Randomized controlled trial comparing the Franseen needle with the Fork-tip needle for EUS-guided fine-needle biopsy.

BACKGROUND AND AIMS: EUS-guided FNA primarily provides cytologic samples. EUS-guided fine-needle biopsy (FNB) with needles that provide histologic specimens may enhance diagnostic yield and facilitate accessory tissue staining. Several different needle designs are currently available and design superiority is unknown. We designed a randomized controlled trial to compare 2 commonly used EUS-FNB needles in their ability to provide histologic tissue samples (primary endpoint) and to reach an accurate diagnosis (secondary endpoint). METHODS: A total of 150 lesions from 134 patients (November 2018 to June 2019) were randomized 1:1 between biopsy with a Franseen needle and a Fork-tip needle. The groups were compared regarding the quality of the tissue samples and diagnostic accuracy. RESULTS: Of 150 lesions, 75 were pancreatic and 75 were other solid lesions in and around the GI tract. There was no statistically significant difference between the Franseen needle and the Fork-tip needle in the yield of adequate histologic samples, 71 of 75 (94.7%) versus 72 of 75 (96%), (P = 1.00), an absolute difference of -1.3% (95% confidence interval [CI], -8.1% to 5.4%). The 2 groups were similar in the diagnostic accuracy of histologic analysis, 64 of 75 (85.3%) versus 68 of 75 (90.7%) (P = .45), absolute difference -5.4% (95% CI, -15.7% to 5%); and in the diagnostic accuracy of combined cytologic and histologic analysis, 65 of 75 (86.7%) versus 69 of 75 (92%) (P = .43), absolute difference -5.3% (95% CI, -15.2% to 4.5%). CONCLUSIONS: There was no significant difference in the performance of the Franseen needle versus the Fork-tip needle. Both needles achieved a high yield of histologic tissue samples and high diagnostic accuracy. (Clinical trial registration number: NCT03672032.).

Long-Term Outcomes of Endoscopic Papillectomy for Ampullary Adenomas.

BACKGROUND AND AIMS: Endoscopic papillectomy is a safe and effective treatment for ampullary adenomas and has mostly replaced surgical local resection. Recent data have discussed the role of endoscopic removal of laterally spreading adenomas associated with ampullary adenomas. We evaluated our long-term results of endoscopic papillectomy for ampullary adenomas. METHODS: We retrospectively analyzed patients who underwent endoscopic papillectomy of biopsy-proven adenomas at our tertiary center between 1994 and 2017. Clinical success was defined as complete excision of an adenoma with no evidence of recurrence during follow-up, no evidence of cancer, and without the need for surgery. RESULTS: A total of 161 patients (73M/88F) with a mean age of 61 (range 19-93) were included. Mean adenoma size was 20 mm (range 5-70). In total, 114/161 patients continued endoscopic surveillance for a minimum of 6 months with a median follow-up of 30 months (range 6-283). Recurrent adenomas were diagnosed in 8 patients (7%) after a median of 36 months (range 12-138). Clinical success was 83%; 35 laterally spreading adenomas were treated, which were larger than adenomas confined to the papilla (mean size 38 mm vs 15 mm, P < 0.05) and required more piecemeal resections (77% vs 15%, P < 0.05). However, no difference was found in recurrence rates between the two groups (8% vs 4%, P = 0.26); 24/161 (15%) of patients had adverse events including bleeding (6%) and pancreatitis (7%). CONCLUSIONS: Endoscopic papillectomy is a safe and effective treatment for ampullary adenomas, including laterally spreading ones. Long-term surveillance demonstrates low recurrence rates at expert centers.

EUS-guided gallbladder drainage with a lumen-apposing metal stent versus endoscopic transpapillary gallbladder drainage for the treatment of acute cholecystitis (with videos).

