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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.

BackgroundDespite the findings of several randomized clinical studies, the role of gentamicin collagen implant (GCI) in rectal cancer surgery is unclear. Local pelvic application of GCI following preoperative radiotherapy and total mesorectal excision (TME) was evaluated to determine the risk of surgical site infections (SSI).MethodsIn this single-center trial, 176 patients with rectal cancer after preoperative, short-term radiotherapy (5 × 5 Gy) were randomized either to the study group in which GCI was used or in the control group without GCI. Prior to surgery and intraoperatively five patients were excluded from the study. The remaining 171 patients were analyzed; 86 were in the study group and 85 in the control group.ResultsThere were no statistically significant differences in the overall rate of early postoperative complications between the study and control group: 25.6 and 34.1 % respectively; p = 0.245, relative risk (RR) 0.750 [95 % confidence interval (CI) 0.471–1.195]. The reoperation rate was similar in both groups: 12.8 versus 9.4 %; p = 0.628; RR 1.359; (95 % CI 0.575–3.212). The total rate of SSI and organ space SSI were 22.2 and 15.8 % without differences between the study and control group. In patients without anastomotic leakage, the risk of organ space SSI was significantly reduced in patients who received GCI: 2.6 versus 13.0 %; p = 0.018.ConclusionsApplication of GCI in the pelvic cavity after short-term preoperative radiotherapy and TME may reduce the risk of organ space SSI but only in the absence of anastomotic leakage.

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PurposeA 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.MethodsPatients 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.ResultsOne 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).ConclusionsThe 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.Electronic supplementary materialThe online version of this article (10.1007/s00384-018-3045-3) contains supplementary material, which is available to authorized users.