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Objectives: This study aimed to analyze the risk factors for poor survival of the patients with anatomically resectable pancreatic ductal adenocarcinoma (PDAC), focusing on detailed computed tomography (CT) findings of tumor extent to the peripancreatic tissue., Methods: The study included 192 patients who underwent upfront pancreaticoduodenectomy for anatomically resectable PDAC. Preoperative CT images were rereviewed by an experienced radiologist for the pattern of tumor extension to the surrounding tissue: biliary, duodenal, serosal, retroperitoneal, portal venous, arterial, extrapancreatic nerve plexus, and other-organ invasion. Imaging findings and other clinical data that could be obtained before surgery were evaluated for their association with a shorter disease-specific survival (DSS) and recurrence-free survival (RFS)., Results: Of the 192 anatomically resectable PDAC patients, extrapancreatic nerve plexus invasion was observed on CT in 38 patients (20%), and this finding was independently associated with a shorter DSS (hazard ratio, 2.258; P < 0.001) and RFS (hazard ratio, 2.665; P < 0.001). The median survival of patients with and without extrapancreatic nerve plexus invasion on CT was 19.7 versus 38.5 months (P < 0.001)., Conclusions: Extrapancreatic nerve plexus invasion was shown as an only CT finding associated with a shorter DSS and RFS after upfront surgery for the patients with anatomically resectable PDAC.

Objectives: Tumor necrosis is often found in pancreatic ductal adenocarcinoma (PDAC). Objective histological assessment and adequate radiological detection of necrosis could be used as biomarkers for therapeutic decision. However, standardized clinical utility of necrosis remains unknown. Here, we aimed to determine the prognostic potential of histological and radiological evaluations of necrosis., Methods: We investigated histological necrosis in 221 patients, who underwent surgery for PDAC, and classified its size as small (≤5 mm) or large (>5 mm). We also evaluated poorly enhanced areas on preoperative computed tomography to assess their ability for predicting histological necrosis and postoperative prognosis., Results: Tumor necrosis was found in 115 patients (52%) and was related to tumor area, lymph node metastasis, and lymphovascular invasion. Size of necrosis was significantly associated with tumor area, perimeter of necrosis, circularity of necrosis, number of ruptured cancer glands, and presence of collagen bundle (P < 0.05 for all). Both presence of necrosis and their size were strongly correlated to postoperative prognosis. Patients with poorly enhanced areas showed worse prognosis (P < 0.01)., Conclusions: Our findings underline the capacity of histological and radiological assessment of tumor necrosis for prognosis prediction in PDAC.

Objective: The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma., Methods: A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed., Results: A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22., Conclusions: The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

Objectives: Because lactate is believed to support tumor growth, monocarboxylate transporters (MCTs), which transport lactate, have been investigated in multiple tumors. However, the significance of MCTs in pancreatic cancer is unclear., Methods: A retrospective survey was conducted on 240 patients who underwent surgical resection for pancreatic ductal adenocarcinoma without preoperative treatment. The expression of MCT1, MCT2, MCT3, MCT4, and the glucose transporter 1 (GLUT1) was assessed in tumor cells and cancer-associated fibroblasts (CAFs) by tissue microarrays and immunohistochemistry. The impact of their expression on patient outcome and clinicopathological characteristics was also analyzed., Results: In tumor cells, MCT1, MCT2, MCT3, MCT4, and GLUT1 were detected in 52 (22%), 31 (13%), 149 (62%), 204 (85%), and 235 (98%) cases, respectively. In CAFs, MCT2, MCT4, and GLUT1 were detected in 9 (3.8%), 178 (74%), and 36 (15%) cases, respectively. In tumor cells, MCT1 expression was associated with extended overall and progression-free survival and decreased nodal metastasis. Conversely, MCT4 expression in CAFs was associated with shortened survival., Conclusions: In tumor cells, MCT1 expression is associated with better prognosis and reduced nodal metastasis in pancreatic cancer, contrary to findings of past in vitro studies. Conversely, MCT4 expression in CAFs is indicative of worse prognosis.

