SUCCOR morbidity: complications in minimally invasive versus open radical hysterectomy in early cervical cancer.

OBJECTIVE: The aim of this study was to compare the incidence of intra-operative and post-operative complications in open and minimally invasive radical hysterectomy for patients with early-stage cervical cancer. METHODS: Data were collected from the SUCCOR database of 1272 patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO), 2009) who underwent radical hysterectomy in Europe between January 2013 and December 2014. We reviewed the duration of the surgeries, estimated blood loss, length of hospital stay, intra-operative and post-operative complications. The inclusion criteria were age ≥18 years and histologic type (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma). Pelvic MRI confirming a tumor diameter ≤4 cm with no parametrial invasion and a pre-operative CT scan, MRI, or positron emission tomography CT demonstrating no extra-cervical metastatic disease were mandatory. Outcomes of interest were any grade >3 adverse events, intra-operative adverse events, post-operative adverse events, length of hospital stay, length of operation, and blood loss. RESULTS: The study included 1156 patients, 633 (54%) in the open surgery group and 523 (46%) in the minimally invasive surgery group. Median age was 46 years (range 18-82), median body mass index 25 kg/m2 (range 15-68), and 1022 (88.3%) patients were considered to have an optimal performance status (ECOG Performance Status 0). The most common histologic tumor type was squamous carcinoma (n=794, 68.7%) and the most frequent FIGO staging was IB1 (n=510, 44.1%). In the minimally invasive surgery group the median duration of surgery was longer (240 vs 187 min, p<0.01), median estimated blood loss was lower (100 vs 300 mL, p<0.01), and median length of hospital stay was shorter (4 vs 7 days, p<0.01) compared with the abdominal surgery group. There was no difference in the overall incidence of intra-operative and post-operative complications between the two groups. Regarding grade I complications, the incidence of vaginal bleeding (2.9% vs 0.6%, p<0.01) and vaginal cuff dehiscence was higher in the minimally invasive surgery group than in the open group (3.3% vs 0.5%, p<0.01). Regarding grade III post-operative complications, bladder dysfunction (1.3% vs 0.2%, p=0.046) and abdominal wall infection (1.1% vs 0%, p=0.018) were more common in the open surgery group than in the minimally invasive surgery group. Ureteral fistula was more frequent in the minimally invasive group than in the open surgery group (1.7% vs 0.5%, p=0.037). CONCLUSION: Our study showed that there was no significant difference in the overall incidence of intra-operative and post-operative complications between minimally invasive radical hysterectomy and the open approach.

An international worldwide retrospective cohort observational study comparing primary cytoreductive surgery with neoadjuvant chemotherapy and interval cytoreductive surgery in patients with carcinoma of the ovary, fallopian tubes, and peritoneum (SUROVA trial).

BACKGROUND: Currently, a lively debate exists within the scientific community regarding the most suitable procedure for treating stages IIIB-IVB carcinoma of the ovary, fallopian tubes, and peritoneum. The options under most consideration are primary cytoreductive surgery or neoadjuvant chemotherapy followed by interval cytoreductive surgery. PRIMARY OBJECTIVE: To compare overall survival at 5 years in patients who underwent primary cytoreductive surgery versus neoadjuvant chemotherapy and interval cytoreductive surgery for stage IIIB-IVB ovarian cancer STUDY HYPOTHESIS: The treatment with primary cytoreductive surgery results in superior patient survival compared with neoadjuvant chemotherapy followed by interval cytoreductive surgery. TRIAL DESIGN: This is a multicenter, retrospective cohort observational study. Data will be collected from patients undergoing surgery in hospitals worldwide. Two arms will be compared: primary cytoreductive surgery and neoadjuvant chemotherapy followed by interval cytoreductive surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: Patients must have suspected or histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stages IIIB-IVB ovarian, peritoneal, or fallopian tube cancers. They must have undergone primary surgery or first course of neoadjuvant chemotherapy between January 1, 2018 and December 31, 2019. Based on all available information before the surgery (primary or interval), the patient must have been considered completely resectable. PRIMARY ENDPOINT: Overall survival at 5 years from the first treatment (chemotherapy in the case of neoadjuvant chemotherapy and cytoreduction in the case of primary cytoreductive surgery). SAMPLE SIZE: An estimated total of 5000 patients will be enrolled in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: March 2025 TRIAL REGISTRATION: NCT06223763.

