Endometriosis-associated ovarian cancer: a different clinical entity.

OBJECTIVE: To compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients. METHODS: This retrospective study included data of consecutive patients with endometrioid or clear cell ovarian cancer treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between January 2010 and June 2021. Patients were assigned to one of two groups according to the absence or presence of endometriosis together with ovarian cancer at final histological examination. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Proportions in recurrence rate and pattern of recurrence were evaluated using the Fisher exact test. RESULTS: Overall, 83 women were included in the endometriosis-associated ovarian cancer group and 144 in the non-endometriosis-associated ovarian cancer group, respectively. Patients included in the non- endometriosis-associated ovarian cancer group had a shorter disease-free survival than those in the endometriosis-associated ovarian cancer group (23.4 (range 2.0-168.9) vs 60.9 (range 4.0-287.8) months; p<0.001). Univariable and multivariable analyses showed that the association with endometriosis, previous hormonal treatment, early stage at presentation, and endometrioid histology were related to better disease-free survival in the entire study population. Similarly, patients in the non-endometriosis-associated ovarian cancer group had a shorter median (range) overall survival than those in the endometriosis-associated ovarian cancer group (54.4 (range 0.7-190.6) vs 77.6 (range 4.5-317.8) months; p<0.001). Univariable and multivariable analyses showed that younger age at diagnosis, association with endometriosis, and early stage at presentation were related to better overall survival. The recurrence rate was higher in the non-endometriosis-associated ovarian cancer group (63/144 women, 43.8%) than in the endometriosis-associated ovarian cancer group (17/83 women, 20.5%; p<0.001). CONCLUSIONS: Endometriosis-associated ovarian cancer patients had significantly longer disease-free survival and overall survival than non-endometriosis-associated ovarian cancer patients, while the recurrence rate was higher in non-endometriosis-associated ovarian cancer patients.

"Pelvic Neuro-Visualization: An Anatomical Illustration of the Autonomic Pelvic Nervous Network in Gynecologic Surgery".

OBJECTIVE: During radical pelvic surgeries fibers of the autonomic pelvic nervous network can be accidentally damaged leading to significant visceral sequelae, which dramatically affect women's quality of life because of urinary, anorectal, and sexual postoperative dysfunctions.1,2 Direct visualization is one way to preserve hypogastric nerves (HNs), pelvic splanchnic nerves (PSNs), and the bladder branches from the inferior hypogastric plexus (IHP). However, the literature lacks critical photos and/or illustrations that are necessary to understand the precise anatomy needed to preserve the pelvic autonomic fibers. DESIGN: Narrated laparoscopic video footage for identifying, dissecting, and preserving the autonomic nerve bundles during pelvic surgery. SETTING: Tertiary level hospital-"IRCCS Istituto Nazionale dei Tumori", Milano, Italy. INTERVENTIONS: Visceral pelvic innervation is established by the superior hypogastric plexus(SHP) located anteriorly to the aortic bifurcation and the median sacral vessels and carries mostly sympathetic fibers. SHP divides in front of the sacrum into the right and left HN. At the level of the paracervix, the HNs join the parasympathetic PSNs coming out from sacral root S2, S3, S4 to form the IHP.2-5 Here, we performed laparoscopic surgery, before "Laparoscopic Approach to Cervical Cancer" trial (LACC) era, identifying key anatomic landmarks useful to highlight the path of the most commonly encountered autonomic pelvic nerves in gynecologic radical surgery: during the narration we describe and illustrate the procedure to identify all autonomic pelvic nerves, the sympathetic fibers, the PSNs, and the bladder branch emerging from the IHP in order to preserve their anatomic and functional integrity. This technique is anatomically and surgically indicated for adequate removal of the parametrical issues and vagina while preserving the total pelvic nervous system. CONCLUSION: Nerve-sparing surgery reduces bowel-, bladder- and sexual- dysfunction without decreasing surgical efficacy.1,2 To accomplish safe and effective surgery, comprehension of the 3 dimensional structure of the vascular and nerve anatomy in the pelvis is essential. This video provides a great resource to educate surgeons, especially the youngest ones, about the retroperitoneal nervous networking: we identified the autonomic nerve pathway from adjacent tissues along the pathway consisting of cardinal, sacro-uterine, rectouterine/vaginal, and vesico-uterine ligaments.

