Clinical factors associated with acute abdominal symptoms induced by gastric anisakiasis: a multicenter retrospective cohort study.

BACKGROUND: Gastric anisakiasis typically causes severe abdominal symptoms; however, we incidentally detected asymptomatic gastric anisakiasis cases during esophagogastroduodenoscopy. The factors associated with developing acute abdominal symptoms induced by gastric anisakiasis remain unclear. Therefore, this study aimed to investigate the clinical factors associated with abdominal symptoms of gastric anisakiasis by comparing symptomatic and asymptomatic cases. METHODS: This was a retrospective cohort study involving 264 patients diagnosed with gastric anisakiasis at nine hospitals in Japan between October 2015 and October 2021. We analyzed patients' medical records and endoscopic images and compared the clinical factors between the symptomatic and asymptomatic groups. RESULTS: One hundred sixty-five patients (77.8%) were diagnosed with abdominal symptoms, whereas 47 (22.2%) were asymptomatic. Older age, male sex, diabetes mellitus, gastric mucosal atrophy, and gastric mucosal atrophy of the Anisakis penetrating area were significantly more common in the asymptomatic group than in the symptomatic group. Multivariate analysis revealed that age (p = 0.007), sex (p = 0.017), and presence or absence of mucosal atrophy (p = 0.033) were independent factors for the occurrence of acute abdominal symptoms. In addition, cases that were Helicobacter pylori naïve, with an elevation of white blood cells, or without an elevation of eosinophils were more common in the symptomatic group than in the asymptomatic group. CONCLUSIONS: Age, sex, and presence or absence of gastric mucosal atrophy were the clinical factors associated with the occurrence of acute abdominal symptoms. Older and male patients and those with gastric mucosal atrophy were less likely to show abdominal symptoms. The mechanisms of the occurrence of symptoms induced by gastric anisakiasis remain unclear; however, our results will help clarify this issue in the future.

Needle tract seeding after endoscopic ultrasound-guided tissue acquisition of pancreatic tumors: A nationwide survey in Japan.

OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan. METHODS: Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed. RESULTS: A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P=0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037). CONCLUSIONS: NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

Adverse events of endoscopic ultrasound-guided fine-needle aspiration for histologic diagnosis in Japanese tertiary centers: Multicenter retrospective study.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS-FNA procedure used for histopathologic diagnoses. METHODS: A retrospective analysis of cases with EUS-FNA-related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis. RESULTS: Of the 13,566 EUS-FNA cases overall, the total number of cases in which adverse events related to EUS-FNA occurred was 234. The incidence of EUS-FNA-related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS-FNA was observed during the follow-up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS-FNA. CONCLUSIONS: This study revealed that the adverse events-related EUS-FNA for histopathologic diagnoses were not severe conditions, and had low incidence.

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

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.

Randomized trial comparing a side-port needle and standard needle for EUS-guided histology of pancreatic lesions.

BACKGROUND AND AIMS: A side-port needle has been developed to improve diagnostic accuracy by obtaining more cellular material during EUS-guided FNA (EUS-FNA). We compared the accuracy rate of histology and the quality of histologic specimens from 22-gauge (G) side-port and standard needles for EUS-FNA of a solid pancreatic mass in a multicenter, prospective, randomized control trial. METHODS: Between January 2013 and September 2013, 160 consecutive patients with a suspected solid pancreatic mass at 5 tertiary referral centers were enrolled. Patients were randomized to the 22G side-port needle or 22G standard needle group. The primary endpoint was the diagnostic accuracy of histology. Secondary endpoints were the quality of the histologic specimen (quantity of tissue, degree of GI contamination, and amount of blood). RESULTS: An analysis of 154 patients (side-port, 76, vs standard, 78) was performed. Six patients were excluded because of no pancreatic mass on EUS. There was no significant difference in the rate of diagnostic accuracy of histology (side-port, 87% [66/76], vs standard, 82% [64/78]; P = .51). Samples that enabled histologic interpretation were obtained in 64% (47/73) and 43% (33/77) of patients from the side-port and standard groups, respectively (P = .009). No significant difference was seen in the degree of GI contamination and amount of blood between groups. CONCLUSIONS: There was no significant difference in the accuracy rate of histology between needle types. The side-port needle was superior to the standard needle in terms of obtaining samples that enabled histologic interpretation.

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.