BACKGROUND AND AIMS: There is an evolving role for EUS-guided transmural gallbladder (GB) drainage. Endoscopic transpapillary GB drainage is a well-established, nonoperative treatment for acute cholecystitis. We compared the outcomes of 78 cases of EUS-guided versus transpapillary GB drainage at a single, U.S.-based, high-volume endoscopy center. METHODS: This was a retrospective analysis performed from May 2013 to January 2018, identified from a database of nonoperative patients with acute cholecystitis. Both electrocautery-enhanced and nonelectrocautery-enhanced lumen-apposing metal stents were used. For transpapillary drainage, guidewire access was obtained and then a transpapillary 7F × 15-cm double-pigtail plastic stent was placed. RESULTS: In patients who had successful transpapillary or transmural drainage, demographics data were similar. Technical success was observed in 39 of 40 patients (97.5%) who underwent first attempt at EUS-guided drainage versus 32 of 38 patients (84.2%) for first-attempt transpapillary drainage (adjusted odds ratio, 9.83; 95% confidence interval, .93-103.86). Clinical success was significantly higher with EUS drainage in 38 of 40 patients (95.0%) versus transpapillary drainage in 29 of 38 patients (76.3%) (adjusted odds ratio, 7.14; 95% confidence interval, 1.32-38.52). Recurrent cholecystitis was lower in the EUS-guided drainage group (2.6% vs 18.8%, respectively; P = .023) on univariate analysis but only trended to significance in a multiple regression model. Duration of follow-up, reintervention rates, hospital length of stay, and overall adverse event rates were similar between groups. CONCLUSIONS: EUS-guided GB drainage results in a higher clinical success rate compared with transpapillary drainage and may be associated with a lower recurrence rate of cholecystitis. However, transpapillary drainage should be considered as the first-line treatment for patients who are surgical candidates but require temporizing measures or require an ERCP for alternative reasons.

Outcomes of Infected versus Symptomatic Sterile Walled-Off Pancreatic Necrosis Treated with a Minimally Invasive Therapy.

Background/Aims: Acute pancreatitis complicated by walled-off necrosis (WON) is associated with high morbidity and mortality, and if infected, typically necessitates intervention. Clinical outcomes of infected WON have been described as poorer than those of symptomatic sterile WON. With the evolution of minimally invasive therapy, we sought to compare outcomes of infected to symptomatic sterile WON. Methods: We performed a retrospective cohort study examining patients who were undergoing dual-modality drainage as minimally invasive therapy for WON at a high-volume tertiary pancreatic center. The main outcome measures included mortality with a drain in place, length of hospital stay, admission to intensive care unit, and development of pancreatic fistulae. Results: Of the 211 patients in our analysis, 98 had infected WON. The overall mortality rate was 2.4%. Patients with infected WON trended toward higher mortality although not statistically significant (4.1% vs 0.9%, p=0.19). Patients with infected WON had longer length of hospitalization (29.8 days vs 17.3 days, p<0.01), and developed more spontaneous pancreatic fistulae (23.5% vs 7.8%, p<0.01). Multivariate analysis showed that infected WON was associated with higher odds of spontaneous pancreatic fistula formation (odds ratio, 2.65; 95% confidence interval, 1.20 to 5.85). Conclusions: This study confirms that infected WON has worse outcomes than sterile WON but also demonstrates that WON, once considered a significant cause of death, can be treated with good outcomes using minimally invasive therapy.

The ASGE grading system for ERCP can predict success and complication rates in a tertiary referral hospital.

BACKGROUND: The utility of the American Society for Gastrointestinal Endoscopy (ASGE) grading scale assessing complexity of endoscopic retrograde cholangiopancreatography (ERCP) has not been evaluated in clinical practice. METHODS: Patients that underwent ERCP between January 2015 and December 2015 were included. Procedural difficulty was graded according to the grading system proposed by the ASGE workshop. Technical success rates and complications were recorded. RESULTS: A total of 1355 ERCPs were performed on 934 patients. Patients were equally divided with respect to gender and had a mean age of 58 years (range 29-86). 391 cases were grade 1, 2 (29%), 695 were grade 3 (51%), and 269 were grade 4 (20%). Altered anatomy was observed in 88% of grade 4 patients. Cannulation was achieved in 98% of cases graded 1-3 and in 88% of cases graded 4 (p < 0.05). Complications were recorded in 10% of all cases with post-ERCP pancreatitis (5.4%) and procedure-related bleeding (1.5%) being the more common ones. No statistically significant difference was noted between the groups with regard to complications. Three perforations were seen in grade 1-3 cases (0.3%) compared to 4 cases in grade 4 cases (1.5%), (p = 0.01). CONCLUSION: The grading system proposed by the ASGE workshop can aid in predicting cannulation success and perforation rates in ERCP. Based on this retrospective study, the most complex ERCP procedures can be achieved with encouraging rates of success. There is a need to validate our study with prospective ones performed in other high-volume centers.