SENECA study: staging endometrial cancer based on molecular classification.

OBJECTIVE: Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. METHODS: The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. RESULTS: Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). CONCLUSIONS: Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.

Ultrasound examination, MRI, or ROMA for discriminating between inconclusive adnexal masses as determined by IOTA Simple Rules: a prospective study.

OBJECTIVE: To determine the best second-step approach for discriminating benign from malignant adnexal masses classified as inconclusive by International Ovarian Tumour Analysis Simple Rules (IOTA-SR). METHODS: Single-center prospective study comprising a consecutive series of patients diagnosed as having an adnexal mass classified as inconclusive according to IOTA-SR. All women underwent Risk of Ovarian Malignancy Algorithm (ROMA) analysis, MRI interpreted by a radiologist, and ultrasound examination by a gynecological sonologist. Cases were clinically managed according to the result of the ultrasound expert examination by either serial follow-up for at least 1 year or surgery. Reference standard was histology (patient was submitted to surgery if any of the tests was suspicious) or follow-up (masses with no signs of malignancy after 12 months were considered benign). Diagnostic performance of all three approaches was calculated and compared. Direct cost analysis of the test used was also performed. RESULTS: Eighty-two adnexal masses in 80 women (median age 47.6 years, range 16 to 73 years) were included. Seventeen patients (17 masses) were managed expectantly (none had diagnosis of ovarian cancer after at least 12 months of follow-up) and 63 patients (65 masses) underwent surgery and tumor removal (40 benign and 25 malignant tumors). Sensitivity and specificity for ultrasound, MRI, and ROMA were 96% and 93%, 100% and 81%, and 24% and 93%, respectively. The specificity of ultrasound was better than that for MRI (p=0.021), and the sensitivity of ultrasound was better than that for ROMA (p<0.001), sensitivity was better for MRI than for ROMA (p<0.001) and the specificity of ROMA was better than that for MRI (p<0.001). Ultrasound evaluation was the most effective and least costly method as compared with MRI and ROMA. CONCLUSION: In this study, ultrasound examination was the best second-step approach in inconclusive adnexal masses as determined by IOTA-SR, but the findings require confirmation in multicenter prospective trials.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators.

INTRODUCTION: Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. OBJECTIVE: To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. METHODS: The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. RESULTS: The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0-84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation. CONCLUSIONS: In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.

BACKGROUND: Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. METHODS: We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. RESULTS: Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52). CONCLUSIONS: Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

Hypopressive technique versus pelvic floor muscle training for postpartum pelvic floor rehabilitation: A prospective cohort study.

AIMS: Abdominal hypopressive technique (AHT) is gaining popularity as an alternative to pelvic floor muscle training (PFMT) during postpartum. Although, there is no solid evidence for its recommendation. METHODS: We conducted a prospective observational cohort study in a university hospital with 105 primiparae who performed a two-month PFMT or AHT program. The aim was to compare the effectiveness of both treatments in terms of morphofunctional changes in 3D transperineal ultrasound, manometry, dynamometry, and differences in urinary incontinence symptoms (ICIQ-IU-SF) and satisfaction. RESULTS: The average change in levator ani muscle was 1.2 mm higher in AHT group vs PFMT (95% confidence interval [CI], -2.2 to -0.2; P = .017). No statistically significant differences were shown in maximal strength changes between groups. After AHT, basal tone change was 63.0 g/cm2 higher than PFMT (95% CI, -129 to 2.9; P = .06). A statistically significant reduction in ICIQ-IU-SF was observed after both treatments [(PFMT, -0.8 points; 95% CI, -1.4 to -0.1; P = .015), (AHT, -0.7 points; 95% CI, -1.3 to -0.1; P = .018]. AHT showed a higher median satisfaction score than PFMT (P = .004). CONCLUSIONS: This preliminary study is the first that analyses the effect of AHT vs PFMT during postpartum. The results suggest a higher improve for AHT in levator muscle thickness and satisfaction compared to PFMT. These must be considered with caution due to the limitations of the study. Further randomized clinical trials about both techniques during postpartum are required.

