GI Pathologists Research Articles

Ex vivo experimental study on the Thulium laser system: new horizons for interventional endoscopy (with videos).

Background and study aims The Thulium laser system (TLS) is an emerging interventional tool adopted in many surgical specialties. Its 2.0-μm wavelength allows precise coagulation (0.2 – 0.4 mm in depth) and cutting, limiting the possibilities of collateral injuries. We tested the impact of the TLS for gastric endoscopic submucosal dissection (ESD) and per oral endoscopic myotomy (POEM) ex vivo in pigs. Materials and methods Ex vivo porcine stomach and esophagus models underwent 2 POEMs, and 3 ESDs (mean diameter 3.5 cm) with TLS using a 272-µm and a 365-µm thick optical fibers. Both continuous and pulsed laser emission were evaluated. Subsequent histopathological analysis was performed by an expert GI pathologist on the whole porcine models. Results Complete POEMs and gastric ESDs were successfully performed in all cases in 30 to 70 and 15 to 20 minutes. Both optical fibers were equally effective and precise. The best power output for mucosal incision was 25 to 30 W during ESD and 25 W for POEM using continuous laser emission. During submucosal dissection and tunneling the favorite power output was 20 W and 15 to 20 W, respectively, operating in continuous mode. No transmural perforation occurred throughout the operations and histopathology confirmed the absence of accidental muscular layer damage. Conclusions The TLS stands out as a precise and manageable instrument in ex vivo models. This technique appears to be a promising tool for advanced interventional endoscopy.

Su1684 70% of Average-Risk Persons of Screening Age Have Colon Adenomas - ADR in a Community Cohort With Biopsies Read by Academic Gi Pathologists

Su1684 70% of Average-Risk Persons of Screening Age Have Colon Adenomas - ADR in a Community Cohort With Biopsies Read by Academic Gi Pathologists

Predictors of Progression in Barrett's Esophagus with Low-Grade Dysplasia: Results from a Multicenter Prospective BE Registry.

Low-grade dysplasia (LGD) is a risk factor for progression in Barrett's esophagus (BE). Progression estimates however vary and predictors of progression are not well established. We aimed to assess predictors of progression in a multicenter BE-LGD cohort. All subjects with LGD (diagnosed by a GI pathologist) in a prospective BE registry were identified. Progression was defined development of HGD/EAC more than 12 months after index date of LGD diagnosis. Clinical, endoscopic factors and impact of histologic review by an independent panel of two GI pathologists were assessed as predictors of progression. Cox proportional hazard models were used to assess their association with risk of progression. 244 BE-LGD subjects met inclusion criteria. Their mean age was 63.2 years. 205 (84%) were males. The median follow up was 4.8 years. Fifty six patients were diagnosed with HGD/EAC in less than 12 months, while 14 progressed to HGD/EAC after 12 months, with an overall annual risk of progression of 1.2%. 29% of LGD subjects were downgraded to non-dysplastic and the remaining re-confirmed as LGD or indefinite dysplasia. The risk of progression in the reconfirmed LGD group was eight fold higher (hazards ratio: 7.6, 95% CI: 1.5-139.4) in a propensity score stratified model. In this large BE-LGD cohort, progression risk increased substantially when an additional panel of two expert GI pathologists re-confirmed a LGD diagnosis. These BE subjects may be candidates for endoscopic therapy. LGD was a marker of prevalent HGD/EAC in 18% of patients.

Su1916 - Efficacy of Ustekinumab for Induction and Maintenance of Histological Healing in patient's with Crohn’s Disease

Introduction Ustekinumab (UST) has been shown to induce and maintain clinical response and remission and to produce clinically meaningful endoscopic improvement in patients with moderate-severe Crohn’s disease (CD). Effects of UST on histologic CD activity were evaluated in a substudy of the induction (UNITI-1 and 2) and maintenance (IM-UNITI) Phase 3 studies. Method Biopsies were taken at induction baseline(I-Wk0), Wk8(I-Wk8), and maintenance Wk44(M-Wk44) from 3 sites (ileum, splenic flexure, rectum) and blindly scored by an expert GI pathologist (GDH) using the Global Histology Activity Score (GHAS1). At I-Wk0, pts received a single IV dose (UST 130 mg, UST~6 mg/kg, or PBO). At I-Wk8, UST induction responders were re-randomised to subcutaneous (SC) PBO, UST 90 mg q12w or UST 90 mg q8w. Histology data from 251 substudy pts with simple endoscopic score for CD (SES-CD)≥3 at I-Wk0 were eligible for analysis. The relationship between GHAS and SES-CD was evaluated by Spearman correlation. Histologic improvements were assessed within groups (UST, PBO) and between groups (UST vs. PBO, at I-Wk0, I-Wk8 and M-Wk44). Results Regional and overall GHAS were moderately correlated with SES-CD at all timepoints (r~0.6, p Conclusion Histologic and endoscopic disease activities were moderately correlated. Consistent with previously reported results, statistically significant histologic improvements were observed in pts induced with UST, but not PBO. Trends for greater and continued histologic improvement were observed in pts who received UST 90 mg q8w maintenance. Disclosure of Interest K Li Conflict with: Janssen R and D, D Chan Conflict with: Janssen R and D, P Pollack Conflict with: Janssen R and D, D Jacobstein Conflict with: Janssen R and D, C Brodmerkel Conflict with: Janssen R and D, C Gasink Conflict with: Janssen R and D, B Feagan: None Declared, W Sandborn: None Declared, P Rutgeerts: None Declared, G De Hertogh: None Declared

