BackgroundPurpose of this study was to analyse the surgical management and long-term clinical outcome of patients diagnosed with colorectal liver metastases (CLM) over a period of 10 years using data from a German tumour registry.MethodsRetrospective analysis of 5772 patients diagnosed with colorectal adenocarcinoma between 2002 and 2007. Follow-up was continued until 2012.Results1426 patients (24.7%) had CLM; 1019 patients (71%) had synchronous, 407 patients (29%) developed metachronous CLM. Hepatic resection was performed in 374 of the 1426 CLM patients (26%). A significant increase in liver resection rate from 16.6% for the 2002 cohort to 32% in later cohorts was observed. In centers specialized in liver surgery, CLM resection rates reached 46.6%. However, up to 52% of patients diagnosed with three or less CLM did not undergo liver surgery, although, if resected, patients with 1 CLM show a similar long-time survival as CRC patients who do not develop any CLM. Univariate and multivariate analyses adjusted for age, sex, year of resection, time of CLM diagnosis and number of CLM revealed a significant survival benefit for CLM resection (HR =0.355; CI 0.305-0.414). Furthermore, significant impact on OS was seen for age at diagnosis, perioperative chemotherapy and number of CLM.ConclusionsWe here present the first long-term, population-based analysis of the surgical management of CLM in Germany. Significant increase in hepatic resection rates, translating to a significant benefit in OS, was seen over years. However, we still see a striking potential for further improvements in interdisciplinary CLM management.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-810) contains supplementary material, which is available to authorized users.

ObjectiveAdvanced and recurrent diseases are the major causes of death in colon cancer. No standard preclinical model addresses advanced disease and spontaneous metastasis after orthotopic tumour growth. In this study, the authors report the establishment of such standardised orthotopic mouse models of colon cancer and their use in evaluating metronomic topotecan alone or in combination with standard chemotherapy.DesignHuman colon cancer cell lines, transfected with human chorionic gonadotropin and luciferase, were injected orthotopically into the caecal wall of severe combined immunodeficient mice, intrasplenically or subcutaneously. For adjuvant therapy, caecal resections were performed 3–5 weeks after tumour cell injection. Chemotherapy drugs tested included uracil/tegafur, folinic acid, oxaliplatin, topotecan, pazopanib and various combinations.ResultsSubcutaneous tumours showed exaggerated sensitivity to treatment by delayed tumour growth (p=0.002) and increased survival (p=0.0064), but no metastatic spread. Intrasplenic cell injection resulted in rapid and extensive but artefactual metastasis without treatment effect. Intracaecal cell injection with tumour take rates of 87.5–100% showed spontaneous metastases at clinically relevant rates. Metronomic topotecan significantly polonged survival and reduced metastasis. In the adjuvant setting, metronomic maintenance therapy (after FOLFOX-like induction) prolonged survival compared with vehicle controls (p=0.0003), control followed by topotecan (p=0.0161) or FOLFOX-like therapy (p=0.0003).ConclusionThe refined orthotopic implantation technique proved to be a clinically relevant model for metastasis and therapy studies. Furthermore, metronomic therapy with oral topotecan may be promising to consider for clinical trials of metastatic colon cancer and long-term adjuvant maintenance therapy of colon cancer.

In 1953, the pioneer of human orthotopic liver transplantation (LT), Thomas E Starzl, was the first to attempt an orthotopic liver transplant into a 3 years old patient suffering from biliary atresia. Thus, the first LT in humans was attempted in a disease, which, up until today, remains the main indication for pediatric LT (pLT). During the last sixty years, refinements in diagnostics and surgical technique, the introduction of new immunosuppressive medications and improvements in perioperative pediatric care have established LT as routine procedure for childhood acute and chronic liver failure as well as inherited liver diseases. In contrast to adult recipients, pLT differs greatly in indications for LT, allocation practice, surgical technique, immunosuppression and post-operative life-long aftercare. Many aspects are focus of ongoing preclinical and clinical research. The present review gives an overview of current developments and the clinical outcome of pLT, with a focus on alternatives to full-size deceased-donor organ transplantation.

Colorectal cancer (CRC) is associated with loss of epithelial barrier integrity, which facilitates the interaction of the immunological microenvironment with the luminal microbiome, eliciting tumor-supportive inflammation. An important regulator of intestinal inflammatory responses is IRAK-M, a negative regulator of TLR signaling. Here we investigate the compartment-specific impact of IRAK-M on colorectal carcinogenesis using a mouse model. We demonstrate that IRAK-M is expressed in tumor cells due to combined TLR and Wnt activation. Tumor cell-intrinsic IRAK-M is responsible for regulation of microbial colonization of tumors and STAT3 protein stability in tumor cells, leading to tumor cell proliferation. IRAK-M expression in human CRCs is associated with poor prognosis. These results suggest that IRAK-M may be a potential therapeutic target for CRC treatment.

In 1988, Rudolf Pichlmayr pioneered split liver transplantation (SLT), enabling the transplantation of one donor liver into two recipients - one pediatric and one adult patient. In the same year, Henri Bismuth and colleagues performed the first full right/full left split procedure with two adult recipients. Both splitting techniques were rapidly adopted within the transplant community. However, a SLT is technically demanding, may cause increased perioperative complications, and may potentially transform an excellent deceased donor organ into two marginal quality grafts. Thus, crucial evaluation of donor organs suitable for splitting and careful screening of potential SLT recipients is warranted. Furthermore, the logistic background of the splitting procedure as well as the organ allocation policy must be adapted to further increase the number and the safety of SLT. Under defined circumstances, in selected patients and at experienced transplant centers, SLT outcomes can be similar to those obtained in full organ LT. Thus, SLT is an important tool to reduce the donor organ shortage and waitlist mortality, especially for pediatric patients and small adults. The present review gives an overview of technical aspects, current developments, and clinical outcomes of SLT.