterology
2013; 108 (9): 1496-1507
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
2013; 22 (9): 1567-1576
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
2013; 11 (9): 1093-1100
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
- Uptake of Genetic Testing by Relatives of Lynch Syndrome Probands: A Systematic Review CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2013; 11 (9): 1093-1100
Cost analysis of a patient navigation system to increase screening colonoscopy adherence among urban minorities
2013; 119 (3): 612-620
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
- An Uncommon Complication of Percutaneous Endoscopic Gastrostomy Tubes CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2013; 11 (2): XXV-XXV
Real-Time Optical Biopsy of Colon Polyps With Narrow Band Imaging in Community Practice Does Not Yet Meet Key Thresholds for Clinical Decisions
2013; 144 (1): 81-91
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
Preferences for outcomes associated with decisions to undergo or forgo genetic testing for Lynch syndrome
2013; 119 (1): 215-225
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
2013; 108 (1): 120-132
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 2013; 144 (1): 5-8
Proximal and Distal Colorectal Cancer Resection Rates in the United States Since Widespread Screening by Colonoscopy
2012; 143 (5): 1227-1236
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 2012; 308 (15): 1581-1583
Influence of Patient Preferences on the Cost-Effectiveness of Screening for Lynch Syndrome
AMERICAN JOURNAL OF MANAGED CARE
2012; 18 (5): E179-U2
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
2012; 8 (3): e24s-30s
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
2012; 118 (6): 1656-1663
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
Preferences for Genetic Testing to Identify Hereditary Colorectal Cancer: Perspectives of High-Risk Patients, Community Members, and Clinicians
JOURNAL OF CANCER EDUCATION
2012; 27 (1): 112-119
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 2012; 57 (3): 625-629
Diagnosis, Comorbidities, and Management of Irritable Bowel Syndrome in Patients in a Large Health Maintenance Organization
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2012; 10 (1): 37-45
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
Economic evaluation of targeted cancer interventions: Critical review and recommendations
GENETICS IN MEDICINE
2011; 13 (10): 853-860
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
2011; 155 (2): 69-U50
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 Web of Science ID 000292822000013
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
2011; 73 (3): 419-422
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
2011; 25 (2): 283-291
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
2010; 19 (11): 2765-2776
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
Rate and yield of repeat upper endoscopy in patients with dyspepsia
WORLD JOURNAL OF GASTROENTEROLOGY
2010; 16 (20): 2520-2525
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
Citalopram Provides Little or No Benefit in Nondepressed Patients With Irritable Bowel Syndrome
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
2010; 8 (1): 42-48
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
2010; 23 (5): E17-E20
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
2009; 104 (9): 2222-2232
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 2009; 7 (9): A20-?
Addressing the Challenges of the Clinical Application of Pharmacogenetic Testing
CLINICAL PHARMACOLOGY & THERAPEUTICS
2009; 86 (1): 28-31
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
2009; 25 (2): 222-231
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
2008; 103 (12): 3094-3105
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
2008; 53 (9): 2480-2485
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
2008; 27 (8): 697-712
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 2007; 56 (12): 1648-1650
Trends in colonoscopy for colorectal cancer screening
2007; 45 (2): 160-167
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
2007; 34 (2): 724-732
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
2006; 3 (4): A117-?
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 2006; 4 (9): 1090-1093
- Consensus development conference on the use of nonsteroidal anti-inflammatory agents, including cyclooxygenase-2 enzyme inhibitors and aspirin CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2006; 4 (9): 1082-1089
Colorectal cancer screening - Differential costs for younger versus older Americans
AMERICAN JOURNAL OF PREVENTIVE MEDICINE
2006; 30 (5): 378-384
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 2005; 129 (5): 1756-1780
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
W B SAUNDERS CO-ELSEVIER INC. 2005: 1151–62
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 2005; 100 (5): 996-1000
Obstipation as a paraneoplastic presentation of small cell lung cancer: case report and literature review
NEUROGASTROENTEROLOGY AND MOTILITY
2005; 17 (1): 16-22
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
2005; 3 (1): 75-84
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
2004; 2 (7): 554-563
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
2004; 19 (11): 1199-1210
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
W B SAUNDERS CO-ELSEVIER INC. 2004: 1270–79
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
2003; 3 (6): 757-771
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 10.1586/1473722.214.171.1247
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
2003; 155 (6): 325-331
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
2003; 114 (7): 546-554
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
2003; 17 (8): 1021-1030
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
2002; 97 (12): 3007-3014
[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
MOSBY-ELSEVIER. 2002: 325–32
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  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
2002; 14 (4): 395-401
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
2002; 16 (8): 1491-1501
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 2002; 55 (7): S64-S66
Current treatment options in gastroenterology
2002; 5 (2): 125-131
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
2001; 135 (9): 769-781
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
NATURE PUBLISHING GROUP. 2001: 2051–57
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
2001; 120 (2): 369-376
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
2001; 280 (2): G201-G208
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
2000; 279 (1): G1-G6
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
Barrett's esophagus with high-grade dysplasia
NEW ENGLAND JOURNAL OF MEDICINE
1999; 341 (19): 1439-1439
View details for Web of Science ID 000083472100005
Images in clinical medicine. Barrett's esophagus with high-grade dysplasia.
New England journal of medicine
1999; 341 (19): 1439-?
View details for PubMedID 10547407
Motility of the small intestine
CURRENT OPINION IN GASTROENTEROLOGY
1999; 15 (2): 125-131
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
1999; 17 (3): 125-132
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
1998; 275 (3): G498-G505
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
1998; 275 (3): G418-G424
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 1998; 115 (2): 514-515