Kotaro Miura

Clinical and pathological features of five-year survivors after pancreatectomy for pancreatic adenocarcinoma

BackgroundClinical factors determining short-term survival after pancreatectomy have been well studied, but factors predicting long-term survival with curative resection are poorly understood in pancreatic carcinoma. Our objective was to identify clinical and pathological features of five-year disease-free survivors after surgical resection of pancreatic adenocarcinoma.MethodsThe clinical and pathological data from 147 patients who underwent a potentially curative resection for pancreatic adenocarcinoma at our institution between 1988 and 2012 were retrospectively analyzed.ResultsOf 147 patients, 18 survived for more than five years after surgery without disease recurrence. A univariate analyses demonstrated that: two or fewer lymph node metastases (P = 0.014), a preoperative serum carbohydrate antigen 19-9 (CA19-9) level of 40 U/mL or less (P = 0.0018), an absence of intrapancreatic nerve invasion (P = 0.028), and undergoing an R0 resection (P = 0.011) were significantly associated with five-year survival. A logistic regression model identified the following independent cancer-related predictors of five-year survivors: having two or fewer lymph node metastases (odds ratio (OR): 6.02; 95% confidence interval (CI): 1.08 to 112.98; P = 0.0385), a preoperative serum CA19-9 level of 40 U/mL or less (OR: 5.02; 95% CI: 1.68 to 16.48; P = 0.0036), and undergoing an R0 resection (OR: 3.63; 95% CI: 1.12 to 14.28; P = 0.0316).ConclusionsWe conclude that number of lymph node metastases being two or less, a preoperative serum CA19-9 level of 40 U/mL or less, and undergoing an R0 resection may be independent predictive factors to identify actual five-year survivors after pancreatectomy for pancreatic adenocarcinoma.

Doublecortin and CaM kinase-like-1 as an independent prognostic factor in patients with resected pancreatic carcinoma

AIM To elucidate the effect of expression of doublecortin and CaM kinase-like-1 (DCLK1) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS Tumor specimens were obtained from 136 patients with pancreatic cancer who had undergone resection without preoperative therapy between January 2000 and December 2013 at the Department of Surgical Oncology, Osaka City University. The resected specimens were analyzed for associations with clinicopathological data, including DCLK1 expression, epithelial mesenchymal transition (EMT) marker expression, and cancer stem cell (CSC) marker expression. Univariate and multivariate survival analyses were performed and we assessed the association between DCLK1 expression and clinicopathological factors, including the EMT marker and CSC marker. RESULTS In total, 48.5% (66/136) of the pancreatic cancer samples were positive for DCLK1. Patients with DCLK1-positive tumors had significantly shorter survival times than those with DCLK1-negative tumors (median, 18.7 mo vs 49.5 mo, respectively; P < 0.0001). Positive DCLK1 expression correlated with histological grade (P = 0.0290), preoperative CA19-9 level (P = 0.0060), epithelial cell adhesion molecule (EpCAM) expression (P = 0.0235), and the triple-positive expression of CD44/CD24/EpCAM (P = 0.0139). On univariate survival analysis, five factors were significantly associated with worse overall survival: histological grade of G2 to G4 (P = 0.0091), high preoperative serum SPan-1 level (P = 0.0034), R1/2 (P < 0.0001), positive expression of DCLK1 (P < 0.0001) or CD44 (P = 0.0245). On multivariate survival analysis, R1/2 [odds ratio (OR) = 2.019, 95% confidence interval (CI): 1.380-2.933; P = 0.0004] and positive DCLK1 expression (OR = 1.848, 95%CI: 1.2854-2.661; P = 0.0009) were independent prognostic factors. CONCLUSION DCLK1 expression was found to be an independent prognostic factor and it may play a crucial prognostic role by promoting acquisition of stemness.

Analysis of the origin of anaplastic pancreatic cancer and the mechanism of its dedifferentiation

We researched the origin and progression of anaplastic pancreatic cancer (APC) from the viewpoints of cell lineage, epithelial‐mesenchymal transition (EMT) and cancer stem‐like cells (CSC).

