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Extrahepatic portal hypertension (EPH) is hypertension that occurs in the extrahepatic portal vasculature in the absence of liver cirrhosis. Portal hypertension (PHTN) is defined as a pressure gradient between the portal vein and hepatic vein/inferior vena cava (IVC) exceeding more than 5 mm Hg. PHTN is more commonly known as a manifestation of cirrhosis and the related elevation in hepatic to venous pressure gradient (HVPG); however, there are other extrahepatic etiologies to PHTN that are important for review. Per our literary review, EPH as a complication of pancreatitis has been known as a manifestation since at least the 1970s. Among the severities of pancreatitis, it occurs most commonly with acute necrotizing pancreatitis and chronic pancreatitis. In this review, we plan to provide an understanding of mechanisms by which EPH occurs, discuss the treatments (e.g., anticoagulation, splenic artery embolization, and splenectomy) for the complications that result from prolonged EPH, and discuss the current endoscopic interventions available to counteract these complications.

Introduction Glucocorticoids contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Natural killer T cells play a role in the pathogenesis of NAFLD and response to steroids. The present study aimed to determine the role of CD1d in steroid-mediated metabolic derangement and the steroid-protective effect of glycosphingolipids. Methods Ten groups of mice were studied. Steroids were orally administered to C57BL/6 mice to assess the therapeutic effect of β-glucosylceramide (GC) on the development of steroid-mediated liver damage and metabolic derangements. The role of CD1d in the pathogenesis of steroid-induced liver damage and in mediating the hepatoprotective effect of GC was studied in CD1d−/− mice. Results A model of oral administration of steroids was established, resulting in insulin resistance, hyperinsulinemia, hypertriglyceridemia, liver steatosis, and hepatocellular injury. Steroid administration to CD1d−/− mice was associated with hyperglycemia and hypertriglyceridemia. However, CD1d−/− mice did not manifest marked steroid-induced steatosis. GC treatment alleviated steroid-associated metabolic derangements and liver injury independent of CD1d expression. Conclusion A steroid-mediated model of NAFLD and metabolic derangements was established in which steroid-mediated steatosis was CD1d-dependent while steroid-induced liver necrosis, inflammation, and metabolic changes were CD1d-independent, which may support a dichotomy between steatosis and steatohepatitis in NAFLD.

Metabolic syndrome is recognized as a proinflammatory condition leading to hepatic steatosis and nonalcoholic steatohepatitis (NASH). We tested the effects of a succulent species Hoodia parviflora N.E. Br., of the genus Hoodia sweetex Dence, on animal models of NASH and insulin resistance (ob/ob mouse and the sand rat Psammomys obesus). IL6 secretion was evaluated by ELISA and hepatic signal transducer and activator of transcription 3 by Western blot. We followed liver enzymes, weight, glucose, hepatic histology, hepatic triglycerides (TGs), and total fat and serum insulin. Oral administration of extracts derived from H. parviflora alleviated the insulin resistance manifested by improved glucose tolerance tests. Treatment alleviated the liver injury noted by a decrease in liver enzyme levels, improved intrahepatic TG content, total hepatic fat, and improved hepatic histology. Similarly, treatment with H. parviflora reduced hepatic inflammation in mice with Concanavalin A-induced hepatitis. These effects were independent of food consumption and weight. H. parviflora was associated with alleviated insulin resistance, hepatic steatosis, and liver injury. The data support its use as a liver protector.