Endoscopic findings and esophageal cancer incidence among Fanconi Anemia patients participating in an endoscopic surveillance program.

BACKGROUND AND AIMS: The primary clinical characteristics of Fanconi Anemia (FA) include typical physical features, progressive bone marrow failure, and an increased incidence of neoplasms, including esophageal carcinoma. Currently, there are no data regarding endoscopic findings or the interval time to malignancy in these patients. Data about the contribution of Human Papilloma Virus (HPV) to esophageal carcinoma is conflicting. Our objective is to document the upper gastrointestinal (GI) findings at baseline, document cancer incidence, and evaluate the role of HPV among these cancers. METHODS: We reviewed endoscopic and clinical data of FA subjects who participated in active surveillance before cancer diagnosis. Incident esophageal cancers were stained for HPV p16 protein. RESULTS: Eight FA patients were included (men 62.5%; median age at first endoscopy 20 years, median endoscopies number: 5.5). At baseline, 8/8 had endoscopic evidence for reflux esophagitis. In 3/8 the reflux esophagitis was mild and in 5/8 it was moderate or severe. During the follow up time (median time 4.5 years 2/8 developed Barrett's esophagus and 2/8 patients had incident esophageal squamous cell carcinoma during follow up, at intervals of eight and eighteen months from the previous upper endoscopy. Both cancers stained negative for HPV P16. CONCLUSIONS: FA subjects have both an extremely high risk for esophageal cancer within short intervals and a very high prevalence of reflux esophagitis with various severities. Active surveillance programs in specialized centers including annual upper endoscopies should be considered in these patients.

The microbiology of infected pancreatic necrosis in the era of minimally invasive therapy.

We aimed to determine the microbiology of infected walled-off pancreatic necrosis (WON) in an era of minimally invasive treatment, since current knowledge is based on surgical specimens performed over two decades ago. We retrospectively analyzed a prospectively maintained database of patients who were treated for symptomatic WON using combined endoscopic and percutaneous drainage between 2008 and 2017. Aspirates from WON at initial treatment were evaluated. One hundred eighty-two patients were included with a mean age of 56 of whom 67% were male. Culture results were obtained at a median of 45 days from onset of acute pancreatitis of which 41% were infected. Candida spp. accounted for 27%; yet, multidrug-resistant organisms were found in only five patients. Approximately 64% were transferred to our institution for continuation of care. Of those, 55% were infected, most frequently with Candida spp., Enterococcus spp., and coagulase-negative Staphylococcus. Patients seen and admitted initially at our institution had milder forms of pancreatitis, fewer comorbidities, and 85% had symptomatic sterile WON. Empiric antibiotic use successfully predicted infection 70% of the time. Multivariate analysis demonstrated that elderly age, severity of pancreatitis, and prior use of antibiotics were indicators of infection. Necrotic pancreatic tissue remains sterile in the majority of cases treated with minimally invasive therapy, enabling judicious selection of antibiotics. Candida and Enterococcus spp. were common. Patients at highest risk for infection were previously treated with antibiotics and those transferred from outside institutions.

Endoscopic ultrasound-guided entero-enterostomy for the treatment of afferent loop syndrome: a multicenter experience.

