Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

OVA-LEAK: Prognostic score for colo-rectal anastomotic leakage in patients undergoing ovarian cancer surgery.

OBJECTIVE: The objective of the present study was to define and validate an anastomotic leak prognostic score based on previously described and reported anastomotic leak risk factors (OVA-LEAK: https://n9.cl/ova-leakscore) and to establish if the use of OVA-LEAK score is better than clinical criteria (surgeon's choice) selecting anastomosis to be protected with a diverting ileostomy. MATERIAL & METHODS: This is a retrospective, multicentre cohort study that included patients who underwent cytoreductive surgery for primary advanced or relapsed ovarian cancer with colorectal resection and anastomosis between January 2011 and June 2021. Data from patients already included in the previous predictive model were not considered in the present analysis. To validate the performance of our logistic regression model, we used the OVA-LEAK formula (Annex I: https://n9.cl/ova-leakscore) for estimating leakage probabilities in a new independent cohort. Then, receiver operating characteristic (ROC) analysis was performed and area under the curve (AUC) was used to measure the performance of the model. Additionally, the Brier score was also estimated. 95% confidence intervals (CI) for each of the estimated performance measures were also calculated. RESULTS: 848 out of 1159 recruited patients were finally included in the multivariable logistic regression model validation. The AUC of the new cohort was 0.63 for predicting anastomotic leak. Considering a cut-off point of 22.1% to be 'positive' (to get a leak) this would provide a sensitivity of 0.45, specificity of 0.80, positive predictive value of 0.09 and negative predictive value of 0.97 for anastomotic leak. If we consider this cut-off point to select patients at risk of leak for bowel diversion, up to 22.5% of the sampled patients would undergo a diverting ileostomy and 47% (18/40) of the anastomotic leaks would be 'protected' with the stoma. Nevertheless, if we consider only the 'clinical criteria' for performing or not a diverting ileostomy, only 12.5% (5/40) of the leaks would be 'protected' with a stoma, with a rate of diverting ileostomy of up to 24.3%. CONCLUSIONS: Compared with subjective clinical criteria, the use of a predictive model for anastomotic leak improves the selection of patients who would benefit from a diverting ileostomy without increasing the rate of stoma use.

Extended vertical rectus abdominis myocutaneous flap for reconstruction of large pelviperineal defects following oncologic resection.

BACKGROUND AND OBJECTIVES: Extended vertical rectus abdominis myocutaneous (eVRAM) flap has been proposed for reconstruction of large pelviperineal defects where traditional VRAM flap is insufficient. We present our experience with eVRAM flap for pelviperineal reconstruction following oncologic resection. METHODS: A retrospective study was conducted, including all the patients who underwent reconstruction with eVRAM flap after complex pelvic resection, between 2012 and 2020. EVRAM flap was indicated when traditional VRAM was considered deficient to cover or reach the skin defect or to fill the dead space. RESULTS: Forty-four patients were included in the study. Successful reconstruction with eVRAM flap was achieved in 40 patients. There were three flap failures, and one patient died in the second postoperative day because of multiple organ failure. Perineal wound complications occurred in 17 patients (38.6%), eight of them requiring surgical reoperation. Donor site problems were present in five patients (11.4%), and only one patient required surgical closure because of a major dehiscence. CONCLUSIONS: The authors found the eVRAM flap to be a useful and reliable flap for reconstruction of complex pelviperineal wounds, with a low rate of donor site morbidity.

A multimodal prehabilitation program for the reduction of post-operative complications after surgery in advanced ovarian cancer under an ERAS pathway: a randomized multicenter trial (SOPHIE).

