Repeated cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with recurrent peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the treatment of choice for resectable peritoneal carcinomatosis (PC) and improved the survival of these patients. The situation changes if PC recurs and repeated CRS with HIPEC is considered. The patient selection and outcome of the repeated approach has not been well described. We analyzed our cohort and share the experiences. METHODS: Ninety-three CRS/HIPEC procedures, performed in 85 patients during the period 2001-2013, were examined in a retrospective analysis. Type of primary, ECOG status, peritoneal cancer index (PCI), completeness of cytoreduction (CC), duration of hospitalization, postoperative morbidity, mortality, and disease-free/overall survival were reviewed. RESULTS: Six patients (7%) underwent a second CRS/HIPEC (median interval between the two procedures: 26 months, range 8-61) including two patients with mesotheliomas, one patient with ovarian adenocarcinoma, one patient with leiomyosarcoma of uterus, one patient with colon adenocarcinoma, and one patient with appendiceal adenocarcinoma. The last two patients underwent a third CRS/HIPEC, 25 and 36 months, after the second procedure. The median PCI was 14 (range, 4-26) during the first and 20 (range, 7-39) during the second CRS/HIPEC of these patients. Completeness of cytoreduction score of 0 (CC-0) was achieved in all first procedures and in 67% of second procedures (CC-0; n=4 and CC-1; n=2). A CC-0 score was possible in both of the third procedures. The mean operating time was 444 min (range, 198-642) and 427 min (range, 239-617) during the first and the second procedure. Median intensive care unit (ICU) was 2 days, and hospital stay after second CRS/HIPEC was 17 days (range, 7-50). The 30-day morbidity after repeated CRS/HIPEC was 33% (16% for grade III-IV complications), and there was no 30-day mortality neither after the second nor after the third CRS/HIPEC. Median disease-free interval between first CRS/HIPEC and peritoneal recurrence was 17 months (range, 8-30). Median disease-free survival of 18 months (range, 4-33) was achieved after the second CRS/HIPEC. After a median follow-up of 74 months (range, 39-151), all patients are alive with disease (n=5) or disease free (n=1) under chemotherapy. CONCLUSIONS: In experienced centers, repeated CRS/HIPEC can be performed with safety. Patient selection and correct timing is of particular importance in achieving control of the disease. Repeated CRS/HIPEC should be considered as treatment option for selected patients with recurrent PC.

Despite aggressive histopathology survival is not impaired in young patients with colorectal cancer : CRC in patients under 50 years of age.

PURPOSE: Colorectal carcinoma (CRC) is generally a disease of persons older than 50 years. Concerning younger patients, controversies still exist regarding features and prognosis of CRC. We performed this study to characterize CRC in young patients (≤50 years) as well as to evaluate outcome in comparison with older patients (>50 years) with CRC. METHODS: Clinical and histopathological parameters of 244 patients aged 50 years or less were compared with 1,718 patients aged more than 50 years. RESULTS: Compared with older patients, the younger had less adenocarcinomas (82.8% vs. 89.1%; p = 0.004) and less postoperative complications (18.4% vs. 28.7%; p = 0.001), and less Union Internationale Contre le Cancer stage I colon cancers (22.9% vs. 13.6%, p = 0.046) but elevated overall 5-year survival rates for M0 colon and rectal cancers (p = 0.005; p < 0.001). In young patients, the minority suffered from hereditary cancer syndromes (7.4%) and inflammatory bowel diseases (7.0%). Furthermore, up to 40% of young patients denied any cancers in their families. Cancer-related survival rates were significantly elevated in young patients with M0 rectal carcinoma (p = 0.014), whereas in M0 colon cancers, no differences were detectable (p = 0.542). In case of the presence of distant metastases, overall and cancer-related survival rates were similar in old and young patients. CONCLUSION: Although young patients present with more aggressive histopathological subtypes and less early stages, cancer-related survival is not less favourable compared with older patients.

Molecular signature for lymphatic metastasis in colorectal carcinomas.

