Hiroyuki Hisai

Japanese multicenter experience of endoscopic necrosectomy for infected walled-off pancreatic necrosis: The JENIPaN study

BACKGROUND AND STUDY AIMS Only a few large cohort studies have evaluated the efficacy and safety of endoscopic necrosectomy for infected walled-off pancreatic necrosis (WOPN). Therefore, a multicenter, large cohort study was conducted to evaluate the efficacy and safety of endoscopic necrosectomy and to examine the procedural details and follow-up after successful endoscopic necrosectomy. PATIENTS AND METHODS A retrospective review was conducted in 16 leading Japanese institutions for patients who underwent endoscopic necrosectomy for infected WOPN between August 2005 and July 2011. The follow-up data were also reviewed to determine the long-term outcomes of the procedures. RESULTS Of 57 patients, 43 (75 %) experienced successful resolution after a median of 5 sessions of endoscopic necrosectomy and 21 days of treatment. Complications occurred in 19 patients (33 %) during the treatment period. Six patients died (11 %): two due to multiple organ failure and one patient each from air embolism, splenic aneurysm, hemorrhage from a Mallory - Weiss tear, and an unknown cause. Of 43 patients with successful endoscopic necrosectomy, recurrent cavity formation was observed in three patients during a median follow-up period of 27 months. CONCLUSIONS Endoscopic necrosectomy can be an effective technique for infected WOPN and requires a relatively short treatment period. However, serious complications can arise, including death. Therefore, patients should be carefully selected, and knowledgeable, skilled, and experienced operators should perform the procedure. Further research into safer technologies is required in order to reduce the associated morbidity and mortality.

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).

Suppressive effect of ethanol on the expression of hepatic asialoglycoprotein receptors augmented by interleukin-1β,interleukin-6, and tumor necrosis factor-α

Abstract: Blood levels of inflammatory-related cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, are elevated in patients with alcoholic liver diseases. We investigated the effects of these cytokines and ethanol on the expression of hepatic asialoglycoprotein receptors (AGPRs) in a human hepatoblastoma cell line, HepG2. An [125I]-asialo-orosomucoid binding assay showed significant increases in surface AGPR numbers in HepG2 cells by treatment with IL-1β, IL-6, and TNF-α, to levels which were approximately 130% of the values in untreated control cells. However, the enhanced AGPR numbers induced by treatment with these cytokines were markedly suppressed, to 70%–80% of the number in the untreated cells, by treatment with ethanol. Immunological detection of AGPR with a specific antibody demonstrated that the modulation of surface AGPR numbers was correlated with the cellular expression levels of AGPR. These results suggest that, although IL-1β, IL-6, and TNF-α stimulate the synthesis of hepatic AGPR, ethanol suppresses the expression of AGPR augmented by these cytokines. This leads to an increase in serum asialo-orosomucoid levels caused by the disordered catabolism mediated by AGPR in patients with alcoholic liver disease.

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.

Image analysis is an excellent tool for quantifying Ki-67 to predict the prognosis of gastrointestinal stromal tumor patients: Ki-67 quantitation in GIST

We investigated the quantification of Ki‐67 staining using digital image analysis (IA) as a complementary prognostic factor to the modified National Institutes of Health (NIH) classification in patients with gastrointestinal stromal tumor (GIST). We examined 92 patients, focusing on the correlation between age, sex, primary tumor site, tumor size, predominant histologic type, mitotic index, modified NIH classification (low/intermediate vs high), Ki‐67 quantitation, and recurrence‐free survival (RFS). We compared two IA processes for whole slide imaging (WSI) and manually captured image (MCI) methods. A Ki‐67 quantitation cutoff was determined by receiver operator characteristics curve analysis. In the survival analysis, the high‐risk group of a modified NIH classification, a mitotic count >5 per 20 high‐powered fields, and Ki‐67 cutoffs of ≥6% and ≥8% obtained by IA of the WSI and MCI methods, respectively, had an adverse impact on RFS. On multivariate analysis, each Ki‐67 quantitation method strongly predicted prognosis, more strongly than the modified NIH classification. In addition, Ki‐67 quantitation using IA of the MCI method could stratify low or intermediate risk and high risk GIST patients. Thus, IA is an excellent tool for quantifying Ki‐67 to predict the prognosis of GIST patients, and this semiautomated approach may be preferable for patient care.

Reply to Kadayifci et al.

We appreciate the comments made by Dr. Kadayifci regarding our study inwhich we concluded that complete endoscopic treatment with a single catheter is more likely when choosing a balloon catheter over a basket catheter for the extraction of bile duct stones ≤10mm [1]. In the basket group, the basket catheter was switched to a balloon catheter when the endoscopist had judged the duct clearance to be complete by the basket catheter. First, the balloon was inflated at the perihilar bile duct and pulled to the bottom of the bile duct, and then balloon-occluded cholangiography (BOC) was performed. During this procedure, if a stone emerged from the papilla of Vater, this was judged to be “incomplete clearance.” In addition, when a defect on BOC was confirmed to be a stone by subsequent endoscopic observation, the outcome was also judged to be “incomplete clearance.” Therefore, “residual stones on BOC (n=9)” were confirmed during this procedure. These failure cases meant that duct clearance had not been completed by basket catheter alone. “Complete clearance by the assigned catheter” in the basket group represented the result obtained by the basket catheter alone, not by the basket catheter plus the balloon catheter. Therefore, we think that using the balloon after the basket for stone extraction was not a confounding factor of our study. As mentioned by Dr. Kadayifci, it is sometimes difficult to check stone removal by direct endoscopic observation after balloon sweep of the duct. Therefore, the performance of the balloon catheter may be overestimated. The actual success rate of each catheter might be lower than the rates determined in our study because BOC and balloon sweep were used to confirm duct clearance in both groups. For true comparison of the two catheters, other modalities, such as peroral cholangioscopy, should be used to evaluate the efficacy of individual catheters. However, it was not realistic to use cholangioscopy to evaluate residual stones in our study because participants included patients with normal common bile ducts, with diameters ≤8mm in general. In addition, evaluating the end point by the same method in both groups is crucial in a randomized controlled trial. When considering clinical trial feasibility, BOC was selected to evaluate the end point in both groups to minimize the methodological bias. However, we identified this issue as a limitation of our study.

Retrospective cohort study on the safety and efficacy of panitumumab for patients with metastatic colorectal cancer: The HGCSG1002 study—Analysis of adverse events.

554 Background: Panitumumab (Pmab) is a fully human monoclonal antibody specific to the epidermal growth factor receptor. It has been associated with very few infusion reactions, but has been point...