Molecular biology as a driver in therapeutic choices for ovarian cancer.

The majority of patients with ovarian cancer relapse within 3 years of first line chemotherapy. Therefore, choosing the most appropriate treatment in the recurrence setting has a fundamental role in defining a patient's prognosis. Treatment options include systemic and intra-peritoneal chemotherapy, secondary cytoreductive surgery, and stereotactic body radiotherapy. The best therapeutic choice depends on multiple factors and not only on treatment-free interval. For systemic therapy, prior lines therapy, residual toxicities, comorbidities, performance status, and patient preferences should be taken into account. Secondary cytoreductive surgery can be proposed in patients in which complete tumor resectability can be predicted and in those with oligometastatic disease. Stereotactic body radiotherapy represents a valid alternative to surgery for oligometastatic disease with high local control and minimal toxicity. Current evidence has demonstrated an emerging role of BRCA mutational status and molecular profiling in the impacting response to systemic and local treatments. Therefore, these could provide guidance in the treatment decision process and help identify patients who respond better to poly(ADP-ribose) polymerase (PARP)-inhibitors or immunotherapy or to a combined approach with surgery rather than to platinum-based chemotherapy. Current knowledge in this field could help widen therapeutic options, especially for platinum-resistant patients. In this review, we offer an overview of the state of the art regarding the role of chemotherapy, radiotherapy, and surgery in this setting and their implications in clinical practice and in the treatment decision process, so as to provide the best tailored therapy in patients with recurrent ovarian cancer.

Predictive factors for adnexal involvement in endometrial cancer FIGO stage IIIA.

OBJECTIVE: Understanding ovarian involvement incidence and risk factors in women with endometrial cancer may inform the decision of ovary preservation. METHODS: Our retrospective study included all consecutive fully surgically staged patients with endometrial cancer who underwent primary surgery between January 2005 and November 2021, assessing the incidence of ovarian metastasis, its role as a prognostic factor for recurrence and death, and evaluated predictors of adnexal involvement. RESULTS: Women with International Federation of Gynecology and Obstetrics (FIGO) 2009 IIIA endometrial cancer comprised 2.3% of the population (36 of 1535 included patients), 23 (63.9%) with endometrioid histology, and a median age of 57.0 years (range 47.7-66.7). A higher body mass index, post-menopausal status, endometrioid histotype, and ß-catenin expression were associated with a lower risk of adnexal involvement. Conversely, dMMR phenotype, p53 expression, myometrial infiltration >50%, lymphovascular space invasion, and cervical stromal invasion were independent predictors of an increased risk of adnexal involvement. A total of 145 (9.5%) patients had adnexal involvement, with an incidence rate of 0.27/100 person-days. Overall survival for FIGO (2009) stage IIIA was 88.9%. CONCLUSIONS: Our study showed that ovarian preservation may be considered for younger patients with low-risk endometrial cancer (G1 and G2 tumors, absence of lymphovascular space invasion, no cervical involvement, and myometrial invasion <50%), adding a favorable predictive role to higher body mass index and high ß-catenin expression.

Assessment of sentinel Lymph node mapping with different volumes of Indocyanine green in early-stage ENdometrial cancer: the ALIEN study.

OBJECTIVE: To evaluate the impact of different volumes of indocyanine green (ICG) on the detection rate and bilateral mapping of sentinel lymph nodes in patients with apparent uterine-confined endometrial cancer. METHODS: All patients who underwent surgical staging with sentinel node mapping in six reference centers were included. Two different protocols of ICG intracervical injection were used: (1) 2 mL group: total volume of 2 mL injected superficially; (2) 4 mL group: total volume of 4 mL, 2 mL deeply and 2 mL superficially. Logistic regression was used to analyze factors that could influence dye migration and detection rates. A sensitivity analysis was carried out to determine how independent variables could affect the sentinel node detection rate. RESULTS: Of 442 eligible patients, 352 were analyzed (172 in the 2 mL group and 180 in the 4 mL group). The bilateral detection rates of the 2 mL and 4 mL groups were 84.9% and 86.1%, respectively (p=0.76). The overall detection rate was higher with a volume of 4 mL than with 2 mL (97.8% vs 92.4%, respectively; p=0.024). In the univariate analysis the rate of bilateral mapping fell from 87.5% to 73.5% when the International Federation of Gynecology and Obstetrics (FIGO) 2009 tumor stage was >IB (p=0.018). In the multivariate analysis, for both overall and bilateral detection rates a statistically significant difference emerged for the volume of ICG injected and FIGO 2009 stage >IB. Increasing body mass index was associated with worse overall detection rates on univariate analysis (p=0.0006), and significantly decreased from 97% to 91% when the body mass index exceeded 30 kg/m2 (p=0.05). CONCLUSIONS: In patients with early-stage endometrial cancer, a volume of 2 mL ICG does not seem to compromise the bilateral detection of sentinel lymph nodes. In women with obesity and FIGO 2009 stage >IB, a 4 mL injection should be preferred.

