Juvenile granulosa cell tumor in an adult woman during pregnancy: A case report and review of the literature.

Objective: To report a case of stage IIIB juvenile granulosa cell tumor (JGCT) complicating pregnancy in a 33 year-old (y.o.) woman. Methods: Retrospective review of the clinical data, imaging studies, and pathology reports of a case of JGCT diagnosed during pregnancy. Patient consent was obtained for review and presentation of the case. A literature review was conducted. Results: A 33 y.o., gravida 3, para 1 was incidentally found to have an 8 cm left ovarian mass on an anatomy scan at 22 weeks gestation. Four days later, she presented to labor and delivery triage with abdominal pain. An ultrasound revealed an 11 cm heterogeneous, solid mass in the left adnexa and free fluid at this level. The diagnosis of degenerating fibroid was made based on her clinical presentation and she was discharged. A follow up outpatient MRI revealed a 15 cm left ovarian mass consistent with a primary malignant ovarian neoplasm with moderate ascites and omental, left cul de sac, and probable paracolic gutter implantation. She re-presented 2 weeks later with an acute abdomen and was admitted for a gynecologic oncology consult. Pre-op tumor markers showed an elevated inhibin B. She underwent an exploratory laparotomy, left salpingo-oophorectomy, omental biopsy, and small bowel resection at 25 weeks gestation. Intra-op findings included a ruptured tumor and metastases. Tumor reductive surgery was completed to R0. Pathology revealed a JGCT, FIGO stage IIIB. The pathology and management were reviewed in collaboration with an outside institution. Chemotherapy was delayed until after delivery with monthly MRI surveillance. She underwent induction of labor at 37 weeks followed by an uncomplicated vaginal delivery. She received 3 cycles of bleomycin, etoposide, and cisplatin starting six weeks postpartum. Last known contact was over five years after the initial diagnosis with no evidence of recurrent disease. Conclusion: JGCTs account for 5% of granulosa cell tumors and 3% are diagnosed after age 30. JGCT is an uncommon neoplasm in pregnancy. 90% are stage I at diagnosis, but advanced stage tumors are aggressive often resulting in recurrence or death within 3 years of diagnosis. We present a surgically treated case with delay in chemotherapy until after delivery with a good outcome after 5 years of follow up.

Implementation of an enhanced recovery protocol in gynecologic oncology.

Enhanced Recovery after Surgery (ERAS) is an evidence-based approach that aims to reduce narcotic use and maintain anabolic balance to enable full functional recovery. Our primary aim was to determine the effect of ERAS on narcotic usage among patients who underwent exploratory laparotomy by gynecologic oncologists. We characterized its effect on length of stay, intraoperative blood transfusions, bowel function, 30-day readmissions, and postoperative complications. A retrospective cohort study was performed at Abington Hospital-Jefferson Health in gynecologic oncology. Women who underwent an exploratory laparotomy from 2011 to 2016 for both benign and malignant etiologies were included before and after implementation of our ERAS protocol. Patients who underwent a bowel resection were excluded. A total of 724 patients were included: 360 in the non-ERAS and 364 in the ERAS cohort. An overall reduction in narcotic usage, measured as oral morphine milliequivalents (MMEs) was observed in the ERAS relative to the non-ERAS group, during the entire hospital stay (MME 34 versus 68, p < 0.001 and within 72 h postoperatively (MME 34 versus 60, p < 0.005). A shorter length of stay and earlier return of bowel function were also observed in the ERAS group. No differences in 30-day readmissions (p = 0.967) or postoperative complications (p = 0.328) were observed. This study demonstrated the benefits of ERAS in Gynecologic Oncology. A significant reduction of postoperative narcotic use, earlier return of bowel function and a shorter postoperative hospital stay was seen in the ERAS compared to traditional perioperative care.

Disparities Among Cervical Cancer Patients Receiving Brachytherapy.

