B. Ardnor

Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer

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.

Expression pattern and circulating levels of endostatin in patients with pancreas cancer

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.

Identification Of Inequalities In The Selection Of Liver Surgery For Colorectal Liver Metastases In Sweden

Background: Liver resection for colorectal liver metastases offers a 5-year survival rate of 25%–58%. This study aimed to analyze whether patients with colorectal liver metastases undergo resection to an equal extent and whether selection factors play a role in the selection process. Material and Methods: Data were retrieved from the Swedish Colorectal Cancer Registry (2007–2011) for colorectal cancer and colorectal liver metastases. The patients identified were linked to the Swedish Registry of Liver and Bile surgery and the National Patient Registry to identify whether liver surgery or ablative treatment was performed. Analyses for age, sex, type of primary tumor and treating hospital (university, county, or district), American Society of Anesthesiologists class, and radiology for detection of metastatic disease were performed. Results: Of 28,355 patients with colorectal cancer, 21.6% (6127/28,355) presented with liver metastases. Of the patients with liver metastases, 18.5% (1134/6127) underwent liver resection or ablation. The cumulative proportion of liver resection/ablation was 4% (1134/28,355) of all colorectal cancer. If “not bowel resected” were excluded, the proportion slightly increased to 4.7% (1134/24,262). Around 15% of the patients with metastases were registered as referrals for liver surgery. In a multivariable analysis patients treated at a university hospital for primary tumor were more frequently surgically treated for liver metastases (p < 0.0001). Patients with liver metastases from rectal cancer (p < 0.0001) and men more often underwent liver resection (p = 0.006). A difference was found between health-care regions for the frequency of liver surgery (p < 0.0001). Patients >70 years and those with American Society of Anesthesiologists class >2 underwent liver resection less frequently. Magnetic resonance imaging of the liver was more often used in diagnostic work-up in men. Conclusion: Patients with colorectal liver metastases are unequally treated in Sweden, as indicated by the low referral rate. The proximity to a hepatobiliary unit seems important to enhance the patient’s chances of being offered liver surgery.

The impact of post-hepatectomy liver failure on mortality: a population-based study

Abstract 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 µg/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 = 46). In 41% (n = 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.

Simultaneous procedures for colorectal cancers with liver metastases, with a special focus on major liver resections

EP01A-076 SIMULTANEOUS PROCEDURES FOR COLORECTAL CANCERS WITH LIVER METASTASES, WITH A SPECIAL FOCUS ON MAJOR LIVER RESECTIONS V. Valdimarsson, I. Syk, G. Lindell, A. Norén, B. Isaksson, P. Sandström, M. Rizell, B. Ardnor and C. Sturesson Department of Clinical Sciences Lund, Department of Clinical Sciences Malmö, Surgery, Lund University, Skane University Hospital, Department of Surgical Sciences, Uppsala University, Division of Surgery, Department for Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute at Karolinska University Hospital, Department of Surgery and Department of Clinical and Experimental Medicine, Linköping University, Department of Transplantation and Liver Surgery, Sahlgrenska Academy, University of Gothenburg, and Department of Surgery, Umeå University Hospital, Sweden Background: Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection. The aim of the present study was to compare outcomes in patients following a simultaneous resection of the primary cancer and the sCRLM and a staged resection where the bowel is resected first and the sCRLM are resected at second stage (classical approach), using data from two nationwide registries in Sweden. Methods: In this retrospective cohort study, clinical, pathological and survival outcomes were compared between the simultaneous approach and the classical approach (2008-2015). Overall survival was calculated. Results:A total of 537 patients were identified, of which 160 were treated with the simultaneous approach and 377 with the classical approach. The median follow-up was 41 months. The patients chosen for the simultaneous approach had more often node-positive primaries (87% vs 63%, p< 0.001), colon primary (78% vs 69%, p=0.046), shorter total hospital stay (11 vs 15 days, p< 0.001) and more often minor liver procedures (84% vs 59%, p< 0.001). The tumour burden score in the liver was the same (P=0.450). There was no difference in 5-year overall survival (p=0.110). A total of 25 patients had a major resection in the simultaneous group and 155 in the classical approach group. No 5year overall survival difference was shown (P=0.198). Discussion: No difference in overall survival was noted between the strategies. The simultaneous approach appears to be safe even when evaluating major liver resection and primary tumour resection.