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Data regarding outcomes of endoscopic retrograde cholangiography (ERC) in liver transplant (LT) recipients with biliary-enteric (BE) anastomosis are limited. We report outcomes of ERC and percutaneous transhepatic biliary drainage (PTBD) as first-line therapies in LT recipients with BE anastomosis.All LT recipients with Roux-BE anastomosis from 2001 to 2020 were divided into ERC and PTBD subgroups. Technical success was defined as the ability to cannulate the bile duct. Clinical success was defined as the ability to perform cholangiography and therapeutic interventions.A total of 36 LT recipients (25 males, age 53.5 ± 13 years) with Roux-BE anastomosis who underwent biliary intervention were identified. The most common indications for a BE anastomosis were primary sclerosing cholangitis (n = 14) and duct size mismatch (n = 10). Among the 29 patients who initially underwent ERC, technical success and clinical success were achieved in 24 (82.8%) and 22 (75.9%) patients, respectively. The initial endoscope used for the ERC was a single balloon enteroscope in 16 patients, a double balloon enteroscope in 7 patients, a pediatric colonoscope in 5 patients, and a conventional reusable duodenoscope in 1 patient. Among the 7 patients who underwent PTBD as the initial therapy, six (85.7%) achieved technical and clinical success (In LT patients with Roux-BE anastomosis requiring biliary intervention, ERC with a balloon-assisted enteroscope is safe with a success rate comparable to PTBD. Both ERC and PTBD can be considered as first-line therapies for LT recipients with a BE anastomosis.

Background and Aims Closure of endoscopic resection defects can be achieved with through-the-scope clips, over-the-scope clips or endoscopic suturing. However, these devices are often limited by their inability to close large, irregular, and difficult to reach defects. Thus, we aimed to assess the feasibility and safety of the novel through-the-scope suture-based closure system that was developed to overcome these limitations. Methods This is a retrospective multicenter study involving 8 centers in the United States. Primary outcomes included feasibility and safety of early use of the device. Secondary outcomes included assessment of need for additional closure devices, prolonged procedure time, and technical feasibility of performing the procedure with an alternative device(s). Results A total of 93 patients (48.4% female) with mean age 63.6 ± 13.1 years were included. Technical success was achieved in 83 patients (89.2%) and supplemental closure was required in 24.7% (n=23) of patients with a mean defect size of 41.6 ± 19.4 mm. Closure with an alternative device was determined to be impossible in 24.7% of patients due to location, size, or shape of the defect. The use of the tack and suture device prolonged the procedure in 8.6% of the cases but was considered acceptable. Adverse events occurred in 2 patients (2.2%) over a duration of follow-up of 34 days (interquartile range: 13-93.5 days) and were mild and moderate in severity. No serious adverse events or procedure-related deaths occurred. Conclusions The novel endoscopic through-the-scope tack and suture system is safe, efficient, and permits closure of large, and irregularly shaped defects that were not possible with predicate devices.

Biliary strictures after donation-after-cardiac-death (DCD) liver transplantation (LT) require multiple endoscopic retrograde cholangiopancreatographies (ERCP). The outcomes of endoscopic dilation and maximal stenting are not well-characterized in this high-risk population.DCD LT recipients who underwent LT and ERCP from 2012-2018 were selected. Anastomotic and non-anastomotic strictures were treated with balloon dilation and maximal stenting. A successful stent-free trial was defined as absence of biochemical, clinical or imaging evidence of strictures on follow-up exceeding 6 months. Adverse events were defined as unplanned admission or inpatient evaluation within 7 days of ERCP.Forty-nine DCD LT recipients underwent ERCP and 34 patients were diagnosed with strictures (20 anastomotic). Stent-free trial was successful in 27 patients. Adverse events occurred after 20 ERCPs. Patients with anastomotic strictures required fewer stents (1.43 ± 1.37 vs 2.63 ± 1.66; P0.001), shorter procedure and fluoroscopy times (34.15 ± 20.9 vs 59.6 ± 30.7 minutes, P0.001; 5.99 ± 7.4 vs 14.73 ± 10.74 minutes, P0.001), fewer relapses (10% vs 57%, P = 0.003), shorter intervals between initial ERCP and stent-free success (136.9 ± 118.3 vs 399.56 ± 234.7; P = 0.003), and between LT and stent-free success (227.8 ± 171.9 vs 464.1 ± 224.6 days; P = 0.005) compared to non-anastomotic strictures.Endoscopic dilation and maximal stenting resolves biliary strictures in DCD LT recipients with sustained success and relatively few adverse events.

It has been 10 years since peroral endoscopic myotomy (POEM) was reported for the first time, and POEM has currently become the standard treatment for achalasia and related disorders globally because it is less invasive and has a higher curative effect than conventional therapeutic methods. However, there are limited studies comparing the long-term outcomes of POEM with those of conventional therapeutic methods, particularly in the occurrence of gastroesophageal reflux disease (GERD) after therapy. With this background, we held a consensus meeting to discuss the pathophysiology and management of GERD after POEM based on published papers and experiences of each expert and to discuss the prevention of GERD and dealing with anti-acid drug refractory GERD. This meeting was held on April 27, 2018 in Tokyo to establish statements and finalize the recommendations using the modified Delphi method. This manuscript presents eight statements regarding GERD after POEM.