Pre-operative assessment of intra-abdominal disease spread in epithelial ovarian cancer: a comparative study between ultrasound and computed tomography.

OBJECTIVE: To compare the diagnostic performance of ultrasound and computed tomography (CT) for detecting pelvic and abdominal tumor spread in women with epithelial ovarian cancer. METHODS: An observational cohort study of 93 patients (mean age 57.6 years) with an ultrasound diagnosis of adnexal mass suspected of malignancy and confirmed histologically as epithelial ovarian cancer was undertaken. In all cases, transvaginal and transabdominal ultrasound as well as CT scans were performed to assess the extent of the disease within the pelvis and abdomen prior to surgery. The exploration was systematic, analyzing 12 anatomical areas. All patients underwent surgical staging and/or cytoreductive surgery with an initial laparoscopy for assessing resectability. The surgical and pathological findings were considered as the 'reference standard'. Sensitivity and specificity of ultrasound and CT scanning were calculated for the different anatomical areas and compared using the McNemar test. Agreement between ultrasound and CT staging and the surgical stage was estimated using the weighted kappa index. RESULTS: The tumorous stage was International Federation of Gynecology and Obstetrics (FIGO) stage I in 26 cases, stage II in 11 cases, stage III in 47 cases, and stage IV in nine cases. Excluding stages I and IIA cases (n=30), R0 (no macroscopic residual disease) was achieved in 36 women (62.2%), R1 (macroscopic residual disease <1 cm) was achieved in 13 women (25.0%), and R2 (macroscopic residual disease >1 cm) debulking surgery occurred in three women (5.8%). Eleven patients (11.8%) were considered not suitable for optimal debulking surgery during laparoscopic assessment. Overall sensitivity of ultrasound and CT for detecting disease was 70.3% and 60.1%, respectively, and specificity was 97.8% and 93.7%, respectively. The agreement between radiological stage and surgical stage for ultrasound (kappa index 0.69) and CT (kappa index 0.70) was good for both techniques. Overall accuracy to determine tumor stage was 71% for ultrasound and 75% for CT. CONCLUSION: Detailed ultrasound examination renders a similar diagnostic performance to CT for assessing pelvic/abdominal tumor spread in women with epithelial ovarian cancer.

Gastrointestinal Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Assessing Suspected Deep Pelvic or Abdominal Recurrence in Gynecologic Cancer: A Feasibility Study.

OBJECTIVES: To assess the feasibility of gastrointestinal endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) for histologic confirmation of cancer recurrence in women with gynecologic cancer. METHODS: This work was a retrospective cohort study comprising 46 consecutive women treated for gynecologic cancer and suspected of having a deep pelvic or abdominal recurrence on ultrasound imaging, computed tomography, positron emission tomography-computed tomography, or magnetic resonance imaging, evaluated at our institution from January 2010 to December 2017. Primary cancer was ovarian (n = 22), cervical (n = 13), endometrial (n = 4), sarcoma (n = 4), and other (n = 3). All women underwent EUS examinations for locating the lesion and guiding FNA. The results of FNA (benign/malignant) were assessed. Procedure-related complications were recorded. RESULTS: The patients' mean age was 57.8 years. A total of 66 procedures were performed. Eleven women underwent 2 procedures; 2 women underwent 3 procedures; and 1 woman underwent 6 procedures at different times during the study period. In 1 case, no lesion was detected on the EUS assessment, and in 2 cases, FNA was not successful. Most lesions were located in the retroperitoneum or involved the intestine. Fine-needle aspiration could be performed in 63 cases (94.5%). Cytologic samples were adequate in 62 of 63 (98.4%). Recurrence was confirmed in 56 cases (90.3%) and ruled out in 6 (9.7%). No patient had any complication related to the procedure. CONCLUSIONS: Endoscopic ultrasound-guided FNA is a minimally invasive, feasible, and safe technique for confirming pelvic/abdominal recurrence of gynecologic cancer.

Three-Dimensional Transvaginal Sonography and Magnetic Resonance Imaging for Local Staging of Cervical Cancer: An Agreement Study.

