Therapeutic Outcome of Multidisciplinary Treatment in Unresectable Biliary Tract Cancer: A Multicenter Retrospective Analysis.

Background: There is little established evidence regarding treatment strategies for unresectable biliary tract cancer (BTC). This study aimed to clarify the situation of multidisciplinary treatment for unresectable BTC in the 2000s when there was no international standard first-line therapy. Methods: We retrospectively reviewed 315 consecutive patients with unresectable BTC who had been treated at seven tertiary institutions in Kanagawa Prefecture, Japan between 1999 and 2008. Results: The unresectable factors were as follows: locally advanced, 101 cases (32.1%); hematogenous metastases, 80 cases (25.4%); and peritoneal dissemination, 30 cases (9.5%). Chemotherapy or radiation therapy was administered to 218 patients (69.2%). The best supportive care was provided in 97 cases (30.8%). The most common regimen was gemcitabine monotherapy, followed by gemcitabine combination therapy and S-1 monotherapy. The 1- and 2-year survival rates of all patients were 34.6% and 12.2%, respectively. The median survival time (MST) was 8 months in all patients. The 1-year survival rate was 65%, and the MST was 12 months among the locally advanced patients, whereas patients with peritoneal dissemination had the worst outcome; the 1-year survival rate was 7%, and the MST was 5 months. Among treated 90 cases of perihilar cholangiocarcinoma, patients who received chemoradiotherapy (n = 24) had a significantly better outcome than those who received chemotherapy alone (MST: 20 vs. 11 months, P < 0.001). Conclusions: Unresectable BTC has heterogeneous treatment outcomes depending on the mode of tumor extension and location. Multidisciplinary treatment seems useful for patients with locally advanced BTC, whereas patients with metastatic disease still have a poor prognosis.

Preoperative serum CA19-9 and dissected peripancreatic tissue margin as determiners of long-term survival in pancreatic cancer.

BACKGROUND: Pancreatic cancer, a particularly deadly form of malignancy, has increased in the last decade worldwide. The purpose of this study is to identify markers for determining and identifying possible long-term survivors in cases of advanced pancreatic cancer. PATIENTS AND METHODS: 117 patients with pancreatic ductal carcinoma, including 89 with invasive tubular adenocarcinoma of the pancreas, Japan Pancreas Society (JPS) stage III-IVb patients, who underwent tumor resection between 1986 and 2006. RESULTS: Univariate prognostic analyses of the 5-year disease-specific survival (DSS) revealed that JPS stage (P < 0.0001), preoperative serum carbohydrate antigen 19-9 (CA19-9) level (preCA19-9; P < 0.0001), dissected peripancreatic tissue margin (DPM; P < 0.0001), residual tumor (R factor; P = 0.0007), lymph node metastasis density over 10% (ND10; P = 0.006), volume of the stromal connective tissue (stroma factor; P = 0.008), growth pattern (P = 0.01), and histology (P = 0.03) were all significantly associated with poor outcome in advanced pancreatic cancer. Multivariate logistic analysis confirmed that preCA19-9 [P = 0.0006, relative risk (RR) = 2.16] and DPM (P = 0.04, RR = 1.62) were prognostic factors that remained, independent of JPS stage (P = 0.001). The higher preCA19-9 was, the worse the prognosis was. Astonishingly, among JPS stage III cases, 76.9% of the patients with preCA19-9 below 37 U/ml survived more than 5 years. This, combined with an analysis of DPM, allowed us to identify those with the potentiality for long-term survival. CONCLUSION: Our results reveal for the first time that it is possible with JPS stage III-IVb invasive tubular adenocarcinomas of the pancreas to differentiate prognostic groups and potential survival rates, like with other cancers.

Urinary trypsin inhibitor improves viability of the liver in brain-dead rats.

