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The prognostic role of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) has not been fully established since few studies on this topic are currently available in the literature. In the present study, we conducted a systematic review and metanalysis of literature data in order to determine if PNI could be an independent prognostic predictor of patient's survival in VSCC. Four electronic databases (PubMed, ISI Web of Science, Scopus and Google Scholar) were searched from their inception to December 2021 for all studies assessing the prognostic value of PNI in VSCC. Multivariate hazard ratios (HRs) for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were pooled. Six studies with 1048 patients were included. PNI was significantly associated with decreased OS (HR = 2.687; p 0.001), DSS (HR = 2.375; p = 0.014) and PFS (HR = 1.757; p = 0.001), with no statistical heterogeneity among studies and no significant risk of bias across studies. The present meta-analysis highlights that PNI is independently associated with unfavorable prognosis in patients with VSCC. Therefore, PNI should be included in the pathological report of VSCC and considered in combination with other risk factors as a possible criteria for prognostic assessment adjuvant treatment planning inclusion.

Resection of bulky lymph nodes in gynecologic oncology is a challenging procedure. Considering the risk of intraoperative vascular injury, a technique to avoid severe complications is mandatory. In this study, we aimed to analyze the feasibility of laparoscopic ultraradical lymph node debulking using Yasargil clamps in patients with gynecologic cancer with bulky lymph node metastases.Multicenter retrospective case series (ClinicalTrialg.gov ID: NCT05318170), between September 2010 and April 2020.Units of Gynecologic Oncology.Patients with gynecologic cancer with bulky lymph node metastases.Laparoscopic ultraradical lymph node debulking using Yasargil clamps.Forty-three patients with gynecologic cancer with bulky pelvic and/or aortic lymph nodes metastases undergoing laparoscopic lymph node debulking surgery using Yasargil clamps were included. Median surgical time was 300 minutes (range, 120-550 minutes); median estimated blood loss was 170 mL (range, 0-700 mL). Median size of lymph nodes was 50 mm (range, 25-100). R0 resection was achieved in all cases. Four intraoperative complications (9.3%) occurred. No conversion to open surgery was required. There were 8 postoperative complications, classified grade 2 or worse. There were no cases with intra- or postoperative mortality.In our experience, in carefully selected patients with gynecologic cancer with bulky lymph nodes, laparoscopic lymph node debulking using Yasargil clamps could be considered a valid option to avoid potential severe vascular intraoperative complications.

Background Exclusive chemoradiation (E-CT/RT) represents the standard of treatment for locally advanced cervical cancer (LACC). Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role for patients with a suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Histologic assessment of residual tumor after CT/RT and RS allows accurate definition of prognostic categories. Methods Data on patients with FIGO stages 1B2 to 4A cervical cancer managed by CT/RT and RS from June 1996 to March 2020 were retrospectively analyzed. Pathologic response on the cervix was defined as complete (pCR), microscopic (persistent tumor foci ≤ 3 mm) (pmicroR), or macroscopic (persistent tumor foci > 3 mm) (pmacroR). Lymph node (LN) residual tumor was classified as absent or present. Results The 701 patients in this study underwent CT/RT and RS. Of the 701 patients, 293 (41.8%) had pCR, 188 (26.8%) had pmicroR, and 220 (31.4%) had pMacroR. Residual tumor was found in the pelvic lymph nodes of 66 (9.4%) patients and the aortic lymph nodes of 29 (4.1%) patients. The 5-year DFS and OS were respectively 86.6% and 92.5% in the pCR cases, 80.3% and 89.1% in the pmicroR cases, and 56.2% and 68.8% in the pmacroR cases. Among the patients with lymph node residual tumor, the 5-year DFS and OS were respectively 16.7% and 40% in the pCR cases, 35.4% and 53.3% in the pmicroR cases, and 31.7% and 31.1% in the pmacroR cases. Cervical residual tumor,, positive pelvic LNs, and positive aortic LNs were associated with worse DFS and OS in both the uni- and multivariate analyses. Conclusions Persistence of pathologic residual tumor on the cervix and LNs after CT/RT are reliable predictors of survival for LACC patients undergoing CT/RT and adjuvant surgery.

Background: The aim of the present study was to assess the prognostic value of tumour-free distance (TFD), defined as the minimum distance of uninvolved stroma between the tumour and peri-cervical stromal ring, in early-stage cervical cancer. Methods: Patients with pathologic FIGO 2009 stage IA1–IIA2 cervical cancer, treated by primary radical surgical treatment between 01/2000 and 11/2019, were retrospectively included. Adjuvant treatment was administered according to the presence of previously established pathologic risk factors. TFD was measured histologically on the hysterectomy specimen. Pre-operative TFD measured at MRI-scan from a cohort of patients was reviewed and compared with pathology TFD. Results: 395 patients were included in the study. 93 (23.5%) patients had TFD ≤ 3.0 mm and 302 (76.5%) had TFD > 3.0 mm. TFD ≤ 3.0 mm together with lymph vascular space involvement represented the strongest predictor for lymph node metastasis at multivariate analysis. TFD ≤ 3.0 mm was associated with worse 5-year disease-free survival (DFS) and overall survival (OS), compared with TFD > 3.0 mm (p = 0.022 and p = 0.008, respectively). DFS difference was more evident in the subgroup of patients with low-risk factors who did not receive adjuvant treatment (p = 0.002). Cohen’s kappa demonstrated an agreement between TFD measured at pre-operative MRI-scan and histology of 0.654. Conclusions: Pathologic TFD ≤ 3.0 mm represents a poor prognostic factor significantly associated with lymph node metastasis and it may be considered a novel marker to select candidates for adjuvant treatment. The possibility to obtain this parameter by radiological imaging makes it a potential easy-measurable pre-operative marker to predict the presence of high-risk pathologic factors in early-stage cervical cancer.

Heart rate variability (HRV) is the physiological variation in the time interval between consecutive heartbeats. Extracellular water (ECW) is the aqueous compartment surrounding cells and has been used as an inflammation index. Medically unexplained symptoms (MUS) refer to persistent psychosomatic bodily complaints, and their presence may be employed as a clinical index of chronic stress and inflammation, useful in distinguishing suffering patients from healthy subjects.To evaluate the clinical performance of SDNN (standard deviation of intracardiac beat time interval of normal sinus beats) and RMSSD (square root of the mean squared differences of successive NN intervals) as indices of HRV, and their correlation with ECW and MUS.A large multicenter retrospective study was conducted in 37 Italian medical practices in Caucasian men and women aged 20 to 70 years. SDNN and RMSSD were measured with the PPG Stress Flow® device (BioTekna, Italy), while ECW was determined with the BIA-ACC® device (BioTekna, Italy). All subjects filled in a MUS® questionnaire with 19 "nonspecific" symptom questions. The study sample was stratified by decade of age into five groups.Data from 9246 subjects comprising 3127 males and 6119 females, with a median age of 47 years, were analyzed. HRV index SDNN and RMSSD distributions in the entire sample and in each of the five age groups were significantly greater in subjects with a limited number of MUS (0-5) than in subjects with six or more symptoms, while both distributions correlated negatively with ECW.SDNN and RMSSD and ECW were predictors of MUS and were successfully used to objectively evaluate chronic stress and inflammation.

The aim of this study was to investigate the prevalence of peritoneal human papillomavirus (HPV) infection in different clinical cervical cancer (CC) settings, and its association with potential clinical and/or histological factors. This is a single-center, prospective, observational study. Consecutive patients with newly diagnosed or recurrent/persistent CC, between March 2019 and April 2020, were included. A group of patients undergoing surgery for benign gynecological conditions was included as control group. All patients underwent HPV-DNA test in the cervix and in the peritoneal cavity simultaneously at time of surgery. Two-hundred seventy-two patients had cervical and peritoneal HPV test analyzed. Cervical and peritoneal HPV positivity (PHP) was found in 235 (88.0%) and 78 (28.7%) patients, respectively; the prevalence of PHP was 17.7% in early stage, 28.8% in locally advanced cervical cancer (LACC) and 46.6% in the metastatic/persistent/recurrent setting (P = .001). No control patient was found to have peritoneal HPV infection. Higher frequency of PHP was documented in patients with larger tumor size (P = .003), presence of cervical HPV 16/18 genotypes (P

