Kazunori Eto

IgG4-related sclerosing cholangitis and autoimmune pancreatitis: histological assessment of biopsies from Vater's ampulla and the bile duct.

Background and Aim:  Autoimmune pancreatitis is commonly associated with immunoglobulin (Ig) G4‐related sclerosing cholangitis (IgG4‐SC). The discrimination between IgG4‐SC and pancreatobiliary malignancies or primary sclerosing cholangitis (PSC) is now an important issue. The present study was carried out to examine the usefulness of endoscopic biopsies from Vaters ampulla and the bile duct to diagnose IgG4‐SC.

Preoperative biliary drainage for hilar cholangiocarcinoma: which stent should be selected?

The controversy over whether and how to perform preoperative biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCA) remains unsettled. Arguments against PBD before pancreatoduodenectomy have recently been gaining momentum. However, the complication-related mortality rate is as high as 10% for patients with HCA who have undergone major liver resection, and liver failure is a major cause of postoperative death. This suggests the need for PBD to treat jaundice in HCA patients scheduled for major surgical resection of the liver and that major surgery should be performed only after the recovery of hepatic function. No definite criteria or guidelines outlining indications for PBD are currently available. In patients with HCA, PBD may be performed by either percutaneous transhepatic biliary drainage (PTBD) or endoscopic biliary drainage (EBD). No consensus, however, has been reached regarding which drainage method is more appropriate. No reported study has compared the effectiveness of PTBD, endoscopic biliary stenting (EBS), and endoscopic nasobiliary drainage (ENBD) in patients with HCA. This review summarizes the results of our study comparing the three methods and outlines the preoperative endoscopic management of segmental cholangitis (SC) in HCA patients undergoing PBD.

Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer

Background:Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC.Methods:The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients with unresectable PDC were quantified using real-time reverse transcription–polymerase chain reactions and examined for correlations with GEM sensitivity.Results:The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and 0.0047, respectively).Conclusion:hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.

Three cases of retroperitoneal schwannoma diagnosed by EUS-FNA.

Schwannomas are peripheral nerve tumors that are typically solitary and benign. Their diagnosis is largely based on surgically resected specimens. Recently, a number of case reports have indicated that retroperitoneal schwannomas could be diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We report the diagnosis of three cases of schwannoma using EUS-FNA. Subjects were two males and one female, ages 22, 40, and 46 years, respectively, all of whom were symptom-free. Imaging findings showed well-circumscribed round tumors. However, as the tumors could not be diagnosed using these findings alone, EUS-FNA was performed. Hematoxylin-eosin staining of the resulting tissue fragments revealed bland spindle cells with nuclear palisading. There was no disparity in nuclear sizes. Immunostaining revealed S-100 protein positivity and all cases were diagnosed as schwannomas. Ki-67 indexes were 3%-15%, 2%-3%, and 3%, respectively. No case showed any signs of malignancy. As most schwannomas are benign tumors and seldom become malignant, we observed these patients without therapy. All tumors demonstrated no enlargement and no change in characteristics. Schwannomas are almost always benign and can be observed following diagnosis by EUS-FNA.

Influence of the safety and diagnostic accuracy of preoperative endoscopic ultrasound-guided fine-needle aspiration for resectable pancreatic cancer on clinical performance

AIM To evaluate the safety and diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in a cohort of pancreatic cancer patients. METHODS Of 213 patients with pancreatic cancer evaluated between April 2007 and August 2011, 82 were thought to have resectable pancreatic cancer on the basis of cross-sectional imaging findings. Of these, 54 underwent EUS-FNA before surgery (FNA+ group) and 28 underwent surgery without preoperative EUS-FNA (FNA- group). RESULTS All 54 lesions were visible on EUS, and all 54 attempts at FNA were technically successful. The diagnostic accuracy according to cytology and histology findings was 98.1% (53/54) and 77.8% (42/54), respectively, and the total accuracy was 98.1% (53/54). One patient developed mild pancreatitis after EUS-FNA but was successfully treated by conservative therapy. No severe complications occurred after EUS-FNA. In the FNA+ and FNA- groups, the median relapse-free survival (RFS) was 742 and 265 d, respectively (P = 0.0099), and the median overall survival (OS) was 1042 and 557 d, respectively (P = 0.0071). RFS and OS were therefore not inferior in the FNA+ group. These data indicate that the use of EUS-FNA did not influence RFS or OS, nor did it increase the risk of peritoneal recurrence. CONCLUSION In patients with resectable pancreatic cancer, preoperative EUS-FNA is a safe and accurate diagnostic method.