Molecular classification of endometrial carcinoma on endometrial biopsy: an early prognostic value to guide personalized treatment.

OBJECTIVE: Molecular features are essential for estimating the risk of recurrence and impacting overall survival in patients with endometrial cancer. Additionally, the surgical procedure itself could be personalized based on the molecular characteristics of the tumor. This study aims to assess the feasibility of obtaining reliable molecular classification status from biopsy specimens collected during hysteroscopy to better modulate the appropriate surgical treatment. METHODS: This monocentric, retrospective, observational study was conducted on 106 patients who underwent a biopsy procedure followed by radical surgery for endometrial cancer, with concurrent molecular investigation. The molecular classification was determined through immunohistochemical staining for p53 and mismatch repair proteins, along with gene sequencing for POLE. RESULTS: Overall, 106 patients underwent molecular investigation, which was finally achieved on 99 patients (93.4%). Among these, the molecular analysis was conducted in 71 patients (67%) on the pre-operative endometrial biopsy and on the final uterine specimen in 28 patients (26.4%). Most of the endometrial biopsies were performed using Bettocchi hysteroscopy (66%). Molecular analysis was not possible in seven patients (6.6%), with six cases due to sample inadequacy and one case attributed to intra-mucosal carcinoma. The molecular results showed that the copy number low sub-group was the most common, and five cases of 'multiple classifiers' were observed in the low-risk category. CONCLUSION: Our experience in obtaining molecular information from biopsy samples underscores the feasibility and efficacy of this technique, even in small tissue samples. This capability helps define the prognostic group of patients, facilitates timely decision-making, and develops a personalized strategy for each patient.

Lidocaine spray vs mepivacaine local infiltration for suturing 1st/2nd grade perineal lacerations: a randomised controlled non-inferiority trial.

BACKGROUND: Perineal lacerations are a very common complication of post-partum. Usually, the repair of 1st and 2nd-grade lacerations is performed after the administration of local anesthesia. Despite the great relevance of the problem, there are only a few studies about the best choice of local anesthetic to use during suturing. We performed a randomised controlled trial to evaluate the efficacy and safety of the use of a local anesthetic spray during the suturing of perineal lacerations in the post-partum. METHODS: We compared the spray with the standard technique, which involves the infiltration of lacerated tissues, using the NRS scale. 136 eligible women who had given birth at University Hospital of Udine were enrolled and randomly assigned to receive nebulization of Lidocaine hydrochloride 10% spray (experimental group) or subcutaneous/submucosal infiltration of mepivacaine hydrochloride (control group) during suturing of perineal laceration. RESULTS: The lacerations included 84 1st-grade perineal traumas (61.7%) and 52 2nd-grade perineal traumas (38.2%). All the procedures were successfully completed without severe complications or serious adverse reactions. There were no statistically significant differences between the two groups in terms of blood losses or total procedure time. Moreover, there were no statistically significant differences in terms of NRS to none of the intervals considered. Regarding the application of the spray in the B group, in 36 cases (52.9%) it was necessary to improve the number of puffs previously supposed to be sufficient (5 puffs). Just in 3 cases, an additional injection was necessary (4.4%). CONCLUSIONS: Our study demonstrates that lidocaine spray alone can be used as a first line of local anesthetic during the closure of I-II-grade perineal lacerations, as it has comparable efficacy to mepivacaine infiltration. TRIAL REGISTRATION: The trial was recorded on https://clinicaltrials.gov . Identification number: NCT05201313. First registration date: 21/01/2022. Unique Protocol ID: 0042698/P/GEN/ARCS.

Efficacy and safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in ovarian cancer: a systematic review of current evidence.

