Objective RAD51D, a gene in the Fanconi Anemia-BRCA homologous recombination pathway, has recently been shown to harbor germline mutations responsible for ovarian carcinoma in multiply affected families. We aimed to extend these results to ovarian carcinoma in the general population. Methods We sequenced RAD51D in germline DNA from 360 individuals with primary ovarian, peritoneal or fallopian tube carcinoma who were not selected for age of cancer onset or family history. We also sequenced RAD51D in 459 probands from 226 high risk breast cancer families who were wild type for 21 breast and ovarian cancer genes. Results Of 360 cases, three (0.8%) carried loss-of-function mutations in RAD51D. All three subjects had ovarian carcinoma; one was also diagnosed with a synchronous endometrial carcinoma. Only one of the three subjects had a family history of breast or ovarian cancer. Combined with previous data for this series, 23.9% of women with unselected ovarian, fallopian tube, or peritoneal carcinoma carried a germline loss-of-function mutation in any of 13 tumor suppressor genes. Among the 449 women and 10 men with familial breast cancer, none carried a loss of function mutation in RAD51D. Conclusions These data support the previous observation that loss-of-function mutations in RAD51D predispose to ovarian carcinoma but not to breast carcinoma. We conclude that inherited ovarian cancer is highly heterogeneous genetically, and that approximately one in four ovarian carcinoma patients carry a germline mutation in a known tumor suppressor gene that confers high risk.

Purpose Lateral pelvic sidewall lymph nodes (PSW LN) may be involved in up to 24% of locoregionally advanced rectal cancers. PSW LN are not resected in total mesorectal excision (TME), and no standard of care regarding the management of PSW LN exists in the United States. We assessed our institutional experience of preoperative radiation therapy (RT) boost to clinically involved PSW LN that were not planned for resection. Methods and materials Data from all patients with rectal adenocarcinoma treated between 2006 and 2018 were reviewed to identify those who received a cumulative dose of >50.4 Gy to suspicious PSW LN during neoadjuvant chemoradiation therapy (nCRT). Demographic, cancer characteristic, treatment, and toxicity data were derived from the chart. Results Of a total of 261 patients, 12 patients met the inclusion criteria. The median age was 47.5 years, and 83% of patients were men. All patients had T3/4 disease, 17% of patients had N1b disease and the remainder had N2 disease, and 33% had M1 disease (all ≤2 metastases). Seventy-five percent of patients had moderately or poorly differentiated histology. The mean distance from the anal verge was 4.85 cm (range, 2-8.9 cm), and 58% had ≥2 PSW LN with an average short axis diameter of 1.11 cm (range, 0.4-3.2 cm). Boost doses ranged from 53.48 Gy to 60.2 Gy in 27 to 30 fractions (1.8-2.15 Gy/fraction). The median follow-up time was 18 months. One patient who received concurrent capecitabine and irinotecan had grade 3 perineal dermatitis and anemia during nCRT. The median hospitalization time for TME was 6.5 days. Within 90 days of TME, 1 patient required surgical exploration for perineal wound breakdown, and another required a blood transfusion for anemia. At the time of the last follow up, 75% of patients were alive. Local control at 12 months was 90%. Conclusions RT dose escalation to nonresected PSW LN during nCRT was well tolerated with a low risk of acute toxicity and perioperative complications and has a high rate of local control at 12 months. RT boost warrants further study in patients with clinically involved nonresected PSW LN.

Surgical simulation programs have the potential to broadly benefit numerous healthcare stakeholders. Patients, hospital, and surgeons themselves all stand to gain, either directly or indirectly, from skills that can be learned and refined through simulation. This is especially true in communities with residencies and fellowships where proficiency of surgical technique remains in development for novice surgeons. With public pressure for increased oversight of surgeons in training, prevention of medical errors, reductions in health care costs and decreased work hours, current residents have a much different training experience today than in years past [1][2][3][4]. Limited work hours have led to reduced exposure of surgical trainees to operative procedures and the ability to practice those associated technical skills [5]. Bridging this educational gap will become more important than ever as proficiency-based evaluation overtakes the traditional time-based model [6][7][8]. Many now look to simulation as the possible solution for deficits emerging in current surgical training and as a way to improve patient safety and possibly overall costs.