Masahiko Kawamoto

Association of microRNA-21 expression with its targets, PDCD4 and TIMP3, in pancreatic ductal adenocarcinoma.

Since the discovery of small non-coding RNAs, the analyses of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. miRNA-21 has been suggested to be one of the miRNAs that have an important role in the development or biological behavior of a variety of malignancies, including pancreatic cancer. This study was conducted to evaluate the relationship between the expression of miRNA-21 and that of its molecular targets, programmed cell death 4 (PDCD4) and tissue inhibitor of metalloproteinase (TIMP3), in pancreatic ductal adenocarcinoma. The study included 65 pancreatic ductal adenocarcinomas and 5 normal pancreatic tissue specimens for comparison. The miRNA expression profiling of five selected pancreatic ductal adenocarcinomas and five normal pancreatic specimens was performed using a microarray platform, and was evaluated by a hierarchical clustering analysis. The miRNA most highly expressed in pancreatic ductal adenocarcinomas (ie, miRNA-21) was further assessed by quantitative real-time reverse transcription PCR (RT-PCR) assays in the 65 pancreatic ductal adenocarcinoma cases. The expression pattern of its molecular targets (eg, PDCD4 and TIMP3) in pancreatic ductal adenocarcinoma was examined immunohistochemically. In the microarray analyses, 28 miRNAs were upregulated in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue, whereas 48 miRNAs were downregulated. miRNA-21 was the most significantly overexpressed miRNA in the pancreatic ductal adenocarcinomas analyzed, and was also highly expressed in 75% of the 65 pancreatic ductal adenocarcinomas examined by real-time RT-PCR. High miRNA-21 expression was correlated with a worse prognosis in the pancreatic ductal adenocarcinoma patients (P=0.045). The immunohistochemical expression patterns of PDCD4 (reduced nuclear staining pattern) and TIMP3 (downregulated expression) were significantly associated with both the upregulated miR-21 expression (P<0.05) and the poor survival of the patients (P<0.001 and P=0.001, respectively). Our data suggest that an overexpression of miRNA-21 is, therefore, associated with the biological behavior of pancreatic ductal adenocarcinoma via the downregulation of the expression of tumor suppressors, PDCD4 and TIMP3, thus resulting in tumor progression and the adverse clinical course of pancreatic ductal adenocarcinoma.

Pancreatic juice cytology in IPMN of the pancreas

Background: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a disease ranging from adenoma to borderline (with moderate dysplasia) and further to carcinoma (noninvasive and invasive) and surgical strategy is different by the grades of dysplasia. Methods: Preoperativepancreatic juice cytology in IPMN was reviewed in 71 patients with IPMN who underwent surgical resection. Results: The IPMN was adenoma in 48 patients, borderline in 13 and carcinoma (invasive) in 10. The sensitivity of pancreatic juice cytology in malignant IPMN was 40% (4/10). In 4 patients with the 48 IPM adenomas, diagnosis of pancreatic juice cytology was class IV or V. One of the 4 cases was considered to be an overdiagnosis of cytology, but the other 3 cases were considered to be a consequence of accompanying carcinoma in situ (or PanIN-3) (2 patients) or invasive ductal adenocarcinoma (1 patient) apart from IPMN. Sensitivity of pancreatic juice cytology was higher in IPMN of the main duct type with mucin hypersecretion and with mural nodules. Conclusions: These findings suggest that pancreatic juice cytology in IPMN is useful especially in the main duct type with mucin hypersecretion and mural nodules. When the diagnosis of pancreatic juice cytology is malignant in otherwise benign-looking IPMNs, coexistence of pancreatic carcinoma should be suspected.

Intraabdominal Roux-en-Y reconstruction with a novel stapling technique after laparoscopic distal gastrectomy

Laparoscopic gastrectomy is widely used as minimally invasive surgery for gastric carcinoma. Billroth I or Roux-en-Y reconstruction is commonly performed after laparoscopic distal gastrectomy (LDG). Roux-en-Y reconstruction after LDG is one of the best methods for reconstruction of the alimentary tract when Billroth I reconstruction is difficult. There are few reports of intracorporeal Roux-en-Y reconstruction after LDG because of the technical difficulties of such a procedure. In particular, in the case of a very small gastric remnant, gastrojejunostomy using endoscopic linear staplers becomes more complicated. We developed a new technique for intracorporeal Roux-en-Y reconstruction: a modified stapling technique to allow the gastrojejunostomy to be made on the stomach transecting line that is applicable even when the residual stomach is very small. Roux-en-Y reconstruction with our modified technique was performed in six patients. There was no intraoperative complication or conversion to minilaparotomy or conventional celiotomy in any patient. Oral intake was easy and adequate after surgery. The present Roux-en-Y reconstruction procedure is feasible. Herein we describe an intraabdominal Roux-en-Y reconstruction with a modified stapling technique after LDG.

