Prospective randomized controlled trial of water exchange plus cap versus water exchange colonoscopy in unsedated veterans.

BACKGROUND AND AIMS: Water exchange (WE) and cap-assisted colonoscopy separately have been shown to reduce pain during insertion in unsedated patients. We hypothesized that compared with WE, WE cap-assisted colonoscopy (WECAC) could significantly lower real-time maximum insertion pain (RTMIP). METHODS: Veterans without escort were recruited, randomized, blinded, and examined at 3 U.S. Veterans Affairs sites. The primary outcome was RTMIP, defined as the highest segmental pain (0 = no pain, 10 = most severe pain) during insertion. RESULTS: Randomization (WECAC, 143; WE, 137) produced an even distribution of a racially diverse group of men and women of low socioeconomic status. The intention-to-treat analysis reported results of WECAC and WE for cecal intubation (93% and 94.2%, respectively), mean RTMIP (2.9 [standard deviation {SD}, 2.5] and 2.6 [SD, 2.4]), proportion of patients with no pain (28.7% and 27.7%), mean insertion time (18.6 minutes [SD, 15.6] and 18.8 minutes [SD, 15.9]), and overall adenoma detection rate (48.3% and 55.1%); all P values were >.05. When RTMIP was binarized as "no pain" (0) versus "some pain" (1-10) or "low pain" (0-7) versus "high pain" (8-10), different significant predictors of RTMIP were identified. CONCLUSIONS: Unsedated colonoscopy was appropriate for unescorted veterans. WE alone was sufficient. Adding a cap did not reduce RTMIP. Patient-specific factors and application of WE with insertion suction of infused water contributed to high and low RTMIP, respectively. For unescorted patients, selecting those with low anxiety, avoiding low body mass index, history of depression or self-reported poor health, and complying with the steps of WE can minimize RTMIP to ensure success of unsedated colonoscopy. (Clinical trial registration number: NCT03160859.).

Randomized Controlled Trial Investigating Cold Snare and Forceps Polypectomy Among Small POLYPs in Rates of Complete Resection: The TINYPOLYP Trial.

INTRODUCTION: Optimizing complete resection during colonoscopy is important because residual neoplastic tissue may play a role in interval cancers. The US Multi-Society Task Force recommends diminutive (≤5 mm) and small (6-9 mm) polyps be removed by cold snare polypectomy (CSP). However, evidence is less clear whether CSP retains significant advantage over cold forceps polypectomy (CFP) for polyps ≤3 mm. METHODS: This study is a single-center prospective noninferiority randomized clinical trial evaluating CFP and CSP for nonpedunculated polyps ≤3 mm. Patients 18 years and older undergoing colonoscopy for any indication were recruited. During each colonoscopy, polyps underwent block randomization to removal with CFP or CSP. After polypectomy, 2 biopsies were taken from the polypectomy margin. The primary noninferiority outcome was the complete resection rate, defined by absence of residual polyp in the margin biopsies. RESULTS: A total of 179 patients were included. Patients had similar distribution in age, sex, race/ethnicity, as well as indication of procedure. A total of 279 polyps ≤3 mm were identified, with 138 in the CSP group and 141 in the CFP group. Mean polypectomy time was longer for CSP compared with CFP (42.3 vs 23.2 seconds, P < 0.001), although a higher proportion of polyps removed by CFP were removed in more than 1 piece compared with CSP (15.6 vs 3.6%, P < 0.001). There were positive margin biopsies in 2 cases per cohort, with a complete resection rate of 98.3% in both groups. There was no significant difference in cohorts in complete resection rates (difference in complete resection rates was 0.057%, 95% confidence interval: -4.30% to 4.53%), demonstrating noninferiority of CFP compared with CSP. DISCUSSION: Use of CFP was noninferior to CSP in the complete resection of nonpedunculated polyps ≤3 mm. CSP required significantly more time to perform compared with CFP. CFP should be considered an acceptable alternative to CSP for removal of polyps ≤3 mm.

Randomized controlled trial investigating use of submucosal injection of EverLift™ in rates of complete resection of non-pedunculated 4-9 mm polyps.

