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.

Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer.

PURPOSE: Evaluate the antitumor activity and safety profile of the combination of mirvetuximab soravtansine and bevacizumab in patients with platinum-resistant ovarian cancer. METHODS: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, whose most recent platinum-free interval was ≤6 months, were administered mirvetuximab soravtansine (6 mg/kg adjusted ideal body weight) and bevacizumab (15 mg/kg), intravenously, once every 3 weeks. Eligibility included FRα expression by immunohistochemistry (IHC; ≥25% of cells with ≥2+ intensity). Prior bevacizumab and/or PARP inhibitor (PARPi) treatment were permitted. The primary endpoint was confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety. RESULTS: Ninety-four patients received combination treatment with mirvetuximab soravtansine and bevacizumab. Median age was 62 years (range, 39-81). Fifty-two percent had ≥3 prior therapies; 59% had prior bevacizumab; and 27% had prior PARPi. ORR was 44% (95% CI 33, 54) with 5 complete responses, median DOR 9.7 months (95% CI 6.9, 14.1), and median PFS 8.2 months (95% CI 6.8, 10.0). Treatment-related adverse events were consistent with the profiles of each agent, with the most common being blurred vision (all grades 57%; grade 3, 1%), diarrhea (54%; grade 3, 1%), and nausea (51%; grade 3, 1%). CONCLUSION: The mirvetuximab soravtansine plus bevacizumab doublet is an active and well-tolerated regimen in patients with FRα-expressing platinum-resistant ovarian cancer. Promising activity was observed for patients regardless of level of FRα expression or prior bevacizumab. These data underscore the potential for mirvetuximab soravtansine as the combination partner of choice for bevacizumab in this setting.

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.

Enhanced Recovery after Surgery (ERAS) Protocol for Early Discharge within 12 Hours after Robotic Radical Hysterectomy.

To evaluate safety of quick discharge after robotic radical hysterectomy (RRH) in a tertiary hospital which has the enhanced recovery after surgery (ERAS) protocol. Among 94 consecutive cervical cancer patients who had undergone RRH, operative outcomes and the rate of unexpected visit after surgery were analyzed retrospectively. Patients were categorized as a surgery-to-discharge time of ≤12 h (early discharge [ED]) or >12 h (late discharge [LD]). About 77% (n = 72) of analyzed 94 patients discharged within 12 h after RRH. The ED group had significant correlation with shorter duration for urinary catheter required, less operative blood loss, and less voiding difficulty after long-term follow up compared to the LD group. There was no difference of perioperative complications and unexpected visit between the two groups. Performing nerve sparing (NS) RRH was only independent predictor for ED (p = 0.043, hazard ratio for LD = 0.22, confidence interval = 0.05-0.95). In conclusion, the ED within 12 h after RRH was safe in the setting of ERAS protocol. The NS-RRH could avoid the delay of genitourinary function recovery after surgery which caused LD. It can become the reasonable clinical pathway to discharge early patients who undergo NS-RRH with ERAS protocol.

The early surgical period in robotic radical hysterectomy is related to the recurrence after surgery in stage IB cervical cancer.

Objective: To identify the pattern of recurrence and assess the clinicopathologic prognostic factors for survival after robotic radical hysterectomy (RRH) in the treatment of stage IB cervical cancer. Methods: From December 2008 to March 2018, 64 cervical cancer patients who underwent RRH with pelvic lymph node dissection by a single surgeon were enrolled in this retrospective historical cohort timeline study. The patient's status was estimated in terms of operative outcomes, pathologic results, and survival outcomes. Results: The median follow-up was 63 months. The recurrence rate was 9.4% (6/64). There were two recurrences at the vaginal vault, two in the pelvic cavity, and two at the peritoneum in the intraabdominal cavity. The overall survival rate was 95.3% (61/64). When patients were divided into three groups in order based on surgery date, the first surgical period showed significantly higher recurrence rate (21%) compared to both the second (10%) and the third period (0%) (p=0.037). Multivariate analysis showed that the early period of RRH (p=0.025) and clinical tumor size more than 3 cm (p=0.003) were prognostic factors related to the recurrence. Although there was no statistical significance, there has been no recurrence since a uterine manipulator was not used. Conclusion: The early surgical period and large tumor were related to the disease recurrence after RRH. We suggest that the achievement of proficiency and appropriate patient selection are critical for prognosis after RRH in stage IB cervical cancer.

