Faculty Bibliography

BACKGROUND:Gastrointestinal bleeding (GIB) is a frequent cause of re-admission in patients with continuous-flow left ventricular assist devices (CF-LVADs) and is associated with multiple endoscopic procedures and high resource utilization. Our aim was to determine the diagnostic and therapeutic yield of endoscopy and to develop a more cost-effective approach for the management of GIB in CF-LVAD recipients. METHODS:We retrospectively reviewed 428 patients implanted with a CF-LVAD between 2009 and 2016 at the Columbia University Medical Center and identified those hospitalized for GIB. Patients were categorized into upper GIB (UGIB), lower GIB (LGIB) and occult GIB (OGIB), based on clinical presentation. RESULTS:Eighty-seven CF-LVAD patients underwent a total of 164 GIBs, resulting in 239 endoscopies. Index presentation was consistent with UGIB in 30 (34.5%), LGIB in 19 (21.8%) and OGIB in 38 (43.7%) patients. On the first GIB, 147 endoscopies localized a bleeding source in 49 (30%), resulting in 24 (16.3%) endoscopic interventions. Of 45 lesions identified, arteriovenous malformations (AVMs) were the most common (22, 48.9%). A gastric or small bowel source (HR 2.8, p = 0.003) and an endoscopic intervention (HR 1.9, p = 0.04) predicted recurrent GIB. The proposed algorithm may reduce the number of endoscopic procedures by 45% and costs by 35%. CONCLUSIONS:Occult GIB is the most common presentation in CF-LVAD patients and carries the lowest diagnostic and therapeutic yield of endoscopy. Performing an intervention was among the strongest predictors of recurrent GIB. Our proposed algorithm may decrease the number of low-yield procedures and improve resource utilization.

OBJECTIVES/OBJECTIVE:Our aim was to identify baseline characteristics associated with disease progression and malignant transformation in low-risk suspected intraductal papillary mucinous neoplasms (IPMNs). METHODS:This is a retrospective cohort study of prospectively maintained databases of pancreatic cysts at 3 international, academic institutions. Five hundred fifty-nine adult patients with clinically suspected asymptomatic IPMN evaluated by radiologic studies or endoscopic ultrasound between 2003 and 2013 without worrisome features and under surveillance for 12 months or longer were included. We evaluated the relationship of baseline demographics and cyst features to disease progression (size increase, development of worrisome features, or high-grade dysplasia/cancer). RESULTS:After a median of 44 months follow-up, 269 (48%) patients experienced cyst size increase, 68 (12%) developed worrisome features, and 11 (2%) developed high-grade dysplasia/cancer. In multivariable Cox-regression analysis, no baseline characteristics were associated with size increase. An initial cyst size of 2 cm or greater, multifocality, history of prostate cancer, and smoking were the strongest predictors of development of new worrisome features. Univariable analysis found male sex, diabetes, and recent weight loss associated with development of high-grade dysplasia/cancer. CONCLUSIONS:Our study demonstrates that low-risk suspected IPMNs carry a small but clinically relevant risk of disease progression and provides data on baseline characteristics that may help in risk stratification.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is the standard of care for tissue sampling of solid lesions adjacent to the GI tract. Fine needle biopsy (FNB) may provide higher diagnostic yield with fewer needle passes. The aim of this study was to assess the difference in diagnostic yield between FNA and FNB. METHODS: This is a multicenter, prospective randomized clinical trial from six large tertiary care centers. Patients referred for tissue sampling of solid lesions were randomized to either FNA or FNB of the target lesion. Demographics, size, location, number of needle passes, and final diagnosis were recorded. RESULTS: After enrollment, 135 patients were randomized to FNA (49.3%) and 139 patients were randomized to FNB (50.7%).The following lesions were sampled: mass (n=210; 76.6%), lymph nodes (n=46, 16.8%), submucosal tumors (n=18, 6.6%). Final diagnosis was malignancy (n=192, 70.1%), reactive lymphadenopathy (n=30, 11.0%), and spindle cell tumors (n=24, 8.8%). FNA had a diagnostic yield of 91.1% compared to 88.5% for FNB (p=0.48). There was no difference between FNA and FNB when stratified by the presence of on-site cytopathology or by type of lesion sampled A median of 1 needle pass was needed to obtain a diagnostic sample for both needles. CONCLUSION: FNA and FNB obtained a similar diagnostic yield with a comparable number of needle passes. Based on these results, there is no significant difference in the performance of FNA compared to FNB in the cytological diagnosis of solid lesions adjacent to the GI tract. (ClincalTrials.gov identifier: NCT01698190).