Lymphatic mapping and sentinel node biopsy in vulvar melanoma: the first multicenter study and systematic review.

OBJECTIVE: This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0). METHODS: Patients who had a proven vulvar melanoma with a Breslow thickness of 1-4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients). RESULTS: A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3-19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6-38.7) and 64.3% (95% CI, 15.5-90.2), respectively. CONCLUSIONS: The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival.

Ten-year outcomes following laparoscopic and open abdominal radical hysterectomy for "low-risk" early-stage cervical cancer: A propensity-score based analysis.

OBJECTIVE: Accumulating evidence suggested the detrimental effects of adopting minimally invasive surgery in the management of early-stage cervical cancer. However, long-term evidence on the role of minimally invasive radical hysterectomy in "low-risk" patients exists. METHODS: This is multi-institutional retrospective study comparing minimally invasive and open radical hysterectomy in low-risk early-stage cervical cancer patients. A propensity-score matching algorithm (1:2) was used to allocate patients into the study groups. Kaplan-Meir model was used to estimate 10-year progression-free and overall survival. RESULTS: Charts of 224 "low-risk" patients were retrieved. Overall, 50 patients undergoing radical hysterectomy were matched with 100 patients undergoing open radical hysterectomy. Minimally invasive radical hysterectomy was associated with a longer median operative time (224 (range, 100-310) vs. 184 (range, 150-240) minutes; p < 0.001), lower estimated blood loss (10 (10-100) vs. 200 (100-1000) ml, p < 0.001), and shorter length of hospital stay (3.8 (3-6) vs. 5.1 (4-12); p < 0.001). Surgical approach did not influence the risk of having intra-operative (4% vs. 1%; p = 0.257) and 90-day severe (grade 3+) postoperative complication rates (4% vs. 8%; p = 0.497). Ten-year disease-free survival was similar between groups (94% vs. 95%; p = 0.812; HR:1.195; 95%CI:0.275, 5.18). Ten-year overall survival was similar between groups (98% vs. 96%; p = 0.995; HR:0.994; 95%CI:0.182, 5.424). CONCLUSIONS: Our study appears to support emerging evidence suggesting that, for low-risk patients, laparoscopic radical hysterectomy does not result in worse 10-year outcomes compared to the open approach. However, further research is needed and open abdominal radical hysterectomy remains the standard treatment for cervical cancer patients.

Real-time Fluorescent ICG and 99m-Tc Nanocolloid Tracer Navigation in Bilateral Sentinel Lymph Node Mapping of Vulvar Cancer.