Prognostic value of CD8+CD45RO+ tumor-infiltrating lymphocytes (TIL) and PD-L1 in cholangiocarcinoma.

286 Background: Cholangiocarcinoma is a malignancy arising from the epithelial cells of the biliary tract with poor prognosis. TILs and PD-L1 have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Methods: Formalin-fixed paraffin-embedded tumor samples from 41 patients with resected and histologically verified cholangiocarcinoma between 1990 and 2015 were identified and immunohistochemically (IHC) stained with anti-CD8, anti-CD45RO and the anti-PDL1 mouse IgG1 (clone 5H1; Thompson) antibodies. Stained tumor samples were reviewed and enumerated by a GI pathologist. PD-L1 positivity was defined ≥ 5% of tumor cells with a minimum of 100 evaluable tumor cells. The association between expression of PDL1, CD8 or CD45RO and survival was investigated using Kaplan-Meier survival and COX proportional hazard regression analyses. Results: The median age of patients was 64 (41-85) with 53% male. 22%, 41% and 37% were stage I, II and III, respectively. CD8 was positive in 16 (39%), CD8CD45RO (memory CD8 cells) was positive in 5 (12%), and PD-L1 was positive in 19 (46%). With a median follow-up of 21.4 months, tumors with CD8+CD45RO+ TIL has better cancer specific survival (median: unreached vs 41.2mo, HR = 0.27, 95% CI: 0.09-0.83, P = 0.023) and overall survival (median: unreached vs 21.4mo, HR = 0.34, 95%CI: 0.14-0.82, P = 0.016) than CD45RO-. The expression of CD8 alone or PD-L1 in tumor was not associated with prognosis. Multivariate analysis showed that CD8+CD45RO+ TIL (HR = 0.13, 95% CI: 0.02-0.99, P = 0.049) as well as stage, adjuvant treatment and R0 resection (microscopically margin-negative) were independent predictors of OS. Conclusions: Presence of CD8 memory T cells (CD8+CD45RO+) in tumor microenvironment was associated with significant better clinical outcome, and the expression of PD-L1 on cholangiocarcinoma cells may suggest a potential therapeutic target of antiPD-L1 antibody therapy in cholangiocarcinoma.

Central validation of HER2 status to determine heterogeneity of marker expression in HER2-positive gastric cancer (GC).

12 Background: 10-20% of GC overexpress HER2, a membrane-bound receptor tyrosine kinase (RTK) which belongs to the epidermal growth factor receptor (EGFR) family. Drugs directed against HER2 have shown mixed success in the treatment of advanced GC. While trastuzumab, a monoclonal antibody addressing HER2 has been approved for 1st-line treatment of stage IV HER2+ GC, trastuzumab-emtansine failed to improve outcomes in 2nd-line and lapatinib, a small molecular RTK inhibitor of HER2 and EGFR was not effective in 1st- and 2nd-line. Until now, primary and secondary resistance against HER2-directed treatment of GC is not well understood. The VARIANZ study aims to assess mechanisms influencing efficacy of trastuzumab in HER2+ GC. Methods: In this multicenter study, patients who receive medical treatment for advanced GC are recruited in 31 sites. The HER2 status is verified centrally by two dedicated GI pathologists using immunohistochemistry (IHC, DCS, HI608C0I) and chromogenic-in-situ hybridization (CISH, Zytomed Systems, C-3022-40). Results: From May 2014 to August 2016, we have enrolled 316 patients in this ongoing project (72% male, median age 64 years). At present, 281 samples were fully characterized for the HER2 status. According to criteria from the Trastuzumab for Gastric Cancer (ToGA) study, 53 of 281 samples were characterized HER2+ by central testing. In 38 samples that were diagnosed as HER2+ by local pathologists the HER2 status could not be verified centrally. 7 HER2- probes in local testing were characterized as HER2+ by central testing. The overall deviation rate between local and central testing is 27%. HER2 gene amplification in HER2+ tumors with deviating local report (mean HER2/CEP17: 2.8 ± 0.9, range between 1.9 and 4.5) is lower compared to HER2+ tumors and confirmed local report (mean HER2/CEP17: 5.5 ± 2.6; range between 2.2 and 11.0; p = 0.014). Conclusions: HER2-expression in GC is heterogeneous and still not easy to assess. Variability between local and central HER2 assessment is significant. Robust biomarkers predicting response or resistance to HER2 and other target therapies are needed. Clinical trial information: NCT02305043.