Data from germline testing in unselected patients with hepatobiliary cancers are limited. Identification of germline predisposition can have important implications on cancer treatment and family counseling. To determine prevalence of pathogenic germline variants (PGV) in patients with hepatobiliary cancer, we undertook a prospective multi-site study of germline sequencing using a >80-gene next-generation sequencing platform among patients with hepatobiliary cancers receiving care at Mayo Clinic Cancer Centers between April 1, 2018 and March 31, 2020. Patients were not selected on the basis of stage, family cancer history, ethnicity, or age. Family cascade testing was offered at no cost. Of 205 patients, the median age was 65 years, 58.5% were male, 81% were White, and 64.4% had cholangiocarcinoma, 21.5% hepatocellular carcinoma, 7.8% gallbladder cancer, and 4.3% carcinoma of ampulla of Vater. PGV were found in 15.6% (n = 32) of patients, including 23 (71%) in moderate and high penetrance cancer susceptibility genes. A total of 75% of patients with a positive result would not have been detected using guidelines for genetic evaluation. Prevalence of PGV was 15.7% in intrahepatic cholangiocarcinoma, 17% in extrahepatic cholangiocarcinoma, 15.9% in hepatocellular cancer, and 33% in carcinoma of ampulla of Vater. On the basis of these genetic findings, 55% were potentially eligible for approved precision therapy and/or clinical treatment trials. Universal multi-gene panel testing in hepatobiliary cancers was associated with detection of heritable mutations in over 15% of patients most of whom would not have been tested using current guidelines. Germline testing should be considered in all patients with hepatobiliary cancers. Prevention Relevance: Universal multi-gene testing in hepatobiliary cancers was associated with heritable mutations in over 15% of patients, most of whom would not have been tested using current guidelines. 55% were potentially eligible for approved precision therapy and/or clinical treatment trials. Germline testing should be considered in all patients with hepatobiliary cancers.

Peroral endoscopic myotomy (POEM) is a novel clinical technique developed in Japan used to treat esophageal achalasia and esophageal motility disorders. This technique has been rapidly accepted and widely disseminated throughout our clinical practice because of its low invasiveness, technical novelty, and high efficacy. Since the advent of POEM, there have been no clinical guidelines that clearly indicated its standard of care, and these guidelines have been anticipated both nationally and internationally by clinicians who engage in POEM practice. In 2017, to meet these needs, the Japan Gastroenterological Endoscopy Society (JGES) launched the guideline committee for POEM. Based on the guideline development process proposed by the Medical Information Network Distribution Service (MINDS), the guideline committee initially created research questions on POEM and conducted a systematic review and meta-analysis on each topic. The clinical research extracted from databases for these clinical questions and the systematic review mainly comprised a few retrospective studies with a small number of participants and short trial periods; hence, the strength of the evidence and recommendations derived from these results was low. Throughout this process, the guideline committee met thrice: once on May 13, 2017, and again on September 17, 2017, to formulate the draft. A consensus meeting was then held on January 14, 2018, in Tokyo to establish the guideline statements and finalize the recommendations using the modified Delphi method. This manuscript presents clinical guidelines regarding current standards of practice and recommendations in terms of the nine chief topics in POEM.

Introduction To report the prevalence and outcomes of unselected pancreatic cancer (PC) patients with pathogenic/likely pathogenic germline variants (PGVs) detected using a universal testing approach. Methods We undertook a prospective, multisite study of germline sequencing using a >80 gene next-generation sequencing platform among 250 patients with PC (not selected for age or family history of cancer) between April 1, 2018, and March 31, 2020. Demographic, tumor characteristics, and clinical outcomes were compared between PGV carriers and noncarriers. Results Of 250 patients, the mean age was 65 years (SD 8.7), 56% was male, 83.6% was White, and 65.6% had advanced disease (stages III and IV). PGVs were found in 15.2% (N = 38) of patients, and 2 patients had more than 1 PGV. Variants of uncertain significance were found in 44.4% (N = 111). Family history of cancer (odds ratio: 2.36, 95% confidence interval: 1.14-5.19, P = 0.025) was associated with a higher risk of PGV. In a median follow-up of 16.5 months, the median overall survival was 16.8 months in PGV carriers compared with 16.5 months in noncarriers (hazard ratio: 0.51, 95% confidence interval: 0.25-1.01, P = 0.05). Higher levels of carbohydrate antigen 19-9 and advanced disease stages (III and IV) were associated with worse outcomes in both groups. Overall, 68% of PGV carriers had mutations in homologous recombination repair genes, including BRCA1, BRCA2, PALB2, ATM, CHEK2, NBN, and RAD51C. Discussion Universal multigene panel testing in PC reveals that 1 in 6 patients are carriers of PGV. Multigene germline testing should be used to aid in treatment selection, prognostication, and familial cancer counseling.

