Complete mesocolic excision for right colonic cancer: prospective multicentre study.

BACKGROUND: Complete mesocolic excision (CME) for right colonic cancer is a more complex operation than standard right hemicolectomy but evidence to support its routine use is still limited. This prospective multicentre study evaluated the effect of CME on long-term survival in colorectal cancer centres in Germany (RESECTAT trial). The primary hypothesis was that 5-year disease-free survival would be higher after CME than non-CME surgery. A secondary hypothesis was that there would be improved survival of patients with a mesenteric area greater than 15 000 mm2. METHODS: Centres were asked to continue their current surgical practices. The surgery was classified as CME if the superior mesenteric vein was dissected; otherwise it was assumed that no CME had been performed. All specimens were shipped to one institution for pathological analysis and documentation. Clinical data were recorded in an established registry for quality assurance. The primary endpoint was 5-year overall survival for stages I-III. Multivariable adjustment for group allocation was planned. Using a primary hypothesis of an increase in disease-free survival from 60 to 70 per cent, a sample size of 662 patients was calculated with a 50 per cent anticipated drop-out rate. RESULTS: A total of 1004 patients from 53 centres were recruited for the final analysis (496 CME, 508 no CME). Most operations (88.4 per cent) were done by an open approach. Anastomotic leak occurred in 3.4 per cent in the CME and 1.8 per cent in the non-CME group. There were slightly more lymph nodes found in CME than non-CME specimens (mean 55.6 and 50.4 respectively). Positive central mesenteric nodes were detected more in non-CME than CME specimens (5.9 versus 4.0 per cent). One-fifth of patients had died at the time of study with recorded recurrences (63, 6.3 per cent), too few to calculate disease-free survival (the original primary outcome), so overall survival (not disease-specific) results are presented. Short-term and overall survival were similar in the CME and non-CME groups. Adjusted Cox regression indicated a possible benefit for overall survival with CME in stage III disease (HR 0.52, 95 per cent c.i. 0.31 to 0.85; P = 0.010) but less so for disease-free survival (HR 0.66; P = 0.068). The secondary outcome (15 000 mm2 mesenteric size) did not influence survival at any stage (removal of more mesentery did not alter survival). CONCLUSION: No general benefit of CME could be established. The observation of better overall survival in stage III on unplanned exploratory analysis is of uncertain significance.

[Asbestos: detection and characterization in tissue]. / Asbest: Nachweis und Charakterisierung im Gewebe.

BACKGROUND: When asbestos fibers are inhaled, asbestos bodies can form in the lungs with the involvement of macrophages. It can take decades from the last exposure to the onset of an asbestos-related disease. OBJECTIVES: The aim of this review is to present methods to detect asbestos bodies in lung tissue, the development of diagnostic criteria and to discuss pros and cons of different methods. MATERIALS AND METHODS: Observations and evaluations from the German Mesothelioma Register, along with relevant literature review and expert recommendations in guidelines are presented. RESULTS: Assessing asbestos-related diseases requires recognition of the person's occupational history, the asbestos fiber burden in the lungs, and determining fiber types. Various methods have been developed and validated, including light microscopy techniques such as bright-field microscopy, phase-contrast microscopy, polarization microscopy, and differential interference microscopy, as well as electron microscopy techniques like field-emission-scanning electron microscopy (e.g., FE-SEM) and transmission electron microscopy (TEM). CONCLUSION: The use of asbestos has been heavily restricted worldwide, even completely banned in Europe. Thus, patients' exposure to asbestos is decreasing. However, asbestos exposure during renovations, demolitions, or through unconscious handling of asbestos-containing materials remains a concern.

Fast and label-free automated detection of microsatellite status in early colon cancer using artificial intelligence integrated infrared imaging.

