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BACKGROUND AND AIM: The natural history of KRAS mutations in mucinous pancreatic cysts (MPCs) over time remains to be fully understood. The aim of this study was to examine the performance of DNA markers and assess changes of KRAS mutations over time. METHODS: Patients who underwent EUS-FNA of pancreatic cysts with at least two separate molecular analysis results were included in the study. We assessed the baseline patient and cyst characteristics, and DNA fluid analysis. The presence of either a KRAS mutation, or a CEA > 192 ng/ml was used as the diagnostic standard for mucinous cysts when surgical pathology was not available. RESULTS: A total of 933 pancreatic cyst fluid samples were collected, including 117 with≥2 FNAs. Examinations were performed over a median of 30 months (range 1–115 months). Forty-three (36%) had a mutant KRAS on the index analysis out of which 26 had a change in their KRAS status to the wild-type. Eighty-one (64%) had a wild-type KRAS on the index analysis out of which 18 had change in their KRAS status to mutant type. There was no significant difference in the index cyst characteristics, presence of symptoms, or main duct involvement based on KRAS status change. Increasing age was associated with a changing KRAS mutation status (p = 0.023). CONCLUSION: KRAS mutations gain and loss in pancreatic cyst fluid appears to occur frequently during long-term surveillance of MPCs. Age appears to be the only predictor for KRAS change over time.

Data on comparative efficacy of various available endoscopic ultrasound-guided liver biopsy (EUS-LB) needles are limited. We sought to compare the performance of a novel Franseen-tip 22G fine-needle biopsy (FNB) device to that of 19G needle platforms for liver parenchyma. Consecutive patients referred for EUS and suspected to have hepatic parenchymal disease underwent EUS-LB using different EUS needles and were included in this retrospective study. Two blinded expert liver pathologists independently reviewed and reported on: total number of tissue fragments, length of longest fragment, number of complete and incomplete portal tracts (CPT and IPT), and specimen adequacy. A 22G Franseen-tip needle (A) was used in 30 patients; 19G Tru-Cut needle (B) in 50 patients; 19G reverse beveled non-Tru-Cut needle (C) in 27 patients; and a 19G flexible non-Tru-Cut needle (D) in 28 patients. In the order of needles, A, B, C and D, > 10 tissue fragments were obtained in 100%, 6%, 82%, and 96% samples, the mean number of CPTs was 6.9; 3.0; 7.3; and 16.9, length of longest fragment was 3.8, 4. 7, 3.9, and 8.4 mm, and specimen adequacy was 66.7%, 46%, 82.1%, and 81.5%, respectively. A positive correlation was obtained between number of CPTs and length of longest fragment in samples accrued by 19G needles. EUS-LB specimens using 22G Franseen-tip needle appear highly fragmented, leading to inferior specimen adequacy compared to 19G non-Tru-Cut needles. We also report on using length of longest fragment as an additional criterion for specimen adequacy as it positively correlates with number of CPTs standard.

A dilated main pancreatic duct in the distal remnant after proximal pancreatectomy for intraductal papillary mucinous neoplasms (IPMN) poses a diagnostic dilemma. We sought to determine parameters predictive of remnant main-duct IPMN and malignancy during surveillance. Three hundred seventeen patients underwent proximal pancreatectomy for IPMN (Indiana University, 1991–2016). Main-duct dilation included those ≥ 5 mm or “dilated” on radiographic reports. Statistics compared groups using Student’s T/Mann-Whitney U tests for continuous variables or chi-square/Fisher’s exact test for categorical variables with P

Endoscopic injection of cyanoacrylate into gastric varices may be performed by EUS-guided fine needle injection (EUS-FNI) or direct endoscopic injection (DEI). The aim of this study is to compare the rate of recurrent GV bleeding and adverse events between DEI and EUS-FNI for treatment of GV. In a single-center study, a retrospective cohort of patients with actively/recently bleeding or high-risk GV treated with DEI were compared with a prospective cohort of similar patients treated with EUS-FNI. Repeat endoscopy after index treatment was performed 3 months later or earlier if rebleeding occurred. The main outcomes assessed were rates of GV or overall rebleeding and adverse events. Forty patients (mean age 57.2 ± 9.1 years, 73% male) and 64 patients (mean age 58.0 ± 12.5 years, 52% male) underwent DEI and EUS-FNI, respectively. Compared to the DEI group, the frequency of isolated gastric varices type 1 (IGV1) were higher (p

Gastric variceal bleeding is associated with significant morbidity and mortality and limited endoscopic therapeutic options. The aim of this study was to evaluate the short- and long-term efficacy and safety of endoscopic therapy with 2-octyl-cyanoacrylate in patients with gastric variceal bleeding. A single-center retrospective review of patients receiving endoscopic therapy for gastric variceal hemorrhage. Patient demographics, laboratory, and procedural data were collected. Patients were followed to death, liver transplantation, or last follow-up. Success rates were defined as immediate control of bleeding; early re-bleeding (1–7 days), short-term re-bleeding (1–12 weeks), overall survival, and serious procedure complications. A total of 41 patients (39 with cirrhosis) underwent 54 cyanoacrylate injections during study period. Mean age was 57 and 73 % were males. Twenty-four (58.5 %) patients had failed or were deemed ineligible for transjugular intra-hepatic portosystemic shunt, and 5 % were done for primary prophylaxis. Immediate hemostasis was achieved in five active bleeders. During a median survival time of 117 days, early re-bleeding was seen in 1 (2.4 %), short-term re-bleeding in five patients (12 %), and varices were eradicated in 15 (46.8 %) patients on follow-up. Mean MELD score at the time of the first injection was 17.1 ± 7.8. Mean volume injected was 3.4 cc and median number of varices injected per session was one. Eight patients died during the long-term follow-up: metastatic cancer (2), infections (3), liver failure (1), and re-bleeding (2). There were no serious procedure-related complications. Endoscopic cyanoacrylate therapy appears effective and safe for treatment of patients with bleeding from gastric varices or high-risk stigmata.

