Factor In Pancreatic Cancer Patients Research Articles

Impact of ABO Blood Types on Survival after Pancreatectomy for Pancreatic Cancer

Background/Purpose: A recent genome-wide association study (PanScan) identified significant association between the ABO gene locus and the risk of pancreatic cancer. The aim of this study was to analyze survival of pancreatic cancer patients who underwent surgical resection based on serotype-defined ABO blood types. Methods: In terms of ABO blood types and gemcitabine-based adjuvant therapy, we investigated the survival of 153 patients who underwent pancreatectomy for pancreatic cancer at the Department of Surgery and Oncology,KyushuUniversity(Fukuoka,Japan). Results: Among the four blood type groups, the O serotype group (median survival time (MST): 47.9 months) showed the best prognostic outcome. The A serotype group (MST: 22.5 months) showed the second best prognostic outcome, followed by the AB serotype group (MST: 20.4 months). The B serotype group (MST: 15 months) showed the worst prognostic outcome when considering the MST after the surgical resection. Next, we examined the effect of adjuvant chemotherapy with gemcitabine based on the ABO blood types. The A serotype group showed the greatest improvement in prognosis by adjuvant therapy with gemcitabine after the surgical resection. The other three serotype groups showed no significant differences in the prognostic outcomes between subgroups with and without gemcitabine therapy. Conclusions: The present data suggest the possibility that ABO blood types are prognostic factors for pancreatic cancer patients after surgical treatment and are also predictive factors for the chemosensitivity to gemcitabine of pancreatic cancer patients after pancreatectomy.

Prognostic Value of18F-Fluorodeoxyglucose Positron Emission Tomography in Patients with Resectable Pancreatic Cancer

PurposeWe evaluated the prognostic value of 18F-2-fluoro-2-deoxyglucose positron emission tomography (FDG PET) in patients with resectable pancreatic cancer.Materials and MethodsWe retrospectively reviewed the medical records of pancreatic cancer patients who underwent curative resection, which included 64 consecutive patients who had preoperative FDG PET scans. For statistical analysis, the maximal standardized uptake value (SUVmax) of primary pancreatic cancer was measured. Survival time was estimated by the Kaplan-Meier method, and Cox's proportional hazard model was used to determine whether SUVmax added new predictive information concerning survival together with known prognostic factors. p<0.05 indicated statistical significance.ResultsOverall survival (OS) and disease-free survival (DFS) were respectively 42.9 months (27.6-58.2; 95% CI) and 14.9 months (10.1-19.7; 95% CI). When subjects were divided into two groups according to SUVmax with a cutoff value of 3.5, the high SUVmax group (n=32; SUVmax >3.5) showed significantly shorter OS and DFS than the low SUVmax group. Multivariate analysis of OS and DFS showed that both high SUVmax and poor tumor differentiation were independent poor prognostic factors.ConclusionOur study showed that degree of FDG uptake was an independent prognostic factor in pancreatic cancer patients who underwent curative resection.

Prognostic factors in patients with pancreatic cancer

The identification of prognostic factors for pancreatic cancer patients could provide insightful information for their management in the clinic. A total of 302 pancreatic cancer patients were enrolled in this study. The clinicopathological characteristics, treatment selection and laboratory test data were retrospectively retrieved from the medical records and follow-up data were obtained via telephone interview. Cox survival analysis was used to assess the potential prognostic factors, and survival curves were obtained by Kaplan-Meier analyses. The mortality rate of the patients was 83.4% (252/302) and the median survival of these patients was 6.1 months, with 1-, 2- and 3-year survival rates of 30.1 (91/302), 10.6 (32/302) and 2.6% (8/302), respectively. The most influential factors for the survival of these patients were the site of primary cancer, tumor stage, treatment selection, serum levels of glutamic-pyruvic transaminase, albumin, lactate dehydrogenase and hemoglobin, and white blood cell counts (P<0.05). The median survival of patients who did not receive any treatment or just received supportive treatment was 1.3 months, while the median overall survival of patients who underwent surgery, chemotherapy, biliary drainage therapy, arterial interventional chemotherapy and comprehensive treatment was 11.0, 7.3, 3.5, 9.0 and 11.0 months, respectively (P<0.05). Furthermore, single-drug chemotherapy was not statistically associated with patient survival in those who received the multi-drug regimen (P>0.05). However, the mortality risk of patients who received platinum chemotherapy was decreased [hazard ratio (HR)=0.56, 95% CI 0.35-0.88, P=0.011] compared to the patients who did not receive this treatment (P<0.05). Tumor stage, treatment selection, serum albumin levels, urea nitrogen, CA19-9, white blood cell and platelet counts were independent prognostic factors for the prediction of survival in pancreatic cancer. Future studies are required in order to verify these data. Chemotherapy with platinum regimens could improve overall survival in patients with pancreatic cancer.