Open‐label, randomized, comparative, phase III study on effects of reducing steroid use in combination with Palonosetron

The purpose of this study is to compare the efficacy of a single administration of dexamethasone (DEX) on day 1 against DEX administration on days 1–3 in combination with palonosetron (PALO), a second‐generation 5‐HT3 receptor antagonist, for chemotherapy‐induced nausea and vomiting (CINV) in non‐anthracycline and cyclophosphamide (AC) moderately‐emetogenic chemotherapy (MEC). This phase III trial was conducted with a multi‐center, randomized, open‐label, non‐inferiority design. Patients who received non‐AC MEC as an initial chemotherapy were randomly assigned to either a group administered PALO (0.75 mg, i.v.) and DEX (9.9 mg, i.v.) prior to chemotherapy (study treatment group), or a group administered additional DEX (8 mg, i.v. or p.o.) on days 2–3 (control group). The primary endpoint was complete response (CR) rate. The CR rate difference was estimated by logistic regression with allocation factors as covariates. The non‐inferiority margin was set at −15% (study treatment group − control group). From April 2011 to March 2013, 305 patients who received non‐AC MEC were randomly allocated to one of two study groups. Overall, the CR rate was 66.2% in the study treatment group (N = 151) and 63.6% in the control group (N = 154). PALO plus DEX day 1 was non‐inferior to PALO plus DEX days 1–3 (difference, 2.5%; 95% confidence interval [CI]: −7.8%–12.8%; P‐value for non‐inferiority test = 0.0004). There were no differences between the two groups in terms of complete control rate (64.9 vs 61.7%) and total control rate (49.7% vs 47.4%). Anti‐emetic DEX administration on days 2–3 may be eliminated when used in combination with PALO in patients receiving non‐AC MEC.

Transpapillary dilation of refractory severe biliary stricture or main pancreatic duct by using a wire-guided diathermic dilator (with video)

Benign and malignant tumors generally cause strictures in the bile duct (BD) or the pancreatic duct (PD) and result in jaundice or abdominal pain. An appropriate technique for dilation of these strictures is therefore necessary. Endoscopic stent placement has been reported to improve the severity of abdominal pain in selected patients with benign and malignant BD and PD strictures. 1 During ERCP, a guidewire is passed through the stricture into the proximal BD or PD. Subsequently, a plastic stent(s) or self-expandable metallic stent is placed at the stricture. Although these stents are sometimes placed after dilation of the stricture, dilation may be unnecessary in most cases. Severe ductal strictures can usually be dilated using balloon dilation or a dilation catheter. However, this type of dilation is not possible when the BD or PD stricture is severe; in such refractory cases, only the guidewire can pass through it, and a screw drill may be used. 2,3 Several investigators have described the dissection of difficult PD strictures using a needle-knife or wire-guided snare forceps. 4-6 Diathermic dilators, which are commonly used for pancreatic fluid collection drainage, are effective for creating and enlarging the fistula channels between the stomach or duodenum and a pancreatic pseudocyst, PD, or gallbladder. 7,8 We recently reported our experience using a diathermic dilator to treat severe BD strictures. 9 The current prospective observational cohort study was conducted to evaluate whether a wire-guided diathermic dilator could pass through BD or PD strictures. We also evaluated the rate of adverse events after diathermic dilation of BD or PD strictures.