Introduction The standard treatment for epithelial early stage ovarian cancer (eEOC) includes laparotomic surgical staging, according to ESGO-ESMO guidelines. In the last decade, many investigators have assessed the safety and feasibility of minimally invasive surgery (MIS) staging in properly selected patients. However, survival data related to different surgical approaches (open versus MIS) are extremely limited. The aim of this study is to analyze the long-term oncological outcomes in eEOC patients treated with MIS. Materials and methods This is a multicenter observational retrospective study conducted in two tertiary oncological centers. We selected all consecutive women who underwent a laparoscopic or robotic staging for eEOC. Results From January 2008 to December 2016, 254 eEOC patients underwent a MIS staging (188 laparoscopic staging and 66 robotic staging). Overall, 18.1% of patients were upstaged due to pathological findings. A total of 203 (79.9%) patients received platinum-based adjuvant chemotherapy. After a median follow-up of 61 months (range 13–118), 39 (15.3%) patients experienced recurrence. The 5-years progression free survival (PFS) and overall survival rates were 84.0% and 93.8%, respectively. In the univariate analysis, favorable variables influencing PFS were young age (≤45 years), non-serous histotype, tumor grade 1-2, and FIGO stage IA/IB. In the multivariate analysis, only grade 3 was shown to keep its negative independent prognostic value (HR = 3.47; p = 0.004), whereas FIGO stage ≥ IC showed a trend toward significance (HR = 1.75; p = 0.099). Conclusion This retrospective study represents the longest follow-up of eEOC patients managed by MIS. The MIS is a valuable therapeutic option in appropriately selected patients, although a randomized controlled trial is needed.

Objective To evaluate feasibility of neoadjuvant chemotherapy (NACT) followed by cold-knife conization (CKC) in patients with 2018 FIGO stage IB2–IIA1 cervical cancer who desired to maintain fertility. Design Pilot study of conization after chemotherapy in stage IB2–IIA1 >2 cm cervical cancer. Setting University hospital. Patient(s) From 2014 to 2018, 25 patients, Interventions(s) After laparoscopic pelvic lymph-node assessment, NACT with cisplatin/paclitaxel q21 was administered to eligible patients. Responsive patients were treated with CKC. Main Outcome Measure(s) Obstetrical outcome: pregnancy rate. Oncologic outcome. Result(s) Thirteen out of 25 patients were eligible for fertility-sparing treatment. Oncologic outcome: The clinical overall response rate was 84.5% (11 out of 13 patients). One patient achieved stable disease, was managed by radical surgery, and is still alive; another one experienced progression of disease and died after 15 months. The optimal pathologic response was 69.1%. In the setting of fertility preservation patients, the median follow-up was 37 months (range 18–76). In this group we registered one distant recurrence, 12 months after CKC, in the liver; the patient is still alive and without evidence of disease. Obstetrical outcome: Among the nine patients amenable, three tried to conceive, and two spontaneous pregnancy occurred a few months after the end of treatment, for a pregnancy rate of 66.7%. Conclusion(s) This pilot study supports the feasibility of CKC after NACT as conservative treatment in stage IB2–IIA1 cervical cancer, with oncologic outcomes similar to those reported for trachelectomy in the same stage and with potential benefits in terms of obstetrical outcomes. Clinical Trial Registration Number NCT02323841.

Background Cytoreductive surgery is currently the main treatment for advanced epithelial ovarian cancer (OC), and several surgical maneuvers, including colorectal resection, are often needed to achieve no residual disease. High surgical complexity carries an inherent risk of postoperative complications, including anastomosis leakage (AL). Albeit rare, AL is a life-threatening condition. The aim of this single-center retrospective study is to assess the AL rate in patients undergoing colorectal resection and anastomosis during primary surgery for advanced epithelial OC through a standardized surgical technique and to evaluate possible pre/intra- and postoperative risk factors to identify the population at greatest risk. Methods A retrospective analysis of clinical and surgical characteristics of 515 patients undergoing colorectal resection and anastomosis during primary or interval debulking surgery between December 2011 and October 2019 was performed. Several pre/intra- and postoperative variables were evaluated by multivariate analysis as potential risk factors for AL. Results The overall anastomotic leakage rate was 2.9% (15/515) with a significant negative impact on postoperative course. Body mass index 2, preoperative albumin value lower than 30 mg/dL, section of the inferior mesenteric artery at its origin, and medium–low colorectal anastomosis ( Conclusions AL is confirmed to be an extremely rare but severe postoperative complication of OC surgery, being responsible for increased early postoperative mortality. Preoperative nutritional status and surgical characteristics, such as blood supply and anastomosis level, appear to be the most significant risk factors.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy and assess its efficacy in increasing bone mineral density (BMD) and modulating biochemical skeletal markers following previous treatments with bisphosphonates in a group of post-menopausal women with osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased efficacy in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

Purpose To assess the rate of bilateral sentinel lymph node (SLN) detection with indocyanine green (ICG), to evaluate the sensitivity and the negative predictive value of cervical cancer patients undergoing open radical hysterectomy; to compare open versus minimally invasive SLN biopsy performance and to assess factors related to no/unilateral SLN mapping. Methods We retrospectively reviewed consecutive patients with FIGO 2018 stage IA1 with lymph-vascular space involvement to IIB and IIIC1p cervical carcinoma who underwent SLN mapping with ICG followed by systematic pelvic lymphadenectomy between 05/2017 and 06/2020. Patients were divided according to surgical approach for statistical analysis. Results Eighty-five patients met inclusion criteria. Twenty-seven (31.8%) underwent open and 58 (68.2%) underwent minimally invasive SLN mapping. No difference in any SLN mapping (laparotomy 92.6% and minimally invasive 91.4%) or in SLN bilateral detection (laparotomy 72.0% and minimally invasive 84.9%) (p = 0.850 and p = 0.222, respectively), in median number of SLNs mapped and retrieved (2 in both groups, p = 0.165) and in site of SLN mapping per hemi-pelvis (right side, p = 0273 and left side, p = 0.618) was evident between open and minimally invasive approach. Per-patient sensitivity of SLN biopsy in laparotomy was 83.3% (95% CI 35.9–99.6%) and the negative predictive value was 95.0% (95% CI 76.0–99.1%). No difference in per-patient sensitivity was noted between two approaches (p = 0.300). None of the analyzed variables was associated with no/unilateral SLN mapping. Conclusion The use of ICG to detect SLN in cervical cancer treated with open surgery allows a bilateral detection, sensitivity and negative predictive value comparable to minimally invasive surgery with potential advantages of ICG compared to other tracers.

Purpose: The purpose of this study was to assess the prognostic role and the perioperative outcomes of conization performed before radical hysterectomy in early-stage cervical carcinoma. Methods: This multicenter, retrospective observational cohort study included patients with FIGO 2009stage IB1 cervical carcinoma treated with radical hysterectomy between June 2004 and June 2019. Patients were divided into two groups according to conization before radical surgery. One-to-one case–control matching was used to adjust the baseline characteristics. Results: A total of 332 patients were included after propensity matching (166, 50% in each group). Twenty-four of 166 (14.4%) and 142 of 166 (85.6%) conization patients had negative and positive surgical margins on the conization specimen, respectively. No difference in intra- and postoperative complications was noted between the two groups (p=0.542 and p=0.180, respectively). Patients undergoing conization before radical hysterectomy received less adjuvant treatment (p20 mm and no conization before radical hysterectomy (p=0.011 and p=0.018, respectively). The only independent variable influencing OS was pathologic tumor diameter >20 mm (p=0.020). Conclusions: Conization before radical hysterectomy was associated with improved DFS and lower probability of receiving adjuvant treatment. No difference in perioperative complications and OS was evident. Tumor diameter >20 mm was found to be the only independent risk factor affecting OS in both groups.

Introduction Recent findings show a detrimental impact of the minimally invasive approach on patients with early stage cervical cancer (ECC). Reasons beyond these results are unclear. The aim of the present article is to investigate the possible role of peritoneal contamination during intracorporeal colpotomy. Methods patients with early stage cervical cancer were divided into 2 groups: no intraperitoneal exposure (N-IPE) intraperitoneal exposure (IPE) during minimally invasive surgery. Patients of the 2 groups were propensity-matched according to the major risk factors. Results 226 cases of the IPE group had a significant worst prognosis than the 142 cases of the N-IPE group (4.5-years disease free survival: 86.6% vs 95.9% respectively, p = 0.005), while N-IPE had similar survival to open surgery (4.5-years disease free survival: 95.0% vs 90.5% respectively, p = 0.164). Distant recurrence was more frequent among IPE patients with a borderline significance (3.5% vs 0.4% among IPE and N-IPE respectively, p = 0.083). On multivariate analysis, intraperitoneal tumor exposure was an independent prognostic factors for worse survival; patients belonging to the N-IPE group had a risk of recurrence of about 3-fold lower compared to patients of the IPE group (hazard ratio: 0.37, 95% confidence interval: 0.15–0.88, p = 0.025). Conclusion it would be advisable that further prospective studies investigating the efficacy of different surgical approach in ECC take into consideration of this issue. Moreover, all other measures that could potentially prevent peritoneal exposure of tumor should be adopted during minimally invasive surgery for early stage cervical cancer to provide higher survival outcomes.