Background and study aims During evaluation of pancreaticobiliary strictures, it is common practice to send biliary stents for cytologic analysis. However, in recent years, complementary tissue acquisition techniques ranging from cholangioscopy to fine-needle biopsy have improved the ability to acquire tissue and diagnose malignancy. Data are limited on the current diagnostic yield and cost effectiveness of biliary stent analysis. Patients and methods We performed a retrospective study of all pancreaticobiliary stents sent for analysis in a tertiary care academic medical center from June 2013 to September 2016. Patient demographics, stent information, and final diagnosis history were collected through chart review. Costs were determined using published reimbursement rates for Medicare. Results Two hundred thirty-one stents from 175 patients were sent for cytologic analysis during the study period. Of the 62 stents obtained from patients ultimately diagnosed with malignancy, only one (1.6 %) had positive cytology for malignant cells, while the others were acellular/non-diagnostic (2/62, 3.2 %), negative (48/62, 77.4 %), or atypical (11/62, 17.7 %). The sensitivity of stent cytology for diagnosis of malignancy was 1.6 % (1/62). No cases were identified in which stent cytology changed clinical management. From a payer perspective, the mean estimated cost for each stent cytologic analysis is greater than $ 70.00. Conclusions While stent cytologic analysis is a common clinical practice, the diagnostic yield and cost effectiveness of the practice must be reevaluated. With the rise of newer diagnostic technologies such as digital cholangioscopy and endoscopic ultrasound-guided fine-needle biopsy, it may be time to “think lean” and acknowledge a sunset for biliary stent cytology.

Contains fulltext : 205162.pdf (Publisher’s version ) (Open Access) BACKGROUND AND AIMS: Colorectal cancer (CRC) is largely preventable with routine screening and surveillance colonoscopy; however, interval cancers arising from precancerous lesions missed by standard colonoscopy still occur. An increased adenoma detection rate (ADR) has been found to be inversely associated with interval cancers. The G-EYE device includes a reusable balloon integrated at the distal tip of a standard colonoscope, which flattens haustral folds, centralizes the colonoscope's optics, and reduces bowel slippage. The insufflated balloon also aims to enhance visualization of the colon during withdrawal, thereby increasing the ADR. METHODS: In this randomized, controlled, international, multicenter study (11 centers), patients (aged >/=50 years) referred to colonoscopy for screening, surveillance, or changes in bowel habits were randomized to undergo either balloon-assisted colonoscopy by using an insufflated balloon during withdrawal or standard high-definition colonoscopy. The primary endpoint was the ADR. RESULTS: One thousand patients were enrolled between May 2014 and September 2016 to undergo colonoscopy by experienced endoscopists; 803 were finally analyzed (standard colonoscopy n = 396; balloon-assisted colonoscopy n = 407). Baseline parameters were similar in both groups. Balloon-assisted colonoscopy provided a 48.0% ADR compared with 37.5% in the standard colonoscopy group (28% increase; P = .0027). Additionally, balloon-assisted colonoscopy provided for a significant increase in detection of advanced (P = .0033) flat adenomas (P < .0001) and sessile serrated adenomas/polyps (P = .0026). CONCLUSION: Balloon-assisted colonoscopy yielded a higher ADR and increased the detection of advanced, flat, and sessile serrated adenomas/polyps when compared with standard colonoscopy. Improved detection by the G-EYE device could impact the quality of CRC screening by reducing miss rates and consequently reducing interval cancer incidence. (Clinical trial registration number: NCT01917513.).

Percutaneous endoscopic gastrostomy (PEG) tubes are routinely used as an effective method for providing enteral nutrition. The need for their exchange is common.We aimed to examine the comparative safety and cost-effectiveness of PEG percutaneous counter-traction "pulling" approach or by endoscopically guided retrieval.A prospective 215 consecutive patients undergoing PEG tube insertion were included. Fifty patients in total were excluded. The patients were examined for demographics, indications for PEG replacement, as well as procedure-related complications and procedural costs.Group A included 70 patients (42%) with PEG tubes replaced endoscopically, whereas group B included 95 patients (58%) with PEG tubes replaced percutaneously. Baselines characteristics were similar between the 2 groups (P=NS). Group A and group B had similar immediate complication rates including 4 patients in group B (4.2%), and 2 patients in group A (2.8%) (P=0.24). Complications included a conservatively managed esophageal perforation, and self-limited mild bleeding groups A and group B, respectively. The mean procedure cost was significantly higher in the endoscopic PEG replacement group compared with the percutaneous PEG replacement group ($650 vs. $350, respectively).Percutaneous PEG replacement appears as safe as endoscopic PEG replacement, however, percutaneous tube exchange is less costly.