BACKGROUND: Afferent loop syndrome (ALS) is traditionally managed surgically and, more recently, endoscopically. The role of endoscopic ultrasound-guided entero-enterostomy (EUS-EE) has not been well described. The aim of this study was to assess the technical and clinical success and safety of EUS-EE. METHODS: This was a multicenter, retrospective series at six centers in patients with ALS treated by EUS-EE. Data on patients treated with enteroscopy-assisted luminal stenting (EALS) at a single center were also collected. RESULTS: 18 patients (mean age 64.2 years, 72 % post-pancreaticoduodenectomy, 10 female) underwent EUS-EE. The most common symptoms were vomiting (27.8 %) and jaundice (33.3 %). Clinical success included resolution of symptoms in 88.9 % and improvement to allow hospital discharge in 11.1 %. Technical success was achieved in 100 % of cases, with a mean procedure time of 29.7 minutes. The most common procedure was a gastro-jejunostomy (72.2 %). Three adverse events (16.7 %) occurred (two mild, one moderate). When compared with data on EALS, patients treated with EUS-EE needed fewer re-interventions (16.6 % vs. 76.5 %; P < 0.001). CONCLUSION: EUS-EE seems to be safe and effective in the treatment of ALS. Indirect comparison with EALS suggested that EUS-EE is associated with a reduced need for re-intervention.

Duration of antibiotic treatment after endoscopic ultrasound-guided drainage of walled-off pancreatic necrosis not affecting outcomes.

BACKGROUND AND AIM: Although society guidelines recommend a short course of antibiotics after drainage of walled-off necrosis (WON), the exact duration is unclear. METHODS: This is a retrospective review of patients with no prior antibiotic exposure who underwent dual-modality drainage (DMD) for sterile WON from 2008 to 2017. Patients were grouped into short duration (SD, ≤5 days) versus long duration (LD, >5 days). The main outcome was the frequency of recurrent infections. RESULTS: Sixty-one patients (25 in the SD group and 36 in the LD group) were included. Patients in the two groups had comparable age, comorbidities, and severity of disease (P = 0.89). Patients in the SD group were treated with antibiotics for a median of 3 days compared with 8.5 days in the LD group. There were no differences in recurrent febrile episodes within 30 days of procedure-44% of SD group versus 39% of LD (P = 0.69). There was also no difference in time to resolution of WON (64 days for both groups, P = 0.72) or duration of hospitalization post-DMD (SD 7.7 days versus LD 7.5 days, P = 0.42). Three cases of Clostridium difficile colitis were observed in the LD group. CONCLUSIONS: Longer course of antibiotics seems to have similar outcomes compared with shorter courses in patients with WON treated with DMD. Prolonged-course therapy may predispose to secondary infections like C. difficile colitis. A randomized controlled trial is needed to evaluate the role and duration of peri-procedural antibiotics after drainage of sterile WON.

Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival?

BACKGROUND: Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit clinically in metastatic pancreatic cancer (PC). The authors present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant treatment (Rx) after surgery with curative intent. METHODS: Patients with de novo resectable PC from January 2010 to December 2015 were identified from the authors' institutional database and registry. The study included only patients who received gem/tax as their initial Rx administered exclusively at the authors' institution with or without chemoradiation (CRTx). Survival analysis was performed using Kaplan-Meier methods, and prognostic factors were investigated by Cox proportional hazard modeling. RESULTS: Of 102 patients identified, 58 met the study criteria. The median age at diagnosis was 65 years, with 55% of the patients undergoing an R1 resection (margin ≤ 1 mm). Tumor characteristics included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx. Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up period was 51.2 months, and the observed median overall survival (OS) was 52 months [95% confidence interval (CI) 27.4-not reached]. The actuarial 5-year OS was 49% (95% CI 33.7-63.4%). In the multivariate analysis, an R1 resection and American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were negatively associated with OS, whereas administration of CRTx was positively associated with OS. CONCLUSIONS: Adjuvant gem/tax with or without CRTx is feasible, with a favorable OS. Future prospective studies of gem/taxane-based adjuvant Rx for PC are warranted.

New guidelines for use of endoscopic ultrasound for evaluation and risk stratification of pancreatic cystic lesions may be too conservative.