Evaluation of Rosemont criteria for non-calcific chronic pancreatitis (NCCP) based on histopathology – A retrospective study

BackgroundRosemont classification for chronic pancreatitis has not been evaluated specifically in non-calcific chronic pancreatitis (NCCP) patients and to this date, it has not been correlated with the gold standard namely histopathology. ObjectiveTo assess the correlation of EUS Rosemont criteria for NCCP with histopathology from surgical specimens and evaluate the impact of age, sex, BMI, smoking and alcohol on Rosemont classification. MethodsAdult patients undergoing TPIAT for NCCP between July 2009 and January 2013 were identified from our institutional database. The presence or absence of standard and Rosemont (major and minor) criteria were determined by expert endosonographers using linear endosonography. Patients were categorized into normal, indeterminate and suggestive with CP based on Rosemont classification. Histology was obtained at time of TPIAT from the resected pancreas by wedge biopsy of head, body and tail. All histopathology were re-reviewed by a GI pathologist blinded to endosonographic features and clinical outcomes. Available pancreatic tissue was graded for severity of intralobular and perilobular pancreatic fibrosis by the Ammann classification system. Results50 patients with NCCP (42 females, mean age± SD = 37.9 ± 10.8) underwent TPIAT with preoperative EUS during the study period. Univariate analysis of features such as age, sex, BMI, smoking and alcohol history showed no significant difference between patients identified as normal and those identified as indeterminate/suggestive (p > 0.05). Rosemont “Normal” was poor in excluding CP as 5/9 patients (55.5%) had CP on histopathology. 25/26 patients (96.2%) with features “suggestive” of CP had evidence of CP on histopathology. 12/15 patients (80.0%) with “indeterminate” features had CP on histopathology. ConclusionsRosemont classification can be used independent of patient characteristics (age, sex and BMI) and environmental factors (smoking and alcohol exposure). In our cohort, Rosemont classification was strongly predictive of CP in patients with features “suggestive” of CP. However, “normal” Rosemont classification had poor correlation in this study. This is maybe due to lack of true comparator “normal” pancreas which cannot be obtained reasonably. The strength of agreement for diagnosis of CP was substantial between the standard and Rosemont criteria.

Prevalence of sessile serrated adenoma/polyp in hyperplastic-appearing diminutive rectosigmoid polyps

The American Society for Gastrointestinal Endoscopy recommends that distal colon hyperplastic lesions can be left in place without resection if adenomatous histology can be excluded with >90% negative predictive value. However, some lesions could be sessile serrated adenomas/polyps (SSA/Ps), which is also precancerous. The aim of this study was to describe the prevalence of SSA/Ps in hyperplastic-appearing diminutive rectosigmoid polyps. We prospectively placed 513 consecutive diminutive rectosigmoid polyps that appeared hyperplastic to an expert endoscopist in individual bottles for pathologic. Each polyp was examined by 3 expert GI pathologists. The prevalence of SSA/P in the study polyps ranged from .6% to 2.1%. The lowest negative predictive value found by the endoscopist for the combination of adenomas plus SSA/Ps was 96.7%. The prevalence of SSA/Ps in diminutive rectosigmoid hyperplastic-appearing polyps is very low. These results support the safety and feasibility of a "do not resect" policy for diminutive hyperplastic-appearing rectosigmoid polyps.

Diarrhea: Always Keep an Open Mind and Be a Skeptic

Background: Microscopic colitis is a well-known cause of chronic diarrhea and, when drug-related, is usually from proton pump inhibitors or non-steroidal anti-inflammatory drugs. To date, only 3 reports have been published on microscopic colitis from leflunomide. Here, we describe the first case of microscopic colitis associated with leflunomide use in North America. Case: description A 48-year-old woman with rheumatoid arthritis (RA) on leflunomide, was sent to our medical center for evaluation of chronic watery, non-bloody diarrhea. The diarrhea started 2 years prior and she described 8-16 episodes daily. Initial colonoscopy and histology were interpreted as ischemic colitis. Trials of prednisone and mesalamine yielded no improvement. Adalimumab, given for RA, resulted in transient improvement in diarrhea. One year later, while the patient was on adalimumab, diarrhea intensified and became associated with malaise and weight loss of 20 lb. Budesonide was added by her gastroenterologist but both adalimumab and budesonide were eventually discontinued due to lack of response. Repeat colonoscopy showed colitis sparing the rectum and again histology was interpreted as ischemic colitis. Magnetic resonance arteriography showed only age-related non-obstructive vascular changes. Upon referral, the patient noted spontaneous improvement in diarrhea; she was having 2-3 bowel movements a day and her only medication was leflunomide. Family history was notable for her brother having Crohn's disease. Physical exam and blood tests, including prometheus® inflammatory bowel disease and celiac panels were unremarkable. Repeat colonoscopy was unremarkable but biopsy specimens from the transverse and left colon showed collagenous colitis. Review of the prior biopsies by a GI pathologist showed collagenous colitis, albeit more severe than the pattern seen on last colonoscopy. The patient's diarrhea resolved after discontinuation of leflunomide. Conclusion: This is the first case report of leflunomide-related collagenous colitis in North America. Gastroenterologists and pathologists should have a high index of suspicion for microscopic colitis in patients with chronic non-bloody diarrhea even if they are not on medications recognized to cause microscopic colitis. Finally, it is always important to have an experienced pathologist review prior histologic material to avoid misdiagnosis.

