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To compare surgical and post-operative outcomes of patients submitted to traditional laparoscopy and percutaneous-assisted laparoscopy for ovarian tissue explant for cryopreservation.This is a single-center retrospective comparative study conducted in IRCCS "Regina Elena" National Cancer Institute of Rome. Patients submitted to laparoscopic excision of ovarian tissue, before starting chemotherapy were enrolled. We compared the classic laparoscopic approach vs percutaneous-assisted laparoscopy, using the Percuvance grasping forceps.Fifty-nine young oncologic women were enrolled; 38 underwent a conventional laparoscopy (LAP), 21 received a percutaneous laparoscopy (PERC). The baseline characteristics were similar in both groups, furthermore no differences were found in terms of peri-operative complications, median estimated blood loss (p = 0.4), operative time (p = 0.2), recovery times (p = 0.1), median time to chemotherapy (p = 0.7), median area of collected samples (p = 0.9). The postoperative pain evaluated by VAS-score, was significantly lower in the PERC group vs LAP group, both the day of surgery (range 0-4 vs 0-2; p = 0.02) and after 1 (range 0-3 vs 0-2; p = 0.002) and 2 days (range 0-3 vs 0-1; p = 0.0001). Moreover, better aesthetic results were detected in the PERC group, 2 months after surgery (median 9 vs 10, range 7-10 vs 9-10; p = 0.0001).Percutaneous-assisted laparoscopy has proven to be an effective and safe procedure for the excision of ovarian tissue for cryopreservation, in young oncologic patients that want to preserve their fertility. The percutaneous procedure appears superior to conventional laparoscopy in terms of aesthetic outcomes and post-operative pain reduction.NCT05134090, 24

Epithelial ovarian cancer (EOC) is the scariest gynaecological cancer. Many advances have been done with evolving knowledge, leading to the introduction of new drugs, most in maintenance setting. The antiangiogenic Bevacizumab and the three approved PARP-inhibitors—olaparib, niraparib and rucaparib—are gradually improving PFS of patients with EOC, with initial effects on OS too. But recurrence is still a heavy sentence and lethality continues to be high. Ovarian cancer is a complex disease, with different clinical presentation, histological aspect, and molecular expression, leading to disappointing results, when using a single drug. Implementation of biobanking and analysis of patients’ tumour samples, before starting a treatment, could be a promising way to better understand molecular aspects of this disease, to identify markers predictive of response and to allow a better use of experimental drugs, as immunomodulators, targeted therapies, and combinations of these, to fight tumour growth and clinical progression. We reviewed the literature on the updated treatments for recurrent ovarian cancer, summarizing all the available drugs and combinations to treat patients with this diagnosis, and focusing the attention on the new approved molecules and the contemporary Clinical Trials, investigating new target therapies and new associations.

The present article aims to highlight the importance of changes of personalized surgical treatment for vulvar cancer. Current international literature regarding surgical treatment of vulvar cancer was evaluated. This included several studies and systematic reviews. Radical surgery approach, such as en bloc resection, was the first therapeutic option and the standard care for many years, even if burdened with a high complication rate and frequently disfiguring. Taussing and Way introduced radical vulvectomy approach with en bloc bilateral inguinal-femoral lymphadenectomy; modified radical vulvectomy was developed, with a wide radical excision of the primary tumor. The role of inguinofemoral lymphadenectomy (mono or bilateral) changed in the years too, particularly with the advent of SLN biopsy as minimally invasive surgical approach for lymph node staging, in patients with unifocal cancer4 cm, without suspicious groin nodes. More personalized and conservative surgical approach, consisting of wide local or wide radical excisions, is necessary to reduce complications as lymphedema or sexual disfunction. The optimal surgical management of vulvar cancer needs to consider dimensions, staging, depth of invasion, presence of carcinoma at the surgical margins of resection and grading, with the goal of making the treatment as individualized as possible.