BACKGROUND & AIMS/OBJECTIVE:It is a challenge to detect malignancies in biliary strictures. Various sampling methods are available to increase diagnostic yield, but these require additional procedure time and expertise. We evaluated the combined accuracy of fluorescence in situ hybridization (FISH) and polymerase chain reaction-based DNA mutation profiling (MP) of specimens collected using standard brush techniques. METHODS:We performed a prospective study of 107 consecutive patients treated for biliary strictures by endoscopic retrograde cholangiopancreatography from June 2012 through June 2014. We performed routine cytology and FISH analyses on cells collected by standard brush techniques, and analyzed supernatants for point mutations in KRAS and loss-of-heterozygosity mutations in tumor-suppressor genes at 10 loci (MP analysis was performed at Interpace Diagnostics). Strictures were determined to be nonmalignant based on repeat image analysis or laboratory test results 12 months after the procedure. Malignant strictures were identified based on subsequent biopsy or cytology analyses, pathology analyses of samples collected during surgery, or death from biliary malignancy. We determined the sensitivity and specificity with which FISH and MP analyses detected malignancies using the exact binomial test. RESULTS:Our final analysis included 100 patients; 41% had biliary malignancies. Cytology analysis identified patients with malignancies with 32% sensitivity and 100% specificity. Addition of FISH or MP results to cytology results increased the sensitivity of detection to 51% (P < .01) without reducing specificity. The combination of cytology, MP, and FISH analyses detected malignancies with 73% sensitivity (P < .001). FISH identified an additional 9 of the 28 malignancies not detected by cytology analysis, and MP identified an additional 8 malignancies. FISH and MP together identified 17 of the 28 malignancies not detected by cytology analysis. CONCLUSIONS:Addition of FISH and mutation analyses to cytology analysis significantly increased the level of sensitivity with which we detected malignancy in biliary strictures, with 100% specificity. These techniques can be performed using standard brush samples collected during endoscopic retrograde cholangiopancreatography, with mutations detected in free DNA in supernatant fluid of samples. The tests are complementary and therefore should be used sequentially in the diagnostic evaluation of biliary strictures.

Background and study aims Staple-line leaks occur in 1 % - 7 % of patients who undergo sleeve gastrectomy, and can be challenging to treat. The success of endoscopic approaches decreases as leaks develop into chronic sinus tracts. Endoscopic septotomy has been used to facilitate healing of refractory leaks by incision and enlargement of the tract to allow direct communication with the gastric lumen and internal drainage. Patients and methods We reviewed the technique and outcomes among patients who underwent endoscopic septotomy at two centers for the management of sleeve gastrectomy-associated gastric fistulas and perigastric collections refractory to occlusive endoscopic therapies. Results Nine patients underwent endoscopic septotomy at a mean of 8.6 weeks after leak diagnosis, following failure of percutaneous and conventional endoscopic modalities. Perigastric collections ranged from 3 cm to 10 cm in size. The mean procedure time for endoscopic septotomy was 87.2 minutes. Multiple endoscopic septotomy procedures (mean 2.3, range 1 - 4) were required to achieve radiological resolution. The mean follow-up period was 21.2 weeks, and all nine patients achieved symptom resolution without the need for surgery. Bleeding at the time of endoscopic septotomy occurred in three patients, and was managed with endoscopic clips and did not require transfusion. No other adverse events or delayed complications were recorded. Conclusions Endoscopic septotomy appears to be a safe and effective technique for the management of sleeve gastrectomy-associated fistulae and collections, including those refractory to other endoscopic and percutaneous methods.

BACKGROUND:Gastric cancer (GC) is the leading cause of cancer death among Korean Americans. Prevention and early detection is improved by screening. METHODS:Between September 2013 and March 2015, ethnic Koreans age 40 or older without history or symptoms of GC and without upper endoscopy (UE) during previous 3 years were enrolled. Participants were offered screening with GC risk assessment followed by UE with biopsies. RESULTS:Risk assessment was provided to 146 participants (age 55.6 ± 8.3 years; 52.1% female; 92.5% uninsured), of whom 99 (67.8%) returned for UE. Undergoing UE was independently associated with family history of GC (OR 12.33, 95% CI:1.52-100.17), being a former smoker (6.68,1.42-31.32), and Hp-negative status (0.25,0.11-0.57). Among UE recipients, half (49.5%) had intestinal metaplasia (IM) only (n = 24), Hp only (n = 12), or both (n = 13). No case of GC was found. Adjusted for age, IM was independently associated with male sex (2.89,1.12-7.42), current Hp (2.90,0.99-8.51), unmarried status (single or divorced) (4.23,1.23-14.56). CONCLUSIONS:High prevalence of risk factors associated with gastric carcinogenesis including Hp infection and IM exists in Korean Americans who underwent upper endoscopic screening. Acceptance of GC screening is informed by personal risk factors. These findings support the need to improve access to screening UE among KAs.

