The multidisciplinary management of cholangiocarcinoma.

Cholangiocarcinoma is a lethal malignancy of the biliary epithelium that can arise anywhere along the biliary tract. Surgical resection confers the greatest likelihood of long-term survivability. However, its insidious onset, difficult diagnostics, and resultant advanced presentation render the majority of patients unresectable, highlighting the importance of early detection with novel biomarkers. Developing liver-directed therapies and emerging targeted therapeutics may offer improved survivability for patients with unresectable or advanced disease. In this article, the authors review the current multidisciplinary standards of care in resectable and unresectable cholangiocarcinoma, with an emphasis on novel biomarkers for early detection and nonsurgical locoregional therapy options.

AGA Clinical Practice Update on Role of EUS-Guided Gallbladder Drainage in Acute Cholecystitis: Commentary.

DESCRIPTION: Endoscopic gallbladder drainage is a feasible and efficacious alternative to percutaneous drainage in the management of acute cholecystitis for high-risk surgical candidates. Endoscopic ultrasound-guided gallbladder drainage and per-oral cholecystoscopy is facilitated by the use of lumen-apposing metal stents. Endoscopic ultrasound-guided gallbladder drainage should be performed by those expert in advanced therapeutic endoscopic ultrasound. Multidisciplinary collaboration between interventional radiology and surgery is paramount in the care of these patients. Choosing the optimal drainage method is dependent on individual patient characteristics. METHODS: This commentary was drawn from a review of the literature to provide practical advice. Because this was not a systematic review, we did not perform any formal rating of the quality of evidence or strength of the presented considerations. This expert commentary was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer-review by the Clinical Practice Updates Committee and external peer-review through standard procedures of Clinical Gastroenterology and Hepatology.

Wilson's Disease.

Wilson's disease (WD) can present with liver disease, neurological deficits, and psychiatric disorders. Results of genetic prevalence studies suggest that WD might be much more common than previously estimated. Early recognition of WD remains challenging because it is a great imitator and requires a high index of suspicion for correct and timely diagnosis. Early diagnosis of WD is crucial to ensure that patients can be started on adequate treatment. In association with other clinical and biochemical tests, liver biopsy results and molecular genetic testing can also be used for diagnosing WD. Medical therapy is effective for most patients; liver transplant can rescue those with acute liver failure or those with advanced liver disease who fail to respond to or discontinue medical therapy. Although novel therapies, such as gene therapy, are on the horizon, screening and prevention of delayed diagnosis remains paramount.

AGA Clinical Practice Update on Management of Subepithelial Lesions Encountered During Routine Endoscopy: Expert Review.

BEST PRACTICE ADVICE STATEMENTS: BEST PRACTICE ADVICE 1: Forceps bite-on-bite or deep-well biopsies or tunnel biopsies can sometimes establish a pathologic diagnosis of SEL. BEST PRACTICE ADVICE 2: EUS is the modality of choice to evaluate indeterminate SEL of the GI track and/or if non-diagnostic tissue by forceps biopsies. BEST PRACTICE ADVICE 3: SEL arising from the submucosa can be sampled using tunnel biopsies (or deep-well biopsies), EUS guided fine-needle aspiration (FNA), EUS guided fine-needle biopsy (FNB), or advanced endoscopic techniques (unroofing or endoscopic submucosal resection). BEST PRACTICE ADVICE 4: SEL arising from muscularis propria should be sampled (preferably using FNB or FNA) to determine whether the lesion is a GIST or leiomyoma. Structural assessment and staining will allow differentiation of mesenchymal tumors and assessing their malignant potential. BEST PRACTICE ADVICE 5: Endoscopic resection techniques have been described for removal of SEL and should be limited to endoscopists skilled in advanced tissue resection techniques. BEST PRACTICE ADVICE 6: Management of each SEL depends on the size of the lesion, histopathology, their malignant potential, and presence of symptoms. BEST PRACTICE ADVICE 7: SEL that have an endoscopic appearance consistent with a lipoma or pancreatic rest and normal mucosal biopsies do not need further evaluation or surveillance. BEST PRACTICE ADVICE 8: For SEL arising from muscularis propria that are less than 2 cm in size, surveillance using EUS should be considered. BEST PRACTICE ADVICE 9: Gastric GIST larger than 2 cm should be considered for resection. BEST PRACTICE ADVICE 10: Subepithelial lesions that are ulcerated, bleeding, or causing symptoms should be considered for resection.