Yersiniosis is the third most reported food-borne zoonosis in Europe. The aim of the present study was to perform the search for Yersinia enterocolitica in food samples collected from Apulia and Basilicata regions (Southern Italy) and to characterize any isolates by classical and modern analytical methods. A total of 130 samples were analyzed between July 2018 and July 2019: most of them were raw milk and dairy products made from it. Furthermore, 8 out of 130 samples were individual milk samples collected from bovines reared in a Brucella-free farm which showed false positive serological reaction for brucellosis due to the presence of pathogenic Y. enterocolitica O:9 biotype 2 in faeces. The Real Time PCR targeting the ail gene and the culture method were performed to detect pathogenic Y. enterocolitica. Isolates were subjected to API 20E (Biomerieux) and MALDI-TOF MS (Matrix Assisted Laser Desorption Ionization Time-of-Flight) for species identification. All samples were negative for the ail gene. The culture method allowed to isolate suspicious colonies from 28 samples. The API 20E system and the MALDI-TOF MS technique identified 20 Y. enterocolitica and 1 Y. intermedia in a concordant way. The remaining 7 strains were all identified as Y. enterocolitica by the API 20E system, while the MALDI-TOF MS recognized 4 Y. intermedia, 1 Y. bercovieri and 2 Y. massiliensis. Genotypic characterization of the discordant strains was performed by rMLST and it confirmed the MALDI-TOF MS’ results. Only non-pathogenic Y. enterocolitica biotype 1A strains were found, although with a non-negligible prevalence (P = 0.15 with CI 95% = ± 0.06). This study indicates a poor circulation of pathogenic Y. enterocolitica in food products made and marketed in the investigated areas. However, the small number of samples, insufficient for some food categories such as meat and vegetable, does not allow to exclude the presence of pathogenic strains at all.

Simple Summary In assessing the risk factors for the recurrence of EC, the length of the vaginal cuff removed during surgery has shown discrepant results. The aim of this study was to investigate the role of the excised vaginal cuff length as a prognostic factor and its correlation with the expression of L1CAM. To our knowledge, this is the first study evaluating this prognostic factor in such a secluded and tidy cohort. According to our results, vaginal cuff length does not seem to be an independent variable in an EC low-risk group in terms of DFS. Moreover, L1CAM seems to be associated with a higher risk of distant recurrence. A prospective randomized trial in an EC low-risk group is needed to confirm its negative prognostic role, and to determine its potential value in clinical practice to detect that subgroup of low-risk patients which is at a higher risk of recurrence, especially at distant. Abstract Objective: The aim of our study was to investigate the role of the excised vaginal cuff length as a prognostic factor in terms of DFS and recurrence rate/site, in low-risk endometrial cancer (EC) patients. Moreover, we correlated the recurrence with the expression of L1CAM. Material and Methods: From March 2001 to November 2016, a retrospective data collection was conducted of women undergoing surgical treatment for low-risk EC according to ESMO-ESGO-ESTRO consensus guidelines. Patients were divided into three groups according to their vaginal cuff length: V0 without vaginal cuff, V1 with a vaginal cuff shorter than 1.5 cm and V2 with a vaginal cuff longer than or equal to 1.5 cm. Results: 344 patients were included in the study: 100 in the V0 group, 179 in the V1 group and 65 in the V2 group. The total recurrence rate was 6.1%: the number of patients with recurrence was 8 (8%), 10 (5.6%) and 3 (4.6%), in the V0, V1 and V2 group, respectively. No statistically significant difference was found in the recurrence rate among the three groups. Although the DFS was higher in the V2 group, the result was not significant. L1CAM was positive in 71.4% of recurrences and in 82% of the distant recurrences. Conclusions: The rate of recurrence in patients with EC at low risk of recurrence does not decrease as the length of the vaginal cuff removed increases. Furthermore, the size of the removed vaginal cuff does not affect either the site of recurrence or the likelihood of survival.

Introduction The aim of this study is to revise the experience of two reference centers for vulvar cancer treatment during the last 2 years, evaluating the ECT procedure in terms of clinical outcome and side effects profile. Methods Data were retrospectively collected from November 2017 to November 2019 in two Italian oncologic Institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli. ECT was offered in a palliative setting to patients with a primary or recurrent vulvar cancer diagnosis unsuitable for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anaesthesia. Intravenous Bleomycin was administered. Follow-up examinations were performed at 1, 3 and 6 months. Results 15 patients were included in the study. No intra-procedure complications occurred. 1 patient had pneumonia during post-operative stay. 1-month overall response rate (2 CR and 10 PR) was 80%. At 3-month follow-up, 3 patients (20%) showed PD, 3 patients (20%) died from the ongoing disease, 1 patients (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. 8 out of 13 patients (61.5%) were alive at 6-month follow-up, whereas 6 out of 12 patients (50%) were alive at 1-year follow-up. Conclusion ECT has proven to be a feasible, easy to perform, reproducible and repeatable procedure. For these reasons, it may have a role in the management of VC, especially as palliative treatment when other therapies are no longer applicable.

