Tatsuya Tsuji

A method for safe pancreaticojejunostomy

We devised a new technique to increase the safety of pancreaticojejunostomy in patients with an extended operation for pancreatic cancer. This new pancreaticojejunostomy was created by end-to-side anastomosis with four layers about 7 cm distal to the jejunal stump. The cut surface of the pancreas was placed on the seromuscular coat of the ventral aspect of the jejunum to cover the posterior surface of the anastomosis, and the anastomosis between the pancreas and the jejunum was created using fibrin glue. The pancreatic duct was intubated with a silicone tube, and its stenting tube was brought out through a opening in the jejunum. The anterior surface of the pancreaticojejunostomy was covered by the proximal jejunum as a serosal patch. We used this technique in seven patients. No patient developed an anastomotic leak or any other complication. The anastomosis is covered by the jejunum and is not open to the peritoneum. This new technique of pancreaticojejunostomy may reduce the risk of pancreatic leak, especially when an extended operation is performed.

Implication of Micrometastases of Lymph Nodes in Patients With Extended Operation for Pancreatic Cancer

Introduction Accurate evaluation of lymph node metastases is very important in planning treatment for pancreatic cancer. Aim To detect micrometastases in lymph nodes dissected from patients with pancreatic cancer. Methodology We used cytokeratin staining of negative lymph nodes in routine hematoxylin–eosin (HE) staining. We examined by cytokeratin staining 239 HE-negative nodes from 7 patients with no pathologic evidence of lymph node metastasis (n0 cases) and 718 HE-negative group 2 nodes from 23 patients with metastasis in group 1 lymph nodes (n1 cases) who underwent extended operation combined with intraoperative radiation therapy (IORT). Results Cytokeratin staining identified 15 positive nodes among the 239 HE-negative nodes from the 7 n0 cases and 8 positive nodes among the 718 HE-negative nodes from the 23 n1 cases. Among the 7 n0 cases, 5 (71.4%) had positive n1 nodes and 2 (28.3%) also had positive n2 nodes. Among the 23 n1 cases, 4 (17.4%) had positive n2 nodes. Patients with micrometastases in n2 nodes died within 25 months. Conclusion Cytokeratin staining is very useful to evaluate the involvement of lymph nodes in pancreatic cancer. Prognosis of pancreatic cancer should be determined in conjunction with evaluation of nodal status by cytokeratin staining. Extended operation was not useful for pancreatic cancer patients with micrometastases of group 2 nodes.

Identification of Prognostic Factors Associated with Early Mortality after Surgical Resection for Pancreatic Cancer—Under-analysis of Cumulative Survival Curve

BackgroundThe cumulative survival curve after surgery for advanced pancreatic cancer is characterized by a steep downward slope in the early postoperative period. The aim of this investigation was to identify the characteristics associated with early mortality in patients undergoing pancreatic resection for pancreatic cancer.MethodsThirty-seven patients with extended radical pancreatectomy combined with intraoperative radiation therapy were studied. The cumulative survival curve in this series was depicted using the Kaplan-Meier method. Assuming that there were two distinct survival curves, below and above the breakpoint, each part of the curve was modeled as an exponential distribution. Three parameters, the breakpoint, the high hazard rate below the breakpoint, and the low hazard rate above the breakpoint were estimated by the maximum likelihood method. Prognostic factors associated with early mortality after surgery were evaluated using univariate and multivariate Cox proportional hazards regression analyses.ResultsThe breakpoint of the survival curve was estimated at 41 months. The short-survival group (SSG) was defined as deceased earlier than 41 months after surgery, and included 31 patients (83.8 %). The long-survival patient group (LSG) consisted of 6 patients who were alive more than 41 months after surgery. Eighteen SSG patients (58.1 %) died of hepatic metastases, whereas no LSG patients died of hepatic metastases. Abdominal pain and/or back pain during clinical course was identified by multivariate analysis as a prognostic factor for patients undergoing pancreatic resection.ConclusionsThe high hazard rate in the early postoperative period was closely linked with death due to liver metastases. The preoperative presence of local pain was a prognostic factor associated with early mortality.

5-fluorouracil intra-arterial infusion combined with systemic gemcitabine for unresectable pancreatic cancer.