Purpose: Reporting the perioperative and survival outcomes of vaginectomy with respect to a matched series of pelvic exenteration (PE) in women with isolated recurrent cervical cancer. Methods: The records of vaginal recurrent cervical cancer patients admitted at Fondazione Policlinico “Agostino Gemelli” IRCCS in Rome from January 2010 to June 2019 were retrospectively analyzed. A propensity-matched score analysis was performed by age, clinical stage, disease-free interval, and R0 resection. Postsurgical complications and survival rates were evaluated. Results: Fifteen women underwent vaginectomy, and 30 patients were submitted to PE. No statistical differences were observed between the two groups at baseline characteristics. The vaginectomy procedures were successfully performed in all women, and no case required conversion to PE. Moreover, a higher rate of major postoperative complications after PE with respect to vaginectomy (p = 0.027) was recorded. Among them, three women required reoperation within 30 postoperative days, and four experienced two or more complications. Twenty-five (55.6%) women experienced recurrence: 8 of 25 (32.0%) in the vaginectomy group, and 17 of 25 (68%) in the PE group, with a median progression-free survival of 20months and 13months, respectively (p = 0.169). In total, 5 of 15 (33.3%) died of disease in the vaginectomy group and 13/30 (43.3%) in the PE group, with a median overall survival of 39 and 18months for vaginectomy and PE, respectively (p = 0.161). Conclusions: The vaginectomy seems to allow for salvage treatment, such as radiotherapy and/or PE, but with a minimal impact on the quality of life in appropriately selected women with local recurrent cervical cancer.

Background The aim of this study was to assess the agreement rate between intraoperative evaluation (IOE) and final diagnosis (FD) in a series of surgically resected endometrial carcinoma (EC), with a preoperative ambiguous or inconclusive diagnosis by endometrial biopsies and imaging. Methods A retrospective study was performed selecting patients who underwent surgery with IOE for suspected EC at our institution from 2012 to 2018. A K coefficient was determined with respect to the histotype, tumor grade, myometrial infiltration and cervical involvement. Results Data analysis has been performed on 202 women. The IOE evaluation was distributed as Endometrioid (n = 180) and Non-Endometrioid (n = 22). The comparison between the frozen section (FS) and the definitive histological subtype showed an overall agreement rate of 93,07% (k = 0.612) and an agreement of 97.2% for Endometrioid vs 59% for Non-Endometrioid tumors. The FIGO system grading was the same in 91,1% of patients, none was upgraded and in 8,9% downgraded. Observed agreements were 89,11% and 95,54% for myometrial and cervical involvement, respectively. Conclusions The good agreement between intraoperative grading, myometrial invasion and their histological definition on permanent sections highlights that FS is a good predictor for surgical outcome, in particular in presence of a preoperative ambiguous or inconclusive diagnostic evaluation.

Introduction: The link between female infertility and gynecological cancer has always been a debated and challenging topic. Although cervical cancer has the worst impact on female fertility, as it is usually diagnosed in patients of reproductive age, endometrial and ovarian cancer are also diagnosed and treated often in relatively younger patients in which fertility preservation is a relevant issue. The aim of this review is to highlight the correlation between therapy for female infertility and the developing cancer’s risk and to describe the fertility sparing treatments in gynecological oncology. Material and methods: A systematic review of the literature through the main scientific search engines (PubMed and Google Scholar) was performed. We selected the most relevant articles based on the largest case series and the latest updates. All selected documents have been listed in the references. Results: Fifty-six relevant articles published between 1996 and 2019 were identified. Results from the available evidence report no significant increased risk of endometrial, cervical, and ovarian cancer in patients having infertility treatments. In young patients diagnosed with gynecological cancer, preservation of fertility is a personalized choice depending on several factors (type, stage, age and desire to conceive, safety of the treatment, and feasibility of fertility sparing surgery). For ovarian cancer FIGO stage IA G1, IA G2 (grade), and IC G1; for endometrial adenocarcinoma grade 1 with no lymphovascular space invasion (LVSI) or myometrial invasion and for early-stage cervical cancer (FIGO stage 2018: IA1-IB1), fertility sparing treatment is possible. The role of fertility sparing treatment with the increase of personalization of therapies therapy is always a theme of discussion and research. Conclusion: At present data regarding the risk of gynecological cancers after infertility treatments are reassuring. Careful evaluation of female fertility-sparing options in young women interested by ovarian, endometrial, or cervical tumors should be carried out involving a multidisciplinary team and ensuring safety and efficacy.

Background Ovarian adult granulosa cell tumours are low-grade malignant sex cord-stromal neoplasm with a low recurrence rate. Prognostic factors for recurrence include tumor stage, tumor rupture in Stage I neoplasms and the presence of residual tumors after surgery. However, in recurrent tumors, prognostic factors for overall survival (OS) are lacking. In the present paper, we conducted a systematic meta-analysis with the aim to assess prognostic factors for OS in patients with recurrent GCT. Methods Electronic databases were searched for all studies assessing prognostic factors in recurrent adult granulosa cell tumor of the ovary. Student T test, Fisher's exact test and Kaplan-Meier survival analysis with long-rank test were used to assess differences among groups; a p value Results Eleven studies analyzing 102 recurrent tumors were included in the systematic review. Tumor stage and localization of recurrent tumors were significantly associated with OS on Kaplan-Meier analysis; Cox regression analysis showed a HR of 0.879 for the stage II, of 3.052 for the stage III, and of 2.734 for stage IV tumor was significantly associated with OS (p = 0.037); observed HRs for abdominal and thoracic locations were of 2.405 and of 4.024, respectively. Conclusions In conclusion, the present article emphasizes the prognostic significance of tumor stage > II and extrapelvic anatomic sites of recurrences in patients with recurrent granuolase cell tumors of the ovary.

Introduction To identify a subset of cervical cancer (CC) patients administered chemoradiation (CT/RT) plus radical surgery (RS), who can be spared lymphadenectomy, and complications. Patients and methods 430 Stage IB2-IIB patients without LN involvement at imaging were accrued (March 1996–December 2015) at Gynecologic Oncology Unit of the Catholic University of Rome/Campobasso. CT/RT consisted of pelvic irradiation plus cisplatin based chemotherapy. Objective response was evaluated according to RECIST criteria; radical hysterectomy and pelvic ± aortic lymphadenectomy was attempted in patients achieving response or stable disease. Surgical morbidity was classified according to the Chassagne grading system. Results 421 cases underwent RS; metastatic pelvic and aortic LNs were documented in 10.7%, and 8.8% of cases, respectively. In patients without residual tumor in the cervix, there was only 1 case (0.53%) with positive pelvic LNs, and 1 case (2.3%) with metastatic aortic LNs. Analysis of patients according to pre- and post-CT/RT imaging was able to select cases without any metastatic LNs: in patients with negative pelvic LNs at pre- and post-CT/RT imaging, none of cases without residual disease in the cervix had metastatic pelvic or aortic LNs. Of 149 early complications, 76 (51.0%) were lymphovascular. The most frequent late complications were lymphovascular (N = 25/61, 41.0%). Conclusion Lymphadenectomy could be avoided in stage IB2-IIB CC patients undergoing preoperative CT/RT, when a careful evaluation of pre- and post-CT/RT imaging and histological assessment of no residual disease in the cervix is made. This approach may avoid lymphadenectomy in 40% of patients with a favourable impact on lymphovascular morbidity.

