Genomic Landscape of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens for Immunoprevention.

BACKGROUND & AIMS: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers. METHODS: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays. RESULTS: Mutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced precancers, and 20% of precancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced precancers, and 107 in precancers. No neoAgs were detected in PWOMP. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced precancers, and 29% of precancers. We observed increased levels of naïve CD8+ and memory CD4+ T cells in mismatch repair-deficient cancers and precancers via transcriptomics analysis. CONCLUSIONS: Shared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS precancers and early-stage cancers.

Telomere dysfunction instigates inflammation in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition driven by diverse genetic and nongenetic programs that converge to disrupt immune homeostasis in the intestine. We have reported that, in murine intestinal epithelium with telomere dysfunction, DNA damage-induced activation of ataxia-telangiectasia mutated (ATM) results in ATM-mediated phosphorylation and activation of the YAP1 transcriptional coactivator, which in turn up-regulates pro-IL-18, a pivotal immune regulator in IBD pathogenesis. Moreover, individuals with germline defects in telomere maintenance genes experience increased occurrence of intestinal inflammation and show activation of the ATM/YAP1/pro-IL-18 pathway in the intestinal epithelium. Here, we sought to determine the relevance of the ATM/YAP1/pro-IL-18 pathway as a potential driver of IBD, particularly older-onset IBD. Analysis of intestinal biopsy specimens and organoids from older-onset IBD patients documented the presence of telomere dysfunction and activation of the ATM/YAP1/precursor of interleukin 18 (pro-IL-18) pathway in the intestinal epithelium. Employing intestinal organoids from healthy individuals, we demonstrated that experimental induction of telomere dysfunction activates this inflammatory pathway. In organoid models from ulcerative colitis and Crohn's disease patients, pharmacological interventions of telomerase reactivation, suppression of DNA damage signaling, or YAP1 inhibition reduced pro-IL-18 production. Together, these findings support a model wherein telomere dysfunction in the intestinal epithelium can initiate the inflammatory process in IBD, pointing to therapeutic interventions for this disease.

Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis.

IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate. OBJECTIVE: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP. DESIGN, SETTING AND PARTICIPANTS: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres. EXPOSURES: Participants self-administered 350 mg of erlotinib by mouth, one time per week for 6 months. MAIN OUTCOMES AND MEASURES: Duodenal polyp burden (sum of polyp diameters) was assessed in the proximal duodenum by esophagogastroduodenoscopy performed at baseline and 6 months, with mean per cent change defined as the primary efficacy outcome of interest. Rate of grade 2-3 AEs was evaluated as a co-primary outcome. Secondary outcomes included changes in total duodenal polyp count, along with changes in lower gastrointestinal (GI) polyp burden and count (for participants examined by optional lower endoscopy). RESULTS: Forty-six participants (mean age, 44.1 years (range, 18-68); women, 22 (48%)) were enrolled; 42 participants completed 6 months of intervention and were included in the per-protocol analysis. Duodenal polyp burden was significantly reduced after 6 months of weekly erlotinib intervention, with a mean per cent change of -29.6% (95% CI, -39.6% to -19.7%; p<0.0001). Similar results were observed in subgroup analyses defined by participants with advanced duodenal polyposis (Spigelman 3) at baseline (mean, -27%; 95% CI, -38.7% to -15.2%; p<0.0001). Post-intervention Spigelman stage was downstaged in 12% of the participants. Lower GI polyp number was also decreased after 6 months of intervention (median, -30.8%; IQR, -47.4% to 0.0%; p=0.0256). Grade 2 or 3 AEs were reported in 71.7% of subjects, with only two experiencing grade 3 toxicity at least possibly related to intervention. CONCLUSION: In this single-arm, multi-centre trial of participants with FAP, erlotinib one time per week resulted in markedly lower duodenal polyp burden, and modestly reduced lower GI polyp burden, after 6 months of intervention. While AEs were still reported by nearly three-quarters of all participants, these events were generally lower grade and well-tolerated. These findings support further investigation of erlotinib as an effective, acceptable cancer preventive agent for FAP-associated GI polyposis. TRIAL REGISTRATION NUMBER: NCT02961374.

Ibrutinib-rituximab followed by R-HCVAD as frontline treatment for young patients (≤65 years) with mantle cell lymphoma (WINDOW-1): a single-arm, phase 2 trial.