Management of Pancreatic Duct Stones.

PURPOSE OF REVIEW: Pancreatic duct stones are sequela of chronic pancreatitis. They can cause pancreatic duct obstruction which is the most important cause of pain in chronic pancreatitis. Stone resolution has shown to improve pain. The goal of this review is to highlight recent endoscopic and surgical advancements in treatment of pancreatic duct stones. RECENT FINDINGS: Stone fragmentation by extracorporeal shock wave lithotripsy has become first line and the mainstay of treatment for majority of patients with pancreatic duct stones. Introduction of digital video pancreatoscopy in the last few years with the capability of guided lithotripsy has provided a robust therapeutic option where extracorporeal shock wave lithotripsy is unsuccessful or unavailable. Historically, surgery has been considered a more reliable and durable option when feasible. However, it had not been compared with more effective endoscopic therapy. Lithotripsy (extracorporeal and pancreatoscopy guided) is evolving as a strong treatment modality for pancreatic stones.

Biliary stenting in patients with malignant biliary obstruction: comparison of double layer, plastic and metal stents.

BACKGROUND AND AIM: The double layer stent (DLS) has a unique design and has been used for palliation of malignant biliary obstruction, but literature on this stent is limited. Our aim was to compare plastic (PS), DLS and metal stents (MS) in terms of complication rates, time to occlusion, and patency rate in patients with malignant biliary obstruction (MBO). METHODS: A retrospective review of stents placed for MBO at our institution in the period between January 2009 and April 2011 was conducted. A total of 114 stents were identified, of which 44 were MS (39 %), 37 DLS (32 %), and 33 PS (29 %). A stent was considered occluded when an unplanned stent removal or intervention occurred due to clinical suspicion of biliary obstruction. RESULTS: Stents remained patent for 95 days (range 7-359 days) in the DLS group and 59 days (range 7-228 days) in the PS group (P = 0.014) and 128.7 days (range 4-602 days) in the metal stent group. Twenty-seven percent (n = 9) of PS occluded after a mean of 60 days while 16 % (n = 7) of MS occluded after a mean of 87 days and 5 % (n = 2) of DLS occluded after a mean of 85 days (DLS vs. PS P = 0.012, DLS vs. MS P = 0.13, MS vs. PS P = 0.22). CONCLUSIONS: DLS are superior to PS in patients with MBO and appear to be comparable to MS. MS had a longer patency rate but were comparable to DLS in early and late complications. We speculate that the less expensive DLS may be a cost effective alternative in the palliation of MBO.

Gastrointestinal Dysfunction in Parkinson's Disease.

There has been exponential growth in the awareness and understanding of gastrointestinal (GI) dysfunction in Parkinson's disease (PD) over the past 3 decades. The clinical features of GI dysfunction in PD have been clearly identified and innovative research has demonstrated the presence of pathology within the enteric nervous system (ENS) in individuals with PD, leading to suggestions that the GI system may be ground zero for the genesis and the portal of entry of PD pathology, which then ascends via the vagus nerve to the central nervous system (CNS). This theory, as well as the more recent recognition of the association of PD with dysbiosis within the gut microbiota, has been the object of intense study and scrutiny. Since most PD medications are absorbed through the GI system, the need for better understanding of changes within the GI tract that may potentially affect the pattern of response to medications has become evident. In this review, current knowledge of the pathophysiology of changes within the GI tract and the gut microbiome of individuals with PD, including changes that occur with progression of the disease, will be addressed. We focus on common clinical GI problems in PD that can arise from different segments of the GI tract. Relevant diagnostic evaluations and treatment options for each of these problems will be reviewed.

Mycophenolate mofetil for the treatment of autoimmune hepatitis in patients refractory or intolerant to conventional therapy.