Factors in the feasibility and safety of outpatient robotic-assisted hysterectomy for endometrial or cervical carcinoma.

OBJECTIVE: Identify factors influencing the feasibility and safety of outpatient robotic-assisted hysterectomy for endometrial or cervical carcinoma. METHODS: A single-institution retrospective chart review of patients who underwent robotic hysterectomy for cervical or endometrial cancer between 2012 and 2016 was performed. Outcomes were measured by length of stay (LOS), which was categorized as an admit-to-discharge time of >12 h or <12 h. Past medical history, surgical history, social history, patient demographics, intraoperative course, and postoperative events were examined as possible factors associated with LOS >12 h. These factors were evaluated using multivariate logistic regression. Readmission rates were compared between the two groups using an independent-samples t-test. RESULTS: Of the 254 patients, 150 (59.1%) had a LOS >12 h and 104 (40.9%) had a LOS < 12 h. The factors associated with a LOS >12 h (p < 0.05) included: Postoperative emesis, inadequate pain control, operating room (OR) time > 180 min, uterine mass > 150 g, start time after 15:00, history of venous thromboembolism (VTE), age > 75 years, body mass index (BMI) 35-40, and post-operative VTE formation. Patients discharged in <12-hours were not more likely than those discharged in >12-hours to be re-admitted (p = 0.92). CONCLUSIONS: Robotic hysterectomy for the treatment of endometrial and cervical carcinoma is both feasible and safe in the outpatient setting, as >40% of patients were successfully discharged within 12 h with no increase in readmission. Multiple risk factors were identified for extended hospitalization, offering potential for the development of a risk stratification model to improve the efficacy of outpatient robotic hysterectomy.

Comparative analysis of genitourinary function after type C1 robotic nerve-sparing radical hysterectomy versus type C2 robotic radical hysterectomy.

BACKGROUND: To compare the return of bladder function and genitourinary complications after type C1 robotic nerve-sparing radical hysterectomy (C1-RRH) to type C2 robotic radical hysterectomy (C2-RRH) in gynecologic cancers. METHODS: A retrospective analysis between C1-RRH (n = 42) and C2-RRH (n = 43) was performed. Operative outcomes and perioperative genitourinary complications between the two groups were analyzed. RESULTS: The C1-RRH group had shorter hospitalization (0.7 vs. 1.7 days, p < 0.001) and shorter DUC (1 vs. 28 days, p < 0.001). About 76% of C1-RRH group required a catheter for less than 1 week while 84% of the C2-RRH group did for more than 1 week (54% for 1-6 weeks; 30% > 6 weeks). In spite of the short stay after surgery (95% of C1-RRH ≤ 1 day), only two patients (4.8%) in C1-RRH group were admitted again because of urinary tract infection. C1-RRH was only independent predictor for early bladder function return within 1 week after surgery. CONCLUSION: The C1-RRH showed early bladder function return and feasible outcomes in spite of early discharge. It can be considered as the first surgical option in gynecologic cancer patients who need RH to preserve their bladder function.

Robotic lower pelvic port placement for optimal upper paraaortic lymph node dissection.

