Lunchbox trial: A randomized phase III trial of cisplatin and irradiation followed by carboplatin and paclitaxel versus sandwich therapy of carboplatin and paclitaxel followed by irradiation then carboplatin and paclitaxel for advanced endometrial carcinoma.

BACKGROUND: The objective was to compare sequencing strategies for treatment of advanced endometrial carcinoma. METHODS: Patients were eligible if they had FIGO 2009 Stage III or IVA endometrial carcinoma or Stage I or II serous or clear cell endometrial carcinoma and positive cytology. Patients were randomized to: Cisplatin 50 mg/m2 IV Days 1 and 29 plus radiation followed by Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2 q 21 days for 4 cycles (chemoRT then chemo) vs. Carboplatin AUC 6 plus Paclitaxel 175 mg/m2 q 21 days for 3 cycles followed by radiation followed by Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2 q 21 days for 3 cycles (sandwich therapy). Futility analysis was planned. The primary objective was to determine if chemoRT then chemo improves recurrence-free survival (RFS) compared to sandwich therapy. RESULTS: Of the 48 patients enrolled at 8 sites, 42 patients were eligible for futility analysis, and the trial was closed early. The median follow-up was 30.9 months. The 3-year RFS was 85.7% (95% confidence interval [CI], 62 to 95) in the chemoRT then chemo arm and 73.4% (95% CI, 43 to 89) in the sandwich therapy group (p = 0.58). The 3-year overall survival (OS) was 88.4% (95% CI, 61 to 97) in the chemoRT then chemo arm and 80.9% (95% CI, 51 to 93) in the sandwich therapy group (p = 0.55). CONCLUSION: There was no observed significant difference between chemoRT then chemo compared to sandwich therapy in terms of RFS, OS, or adverse events, although the trial was underpowered and closed early due to low accrual.

Small cell carcinoma of the ovary, pulmonary type: A role for adjuvant radiotherapy after carboplatin and etoposide?

BACKGROUND: Primary small cell ovarian cancer of pulmonary type (SCCOPT) remains a rare ovarian tumor. Its aggressive nature is associated with poor survival outcomes. Current treatment algorithms rely on systemic chemotherapy, primarily involving platinum agents. However, given its low incidence, less is known about the potential benefits of other treatments. CASE PRESENTATION: We report a case of an 80-year-old woman who was found to have a complex pelvic mass with a mildly elevated CA-125. She underwent a laparotomy for staging with tumor debulking; she had bulky unresectable adenopathy and pathology was consistent with stage IIIC SCCOPT. Postoperative imaging revealed progression of disease. She received six cycles of carboplatin and etoposide followed by consolidative radiation therapy to her para-aortic lymph nodes. She remains disease-free for over four years after completion of adjuvant therapy. DISCUSSION: Histologically, SCCOPT resembles small cell carcinomas of the lung, which are treated with a combination of chemotherapy and radiation therapy. New approaches that build upon the current treatment approaches and incorporate strategies from non-gynecologic tumor types could be beneficial.

Digital Colposcopy With Dynamic Spectral Imaging for Detection of Cervical Intraepithelial Neoplasia 2+ in Low-Grade Referrals: The IMPROVE-COLPO Study.

OBJECTIVE: The aim of the study was to determine, in a wide "real-world" setting, whether digital colposcopy with adjunctive dynamic spectral imaging (DSI) mapping increases the detection of women with high-grade cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: A multicenter, two-arm, observational, cross-sectional study that recruited women 21 years and older, having colposcopy after a low-grade abnormality screening result. The prospective arm collected outcomes of digital colposcopy with DSI used for identifying biopsy sites at the colposcopists' discretion. The retrospective control arm (number of subjects matched 1:1 per colposcopist) collected outcomes of standard colposcopy. The primary outcome was histopathological detection of women with CIN 2+ by colposcopic biopsy. RESULTS: The study included 1,788 women in the retrospective and 1,857 in the prospective arm from 39 US community-based clinics. Subject characteristics were comparable. A total of 71.6% of the women in the retrospective and 71.5% in the prospective arm underwent biopsy. The average number of biopsies increased from 1.032 (retrospective) to 1.256 (prospective). The yield of CIN 2+ patients was 7.21% in the retrospective and 9.48% in the prospective arm, a 2.27% difference (95% confidence interval = 0.47%-4.07%, p = .014) and 31.4% relative increase. The yield of CIN 3+ patients was 2.07% in the retrospective and 3.23% in the prospective arm, a 1.16% (95% confidence interval = 0.12%-2.24%, p = .031) absolute difference and 56.1% relative increase. The false-positive rates for biopsied patients were comparable (64.43% vs 62.04%, p = .139). CONCLUSIONS: Digital colposcopy with the adjunctive DSI increased CIN 2+ and CIN 3+ detection in low-grade referrals compared with standard colposcopy, with a similar number of women undergoing biopsy.