BACKGROUND: PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis. A systematic review was conducted to assess current evidence on the efficacy and outcomes of PIPAC in patients affected by ovarian cancer. METHODS: The study adhered to the PRISMA guidelines. PubMed, Google Scholar and ClinicalTrials.gov were searched up to December 2023. Studies reporting data on patients with OC treated with PIPAC were included in the qualitative analysis. RESULTS: Twenty-one studies and six clinical trials with 932 patients who underwent PIPAC treatment were identified. The reported first access failure was 4.9%. 89.8% of patients underwent one, 60.7% two and 40% received three or more PIPAC cycles. Pathological tumour response was objectivated in 13 studies. Intra-operative complications were reported in 11% of women and post-operative events in 11.5% with a 0.82% of procedure-related mortality. Quality of life scores have been consistently stable or improved during the treatment time. The percentage of OC patients who became amenable for cytoreductive surgery due to the good response after PIPAC treatment for palliative purposes is reported to be 2.3%. CONCLUSION: The results showed that PIPAC is safe and effective for palliative purposes, with a good pathological tumour response and quality of life. Future prospective studies would be needed to explore the role of this treatment in different stages of the disease, investigating a paradigm shift towards the use of PIPAC with curative intent for women who are not eligible for primary cytoreductive surgery.

Major determinants of survival in recurrent endometrial cancer-the role of secondary cytoreductive surgery: a multicenter study.

OBJECTIVE: The main objective of the study was to assess the influence of different clinical and therapeutic variables on the oncological outcomes of patients with endometrial cancer relapse. In particular, we evaluated the impact of cytoreductive surgery with the achievement of complete gross resection. METHODS: This is a multicenter retrospective cohort study conducted in three centers in Italy and including all patients with first relapse of endometrial cancer from January 2010 to December 2021. RESULTS: Data from 331 women with recurrent endometrial cancer were analyzed. Secondary cytoreductive surgery was performed in 56.2% of cases (186 patients). Complete gross resection was achieved in 178 patients (95.7%). Complete gross resection conferred a statistically significant survival benefit both for post-relapse survival and post-relapse free survival (3 years post-relapse survival: 75.4% vs 56.4%, p<0.001; 3 years post-relapse free survival: 32.6% vs 26.5%, p=0.027). At multivariate Cox regression analysis, age ≥75 years, Eastern Cooperative Oncology Group Performance Status ≥2, the advanced-metastatic risk group, complete gross resection, and multiple site relapses were identified as independent significant predictors for post-relapse survival; regarding post-relapse free survival, only age ≥75, the high and advanced-metastatic risk groups, and complete gross resection confirmed their statistical significance. CONCLUSIONS: Secondary cytoreductive surgery with achievement of complete gross resection was confirmed to be an independent positive predictor for survival in patients with recurrent endometrial cancer and should be considered a valid primary treatment in the therapeutic decision-making process.

Evaluation of the one-step nucleic acid amplification method for rapid detection of lymph node metastases in endometrial cancer: prospective, multicenter, comparative study.

OBJECTIVE: To evaluate the diagnostic performance of the one-step nucleic acid amplification (OSNA) method for the detection of sentinel lymph node (SLN) metastases in women with apparent early-stage endometrial cancer compared with standard ultrastaging. METHODS: Prospective, multicentric, interventional study. Patients with apparent early-stage endometrial cancer who underwent primary surgical staging with SLN mapping were included. SLNs were serially sectioned with 2 mm slices perpendicular to the longest axis of the node: the odd slices were submitted to ultrastaging, whereas the even slices were submitted to the OSNA analysis. Diagnostic performance was calculated taking ultrastaging as referral standard. RESULTS: Three-hundred and sixteen patients with 668 SLNs were included. OSNA assay detected 22 (3.3%) positive SLNs, of which 17 (2.5%) were micrometastases and 5 (0.7%) macrometastases, whereas ultrastaging detected 24 (3.6%) positive SLNs, of which 15 (2.2%) were micrometastases and 9 (1.3%) macrometastases (p=0.48). Regarding negative SLNs, OSNA detected 646 (96.7%) negative nodes, including 8 (1.2%) isolated tumor cells, while ultrastaging detected 644 (96.4%) negative nodes with 26 (3.9%) isolated tumor cells. Specificity of OSNA was 98.4% (95% CI 97.5 to 99.4), accuracy was 96.7% (95% CI 95.4 to 98.1), sensitivity was 50% (95% CI 30.0 to 70.0), while negative predictive value was 98.1% (95% CI 97.1 to 99.2). Discordant results were found in 22 SLNs (3.3%) corresponding to 20 patients (6.3%). These were 10 (1.5%) false-positive SLNs (all micrometastases): one (0.1%) of these was a benign epithelial inclusion at ultrastaging. There were 12 (1.8%) false-negative SLNs of OSNA, of which 9 (1.3%) were micrometastases and 3 (0.5%) macrometastases. Overall, 17/668 (2.5%) benign epithelial inclusions were detected at ultrastaging. CONCLUSION: The OSNA method had high specificity and high accuracy in detecting SLN metastasis in apparent early-stage endometrial cancer. The advantage of the OSNA method could be represented as the possibility to analyze the entire lymph node thus eliminating sampling bias.

