Remarkably limited information is available about biological mechanisms that determine the disease entity of metastatic colorectal cancer in the liver (CRCLM) with no good clinical parameters to estimate prognosis. For the last few years, understanding the relationship between tumor characteristics and local immune response has gained increasing attention. Given the multifaceted roles of B-cell-driven responses, we aimed to elucidate the immunological imprint of B lymphocytes at the metastatic site, the interrelation with macrophages, and their prognostic relevance. Here we present novel algorithm allowing to assess a link between the local patient-specific immunological capacity and clinical outcome. The microscopy-based imaging platform was used for automated scanning of large-scale tissue sections and subsequent qualitative and quantitative analyses of immune cell subtypes using lineage markers and single-cell recognition strategy. Results indicate massive infiltration of CD45-positive leukocytes confined to the metastatic border. We report for the first time the accumulation of CD20-positive B lymphocytes at the tumor – liver interface comprising the major population within the large CD45-positive aggregates. Strikingly, functionally active, activation-induced cytidine deaminase (AID)-positive ectopic lymphoid structures were found to be assembled within the metastatic margin. Furthermore, the CD20-based data set revealed a strong prognostic power: patients with high CD20 content and/or ectopic follicles had significantly lower risk for disease recurrence as revealed by univariate analysis (p<0.001 for both) and in models adjusted for clinicopathological variables (p<0.001 and p = 0.01, respectively), and showed prolonged overall survival. In contrast, CD68 staining-derived data set did not show an association with clinical outcome. Taken together, we nominate the magnitude of B lymphocytes, including those organized in ectopic follicles, as novel prognostic marker which is superior to clinicopathological parameters. Findings emphasize anti-tumoral role of B cell-driven mechanism(s) and thus indicate a new way of thinking about potential treatment strategies for CRCLM patients.

Operation time is the only significant risk factor associated with mesh graft infection following incisional hernia repair. Conservative treatment should be applied in case of infection of absorbable mesh grafts such as polypropylene/polyglactin, while nonabsorbable meshes such as PTFE/polypropylene or pure polypropylene are much less amenable to conservative treatment, usually requiring early surgical removal.

This study provided further evidence for the prognostic importance of KRAS status in terms of recurrence-free and overall survival. Neoadjuvant chemotherapy including bevacizumab elicited a response, irrespective of KRAS status, in this selected group of patients with CLM.

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Chronic wounds are a growing challenge for physicians and health insurance agencies. The burden of affected patients is enormous, because of pain but also because of long-lasting therapies and dependence on nursing services. In other areas of medicine, computer-based diagnostics is established, yet, accurate wound documentation is rarely conducted and is often limited to size measurement with a ruler and a rough photo documentation. Objective assessment of lesions by evaluation of granulation tissue, fibrin coverage and necrosis is not performed. The aim of this study was to investigate the spread and variety in judgement of a chronic wound. A diabetic ulcer was described by 16 wound therapists (eight physicians and eight nurses). Granulation tissue, fibrin coverage, necrosis, size and depth of the lesion, wound exudate and wound edges were judged, and the therapeutical consequences were determined. Study data show an extensive inhomogeneity and a wide spread of the results, like in no other field of medical diagnostics. This could be shown in the group of physicians, as well as in the group of nursing personnel. As the choice of treatment by a specialist is based upon the assessment of the wound, it is possible that in practice it can lead to suboptimal therapy. This is a consequence of varying treating physicians and subsequent changes in treatment regimens. This results in a prolongation of treatment and burden for the patient. Circumstances like this contribute to rising of costs in this area of the health care system. The goal is to apply objective wound diagnostic technologies in the field of chronic wounds to catch up with other diagnostic procedures.

Our data suggest that serial measurements of CRC-associated methylation markers could be a particularly valuable tool for early response assessment in patients receiving neoCTx for CLM.

BackgroundPostoperative liver dysfunction may lead to morbidity and mortality after liver resection. Preoperative liver function assessment is critical to identify preexisting liver dysfunction in patients prior to resection. The aim of this study was to evaluate the predictive potential of perioperative indocyanine green (ICG)-clearance testing to prevent postoperative liver dysfunction and morbidity using standardized outcome parameters in a routine Western-clinical-setting.Study Design137 patients undergoing partial hepatectomy between 2011 and 2013, at the general hospital of Vienna, were included. ICG-clearance was recorded one day prior to surgery as well as on the first and fifth postoperative day. Postoperative liver dysfunction was defined according to the International Study Group of Liver Surgery and evaluation of morbidity was based on the Dindo-Clavien classification. Statistical analyses were based on non-parametric tests.ResultsPreoperative reduced ICG—plasma disappearance rate (PDR) as well as increased ICG—retention rate at 15 min (R15) were able to significantly predict postoperative liver dysfunction (Area under the curve = PDR: 0.716, P = 0.018; R15: 0.719, P = 0.016). Furthermore, PDR <17%/min. or R15 >8%, were able to accurately predict postoperative complications prior to surgery. In addition to this, ICG-clearance on postoperative day 1 comparably predicted postoperative liver dysfunction (Area under the curve = PDR: 0.895; R15: 0.893; both P <0.001), specifically, PDR <10%/min or R15 >20% on postoperative day 1 predicted poor postoperative outcome.ConclusionPDR and R15 may represent useful parameters to distinguish preoperative high and low risk patients in a Western collective as well as on postoperative day 1, to identify patients who require closer monitoring for potential complications.

Tumor recurrence after curative resection remains a major problem in patients with locally advanced colorectal cancer (CRC) treated with adjuvant chemotherapy. Genetic single nucleotide polymorphisms (SNPs) may serve as useful molecular markers to predict clinical outcomes in these patients and identify targets for future drug development. Recent in vitro and in vivo studies have demonstrated that the plastin genes, PLS3 and LCP1, are overexpressed in colon cancer cells and play an important role in tumor cell invasion, adhesion and migration. Hence, we hypothesized that functional genetic variations of plastin may direct effects on the progression and prognosis of locally advanced CRC. We tested whether functional tagging polymorphisms of PLS3 and LCP1 predict time to tumor recurrence (TTR) in 732 patients (training set: 234; validation set: 498) with stage II/III CRC. The PLS3 rs11342 and LCP1 rs4941543 polymorphisms were associated with a significantly increased risk for recurrence in the training set. PLS3 rs6643869 showed a consistent association with TTR in the training and validation set, when stratified by gender and tumor location. Female patients with the PLS3 rs6643869 AA genotype had the shortest median TTR compared to those with any G allele in the training set [1.7 vs. 9.4 years; HR2.84 (95% CI=1.32–6.1); p=0.005] and validation set [3.3 vs. 13.7 years; HR2.07 (95%CI=1.09–3.91); p=0.021]. Our findings suggest that several SNPs of the PLS3 and LCP1 genes could serve as gender and/or stage-specific molecular predictors of tumor recurrence in stage II/III CRC patients as well as potential therapeutic targets.