BACKGROUND: Sentinel lymph node (SLN) biopsy has emerged as one of the most appreciated techniques for reducing the rate of complete lymph node dissection (LND) performed in patients with early-stage cervical cancer (ECC). However, its performances are still a matter of debate and, to improve them, international guidelines recommend performing at least unilateral LND in case of SLN mapping. In a prior study, we identified a group of patients without evidence of lymph node metastasis (LNM). Our objective is to define a precise risk of LNM for each ECC patient in order to significantly tailor surgery for ECC. METHODS: Clinical and pathological data of ECC patients were retrospectively collected by eight Italian institutions. Chi-square test or Fisher's exact test along with logistic regression analysis was used to determine the association of each variable between patients with or without LNM. Results of logistic regression have been used as a basis to calculate the probability to harboring LNM. RESULTS: A total of 463 ECC patients were identified. No LNM was detected among the 161 (34.8%) patients who met the criteria and were defined as Very Low Risk. In the other 302 patients, the precise risk of LNM was calculated, and it was

Objective To report morbidity and oncological outcomes in a consecutive series of lateral isolated recurrent gynecological cancer involving the pelvic side wall (PSW) including the iliopsoas muscle. Material and methods We retrospectively evaluated a consecutive series between 6/2013 and 12/2015 of lateral isolated recurrent gynecological malignancies treated with a lateral endopelvic resection (LEPR). LEPR was defined as an en-bloc lateral resection of a pelvic tumor with sidewall muscle, and/or bone, and/or major nerve, and/or major vascular structure. Post-surgical complications, quality of life (QoL) and survivals were computed. Results Seventy-four women with pelvic isolated relapse were admitted for surgery during the study period. Among them, 8 cases (10.8%) showed lateral isolated relapse involving the iliopsoas muscle and were treated with LEPR. R0 resection was achieved in 6/8 patients (75.0%), while the pathologic margins were microscopically and macroscopically positive in 1 patient (12.5%), respectively. There were no perioperative mortalities. Major postoperative complications occurred in 3 patients (37.5%) through peripheral neuropathies, thrombosis of the vascular graft and compartment syndrome of the leg. Median follow-up time was 21 months (range, 12–28). The 2-year overall survival (OS) was 88% improving up to 100% if R0 resection was achieved. In patients with positive pathologic margins (n = 2), the 2-year OS was 50%. All women showed an improved QoL after surgery. Conclusion LEPR with iliopsoas resection can be safely performed in selected cases with lateral isolated gynecological relapse involving the PSW and was associated with improved QoL and prolonged survival when an R0 resection was achieved.

Background: Recently, it was reported that minimally invasive surgery (MIS) has a negative impact on early-stage cervical cancer (ECC) patient survival. At the same time, advantages of MIS regarding quality of life and low rate of intra- and postoperative complications are well known. Therefore, it is essential to select patients who may benefit from MIS without worsening their oncologic outcomes. The aim of this study is to investigate which pathological factors could guide surgeons’ choice about the best approach in ECC. Patients and Methods: Patients with 2009 FIGO stage from IA1 with lymphovascular space invasion (LVSI) to IB1/IIA1 treated by open or laparoscopic surgery were judged eligible for the study. Disease-free survivals (DFS) of both approaches were tested in subgroups, defined according to histology, tumor size, grading, LVSI, parametrial involvement, and nodal status. Results: A total of 423 patients were enrolled (217 in the open and 206 in the laparoscopic group). No difference between open surgery and laparoscopy was found among subgroups defined according to histology, grading, LVSI, parametrial involvement, or nodal status. Among patients with tumor > 20mm, laparoscopy showed a significantly higher relapse risk [hazard ratio (HR): 2.103, p = 0.030]. Among patients with tumor < 20mm, laparoscopy showed DFS superimposable to open surgery (HR: 0.560, p = 0.128). Conclusions: Tumor size of 20mm appeared as the only independent discrimination criterion in patients whose prognosis is affected by surgical approaches.

Purpose Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role in locally advanced cervical cancer (LACC) patients with suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Our aim is to evaluate oncological and surgical outcomes of minimally invasive radical surgery (MI-RS) compared with open radical surgery (O-RS). Patients and Methods Data for stage IB2–IVA cervical cancer patients managed by CT/RT and RS were retrospectively analyzed. Results Beginning with 686 patients, propensity score matching resulted in 462 cases (231 per group), balanced for FIGO stage, lymph node status, histotype, tumor grade, and clinical response to CT/RT. The 5-year disease-free survival (DFS) was 73.7% in the O-RS patients and 73.0% in the MI-RS patients (HR 1.034, 95% CI 0.708–1.512, p = 0.861). The 5-year locoregional recurrence rate was 12.5% (O-RS) versus 15.2% (MI-RS) (HR 1.174, 95% CI 0.656–2.104, p = 0.588). The 5-year disease-specific survival (DSS) was 80.4% in O-RS patients and 85.3% in the MI-RS group (HR 0.731, 95% CI 0.438–1.220, p = 0.228). Estimated blood loss was lower in the MI-RS group (p p p = 0.331). Fifty-six (24.2%) patients experienced late postoperative complications in the O-RS group, versus 61 patients (26.4%) in the MI-RS group (p = 0.668). Conclusion MI-RS and O-RS are associated with similar rates of recurrence and death in LACC patients managed by surgery after CT/RT. No difference in early or late complications was reported.

ObjectivesPelvic side wall infiltration by gynecological malignancies has been considered for a long time an absolute contraindication to curative resection. The development of the laterally extended endopelvic resection (LEER) has challenged this surgical paradigm. Although the LEER has been standardized in open surgery, only small studies have been published about its endoscopic feasibility. The objective of this study is to analyze the safety of LEER in patients with gynecological malignancies involving the pelvic side wall.MethodsWe retrospectively evaluated a consecutive series of patients who underwent a laparoscopically modified LEER between July 2014 and November 2018. This indicated gynecological tumors involving the pelvic sidewall and surgeries were conducted in two Italian institutions. All patients underwent pre-operative CT scan or PET to evaluate for distant metastases. Patients without suspicioun of distant metastasis underwent pelvic MRI and examination under anesthesia to establish the resectability of the disease and concomitant diagnostic laparoscopy to exclude intraperitoneal dissemination. All women with disease-free interval >2 ECOG were excluded. Type of resection was defined based on the status of the pathologic margins: R0, microscopically negative (free margin <5 mm); R1, microscopically positive; and R2, macroscopically (grossly) positive. Disease-free survival was calculated from the date of primary surgery to the time of recurrence. Overall survival was defined as the time from primary surgery to death.ResultsOverall, 39 patients underwent a laparoscopic LEER and 18 (46.2%) patients were eligible for a laparoscopic approach. Laparoscopic LEER was performed as primary treatment for newly diagnosed tumors in eight patients (44.4%), and for recurrences in the other 10 patients (55.6%). No laparotomic conversions were registered. R0 resection was achieved with negative margins in all patients. The median operative time was 415 min (range, 285–615), median estimated blood loss was 285 mL (range, 100–600), and the median length of hospital stay was 10 days (range; 4–22). Only four patients (22.2%) needed blood intraoperative transfusion. In seven patients (38.9%), post-operative admission to intensive care unit was required. There were three (16.7%) intraoperative complications, all managed laparoscopically. In total there were six (33.3%) major postoperative complications: three patients (16.7%) experienced moderate hydronephrosis with normal renal function, which required temporary placement of nephrostomy; one patient (5.6%) had permanent urinary retention; and two patients (11.1%) had a reoperation, one for post-operative hemoperitoneum and another for complete vaginal cuff dehiscence.DiscussionLaparoscopic LEER can be safely performed by experienced laparoscopic surgeons, in carefully selected patients with gynecological malignancies involving the lateral pelvic side wall, even for those in which a bladder and rectum sparing surgery appears possible. Further larger prospective trials are needed to evaluate the oncological and the long-term functional outcomes.

Objective This study is aimed to analyze the clinical outcome of recurrent ovarian cancer patients bearing isolated lymph-node recurrence (ILNR) who underwent salvage lymphadenectomy (SL). The prognostic role of clinicopathological variables and the mutational status of BRCA1/2 have also been investigated. Methods This retrospective, single-institutional study included women with platinum-sensitive lymph node recurrence underwent to SL between June 2008 and June 2018. Univariate and multivariate analysis was performed to evaluate the impact of clinical parameters, and BRCA1/2 mutational status on post salvage lymphadenectomy progression-free survival (PSL-PFS). Results As of June 2019, the median follow-up after SL was 30 months, and the relapse has been documented in 48 (56.5%) patients. In the whole series, the median PSL-PFS was 21 months, and the 3-year PSL-PFS was 36.7%. The median PSL-PFS, according to patients with ILNR (N = 71) versus patients with lymph-nodes and other sites of disease (N = 14), was 27 months versus 12 months, respectively. Univariate analysis of variables conditioning PSL-PFS showed that platinum-free interval (PFI) ≥12 months, normal Ca125 serum levels, and number of metastatic lymph-nodes ≤3 played a statistically significant favorable role. In multivariate analysis, PFI duration ≥12 months and the number of metastatic lymph nodes ≤3 were shown to keep their favorable, independent prognostic value on PSL-PFS. Conclusions In the context of SL, the patients with long PFI and low metastatic lymph node numbers at ILNR diagnosis have the best outcome. The BRCA mutational status seems not associated with clinical variables and PSL-PFS, differently from other sites of disease in ROC patients.

