Takashi Kaizu

Homeobox-Only Protein Expression Is a Critical Prognostic Indicator of Pancreatic Neuroendocrine Tumor and Is Regulated by Promoter DNA Hypermethylation.

Objectives We have identified homeobox-only protein (HOPX) as a tumor suppressor gene in various human cancer, and its expression was reduced by promoter DNA hypermethylation. Homeobox-only protein is strongly expressed on pancreatic islet cells; however, clinical relevance of HOPX expression has remained elusive in pancreatic neuroendocrine tumor (pNET). Methods We investigated 36 patients with pNET who undertook surgical resection between 1988 and 2012 for HOPX expression and DNA methylation to reveal its clinical significance. Results (1) Homeobox-only protein is strongly expressed on pancreatic islet cells by immunohistochemistry (IHC). Homeobox-only protein expression was recognized on pNET tumor cells for 1+ in 15, for 2+ in 16, and for 3+ in 5. (2) Homeobox-only protein IHC expression was significantly associated with prognosis (P = 0.03), and survival rate was 37.5%, 70.3%, and 100% in HOPX 1+, 2+, and 3+, respectively. (3) Promoter DNA methylation was quantitatively assessed, and HOPX hypermethylation is found in 6.3%, 11.8%, and 66.7% of G1/G2/G3 pNET, respectively (P = 0.02). (4) Multivariate Cox proportional hazards model identified HOPX IHC expression and HOPX promoter DNA hypermethylation as independent prognostic factors in pNET. Conclusions Homeobox-only protein expression is a critical prognostic indicator of pNET, and its regulation may be made through promoter DNA methylation.

A rapidly growing epidermoid cyst in an intrapancreatic accessory spleen treated by laparoscopic spleen-preserving distal pancreatectomy: Report of a case.

Epidermoid cysts arising in an intrapancreatic accessory spleen are exceedingly rare, furthermore the natural course of them is hardly known. We report a case correctly diagnosed with epidermoid cyst in an intrapancreatic accessory spleen, followed by 1 year observation, finally underwent surgical treatment. The patient presented with diarrhea. Contrast-enhanced computed tomography (CT) revealed a pancreatic cyst 20 mm in diameter, surrounded by a solid component showing the same enhancement as the spleen, suggesting the presence of an epidermoid cyst in an intrapancreatic accessory spleen. One year later, back discomfort developed, and a CT scan revealed that the cyst had grown to 38 mm in diameter. To obtain a definitive diagnosis, we performed a laparoscopic spleen-preserving distal pancreatectomy. The histopathological diagnosis was compatible with an epidermoid cyst in an intrapancreatic accessory spleen, which is benign. The postoperative course was uneventful. This case demonstrates that an epidermoid cyst arising in an intrapancreatic accessory spleen can rapidly grow, even if it is benign. Laparoscopic spleen-preserving distal pancreatectomy can be a useful procedure, with the advantages of low invasiveness and organ preservation, for the treatment of benign or low-grade malignant tumors located in the pancreatic body or tail.

Methylated promoter DNA of CDO1 gene and preoperative serum CA19-9 are prognostic biomarkers in primary extrahepatic cholangiocarcinoma

Background Promoter DNA methylation of Cysteine dioxygenase type1 (CDO1) gene has been clarified as a molecular diagnostic and prognostic indicator in various human cancers. The aim of this study is to investigate the clinical relevance of CDO1 methylation in primary biliary tract cancer (BTC). Methods CDO1 DNA methylation was assessed by quantitative methylation-specific PCR in 108 BTC tumor tissues and 101 corresponding normal tissues. BTC was composed of extrahepatic cholangiocarcinoma (EHCC) (n = 81) and ampullary carcinoma (AC) (n = 27). Results The CDO1 methylation value in the tumor tissues was significantly higher than that in the corresponding normal tissues (p<0.0001). The overall survival (OS) in EHCC patients with hypermethylation was poorer than those with hypomethylation (p = 0.0018), whereas there was no significant difference in AC patients. Multivariate analysis identified that CDO1 hypermethylation, preoperative serum CA19-9 and perineural invasion were independent prognostic factors in EHCC. The EHCC patients with CDO1 hypermethylation exhibited more dismal prognosis than those with hypomethylation even in low group of CA19-9 level (p = 0.0006). Conclusions Our study provided evidence that promoter DNA methylation of CDO1 gene could be an excellent molecular diagnostic and prognostic biomarker in primary EHCC. The combination of CDO1 methylation and preoperative serum CA19-9 effectively enriched EHCC patients who showed the most dismal prognosis. These markers would be beneficial for clinical clarification of the optimal strategies in EHCC.

Neutrophil‑to‑lymphocyte ratio as a predictor of postoperative morbidity in patients with distal cholangiocarcinoma

Systemic inflammatory-, immunological- and nutritional-based indices, such as the neutrophil-to-lymphocyte ratio (NLR), the prognostic nutritional index (PNI) and the Glasgow prognostic score (GPS), are drawing considerable research attention to predict the long-term prognosis of many types of cancer. Recently, these parameters have also been reported to be useful in predicting postoperative morbidity in several fields, including colorectal and otolaryngological cancer. However, while distal cholangiocarcinoma exhibits a high morbidity rate, its risk factors of morbidity have not yet been established. This is because previous studies have analyzed distal cholangiocarcinoma as periampullary tumors combined with pancreatic head cancer. Therefore, the aim of the present study was to investigate the application of the NLR, the PNI and the GPS in evaluating risk factors for postoperative morbidity in patients with distal cholangiocellular or ampullary carcinoma. Eighty-four patients who underwent pancreaticoduodenectomy (PD) for distal cholangiocellular or ampullary carcinoma at the Department of Surgery in Kitasato University Hospital between 2008 and 2016 were enrolled. Associations between perioperative characteristics (NLR, PNI and GPS) and postoperative complications (Clavien-Dindo classification grade III or higher) were retrospectively analyzed. In the univariate analysis, neutrophil and lymphocyte counts, body mass index (BMI) and the NLR were associated with postoperative complications (P<0.05). In the multivariate analysis, BMI [>23.0 kg/m2; odds ratio (OR): 3.80, 95.0% confidence interval (CI): 1.35–11.83; P=0.011] and the NLR (>2.0; OR: 6.77, 95.0% CI: 2.44–21.13; P<0.001) were independent risk factors for postoperative complications. BMI and the NLR are valuable predictors of postoperative morbidity following PD in patients with distal cholangiocarcinoma. It would be beneficial to determine treatment strategies for distal cholangiocarcinoma based on the NLR to reduce postoperative complications.

No-needle blood access device for hemodialysis and no-needle connecting cannula assembly (K-NOBA PAT./JAP2983540)

Our group is developing a no-needle blood access for maintenance hemodialysis. The device is made from titanium. The device is connected at the middle part of the prosthetic graft A-V shunt. It has two wells on the conduit and they are closed by shutters. The specially designed cannulas are inserted in the wells and hemodialysis is performed. Patients have no pain and good QOL. Selfcannulation and home dialysis are possible.