BACKGROUND: Induction with ibrutinib and rituximab provides an opportunity to minimise chemotherapy exposure, because upfront use of these targeted therapies could result in remission without chemotherapy and allow for consolidation with only four cycles of chemotherapy instead of the conventional eight. We aimed to determine the activity and safety of ibrutinib-rituximab induction followed by shortened chemoimmunotherapy (four cycles) with rituximab plus hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HCVAD) alternating with methotrexate-cytarabine in previously untreated patients with mantle cell lymphoma. METHODS: We did a single-centre, single-arm, phase 2 trial in previously untreated patients with mantle cell lymphoma. Eligible patients were aged 65 years or younger and had serum bilirubin of less than 1·5 mg/dL, creatinine clearance of 30 mL/min or more, Eastern Cooperative Oncology Group performance status of 2 or less, and cardiac ejection fraction 50% or more by echocardiogram. Patients received 12 cycles of ibrutinib-rituximab induction (part A; oral ibrutinib 560 mg daily and intravenous rituximab 375 mg/m2 weekly for the first 4 weeks and then on day 1 of cycles 3-12). As soon as patients had a complete response, four cycles of R-HCVAD alternating with methotrexate-cytarabine (part B) were administered. If they did not have a complete response or had a partial response, patients received two cycles of R-HCVAD alternating with methotrexate-cytarabine followed by reassessment, up to a total of eight cycles. Patients were taken off study if they had stable disease or progression during R-HCVAD. The primary outcome was the overall response rate after part A. The analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02427620. FINDINGS: 131 patients were enrolled between June 12, 2015, and Dec 6, 2018. The median age was 56 years (IQR 49-60). 58 (50%) of 117 patients had high Ki-67 (≥30%). 129 (98%, 95% CI 95-100) of 131 patients had an overall response in part A. The most common grade 3-4 adverse events were lymphocytopenia (19 [14%] of 131), skin rash (16 [12%]), thrombocytopenia (12 [9%]), infections (11 [8%]), and fatigue (ten [8%]) in part A and lymphocytopenia (96 [73%]), leukocytopenia (42 [32%]), thrombocytopenia (40 [30%]), and neutropenia (26 [20%]) in part B. There was one on-study death, which was not deemed to be treatment-related. INTERPRETATION: Induction with ibrutinib-rituximab in the frontline treatment of young patients with mantle cell lymphoma is active and safe. This approach allowed minimisation of the number of chemotherapy cycles, thereby reducing the adverse events associated with chemotherapy. Newer trials bringing the next-generation Bruton's tyrosine kinase inhibitors into the frontline setting might obviate the need for chemotherapy altogether in patients with mantle cell lymphoma. FUNDING: Pharmacyclics, Janssen.

Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL) - outcomes and mutation profile from venetoclax resistant MCL patients.

Venetoclax is effective in relapsed patients with mantle cell lymphoma (MCL). Mechanisms of resistance to venetoclax in MCL are poorly understood. We describe the clinical outcomes and genomic characteristics of 24 multiply relapsed patients (median of five prior lines of therapy) who received venetoclax-based therapies; 67% had progressed on BTK inhibitors (BTKi) and 54% had blastoid or pleomorphic histology. Median follow up after venetoclax treatment was 17 months. The overall response rate was 50% and complete response (CR) rate was 21%, 16 patients had progressed and 15 died. The median progression free, overall and post venetoclax survival were 8, 13.5 and 7.3 months respectively. Whole-exome sequencing (WES) was performed on samples collected from seven patients (including five pairs; before starting venetoclax and after progression on venetoclax). The SMARCA4 and BCL2 alterations were noted only after progression, while TP53, CDKN2A, KMT2D, CELSR3, CCND1, NOTCH2 and ATM were altered 2-4-fold more frequently after progression. In two patients with serial samples, we demonstrated clonal evolution of novel SMARCA4 and KMT2C/D mutations at progression. Mutation dynamics in venetoclax resistant MCL is demonstrated. Our data indicates that venetoclax resistance in MCL is predominantly associated with non-BCL2 gene mutations. Further studies are ongoing in MCL patients to evaluate the efficacy of venetoclax in combination with other agents and understand the biology of venetoclax resistance in MCL.