Background and Aims The role of per-oral pancreatoscopy (POP) in the evaluation of occult pancreatic duct (PD) lesions remains limited to case series. The aim of this study was to evaluate the ability of POP to differentiate malignant from benign diseases of the PD. Methods Patients who underwent POP between 2000 and 2013 for the evaluation of indeterminate PD strictures, dilatations, or with suspected or known main duct intraductal papillary mucinous neoplasm were identified. Main outcome measurements were visual impression accuracy, POP tissue sampling, efficacy, and safety of POP. Results During the study period, 79 patients who underwent POP for the evaluation of pancreatic stricture or dilatation were identified. Technical success was achieved in 78 (97%). In the PD neoplasia group (n = 33), the final diagnosis was based on index confirmatory POP-guided tissue sampling in 29 (88%). For the detection of PD neoplasia, POP visual impression had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 87%, 86%, 83%, 91%, and 87%, respectively. When combined with POP-guided tissue sampling, the values were 91%, 95%, 94%, 93%, and 94%, respectively. Of 102 POPs performed, adverse events were noted in 12 (12%) cases. Conclusions This study demonstrates a high technical success rate, visual impression accuracy, and tissue sampling capability of POP. Examinations were performed by endoscopists with expertise in pancreatoscopy interpretation, and the results may not be generalizable.

Background & Aims Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. Methods We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. Results Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. Conclusions ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis-associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence of acute pancreatitis. Pancreatic triglyceride lipase (PNLIP) increased in adipose tissue during pancreatitis and entered adipocytes by multiple mechanisms, hydrolyzing adipose triglyceride and generating excess NEFAs. During pancreatitis, obese PNLIP-knockout mice, unlike obese adipocyte-specific ATGL knockouts, had lower visceral adipose tissue lipolysis, milder inflammation, less severe organ failure, and improved survival. PNLIP-knockout mice, unlike ATGL knockouts, were protected from adipocyte-induced pancreatic acinar injury without affecting NEFA signaling or acute pancreatitis induction. Therefore, during pancreatitis, unlike diverticulitis, PNLIP leaking into visceral adipose tissue can cause excessive visceral adipose tissue lipolysis independently of adipocyte-autonomous ATGL, and thereby worsen organ failure.

Achalasia refers to the lack of smooth muscle relaxation of the distal esophagus. Although nonsurgical treatments such as pneumatic dilatation of the distal esophagus and botulinum toxin injections have been performed, these procedures have limited duration. Similarly, surgical treatment with Heller myotomy is associated with complications. At our institution, we perform the peroral endoscopic myotomy (POEM) in qualified patients. Briefly, POEM involves endoscopic creation of a mid-esophageal submucosal bleb, creation of a submucosal tunnel with the endoscope, and then a distal myotomy, resulting in relaxation of the distal esophagus. The aim of our study is to document perioperative pain and associated pain management for our initial patients undergoing POEM and to review the literature for perioperative complications of this procedure. Therefore, anesthetic and pain management for our initial eleven patients undergoing POEM were reviewed. Patient demographics, pre-POEM pain medication history, perioperative pain medication requirements, and post-POEM pain scores were examined. We found post-POEM pain was usually in the mild–moderate range; a combination of medications was effective (opioids, nonsteroidal anti-inflammatory drugs, acetaminophen). Our literature search revealed a wide frequency range of complications such as pneumoperitoneum and subcutaneous emphysema, with rare serious events such as capnopericardium leading to cardiac arrest. In conclusion, our experience with POEM suggests pain and can be managed adequately with a combination of medications; the procedure appears to be safe and reasonable to perform in an outpatient endoscopy unit., Video abstract

Background Accurate staging of superficial esophageal squamous cell cancer (ESCC) for endoscopic therapy is challenging. Optical coherence tomography (OCT) has been shown to be superior to high-resolution endoscopic ultrasound (EUS). Volumetric Laser Endomicroscopy (VLE), a second-generation OCT, has recently become commercially available. Objective To assess if VLE can determine which patients with superficial ESSC can undergo endoscopic therapy. Methods This is a multi-center retrospective study. Patients were included if (a) they had visible ESCC, (b) they underwent VLE and EUS for staging, and c) if superficial disease was suspected then endoscopic resection had to be performed to have accurate histology to compare the VLE scan to. VLE scans were then compared to the gold standard: histology for superficial disease and EUS for disease T1b and greater. Results Seventeen patients were included with the following disease: squamous intraepithelial neoplasia (4 patients), T1a disease (6 patients), T1b (2 patients), T2 disease (2 patients) and T3 disease (3 patients). VLE was able to distinguish superficial disease, defined as disease limited up to the lamina propria, from non-superficial disease in all cases. Conclusions VLE may be able to determine which ESCC patients are candidates for endoscopic therapy. Prospective studies are needed to confirm this.

