SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo.

SNAIL, a potent repressor of E-cadherin expression, plays a key role in inducing epithelial-to-mesenchymal transition (EMT) in epithelial cells. During EMT, epithelial cells lose cell polarity and adhesion, and undergo drastic morphological changes acquiring highly migratory abilities. Although there is increasing evidence that EMT is involved in the progression of some human cancers, its significance in the progression of pancreatic cancer remains elusive. In Panc-1, a well-known human pancreatic cancer cell line in which EMT is triggered by TGF-ß1 treatment, SNAIL and vimentin are highly expressed, whereas E-cadherin expression is scant. In contrast, another human pancreatic cancer cell line, BxPC3, in which SNAIL expression is not detected, has high levels of E-cadherin expression and does not undergo EMT upon TGF-ß1 treatment. After transfecting the SNAIL gene into BxPC3, however, the cells undergo EMT with remarkable alterations in cell morphology and molecular expression patterns without the addition of any growth factors. Furthermore, in an orthotopic transplantation model using SCID mice, SNAIL-transfected BxPC3 displayed highly metastatic and invasive activities. In the immunohistochemical analysis of the tumor derived from the SNAIL-expressing BxPC3, alterations suggestive of EMT were observed in the invasive tumor front. SNAIL enabled BxPC3 to undergo EMT, endowing it with a highly malignant potential in vivo. These results indicate that SNAIL-mediated EMT may be relevant in the progression of pancreatic cancer, and SNAIL could be a molecular target for a pancreatic cancer intervention.

A central pancreatectomy for benign or low-grade malignant neoplasms.

INTRODUCTION: A central pancreatectomy is a parenchyma-sparing procedure that is performed to reduce long-term endocrine and exocrine insufficiency. METHOD: In this study, we analyzed the perioperative course, the frequency of postoperative onset of diabetes mellitus, and long-term change of body weight in patients undergoing a central pancreatectomy, in comparison to the patients undergoing a distal pancreatectomy for low-grade neoplasms including cystic neoplasms and neuroendocrine tumors. RESULTS AND DISCUSSION: The rate of postoperative complications including grade B/C pancreatic fistula was no different between both groups. Only one patient undergoing a central pancreatectomy (4.7%) developed new onset of mild diabetes, whereas 35% in the distal pancreatectomy group developed new onset or worsening diabetes (p = 0.0129). The body weight in the distal pancreatectomy group was significant lower than that in the central pancreatectomy group at 1 and 2 years after surgery (1 year; P < 0.0001, 2 years; P = 0.0055), and the body weight in the patients undergoing a central pancreatectomy improved to preoperative values within 2 years after surgery. CONCLUSION: A central pancreatectomy is a safe procedure for the treatment of low-grade malignant neoplasms in the pancreatic body; the rate of onset of diabetes is minimal, and the body weight improves early in the postoperative course.

A pancreaticoduodenectomy is acceptable for periampullary tumors in the elderly, even in patients over 80 years of age.

BACKGROUND: Although the mortality rates for pancreaticoduodenectomy have been reported to be low for periampullary tumors at high-volume centers, postoperative results still remain unclear for elderly patients over 80 years of age. METHODS: This was a retrospective study of patients who underwent a pancreaticoduodenectomy and consisted of 335 patients who were treated for periampullary tumors between January 1994 and August 2008. The main outcomes were postoperative complications, mortality, and the length of hospital stay among the elderly patients, and they were analyzed in three groups: elderly patients over 80 years old, septuagenarians, and those under 70 years of age. RESULTS: The performance status of elderly patients was lower than that of the patients under 70 (P < 0.05), and the elderly had a higher American Society of Anesthesiologists physical status classification score (P < 0.001) as well as low hemoglobin and serum albumin levels (P < 0.01 and P < 0.001, respectively). The incidence of delayed gastric emptying in the elderly was higher; however, there was no significant difference. The other outcomes in the elderly group were similar to those of the other groups. CONCLUSIONS: Pancreaticoduodenectomy was considered to be a feasible surgical procedure for elderly patients who had a good performance status.