BACKGROUND: Autoimmune hepatitis is characterized by hepatocellular inflammation often progressing to cirrhosis. Standard treatment consists of corticosteroids and azathioprine. For the 20% of patients with refractory disease or those who are intolerant to medication, there is no standardized treatment. OBJECTIVE: To evaluate mycophenolate mofetil (MMF) as an alternative therapy for autoimmune hepatitis.  METHODS: The present retrospective study identified all patients with autoimmune hepatitis who were treated with MMF over a 10-year period at the Henry Ford Hospital (Michigan, USA). These patients were evaluated for tolerance and response. RESULTS: Of the 90 patients participating in the study, 48% had a complete response, 32% experienced relapses and 21% were refractory. MMF was initiated in 21 patients - 12 (57%) for refractory disease and nine (43%) for medication intolerance. Of the 12 patients converted for refractory disease, all showed biochemical improvement but none had a complete response. Of the patients converted due to intolerance, 88% maintained complete remission. For all patients converted to MMF, there was a mean decrease in steroid dose from 18.9 mg/day to 7.8 mg/day (P=0.01). CONCLUSIONS: In patients with autoimmune hepatitis who were intolerant to conventional therapy, MMF was well tolerated, with 88% of patients maintained in remission. MMF did not induce remission in those refractory to conventional therapy; however, it resulted in a significant decrease in steroid use. Prospective studies are needed to better assess the role of MMF as an alternative therapy.

Endoscopic or Conservative Management of Iatrogenic Duodenal Perforations Caused by Long Plastic Biliary Stent Distal Migration.

Plastic biliary stents are associated with rare but potentially life-threatening distal stent migration. We present 4 patient cases with distal migration, whereas the proximal aspect remained in the bile duct. Time to stent migration ranged from 1 week to 2 months. Stent migration caused contralateral duodenal wall perforation; 2 underwent endoscopic over-the-scope clip placement for defect closure. All required previous stent removal and stent exchange. This case series highlights that proximal stricture and longer stents have higher migration risk, also shown in the literature. We also show that duodenal perforation can successfully be managed endoscopically with an over-the-scope clip.

Diabetes and the Pancreatobiliary Diseases.

PURPOSE OF REVIEW: The emphasis of this review article is to bring to the forefront the spectrum of pancreatobiliary disorders and their association with diabetes. We hope to systematically discuss the link between diabetes and disorders of the pancreas including acute and chronic pancreatitis, as well as pancreatic cancer. We also hope to review and highlight the literature with respect to other cancers of the biliary tree including gallbladder and cholangiocarcinoma. Lastly, we discuss diabetes and biliary dyskinesia. RECENT FINDINGS: Newer cohort studies suggest the presence of diabetes to increase the severity and worsen outcomes in acute pancreatitis. Post pancreatitis diabetes is a novel disease entity being increasingly recognized. The use of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis may attenuate the risk of endocrine dysfunction. Pancreatic cancer may either be the consequence of diabetes or a presenting manifestation. The use of anti-diabetic medications may confer protection against development of pancreatic cancer. Gallbladder adenocarcinoma and cholangiocarcinoma risks are elevated in those with underlying diabetes. Diabetes can directly impact or deteriorate outcome of acute and chronic pancreatitis and well as pancreatobiliary malignancies. It could also occur as a result of loss of endocrine function after pancreatitis. Like many areas of the digestive tract, biliary motility could be impacted by diabetes.

Detection of small bowel tumor in wireless capsule endoscopy images using an adaptive neuro-fuzzy inference system.

Automatic diagnosis tool helps physicians to evaluate capsule endoscopic examinations faster and more accurate. The purpose of this study was to evaluate the validity and reliability of an automatic post-processing method for identifying and classifying wireless capsule endoscopic images, and investigate statistical measures to differentiate normal and abnormal images. The proposed technique consists of two main stages, namely, feature extraction and classification. Primarily, 32 features incorporating four statistical measures (contrast, correlation, homogeneity and energy) calculated from co-occurrence metrics were computed. Then, mutual information was used to select features with maximal dependence on the target class and with minimal redundancy between features. Finally, a trained classifier, adaptive neuro-fuzzy interface system was implemented to classify endoscopic images into tumor, healthy and unhealthy classes. Classification accuracy of 94.2% was obtained using the proposed pipeline. Such techniques are valuable for accurate detection characterization and interpretation of endoscopic images.

EUS-guided biliary drainage or enteroscopy-assisted ERCP in patients with surgical anatomy and biliary obstruction: an international comparative study.

