Nobuhiko Harada

Nuclear accumulation of p53 correlates significantly with clinical features and inversely with the expression of the cyclin-dependent kinase inhibitor p21^<WAF1/CIP1) in pancreatic cancer

Recent studies have suggested a p53-independent expression of p21(WAF1/CIP1). We investigated the correlation between p53 overexpression and the expression of p21(WAF1/CIP1) in 57 patients with pancreatic adenocarcinoma. By means of reverse transcription and polymerase chain reaction (RT-PCR), we examined the mRNA levels of WAF1/CIP1 and compared them with the p53 status in 20 patients and in a further six pancreatic tumour cell lines. In pancreatic cancer tissues, immunohistological evaluation revealed a significant correlation between active p53 and p21(WAF1/CIP1) (P < 0.005) as well as WAF1/CIP1 mRNA expression (P < 0.005). This coherence was also evident in human pancreatic carcinoma cell lines. The analysis of p53 and p21(WAF1/CIP1) expression in relation to clinicopathological features revealed a significant correlation between p53 overexpression and tumour stage, tumour size, grading and lymph node metastases, whereas p21(WAF1/CIP1) expression correlated only with tumour size. We conclude that the expression of p21(WAF1/CIP1) normally depends on active p53, but that there may also exist p53-independent pathways of induction that reduce the correlation of p21(WAF1/CIP1) to clinicopathological features.

Stenting is unnecessary in duct-to-mucosa pancreaticojejunostomy even in the normal pancreas

Background: There is a high risk of anastomotic leakage after pancreaticojejunostomy after pancreaticoduodenectomy (PD) in patients with a normal pancreas because of the high degree of exocrine function. These PD are therefore generally performed using a stenting tube (stented method). In recent years, we have performed pancreaticojejunostomy with duct-to-mucosa anastomosis without a stenting tube (nonstented method) and obtained good results. Methods: The point of this technique is to preserve adequate patency of the pancreatic duct by carefully picking up the pancreatic duct wall with a fine atraumatic needle and monofilament thread. The results of end-to-side pancreaticojejunostomy of the normal pancreas were compared between the nonstented method (n = 109) and the stented method (n = 39). Results: There were no differences in background characteristics between the groups, including age, gender and disease. The mean duration to complete pancreaticojejunostomy was 26.6 min in the nonstented group and 29.2 min in the stented group. The mean durations of surgical procedure and intraoperative blood loss were also similar in the groups. Morbidity rates due to early postoperative complications were 20.2 and 23.1%, with pancreatic leakage occurring in 7.3 and 7.7% of patients, respectively. These differences were not statistically significant. One patient in the stented group died of sepsis following leakage of pancreaticojejunostomy. There were also no significant differences in the mean time to initiation of solid food intake or postoperative hospital stay. Conclusion: We conclude that a stenting tube is unnecessary if the duct-to-mucosa anastomosis is completely performed. This operative technique can be considered a basic procedure for pancreaticojejunostomy because of the low risk.

Benign tumour of the ampulla of vater: surgical treatment and prognosis

OBJECTIVE To find out whether wide local resection is adequate treatment for patients with benign tumours of the papilla of Vater. DESIGN Retrospective study. SETTING University hospital, Germany. SUBJECTS 31 patients with benign tumours out of a total of 129 with lesions of the ampulla of Vater treated between May 1978 and February 1995. INTERVENTIONS Histological examination of specimens before, during, and after the operation. MAIN OUTCOME MEASURES Sensitivity and positive predictive value of histological examination, and outcome of treatment. RESULTS Histological examination before and during the operation had a sensitivity of 89% and 97%, respectively. 28 patients were treated by wide excision of the ampulla and 3 by pylorus-preserving partial pancreaticoduodenectomy. At a median follow up of 43 months (range 6-156) there was no evidence of recurrent disease. CONCLUSION Wide excision of the ampulla with reconstruction and reimplantation of the duct is adequate treatment for benign lesions. If the histological picture is uncertain, partial pancreaticoduodenectomy is justified in patients at low risk.

Pancreatic invasion is a prognostic indicator after radical resection for carcinoma of the ampulla of Vater

Sixty-three patients who had undergone pancreatoduodenectomy for carcinoma of the ampulla of Vater were analyzed with respect to tumor extent and prognosis. The postoperative mortality rate was 3% and overall survival rates 3 and 5 years after surgery were 55% and 46%, respectively. pTNM stage did not reflect prognosis after resection in patients at stages 2 and 3, while pancreatic invasion and regional lymph node metastasis clearly reflected prognosis after resection. Of the 26 patients who had no pancreatic invasion, regional lymph node metastasis was seen in only 19%, whereas of the 37 patients with pancreatic invasion, 62% exhibited lymph node metastasis. These factors were significantly correlated (P<0.001). Pancreatic invasion appeared to be an indirect indicator of regional lymph node metastasis. We conclude that, to improve prognosis for patients with pancreatic invasion, extended resection including extended lymphadenectomy, is a preferable additional procedure.