The Pelvis-First Approach for Robotic Proctectomy in Patients with Redundant Abdominal Colon.

BACKGROUND: Robotic surgery is increasingly performed for low rectal cancer.1 A redundant sigmoid colon makes retraction and pelvic dissection challenging. We present a 'pelvis-first' approach to robotic proctectomy where pelvic dissection occurs prior to colonic mobilization. METHODS: A 26-year-old woman was diagnosed with a clinical T3N1 rectal adenocarcinoma at 3 cm from the anal verge. The patient had Lynch syndrome, with a germline mutation in the PMS2 gene. A near-complete clinical response was observed after neoadjuvant chemoradiation (NCRT), and the patient wished to delay surgery and permanent colostomy. Additional FOLFOX was administered and led to a complete clinical response. After 2.5 months of watchful delay of surgery, the tumor regrew, and the patient then underwent robotic abdominoperineal resection (APR). RESULTS: Initial exploration revealed a highly redundant sigmoid colon. A pelvis-first approach was undertaken. The colon was left tethered and outside of the pelvis during the pelvic dissection. The levator ani was divided transabdominally. Vascular dissection and left colon mobilization were completed after pelvic dissection.2 The specimen was removed transanally, obviating the need for abdominal incision. An end colostomy was created laparoscopically, and the perineum was closed primarily after omental flap. The patient recovered without complications. CONCLUSIONS: The 'pelvis-first' approach to proctectomy is advantageous for patients with a highly redundant sigmoid colon. Transabdominal division of the levator ani during APR ensures excellent circumferential margin. Although Lynch syndrome-associated rectal cancer can show excellent response to NCRT,3 patients undergoing watchful delay of surgery require close monitoring and prompt triggering of salvage proctectomy when tumor regrowth is observed.4,5.

Safety and efficacy of metal stents for malignant colonic obstruction in patients treated with bevacizumab.

BACKGROUND AND AIMS: The aim of this study was to examine clinical outcomes and adverse events (AEs) of self-expandable metal stents (SEMSs) in the management of malignant colonic obstruction (MCO). METHODS: Patients with SEMSs for MCO treated at our institution from 2007 to 2016 were included. Clinical success was defined as successful oral intake after the procedure and technical success as stent deployment across the stricture in the desired location. RESULTS: Of 199 patients, the mean age was 58, 54% were men, and 99% had stage IV cancer. MCO etiology was colorectal cancer in 82% and extrinsic compression in 17%. Technical success was achieved in 99.5% and clinical success in 89%. The SEMSs were palliative in 97% and were a bridge to surgery in 4%. MCO occurred in the left side of the colon in 90%, transverse in 4.5%, and ascending colon in 5.5%. SEMSs were placed in curved segments in 30% and straight segments in 70%. Tandem SEMSs were required in 27 patients. Forty-six patients had 48 AEs (24%), including 2% periprocedure, 15% postprocedure, and 83% after 72 hours. Stent-related AEs (n = 25) included persistent obstruction (n = 14), occlusion (n = 10), and failure of expansion (n = 1). Procedural AEs (n = 23) included minor bleeding (n = 2), perforations (n = 4), abdominal pain (n = 12), stent migration (n = 4), and respiratory insufficiency (n = 1). Repeat procedures were performed in 21 of 46 patients. After SEMSs, 48 patients underwent surgery, including resection with primary anastomosis (n = 8), resection with definitive stoma (n = 18), and diverting stoma without resection (n = 19). Mean time to surgery after SEMS placement was 175 days. Postsurgical AEs occurred in those with resections (leak, 2; infection, 2). Of 104 receiving bevacizumab, 22% had AEs, including 1 perforation compared with 3 in the nonbevacizumab group (P = .549). Mean overall survival was 5.6 months. Extrinsic compression and curved strictures were associated with poor clinical success by univariate analysis and etiology (noncolonic with poor outcome) by multivariate analysis. CONCLUSIONS: SEMSs for MCO has high technical but suboptimal clinical success. Curved strictures and extrinsic compression are associated with poor outcomes. The perforation rate was not higher in the bevacizumab compared with the nonbevacizumab group, although this should be further validated in a larger population.

Screening high-risk populations for colon and rectal cancers.