OBJECTIVE: To evaluate the effects of race and insurance status on the use of brachytherapy for treatment of cervical cancer. METHODS: This is a retrospective cohort study of the National Cancer Database. We identified 25,223 patients diagnosed with stage IB2 through IVA cervical cancer who received radiation therapy during their primary treatment from 2004 to 2015. A univariate analysis was used to assess covariate association with brachytherapy. A multivariable regression model was used to evaluate the effect of race and insurance status on rates of brachytherapy treatment. The Cox proportional hazards model and the multiplicative hazard model were used to evaluate overall survival. P<.05 indicated a statistically significant difference for comparisons of primary and secondary outcomes. RESULTS: Non-Hispanic black patients received brachytherapy at a significantly lower rate than non-Hispanic white patients (odds ratio [OR] 0.93; 95% CI 0.86-0.99; P=.036); Hispanic (OR 0.93; 95% CI 0.85-1.02; P=.115) and Asian (OR 1.13; 95% CI 0.99-1.29; P=.074) patients received brachytherapy at similar rates. Compared with patients with private insurance, those who were uninsured (OR 0.72; 95% CI 0.65-0.79; P<.001), had Medicaid (OR 0.83; 95% CI 0.77-0.89; P<.001) or Medicare insurance (OR 0.85; 95% CI 0.78-0.92; P<.001) were less likely to receive brachytherapy. Brachytherapy was not found to be a mediator of race and insurance-related disparities in overall survival. CONCLUSION: Racial and insurance disparities exist for those who receive brachytherapy, with many patients not receiving the standard of care, but overall survival was not affected.

Implementation of an abdominal closure bundle to reduce surgical site infection in patients on a gynecologic oncology service undergoing exploratory laparotomy.

OBJECTIVE: Surgical site infections (SSI) are associated with increased morbidity, mortality, and healthcare costs. This study investigated whether implementation of an abdominal closure bundle reduces surgical site infection rates. We aimed to identify sub-populations that would benefit the most from this intervention. METHODS: We conducted a retrospective cohort study of all patients that underwent exploratory laparotomy by a Gynecologic Oncologist from January 1, 2011 to April 1, 2017. The abdominal closure bundle was implemented on May 6, 2014. SSI rates were assessed overall and within subgroups. RESULTS: 875 patients were included in the analysis. Overall, SSI rate was reduced, albeit not significantly, from 48/471 (10.2%) to 32/404 (7.9%) (p=0.148) with implementation of the closing bundle. In patients that underwent a tumor debulking procedure, SSI was noted in 36/277 (13.0%) in the pre-bundle group and 14/208 (6.7%) in the post-bundle cohort (p=0.017). In patients with malignant pathology, the pre-bundle cohort had an SSI rate of 38/282 (13.5%), which reduced to 18/215 (8.4%) in the post-bundle group (p=0.049). In patients with FIGO stage III or IV disease, the SSI rate was reduced from 21/114 (18.4%) to 8/87 (8.4%) with implantation of the closure bundle (p=0.028). In patients with intra-operative ascites, SSI rate decreased from 19/119 (15.9%) pre-bundle to 4/104 (3.8%) in the post-bundle group (p=0.002). CONCLUSIONS: Implementation of an abdominal closure bundle was not associated with a significant reduction in overall SSI rate. However, multiple subpopulations associated with advanced gynecologic cancer benefited from this intervention.

Recognition and Therapeutic Options for Malignancy of the Cervix and Uterus.

An update on the current epidemiology and a review of the risk factors of cervical and endometrial cancers are discussed. Cervical cancer prevention with a focus on human papillomavirus vaccination and cervical cancer screening is reviewed, emphasizing the new focus of less frequent intervention in an effort to maintain high rates of early detection of disease while decreasing unnecessary and anxiety-provoking colposcopies, biopsies, and excisional procedures. The replacement of traditional endometrial hyperplasia terminology with more relevant clinical categories, with an emphasis on the introduction of endometrial intraepithelial neoplasia, is presented. Fertility-sparing options in the management of early cervical and endometrial cancers are reviewed.

Endometrial cancer.