Endoscopic submucosal dissection (ESD) is an established endoscopic resection method in Asian countries, which is increasingly practiced in Europe and by early adopters in the United States for removal of early cancers and large lesions from the luminal gastrointestinal tract. The intent of this expert review is to provide an update regarding the clinical practice of ESD with a particular focus on its use in the United States. This review is framed around the 16 best practice advice points agreed upon by the authors, which reflect landmark and recent published articles in this field. This expert review also reflects our experience as advanced endoscopists with extensive experience in performing and teaching others to perform ESD in the United States. Best Practice Advice 1: Endoscopic submucosal dissection should be recognized as a mature endoscopic technique that enables complete removal of lesions that are too large for en bloc endoscopic mucosal resection or are at increased risk of containing cancer. Best Practice Advice 2: The safety and feasibility of endoscopic submucosal dissection for early gastric cancer is well established. The absolute indications for curative endoscopic resection include moderately and well-differentiated, nonulcerated, mucosal lesions that are ≤2 cm in size. Best Practice Advice 3: Other relative (expanded) indications for gastric endoscopic submucosal dissection include moderately and well-differentiated superficial cancers that are >2 cm, lesions ≤3 cm with ulceration or that contain early submucosal invasion, and poorly differentiated superficial cancers ≤2 cm in size. The risk of lymph node metastasis when endoscopic submucosal dissection is performed for these indications is higher than when it is performed for absolute indications but remains acceptably low. Best Practice Advice 4: Endoscopic submucosal dissection may be considered in selected patients with Barrett's esophagus with the following features: large or bulky area of nodularity, lesions with a high likelihood of superficial submucosal invasion, recurrent dysplasia, endoscopic mucosal resection specimen showing invasive carcinoma with positive margins, equivocal preprocedural histology, and intramucosal carcinoma. Best Practice Advice 5: Endoscopic submucosal dissection is the primary modality for treatment of squamous cell dysplasia and cancer confined to the superficial esophageal mucosa. Any degree of submucosal invasion caries an increased risk of lymph node metastasis and alternative/additional therapy should be considered. Best Practice Advice 6: Duodenal endoscopic submucosal dissection is associated with an increased risk of intraprocedural perforation and delayed adverse events. Duodenal endoscopic submucosal dissection should be limited to endoscopists with extensive experience in performing endoscopic submucosal dissection in other locations. It is strongly suggested that endoscopists in the United States refrain from performing duodenal endoscopic submucosal dissection during the early phase of their endoscopic submucosal dissection practice. Best Practice Advice 7: All colorectal lesions should be evaluated for suitability for endoscopic resection. Accumulating evidence has shown that the majority of colorectal neoplasms without signs of deep submucosal invasion or advanced cancer can be treated by advanced endoscopic resection techniques. Best Practice Advice 8: Colorectal neoplasms containing dysplasia confined to the mucosa have no risk for lymph node metastasis and endoscopic resection should be considered as the criterion standard. Best Practice Advice 9: Large (>2 cm) colorectal lesions frequently (>43%) require piecemeal removal when endoscopic mucosal resection is used, which is associated with increased (up to 20%) rates of recurrent neoplasia. Endoscopic submucosal dissection enables higher rates of en bloc resection and lower recurrence rates for these lesions. Patients with large complex colorectal polyps should be referred to a high-volume, specialized center for endoscopic removal by endoscopic mucosal resection or endoscopic submucosal dissection. Best Practice Advice 10: Endoscopic resection for colorectal lesions offers significant cost benefit compared with surgery, and case-based endoscopic submucosal dissection selection for high-risk lesions could offer cost savings. Best Practice Advice 11: Endoscopists in the United States embarking on performing endoscopic submucosal dissection should be familiar with currently available endoscopic tissue closure devices. Both clip closure and endoscopic suturing techniques have been shown to be effective in managing intraprocedural perforation. Complete closure of a post–endoscopic submucosal dissection site may be considered in certain circumstances based on patient factors, procedural factors, and the location of the lesion. Best Practice Advice 12: Careful coagulation of exposed blood vessels in the resection site may reduce the risk of delayed bleeding after endoscopic submucosal dissection. The use of low-voltage coagulation current is recommended for this technique. Best Practice Advice 13: Endoscopists should affix the endoscopic submucosal dissection specimen to a flat surface (eg, pin the specimen to cork board) and immerse it in formalin. An expert gastrointestinal pathologist should evaluate the specimen for margin involvement, degree of differentiation, presence or absence of lymphovascular invasion, depth of submucosal invasion (if present), and tumor budding. Best Practice Advice 14: Acquiring high-level competency in endoscopic submucosal dissection is achievable in the United States. Alternative educational models should be used in the United States because of the limited number of experts and the differing prevalence of gastrointestinal luminal diseases as compared with Asia. Best Practice Advice 15: The endoscopic submucosal dissection educational model most suited for the current environment in the United States is a stepwise approach consisting of didactic self-study, attending training courses with increasing levels of complexity, self-practice on animal models, and observation of live cases performed by experts. Endoscopists should perform their initial endoscopic submucosal dissections on patients with lesions that have well-established indications for endoscopic submucosal dissection and are of the lowest technical complexity. Best Practice Advice 16: Endoscopists in the United States who perform endoluminal resection should educate referring physicians to avoid practices that may induce submucosal fibrosis hampering future endoscopic mucosal resection or endoscopic submucosal dissection. These practices include tattooing in close proximity to or beneath a lesion for marking and partial snare resection of a portion of a lesion for histopathology.

