The Morcellation "Debate" and the FDA 510(k) Process-A Call for Further Reform.

IMPORTANCE: Few gynecologic surgeons understand the mechanism by which surgical instruments are approved for human use and marketing or do they appreciate the central role they play in postmarket surveillance and reporting after instruments have come to market. OBJECTIVE: Using the experience with the uterine morcellator, this review will detail the Food and Drug Administration (FDA) system for approving surgical instruments and the potential pitfalls of this process. EVIDENCE ACQUISITION: Literature review and public documents from the FDA. RESULTS: The FDA 510(k) approval process for surgical instruments relies largely on postmarket surveillance as exemplified by the uterine power morcellator, which was approved before sufficient evidence was available regarding its potential harms. CONCLUSIONS: The current system currently transfers the responsibility of ensuring safety and efficacy to the public, patients, and providers. To minimize potential harm, the FDA needs to incorporate a greater standard of evidence into its framework for the approval and regulation of medical devices. The burden of these requirements should be borne at least in part by the companies bringing equipment to market. RELEVANCE: It is incumbent on all surgeons to be vigilant in their objective critical assessment of new instrumentation and report their outcomes after they come to market.

Cancer Stem Cells in the Development of Novel Therapeutics for Refractory Pediatric Leukemia.

Although treatment strategies for pediatric leukemia have improved overall survival rates in the recent past, relapse rates in certain subgroups such as infant leukemia remain unacceptably high. Despite undergoing extensive chemotherapy designed to target the rapidly proliferating leukemia cells, many of these children experience relapse. In refractory leukemia, the existence of cell populations with stemness characteristics, termed leukemia stem cells (LSCs), which remain quiescent and subsequently replenish the blast population, has been described. A significant body of evidence exists, derived largely from xenograft models of adult acute myeloid leukemia, to support the idea that LSCs may play a fundamental role in refractory disease. In addition, clinical studies have also linked LSCs with increased minimal residual disease, higher relapse rate, and decreased survival rates in these patients. Recently, a number of reports have addressed effective ways to utilize new-generation genomic sequencing and transcriptomic analyses to identify targeted therapeutic agents aimed at LSCs, while sparing normal hematopoietic stem cells. These data underscore the value of timely translation of knowledge from adult studies to the unique molecular and physiological characteristics seen in pediatric leukemia. We aim to summarize this article in the rapidly expanding field of stem cell biology in hematopoietic malignancies, focusing particularly on relevant preclinical models and novel targeted therapeutics, and their applicability to childhood leukemia.

Surgeon Volume in Benign Gynecologic Surgery: Review of Outcomes, Impact on Training, and Ethical Contexts.

It is becoming increasingly clear that surgeon volume affects surgical outcomes. High-volume surgeons demonstrate reduced perioperative complications, shorter operative times, and reduced blood loss during multiple modalities of benign gynecologic surgery. Furthermore, high-volume surgeons consistently demonstrate higher rates of minimally invasive approaches, low rates of conversion to laparotomy, and lower per-procedure case costs. It is suggested that surgeons who have completed postresidency training have improved surgical outcomes, although these data are limited. Surgical exposure in obstetrics and gynecology residency is varied and does not consistently meet demonstrated surgical learning curves. Deficiencies in residency surgical training may be related to the volume-outcome relationship. We suggest reforming residency surgical training and tracking postresidency practice to provide optimal surgical care. Additionally, surgeons may have an ethical obligation to inform patients of their surgical volume and outcomes, with options for referrals if needed.