High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Surgical Management of Early Cervical Cancer: When Is Laparoscopic Appropriate?

PURPOSE OF REVIEW: This paper reviews the recent literature data on minimally invasive surgical approach to early cervical cancer compared to abdominal approach, with the aim of evaluate the oncological outcomes and the appropriateness of current indications. RECENT FINDINGS: A recent multicenter randomized controlled trial and a concurrent large epidemiological study, contrary to the previous retrospective data, showed that minimally invasive surgery is associated with significantly poorer survival than the open approach. Open surgery is to be considered the standard of care for early cervical cancer as implemented in the current guidelines, and the patients must be carefully counseled if minimally invasive surgery is offered. Minimally invasive surgery can be considered safe only for sentinel lymph node mapping in a fertility-sparing setting and could be considered after preoperative conization and for small tumors, adopting preventive surgical maneuvers and in reference centers. However, prospective evidences about the suggested indications are not yet available.

Evaluation of surgical resection in advanced ovarian, fallopian tube, and primary peritoneal cancer: laparoscopic assessment. A European Network of Gynaecological Oncology Trial (ENGOT) group survey.

OBJECTIVE: Laparoscopy is one of the diagnostic tools available for the complex clinical decision-making process in advanced ovarian, fallopian tube, and peritoneal carcinoma. This article presents the results of a survey conducted within the European Network of Gynaecological Oncology Trial (ENGOT) group aimed at reviewing the current patterns of practice at gynecologic oncology centers with regard to the evaluation of resection in advanced ovarian, fallopian tube, and peritoneal carcinoma. METHODS: A 24-item questionnaire was sent to the chair of the 20 cooperative groups that are currently part of the ENGOT group, and forwarded to the members within each group. RESULTS: A total of 142 questionnaires were returned. Only 39 respondents (27.5%) reported using some form of clinical (not operative) score for the evaluation of resection. The frequency of use of diagnostic laparoscopy to assess disease status and feasibility of resection was as follows: never, 21 centers (15%); only in select cases, 83 centers (58.5%); and routinely, 36 centers (25.4%). When laparoscopy was performed, 64% of users declared they made the decision to proceed with maximal effort cytoreductive surgery based on their personal/staff opinion, and 36% based on a laparoscopic score. To the question of whether laparoscopy should be considered the gold standard in the evaluation of resection, 71 respondents (50%) answered no, 66 respondents (46.5%) answered yes, whereas 5 respondents (3.5%) did not provide an answer. CONCLUSIONS: This study found that laparoscopy was routinely performed to assess feasibility of cytoreduction in only 25.4% of centers in Europe. However, it was commonly used to select patients and in a minority of centers it was never used . When laparoscopy was adopted, the treatment strategy was based on laparoscopic scores only in a minority of centers.

Atypical Uterine Smooth Muscle Tumors: A Retrospective Evaluation of Clinical and Pathologic Features.

BACKGROUND: Clinical characteristics combined with new biomarkers help discriminate between atypical uterine smooth muscle tumors (AUSMT) and leiomyosarcomas (LMS). PATIENTS AND METHODS: We retrospectively collected a series of leiomyomas (LM), AUSMT, and LMS. Estrogen receptors (ER), progesterone receptors (PR), p16, Ki-67, and p53 expression were assessed by immunohistochemistry. For AUSMT patients, immunohistochemistry evaluations were performed at the time of diagnosis and at recurrences. RESULTS: A total of 27 cases of AUSMT, 22 LM, and 31 LMS were identified. The expression of ER and PR decreased from LM to LMS (ER+: LM 95.5%, AUSMT 88.9%, LMS 41.9%, p < 0.001; PR+: LM 100%, AUSMT 88.9%, LMS 38.2%, p = 0.002). By contrast, p16 and p53 expression increased (p16+: LM 4.5%, AUSMT 40.7%, LMS 45.2%, p = 0.004; p53: LM 9.1%, AUSMT 33.3%, LMS 58.1%, p = 0.001). At a median follow-up of 33.47 months, 40.7% of patients with AUSMT experienced recurrent disease, 6 patients relapsed as AUSMT and 5 as LMS. In univariate analysis was observed that ER status (p = 0.027) and p53 expression (p = 0.015) predicted risk of relapse. CONCLUSIONS: Treatment of AUSMT should be centralized in dedicated centers. International collaborations are needed to optimize research strategy, which may lead to the identification of new useful biomarkers and to improvement in the clinical management of this rare disease.

