Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants.

PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient-participants and their clinicians. We queried patient-participants' electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient-participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient-participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer-including a stage 1C fallopian tube cancer-via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.

Dual-console robotic surgery compared to laparoscopic surgery with respect to surgical outcomes in a gynecologic oncology fellowship program.

OBJECTIVE: Minimally invasive surgical techniques decrease surgical morbidity and recovery time. Studies demonstrate similar surgical outcomes comparing robotic to laparoscopic surgery. These studies have not accounted for the incorporation of fellow education. With the dual-console da Vinci Si Surgical System®, a two surgeon approach could be performed. We sought to compare surgical outcomes at a gynecologic oncology fellowship program of traditional laparoscopic to robotic surgeries using the dual-console system. METHODS: We identified patients who underwent laparoscopic or robotic surgery performed by a gynecologic oncologist from November 2009-November 2010. Robotic surgeries were conducted using the dual-console, utilizing a two surgeon approach. Surgeries involved a staff physician with a gynecologic oncology fellow. Statistical analysis was performed using student t-test and chi-squared analysis. RESULTS: A total of 222 cases were identified. Cases were analyzed in groups: all cases identified, all cancer cases, and endometrial cancer cases only. When analyzing all cases, no statistical difference was noted in total operating room time (172 vs. 175 min; p=0.6), pelvic lymph nodes removed (10.1 vs. 9.6; p=0.69), para-aortic lymph nodes dissected (3.7 vs. 3.8; p=0.91), or length of stay (1.5 vs. 1.3 days; p=0.3). There was a significant difference in total surgical time (131 vs.110 min; p<0.0001) and EBL (157 vs.94 ml; p<0.0001), favoring robotic surgery. When analyzing all cancer cases, the advantage in total surgical time for robotic surgery was lost. Complications were similar between cohorts. CONCLUSION: Incorporating fellow education into robotic surgery does not adversely affect outcomes when compared to traditional laparoscopic surgery.

Outcomes of robotic surgery in morbidly obese patients with endometrial cancer: a retrospective study.

With advances in minimal invasive surgery, robotic surgery has become the widespread approach for surgical staging of endometrial cancer in the obese population. This study aimed to evaluate safety and surgical outcomes of robotic surgery in the morbidly obese and extremely morbidly obese patients with endometrial cancer. Retrospective cohort study. A total of 391 obese women undergoing robotic-assisted surgical staging were identified and included in the study. Surgical outcomes for obese patients (BMI > 30 kg/m2) who underwent surgical staging between 2011 and 2019 were retrospectively collected. Preoperative characteristics, perioperative outcomes and postoperative complications were analyzed among the categories of obesity (BMI ≥ 30-34.9 kg/m2, ≥ 35-39.9 kg/m2, ≥ 40-49.9 kg/m2) including the extremely morbid obese (BMI > 50 kg/m2). Comparative analysis revealed a higher percentage of postoperative complications with increasing BMI, although the results were not statistically significant. Postoperative complications are observed at higher rates among women with increasing BMI.

Conservative surgery in early-stage cervical cancer: what percentage of patients may be eligible for conization and lymphadenectomy?

OBJECTIVE: To determine the proportion of young patients with early-stage invasive cervical cancer treated with radical hysterectomy who may have been eligible for fertility-sparing surgery consisting of cervical conization with pelvic lymph node dissection. METHODS: We retrospectively identified all patients with early-stage cervical cancer (stages IA1-IB1) who underwent a radical hysterectomy at The University of Texas M. D. Anderson Cancer Center between 1990 and 2009. We reviewed these patients' records to identify patients who were <40 years who had not previously undergone tubal ligation and who would have been considered candidates for cold-knife conization with pelvic lymph node dissection-i.e., women with tumors smaller than 2 cm, low-risk histology (squamous, adenocarcinoma, or adenosquamous), and no lymphovascular space invasion (LVSI). RESULTS: A total of 507 patients with early-stage cervical cancer were identified who underwent radical hysterectomy during the review period. Of these women, 277 (55%) were 40 years or younger. Of these 277 patients, 75 (27%) had had a previous tubal ligation and 202 (73%) had not. Of these 202 patients potentially interested in fertility preserving surgery, 53 (26%) had favorable pathologic characteristics including low-risk histology, tumors ≤2 cm in size and no LVSI present. Of these 53 patients, none had parametrial involvement or positive lymph nodes. CONCLUSION: Among 202 women with age younger than 40 years and no previous tubal ligation who underwent radical hysterectomy, 53 (26%) may have been eligible for fertility-sparing surgery such as cold-knife conization with pelvic lymph node dissection.