Increased detection of precancerous cervical lesions with adjunctive dynamic spectral imaging.

OBJECTIVE: To validate, in US community-based colposcopy clinics, previous reports of increased detection of high-grade cervical intraepithelial neoplasia (CIN2+) with biopsies selected using dynamic spectral imaging (DSI) mapping after standard colposcopy. STUDY DESIGN: Cross-sectional observational study of 26 colposcopists across nine clinics recruiting consecutive colposcopy patients. Standard assessment with biopsy selections was completed before seeing the DSI map which was subsequently interpreted and used for additional biopsies per clinical judgment. Primary measure was the number of women with CIN2+ detected by DSI-assisted biopsies, over those detected by standard colposcopy biopsies. RESULTS: A total of 887 women were recruited. After exclusions, 881 women and 1,189 biopsies were analyzed. Standard biopsy detected 78 women with CIN2+ and DSI-assisted biopsies another 34, increasing the detection rate from 8.85% to 12.71% (p=0.00016). This was achieved with 16.16% of DSI-assisted biopsies finding CIN2+ compared to 13.24% for the preceding standard biopsies. For secondary specificity analysis, 431 women had only

Lymphovascular space invasion (LVSI) is an isolated poor prognostic factor for recurrence and survival among women with intermediate- to high-risk early-stage endometrioid endometrial cancer.

OBJECTIVES: Whereas previous studies have shown that lymphovascular space invasion (LVSI) is associated with an increased risk for recurrent endometrioid endometrial cancer and worse survival, the magnitude of this risk in relationship to the other high-risk features is poorly understood. Our aim was to study the impact of LVSI in comparison with the other high-risk features in recurrence and survival. MATERIALS AND METHODS: Women with stage I or II endometrial cancer were included in this study if they had LVSI, International Federation of Gynecology and Obstetrics grade 2 or 3 histology, or outer-half myometrial invasion. We performed multivariate regression analyses to identify prognostic factors for recurrence. We performed Kaplan-Meier survival curve predictions of progression-free survival (PFS), overall survival (OS), and disease-specific survival; and Cox proportional hazard models to adjust for other variables. RESULTS: Three hundred eighty-eight patients met the inclusion criteria; their median follow-up was 59 months. The rates of recurrence were the following: overall, 17%; pelvic, 11%; vaginal cuff, 8%, and distant, 11%. Twenty-six percent of the patients died during follow-up. After adjusting for age, body mass index, grade, depth of invasion, cervical invasion, lymphadenectomy, and adjuvant treatment(s), LVSI was the only significant independent risk factor for total (odds ratio, 2.6) and distant (odds ratio, 3.3) recurrences and was also a risk factor for local and vaginal recurrences. Lymphovascular space invasion was also a significant poor prognostic factor for PFS (hazard ratio [HR], 2.8), OS (HR, 2.8), and disease-specific survival (HR, 7.0). Among the other risk factors, age was significantly associated with worse PFS and OS, whereas grade 3 histology was significantly associated with worse OS. CONCLUSION: In our study, LVSI is the only significant and consistent poor prognostic factor for all the outcomes studied: recurrences and survival. Lymphovascular space invasion seems to be a better predictor than the other risk factors. This suggests a potential role for adjuvant systemic therapies in patients with LVSI, even in the absence of other high-risk features.

da Vinci® single-site platform: anthropometrical, docking and suturing considerations for hysterectomy in the cadaver model.

BACKGROUND: The paper describes specific technical requirements, limitations, anthropometrical, docking and suturing considerations on the performance of robotic hysterectomy using the da Vinci® Single-Site Platform in the cadaver model METHODS: A data set was collected for each procedure including port placement, docking sequence, robotic arms placement and angles, robotic instrumentation, optimal ergonomics, operative time, and cadaver anthropometrical measurements. Pearson correlation coefficients were calculated to determine whether age, BMI or docking approach were correlated with docking difficulty and likelihood of successful procedure completion. Analysis of the data was performed using SPSS v19.0.0. RESULTS: The planned surgical procedure was successfully completed with single-port robotics in 87.5% of cases. High BMI was correlated with difficulty docking the robot, correlation coefficient 0.98. CONCLUSIONS: Further work is needed in the development and advancement of single-site robotic platforms, articulated instrumentation, and optics.

Robotic surgery in gynecology: an updated systematic review.