Locally Advanced Cervical Cancer: Is a Trimodality Treatment a Safe and Effective Approach?

BACKGROUND: Chemoradiotherapy (CRT) is the standard of care for locally advanced cervical cancer (LACC). Pre-treatment lymph nodes (LN) assessment may have an important therapeutic role. CRT followed by adjuvant chemotherapy increased progression free survival (PFS) and overall survival (OS). Our study evaluated the feasibility and the effectiveness of a trimodality strategy in patients with LACC and positive LN. METHODS: Consecutive patients with LACC treated at the National Cancer Institute of Milan were enrolled. All patients underwent pelvic and para-aortic extraperitoneal laparoscopic lymphadenectomy to assess the nodal status. After surgery, patients received radiotherapy followed by chemotherapy according to the stage of disease. RESULTS: Between April 2012 and October 2013, 19 cervical cancer patients were enrolled. Overall, 10 (52.6%) patients presented with positive LN: 6 in the pelvic area and 4 both in the pelvic and para-aortic area. No perioperative major complications occurred. The most common surgical-related adverse events were bleeding (26%), respiratory distress (5%), infection (5%) and the development of lymphoceles (25%). Overall, 15 (78.9%) complete responses and 2 (10.5%) partial responses were registered. After a median follow-up of 43.3 months, 89.5% of patients were alive at the last visit, and 3-year PFS was 63%. CONCLUSIONS: Trimodality treatment appears feasible, well tolerated and promising in terms of oncologic outcome.

Invasive Paget Disease of the Vulva.

OBJECTIVE: Extramammary Paget disease of the vulva (EPDV) is a rare occurrence with an indolent and relapsing course. Progression to invasion occurs in 4% to 19% of cases. The aim of this study is to report clinical-pathological features and outcomes of patients treated for invasive EPDV. METHODS: Data of consecutive patients treated between 2000 and 2017 for invasive EPDV were reviewed. RESULTS: Among 79 patients with EPDV, 10 (12.7%) presented a microinvasive or invasive form at first diagnosis or during follow-up. All of them underwent upfront radical surgery; 7 (70%) received subsequent radiotherapy, chemotherapy, or both. The mortality rate was 40%. The recurrence rate after treatment for invasive forms was 60%, with a mean time to first recurrence of 20 (range, 5-36) months. CONCLUSIONS: Our study confirms that invasive EPDV remains a rare gynecological neoplasm with a poor prognosis. Multicentre trials or well-organized prospective data collection could improve the knowledge about the management of invasive EPDV.

Nerve-Sparing Approach Improves Outcomes of Patients Undergoing Minimally Invasive Radical Hysterectomy: A Systematic Review and Meta-Analysis.