OBJECTIVE: Upper paraaortic lymph node dissection (UPALD) to the infrarenal level is one of the most challenging robotic procedures. Because robotic system has the limitation in robotic arm mobility. This surgical video introduces a novel robotic approach, lower pelvic port placement (LP3), to perform optimally and simultaneously both UPALD and pelvic procedures in gynecologic cancer patients using da Vinci Xi system. METHODS: The patient presented with high-grade endometrial cancer. She underwent robotic surgical staging operation. For the setup of the LP3, a line was drown between both anterior superior iliac spines. At 3 cm below this line, another line was drown and four robotic ports were placed on this line. RESULTS: After paraaortic lymph node dissection (PALD) was completed, the boom of robotic system was rotated 180° to retarget for the pelvic lateral displacement. Robotic ports were placed and docked again. The operation was completed robotically without any complication. CONCLUSION: The LP3 was feasible for performing simultaneously optimal PALD as well as procedures in pelvic cavity in gynecologic cancer patients. The advantage of LP3 technique is the robotic port placement that affords for multi-quadrant surgery, abdominal and pelvic dissection. The LP3 is facilitated by utilizing advanced technology of Xi system, including the patient clearance function, the rotating boom, and 'port hopping' that allows using every ports for a camera. The LP3 will enable surgeons to extend the surgical indication of robotic surgical system in the gynecologic oncologic field.

How to prepare the patient for robotic surgery: before and during the operation.

Robotic surgery in the treatment of gynecologic diseases continues to evolve and has become accepted over the last decade. The advantages of robotic-assisted laparoscopic surgery over conventional laparoscopy are three-dimensional camera vision, superior precision and dexterity with EndoWristed instruments, elimination of operator tremor, and decreased surgeon fatigue. The drawbacks of the technology are bulkiness and lack of tactile feedback. As with other surgical platforms, the limitations of robotic surgery must be understood. Patient selection and the types of surgical procedures that can be performed through the robotic surgical platform are critical to the success of robotic surgery. First, patient selection and the indication for gynecologic disease should be considered. Discussion with the patient regarding the benefits and potential risks of robotic surgery and of complications and alternative treatments is mandatory, followed by patient's signature indicating informed consent. Appropriate preoperative evaluation-including laboratory and imaging tests-and bowel cleansing should be considered depending upon the type of robotic-assisted procedure. Unlike other surgical procedures, robotic surgery is equipment-intensive and requires an appropriate surgical suite to accommodate the patient side cart, the vision system, and the surgeon's console. Surgical personnel must be properly trained with the robotics technology. Several factors must be considered to perform a successful robotic-assisted surgery: the indication and type of surgical procedure, the surgical platform, patient position and the degree of Trendelenburg, proper port placement configuration, and appropriate instrumentation. These factors that must be considered so that patients can be appropriately prepared before and during the operation are described.

Multicenter analysis comparing robotic, open, laparoscopic, and vaginal hysterectomies performed by high-volume surgeons for benign indications.

OBJECTIVE: To compare perioperative outcomes between robotic-assisted benign hysterectomies and abdominal, vaginal, and laparoscopic hysterectomies when performed by high-volume surgeons. METHODS: A multicenter data analysis compared 30-day outcomes from consecutive robotic-assisted hysterectomies performed by high-volume surgeons (≥60 prior procedures) at nine centers with records retrieved from the Premier Perspective database for abdominal, vaginal, and laparoscopic hysterectomies performed by high-volume gynecologic surgeons. Data on benign hysterectomy disorders from January 1, 2012 to September 30, 2013 were included. RESULTS: Data from 2300 robotic-assisted, 9745 abdominal, 8121 vaginal, and 11 952 laparoscopic hysterectomies were included. The robotic-assisted patient cohort had a significantly higher rate of adhesive disease compared with the vaginal (P<0.001) and laparoscopic cohorts (P<0.001), a significantly higher rate of morbid obesity than the vaginal (P<0.001) or laparoscopic cohorts (P<0.001), and a significantly higher rate of large uteri (>250g) than the abdominal (P<0.001), vaginal (P<0.001), or laparoscopic cohorts (P=0.017). The robotic-assisted cohort experienced significantly fewer intraoperative complications than the abdominal (P<0.001) and vaginal cohorts (P<0.001), and experienced significantly fewer postoperative complications compared with all the comparator cohorts (P<0.001). CONCLUSION: When performed by gynecologic surgeons with relevant high-volume experience, robotic-assisted benign hysterectomy provided improved outcomes compared with abdominal, vaginal, and laparoscopic hysterectomy.

Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: A Gynecologic Oncology Group Study.

PURPOSE: To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. PATIENTS AND METHODS: Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage. RESULTS: Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036). CONCLUSION: History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.

Karyometry in atypical endometrial hyperplasia: a Gynecologic Oncology Group study.

OBJECTIVES: Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). METHODS: Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. RESULTS: Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is the percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. CONCLUSIONS: AEH comprises cases which may constitute a low risk group involving <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have >40% of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. The percentage of nuclei of the preneoplastic phenotype in AEH esions might serve as criterion for assessment of risk for the development of invasive disease.

Phase III trial of induction gemcitabine or paclitaxel plus carboplatin followed by paclitaxel consolidation in ovarian cancer.

OBJECTIVE: The safety and efficacy of gemcitabine plus carboplatin (GC) or paclitaxel plus carboplatin (TC) induction regimens with or without paclitaxel consolidation therapy were assessed in ovarian cancer (OC). METHODS: Patients with stage IC-IV OC were randomized to either GC (gemcitabine 1,000 mg/m(2), days 1 and 8, plus carboplatin area under the curve [AUC] 5, day 1) or TC (paclitaxel 175 mg/m(2) plus carboplatin AUC 6, day 1) every 21 days for up to six cycles. Patients with complete response (CR) were allowed optional consolidation with paclitaxel 135 mg/m(2) every 28 days for ≤ 12 months. Patients without CR received single-agent crossover therapy at induction doses/schedules until CR, disease progression (PD), or unacceptable toxicity. PD or death in 636 patients was required to compare induction arms with 80% statistical power for progression-free survival (PFS), the primary endpoint. RESULTS: Randomized induction therapy was received by 820 of 919 patients enrolled; 352 patients with CR received paclitaxel consolidation whereas 155 patients without CR received single-agent crossover therapy. PFS was similar for GC and TC (median, 20.0 and 22.2 months, respectively; P=.199). Despite high censoring rates (>52%), overall survival was longer for TC (median, 57.3 versus 43.8 months for GC; P=.013). Controlling for patient characteristics including performance status, residual tumor size, and tumor stage, there was no statistical difference in a multivariate analysis (HR=1.22; 95% CI=0.99-1.52; P=.067). CONCLUSIONS: GC does not improve PFS over TC as first-line induction chemotherapy in OC. Although favoring TC, overall survival analyses were limited by the study design and high censoring rates.

A comparative detail analysis of the learning curve and surgical outcome for robotic hysterectomy with lymphadenectomy versus laparoscopic hysterectomy with lymphadenectomy in treatment of endometrial cancer: a case-matched controlled study of the first one hundred twenty two patients.

GOAL: To determine the learning curve and surgical outcome for the first one hundred twenty-two robotic hysterectomy with lymphadenectomy patients in comparison to the first one hundred twenty-two patients who underwent the same procedure laparoscopically. MATERIALS AND METHODS: An analysis of the first 122 patients who underwent a robotic assisted hysterectomy with lymphadenectomy (RHBPPALND) was compared to the first 122 patients who underwent a total laparoscopic hysterectomy with lymphadenectomy (LHBPPALND). The learning curve of the surgical procedure was determined by measuring operative time with respect to chronological order of each patient who had undergone their respective procedure. Number of lymph nodes, estimated blood loss, days of hospitalization, and complications of all patients were also analyzed and compared. RESULTS: The learning curve of the surgical procedure was determined by measuring operative time with respect to chronological order of each patient who had undergone their respective procedure. Data were analyzed for mean age, body mass index, operative time, estimated blood loss, lymph node retrieval and complications for both surgical procedures. The mean operative time was 147.2±48.2 and 186.8±59.8 for RHBPPALND and LHBPPALND respectively. The mean EBL was statistically significant at 81.1±45.9 and 207.4±109.4 for RHBPPALND and LHBPPALND respectively. The total number of pelvic and aortic lymph nodes was 25.1±12.7 for RHBPPALND and 43.1±17.8 for LHBPPALND. The number of pelvic lymph node was 19.2±9.0 and 24.7±11.9 for RHBPPALND and LHBPPALND. The days of hospitalization of RHBPPALND and LHBPPALND were 1.5±0.9 and 3.2±2.3. The number of intraoperative complications for RHBPPALND, and LHBPPALND was 1 and 7, respectively. CONCLUSION: Robotic hysterectomy with lymphadenectomy has a faster learning curve in comparison to laparoscopic hysterectomy with lymphadenectomy. The adequacy of surgical staging was comparable between the two surgical methods. RHBPPALND is associated with shorter hospitalization, less blood loss and less intraoperative and major complications, and lower rate of conversion to open procedure.

