Surgical Approach to Hemipalatal Discrepancy in Tessier 7 Reconstruction: Review of Literature and Case Series.

OBJECTIVE: The authors present findings and techniques to address hemipalatal discrepancy in patients with Tessier 7 cleft and associated cleft palate during cleft palatoplasty. DESIGN: The authors report 2 cases of pediatric patients with Tessier 7 facial clefts and associated cleft palate. One patient presents on the broader oculo-auriculo-vertebral spectrum and the other is has isolated Tessier cleft 7. Additionally, a PubMed search was performed using the MeSH terms "tessier 7," "cleft palate", "macrostomia," "tessier 7 AND cleft palate," "macrostomia AND cleft palate," AND "hemipalatal discrepancy." All relevant literature was identified and underwent full review for qualitative analysis. RESULTS: Two patients met criteria for inclusion in this article. The surgical techniques utilized to mitigate the hemipalatal length discrepancy are detailed, and intraoperative photographs are provided. The results of the literature review are also presented. Tessier 7 craniofacial cleft and palatal clefts, when occurring in combination, is noted to result in discrepant hemipalatal length with short maxillary palate length on the affected side as well hypoplasia of the associated speech musculature. The postoperative palatal length after palatoplasty in both patients was longer than the preoperative hypoplastic palatal length. CONCLUSIONS: When occurring in combination, Tessier 7 craniofacial cleft and concomitant palatal cleft results in discrepant hemipalatal length, and deficiency of the bony maxillary palatal shelves, and associated speech musculature and soft tissues. The techniques described in this article may assist in maximizing postoperative palatal length.

Genomic Characterization of de novo Metastatic Breast Cancer.

PURPOSE: In contrast to recurrence after initial diagnosis of stage I-III breast cancer [recurrent metastatic breast cancer (rMBC)], de novo metastatic breast cancer (dnMBC) represents a unique setting to elucidate metastatic drivers in the absence of treatment selection. We present the genomic landscape of dnMBC and association with overall survival (OS). EXPERIMENTAL DESIGN: Targeted DNA sequencing (OncoPanel) was prospectively performed on either primary or metastatic tumors from 926 patients (212 dnMBC and 714 rMBC). Single-nucleotide variants, copy-number variations, and tumor mutational burden (TMB) in treatment-naïve dnMBC primary tumors were compared with primary tumors in patients who ultimately developed rMBC, and correlated with OS across all dnMBC. RESULTS: When comparing primary tumors by subtype, MYB amplification was enriched in triple-negative dnMBC versus rMBC (21.1% vs. 0%, P = 0.0005, q = 0.111). Mutations in KMTD2, SETD2, and PIK3CA were more prevalent, and TP53 and BRCA1 less prevalent, in primary HR+/HER2- tumors of dnMBC versus rMBC, though not significant after multiple comparison adjustment. Alterations associated with shorter OS in dnMBC included TP53 (wild-type: 79.7 months; altered: 44.2 months; P = 0.008, q = 0.107), MYC (79.7 vs. 23.3 months; P = 0.0003, q = 0.011), and cell-cycle (122.7 vs. 54.9 months; P = 0.034, q = 0.245) pathway genes. High TMB correlated with better OS in triple-negative dnMBC (P = 0.041). CONCLUSIONS: Genomic differences between treatment-naïve dnMBC and primary tumors of patients who developed rMBC may provide insight into mechanisms underlying metastatic potential and differential therapeutic sensitivity in dnMBC. Alterations associated with poor OS in dnMBC highlight the need for novel approaches to overcome potential intrinsic resistance to current treatments.

Surgical Management of Pediatric Lymphedema: A Systematic Review.

BACKGROUND: Lymphedema is a rare, progressive, and debilitating condition caused by failure of the lymphatic system to adequately drain the protein-rich fluid exiting the capillaries. Conservative management is often emphasized in pediatric patients, resulting in a paucity of literature describing surgical treatment in this population. METHODS: A systematic review was performed using PubMed, ScienceDirect, and Google Scholar to identify all studies describing surgical management of lymphedema in the pediatric population. RESULTS: Of the 343 relevant articles identified, 14 met the criteria for full review. Articles were divided into the following treatment categories: genital lymphedema, excisional procedures for extremity lymphedema, and physiologic procedures for extremity lymphedema. Outcomes for genital lymphedema were overall positive. For extremity lymphedema, excisional procedures yielded good results overall and included the majority of patients in this study. Physiologic procedures had mixed outcomes in the small population included in this study, but definitive conclusions cannot be drawn due to the paucity of existing data. CONCLUSION: While conservative management of pediatric lymphedema is well described, the literature remains sparse regarding surgical treatment. Further studies are needed to evaluate efficacy and outcomes in all three categories in this population.

Identifying ERBB2 Activating Mutations in HER2-Negative Breast Cancer: Clinical Impact of Institute-Wide Genomic Testing and Enrollment in Matched Therapy Trials.

PURPOSE: The yield of comprehensive genomic profiling in recruiting patients to molecular-based trials designed for small subgroups has not been fully evaluated. We evaluated the likelihood of enrollment in a clinical trial that required the identification of a specific genomic change based on our institute-wide genomic tumor profiling. PATIENTS AND METHODS: Using genomic profiling from archived tissue samples derived from patients with metastatic breast cancer treated between 2011 and 2017, we assessed the impact of systematic genomic characterization on enrollment in an ongoing phase II trial (ClinicalTrials.gov identifier: NCT01670877). Our primary aim was to describe the proportion of patients with a qualifying ERBB2 mutation identified by our institutional genomic panel (OncoMap or OncoPanel) who enrolled in the trial. Secondary objectives included median time from testing result to trial registration, description of the spectrum of ERBB2 mutations, and survival. Associations were calculated using Fisher's exact test. RESULTS: We identified a total of 1,045 patients with metastatic breast cancer without ERBB2 amplification who had available genomic testing results. Of these, 42 patients were found to have ERBB2 mutation and 19 patients (1.8%) were eligible for the trial on the basis of the presence of an activating mutation, 18 of which were identified by OncoPanel testing. Fifty-eight percent of potentially eligible patients were approached, and 33.3% of eligible patients enrolled in the trial guided exclusively by OncoPanel testing. CONCLUSION: More than one half of eligible patients were approached for trial participation and, significantly, one third of those were enrolled in NCT01670877. Our data illustrate the ability to enroll patients in trials of rare subsets in routine clinical practice and highlight the need for these broadly based approaches to effectively support the success of these studies.