Ken Hirao

COMBINED DUODENAL STENT PLACEMENT AND ENDOSCOPIC ULTRASONOGRAPHY-GUIDED BILIARY DRAINAGE FOR MALIGNANT DUODENAL OBSTRUCTION WITH BILIARY STRICTURE

Patients with malignant pancreatobiliary neoplasm sometimes manifest duodenal obstruction and biliary stricture synchronously or metachronously. In this paper, we reviewed our experience with and technique for combined endoscopic duodenal stent placement and endoscopic ultrasonography (EUS)‐guided biliary drainage. Between May 2007 and September 2009, this combined technique was performed on seven patients with distal biliary strictures and duodenal obstructions. The clinical success rate of the procedure, complications, patency periods of duodenal stents and patency periods of biliary stents were retrospectively evaluated. Clinical success was achieved in all seven cases for both procedures. Complications related to EUS‐biliary drainage, namely localized peritonitis due to bile leakage, occurred in two cases. Both patients recovered without additional interventions. Occlusion of a duodenal stent was observed in one patient, but additional intervention could not be performed due to sepsis. Occlusion of both a duodenal stent and a biliary stent was also observed in one patient, and this was resolved with the insertion of an additional duodenal stent and a biliary stent exchange. In conclusion, combined duodenal stent placement and EUS‐guided biliary drainage is a therapeutic option in case of failed endoscopic retrograde cannulation of malignant strictures with a malignant duodenal obstruction.

Long-term outcomes of endoscopic management for biliary strictures after living donor liver transplantation with duct-to-duct reconstruction

Biliary strictures after living donor liver transplantation (LDLT) with duct‐to‐duct (D‐D) reconstruction are associated with postoperative morbidity and mortality. The aims of this study were to evaluate the long‐term outcomes of endoscopic deployment of plastic stents, and to investigate factors associated with the stent deployment failure. Between April 2001 and May 2007, 96 patients received LDLT with D‐D reconstruction at Okayama University Hospital. Among them, 41 patients (43%) had anastomotic biliary strictures, and all were referred first for endoscopic retrograde cholangiography (ERC). When deployment was unsuccessful, a percutaneous transhepatic procedure was employed. Successful stent deployment was achieved in 35 out of total 41 patients (85%) by both procedures. Among the 35 patients, 28 had their stents removed as a result of strictures resolution. Eight patients underwent ERC and repeated stent deployment as a result of recurrence of the strictures. Finally, 21 out of 41 (51%) patients with biliary stricture were completely treated by endoscopic therapy during the observation period (median 873 days: range 77–2060). By multivariate analysis, biliary leakage was associated with stent deployment failure. Endoscopic deployment of plastic stents is a first‐line therapy for patients with biliary stricture after LDLT.

Endoscopic deployment of multiple JOSTENT SelfX is effective and safe in treatment of malignant hilar biliary strictures.

BACKGROUND & AIMS For the treatment of unresectable biliary tract carcinoma with hilar biliary stricture, antitumor therapy and biliary stenting should be addressed in terms of prolonged survival with a good quality of life. However, the endoscopic management of malignant hilar biliary strictures is difficult even for an expert endoscopist. We evaluated the efficacy and safety of the endoscopic deployment of multiple JOSTENT SelfX units in patients with hilar biliary strictures treated with or without chemotherapy. METHODS Between November 2003 and December 2006, endoscopic deployment of multiple JOSTENT SelfX units in hilar biliary strictures by using a partial stent-in-stent procedure was performed on 41 consecutive patients with primary cholangiocarcinoma (n = 34) and gallbladder carcinoma (n = 7) at a gastroenterologic center of Okayama University Hospital. Thirty-three patients were treated with gemcitabine (n = 25) or S-1 (n = 8). RESULTS Metallic stent deployment was successfully accomplished in all cases via only endoscopic procedures. During the follow-up period (mean, 210 days), mean patency time was 150 days, and metallic stent obstruction occurred in 15 cases (37%). Although a repeat intervention was required in all metallic stent obstructed cases, the deployment of the second metallic or plastic stent was completed successfully. The remaining 26 cases (63%) required no interventions. The median overall survival period was only 235 days. However, that of the patients receiving chemotherapy was 392 days. CONCLUSIONS Endoscopic partial stent-in-stent deployment with multiple JOSTENT SelfX prostheses is effective and safe for the treatment of malignant hilar biliary stricture even in patients receiving chemotherapy.

