Outcomes of minimally invasive versus open abdominal hysterectomy in patients with gestational trophoblastic disease.

OBJECTIVE: The aim of this study is to compare surgical and oncologic outcomes for women undergoing MIH or open abdominal hysterectomy (OAH) for management of gestational trophoblastic disease (GTD). METHODS: Patients who underwent hysterectomy for GTD between January 1, 2009 and December 31, 2018 were identified using an institutional database and tumor registry. Patients were stratified based on indication for and mode of hysterectomy. RESULTS: 39 patients underwent hysterectomy for GTD - 22 MIH and 17 OAH. 26 hysterectomies (66.7%) were performed for primary treatment of GTD, 7 (17.9%) for chemoresistance, 2 (5.1%) for uterine hemorrhage, and 4 (10.3%) for other indications. Mean tumor size (4.2 vs 4.6 cm; p = .81) and operative time (136 vs 163 mins; p = .42) were similar in both groups. MIH was associated with significantly less blood loss (71.5 vs 427.3 ml; p = .03) and shorter hospital stay (1.5 vs 3.9 days, p = .02) than OAH. Postoperative histology comprised 12 complete moles (6 invasive), 8 choriocarcinomas, 9 placental site trophoblastic tumors and 9 epithelioid trophoblastic tumors. Median follow-up was 67.2 months (50.2 MIH, 79.3 OAH; range 11.1-131.2) and there was no difference in remission (81.8% MIH vs 76.5% OAH; p = .68). There were 7 recurrences (4 MIH, 3 OAH) and 3 deaths (2 MIH, 1 OAH). Overall survival was 97.3% at 2 years and 88.5% at 5 years. There was no significant difference in 5-year survival by mode of surgery (MIH 90.9%, OAH 83.3%; p = .40). CONCLUSIONS: Patients undergoing MIH at our centers have similar oncologic outcomes, lower surgical blood loss and shorter hospital stay compared to those undergoing OAH. Overall survival is similar regardless of mode of surgery.

Multivariable analysis of association of beta-blocker use and survival in advanced ovarian cancer.

OBJECTIVE: In this study, we sought to evaluate the relationship between survival and beta blocker use in both the primary and interval debulking setting while adjusting for frequently co-administered medications. METHODS: We performed a retrospective cohort study reviewing charts of women who underwent primary or interval cytoreduction for stage IIIC and IV epithelial ovarian cancer. The exposure of interest was beta-blocker use identified at the time of cytoreduction. The outcomes of interest were PFS and OS. We collected demographic/prognostic variables and information about use of aspirin, metformin, and statins. We used the Kaplan-Meier method and Cox proportional hazards models in survival analyses. RESULTS: 534 women who underwent surgery for stage IIIC or IV ovarian cancer were included in the study. The median age at diagnosis was 64 and 84.8% of women had serous carcinoma. We identified 105 women (19.7%) on a beta-blocker of whom 94 (90%) were on a cardioselective beta-blocker. Additionally, 24 women (4.5%) were on metformin, 91 (17%) on aspirin, and 128 (24%) on a statin. In univariable analysis, beta-blocker users had a median overall survival of 29 months vs 35 months among non-users (hazard ratio HR = 1.52, p = 0.007). After adjustment for important demographic, clinical, and histopathologic factors, as well as use of other common medications, beta-blocker use remain associated with an increased hazard of death (adjusted HR 1.57, p = 0.006). CONCLUSION: In this retrospective study, we found that patients identified as being on a beta-blocker at the time of surgery had worse overall survival and greater risk of death when compared to those patients not on betablockers. Importantly, 90% of patients on beta-blockers were identified as being on a cardioselective beta-blocker.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study.

OBJECTIVE: To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. METHODS: Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). RESULTS: The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. CONCLUSIONS: The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors.

Epithelioid trophoblastic tumor: A single institution case series at the New England Trophoblastic Disease Center.

OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is a rare form of gestational trophoblastic neoplasm which is distinct based on its development from intermediate trophoblast cells and nodular growth pattern. The aim of this study is to describe a case series from a single institution with a review of the literature to better understand the clinical characteristics and outcomes for patients with ETT. METHODS: A retrospective review was performed using the IRB approved New England Trophoblastic Disease Center (NETDC) database from 1998 to 2014. Eight patients were identified of which seven had complete records. Follow-up data was obtained from the longitudinal medical records. RESULTS: Four (57.1%) patients presented with vaginal bleeding and two (28.6%) patients were asymptomatic at presentation. Three (42.9%) patients had extrauterine disease. All three patients with extrauterine disease who received chemotherapy had stable or progressive disease at follow-up. Only two (29%) patients who presented with non-metastatic disease and underwent hysterectomy were alive with no evidence of disease. The mean interval following antecedent pregnancy was 104months. All patients with an interval >4years demonstrated stable or progressive disease despite intensive chemotherapy. Two patients with non-metastatic disease who declined hysterectomy developed stable or progressive disease despite chemotherapy. CONCLUSIONS: This series highlights several features of ETT including the potential for asymptomatic presentation of extrauterine disease. The series also demonstrates chemoresistance, even with multi-agent therapy and a poor prognosis with extrauterine disease and an interval greater than 4years following the antecedent pregnancy suggesting that surgery remains critical in disease control.

Phase II trial of erlotinib in women with squamous cell carcinoma of the vulva.

OBJECTIVE: To evaluate the efficacy and toxicity of erlotinib in the management of squamous cell carcinoma (SCC) of the vulva. METHODS: Patients with vulvar lesions amenable to surgery or chemoradiation (cohort 1) or those with metastatic measurable disease (cohort 2) received erlotinib 150 mg daily. Patients were monitored for toxicity. Responses were determined by digital photography or RECIST 1.1. Cohort 1 underwent pre and post treatment biopsies. EGFR immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and mutational analysis were performed. RESULTS: 41 patients were enrolled: 17 in cohort 1 and 24 in cohort 2. Notable grade 3 or 4 toxicities included allergic reaction (1), diarrhea/electrolyte abnormalities (3), ischemic colitis (1), and renal failure (3) and electrolyte abnormalities (n=2). Mean number of cycles for cohort 2 was 3.3. Overall clinical benefit rate was 67.5% with 11 (27.5%) partial responses (PR), 16 (40.0%) stable disease (SD), and 7 (17.5%) progressive disease. Responses were of short duration. All pre and post treatment biopsies exhibited 2-3+ EGFR staining. 5 of 14 patients (35%) were found to have EGFR amplification (n=3) or high polysomy/trisomy (n=2). These five patients had either a PR (n=3) or SD (n=2). Gain of function mutations were not been identified. CONCLUSIONS: This is the first reported controlled trial evaluating erlotinib for the management of vulvar carcinoma. Toxicities were acceptable given the lack of treatment options for these patients. Given the observed clinical benefits erlotinib may represent one of the most active agents available to treat vulvar SCC.

A comparison of outcome in patients with stage 1 clear cell and grade 3 endometrioid adenocarcinoma of the endometrium with and without adjuvant therapy.

OBJECTIVE: To determine the outcomes in patients with Stage I uterine clear cell carcinoma (UCCC) treated with and without adjuvant therapy, and to compare the outcomes in these patients to that of matched controls, patients with Stage I, grade 3, endometrioid adenocarcinoma of the endometrium (EC). METHODS: Patients with FIGO Stage I UCCC who underwent comprehensive surgical staging between January 1996 and January 2007 were identified. Cases (UCCC) were matched by age, stage, adjuvant therapy, and year of diagnosis to controls consisting of patients with grade 3 EC. Recurrence and survival were analyzed using the Kaplan-Meier method. RESULTS: 25 patients with Stage I UCCC were identified of whom 13 (52%) received no adjuvant therapy and 12 (48%) received adjuvant radiation therapy (XRT). The 5-year disease-free survival and overall survival rates for the observation and the XRT groups were 78% and 75%, (p = 0.7) and 85% and 82% (p = 0.1), respectively. When compared to controls, the 5-year disease-free survival rates and overall survival rates of patients with Stage I UCCC were not significantly different, 77% vs 75% (p = 0.8) and 84% vs 88% (p = 0.5), respectively. CONCLUSIONS: In patients with Stage I UCCC tumors there was no clear benefit to adjuvant radiation given the absence of improvement in recurrence risk or any survival benefit. These data question the benefit of radiation therapy in UCCC patients with disease confined to the uterus.