OBJECTIVES: To evaluate the agreement of clinical examination, 2-dimensional (2D) sonography, and 3-dimensional (3D) sonography with magnetic resonance imaging (MRI) for local staging of cervical cancer. METHODS: We conducted a prospective study including women with a diagnosis of carcinoma of the cervix. All women were staged clinically and underwent 2D and 3D transvaginal sonography and MRI before treatment for assessing tumor size and parametrial, bladder, and rectal involvement using the examiner's subjective impression. Agreement between sonography and MRI was assessed by calculating the κ index and percentage of agreement. RESULTS: Forty women were included (mean age ± SD, 46.6 ± 11.4 years). Eleven had early-stage (IA and IB1) disease, and 29 had advanced-stage (IB2-IVB) disease. A significant correlation for tumor size estimation was found between MRI and pelvic examination (r = 0.754; P < .001), MRI and 2D sonography (r = 0.649; P < .001), and MRI and 3D sonography (r = 0.657; P< .001). Agreement for parametrial infiltration between MRI and pelvic examination was fair (κ = 0.26; 95% confidence interval [CI], 0.10-0.54; 62.5% agreement), between MRI and 2D sonography was moderate (κ = 0.41; 95% CI, 0.15-0.66; 70.0% agreement), and between MRI and 3D sonography was good (κ = 0.60; 95% CI, 0.35-0.85; 80.0% agreement). Agreement for bladder involvement between MRI and pelvic examination was moderate (κ = 0.48; 95% CI, 0.10-0.99; 95.0% agreement), between MRI and 2D sonography was moderate (κ = 0.48; 95% CI, 0.10-0.99; 95.0% agreement), and between MRI and 3D sonography was very good (κ = 0.84; 95% CI, 0.55-1.0; 97.5% agreement). Agreement for rectal involvement was not calculated because of the very small number of cases. CONCLUSIONS: Three-dimensional sonography showed good agreement with MRI for assessing parametrial infiltration and bladder involvement in cervical cancer.

Prognostic value of systemic inflammation response indexes obtained from the complete blood count in patients treated for advanced ovarian carcinoma in front line.

OBJECTIVE: Various systemic inflammation response indexes (SIRI) have repeatedly been described as prognostic factors in ovarian cancer. They have not been validated in prospective trials and published results are sometimes contradictory. We aimed to explore their role in a cohort of patients diagnosed with stage III and IV ovarian cancer treated at our institution. METHODS: We retrospectively examined the prognostic influence of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), the red cell distribution width (RDW), and the mean platelet volume (MPV). RESULTS: A total of 77 patients were analyzed. NLR > 2.243 at diagnosis, NLR before primary surgery, MLR at diagnosis, PLR > 289.1 at diagnosis, and PLR at diagnosis were significant in univariate Cox regression for progression-free survival, but none of them retained their significance in the multivariate Cox regression analysis. For overall survival, NLR > = 2.53 at diagnosis, MLR > = 0.245 at diagnosis, and PLR > = 198.3 at diagnosis resulted significant in univariate COX regression; only PLR > = 198.3 at diagnosis retained its significance in the multivariate analysis. CONCLUSION: In our cohort, PLR > = 198.3 was an independent prognostic factor for worse OS. The definitive role of SIRI in ovarian cancer has not yet been established. If their value as prognostic factors could finally be established, they would become a simple and economical method to predict prognosis in patients with advanced ovarian cancer. Therefore, it is time to conduct prospective, multicenter studies with larger samples to definitively establish its role in ovarian cancer, if any.

Short-term cultured tumor fragments to study immunotherapy combinations based on CD137 (4-1BB) agonism.

Biomarkers for cancer immunotherapy are an unmet medical need. The group of Daniela Thommen at the NKI recently reported on novel methodologies based on short-term cultures of patient-derived tumor fragments whose cytokine concentrations in the supernatants and activation markers on infiltrating T cells were associated with clinical response to PD-1 blockade. We set up a similar culture technology with tumor-derived fragments using mouse tumors transplanted into syngeneic immunocompetent mice to test an agonist anti-CD137 mAb and its combinations with anti-PD-1 and/or anti-TGF-ß. Increases in IFNγ concentrations in the tissue culture supernatants were detected upon in-culture activation with the anti-CD137 and anti-PD-1 mAb combinations or concanavalin A as a positive control. No other cytokine from a wide array was informative of stimulation with these mAbs. Interestingly, increases in Ki67 and other activation markers were substantiated in lymphocytes from cell suspensions gathered at the end of 72 h cultures. In mice bearing bilateral tumors in which one was excised prior to in vivo anti-CD137 + anti-PD-1 treatment to perform the fragment culture evaluation, no association was found between IFNγ production from the fragments and the in vivo therapeutic outcome in the non-resected contralateral tumors. The experimental system permitted freezing and thawing of the fragments with similar functional outcomes. Using a series of patient-derived tumor fragments from excised solid malignancies, we showed IFNγ production in a fraction of the studied cases, that was conserved in frozen/thawed fragments. The small tumor fragment culture technique seems suitable to preclinically explore immunotherapy combinations.

