Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

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Bladder preservation or complete cystectomy during pelvic exenteration of patients with locally advanced or recurrent rectal cancer,what should we do?

IntroductionIn patients with locally advanced (LARC) or locally recurrent (LRRC) rectal cancer and bladder involvement, pelvic exenteration (PE) with partial (PC) or radical (RC) cystectomy can potentially offer a cure. The study aim was to compare PC and RC in PE patients in terms of oncological outcome, post-operative complications and quality-of-life (QoL).Materials & methodsThis was a retrospective cohort analysis of a prospectively maintained surgical database. Patients who underwent PE for LARC or LRRC cancer with bladder involvement between 1998 and 2021 were included. Post-operative complications and overall survival were compared between patients with PC and RC.Results60 PC patients and 269 RC patients were included. Overall R0 resection was 84.3%. Patients with LRRC and PC had poorest oncological outcome with 69% R0 resection; patients with LARC and PC demonstrated highest R0 rate of 96.3% (P = 0.008). Overall, 1-, 3- and 5-year OS was 90.8%, 68.1% and 58.6% after PC, and 88.7%, 62.2% and 49.5% after RC. Rates of urinary sepsis or urological leaks did not differ between groups, however, RC patients experienced significantly higher rates of perineal wound- and flap-related complications (39.8% vs 25.0%, P = 0.032).ConclusionPC as part of PE can be performed safely with good oncological outcome in patients with LARC. In patients with LRRC, PC results in poor oncological outcome and a more aggressive surgical approach with RC seems justified. The main benefit of PC is a reduction in wound related complications compared to RC, although more urological re-interventions are observed in this group.     

Development of a machine learning algorithm to predict complications of total laparoscopic anterior resection and natural orifice specimen extraction surgery in rectal cancer

BackgroundTotal laparoscopic anterior resection (tLAR) and natural orifice specimen extraction surgery (NOSES) has been widely adopted in the treatment of rectal cancer (RC). However, no study has been performed to predict the short-term outcomes of tLAR using machine learning algorithms to analyze a national cohort.MethodsData from consecutive RC patients who underwent tLAR were collected from the China NOSES Database (CNDB). The random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), deep neural network (DNN), logistic regression (LR) and K-nearest neighbor (KNN) algorithms were used to develop risk models to predict short-term complications of tLAR. The area under the receiver operating characteristic curve (AUROC), Gini coefficient, specificity and sensitivity were calculated to assess the performance of each risk model. The selected factors from the models were evaluated by relative importance.ResultsA total of 4313 RC patients were identified, and 667 patients (15.5%) developed postoperative complications. The machine learning model of XGBoost showed more promising results in the prediction of complication than other models (AUROC 0.90, P < 0.001). The performance was similar when internal and external validation was used. In the XGBoost model, the top four influential factors were the distance from the lower edge of the tumor to the anus, age at diagnosis, surgical time and comorbidities. In risk stratification analysis, the rate of postoperative complications in the high-risk group was significantly higher than in the medium- and low-risk groups (P < 0.001).ConclusionThe machine learning model shows potential benefits in predicting the risk of complications in RC patients after tLAR. This novel approach can provide reliable individual information for surgical treatment recommendations.     

Genomic tools for health: Secondary findings as findings to be shared

PurposeWhether and how to disclose secondary finding (SF) information to children is ethically debated. Some argue that genetic testing of minors should be limited to preserve the child’s future autonomy. Others suggest that disclosure of SFs can occur if it is in the best interests of the child. However, the ways that parents conceptualize and weigh their child’s future autonomy against the interests of their child and other family members are unknown.MethodsTo explore how parents understand SF disclosure in the context of their child and other family members’ lives, we conducted semistructured interviews with 30 families (40 parents in total). All parents had children who were enrolled in a genetic sequencing protocol that returned results by default.ResultsWe found that parents did not routinely conceptualize SFs as distinctive health information. Rather parents saw this information as part of their child’s overall health. To make decisions about disclosure, parents weighed their child’s ability to understand the SF information and their other family member’s need to know.ConclusionBecause most families desired SF information, we argue that disclosure of SF be reconceptualized to reflect the lived experiences of those who may receive this information.