A phase III, multicenter, randomized study of olvimulogene nanivacirepvec followed by platinum-doublet chemotherapy and bevacizumab compared with platinum-doublet chemotherapy and bevacizumab in women with platinum-resistant/refractory ovarian cancer.

BACKGROUND: Treatment options for patients with platinum-resistant/refractory ovarian cancers are limited and only marginally effective. The development of novel, more effective therapies addresses a critical unmet medical need. Olvimulogene nanivacirepvec (Olvi-Vec), with its strong immune modulating effect on the tumor microenvironment, may provide re-sensitization to platinum and clinically reverse platinum resistance or refractoriness in platinum-resistant/refractory ovarian cancer. PRIMARY OBJECTIVE: The primary objective is to evaluate the efficacy of intra-peritoneal Olvi-Vec followed by platinum-based chemotherapy and bevacizumab in patients with platinum-resistant/refractory ovarian cancer. STUDY HYPOTHESIS: This phase III study investigates Olvi-Vec oncolytic immunotherapy followed by platinum-based chemotherapy and bevacizumab as an immunochemotherapy evaluating the hypothesis that such sequential combination therapy will prolong progression-free survival (PFS) and bring other clinical benefits compared with treatment with platinum-based chemotherapy and bevacizumab. TRIAL DESIGN: This is a multicenter, prospective, randomized, and active-controlled phase III trial. Patients will be randomized 2:1 into the experimental arm treated with Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab or the control arm treated with platinum-doublet chemotherapy and bevacizumab. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent, platinum-resistant/refractory, non-resectable high-grade serous, endometrioid, or clear-cell ovarian, fallopian tube, or primary peritoneal cancer. Patients must have had ≥3 lines of prior chemotherapy. PRIMARY ENDPOINT: The primary endpoint is PFS in the intention-to-treat population. SAMPLE SIZE: Approximately 186 patients (approximately 124 patients randomized to the experimental arm and 62 to the control arm) will be enrolled to capture 127 PFS events. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Expected complete accrual in 2024 with presentation of primary endpoint results in 2025. TRIAL REGISTRATION: NCT05281471.

The MEMORY Study: MulticentEr study of Minimally invasive surgery versus Open Radical hYsterectomy in the management of early-stage cervical cancer: Survival outcomes.

OBJECTIVE: The Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. METHODS: This is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007-12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. RESULTS: We identified 1093 cases for analysis-715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03-149.51) and 54.98 months (range, 0.03-145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9-90.4%) and 89% (95% CI: 84.9-92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47-1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6-97.2%) and 96.6% (95% CI: 93.8-98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43-1.52; P = 0.5). CONCLUSION: This multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS.

The Impact of an Enhanced Recovery After Surgery Program on Patients Treated for Gynecologic Cancer in the Community Hospital Setting.

OBJECTIVES: The purpose of this study was to compare the outcomes of gynecologic oncology patients treated in the community hospital setting either under the auspices of an enhanced recovery after surgery (ERAS) protocol or in accordance with physician discretion. METHODS: We retrospectively evaluated a series of consecutive gynecologic oncology patients who were managed via open surgery in coincident with an ERAS pathway from January 2015 to December 2016. They were compared with a historical open surgery cohort who was treated from November 2013 to December 2014. The primary clinical end points encompassed hospital length of stay, hospital costs, and patient readmission rates. RESULTS: There were 86 subjects accrued in the ERAS group and 91 patients in the historical cohort. The implementation of ERAS occasioned a greater than 3-day mean reduction in hospital stay (8.04 days for the historical group vs 4.88 days for the ERAS subjects; P = 0.001) and correspondingly diminished hospital costs ($11,877.47/patient vs $9305.26/patient; P = 0.04). Moreover, there were 2 readmissions (2.3%) in the ERAS group compared with 4 (4.4%) in the historical cohort (P = 0.282). CONCLUSIONS: The results from our investigation suggest that adhering to an ERAS protocol confers beneficial hospital length of stay and hospital cost outcomes, without compromising patient readmission rates. Additional investigation scrutinizing the impact of ERAS enactment with more defined study variables in a larger, randomized setting is warranted.

