BackgroundThe first-line treatment for resectable pancreatic cancer (RPC) is surgical resection. However, our patients have often experienced early recurrence after curative resection for RPC, with desperately poor prognosis. Some reports indicated that minimally distant metastasis not detected at operation might cause early recurrence. The present study aimed to identify preoperative clinicopathological features of early recurrence after curative resection of RPC.MethodsNinety RPC patients who underwent curative resection between 2000 and 2014 at our institution were retrospectively analyzed.ResultsOf the 90 patients, 32 had recurrence within 1 year. Univariate analysis demonstrated that preoperative serum carbohydrate antigen (CA19-9) ≥529 U/mL (P = 0.0011), preoperative serum s-pancreas-1 antigen (SPan-1) ≥37 U/mL (P = 0.0038), and histological grades G2–G4 (P = 0.0158) were significantly associated with recurrence within 1 year after curative resection. Multivariate analysis demonstrated that preoperative serum CA19-9 ≥ 529 U/mL (P = 0.0477) and histological grade G2–G4 (P = 0.0129) were independent predictors of recurrence within 1 year. Recurrent cases within 1 year postoperatively had significantly more distant metastasis than cases with no recurrence within 1 year (P < 0.001).ConclusionsPreoperative serum CA19-9 ≥ 529 U/mL and histological grades G2–G4 were independent predictive factors for recurrence within 1 year after pancreatectomy for RPC. Furthermore, recurrent cases within 1 year had more frequent distant metastasis than cases with no recurrence within 1 year. These results suggest that RPC patients with preoperative serum CA19-9 ≥ 529 U/mL should receive preoperative therapy rather than surgery.

HER2 overexpression has been linked to clinical outcomes in several solid tumors, such as breast cancer. However, the correlation between HER2 overexpression and survival in pancreatic carcinoma remains unclear. The impact of HER2 overexpression on survival in pancreatic ductal cancer was examined. Immunohistochemical staining of 129 pancreatic cancers without hematogenous metastases or peritoneal dissemination treated by macroscopically curative resection were analyzed in association with survival data. To determine HER2 overexpression in this pancreatic cancer series, the polyclonal antibody included in HercepTest, which is used worldwide for clinical examination of HER2 overexpression in breast cancer, was used. Immunoreactivity was classified according to the scale presented in the HercepTest Scoring Guidelines. Twenty-two cases (17.1%) had a score of 0, 28 cases (21.7%) had of a score of 1+, 41 cases (31.8%) had a score of 2+, and 38 cases (29.4%) had a score of 3+. Therefore, HER2 overexpression (score 2+ or 3+) was observed in 79 cases (61.2%). Patients with HER2 overexpression tumors had significantly shorter survival times than those with HER2 normal expression (score 0 or 1+) tumors (median survival time, 14.7 vs 20.7 months, respectively; P = 0.0078 on the logrank test). On multivariate survival analysis, HER2 overexpression remained an independent prognostic factor (hazard ratio, 1.806; P = 0.0258). A significant percentage of pancreatic cancers were demonstrated to have HER2 overexpression, and overexpression of this tyrosine kinase receptor proved to be an independent factor for a worse prognosis. These results should encourage further investigation of treatments using new molecular targeting agents against HER2 protein to improve the survival of pancreatic cancer patients. (Cancer Sci 2009; 100: 1243-1247) T he HER2 gene, known as ErbB-2/neu, is located on the long arm of chromosome 17 (17q12-21.32) and encodes the 185-kDa transmembrane tyrosine kinase receptor.(1) HER2 is recognized as a member of the epidermal growth factor receptor family of transmembrane receptors encoded by erbB1 (HER1 or EGFR), erbB3 (HER3), and erbB4 (HER4).(2) EGFR is the coreceptor for the formation of dimers with HER2. After a ligand binds to a single-chain EGFR, the receptor forms a dimer with HER2 that signals within the cell by activating receptor autophosphorylation through tyrosine kinase activity.(2) These dimers play a role in tumor cell proliferation, survival, adhesion, and migration. Many studies have demonstrated that HER2 overexpression is correlated with aggressiveness in breast, (4)(5)(6)(7)(8) lung, (9) and gastric carcinomas.(10,11) However, investigations correlating HER2 overexpression with survival in pancreatic carcinoma have been very limited. (12)(13)(14) The objective of this study was to examine the impact of HER2 overexpression on the survival of patients with pancreatic ductal carcinoma. Materials and MethodsPatients. Pancreatic cancer tissue samples were obtained from 129 patients who underwent...