Post Treatment Sexual Function and Quality of Life of Patients Affected by Cervical Cancer: A Systematic Review.

Introduction: The aim of this study is to analyze the available scientific evidence regarding the quality of life (QoL) and sexual function (SF) in patients affected by cervical cancer (CC) after surgical and adjuvant treatments. Materials and Methods: Preliminary research was conducted via electronic database (MEDLINE, PubMed and Cochrane Library) with the use of a combination of the following keywords: SF, QoL, and CC. The principal findings considered in the present review were the study design, the number of patients included in each study, the information about the malignancy (histology and stage of disease), the questionnaires administered, and the principal findings concerning SF and QoL. Results: All studies were published between 2003-2022. The studies selected consisted of one randomized control study, seven observational studies (three prospective series), and nine case control studies. The scores used were focused on SF, QOL, fatigue, and psychological aspects. All studies reported a decreased SF and QOL. The most developed questionnaires were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression scale (HADS), and the Female Sexual Distress Scale (FSDS). Discussion: All studies reported a decreased SF and QOL. In addition to the perception of body image, several factors coexist in influencing the outcomes such as the physical, hormonal, psychological. Conclusions: Sexual dysfunction after CC treatment has a multifactorial aetiology which negatively affects the quality of life. For these reasons, it is important to follow and support patients with a multidisciplinary team (doctors, nurses, psychologists, dieticians) before and after therapy. This type of tailored therapeutic approach should become a standard. Women should be informed about possible vaginal changes and menopausal symptoms after surgery and on the positive effects of psychological therapy.

Exploring Surgical Strategies for Uterine Fibroid Treatment: A Comprehensive Review of Literature on Open and Minimally Invasive Approaches.

Background and Objectives: Uterine myomas represent one of the most prevalent pathologies affecting the female population. These benign neoplasms originate from the smooth muscular cells of the uterus, and they can be either single or multiple. Often associated with debilitating symptoms such as pelvic heaviness, pain, constipation, and urinary dysfunctions, the surgical management of myomectomy exhibits considerable variability. This diversity in approaches is influenced by factors such as the number and size of myomas, the patient's age, and overall clinical conditions. This study aims to elucidate and compare the advantages and disadvantages of different surgical approaches, specifically endoscopic procedures versus open surgery, providing valuable insights for clinical decision making. Materials and Methods: A comprehensive bibliographic search spanning from 2013 to 2023 was systematically conducted across databases including Medline, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. The search utilized keywords such as "myomectomy laparoscopic and open", "myomectomy open and minimally invasive", "myomectomy open and laparoscopic", and "myomectomy open vs. laparoscopic." The research methodology, along with predetermined inclusion and exclusion criteria, was established prior to the search, ensuring a systematic and rigorous approach. Subsequently, data analysis was carried out. Results: Following the study selection process, 25 articles met the eligibility criteria for inclusion in this analysis. The average numbers of myomas were 3.7 (ranging from 1 to 13.7) and 5.4 (ranging from 1 to 13.5) for the minimally invasive surgery and open surgery groups, respectively. In terms of myoma size, the total averages across studies were 7 cm (ranging from 4.8 to 14) for the minimally invasive group and 8 cm (ranging from 3.9 to 11.2) for the open surgery group. The average pregnancy and delivery rates were 29.7% (ranging from 1.8 to 100) for the minimally invasive group and 28.5% (ranging from 1.8 to 100) for the open surgery group. Regarding complications, the average rate was 14.2% (ranging from 0 to 50) for the endoscopic group and 22.3% (ranging from 0 to 60.3) for the laparotomic group. Conclusions: In conclusion, a critical factor influencing the choice of surgical approach is primarily the size and quantity of fibroids. The mini-laparotomic approach emerges as a viable alternative to endoscopy, demonstrating favorable surgical outcomes and aesthetic results. Interestingly, the type of surgical procedure appears to have no significant impact on the pregnancy rate.

