Isaku Yoshioka

Prognostic significance of aquaporins in human biliary tract carcinoma

Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Coxs proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.

Expression of GLUT-1 and GLUT‐3 in Xanthogranulomatous Cholecystitis Induced a Positive Result on 18F-FDG PET: Report of a Case

Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of (18)F-FDG PET are not specific for malignancy because (18)F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for (18)F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on (18)F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on (18)F-FDG PET.

Prognostic significance of KLF4 expression in gastric cancer

To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients.

A patient with paroxysmal nocturnal hemoglobinuria being treated with eculizumab who underwent laparoscopic cholecystectomy: report of a case

Paroxysmal nocturnal hemoglobinuria (PNH) is acquired hemolytic anemia characterized by symptoms such as anemia and hemoglobinuria. In recent years, eculizumab as an anti-complement (C5) monoclonal antibody has been used for PNH and shown to have marked effects. We performed laparoscopic cholecystectomy in a patient with PNH being treated with eculizumab, and could avoid the risk of perioperative hemolysis and thrombosis. [Patient] The patient was a 48-year-old female who had developed PNH when she was 39 years old. At the age of 46 years, eculizumab administration was initiated once every 2 weeks. During the administration period, neither the progression of anemia nor hemoglobinuria was observed. In March 2013, gallstones were detected, and she was referred to our hospital for surgery. Eculizumab was administered 10 days before surgery, and laparoscopic cholecystectomy was performed in May 2013. After the operation, for the prevention of thrombosis, elastic stockings and a foot pump were used without anticoagulant administration. After the operation, neither the progression of anemia nor hemoglobinuria was observed. On postoperative day 5, eculizumab was administered as planned, and she showed a favorable general condition and was discharged. [Discussion] Perioperative care in PNH patients was conventionally considered to involve a high risk of developing anemia, thrombosis, or infection. However, after the advent of eculizumab, the control of the symptoms of PNH became possible in many patients. In this patient with PNH being treated with eculizumab, safe perioperative management was possible without the development of complications.

The efficacy of steroids for postoperative persistent inflammatory reaction in a patient with barium peritonitis: A case report

Highlights • Residual barium in intraperitoneal cavity causes persistent inflammatory reaction.• Steroids are effective for persistent inflammation caused by residual barium.• If infectious or other inflammation origins exist, steroids should be avoided.

Abstract 2720: Newly established Barrett's adenocarcinoma cell line (TYAE-1).

Although 10 esophageal adenocarcinoma cell lines have been reported, only 5 were Barrett9s adenocarcinoma cell lines. Furthermore, there was only one mouse-inoculated esophageal adenocarcinoma cell line. In this paper, we present a newly established Barrett9s esophageal adenocarcinoma cell line (TYAE-1). Material and Method: The Barrett9s esophageal adenocarcinoma cells were obtained from the resected tumor of a patient (74 years-old male). The resected tumor was confirmed as well-differentiated intraepithelial Barrett9s adenocarcinoma without lymphnode metastasis. The tumor was too small (T1a) for a primary culture, so we transplanted the tumor in the back of a nude mouse. Results: One month later, the tumor grew rapidly and was able to be re-transplanted to other mice. Up to the writing of this report, the tumor (TYAE-1m) was able to be re-transplanted 10 times every month. The histology of the transplanted tumor was slightly different from the primary tumor. The majority of the tumor was cribriform type and there were a few tubular-trabecular type cells. The expression of beta-Catenin was cytoplasmic in the cribriform part and membranous in the tubular part. Both cell types did express VEGF slightly however they did not express HER-2. We also started to perform in vitro cultures from the mice transplanted tumor and established TYAE-1c cell. TYAE-1c cells were able to be transplanted in nude mice and transplanted tumor showed the same histological features as TYAE-1m. TYAE-1m and TYAE-1c cells were sensitive to Gemcitabine treatment. On the other hand, both tumors did not show sensitivity for Docetaxel treatment. In conclusion: Although the tumor was small and had no invasive characteristics by clinicopathological examination, this tumor has aggressive behavior. This in vitro and in vivo Barrett9s adenocarcinoma model may useful for understanding the behavior of Barrett9s adenocarcinoma. Citation Format: Yutaka Shimada, Makoto Moriyama, Tomoyuki Okumura, Shinichi Sekine, Shigeaki Sawada, Koshi Matsui, Shozo Hojo, Kazuto Shibuya, Isaku Yoshioka, Toru Yoshida, Takuya Nagata, Kazuhiro Tsukada. Newly established Barrett9s adenocarcinoma cell line (TYAE-1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2720. doi:10.1158/1538-7445.AM2013-2720