IntroductionGrowing evidence in the literature supports the accuracy of sentinel lymph node (SLN) biopsy in early-stage cervical cancer. One-step nucleic acid amplification (OSNA) is a rapid assay able to detect cytokeratin 19-mRNA in SLNs, and it can be used for intra-operative detection of low-volume metastases. The aim of this study was to evaluate the rate of low-volume metastasis in SLNs detected by OSNA in patients with early-stage cervical cancer. Secondary aims were to define the sensitivity and the negative predictive value of SLN biopsy assessed with OSNA.MethodsAfter IRB approval, consecutive patients who underwent surgery for International Federation of Gynecology and Obstetrics stage IA1 with lymph-vascular space involvement to IB1 between November 2017 and July 2019 and had SLN biopsy and pelvic lymphadenectomy were included. SLNs were detected with indocyanine-green cervical injection and sent intra-operatively for OSNA.ResultsEighteen patients underwent SLN assessment with OSNA and systematic pelvic lymphadenectomy in the study period. Four (22.2%) patients had unilateral and 14 (77.8%) had bilateral mapping. OSNA detected micro-metastasis in 6/18 (33.3%) patients. All micro-metastases were detected in patients with bilateral SLN mapping. The sensitivity and negative predictive value of SLN in detecting lymph node metastasis with OSNA calculated per pelvic sidewall were 85.7% and 96.1%, respectively. The false negative rate in mapped sidewalls was 14.3%.DiscussionThis is the first series entirely processing SLNs for OSNA in early-stage cervical cancer. OSNA is able to intra-operatively detect low-volume metastases in SLNs. Further studies are necessary to confirm the accuracy of this technique and to assess survival implications of low-volume metastases detected by OSNA.

In 6.2% of gynaecologic malignancies, vascular involvement is reported. Cytoreductive surgery presents in those cases a higher rate of major complications. Arterial-enteric fistula is a very rare post-surgical complication with serious repercussions on the patient's life due to intestinal haemorrhage and the overlapping sepsis. This is the first case report about iliac-colonic fistula formation in recurrent ovarian cancer with lymph-node metastasis after laparoscopic secondary cytoreductive surgery in a 75-year-old woman and its successful surgical management. A literature review about arterial-enteric fistula formation in gynaecologic cancer treatment, specifically ovarian cancer, is also reported, hypothesising the risk factors of this severe postoperative complication and possible surgical solutions.

Objective To describe accurately the oncological outcomes after hepatic resection (HR) in recurrent ovarian carcinoma (ROC) evaluating clinic-pathological variables and mutational status of BRCA1/2. Although HR is considered a challenging situation in ROC patients, assessment of BRCA1/2 mutational status seems to have a relevant clinical value to guide surgical therapy. Methods Patients who underwent HR for ROC at the Catholic University of Rome, between June 2012 and October 2017 were included. Exclusion criteria were represented by extra-abdominal disease and presence of diffuse peritoneal carcinomatosis requiring more than 2 bowel resections. Details relative to HR were collected and BRCA analysis was performed. Predictive factors of post-HR progression free survival (PHR-PFS) were assessed by univariate analyses using Cox-proportional hazard regression models. Results Thirty-four patients undewent HR within secondary cytoreductive surgery (SCS). Six patients (17.6%) presented with hepatic relapse only, while the remaining 28 patients (82.4%) had concomitant extra-hepatic disease. In the whole series, the 3-yr PHR-PFS was 49.1% and the 3-yr post-HR overall survival was 72.9%. Univariate analysis of variables conditioning PHR-PFS showed that only BRCA mutational status played a statistically significant favourable role: the 3-yr PHR-PFS rate was 81.0% in BRCA mutated patient compared to 15.2% in wild type ones (p value: 0.001). Conclusions Our clinical analyses suggest that in ROC patients with liver disease the assessment of germline and somatic BRCA mutational status can help to select patients elegible for SCS.

Aims of this study were: to verify if Recurrence Quantification Analysis (RQA) of Heart Rate Variability (HRV) time series could determine both ventilatory thresholds in individuals with different fitness levels, and to assess the validity of RQA method compared to gas-exchange method (GE). The two thresholds were estimated in thirty young individuals during incremental exercise on cycle-ergometer: Heart rate (HR), Oxygen consumption (VO2) and Workload were measured by the two methods (RQA and GE). Repeated measures ANOVA was used to assess main effects of methods and methods-by-groups interaction effects for HR, VO2 and Workload at aerobic (AerT) and anaerobic (AnT) thresholds. Validity of RQA at both thresholds was assessed for HR, VO2 and Workload by Ordinary Least Products (OLP) regression, Typical Percentage Error (TE), Intraclass Correlation Coefficients (ICC) and the Bland Altman plots. No methods-by-groups interaction effects were detected for HR, VO2 and Workload at AerT and AnT. The OLP analysis showed that at both thresholds RQA and GE methods had very strong correlations (r >0.8) in all variables (HR, VO2 and Workload). Slope and intercept values always included the 1 and the 0, respectively. At AerT the TE ranged from 4.02% (5.48 bpm) to 10.47% (8.53 Watts) (HR and Workload, respectively) and in all variables ICC values were excellent (≥0.85). At AnT the TE ranged from 2.53% (3.98 bpm) to 6.64% (7.81 Watts) (HR and Workload, respectively) and in all variables ICC values were excellent (≥0.90). Therefore, RQA of HRV time series is a new valid approach to determine both ventilatory thresholds in individuals with different physical fitness levels, it can be used when gas analysis is not possible or not convenient.

The present paper concerns a new description of changing in metabolism during incremental exercises test that permit an individually tailored program of exercises for obese subjects. We analyzed heart rate variability from RR interval time series (tachogram) with an alternative approach, the recurrence quantification analysis, that allows a description of a time series in terms of its dynamic structure and is able to identify the phase transitions. A transition in cardiac signal dynamics was detected and it perfectly reflects the aerobic threshold, as identified by gas exchange during an incremental exercise test, revealing the coupling from the respiratory system toward the heart. Moreover, our analysis shows that, in the recurrence plot of RR interval, it is possible to identify a specific pattern that allows to identify phase transitions between different dynamic regimes. The perfect match of the occurrence of the phase transitions with changes observed in the VO2 consumption, the gold standard approach to estimate thresholds, strongly supports the possibility of using our analysis of RR interval to detect metabolic threshold. In conclusion, we propose a novel nonlinear data analysis method that allows for an easy and personalized detection of thresholds both from professional and even from low-cost wearable devices, without the need of expensive gas analyzers.

The role of dose-dense schedules in the neo-adjuvant treatment (NACT) of locally advanced cervical cancer (LACC) has been reported. This phase II study investigated activity of dose-dense paclitaxel/platinum before radical surgery (RS) in LACC patients. The primary end-point was the rate of optimal pathological response (OPR: pathological complete/microscopic response). NACT (paclitaxel: 80 mg/m2) and carboplatin (AUC 2) were administered for 6 weeks. Overall response rate (ORR) to NACT was assessed by the RECIST criteria. Patients amenable to surgery were triaged to RS. The null hypothesis was that the OPR rate would improve from 30.0 to 45.0% (α error: 0.05, β error: 0.2). The regimen would be considered active if > 25 OPRs were found. 36 patients were enrolled; 19 patients were stage IIB (52.8%) and 16 (44.4%) patients had pelvic lymph-node involvement at imaging. All patients completed neo-adjuvant chemotherapy; ORR was of 75.0%. RS was performed in 29 (93.5%) patients. Since the OPR was 16.1%, we evaluated the real chances to achieve the number of OPR required by the Simon design and decided to close the study. Grade 3/4 hematological toxicity occurred in 5 patients; surgical morbidity occurred in 14 patients. The 2-year PFS rate was 69.0%. Dose-dense neo-adjuvant paclitaxel/carboplatin is feasible and safe in LACC patients; however, failure to achieve the primary end-point has to be recognized. Given the heterogeneity of the available studies, robust data from an adequately sized prospective study focused on more homogeneous series are required.