STUDY OBJECTIVE: The effectiveness of sentinel lymph node (SLN) biopsy has been validated by 2 prospective trials, GROINS VI and GOG 173 [1,2]. According to the European Society of Gynaecological Oncology guideline in patients with unifocal tumors with a diameter of <4 cm, in the absence of suspected inguinal lymph nodes, SLN biopsy is recommended. The use of a radioactive tracer is mandatory [2]. Using indocyanine green (ICG) increases the detection of the vulvar sentinel node from 89.7% to 100% [3]. This video aimed to share our experience about the feasibility, safety, and usefulness of the surgical identification of SLN in vulvar cancer using real-time fluorescent ICG with 99m-technetium (Tc) nanocolloid. DESIGN: A stepwise demonstration of the technique with narrated video footage. SETTING: Tertiary level hospital "IRCCS Istituto Nazionale dei Tumori," Milano, Italy. INTERVENTIONS: A 50-year-old woman was diagnosed as having vulvar cancer on biopsy of 1.5 cm size vulvar lesion under the clitoris area and referred to our operative unit. F-18 fluorodeoxyglucose positron emission tomography computed tomography showed no extravulvar disease. The patient was scheduled for radical vulvectomy and bilateral inguinal SLN biopsy. (Video still 1) In this video, the surgical procedure involved double location of SLN, first with the 99m-Tc detector followed by ICG identification. We used an ICG dilution of 2.5 mg/mL in sterile water and injected 4 mL around the tumor 5 to 10 minutes before visualization. First a handheld gamma probe used to identify the location of the SLNs with 99m-Tc. The fluorescence imaging was performed by the quest imaging system (FLUOPTICS, Middenmeer, The Netherlands) that combines autofluorescence and fluorescence perfusion imaging (Video Still 2). Second, we performed the SLN biopsy using a dark mode procedure to identify the IGC tracer (Video Still 3). The fluorescence imaging enables the detection of these markers through some millimeters of tissue, and ICG has the advantage that is visible through the skin [4]. CONCLUSION: This video shows a successful combined 99m-Tc and ICG fluorescence image-guided bilateral SLN biopsy in a vulvar cancer patient using a near-infrared optical imaging system (FLUOPTICS). ICG for SLN mapping seems to be safe in women with vulvar cancer with a satisfactory detection rate. This may help in retaining surgical radicality while minimizing operative complications.

Spotlight on the role of human papillomavirus vaccines.

In high income setting, the massive implementation of screening programs has reduced the incidence of cervical cancer, dramatically. However, cervical cancer still remains a major health concern, being one of the most common cause of death for cancer among women. The adoption of primary prevention through vaccination against HPV aims to reduce the prevalence of HPV-related lesions and cervical cancer. Accumulating data highlighted the cost-effectiveness of introducing HPV vaccination for adolescent and young adults. In the present review, we critically evaluated the role of vaccination against HPV, focusing much more on the role of vaccination in specific cluster of subjects (eg, post-treatment and older adults). Additionally, we evaluated the available evidence on the role of vaccination in HIV-positive subjects and in women receiving solid organs transplantation. We observed that although vaccination might be considered effective in those cluster of subjects; further evidence is needed to assess the cost-effectiveness of vaccination in these settings.

Sentinel node mapping vs. sentinel node mapping plus back-up lymphadenectomy in high-risk endometrial cancer patients: Results from a multi-institutional study.

OBJECTIVE: Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). METHODS: This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. RESULTS: Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p = 0.416, log-rank test) and overall survival (p = 0.940, log-rank test) than patients undergoing SLN alone. CONCLUSIONS: Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed.

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

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

Conization and lymph node evaluation as a fertility-sparing treatment for early stage cervical cancer.

INTRODUCTION: To evaluate oncological and obstetrical outcomes of early stage cervical cancer patients who underwent conservative management to retain childbearing potential. METHODS: Data of women (aged <40 years) who underwent fertility sparing treatment for International Federation of Gynecology and Obstetrics (FIGO) stage IA1 with lymphovascular invasion (LVSI) and IB1 cervical cancer were prospectively collected. All patients underwent cervical conization/s and laparoscopic nodal evaluation (pelvic lymphadenectomy/sentinel node mapping). Oncological and obstetrical outcomes were assessed. RESULTS: Overall, 39 patients met inclusion criteria; 36 (92.3%) women were nulliparous. There were: 3 (7.7%) IA1-LVSI+; 11 (28.2%) IA2; and 25 (64.1%) IB1 cervical cancers, according to 2018 FIGO stage classification. Histological types were 22 (56.4%) squamous carcinoma and 17 (43.6%) adenocarcinoma. Pelvic lymphadenectomy was performed in 29 (74.4%) patients, while 10 (25.6%) patients had only sentinel node mapping. In 4 (10.3%) patients conservative treatment was discontinued due to nodal involvement and 2 (5.1%) patients requested definitive treatment (hysterectomy) after a negative lymph node evaluation. Among 33 (84.6%) patients who retained their childbearing potential, 17 (51.5%) had a second conization. 2 (6.1%) patients relapsed and underwent definitive treatment. After a median follow-up of 51 months (range 1-184) no deaths were reported. 22 (70.9%) patients attempted to conceive. There were 13 natural pregnancies among 12 (54.5%) women who got pregnant. Live birth rate was 76.9%: 9 (69.2%) term and 1 (7.7%) preterm (at 32 weeks) deliveries. 2 (15.4%) miscarriages (first and second trimester) and 1 (7.7%) termination of pregnancy for medical reasons were recorded. CONCLUSION: Conization plus laparoscopic nodal evaluation may be a safe and feasible conservative option in the setting of fertility-sparing treatment for early-stage cervical cancer patients.