Recurrent breast carcinoma presenting as postmenopausal vaginal bleeding: A case report.

•We discuss the recurrence of breast carcinoma presenting as postmenopausal vaginal bleeding in a patient on Tamoxifen therapy.•Case report illustrates widespread genital tract manifestation of recurrent disease at time of presentation and rapid disease progression.•Discusses the importance of maintaining broad differential in diagnosis of postmenopausal vaginal bleeding.

Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity.

PURPOSE: Bevacizumab (Bev) is associated with improved progression-free survival in advanced epithelial ovarian cancer. The use of Bev in patients with gynecologic malignancy is increasing; however, little is known about cumulative toxicity and response in patients retreated with Bev. Our goal was to determine cumulative side effects and response in patients retreated with Bev. PATIENTS AND METHODS: Women with recurrent gynecologic malignancy treated with Bev between January 2007 and March 2012 at a single institution were identified, including a subset who received Bev in a subsequent regimen. The primary outcome was Bev-associated toxicity, and the secondary outcome was response. RESULTS: Of 83 patients that received Bev for recurrent disease, 23 were retreated with Bev and four received Bev maintenance. Three patients (13%) developed grade 3 or 4 hypertension; all had a history of chronic hypertension. One (4.3%) patient developed grade 3 proteinuria, and one (4.3%) developed an enterovaginal fistula. Four patients discontinued Bev secondary to toxicity. Toxicity was not related to the cumulative number of cycles. Twenty-six percent of patients responded to Bev retreatment. On univariate analysis, there was a significant (P=0.003) overall survival advantage when the Bev-free interval was >9 months (95% confidence interval [CI] 4.9-43.7) compared to ≤9 months (95% CI 2.1-11.5), 24.3 months, and 6.8 months. CONCLUSION: Retreatment of patients with recurrent gynecologic malignancy with Bev did not increase morbidity and was associated with treatment response. Physicians treating women with recurrent disease may consider a Bev-containing regimen even if prior regimen(s) included Bev. Future studies should prospectively evaluate the efficacy of this treatment strategy.

Dual-console robotic surgery: a new teaching paradigm.

Robotic surgery has emerged as an alternative option in minimally invasive gynecologic surgery. The development of the dual-console da Vinci Si Surgical System(®) has enabled modification of the training atmosphere. We sought to investigate operative times and surgical outcomes while operating with the dual-console model in a training environment for our first fifty cases. We identified the first fifty patients who underwent robot-assisted total hysterectomy (TRH), with or without bilateral salpingo-oophorectomy (BSO), with or without pelvic and para-aortic lymph node dissection (PPALND), by use of the dual-console robotic system. Records were reviewed for patient demographics and surgical details. All surgery was conducted using the dual-console system and performed by staff physicians and fellows. Operative time was calculated from robotic docking until completion of the procedure. Cases were identified from November 2009 through July 2010. Mean age was 56.2 years (SD 13.35, 95 % CI 52.46-59.86). Mean BMI was 29.5 (SD 7.67, 95 % CI 27.35-31.61). Seventy-eight percent of these patients were considered overweight, including 12 defined as obese (BMI 30-34.9) and 10 patients classified as morbidly obese (BMI ≥ 35). Surgery completed included PPALND alone (n = 1); radical hysterectomy (n = 1); TRH only (n = 3); TRH/BSO (n = 25); and TRH/BSO/PPALND (n = 20). Mean total operating room time was 188.8 min (SD 55.31, 95 % CI 173.45-204.11). Mean total surgical time for all cases was 118.1 min (SD 44.28, 95 % CI 105.87-130.41). Two vascular injuries were encountered, with one requiring conversion to laparotomy. These results compare favorably with historically reported outcomes from single-console systems. Utilizing the dual-console enables use of an integrated teaching and supervising environment without compromising operative times or patient outcomes.

Proteomic Analysis of Matched Formalin-Fixed, Paraffin-Embedded Specimens in Patients with Advanced Serous Ovarian Carcinoma.