Few studies have investigated the efficacy and safety of the nerve-sparing approach via minimally invasive surgery for the treatment of cervical cancer. We aimed to review the current evidence comparing nerve-sparing minimally invasive radical hysterectomy (NS-MRH) with conventional minimally invasive radical hysterectomy (MRH). This systematic review was registered in the International Prospective Register of Systematic Reviews (CRD#57655). Overall, 675 patients were included: 350 (51.9%) and 325 (48.1%) patients undergoing MRH and NS-MRH, respectively. MRH was associated with a shorter operative time in comparison with NS-MRH (mean difference = 32.57 minutes; 95% CI, 22.87-42.48). The estimated blood loss (mean difference = 97.14 mL, 20.01-214.29) and transfusion rate (odds ratio [OR] = 0.67; 95% confidence interval [CI], 0.15-3.01) did not differ statistically between the 2 groups. The risk of developing intraoperative (OR = 0.43; 95% CI, 0.08-2.23) and severe postoperative (OR = 0.63; 95% CI, 0.17-2.39) complications was similar between NS-MRH and MRH. Patients undergoing NS-MRH experienced lower voiding (OR = 0.39; 95% CI, 0.19-0.81) dysfunction rates than patients undergoing MRH. Moreover, a trend toward lower sexual (OR = 0.25; 95% CI, 0.06-1.07) and rectal (OR = 0.12; 95% CI, 0.01-1.02) issues was observed for patients having NS-MRH compared with patients undergoing MRH. Survival outcomes are not influenced by the type of surgical approach (recurrence [OR = 1.27; 95% CI, 0.49-3.28] and death [OR = 1.01; 95% CI, 0.36-2.83]) rates. The pooled data suggested that NS-MRH is equivalent to MRH for the treatment of cervical cancer and may be superior in reducing pelvic floor dysfunction rates. However, because of the low level of evidence of the included studies, further randomized trials are warranted.

Implementation of Extensive Cytoreduction Resulted in Improved Survival Outcomes for Patients with Newly Diagnosed Advanced-Stage Ovarian, Tubal, and Peritoneal Cancers.

BACKGROUND: Residual disease (RD) after primary debulking surgery (PDS) is one of the main factors driving ovarian cancer prognosis. The primary end point of this study was assessment of the impact that surgery had on survival outcomes for patients with advanced ovarian cancer. METHODS: Data on the effect of newly diagnosed advanced-stage ovarian, tubal, and peritoneal cancers were analyzed during two study periods (T1: 2001-2006 and T2: 2007-2012), in which the concepts of optimal and complete cytoreduction were introduced and implemented. RESULTS: In this study, 260 patients (36%) had surgery during T1 and 462 patients (64%) had surgery during T2. The rate of PDS increased, from 55.4% (144/260) during T1 to 85.5% (395/462) during T2 (p < 0.001). At the time of PDS, complete resection (RD0) was achieved for 45.1% of the patients during T1 and 76.7% of the patients during T2 (p < 0.001), whereas optimal resection (RD < 1 cm) was achieved for 60.4% of the patients during T1 and 85.3% of the patients during T2 (p < 0.001). Disease-free survival improved during the study periods (p = 0.006). Overall survival was similar in T1 and T2 (p = 0.18). The preoperative CA125 level, disease stage, and RD remained independently associated with disease-free survival (p ≤ 0.05). The performance of interval debulking surgery (IDS) instead of PDS correlated with worse survival outcomes (hazard ratio [HR] 1.47; 95% confidence interval [CI] 1.24-1.92; p = 0.02), whereas achievement of RD0 and RD < 1 cm independently improved overall survival (HR 0.45; 95% CI 0.22-0.91; p = 0.02 for RD0 and HR 0.47; 95% CI 0.23-0.96; p = 0.03 for RD0). CONCLUSIONS: The implementation of extensive cytoreduction allows improvement of patient outcomes. Further studies are needed to assess the risk-to-benefit ratio between PDS and IDS and to identify patients who benefit much more from one treatment method than from another.

Sentinel node mapping in endometrial cancer following Hysteroscopic injection of tracers: A single center evaluation over 200 cases.