Robot-assisted total intracorporeal low anterior resection with primary anastomosis and radical dissection for treatment of stage IV endometriosis with bowel involvement: morbidity and its outcome.

Robot-assisted low anterior resection with primary sigmoid rectal anastomosis/ureterolysis/hysterectomy with bilateral salpingo-oophorectomy (RALARH), and exploratory laparotomy low anterior resection with primary sigmoid rectal anastomosis/ureterolysis/hysterectomy with bilateral salpingo-oophorectomy (ELLARH). A total of eighteen patients (8 RALARH and 10 ELLARH) met the inclusion criteria. The mean age of the RALARH group was 47 and that of the ELLARH group was 36.9. There was no difference between body mass index (RALARH = 30.3 ± 6.6, 95% CI (25.7, 56.0) vs. ELLARH = 26.7 ± 7.5). Total operative time for the RALARH group was 238.5 ± 57.8 min, 95% CI: (164.5, 279.9) whereas that for the ELLARH group was 237 ± 117.7 min. There were no statistically significant differences between blood loss (RALARH = 425 ± 462.1 cc, 95% CI: (104.8, 745.2). ELLARH = 630 ± 432.2 cc) or days of hospitalization (RALARH = 5.5 ± 2.4 days, 95% CI: (3.8, 7.2) vs. ELLARH = 6.2 ± 1.6 days) in the RALARH and ELLARH groups. There were fewer complications in the RALARH group than in the ELLARH group (RALARH two complications vs. ELLARH two blood transfusion and two rectovaginal fistula), but the difference was not significant because of the small sample size. Robotic low anterior resection with primary sigmoid rectal anastomosis with ureterolysis at the time of hysterectomy and bilateral salpingo-oophorectomy for treatment of Stage IV endometriosis is a feasible and safe procedure.

Learning curve and surgical outcome for robotic-assisted hysterectomy with lymphadenectomy: case-matched controlled comparison with laparoscopy and laparotomy for treatment of endometrial cancer.

