BACKGROUND: Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients. METHODS: The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques. RESULTS: Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival. CONCLUSION: Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.
Background: Post-hepatectomy liver failure (PHLF) is considered a main reason for death after major hepatectomy. The reported PHLF-related mortality differs largely and the data mainly originate from single centers. Aim: A retrospective, population-based register study was designed to evaluate the impact of PHLF on 90-day mortality after hepatectomy. Method: All patients who underwent liver resection in Sweden between 2005 and 2009 were retrospectively identified using the Swedish Hospital Discharge Registry. 30-and 90-day mortality were identified by linkage to the Registry of Causes of Death. Additional clinical data were obtained from the medical charts in all seven university hospitals in Sweden. PHLF was defined according to Balzan criteria (Bilirubin >50 mg/L and international normalized ratio >1.5) on postoperative day 5. Results: A total of 2461 liver resections were performed (2194 in university hospitals). 30-and 90-day mortality were 1.3% and 2.5%, respectively. 90-day mortality at university hospitals was 2.1% (n ¼ 46). In 41% (n ¼ 19) of these patients, PHLF alone or in combination with multi-organ failure was identified as cause of death. Between the PHLF and non-PHLF group, there was no significant difference regarding age, sex, American Society of Anesthesiologists-classification, or preoperative chemotherapy. Cholangiocarcinoma as indication for surgery, need for vascular reconstruction and an extended resection were significantly overrepresented in the PHLF-group. Between groups, the incidence of 50:50 criteria differed significantly already on postoperative day 3.
Conclusion:Overall mortality is very low after hepatectomy in Sweden. PHLF represents the single most important cause of death even in a population-based setting.
Endostatin is a potent inhibitor of angiogenesis that is cleaved from the basement membrane protein type XVIII collagen. Expression of endostatin has recently been shown by Western blot analysis of tissue lysates in normal pancreas and pancreas cancer tissue. We show here that the expression pattern of type XVIII collagen/endostatin is shifted from a general basement membrane staining and is mainly located in the vasculature during tumor progression. This shift in type XVIII collagen/endostatin expression pattern coincides with an up-regulation of MMPs involved in endostatin processing in the tumor microenvironment, such as MMP-3, MMP-9 and MMP-13. The circulating levels of endostatin was analyzed in patients with pancreas cancer and compared to that of healthy controls, as well as after surgical treatment or in a group of nonoperable patients after intraperitoneal fluorouracil (5-FU) chemotherapy. The results show that patients with pancreas cancer have increased circulating levels of endostatin and that these levels are normalized after surgery or intraperitoneal chemotherapy. These findings indicate that endostatin could be used as a biomarker for pancreas cancer progression.
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