BACKGROUND/AIMS: The present study examined the effect of urinary trypsin inhibitor (UTI) on liver injury in hypotensive brain-dead rats. METHODS: Brain death was induced by inflating a balloon catheter placed in the epidural space. UTI (100,000 units/kg/hour) was intravenously administered from 30 min until 6 hours after the induction of brain death. Systemic hemodynamics and hepatic tissue flow (HTF) were measured, and blood samples and hepatic tissue specimens for morphological examinations were obtained during the experiments. RESULTS: The induction of brain death caused a 30% decrease in both mean arterial pressure and HTF, and an increase in the serum transaminase level in comparison with sham-operated rats. Brain death also increased the serum concentration of cytokine-induced neutrophil chemoattractant (CINC) (4.4-fold), as well as the number of CINC-positive cells (4.4-fold) and sequestered neutrophils in the sinusoids (3.1-fold). Post-treatment of brain-dead rats with UTI restored the HTF and reduced serum transaminase level. UTI decreased plasma CINC level and the number of neutrophils and CINC-positive cells in the sinusoids. CONCLUSIONS: The results suggest that treatment with UTI after the establishment of brain death improved the viability of the liver in hypotensive brain-dead rats by inhibiting CINC production.

The advantage of Kakita's method with pancreaticojejunal anastomosis for pancreatic resection.

In 1996, we reported the technical aspects of our new method for end-to-side pancreatojejunostomy (Kakita's method) that we performed in combination with the Whipple procedure without any complications related to failure in the anastomosis. In this chapter, we will introduce our technique in end-to-end style pancreatojejunal anastomosis with fewer anastomotic complications. The purpose of this study was to review Kakita's method with pancreatoduodenectomy. From April 1990 to December 2005, 324 consecutive cases of pancreatoduodenectomy were performed in the Department of Surgery at Kitasato University. In our institute, reconstruction in pancreatoduodenectomy is basically performed according to a modified Child's procedure. Our method is simple and can be applied wherever an end-to-side pancreatojejunal anastomosis is required. It consists of three steps: First, a drainage tube is inserted into the pancreatic duct. The second step, which is the unique aspect of our method, is an attachment of the jejunal wall and the cut surface of the pancreas using a single-layer suture technique. This allows us not only to reduce the number of sutures but also to eliminate some of the complicated manipulations required by other methods. The jejunal wall fully covers the cut surface of the pancreas, leaving no uncovered area between the wall and the pancreas. Third, a direct anastomosis between the pancreatic duct and the mucosal layer of the jejunal loop is applied. In our series, pancreatojejunal anastomotic leakage occurred only in 4 out of 324 patients, which was 1.23%. All patients were successfully treated with conservative therapy using drainage for an extended period postoperatively. The newly devised pancreatojejunostomy in our department is a simple, safe, and reliable procedure with excellent results.

Perineural invasion and preoperative serum CA19-9 as predictors of survival in biliary tract cancer.

BACKGROUND: Billiary tract cancer requires invasive surgical procedures for cure, and the risk factors related to patient prognosis remain controversial. PATIENTS AND METHODS: Out of the 111 patients who underwent resection of extrahepatic biliary tract tumors from 1986 to 2010, the records for 88 with both ampullary and extrahepatic bile duct cancer, which included all information for evaluation of the clinicopathological factors, were employed in a multivariate analysis. RESULTS: On univariate analysis, significant prognostic factors of poor survival unrelated to TNM factors were preoperative biliary drainage, high preoperative CA19-9 value, high preoperative CEA value, lymphatic invasion, perineural invasion, macroscopic growth pattern, histology, operative procedures (surgery), tumor persistence, high postoperative CA19-9 value, and postoperative chemotherapy. On multivariate analysis, perineural invasion (p=0.025) was the only prognostic factor independent of stage, for survival of patients with biliary tract cancer including ampullary cancer. When ampullary cancer was excluded, both perineural invasion and preoperative CA19-9 were the remaining prognostic factors independent of stage. The combination of both factors can very accurately identify long-term and short-term survivors of biliary tract cancer. CONCLUSION: The present study, to our knowledge, for the first time shows that both perineural invasion and preoperative CA19-9 are important prognostic factors in biliary tract cancer, and this would be beneficial for clinical clarification of the optimal strategies for this type of cancer.