Currently, colorectal cancers accounted for the second-highest number of cancer deaths in the US. Hereditary syndromes, strong family history, and inflammatory bowel disease are all conditions that confer predisposition risks. In hereditary syndromes, screening must be more frequent and start earlier. With familial risk, screening should depend on the age of cancer onset and number of affected relatives. For inflammatory bowel disease, surveillance should depend on duration, severity, and extent of colitis.

Physical activity and the risk of colorectal cancer in Lynch syndrome.

Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk in people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n = 807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49 and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-hr/week) during the age-period of cancer diagnosis or censoring (near-term exposure) and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. <3.5 MET-hr/week, 0.71; 95% CI, 0.53-0.96). The strength and direction of associations were similar for long-term physical activity, although the associations were not nominally significant. Our results suggest that physical activity is inversely associated with the risk of colorectal cancer for people with Lynch syndrome; however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk in people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk.

Incidence of immune-related adverse events and its association with treatment outcomes: the MD Anderson Cancer Center experience.

Background Immunotherapy is emerging as the cornerstone for treatment of patients with advanced cancer, but significant toxicity (immune-related adverse events [irAEs]) associated with unbridled T cell activity remains a concern. Patients and methods A retrospective review of the electronic medical records of 290 patients with advanced cancer treated on an immunotherapy-based clinical trial in the Department of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center between February 2010 and September 2015 was performed. Clinical and laboratory parameters were collected to determine the incidence of irAEs, risk factors, and their association with treatment outcomes. Results Ninety eight of 290 patients (34%) experienced any grade irAEs. Among the 15 (5.2%) patients with grade ≥ 3 irAEs, the most common irAEs were dermatitis and enterocolitis. Although 80% of the patients with grade ≥ 3 irAEs required systemic corticosteroids, all the 15 patients recovered from the irAEs. On re-challenge, 4 of the 5 patients who had received systemic corticosteroids for irAE continued to respond. There were no irAE-related deaths. Importantly, patients with grade ≥ 3 irAEs had improved overall response rate (25 vs. 6%; p = 0.039) and longer median time to progression (30 weeks vs. 10 weeks; p = 0.0040) when compared to those without grade ≥ 3 irAEs. Conclusion Incidence of irAEs with immunotherapeutic agents indicates an active immune status, suggestive of potential clinical benefit to the patient. Further validation of this association in a large prospective study is warranted.

How to deal with large colorectal polyps: snare, endoscopic mucosal resection, and endoscopic submucosal dissection; resect or refer?

PURPOSE OF REVIEW: The importance of accurate polyp detection and removal is paramount to preventing colon cancer. Resection of large polyps can be challenging to the endoscopist based on their size, shape, or location. Large polyps have the potential of harboring malignancy and a higher risk of complications with resection. Careful assessment of each lesion and meticulous resection using the appropriate tools and techniques is essential. RECENT FINDINGS: Over the last 15 years, the development of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) techniques has presented the endoscopist with the opportunity to manage patients with large and flat lesions thereby avoiding the need for surgery. However, these techniques are complex and require extensive knowledge and skill in the use of various devices to resect a lesion completely and manage bleeding and perforation associated with these procedures. SUMMARY: Large colon polyps manifest as either polypoid or nonpolypoid (flat) lesions. Polypoid lesions, especially those with pedicles, are removed with snare resection, whereas flat lesions may require the use of EMR or ESD. Resection of large polyps (>1 cm) requires additional tools and techniques to ensure safe and complete resection. We will discuss our approach to dealing with large colorectal polyps: snare, EMR, and ESD; resect or refer?

Outcome of EMR as an alternative to surgery in patients with complex colon polyps.