Clinical analysis of TS1 carcinoma of the pancreas

In 40 patients with tumor size (TS)1 pancreatic cancer with a TS of 2 cm or less, the tumor was classified as without direct extrapancreatic invasion in 11 patients (t1a, group) and as with direct extrapancreatic invasion in 29 patients (t2t3 group). Ultrasonography (US) and endoscopic retrograde cholangio-pancreatography (ERCP) were useful for the diagnosis, with accuracy rates of 80% and 75%, respectively, in the t1a group and 78% and 75% in the t2t3 group. The accuracy rate of preoperative integrated imaging diagnosis was 83% in the t2t3 group but only 55% in the t1a group. All of the t2t3 patients were stage III or higher and 18% of the t1a patients had lymph node metastasis, indicating the need for extended radical operation in TS1 pancreatic cancer. Because standard operation is indicated when the preoperative diagnosis is not pancreatic cancer, accurate preoperative diagnosis is very important. The rate of curative resection and the 5-year survival rate were 100% and 56%, respectively, in the t1a group and there were two 5-year survivors. The rate of non-curative resection and the 5-year survival rate were 31% and 35%, respectively, in the t2t3 group and there were three 5-year survivors. In the light of these findings, it is therefore important to make an accurate diagnosis of t1a pancreatic cancer of TS1 pancreatic cancer without direct extrapancreatic invasion. As liver metastasis was frequently observed in both the t1a and t2t3 groups, the establishment of effective measures to inhibit liver metastasis is considered urgent to improve the result of TS1 pancreatic cancer surgery.

Pancreatoduodenectomy for Benign Disease: Indication and Results

In benign lesions of the periampullary region, several modifications of pancreaticoduodenectomy have been developed to avoid major surgical resection. The pylorus-preserving pancreatic head resection provides the advantage of preservation of the stomach and the first segment of the postpyloric duodenum, whereas the duodenum-preserving head resection is a limited surgical procedure that leads to a local resection of the lesion with complete conservation of stomach and duodenum and, in most instances, spares the hepatobiliary extrahepatic tree. The ampullectomy results in a complete excision of the ampulla of Vater as a local excision of the wall of the duodenum with some parts of the head of the pancreas. In 478 patients with benign lesions in the periampullary region, a resection was carried out with a total hospital mortality of 0.6%. An indication for a limited resection exists in cases of benign adenoma of the papilla, in an endocrine tumor of the head of the pancreas, in a cystadenoma of the head of the pancreas, in pancreas divisum with an inflammatory process in the head of the pancreas, and in chronic pancreatitis with an inflammatory tumor in the head of the pancreas. The duodenum-preserving pancreatic head resection is indicated in benign, serous, or mucinous cystadenoma of the head of the pancreas and in large endocrine tumors located in the head. In chronic pancreatitis with an inflammatory mass in the head, the duodenum-preserving resection is the procedure of choice.

Duodenum-Preserving Head Resection: A Standard Operation for Chronic Pancreatitis

Duodenum-preserving head resection of the pancreas has become a standard surgical procedure in benign lesions of the head of the pancreas. In patients with chronic pancreatitis and an inflammatory mass in the head of the pancreas, duodenum-preserving head resection offers major advantages in comparison to the Whipple resection: conservation of the stomach, duodenum, and biliary tree, and minimal restriction of endocrine pancreatic function. In 380 patients with chronic pancreatitis and an inflammatory mass, the duodenum-preserving head resection was carried out with a median postoperative hospitalization of 13.9 days, a frequency of reoperation of 5.3%, and a hospital mortality of 0.8%. The duodenum-preserving subtotal pancreatic head resection resulted in an improved glucose metabolism in 9% of the patients, preoperatively suffering latent or insulin-dependent diabetes. Only 2% of the patients showed deterioration with newly developed diabetes mellitus in the early postoperative phase. The late mortality after a median follow-up of more than 6 years is around 6%. In terms of the disease chronic pancreatitis, duodenum-preserving head resection leads to an interruption of the progression of the chronic inflammation of the pancreas.

Usefulness of Intraductal Ultrasonography (IDUS) for Diagnosing Mucin‐producing Pancreatic Tumors

Abstract: While it is very important to detect protruded lesions in order to determine the optimal treatment modality for mucin‐producing tumors of the pancreas (MPT), it can be very difficult to discriminate between mucinous substance and tumor. Intraductal ultrasonography (IDUS) (2.0 mm diameter, 15 or 20 MHz) was performed in five MPT cases. The sizes of the tumors were 2, 5, 12, 12 and 30 mm. Histological findings of the resected specimens demonstrated adenocarcinoma in two cases, adenoma in one, and hyperplasia in one. IDUS visualized all tumors, i. e. the visualization rate was 100%. The visualization rate for US and CT was 40% with 12 and 30 mm tumors, and that for EUS was 60% with 2, 12, and 30 mm tumors. We found IDUS to be a very useful method for visualizing small protruded lesions in MPT.