Objectives: Processing of pancreatoduodenectomy specimens is not standardized; the clinical impact of pathologic surgical margins remains controversial. We used the color-coding method using tissue-marking dyes to evaluate margin status of resected specimens to assess its association with postoperative recurrence., Methods: We developed a unified processing approach to assess pancreatoduodenectomy specimens. Five surgical margins of resected pancreatic specimens were marked with 5 colors. Microscopic resection margin distance (RMD) from margin closest to the tumor was evaluated for each surgical margin. Forty patients assessed using nonunified protocols, and 98 patients assessed using unified protocols were included., Results: The frequency of tumors with RMD of 1 mm or less in posterior margin was significantly lower and that in portal vein/superior mesenteric vein margin was significantly higher in unified protocol group than in nonunified protocol group (P < 0.001). In unified protocol group, tumors with RMD of 1 mm or less correlated with locoregional recurrence (P = 0.025) and recurrence-free survival (P = 0.030). Multivariate analysis revealed that tumor size and lymph node metastasis were independent indicators for disease recurrence., Conclusions: Resection margin distance of 1 mm or less was a predictor for disease recurrence, particularly for locoregional recurrence. Early detection of small-sized tumors without lymph node metastasis is necessary for improved clinical outcomes in pancreas cancers.

Objectives: We evaluated geminin labeling index (LI) as a new prognostic indicator of pancreatic neuroendocrine tumor., Methods: Twenty-seven patients who underwent surgery were retrospectively referred. Labeling indices for geminin and Ki-67 were calculated and compared with clinicopathologic factors. Then, the concordance of positivity between 2 LIs was evaluated using the color difference quotation., Results: The median (range) of LIs for geminin and Ki-67 was 1.0% (0.05%-14.9%) and 1.5% (0.02%-8.8%), respectively. When the high LI was defined as more than 2.0% according to the receiver operating characteristic curves determining the metastasis, both geminin LI (hazard ratio [HR], 31.382; 95% confidence interval [CI], 3.177-309.99; P = 0.003) and Ki-67 LI (HR, 6.182; 95% CI, 1.221-31.298; P = 0.028) were significant risk factors of recurrence in the univariate analysis. The Kaplan-Meier curves consistently exhibited the superiority of geminin LI (log rank, P < 0.001) to Ki-67 LI (log rank, P = 0.041) in predicting the disease-free survival. In the color difference quotation, the median ΔE of geminin stain (16.12; range, 5.8-41.9) was significantly larger than that of Ki-67 stain (13.17; range, 3.4-37.9)., Conclusions: The geminin LI was suggested to be more closely correlated with outcome and had more consistent positivity than the Ki-67 LI.

Objective: We evaluated prognostic indicators for distal pancreatectomy with regional lymph node dissection in pancreatic body or tail carcinoma., Methods: Between 1993 and 2008, 50 patients with ductal carcinoma of the body or tail of the pancreas who underwent distal pancreatectomy with regional lymph node dissection were retrospectively analyzed. Clinicopathological factors associated with patient survival were evaluated., Results: No in-hospital deaths occurred among the study patients. The overall 5-year survival rate was 19.3%, and median survival was 22.6 months. Univariate analysis revealed that lymph node metastasis, intrapancreatic neural infiltration, peripancreatic nerve plexus infiltration, and tumor differentiation affected patient survival significantly. Multivariate analysis validated lymph node metastasis as an independent prognostic factor. Moreover, the lymph nodes attached to the pancreas were the most frequent metastatic nodes, and the number of metastasis in the lymph nodes attached to the pancreas was significantly associated with survival after surgical resection., Conclusions: Lymph node metastasis was a significant and independent prognostic factor for the surgically resected pancreatic body or tail carcinoma. Furthermore, the lymph nodes attached to the pancreas were the most frequent metastatic nodes, and these lymph nodes were potential indicators predicting both tumor extension and survival after surgery for pancreatic body or tail carcinoma.

Objectives: Systemic disorder is a characteristic of advanced pancreatic cancer. Clinical prognostic factors in earlier disease state than terminal stage are expected to be sensitive markers for the foresight of systemic disorder. This study aimed to find the associations between these sensitive markers and morphological factors of primary tumor that may indicate finding a way of pathogenesis of systemic disorder., Methods: The current study examined 75 patients who received macroscopic curative resection for pancreatic cancer in our institution as follows: (1) identification of clinical prognostic factors at initial recurrence after resection of primary tumor and (2) analysis of correlations between clinical prognostic factors and histological findings in primary tumor., Results: Important prognostic factors were peritoneal dissemination and serum levels of carbohydrate antigen 19-9 and cholinesterase. Only low levels of serum cholinesterase correlated to nerve plexus invasion in histological findings of primary tumor. Patients with low cholinesterase levels show systemic disorder, including poor performance status, anemia, and hypoalbuminemia., Conclusions: Nerve invasion may thus result in low functional state of the liver followed by systemic disorder. This mechanism may be useful for elucidating cancer cachexia in future studies.