Hypoxia inducible factor-1 alpha plays a pivotal role in hepatic metastasis of pancreatic cancer: an immunohistochemical study.

BACKGROUND: Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma (PDAC). We evaluated whether the immunohistochemistry for hypoxia inducible factor-1α (HIF-1α) was correlated with hepatic metastases in PDAC. METHODS: We examined the expression of HIF-1α, vascular endothelial growth factor-A (VEGF-A), thymidine phosphorylase (TP) and basic fibroblast growth factor (bFGF) in a total of 100 paraffin-embedded PDAC primary tumors using immunohistochemical staining, and assessed their clinicopathological correlations. We determined microvessel count (MVC) and apoptotic index (AI), and assessed their correlations with hepatic metastases. Student's t-test, the Mann-Whitney U-test, and Spearman correlation coefficients were used to validate the model, and regression analysis was used to test the model. RESULTS: Hypoxia inducible factor-1α expression induced the expression of multiple angiogenic factors, leading to a higher MVC and a lower AI. HIF-1α expression (P = 0.0087) and angiogenic factors (P = 0.0079) were significantly associated with not only the microvessel status (P = 0.022) but also the high incidence of hepatic metastasis (P = 0.02), resulting in the worse survival of PDAC patients (P < 0.05). CONCLUSIONS: Hypoxia inducible factor-1α plays a pivotal role in hepatic metastasis through its association with the expression of angiogenic factors in PDAC patients. These results may contribute future therapeutic strategies to prevent pancreatic cancer metastasis.

Value of magnetic resonance cholangiopancreatography with secretin stimulation in the evaluation of pancreatic exocrine function after pancreaticogastrostomy.

BACKGROUND/PURPOSE: The aim of this study was to assess the value of magnetic resonance cholangiopancreatography with secretin stimulation (secretin-MRCP) in evaluating the remnant pancreatic exocrine reserve after pancreaticogastrostomy with pancreaticoduodenectomy. METHODS: Forty-three patients who had undergone pancreaticoduodenectomies and who were given pancreaticogastrostomies for reconstruction were studied. Dynamic MRCPs, using a half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence were obtained before and up to 10 min after secretin administration. The morphologic features and diameter of the main pancreatic duct were monitored and graded before and after secretin stimulation. The results were compared with those of endoscopic findings, secretin stimulation testing with a collection of pancreatic fluid, N-benzoyl- L-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion testing, and fecal chymotrypsin concentration. RESULTS: The results of secretin-MRCP were classified into three distinct groups: a good-secretion group (group 1; n=22; 51%), a moderate-secretion group (group 2; n=10; 23%), and a poor-secretion group (group 3; n=11; 26%). This MRCP classification correlated significantly with the concentrations of the pancreatic enzymes p-type amylase, lipase, and trypsin in the gastric juice. The BT-PABA test value was 59.8% in group 1, 46.1% in group 2, and 46.5% in group 3, and was significantly higher in group 1 than in groups 2 or 3. The fecal chymotrypsin concentration was 20.5 U/g in group 1, 14.5 U/g in group 2, and 0.7 U/g in group 3, and there was a significant correlation between the MRCP classification and fecal chymotrypsin concentration. CONCLUSIONS: MRCP with secretin stimulation favorably reflected the presence of remnant pancreatic exocrine function. Therefore, secretin-MRCP is a feasible and effective follow-up examination method to evaluate remnant pancreatic exocrine function after pancreaticogastrostomy.

Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer.

PURPOSE: The purpose of this study was to evaluate whether external-beam radiotherapy (EBRT) with concurrent continuous 5-fluorouracil (5-FU) infusion affects the length and quality of survival in patients with locally unresectable pancreatic cancer. METHODS: Thirty-one patients with histologically proven locally advanced and unresectable pancreatic cancer without distant metastases were evaluated in this prospective randomized trial. Sixteen patients received EBRT (50.4 Gy/28 fractions) with concurrent continuous infusion of 5-FU (200 mg/m(2)/day), whereas 15 patients received no chemoradiation. The length and quality of survival was analyzed and compared for the two groups. RESULTS: The median survival of 13.2 months and the 1-year survival rate of 53.3% in the chemoradiation group were significantly better than the respective 6.4 months and 0% in the group without chemoradiotherapy (p = 0.0009). The average monthly Karnofsky score, a quality of life indicator, was 77.1 in the chemoradiation group, which was significantly higher than the 65.5 in the group without chemoradiotherapy (p < 0.0001). The number of hospital days per month of survival was significantly less in the chemoradiation than in the no-therapy group (12.3 vs. 19.0 days, p < 0.05). In the chemoradiation group, 5 patients (31%) had a partial response, and 9 (56%) had radiologically stable disease at a median duration of 6.1 months. The patients who had chemoradiation had a lower rate of liver and peritoneal metastases than patients without chemoradiotherapy (31% vs. 64%). Of 10 patients who experienced pain before chemoradiation, 8 (80%) received pain relief that lasted a median of 5.2 months. CONCLUSIONS: EBRT with concurrent continuous 5-FU infusion increased the length and quality of survival as compared to no chemoradiotherapy and provided a definite palliative benefit for patients with unresectable pancreatic cancer.