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Abstract Background Analysis of gene expression and gene mutation may add information to be different from ordinary pathological tissue diagnosis. Since samples obtained endoscopically are very small, it is desired that more sensitive technology is developed for gene analysis. We investigated whether gene expression and gene mutation analysis by newly developed ultra-sensitive three-dimensional (3D) microarray is possible using small amount samples from endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens and pancreatic juices. Methods Small amount samples from 17 EUS-FNA specimens and 16 pancreatic juices were obtained. After nucleic acid extraction, the samples were amplified with labeling and analyzed by the 3D microarray. Results The analyzable rate with the microarray was 46% (6/13) in EUS-FNA specimens of RNAlater® storage, and RNA degradations were observed in all the samples of frozen storage. In pancreatic juices, the analyzable rate was 67% (4/6) in frozen storage samples and 20% (2/10) in RNAlater® storage. EUS-FNA specimens were classified into cancer and non-cancer by gene expression analysis and K-ras codon 12 mutations were also detected using the 3D microarray. Conclusions Gene analysis from small amount samples obtained endoscopically was possible by newly developed 3D microarray technology. High quality RNA from EUS-FNA samples were obtained and remained in good condition only using RNA stabilizer. In contrast, high quality RNA from pancreatic juice samples were obtained only in frozen storage without RNA stabilizer.

Objectives: The time to recurrent biliary obstruction (TRBO) of unresectable distal malignant biliary obstruction is generally thought to be longer when a self‐expandable metal stent (SEMS) with a thicker inner diameter is used for drainage, but the dependence on the inner diameter using a fully covered SEMS (FCSEMS) is uncertain. The objective of this multicenter prospective study was to compare TRBO and adverse events, such as cholecystitis and pancreatitis, in treatment of patients with unresectable malignant biliary obstruction using 8‐ and 10‐mm diameter FCSEMS. Methods: Eighteen tertiary‐care centers participated in the study. Patients were allocated to the 8‐ and 10‐mm diameter groups. TRBO, non‐inferiority of the 8‐mm FCSEMS, overall survival time, frequency and type of adverse events, and non‐recurrent biliary obstruction (RBO) rate at the time of death were compared between the two groups. Results: Median TRBO did not differ significantly between the 8‐mm (n = 102) and 10‐mm (n = 100) groups (275 vs 293 days, P = 0.971). The hazard ratio of the 8‐ to 10‐mm groups was 0.90 (80% confidence interval, 0.77–1.04; upper limit lower than the acceptable hazard ratio [1.33] of the null hypothesis). Based on these findings, the 8‐mm diameter stent was determined to be non‐inferior to the 10‐mm diameter stent. Survival time, incidence of adverse events and non‐RBO rate at the time of death did not differ significantly between the two groups. Conclusions: Time to RBO with an 8‐mm diameter FCSEMS was non‐inferior to that with a 10‐mm diameter FCSEMS. This finding is important for development of future SEMS. [ABSTRACT FROM AUTHOR]

Presents letters to the editor discussing gastroenterology-related research studies.

A 70-year-old woman presented to our hospital with jaundice. Abdominal ultrasonography showed biliary duct dilatation. Blood tests revealed elevated total bilirubin and hepatobiliary enzyme levels. A contrast-enhanced computed tomography of the abdomen showed bile duct thickening with wall enhancement. Transpapillary bile duct biopsy showed an invasive carcinoma proliferating in a follicular pattern. Pathology revealed positive synaptophysin and chromogranin A and a Ki67 index >40%, consistent with a diagnosis of neuroendocrine carcinoma (NEC). After confirming the absence of distant metastases, a subtotal stomach-preserving pancreaticoduodenectomy was performed. The result of the postoperative pathology was the same as the preoperative biopsy. According to previous reports, 7 out of 28 cases with NEC/mixed adenoneuroendocrine carcinoma could be diagnosed as NEC before surgery. However, biliary cytology and bile duct scraping cytology were used in many cases;only 11 cases underwent bile duct biopsy. For the latter, 5 out of 11 cases could be diagnosed preoperatively. NEC of the extrahepatic duct often exhibits a submucosal tumor-like morphology, which may result in a false negative result with biliary cytology or bile duct scraping cytology. In our case, the transpapillary bile duct biopsy sample was sufficient to diagnose NEC. This method could be an attractive option for the diagnosis of these tumors.

Objective: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study., Methods: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events., Results: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741-1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044)., Conclusion: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified., (© 2018 S. Karger AG, Basel.)

A 65-year-old man was referred for a gallbladder elevated lesion. Abdominal US showed a hypoechoic tumor with wide base at the gallbladder body. The maximum velocity of the gallbladder wall blood flow was 20 cm/s. The outermost hyperechoic layer was irregular, but not disrupted on EUS images. We diagnosed the lesion as gallbladder carcinoma with the depth of subserosa. Cholecystectomy was performed and the tumor was diagnosed as tubular adenoma of the gallbladder. The p53 immumostaining was negative. A gallbladder adenoma with wide base is rare, here we report this case with the several considerations.

Aim: We investigated pathological features of Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3)-positive hepatocellular carcinoma (HCC) in order to seek a pathological basis of poor prognosis of HCC patients with elevated AFP-L3., Methods: A total of 111 patients with HCC < or =5 cm in diameter who underwent hepatic resection were studied. Serum AFP-L3 concentration was measured within a month prior to surgery by lectin-affinity electrophoresis coupled with antibody-affinity blotting, and expressed as AFP-L3 percentage of total AFP. AFP-L3 of 10% or higher was judged to be positive. Pathologic features of resected HCC specimens were evaluated and classified concerning growth pattern (expansive or infiltrative growth), capsule formation, capsule infiltration, septal formation, portal vein invasion, hepatic vein invasion, bile duct invasion, and intrahepatic metastasis. These macroscopic and microscopic findings were compared between AFP-L3-positive and negative HCC specimens., Results: Thirty-three (29.7%) were positive for AFP-L3. The prevalence of HCC with infiltrative growth, with capsule infiltration, with septum formation, with portal vein invasion, and with hepatic vein invasion was significantly higher in AFP-L3-positive group (P=0.0121, 0.0290, 0.0442, 0.0314, and 0.0433, respectively). These pathologic features reportedly indicate the progression of the tumor., Conclusions: AFP-L3-positive HCC had several pathologic features of progressed state of HCC, which accounted for the AFP-L3 as an indicator of poor prognosis of HCC.