Oncological outcomes of laparoscopic radical hysterectomy versus radical abdominal hysterectomy in patients with early-stage cervical cancer: a multicenter analysis.

INTRODUCTION: Recent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy. METHODS: We performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models. RESULTS: A total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8-201.2) in the laparoscopic group and 52.6 months (range, 0.4-166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09-2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05-4.37; P=0.03). CONCLUSION: In this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.

Transmission of SARS-CoV-2 in Surgical Smoke during Laparoscopy: A Prospective, Proof-of-concept Study.

STUDY OBJECTIVE: There are growing concerns regarding the potential risk of coronavirus disease transmission during surgery and in particular during minimally invasive procedures owing to the aerosolization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particles. However, no study has demonstrated this hypothesis. Here, we aimed to investigate the presence of SARS-CoV-2 in surgical smoke. DESIGN: A prospective pilot study. SETTING: A tertiary cancer center in northern Italy. PATIENTS: Overall, 17 patients underwent laparoscopic procedures for the management of suspected or documented gynecologic malignancies. The median age was 57 years (range 26-77). The surgical indications included endometrial cancer (n = 11), borderline ovarian tumor (n = 3), early-stage ovarian cancer (n = 1), stage IA cervical cancer after diagnostic conization (n = 1), and an ovarian cyst that turned out to be benign at final histologic examination (n = 1). INTERVENTIONS: We evaluated all consecutive women scheduled to have laparoscopic procedures for suspected or documented gynecologic cancers. The patients underwent planned laparoscopic surgery. At the end of the laparoscopic procedures (after extubation), we performed reverse transcription-polymerase chain reaction (RT-PCR) tests for the detection of SARS-CoV-2 from both the endotracheal tube and the filter applied on the trocar valve. MEASUREMENTS AND MAIN RESULTS: In 1 patient, both swab tests (endotracheal tube and trocar valve filter) showed amplification of the N gene on RT-PCR analysis. This case was considered to be a presumptive positive case. In another case, the RT-PCR analysis showed an amplification curve for the N gene only in the swab test performed on the filter. No ORF1ab amplification was detected. CONCLUSION: Our study suggested the proof of principle that SARS-CoV-2 might be transmitted through surgical smoke and aerosolized native fluid from the abdominal cavity.

Preoperative Conization and Risk of Recurrence in Patients Undergoing Laparoscopic Radical Hysterectomy for Early Stage Cervical Cancer: A Multicenter Study.