Single‐stage endoscopic treatment for mild to moderate acute cholangitis associated with choledocholithiasis: a multicenter, non‐randomized, open‐label and exploratory clinical trial

Two‐stage treatment involving stone removal after drainage is recommended for mild to moderate acute cholangitis associated with choledocholithiasis. However, single‐stage treatment has some advantages. We aimed to assess the efficacy and safety of single‐stage endoscopic treatment for mild to moderate acute cholangitis associated with choledocholithiasis.

Lower incidence of complications in endoscopic nasobiliary drainage for hilar cholangiocarcinoma.

AIM To identify the most effective endoscopic biliary drainage technique for patients with hilar cholangiocarcinoma. METHODS In total, 118 patients with hilar cholangiocarcinoma underwent endoscopic management [endoscopic nasobiliary drainage (ENBD) or endoscopic biliary stenting] as a temporary drainage in our institution between 2009 and 2014. We retrospectively evaluated all complications from initial endoscopic drainage to surgery or palliative treatment. The risk factors for biliary reintervention, post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis, and percutaneous transhepatic biliary drainage (PTBD) were also analyzed using patient- and procedure-related characteristics. The risk factors for bilateral drainage were examined in a subgroup analysis of patients who underwent initial unilateral drainage. RESULTS In total, 137 complications were observed in 92 (78%) patients. Biliary reintervention was required in 83 (70%) patients. ENBD was significantly associated with a low risk of biliary reintervention [odds ratio (OR) = 0.26, 95%CI: 0.08-0.76, P = 0.012]. Post-ERCP pancreatitis was observed in 19 (16%) patients. An absence of endoscopic sphincterotomy was significantly associated with post-ERCP pancreatitis (OR = 3.46, 95%CI: 1.19-10.87, P = 0.023). PTBD was required in 16 (14%) patients, and Bismuth type III or IV cholangiocarcinoma was a significant risk factor (OR = 7.88, 95%CI: 1.33-155.0, P = 0.010). Of 102 patients with initial unilateral drainage, 49 (48%) required bilateral drainage. Endoscopic sphincterotomy (OR = 3.24, 95%CI: 1.27-8.78, P = 0.004) and Bismuth II, III, or IV cholangiocarcinoma (OR = 34.69, 95%CI: 4.88-736.7, P < 0.001) were significant risk factors for bilateral drainage. CONCLUSION The endoscopic management of hilar cholangiocarcinoma is challenging. ENBD should be selected as a temporary drainage method because of its low risk of complications.

Balloon catheter versus basket catheter for endoscopic bile duct stone extraction: a multicenter randomized trial.

BACKGROUND AND STUDY AIMS Endoscopic bile duct stone (BDS) removal is a well-established treatment; however, the preference for basket or balloon catheters for extraction is operator-dependent. We therefore conducted a multicenter prospective randomized trial to compare catheter performance. PATIENTS AND METHODS We enrolled patients with a BDS diameter ≤ 10 mm and common bile duct diameter ≤ 15 mm. Participants were randomly assigned to groups that were treated with basket or balloon catheters between October 2013 and September 2014. The primary endpoint was the rate of complete clearance of the duct; the secondary endpoints were the rate and time to complete clearance in one endoscopic session. RESULTS We initially enrolled 172 consecutive patients; 14 were excluded after randomization. The complete clearance rates were 92.3 % (72/78) in the balloon group and 80.0 % (64 /80) in the basket group. The difference in the rates between the two groups was 12.3 percentage points, indicating non-inferiority of the balloon method (non-inferiority limit -10 %; P < 0.001 for non-inferiority). Moreover, the balloon was superior to the basket (P = 0.037). The rate of complete clearance in one endoscopic session was 97.4 % using the balloon and 97.5 % using the basket (P = 1.00). The median times to complete clearance in one endoscopic session were 6.0 minutes (1 - 30) and 7.8 minutes (1 - 37) in the balloon and basket groups, respectively (P = 0.15). CONCLUSIONS For extraction of BDSs ≤ 10 mm, complete endoscopic treatment with a single catheter is more likely when choosing a balloon catheter over a basket catheter.University Hospital Medical Information Network Trials Registry: UMIN000011887.