Ectopic pancreas rarely causes symptoms or complications. We analyzed 2 atypical cases of ectopic pancreas associated with acute ectopic pancreatitis, 1 of which was induced by endoscopic ultrasound with fine-needle aspiration (EUS-FNA). The patients were seen at a tertiary medical center where they had undergone computed tomography, esophagogastroduodenoscopy, and EUS-FNA analyses. They initially received conservative medical treatment and were later treated by surgery. Both patients were diagnosed with ectopic pancreas of the stomach on the basis of computed tomography, esophagogastroduodenoscopy, or EUS-FNA. Surgical resection cured both patients and confirmed the diagnosis of ectopic pancreas. Acute ectopic pancreatitis is an unusual complication of ectopic pancreas that can be induced by EUS-FNA and diagnosed and cured with surgery.

BACKGROUND. Lymphovascular invasion (LVI) and/or lymph node metastases (LNM) adversely influence the overall survival (OS) of patients with T1 esophageal adenocarcinoma. Although endoscopic therapy may be adequate for patients with T1a cancer, patients with T1b cancer require esophagectomy/lymphadenectomy. The authors hypothesized that LVI status would subclassify T1b cancers and facilitate new therapeutic strategies. METHODS. Ninety-nine consecutive patients with T1 adenocarcinoma were analyzed after they underwent esophagectomy/lymphadenectomy. LNM was assessed in all patients, and LVI was assessed in 89 patients. OS was correlated with pathologic cancer stage in association with LVI and LNM. RESULTS. The 5-year OS rate for patients with T1a tumors (88%) was superior to that for patients with T1b tumors (62%; P = .001). The 5-year OS rate for patients who had cancers without LVI (85%) was superior to the rate for patients who had cancers with LVI (36%; P = .0001). It is noteworthy that, for cancers without LVI, the 5-year OS rate for patients with T1b tumors (77%) was similar to the rate for patients with T1a tumors (90%; P = .08), but it was superior to the rate for patients with T1b tumors that had LVI (27%; P = .006). The presence of LVI and/or LNM resulted in worse 5-year OS (≤37%) compared with the lack of LVI and/or LNM (88%; P < .001). The rate of LNM for patients who had T1b tumors without LVI still was 19%, and the relapse rate was 16%. CONCLUSIONS. The current results demonstrated that LVI distinguishes the biologic behavior of early esophageal cancer, and patients who have T1b cancer without LVI have a clinical biology similar to that of patients with T1a cancer. If LNM before surgery can be diagnosed with high sensitivity by better endoscopic techniques and/or molecular biomarkers, then a new therapeutic paradigm for T1b cancers could emerge. Further research is needed on patients with T1b esophageal adenocarcinoma. Cancer 2008. © 2008 American Cancer Society.

Purpose: Resistance to preoperative chemoradiotherapy (CTXRT) in 75% of patients with esophageal adenocarcinoma (EAC) underscores the need for identification of biomarkers of CTXRT response. We previously noted an association between decreased expression of epidermal differentiation complex (EDC) genes S100A2 and SPRR3 at chromosome 1q21 and CTXRT resistance. In the current study, we did an in-depth investigation of the expression of 1q21-1q25 region genes to uncover the role of the EDC and its flanking genes in CTXRT response. Experimental Design: We compared 19 pretreatment EAC specimens with normal squamous mucosa for the expression of 517 genes at chromosome 1q21-1q25 and selected target genes based on their differential expression. Using the pathologic complete-response (pathCR) status of the resected specimens as a representation of CTXRT sensitivity, we assessed the association between the expression of target genes and CTXRT response and clinical outcomes. Results: On the basis of the expression levels of IVL, CRNN, NICE-1, S100A2, and SPPR3, genes within and in close proximity to the EDC, cancers were segregated into high (subgroup I) or low (subgroup II) expressers. Four of the five pathCRs were high expressers. Thus, low expressers, with one exception, were all nonresponders. Patients in subgroup I also had longer survival than those in subgroup II, although this result was not statistically significant owing to the small study number. Conclusions: The expression levels of genes mapping within and close to the EDC define CTXRT response subgroups in EACs.