STUDY OBJECTIVE: To investigate the factors associated with poorer oncologic outcomes in patients undergoing laparoscopic radical hysterectomy (LRH) for early stage cervical cancer. DESIGN: Multicenter retrospective study. SETTING: Three gynecologic oncology referral centers. PATIENTS: Patients with International Federation of Gynecology and Obstetrics 2009 stage IA (positive lymphovascular space invasion)-IB1 cervical cancer between January 2006 and June 2018. INTERVENTIONS: LRH (Piver type II-III hysterectomies). Lymph-node dissection was accomplished according to the tumor characteristics. MEASUREMENTS AND MAIN RESULTS: Surgical and oncologic outcomes were analyzed. Overall, 186 patients met the inclusion criteria, 16 (8.6%) experienced a recurrence, and 9 (4.8%) died of the disease (median follow-up period 37.9 months). Surgery-related complications did not influence disease-free survival. All the recurrences (16/16; 100%) occurred in patients with stage IB1 disease (p = .02), and 15 (93.7%) in cases involving tumors ≥2 cm. No association between positive lymph node and recurrence was detected (p =.82). Patients who had a preoperative diagnosis through conization (93; 50%) had a significantly lower rate of recurrence than those who underwent cervical biopsy (93; 50%): 1/93 (1.1%) vs 15/93 (16.1%); p <.001). The subanalysis of patients with International Federation of Gynecology and Obstetrics stage IB1 cervical cancer showed that patients undergoing preoperative conization (vs cervical biopsy) were less likely to experience a recurrence (odds ratio 0.09; 95% confidence interval 0.01-0.55). CONCLUSION: We confirmed that LRH was associated with a recurrence rate similar to that reported in the Laparoscopic Approach to Cervical Cancer trial. Tumor size ≥2 cm represents the most important risk factor influencing disease-free survival. However, we found that preoperative conization plays a potentially protective role in patients with an IB1 tumor.

Cancer patients affected by COVID-19: Experience from Milan, Lombardy.

OBJECTIVE: SARS-CoV-2 pandemic is continuing to spread. There are growing concerns on the impact of COVID-19 in cancer patients. Several papers reporting recommendations and guidelines are published. But few data on cancer patients affected by COVID-19 are available. METHODS: This is a retrospective study including all consecutive patients affected by gynecological cancer who developed COVID-19. All patients were treated in an academic setting (in Milan, Lombardy, Italy) between February and March 2020. RESULTS: Overall, 355 patients had active treatment during the study period due to newly diagnosed or recurrent gynecological disease. Among those, 19 (5.3%) patients affected developed COVID-19. All patients were asymptomatic at the time of COVID-19 detection. Six patients were diagnosed before starting planned treatments; while the remaining 13 were diagnosed for COVID-19 after their started their treatments. Considering the first group of six patients, one patient died due to COVID-19 3 days after the diagnosis; while the other patients recovered from COVID-19 after a median of three weeks. The latter group of 13 patients (treatments started) included five patients who underwent surgery and eight patients who underwent chemotherapy. Focusing on five patients who were diagnosed after surgery, we observed that two patients died during postoperative course, while in other two cases prolonged hospitalization was needed. One patient had no issues. Chemotherapy was delayed for the remaining patents without sequelae. CONCLUSIONS: Our report highlights that COVID-19 impacts the quality of treatments for cancer patients. Mortality rate is high, especially after surgery. More important, patients under active treatment for cancer are at high risk of developing severe evolution of COVID-19. Prioritizing patients journey during COVID-19 is of paramount importance.

Adjuvant chemotherapy vs. observation in stage I clear cell ovarian carcinoma: A systematic review and meta-analysis.

The role of adjuvant chemotherapy in surgically staged stage I clear cell ovarian cancer (OCCC) is unclear. Here, we performed a systematic review and meta-analysis in order to evaluate the role of chemotherapy vs. observation in stage I OCCC. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; ID: #129628). A protocol was defined prior to the search include the population criteria, description of interventions, comparisons, and the outcomes of interest, according to the PRIMA guidelines. Overall, the study population included 5073 women. Stage I OCCC experienced a 5-year disease-free survival and a 5-year overall survival of 83.7% and 86.9%, respectively. Pooled data suggested that in the overall population adjuvant chemotherapy did not impact on 5-year disease free survival (test for overall effect, Z = 0.18; p = 0.86) and 5-year overall survival (test for overall effect, Z = 0.62; p = 0.53). Focusing on 2264 stage IC OCCC we observed that adjuvant correlated with an improvement in overall survival (OR: 0.70 (95%CI: 0.52 to 0.93); Z = 2.44; p = 0.01). In conclusion our study underlines that adjuvant chemotherapy could be reserved for patients with stage IC OCCC; while in stage IA and IB it could be safely omitted. Owing to the inherent biases of the studies included in the meta-analysis further prospective evidences are needed.