BACKGROUND: Radiofrequency ablation (RFA) has been used to treat various abdominal tumors including pancreatic tumors. Multiple approaches such as laparoscopic, open, and percutaneous have been used for pancreatic tissue ablation. More recently, endoscopic ultrasound (EUS)-guided RFA has emerged as a new technique for pancreatic tissue ablation. The role of EUS-RFA in management of pancreatic lesions is still not well-established. In this study, our aim is to assess efficacy and safety of EUS-RFA for management of pancreatic lesions. METHODS: MEDLINE, Scopus, and Cochrane Library databases were searched to identify studies reporting EUS-RFA of pancreatic lesions with outcomes of interest. Studies with

Glucocorticoids have been implicated in the pathogenesis of all stages of non-alcoholic fatty liver disease (NAFLD). Natural killer T cells play a role in the pathogenesis of NAFLD and in the response to steroids. The aim of the present study was to determine the role of CD1d in steroid-mediated metabolic derangement and the steroid-protective effect of glycosphingolipids. Methods: Ten groups of mice were studied. Steroids were orally administered to C57BL/6 mice to assess the therapeutic effect of β-glucsylceramide (GC) on the development of steroid-mediated liver damage and metabolic derangements. The role of CD1d in the pathogenesis of steroid-induced liver damage, and in mediating the hepatoprotective effect of GC were studied in CD1d−/− mice. Results: A model of oral administration of steroids was established, resulting in insulin resistance, hyperinsulinemia, hypertriglyceridemia, liver steatosis, and hepatocellular injury. Steroid administration to CD1d−/− mice was associated with hyperglycemia and hypertriglyceridemia. However, CD1d−/− mice were relatively resistant to steroid-induced steatosis. GC treatment alleviated steroid-associated metabolic derangements and liver injury independent of CD1d expression. Conclusion: A steroid-mediated model of NAFLD and metabolic derangements was established in which steroid-mediated steatosis was CD1d-dependent while steroid-induced liver necrosis, inflammation, and metabolic changes were CD1d-independent, further supporting a dichotomy between steatosis and steatohepatitis in NAFLD.

BACKGROUND AND AIMS: Endoscopic full thickness resection (eFTR) is a field of increasing interest that offers a minimally invasive resection modality for lesions that are not amenable for resection by conventional methods. Full-thickness resection device (FTRD) is a new device that was developed for a single-step eFTR using an over-the scope-clip (OTSC). In this meta-analysis, we aim to assess the efficacy and safety of FTRD for eFTR of colorectal lesions. METHODS: A Comprehensive literature review of different databases to identify studies reporting FTRD with outcomes of interest was performed. Studies with

Background The use of fully covered lumen-apposing metal stents (LAMS) for benign short gastrointestinal (GI) strictures has been reported. This study aimed to evaluate the safety and efficacy of LAMS for refractory GI strictures. Methods A retrospective analysis was performed of patients who underwent LAMS placement for benign GI strictures in 8 United States centers. The primary outcomes were technical success and initial clinical response. Secondary outcomes were reintervention rate and adverse events. Results A total of 51 patients underwent 61 LAMS placement procedures; 33 (64.7%) had failed previous treatments. The most common stricture location was the pylorus (n=17 patients). Various sizes of stents were used, with 15-mm LAMS placed in 45 procedures, 20-mm LAMS in 14 procedures, and 10-mm LAMS in 2 procedures. The overall technical success, short-term clinical response and reintervention rate after stent removal were 100%, 91.8% and 31.1%, respectively. Adverse events were reported in 17 (27.9%) procedures, with stent migration being the most common (13.1%). In subgroup analysis, both 15 mm and 20 mm stents had comparable short-term clinical response and adverse event rates. However, stent migration (15.6%) was the most common adverse event with 15-mm LAMS while pain (14.3%) was the most common with 20-mm LAMS. The reintervention rate was 80% at 200-day follow up after stent removal. Conclusions Using LAMS for treatment of short benign GI strictures is safe and effective. Larger LAMS, such as the new 20 mm in diameter, may have a lower stent migration rate compared to smaller diameter LAMS.