Impact of bowel obstruction at the time of initial presentation in women with ovarian cancer.

OBJECTIVE: To determine whether the presence of bowel obstruction at the time of initial presentation has any prognostic significance in these women. DESIGN: Retrospective cohort study. SETTING: Dedicated gynaecological oncology service of a large tertiary institution. POPULATION: Women who had a bowel obstruction as part of their initial presentation of ovarian cancer were identified between 1995 and 2007. Each woman was matched with four control women (with disease but no obstruction). METHODS: Women with disease were compared with controls to determine the impact, if any, of bowel obstruction at presentation. Several prognostic variables including bowel obstruction were also evaluated in a Cox proportional hazard model. MAIN OUTCOME MEASURES: Progression-free survival (PFS) and overall survival (OS). RESULTS: Forty-eight women with disease and 192 controls were identified during the study period. The median follow-up period was 19 months among women with disease versus 20 months in controls. No differences were seen in demographics and clinical characteristics of the women. Optimal cytoreduction rate was similar between the two groups (75% versus 78%, P = 0.7). Patients with bowel obstruction had a shorter PFS and OS compared with controls [19 months versus 21 months (P = 0.01) and 22 versus 35 months (P = 0.008)], respectively. Bowel obstruction at presentation was an independent prognostic variable with a hazard ratio of 1.5 (P = 0.009). Other prognostic variables were age, stage and extent of surgical cytoreduction. CONCLUSIONS: Bowel obstruction at the time of initial presentation is an adverse prognostic factor in women with ovarian cancer.

The epidemiology of ovarian granulosa cell tumors: a case-control study.

OBJECTIVE: This study identified risk factors for ovarian granulosa cell tumors (GCT) through a case-control study comparing women with GCT to women with epithelial ovarian cancers (OC) and general population (GP) controls. METHODS: Women with GCT and OC were identified from our hospital tumor board and the Massachusetts and New Hampshire Statewide Cancer Registries between January, 1988 and November, 2008. Age, gender and county matched GP controls were identified through town books in Massachusetts and drivers' license lists in New Hampshire. Epidemiologic factors including age, race, obesity, pregnancy history, smoking, and family history were evaluated. Odds ratio (OR) was calculated and adjusted for race and age. RESULTS: Seventy-two women with GCT, 1578 GP controls, and 1511 OC controls were identified. Patients with GCT were significantly more likely to be non-white (OR 8.49; 4.07, 17.7), obese with a BMI >30 (OR 5.80; 3.01, 11.2), and have a family history of breast (OR 2.13; 1.19, 3.80) or ovarian cancer (OR 2.89; 1.08, 7.72) than GP controls. The risk of developing GCT was significantly decreased in women who smoked (OR 0.46; 0.27, 0.78), used oral contraceptive pills (OR 0.32; 0.17, 0.63) or were parous with 1-2 (OR 0.30; 0.16-0.56) or greater than 2 births (OR 0.50; 0.27, 0.94) when compared to GP controls. CONCLUSION: These findings suggest an independent association between non-white race and obesity as a hyperestrogenic state in the development of GCT while parity and OCP use may be protective. An unknown familial predisposition for GCT may exist.

Role of the ultrasonic surgical aspirator in gynecology.