Decreasing Eosinophilia Along the Esophageal Axis in Eosinophilic Esophagitis: Implications on Disease Pathogenesis

Introduction: Eosinophilic esophagitis is hypothesized to be an allergy-mediated condition in which eosinophils selectively migrate into esophageal mucosa in response to esophageal exposure to food antigens. As such, eosinophils would be expected to be present along the entire esophageal axis. However, there are currently no data on the most proximal extent of esophageal mucosal involvement. Mucosal impedance (MI) assesses esophageal epithelial integrity, with low MI values having previously been shown to correlate strongly with EoE activity. Employing MI, histology and endoscopic assessments, the aim of this prospective study was to determine the extent of eosinophilia along the esophageal axis in patients with EoE. Methods: Patients undergoing EGD for evaluation of dysphagia were enrolled. Biopsies were obtained at three different locations axially along the esophagus: 3 cm above SCJ (distal), 10 cm above SCJ (proximal), and at a region just inside the upper esophageal sphincter (“sub-UES”). Esophageal mucosa was assessed endoscopically and MI measurements were obtained at the same locations before biopsies. All endoscopies were performed by one investigator in a uniform fashion. Biopsies were subsequently examined by GI pathologists blinded to patient information. Results: 41 patients [median (IQR) age = 37 (29-46), BMI = 25.6 (21.5-29), 61% male, 98% white], 18 with EoE and 23 without EoE (controls), constituted the study population. Eosinophils were only present in those with EoE (Figure 1). Median (IQR) number of eosinophils was higher in the distal than in the proximal esophagus [40 (23.8-63.5) and 25 (17-43.5), respectively], with both areas showing characteristically low MI values (less than 2000 Ω). Importantly, eosinophil counts were significantly lower in the sub-UES region [median 0.5 (0-2)], which was confirmed by normal MI values (3000 Ω). A clear transition to normal epithelium was identified at 16-17 cm from the incisors, which was confirmed endoscopically, histologically, and by MI. Conclusion: There is a gradual decrease in eosinophil counts axially along the esophagus with a ‘transition zone” to normality at 16-17 cm from the incisors. Mucosal impedance values corroborate histologic and endoscopic findings. These results raise questions about the pathophysiologic basis of EoE and suggest that there are other unknown factors that may contribute to eosinophilic migration.

Significant Individual Variation Between Pathologists in the Evaluation of Colon Cancer Specimens After Complete Mesocolic Excision.

After the introduction of complete mesocolic excision, a new pathological evaluation of the resected colon cancer specimen was introduced. This concept has quickly gained acceptance and is often used to compare surgical quality. The grading of colon cancer specimens is likely to depend on both surgical quality and the training of the pathologist. The purpose of this study was to validate the principles of the pathological evaluation of colon cancer specimens. This was an exploratory study. The study was conducted in Aarhus, Denmark, and Leeds, United Kingdom. Colon cancers specimens were used. The agreement of gradings between participants was of interest. Four specialist GI pathologists and 2 abdominal surgeons evaluated 2 rounds of colon cancer specimens, each at 2 separate time points. Each round contained 50 specimens. After the first round, a protocol of detailed principles for the grading procedure was agreed on. Results from an experienced pathologist were considered as the reference results. In the first round, the distribution of gradings between participants showed substantial variation. In the second round, the variation was reduced. Intraobserver agreement was mostly fair to good, whereas interobserver agreement was frequently poor. This did not significantly change from round 1 to round 2. The small sample size of 100 specimens provided a very small number of specimens resected in the muscularis propria plane, which renders the evaluation of this group potentially unreliable. The evaluations were made on photos and not on fresh specimens. This study demonstrates significant variation in the pathological evaluation of colon cancer specimens. It demonstrates that it cannot be used in clinical studies, and care should be taken when comparing results between different hospitals.

PTU-033 Endoscopic Mucosal Resection of Adenomas and Sessile Serrated Polyps, is there a Difference in Complication Rates?