Treatment strategy for intraductal papillary mucinous neoplasm of the pancreas based on malignant predictive factors.

BACKGROUND: Noninvasive intraductal papillary mucinous neoplasms (IPMNs) have a favorable prognosis; however, the prognosis of invasive intraductal papillary mucinous carcinoma (invasive IPMC) is poor. Identification of predictive factors for differentiating IPMC from benign IPMNs would assist in providing appropriate treatment. DESIGN: Retrospective study (1999-2006). SETTING: Wakayama Medical University Hospital, Wakayama, Japan. PATIENTS: Fifty-four patients with IPMN who underwent surgery; histologic examination showed benign adenomas in 29, carcinoma in situ in 14, and invasive carcinoma in 11 patients. MAIN OUTCOME MEASURES: Clinical data, preoperative imaging findings, cytologic findings, tumor markers in serum and pancreatic juice, and overall survival. RESULTS: Age of 70 years or older, presence of mural nodules, mural nodule size of 5 mm or larger, and carcinoembryonic antigen (CEA) level in pancreatic juice of 110 ng/mL or higher (as obtained by preoperative endoscopic retrograde pancreatography) were predictive of a malignant IPMN by univariate analysis, and a CEA level of 110 ng/mL or higher in pancreatic juice was identified as the only independent predictive factor for the malignant entity. The presence of jaundice or body weight loss, main pancreatic duct type, presence of mural nodules, mural nodule size of 5 mm or larger, and CEA level in the pancreatic juice of 110 ng/mL or higher were all predictive of invasive IPMCs by univariate analysis. CONCLUSION: Measurement of the CEA level in pancreatic juice should be considered in the diagnosis of IPMC.

Liver metastasis as an initial recurrence has no impact on the survival of patients with resectable pancreatic adenocarcinoma.

BACKGROUND: Prognosis of the patients with pancreatic adenocarcinoma is still poor due to a recurrence, and liver metastasis is a distant metastasis that is foreboded the short survival period. METHODS: Between 1999 and 2005, 68 patients for pancreatic adenocarcinoma underwent a pancreaticoduodenectomy (n = 17), a pylorus-preserving pancreaticoduodenectomy (n = 27), distal pancreatectomy (n = 22), or total pancreatectomy (n = 2) with an extensive lymph node dissection. RESULTS: A tumor recurrence occurred to 55 patients (13 of the liver, 21 of the local recurrence, 16 of peritoneal dissemination, three of the lymph node, and two of lung). The low tumor grade and female demonstrated a risk factor for a liver metastasis (P = 0.043, P = 0.031). A logistic regression analysis demonstrated female (P = 0.02) and low tumor grade (P = 0.04) as independent risk factors for recurrence with liver metastasis. The median survival time (MST) was 13.6 months, and MST of patients with a liver metastasis as an initial recurrent site was 13.7 months; the liver metastasis as an initial recurrent site has no impact on the MST after pancreatic resection. CONCLUSIONS: We concluded potentially supporting the hypothesis that even patients thought to be at higher risk of liver metastasis may still be given the chance of resection, considering the satisfying survival.

Phase 2 trial of oral S-1 combined with low-dose cisplatin for unresectable advanced pancreatic cancer.

OBJECTIVES: A phase 2 trial of S-1 combined with cisplatin was conducted for unresectable pancreatic cancer. PATIENTS AND METHODS: S-1 was administered for 28 days followed by a rest of 14 days. Cisplatin was infused on days 1-5, 8-12, 15-19 and 22-26 of the first course. After the second course, S-1 was administered as maintenance chemotherapy. RESULTS: Thirty patients were enrolled and the responses observed were 0 complete response, 5 partial response, 22 stable disease and 3 progressive disease, with an overall response rate of 17% (95% confidence internal (CI), 6-35%). Toxicity was tolerable, with grade 3 toxicities observed for leukocytopenia (10%), neutropenia (7%), anemia (3%), thrombocytopenia (3%), anorexia (13%), and nausea and vomiting (7%). The median survival time (MST) and the 1-year survival rate were 9.0 months (95% CI, 6.0-14.5 months) and 35.7% (95% CI, 19-55%), respectively. CONCLUSION: S-1 with low-dose cisplatin is well tolerated and effective for advanced pancreatic cancer.