OBJECTIVES: To analyze detection-rate(DR) and diagnostic-accuracy (A) of sentinel-nodes(SLNs) mapping following hysteroscopic-injection of tracer. To compare DR and A between tracers: ICG and Tc99m. METHODS: Evaluation of endometrial-cancer patients who underwent SLNs mapping after hysteroscopic-peritumoral-injection of tracer±lymphadenectomy. Analysis of DR (overall-bilateral-aortic) and A in the entire cohort and comparison between tracers. RESULTS: 202 procedures were performed from January/2005 to February/2017. Mean age:60years (28-82); mean BMI: 26.8 kg/m2 (15-47). In 133 cases (65.8%) hysterectomy and mapping procedure were performed laparoscopically. The overall-DR of the technique was 93.2% (179/192) (10 cases were excluded: 9 for technical-equipment failure; 1 for vagal reaction). Bilateral pelvic mapping was found in 59.7% of cases (107/179) and was more frequent in the ICG group (72.8% vs 53.3%; p: 0.012). In 50.8% of cases (91/179) SLNs were mapped both in pelvic and aortic nodes, and in 5 cases (2.8%) only in the aortic area. The mean number of detected SLNs was 3.7 (1-8). 22 patients (12.3%) had nodal involvement: 10-(45.5%)-macrometastases; 5-(22.7%)-micrometastases; 7-(31.8%)-ITCs. In 6 cases (27.3%) only aortic nodes were positive; in 5 cases (22.7%) both pelvic and aortic nodes and in 11 cases (50%) only pelvic nodes were involved. Three false-negative results were found, all in the Tc99m group. All had isolated aortic metastases with negative pelvic nodes. Overall-sensitivity was 86.4% (95%CI: 68.4-100) and overall-negative-predictive-value (NPV) was 96.4% (95%CI 86.7-100). No differences in terms of overall-DR, overall-sensitivity and overall-NPV were found between the two tracers. CONCLUSIONS: Hysteroscopic-injection of tracer for SLNs mapping in endometrial cancer is as accurate as cervical injection with a higher DR in the aortic area. ICG improves bilateral-DR. Further investigation is warranted on this topic.

Assessing the risk of pelvic and para-aortic nodal involvement in apparent early-stage ovarian cancer: A predictors- and nomogram-based analyses.

OBJECTIVE: To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. METHODS: Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. RESULTS: Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively (p=0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement (p<0.05). Nomograms displaying the risk of nodal involvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. CONCLUSIONS: Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging.

The Impact of Number of Cycles of Neoadjuvant Chemotherapy on Survival of Patients Undergoing Interval Debulking Surgery for Stage IIIC-IV Unresectable Ovarian Cancer: Results From a Multi-Institutional Study.

OBJECTIVES: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) may be a valuable treatment option in advanced ovarian cancer when primary cytoreduction is not feasible. However, a consensus on the ideal number of NACT cycles is still lacking. In the present investigation, we aimed to evaluate how number of cycles of NACT influenced patients' outcomes. METHODS: Data of consecutive patients undergoing NACT and IDS were retrospectively reviewed in 4 Italian centers, and survival outcomes were evaluated. RESULTS: Overall, 193 patients were included. Cycles of NACT were 3, 4, and at least 5 in 77 (40%), 74 (38%), and 43 (22%) patients, respectively. Patients undergoing 3 cycles experienced a similar disease-free survival (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.89-1.65; P = 0.20) but an improved overall survival (HR, 1.64; 95% CI, 1.05-2.4; P = 0.02) in comparison to patients receiving at least 4 cycles. Five-year overall survival was 46% and 31% for patients having 3 and at least 4 cycles. Ten-year overall survival was 26% and 18% for patients having 3 and at least 4 cycles (HR, 1.70; 95% CI, 1.13-2.55; P = 0.009). Using multivariate analysis, we observed that only Eastern Cooperative Oncology Group performance status correlated with overall survival (HR, 1.76; 95% CI, 1.2-2.49; P = 0.001). In addition, a trend toward worse overall survival was observed for patients with residual disease at IDS (HR, 1.29; 95% CI, 0.98-1.70; P = 0.06) and patients receiving at least 4 cycles (HR, 1.76; 95% CI, 0.95-3.22; P = 0.06). CONCLUSION: Our data underline the potential implication of number of cycles of NACT before IDS. Further prospective studies are warranted to assess this correlation.

Minimally Invasive Surgical Staging for Ovarian Carcinoma: A Propensity-Matched Comparison With Traditional Open Surgery.