The impact of total parenteral nutrition on postoperative recovery in patients treated for advanced stage ovarian cancer.

OBJECTIVES: Total parenteral nutrition (TPN) presumably benefits cancer patients although reports have disputed the significance of this nutritional intervention. We sought to compare the postoperative outcomes of ovarian cancer patients treated with either TPN or conservative management. METHODS: We retrospectively evaluated the impact of TPN and conservative management in ovarian cancer patients who underwent debulking surgery and a bowel resection. The primary study variables encompassed patient time until restoration of bowel function, number of postoperative complications and duration of hospital stay. RESULTS: There were 147 subjects who were selected for this study. The patients who were treated with TPN (n = 69) demonstrated a longer time until restoration of bowel function (5.77 vs. 4.70 days; P < 0.001), experienced lower pre-operative albumin levels (2.22 vs. 2.97 g/dL; P < 0.001) and endured a significantly longer hospital stay (11.46 vs. 7.14 days; P < 0.001) compared to the conservative management (n = 78) cohort. CONCLUSIONS: Postoperative TPN in ovarian cancer patients may be inadvisable because of the increased risk for complications. Moreover, in the hypoalbuminemic patients, TPN may have not only delayed their postoperative recovery and increased hospital stay duration, but further precipitated the manifestation of nosocomial sequelae.

A Randomized Controlled Pilot Study Comparing the Impact of Aprepitant and Fosaprepitant on Chemotherapy Induced Nausea and Vomiting in Patients Treated for Gynecologic Cancer.

OBJECTIVE: The purpose of this pilot study was to compare the response rates and daily living activities of patients with newly diagnosed gynecologic cancer treated with fosaprepitant or aprepitant in the management of chemotherapy-induced nausea and vomiting. METHODS AND MATERIALS: Eligible participants were randomized to either intravenous fosaprepitant (150 mg, day 1) or oral aprepitant (125 mg on day 1 and 80 mg on days 2-3) before undergoing weekly paclitaxel (80 mg/2)(2) and monthly carboplatin (AUC 6)-based chemotherapy. In addition, standard premedications (eg, ranitidine, dexamethasone, and diphenhydramine) were administered intravenously on day 1. Response evaluation and impact on daily life were measured throughout the acute phase (0-24 hours), delayed period (days 2-4), and overall phase (0-120 hours) of the patients' initial chemotherapy cycle via the Functional Living Index-Emesis. RESULTS: In the current investigation, 20 gynecologic cancer subjects were treated with either fosaprepitant (n = 10) or aprepitant (n = 10) before their first chemotherapy cycle. We observed 7 overall complete responses (70%, no emetic episodes or rescue medications) in the aprepitant group and 6 (60%) in the fosaprepitant cohort (P = 0.660). In addition, both treatment groups reported similarly, favorable rates of daily living activities throughout the acute (P = 0.626) and delayed (P = 0.648) phases of cycle 1 chemotherapy. CONCLUSIONS: The findings from the current analysis suggest that intravenous fosaprepitant and oral aprepitant confer beneficial antiemetic prevention. Moreover, the 2 medications theoretically afford a favorable impact on daily living, thereby potentially facilitating the completion of a patient's clinically prescribed chemotherapy regimen.