BackgroundPlatinum-based chemotherapy plus bevacizumab is the new standard of care in stage IVB cervical cancer (CC) patients. In this new scenario, radical surgery could be offered in selected cases with an optimal clinical response. Potential surgical complications related to previous bevacizumab treatment have never been described before in this type of setting.MethodsThis is a single-institutional retrospective study on women with CC who received radical pelvic surgery after platinum-based chemotherapy (platinum-taxol) plus bevacizumab.ResultsBetween April 2016 and September 2017, 15 patients with CC underwent radical surgery after bevacizumab-containing chemotherapy (platinum-taxol) at the Division of Gynecologic Oncology, Catholic University of the Sacred Heart in Rome, Italy.All patients received at least 3 cycles of treatment. Fourteen (93.4%) patients underwent radical hysterectomy, whereas 1 patient received pelvic anterior exenteration. Median operating time was 290 minutes (range, 220–400), and estimated blood loss was 250 mL (range, 50–1500). Median time of hospitalization was 5 days (range, 2–21). Pathological response in the cervix was complete in 3 cases and microscopic in 1 patient (26.7%). Intraoperative complications occurred in 3 cases: 2 vascular injuries and 1 ureteral injury. Three patients (20.0% of the whole series) experienced grade 3 complications.At last follow-up (median time, 9 months), the median overall survival is 13 months (range, 6–31): 7 (46.7%) women were free of disease, 8 (53.3%) patients progressed, and 3 of them died of disease.ConclusionsRadical surgery can be performed in women with CC previously treated with a bevacizumab-containing regimen.

To identify women affected by recurrent ovarian cancer who benefit from secondary cytoreductive surgery (SCS), analyse their clinical and biological features and investigate the role of minimally invasive surgery (MIS) and hyperthermic intraperitoneal-based chemotherapy (HIPEC) in this subset of patients. This narrative review examines the data available from the updated literature. An electronic literature search was conducted in PubMed Medline databases for articles published from 1990 to 2018. Retrospective studies and preliminary data from the AGO-Desktop III trial show that cytoreductive surgery is associated with improved post-relapse survival in patients with platinum-sensitive relapse, compared to chemotherapy alone. This benefit is more evident in patients treated with complete or optimal primary debulking surgery at referral centres, who did not receive bevacizumab in first-line chemotherapy, and who present a localized pattern of disease. MIS has been proven to be a favourable approach to achieve a complete secondary debulking, reducing peri- and postoperative comorbidities. The application of HIPEC to SCS is associated with an improvement in oncological outcomes by preliminary results. While waiting for the final results of the ongoing randomized controlled trials, SCS seems feasible and safe in selected patients with recurrent ovarian cancer. Recently, more attention has been focused on the biological features of ovarian tumours, such as BRCA status. Further studies and molecular research should be conducted to identify individualized and targeted therapies in the treatment of ovarian cancer recurrences.

Study Objective To describe the potential role of intraoperative ultrasound (IOUS) in the detection and localization of recurrent disease in gynecologic cancer patients during minimally invasive surgery (MIS). Design A prospective cohort study (Canadian Task Force classification II-1). Setting A university hospital. Patients Fifty-one gynecologic cancer patients with isolated recurrent disease. Interventions IOUS during secondary cytoreductive surgery (SCS) by MIS. Measurements and Main Results From November 2015 to February 2017 51 gynecologic cancer patients with isolated recurrent disease and candidates for SCS were treated by MIS. Recurrent tumor was preoperatively assessed at clinical examination, transvaginal and transabdominal sonography, and radiologic evaluation in all women. Twelve of 51 women (23.5%) needed IOUS. Type of disease was ovarian in 5 women (42%), endometrial in 4 (33%), cervical in 1 (8%), vaginal cancer in 1 (8%), and uterine sarcoma in 1 (8%). Recurrence was localized deep in the pelvis in 7 cases (58%), lymph nodes in 3 (25%), and extraperitoneal in 2 cases (17%). Recurrence was dimmed in the surgical field, due to either presence of adherences, deep anatomic position, small size, and/or lack of tactile feeling. IOUS was able to identify the lesions in all women, allowing MIS (83% laparoscopy and 17% robotic) complete cytoreduction, with no conversion to laparotomy. Median operative time was 150 minutes (range, 77–280). No intraoperative/postoperative complications occurred. Histologic examination confirmed the presence of recurrence in 11 of 12 cases (92%), whereas the remaining case showed inflammatory tissue. With a median follow-up time of 15 months (range, 6–19), all patients except 2 were still alive. Conclusions About 1 of 4 patients (25%) with single gynecologic cancer recurrence needs IOUS to benefit from MIS for complete secondary cytoreduction.

Purpose The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced cervical cancer (LACC) patients. Methods and materials The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m2, carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients. Results 45 patients were enrolled into the study; 25 patients (55.5%) were FIGO stage IIB, 9 cases (20.0%) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4%) patients; pCR was documented in 18 out of 40 patients (45.0%). Grade 3–4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0% and 86.0%, respectively. Conclusions NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity.

ObjectiveThe aim of this retrospective study was to assess the surgical and oncological outcome of 3 different surgical approaches (laparotomy, laparoscopy, and robotic surgery) in the treatment of early-stage cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IB1.MethodsAll patients with a histologically confirmed diagnosis of early-stage cervical cancer, FIGO stage IB1, who underwent abdominal radical hysterectomy (ARH), laparoscopic radical hysterectomy, or robotic radical hysterectomy with or without pelvic and aortic lymphadenectomy were included in the study. A review of the literature was conducted.ResultsThree hundred forty-one patients, between January 2001 and December 2016, were included in this study: 101 patients were submitted to ARH, 152 to laparoscopic radical hysterectomy, and 88 to robotic radical hysterectomy. In 97% and 11.5% of cases, bilateral pelvic and aortic lymph node dissections were performed, respectively. The 3 groups were similar in regard to clinical characteristics. Compared with ARH, the minimally invasive surgery group was safer in terms of estimated blood loss, transfusion rates, and hospital stay. Above all, robotic surgery was equivalent to laparoscopy in terms of intraoperative and postoperative complications, hospital stay, conversions, and reintervention. On the other hand, robotic surgery had better outcomes compared with laparoscopy in terms of transfusion rates and was equivalent to abdominal surgery and laparoscopy in regard to oncological outcomes.ConclusionsOur study confirmed that minimally invasive surgery (laparoscopy or robotics) was as adequate and effective as abdominal surgery in terms of surgical and oncological outcomes in the surgical treatment of EEC FIGO stage IB1.

Study Objective To investigate the feasibility and safety of laparoscopic cytoreduction in ovarian cancer patients with localized carcinomatosis or lymph node involvement. Design Retrospective cohort study (Canadian Task Force classification II-2). Setting Multi-institutional study performed in 6 referral gynecologic oncology units. Patients Between June 2005 and December 2014, preoperatively presumed early-stage ovarian cancer patients, who accidentally revealed localized carcinomatosis or lymph node involvement at laparoscopic evaluation or at postoperative pathological examination managed by the laparoscopic approach. Interventions All patients with limited carcinomatosis and/or lymph node metastases underwent complete laparoscopic cytoreduction. Measurements and results Sixty-nine patients were included in the analysis. Twenty-eight (40.6%) patients were staged III C because they had lymph node metastases. Pelvic lymphadenectomy was performed in 75.4% of cases, whereas aortic lymphadenectomy was performed in 79.7% of cases. Lymph node metastases were found in pelvic and aortic regions in 11 and 13 patients, respectively, whereas 4 patients had lymph node metastases in both regions. Twelve (17.4%) patients underwent complete pelvic peritonectomy because of the presence of nodules localized in several pelvic region sites. As of May 2015, the median follow-up was 35 months, and the median disease-free survival was 29 months. The 2-year disease-free survival rate was 77.1%, whereas the 2-year overall survival rate was 90.6%. The median time to recurrence was 26 months (range, 6 -55 months); 15 (21.7%) patients developed recurrence. Conclusion The present study shows the technical and clinical feasibility of laparoscopic cytoreduction in ovarian cancer patients with limited carcinomatosis or lymph node involvement.

Study Objective To investigate the feasibility of laparoscopic splenectomy in patients with recurrent ovarian cancer with isolated spleen metastasis. Design (Canadian Task Force classification III). Setting Tertiary referral centre in Rome, Italy. Patients Eight women with an isolated platinum-sensitive splenic relapse of ovarian cancer. Intervention Between February 2013 and May 2015, 8 women with an isolated platinum-sensitive splenic relapse of ovarian cancer were submitted to laparoscopic splenectomy. Measurements and Main Results All patients underwent laparoscopic splenectomy without conversion to an open approach. The median estimated intraoperative blood loss was 100 mL (range, 50–200 mL). The median operating room time was 200 minutes (range, 80–275 mL). No intraoperative complication occurred, and no intraoperative blood transfusions were required. The median length of hospital stay was 3 days (range, 2–5 days). Complete tumor resection was achieved in all patients. The median interval from surgery to adjuvant chemotherapy was 16 days (range, 14–24 days). After a median follow-up of 23 months (range, 6–32 months), no secondary recurrence or death of disease has been observed. Conclusion Our findings indicate that a laparoscopic approach for spleen removal is feasible in selected patients with a splenic relapse of ovarian cancer when performed in a tertiary referral center by a well-trained surgeon.