Introduction Introduction: within a regional, DGH based, EMR service, we evaluated whether there is a difference in the complication rate of EMR of adenomas and SSA/P’s. Methods Method: from January 2007 to February 2016 we prospectively collected data for a single endoscopist (a consultant gastroenterologist, within our institution), for EMR of all large (>19mm) non-pedunculated polyps. A standard EMR technique was used in all patients, a lifting solution consisting of colloid, methylene blue and adrenaline was injected into the submucosal plane. Appropriately lifting lesions were removed with the use of diathermy through a range of standard snare’s. A CONMED diathermy unit using Endocut setting was used for all EMR’s. Lesions were removed either en bloc or piecemeal dependent upon the safety of either resection technique. Following snare resection any residual polyp tissue was treated with APC. Following uncomplicated EMR’s patients were discharged home with two follow up telephone interviews with a sister in the endoscopy unit scheduled for day 1 and 14 post procedure assessing for complications. Adverse events recorded included perforation, late bleeding or admission. A “site check” was routinely performed at 3 months and if clear at 12 months following the EMR, to assess for recurrence. Histological analysis was carried out by a GI pathologist at our hospital, sessile serrated lesions were classified as per the WHO (2010) classification: 1 SSA/P’s without cytological dysplasia, SSA/P’s with cytological dysplasia, traditional serrated adenomas and hyperplastic polyps. Results A single endoscopist attempted 386 adenoma resections, completing 379 of these. 3 (0.8%) perforations were diagnosed. 20 (5.2%) late bleeds occurred in the adenoma group, 12 (3.1%) of patients with late bleeding required admission. Recurrence in the adenoma group was 10.9% at 12 months(249 patients have completed there 1 year follow up to date). During the same period the same endoscopist attempted the resection of 19 SSP’s. In this group 3 (16.7%) perforations were diagnosed, there was the same number of patients with delayed bleeding but only 2 (11.1%) patients required admission for bleeding. Recurrence of SSP’s at 12 months 0%(5 patients have completed their 1 year follow up colonoscopy to date). Conclusion Though a clear difference in size of the cohorts, our data demonstrates a strikingly higher rate of perforations in the SSP group. We note no significant difference in complication rates was observed in a large prospective, multicentre study of 2000 lesions. 2 References 1 Snover DC, et al . Serrated polyps of the colon and rectum. WHO Classification Tumours of Digestive System. 2010:160–165. 2 Pellise M, et al . EMR for large serrated lesions in comparison with adenomas: a prospective multicentre study of 2000 lesions. Gut online first, January 2016. Disclosure of Interest None Declared

OC-053 Lectin-Based Near infra-red Molecular Imaging for Dysplasia Detection in Barrett’s Oesophagus: An ex-vivo Study on Human Tissue

Introduction Detection of early neoplasia in Barrett’s oesophagus (BO) by white-light endoscopy is challenging due to the inconspicuous nature of dysplasia. Molecular imaging using fluorescently labelled wheat-germ agglutinin (WGA) is a promising tool as this topically applied imaging agent shows lower binding to dysplastic versus non-dysplastic BO. 1 However in an endoscopy setting, the detection of fluorescence in the blue/green range is limited by high-levels of tissue autofluorescence. This limitation can be overcome by using near infra-red (NIR) imaging. We aimed to assess in an ex-vivo model the feasibility of WGA-based NIR imaging for detection of dysplasia in BO. Methods we recruited patients with early BO-related neoplasia undergoing endoscopic mucosal resection (EMR). Freshly collected EMR specimens were sprayed with WGA-IR800CW and then imaged with a high-sensitivity NIR camera. Fluorescence images were captured and up to two punch biopsies were collected from each EMR under fluorescence guidance. The EMRs were paraffin embedded, cut every 2 mm and processed for histopathological assessment. Each section was scored by an expert GI pathologist every 1 mm to construct a pathology grid, which was manually co-registered with the fluorescence image. The mean fluorescence intensity (MFI) of cells in dysplastic and non-dysplastic areas was compared by the Wilcoxon matched-pairs signed rank test. Only EMR specimens with at least one dysplastic gland were included in the analysis. In addition, the MFI of punch biopsies taken from dysplastic and non-dysplastic areas was also compared by Mann-Whitney test. Results Ten patients were recruited at a single centre. A total of 18 EMR specimens and 33 punch biopsies were collected, of which 10 were dysplastic. In the whole EMR analysis, we found a significantly lower MFI for dysplastic versus non-dysplastic areas (P = 0.0012), in accordance with the reported reduced binding of WGA to neoplastic BO epithelium. Similarly, we found a nearly 2 fold reduction in the MFI of punch biopsies taken from dysplastic as compared to non-dysplastic (ND) areas (P = 0.0002) (Figure 1). Conclusion WGA-based NIR imaging is an effective method for differentiating dysplastic from non-dysplastic BO mucosa ex vivo , which reduces the effects of tissue autofluorescence. In-vivo studies are now required to test the efficacy of this method for detecting dysplasia during endoscopic surveillance. Reference 1 Bird-Lieberman, et al . Nat Med 2012. Disclosure of Interest None Declared