INTRODUCTION: Currently, cold snare polypectomy (CSP) without submucosal injection is recommended for removing polyps < 10 mm. Use of viscous submucosal agents has not been previously evaluated in CSP. We investigate the potential role of EverLift™ (GI Supply, Pennsylvania) in CSP. METHODS: The study is a single-center prospective randomized non-inferiority clinical trial evaluating CSP of non-pedunculated 4-9 mm polyps, with or without submucosal injection of EverLift™. Patients 18-80 years of age presenting for colonoscopy were recruited. Eligible polyps underwent block randomization to CSP with or without EverLift™. Following CSP, two biopsies were performed at the CSP site margin. The primary non-inferiority outcome was complete resection rate, defined by absence of residual polyp in the margin biopsies (non-inferiority margin -10%). RESULTS: A total of 291 eligible polyps underwent CSP, with 142 removed using EverLift™. There was similar polyp size and distribution of pathology between the two groups. Overall, there was a low rate of positive margins with (1.4%) or without submucosal injection (2.8%), with no significant difference in complete resection (difference 1.28%, 95% CI: -2.66 to 5.42%), demonstrating non-inferiority of EverLift™ injection. Use of EverLift™ significantly increased CSP time (109.8 vs 38.8 s, p < 0.0001) and frequency of use of hemostatic clips (13.4 vs 3.6%, p = 0.002). CONCLUSION: Submucosal injection of EverLift™ was non-inferior to CSP of 4-9 mm polyps without injection and increased time for resection as well as use of hemostatic clips to control acute bleeding. Our results suggest that polypectomy of 4-9 mm polyps can be safely performed without submucosal injection of EverLift™.

Worldwide Practice Patterns in Lynch Syndrome Diagnosis and Management, Based on Data From the International Mismatch Repair Consortium.

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

Adherence to Recommendations for Repeat Surveillance After Publication of New Postpolypectomy Guidelines.

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

Association of Aurora-A (STK15) kinase polymorphisms with clinical outcome of esophageal cancer treated with preoperative chemoradiation.

BACKGROUND: Aurora-A/STK15 is a serine/threonine kinase critical for regulated chromosome segregation and cytokinesis. We investigated the association between 2 nonsynonymous single nucleotide polymorphisms in the coding region of STK15, T91A (Phe31Ile) and G169A (Val57Ile), and clinical outcome of esophageal cancer treated with preoperative chemoradiation. METHODS: Genotypes at Phe31Ile and Val57Ile were assessed from peripheral blood lymphocytes of 190 esophageal cancer patients and were correlated to response to treatment, recurrence rate, risk of death, disease-free survival (DFS) and median survival time (MTS). RESULTS: All patients had resectable esophageal or gastroesophageal junction cancer and received preoperative chemoradiation followed by esophagectomy. The heterozygous variant Phe31/Ile variant was significantly associated with tumor recurrence (odds ratio [OR] = 4.39; 95% confidence interval [CI], 2.12-8.94; P < .001), shorter DFS (P = .0001), and shorter MTS (P = .012). For patients receiving cisplatin-based therapy, only the variant Phe31/Ile had an adverse effect on response (OR = 2.8; 95% CI, 1.01-5.17; P = .048) and MTS (P = .026). The variant 91A-169G haplotype carried a significant risk for lack of complete response (OR = 2.54; 95% CI, 1.15-5.54) and higher rate of recurrence (OR = 2.73; 95%CI, 1.00-7.29). The presence of at least 1 variant allele at each locus further increased the risk of recurrence (adjusted OR = 6.21; 95% CI, 2.28-17.11; P = <.001), and was associated significantly shorter DFS (P = .003). CONCLUSIONS: Our study shows that functional SNPs in the STK15 gene are associated with higher rate of recurrence, higher likelihood of chemoratiotherapy-resistance, shorter DFS, and shorter MTS. Confirmation of our data and understanding the mechanisms through which STK15 functional SNPs mediate resistance to chemoradiotherapy are warranted.

Predictive factors for adenoma detection rates: a video study of endoscopist practices.