STUDY OBJECTIVE: To determine the learning curve for robotic-assisted hysterectomy with lymphadenectomy for surgical treatment of endometrial cancer. DESIGN: An analysis of robotic-assisted hysterectomy with lymphadenectomy vs total laparoscopic hysterectomy with lymphadenectomy and laparotomy with total abdominal hysterectomy with lymphadenectomy (Canadian Task Force classification II-1). SETTING: Solo, experienced, minimally invasive gynecologic oncology practice in a tertiary hospital. PATIENTS: One hundred forty-eight patients including 56 patients who underwent robotic-assisted hysterectomy with bilateral pelvic and paraaortic lymph node dissection, 56 patients who underwent total laparoscopic hysterectomy with bilateral pelvic and paraaortic lymph node dissection, and 36 patients who underwent traditional total abdominal hysterectomy with bilateral pelvic and paraaortic lymph node dissection performed by the same surgeon for treatment of endometrial cancer. INTERVENTIONS: Robotic-assisted hysterectomy with bilateral lymphadenectomy, total laparoscopic hysterectomy with bilateral lymphadenectomy, and traditional total abdominal hysterectomy with bilateral lymphadenectomy were performed. Data were categorized by chronologic order of cases into groups of 20 patients each. The learning curve of the surgical procedure was estimated by measuring operative time with respect to chronologic order of each patient who had undergone the respective procedure. MEASUREMENTS AND MAIN RESULTS: For the 3 surgical procedures, data analyzed included mean age, body mass index, operative time, blood loss, lymph node retrieval, and complications. Mean (SD); 95% confidence interval [CI]) operative time for the 3 procedures was statistically significant: 162.5 (53) minutes (95% CI, 148.6-176.4]), 192.3 (55.5) minutes (95% CI, 177.6-207.0), and 136.9 (32.3) minutes (95% CI, 126.3-147.5), respectively. Analysis of operative time for robotic-assisted hysterectomy with bilateral lymph node dissection with respect to chronologic order of each group of 20 cases demonstrated a decrease in operative time: 183.2 (69) minutes (95% CI; 153.0-213.4) for cases 1 to 20, 152.7 (39.8) minutes (95% CI, 135.3-170.1) for cases 21 to 40, and 148.8 (36.7) minutes (95% CI, 130.8-166.8) for cases 41 to 56. For the groups with laparoscopic hysterectomy with lymphadenectomy and traditional total abdominal hysterectomy with lymphadenectomy, there was no difference in operative time with respect to chronologic group order of cases. There was a difference between the number of lymph nodes retrieved between robotic-assisted hysterectomy with bilateral lymphadenectomy (26.7 [12.8]; 95% CI, 23.3-30.1) compared with laparoscopic hysterectomy with bilateral lymphadenectomy (45.1 [20.9]; 95% CI, 39.6-50.6) and traditional total abdominal hysterectomy with lymphadenectomy (55.8 [23.4]; 95% CI, 48.2-63.4). The rate of intraoperative complications for laparoscopic hysterectomy with bilateral lymphadenectomy was 12.5% (7 of 56) compared with 0 % for robotic-assisted hysterectomy with bilateral lymphadenectomy. The rate of postoperative complications was 14.3% (8 of 56), 21.4% (12 of 56), and 19.4% (7 of 36), respectively, for the 3 groups. There was less blood loss with robotic-assisted hysterectomy with bilateral lymphadenectomy (89.3 [45.4]; 95% CI, 77.4-101.2) compared with laparoscopic hysterectomy with bilateral lymphadenectomy (209.1 [91.8]; 95% CI, 185.1-233.1) and traditional total abdominal hysterectomy with lymphadenectomy (266.0 [145.1]; 95% CI, 218.6-313.4). Duration of hospitalization was shorter in the group with robotic-assisted hysterectomy with bilateral lymphadenectomy (1.6 [0.7]; 95% CI, 1.4-1.8) compared with the groups who underwent laparoscopic hysterectomy with bilateral lymphadenectomy (2.6 [0.9]; 95% CI, 2.4-2.8) or traditional total abdominal hysterectomy with lymphadenectomy (4.9 [1.9]; 95% CI, (4.3-5.5). CONCLUSION: The learning curve for robotic-assisted hysterectomy with lymph node dissection seems to be easier compared with that for laparoscopic hysterectomy with lymph node dissection for surgical management of endometrial cancer.

Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study.