The epidemiology, prevention, diagnosis, treatment, prognosis, and new International Federation of Gynecology and Obstetrics staging system of endometrial carcinoma are reviewed. Endometrial cancer has increased 21% in incidence since 2008, and the death rate has increased more than 100% over the past two decades. Precursor lesions of complex hyperplasia with atypia are associated with an endometrial carcinoma in more than 40% of cases. Endometrial cancer in white women occurs at twice the incidence as in black women, but, stage for stage, black women have a less favorable prognosis. Preoperative imaging cannot accurately assess lymph node involvement. Gross examination of depth of myometrial invasion does not have the sensitivity, specificity, positive predictive value, or negative predictive value to select women who can have lymphadenectomy safely omitted from the surgical procedure. Although surgical staging remains the most accurate method of determining the extent of disease, the therapeutic value of pelvic lymphadenectomy has not been established. The anatomical extent of lymphadenectomy and the number of lymph nodes removed to establish prognostic and therapeutic benefit are controversial. Research efforts are directed at identifying women with early stage endometrial cancer who only require total hysterectomy and bilateral salpingo-oophorectomy. Minimally invasive surgical techniques have become established as standard therapy for treating women with endometrial cancer. Women with a family history of hereditary nonpolyposis colorectal cancer are at increased risk for endometrial cancer. Conservative treatment to allow for childbearing is possible in select situations. Women with endometrial cancer should be managed by physicians experienced in the complex multimodality treatment of this disease.

Changes in tumor blood flow as measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) may predict activity of single agent bevacizumab in recurrent epithelial ovarian (EOC) and primary peritoneal cancer (PPC) patients: an exploratory analysis of a Gynecologic Oncology Group Phase II study.

OBJECTIVE: To explore feasibility of measuring tumor blood flow as marker for antiangiogenic activity using DCE-MRI (Dynamic Contrast-Enhanced Magnetic Resonance Imaging) in women with recurrent EOC/PPC treated with bevacizumab. METHODS: In a phase II study, 62 patients with recurrent/persistent EOC/PPC were treated with bevacizumab (15 mg/kg IV q21 days) until disease progression. DCE-MRI was performed pre-cycle 1 and 4 of bevacizumab. Images were analyzed retrospectively by a single experienced blinded radiologist. Tumor and muscle contrast enhancement was measured by region of interest signal intensity within the same DCE-MRI images. Flow rates were obtained with concentration of dye as a function of time. Relative blood flow (RBF) was calculated as a ratio of average blood flow into tumor to muscle tissue. Associations between RBF and characteristics/outcomes were explored. RESULTS: Sixty-two patients were eligible for study. Unfortunately, only 14 (23%) patients had imaging data available for analysis at baseline and 13 of those same patients (21%) had imaging data available for analysis pre-cycle 4. The RBF distribution was similar from pre-cycle 1 to 4. RBF remained stable for the majority of the cases (median change -0.21). Baseline RBF was not significantly associated with being progression-free at 6 months, microvessel density, 17 month overall survival, tumor response, or platinum sensitivity. However, increases in blood flow rates were associated with likelihood to be progression-free at 6 months. CONCLUSION: Functional imaging of tumor blood flow is a potential research endpoint that may be explored further. Consideration should be given to timing of endpoint and standardizing the technique.

Predictive value of serum CA-125 levels in patients with persistent or recurrent epithelial ovarian cancer or peritoneal cancer treated with bevacizumab on a Gynecologic Oncology Group phase II trial.

