The gentamicin-collagen implant and the risk of distant metastases of rectal cancer following short-course radiotherapy and curative resection: the long-term outcomes of a randomized study.

PURPOSE: A previous randomized study conducted by our group showed that application of gentamicin-collagen implant (GCI) into the pelvic cavity after total mesorectal excision (TME) reduced the incidence of distant metastases. Therefore, we decided to conduct a confirmatory study. METHODS: Patients with rectal cancer were included in the study if they met the following criteria: adenocarcinoma of the rectum, preoperative short-term radiotherapy (5 × 5 Gy), and WHO performance score 0-1. RESULTS: One hundred seventy-six patients were randomly assigned either to an experimental group in which GCI was applied (n = 81) or to a control group without GCI (n = 81). Median follow-up was 80 months. Cumulative incidence of distant metastases at 5 years was higher in the control group compared to the experimental group: 23.5 vs 8.6% (HR 2.4 [95% CI 1.1-5.5], P = 0.005). Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) did not differ between the experimental group and the control group: HR 0.95 [95% CI 0.55-1.70], P = 0.864; HR 0.85 [95% CI 0.50-1.45], P = 0.548, and HR 0.5 [95%CI 0.22-1.22], P = 0.093, respectively. The predefined by the protocol subgroup analysis for yp stage III disease showed better DFS in the experimental group compared to the control group; HR 0.47 [95%CI 0.23-0.97], P = 0.042). CONCLUSIONS: The results confirmed our previous finding that GCI applied in the pelvis significantly reduced the rate of distant metastases in patients after radical rectal cancer resection.

Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts.

Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death worldwide. Patient-derived xenograft (PDX) models maintain complex intratumoral biology and heterogeneity and therefore remain the platform of choice for translational drug discovery. In this study, we implanted 37 primary CRC tumors and five CRC cell lines into NU/J mice to develop xenograft models. Primary tumors and established xenografts were histologically assessed and surveyed for genetic variants and gene expression using a panel of 409 cancer-related genes and RNA-seq, respectively. More than half of CRC tumors (20 out of 37, 54%) developed into a PDX. Histological assessment confirmed that PDX grading, stromal components, inflammation, and budding were consistent with those of the primary tumors. DNA sequencing identified an average of 0.14 variants per gene per sample. The percentage of mutated variants in PDXs increased with successive passages, indicating a decrease in clonal heterogeneity. Gene Ontology analyses of 4180 differentially expressed transcripts (adj. p value < 0.05) revealed overrepresentation of genes involved in cell division and catabolic processes among the transcripts upregulated in PDXs; downregulated transcripts were associated with GO terms related to extracellular matrix organization, immune responses, and angiogenesis. Neither a transcriptome-based consensus molecular subtype (CMS) classifier nor three other predictors reliably matched PDX molecular subtypes with those of the primary tumors. In sum, both genetic and transcriptomic profiles differed between donor tumors and PDXs, likely as a consequence of subclonal evolution at the early phase of xenograft development, making molecular stratification of PDXs challenging.

The risk of anastomotic leakage after anterior resection: retrospective analysis of 501 rectal cancer patients operated without protective stoma.

BACKGROUND: The aim of this study was to verify the accuracy of the existing scoring system for the assessment of anastomotic leakage risk after anterior resection and to identify additional risk factors that were not included in this classification. METHODS: The study included 501 consecutive rectal cancer patients who underwent anterior resection without formation of protective stoma. The risk for anastomotic leakage was determined using a previously proposed scoring system based on three factors: male sex, intraoperative blood loss and level of anastomosis. RESULTS: Symptomatic leakage occurred in 12.2% (61/501) of our patients. Lower level of anastomosis (P<0.001) and longer duration of surgery (P=0.018) were identified as independent risk factors for the leakage. Anastomotic dehiscence occurred in 7.3% (24/327), 20.1% (29/144) and 26.7% (8/30) of patients at low, intermediate and high risk of leakage according to the previously proposed scoring system. No differences were found in the leakage rates of patients from the intermediate and high risk groups (20.1% vs. 26.7%, P=0.427, RR=0.755 (95% CI: 0.384-1.486). CONCLUSIONS: The new scoring system is necessary for the identification of patients at increased risk of anastomotic leakage after anterior resection.

Risk of permanent stoma after resection of rectal cancer depending on the distance between the tumour lower edge and anal verge.

The distance between the anal verge and lower edge of rectal cancer is one of the most important factors affecting the feasibility of sphincter-preserving resection.The aim of the study was to assess the risk of permanent stoma after resection of rectal tumour depending on the distance between the tumour and the anal verge.Material and methods. The retrospective analysis covered 884 patients after resection of rectal cancer. The distance between the anal verge and the lowest edge of the tumour was measured during endoscopic examination. Surgical technique was similar in all cases. For statistical analysis, the chi-square test and Fisher exact test were used.Results. The overall rate of sphincter-preserving procedures was 71.8%, 90.1% of which were anterior resections. The greatest differences between the rate of anterior resections were noted for the segment between the 4th and the 5th centimetres: 30.1% for 4 cm vs 66.7% for 5 cm, p = 0.005. Overall, in 328 patients (37.1%) surgical treatment resulted in a permanent stoma. The number included: 246 (75.0%) patients after abdominosacral resection, 44 (13.4%) patients after the Hartmann procedure, three (0.9%) patients after proctocolectomy, and 28 (8.5%) patients after anterior resection, with a permanent stoma as a result of anastomotic leak. The overall rate of anastomotic leak was 11.7%. Formation of a defunctioning stoma in patients with a low-lying (6 cm from the anal verge) tumour reduced the risk of symptomatic anastomotic leak: 6.3% vs 20.5%; p = 0.049.Conclusions. Anterior resection of tumours located 6 cm from the anal verge is feasible in 90%. Anastomotic leak that requires reoperation increases the risk of permanent colostomy. In selected cases, formation of a defunctioning stoma after resection of low-lying rectal cancer can reduce the risk of permanent colostomy.

Hepatocyte growth factor levels in liver and blood, and post-operative liver cell proliferation in patients with benign and malignant liver tumors after partial hepatectomy.

BACKGROUND: The purpose of our study was to investigate hepatocyte proliferation and the expression of hepatocyte growth factor (HGF) in liver tissue and blood from patients with benign and malignant liver tumors after partial hepatectomy. MATERIAL/METHODS: We studied 25 consecutive patients undergoing partial hepatectomy for metastatic colorectal adenocarcinoma (15 cases) and benign liver tumors (10 cases). Immunohistochemical examination for the presence of PCNA and HGF, c-MET/HGF-receptor expression was performed on formalin-fixed samples from: a) sections of resected fragments of liver tissue remote from the tumor; b) tumor tissue; c) remnant liver, 30 min after hepatectomy; d) fine needle aspiration liver biopsy, 7 days after liver resection. Circulating HGF and the level of AFP and GGT as biomarkers for liver cell regeneration were measured in the patients' blood at the same time. RESULTS: The proliferation rate of liver cells was higher in patients with malignant than benign liver tumors. This correlated with increased HGF in blood, but not with the expression of HGF and c-MET/HGF-R in liver tissue. The expression of HGF was detected in specimens from colorectal liver metastases. CONCLUSIONS: The mutual interactions between tumor and other cells may influence the proliferation of hepatocytes throughout the regenerative process in patients with colorectal carcinoma metastases after partial hepatectomy.