Predictive Score of Nodal Involvement in Endometrial Cancer Patients: A Large Multicentre Series.

BACKGROUND: Sentinel lymph node (SLN) biopsy is considered the standard of care in early-stage endometrial cancer (EC). For SLN failure, a side-specific lymphadenectomy is recommended. Nevertheless, most hemipelvises show no nodal involvement. The authors previously published a predictive score of lymphovascular involvement in EC. In case of a negative score (value 3-4), the risk of nodal metastases was extremely low. This multicenter study aimed to analyze a predictive score of nodal involvement in EC patients. METHODS: The study enrolled patients with EC who had received comprehensive surgical staging with nodal assessment. A preoperative predictive score of nodal involvement was calculated for all the patients before surgery. The score included myometrial infiltration, tumor grading (G), tumor diameter, and Ca125 assessment. The STARD (standards for Reporting Diagnostic accuracy studies) guidelines were followed for score accuracy. RESULTS: The study analyzed 1038 patients and detected 155 (14.9%) nodal metastases. The score was negative (3 or 4) for 475 patients and positive (5-7) for 563 of these patients. The score had a sensitivity of 83.2%, a specificity of 50.8%, a negative predictive value of 94.5%, and a diagnostic value of 55.7%. The area under the curve was 0.75. The logistic regression showed a significant correlation between a negative score and absence of nodal metastasis (odds ration [OR], 5.133, 95% confidence interval [CI], 3.30-7.98; p < 0.001). CONCLUSION: The proposed predictive score is a useful test to identify patients at low risk of nodal involvement. In case of SLN failure, the application of the current score in the SLN algorithm could allow avoidance of unnecessary lymphadenectomies.

The impact of hysterectomy on oncological outcomes in patients with borderline ovarian tumors: A systematic review and meta-analysis.

BACKGROUND: Surgical management of Borderline ovarian tumors (BOT) can range from unilateral cystectomy to a more extensive surgical staging. However, the role of hysterectomy within the surgical staging is still debated. AIM: To assess the impact of hysterectomy on survival outcomes in BOT patients. MATERIALS AND METHODS: 5 electronic databases were searched from their inception to April 2021 for all peer-reviewed, retrospective or prospective studies, which compared treatment including hysterectomy versus treatment not including hysterectomy for BOT, in terms of recurrence and/or death. Pooled odds ratios (OR) with 95% confidence interval for recurrence, death due to BOT and death of any cause were calculated comparing hysterectomy group versus no hysterectomy group. Subgroup analyses for recurrence were based on BOT histotype (mucinous and serous) and FIGO stage (I and II-III). RESULTS: Twelve studies assessing 2223 patients were included. Compared to no hysterectomy group, hysterectomy group showed an OR of 0.23 (p = 0.00001) for recurrence, 1.26 (p = 0.77) for death due to BOT and 4.23 (p = 0.11) for death of any cause. At subgroup analyses, compared to no hysterectomy group, hysterectomy group showed an OR for recurrence of 0.21 (p = 0.003) in serous subgroup, of 0.46 (p = 0.18) in mucinous subgroup, of 0.23 (p = 0.0006) in FIGO stage I subgroup, and of 0.29 (p = 0.04) in FIGO stage II-III subgroup. CONCLUSIONS: Uterine-sparing surgery might be recommended in all BOT patients since it seems to increase the risk of recurrence, but not those of death due to disease or death of any cause.

Anatomical distribution of sentinel lymph nodes in patients with endometrial cancer: a multicenter study.