OBJECTIVE:The purpose of this study was to assess risk of progression and rate of growth of presumed low-risk branch duct intraductal papillary mucinous neoplasms surveyed for more than 4 years. MATERIALS AND METHODS/METHODS:A keyword search of electronic medical charts was performed for the years 2001-2013. Cystic lesions that met the criteria for clinical branch duct intraductal papillary mucinous neoplasm, lacked baseline high-risk or worrisome features, and had more than 4 years of surveillance were included in this study. Two radiologists performed cyst size measurements to assess interreader variability. Cyst progression was defined either as 2-mm or greater or 20% or greater increase in diameter or as development of worrisome features. Kaplan-Meier curves were generated to evaluate cyst progression time and linear mixed models to evaluate growth rates. RESULTS:The search revealed 2423 patients with cystic pancreatic lesions. Among these patients 228 had imaging follow-up for 4 or more years, and 131 met the clinical criteria for branch duct intraductal papillary mucinous neoplasms. Among the 131 cysts, 73 (55.7%) progressed: 61 (46.6%) increased in size, 10 (7.6%) increased in size and developed worrisome features, and two (1.5%) developed worrisome features only. Of the 71 cysts that increased in size, 50 (70.4%) did so within the first 5 years, and 21 (29.6%) grew after 5 years. No patient had adenocarcinoma. There was no significant difference in growth rate based on cyst size within the first 50 months. After 50 months, cysts larger than 20 mm continued to increase in size (p < 0.05) and had faster growth rates. CONCLUSION/CONCLUSIONS:Among presumed low-risk branch duct intraductal papillary mucinous neoplasms, most increased in size, approximately 30% after 5 years. Cysts with baseline size larger than 20 mm continued to grow beyond 5 years at a faster rate.

Asymptomatic pancreatic cysts are a common clinical problem but only a minority of these cases progress to cancer. Our aim was to compare the accuracy to detect malignancy of the 2015 American Gastroenterological Association (AGA), the 2012 International Consensus/Fukuoka (Fukuoka guidelines [FG]), and the 2010 American College of Radiology (ACR) guidelines.We conducted a retrospective study at 3 referral centers for all patients who underwent resection for an asymptomatic pancreatic cyst between January 2008 and December 2013. We compared the accuracy of 3 guidelines in predicting high-grade dysplasia (HGD) or cancer in resected cysts. We performed logistic regression analyses to examine the association between cyst features and risk of HGD or cancer.A total of 269 patients met inclusion criteria. A total of 228 (84.8%) had a benign diagnosis or low-grade dysplasia on surgical pathology, and 41 patients (15.2%) had either HGD (n = 14) or invasive cancer (n = 27). Of the 41 patients with HGD or cancer on resection, only 3 patients would have met the AGA guideline's indications for resection based on the preoperative cyst characteristics, whereas 30/41 patients would have met the FG criteria for resection and 22/41 patients met the ACR criteria. The sensitivity, specificity, positive predictive value, negative predictive value of HGD, and/or cancer of the AGA guidelines were 7.3%, 88.2%, 10%, and 84.1%, compared to 73.2%, 45.6%, 19.5%, and 90.4% for the FG and 53.7%, 61%, 19.8%, and 88% for the ACR guidelines. In multivariable analysis, cyst size >3 cm, compared to ≤3 cm, (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11, 4.2) and each year increase in age (OR = 1.07, 95% CI = 1.03, 1.11) were positively associated with risk of HGD or cancer on resection.In patients with asymptomatic branch duct-intraductal papillary mucinous neoplasms or mucinous cystic neoplasms who underwent resection, the prevalence rate of HGD or cancer was 15.2%. Using the 2015 AGA criteria for resection would have missed 92.6% of patients with HGD or cancer. The more "inclusive" FG and ACR had a higher sensitivity for HGD or cancer but lower specificity. Given the current deficiencies of these guidelines, it will be important to determine the acceptable rate of false-positives in order to prevent a single true-positive.

Significant advances have been made in the last few years in the technologies for sampling pancreatic masses, and in the understanding of the biology of pancreatic cancer. Better and more targeted treatments are likely to become available. Because most pancreatic cancers are likely to remain unresectable at diagnosis, high-quality, high-cellularity specimens are essential. A tailored approach that considers indication, location, and treatment possibilities needs to be taken before embarking on a pancreatic biopsy. Because the demand from oncologists and patients for increasingly personalized therapy is likely to grow, optimal sampling beyond diagnostic accuracy is likely to become increasingly critical.