BACKGROUND: Adenocarcinoma of the endometrium is the most common gynecologic malignancy in the United States, accounting for approximately 36,000 diagnoses of invasive carcinoma annually. The most common histologic type, endometrioid adenocarcinoma (EC), accounts for 75-80% of patients. The objective of this work was to estimate the prevalence of concurrent carcinoma in women with a biopsy diagnosis of the precursor lesion, atypical endometrial hyperplasia (AEH). METHODS: This prospective cohort study included women who had a community diagnosis of AEH. Diagnostic biopsy specimens were reviewed independently by three gynecologic pathologists who used International Society of Gynecologic Pathologists/World Health Organization criteria. Study participants underwent hysterectomy within 12 weeks of entry onto protocol without interval treatment. The hysterectomy slides also were reviewed by the study pathologists, and their findings were used in the subsequent analyses. RESULTS: Between November 1998 and June 2003, 306 women were enrolled on the study. Of these, 17 women were not included in the analysis: Two patients had unreadable slides because of poor processing or insufficient tissue, 2 patients had only slides that were not endometrial, the slides for 5 patients were not available for review, and 8 of the hysterectomy specimens were excluded because they showed evidence of interval intervention, either progestin effect or ablation. In total, 289 patients were included in the current analysis. The study panel review of the AEH biopsy specimens was interpreted as follows: 74 of 289 specimens (25.6%) were diagnosed as less than AEH, 115 of 289 specimens (39.8%) were diagnosed as AEH, and 84 of 289 specimens (29.1%) were diagnosed as endometrial carcinoma. In 5.5% (16 of 289 specimens), there was no consensus on the biopsy diagnosis. The rate of concurrent endometrial carcinoma for analyzed specimens was 42.6% (123 of 289 specimens). Of these, 30.9% (38 of 123 specimens) were myoinvasive, and 10.6% (13 of 123 specimens) involved the outer 50% of the myometrium. Among the women who had hysterectomy specimens with carcinoma, 14 of 74 women (18.9%) had a study panel biopsy consensus diagnosis of less than AEH, 45 of 115 women (39.1%) had a study panel biopsy consensus diagnosis of AEH, and 54 of 84 women (64.3%) had a study panel diagnosis of carcinoma. Among women who had no consensus in their biopsy diagnosis, 10 of 16 women (62.5%) had carcinoma in their hysterectomy specimens. CONCLUSIONS: The prevalence of endometrial carcinoma in patients who had a community hospital biopsy diagnosis of AEH was high (42.6%). When considering management strategies for women who have a biopsy diagnosis of AEH, clinicians and patients should take into account the considerable rate of concurrent carcinoma.

Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study.

BACKGROUND: Most gynecologists determine therapy based on current International Society of Gynecologic Pathologists (ISGP)/World Health Organization classification of endometrial hyperplasia, the reproducibility of which has been questioned. The Gynecologic Oncology Group (GOG) initiated a protocol to assess the efficacy of hormonal therapy of atypical endometrial hyperplasia (AEH). Primary goals of the first phase (Part A) were to prospectively determine reproducibility of referring institution's pathologist's diagnosis of AEH by a panel of 3 gynecologic pathologists and to determine reproducibility of diagnoses by panel members. METHODS: Three hundred six women were entered on this protocol with a referring institution's pathologist diagnosis of AEH based on biopsy or curettage. Available slides were assessed independently and interpreted by each of a panel of 3 gynecologic pathologists who used International Society of Gynecologic Pathologists (ISGP)/World Health Organization criteria. The majority diagnosis was based on diagnostic concordance by at least 2 of the 3 panelists. RESULTS: The referring institution's pathologist's diagnosis of AEH was supported by the majority of the panel in only 38% of cases. Overall kappa value for the panel diagnosis of AEH was 0.28. The majority diagnosis was adenocarcinoma in 29%, cycling endometrium in 7%, and nonatypical hyperplasia in 18% of cases. Unanimous agreement for any diagnosis was reached among all 3 of the panel in 40% of cases. For the panel, paired kappa values for any diagnosis ranged 0.34-0.43, with an overall kappa value of 0.40. CONCLUSION: Reproducibility of referring institution's pathologists' diagnosis of AEH by a panel of gynecologic pathologists is poor. Both underestimation and overestimation of the severity of the lesion are very common. The level of reproducibility among subspecialist panel members for diagnosis of AEH in these specimens also is poor. Better criteria and better sampling are needed to improve reproducibility of this diagnosis, particularly if it is to be used for clinical decisions.