BACKGROUND AND AIMS: Patients with complex colon polyps were traditionally referred for surgery to avoid adverse events associated with endoscopic resection. Recent advances in endoscopic imaging as well as endoscopic hemostasis and clip closure allow for the use of EMR as an alternative to surgery for such lesions. To determine the outcome of treatment of complex colon polyps with EMR as an alternative to surgery, we conducted a retrospective observational study. METHODS: Two hundred three patients with complex colon polyps were referred to an EMR center as an alternative to surgery. Patients underwent a protocol-driven EMR. The primary endpoint was the complete resection rate. Secondary endpoints were safety, residual adenoma rate, and incidence of missed synchronous polyps. RESULTS: EMR was performed in 155 patients and was deferred in 48 patients who were referred to surgery. EMR specimens revealed benign polyps in 149 and cancer in 6 patients. EMR adverse events occurred in 7 patients, requiring hospitalization in 5 of them. None of the patients died as a result of their adverse events. Surveillance colonoscopy at 4 to 6 months after resection of a benign lesion in 137 patients revealed residual adenoma at the scar site in 6 patients and additional synchronous precancerous lesions in 117 patients that were not removed by the referring endoscopist. None underwent surgery for failure of EMR. The overall precancerous lesion burden was 2.83 per patient, the adenoma burden was 2.13 per patient, and the serrated polyp burden was .69 per patient. CONCLUSIONS: EMR can be used instead of surgery for complex colon polyps in 75% of patients with few adverse events and few residual adenomas at resection sites. In addition, careful repeat examination of the entire colon for synchronous lesions overlooked by the referring endoscopist is required for most patients. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01827241.).

Can Technology Improve the Quality of Colonoscopy?

In order for screening colonoscopy to be an effective tool in reducing colon cancer incidence, exams must be performed in a high-quality manner. Quality metrics have been presented by gastroenterology societies and now include higher adenoma detection rate targets than in the past. In many cases, the quality of colonoscopy can often be improved with simple low-cost interventions such as improved procedure technique, implementing split-dose bowel prep, and monitoring individuals' performances. Emerging technology has expanded our field of view and image quality during colonoscopy. We will critically review several technological advances in the context of quality metrics and discuss if technology can really improve the quality of colonoscopy.

Detection rates of premalignant polyps during screening colonoscopy: time to revise quality standards?

BACKGROUND: Standards for the detection of adenomas during screening colonoscopy are widely used to measure examination quality. No such standards exist for sessile serrated adenomas (SSAs). OBJECTIVE: To measure both the adenoma detection rate (ADR) and SSA detection rate (SSADR) during screening colonoscopy before and after quality improvement/financial incentive measures. DESIGN: Retrospective determination of baseline ADR/SSADR by the endoscopist, followed by prospective collection of data after informing physicians of baseline detection rates. SETTING: Tertiary cancer center with a large cancer screening program. PATIENTS: A total of 2833 average-risk colorectal cancer screening patients 50 to 75 years of age undergoing initial colonoscopy. DATA COLLECTION: Electronic medical records for indication and demographics, endoscopy report, and pathology report. MAIN OUTCOME MEASUREMENTS: Detection rates of adenomas and SSAs by sex. RESULTS: The overall ADR in male and female patients was 50.6% and 36.6%, respectively. The overall detection rate of advanced adenomas in male and female patients was 12.4% and 6.5%, respectively. The overall SSADR in male and female patients was 10.1% and 7.1%, respectively. In 108 patients (3.8% of entire group), SSAs were the only premalignant lesions found. Detection rates of both types of premalignant polyps improved over time but did not reach statistical significance. LIMITATIONS: Single-center experience with limited sample size and small group of endoscopists. CONCLUSION: ADRs far in excess of current standards are achievable. Cecal withdrawal time is associated with the ADR. Prevalence of SSA rivals that of advanced adenomas and is greater than current medical literature suggests. The combination of monitoring and financial incentives did not result in statistically significant improvement in ADRs.

Natural language processing as an alternative to manual reporting of colonoscopy quality metrics.

BACKGROUND AND AIMS: The adenoma detection rate (ADR) is a quality metric tied to interval colon cancer occurrence. However, manual extraction of data to calculate and track the ADR in clinical practice is labor-intensive. To overcome this difficulty, we developed a natural language processing (NLP) method to identify adenomas and sessile serrated adenomas (SSAs) in patients undergoing their first screening colonoscopy. We compared the NLP-generated results with that of manual data extraction to test the accuracy of NLP and report on colonoscopy quality metrics using NLP. METHODS: Identification of screening colonoscopies using NLP was compared with that using the manual method for 12,748 patients who underwent colonoscopies from July 2010 to February 2013. Also, identification of adenomas and SSAs using NLP was compared with that using the manual method with 2259 matched patient records. Colonoscopy ADRs using these methods were generated for each physician. RESULTS: NLP correctly identified 91.3% of the screening examinations, whereas the manual method identified 87.8% of them. Both the manual method and NLP correctly identified examinations of patients with adenomas and SSAs in the matched records almost perfectly. Both NLP and the manual method produced comparable values for ADRs for each endoscopist and for the group as a whole. CONCLUSIONS: NLP can correctly identify screening colonoscopies, accurately identify adenomas and SSAs in a pathology database, and provide real-time quality metrics for colonoscopy.