PURPOSE: Microsatellite instability (MSI) due to mismatch repair (MMR) defects accounts for 15-20% of colon cancers (CC). MSI testing is currently standard of care in CC with immunohistochemistry of the four MMR proteins representing the gold standard. Instead, label-free quantum cascade laser (QCL) based infrared (IR) imaging combined with artificial intelligence (AI) may classify MSI/microsatellite stability (MSS) in unstained tissue sections user-independently and tissue preserving. METHODS: Paraffin-embedded unstained tissue sections of early CC from patients participating in the multicentre AIO ColoPredict Plus (CPP) 2.0 registry were analysed after dividing into three groups (training, test, and validation). IR images of tissue sections using QCL-IR microscopes were classified by AI (convolutional neural networks [CNN]) using a two-step approach. The first CNN (modified U-Net) detected areas of cancer while the second CNN (VGG-Net) classified MSI/MSS. End-points were area under receiver operating characteristic (AUROC) and area under precision recall curve (AUPRC). RESULTS: The cancer detection in the first step was based on 629 patients (train n = 273, test n = 138, and validation n = 218). Resulting classification AUROC was 1.0 for the validation dataset. The second step classifying MSI/MSS was performed on 547 patients (train n = 331, test n = 69, and validation n = 147) reaching AUROC and AUPRC of 0.9 and 0.74, respectively, for the validation cohort. CONCLUSION: Our novel label-free digital pathology approach accurately and rapidly classifies MSI vs. MSS. The tissue sections analysed were not processed leaving the sample unmodified for subsequent analyses. Our approach demonstrates an AI-based decision support tool potentially driving improved patient stratification and precision oncology in the future.

Reactive mesothelial hyperplasia mimicking mesothelioma in an African green monkey (Chlorocebus aethiops).

A spontaneous reactive mesothelial hyperplasia occurred in a female, 15.7-year-old African green monkey (grivet; Chlorocebus aethiops). At necropsy, massive effusions were found in the abdomen, the thorax, and the pericardium. Additionally, multiple small, beige-gray nodules were detected on the serosal surfaces of the abdominal organs. Histopathologically, the mesothelial cells resembled the epithelioid subtype of a mesothelioma, but no infiltrative or invasive growth could be demonstrated. The mesothelial cells on the thoracis, liver, and intestinal serosa were accompanied by chronic serositis. Mesothelial cells expressed cytokeratin, vimentin, calretinin, desmin, Wilms Tumor 1 (WT-1) protein, and epithelial membrane antigen (EMA). Cells were negative for carcinoembryonic antigen (CEA), cluster of differentiation 15 (CD15), and podoplanin. Ultrastructurally, cells revealed a moderate amount of microvilli of medium length, perinuclear tonofilament bundles, and long desmosomes. In fluorescence in situ hybridization (FISH) for the detection of characteristic gene loss (p16; CDKN2A), NF2, and MTAP, no deletions were detected. No asbestos fibers and no presence of Simian virus 40 antigen (SV40) could be demonstrated.

A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors.

PURPOSE: According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used to assist in making treatment decisions after consideration of conventional markers. We developed and validated a gene expression signature predicting the likelihood of distant recurrence in patients with estrogen receptor (ER)-positive, HER2-negative breast cancer treated with adjuvant endocrine therapy. EXPERIMENTAL DESIGN: RNA levels assessed by quantitative reverse transcriptase PCR in formalin-fixed, paraffin-embedded tumor tissue were used to calculate a risk score (Endopredict, EP) consisting of eight cancer-related and three reference genes. EP was combined with nodal status and tumor size into a comprehensive risk score, EPclin. Both prespecified risk scores including cutoff values to determine a risk group for each patient (low and high) were validated independently in patients from two large randomized phase III trials [Austrian Breast and Colorectal Cancer Study Group (ABCSG)-6: n = 378, ABCSG-8: n = 1,324]. RESULTS: In both validation cohorts, continuous EP was an independent predictor of distant recurrence in multivariate analysis (ABCSG-6: P = 0.010, ABCSG-8: P < 0.001). Combining Adjuvant!Online, quantitative ER, Ki67, and treatment with EP yielded a prognostic power significantly superior to the clinicopathologic factors alone [c-indices: 0.764 vs. 0.750, P = 0.024 (ABCSG-6) and 0.726 vs. 0.701, P = 0.003 (ABCSG-8)]. EPclin had c-indices of 0.788 and 0.732 and resulted in 10-year distant recurrence rates of 4% and 4% in EPclin low-risk and 28% and 22% in EPclin high-risk patients in ABCSG-6 (P < 0.001) and ABCSG-8 (P < 0.001), respectively. CONCLUSIONS: The multigene EP risk score provided additional prognostic information to the risk of distant recurrence of breast cancer patients, independent from clinicopathologic parameters. The EPclin score outperformed all conventional clinicopathologic risk factors.