Yuji Kitahata

The carcinoembryonic antigen level in pancreatic juice and mural nodule size are predictors of malignancy for branch duct type intraductal papillary mucinous neoplasms of the pancreas.

Objective:Identification of predictors of malignancy for branch duct type intraductal papillary mucinous neoplasms (IPMN). Background:Main duct type IPMN has been recommended for resection. However, the indications for resection of the branch duct type IPMN have been controversial. Methods:We retrospectively analyzed the clinicopathological factors of 134 patients undergoing resection for branch duct type IPMN, excluding main duct type IPMN, to identify predictors of the malignant behavior of this neoplasm. The cutoff values of tumor size, main pancreatic duct (MPD) size, mural nodule size, and carcinoembryonic antigen (CEA) level in the pancreatic juice obtained during preoperative endoscopic retrograde pancreatography (ERP) were analyzed using receiver–operator characteristic curves. Results:We found 7 significant predictors for malignancy in the branch duct type IPMN in a univariate analysis; jaundice, tumor occupying the pancreatic head, MPD size >5 mm, mural nodule size >5 mm, serum carbohydrate antigen (CA)19–9 level, positive cytology in the pancreatic juice, and CEA level in the pancreatic juice >30 ng/mL. In a multivariate analysis, a mural nodule size >5 mm and a CEA level in the pancreatic juice >30 ng/mL were independent factors associated with malignancy. The positive predictive value of a mural nodule size >5 mm and a CEA level in the pancreatic juice >30 ng/mL was 100%, and the negative predictive value was 96.3%. Conclusions:We identified 2 useful predictive factors for malignancy in branch duct type IPMN; a mural nodule size >5 mm and a CEA level in the pancreatic juice obtained by preoperative ERP >30 ng/mL.

Surgical strategy for patients with pancreatic body/tail carcinoma: Who should undergo distal pancreatectomy with en-bloc celiac axis resection?

BACKGROUND Indications for distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) in pancreatic carcinoma remain controversial. METHODS Fifty-two consecutive patients with pancreatic cancer who underwent distal pancreatectomy, including 36 standard distal pancreatectomies (standard DP) and 16 DP-CAR were reviewed retrospectively. RESULTS After standard DP, microscopically positive margins were identified at the dissection sites around the transection margins of the splenic arteries and were detected more frequently in the patients with tumors within 10 mm from the root of the splenic artery (14%). After DP-CAR, the estimated overall survival rate in patients who were pathologically negative for portal venous and artery invasion (n = 7) was greater than that of the other patients (n = 9; P = .023, log-rank test). The estimated overall 1- and 2-year survival rates after standard DP/DP-CAR were 81/81% and 52/53%, and the median survival times were 32/25 months, respectively, with no differences noted between the groups. There were no differences in the mortality rates and the incidence of each complication between the 2 groups except for delayed gastric emptying. CONCLUSION DP-CAR was a feasible and safe procedure, similar to standard DP. DP-CAR should be reserved for patients without tumor infiltrating either the portal venous or arterial systems.

Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma.

The invasion process is a crucial step for pancreatic ductal adenocarcinoma (PDAC); however, the genes related to invasion remain unclear. To identify specific genes for the invasion process, we compared microarray data for infiltrating cancer and PanIN‐3, which were harvested from an individual PDAC patient by microdissection. Furthermore, immunohistochemical, coimmunoprecipitation and invasion analyses were performed to confirm the biologic significance of molecules identified by expression profile. In the present study, we focused on MUC16 and mesothelin among 87 genes that were significantly upregulated in infiltrating components compared to PanIN‐3 in all PDAC patients, because MUC16 was the most differently expressed between two regions, and mesothelin was reported as the receptor for MUC16. Immunohistochemical analysis revealed that MUC16 and mesothelin were expressed simultaneously only in infiltrating components and increased at the invasion front, and binding of MUC16 and mesothelin was found in PDAC by immunoprecipitation assay. The downregulation of MUC16 by shRNA and the blockage of MUC16 binding to mesothelin by antibody inhibited both invasion and migration of pancreatic cancer cell line. MUC16 high/mesothelin high expression was an independent prognostic factor for poor survival in PDAC patients. In conclusion, we identified two specific genes, MUC16 and mesothelin, associated with the invasion process in patients with PDAC. (Cancer Sci 2012; 103: 739–746)

Stump closure of a thick pancreas using stapler closure increases pancreatic fistula after distal pancreatectomy.