Background and aims: Endoscopic ultrasound with fine needle aspiration (EUS-FNA) has become the standard of care in the evaluation of solid pancreatic lesions. Limited data exist on interobserver agreement (IOA) among cytopathologists in assessing solid pancreatic EUS-FNA specimens. This study aimed to evaluate IOA among cytopathologists in assessing EUS-FNA cytology specimens of solid pancreatic lesions using a novel standardized scoring system and to assess individual clinical and cytologic predictors of IOA. Methods: Consecutive patients who underwent EUS-FNA of solid pancreatic lesions at a tertiary care referral center were included. EUS-FNA slides were evaluated by four blinded cytopathologists using a standardized scoring system that assessed final cytologic diagnosis and quantitative (number of nucleated/diagnostic cells) and qualitative (bloodiness, inflammation/necrosis, contamination, artifact) cytologic parameters. Final clinical diagnosis was based on final cytology, surgical pathology, or 1-year clinical follow-up. IOA was calculated using multi-rater kappa (κ) statistics. Bivariate analyses were performed comparing cases with and without uniform agreement among the cytopathologists followed by logistic regression with backward elimination to model likelihood of uniform agreement. Results: Ninety-nine patients were included (49 % males, mean age 64 years, mean lesion size 26 mm). IOA for final diagnosis was moderate (κ = 0.45, 95 % confidence interval (CI) 0.4 – 0.49) with minimal improvement when combining suspicious and malignant diagnoses (κ = 0.54, 95 %CI 0.49 – 0.6). The weighted kappa value for overall diagnosis was 0.65 (95 %CI 0.54 – 0.76). IOA was slight to fair (κ = 0.04 – 0.32) for individual cytologic parameters. A final clinical diagnosis of malignancy was the most significant predictor of agreement [OR 3.99 (CI 1.52 – 10.49)]. Conclusions: Interobserver agreement among cytopathologists for pancreatic EUS-FNA specimens is moderate-substantial for the final cytologic diagnosis. The final clinical diagnosis of malignancy was the strongest predictor of agreement. These results have significant implications for patient management and need to be validated in future trials.

BACKGROUND Endoscopic ultrasound (EUS) is an accurate staging modality for esophageal malignancy. Studies have determined that EUS does not retain this accuracy after chemoradiation and that it should not be used as a restaging tool for esophageal carcinoma. In this study, the authors examined their experience with esophageal carcinoma and restaging after neoadjuvant therapy with EUS. METHODS A retrospective chart review was conducted that included 83 patients with locoregional esophageal adenocarcinoma who were treated with chemoradiation under protocol. All patients underwent surgical resection. EUS was performed for restaging, and the results were compared with findings at surgical pathology using the TNM classification system. RESULTS All 83 patients identified underwent surgery. There were 77 males, and the mean patient age was 59 years. At restaging, the tumor status (T classification) was assessed correctly by EUS in 22 of 83 patients (29%). The sensitivity of EUS for the individual T classifications were 0% for T0 tumors, 19% for T1 tumors, 27% for T2 tumors, 52% for T3 tumors, and 0% for T4 tumors. In 19 of 83 patients, the tumor classification was correct, whereas 42 of 83 patients were over classified, and 15 of 83 patients were under classified when the EUS results were compared with the surgical pathology results. The lymph node status (N classification) was assessed correctly by EUS in 41 of 83 patients. The sensitivity of EUS for N classification was 48% for N0 disease and 52% for N1 disease. Twenty-two patients were restaged with residual disease according to the EUS results but had no evidence of residual tumor or lymph node involvement according to the surgical pathology results. CONCLUSIONS EUS did not retain its usefulness as a restaging modality after neoadjuvant chemoradiation for esophageal adenocarcinoma when the standard TNM classification system was used. Cancer 2004. © 2004 American Cancer Society.

Positron emission tomography can be useful in predicting response of esophageal cancer after preoperative chemo-radiation therapy (CRT). We evaluated the use of integrated computed tomography (CT)-PET among patients with esophageal cancer being considered for resection after CRT.Three reviewers blinded to clinical and pathologic staging retrospectively reviewed the CT-PET scans of patients with esophageal cancer after preoperative CRT who underwent esophagectomy. [F]-fluoro-2-deoxy-D-glucose uptake for residual malignancy was determined by visual analysis and semi-quantitatively when standardized uptake value (SUV) wasor =4.Forty-two patients underwent esophageal resection. Using visual analysis, CT-PET had a sensitivity of 47% and specificity of 58% in detecting residual malignancy. Using semi-quantitative analysis, 19 patients had a SUVor =4 in the region of the primary esophageal tumor and were interpreted as having residual malignancy (sensitivity 43%, specificity 50%). Of these 19, six had complete pathologic response to CRT. These false-positive results, due to therapy-induced ulceration detected at endoscopy, limit the use of CT-PET alone in detecting residual malignancy. Similarly, sensitivity (25%) and specificity (73%) of endoscopy/biopsy in detecting residual malignancy were poor. However, the accuracy of CT-PET in detecting residual malignancy was improved when combined with endoscopic findings. In the absence of ulceration at endoscopy, 8 of 8 patients with SUVor =4 after chemo-radiation had residual malignancy at surgery.CRT-induced ulceration results in false-positive results on CT-PET and precludes accurate detection of residual esophageal tumor. However, CT-PET in combination with endoscopy is useful in identifying patients with a high risk of residual tumor post-CRT.