PTH-023 Histology, Cytology or Both for Sampling of Solid Pancreatic Masses? Prospective Evaluation of A New 22G Biopsy Needle: Abstract PTH-023 Table 1

Introduction For solid pancreatic masses (SPM), EUS-fine needle aspiration cytology (FNA-C) has a variable diagnostic yield and sensitivity for diagnosis of malignancy, given the limited material, presence of inflammation and inherent difficulties in cytologic interpretation. Histology of formalin-fixed biopsies is simpler, cheaper and may allow extra marker studies more often. This study evaluated the ability of a new EUS biopsy needle (1) to obtain histological biopsies (FNB) with a limited number of passes; (2) to compare specimen adequacy and diagnostic sensitivity with FNA-C; (3) compare specimen quality between FNA-C and FNB. Methods Over 5 months, consecutive patients with SPM underwent EUS biopsy sampling using a standardised protocol. Patients in whom lesions were predominantly cystic, taking anticoagulants or in whom access with a 22 g needle was deemed impossible were excluded. Using a 22 g ‘Sharkcore’ needle (Medtronic, Dublin, Ireland), 4 passes were made, using slow stylet withdrawal and material expelled into Cytolyt cytology fixative (2 passes) or into formalin for histology processing. Sampling sequence was randomised (passes 1&3 into cytology with passes 2&4 into formalin, or vice versa). Pathological assessment was performed by one of 2 specialist GI pathologists using a structured proforma, to rate specimen adequacy, sample quality, diagnosis and subjective superiority. Results 43 patients were included (23 M, 20 F, mean age 66 years, range 46–83 y). One patient was excluded from analysis due to incomplete follow-up. Final diagnoses were pancreatic malignancy (35, 83.3%) and benign pancreaticobiliary disorders (7, 16.7%). Results (n = 42) are shown in Table 1: In 2 cases FNA-cytology was negative for malignancy but FNB histology was positive; in contrast there were no cases where cytology was positive but histology was negative. Subjectively, FNB histology samples were scored as superior in 28 cases (66.7%), compared to FNA-C samples (4, 9.5%). In the remainder, samples were judged to be of equivalent quality (10, 23.8%). Conclusion The 22 g Sharkcore needle provides histological-quality samples in almost all cases of pancreatic or peripancreatic masses, with only 2 passes. Samples are more often superior to those obtained by cytology. This offers the prospect of shorter procedure times, easier sample processing and more reliable diagnosis. Disclosure of Interest None Declared

Diagnostic Performance of Endoscopic Ultrasound (EUS) for Non-Calcific Chronic Pancreatitis (NCCP) Based on Histopathology.

Studies correlating endoscopic ultrasound (EUS) with histopathology for chronic pancreatitis (CP) are limited by small sample size, and/or inclusion of many patients without CP, limiting applicability to patients with painful CP. The aim of this study was to assess correlation of standard EUS features for CP with surgical histopathology in a large cohort of patients with non-calcific CP (NCCP). Adult patients undergoing total pancreatectomy and islet autotransplantation (TPIAT) for NCCP, between 2008 and 2013, with EUS <1 year before surgery. Histology from resected pancreas at the time of TPIAT (from head, body, and tail) was graded by a GI pathologist blinded to the EUS features. A fibrosis score (FS) ≥2 was abnormal, and FS≥6 was considered severe fibrosis. A multivariate regression analysis for the EUS features predicting fibrosis, after taking age, sex, smoking, and body mass index into consideration, was performed. A quantitative receiver operating characteristic (ROC) curve analysis was performed and Spearman rank correlation co-efficient (r) was calculated. 68 patients (56 females, mean±s.d. age-38.77±10.92) underwent TPIAT for NCCP with pre-operative EUS. ROC curve showed that four or more EUS features provided the best balance of sensitivity (61%), specificity (75%), and accuracy (63%). Although significant, correlation between standard EUS features and degree of fibrosis was poor (r=0.24, P<0.05). Multivariate regression analysis showed that main pancreatic duct irregularity was the only independent EUS feature (P=0.02) which predicted CP. Correlation between standard EUS features and histopathology is poor in NCCP. MPD irregularity is an independent predictor for NCCP.

Impact of reassessment of colonic hyperplastic polyps by expert GI pathologists.

