Brian Lee

All Publications

• The Role of Clips in Preventing Delayed Bleeding After Colorectal Polyp Resection: An Individual Patient Data Meta-Analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Turan, A. S., Pohl, H., Matsumoto, M., Lee, B. S., Aizawa, M., Desideri, F., Albéniz, E., Raju, G. S., Luba, D., Barret, M., Gurudu, S. R., Ramirez, F. C., Lin, W. R., Atsma, F., Siersema, P. D., van Geenen, E. J. 2022; 20 (2): 362-371.e23

  Abstract

  Nonpedunculated colorectal polyps are normally endoscopically removed to prevent neoplastic progression. Delayed bleeding is the most common major adverse event. Clipping the resection defect has been suggested to reduce delayed bleedings. Our aim was to determine if prophylactic clipping reduces delayed bleedings and to analyze the contribution of polyp characteristics, extent of defect closure, and antithrombotic use.An individual patient data meta-analysis was performed. Studies on prophylactic clipping in nonpedunculated colorectal polyps were selected from PubMed, Embase, Web of Science, and Cochrane database (last selection, April 2020). Authors were invited to share original study data. The primary outcome was delayed bleeding ≤30 days. Multivariable mixed models were used to determine the efficacy of prophylactic clipping in various subgroups adjusted for confounders.Data of 5380 patients with 8948 resected polyps were included from 3 randomized controlled trials, 2 prospective, and 8 retrospective studies. Prophylactic clipping reduced delayed bleeding in proximal polyps ≥20 mm (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.44-0.88; number needed to treat = 32), especially with antithrombotics (OR, 0.59; 95% CI, 0.35-0.99; number needed to treat = 23; subgroup of anticoagulants/double platelet inhibitors: n = 226; OR, 0.40; 95% CI, 0.16-1.01; number needed to treat = 12). Prophylactic clipping did not benefit distal polyps ≥20 mm with antithrombotics (OR, 1.41; 95% CI, 0.79-2.52).Prophylactic clipping reduces delayed bleeding after resection of nonpedunculated, proximal colorectal polyps ≥20 mm, especially in patients using antithrombotics. No benefit was found for distal polyps. Based on this study, patients can be identified who may benefit from prophylactic clipping. (PROSPERO registration number CRD42020104317.).

  View details for DOI 10.1016/j.cgh.2021.05.012

  View details for PubMedID 33991691

• Long-term follow-up of branch-duct intraductal papillary mucinous neoplasms with No change in first 5 Years of diagnosis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Lee, B. S., Nguyen, A. K., Tekeste, T. F., Chang, K., Girgis, A., Adeyemo, M., Hanna, M. S., Yao, J. F., Kwok, K. K., Giap, A. Q., Hunt, G. C., Chaya, C. T., Kao, K. T., Attam, R., Ko, A., Pio, J. R., Tovar, S., Lim, B. S. 2021; 21 (1): 144-154

  Abstract

  Discontinuation of branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) surveillance after 5 years of no change remains controversial. Long-term outcomes of BD-IPMN without significant changes in the first 5 years were evaluated.We performed a multi-center retrospective analysis of patients with BD-IPMN diagnosis from 2005 to 2011 (follow-up until 2017). Significant changes were defined as pancreatic cancer (PC), pancreatectomy, high-risk stigmata (HRS), worrisome features (WF) and worrisome EUS features (WEUS).Of 982 patients who had no significant changes, 5 (0.5%), 7 (0.7%), 99 (10.1%), 4 (0.4%) patients developed PC, HRS, WF, WEUS, respectively, post-5 years. PC and HRS/WF/WEUS incidences at 12 years were 1.0% and 29.0%, respectively. Patients that developed HRS/WF/WEUS had larger cyst size in first 5 years compared to those that did not [16 (12-23) vs. 12 (9-17) mm, p = 0.0001], cyst size of >15 mm having higher cumulative incidence of HRS/WF/WEUS. PC mortality was 0.8%; all-cause mortality was 32%. Incidence of mortality due to PC was higher in HRS/WF/WEUS group, p < 0.0001. The mortality rate at 12 years for ACCI (age-adjusted Charlson Comorbidity Index) of ≤3, 4-6, and ≥7 were 3.5%, 19.9%, and 57.6% (p < 0.0001), respectively.Incidence of PC in patients with BD-IPMN without significant changes in first 5 years of diagnosis remains low at 1.0%. Incidence of HRS/WF/WEUS was higher at 29.0%. PC-related mortality was higher in HRS/WF/WEUS group. These risks should be weighed against patients' overall mortality (utilizing scoring systems such as ACCI) when making surveillance decision of BD-IPMN beyond 5 years.