Background and study aims: How enteroscopy-assisted ERCP (e-ERCP) and endoscopic ultrasound-guided biliary drainage (EUS-BD) compare in patients with surgically altered upper gastrointestinal anatomy is currently unknown. The aims of this study were to compare efficacy and safety of both techniques and study predictors of these outcomes. Patients and methods: This was an international, multicenter comparative cohort study at 10 tertiary centers. Outcomes data included technical success (biliary access with cholangiography and stent placement [when indicated]), clinical success (resolution of biliary obstruction) and adverse events (AEs) (graded according to the ASGE lexicon). Results: A total of 98 patients underwent EUS-BD (n = 49) or e-ERCP (n = 49). Technical success was achieved in 48 (98 %) patients in the EUS-BD group as compared to 32 (65.3 %) patients in the e-ERCP group (OR 12.48, P = 0.001). Clinical success was attained in 88 % of patients in EUS-BD group as compared to 59.1 % in the e-ERCP group (OR 2.83, P = 0.03). Procedural time was significantly shorter in the EUS-BD group (55 min vs 95 min, P < 0.0001). AEs occurred more commonly in the EUS-BD group (20 % vs. 4 %, P = 0.01). However, the majority (90 %) of AEs were mild/moderate. Length of stay was significantly longer in the EUS-BD group (6.6 d vs. 2.4 d, P < 0.0001). Conclusions: EUS-BD can be performed with a higher degree of clinical efficacy and shorter procedure time than e-ERCP in patients with surgically-altered upper gastrointestinal anatomy. Whether or not this approach should be first-line therapy in this patient population is highly dependent on the indication for the procedure, the patient's anatomy, and local practice and expertise.

Initial experience with a novel EUS-guided core biopsy needle (SharkCore): results of a large North American multicenter study.

BACKGROUND AND AIMS: The ability to safely and effectively obtain sufficient tissue for pathologic evaluation by using endoscopic ultrasound (EUS) guidance remains a challenge. Novel designs in EUS needles may provide for improved ability to obtain such core biopsies. The aim of this study was to evaluate the diagnostic yield of core biopsy specimens obtained using a novel EUS needle specifically designed to obtain core biopsies. PATIENTS AND METHODS: Multicenter retrospective review of all EUS-guided fine-needle biopsies obtained using a novel biopsy needle (SharkCore FNB needle, Medtronic, Dublin, Ireland). Data regarding patient demographics, lesion type/location, technical parameters, and diagnostic yield was obtained. RESULTS: A total of 250 lesions were biopsied in 226 patients (Median age 66 years; 113 (50 %) male). Median size of all lesions (mm): 26 (2 - 150). Overall, a cytologic diagnosis was rendered in 81 % specimens with a median number of 3 passes. When rapid onsite cytologic evaluation (ROSE) was used, cytologic diagnostic yield was 126/149 (85 %) with a median number of 3 passes; without ROSE, cytologic diagnostic yield was 31/45 (69 %, P = 0.03) with a median number of 3 passes. Overall, a pathologic diagnosis was rendered in 130/147 (88 %) specimens with a median number of 2 passes. Pathologic diagnostic yield for specific lesion types: pancreas 70/81 (86 %), subepithelial lesion 13/15 (87 %), lymph node 26/28 (93 %). Ten patients (10/226, 4 %) experienced adverse events: 4 acute pancreatitis, 5 pain, 1 fever/cholangitis. CONCLUSIONS: Initial experience with a novel EUS core biopsy needle demonstrates excellent pathologic diagnostic yield with a minimum number of passes.

Hemorrhagic complications of paracentesis: a systematic review of the literature.

Introduction. Large volume paracentesis is considered a safe procedure carrying minimal risk of complications and rarely causing morbidity or mortality. The most common complications of the procedure are ascitic fluid leakage, hemorrhage, infection, and perforation. The purpose of this study was to evaluate all hemorrhagic complications and their outcomes and to identify any common variables. Methods. A literature search for all reported hemorrhagic complications following paracentesis was conducted. A total of 61 patients were identified. Data of interest were extracted and analyzed. The primary outcome of the study was 30-day mortality, with secondary endpoints being achievement of hemostasis after intervention and mortality based on type of intervention. Results. 90% of the patients undergoing paracentesis had underlying cirrhosis. Three types of hemorrhagic complications were identified: abdominal wall hematomas (52%), hemoperitoneum (41%), and pseudoaneurysm (7%). Forty percent of the patients underwent either a surgical (35%) or an IR guided intervention (65%). Patients undergoing a surgical intervention had a significantly higher rate of mortality at day 30 compared to those undergoing IR intervention. Conclusion. Abdominal wall hematomas and hemoperitoneum are the most common hemorrhagic complications of paracentesis. Transcatheter coiling and embolization appear to be superior to both open and laparoscopic surgery in treatment of these complications.