Review article: Asia-Pacific consensus recommendations on endoscopic tissue acquisition for biliary strictures.

BACKGROUND: Pre-operative tissue diagnosis for suspected malignant biliary strictures remains challenging. AIM: To develop evidence-based consensus statements on endoscopic tissue acquisition for biliary strictures. METHODS: The initial draft of statements was prepared following a systematic literature review. A committee of 20 experts from Asia-Pacific region then reviewed, discussed, and modified the statements. Two rounds of independent voting were conducted to reach a final version. Consensus was considered to be achieved when 80% or more of voting members voted "agree completely" or "agree with some reservation." RESULTS: Eleven statements achieved consensus. The choice of tissue sampling modalities for biliary strictures depends on the clinical setting, the location of lesion, and availability of expertise. Detailed radiological and endoscopic evaluation is useful to guide the selection of appropriate tissue acquisition technique. Standard intraductal biliary brushing and/or forceps biopsy is the first option when endoscopic biliary drainage is required with an overall (range) sensitivity and specificity of 45% (26%-72%) and 99% (98%-100%), and 48% (15%-100%) and 99% (97%-100%), respectively, in diagnosing malignant biliary strictures. Probe-based confocal laser endomicroscopy and fluorescence in situ hybridisation using 4 fluorescent-labelled probes targeting chromosomes 3, 7, 17 and 9p21 locus may be added to improve the diagnostic yield. Cholangioscopy-guided biopsy and EUS-guided tissue acquisition can be considered after prior negative conventional tissue sampling with an overall (range) sensitivity and specificity of 60% (38%-88%) and 98% (83%-100%), and 80% (46%-100%) and 97% (92%-100%), respectively, in diagnosing malignant biliary strictures. CONCLUSION: These consensus statements provide evidence-based recommendations for endoscopic tissue acquisition of biliary strictures.

Evidence-based clinical practice guidelines for cholelithiasis 2016

BACKGROUND: This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society (ATS) and the American College of Chest Physicians (CHEST). METHODS: A multidisciplinary panel posed six clinical questions in a population, intervention, comparator, outcomes (PICO) format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, confidence in the evidence, certainty about how much the public values the main outcomes, magnitude and balance of desirable and undesirable outcomes, resources and costs associated with the intervention, impact on health disparities, and acceptability and feasibility of the intervention. RESULTS: Evidence-based recommendations were formulated and graded initially by subcommittees and then modified following full panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation. CONCLUSIONS: The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and CHEST

Endoscopic ultrasound-guided celiac ganglia neurolysis vs. celiac plexus neurolysis: a randomized multicenter trial.

BACKGROUND AND STUDY AIMS: No prospective comparison of endoscopic ultrasonography-guided direct celiac ganglia neurolysis (EUS - CGN) vs. EUS-guided celiac plexus neurolysis (EUS - CPN) has been reported. The aim of the current study was to compare the effectiveness of EUS - CGN and EUS - CPN in providing pain relief from upper abdominal cancer pain in a multicenter randomized controlled trial. PATIENTS AND METHODS: Patients with upper abdominal cancer pain were randomly assigned to treatment using either EUS - CGN or EUS - CPN. Evaluation was performed at Day 7 postoperatively using a pain scale of 0 to 10. Patients for whom pain decreased to ≤ 3 were considered to have a positive response, and those experiencing a decrease in pain to ≤ 1 were considered to be completely responsive. Comparison between the two groups was performed using intention-to-treat analysis. The primary endpoint was the difference in treatment response rates between EUS - CGN and EUS - CPN at postoperative Day 7. Secondary endpoints included differences in complete response rates, pain scores, duration of pain relief, and incidence of adverse effects. RESULTS: A total of 34 patients were assigned to each group. Visualization of ganglia was possible in 30 cases (88 %) in the EUS - CGN group. The positive response rate was significantly higher in the EUS - CGN group (73.5 %) than in the EUS - CPN group (45.5 %; P = 0.026). The complete response rate was also significantly higher in the EUS - CGN group (50.0 %) than in the EUS - CPN group (18.2 %; P = 0.010). There was no difference in adverse events or duration of pain relief between the two groups. CONCLUSIONS: EUS - CGN is significantly superior to conventional EUS - CPN in cancer pain relief. CLINICAL TRIAL REGISTRATION: http://www.umin.ac.jp/ctr/index.htm (ID: UMIN-000002536).

A comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas.