  View details for DOI 10.1016/j.pan.2020.10.040

  View details for PubMedID 33309223

• The effect of prophylactic hemoclips on the risk of delayed post-endoscopic mucosal resection bleed for upper and lower gastrointestinal lesions: a retrospective cohort study. BMC gastroenterology Chang, K., Lee, B. S., Tekeste, T., Nguyen, A., Adeyemo, M., Girgis, A., Kwok, K. K., Crowson, H. M., Burris, A. O., Attam, R., Chaya, C. T., Durbin, T. E., Giap, A. Q., Hunt, G. C., Iskander, J., Kao, K. T., Lim, B. S. 2020; 20 (1): 60

  Abstract

  Endoscopic mucosal resection (EMR) is a minimally invasive procedure used for the treatment of lesions in the gastrointestinal (GI) tract. There is increased usage of hemoclips during EMR for the prevention of delayed bleeding. This study aimed to evaluate the effect of hemoclips in the prevention of delayed bleeding after EMR of upper and lower GI tract lesions.This is a retrospective cohort study using the Kaiser Permanente Southern California (KPSC) EMR registry. Lesions in upper and lower GI tracts that underwent EMR between January 2012 and December 2015 were analyzed. Rates of delayed bleeding were compared between the hemoclip and no-hemoclip groups. Analysis was stratified by upper GI and lower GI lesions. Lower GI group was further stratified by right and left colon. We examined the relationship between clip use and several clinically-relevant variables among the patients who exhibited delayed bleeding. Furthermore, we explored possible procedure-level and endoscopist-level characteristics that may be associated with clip usage.A total of 18 out of 657 lesions (2.7%) resulted in delayed bleeding: 7 (1.1%) in hemoclip group and 11 (1.7%) in no-hemoclip group (p = 0.204). There was no evidence that clip use moderated the effects of the lesion size (p = 0.954) or lesion location (p = 0.997) on the likelihood of delayed bleed. In the lower GI subgroup, clip application did not alter the effect of polyp location (right versus left colon) on the likelihood of delayed bleed (p = 0.951). Logistic regression analyses showed that the clip use did not modify the likelihood of delayed bleeding as related to the following variables: use of aspirin/NSAIDs/anti-coagulants/anti-platelets, pathologic diagnoses (including different types of colon polypoid lesions), ablation, piecemeal resection. The total number of clips used was 901 at a minimum additional cost of $173,893.Prophylactic hemoclip application did not reduce delayed post-EMR bleed for upper and lower GI lesions in this retrospective study performed in a large-scale community practice setting. Routine prophylactic hemoclip application during EMR may lead to significantly higher healthcare cost without a clear clinical benefit.

  View details for DOI 10.1186/s12876-020-01199-x

  View details for PubMedID 32143633

  View details for PubMedCentralID PMC7060595

• Autoimmune Hepatitis Associated With Turmeric Consumption. ACG case reports journal Lee, B. S., Bhatia, T., Chaya, C. T., Wen, R., Taira, M. T., Lim, B. S. 2020; 7 (3): e00320

  Abstract

  Turmeric is a popular herbal dietary supplement that has been considered safe and even shown to have hepatoprotective properties. In the recent times, however, there have been a few case reports of turmeric-induced liver injury. We report a 55-year-old woman with chronic turmeric consumption whose initial diagnosis was acute autoimmune hepatitis. She declined steroid treatment, and hence, we recommended discontinuing her long-term turmeric usage. A month after discontinuation, her liver function returned to normal. This case demonstrates the importance of recognizing the potential adverse effects of herbal dietary supplement.

  View details for DOI 10.14309/crj.0000000000000320

  View details for PubMedID 32337301

  View details for PubMedCentralID PMC7162126

• Acute pancreatitis due to pancreatic tail herniation above the left hemidiaphragm Journal of Case Reports and Images in Medicine Lee, B. S., Guharoy, V., Beydoun, A., Saffouri, G. B. 2020

  View details for DOI 10.5348/100056Z09BL2020CI

• Colonoscopy Leading to the Diagnosis of AL Amyloidosis in the Gastrointestinal Tract Mimicking an Acute Ulcerative Colitis Flare. ACG case reports journal Lee, B. S., Chudasama, Y., Chen, A. I., Lim, B. S., Taira, M. T. 2019; 6 (11): e00289

  Abstract

  The 2 most common types of amyloidosis are light chain (AL) and reactive (AA). AL is associated with plasma cell dyscrasias; reactive (AA) is associated with chronic inflammatory conditions. A few cases have described AL amyloidosis mimicking colitis. However, endoscopic findings leading to the diagnosis of AL amyloidosis are rare. We report a 77-year-old woman with a medical history of ulcerative colitis who presented with recurrent nonbloody watery diarrhea. Colonoscopy revealed features suspicious for amyloidosis. Bone marrow biopsy showed multiple myeloma and AL amyloidosis. This case demonstrates the importance of generating a broad differential and the pivotal role of endoscopic findings in diagnosing uncommon diseases.