Aims We evaluated the 1-year clinical events, pharmacological management, and quality of life in a contemporary cohort of stable coronary artery disease (CAD) patients managed by cardiologists. Methods and results START (STable Coronary Artery Diseases RegisTry) was a prospective, observational, nationwide study that enrolled 5070 stable CAD patients over 3 months in 183 cardiology centres in Italy. At 1 year, 4790 (94.5%) patients had data on vital status. Death occurred in 107 (2.2%) patients and the cause of death was cardiovascular in 41 (38.3%) of cases. Among the 4775 patients with follow-up data on clinical events available, a hospitalization due to cardiovascular and non-cardiovascular causes occurred in 523 (11.0%) and in 231 (4.8%) of cases, respectively. Over 60% of patients reported as ‘no problems’ in all domains (61.4–84.5%) of the EuroQoL quality of life 5D-5L questionnaire. Among the 3239 patients with clinical visit/telephone interview at follow-up, in whom optimal medical therapy (OMT; aspirin or thienopyridine, β-blocker, and statin) was prescribed at enrolment, 2971 (91.7%) were still receiving OMT at follow-up. At multivariable analysis, only increasing age (odds ratio 0.98; 95% confidence interval 0.97–0.99; P = 0.04) resulted as independent negative predictor of OMT persistence at 1 year from enrolment. Conclusion In this large, contemporary registry, stable CAD patients managed by cardiologists presented a high rate of clinical events at 1 year. Nevertheless, the persistence to OMT and quality of life appeared reasonable.

Introduction In the last decade, laparoscopy has been progressively introduced in the management of advanced-stage ovarian cancer (AOC) to evaluate tumor resectability, avoiding an explorative laparotomy, to identify non-responders to submit to second-line chemotherapy and to perform primary or interval minimally invasive debulking surgery in selected patients. This review aims to deeply focus on the differences between laparoscopy and laparotomy in the management of advanced ovarian cancer. Evidence acquisition The electronic database search provided a total of 80 results. Out of these, 63 results were excluded because considered not relevant to the review, for linguistic reasons or case reports. A total of 17 articles were considered eligible for the review. Evidence synthesis Many studies have assessed the value of laparoscopy in predicting the optimal resectability of AOC patients avoiding exploratory laparotomies. More recently, its role in primary and interval cytoreduction has been investigated for selected patients in terms of safety, feasibility and oncological outcomes. Published data are comparable to the standard laparotomic management in terms of oncological outcomes but with improved perioperative and psychological results. The selection of patients is crucial to perform a successful surgery. Conclusions To date, laparoscopy has replaced the primary laparotomic approach in the evaluation of optimal resectability. As far as primary and interval minimally invasive debulking surgery are concerned, instead, most of the works report an overlap of oncological outcomes compared to traditional surgery. The selection of patients is a crucial point to reach a successful minimally invasive surgical treatment, taking into account surgical complexity and surgical adequacy.

A hysterectomy for enlarged uteri is considered a challenge for gynaecologic surgeons, due to the limit of exposure to surgical spaces. Our objective is to investigate the different variables that may have an impact on the risk of conversion to open surgery. This is a retrospective cohort study consisting of 133 women who were submitted to surgery for uterine fibroids and who underwent total hysterectomy by laparoscopic approach attempt. The median uterus weight was 622 grams (range 301–3882) and the median maximum diameter of the bigger fibroid was 74 mm (range 33–148). We registered 13 (9.8%) cases of conversion to laparotomy. Minor and major post-operative complications were recorded in 4 (3%) and in 4 (3%) cases, respectively. After multivariable analysis, the surgeon’s experience (OR: 0.24; 95% CI: 0.06–0.94, p =.027) and a maximum diameter of the biggest fibroid ≥10 cm (4.7; 1.39–15.87; p =.046), but not the uterus weight were associated with the risk of conversion to open surgery.IMPACT STATEMENTWhat is already known on this subject? Laparoscopic procedures for enlarged uteri are well described in literature; however, the only parameters that have been studied for the success of a laparoscopic procedure have been the uterus weight and the surgeon’s experience. What do the results of this study add? This study aimed to value all the possible variables related to the successful of laparoscopic procedures; in fact, we investigated not only the uterine weight, but in our multivariate analysis, the position of the fibroids, the trocar’s setting, etc. were analysed. What are the implications of these findings for clinical practice and/or further research? This study reported novel data about the feasibility of laparoscopic hysterectomy for enlarged uteri. In opposition to the literature, the uterine weight is not a predictive value for laparotomic conversion. Moreover, we discussed the possible reasons of our novel findings. It opens new perspective to create a predictive value of laparoscopic feasibility for the different types of enlarged uteri.

Objective To investigate the safety, feasibility and oncological adequacy of the Percutaneous Surgical System - PSS in a consecutive series of low-risk endometrial cancer staging. Study Design From May 2015 to April 2017, we prospectively performed 30 consecutive percutaneous staging for low/intermediate risk endometrial cancer (FIGO stage IA G1-G2, IB G1-G2, IA G3). All patients were divided in two different groups on the basis of surgical procedure received: Group A included patients submitted to radical Class A hysterectomy and bilateral salpingo-oophorectomy; Group B concerned patients that received a lymph nodal assessment also. Results The time needed to install percutaneous instruments and suprapubic trocar was 4 min. (range 2–10). The recorded median operative time (OT) was 80 min. (range 65–120) for Gr.A and 143 min. (range 107–190) for Gr.B, in which the median time of lymph nodal assessment was 55 min. (range 20–76). The median time for hysterectomy was 60 min. (range 40–110) in all cases. Lymph nodal assessment was performed in 14 (46.6%) cases: 7 sentinel node mapping, 7 pelvic lymphadenectomy. No intraoperative complications or LPS/LPT conversions were recorded. Median discharge time was 2 days (range 1–4), 5 patients were discharged in 3rd post-op day, and only 1 patient was discharged in 4th day for fever. All patients conveyed high satisfaction with the cosmetic results. A progressive overall reduction of pain perception was observed at 24 h after surgery. Median follow-up was of 14 months (range 12–36), no recurrences have been detected. Conclusions PSS seems to be a feasible approach for endometrial cancer staging. Larger experiences and prospective comparative studies are important to assess our assumptions and further investigate the real benefits of percutaneous surgical system.

Study Objective To assess the feasibility and efficacy of minimally invasive pelvic exenteration (MIPE) in a multi-institutional Italian case series of women with gynecologic cancer and a review of the literature. Design Retrospective cohort study (Canadian Task Force classification II-2). Setting Three Italian university/teaching hospitals: “Agostino Gemelli” Foundation University Hospital in Rome, "ARNAS Civico Di Cristina Benfratelli” Hospital in Palermo, and “Maggiore della Carita” Hospital in Novara. Patients We reviewed all consecutive cases with gynecologic malignancies in this multi-institutional setting recorded between March 2014 and June 2017. Women with primary or central recurrent/persistent gynecologic cancer considered suitable for exenterative surgery after multidisciplinary tumor board discussion were included. Clinicopathological, perioperative, and survival data were retrieved from the institutional electronic database (STAR center). Interventions All patients underwent total or anterior MIPE with a laparoscopic or robotic approach. Measurements and Main Results Twenty-three patients underwent MIPE during the study period, including 12 (52.1%) by a laparoscopic approach and 11 (47.9%) by a robotic approach. All but 1 woman underwent MIPE for recurrent disease. The overall median operative time was 540 minutes (range, 310–720 minutes) with laparoscopy, slightly longer than with the robotic approach (p = .04). Median estimated blood loss was 400 mL (range, 200–600 mL). R0 resection was achieved in 17 of 23 patients (73.9%). There were no perioperative deaths. Early major postoperative complications occurred in 2 patients (8.7%). The median duration of hospitalization was 10 days (range, 6–33 days). With a median follow-up of 15 months, 11 patients (47.8%) developed recurrence. The median disease-free survival was 11 months (range, 5–18 months). To date, 155 MIPEs for gynecologic cancers have been reported in the literature. Among these, 12.6% had major postoperative complications, and overall postoperative mortality was 0.6%. Conclusion MIPE is a feasible procedure with low rate of intraoperative and postoperative complications. Careful patient selection is crucial to balance perioperative risks and potential survival benefits and to achieve complete tumor resection.