OBJECTIVE: Sentinel lymph node (SLN) mapping represents the standard approach in uterine confined endometrial cancer patients. The aim of this study was to evaluate the anatomical distribution of SLNs and the most frequent locations of nodal metastasis. METHODS: This was an observational retrospective multicenter study involving eight high volume gynecologic cancer centers in Italy. We reviewed 1576 patients with a histologically confirmed diagnosis of endometrial cancer from September 2015 to June 2020. All patients underwent total hysterectomy with salpingo-ophorectomy and SLN mapping. RESULTS: A total of 3105 SLNs were mapped and removed, 2809 (90.5%) of these were bilateral and 296 (9.5%) unilateral. The overall detection rate was 93.4% (77.9% bilateral and 15.5% unilateral). The majority of SLNs (80%) and positive SLNs (77.8%) were found at the external iliac and obturator level in both endometrioid and non-endometrioid endometrial cancer. Negative SLNs were more frequent in patients with endometrioid compared with non-endometrioid cancer (91.9% vs 86.1%, p<0.0001). Older patients, a higher body mass index, and non-endometrioid histology were more likely to have 'no mapping' (p<0.0001). Univariate and multivariate analysis showed that higher body mass index and age at surgery were independent predictive factors of empty node packet and fat tissue (p=0.029 and p<0.01, respectively). CONCLUSION: The most frequent sites of SLNs and metastases were located in the pelvic area below the iliac vessel bifurcation. Our findings showed that older age, a higher body mass index, and non-endometrioid histology had a negative impact on mapping.

Surgical Treatment Following Failed Medical Treatment of an Interstitial Pregnancy.

Interstitial pregnancy (IP) is a type of ectopic pregnancy in which the embryo implants in the interstitial part of the Fallopian tube. It accounts for 2% of all ectopic pregnancies. Signs and symptoms appear later than the other forms of ectopic pregnancies because of its peculiar location. The gold standard for its diagnosis is transvaginal ultrasound. The treatment can be medical or surgical. Medical treatment is based on the systemic or local injection of methotrexate (MTX); a dose of mifepristone can be added with a reported 85-90% success rate. The surgical option is laparoscopic unilateral cornuostomy or unilateral salpingectomy. The therapeutic choice is based on symptoms, serum ß-human chorionic gonadotropin (ß-hCG) values, and sonographic features. Furthermore, the patient's fertility perspectives should be considered. We report a case of IP in a Caucasian woman of 29 years old, with a previous salpingectomy for ectopic pregnancy medically treated by a double dose of intramuscular MTX 50 mg/m2 combined with a single dose of leucovorin 15 mg and a single dose of mifepristone 600 mg orally. Medical therapy failed as suggested by the sudden onset of intense pelvic pain after 10 days. Because of the clinical symptoms and the sonographic suspicious of pregnancy rupture due to the modest amount of fluid in the pouch of Douglas, clinicians decided on an urgent unilateral laparoscopic salpingectomy. The hemoperitoneum was drained. The patient was discharged two days later and ß-hCG serum levels became negative after 45 days. The advantages of fertility sparing should be weighted according to the patient's reproductive perspectives. Appropriate counseling is therefore key in managing the treatment of interstitial pregnancy.

Scar-Free Laparoscopy in BRCA-Mutated Women.

Background and Objectives: BRCA 1 and 2 mutations have a cumulative risk of developing ovarian cancer at 70 years of 41% and 15%, respectively, while a cumulative risk of breast cancer by 80 years of age was 72% for BRCA1 mutation carriers and 69% for BRCA2 mutation carriers. The NCCN recommends risk-reducing salpingo-oophorectomy (RRSO), typically between 35 and 40 years, and upon completion of childbearing in BRCA1 mutation, while it is reasonable to delay RRSO for management of ovarian cancer risk until age 40-45 years in patients with BRCA2. In recent years there have been two main lines of evolution in laparoscopy. The former concerning the development of a single-site laparoscopic and the latter concerning the miniaturisation of laparoscopic instruments (mini/micro-laparoscopy). Materials and Methods: In this case report, we show our experience in prophylactic adnexectomy, on a mutated-BRCA patient, using the MiniLap® percutaneous surgical system. Results: This type of technique is safe and effective and does not require a particular learning curve compared to single-port laparoscopy. Conclusions: The considerable aesthetic advantage of the scars, we believe, albeit to a lesser extent, is useful to find in these patients burdened by an important stress load.

The role of semiquantitative evaluation of lympho-vascular space invasion in early stage cervical cancer patients.