No Benefit of Oral Diclofenac on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

BACKGROUND: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a serious complication. Rectal diclofenac (100 mg) has been shown to reduce the incidence of pancreatitis; however, this dosage form is unavailable in several countries. AIMS: We aimed to investigate the preventive effect of oral diclofenac on pancreatitis after ERCP in a multicenter, randomized, prospective, placebo-controlled, double-blind trial. METHODS: Patients undergoing a first ERCP in seven high-volume centers between July 2012 and August 2014 were considered eligible. Participants were administered oral diclofenac (50 mg) or placebo before and after ERCP. The primary endpoint was the incidence of pancreatitis. A subgroup analysis was performed for patients at high or low risk of pancreatitis. Secondary endpoints were pancreatic enzyme levels (amylase and lipase). RESULTS: We initially enrolled 430 patients (216 in the diclofenac and 214 in the placebo group), and 23 were excluded after randomization. The overall incidence of pancreatitis was 9.8 % (20/205) and 9.4 % (19/202) in the diclofenac and placebo groups, respectively (p = 0.90). The incidence of pancreatitis was 20.3 % (13/64) and 21.3 % (13/61) in patients at high risk of pancreatitis (p = 0.78) and 5.0 % (7/141) and 4.3 % (6/141) in patients at low risk of pancreatitis in the diclofenac and placebo groups (p = 0.94), respectively. There were no significant differences in serum amylase and lipase levels between the two groups before and 24 h after ERCP. CONCLUSIONS: Oral administration of diclofenac before and after ERCP showed no benefit in the prevention of pancreatitis. CLINICAL TRIALS REGISTRY NO: UMIN000008109.

No benefit of endoscopic sphincterotomy before biliary placement of self-expandable metal stents for unresectable pancreatic cancer.

BACKGROUND & AIMS: Endoscopic sphincterotomy (ES) is performed routinely before self-expandable metallic stents (SEMS) are placed in malignant distal biliary strictures to prevent postprocedural pancreatitis. However, it is not clear whether ES actually prevents pancreatitis or affects other adverse events (AEs). We conducted a noninferiority trial to examine the necessity of ES before SEMS placement. METHODS: Two hundred patients with distal biliary strictures caused by unresectable pancreatic cancer were assigned randomly to groups that received ES or did not receive ES (non-ES) before SEMS placement, at 25 hospitals in Hokkaido, Japan, from August 2010 through November 2012. The primary outcome was early AEs (≤30 d) specifically related to the presence or absence of ES (pancreatitis, bleeding, or perforation). Secondary outcomes measured included the effect of ES omission on time to SEMS dysfunction and patient survival times. RESULTS: The proportions of patients with early AEs were 9.2% in the non-ES group and 10.4% in the ES group (a difference of 1.2%, noninferior). The median times to SEMS dysfunction was longer than 594 days in the non-ES group and 541 days in the ES group (P = .88). The median overall survival times were 202 in the ES group vs 255 days in the non-ES group; P = .20). CONCLUSIONS: ES before SEMS does not affect the incidence of AEs, SEMS patency, or patient survival times. Our data provide no evidence for a benefit of ES to patients undergoing SEMS placement for a biliary stricture caused by pancreatic cancer. UMIN clinical trials registry number: 000004044.

FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma.

UNLABELLED: The response rate to sorafenib in hepatocellular carcinoma (HCC) is relatively low (0.7%-3%), however, rapid and drastic tumor regression is occasionally observed. The molecular backgrounds and clinico-pathological features of these responders remain largely unclear. We analyzed the clinical and molecular backgrounds of 13 responders to sorafenib with significant tumor shrinkage in a retrospective study. A comparative genomic hybridization analysis using one frozen HCC sample from a responder demonstrated that the 11q13 region, a rare amplicon in HCC including the loci for FGF3 and FGF4, was highly amplified. A real-time polymerase chain reaction-based copy number assay revealed that FGF3/FGF4 amplification was observed in three of the 10 HCC samples from responders in which DNA was evaluable, whereas amplification was not observed in 38 patients with stable or progressive disease (P = 0.006). Fluorescence in situ hybridization analysis confirmed FGF3 amplification. In addition, the clinico-pathological features showed that multiple lung metastases (5/13, P = 0.006) and a poorly differentiated histological type (5/13, P = 0.13) were frequently observed in responders. A growth inhibitory assay showed that only one FGF3/FGF4-amplified and three FGFR2-amplified cancer cell lines exhibited hypersensitivity to sorafenib in vitro. Finally, an in vivo study revealed that treatment with a low dose of sorafenib was partially effective for stably and exogenously expressed FGF4 tumors, while being less effective in tumors expressing EGFP or FGF3. CONCLUSION: FGF3/FGF4 amplification was observed in around 2% of HCCs. Although the sample size was relatively small, FGF3/FGF4 amplification, a poorly differentiated histological type, and multiple lung metastases were frequently observed in responders to sorafenib. Our findings may provide a novel insight into the molecular background of HCC and sorafenib responders, warranting further prospective biomarker studies.

