Surgical Management and Outcomes of Patients with Multifocal Hepatoblastoma.

OBJECTIVE: To compare the outcomes of patients with multifocal hepatoblastoma (HB) treated at our institution with either orthotopic liver transplant (OLTx) or hepatic resection to determine outcomes and risk factors for recurrence. BACKGROUND: Multifocality in HB has been shown to be a significant prognostic factor for recurrence and worse outcome. The surgical management of this type of disease is complex and primarily involves OLTx to avoid leaving behind microscopic foci of disease in the remnant liver. METHODS: We performed a retrospective chart review on all patients <18 years of age with multifocal HB treated at our institution between 2000 and 2021. Patient demographics, operative procedure, post-operative course, pathological data, laboratory values, short- and long-term outcomes were analyzed. RESULTS: A total of 41 patients were identified as having complete radiologic and pathologic inclusion criteria. Twenty-three (56.1%) underwent OLTx and 18 (43.9%) underwent partial hepatectomy. Median length of follow-up across all patients was 3.1 years (IQR 1.1-6.6 years). Cohorts were similar in rates of PRETEXT designation status identified on standardized imaging re-review (p = .22). Three-year overall survival (OS) estimate was 76.8% (95% CI: 60.0%-87.3%). There was no difference in rates of recurrence or overall survival in patients who underwent either resection or OLTx (p = .54 and p = .92 respectively). Older patients (>72 months), patients with a positive porta hepatis margin, and patients with associated tumor thrombus experienced worse recurrence rates and survival. Histopathology demonstrating pleomorphic features independently associated with worse rates of recurrence. CONCLUSIONS: Through proper patient selection, multifocal HB was adequately treated with either partial hepatectomy or OLTx with comparable outcome results. HB with pleomorphic features, increased patient age at diagnosis, involved porta hepatis margin on pathology, and the presence of associated tumor thrombus may be associated with worse outcomes regardless of the local control surgery offered. LEVEL OF EVIDENCE: III.

Association of Second-generation Antiandrogens With Cognitive and Functional Toxic Effects in Randomized Clinical Trials: A Systematic Review and Meta-analysis.

Importance: The use of second-generation antiandrogens (AAs) in the treatment of prostate cancer is increasing. Retrospective evidence suggests an association between second-generation AAs and adverse cognitive and functional outcomes, but further data from prospective trials are needed. Objective: To examine whether evidence from randomized clinical trials (RCTs) in prostate cancer supports an association between second-generation AAs and cognitive or functional toxic effects. Data Sources: PubMed, EMBASE, and Scopus (inception to September 12, 2022). Study Selection: Randomized clinical trials of second-generation AAs (abiraterone, apalutamide, darolutamide, or enzalutamide) among individuals with prostate cancer that reported cognitive toxic effects, asthenic toxic effects (eg, fatigue, weakness), or falls were evaluated. Data Extraction and Synthesis: Study screening, data abstraction, and bias assessment were completed independently by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Enhancing the Quality and Transparency of Health Research reporting guidelines. Tabular counts for all-grade toxic effects were determined to test the hypothesis formulated before data collection. Main Outcomes and Measures: Risk ratios (RRs) and SEs were calculated for cognitive toxic effects, asthenic toxic effects, and falls. Because fatigue was the asthenic toxic effect extracted from all studies, data on fatigue are specified in the results. Meta-analysis and meta-regression were used to generate summary statistics. Results: The systematic review included 12 studies comprising 13 524 participants. Included studies had a low risk of bias. An increased risk of cognitive toxic effects (RR, 2.10; 95% CI, 1.30-3.38; P = .002) and fatigue (RR, 1.34; 95% CI, 1.16-1.54; P < .001) was noted among individuals treated with second-generation AAs vs those in the control arms. The findings were consistent in studies that included traditional hormone therapy in both treatment arms for cognitive toxic effects (RR, 1.77; 95% CI, 1.12-2.79; P = .01) and fatigue (RR, 1.32; 95% CI, 1.10-1.58; P = .003). Meta-regression supported that, across studies, increased age was associated with a greater risk of fatigue with second-generation AAs (coefficient, 0.75; 95% CI, 0.04-0.12; P < .001). In addition, the use of second-generation AAs was associated with an increased risk of falls (RR, 1.87; 95% CI, 1.27-2.75; P = .001). Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that second-generation AAs carry an increased risk of cognitive and functional toxic effects, including when added to traditional forms of hormone therapy.

No Association of Sirolimus with Wound Complications in Children With Vascular Anomalies.

INTRODUCTION: Sirolimus has demonstrated effectiveness as a treatment option for several types of vascular anomalies; however, it has a potential side effect of delayed surgical wound healing. The purpose of this study was to evaluate the association of sirolimus with postoperative complications in the pediatric vascular anomaly population. METHODS: A retrospective cohort study was performed for children with a vascular anomaly who underwent excision or debulking of the anomaly from 2015 to 2020. Patient demographics, vascular anomaly characteristics, operative variables, sirolimus dosing information, and perioperative outcomes were collected. Univariate analysis was performed to compare outcomes based on the administration of sirolimus. RESULTS: Forty-seven patients with vascular anomalies underwent 57 surgical procedures (36 without perioperative sirolimus, 21 with perioperative sirolimus). The median age at the time of surgery was seven years (IQR 1.7-14.0). The most common anomalies were lymphatic and venolymphatic malformations. Of the patients administered perioperative sirolimus, the median preoperative and postoperative sirolimus levels were comparable (preoperative 6.9 ng/mL (IQR 4.9-10.1), postoperative 6.5 ng/mL (IQR 4.7-9.4)). The rate of postoperative complications (sirolimus 19%, without sirolimus 11%; p = 0.45) and wound complications (sirolimus 14%, without sirolimus 6%; p = 0.26) were comparable between the cohorts. CONCLUSION: Our results suggest sirolimus may not significantly increase perioperative complication rates in pediatric patients undergoing resection of their vascular anomaly. LEVEL OF EVIDENCE: Level III.