BACKGROUND. The objective of the study was to determine the utility of integrated computed tomography / positron emission tomography (CT-PET) imaging for detecting interval distant metastases and assessing therapeutic response in patients with locally advanced, potentially resectable esophageal carcinoma after neoadjuvant therapy. METHODS. A retrospective study was performed of 88 patients with potentially resectable esophageal carcinoma who received neoadjuvant therapy before planned surgical resection. CT-PET before and after completion of neoadjuvant was used for evaluating therapeutic response; response criteria were based on qualitative and semiquantitative analyses. RESULTS. Neoadjuvant therapy comprised chemoradiotherapy in 85 patients, with prior induction chemotherapy in 39 patients. Fifty-five patients proceeded to esophagectomy. Repeat CT-PET was performed after induction chemotherapy (n = 23) and after completing chemoradiotherapy (n = 85). CT-PET identified the interval appearance of metastatic disease in 7 (8%) patients. For assessment of locoregional therapeutic response, CT-PET was unable to predict pathological response to neoadjuvant therapy in the primary tumor or locoregional lymph nodes. CT-PET had sensitivity, specificity, and positive and negative predictive values of 57%, 46%, 39%, and 64%, respectively, for detection of residual macroscopic malignancy within the primary tumor; and sensitivity, specificity, and positive and negative predictive values of 0%, 90%, 0%, and 69% for detection of residual malignancy within resected lymph nodes. CONCLUSIONS. CT-PET performed after neoadjuvant therapy in patients with potentially resectable esophageal carcinoma is important for detecting interval metastases that preclude surgical resection, but is of limited utility for assessing locoregional therapeutic response. Cancer 2007. © 2006 American Cancer Society

AIM: To study the clinical, endoscopic, sonographic, and cytologic features of ectopic pancreas (EP). METHODS: This was a retrospective study performed at an academic referral center including two hospitals. Institutional review board approval was obtained. Patients referred to the University Hospital or Denver Health Medical Center Gastrointestinal Endoscopy Lab for gastroduodenal subepithelial lesions (SEL) with a final diagnosis of EP between January 2009 and December 2013 were identified. Patients in this group were selected for the study if they underwent endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) or deep biopsy. A review of the medical record was performed specifically to review the following information: presenting symptoms, endoscopic and EUS findings, computed tomography or magnetic resonance imaging findings, pathology results, procedure-related adverse events, and subsequent treatments after EUS-FNA. EUS with FNA or deep submucosal biopsy was performed in all patients on an outpatient basais by one of two physicians (Attwell A, Fukami N). Review of all subsequent clinic notes and operative reports was performed in order to determine follow-up and final diagnoses. RESULTS: Between July 2009 and December 2013, 10 patients [3 males, 7 females, median age 52 (26-64) years] underwent EUS for a gastroduodenal SEL and were diagnosed with EP. One patient was symptomatic. Six (60%) lesions were in the antrum, 3 (30%) in the body, and 1 (10%) in the duodenum. A mucosal dimple was noted in 6 (60%). Mean lesion size was 17 (8-25) mm. Gastrointestinal wall involvement: muscularis mucosae, 10%; submucosa, 70%; muscularis propria, 60%; and serosa, 10%. Nine (90%) lesions were hypoechoic and 5 (50%) were homogenous. A duct was seen in 5 (50%). FNA was attempted in 9 (90%) and successful in 8 (80%) patients after 4 (2-6) passes. Cytology showed acini or ducts in 7 of 8 (88%). Superficial biopsies in 7 patients (70%) showed normal gastric mucosa. Deep endoscopic biopsies were taken in 2 patients and diagnostic in one. One patient (10%) developed pancreatitis after EUS-FNA. Two patients (20%) underwent surgery to relieve symptoms or confirm the diagnosis. The main limitation of the study was the fact that it was retrospective and performed at a single medical center. CONCLUSION: EUS features of EP include antral location, mucosal dimple, location in layers 3-4, and lesional duct, and FNA or biopsy is accurate and effective.

had familiar history ofIBD.Among the 93 IBD pts with arthralgias, rheumatologic assessment diagnosed rheumatologic diseases in 33 (88%) UC and in 44 (80%) CD pts. In particular, a diagnosis of SpAewas made in 50 (54%) IBD pts(54% peripheral SpA, 24%, axial SpA, 22% both), 24 (26%)Osteoarthritis, 6 (7%)Fybromialgia,3 (3%), Gout, 3 (3%)Rheumatoid Arthritis, 2 (2%) Psoriatic Arthritis, while diagnosis was inconclusive in 5 (6%) pts. After rheumatological assessment, a higher percentage of IBD pts were treated with diseasemodifying anti-rheumatic drugs (including anti-TNFs)(5.3% vs 15%, p=0.03, RR 1.6)and/ or with anti-COX2 (6.4% vs 27%; p