Tumors arising from the liver, biliary tract and pancreas, which originate in the foregut and are in close anatomical proximity to each other, sometimes show similar histological features. No studies have focused on genetic similarities and differences between tumors of these organs. To elucidate the similarities and differences in DNA copy number alterations between tumors of these organs, we applied comparative genomic hybridization (CGH) to cancers of the liver (31 cases), biliary tract (42 cases) and pancreas (27 cases). Some alterations were common to tumors of all three organs, and some were preferential in certain types of tumor. Gains of 1q and 8q and losses of 8p and 17p were common to all tumors. In contrast, 13q14 and 16q losses were detected exclusively in hepatocellular carcinomas (HCCs; p < 0.01). The incidence of 17q21 gain and 5q loss was higher in biliary tract cancers than in the other two types (p < 0.05). Pancreatic cancers exhibited higher incidence of 5q14-q23 gain and 19p loss than tumors of other organs (p < 0.01). Gains of 7p, 7q, 12p and 20q and losses of 3p, 6q, 9p and 18q were frequent in both biliary tract and pancreatic cancers but rare in HCCs (p < 0.05). The present results suggest that although genes located at 1q, 8p, 8q and 17p are frequently involved in HCC, biliary tract and pancreatic cancer, at least some of the genes implicated in carcinogenesis are different between these three types. It is also suggested that CGH analysis is useful as a potential adjunct for the diagnosis and management of these tumors of organs that are anatomically close to one another.

Detection of Ki-ras and p53 gene mutations in tissue and pancreatic juice from pancreatic adenocarcinomas.

Pancreatic carcinomas have a high incidence of Ki-ras mutations, and the genetic change is thought to occur at an early stage in the carcinogenesis. The aim of this study was to evaluate the usefulness of detecting genetic mutations in pure pancreatic juice (PPJ). DNA was extracted from tissue specimens of pancreatic carcinomas and from cells in PPJ, and subjected to polymerase chain reaction-single-strand conformation polymorphism analysis. Two types of mobility shifts that indicate Ki-ras mutations were observed in 13 of the 20 (65%) tissue specimens obtained by operation or autopsy. Ten of 15 specimens (67%) of PPJ collected from patients with pancreatic carcinomas showed two types of mobility shifts. Conventional imaging techniques did not show two in 10 of these patients. PPJ from patients with non-cancerous pancreatic diseases showed no Ki-ras mutations. The p53 tumor suppressor gene, examined by PCR-SSCP analysis, was mutated in 8 of the 20 tissue specimens obtained by operation or autopsy (40%). The detection of Ki-ras and p53 mutations in PPJ could be useful for the early diagnosis of pancreatic carcinomas, especially for neoplastic lesions of the intraductal type.

Macroscopic and stereomicroscopic diagnosis of superficial flat-type early carcinomas of the gallbladder.

Superficial flat early carcinomas of the gallbladder are rarely detected clinically. We previously reported that these carcinomas display granular, flat, or gastric area-like surface mucosal patterns. However, these patterns are also seen in some non-neoplastic conditions. To more definitively differentiate carcinomas from non-neoplastic lesions, we analyzed the stereomicroscopic structure of macroscopically granular, flat, or gastric area-like mucosal lesions with a methylene-blue contrast technique. Sixteen superficial flat early carcinomas and 65 non-neoplastic flat lesions from surgically resected gallbladders were studied by stereomicroscopy. The fine mucosal structures were classified into three patterns: grooved, pitted, or papillary, each of which was further subdivided into regular and irregular. The frequency of the grooved (52.2%) and papillary (52.2%) patterns was significantly higher in the carcinomas than in the non-neoplastic lesions (24.7% and 1.3%, respectively). The pitted pattern was present in 69.6% of the carcinomas and in 53.2% of the non-neoplastic lesions (the difference was not significant). In the grooved and pitted patterns, the irregular subtypes predominated in the carcinomas (100% and 81.3%, respectively), while the regular subtypes were more frequent in the non-neoplastic lesions (84.2% and 97.6%, respectively). Stereomicroscopic examination of the fine mucosal structures of flat lesions of the gallbladder is very useful in differentiating carcinomas from non-neoplastic lesions.

p53 mutations in two patients with intraductal papillary adenoma of the pancreas.

There has been no report on p53 gene mutation in benign human pancreatic intraductal tumors. We examined pancreatic juice and tissue specimens from two patients with intraductal papillary adenoma of the pancreas by polymerase chain reaction-single-strand conformation polymorphism analysis and direct sequencing and found point mutations of p53 gene resulting in amino acid substitutions in exons 6 and 8. Thus, p53 gene mutation may be an early event in the neoplastic process of some pancreatic intraductal tumors and may play an important role in tumorigenesis.