STUDY OBJECTIVE: Growing evidence supports the safety of a laparoscopic approach for patients affected by apparent early-stage ovarian cancer. However, no well-designed studies comparing laparoscopic and open surgical staging are available. In the present investigation we aimed to provide a balanced long-term comparison between these 2 approaches. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: Tertiary center. PATIENTS: Data of consecutive patients affected by early-stage ovarian cancer who had laparoscopic staging were matched 1:1 with a cohort of patients undergoing open surgical staging. The matching was conducted by a propensity-score comparison. INTERVENTION: Laparoscopic and open surgical staging. MEASUREMENTS AND MAIN RESULTS: Fifty patient pairs (100 patients: 50 undergoing laparoscopic staging vs 50 undergoing open surgical staging) were included. Demographic and baseline oncologic characteristics were balanced between groups (p > .2). We observed that patients undergoing laparoscopic staging experienced longer operative time (207.2 [71.6] minutes vs 180.7 [47.0] minutes; p = .04), lower blood loss (150 [52.7] mL vs 339.8 [225.9] mL; p < .001), and shorter length of hospital stay (4.0 [2.6] days vs 6.1 [1.6] days; p < .001) compared with patients undergoing open surgical staging. No conversion to open surgery occurred. Complication rate was similar between groups. No difference in survival outcomes were observed, after a mean (SD) follow-up of 49.5 (64) and 52.6 (31.7) months after laparoscopic and open surgical staging, respectively. CONCLUSIONS: Our findings suggest that the implementation of minimally invasive staging does not influence survival outcomes of patients affected by early-stage ovarian cancer. Laparoscopic staging improved patient outcomes, reducing length of hospital stay. Further large prospective studies are warranted.

Minimally Invasive Surgical Staging in Early-stage Ovarian Carcinoma: A Systematic Review and Meta-analysis.

Few studies investigated the efficacy and safety of minimally invasive surgery for the treatment of early-stage epithelial ovarian cancer (eEOC). In this context, we aimed to review the current evidence comparing laparoscopy and the laparotomic approach for staging procedures in eEOC. This systematic review was registered in the International Prospective Register of Systematic Reviews. Overall, 3065 patients were included: 1450 undergoing laparoscopy and 1615 undergoing laparotomic staging. Patients undergoing laparoscopy experienced a longer (but not statistically significant) operative time (weighted mean difference [WMD] = 28.3 minutes; 95% confidence interval [CI], -2.59 to 59.2), a lower estimated blood loss (WMD = -156.5 mL; 95% CI, -216.4 to -96.5), a shorter length of hospital stay (WMD = -3.7 days; 95% CI, -5.2 to -2.1), and a lower postoperative complication rate (odds ratio [OR] = 0.48; 95% CI, 0.29-0.81) than patients undergoing laparotomy. The upstaging (OR = 0.81; 95% CI, 0.55-1.20) and cyst rupture (OR = 1.32; 95% CI, 0.52-3.38) rates were similar between groups. Laparoscopic staging is associated with a shorter time to chemotherapy than laparotomic procedures (WMD = -5.16 days; 95% CI, -8.68 to -1.64). Survival outcomes were not influenced by the route of surgery. Pooled data suggested that the minimally invasive surgical approach is equivalent to laparotomy for the treatment of eEOC and may be superior in terms of perioperative outcomes. However, because of the low level of evidence of the included studies, further randomized trials are warranted.

Impact of Surgical Route in Influencing the Risk of Lymphatic Complications After Ovarian Cancer Staging.