Recommended follow-up intervals after endoscopic removal of hyperplastic polyps (HP) and sessile serrated adenomas (SSA) differ because of assumed differences in biological behaviour. However, histopathologic differentiation is difficult, with higher SSA rates reported from specialist GI histopathologists. The objective of this study was to clarify the relevance of histologic reassessment of HP. From a prospective screening colonoscopy study relevant serrated lesions (excluding distal small HP ≤5 mm) diagnosed by private practice pathologists were reassessed by four specialized GI pathologists One thousand sixty-nine screening colonoscopies were performed in patients. In terms of main outcome measurements, there is a likelihood of changes of the HP diagnosis on reassessment, as well as interrater variability. SSA were initially diagnosed in 7 cases (0.7%) and relevant HP in 83 (7.8%; 101 lesions). Of the latter, the chance of a change in diagnosis from HP to SSA by any of the four specialist histopathologists was higher for larger (>5 mm) and right-sided lesions (19.1 vs 1.3%, OR 18.4, p = 0.04) including a higher likelihood to change recommended follow-up intervals (32.1 vs 3.3%, p < 0.01). However, follow-up intervals were determined by concomitant adenomas in 41%. Interrater variability was also higher for these lesions (p = 0.04), with an overall kappa value of 0.48. However, this issue related to only 1.2% of the 1069 study cases. The limitations this study are the limited case number as well as limited retrospective assessment. Right-sided HP >5 mm had a higher chance of change in diagnosis to SSA; therefore, they should probably be treated like adenomas and be removed. However, reliable data for recommendations on follow-up intervals of HP or SSA will require follow-up studies.

Inter-Observer Variability in the Interpretation of Endoscopic Mucosal Resection Specimens of Esophageal Adenocarcinoma

IntroductionEndoscopic resection (ER) has revolutionized the staging and therapy of superficial esophageal adenocarcinoma. Pathologic evaluation allows an assessment of the risk of lymph node metastases based on tumor characteristics. The aim of this study was to assess the inter-observer variability in pathologic assessment of ER specimens of esophageal adenocarcinoma. MethodsWe performed a retrospective study on ER specimens of superficial esophageal adenocarcinoma from four US institutions. Original endoscopic resection slides were re-reviewed by two blinded, experienced (study) gastrointestinal pathologists for the depth of tumor invasion, tumor grade, and the presence of lymphovascular invasion (LVI). Discordance was considered present only when both study pathologists disagreed with the original report. ResultsThere were 25 ER specimens reviewed for this study, and discordance occurred in 12 of the 25 specimens (48 %) for the depth of tumor invasion. In most cases (83 %), the discordance was related to overstaging a true T1a lesion. We found that only 38 % of true T1a lesions were correctly staged for depth of invasion. Less commonly discordance was secondary to understaging a true T1b lesion. There was concordance between the two study pathologists in 22/25 cases (88 %) on the depth of invasion. Discordance was present for tumor grade in 8/18 cases (44 %) and for LVI in 4/16 cases (25 %). Concordance between the study pathologists was 80 % for tumor grade and 88 % for LVI. ConclusionsThere was an alarmingly high rate of discordance (48 %) between the study pathologists and the original pathology assessment for the depth of tumor invasion in ER specimens. This was particularly common for lesions called T1b on the original pathology report. Since critical decisions are made regarding esophageal preservation or esophagectomy on the basis of the pathologic interpretations of ER specimens, it behooves surgeons to understand the inter-observer variability. Review of ER specimens by an experienced GI pathologist is recommended to ensure that patients receive the appropriate treatment for superficial esophageal adenocarcinoma.

Prevalence of Eosinophilic Esophagitis (EOE) in Hispanic Patients Presenting With Dysphagia and Food Impaction

Introduction: The prevalence of EOE in patients complaining of dysphagia and or food impaction is 10-15% in the Caucasian population1. The prevalence in Hispanics isn't well documented. The primary aim of this study was to define the prevalence of EoE in a predominantly Hispanic population presenting to a County Hospital with these complaints. Methods: This was a retrospective cohort study of adult patients presenting with dysphagia and/or food impaction having an EGD performed between August 2009 and September 2014. EoE was defined as >15 eosinophils/hpf on esophageal biopsy. Biopsies that met this criteria were reviewed and confirmed by a GI pathologist. Results: 311 patients underwent endoscopy for dysphagia and/or food impaction and 232 had 1 or more esophageal biopsies. 155 were Hispanic, 22 were Caucasian and 55 were “other”. The patients' age, gender and number of biopsies were noted. Eight patients with >15 eos/hpf were identified (3.4%) and were diagnosed with EOE. 5 of 155 Hispanic patients met this histologic criteria for EOE (3.2%) while 2/22 Caucasians (9.1%) and 1/55 “other” (1.8%) also met this criteria (Table 1). All patients with EOE (n=8) were male and less than 50 years of age. Endoscopic findings (rings, strictures, narrowing) were found in 4 of the 5 Hispanic patients (Table 2). Conclusion: The prevalence EOE in Hispanic patients in this study was considerable lower than that noted in the Caucasian patients in this study and is lower than that reported in Caucasian patients in the literature.1 - Hispanic patients in this study were male and younger than 50years of age. - Hispanic patients with EOE in this study frequently had visible endoscopic changes compatible with EOE. - Our study raises intriguing questions regarding the potential role for hygiene, diet, genetic and other factors that may have led to these findings.Figure 1Figure 2