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

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

Management of patients with ovarian cancer in the COVID-19 era.

At the beginning of 2020, coronavirus disease 2019 (COVID-19) spreads worldwide. Patients with ovarian cancer should be considered at high-risk of developing severe morbidity related to COVID-19. Most of them are diagnosed in advanced stages of disease, and they are fragile. Here, we evaluated the major impact of COVID-19 on patients with ovarian cancer, discussing the effect of the outbreak on medical and surgical treatment.

Sentinel lymph node mapping in endometrial cancer: performance of hysteroscopic injection of tracers.

OBJECTIVE: To report on the performance of hysteroscopic injection of tracers (indocyanine green (ICG) and technetium-99m (Tc-99m)) for sentinel lymph node (SLN) mapping in endometrial cancer. METHODS: Single-center retrospective evaluation of consecutive patients who underwent SLN mapping following hysteroscopic peritumoral injection of tracer. Detection rate (overall/bilateral/aortic) diagnostic accuracy, and oncologic outcomes were evaluated. RESULTS: A total of 221 procedures met the inclusion criteria. Mean patient age was 60 (range 28-84) years and mean body mass index was 26.9 (range 15-47) kg/m2 . In 164 cases (70.9%) mapping was performed laparoscopically. The overall detection rate of the technique was 94.1% (208/221 patients). Bilateral pelvic mapping was found in 62.5% of cases with at least one SLN detected and was more frequent using ICG than with Tc-99m (73.8% vs 53.3%; p<0.001). In 47.6% of cases SLNs mapped in both pelvic and aortic nodes, and in five cases (2.4%) only in the aortic area. In eight patients (3.8%) SLNs were found in aberrant (parametrial/presacral) areas. Mean number of detected SLNs was 3.7 (range 1-8). In 51.9% of cases at least one node other than SLNs was removed. Twenty-six patients (12.5%) had nodal involvement: 12 (46.2%) macrometastases, six (23.1%) micrometastases, and eight (30.7%) isolated tumor cells. In 12 cases (46.8%) the aortic area was involved. Overall, 6/221 (2.7%) patients had isolated para-aortic nodes. Three false-negative results were found, all in the Tc-99m group. All had isolated aortic metastases. Overall sensitivity was 88.5% (95% CI 71.7 to 100.0) and overall negative predictive value was 96.5% (95% CI 86.8 to 100.0). There were 10 (4.8%) recurrences: five abdominal/distant, four vaginal, and one nodal (in the aortic area following a unilateral mapping plus side-specific pelvic lymphadenectomy). Most recurrences (9/10 cases) were patients in whom a completion lymphadenectomy was performed. No deaths were reported after a mean follow-up of 47.7 months. CONCLUSIONS: Hysteroscopic injection of tracers for SLN mapping in endometrial cancer is as accurate as cervical injection with a higher detection rate in the aortic area. ICG improves the bilateral detection rate. Adding lymphadenectomy to SLN mapping does not reduce the risk of relapse.

Patterns of recurrence after laparoscopic versus open abdominal radical hysterectomy in patients with cervical cancer: a propensity-matched analysis.