[A case of delayed colonic perforation after metallic stent placement for advanced descending colon cancer during bevacizumab-based chemotherapy].

A 73-year-old man with advanced descending colon cancer and peritoneal metastases underwent a self-expandable metallic stent placement under fluoroscopic guidance on October 2007. The stent placement was successful without early complication. After 6 courses of FOLFOX4 followed by 7 courses of FOLFIRI, he received Bevacizumab-based chemotherapy from August 2008. In April 2009, he was admitted to our hospital with severe abdominal pain due to perforation of descending colon. Although emergent surgery was performed, he developed DIC and died on the 21 postoperative days. This case suggests that metallic stent placement for colorectal cancer cases might increase the risk of bowel perforation during Bevacizumab-based chemotherapy.

Prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis by an endoscopic pancreatic spontaneous dislodgement stent.

BACKGROUND & AIMS: Pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is the most common and potentially serious complication of ERCP. The frequency of post-ERCP pancreatitis generally is reported to be between 1% and 9%. One cause of pancreatitis is retention of pancreatic juice resulting from papilledema after the procedure. We conducted a randomized controlled multicenter study to evaluate whether placement of a temporary pancreatic stent designed for spontaneous dislodgement prevents post-ERCP pancreatitis. METHODS: The subjects were 201 consecutive patients who underwent ERCP. The patients were randomized into the stent placement group (S group = 98) or the nonstent placement group (nS group = 103). The stent used was 5F in diameter, 3 cm in length, straight, and unflanged inside. RESULTS: Stents were placed successfully in 96% of the S group, and spontaneous stent dislodgment was recognized in 95.7% of those. The mean duration to dislodgment was 2 days, and there were no severe complications. The overall frequency of post-ERCP pancreatitis was 8.5%. The frequency of post-ERCP pancreatitis in the S and nS groups was 3.2% and 13.6%, respectively, showing a significantly lower frequency in the S group (P = .019). The mean increase in amylase level in the pancreatitis patients was significantly higher in the nS group (P = .014). CONCLUSIONS: The randomized controlled multicenter trial showed that placement of a pancreatic spontaneous dislodgment stent significantly reduces post-ERCP pancreatitis.

Complex Pattern of Resistance-Associated Substitutions of Hepatitis C Virus after Daclatasvir/Asunaprevir Treatment Failure.

BACKGROUNDS & AIMS: We aimed to clarify the characteristics of resistance-associated substitutions (RASs) after treatment failure with NS5A inhibitor, daclatasvir (DCV) in combination with NS3/4A inhibitor, asunaprevir (ASV), in patients with chronic hepatitis C virus genotype 1b infection. METHODS: This is a nationwide multicenter study conducted by the Japanese Red Cross Liver Study Group. The sera were obtained from 68 patients with virological failure after 24 weeks of DCV/ASV treatment. RASs in NS5A and NS3 were determined by population sequencing. RESULTS: The frequency of signature RASs at position D168 of NS3 was 68%, and at positions L31 and Y93 of NS5A was 79 and 76%, respectively. The frequency of dual signature RASs in NS5A (L31-RAS and Y93-RAS) was 63%. RASs at L28, R30, P32, Q54, P58, and A92 in addition to dual signature RAS were detected in 5, 5, 1, 22, 2, and 0 patients, respectively. In total, triple, quadruple, and quintuple RASs in combination with dual signature RAS were detected in 35, 10, and 1.5% patients, respectively. These RASs were detected in patients without baseline RASs or who prematurely discontinued therapy. Co-existence of D168 RAS in NS3 and L31 and/or Y93 RAS in NS5A was observed in 62% of patients. CONCLUSION: Treatment-emergent RASs after failure with DCV/ASV combination therapy are highly complex in more than 50% of the patients. The identification of complex RAS patterns, which may indicate high levels of resistance to NS5A inhibitors, highlights the need for RAS sequencing when considering re-treatment with regimens including NS5A inhibitors.

Increased expression of angiogenin in hepatocellular carcinoma in correlation with tumor vascularity.