Prevention of biliary complication in radiofrequency ablation for hepatocellular carcinoma—Cooling effect by endoscopic nasobiliary drainage tube

BACKGROUND AND STUDY AIMS Biliary stricture after radiofrequency ablation (RFA) for nodules of hepatocellular carcinoma (HCC) close to major bile ducts sometimes causes septic complications and liver failure. Therefore, it may require interventional drainage for decompression during the follow-up period. The purpose of this study is to clarify the feasibility and safety of bile duct cooling using an endoscopic nasobiliary drainage (ENBD) tube in RFA for HCC close to major bile ducts. PATIENTS AND METHODS Between August 2003 and July 2007, 14 consecutive patients (14 nodules) undergoing RFA with cooling by an ENBD tube for HCCs close to major bile ducts were enrolled in this study. We infused chilled saline solution via the ENBD tube at 1ml/s to prevent heat damage during RFA. As controls, 11 patients (13 nodules) undergoing RFA without cooling close to major bile ducts between April 2001 and August 2003 were reviewed. The major outcomes for evaluation were biliary complications and the secondary outcome was local tumor recurrence. RESULTS There were no significant differences in tumor recurrence between the two groups. However, the rate of biliary complications was significantly lower in the cooling group than in the non-cooling group (0% vs. 39%, P=0.02). CONCLUSIONS Cooling of bile ducts via an ENBD tube can prevent biliary complications induced by RFA of HCC close to major bile ducts without increasing local recurrence. This technique increases indication of RFA in difficult cases.

Single-pattern convergence of K-ras mutation correlates with surgical indication of intraductal papillary mucinous neoplasms.

Objectives: One or more patterns of 6 K-ras mutations are detected in cells from the pancreatic juice of patients with intraductal papillary mucinous neoplasms (IPMNs). We investigated whether these mutations are associated with malignant progression. Methods: Between January 2002 and December 2007, 53 patients with IPMN were subjected to collection of pure pancreatic juice to evaluate K-ras mutation. According to the histological and radiological findings, the IPMNs were classified into 4 groups: carcinoma group, adenoma group, high-risk group, and low-risk group. We retrospectively investigated the mutation with these groups. Results: In patients with a positive K-ras mutation, a single pattern of K-ras mutation was observed in 80% (8/10) of the carcinoma group, in 71% (5/7) of the adenoma group, in 40% (2/5) of the high-risk group, and in 38% (8/21) of the low-risk group. The rate of a single pattern of K-ras mutation decreased in a stepwise order (P = 0.017). The incidence of a single pattern of K-ras mutation was significantly higher in the patients who received surgical therapy (75%, 12/16) than in those who did not (38%, 10/26; P = 0.033). Conclusions: The present study suggests that the single-clonal convergence of K-ras mutation is associated with the malignant progression of IPMNs.

Nonprevention of post-endoscopic retrograde cholangiopancreatographic pancreatitis by pancreatic stent after aspiration of pure pancreatic juice in patients with intraductal papillary mucinous neoplasms of the pancreas

Objectives: The objective of this study was to evaluate the efficacy of a pancreatic stent regarding the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis after aspiration of pure pancreatic juice in patients with intraductal papillary mucinous neoplasms. Methods: A retrospective study was made to assess the outcome in 121 consecutive patients with intraductal papillary mucinous neoplasms who underwent endoscopic aspiration of pure pancreatic juice for cytologic examination between July 2001 and October 2007. From July 2001 to March 2004, 58 patients did not undergo pancreatic stent insertion (the no-stent [nS] group). The remaining 63 patients did undergo stent insertion (stent [S] group). Results: The overall incidences of post-ERCP pancreatitis was 11 (9.1%). The incidences of post-ERCP pancreatitis in the S and nS groups were 8 (12.7%) and 3 (5.2%; P = 0.21), respectively. In the male patients and the patients with a smaller diameter of the main pancreatic ducts, post-ERCP pancreatitis was seen more frequently in those in the S group (13% and 21%, respectively) than in those in the nS group (0% and 0%, respectively; P = 0.04, 0.03). Conclusions: The pancreatic stent did not seem to decrease the incidence of post-ERCP pancreatitis in patients with intraductal papillary mucinous neoplasms. Furthermore, the pancreatic stent seems to be potentially detrimental in male patients and in patients with small-diameter main pancreatic ducts.Abbreviations: ERCP - endoscopic retrograde cholangiopancreatography, IPMNs - intraductal papillary mucinous neoplasms, ERP - endoscopic retrograde pancreatography, IDUS - intraductal ultrasonography

Perforation of jejunum induced by the deployment of a temporary prophylactic pancreatic stent in the patient with peritonitis carcinomatosa

A great deal of medical literature describes the efficacy and safety of the prophylactic pancreatic stent in reducing the incidence of post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis. At the moment, no serious complication due to the migration of this stent has been reported. We describe a case with perforation of jejunum induced by the migration of a temporary prophylactic pancreatic stent. This report indicates that we should pay attention to this severe complication when we place a temporary prophylactic pancreatic stent in patients who have peritonitis carcinomatosa or adherence of the intestine irrespective of oral intake.