Clinical and ultrasound features of type I and type II epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to assess whether there are differences on ultrasound features between epithelial ovarian cancer (EOC) type I and type II. METHODS: This was a retrospective study comprising 244 women (mean age, 55.2 years old) with histologically proven EOC treated at our institution over a 12-year period. Clinical (patient age and symptoms and tumor stage), ultrasound (tumor volume, tumor appearance on gray-scale ultrasound, and color score), and histopathologic records were reviewed. Tumors were classified as EOC type I or type II. Type I tumors comprise low-grade serous, low-grade endometrioid, clear cell, mucinous, and transitional cell carcinomas, whereas type II tumors comprise high-grade serous, high-grade endometrioid, malignant mixed mesodermal tumors, and undifferentiated carcinomas. Categorical variables were compared using χ(2) test. Continuous variables were compared using 1-way analysis of variance with Bonferroni post hoc test or Mann-Whitney U or Kruskal-Wallis test, depending on data distribution. RESULTS: Sixty-seven women (27.5%) had type I EOC, and 177 (72.3%) had type II EOC. We observed that women with type I EOC were younger, presented asymptomatic at diagnosis more frequently, and had lower CA-125 levels and lower tumor stage than women with type II EOC. Type II EOCs were more frequently identified as a solid mass and were smaller lesions than type I EOC. CONCLUSIONS: Some differences exist between type I and type II EOC in clinical and ultrasound manifestations. Although the clinical significance of these findings is still to be determined, this information could provide some clues to clinicians faced with the diagnosis of ovarian cancer.

Microsurgical anastomosis of the fallopian tubes after tubal ligation: a systematic review and meta-analysis.

OBJECTIVE: Between 20% and 30% of women who have undergone tubal ligation regret their decision. The alternative to regain fertility for these women is either in vitro fertilization or tubal re-anastomosis. This article presents a systematic review with meta-analysis to assess the current evidence on the efficacy of tubal recanalization surgery in patients who have previously undergone tubal ligation. STUDY DESIGN: The search was conducted in the World of Science (WOS) database, The Cochrane Library and ClinicalTrials.gov record using the keywords "tubal reversal", "tubal reanastomosis" and "tubal anastomosis". The review was carried out by two of the authors. Data from 22 studies were evaluated, comprising over 14,113 patients who underwent the studied surgery, following strict inclusion criteria: articles published between January 2012 and June 2022, in English and with a sample size bigger than 10 patients were included. A random-effects meta-analysis was performed. RESULTS: The overall pregnancy rate after anastomosis was found to be 65.3 % (95 % CI: 61.0-69.6). The percentage of women who had at least one live birth, known as the birth rate, was 42.6 % (95 % CI: 34.9-51.4). Adverse outcomes after surgery were also examined: the observed abortion rate among women who underwent surgery was 9.4 % (95 % CI: 7.0-11.7), and the overall ectopic pregnancy rate was 6.8 % (95 % CI: 4.6-9.0). No differences were found between the outcomes when differentiating surgical approaches: laparotomy, laparoscopy, or robotic-assisted surgery. The patient's age was identified as the most significant determining factor for fertility restoration. Finally, when comparing the results of tubal reversal with in vitro fertilization, reversal procedures appear more favorable for patients over 35 years old, while the results are similar for patients under 35 years old, but more data is needed to evaluate this finding. CONCLUSION: Therefore, the available literature review demonstrates that surgical anastomosis following tubal ligation is a reproducible technique with relevant success rates, performed by multiple expert groups worldwide.

Vaginal evisceration in a patient with previous sacrocolpopexy.