Objectives: The aim of this study was to define assessment of response and adverse events of the combination chemotherapy of 5-fluorouracil (5-FU) pancreatic and hepatic arterial continuous infusion and systemic gemcitabine administration for unresectable pancreatic cancer. Methods: We treated 24 chemotherapy-naive patients with unresectable pancreatic cancer. To prevent gastroduodenal injury from 5-FU infusion, the catheter was placed to allow the distribution of 5-FU to the pancreatic tumor and the liver after occlusion of the gastric and pancreaticoduodenal arteries. 5-FU was administered at a dose of 250 mg/d on days 1 to 5 every week as a continuous arterial infusion. Gemcitabine was infused intravenously at a dose of 1000 mg once weekly for 3 consecutive weeks of every 4 weeks. Results: The partial response rate was 20.8% (5 of 24), although there was no case of complete response. Fourteen cases (58.3%) were stable disease, and 5 cases (20.8%) were progressive disease. The most common toxicities were hematological and gastrointestinal events. No patients died of adverse effects using this chemotherapy. Gastric and/or duodenal ulcers occurred because of 5-FU intra-arterial infusion. Catheter-related cholangitis occurred in patients with biliary drainage for obstructive jaundice. Median survival time was 14 months, with a 50.9% 1-year survival rate, although patients with performance status 2 and multiple organ metastases had a poor prognosis. Conclusions: This combination chemotherapy was well tolerated and seemed to be effective for patients with unresectable pancreatic cancer.

Treatment Strategies for Hepatic Metastases From Pancreatic Cancer in Patients Previously Treated With Radical Resection Combined With Intraoperative Radiation Therapy

Since 1984, we have performed extended radical resection combined with extended intraoperative radiation therapy (IORT) for pancreatic cancer. This approach has provided a dramatic improvement in long-term survival and control of local recurrence. Hepatic metastases, however, remain an unsolved problem. Among patients with this combined therapy, we found hepatic metastases in 8 of 22 patients postoperatively. Four of these 8 were considered candidates for further therapy and underwent treatment for their hepatic metastases, the other 4 had too extensive disease. Two patients with multiple hepatic metastases underwent percutaneous ethanol injection therapy and chemotherapy, but they died within a year. Two patients with a solitary hepatic metastases underwent hepatic resection. One patient died two years and six months after the first operation because of multiple metastases in the liver and both lungs, while the other patient is still alive over six years after the first operation with an excellent performance status. When a patient has no local recurrence and a solitary metastasis in the liver, surgical resection of the liver metastasis should be performed.

Long-term outcomes of extended radical resection combined with intraoperative radiation therapy for pancreatic cancer

BACKGROUND/PURPOSE Systemic and/or local recurrence often occurs even after curative resection for pancreatic cancer (PC). To prevent local relapse we adopted an extended radical resection combined with intraoperative radiation therapy in patients with PC, and all the patients were followed for more than 5 years. METHODS We assessed the long-term outcomes of 41 patients who underwent this combined therapy. The cumulative survival curve in this series was depicted using the Kaplan-Meier method. Statistical analyses were performed using the log-rank test. RESULTS The actual 5-year survival rate was 14.6%, with a median survival time of 17.6 months. Six patients have been 5-year survivors. Local recurrence occurred in only 2 patients (5.0%). Cancer-related death occurred in 32 patients, 18 of whom had liver metastases. The patients with liver metastases had a significantly shorter survival time than those with other cancer-related causes of death. Patients with n3 lymph node involvement, extrapancreatic nerve plexus invasion, and stage IV disease had significantly poorer prognoses than patients without these characteristics. CONCLUSIONS Our combined therapy for patients with PC contributed to local control; however, it provided no survival benefit, because of liver metastases.

Metastatic gastric tumor secondary to pancreatic adenocarcinoma

Metastatic disease, from the pancreas, involving the stomach is an unusual clinical event. Local recurrence, liver metastases, and peritoneal spread are the most common recurrent patterns after curative resection of pancreatic cancer. We report a patient who suffered from gastric metastasis secondary to pancreatic adenocarcinoma 1 year after pancreatectomy. A 49-year-old woman underwent distal pancreatectomy with intraoperative radiation therapy for cancer of the body of the pancreas in October 2002. The histological diagnosis was well-differentiated adenocarcinoma of the pancreas, stage IIB; T1N1M0. Multiple liver metastases were detected on computed tomography (CT) in March 2003. Combination chemotherapy of 5-fluorouracil hepatic arterial continuous infusion and systemic gemcitabine administration led to the disappearance of the liver metastases on CT in September 2003. One month later, she complained of epigastric pain and underwent gastric endoscopy, which revealed a submucosal tumor in the fornix posterior wall. Histological diagnosis of the biopsy specimen was well-differentiated adenocarcinoma, and immunohistochemical studies, using anti-cytokeratin 7 and -20 monoclonal antibodies, were compatible with gastric metastasis from pancreatic carcinoma. A F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) scan revealed a high-uptake lesion, which coincided with the gastric tumor. No other abnormal uptake could be found. Histopatholoical examination of the resected specimen revealed submucosal growth of the metastatic cancer (well-differentiated adenocarcinoma).