Duodenum is important for the sphincter of Oddi motor response to cholecystokinin octapeptide in conscious dogs

BackgroundWe investigated the role of the duodenum in the sphincter of Oddi response to cholecystokinin-octapeptide (CCK-OP), using conscious dogs.MethodsIn controls, a cannula was inserted into the duodenum opposite the papilla for retrograde manometry. In the duodenectomy group, the entire duodenum was resected, while preserving the papilla, which was implanted into the jejunum, and the cannula was placed. Sphincter motility was recorded after bolus injections of 20 and 100 ng/kg of CCK-OP.ResultsCCK-OP at 20 ng/kg produced sphincter relaxation followed by contraction in the controls, but produced no changes after duodenectomy. CCK-OP at 100 ng/kg caused strong contractions followed by relaxation in the controls, but caused only contractions after duodenectomy.Conclusions(1) Relaxation and delayed contraction of the sphincter induced by 20 ng/kg of CCK-OP require the presence of the duodenum; (2) early contractions of the sphincter induced by 100 ng/kg of CCK-OP do not require the duodenum; (3) the duodenum plays an important role in the actions of CCK-OP on sphincter motility.

Role of Duodenum on Sphincter of Oddi Motility in Conscious Dogs

Our aim was to determine the role of the duodenum in controlling sphincter of Oddi motility using conscious dogs after total duodenectomy. In a control group (N = 6), a cannula was implanted into the duodenum opposite to the papilla to allow retrograde sphincter manometry. In a duodenectomy group (N = 6), the papillae were preserved at total duodenectomy and sutured to the jejunum anastomosed to the stomach (neoduodenum). The cannula was implanted opposite to the implanted papillae. Interdigestive and postprandial sphincter and duodental or neoduodenal motility were recorded by manometric and myoelectric methods. Duodenectomy disrupted sphincter cyclic motility associated with the intestinal migrating motor complex and increased sphincter activity throughout the cycle. Sphincter activity increased immediately after feeding and did not differ between the two groups. In conclusion, during the interdigestive period, the duodenum has a distinct role in regulating sphincter cyclic motility. The initiation of the fed pattern of sphincter motility does not need the duodenum.

Manometric evidence of earlier recovery of fasting gastric motility after antecolic duodenojejunostomy than after retrocolic duodenojejunostomy following PPPD.

BACKGROUNDS/AIMS Gastric stasis is a unique complication of pylorus-preserving pancreatoduodenectomy (PPPD). Although some studies reported less prevalence of gastric stasis after antecolic duodenojejunostomy, there have been no reports on detailed comparison of gastric motility after antecolic vs. retrocolic duodenojejunostomy after PPPD. METHODOLOGY Thirty-six patients underwent PPPD with the modified Child reconstruction. Retrocolic duodenojejunostomy was utilized in initial 13 patients (retrocolic group). For comparison, antecolic duodenojejunostomy was employed in subsequent 23 patients (antecolic group). A manometric tube assembly was inserted into the gastric antrum and jejunum during PPPD. Gastrointestinal motility was recorded for 3 hours a day, starting on 6 to 14 days after surgery and repeated at a weekly interval until the first appearance of phase 3 gastric motility. Various clinical parameters were also assessed. RESULTS Recovery of gastric phase 3 was identified in 19 of 36 patients. Recovery of phase 3 was faster in antecolic group than in retrocolic group (p<0.01). The amount of the gastric juice output during 14 postoperative days was larger in retrocolic group than in antecolic group (p<0.01). Resumption of water intake and food intake was earlier and the length of intravenous hyperalimentation and hospital stay was shorter in antecolic group than in retrocolic group (p<0.05). CONCLUSIONS Antecolic duodenojejunostomy contributes to early recovery of gastric phase 3 motility in patients after PPPD, leading to prevention of early gastric stasis.