PURPOSE: TNM-staging of colorectal carcinomas (CRC) relies on the histopathologic workup of the surgically removed specimen. If valid preoperative staging methods existed, patients could be selected for adequate individual therapy before surgery. Microarray techniques provide a promising tool to identify stage-specific molecular signatures on primary tumor biopsies. MATERIAL AND METHODS: Forty tumor samples of stage UICC I, II CRC, 40 samples of stage III CRC, and 25 biopsies of healthy mucosa (MC) were shock frozen in liquid nitrogen and underwent cryotomy after manual dissection for tumor tissue or MC enrichment. Isolated RNA was hybridized to GeneChips (HG-U133A, Affymetrix). Preprocessing of the microarray results was done by the robust multichip average method, and differentially expressed genes were selected by the maximum Wilcoxon statistic over 22,215 probe sets. The results were validated at an independent clinical study. RESULTS: Fifty differently expressed genes between stage UICC I, II versus III CRC were identified respecting the selection criteria by allowing for multiple testing. The data validation by the independent clinical study confirmed our results. In comparison to MC, the genes were over- or underexpressed. They belong to various functional groups such as cellular adhesion, transporters, signaling, metabolism, protein synthesis, gene control, and immune system. CONCLUSION: Our large patient cohort and the data validation on an independent study identified 50 differentially expressed genes between CRC of different histopathologic stages. These findings indicate that molecular staging of CRC may be possible, which could help to guide individual CRC treatment before surgery.

Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma.

PURPOSE: Desmoid tumors, also known as aggressive fibromatosis, occur with an incidence of 10 to 15 percent in patients affected by familial adenomatous polyposis, an autosomal inherited disease caused by germline mutations in the APC gene. However, sporadic forms with no hereditary background exist. The aim of this study was to find out whether there are APC germline mutations in apparently sporadic desmoid tumor patients without clinical or familial signs of familial adenomatous polyposis but with a family history of colorectal carcinoma in at least one family member. METHODS: Genomic DNA and mRNA were isolated from peripheral blood leukocytes of index patients of eight nonrelated families. Mutation screening was performed using reverse transcriptase polymerase chain reaction-based protein truncation test for APC exons 1-14. The large APC exon 15 was scrutinized by the protein truncation test of four overlapping genomic fragments. Additionally, genomic DNA from five desmoid tumors was analyzed for loss of heterozygosity at D5S346 close to the APC locus. RESULTS: No translational stop mutations typical for familial adenomatous polyposis could be found in the APC gene in any of the analyzed blood samples from the desmoid tumor patients. Additionally, no loss of heterozygosity at D5S346 was found in four of five desmoids; one tumor was not informative. CONCLUSIONS: These results may suggest that patients with sporadic desmoids and no clinical signs of familial adenomatous polyposis detected on careful examination, esophagogastroduodenoscopy, and complete colonoscopy do not need to be tested routinely for germline mutations of the APC gene. However, as large studies dealing with this problem are absent, it might be more time and cost effective to perform an APC mutational analysis instead.

Liver transplantation for hepatocellular carcinoma: a single European centre experience.

BACKGROUND: With respect to deficient donor grafts and the risk of tumour recurrence, indication for orthotopic liver transplantation (OLT) is still controversial. OLT offers the only chance for both the tumour and the underlying liver disease to be eliminated in patients with hepatocellular carcinoma (HCC) and cirrhosis. The aim of this study was to assess survival and related factors of recurrence. PATIENTS AND METHODS: This retrospective study analyses data from 45 patients with HCC (UICC stage I/II, n=16; III, n=13; IV, n=12) treated with OLT between 1992 and 2002 in our centre. There were 39 primary tumours and two recurrent ones after previous surgical resection. Four perioperative deaths were excluded from analysis. RESULTS: Mean follow-up was 50.4 months. Five-year rates after OLT were 64% for overall survival, 78% for disease-specific survival, 73% for recurrence-free survival, and 22% for tumour recurrence. No tumour recurrence has been observed so far in patients with tumours of UICC stage I/II. None of the patient characteristics had a significant impact on survival, while tumour stage was significantly correlated with freedom from recurrence. CONCLUSION: Our results demonstrate that the risk of recurrent HCC in liver transplanted patients is low for small and solitary tumours with no vascular invasion (UICC I/II). Even in advanced tumour stages (UICC III/IV), there is a real chance of cure or at least a survival benefit in selected patients.