Lymphatic complications are a common occurrence after staging surgery for early-stage ovarian cancer (eEOC). We investigated whether the introduction of minimally invasive surgery influences the risk of developing lymphoceles and lymphorrhea in patients undergoing staging for eEOC. For this purpose, data of consecutive patients affected by eEOC undergoing staging surgery between January 1980 and January 2016 were retrospectively reviewed, and a systematic review and meta-analysis was performed. This systematic review was registered in the International Prospective Register of Systematic Review. Among 341 patients included in the present study, 47 severe postoperative complications occurred (13.7%), including 40 lymphatic complications: 31 symptomatic lymphoceles (9%) and 9 cases of lymphorrhea (2.6%), respectively. Laparoscopic staging correlated with a lower risk of developing any severe lymphatic complications in comparison with open surgery (p = .02). In particular, the laparoscopic approach and para-aortic node involvement were associated with a trend toward lower lymphoceles (odds ratio, .13; 95% confidence interval, .07-2.20; p = .05) and a trend toward higher risk of lymphorrhea developing (odds ratio, 4.02; 95% confidence interval, .93-17.3; p = .06), respectively. In conclusion, the implementation of a minimally invasive approach might result in a slight reduction of lymphatic complications after eEOC staging.

Assessing the Risk of Occult Cancer and 30-day Morbidity in Women Undergoing Risk-reducing Surgery: A Prospective Experience.

STUDY OBJECTIVE: To investigate the incidence and predictive factors of 30-day surgery-related morbidity and occult precancerous and cancerous conditions for women undergoing risk-reducing surgery. DESIGN: A prospective study (Canadian Task Force classification II-1). SETTING: A gynecologic oncology referral center. PATIENTS: Breast-related cancer antigen (BRCA) mutation carriers and BRCAX patients (those with a significant family history of breast and ovarian cancer). INTERVENTIONS: Minimally invasive risk-reduction surgery. MEASUREMENTS AND MAIN RESULTS: Overall, 85 women underwent risk-reducing surgery: 30 (35%) and 55 (65%) had hysterectomy plus bilateral salpingo-oophorectomy (BSO) and BSO alone, respectively. Overall, in 6 (7%) patients, the final pathology revealed unexpected cancer: 3 early-stage ovarian/fallopian tube cancers, 2 advanced-stage ovarian cancers (stage IIIA and IIIB), and 1 serous endometrial carcinoma. Additionally, 3 (3.6%) patients had incidental finding of serous tubal intraepithelial carcinoma. Four (4.7%) postoperative complications within 30 days from surgery were registered, including fever (n = 3) and postoperative ileus (n = 1); no severe (grade 3 or more) complications were observed. All complications were managed conservatively. The presence of occult cancer was the only factor predicting the development of postoperative complications (p = .02). CONCLUSION: Minimally invasive risk-reducing surgery is a safe and effective strategy to manage BRCA mutation carriers. Patients should benefit from an appropriate counseling about the high prevalence of undiagnosed cancers observed at the time of surgery.

Long-Term Toxicity and Quality of Life in Patients Treated for Locally Advanced Cervical Cancer.

OBJECTIVE: The aim of this study was to analyze the long-term toxicity and quality of life (QOL) in patients with locally advanced cervical cancer (LACC) treated with chemoradiation [chemotherapy/radiotherapy (CT/RT)] or neoadjuvant CT (NACT) followed by radical surgery (RS). METHODS: Fifty-nine patients with LACC in remission after treatment with NACT + RS (n = 34) or CT/RT (n = 25) were interviewed with an Incontinence Impact Questionnaire (IIQ-7), a Quality of Life Questionnaire (EORTC QLQ-C30), and a Quality of Life Questionnaire for Cervical Cancer (EORTC QLQ-CX24) to compare long-term toxicity and QOL. RESULTS: The mean age was 53 ± 9.8 and 59 ± 11.5 years in the NACT + RS and CT/RT groups, respectively. Overall, diarrhea and constipation were reported in 15 and 68%, respectively, while bladder complaints and a low level of sexual enjoyment were reported in 36 and 47%, respectively. The NACT + RS patients showed a worse sexual activity (74.71 ± 33.57 vs. 92.06 ± 17.96; p = 0.019) and sexual enjoyment (71.21 ± 23.67 vs. 88.88 ± 21.71; p = 0.040) and more frequently complained of constipation (49.01 ± 34.06 vs. 26.66 ± 31.66; p = 0.013), while CT/RT patients more frequently suffered from diarrhea (1.96 ± 7.96 vs. 14.66 ± 28.40; p = 0.017). CONCLUSIONS: Many patients treated for LACC have long-term complaints regarding sexual activity and bladder and bowel function. The majority of QOL aspects were similar in the two groups at long-term follow-up. However, diarrhea was more frequent and severe in CT/RT patients, while constipation was more frequent and severe in NACT + RS patients, and they showed a worse sexual life perception. Larger randomized trials addressing these issues are needed.

