Keiichiro Hirata

IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer

BackgroundThe present study aimed to elucidate the clinicopathologic role of insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3) in patients with pancreatic cancer. The function of IGFBP3 is controversial, because both inhibition and facilitation of the action of IGF as well as IGF-independent effects have been reported. In this study, IGF1R and IGFBP3 expression was examined, and their potential roles as prognostic markers in patients with pancreatic cancer were evaluated.MethodsClinicopathological features of 122 patients with curatively resected pancreatic cancer were retrospectively reviewed, and expression of IGF1R and IGFBP3 was immunohistochemically analyzed.ResultsExpression of IGF1R and IGFBP3 was observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression was significantly associated with histological grade (p = 0.037). IGFBP3 expression had a significant association with tumor location (p = 0.023), and a significant inverse association with venous invasion (p = 0.037). Tumors with IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive patients was significantly poorer than that for IGF1R negative patients (p = 0.0181). IGFBP3 protein expression did not correlate significantly with patient survival. The subset of patients with both positive IGF1R and negative IGFBP3 had worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001).ConclusionIGF1R signaling might be associated with tumor aggressiveness, and IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R expression and low IGFBP3 expression represent useful prognostic markers for patients with curatively resected pancreatic cancer.

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.

Portal Vein Stenting to Treat Portal Vein Stenosis in a Patient With Malignant Tumor and Gastrointestinal Bleeding

This report describes the successful use of portal venous stent placement for a patient with recurrent melena secondary to jejunal varices that developed after subtotal stomach preserved pancreatoduodenectomy (SSPPD). A 67-year-old man was admitted to our hospital with tarry stool and severe anemia at 2 years after SSPPD for carcinoma of the head of the pancreas. Abdominal computed tomography examination showed severe stenosis of the extrahepatic portal vein caused by local recurrence and showed an intensely enhanced jejunal wall at the choledochojejunostomy. Gastrointestinal bleeding scintigraphy also revealed active bleeding near the choledochojejunostomy. Based on these findings, jejunal varices resulting from portal vein stenosis were suspected as the cause of the melena. Portal vein stenting and balloon dilation was performed via the ileocecal vein after laparotomy. Coiling of the jejunal varices and sclerotherapy of the dilate postgastric vein with 5% ethanolamine oleate with iopamidol was performed. After portal stent placement, the patient was able to lead a normal life without gastrointestinal hemorrhage. However, he died 7 months later due to liver metastasis.

Nonfunctional adrenocortical carcinoma initially presenting as retroperitoneal hemorrhage.

BackgroundAcute adrenal hemorrhage is an uncommon entity. Although trauma is the most common cause of adrenal hemorrhage, non-traumatic etiologies have also been reported. We report an unusual case of a spontaneously ruptured adrenocortical carcinoma that initially presented as a critical massive retroperitoneal hemorrhage. The case was treated successfully using a combination of emergency interventional radiology and elective surgery.Case presentationA 47-year-old woman was transported to our hospital because of the sudden onset of severe pain in her left lower back. The shadow of a tumor-like soft mass accompanied by bleeding was observed in the upper pole of the left kidney, together with vascular leakage from the middle suprarenal artery on computed tomography. Transcatheter embolization of the left middle adrenal artery was administered based on a diagnosis of acute adrenal hemorrhage. Further observation indicated that the bleeding was caused by rupture of an adrenocortical carcinoma. Left adrenalectomy was subsequently carried out via laparotomy.ConclusionsWe experienced an unusual case of acute massive adrenal hemorrhage caused by the rupture of a non-functional adrenocortical carcinoma, which was treated successfully by ambulatory transcatheter embolization therapy and elective surgery.

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 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