Recently, it has been reported that p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis by regulating expression of vascular endothelial growth factor (VEGF), which is a well-characterized angiogenic inducer. In this study, we investigated these antigens’ expression together with microvessel density, and investigated their clinical importance. One hundred twenty specimens resected from patients with gastric carcinoma were investigated using immunohistochemical methods. p53 and VEGF expression was observed in 42 and 35% tumors, respectively. p53 and VEGF staining status was coincided in 72% tumors, and a significant correlation was found between p53 and VEGF status. The microvessel density, determined by immunostaining for factor VIII-related antigen, was significantly higher in p53-positive or VEGF-positive tumors. According to prognosis, patients with p53-positive tumors had significantly worse survival than those with p53-negative tumors. There was also a significant worse survival in the patients with VEGF-positive tumors than those with VEGF-negative tumors. Moreover, the 5-year survival rate was lowest in the patients with p53-positive and VEGF-positive tumors, while it was highest in the patients with p53-negative and VEGF-negative tumors. In conclusion, both p53 and VEGF significantly correlated with tumor vascularity and prognosis in patients with gastric carcinoma.

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.

Saini, 1992). The intensity of neovasculan'sation reflects tumour cell angiogenic activity (Blood and Zetter, 1990; Folkman, 1990). Microvessel density has been shown to be a prognostic predictor in patients with lung cancer (Macchiarini et al., 1992), prostatic cancer (Weidner et al., 1993) and malignant melanoma (Srivasta et al., 1988). With regard to breast cancer, Weidner et al. (1991) found a significant correlation between microvessel density and the presence of metastatic disease. They also reported a relationship between microvessel count (MVC) and prognosis (Weidner et al.. 1992). Since mortality in breast cancer is related to the occurrence of distant metastasis, the histological quantitation of intra-tumour microvessels may predict prognosis in some subsets of breast cancer patients and provide useful information for deciding therapeutic strategies.The purpose of this study was to examine the correlation between tumour (MVCs) and clinicopathological factors, and to determine whether microvessel quantitation could identify breast cancer patients at high risk for recurrence and death. using immunohistochemical staining of formalin-fixed, paraffin-embedded sections for factor VIII-related antigen. Materials and metbods PatientsThe study population was composed of 155 women with invasive breast cancer surgically treated at the First DepartCorrespondence: Y Ogawa

Recent studies have demonstrated that the p53 tumor suppressor gene plays an important role in controlling tumor angiogenesis. We examined the expression of p53 and vascular endothelial growth factor (VEGF), a well-characterized angiogenic inducer, together with microvessel density to investigate the role of p53 in the regulation of angiogenesis and its clinical significance in human colorectal carcinoma. Surgically resected specimens of 163 colorectal carcinomas were studied by immunohistochemical staining for p53 protein, VEGF and factor VIII-related antigen. Positive p53 protein accumulation and VEGF expression was found in 41.7% and 49.1% of tumors, respectively. p53 and VEGF staining status was identical in 65.6% of tumors. The incidence of p53-or VEGF-positive tumors was significantly higher in patients with venous invasion and liver metastases than in those without. The microvessel count (MVC) in p53-or VEGF-positive tumors was significantly higher than that in negative tumors, and MVC in both p53-and VEGF-positive tumors was significantly higher than that in the other subgroups. Neither synchronous nor metachronous hepatic metastases were found in patients with p53-and VEGF-negative tumors, while 52.2% of patients with both-positive tumors had liver metastases and had a poorer prognosis than those with both-negative tumors. Our findings suggest the presence of a p53-VEGF pathway regulating tumor angiogenesis in human colorectal carcinoma. Combined analysis of p53 and VEGF expression might be useful for predicting the occurrence of liver metastasis in patients with this disease.

RESULTS.A complete response was observed in 2 cases and a partial response in 1 First Department of Surgery, Osaka City Uni-11 cases, for an overall response rate of 50%. Patients with good performance versity Medical School, Osaka, Japan.status (PS) (0-1) and differentiated histologic type showed higher response rates (50.0% and 63.6%, respectively) than patients with poor PS (2 or 3) and undifferenti-2 Institute for Pathogenic Biochemistry in Medicine, Taiho Pharmaceutical Company, Tokyo, ated histologic type (28.6% and 35.3%, respectively), although there were no sigJapan.nificant differences. Patients with low serum levels of immunosuppressive acidic protein (IAP) showed a significantly higher response rate (71.4%) than those with high IAP levels (0%). Toxic effects included leukopenia, thrombocytopenia, nausea, and vomiting; these were not life-threatening and did not require treatment interruption.CONCLUSIONS. FP therapy is a promising regimen for patients with advanced and recurrent gastric adenocarcinoma. Serum levels of IAP may predict chemosensitivity.

The occurrence rates of postoperative mortality and morbidities including pancreatic fistula and renal failure of moderate to severe degrees were almost same between patients with and without preoperative DM. The influence of preoperative DM on long term survival after pancreatectomy should be elucidated by future studies under accurate and consistent definitions of DM.