OBJECTIVE: Lymph vascular space involvement (LVSI) is one of the most important prognostic factors in early stage cervical cancer. Its qualitative evaluation represents a milestone for patient risk stratification and treatment choice, but a semi-quantitative analysis of LVSI may offer a more truthful risk model, as already demonstrated for endometrial cancer. The present study aims to investigate the performances of a semi-quantitative evaluation of LVSI in terms of patient risk assessment. METHODS: In this retrospective study were enrolled patients underwent surgical treatment for early cervical cancer from January 2009 to October 2018. A semi-quantitative evaluation such as the "three-tiered approach" was used to classify the LVSI pathway: negative vs. focal vs. diffuse. RESULTS: Diffuse LVSI was found to be a risk factor for lymph node metastasis (OR: 9.844, p < 0.001), and parametrial involvement (OR: 5.566, p < 0.001). Lymph nodal recurrences were more frequent in diffuse LVSI group (LVSI negative vs. focal LVSI p = 0.369; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.214); and so distant recurrences (LVSI negative vs. focal LVSI p = 0.623; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.026). Patients with diffuse LVSI showed a worse disease-free survival (DFS) than patients with focal or absent involvement (DFS LVSI negative vs. focal LVSI p = 0.938; LVSI negative vs. diffuse LVSI p < 0.001; focal LVSI vs. diffuse LVSI p = 0.036). CONCLUSION: Semi-quantitative evaluation of LVSI may be useful to identify risk patients for shorter disease-free survival and lymphatic and distant recurrences in patients with early stage.

Laparoscopic sentinel node mapping with intracervical indocyanine green injection for endometrial cancer: the SENTIFAIL study - a multicentric analysis of predictors of failed mapping.

OBJECTIVES: Laparoscopy is commonly used for endometrial cancer treatment, and sentinel lymph node (SLN) mapping has become the standard procedure for nodal assessment. Despite the standardization of the technique, there is no definitive data regarding its failure rate. The objective of this study is to identify factors associated with unsuccessful SLN mapping in endometrial cancer patients undergoing laparoscopic SLN mapping after intracervical indocyanine green (ICG) injection. METHODS: We retrospectively evaluated a consecutive series of endometrial cancer patients who underwent laparoscopic SLN mapping with intracervical ICG injection, in four oncological referral centers from January 2016 to July 2019. Inclusion criteria were biopsy-proven endometrial cancer, total laparoscopic approach, and intracervical ICG injection. Exclusion criteria were evidence of lymph node involvement or extrauterine disease at pre-operative imaging, synchronous invasive cancer, the use of tracers different from ICG, and the use of neoadjuvant treatment. Bilateral and failed bilateral SLN mapping groups were compared for clinical and pathological features. In patients with an unsuccessful procedure, side-specific lymphadenectomy was performed. Logistic regression was used to identify predictors of failure. RESULTS: A total of 376 patients were included in the study. The overall bilateral and unilateral SLN detection rates were 96.3%, 76.3%, and 20.0% respectively. The failed bilateral mapping detection rate was 23.7%. The median number of sentinel nodes removed was 2.2 (range, 0-5). After multivariate analysis, lymph vascular space involvement [OR 2.4 (1.04-1.12), P=0.003], non-endometrioid histology [OR 3.0 (1.43-6.29), P=0.004], and intraoperative finding of enlarged lymph node [OR 2.3 (1.01-5.31), P=0.045] were identified as independent predictors of failure of SLN mapping. CONCLUSION: Lymph vascular space involvement, non-endometrioid histology, and intra-operative finding of enlarged lymph nodes were identified as independent risk factors for unsuccessful mapping in patients undergoing laparoscopic SLN mapping.

Clinical outcome of recurrent endometrial cancer: analysis of post-relapse survival by pattern of recurrence and secondary treatment.

INTRODUCTION: Recurrence of endometrial cancer is an important clinical challenge, with median survival rarely exceeding 12 months. The aim of this study was to analyze patterns of endometrial cancer recurrence and associations of these patterns with clinical outcome. METHODS: The study included patients with endometrial cancer who underwent primary surgical treatment with or without adjuvant treatment between July 2004 and June 2017 at the Gynaecologic Oncology Unit of one of three tertiary hospitals of the Catholic University Network in Italy with complete follow-up data available. Information on the date and pattern of recurrence was retrieved for each relapse. Post-relapse survival was recorded as the time from the date of recurrence to the date of death or last follow-up. Survival probabilities were compared using log rank tests, and associations of clinico-pathological characteristics with post-relapse survival were tested using Cox's regression models. RESULTS: A total of 1503 patients were included in the analysis. We identified 210 recurrences (14.0%) and 105 deaths (7.0%) at a median follow-up of 34 months (range 1-162). One hundred and fifty-eight recurrences (78.1%) occurred during the first two years of follow-up. Most recurrences were multifocal (n=121, 57.6%) and involved extrapelvic sites (n=38, 65.7%). Parameters associated with post-relapse survival in the univariate analysis included histotype, grade, time to recurrence, pattern of recurrence, number of relapsing lesions, and secondary radical surgery. Only the pattern of recurrence and secondary radical surgery were independent predictors of post-relapse survival in the multivariate analysis (p=0.025 and p=0.0001, respectively). CONCLUSION: Lymph node recurrence and the feasibility of secondary radical surgery were independent predictors of post-relapse survival in patients with recurrent endometrial cancer.