Consolidation hyperthermic intraperitoneal chemotherapy and maintenance chemotherapy following laparoscopic cytoreductive surgery in the treatment of ovarian carcinoma.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an intriguing method of delivery wherein the cytotoxic agent is continuously heated and circulated throughout the peritoneum in an attempt to improve efficacy. Despite the potential of HIPEC in the treatment of ovarian cancer, there are limited safety, feasibility and survival data involving this procedure, particularly in conjunction with maintenance chemotherapy. PATIENTS AND METHODS: We retrospectively evaluated ovarian cancer patients who underwent laparoscopic debulking surgery, attained a complete response to their primary chemotherapy and subsequently received consolidation HIPEC with carboplatin area under the curve of 10 (AUC of 10) and a planned 12 cycles of paclitaxel (135 mg/m(2)) maintenance chemotherapy. The following demographic and clinical characteristics were abstracted: patient age, body mass index, surgery and pathology data, chemotherapy regimen, intra-operative results, toxicity, post-operative complications, length of hospital stay and disease-free/overall survival. RESULTS: We identified 37 patients who were the subject of this study. There were no intra-operative complications during the administration of HIPEC; median estimated blood loss was 50 mL and length of hospital stay was 1.25 days. In the overall study population, six patients developed grade 3/4 anaemia and 24 patients exhibited grade ≤ 2 thrombocytopenia and neutropenia. Ten patients developed grade ≤ 2 nausea on postoperative day 1; there were no hospital readmissions. Median disease-free survival and overall survival was 13 months and 14 months, respectively. CONCLUSION: The results from this ovarian cancer treatment evaluation suggest that the combination of consolidation HIPEC and maintenance chemotherapy is feasible and reasonably well tolerated.

Intra-abdominal temperature distribution during consolidation hyperthermic intraperitoneal chemotherapy with carboplatin in the treatment of advanced stage ovarian carcinoma.

PURPOSE: Hyperthermic intraperitoneal chemotherapy (HIPEC) involves the continuous heating and circulation of chemotherapy throughout the abdominal cavity in an attempt to enhance cytotoxicity. Despite the potential of this chemotherapy procedure, there are scant anatomical temperature distribution studies reporting on this therapeutic process. PATIENTS AND METHODS: We prospectively evaluated the temperature of select anatomical (e.g. upper abdominal, mid-abdominal and supra-pubic) sites in 11 advanced stage ovarian cancer patients who were treated with consolidation HIPEC carboplatin (AUC 10). The temperature of the aforementioned anatomical regions and the inflow/outflow tubing was measured at baseline and at 15-min intervals until the procedure's completion. RESULTS: The lowest observed mean composite temperature was 41.1 °C at the supra-pubic site whereas the highest temperature was 42.6 °C, in association with the inflow/outflow tubing. During the various time intervals we also ascertained that the lowest composite temperature was 40.9 °C at baseline (i.e. time 0), whereas the highest value (41.8 °C) occurred at multiple time periods (e.g., 15, 45 and 60 min). CONCLUSION: The HIPEC temperature variation amongst the various abdominal sites and time intervals was minimal. We also discerned that uniform temperature distribution throughout the abdominal cavity was facilitated when the abdomen was both maximally distended with fluid and a high flow rate was maintained.

The feasibility of administering varying high-dose consolidation hyperthermic intraperitoneal chemotherapy with carboplatin in the treatment of ovarian carcinoma.

OBJECTIVES: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an intriguing method of delivery wherein the cytotoxic agent is continuously heated and circulated throughout the peritoneum in an attempt to bolster drug efficacy. Despite HIPEC's potential, ascertaining the optimal dose without compromising patient tolerability remains indeterminate. METHODS: We retrospectively evaluated 52 advanced stage ovarian cancer patients who were treated with consolidation HIPEC with carboplatin at varying doses (e.g., AUC 6, 8 or 10) subsequent to optimal debulking surgery and the attainment of a clinical complete response to their primary chemotherapy regimen. The following patient and operative characteristics were abstracted: demographics, surgery and pathology data, chemotherapy regimen, intraoperative results, toxicity, postoperative complications, length of hospital stay and survival data. RESULTS: Twelve patients received HIPEC carboplatin at an AUC 6, 15 subjects were treated with carboplatin at an AUC 8 and 25 underwent carboplatin at an AUC 10. There were no intraoperative complications during the administration of HIPEC; mean estimated blood loss was 50 mL and length of hospital stay was 1.65 days. In the overall study population, 5 patients developed grade 3/4 anemia and 33 subjects exhibited grade ≤2 thrombocytopenia and neutropenia. Thirteen patients also developed grade ≤2 nausea on postoperative day 1, which was successfully addressed with anti-emetic therapy; there were no hospital readmissions. CONCLUSIONS: The results from the current evaluation suggest that consolidation hyperthermic intraperitoneal chemotherapy with carboplatin is both feasible and reasonably tolerated, even at an AUC of 10. However, additional, randomized study of this procedure incorporating chemotherapy dose escalation with a more extensive patient population is warranted.