The introduction of da Vinci Robotic Surgery to the field of Gynecology has resulted in large changes in surgical management. The robotic platform allows less experienced laparoscopic surgeons to perform more complex procedures. In general gynecology and reproductive gynecology, the robot is being increasingly used for procedures such as hysterectomies, myomectomies, adnexal surgery, and tubal anastomosis. Among urogynecology the robot is being utilized for sacrocolopexies. In the field of gynecologic oncology, the robot is being increasingly used for hysterectomies and lymphadenectomies in oncologic diseases. Despite the rapid and widespread adoption of robotic surgery in gynecology, there are no randomized trials comparing its efficacy and safety to other traditional surgical approaches. Our aim is to update previously published reviews with a focus on only comparative observational studies. We determined that, with the right amount of training and skill, along with appropriate patient selection, robotic surgery can be highly advantageous. Patients will likely have less blood loss, less post-operative pain, faster recoveries, and fewer complications compared to open surgery and potentially even laparoscopy. However, until larger, well-designed observational studies or randomized control trials are completed which report long-term outcomes, we cannot definitively state the superiority of robotic surgery over other surgical methods.

Survival and reproductive outcomes in women treated for malignant ovarian germ cell tumors.

OBJECTIVE: The objective of this study is to review all malignant germ-cell tumors (MOGCTs) treated at our institution, focusing on reproductive outcomes and menstrual function of patients treated with fertility-sparing surgery and adjuvant chemotherapy. METHODS: We performed a retrospective chart review of patients treated for MOGCTs between January 1, 1979 and March 31, 2008. Charts of identified patients were abstracted and data were collected. Patients who had fertility-sparing surgery were contacted and a telephone questionnaire was performed to gather reproductive and menstrual history. RESULTS: Forty patients were treated for MOGCTs at our institution. Mean age at the time of diagnosis was 26.5years (range, 10-48years). Histologic subtypes were: immature teratoma (52.5%), dysgerminoma (27.5%), yolk sac tumor (10.0%), mixed germ cell tumor (7.5%), and choriocarcinoma (2.5%). Thirty-five percent of tumors were FIGO stages II-IV. Twenty-seven patients (67.5%) were treated with chemotherapy postoperatively, 23 (85%) of whom received bleomycin, etoposide and cisplatin (BEP). There were three recurrences, but no deaths. Fertility-sparing surgery was performed in 22 patients (55%), 16 of whom received adjuvant chemotherapy. Fourteen of these patients were contacted. Of the 10 remaining patients desiring pregnancy, 8 (80%) had 11 successful spontaneous pregnancies, one required in-vitro fertilization, and the other required donor egg in-vitro fertilization, resulting in 14 live births. All 14 patients had normal menstrual cycles within one year of completing chemotherapy. CONCLUSIONS: Overall survival was 100% among patients with both local and advanced MOGCTs, including those who underwent fertility-sparing surgery. Fertility-sparing surgery plus adjuvant chemotherapy appeared to have little or no effect on fertility or menstrual cycles.

Severe hydramnios and preterm delivery in association with transient maternal diabetes insipidus.

BACKGROUND: Diabetes insipidus is rare in pregnancy. It is characterized by hypoosmolar polyuria and may be central, nephrogenic, or transient in etiology; the latter is presumably related to excess placental vasopresinase production. In theory, fetal effects of this endocrine condition may include hydramnios secondary to fetal polyuria. CASE: A pregnant patient developed rapid-onset second-trimester hydramnios that prompted a thorough fetal and maternal evaluation. She ultimately was diagnosed with transient diabetes insipidus of pregnancy because of an abrupt change in her voiding pattern at 20 weeks of gestation, significant polydipsia, and laboratory studies that revealed a hypoosmolar polyuria with normal serum and urine electrolytes. Transient neonatal polyuria also was confirmed in association with this unique maternal endocrine syndrome. CONCLUSION: The most likely cause of hydramnios in this case is transient maternal diabetes insipidus of pregnancy from excessive secretion of placental vasopressinase resulting in fetal polyuria. In cases of hydramnios of unknown etiology, if a history of maternal polyuria is elicited and confirmed, diabetes insipidus of pregnancy may play a role in some cases.

The role of neoadjuvant chemotherapy in treating advanced epithelial ovarian cancer.

The current management of advanced ovarian cancer consists of aggressive primary cytoreductive surgery (PCS) followed by combination platinum based chemotherapy. Recent studies have suggested that platinum-based chemotherapy may be of benefit in patients with advanced ovarian cancer prior to cytoreductive surgery (neoadjuvant chemotherapy, NACT). The concept of NACT has not been completely validated in the treatment of ovarian cancer. This review will discuss the role of NACT in patients with advanced epithelial ovarian cancer.