Introduction In patients with locally advanced rectal cancer, restaging pelvis magnetic resonance imaging (MRI) after neoadjuvant concurrent chemoradiotherapy is recommended despite its limited accuracy in predicting pathologic T (ypT) and N (ypN) stage. Neoadjuvant rectal (NAR) score is a novel short-term surrogate endpoint for disease-free survival (DFS) and overall survival (OS). We tested the agreement between restaging MRI T (yT) and N (yN) with ypT and ypN stages, respectively, and explored the prognostic significance of restaging MRI NAR (mNAR) score. Patients and Methods Between 2014 and 2018, 43 patients with locally advanced rectal cancer completed neoadjuvant concurrent chemoradiotherapy, had a restaging MRI, and underwent surgery. Weighted kappa was used to test the agreement between yT and yN with ypT and ypN, respectively. A kappa value of less than 0.5 was deemed unacceptable. Paired t test was used to compare NAR and mNAR mean scores. Survival was estimated by Kaplan-Meier curves. Results Restaging MRI could not predict ypT stage (slight agreement, κ = 0.111) or ypN stage (fair agreement, κ = 0.278). The mean mNAR score was higher than the mean NAR score (20 vs. 16, P = .0079). The median DFS for patients with low-intermediate NAR and high NAR was not reached vs. 30 months (P = .0063). The median OS for patients with low-intermediate NAR and high NAR was not reached vs. 40 months (P = .0056). There was a trend for longer DFS and OS in patients with low-intermediate mNAR scores (not reached in both groups, P = .058) compared to patients with high mNAR scores (not reached in both groups, P = .15). Conclusion Restaging MRI could not predict ypT and ypN stage. The mean mNAR score was higher than the mean NAR score. There was a trend for longer DFS and OS in patients with low-intermediate mNAR scores compared to patients with high mNAR scores.

Endoscopic full-thickness resection device (FTRD) is a new and promising device for endoscopic full-thickness resection of gastrointestinal lesions. Limited data is available regarding its role in endoscopic full-thickness resection of upper gastrointestinal lesions compared with its well-studied role in colorectal lesions. Colonic FTRD is a preloaded device with a large cap which limits peroral insertion. A 49-year-old woman was referred to us for submucosal gastric lesion resection. Gradual dilatation of the upper esophagus was performed before successful advancement of the endoscope mounted with a FTRD system into the stomach. The lesion was successfully resected with no complications.

Endoscopic ultrasound (EUS)-guided fine needle aspiration with or without biopsy (FNA/FNB) are the primary diagnostic tools for gastrointestinal submucosal tumors. EUS-guided fine needle aspiration (EUS-FNA) is considered a first line diagnostic method for the characterization of pancreatic and upper gastrointestinal lesions, since it allows for the direct visualization of the collection of specimens for cytopathologic analysis. EUS-FNA is most effective and accurate when immediate cytologic assessment is permitted by the presence of a cytopathologist on site. Unfortunately, the accuracy and thus the diagnostic yield of collected specimens suffer without this immediate analysis. Recently, a EUS-FNB needle capable of obtaining core samples (fine needle biopsy, FNB) has been developed and has shown promising results. This new tool adds a new dimension to the diagnostic and therapeutic utility of this technique. The aim of the present review is to compare the efficacy of EUS-FNA to that afforded by EUS-FNB in the characterization of pancreatic masses and of upper and lower gastrointestinal submucosal tumors.

Background The etiology of primary sclerosing cholangitis (PSC) is unknown. PSC and Cystic Fibrosis related liver disease have common features: chronic inflammation, biliary damage and similar cholangiographic findings. It is unknown whether or not PSC is related to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. We hypothesize that a sub-group of PSC patients may be a “single-organ” presentation of CF. Methods Patients with PSC underwent nasal potential difference (NPD) measurement, sweat chloride measurement and complete CFTR sequencing by new generation sequencing. Results 6/32 patients aged 46 ± 13 yrs. had CFTR causing mutations on one allele and 19 had CFTR polymorphisms; 6/23 tested had abnormal and 21 had intermediate sweat tests; 4/32 patients had abnormal NPD. One patient had chronic pancreatitis and was infertile. Conclusions 19% of PSC patients had features of CFTR related disorder, 19% carry CFTR mutations and 50% had CFTR polymorphisms. In some patients, PSC may be a single organ presentation of CF or a CFTR-related disorder.