Aims Microcystic, elongated, and fragmented (MELF) pattern of myoinvasion has been related with increased risk of lympho-vascular space invasion (LVSI) and lymph node metastasis. We analysed a cohort of endometrioid endometrial carcinomas (EECs) to examine the relationships between the MELF pattern of invasion and the clinico-pathological and immunohistochemical features of EEC. Methods and results 129 EECs were evaluated for the presence of MELF pattern and immunohistochemically tested for Mismatch repair (MMR) proteins, p16, p53 and beta-catenin. We observed 28 MELF + EECs and 101 MELF- EECs. LVSI was observed in 20 MELF + cases and in MELF- tumors. Lymph-node metastases were observed in 7 MELF + cases (2 macrometastases, 3 micrometastases and 2 ITCs). None of the MELF- cases showed micrometastases or ITCs, 18 cases had macrometastatic lymph-nodes. Statistical analysis showed that MELF + tumors carry an increased risk of developing nodal metastasis independent of tumor dimension and LVSI. Loss of MMR proteins expression was observed in 11 MELF + cases and 45 MELF- cases, respectively. Our data showed a higher frequency of immunohistochemical MLH1-PMS2 loss in MELF- pattern of invasion (32.67% of MELF- cases vs 21.43% of MELF + cases) but a higher prevalence of MSH2-MSH6 loss in MELF + pattern (7.14% in MELF + population vs 3.96% of MELF- population) Conclusions The morphological recognition of MELF pattern is more reliable than immunohistochemical and molecular signatures of EEC in predicting the risk of nodal involvement. The observed higher prevalence of MSH2-MSH6 loss in MELF + group and MLH1-PMS2 loss in MELF- group may suggest a different molecular signature.

Introduction Describing the surgical and oncological outcome of bladder-preserving ureter reconstruction (BPUR) with segmental ureteral resection after major gynecologic surgery. Matherials and methods Patients with BPUR admitted at a single institution between March 2012 and July 2018 were retrospectively analyzed. Surgical and oncological data were assessed. Results Forty-six women with gynecologic tumors involving the ureter were treated with BPUR. R0 resection was achieved in 40/46 patients (86.9%), while pathologic margins were microscopically positive in 6 women (13.1%). Overall, 12 women (26.0%) received radiotherapy before surgery: among them, 8 patients received neoadjuvant chemoradiotherapy. Twenty-six women underwent BPUR during primary surgery, whereas 20 (43.4%) required BPUR upon recurrence. Twenty-six patients (56.2%) were found to have hydronephrosis at pre-operative workup. The psoas bladder hitch was the most common procedure performed for urinary reconstruction (63%) with respect to direct reimplantation (37%). Fourteen patients (14/46 = 30.4%) experienced urological complications. Urinary leakage occurred in 9 patients (19.5%), specifically: 5 uretero-vaginal fistula, 3 uroperitoneum, 1 uretero-enteral fistula. There were 3 cases (6.5%) of hydronephrosis at the side of ureteroneocystostomy and 2 cases (4.3%) of unilateral renal impairment requiring nephrectomy. At multivariate analysis only pre-operative radiotherapy (p = 0.047) and a history of pelvic irradiation (p = 0.025) were independently associated with an increased risk of developing severe urinary complications. Conclusions BPUR is feasible in gynecologic cancer with invasion of the urinary tract. However, since a slight increase of post-operative urological complications was observed in the previously irradiated fields, a personalized surgical planning is recommended for these women in the next future.

We discuss the diagnosis and the management of endometrial carcinoma in a single horn of bicornuate uterus in a 64-year-old woman as a case report. The case underwent laparoscopic radical hysterectomy and bilateral iliac lymphadenectomy.The gross examination of the uterus revealed a bicornuate uterus with a greater horn of 12 × 9 × 8 cm and a smaller horn of 10 × 3 cm. The cavity of the greater horn showed a neoplastic growth of 10 cm with infiltration of about 1,8 cm of the myometrium from whole thickness of 1.9 cm. while the other horn was free of tumor tissue.The microscopic examination of the uterus revealed G2 endometrioid adenocarcinoma of the endometrium of the greater horn with infiltration of more than 50% of the myometrium.In the presence of bicornuate uterus, a bilateral endometrial biopsy should be performed in order to reduce the risk of delayed or missed diagnosis.The management of a case of bicornuate unicollis uterus with endometrial carcinoma in only one horn is the same as patients with endometrial cancer in single uterus and depends mainly on stage and histological grade of the tumor.The possibility of existence of a separate uterine cavity should always be considered when endometrial cancer is clinically suspected but pathology fails to confirm the diagnosis. This points out the importance of a careful physical examination and radiographic evaluation in such cases. Keywords: Bicornuate uterus, Endometrial cancer

Background Osteoarthritis (OA) is one of the main causes of disability and its frequent hip and knee joint localization requires surgical joint replacement treatment. Patients after total hip (THA) or knee (TKA) arthroplasty often show gait abnormalities, whose comprehension is crucial in order to plan an appropriate rehabilitative treatment. Wearable sensor devices can be a valid tool for gait assessment in clinical practice, being relatively inexpensive and easy to use. Research question Does the use of crutches influence the ability of a single inertial measurement unit (IMU), placed on the lower trunk, to correctly record the spatial-temporal gait parameters in patients after recent THA or TKA? Methods 20 patients walking with crutches after recent THA or TKA and 10 healthy subjects were recruited. Each participant was recorded simultaneously with an IMU and with an optoelectronic motion capture system during 5 consecutive walking tests. Results Intraclass correlation index of spatial-temporal parameters recorded with the IMU showed moderate to excellent reliability results both for healthy subjects (ICC range 0.626–0.897) and for patients (ICC range 0.596–0.951). In terms of concurrent validity, Pearson’s r coefficient of healthy subjects, showed strong to very strong levels of correlations for some spatial-temporal parameters (speed, mean cadence, left and right stride length and stride duration) (r range 0.646–0.977) and very week to moderately week levels of correlation for gait cycle phases (swing, stance, single support and double support) (r range 0.390–0.633). Patients’ data analysis showed similar results for general spatial-temporal parameters (r range 0.704–0.986) and slightly lower values for gait cycle phases (r range 0.077–0.464). Significance We can consider the single IMU as a reliable tool for the detection of some spatial-temporal gait parameters. Crutches seem to interfere with the detection of the gait cycle phases.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Airway closure causes lack of communication between proximal airways and alveoli, making tidal inflation start only after a critical airway opening pressure is overcome. The authors conducted a matched cohort study to report the existence of this phenomenon among obese patients undergoing general anesthesia. Methods Within the procedures of a clinical trial during gynecological surgery, obese patients underwent respiratory/lung mechanics and lung volume assessment both before and after pneumoperitoneum, in the supine and Trendelenburg positions, respectively. Among patients included in this study, those exhibiting airway closure were compared to a control group of subjects enrolled in the same trial and matched in 1:1 ratio according to body mass index. Results Eleven of 50 patients (22%) showed airway closure after intubation, with a median (interquartile range) airway opening pressure of 9 cm H2O (6 to 12). With pneumoperitoneum, airway opening pressure increased up to 21 cm H2O (19 to 28) and end-expiratory lung volume remained unchanged (1,294 ml [1,154 to 1,363] vs. 1,160 ml [1,118 to 1,256], P = 0.155), because end-expiratory alveolar pressure increased consistently with airway opening pressure and counterbalanced pneumoperitoneum-induced increases in end-expiratory esophageal pressure (16 cm H2O [15 to 19] vs. 27 cm H2O [23 to 30], P = 0.005). Conversely, matched control subjects experienced a statistically significant greater reduction in end-expiratory lung volume due to pneumoperitoneum (1,113 ml [1,040 to 1,577] vs. 1,000 ml [821 to 1,061], P = 0.006). With airway closure, static/dynamic mechanics failed to measure actual lung/respiratory mechanics. When patients with airway closure underwent pressure-controlled ventilation, no tidal volume was inflated until inspiratory pressure overcame airway opening pressure. Conclusions In obese patients, complete airway closure is frequent during anesthesia and is worsened by Trendelenburg pneumoperitoneum, which increases airway opening pressure and alveolar pressure: besides preventing alveolar derecruitment, this yields misinterpretation of respiratory mechanics and generates a pressure threshold to inflate the lung that can reach high values, spreading concerns on the safety of pressure-controlled modes in this setting.