The incidence of genitourinary and gastrointestinal complications in open and endoscopic gynecologic cancer surgery.

OBJECTIVES: The purpose of this study was to examine the incidence of genitourinary and intestinal tract injuries in an effort to identify which factors might predispose a patient to developing one of these surgical complications. METHODS: We retrospectively evaluated the charts of gynecologic cancer patients who were treated at a single medical institution from January 2002 to February 2011. The following study variables were noted for evaluation: age, BMI, cancer origin, disease recurrence, a history of pelvic surgery, surgery type, operative approach and injury classification (genitourinary or gastrointestinal). RESULTS: In our group of 1,618 patients, a total of 47 (2.9%) gastrointestinal and 18 (1.1%) genitourinary tract injuries were encountered. There were no intraoperative-related deaths but 2 patients expired 1 month after surgery. Logistic regression indicated that surgery type, undergoing an open procedure, cancerous involvement of the bowel or genitourinary tract and a history of pelvic surgery were significant predictors of operative injury occurrence [χ(2) (28) = 167.22; p < 0.001]. CONCLUSIONS: We ascertained a relatively low incidence of gastrointestinal and genitourinary complications. Nevertheless, undergoing an open procedure, a history of pelvic surgery and surgical involvement of the bowel or genitourinary tract were predictive of an increased risk for these aforementioned injuries.

The safety and feasibility of robotic-assisted lymph node staging in early-stage ovarian cancer.

OBJECTIVES: The purpose of this study was to report on the safety and feasibility of robotic-assisted systematic lymph node staging in the management of early-stage ovarian cancer. METHODS: We retrospectively reviewed the charts of presumed early-stage (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) ovarian cancer patients who underwent robotic-assisted surgery that incorporated a systematic pelvic and para-aortic lymphadenectomy from January 2009 until December 2013. Patient demographics, operative characteristics, pathology, lymph node counts, surgical complications, and hospital stay were evaluated. RESULTS: A total of 26 early-stage ovarian cancer patients were identified. The mean operating time was 2.90 hours, and the estimated blood loss was 63 mL; there were no intraoperative complications although 1 patient's surgery was significantly prolonged due to pelvic adhesions. The mean number of pelvic and para-aortic lymph nodes removed was 14.6 (2.3% incidence of pelvic lymph node metastases) and 5.8 (3.3% incidence of para-aortic lymph node metastases), respectively. The patients' mean duration of hospital stay was 18.4 hours, and 2 patients were readmitted for either a postoperative wound infection or vaginal dehiscence. CONCLUSIONS: The results from this study suggest that robotic-assisted surgical staging in the management of presumed early-stage ovarian cancer is both feasible and associated with a minimal patient complication rate. We encountered a low incidence of lymph node metastases, and the readmission rate was favorable. Nevertheless, because the prevalence of lymph node metastases can approach 20% in select patients, physicians should consider a systematic lymph node resection to confer an optimal clinical assessment.

Increased incidence of severe gastrointestinal events with first-line paclitaxel, carboplatin, and vorinostat chemotherapy for advanced-stage epithelial ovarian, primary peritoneal, and fallopian tube cancer.