Lessons from Paradise: The Many Subtleties of Tropical Sprue

Tropical Sprue (TS) classically presents as chronic diarrhea and symptoms of malabsorption in countries located within 30 degrees latitude of the equator, mostly affecting the indigenous population. Although the etiology is unclear, bacterial overgrowth, toxigenic bacterial species, and viral sources have all been theorized to play roles in the disease pathogenesis. Duodenal biopsies are the gold standard. However, TS is often a diagnosis of exclusion and histopathologic findings can mimic celiac disease. Timely diagnosis may be assisted by a dedicated GI pathologist when clinical suspicion for TS is high. Long term treatment with folic acid and broad spectrum antibiotics are the mainstay of therapy. We present a case of TS in a man visiting Haiti whose diagnosis was initially delayed due to misdiagnosis. Case: A 61 year old man with a medical history of Chronic Lymphocytic Leukemia presented after a six week trip to Haiti with watery, non-bloody diarrhea associated with bloating and a 20lb weight loss. From another GI provider, stool studies and routine blood-work were unremarkable and infectious and autoimmune work-ups were negative. After failing an empiric trial of antibiotics, Esophagastroduodenoscopy (EGD) and Colonoscopy (CF) were performed with unremarkable endoscopic findings. Duodenum, colon and ileum biopsies were interpreted as normal per the assigned pathologist. Four months later, the patient presented to our clinic seeking a second opinion. The prior EGD and CF biopsies were reviewed with an expert GI pathologist. CF biopsies were interpreted as normal. However, the duodenal biopsies were significant for moderate villous blunting and increased intraepithelial lymphocytosis consistent with indeterminate sprue. Having no relief with a gluten free diet and given his risk of TS, Doxycycline and folic acid were started, resulting in immediate improvement. He has since returned to his regular body weight and feels well. Conclusion: Our case highlights two important details. TS must be kept in the differential diagnosis for persons traveling to countries at risk for this infection. A high level of clinical suspicion must be maintained when diagnosing TS, as serologic testing does not exist and histopathology can be misleading. In addition, reviewing biopsies with a dedicated GI pathologist for patients with any GI disorder is imperative not only to improve our own knowledge base but to assure that our patients receive the best care possible.

Symptomatic Primary (AL) Amyloidosis of the GIT: Challenging Presentation of a Rare Diagnosis

Introduction: Primary Amyloidosis of the gastrointestinal tract (GIT) without clinical involvement of other organs is extremely rare. We report a unique case of primary GIT Amyloidosis (AL) presenting with severe GI bleeding and ultimately leading to patient demise. Case description: A 68-year-old female with history of diabetes mellitus, coronary artery disease presented with 5-month history of diffuse abdominal pain, nausea, vomiting, and weight loss of about 40 lbs. She underwent upper and lower endoscopy showing ulcerative gastro-duodenitis with partial gastric outlet obstruction and hemorrhagic colitis. Biopsies from stomach and duodenum showed amyloid deposition. Serum and urine protein electrophoresis showed elevated monoclonal protein, IgG lambda type. Serum free lambda chains were also elevated. Both bone marrow and abdominal fat pad biopsies were negative for amyloid deposition. No other major organ systems seemed to be involved. Partial obstruction was managed with nasogastric tube placement and supportive care. Within a few days she developed severe hematemesis. Repeat upper endoscopy showed several mucosal bleeding spots in stomach with evolving submucosal hematomas. Mucosa was extremely friable and bled on minimal contact. Bleeding was eventually controlled with epinephrine injection and argon plasma coagulation. She was started on total parenteral nutrition as gastrostomy or jejunostomy were ruled out given widespread GI involvement with amyloidosis and risk of potentiating bleeding. During the course of next few weeks she continued to have issues with GI bleeding requiring frequent blood transfusions. She was started on cyclophosphamide, bortezomib and dexamethasone (CyBorD) and received 2 cylces. Unfortunately, 2 weeks later she died of acute myocardial infarction in the face of worsening anemia and need to withhold anti-platelets. Discussion: This is a rare presentation of Primary Amyloidosis limited to GIT. Our case has several unique features and learning points. Amyloidosis of GIT should be considered in patients with multiple GI complaints and pathologist should always rule it out even in absence of other organ system involvement. GI bleeding from amyloidosis is rare but can be extremely challenging and even be potentially fatal in the absence of amyloid-targeted therapy. Nasogastric tube placement in such patients can precipitate bleeding. The role of myelosuppressive chemotherapy in the absence of bone marrow involvement and in the presence of GI bleeding is debatable.Figure 1Figure 2Figure 3