Gastroparesis is a debilitating progressive disease that significantly impacts a patient's life with limited and challenging treatments available. Although the pathogenesis is multifactorial, pylorospasm is believed to have a major underlying role. Several therapeutic interventions directed to the pylorus have been developed over the last decade, including intra-pyloric injections of botulinum toxin, transpyloric stenting, and surgical pyloroplasty. All of these treatment options had limited and disappointing results. More recently, gastric peroral endoscopic myotomy (G-POEM) has been reported as a treatment for refractory gastroparesis. In this review article, we provide an overview on gastroparesis with a focus on the therapeutic interventions. In addition, we provide a literature summary and pool analysis of the clinical efficacy, scintigraphic efficacy, and safety profile of all studies that evaluated G-POEM in gastroparesis. Overall, seven studies have reported on the use of G-POEM in gastroparesis, and the pooled analysis of these studies showed a technical success of 100%, with clinical efficacy as assessed by the Gastroparesis Cardinal Symptoms Index of 81.5%, gastric emptying scintigraphy normalization in approximately 55.5% of the cases, perioperative complications in 7.6%, and intraoperative complications in 6.6%. This suggests that G-POEM is a new promising therapeutic intervention for the treatment of gastroparesis with durable effect and limited potential adverse events.

Background While the fiberoptic single-operator cholangiopancreatoscopy (FSOCP) system has demonstrated efficacy in the diagnosis and management of pancreaticobiliary diseases, the digital SOCP (DSOCP) appears to provide higher resolution digital imaging, however a comparison of these devices has not been established. The aim of this work was to compare the efficacy of FSOCP and DSOCP in biliary stone disease and indeterminate biliary strictures. Methods A retrospective analysis of a prospective cohort was performed in patients undergoing FSOCP or DSOCP demographics included indication, diagnostic yield, procedure time, radiation dose, and complications. Results 324 patients underwent cholangioscopy. FSOCP and DSOCP were utilized in 198 and 126 patients respectively. Male/female ratio was similar and mean age was 66 ± 13 years. Indications included stone disease, indeterminate stricture evaluation and “other” were 47%, 42% and 11% respectively. Mean procedure time for stone disease and the amount of radiation doses in DSOCP group were lower than the FSOCP group ( P = 0.032 and P = 0.02, respectively). Diagnostic yield in indeterminate strictures was higher 78% with DSOCP system compared to 37% with FSOCP system ( P = 0.004). Complication were low and similar between the groups. Conclusions DSOCP system provides enhanced diagnostic yield, shorter procedure times and less radiation exposure compared to FSOCP system.

Background and Aims: Acetaminophen (APAP) and HMG-CoA reductase inhibitors are common causes of drug-induced liver injury (DILI). This study aimed to determine the ability to reduce APAP- and statins-mediated liver injury by using formulations that combine glycosphingolipids and vitamin E. Methods: Mice were injected with APAP or with statins and treated before and after with β-glucosylceramide (GC), with or without vitamin E. Mice were followed for changes in liver enzymes, liver histology, hepatic expression of JNK, STAT3 and caspase 3, as well as intrahepatic natural killer T cells (NKT) and the serum cytokine levels by flow cytometry. Results: Administration of GC before or after APAP alleviated the liver damage, as noted by a reduction of the liver enzymes, improvement in the liver histology and decreased hepatic caspase 3 expression. Beneficial effect was associated with a reduction of the intrahepatic NKT, JNK expression in the liver, and increased glutathione in the liver, and decreased TNF-α serum levels. Synergistic effect of co-administration of GC with vitamin E was observed. Similar protective effect of GC on statin-mediated liver damage was documented by a reduction in liver enzymes and improved liver histology, which was mediated by reduction of NKT, increased STAT3 expression in the liver, and reduced the TGF-β and IL17 levels. Conclusions: β-glycosphingolipids exert a hepatoprotective effect on APAP- and statins-mediated liver damage. Vitamin E exerted a synergistic effect to that of GC. The generation of “safer drug” formulations, which include an active molecule combined with a hepatoprotective adjuvant, may provide an answer to the real unmet need of DILI.