Surgery in suspected/confirmed COVID-19 patients is a high-risk venture. In infected patients, COVID-19 is present in the body cavity. During surgery it could be nebulized in the spray generated by surgical instruments and could theoretically infect members of the surgical team. Nevertheless, some surgical gynecologic pathologies cannot be postponed. We present a list of the most frequent gynecologic diseases and recommendations on their surgical management during the COVID-19 pandemic, based on expert opinion, current available information, and international scientific society recommendations to support the work of gynecologists worldwide. In brief, any kind of surgical treatment should be scrutinized and postponed if possible. Nonoperative conservative treatment including pharmacological therapies for hormone-sensitive pathologies should be implemented. Health risk assessment by patient history and COVID-19 test before elective surgery are pivotal to protect both patients and healthcare providers. In confirmed COVID-19 patients or highly suspected cases, elective surgery should be postponed until full recovery.

ObjectiveSince vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer.MethodsData were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer.ResultsA total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3–42) and median operative time was 13 (range 7–20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up.ConclusionsElectrochemotherapy is a feasible, easy to perform, and reproducible procedure in patients with primary or recurrent vulvar cancer who are unable to undergo surgery. Survival after 1 year in this population was 50%. Electrochemotherapy may have a role in the management of vulvar cancer, especially as palliative treatment when other therapies are no longer applicable.

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.

ObjectiveThe objective of this study was to evaluate the cosmetic outcome of robotic single-site hysterectomy (RSSH) in early-stage endometrial cancer.MethodsWe prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients who underwent RSSH for early-stage endometrial cancer. The Patient and Observer Scar Assessment Scale (POSAS) was used for the evaluation of the cosmetic outcome.ResultsForty-five patients were included in our study from January 2012 to October 2015. The median age of patients was 63 years (range, 35–84 years), and the median body mass index was 26.5 kg/m2 (range, 18–39 kg/m2). No laparoscopic/laparotomic conversion was registered. The median docking time, console time, and total operative time were 7 minutes (range, 4–14 minutes), 46 minutes (range, 20–100 minutes), and 90 minutes (range, 45–150 minutes), respectively. The median blood loss was 50 mL (range, 10–150 mL). Nine patients underwent pelvic lymphadenectomy, and the median number of pelvic lymph nodes was 13 (range, 10–32). The median time to discharge was 3 days (range, 2–6 days). No intraoperative complications occurred, whereas we did observe 1 early postoperative complication. The oncological outcome was directly comparable to the literature. Patients reported low pain scores and high satisfaction in terms of postoperative scarring. The POSAS scores confirmed excellent cosmetic outcome of RSSH.ConclusionRobotic single-site hysterectomy provided an efficient option for gynecologic oncologic surgery. The POSAS revealed high objective and patient-evaluated outcome, and patients were highly satisfied with the overall outcome of the appearance of their scars.

Introduction/Background Endometrial cancer (EC) is mostly diagnosed at an early stage with a favorable overall survival. 5-year survival decreases from 95% for localized disease to less than 20% for metastatic disease. Survival is related to known prognostic factors. Nevertheless, they are not sufficient to predict either outcome or recurrence rate/site: to decipher the underlying aberrant biomolecular pathways seems to be promising, although it is not yet applicable in a clinical setting. In that purpose, to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for an early recurrences detection and treatment with a survival rate improvement. Methodology 758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and high risk HR) and surgically treated as recommended, followed by adjuvant therapy, when appropriated. Results Recurrences were detected in 19,5%. Higher recurrence rate (RR) was significantly detected (p Conclusion These results strengthen the need to identify biological factors to stratify patients at higher risk of relapse, independently or in addition to their risk class prognosis and current surgical and clinical managements. Disclosure Nothing to disclose.

Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule.758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate.Higher recurrence rate (RR) was significantly detected (p 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01).To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.