OBJECTIVE: To compare two methods of determining therapeutic response and disease progression - modified Gynecologic Cancer Intergroup (GCIG) criteria based on CA-125 and Radiographic Evaluation Criteria in Solid Tumors (RECIST), in a phase II trial of bevacizumab for patients with recurrent or persistent epithelial ovarian and peritoneal carcinoma. METHODS: Patients were treated with bevacizumab 15 mg/kg every 21 days. Modified GCIG definitions of progression and response were retrospectively applied and compared to RECIST-defined progression and response. The prognostic significance of CA-125- and RECIST-defined responses and progressions were explored. RESULTS: Sixty-two patients were evaluable by RECIST, 59 for progression by CA-125, and 45 for response by CA-125. Median progression-free survival (PFS) by RECIST and progression-free interval (PFI) by CA-125 were 4.7 and 5.2 months respectively. However, 12.9% of those with CA-125 defined progression remained progression-free according to RECIST for at least 8 months. Thirteen of 62 patients (21%) had response by RECIST and 14/45 (31%) by CA-125. Time dependent analyses indicated that progression by CA-125 was associated with a 5.2 fold increased risk of progression by RECIST, and response by CA-125 had a 5 fold decrease in risk of progression by RECIST. Landmark and time dependent analyses showed prognostic value of responses by CA-125 and RECIST. CONCLUSIONS: In this study, disease assessment by RECIST and CA-125 appears to correlate in general. However, approximately 10% of patients might demonstrate progression earlier by CA-125.

Prevalence of the human papillomavirus in an inner-city indigent population with previously normal Pap tests.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) in our inner-city indigent population (clinic population) of women with previously normal Pap tests and to identify any associated risk factors. MATERIALS AND METHODS: A prospective cohort of 187 women between the ages of 15 and 49 years, with previously normal Pap tests, was recruited from a university affiliated outpatient clinic. A demographic questionnaire of social and sexual history was elicited, and ThinPrep cytology (Cytyc, Marlborough, MA) and HPV Digene Hybrid Capture II results (Digine, Gaithersburg, MD) were obtained. RESULTS: The prevalence of HPV in our primarily Hispanic clinic population was 21%. The mean age of women with HPV was 28.9 years and those without were 32.1 years (p <.046). In women with HPV, 24% had abnormal Pap tests, whereas in those without HPV, 5% had abnormal Pap tests (p <.001). Women who were older and parous were less likely to have HPV (7.5%; p <.024). The presence of HPV was not influenced by sexual behaviors, sexually transmitted diseases, smoking, race, or contraceptive use. CONCLUSIONS: The prevalence of HPV in an inner-city indigent population, despite previously normal cytology, was consistent with earlier reported rates of HPV. Our data suggest that younger, nulliparous women have a high prevalence of HPV.

Placental-site trophoblastic tumor with PET scan-detected surgically treated lung metastasis.

Metastatic placental-site trophoblastic tumor (PSTT) continues to be a diagnostic and management dilemma due to its relative resistance to chemotherapy and the difficulties in diagnosing such a rare tumor. We describe a 35-year-old woman with PSTT presenting with irregular bleeding and a mass in the lung. Dilation and curettage provided the diagnosis of PSTT by frozen section of the specimen. Subsequently, a total abdominal hysterectomy was performed and the patient received three cycles of EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine) Positron emission tomography (PET) scan confirmed a persistent lung nodule that was treated with wedge resection. She is currently in clinical remission. Surgery may have a role in salvaging a patient with persistent PET-positive disease after chemotherapy.

Endometrial cancer.

This review summarizes the epidemiology, prevention, diagnosis and treatment, and prognosis of endometrial carcinoma. Although the incidence of disease has remained stable, the death rate has increased over 100% over the last two decades. Precursor lesions of complex hyperplasia with atypia are associated with an endometrial carcinoma in over 40% of cases. The percentage of obese women with endometrial cancer is increasing. The incidence of endometrial cancer in white women is twice the incidence in African-American women, but stage for stage, African-American women have a less favorable prognosis. Preoperative imaging cannot accurately assess lymph node involvement. Gross examination of depth of myometrial invasion does not have the sensitivity, specificity, and positive or negative predictive value to select women who can have lymphadenectomy safely omitted from the surgical procedure. In the absence of ideal noninvasive preoperative testing, surgical staging remains the most accurate method of determining the extent of disease. There has been an increase in surgical staging and a decrease in postoperative adjuvant pelvic radiation therapy over the past two decades. Women with a family history of hereditary nonpolyposis colorectal colon cancer are at increased risk for endometrial cancer. Conservative treatment to allow for childbearing is possible in select situations. Women with endometrial cancer should be managed by physicians experienced in the treatment of this disease.