Safety of endoscopic interventions in patients with thrombocytopenia.

BACKGROUND: The risk of endoscopic interventions in thrombocytopenia has received little attention in the medical literature. OBJECTIVE: The aim of this study was to assess the safety of endoscopic interventions including evaluation of GI bleeding (GIB) in patients with thrombocytopenia. DESIGN AND SETTING: Retrospective study, tertiary oncology center. PATIENTS AND INTERVENTION: Review of consecutive endoscopies with preprocedure platelet counts (PCs) of 75 × 10(3)/µL or lower. MAIN OUTCOME MEASUREMENTS: Risk of bleeding with routine endoscopic interventions and transfusion requirement after evaluation of GIB. RESULTS: A total of 617 (351 upper, 266 lower [90 colonoscopies]) endoscopies were performed in 395 patients. Forceps-biopsy specimens were obtained in 398 endoscopies (mean ± standard deviation [SD] PC: 38.21 ± 11.7 × 10(3)/µL) and 45 polypectomies were performed in 17 endoscopies (mean ± SD PC: 39.65 ± 8.53 × 10(3)/µL). The risk of bleeding was 1.5% (6 of 398 endoscopies) at the biopsy site and 4% (2 of 45 polypectomies) at the polypectomy site. Active GIB (mean ± SD PC: 32.85 ± 4.0 × 10(3)/µL) was observed in 68 (11% of 617) endoscopies and intervention (mean ± SD PC: 33.68 ± 4.6 × 10(3)/µL) was performed in 41 procedures. Together, angiodysplasias and ulcers were the most common etiology (51.2% of 41). Hemostasis was achieved in 39 (95.1% of 41) procedures. Comparison of blood transfusions ± 3 days of successful therapy showed a 52% reduction (P < .001). By multivariate analysis, a higher aggregate blood transfusion 3 days preceding endoscopy (odds ratio 1.32; 95% confidence interval, 1.16-1.50; P < .001) predicted endoscopic findings of active GIB. LIMITATIONS: Retrospective design, single center. CONCLUSIONS: In the largest endoscopic experience reported in thrombocytopenic patients (Common Terminology Criteria for Adverse Events grade 3 or lower), bleeding caused by standard forceps biopsy and polypectomy (≤10 mm) was minor and easily controlled. Endoscopic therapy for GIB is safe and significantly reduces the packed red blood cell requirement and should be considered in patients with thrombocytopenia in the setting of an appropriate transfusion strategy.

Radiation exposure from diagnostic imaging studies among patients with inflammatory bowel disease in a safety-net health-care system.

BACKGROUND/AIMS: Radiographic imaging studies are important in the management of patients with inflammatory bowel disease (IBD), but are associated with radiation exposure. IBD patients in a safety-net health-care system may be at risk of high exposure to radiation. Our purpose was to identify associations of high-dose radiation exposure among an ethnically diverse cohort of IBD patients in a safety-net health-care system. METHODS: A study was performed on patients with IBD receiving care from the Harris County Hospital District. Radiation exposure was calculated using total number of imaging studies performed between from 2000 and 2010 and estimates of radiation dose per study. Associations of high-dose radiation exposure, defined as a cumulative effective dose (CED) >50 mSv, were identified by using univariate and multivariate logistic regression. RESULTS: The study cohort of 278 patients with IBD was ethnically diverse, with 30 % Caucasian, 44 % African-American, and 26 % Hispanic. The median CED was 10.40 mSv (SD 20.02). Annualized radiation doses were 3.45 mSv/year among patients with Crohn's disease (CD) and 1.27 mSv/year among patients with ulcerative colitis, p < 0.02. Approximately 13 % of IBD patients received a CED >50 mSv. There were no differences in radiation exposure based on age, gender, or race/ethnicity. CONCLUSIONS: A small proportion of IBD patients in a safety-net health-care system received high doses of diagnostic radiation exposure. Use of diagnostic imaging studies that limit radiation exposure should be encouraged.