Technische Prinzipien der Narbenhernienchirurgie

Many publications are available on the best surgical techniques and treatment of incisional hernias with reports of experiences and randomized clinical studies at the two extremes of the evidence scale. The ultimate proof of the best operative technique has, however, not yet been achieved. In practically no other field of surgery are the variability and the resulting potential aims of surgery so great. The aim of surgery is to provide patients with the optimal recommendation out of a catalogue of possibilities from a holistic perspective. This article describes the surgical techniques using meshes for strengthening (in combination with an anatomical reconstruction) and for replacement of the abdominal wall (with bridging of the defect).     

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients

Background:

Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy.

Methods:

Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status.

Results:

In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01).

Conclusions:

TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30–40% of CRC patients, may represent a new avenue of investigation for targeted therapy.     

Lebermetastasen

Liver metastases are most often caused by colorectal cancer, followed by pancreatic and breast cancer. Metastasis constitutes the last step of malignant tumor progression. Molecular investigations point towards an important role of the epithelial-mesenchymal transition (EMT) as a mechanism of local invasion and distant metastasis formation. Furthermore, the existence of a subpopulation of cancer stem cells (CSC) could be demonstrated in solid tumors. Recent observations show a dynamic induction of CSC properties by EMT. Therefore, theoretically migrating cancer stem cells (MCSC) can be induced which form the basis for the development of distant metastases.     

Tumour-mediated TRAIL-Receptor expression indicates effective apoptotic depletion of infiltrating CD8+ immune cells in clinical colorectal cancer

Expression of apoptosis-related proteins on tumour cells has been shown in several experimental models to be an efficient mechanism for a counterattack against host anti-tumour immune responses in solid tumours. Here we provide a clinical evidence for such a tumour immune escape mechanism by demonstrating tumour to T cell-directed death receptor signalling (TRAIL/TRAIL-Receptor (TRAIL-R)) in colorectal cancer (CRC). In a series of patients with CRC and completed 5-year follow up, we investigated apoptosis and expression levels of apoptosis-related proteins. Gene and protein profiles in the tumours demonstrated intratumoural upregulated gene expression for Fas, Fas-L, TRAIL, TRAIL-R and TNF-α (RT-qPCR). Levels of terminaldeoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labelling (TUNEL)-positive events were positively correlated with TRAIL-R1-expression on tumour infiltrating immune cells. Among the immune cells, preferentially CD8+ T cells were found to express TRAIL-R1 while serial immunostaining in the same patient tumours showed abundant apoptotic (TUNEL-positive) immune cells. In conclusion, our results in tumour samples from CRC patients suggest TRAIL-R1-mediated apoptotic depletion of infiltrating immune cells (CD8+) in response to TRAIL expression by the tumour itself. This supports the notion of an efficient escape from tumour immune response and thus evasion from the attack of activated CD8+ T cells. These findings may enhance our understanding of tumour progression in CRC and might be helpful for the development of TRAIL and its death receptor-based therapy.     

Evaluation of Best Supportive Care and Systemic Chemotherapy as Treatment Stratified according to the retrospective Peritoneal Surface Disease Severity Score (PSDSS) for Peritoneal Carcinomatosis of Colorectal Origin

Background  

We evaluate the long-term survival of patients with peritoneal carcinomatosis (PC) treated with systemic chemotherapy regimens, and the impact of the of the retrospective peritoneal disease severity score (PSDSS) on outcomes.     

Leitliniengerechte Therapie der Divertikulitis

Diverticular disease represents one of the most frequent gastrointestinal diseases in the clinical routine. Decisive for treatment is not only who should receive inpatient or outpatient treatment but also the indications and timing for surgery. Due to international differences in classification systems, treatment recommendations are varied. This article presents the essential aspects of the indications for and timing of surgery oriented to the new classification of the German S2k guidelines. The indications for and timing of surgery can only be determined by evaluating all essential information on diverticular disease. A crucial requirement for guideline-conform treatment is an exact, comprehensive and applicable classification of the disease before treatment. An adequate assessment cannot be made using morphological information obtained by imaging alone. The new classification according to the German guidelines enables an appropriate strategy for evaluating the indications and selection of the time for surgery.