OBJECTIVE: Recent evidence has suggested that laparoscopic radical hysterectomy is associated with an increased risk of recurrence in comparison with open abdominal radical hysterectomy. The aim of our study was to identify patterns of recurrence after laparoscopic and open abdominal radical hysterectomy for cervical cancer. METHODS: This a retrospective multi-institutional study evaluating patients with recurrent cervical cancer after laparoscopic and open abdominal surgery performed between January 1990 and December 2018. Inclusion criteria were: age ≥18 years old, radical hysterectomy (type B or type C), no recurrent disease, and clinical follow-up >30 days. The primary endpoint was to evaluate patterns of first recurrence following laparoscopic and open abdominal radical hysterectomy. The secondary endpoint was to estimate the effect of the primary surgical approach (laparoscopy and open surgery) in post-recurrence survival outcomes (event-free survival and overall survival). In order to reduce possible confounding factors, we applied a propensity-matching algorithm. Survival outcomes were estimated using the Kaplan-Meier model. RESULTS: A total of 1058 patients were included in the analysis (823 underwent open abdominal radical hysterectomy and 235 patients underwent laparoscopic radical hysterectomy). The study included 117 (14.2%) and 35 (14.9%) patients who developed recurrent cervical cancer after open or laparoscopic surgery, respectively. Applying a propensity matched comparison (1:2), we reduced the population to 105 patients (35 vs 70 patients with recurrence after laparoscopic and open radical hysterectomy). Median follow-up time was 39.1 (range 4-221) months and 32.3 (range 4-124) months for patients undergoing open and laparoscopic surgery, respectively. Patients undergoing laparoscopic radical hysterectomy had shorter progression-free survival than patients undergoing open abdominal surgery (HR 1.98, 95% CI 1.32 to 2.97; p=0.005). Patients undergoing laparoscopic radical hysterectomy were more likely to develop intrapelvic recurrences (74% vs 34%; p<0.001) and peritoneal carcinomatosis (17% vs 1%; p=0.005) than patients undergoing open surgery. CONCLUSIONS: Patients undergoing laparoscopic radical hysterectomy are at higher risk of developing intrapelvic recurrences and peritoneal carcinomatosis. Further evidence is needed in order to corroborate our findings.

Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes.

OBJECTIVE: Women with Lynch syndrome have a risk up to 40-60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer. METHODS: Data from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case-control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models. RESULTS: Overall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1-295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls. CONCLUSIONS: Non-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

Sentinel node mapping vs. lymphadenectomy in endometrial cancer: A systematic review and meta-analysis.

Sentinel node mapping is increasingly being utilized for endometrial cancer staging. However, only limited evidence supporting the adoption of sentinel node mapping instead of conventional lymphadenectomy is still available. Here, we aimed to review the current evidence comparing sentinel node mapping and lymphadenectomy in endometrial cancer staging. This systematic review was registered in the International Prospective Register of Systematic Reviews. Six comparative studies were included. Overall, 3536 patients were included: 1249 (35.3%) and 2287 (64.7%), undergoing sentinel node mapping and lymphadenectomy, respectively. Pooled data suggested that positive pelvic nodes were detected in 184 out of 1249 (14.7%) patients having sentinel node mapping and 228 out of 2287 (9.9%) patients having lymphadenectomy (OR: 2.03; (95%CI: 1.30 to 3.18); p = 0.002). No difference in detection of positive nodes located in the paraaortic was observed (OR: 93 (95%CI: 0.39 to 2.18); p = 0.86). Overall recurrence rate was 4.3% and 7.3% after sentinel node mapping and lymphadenectomy, respectively (OR: 0.90 (95%CI: 0.58 to 1.38); p = 0.63). Similarly, nodal recurrences were statistically similar between groups (1.2% vs. 1.7%; OR: 1.51 (95%CI: 0.70 to 3.29); p = 0.29). In conclusion, our meta-analysis underlines that sentinel node mapping is non-inferior to standard lymphadenectomy in term of detection of paraaortic nodal involvement and recurrence rates (any site and nodal recurrence); while, focusing on the ability to detect positive pelvic nodes, sentinel node mapping could be consider superior to lymphadenectomy. Further randomized studies are needed to asses long term effectiveness of sentinel node mapping.