Primary surgical cytoreduction in advanced ovarian cancer: An outcome analysis within the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group.

OBJECTIVE: To draw a reliable picture of the surgical management of advanced ovarian cancer (AOC) within the MITO Group, trying to correlate the disease extent at presentation, the category of center, and surgical outcome. METHODS: Three tertiary referral centers for gynecologic oncology and four non-oncologic referral gynecologic surgical centers, participated in the project. A questionnaire was adopted to register perioperative data on AOCs (FIGO Stage IIICIV) consecutively operated on for a period of 12months. RESULTS: A total of 205 patients were registered into the study: 140 and 65 were recruited in oncological referral centers and non-referral centers, respectively. Following a multivariate analysis, the Eisenkop score and the category of center resulted the most potent predictors of complete surgical cytoreduction followed by PCI, preoperative CA125, and ASA score. Complete surgical cytoreduction was associated with oncological referral centers (60% vs 24.6%, p<0.001). The proportion of patients undergoing additional surgical procedures was significantly different comparing the two categories of centers (at least one additional procedure was performed in 81.4% vs 50.8% in oncological referral centers compared to the others, p<0.001). Despite the more aggressive surgery performed in oncological referral centers, the perioperative outcome measures were not significantly different in the two groups. CONCLUSIONS: The chance of obtaining a complete cytoreduction mainly depends on patient characteristics, tumor spread, and quality of treatment. The latter is amenable for direct influence, and therefore, seems to be of utmost importance when considering efforts aiming at improvement in the outcome of this disease.

Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis.

OBJECTIVE: We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. METHODS: On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. RESULTS: Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. CONCLUSIONS: In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested.

Extraperitoneal Robotic-Assisted Para-Aortic Lymphadenectomy in Gynecologic Cancer Staging: Current Evidence.

We reviewed the current evidence on the safety, effectiveness, and applicability of extraperitoneal robotic-assisted para-aortic lymphadenectomy (ExtRA-PAL) as the staging procedure of gynecologic malignancies. PubMed (MEDLINE), Scopus, Web of Science databases, and ClinicalTrials.gov were searched for original studies reporting outcomes of ExtRA-PAL. Quality of the included studies and their level of recommendation were assessed using the Grading of Recommendations, Assessment, Development, and Evaluation and the American College of Obstetricians and Gynecologists guidelines, respectively. Overall, 62 studies were identified; after a process of evidence acquisition 5 original investigations were available for this review that included 98 patients undergoing ExtRA-PAL. The main surgical indication was staging for cervical cancer (n = 71, 72%). The mean (SD) number of para-aortic node yielded was 15.4 (±4.7) nodes. Blood transfusion and intraoperative complication rates were 2% and 6%, respectively. ExtRA-PAL was completed in 88 patients (90%). Six (6%) and 4 (4%) patients had conversion to other minimally invasive procedures and open surgery, respectively. Success rate was 99% among patients undergoing ExtRA-PAL without concomitant procedures. Overall, mean (SD) length of hospital stay was 2.8 (±0.5) days. Twenty-four patients (24%) developed postoperative events. According to the Clavien-Dindo grading system, grades IIIa and IIIb morbidity rates were 12% and 2%, respectively. No grades IV and V morbidity occurred. ExtRA-PAL is associated with a high success rate and a relative low morbidity rate. However, because of the limited data on this issue, further studies are warranted to assess the long-term effectiveness of this procedure.