OBJECTIVES: We sought to assess the response rate and toxicity of paclitaxel, carboplatin, andvorinostat primary induction therapy for the treatment of advanced-stage ovarian carcinoma. METHODS: Patients were treated with 6 cycles of weekly paclitaxel (80 mg/m), carboplatin (6 times area under the curve), and vorinostat (200 mg) every 28 days according to an institutional review board-approved protocol. The subjects were eligible for response evaluation; in patients who achieved stable disease or better following the conclusion of primary induction chemotherapy, they were subsequently treated with a planned 12 cycles of paclitaxel (135 mg/m) and vorinostat (400 mg) maintenance chemotherapy every 28 days. RESULTS: Eighteen patients received a combined 90 cycles (median, 6 cycles; range, 1-6 cycles) of primary induction chemotherapy. Of the 18 subjects, 7 demonstrated a complete response, and 2 subjects exhibited a partial response (a total response rate of 50.0%). Eight patients also received a combined total of 50 cycles (median, 5 cycles; range, 1-12 cycles) of consolidation therapy. Grade 3/4 neutropenia and thrombocytopenia were observed in 9 (56.3%) and 2 (12.5%) patients. One patient (6.3%) developed grade 3 anemia, and another (6.3%) manifested a grade 3 neuropathy. Remarkably, we observed a significant gastrointestinal event (eg, bowel anastomotic perforation) in 3 patients, which effectuated the study's closure. CONCLUSIONS: Because the current study was prematurely terminated, we cannot derive a conclusive assessment regarding the efficacy of this treatment. Nevertheless, the high incidence of severe gastrointestinal toxicity warrants further consideration when using vorinostat in the adjuvant setting for patients who have undergone a bowel resection as part of their initial tumor debulking.

Clinical Activity of Olvimulogene Nanivacirepvec-Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer: The Nonrandomized Phase 2 VIRO-15 Clinical Trial.

Importance: Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need. Objective: To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC. Design, Setting, and Participants: This open-label, nonrandomized multisite phase 2 VIRO-15 clinical trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022. Interventions: Olvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab. Main Outcomes and Measures: Primary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS). Results: Twenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths. Conclusions and Relevance: In this phase 2 nonrandomized clinical trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02759588.

Same-day discharge in clinical stage I endometrial cancer patients treated with total laparoscopic hysterectomy, bilateral salpingo-oophorectomy and bilateral pelvic lymphadenectomy.

OBJECTIVES: The purpose of this retrospective study was to evaluate the capacity for same-day discharge in clinical stage I endometrial cancer (EC) patients treated with total laparoscopic hysterectomy (TLH), bilateral salpingo-oophorectomy (BSO) and bilateral pelvic lymph node dissection (BPLND). METHODS: We retrospectively reviewed the charts of stage I EC patients who were treated with TLH, BSO and BPLND and discharged on the same day. The intra- and postoperative clinical variables (e.g., age, complications, surgery time, patient hospital stay) were evaluated in an attempt to discern which factors may predispose a patient to same-day discharge. RESULTS: Twenty-one patients were successfully discharged on the same day of surgery. Mean operative time was 1.48 h and length of hospital stay was 6.35 h. There were no intraoperative complications or hospital readmissions. CONCLUSIONS: We present a single, institutional experience solely assessing the capacity for same-day discharge in clinical stage I EC patients treated with TLH, BSO and BPLND. Since the postoperative complication rate was minimal with no hospital readmissions, we suggest that particularly selected stage I EC patients are amenable to outpatient management.

Paget's disease of the vulva: a clinicopathologic institutional review.

BACKGROUND: The aim of this study was to assess the clinicopathologic characteristics of patients with Paget's disease of the vulva who were treated by our gynecologic oncology service between 1985 and 2010. METHODS: Vulvar Paget's disease patient demographics, pathologic diagnosis, treatment and follow-up data were reviewed over a 25-year period. RESULTS: The vulvar Paget's disease patients were primarily (62.5%) treated with a partial simple vulvectomy. Three patients had a history of malignancy, although none of them was intercurrent. Eleven patients had microscopically positive margins, 5 of whom developed progressive disease. Conversely, 5 patients had negative margins, of whom 4 had recurrent disease. There was a significant relationship between the presence of invasive disease and patient progression-free interval (PFI) (p = 0.007), but margin status and lesion size did not correlate with PFI (p > 0.05). Median patient PFI and follow-up was 30 and 53 months, respectively. CONCLUSIONS: We found a significant relationship between the presence of invasive disease and patient PFI in vulvar Paget's disease although the presence of microscopic positive margins and lesion size were not prognostic indicators. In patients with high risk factors, prolonged surveillance should be considered an essential component of optimal patient management.