As is true in neurosurgery and general surgery, the ultrasonic surgical aspirator is a powerful tool for the general gynecologist and gynecologic oncologist in assisting in the treatment and management of benign and malignant diseases. The physical properties of ultrasonic sound waves along with the composition of the tissues in question allow for safe, selective, and precise tissue resection. Although the ultrasonic surgical aspirator has had favorable results to date and future applications seem promising, the ultimate role of this device needs to be established with clinical trials.

Pretreatment scalene node biopsy in gynecologic malignancy: prudent or passé?

OBJECTIVES: Surgicopathologic evaluation of the scalene fat pad is considered a critical step in the pretreatment evaluation of patients at our institution with cervical or corpus carcinoma when the periaortic lymph nodes (PAN) are involved. However, enthusiasm for this procedure at other centers has waned, largely due to a wide discrepancy in the reported rates of occult scalene node involvement. In an attempt to clarify the benefit of pretreatment scalene node sampling in gynecologic malignancies, we present our experience over the past 18 years. MATERIALS AND METHODS: We identified 57 patients who underwent scalene node sampling between 1980 and 1998. In 39 of 49 (80%), the decision to proceed with scalene node sampling was based entirely on histologically documented PAN metastases. In the remainder, scalene node sampling was prompted by the presence of suspicious clinical findings. RESULTS: Of the 49 patients included in the study, 33 had carcinoma of the cervix, while 16 had corpus carcinoma. Ninety percent of scalene node sampling was performed at the time of primary diagnosis. Overall, 9 patients (18%) had scalene node metastases. Notably, not a single patient with corpus cancer was found to have scalene node metastases in the absence of clinically evident scalene node enlargement independent of PAN status. In cervix cancer cases, the presence of grossly involved PAN was predictive of a high likelihood of scalene node metastases (44%), while no patient with occult PAN metastases had involvement of the scalene node. Only 1 minor complication was encountered following scalene node sampling. The 40 scalene node-negative patients were treated with either extended field radiation or whole abdominal radiation therapy, and 20% developed a major, RTOG grade >/=3 complication such as fistula formation, bowel obstruction, or ureteral stenosis. Only 1 case of mild radiation enteritis and cellulitis occurred during palliative radiation in the group of patients with scalene node metastases. CONCLUSIONS: Scalene node sampling may be of benefit in the pretreatment evaluation of patients with cervical carcinoma when PAN are grossly involved. Given that scalene node involvement satisfies the criteria for distant metastases, identification of such allows the clinician to avoid the morbidity of extended field radiotherapy in a setting without the chance for cure.

Effect of bismuth salts on systemic and mucosal immune responses to orally administered cholera toxin.

While the antimicrobial and antisecretory effects of bismuth salts are well documented, little is known regarding their effects on immune responses to enterotoxins such as that of V. cholerae or to orally administered vaccine antigens. To evaluate the effects of Pepto Bismol (PB) on the induction of systemic and mucosal immune responses to cholera toxin (CT), C57BL/6 mice were orally administered 10 micrograms CT and PB, or mice were pretreated with PB 30 min prior to CT administration. When co-administered with CT, PB attenuated serum IgG1, IgG2a, IgG2b and IgG3 anti-CT responses in a dose-dependent manner and also reduced levels of circulating anti-CT IgA and total serum IgE. Similarly, anti-CT intestinal IgA responses were also decreased. However, when administered 30 min prior to CT, PB had little to no effect on serum or intestinal anti-CT immunoglobulin responses. Administration of bismuth subsalicylate (BSS), the active component of PB, or sodium salicylate did not reduce immune responses to CT, suggesting that the combination of BSS plus other constituents contained within PB contributed to the decreased immune response to CT. Moreover, bismuth subgallate alone inhibited antibody responses to CT. Our data are consistent with the hypothesis that, when administered orally with CT, PB and bismuth subgallate create a physical barrier to antigen uptake.