Background: Endoscopic ablation of neoplastic tissue distal to the tubular esophagus presents a technical challenge with currently available modalities. Liquid nitrogen spray cryotherapy (LN2SC) is a catheter-based technique which has been used to treat Barrett's esophagus (BE), esophageal cancer and non-esophageal diseases. It does not require tissue contact for efficacy and treats flat and raised lesions. Recent technical improvements have permitted use of LN2SCwhile in retroflexion. There have been no published reports using this technique. We describe the feasibility and safety of treating lesions at the esophagogastric junction (EGJ) and gastric cardia with retroflexed LN2SC. Methods: We performed a retrospective study of subjects treated with LN2SC in retroflexion at 4 U.S. tertiary care centers. Eligible subjects were treated for dysplastic BE or adenocarcinoma with either curative or palliative intent. Cases were treated with LN2SC using the G2 or truFreeze catheter systems (CSA Medical, Lutherville MD). Dosimetry was at the discretion of the operator and varied with lesion size and morphology. De-identified data, including demographic and endoscopic details, were obtained using a standardized collection form. Results were aggregated for analysis. Results: In total, 13 patients underwent 18 retroflexed LN2SC administrations. While 9 patients had 1 retroflexed session, 4 had at least 2 sessions of retroflexed treatment. All but 1 patient was male, with a mean age of 74 years. Histologic grading of targeted lesions included 4 cases of invasive adenocarcinoma, 4 of intramucosal adenocarcinoma, 4 of BE with high grade dysplasia and 1 of BE with low grade dysplasia. Only 2 patients were treatment-Naive, while 8 had prior ablation with LN2SC, radiofrequency ablation or photodynamic therapy, and 8 had prior endoscopic mucosal resection. Lesions targeted for treatment included 3 EGJ nodules/masses, 3 cardia nodules/masses, 1 area of nodularity including the EGJ and cardia and 6 flat EGJ lesions. Retroflexed LN2SC was chosen either for lesions extending beyond the EGJ that were not fully visible en face or due to concerns for incomplete treatment with prior ablation. Four cases were performed using the older G2 catheter, which has greater stiffness and a limited bend radius compared to the truFreeze catheter used for the other cases. Only 1 adverse event was reported: hypoxemia leading to premature termination of the endoscopy. The event was not felt to be related to LN2SC or its retroflexed use. Conclusion: Experience to date demonstrates the feasibility and safety of LN2SC in retroflexion for treatment of lesions at the EGJ and cardia. The ability to use LN2SC in both en face and retroflexed positions expands the treatment options available for lesions in the upper gastrointestinal tract, especially those previously unreachable by other methods. Patients Treated With LN2SC In Retroflexion

Introduction: The nature of pancreatic cysts often remains uncertain, despite several tests, resulting in unoptimal management for patients. nCLE is an imaging technique, enabling microscopic observation of solid organs, in vivo and in real-time, during an EUS-FNA procedure. This technique could potentially provide useful information to establish a differential diagnosis between mucinous and non mucinous neoplasms. A recent study, INSPECT, described nCLE criteria for the characterization of intraductal papillary mucinous neoplasms (IPMN). Further descriptions were needed to identify nCLE criteria for the characterization of mucinous cystadenomas neoplasms (MCN) and non mucinous lesions. A prospective multicenter French study (CONTACT) aims at assessing the yield of nCLE for the diagnosis of pancreatic cystic tumors. Interim results presented criteria specific of serous cystadenomas (SCA). However, nCLE criteria for the characterization of MCN are still unknown. Materials and methods: Over 10 months, 31 patients without chronic pancreatitis and with a lonely pancreatic cyst > 2 cm large were enrolled. Following EUS examination, the AQ-Flex 19 miniprobe was introduced in a 19G needle and real-time video sequences of the cyst wall were recorded. Intracystic fluid obtained was analyzed. Final diagnosis of MCN (n=6) was based on surgery. The other lesions were considered as IPMN (n=5), pseudocysts (n=7) and SCA (n=13) on pathological consideration or expert consensus. Four gastroenterologists and two pathologists, unblinded to the final diagnosis studied the 31 nCLE videos records and compared their findings to the pathological specimen. Results: A particular pattern was furtively and recurrently seen in sequences acquired in three of the MCN lesions: an epithelial border lined the cyst wall, with or without deep blood vessels, and without papillary organization. These features were only observed in MCN sequences. These criteria correlate with the histological structure of those tumors that are characterized by a tall columnar mucin-producing epithelium underlined by a thick fibrous tissue with pseudo-ovarian stroma and vessels. Conclusions: The mucinous columnar epithelial border of MCN can be highlighted by nCLE. The validation of this criterion by an external group is undergoing and results will be available by the beginning of 2014. If proven to be accurate, this new sign might be useful for the diagnosis of mucinous cystadenoma neoplasms.