Background and study aims In 2015, the American Society for Gastrointestinal Endoscopy (ASGE) and American College of Gastroenterology (ACG) Task Force on Quality in Endoscopy deemed adenoma detection rate (ADR) the most important quality measure for colonoscopy. There has been much interest in factors that can increase ADR. To date, however, few studies have looked at what intra-procedural endoscopist practices are associated with improving ADR. We conducted a retrospective review of colonoscopy videos to evaluate intra-procedural practices that could be associated with ADR. Methods Videos were recorded of colonoscopies performed between September and December 2017 at the Palo Alto Veterans Affairs Health Care System. Colonoscopies for screening and surveillance were included for video review. Factors assessed included withdrawal time, intra-procedural cleaning, inspection technique, and other variables (colon distention, removal of equivocal/hyperplastic polyps). A series of multiple regression analyses was conducted on variables of interest before running a final model of significant predictors. Results A total of 130 videos were reviewed from nine endoscopists whose ADRs ranged between 37.5 % and 73.7 %. The final regression model was significant (F = 15.35, df = 2, P  = 0.0044), R 2  = 0.8365) with close inspection of behind folds and quality of cecal inspection being the factors highly correlated with predicting ADR. Withdrawal and inspection times, colonic wall distention, removal of equivocal/hyperplastic polyps, quality of rectal inspection, suctioning, and washing were factors moderately correlated with predicting ADR. Conclusions We found that behind-fold inspection and a meticulous cecal inspection technique were predictive of a high ADR.

Thalidomide Use Reduces Risk of Refractory Gastrointestinal Bleeding in Patients with Continuous Flow Left Ventricular Assist Devices.

Gastrointestinal (GI) bleeding is a common complication seen in patients with implanted continuous flow left ventricular assist devices (CF-LVAD), often attributed to arteriovenous malformations (AVMs). Whether thalidomide reduces recurrent GI bleeding risk in CF-LVAD patients has been incompletely evaluated. We conducted a retrospective review of all CF-LVAD patients at our institution with GI bleeding from AVMs who had a trial both off and on thalidomide. The primary endpoint was time to rebleed, while secondary endpoints included overall GI bleeding events, packed red blood cell (PRBC) transfusion requirements, and adverse events related to thalidomide. We report on 24 patients with recurrent AVM-associated GI bleeding who met criteria for and received thalidomide therapy, of which 17 had sufficient follow-up to be ultimately included for final analysis. We found the risk of rebleeding was significantly reduced in those on thalidomide therapy versus off (hazard ratio = 0.23, p = 0.022). The median number of GI bleeds per year was reduced from 4.6 to 0.4 (p = 0.0008) and the PRBC requirement was lower (36.1 vs. 0.9 units per year, p = 0.004) in those on thalidomide therapy. The adverse event rate with thalidomide was 59%, with symptoms resolution in most following dose reduction without increased bleeding. Thalidomide reduced the risk of AVM-associated GI rebleeding, number of bleeding events, and PRBC requirements in CF-LVAD patients. When initiating therapy, potential side effects and overall clinical context should be considered.

Arteriovenous malformations respond poorly to argon plasma coagulation in patients with continuous flow left ventricular assist devices.

BACKGROUND: Gastrointestinal bleeding in patients with continuous flow left ventricular assist devices (LVADs) causes significant morbidity. Arteriovenous malformations (AVMs) cause 30-60% of bleeds, yet the efficacy of endoscopic interventions and risk factors for rebleeding have not been studied. PATIENTS AND METHODS: The charts of all LVAD patients undergoing endoscopy for gastrointestinal bleeding at Stanford between January 2010 and December 2017 were reviewed. Cox proportional hazard modeling was used to evaluate risk factors for rebleeding, including the type of endoscopic treatment, patient characteristics, and endoscopic findings. RESULTS: Of 54 total LVAD patients presenting with gastrointestinal bleeding, 23 (42.6%) had AVMs documented on endoscopy. Treatment with argon plasma coagulation (APC) alone was associated with a higher risk of rebleeding compared to no treatment [hazard ratio (HR)=4.77, P=0.012], and compared with clip±APC (HR=7.47, P=0.012). The 90-day bleed-free rate was 10.9% with APC, 100% with clipping±APC, and 83.3% with no endoscopic treatment. Additional risk factors for rebleeding included the presence of gastric AVMs (HR=3.64, P=0.024), and presence of hematochezia (HR=5.15, P=0.05). In a multiple Cox regression model, only the presence of gastric AVMs (HR=5.50, P=0.029) and APC use (HR=14.3, P=0.008) remained significant predictors of rebleeding. CONCLUSION: The use of APC alone for the treatment of AVMs in LVAD patients had a high failure rate. The presence of gastric AVMs was a significant risk factor for rebleeding in LVAD patients. Management decisions should take these factors into account.