Vaginal evisceration is a rare gynecologic complication with less than 100 cases reported in the literature. We present a case of vaginal evisceration in a woman with multiple previous surgeries including a sacrocolpopexy. Vaginal mesh grafts have to be applied properly during sacrocolpopexy.

Adding cancer antigen 125 screening to gray scale sonography for predicting specific diagnosis of benign adnexal masses in premenopausal women: is it worthwhile?

OBJECTIVES: The purpose of this study was to assess whether a single determination of the serum cancer antigen 125 (CA-125) level provides additional information to sonography for specific diagnosis of benign adnexal masses in premenopausal women. METHODS: We conducted a retrospective study comprising 1058 premenopausal women (mean age, 34.8 years) with histologically proven benign adnexal masses. All women had undergone transvaginal sonography and serum CA-125 determination within 1 week before surgery and tumor removal. According to "pattern recognition" analysis, a presumptive diagnosis was provided on gray scale transvaginal sonography for all masses. Positive and negative likelihood ratios were calculated for gray scale sonography and gray scale sonography plus CA-125. RESULTS: Eighty-five women had bilateral masses (1143 masses analyzed). In 7 women with bilateral masses, the histologic diagnoses of the masses were discordant and were excluded. Histologic diagnoses were as follows: endometrioma, n = 452; dermoid cyst, n = 180; serous cyst, n = 158; hemorrhagic cyst, n = 119; mucinous cyst, n = 54; hydrosalpinx, n = 37; and other, n = 109. The median CA-125 level was significantly higher in endometrioma (71.9 IU/mL; range: 5-2620 IU/mL) and hydrosalpinx (59.2 IU/mL; range, 5-601 IU/mL) compared to all other tumor types (P < .001). The CA-125 level was 35 IU/mL or higher in 74% of endometriomas, 58% of hydrosalpinges, 34% of hemorrhagic cysts, 18% of mucinous cysts, 14% of dermoid cysts, and 8% of serous cysts. The positive and negative likelihood ratios for sonography and sonography plus CA-125 (335 IU/mL) for each kind of tumor were not statistically different except for endometrioma, for which the positive likelihood ratio for sonography plus CA-125 (55.0; 95% confidence interval, 27.5-109.9) was significantly higher than for sonography alone (19.2; 95% confidence interval, 13.6-27.1). CONCLUSIONS: Cancer antigen 125 screening does not add useful information for specific diagnosis of benign adnexal tumors, except for endometrioma. An elevated CA-125 level significantly increases the probability of such a lesion.

En-bloc rectosigmoid and mesorectum resection as part of pelvic cytoreductive surgery in advanced ovarian cancer

Objective: "En-bloc" resection of pelvic tumor in ovarian cancer (OC) is still controversial. The aim was to analyze results in an OC series from a single center, all of whom underwent "en-bloc" resection as part of cytoreductive surgery. Material and Methods: Clinical and surgical records from sixty patients with ovarian carcinoma who underwent "en-bloc" resection surgery were retrospectively analyzed. Results: Patients' mean age was 56 years; 36 patients had primary disease and 24 had recurrent disease. Carcinomatosis was present in 46.7% of patients. Primary surgery was performed in 49 and interval debulking surgery in eleven. Complete cytoreduction was achieved in 55.0% and optimal in 38.3% of patients. Carcinomatosis significantly decreased the probability of complete cytoreduction [odds ratio (OR): 0.22; p=0.021]. Mesorectal infiltration occurred in 83% of patients. Risk of death was non-significantly higher (hazard ratio: 1.9) in women with mesorectal infiltration. Median overall survival was longer for patients without infiltration (46.1 vs 79.1 months; p=0.15). Eighty-five percent suffered from mild to moderate complications and colorectal anastomosis (CRA) leak occurred in two patients (3.6%) with CRA below 6 cm. Diaphragm resection had >5 times the risk for major complications (OR: 5.35; p=0.014). There was no three month mortality. Conclusion: When contiguous gross extension of disease to pelvic peritoneum and sigmoid colon is found, in patients with advanced OC, microscopic involvement of the mesorectum and intestinal wall is present in most cases making "en-bloc" resection necessary if complete cytoreduction is to be achieved. The associated morbidity is acceptable.