PURPOSE: Neovascularization is known to be one of the major characteristics of human hepatocellular carcinoma (HCC). Angiogenin (ANG), originally discovered in a human colon cancer cell line, is a liver-derived polypeptide that shows strong angiogenic activity in vivo. However, the role of ANG on the development of HCC remains unknown. The present study was designed to examine the implication of ANG in the neovascularization of human HCC. EXPERIMENTAL DESIGN: Forty-one HCC patients who had undergone conventional celiac angiography were used in this study. ANG protein expression and microvessel density (MVD) in HCC specimens obtained by liver biopsy or surgical resection were examined by immunohistochemistry, and the levels were quantified by the KS-400 image analyzing system. ANG mRNA expression in liver tissues was evaluated by in situ hybridization. Serum ANG concentrations were measured by an ELISA. Survival rates were calculated using the Kaplan-Meier method. RESULTS: Immunohistochemistry and in situ hybridization showed greater increments of ANG protein expression and mRNA expression, respectively, in HCC tissues than in the surrounding nontumorous tissues. MVD within tumorous tissues increased according to dedifferentiation of the histological grade of HCC, showing a significant correlation (r = 0.877, P = 0.0009) with ANG expression levels. Mean +/- SD serum ANG levels of healthy subjects and chronic hepatitis (CH) patients were 362.3 +/- 84.1 ng/ml and 331.9 +/- 133.8 ng/ml, respectively, with no significant difference. Serum ANG levels of liver cirrhosis patients (242.4 +/- 126.9 ng/ml) were lower than those of healthy subjects or CH patients and decreased as the fibrosis grade advanced. In HCC patients, despite the cirrhotic background, serum ANG levels increased as the tumor vascularity increased (197.8 +/- 64.9 ng/ml for hypovascular, 326.7 +/- 148.6 ng/ml for hypervascular, and 405.0 +/- 121.3 ng/ml for very hypervascular), in good accordance with histological grading, and significantly decreased (P = 0.015) after successful treatment with transcatheter arterial embolization or percutaneous ethanol injection. HCC patients were conventionally divided into two groups according to the serum level of ANG, those with values higher than the mean level (332.9 +/- 143.8 ng/ml) and those with values lower than the mean,; the 5-year survival rate of the latter group was determined to be significantly higher than that in the former group. CONCLUSIONS: These results suggest that ANG is one of the neovascularization defining factors of HCC. Thus, measuring serum ANG may assist in monitoring the disease, and targeting ANG may provide a new strategy for treating advanced HCC.

Successful treatment with entecavir for reactivation of hepatitis B virus following systemic chemotherapy in a hepatitis B surface antigen-negative patient with colorectal cancer.

Reactivation of hepatitis B virus (HBV) has recently been reported as a fatal complication in patients undergoing cytotoxic chemotherapy. We herein describe a case of reactivation in a 76-year-old man who had undergone pelvic exenteration for colorectal cancer (CRC). He was treated with a modified FOLFOX6 chemotherapy regimen after the operation. Thirteen months later, his laboratory data showed severe liver dysfunction. His hepatitis B surface antigen (HBsAg) test was positive, and his HBV-DNA level was elevated. We diagnosed the patient with HBV reactivation as his HBsAg test was negative before starting chemotherapy. His liver dysfunction improved after administration of entecavir. This is the first report describing HBV reactivation following chemotherapy for an HBsAg-negative CRC patient.

A prospective randomized controlled multicenter trial of duodenoscopes with 5 degrees and 15 degrees backward-oblique angle using wire-guided cannulation: effects on selective cannulation of the common bile duct in endoscopic retrograde cholangiopancreatography.

BACKGROUND: In duodenoscopy, during endoscopic retrograde cholangiopancreatography (ERCP), a backward-oblique angle duodenoscope (BOAD) is generally used. In Japan, 15 degrees BOAD are mainly used, but in Western countries, 5 degrees BOAD are mostly used. In bile duct cannulation associated with ERCP, a catheter for contrast imaging is used in Japan, but wire-guided cannulation (WGC) using a papillotome is standard in Western countries. We conducted a randomized controlled multicenter trial to evaluate the contributions of different duodenoscopes using WGC to selective common bile duct cannulation. METHODS: Subjects comprised 179 consecutive patients who underwent ERCP. Patients were randomized into the 15 degrees BOAD group (15 degrees group, n = 90) or the 5 degrees BOAD group (5 degrees group, n = 89). RESULTS: The duodenal papilla could not be accessed endoscopically in two cases from each group. Success rates for bile duct cannulation by WGC without bow-up for the 15 degrees and 5 degrees groups were 85.6 and 56.2%, respectively (P < 0.01). Success rates for bile duct cannulation by WGC with bow-up for the 15 degrees and 5 degrees groups were 88.9 and 78.7%, respectively. Total rates of bile duct cannulation for the 15 degrees and 5 degrees groups were 94.4 and 92.1%, respectively. As for accidents, incidences of acute pancreatitis for the 15 degrees and 5 degrees groups were 5.6 and 9.0%, respectively, with no significant difference seen. CONCLUSIONS: With 15 degrees BOAD, bile duct cannulation was favorable without papillotome bow-up. With 5 degrees BOAD, the success rate of WGC may be improved by adjusting the angle based on papillotome bow-up.