Dysplasia and malignancy in endocervical polyps.

OBJECTIVE: The objective was to estimate the prevalence of malignancy or dysplasia in cervical polyps. METHODS: A convenience sample was identified by retrospectively searching the Hartford Hospital pathology database for cases of endocervical polyps removed from January 1, 1999, through January 31, 2006. The presence of malignancy, dysplasia, atypia, and other modifiers was recorded along with demographic information, including age, race/ethnicity, residence, and the ordering practitioner. RESULTS: The sample size consisted of 2246 polyps obtained from 2100 women, who ranged in age from 16 to 95 years (mean +/- SD, 48.6 +/- 10.9). The women were 82.4% white, 3.4% African American, 5.4% Hispanic, 0.4% Asian, and 8.3% other. The majority of women were from private practices (95.2%), and obstetrics/gynecology providers sent 98.3% of the polyp samples. Malignancy was diagnosed in 0.1% of cases. Polyps showed dysplasia in 0.5% of cases, and reactive atypia was seen in 1.6%. Inflammatory changes were seen in 27.7% of polyps, metaplasia in 13.6%, and microglandular hyperplasia in 6.8%. The recurrence rate was 6.2%. CONCLUSIONS: The prevalence of malignancy and dysplasia in cervical polyps removed over a 7-year span was 0.1% and 0.5%, respectively. Cervical polyps can harbor disease from sources beyond the cervix. Because there were no cases of primary malignancy in this large series of cervical polyps, it appears unlikely that cervical polyps progress to malignancy. Additionally, polyp recurrence is not uncommon. This information has significant implications as physicians plan appropriate counseling and management for the common diagnosis of cervical polyps.

Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study.

PURPOSE: Vascular endothelial growth factor (VEGF) seems to be a promoter of tumor progression for epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC). We conducted a phase II trial to assess the efficacy and tolerability of single-agent bevacizumab, an anti-VEGF monoclonal antibody. PATIENTS AND METHODS: Eligible patients had persistent or recurrent EOC/PPC after one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of at least 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and clinical response. RESULTS: The study consisted of 62 eligible and assessable patients, median age 57 years, 41 (66.1%) having received two prior regimens and 36 (58.1%) [CORRECTED] considered platinum resistant. Grade 3 adverse events at least possibly related to bevacizumab were hematologic (1), GI (3), hypertension (6), thromboembolism (1), allergy (2), hepatic (1), pain (3), coagulation (1), constitutional (1), and dyspnea (1). Grade 4 adverse events included pulmonary embolus (1), vomiting and constipation (1), and proteinuria (1). Thirteen patients (21.0%) experienced clinical responses (two complete, 11 partial; median response duration, 10 months), and 25 (40.3%) survived progression free for at least 6 months. Median PFS and overall survival were 4.7 and 17 months, respectively. There was no significant association of prior platinum sensitivity, age, number of prior chemotherapeutic regimens, or performance status with the hazard of progression or death. CONCLUSION: Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with EOC/PPC and merits phase III investigation.

Patient choice: comparing criteria for selecting an obstetrician-gynecologist based on image, gender, and professional attributes.

OBJECTIVE: The purpose of this study was to compare gender, humanistic qualities or technical competence (HQTC), and age when an obstetrician-gynecologist is selected. STUDY DESIGN: Participants saw photographs (2 women, 2 men) without descriptors then the same photographs with descriptors. To test whether HQTC were more important than gender, the men in the photographs were given HQTC descriptors. Female patients, visitors, and staff at Hartford Hospital along with community and outpatient sites were recruited. Demographic information was collected. RESULTS: From 901 participants, 83% chose a woman, 59% of whom selected gender or age as the reason. Single and younger patients were more likely to choose female and younger providers, respectively. With descriptors, 62% of the women chose a male provider. A significant number chose a different gender provider (P < .001) and made their selection for a different reason (P < .001). CONCLUSION: More women chose a female provider when no additional information is known. A significant number changed their selection when male providers were described with HQTC.