The aim of this study was to evaluate the prognostic role of positive peritoneal cytology (PPC) in a cohort of patients with endometrial cancer (EC). The secondary objective was to correlate the PPC and the expression of L1CAM in a group of patients with recurrence endometrial disease.All women diagnosed with EC and who performed a peritoneal cytology at "Regina Elena" National Cancer Institute of Rome from 2001 to 2013 were included in the study. Patients were divided into two groups according to positivity at peritoneal cytology. Moreover, patients with a recurrence disease and whose a tissue microarray (TMA) tumor sample was available underwent a L1CAM analysis.Seven hundred sixty six patients underwent to EC staging in our Institute: 696 (90.8%) with negative and 70 (9.2%) with positive cytology. Five-year recurrence rate was higher in women with PPC (46.9% vs 18.4%, p = 0 0.0001) and, in particular, distant recurrence (86.7% vs 53.4%, p = 0.03). Moreover, we found an interesting pattern of recurrence disease in the group of early stage of EC with NPC and positive L1CAM.Our results support the data that PPC may be a potential prognostic factor in early EC, due to its significant association with other risk factors and its significant influence on survival. Our findings confirm the need for large studies that point out the role of PPC and new prognostic factors, including biomarkers as L1CAM.

Study Objective The aim of this study was to evaluate the surgical and oncologic outcomes of robotic hysterectomy with or without or less pelvic and aortic lymphadenectomy in severely obese patients (body mass index [BMI] ≥ 40 kg/m 2 ) with endometrial cancer. Material and Methods Between August 2010 and November 2014, patients with histologically confirmed endometrial cancer and BMI ≥40 kg/m 2 were deemed eligible for the study and underwent RH with or without pelvic and aortic lymphadenectomy. Results Seventy patients were divided into 3 groups according to their BMI: group A, BMI between 40 and 45 kg/m 2 (50 patients); group B, BMI between 45 and 50 kg/m 2 (10 patients); and group C, BMI above 50 kg/m 2 (10 patients). No significant statistical differences were found between the 3 groups in terms of operation time, blood loss, hospital stay, and oncologic results. Pelvic lymphadenectomy was performed in 42%, 30%, and 20% of patients in groups A, B, and C, respectively. An intraoperative complication occurred in 1 patient in group A, early postoperative complications in 4 patients in group A and in 1 patient in group C, and a late postoperative complication occurred in 1 patient in group A. No conversions to laparotomy were necessary; however, 3 patients underwent conversions to laparoscopy in group A and 1 patient in both groups B and C. Conclusion Our study showed that robotic surgery in severely obese patients with endometrial cancer is safe and feasible. Moreover, it seems that an increase in BMI does not change the surgical and oncologic outcomes. However, randomized controlled trials are needed to confirm these results.

Objective The aim of this study was to evaluate the surgical and oncological outcome of robotic surgical staging with hysterectomy (RH) plus or less pelvic and aortic lymphadenectomy, compared to the same procedures performed by laparoscopic surgery (LH) in obese patients (BMI≥30 kg/m2) with endometrial cancer. Material and methods From October 2001 to April 2017, obese patients (BMI > 30 kg/m2) with primary, histologically confirmed endometrial carcinoma who underwent LH or RH using the Da Vinci Si or Xi Surgical System® (Intuitive Surgical Inc®, 1266 Kifer Road, Building 101 Sunnyvale, CA) were eligible for the study. Results We identified 655 women with endometrial cancer and BMI >30 kg/m2. Out of 655 patients, 249 (38%) underwent RH and 406 (62%) underwent LH plus or less pelvic and aortic lymphadenectomy. Our study showed that, compared to the 406 patients treated in LPS, 249 patients treated in robotics have a statistically significant difference in terms of increased operating time and a decreased conversion rate. In addition, the rate of pelvic lymphadenectomies in robotic surgeries is twice the one reported in LPS surgeries. Furthermore, a reduction in hospital stay was observed in the robotic group. We observed that the oncological outcomes do not vary according to the surgical approach and BMI variation. Conclusions: robotic surgery in severely obese women with endometrial cancer is feasible, safe, and reproducible and could be a valid alternative to laparoscopy in the treatment of these patients. Prospective studies could confirm our results.

