Exploring new strategies in diagnosis and treatment of hilar cholangiocarcinoma

Hilar cholangiocarcinoma is a rare form of cancer arising at the confluence of the right and left bile duct. The disease is known for its difficult diagnosis and treatment. The chapters in this thesis describe different aspects of hilar cholangiocarcinoma with the aim to improve diagnosis and treatment. Finding a suitable molecular marker is important for the development of innovative diagnostic techniques. It was found that the molecule MUC1 seems to be the most promising target for so called near-infrared optical imaging of hilar cholangiocarcinoma. To improve the surgical treatment of hilar cholangiocarcinoma the value of intraoperative frozen section analysis was investigated. It was found that frozen section analysis of the bile ducts does not improve outcome after surgery. Next, it was investigated whether postoperative staging of hilar cholangiocarcinoma can be improved. It was found that detection of lymph node micrometastases is associated with worse survival and therefore important for the prognosis after surgery. Liver transplantation has recently regained attention for the treatment of hilar cholangiocarcinoma. Excellent results have been achieved with a protocol consisting of a regimen of chemoradiotherapy followed by liver transplantation. In this thesis it was found that preoperative chemoradiotherapy is associated with a high rate of vascular complications after liver transplantation. Further, the effect of strict selection alone (without preoperative chemoradiotherapy) on the outcome of liver transplantation for hilar cholangiocarcinoma was assessed

Exploring new strategies in diagnosis and treatment of hilar cholangiocarcinoma

Hilar cholangiocarcinoma is a rare form of cancer arising at the confluence of the right and left bile duct. The disease is known for its difficult diagnosis and treatment. The chapters in this thesis describe different aspects of hilar cholangiocarcinoma with the aim to improve diagnosis and treatment. Finding a suitable molecular marker is important for the development of innovative diagnostic techniques. It was found that the molecule MUC1 seems to be the most promising target for so called near-infrared optical imaging of hilar cholangiocarcinoma. To improve the surgical treatment of hilar cholangiocarcinoma the value of intraoperative frozen section analysis was investigated. It was found that frozen section analysis of the bile ducts does not improve outcome after surgery. Next, it was investigated whether postoperative staging of hilar cholangiocarcinoma can be improved. It was found that detection of lymph node micrometastases is associated with worse survival and therefore important for the prognosis after surgery. Liver transplantation has recently regained attention for the treatment of hilar cholangiocarcinoma. Excellent results have been achieved with a protocol consisting of a regimen of chemoradiotherapy followed by liver transplantation. In this thesis it was found that preoperative chemoradiotherapy is associated with a high rate of vascular complications after liver transplantation. Further, the effect of strict selection alone (without preoperative chemoradiotherapy) on the outcome of liver transplantation for hilar cholangiocarcinoma was assessed

Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma Is Associated with Improved Survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five–year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience

Strict Selection Alone of Patients Undergoing Liver Transplantation for Hilar Cholangiocarcinoma is Associated with Improved Survival

Liver transplantation for hilar cholangiocarcinoma (hCCA) has regained attention since the Mayo Clinic reported their favorable results with the use of a neo-adjuvant chemoradiation protocol. However, debate remains whether the success of the protocol should be attributed to the neo-adjuvant therapy or to the strict selection criteria that are being applied. The aim of this study was to investigate the value of patient selection alone on the outcome of liver transplantation for hCCA. In this retrospective study, patients that were transplanted for hCCA between 1990 and 2010 in Europe were identified using the European Liver Transplant Registry (ELTR). Twenty-one centers reported 173 patients (69%) of a total of 249 patients in the ELTR. Twenty-six patients were wrongly coded, resulting in a study group of 147 patients. We identified 28 patients (19%) who met the strict selection criteria of the Mayo Clinic protocol, but had not undergone neo-adjuvant chemoradiation therapy. Five-year survival in this subgroup was 59%, which is comparable to patients with pretreatment pathological confirmed hCCA that were transplanted after completion of the chemoradiation protocol at the Mayo Clinic. In conclusion, although the results should be cautiously interpreted, this study suggests that with strict selection alone, improved survival after transplantation can be achieved, approaching the Mayo Clinic experience

Lack of Association of SULT1A1 R213H Polymorphism with Colorectal Cancer: A Meta-Analysis

BACKGROUND: A number of case-control studies were conducted to investigate the association of SULT1A1 R213H polymorphisms with colorectal cancer (CRC) in humans. But the results were not always consistent. We performed a meta-analysis to examine the association between the SULT1A1 R213H polymorphism and CRC. METHODS AND FINDINGS: Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, and Chinese Biomedical Literature Database, with the last report up to September 2010. A total of 12 studies including 3,549 cases and 5,610 controls based on the search criteria were involved in this meta-analysis. Overall, no significant association of this polymorphism with CRC was found (H versus R: OR = 1.04, 95%CI = 0.94-1.16, P = 0.46; HR+HH versus RR: OR = 1.01, 95%CI = 0.92-1.11, P = 0.81; HH versus RR+HR: OR = 1.01, 95%CI = 0.74-1.38, P = 0.95; HH versus RR: OR = 1.00, 95%CI = 0.77-1.31, P = 0.98; HR versus RR: OR = 1.01, 95%CI = 0.92-1.11, P = 0.86). In subgroup analysis, we also did not find any significant association in Cauasians (H versus R: OR = 1.02, 95%CI = 0.92-1.15, P = 0.68; HR+HH versus RR: OR = 0.99, 95%CI = 0.91-1.09, P = 0.90; HH versus RR+HR: OR = 1.01, 95%CI = 0.73-1.39, P = 0.97; HH versus RR: OR = 0.99, 95%CI = 0.75-1.31, P = 0.94; HR versus RR: OR = 0.99, 95%CI = 0.90-1.09, P = 0.85). The results were not materially altered after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded (H versus R: OR = 1.06, 95%CI = 0.95-1.19, P = 0.31; HR+HH versus RR: OR = 1.03, 95%CI = 0.93-1.13, P = 0.56; HH versus RR+HR: OR = 1.10, 95%CI = 0.78-1.56, P = 0.57; HH versus RR: OR = 1.09, 95%CI = 0.83-1.44, P = 0.53; HR versus RR: OR = 1.02, 95%CI = 0.92-1.13, P = 0.75). CONCLUSION: This meta-analysis demonstrates that there is no association between the SULT1A1 R213H polymorphism and CRC