Minimally invasive liver surgery for metastases from colorectal cancer: oncologic outcome and prognostic factors

Background

Few reports exist on long-term survival after minimally invasive liver surgery (MILS) for colorectal liver metastases (CRLM). No data are available assessing prognostic factors in the era of current modern treatment strategies.

Methods

Between October 2002 and December 2008, 274 consecutive patients were analyzed on an intention-to-treat basis. Open liver surgery (OLS) was performed in 193 patients for a total of 437 metastases, and MILS was performed in 81 patients for 176 metastases. Systemic chemotherapy was administered preoperatively in 173 and postoperatively in 174 patients. The impact of 23 potential prognostic factors on disease-free (DFS) and overall survival (OS) was evaluated using univariable and multivariable Cox regression models.

Results

Postoperative complications were observed in 54 patients after OLS and in 11 after MILS (p = 0.016). The median postoperative length of hospital stay was 9 days after OLS and 5 days after MILS (p < 0.0001). For the entire patient population, the 5 year DFS and OS rates were 29.9 and 59.5%, respectively. No differences in survival between patients treated with MILS and OLS were observed (p = 0.63). In univariable analyses, the number of liver metastases and the overall Fong’s clinical risk score (CRS) were the only two variables that predicted DFS (p ≤ 0.0035) and OS (p ≤ 0.0005). In multivariable analyses, the total CRS was the only independent predictor of both DFS (p = 0.0002) and OS (p = 0.002).

Conclusion

The long-term oncologic outcome of surgically treated patients with CRLM is determined by the Fong’s CRS. Although MILS does not influence long-term survival, it has a beneficial impact on the immediate postoperative clinical outcome.     

DNA methylation based glioblastoma subclassification is related to tumoral T-cell infiltration and patient survival

BackgroundHistologically classified glioblastomas (GBM) can have different clinical behavior and response to therapy, for which molecular subclassifications have been proposed. We evaluated the relationship of epigenetic GBM subgroups with immune cell infiltrations, systemic immune changes during radiochemotherapy, and clinical outcome.Methods450K genome-wide DNA methylation was assessed on tumor tissue from 93 patients with newly diagnosed GBM, treated with standard radiochemotherapy and experimental immunotherapy. Tumor infiltration of T cells, myeloid cells, and Programmed cell death protein 1 (PD-1) expression were evaluated. Circulating immune cell populations and selected cytokines were assessed on blood samples taken before and after radiochemotherapy.ResultsForty-two tumors had a mesenchymal, 27 a receptor tyrosine kinase (RTK) II, 17 RTK I, and 7 an isocitrate dehydrogenase (IDH) DNA methylation pattern. Mesenchymal tumors had the highest amount of tumor-infiltrating CD3+ and CD8+ T cells and IDH tumors the lowest. There were no significant differences for CD68+ cells, FoxP3+ cells, and PD-1 expression between groups. Systemically, there was a relative increase of CD8+ T cells and CD8+ PD-1 expression and a relative decrease of CD4+ T cells after radiochemotherapy in all subgroups except IDH tumors. Overall survival was the longest in the IDH group (median 36 mo), intermediate in RTK II tumors (27 mo), and significantly lower in mesenchymal and RTK I groups (15.5 and 16 mo, respectively).ConclusionsMethylation based stratification of GBM is related to T-cell infiltration and survival, with IDH and mesenchymal tumors representing both ends of a spectrum. DNA methylation profiles could be useful in stratifying patients for immunotherapy trials.     

Biomechanical gait features associated with hip osteoarthritis: Towards a better definition of clinical hallmarks

Critical appraisal of the literature highlights that the discriminative power of gait‐related features in patients with hip osteoarthritis (OA) has not been fully explored. We aimed to reduce the number of gait‐related features and define the most discriminative ones comparing the three‐dimensional gait analysis of 20 patients with hip osteoarthritis (OA) with those of 17 healthy peers. First, principal component analysis was used to reduce the high‐dimensional gait data into a reduced set of interpretable variables for further analysis, including tests for group differences. These differences were indicative for the selection of the top 10 variables to be included into linear discriminant analysis models (LDA). Our findings demonstrated the successful data reduction of hip osteoarthritic‐related gait features with a high discriminatory power. The combination of the top variables into LDA models clearly separated groups, with a maximum misclassification error rate of 19%, estimated by cross‐validation. Decreased hip/knee extension, hip flexion and internal rotation moment were gait features with the highest discriminatory power. This study listed the most clinically relevant gait features characteristics of hip OA. Moreover, it will help clinicians and physiotherapists understand the movement pathomechanics related to hip OA useful in the management and design of rehabilitation intervention. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1498–1507, 2015.     

Quantifying the potential of morphological parameters for human dental identification: part 3—selecting the strongest skeletal identifiers in the mandible

International Journal of Legal Medicine - The current study aimed to select the best mandibular morphological identifiers. One-hundred eighty-five panoramic radiographs were retrospectively...     

Outcome Predictors of Radical Prostatectomy in Patients With Prostate-Specific Antigen Greater Than 20 ng/ml: A European Multi-Institutional Study of 712 Patients

Background

Prostate cancer (PCa) patients with pretreatment prostate-specific antigen (PSA) >20 ng/ml have a high risk of biochemical and clinical failure and even cancer-related death after local therapy. Pretreatment predictors of outcome after radical prostatectomy (RP) in this patient group are necessary.

Objective

Our aim was to assess how the use of additional high-risk factors (biopsy Gleason score [bGS] ≥8 or clinical stage 3–4) can improve prediction of treatment failure and cancer-related death after RP in patients with PSA >20.

Design, setting, and participants

In a retrospective multicentre cohort study from six European centres between 1987 and 2005, 712 patients with PSA >20 ng/ml underwent RP and bilateral pelvic lymphadenectomy.

Measurements

Subgroups were analysed to determine the relationship between the number of high-risk factors and histopathology, biochemical progression-free survival, clinical evidence of progressive disease, prostate cancer–specific mortality (PCSM), and overall mortality. Kaplan-Meier analysis with log-rank test and Cox multivariable analysis were applied.

Results and limitations

Median follow-up was 77 mo. The number of high-risk factors was significantly associated with unfavourable histopathology. Among patients with only PSA >20 ng/ml, 33% had pT2 PCa, 57.9% had bGS <7, 54% had negative surgical margins, and 85% were lymph node negative (pN0), whereas among patients with all three high-risk factors, 4.5% had pT2 PCa, 2.3% had bGS <7, 20.5% had negative margins, and 49% were pN0 (p < 0.001). The strongest predictor of progression and mortality was bGS. PSA >20 ng/ml associated with bGS ≤7 resulted in 10-yr PCSM of 5%; when associated with bGS ≥8, PCSM was 35%. The main limitations of the study were retrospective design and varying treatment modalities.

Conclusions

PCa patients with PSA >20 ng/ml have varying risk levels of disease progression and PCSM. Considering additional risk factors further stratifies this group into four subgroups that can guide the clinician in preoperative patient counselling.