  View details for DOI 10.14309/crj.0000000000000289

  View details for PubMedID 32309484

  View details for PubMedCentralID PMC7145203

• FOXD3 Regulates CSC Marker, DCLK1-S, and Invasive Potential: Prognostic Implications in Colon Cancer. Molecular cancer research : MCR Sarkar, S., O'Connell, M. R., Okugawa, Y., Lee, B. S., Toiyama, Y., Kusunoki, M., Daboval, R. D., Goel, A., Singh, P. 2017; 15 (12): 1678-1691

  Abstract

  The 5' (α)-promoter of the human doublecortin-like kinase 1 (DCLK1) gene becomes epigenetically silenced during colon carcinogenesis, resulting in loss of expression of the canonical long(L)-isoform1 (DCLK1-L) in human colon adenocarcinomas (hCRCs). Instead, hCRCs express a short(S)-isoform2 (DCLK1-S) from an alternate (β)-promoter of DCLK1. The current study, examined if the transcriptional activity of the (β)-promoter is suppressed in normal versus cancerous cells. On the basis of in silico and molecular approaches, it was discovered that FOXD3 potently inhibits the transcriptional activity of the (β)-promoter. FOXD3 becomes methylated in human colon cancer cells (hCCC), with loss of FOXD3 expression, allowing expression of the DCLK1(S) variant in hCCCs/hCRCs. Relative levels of FOXD3/DCLK1(S/L) were measured in a cohort of CRC patient specimens (n = 92), in relation to overall survival (OS). Patients expressing high DCLK1(S), with or without low FOXD3, had significantly worse OS compared with patients expressing low DCLK1(S). The relative levels of DCLK1-L did not correlate with OS. In a pilot retrospective study, colon adenomas from high-risk patients (who developed CRCs in <15 years) demonstrated significantly higher staining for DCLK1(S) + significantly lower staining for FOXD3, compared with adenomas from low-risk patients (who remained free of CRCs). Latter results strongly suggest a prognostic value of measuring DCLK1(S)/FOXD3 in adenomas. Overexpression of DCLK1(S), but not DCLK1(L), caused a significant increase in the invasive potential of hCCCs, which may explain worse outcomes for patients with high DCLK1-S-expressing tumors. On the basis of these data, FOXD3 is a potent repressor of DCLK1-S expression in normal cells; loss of FOXD3 in hCCCs/hCRCs allows upregulation of DCLK1-S, imparting a potent invasive potential to the cells. Mol Cancer Res; 15(12); 1678-91. ©2017 AACR.

  View details for DOI 10.1158/1541-7786.MCR-17-0287

  View details for PubMedID 28851816

  View details for PubMedCentralID PMC5748292

• A novel antibody against cancer stem cell biomarker, DCLK1-S, is potentially useful for assessing colon cancer risk after screening colonoscopy. Laboratory investigation; a journal of technical methods and pathology Sarkar, S., Popov, V. L., O'Connell, M. R., Stevenson, H. L., Lee, B. S., Obeid, R. A., Luthra, G. K., Singh, P. 2017; 97 (10): 1245-1261

  Abstract

  DCLK1 expression is critically required for maintaining growth of human colon cancer cells (hCCCs). Human colorectal tumors (CRCs) and hCCCs express a novel short isoform of DCLK1 (DCLK1-S; isoform 2) from β-promoter of hDCLK1 gene, while normal colons express long isoform (DCLK1-L; isoform 1) from 5'(α)-promoter, suggesting that DCLK1-S, and not DCLK1-L, marks cancer stem cells (CSCs). Even though DCLK1-S differs from DCLK1-L by only six amino acids, we succeeded in generating a monospecific DCLK1-S-Antibody (PS41014), which does not cross-react with DCLK1-L, and specifically detects CSCs. Subcellular localization of S/L-isoforms was examined by immune-electron-microscopy (IEM). Surprisingly, besides plasma membrane and cytosolic fractions, S/L also localized to nuclear/mitochondrial fractions, with pronounced localization of S-isoform in the nuclei and mitochondria. Sporadic CRCs develop from adenomas. Screening colonoscopy is used for detection/resection of growths, and morphological/pathological criteria are used for risk assessment and recommendations for follow-up colonoscopy. But, these features are not precise and majority of the patients will never develop cancer. We hypothesized that antibody-based assay(s), which identify CSCs, will significantly improve prognostic value of morphological/pathological criteria. We conducted a pilot retrospective study with PS41014-Ab, by staining archived adenoma specimens from patients who developed (high-risk), or did not develop (low-risk) adenocarcinomas within 10-15 years. PS41014-Ab stained adenomas from initial and follow-up colonoscopies of high-risk patients, at significantly higher levels (three to fivefold) than adenomas from low-risk patients, suggesting that PS41014-Ab could be used as an additional tool for assessing CRC risk. CRC patients, with high DCLK1-S-expressing tumors (by qRT-PCR), were reported to have worse overall survival than low expressers. We now report that DCLK1-S-specific Ab may help to identify high-risk patients at the time of index/screening colonoscopy.

  View details for DOI 10.1038/labinvest.2017.40

  View details for PubMedID 28414327

  View details for PubMedCentralID PMC5623180