Synchronous double cancer of the common bile duct and the ampulla of Vater without pancreaticobiliary maljunction: A case report

Abstract Introduction: Synchronous double cancers in the biliary system are rare. Double cancer of the CBD and the ampulla of Vater without PBM is extremely rare; to our knowledge, only seven cases have been reported previously. Here we report a case of synchronous double cancer of the CBD and the ampulla of Vater without PBM. Case presentation: A 63-year-old man was referred to our hospital with epigastric pain and jaundice. Computed tomography (CT) showed dilatation of both intrahepatic and intrapancreatic bile ducts, and slightly enhanced tumor in the middle part of the CBD and the ampulla of Vater. Endoscopic retrograde cholangiopancreatography (ERCP) showed a tuberous filling defect in the middle part of the CBD and an exposed tumor of the ampulla of Vater. Conclusion: Under a diagnosis of synchronous double cancer of the middle bile duct and the ampulla of Vater, pancreaticoduodenectomy was performed. Histopathologically, the ampulla of Vater tumor was well-differentiated tubular adenocarcinoma whil...

Abstract 5276: Epithelial mesenchymal transition may contribute to anaplastic change of pancreatic ductal adenocarcinoma

Introduction: Anaplastic pancreatic cancer (APC) is a rare subtype of pancreatic ductal adenocarcinoma (PDA). The prognosis of APC is poorer than that of ordinary PDA. There is no established therapeutic strategy as well as PDA. In this study, we compared the expression of molecular markers in intratumoral different lesions which are undifferentiated lesion (UL) and ductal lesion (DL) to reveal progression pattern of APC and hold important clue for the therapy of APC. Materials & Methods: Formalin fixed paraffin embedded blocks were made from the primary APC tissues obtained from 6 patients. Each block was manipulated for staining with Hematoxylin and Eosin (HE 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5276. doi:10.1158/1538-7445.AM2015-5276

Abstract 3924: Establishment and characterization of two cell lines of anaplastic pancreatic cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Anaplastic pancreatic cancer is a rare malignancy with a poor prognosis. As a whole, pancreatic cancer is a devastating prognosis but its therapeutic strategy has not still well developed. Thus, new models are needed to research its biology. Purpose: We have established and characterized 2 anaplastic cancer cell lines (OCUP-A1 and OCUP-A2) for revealing tumor worsening factors and the mechanism of dedifferentiation. Methods: We researched the present studies by comparing with established 2 cell lines and well-known pancreatic cancer cell lines. In vitro proliferation, migration and invasion assays was examined in each cell lines under normoxia and hypoxia by CellPlayer™ 96-Well Kinetic Cell Proliferation, Migration and Invasion Assays. Furthermore,as assessment of chemosensitivity, IC50 values against 5Fu and gemcitabine ware measured by MTT assay. As In vivo assays, the growth of the xenografts in each cell lines was also measured for a month. The immunohistochemistry (IHC) of E-cadherin and vimentin for primary tumors and the xenografts was performed to confirm the induction of epitherial-mesenchymal transition (EMT). Result: Both OCUP-A1 and OCUP-A2 were pleomorphic cells derived from ascites of anaplastic pancreatic cancer patients. The doubling time of OCUP-A1 and OCUP-A2 was 30.9 h and 20.4 h, respectively. In migration and invasion assays, relative wound density in new 2 cell lines ranged from 47.1 % to 98.1 % at 48 hours. The values were not so different from that of other cell lines. Interestingly, although a large part of OCUP-A1 is spindle shape in normoxia, the subpopulation with polygonal structure has increased in hypoxia. Furthermore, OCUP-A1 rapidly proliferated in hypoxia. The IC50 values of gemcitabine for OCUP-A1 and OCUP-A2 were 8.77 nM and 4.90 nM, respectively. And the values of 5-Fu for OCUP-A1 and OCUP-A2 were 48.5 μM and 14.8μM, respectively. Chemosensitivity of 2 established cell lines was not superior to other cell lines. The xenografts of OCUP-A1 and OCUP-A2 more rapidly increased than other cell lines (MIAPaCa2 and Panc-1). In IHC, the E-cadherin expression was reduced and the vimentin expression was enhanced in both specimens. Conclusion: We established 2 anaplastic pancreatic cancer cell lines. It was suspected that these cell lines would have aggressive characters affected by TME and EMT. Citation Format: Kotaro Miura, Kenjiro Kimura, Ryosuke Amano, Sadaaki Yamazoe, Keiichiro Hirata, Masatsune Shibutani, Katsunobu Sakurai, Hisashi Nagahara, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Hiroshi Otani, Masakazu Yashiro, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa. Establishment and characterization of two cell lines of anaplastic pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3924. doi:10.1158/1538-7445.AM2014-3924