Acute and delayed complications from surgery and adjuvant radiotherapy in the treatment of high-risk endometrial cancer.

OBJECTIVES: This retrospective study assessed the number and type of complications following surgery and adjuvant radiotherapy in the treatment of high-risk endometrial cancer. METHODS: Endometrial cancer patients who received surgery and postoperative radiotherapy (pelvic radiotherapy and/or vaginal brachytherapy) from April 1997 until October 2010 were evaluated. Short-term (≤6 months) and long-term (>6 months) complications (e.g., genitourinary/gastrointestinal complications) were comprehensively reviewed. RESULTS: We identified 109 high-risk endometrial cancer patients who completed adjuvant radiotherapy following either a total abdominal hysterectomy (TAH; n = 53) or minimally invasive hysterectomy (MIS; n = 56). The combined impact of surgery and radiotherapy on complication type did not reach statistical significance (p > 0.05). However, surgery type and the development of a complication were significantly related (p < 0.001). The MIS patients developed complications at a more accelerated rate compared to the TAH patients (21 vs. 45 months), although the incidence of toxicity of grade 3 or 4 was much higher in the TAH group. CONCLUSIONS: The impact of MIS and adjuvant radiotherapy may have adversely affected the development of complications compared to TAH patients who received adjuvant radiotherapy, although higher-grade patient toxicity was more prevalent in the TAH group.

Endometrioid adenocarcinoma arising from endometriosis: a case report.

BACKGROUND: Endometriosis is frequently identified in the ovaries, rectum, pelvic peritoneum, cervix and vagina. However, endometriosis undergoing malignant transformation is a rare event, particularly when the condition manifests itself promptly after initial surgical management. CASE: We present a case involving a 52-year-old woman who tested positive for the BRCA1 mutation and was diagnosed with endometriosis in 1999. Two years following treatment, the patient presented with an endometrioid adenocarcinoma; pathologic evaluation indicated that the neoplasm originated from the endometriosis. CONCLUSION: Malignant transformation is a very unusual event and reportedly occurs over several years. Nevertheless, considering the current patient's relatively sudden onset of disease, oncologists should maintain a high index of suspicion in high-risk patients treated surgically for endometriosis who re-present with pelvic symptoms.

Survival outcomes for women undergoing type III robotic radical hysterectomy for cervical cancer: a 3-year experience.

OBJECTIVES.: To assess progression-free (PFS) and overall survival (OS) for women with cervical cancer who underwent type III robotic radical hysterectomy (RRH). METHODS.: A retrospective analysis of women who underwent RRH from 2005 to 2008 was performed. The data analyzed included patient demographics, histology, clinical stage, surgical margins, lymph node and disease status. Comparison was made to a group of historical open radical hysterectomies. Survival statistics were analyzed using the Kaplan-Meier method. RESULTS.: Seventy-one women underwent attempted RRH during the study period. Eight were excluded from analysis, 4 for non-cervical primary and 4 cases aborted due to extent of disease. Squamous was the most common histology (62%) followed by adenocarcinoma (32%). Median patient age was 43 years. There was one intraoperative complication (asystole after induction) and two postoperative complications (ICU admission to rule out myocardial infarction and reoperation for cuff dehiscence). Of the patients who underwent RRH, 32% received whole-pelvis radiation with chemo sensitization. The median follow-up was 12.2 months (range 0.2-36.3 months). Kaplan-Meier survival analysis demonstrated 94% PFS and OS at 36 months due to the recurrence and death of one patient. Compared with a historical cohort at our institution, there was no statistically significant difference in PFS (P=0.27) or OS (P=0.47). CONCLUSIONS.: RRH is safe and feasible and has been shown to be associated with improved operative measures. This study shows that at 3 years, RRH appears to have PFS and OS equivalent to that of traditional laparotomy. Longer follow-up is needed, but early data are supportive of at least equivalent oncologic outcomes compared with other surgical modalities.