BACKGROUND: The role of EUS in managing asymptomatic pancreatic cystic lesions (PCLs) remains unresolved. We retrospectively evaluated EUS in risk stratification of PCLs when adhering to the most recent AGA guidelines. METHODS: Asymptomatic PCLs that were evaluated by EUS from January 2014 to December 2014 were retrospectively reviewed including associated cytology, fluid analysis, and relevant surgical pathology. Cross-sectional imaging reports were reviewed blindly by an expert radiologist using AGA risk stratification terminology. Accepted imaging high-risk features (HRF) included cyst diameter > 3 cm, dilated upstream pancreatic ducts, and a solid component in the cyst. RESULTS: We reviewed 125 patients who underwent EUS. Expert review of cross-sectional imaging resulted in a different interpretation 25% of the time including 1 malignant cyst. Ninety-three patients (75%) had no HRFs on cross-sectional imaging; 28 patients (22%) were diagnosed with 1 HRF and 4 patients (3%) had 2 HRFs. Adhering to AGA guidelines using 2 HRF as threshold for use of EUS, the diagnosis of malignant and high-risk premalignant lesions (including pancreatic adenocarcinoma, mucinous cystadenoma, neuroendocrine tumors, and IPMN with dysplasia) had a 40% sensitivity and 100% specificity. Had EUS been utilized based on a threshold of 1 HRF on imaging, malignant and high-risk premalignant lesions would have been identified with 80% sensitivity and 95% specificity. By adding EUS to radiographic imaging, the specificity for detecting carcinomas (p = 0.0009) and detection of all premalignant lesions (p = 0.003) statistically improved. Furthermore, EUS allowed 14 patients (11%) to avoid further surveillance by lowering their risk stratification. CONCLUSION: EUS remains an essential risk stratification modality for incidental PCLs. Current guideline suggestions of its utility may be too stringent. Our study justifies expert radiology review when managing PCLs. Further studies are required to identify the optimal approach to PCL management.

[THE FAILURE MODES AND EFFECTS ANALYSIS FACILITATES A SAFE, TIME AND MONEY SAVING OPEN ACCESS COLONOSCOPY SERVICE].

BACKGROUND: Failure modes and effects analysis (FMEA) is used for the identification of potential risks in health care processes. We used a specific FMEA - based form for direct referral for colonoscopy and assessed it for procedurerelated perforations. METHODS: Ten experts in endoscopy evaluated and computed the entire referral process, modes of preparation for the endoscopic procedure, the endoscopic procedure itself and the discharge process. We used FMEA assessing for likelihood of occurrence, detection and severity and calculated the risk profile number (RPN) for each of the above points. According to the highest RPN results we designed a specific open access referral form and then compared the occurrence of colonic perforations (between 2010 and 2013) in patients who were referred through the open access arm (Group 1) to those who had a prior clinical consultation (non-open access, Group 2). RESULTS: Our experts in endoscopy (5 physicians and 5 nurses) identified 3 categories of failure modes that, on average, reached the highest RPNs. We identified 9,558 colonoscopies in group 1, and 12,567 in group 2. Perforations were identified in three patients from the open access group (1:3186, 0.03%) and in 10 from group 2 (1:1256, 0.07%) (p = 0.024). Direct referral for colonoscopy saved 9,558 pre-procedure consultations and the sum of $850,000. CONCLUSIONS: The FMEA tool-based specific referral form facilitates a safe, time and money saving open access colonoscopy service. DISCUSSION: Our form may be adopted by other gastroenterological clinics in Israel.

Tumor lysis syndrome and malignant melanoma.

Tumor lysis syndrome (TLS) is an oncological emergency that results from massive cytolysis of malignant cells with a sudden release of their contents into the systemic circulation. TLS was rarely described in patients with malignant melanoma. In this article, we describe two patients with malignant melanoma who developed this syndrome. In one of them, the syndrome occurred spontaneously, and this is the second description of spontaneous tumor lysis in a patient with melanoma. We reviewed the previous patients with melanoma-induced TLS and discussed the manifestations and the pathophysiology of the syndrome in our patients.

Hairy cell leukemia presenting as multiple discrete hepatic lesions.

The involvement of hairy cell leukemia in the liver is in the form of portal and sinusoidal cellular infiltration. Here we describe the first case of hepatic hairy cell leukemia presenting as multiple discrete lesions, which was treated successfully. We suggest that in the investigation of discrete hepatic lesions in cases of cancer of unknown primary, hairy cell leukemia should be considered. The excellent response of hairy cell leukemia to therapy highlights the need for such a consideration.