BACKGROUND The appropriate surgical stump closure after distal pancreatectomy (DP) is still controversial. This study investigated the benefits and risks of stapler closure during DP. METHODS The risk factors of pancreatic fistulas were investigated in 122 DPs among 3 types of stump closure: hand-sewn suture (n = 32), bipolar scissors (n = 45), and stapler closure (n = 45). RESULTS There was no significant difference in the incidence of pancreatic fistula between the 3 types of stump closure (hand-sewn suture [44%] vs bipolar scissors [37.7%] vs stapler closure [35.5%]). By using receiver operating characteristics curves, 12 mm was the best cutoff value of the thickness of the pancreas for pancreatic fistulas after DP using stapler closure. Three factors (ie, male sex, body mass index >25 kg/m(2), and stapler closure) were independent risk factors of pancreatic fistulas after DP with a pancreas thicker than 12 mm. CONCLUSIONS A pancreas thicker than 12 mm significantly increased the incidence of pancreatic fistulas after DP using stapler closure.

Randomized clinical trial of isolated Roux-en-Y versus conventional reconstruction after pancreaticoduodenectomy.

Pancreaticoduodenectomy (PD) is associated with a high incidence of postoperative complications including pancreatic fistula. This randomized clinical trial compared the incidence of pancreatic fistula between the isolated Roux‐en‐Y (IsoRY) and conventional reconstruction (CR) methods.

Preoperative cholangitis during biliary drainage increases the incidence of postoperative severe complications after pancreaticoduodenectomy

BACKGROUND It remains controversial how preoperative biliary drainage affects occurrence of severe complications after pancreaticoduodenectomy (PD). METHODS One hundred twenty-seven patients (60 external drainage and 67 internal drainage) required biliary drainage before PD were retrospectively reviewed. RESULTS Preoperative cholangitis in internal drainage group (22.4%) occurred significantly more often than in external drainage group (1.7%; P < .001). The incidence of severe complications (grade III or more) was significantly higher in patients with cholangitis (62.5%) than in those without it (25.2%; P = .002). The incidence of delayed gastric emptying was significantly higher in patients with cholangitis (31.2%) than in those without it (5.4%; P = .001). A multivariate logistic regression analysis revealed that preoperative cholangitis (odds ratio 4.61, 95% confidence interval 1.3 to 16.5; P = .019) was the independent risk factor for severe complications after PD. CONCLUSIONS Preoperative cholangitis during biliary drainage significantly increases incidence of severe complications after PD.

Preoperative evaluation of the confluent drainage veins to the gastrocolic trunk of Henle: understanding the surgical vascular anatomy during pancreaticoduodenectomy.

The aim of this study was to classify the variations of the anatomical tributaries of the colic drainage veins into the gastrocolic trunk of Henle detected by three‐dimensional multidetector computed tomography to understand the surgical vascular anatomy during pancreaticoduodenectomy.

Isolated Roux‐en‐Y anastomosis of the pancreatic stump in a duct‐to‐mucosa fashion in patients with distal pancreatectomy with en‐bloc celiac axis resection

A pancreatic fistula is one of the most serious complications in distal pancreatectomy with en bloc celiac axis resection (DP‐CAR), because the pancreatic transection is performed on the right side of the portal vein, which results in a large cross‐section surface, and because post‐pancreatectomy hemorrhage is hard to treat by interventional radiology. Therefore, a procedure to decrease the incidence of postoperative pancreatic fistula is urgently needed.

Treatment Strategy for Borderline Resectable Pancreatic Cancer With Radiographic Artery Involvement.

Objectives We evaluated whether neoadjuvant therapy followed by surgical resection improves the clinical outcome for patients with borderline resectable pancreatic cancer with radiologic artery involvement (BRPC-A). Methods We reviewed 143 BRPC-A patients from among 330 pancreatic cancer patients, including 111 potentially resectable pancreatic cancer patients and 76 borderline resectable pancreatic cancer with portal/superior mesenteric vein involvement patients, who underwent surgery at Wakayama Medical University Hospital. We compared the clinicopathological factors of 40 BRPC-A patients treated with neoadjuvant therapy followed by surgery and those of 103 BRPC-A patients treated with upfront surgery. Results The R0 rate and progression-free survival of BRPC-A patients who received neoadjuvant therapy and subsequent surgical resection were significantly better compared to those who received upfront surgery (R0: P = 0.041; progression-free survival: P = 0.033), but overall survival was not significantly different. A multivariate analysis showed that intraoperative transfusion (P = 0.007), moderately or poorly differentiated pathological adenocarcinoma (P = 0.019), and failure to complete postoperative adjuvant therapy (P < 0.001) independently predicted a poor prognosis for BRPC-A patients who underwent surgical resection. Conclusions Neoadjuvant treatment followed by surgery might provide clinical benefits for BRPC-A patients; however, the establishment of the most appropriate neoadjuvant therapy is needed by further studies.

Predicting factors for unresectability in patients with pancreatic ductal adenocarcinoma.

The aim of the present study was to identify the predicting factors for unresectability and to clarify who should receive precise evaluations for distant metastasis and locally advanced unresectability in patients with pancreatic ductal adenocarcinoma (PDAC).