Metformin is a potent inhibitor of endometrial cancer cell proliferation--implications for a novel treatment strategy.

OBJECTIVES: Obesity and diabetes are strong risk factors that drive the development of type I endometrial cancers. Recent epidemiological evidence suggests that metformin may lower cancer risk and reduce rates of cancer deaths among diabetic patients. In order to better understand metformin's anti-tumorigenic potential, our goal was to assess the effect of metformin on proliferation and expression of key targets of metformin cell signaling in endometrial cancer cell lines. METHODS: The endometrial cancer cell lines, ECC-1 and Ishikawa, were used. Cell proliferation was assessed after exposure to metformin. Cell cycle progression was evaluated by flow cytometry. Apoptosis was assessed by ELISA for caspase-3 activity. hTERT expression was determined by real-time RT-PCR. Western immunoblotting was performed to determine the expression of the downstream targets of metformin. RESULTS: Metformin potently inhibited growth in a dose-dependent manner in both cell lines (IC(50) of 1 mM). Treatment with metformin resulted in G1 arrest, induction of apoptosis and decreased hTERT expression. Western immunoblot analysis demonstrated that metformin induced phosphorylation of AMPK, its immediate downstream mediator, within 24 h of exposure. In parallel, treatment with metformin decreased phosphorylation of S6 protein, a key target of the mTOR pathway. CONCLUSIONS: We find that metformin is a potent inhibitor of cell proliferation in endometrial cancer cell lines. This effect is partially mediated through AMPK activation and subsequent inhibition of the mTOR pathway. This work should provide the scientific foundation for future investigation of metformin as a strategy for endometrial cancer prevention and treatment.

Perioperative outcomes of robotically assisted hysterectomy for benign cases with complex pathology.

OBJECTIVE: To report on the perioperative outcomes after robotically assisted total hysterectomy for benign indications in a large patient population with predominantly complex pathology. METHODS: One hundred fifty-two patients underwent robotic hysterectomy for noncancer indications from May 2005 to May 2008. A systematic chart review of consecutive robotic cases was conducted based on preoperative and perioperative characteristics of each patient. Each case was evaluated for its complexity based on preoperative diagnosis, prior pelvic or abdominal surgery, patient's body mass index, and uterine weight. RESULTS: The overall operative time was 122.9 minutes, estimated blood loss was 79.0 mL, and there were three (2.1%) intraoperative complications, with no perioperative blood transfusions or conversions. There were five (3.5%) patients with postoperative complications, and length of hospital stay was 1.0 days on average. Of the characteristics indicating complexity, only uterine weight greater than 250 g resulted in significantly increased operative times, attributable to increased morcellation time. CONCLUSION: Robotically assisted total hysterectomy for benign indications in patients with complex pathology is feasible, with low morbidity and a short hospital stay. This study suggests that robotic assistance facilitates the use of a minimally invasive approach in high-risk patient populations. LEVEL OF EVIDENCE: III.

Emergence of robotic assisted surgery in gynecologic oncology: American perspective.

OBJECTIVES: To discuss the emergence of robotic surgery in gynecologic oncology and describe the growth of robotic surgery in a university medical center and a community based practice. METHODS: In addition to the historical evolution of the robotic assisted surgery medicine, a survey of robotic cases was performed on two robotic programs since the inception of the programs. A review of the current literature on the use of the da Vinci robot in gynecologic oncology was also performed. RESULTS: The robotic surgery programs at UNC Hospital and Florida Hospital are growing steadily since the inception of the programs in 2005 and 2006, respectively. Since 2005 there have also been numerous publications detailing the effectiveness, safety, and efficiency of the robot. CONCLUSIONS: Robotic surgery is gaining acceptance and is rapidly growing as evidenced by an increased number of publications on the topic; these publications demonstrate the safety, efficacy, and improved outcomes compared to open surgery and conventional laparoscopy.