CLIP method (preoperative CT image-assessed ligation of inferior pancreaticoduodenal artery) reduces intraoperative bleeding during pancreaticoduodenectomy.

BACKGROUND: No previous reports have prospectively discussed an operative approach to reducing intraoperative bleeding during pancreaticoduodenectomy (PD). We have established the preoperative CT image-assessed ligation of inferior pancreaticoduodenal artery (IPDA) method (CLIP), which uses a preoperative three-dimensional computed tomographic (3D-CT) image to precisely detect the IPDA root intraoperatively and ligates the IPDA before the pancreas head is isolated. The aim of this study was to clarify whether the new operative approach reduces intraoperative bleeding compared with classical PD. METHOD: Between October 2003 and May 2005, classical PD was performed (n = 48), and from June 2005 to September 2006, PD with the CLIP method was prospectively performed (n = 48) at Wakayama Medical University Hospital. The perioperative status of the patients in the two groups, including intraoperative bleeding, was compared. RESULTS: Median intraoperative bleeding in patients with the CLIP method was significantly reduced compared with classical PD (867 ml versus 728 ml; p = 0.026). Moreover, operative time, red blood cell transfusion (units), and red blood cell transfusion in patients with the CLIP method were significantly reduced compared with classical PD (p = 0.033, 0.042, 0.014, respectively). There were no differences in length from the SMA to the IPDA root when the preoperative measurement by 3D-CT image (37.9 +/- 8.9 mm) and the intraoperative findings (38.0 +/- 8.8 mm) were compared (p = 0.6283). CONCLUSIONS: The CLIP method is a useful and reliable operative technique for reducing intraoperative bleeding in PD.

Early removal of prophylactic drains reduces the risk of intra-abdominal infections in patients with pancreatic head resection: prospective study for 104 consecutive patients.

OBJECTIVE: The aim of this study was designed to determine whether the period of drain insertion influences the incidence of postoperative complications. BACKGROUND DATA: The significance of prophylactic drains after pancreatic head resection is still controversial. No report discusses the association of the period of drain insertion and postoperative complications. METHODS: A total of 104 consecutive patients who underwent pancreatic head resection were enrolled in this study. To assess the value of prophylactic drains, we prospectively assigned the patients into 2 groups: group I underwent resection from January 2000 to January 2002 (n = 52, drain to be removed on postoperative day 8); group II underwent resection from February 2002 to December 2004 (n = 52, drain to be removed on postoperative day 4). Postoperative complications in the 2 groups were compared. RESULTS: The rate of pancreatic fistula was significantly lower in group II (3.6%) than in group I (23%) (P = 0.0038). The rate of intra-abdominal infections, including intra-abdominal abscess and infected intra-abdominal collections, was significantly reduced in group II (7.7%) compared with group I (38%) (P = 0.0003). Eighteen of 52 (34.6%) patients in group I had an inserted drain beyond 8 days, whereas only 2 of 52 (3.7%) patients in group II had an inserted drain beyond 4 days (P = 0.0002). Cultures of drainage fluid were positive in 16 of 52 (30.8%) patients in group I, and in 2 of 52 (3.7%) patients in group II (P = 0.0002). Intraoperative bleeding (> 1500 mL), operative time (> 420 minutes, and the period of drain insertion were significant risk factors for intra-abdominal infections (P = 0.043, 0.025, 0.0003, respectively). The period of drain insertion was the only independent risk factor for intra-abdominal infections by multivariate analysis (odds ratio, 6.7). CONCLUSION: Drain removal on postoperative day 4 was shown to be an independent factor in reducing the incidence of complications with pancreatic head resection, including intra-abdominal infections.