Standard ultra-staging compared to one-step nucleic acid amplification for the detection of sentinel lymph node metastasis in endometrial cancer patients: a retrospective cohort comparison.

INTRODUCTION: The objective of this study was to compared standard ultra-staging (SU) with one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis in women with apparent uterine-confined endometrial cancer. METHODS: All women underwent SLN identification with complete surgical staging. All SLNs were cut perpendicular to the long axis and two adjacent 5 µm sections were cut at each of two levels 50 µm apart. At each level, one slide was stained with hematoxylin and eosin and the other with immunohistochemistry using the AE1/AE3 anti-cytokeratin antibody, as well as one negative control slide for a total of five slides per block. For OSNA analysis, the 2 mm sections of the lymph nodes were homogenized to form a lysate. The lysate was then centrifuged and inserted into the RD 100i instrument where the isothermal amplification of CK19 mRNA was executed. RESULTS: Of the 396 patients included in the retrospective analysis, 214 were in the SU group, and 182 in the OSNA group. Overall 869 SLNs were identified (490 SU, 379 OSNA). Sixty patients exhibited SLN metastasis (34 SU, 26 OSNA). Macrometastasis, micrometastases, and isolated tumor cells (ITC) were 5.1%, 4.1%, and 0.2%, respectively, in the US group, and 2.4%, 6.3%, and 0.1%, respectively, in the OSNA group (p=0.022). CONCLUSIONS: The OSNA assay detected a higher rate of micrometastasis and a lower rate of macrometastasis and ITC when compared with SU. The clinical and prognostic impact of ITC is debatable and controversial. Further studies are needed to clarify the respective roles of the OSNA and SU methods, and the possible role of ITC in the prognosis of patients with apparent early-stage endometrial cancer.

Step by Step Total Laparoscopic Hysterectomy with Uterine Arteries Ligation at the Origin.

STUDY OBJECTIVE: To reveal principles and the feasibility of a total laparoscopic hysterectomy (TLH) with uterine artery ligation at the origin. DESIGN: Step-by-step demonstration and explanation of technique using videos from patients. SETTING: Gynecologic oncology unit at a university hospital. PATIENT: A 54-year-old woman with uterine fibromatosis and metrorrhagia. INTERVENTION: TLH has 7 common components. First, round ligaments are coagulated and cut to enter the retroperitoneum. The ureter is identified. Second, pararectal spaces are entered between the ureter and the internal iliac artery. This maneuver allows the identification of the uterine artery as it leaves its origin from the internal iliac artery. The uterine vessels are stapled with a vascular endoscopic stapler at their origin from the hypogastric vessels or sealed with a bipolar device. Third, adnexal structures are separated from the uterine corpus for subsequent preservation or removal. Fourth, the blood supply is dissected, occluded, and divided before extirpation of the uterine corpus. Fifth, the cardinal ligament complex is transected with colpotomy, and the cervix is amputated from the vaginal apex. Sixth, the specimen is removed. Finally, the vaginal cuff is closed [1]. MEASUREMENTS AND MAIN RESULTS: Laparoscopic hysterectomy was first described by Reich et al. [2] in 1989 and has slowly gained popularity. Today, hysterectomy is the most common gynecologic procedure performed. TLH is where the entire operation (including suturing of the vaginal vault) is performed laparoscopically and there is no vaginal component except for the removal of the uterus. Currently, hysterectomies are performed by different approaches, and individual surgeons have different indications for the approach to hysterectomy based largely on their own array and patient characteristics. TLH requires the highest degree of laparoscopic surgical skills [3], and knowledge of pelvic anatomy defines a safe space for sharp entry into the retroperitoneum and safe identification of pelvic vasculature. CONCLUSION: We present an educational video with step-by-step explanation of the technique to highlight the anatomic landmarks that guides the procedure.