Main pancreatic duct (MPD) involvement is a well-demonstrated risk factor for malignancy in intraductal papillary mucinous neoplasm (IPMN). Preoperative radiographic determination of IPMN type is heavily relied upon in oncologic risk stratification. We hypothesized that radiographic assessment of MPD involvement in IPMN is an accurate predictor of pathological MPD involvement. Data regarding all patients undergoing resection for IPMN at a single academic institution between 1992 and 2012 were gathered prospectively. Retrospective analysis of imaging and pathologic data was undertaken. Preoperative classification of IPMN type was based on cross-sectional imaging (MRI/magnetic resonance cholangiopancreatography (MRCP) and/or CT). Three hundred sixty-two patients underwent resection for IPMN. Of these, 334 had complete data for analysis. Of 164 suspected branch duct (BD) IPMN, 34 (20.7 %) demonstrated MPD involvement on final pathology. Of 170 patients with suspicion of MPD involvement, 50 (29.4 %) demonstrated no MPD involvement. Of 34 patients with suspected BD-IPMN who were found to have MPD involvement on pathology, 10 (29.4 %) had invasive carcinoma. Alternatively, 2/50 (4 %) of the patients with suspected MPD involvement who ultimately had isolated BD-IPMN demonstrated invasive carcinoma. Preoperative radiographic IPMN type did not correlate with final pathology in 25 % of the patients. In addition, risk of invasive carcinoma correlates with pathologic presence of MPD involvement.

Limited data are available regarding the natural history of patients undergoing primary surveillance for intraductal papillary mucinous neoplasm (IPMN). We hypothesize that symptoms, radiologic characteristics, and cytopathology will predict cancer risk during surveillance. Between March 2002 and March 2010, 522 patients were diagnosed with IPMN at a single, high-volume institution. Low versus high oncologic risk was stratified prospectively. Patients with under 3 months of surveillance were excluded. Two hundred ninety-two patients underwent primary surveillance for IPMN. Two hundred forty-four (84%) were classified as low-risk IPMN. Mean surveillance duration was 35 (4–99) months. Thirty (12%) patients initially stratified as low-risk developed a new indication for pancreatic resection. Only 28 underwent resection, and pathologic tissue analysis revealed 27 (96%) low-grade IPMN and one (4%) high-grade dysplastic IPMN. Overall, two (1%) patients initially determined to be low-risk developed invasive cancer. Forty-eight (16%) patients stratified as high-risk IPMN were initially managed nonoperatively. Of the 13 (27%) high-risk patients that died during follow-up, two (15%) died from pancreatic cancer. Progression to pancreatic cancer during surveillance for low-risk IPMN was rare. Current indications for resection did not forecast malignancy. Poor operative candidates with high-risk IPMN progressed to invasive cancer more commonly, though a substantial portion succumbed to non-IPMN-related death.

Data on the utility of endoscopic ultrasound-guided Trucut biopsy (EUS-TCB) for suspected gastrointestinal mesenchymal tumor (GIMT) are limited. This study aimed to determine the diagnostic yield and complications from EUS-TCB for GIMT. Consecutive patients with suspected upper gastrointestinal or rectal GIMT from the muscularis propria with a maximal diameter of 20 mm or more were enrolled in a prospective, single-center cohort. An EUS-TCB was performed when on-site fine-needle aspiration (FNA) cytology review of the lesion was deemed suboptimal. Gastrointestinal stromal tumor (GIST) and leiomyoma were defined by the presence or absence of positive immunochemistry (IC) for c-kit, respectively. All GIMTs with a nondiagnostic IC were considered as unspecified. The outcomes assessed included diagnostic pathologic and IC yield (when tested) and procedural complications. In this study, 38 patients (24 women; median age, 62 years) with suspected GIMT (median maximal diameter, 42 mm; range, 20–120 mm) in the esophagus (n = 6), stomach (n = 28), duodenum (n = 3), or rectum (n = 1) underwent EUS-TCB without complications. Final diagnoses included GIST for 20 patients, leiomyoma for 13 patients, unspecified GIMT for 3 patients, and unknown disorder for 2 patients. An EUS-FNA was performed for 33 (87%) of the 38 patients, a diagnostic final cytology for 25 (76%) of 33 patients, and an FNA-IC for 12 (50%) of 24 patients. The EUS-TCB (median, 3 passes; range, 1–8 passes) obtained a visible tissue specimen in 37 (97%) of the 38 patients, with a median overall maximal fragment length of 3.5 mm (range, 0–15 mm). The diagnostic final TCB histology and TCB-IC were obtained, respectively, in 79 and 97% of the samples tested. In this cohort, EUS-TCB provided diagnostic histology and IC for 79 and 97% of the patients, respectively. For the initial biopsy of GIMT, EUS-TCB may be considered an acceptable alternative to EUS-FNA.

Tuberculosis is the most widespread and lethal infectious disease affecting humans. Immunization of mice with plasmid DNA constructs encoding one of the secreted components of Mycobacterium tuberculosis, antigen 85 (Ag85), induced substantial humoral and cell-mediated immune responses and conferred significant protection against challenge with live M. tuberculosis and M. bovis bacille Calmette-Guerin (BCG). These results indicate that immunization with DNA encoding a mycobacterial antigen provides an efficient and simple method for generating protective immunity and that this technique may be useful for defining the protective antigens of M. tuberculosis, leading to the development of a more effective vaccine.