Cancer cells spread through lymph vessels in the submucosal layer of the common bile duct in gallbladder carcinoma.

INTRODUCTION In the present study, we performed immunohistochemical staining with a lymphatic epithelium-specific marker, D2-40, to analyze the status of lymphatic spreading in the hepatoduodenal ligament in T2 gallbladder carcinoma (GC). METHODS One hundred and eighty-six paraffin-embedded specimens from 15 T2 GC patients were reviewed. RESULTS Lymph vessels lined with D2-40 were visualized in the submucosal layer of the common bile duct in all cases. In 3 of 15 patients, clusters of cancer cells were identified in the submucosal lymph vessels of the extrahepatic bile duct, and this lymphatic invasion of cancer cells failed to be detected with only conventional hematoxylin-eosin staining. The frequency of the invasion to the submucosal lymph vessels in T2 GC correlated with presence of microscopic invasion to hepatoduodenal ligament and perineural invasion. CONCLUSION There were lymph vessels in the submucosal layer of the common bile duct, and cancer cells can spread through these channels in addition to the large lymph vessels in subserosal layer around the extrahepatic bile duct in GC. The present results would support the concept of en bloc resection of the extrahepatic bile duct in curative resection for T2 GC.

Evaluation of the Efficacy of Combined Continuous Arterial Infusion and Systemic Chemotherapy for the Treatment of Advanced Pancreatic Carcinoma

PurposeTo evaluate the effects of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in patients with advanced pancreatic carcinoma.MethodsCTAI was performed in 17 patients with stage IV pancreatic cancer with (n = 11) or without (n = 6) liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The inferior pancreatic artery (IPA) was embolized to achieve delivery of the pancreatic blood supply through only the celiac artery. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. Treatment effects were evaluated based on the primary tumor size, liver metastasis, and survival time and factors such as tumor size, tumor location, and stage of pancreatic carcinoma; the embolized arteries were analyzed with respect to treatment effects and prognosis.ResultsA catheter was fixed in the gastroduodenal artery and splenic artery in 10 and 7 patients, respectively. Complete peripancreatic arterial occlusion was successful in 10 patients. CT showed a decrease in tumor size in 6 of 17 (35%) patients and a decrease in liver metastases in 6 of 11 (55%) patients. The survival time ranged from 4 to 18 months (mean ± SD, 8.8 ± 1.5 months). Complete embolization of arteries surrounding the pancreas was achieved in 10 patients; they manifested superior treatment effects and prognoses (p < 0.05).ConclusionIn patients with advanced pancreatic cancer, long-term CTAI with systemic chemotherapy appeared to be effective not only against the primary tumor but also against liver metastases. Patients with successfully occluded peripancreatic arteries tended to survive longer.

Complete remission of pancreatic cancer after multiple resections of locally pancreatic recurrent sites and liver metastasis: Report of a case

Pancreatic cancer has the most dismal prognosis of all gastrointestinal cancers. We herein report a case of complete remission from pancreatic cancer by multire-sections of locally pancreatic recurrent sites and liver metastasis over a 14-year period. A 60-year-old man was admitted to our hospital because of a neoplasm of the tail of the pancreas in April 1992. A distal pancreatectomy was curatively performed on this patient. At 1 year after surgery a solitary liver metastasis appeared, and we thus performed a partial hepatectomy. Thereafter, local recurrences appeared twice and we performed a pancreatectomy each time. Finally, we performed a total pancreatectomy. The histopathological findings of specimens of the pancreas showed papillary adenocarcinoma, although the original pancreatic tumor also demonstrated areas of tubular adenocarcinoma. Metastatic liver tumor showed tubular adenocarcinoma. The patient has survived for 14 years since the first operation. This is a rare case of a long survival of a patient with pancreatic cancer due to its histopathology and biologic characteristics.