Hypoxia Predicts Aggressive Growth and Spontaneous Metastasis Formation from Orthotopically Grown Primary Xenografts of Human Pancreatic Cancer

Hypoxia in solid tumors is associated with treatment resistance and increased metastatic potential. Although hypoxia has been reported in pancreatic cancer patients, there is little direct evidence that this contributes to their overall poor prognosis. To address this, we examined the associations between hypoxia and biological aggression in a series of patient-derived xenografts grown orthotopically. Early passage xenografts were established from 16 patients undergoing surgery for pancreatic cancer and maintained in the pancreas of immune-deprived mice. Hypoxic cells were labeled using the 2-nitroimidazole probe EF5 and stained for immunofluorescence microscopy of tissue sections or as cell suspensions for flow cytometry. Bromodeoxyuridine (BrdUrd) uptake, microvessel density, cleaved caspase-3, and the differentiation markers E-cadherin, cytokeratin 19, and vimentin were analyzed in relation to hypoxia. Orthotopic implants closely resembled the histology of the original surgical samples. The 16 primary xenografts showed a wide range in their growth rates and metastatic potential, reminiscent of the spectrum of behavior seen in the clinic. EF5 labeling, tumor growth rates, and metastatic patterns were highly consistent within replicates, indicating a significant transmissible (genetic or epigenetic) component. Hypoxia was highly correlated with rapid tumor growth, increased BrdUrd uptake, and with spontaneous metastasis formation. mRNA expression analysis showed increased expression of genes involved in cell survival and proliferation in the hypoxic models. The results suggest that hypoxia is a major adverse prognostic factor in pancreatic cancer patients and support the introduction of techniques to measure hypoxia directly in patients and the development of treatment protocols to target hypoxia.

Ep-CAM is a significant prognostic factor in pancreatic cancer patients by suppressing cell activity

The identification of molecular markers useful for predicting prognosis in pancreatic cancer patients is crucial for advances in disease management. The epithelial cell adhesion molecule (Ep-CAM) is known to express in most epithelial malignancies and was reported as a tumor marker or a candidate of molecular targeting therapy. However, the clinical significance of Ep-CAM expression in pancreatic cancer is not well-known. We determined the difference of malignant potential between parental and Ep-CAM-transfected pancreatic cancer cell lines by using proliferation, invasion and migration assay. Furthermore, we determined the relationship between tumoral Ep-CAM expression of resected specimens and clinical prognosis in 95 pancreatic cancer patients receiving radical surgery at two different cancer centers. One of the three Ep-CAM-transfected cell lines showed significantly low proliferation rate compared with the parental cell, while there was no difference in the other two cell lines. In invasion and migration assays, Ep-CAM-transfected cells showed significantly lower malignant potential than parental in all of the three cell lines. In 95 pancreatic cancer patients, 47 patients showed high-Ep-CAM expression, while 48 patients showed low, and there was no difference of clinicopathological features between Ep-CAM high and low-expression group. High-Ep-CAM expression group showed significantly good prognosis in overall survival (3-year survival; 56.2 versus 19.2%, P=0.0018) as well as in disease-free survival (3-year survival; 40.3 versus 14.4%, P=0.038) compared with low-expression group. In addition, the impact of Ep-CAM was observed strongly in LN-negative group when the influence of Ep-CAM was examined with dividing patients into LN-positive and negative group. In multivariate analysis, Ep-CAM expression was one of the independent prognostic factors as well as histology and lymph node metastasis. Ep-CAM expression was found to be related to the suppression of pancreatic cancer cell activity and the good prognosis in pancreatic cancer patients receiving the curative resection.

Circulating dendritic cell as a new prognostic factor in pancreatic cancer patients

4095 Background: Pancreatic cancer is a cancer with very poor prognosis that might be associated with impaired immune defense. Dendritic cells (DC) are important for immune surveillance and play a central role in protection against infection and malignancy. A defective host antitumor immune response may allow tumor cells to escape from the host immune system. The aim of this study is to determine whether circulating DC could be one of new immunological markers that may predict the prognosis of the pancreatic cancer. Methods: We evaluated pretreatment circulating myeloid-lineage DC (C-DC1) rate in the peripheral blood mononuclear cell and various clinical parameters to determine their prognostic value in 104 pancreatic cancer patients (41 resected and 63 unresected patients) seen at our institution. Results: In unresected patients, univariate analysis demonstrated two risk factors for prognosis of albmin &lt; 3.8g/dl (p = 0.0468), and C-DC1 &lt; 0.27% (p = 0.0006), when all patients were divided by the median value of C-DC1 rate. Consequently, multivariate analysis demonstrated that only C-DC1 was a predominant independent predictor of survival (Hazard ratio; 9.330, 95% Confidential interval; 2.595–33.549, p = 0.0006). In resected patients, C-DC1 in patients with advanced disease (Stages 2b-4, n=28) was significantly lower than that in patients with lower staged cancer (Stage 1–2a, n = 13: 0.43 ± 0.67%, Stage 2b-4: 0.24 ± 0.30%, p &lt; 0.05). The overall survival rates in patients with C-DC1 ≥ 0.27% were significantly longer than those in patients with C-DC1 &lt; 0.27 (C-DC1 ≥ 0.27%, n = 20, 1/3 year survival: 100%/64%. C-DC1 &lt; 0.27, n = 21, 1/3 year survival: 68%/26%. P &lt; 0.05). Conclusions: The C-DC1 less than 0.27% could be one of prognostic factors in patients with pancreatic cancer, and such patients could be targets for the future therapeutic trials. No significant financial relationships to disclose.