Anisakis spp. and Hysterothylacium spp. are nematodes that commonly parasitize several fish species. Nematode larvae can be recovered in coelomic cavity and viscera, but also in flesh and have an important economic and public health impact. A total of 1144 subjects of wild teleosts, 340 samples of cephalopods and 128 specimens of farmed fish collected from Apulia region were analysed for anisakid larvae detection by visual inspection of coelomic cavity and viscera and by digestion of the flesh. No nematode larvae were found in farmed fish and cephalopod molluscs. All examined wild-caught fish species were parasitized, except for 5 species for each of which only a few subjects belonging to the same batch were sampled, therefore the results are just indicative. A total of 6153 larvae were isolated; among these, 271 larvae were found in the muscular portion. Larvae were identified by morphological method as belonging to the genera Anisakis (97.2%) (type I and type II) and Hysterothylacium (2.8%). Both nematodes could be found in all fish species, except for round sardinella (Sardinella aurita), infected only by Hysterothylacium spp. and for Mediterranean scaldfish (Arnoglossus laterna), little tunny (Euthynnus alleteratus) and chub mackerel (Scomber japonicus) infected only with Anisakis spp.. A sample of 185 larvae was sent to the National Reference Centre for Anisakiasis (C.Re.N.A.) of Sicily for identification at the species level: 180 larvae belonged to the species A. pegreffii and 2 larvae to A. physeteris. The remaining 3 larvae were identified at genus level as Hysterothylacium. Statistical indices such as prevalence, mean intensity and mean abundance were calculated. Chub mackerel (S. japonicus) was the species with the highest prevalence and mean intensity. Moreover, the average and the median values of larvae per 100 g of edible part for each fish species were determined to estimate the consumer exposure to Anisakis spp.. The obtained values were then recalculated by referring to the edible part of all specimens (infected and non-infected) forming a single parasitized batch, getting more realistic and objective data useful for risk assessment. Our results indicate that the consumption of raw or undercooked wild fish caught off Apulian coasts could result in the acquisition of anisakiasis; on the contrary, farmed fish and cephalopods appear to be safer for the consumer.

Circulating cell-free DNA (cfDNA) and its integrity index may represent a rapid and noninvasive "liquid biopsy" biomarker, which gives important complementary information for diagnosis, prognosis, and treatment stratification in cancer patients. The aim of our study was to evaluate the possible role of cfDNA and its integrity index as a complementary tool for endometrial cancer (EC) management.Alu-quantitative real-time PCR (qPCR) analysis wasprformed on 60 serum samples from preoperative EC patients randomly recruited. Both cfDNA content and DNA integrity index were measured by qPCR-Alu115 (representing total cfDNA) and qPCR-Alu247 (corresponding to high molecular weight DNA) and correlated with clinicopathologic characteristics. Lymphovascular space invasion (LVSI) was detected by hematoxylin and eosin staining. In case of doubt, LVSI status was further evaluate by immunohistochemistry using anti-CD31 and anti-CD34 antibodies.Total cfDNA content significantly increases in high grade EC. A significant decrease of DNA integrity index was detected in the subset of hypertensive and obese high grade EC. Serum DNA integrity was higher in samples with LVSI. The ordinal regression analysis predicted a significant correlation between decreased integrity index values and hypertension specifically in tumors presenting LVSI.Our study supports the utility of serum DNA integrity index as a noninvasive molecular biomarker in EC. We show that a correlation analysis between cfDNA quantitative and qualitative content and clinicopathologic features, such as blood pressure level, body mass index (BMI) and LVSI status, could represent a potential predictive signature to help stratification approaches in EC.

Background Circulating cell-free DNA (cfDNA) and its integrity index may represent a rapid and noninvasive “liquid biopsy” biomarker, which gives important complementary information for diagnosis, prognosis, and treatment stratification in cancer patients. The aim of our study was to evaluate the possible role of cfDNA and its integrity index as a complementary tool for endometrial cancer (EC) management. Methods Alu-quantitative real-time PCR (qPCR) analysis wasprformed on 60 serum samples from preoperative EC patients randomly recruited. Both cfDNA content and DNA integrity index were measured by qPCR-Alu115 (representing total cfDNA) and qPCR-Alu247 (corresponding to high molecular weight DNA) and correlated with clinicopathologic characteristics. Lymphovascular space invasion (LVSI) was detected by hematoxylin and eosin staining. In case of doubt, LVSI status was further evaluate by immunohistochemistry using anti-CD31 and anti-CD34 antibodies. Results Total cfDNA content significantly increases in high grade EC. A significant decrease of DNA integrity index was detected in the subset of hypertensive and obese high grade EC. Serum DNA integrity was higher in samples with LVSI. The ordinal regression analysis predicted a significant correlation between decreased integrity index values and hypertension specifically in tumors presenting LVSI. Conclusions Our study supports the utility of serum DNA integrity index as a noninvasive molecular biomarker in EC. We show that a correlation analysis between cfDNA quantitative and qualitative content and clinicopathologic features, such as blood pressure level, body mass index (BMI) and LVSI status, could represent a potential predictive signature to help stratification approaches in EC. Electronic supplementary material The online version of this article (doi:10.1186/s13046-018-0688-4) contains supplementary material, which is available to authorized users.