Dexmedetomidine for conscious sedation with colorectal endoscopic submucosal dissection: a prospective double-blind randomized controlled study

Objective: Conscious sedation for colorectal endoscopic submucosal dissection (ESD) has not been standardized, and there are no studies of sedation for colorectal ESD. Methods: We conducted a prospective double‐blind randomized controlled trial to clarify the usefulness of DEX during colorectal ESD. In total 80 patients with colorectal ESD from April 2016 to May 2017 were assigned to the placebo group or the DEX group (40 cases each). The primary outcome was patient satisfaction (visual analogue scale: VAS). Secondary outcomes were evaluated for 13 factors, including patient pain level (VAS), endoscopist satisfaction (VAS), objective patient pain level viewed from the endoscopists perspective (VAS), rate of patient response, rate of side effects, etc., from the patients and endoscopists perspectives. Results: Patient satisfaction was 8.4 and 9.1 (P = 0.018) in the placebo group and the DEX group, respectively. Secondary outcomes of patient pain level, endoscopist satisfaction, objective patient pain level from the endoscopists perspective for the placebo and DEX groups were 1.2 and 0.4 (P = 0.045), 8.2 and 9.3 (P < 0.001), and 1.2 and 0.5 (P = 0.002), respectively. All of these were significantly positive results (more comfortable and less pain) in the DEX group. The rate of a patient response was 100% in all cases. The side effects (hypoxia/bradycardia/hypotension) were 0%/0%/0% and 7.5%/7.5%/5% (P = 0.030). However, these rates were less than the reported side effect occurrence rate, and no additional medication was needed. Conclusion: DEX enables conscious sedation, and is useful not only for patient and endoscopist satisfaction but also for pain relief. DEX is an effective sedation method for colorectal ESD.

Comparison of two fluoroscopic images to ensure efficient scope insertion for biliary intervention in patients with Roux-en-Y hepaticojejunostomy

Background and study aims No standard procedure for endoscopic retrograde cholangiopancreatography is available for patients with Roux-en-Y hepaticojejunostomy (RYHJ) with side-to-end hepaticojejunostomy. We therefore explored methods of efficient scope insertion at a hepaticojejunostomy site. Patients and methods Patients with suspected biliary disease were prospectively enrolled. Based on two fluoroscopic images obtained on scope insertion into each lumen of a two-pronged Roux-en-Y anastomosis, we selected the lumen in which the distal end of the scope progressed toward the patients liver or head. The accuracy of this method for selecting the correct lumen leading to the hepaticojejunostomy site was investigated. Results Of the 33 included patients, successful insertion to the hepaticojejunostomy site was achieved in 32 (97 %), 26 (81 %) of whom had undergone the imaging method. The accuracy of the method was 88 % (23/26). The time required for insertion between the anastomotic site and the hepaticojejunostomy site was shorter when the lumen selection had been correct (13 minutes [7 - 30] (n = 23) vs. 18 minutes [8 - 28] (n = 9); P = 0.95). Conclusion This method based on two fluoroscopic images was useful for achieving efficient scope insertion in patients with RYHJ.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000014183).

S1019 A Randomized Phase II Study Designed to Compare Toxicity and Dose Intensity Between Four-Week Versus Three-Week Schedule of Gemcitabine for Advanced Pancreatic Cancer

Purpose: The aim of this phase II study is to compare toxicity and dose intensity (DI) between four-week (4w) and three-week (3w) schedule of gemcitabine (GEM) for advanced pancreatic cancer (PC). Methods: Patients with histologically or cytologically proven locally advanced and/or metastatic PC were assigned to receive GEM in 4w schedule or 3w schedule. The protocol of GEM was as follows: 4w schedule (1,000mg/m2 on days 1, 8 and 15 of each 28-day cycle), 3w schedule (1,000mg/m2 on days 1 and 8 of each 21-day cycle). If grade 3 to 4 hematological toxicity (only a platelate count was defined = 50%, age between 20 and 80 years, and adequate organ function. Written informed consent was obtained from all patients. The primary endpoint was a compliance rate of protocol regimen within eight weeks after initiation of chemotherapy, which was defined as the proportion of patients without a dose reduction or a delay in administration of GEM. Secondary endpoints were DI, safety, response rate and overall survival. Results: A total of 90 patients (4w: 3w schedule= 45: 45) were enrolled between January 2006 and October 2008. Baseline patient and disease characteristics were similar in both schedules. Median age was 67 (range, 49-79) years in 4w schedule vs. 66 (range, 33-79) years in 3w schedule; p=0.67. KPS (70-80: 90-100%) was (4: 41) vs. (5: 40); p=0.99. Disease (locally advanced: metastatic) was (7: 38) vs. (7: 38); p=0.99. The eight week-compliance rate of protocol regimen was the same; 53.3% (24/45) in both schedules. However, median duration of accumulative rate for adverse events tended to be extended in 3w schedule; 35days (6-334) vs. 49 (6-414), p=0.20. Consequently, the mean received DI was equivalent in both schedules; 588 +/130 mg/m2/week vs. 550 +/116, p=0.14. Grade 3-4 neutropenia was a major adverse event in both schedules; 37.7% (17/ 45) vs. 35.5 (16/45); p=0.82, in contrast, thrombocytopenia was significantly increased in 4w schedule; 26.6% (12/45) vs. 4.4 (2/45); p=0.009. Tumor response rate was 14.2% (5/ 35) vs. 17.1(6/35); p=0.92, and the disease control rate (PR, SD) was 60.0% (27/45) vs. 62.2 (28/45); p=0.82. Median survival time was 206 (33-802) days vs. 250 (39-681); p= 0.84. Conclusions: These results support the efficacy and safety in 3w schedule of GEM for PC.