Temozolomide (TMZ) is an alkylating agent used for treatment of brain neoplasms and levetiracetam (LEV) is a commonly used antiepileptic. When administered separately each medication has few negative side effects impacting the liver.We sought to determine the risk of liver injury associated with the co-administration of TMZ and LEV.A case-control study was performed comparing patients who received combination therapy of TMZ and LEV (group A) with matched controls (group B) who received monotherapy with one of either TMZ or LEV. We assessed patient demographics, laboratory results including presence of liver injury, and mortality.Twenty-six patients were included in group A and 68 patients were included in group B. Both groups were similar with respect to demographics and baseline liver function tests (P0.05). There was a significant elevation in liver enzymes in 73%, 46%, 19%, 31% and 27% of ALT, AST, ALK-P, GGT and bilirubin, respectively, in group A, as compared to elevations of 10.3%, 19%, 1.5%, 7% and 1.5%, respectively in group B (P0.05). One patient in group A died as a result of acute liver failure while no deaths from acute liver failure occurred in group B (P=0.05). Univariate analysis identified combination therapy as a risk factor for liver injury. Multivariate regression showed that only co-treatment with TMZ and LEV was an independent risk factor for liver injury with an odds ratio of 19.1 (95 CI, 2.16-160).Combination therapy with TMZ and LEV may precipitate acute liver injury and even death.

Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Metabolic syndrome is recognized as a proinflammatory condition leading to hepatic steatosis and nonalcoholic steatohepatitis (NASH). We tested the effects of a succulent species

Background: Exosomes are important mediators of intercellular communications and play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. In patients with pancreatic ductal adenocarcinoma (PDAC), positive correlation between CD9 expression and overall survival (OS) was reported. CD63 expression was conserved in all patients with no reported prognostic significance. This study explored the prognostic significance of CD63 and CD9 expression using immunohistochemistry (IHC) in patients with PDAC of mixed racial background. Methods: Between 2012 and 2016, 49 patients with PDAC had available tissues for CD63 and CD9 staining using IHC. Two pathologists independently scored the CD63 and CD9 expression. Staining intensity was graded from 1–3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (Intensity X Percentage of staining) was calculated. Results: The mean Q-score for CD63 and CD9 are higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites (185 vs . 102, P=0.0002) and (48 vs . 20, P=0.0418) respectively. We fitted Cox proportion hazard regression models to investigate the impact of the covariates CD63 and CD9 on progression free survival (PFS) and OS. CD63 has significant impact on PFS (P=0.0135) and OS (P=0.003). The higher the CD63 Q-score, the longer the PFS and OS. CD9 doesn’t have significant impact on PFS (P=0.5734) or OS (P=0.2682). The mean CD63 and CD9 Q-scores are slightly higher in African American (AA) compared to Caucasians (157 vs . 149, P=0.76) and (45 vs . 29, P=0.43) respectively. Conclusions: CD63 and CD9 expression is higher in primary tumor from the pancreas compared to pancreatic tumor from metastatic sites. There is correlation between CD63 expression (but not CD9 in this cohort) and PFS and OS. To our knowledge, this is the first study to show prognostic significance of CD63 expression in patients with PDAC using IHC. A trend of higher expression of CD63 and CD9 among AA compared to Caucasians was also noticed.

Distal biliary stricture secondary to pancreatic cancer or primary biliary cancer such as cholangiocarcinoma, gallbladder cancer, carcinoma of the ampulla of Vater, or metastatic disease caries poor prognosis mainly due to lack of initial symptoms and advanced stage prognosis. Every year more then 40,000 new patients are diagnosed with pancreatic cancer. Pancreatic cancer is responsible for almost 90% of distal biliary obstruction. The main symptom is painless jaundice, but patients may also present with weight loss, anorexia, epigastric pain, and back pain. Different imaging modalities are required for the differential and final diagnosis; computed tomography (CT), magnetic resonance (MRI), endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound (EUS) are few of the modalities used for diagnosing and staging in cases of distal biliary strictures. In this chapter we will review the epidemiology, natural history, clinical presentation, diagnosis, and curative and palliative treatment of distal bilary strictures.