OBJECTIVE: The biology of high grade serous ovarian carcinoma (HGSOC) is poorly understood. Little has been reported on intratumoral homogeneity or heterogeneity of primary HGSOC tumors and their metastases. We evaluated the global protein expression profiles of paired primary and metastatic HGSOC from formalin-fixed, paraffin-embedded (FFPE) tissue samples. METHODS: After IRB approval, six patients with advanced HGSOC were identified with tumor in both ovaries at initial surgery. Laser capture microdissection (LCM) was used to extract tumor for protein digestion. Peptides were extracted and analyzed by reversed-phase liquid chromatography coupled to a linear ion trap mass spectrometer. Tandem mass spectra were searched against the UniProt human protein database. Differences in protein abundance between samples were assessed and analyzed by Ingenuity Pathway Analysis software. Immunohistochemistry (IHC) for select proteins from the original and an additional validation set of five patients was performed. RESULTS: Unsupervised clustering of the abundance profiles placed the paired specimens adjacent to each other. IHC H-score analysis of the validation set revealed a strong correlation between paired samples for all proteins. For the similarly expressed proteins, the estimated correlation coefficients in two of three experimental samples and all validation samples were statistically significant (p < 0.05). The estimated correlation coefficients in the experimental sample proteins classified as differentially expressed were not statistically significant. CONCLUSION: A global proteomic screen of primary HGSOC tumors and their metastatic lesions identifies tumoral homogeneity and heterogeneity and provides preliminary insight into these protein profiles and the cellular pathways they constitute.

Epithelioid trophoblastic tumor: a case report and review of the literature.

Epithelioid trophoblastic tumor (ETT) is a rare gestational trophoblastic tumor. Cases of ETT present as abnormal vaginal bleeding in women of reproductive age, with low human chorionic gonadotropin (hCG) levels. ETT can be a sequela of any gestational event and can present in both intrauterine and extrauterine sites. Metastasis and death have been reported. We present a case of a 44-year-old female incidentally diagnosed with ETT following laparoscopic-assisted vaginal hysterectomy. Postoperative evaluation for metastatic disease was negative. The patient has been closely followed and remains disease free 8 months postoperatively. ETT presents a diagnostic challenge due to its rarity and histologic resemblance to other pathologies. ETT is relatively chemoresistant and managed surgically. Misdiagnosis delays effective treatment and affects survival.

Malignant transformation of a mature cystic ovarian teratoma into thyroid carcinoma, mucinous adenocarcinoma, and strumal carcinoid: a case report and literature review.

Malignant transformation of a mature cystic teratoma (MCT) is an infrequent, often asymptomatic event. We report the first example of a struma ovarii with a focus of follicular variant of papillary thyroid carcinoma (a), mucinous adenocarcinoma (b), and strumal carcinoid tumor (c)-all three arising in one mature cystic teratoma of the ovary. From our reviews, we found limited data to guide management when these malignant foci occur within an MCT. Consideration should be given to thyroidectomy followed by total-body scanning and serum studies for foci of thyroid carcinoma and adjuvant therapy with thyroidectomy and radioablation if residual disease is identified (a). Additionally, extrapolating from data for mucinous adenocarcinomas, consideration could be given to adjuvant chemotherapy after appropriate staging (b). Strumal carcinoid tumors should be treated as tumors of low malignant potential. Observation is appropriate if after complete staging, no invasive implants are noted (c).

Hormone response in ovarian cancer: time to reconsider as a clinical target?

Ovarian cancer is the sixth most common cancer worldwide among women in developed countries and the most lethal of all gynecologic malignancies. There is a critical need for the introduction of targeted therapies to improve outcome. Epidemiological evidence suggests a critical role for steroid hormones in ovarian tumorigenesis. There is also increasing evidence from in vitro studies that estrogen, progestin, and androgen regulate proliferation and invasion of epithelial ovarian cancer cells. Limited clinical trials have shown modest response rates; however, they have consistently identified a small subset of patients that respond very well to endocrine therapy with few side effects. We propose that it is timely to perform additional well-designed trials that should include biomarkers of response.

The diagnostic challenge of identifying isolated fallopian tube torsion: a case report of laparoscopic management.

Torsion of adnexal structures is a relatively uncommon occurrence. Isolated fallopian tube torsion is an even rarer gynecologic cause of acute low abdominal pain. Diagnosis of this condition is frequently delayed because of the rarity of its occurrence and prolonged investigations to rule out more common causes of acute abdominal pain on a differential diagnosis. A case of a 32-year-old woman with isolated right fallopian tube torsion managed laparoscopically is presented.