A retained surgical sponge presenting as chronic pelvic pain.

BACKGROUND: Gossypiboma, the term for a retained sponge, is an underestimated occurrence related to gynecologic surgery. The postoperative presentation can be acute or subacute with symptoms that include pelvic pain. CASE: A 39-year-old G7P3043 female presented with chronic pelvic pain. Her only past surgeries were 16 and 21 years prior. After failing to respond to conservative options, she was taken to the operating room for a hysterectomy and possible salpingoophorectomy. During the surgery, a retained sponge was found and removed. Postoperatively, the pain resolved completely. CONCLUSION: Although gossypiboma is an uncommon cause of chronic pelvic pain, patients can present years later with minimal complications other than discomfort. Accurate sponge and instrument counts, along with radiologic evaluation when a discrepancy is found, can be helpful. Newer technologies are also being developed to help avoid this complication.

Serial therapy-induced changes in tumor shape in cervical cancer and their impact on assessing tumor volume and treatment response.

OBJECTIVE: The purpose of this study was to evaluate the patterns and distribution of tumor shape and its temporal change during radiation therapy (RT) in cervical cancer and the effect of tumor configuration changes on the correlation between region of interest (ROI)-based and diameter-based MRI tumor measurement. MATERIALS AND METHODS: Serial MRI examinations (T1-weighted and T2-weighted images) were performed in 60 patients (age range, 29-75 years; mean, 53.3 years) with advanced cervical cancer (stages IB2-IVB/recurrent) who were treated with RT at four time points: start of RT, during RT (at 2-2.5 and at 4-5 weeks of RT), and post-RT. Tumor configuration was classified qualitatively into oval, lobulated, and complex based on MR film review. Two methods of tumor volume measurement were compared: ellipsoid computation of three orthogonal diameters (diameter based) and ROI volumetry by delineating the entire tumor volume on the MR workstation (ROI based). Temporal changes of tumor shape and the respective tumor volumes measured by the two methods were analyzed using linear regression analysis. RESULTS: Most tumors (70%) had a non-oval (lobulated and complex) shape before RT and became increasingly irregular during and after RT: 84% at 2-2.5 weeks of RT (p = 0.037), 86% (p = 0.025) at 4-5 weeks, and 96% post-RT (p = 0.010), compared with 70% pre-RT. Diameter-based and ROI-based measurement correlated well before RT (r = 0.89) but not during RT (r = 0.68 at 2-2.5 weeks, r = 0.67 at 4-5 weeks of RT). CONCLUSION: Most cervical cancers are not oval in shape pretherapy, and they become increasingly irregular during and after therapy because of nonconcentric tumor shrinkage. ROI-based volumetry, which can optimally measure irregular volumes, may provide better response assessment during treatment than diameter-based measurement.

Phase II study of oxaliplatin as second-line chemotherapy in endometrial carcinoma: a Gynecologic Oncology Group study.

OBJECTIVE: A phase II study was conducted to determine the efficacy of oxaliplatin therapy in patients with advanced or recurrent endometrial cancer who had received one prior platinum therapy. METHODS: Eligible patients were to have measurable disease and one prior chemotherapy regimen which could include cisplatin or carboplatin. Oxaliplatin 130 mg/m2 was administered intravenously over 2 h. This treatment was repeated every 21 days until progression of disease or adverse effects prohibited further therapy. RESULTS: Fifty-four patients were entered on study, of which 52 were eligible and 50 had had prior platinum therapy. The overall response rate was 13.5%, with three patients (5.8%) achieving a complete response and four patients (7.7%) achieving a partial response. Median duration of response was 10.9+ (range: 4.1-50.3+) months. Stable disease was reported in 15 (28.8%) patients, with an associated median duration of 5.4 (range: 2.2-19.6) months. Drug-related toxicities consisted of anemia, nausea and vomiting, and neurotoxicity. CONCLUSIONS: Oxaliplatin at the dose and schedule employed has limited activity in patients with advanced or recurrent endometrial carcinoma who have had previous platinum therapy.