Objective To evaluate the feasibility and the safety of robotic single-site radical hysterectomy (RSSRH) plus pelvic lymphadenectomy (PL) in endometrial or cervical cancer. Methods Patients with endometrial cancer (EC) International Federation of Gynecology and Obstetrics (FIGO) stage II, early cervical cancer (ECC) FIGO stage IB1 or locally advanced cervical cancer (LACC) FIGO stage IB2-IIB with clinical response ≥50% after neo-adjuvant chemotherapy (NACT) were enrolled in a prospective cohort trial. All cases were performed using the da Vinci Si Surgical Single Site System®. Results Between April 2014 and November 2016, twenty patients were included in our pilot study. Three and 17 patients underwent type B1 or C1 RSSRH plus PL, respectively. The median age of patients was 46 years (range, 36-68 years) and the median body mass index was 23.5 kg/m² (range, 19.1-36.3 kg/m²). The median total operative time was 190 minutes (range, 90-310 minutes). The median blood loss was 75 mL (range, 20-700 mL) and the median number of pelvic lymph nodes removed was 16 (range, 5-27). No laparoscopic/laparotomic conversions were reported and the median time to discharge was 6 days (range, 4-16 days). No intra-operative complications occurred while 4 (20%) post-operative complications were reported: one pelvic abscess, one lymphorrea, one bowel perforation, and one vaginal dehiscence. Conclusion RSSRH plus PL is technically feasible in patients affected by gynecological cancer.

ObjectiveThe purpose of this study was to evaluate the feasibility and morbidity of total laparoscopic debulking surgery in the treatment of advanced ovarian cancer after neoadjuvant chemotherapy.Methods/MaterialsWe performed a retrospective review of laparoscopic approach in patients with histologically confirmed epithelial ovarian cancer (International Federation of GynaecologyObstetrics stages IIIC-IV) who received 3 courses of neoadjuvant chemotherapy, from January 2010 to December 2014, at the Gynaecologic Oncologic Unit, “Regina Elena” National Cancer Institute, Rome, Italy.ResultsA total of 30 patients were included. The median age was 50 years (range, 26–73 years), median body mass index was 24.5 kg/m2 (range, 19–39 kg/m2). All patients had good clinical response to 3 cycles of neoadjuvant chemotherapy. All women underwent a complete debulking surgery with no residual disease. The median operating time was 152 minutes (range, 70–335 minutes), the median blood loss was 70 mL (range, 50–200 mL). The median number of removed pelvic lymph nodes was 15 (range, 13–25). There was 1 (3.3%) intraoperative complication and 2 (6.6%) postoperative short-term complications. The median length of hospital stay was 4 days (range, 3–13 days). The median follow-up was 15 months (range, 2–54 months). Twenty-six patients are free from recurrence at the time of this report.ConclusionsLaparoscopic cytoreduction in patients with advanced ovarian cancer after neoadjuvant chemotherapy, when performed by skilled surgeons, seems feasible and may decrease the impact of aggressive surgery on high-morbidity patients, such as on women after chemotherapy.

// Lucia Cicchillitti 1, * , Giacomo Corrado 2, * , Martina De Angeli 3 , Emanuela Mancini 1 , Ermelinda Baiocco 1 , Lodovico Patrizi 3 , Ashanti Zampa 1 , Roberta Merola 4 , Aline Martayan 4 , Laura Conti 4 , Giulia Piaggio 5, ** and Enrico Vizza 1, ** 1 Department of Experimental Clinical Oncology, Gynecologic Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy 2 Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, Catholic University of Sacred Heart, Rome, Italy 3 Department of Biomedicine and Prevention, Obstetrics and Gynecology Unit, University of Rome “Tor Vergata”, Rome, Italy 4 Clinical Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy 5 Department of Research, Advanced Diagnostics and Technological Innovation, Area of Translational Research, IRCCS Regina Elena National Cancer Institute, Rome, Italy * These authors have contributed equally to this work ** Co-last authors Correspondence to: Giacomo Corrado, email: giacomo.corrado@alice.it Lucia Cicchillitti, email: luciacicchi@gmail.com Keywords: endometrial cancer; circulating cell-free DNA; circulating cell-free mitochondrial DNA; bio-markers; liquid biopsy Received: July 21, 2017 Accepted: December 01, 2017 Published: December 14, 2017 ABSTRACT Background: Altered circulating cell-free DNA (cfDNA) levels are related to cancer development and aggressiveness. Up to now, very few studies have been performed for evaluating cfDNA content in endometrial cancer (EC). Methods: First, we measured cfDNA release in blood serum of EC cancer patients collected before surgery and before the beginning of any treatment by SYBR Gold assay and correlated it with tumor aggressiveness. We also assessed the relative mitochondrial cell-free DNA (cfmtDNA) content by qRT-PCR. Next, we correlated cfDNA levels with BMI, age, hypertension and inflammation markers. Results: CfDNA levels are higher in G2 and G3 compared with G1 EC sera. A significant modulation of cfDNA content was detected in sera from patients with BMI>30 compared with those with BMI

Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women.

Background: The aim of this study was to assess the surgical and oncological outcome for the management of endometrial cancer (EC) by laparoendoscopic single-site surgery (LESS). Patients and Methods: We performed a retrospective chart review of patients who underwent a LESS for EC. All the patients were treated by the same surgical team between July 2009 and June 2013 at the Gynaecologic Oncologic Unit, Regina Elena National Cancer Institute, Rome, Italy. Results: A total of 50 women were included, with a median age of 45 years (range, 39-84 years) and a median body mass index (BMI) of 21.8 kg/m2 (range, 19-48 kg/m2). Median operative time was 100 min (range, 50-240 min), median blood loss was 90 mL (range, 10-300 mL) and median hospital stay was 3 days (range, 2-9 days). The median number of pelvic lymph nodes retrieved was 14 (range, 5-20). No intraoperative complications occurred, but there were 4 postoperative complications. Two patients required a laparoscopic conversion. The median follow-up was 36 months (range, 16-62 months) and no recurrence occurred. Conclusion: Our report showed that the LESS approach in the treatment of early EC can be a safe and reliable technique in terms of surgical and oncological outcomes.

Objective The primary aim is to evaluate the surgical and oncological outcome of robotic radical hysterectomy (RRH) plus pelvic lymphadenectomy in locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). The secondary aim is to compare the surgical and oncological results of RRH after NACT with a historical cohort of patients undergoing laparoscopic radical hysterectomy or abdominal radical hysterectomy plus pelvic lymphadenectomy for LACC after NACT. Methods We enrolled a total of 41 patients in this study with LACC undergoing RRH, who achieved a clinical partial or complete response to NACT. The surgical and oncological outcomes of 2 historical groups were compared: the laparoscopic group (41 patients) with the laparotomic group (43 patients). Results The median estimated blood loss, operative time, and length of hospital stay were statistically significant and in favor of the robotic group. No conversion to laparotomy in the robotic group was necessary. There were no significant differences between the 3-year overall survival and disease-free survival rates in the minimally invasive groups; nevertheless, the robotic group showed the same recurrence rate of laparoscopic in a short-interval follow-up. Conclusions The robotic approach could be considered a feasible and safe alternative to other surgical options. Multicenter randomized clinical trials with longer follow-ups are necessary to evaluate the overall oncologic outcomes of this procedure.

Objective To compare surgical outcomes and cost of robotic single-site hysterectomy (RSSH) versus robotic multiport hysterectomy (RMPH) in early stage endometrial cancer. Methods This is a retrospective case-control study, comparing perioperative outcomes and costs of RSSH and RMPH in early stage endometrial cancer patients. RSSH were matched 1:2 according to age, body mass index, comorbidity, the International Federation of Gynecology and Obstetric (FIGO) stage, type of radical surgery, histologic type, and grading. Mean hospital cost per discharge was calculated summarizing the cost of daily hospital room charges, operating room, cost of supplies and length of hospital stay. Results A total of 23 women who underwent RSSH were matched with 46 historic controls treated by RMPH in the same institute, with the same surgical team. No significant differences were found in terms of age, histologic type, stage, and grading. Operative time was similar: 102.5 minutes in RMPH and 110 in RSSH (p=0.889). Blood loss was lower in RSSH than in RMPH (respectively, 50 mL vs. 100 mL, p=0.001). Hospital stay was 3 days in RMPH and 2 days in RSSH (p=0.001). No intraoperative complications occurred in both groups. Early postoperative complications were 2.2% in RMPH and 4.3% in RSSH. Overall cost was higher in RMPH than in RSSH (respectively, $7,772.15 vs. $5,181.06). Conclusion Our retrospective study suggests the safety and feasibility of RSSH for staging early endometrial cancer without major differences from the RMPH in terms of surgical outcomes, but with lower hospital costs. Certainly, further studies are eagerly warranted to confirm our findings.

