Colorectal and appendiceal peritoneal metastases: From population studies to genetics

Peritoneal dissemination of colorectal and appendiceal origin was previously considered the end-stage of malignant disease. Today, treatment with cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) has prolonged survival and cured some patients with peritoneal metastases (PM). Unfortunately, a majority of patients still have fatal outcomes. In this thesis, colorectal and appendiceal PM were studied from a wide population-based perspective down to the detailed perspectives of histopathology and genetics, with the aim of further contributing to prolonged survival. In Paper I, the heterogeneous histopathology of PM was investigated and a substantial proportion of patients undergoing CRS and HIPEC were found to have surgical specimens lacking neoplastic epithelium. These patients had a favourable prognosis and the results illustrate the importance of thorough analysing and reporting of histopathology for understanding differences in survival outcomes and for improving patient selection. In Paper II, the role of inflammation in colorectal and appendiceal carcinogenesis was investigated at a population-based level. Patients with non-surgical treatment of appendicitis had an increased incidence of cancer (especially of appendiceal and right-sided colon cancer) compared to the general population. This should be taken into consideration in the discussion of optimal management of patients with appendicitis. In Paper III, risk factors for PM were studied with the aim of aiding in the detection of PM at earlier stages. Appendiceal and right-sided colon cancer, advanced tumour and node stages, mucinous histopathology and vascular invasion were identified as high risk features for developing PM, and should increase awareness of potential PM. In Paper IV, genome-wide chromosomal copy number alterations of PM were explored and associated with prognosis after CRS and HIPEC. Colorectal PM exhibited a wide range of alterations of which copy number gain on parts of chromosome 1p and 15q were significantly associated with poor prognosis and have the potential to be used as prognostic molecular markers in the future. In conclusion, this thesis provides new insights into the field of colorectal and appendiceal cancer and PM to be used for improved patient selection, early detection and prevention, ultimately contributing to improved survival.