Objective To compare different techniques of minimally invasive surgery (laparoscopy and robotics) to abdominal surgery in order to identify the optimal surgical technique in the treatment of endometrial cancer. Methods and materials A single-institutional, matched, retrospective, cohort study was performed. All patients with clinical stage I or occult stage II endometrial cancer who underwent robotic hysterectomy, bilateral salpingo-oophorectomy ± lymphadenectomy from August 2010 and December 2013 were identified. Surgical and oncological outcomes were compared with patients matched by age, body mass index, tumor histology, and grade, who underwent abdominal or laparoscopic surgery between January 2001 and December 2013. Results Three groups were identified: 177 laparotomies (group A), 277 laparoscopies (group B) and 72 robotics (group C). There were no statistically significant differences between the three groups in terms of age, BMI and FIGO stage. The operative time was shortest in group B (p = 0.0001). Blood loss and transfusions were equivalent in group B and C, while they were greater in group A (p = 0.0001). The intra-operative, early and late postoperative complications, rate of conversion, the re-intervention and median hospital stay were lower in group C. The rate of recurrence and death from disease was similar in all three groups. Conclusions Minimally invasive surgery was superior to abdominal surgery in terms of surgical outcomes. Robotic surgery was superior to laparoscopy in terms of intra- and post-operative complications, conversion rates, length of hospital stay and re-interventions. In terms of oncological outcomes the three groups were equivalent.

Objective The aim of this study was to verify possible differences in terms of perioperative outcomes and complications between mini-laparoscopic radical hysterectomy with lymphadenectomy (mLRH) and robotic radical hysterectomy with lymphadenectomy (RRH) in patients with early cervical cancer (ECC). Material and methods In this retrospective study, thirty women with early stage cervical cancer who underwent mini-laparoscopic radical hysterectomy plus lymphadenectomy (mLRH) were compared with a cohort of thirty women who underwent robotic multiport radical hysterectomy (RRH). The study involved patients, between August 2010 and December 2012, from three Italian institutions: National Cancer Institute of Rome, University of Insubria, Varese, and the Catholic University of the Sacred Heart of Rome. Results No significant differences between groups were observed in terms of age, BMI, previous abdominal surgery or FIGO stage. Operative time, blood loss, need of blood transfusion, risk of intra- and post-operative complications, and lymph nodes yield were similar between mLRH and RRH in patients with ECC. The median length of hospital stay was 2 days in the mLRH group and 3 days in the RRH group (p Conclusions The few differences we registered do not seem clinically relevant, thus making the two procedures comparable. The decision on how to gain best access for radical hysterectomy considers the surgeon's skill and experience with the different possible approaches. Further randomized trials are needed to determine whether mini-laparoscopic techniques truly offer any advantages.

Objective To compare the surgical outcome of robotic radical hysterectomy (RRH) versus laparoscopic radical hysterectomy (LRH) for the treatment of locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). Materials and methods From August 1st 2010 to July 1st 2012 a prospective data collection of women undergoing RRH for cervical cancer stage FIGO IB2 to IIB, after neoadjuvant chemotherapy, was conducted at National Cancer Institute “Regina Elena” of Rome. All patients deemed operable underwent class C1 RRH with pelvic lymphadenectomy within 4 weeks from the last chemotherapy cycle. Results A total of 25 RRH were analyzed, and compared with 25 historic LRH cases. The groups did not differ significantly in body mass index, stage, histology, number of pelvic lymph nodes removed. The median operative time was the same in the two groups with 190 min respectively. The median estimated blood loss (EBL) was statistically significant in favor of RRH group. Median length of stay was shorter, for the RRH group (4 versus 6 days, P = 0.28). There was no significant difference in terms of intraoperative and postoperative complications between groups but in the RRH group we observed a greater number of total complications compared to the control group. Conclusion This study shows that RRH is safe and feasible in LACC after NACT compare to LRH. However, a comparison of oncologic outcomes and cost–benefit analysis is still needed and it has to be carefully evaluated in the future.