BACKGROUND: Multimodal prehabilitation programs that combine exercise training, nutritional support, and optimize psychological status have demonstrated efficacy in reducing post-operative complications in non-gynecological abdominal surgeries; however, the benefit in advanced ovarian cancer is unclear. PRIMARY OBJECTIVE: To compare the post-operative complications of a multimodal prehabilitation program in patients undergoing cytoreductive surgery for advanced ovarian cancer with standard pre-operative care. STUDY HYPOTHESIS: Multimodal prehabilitation reduces post-operative complications in patients undergoing cytoreductive surgery for advanced ovarian cancer and subsequently reduces the length of hospital stay and time to initiation of adjuvant therapy. TRIAL DESIGN: This prospective, multi-institutional, randomized clinical trial will randomize candidates for surgery to either the standard of care or multimodal prehabilitation consisting of (1) 2- or 3-weekly supervised high-intensity resistance training sessions and promotion of physical activity through a mobile phone application; (2) respiratory physiotherapy; (3) nutrition counseling with supplementation as needed; and (4) weekly psychological and cognitive behavioral sessions. Baseline, pre-operative and 1 month post-operative data will be collected. An independent blinded evaluator will collect intra- and post-operative surgical data. MAJOR INCLUSION/EXCLUSION CRITERIA: Women with advanced ovarian cancer International Federation of Gynecology and Obstetrics (2014) stage III or IV scheduled to undergo primary debulking surgery, interval debulking surgery,or secondary or tertiary cytoreductive surgery will be included. Women are eligible if they are able to undergo a minimum of 2 weeks of prehabilitation prior to surgery. Patients with <75% adherence to the total program will be excluded. PRIMARY ENDPOINT: Post-operative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery according to the Comprehensive Complication Index. SAMPLE SIZE: 146 patients will be included, 73 in each group. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual should be completed in December 2024 with results reported soon thereafter. TRIAL REGISTRATION NUMBER: NCT04862325.

Oncological safety of hysteroscopy in endometrial cancer.

OBJECTIVE: It has been suggested that the manipulation of neoplastic tissue during hysteroscopy may lead to dissemination of tumor cells into the peritoneal cavity and worsen prognosis and overall survival. The goal of this study was to assess the oncological safety comparing hysteroscopy to Pipelle blind biopsy in the presurgical diagnosis of patients with endometrial cancer. METHODS: We performed a retrospective multicentric study among patients who had received primary surgical treatment for endometrial cancer. A multivariate statistical analysis model was used to compare relapse and survival rates in patients who had been evaluated preoperatively either by hysteroscopy or Pipelle biopsy. The relapse rate, disease-free survival, and overall survival were assessed as the main outcomes. The histological type, tumor size, myometrial invasion, International Federation of Gynecology and Obstetrics (FIGO) stage, surgical approach, use of a uterine manipulator, and adjuvant treatment were also included in the analysis. RESULTS: A total of 1731 women from 15 centers were included: 1044 in the hysteroscopy group and 687 in the Pipelle sampling group. 225 patients relapsed during the 10 year follow-up period: 139 (13.3%) in the hysteroscopy group and 86 (12.4%) in the Pipelle sampling group. There is no evidence of an association between the use of hysteroscopy as a diagnostic method and relapse rate (HR 1.24, 95% CI 0.92 to 1.66; p=0.16), lower disease-free survival (HR 1.23, 95% CI 0.92 to 1.66; p=0.15), or overall survival (HR 0.95, 95% CI 0.70 to 1.29; p=0.76). CONCLUSION: Hysteroscopy is a safe diagnostic method for patients with endometrial cancer with no impact on oncological outcomes when compared with sampling by Pipelle.

Laparoscopic Debulking of Enlarged Pelvic Nodes during Surgical Para-aortic Staging in Locally Advanced Cervical Cancer: A Retrospective Comparative Cohort Study.

STUDY OBJECTIVE: To evaluate laparoscopic pelvic lymph node debulking during extraperitoneal aortic lymphadenectomy in diagnosis, therapeutic planning, and prognosis of patients with locally advanced cervical cancer and enlarged lymph nodes on imaging before chemoradiotherapy. DESIGN: Retrospective, multicenter, comparative cohort study. SETTING: The study was carried out at 11 hospitals with specialized gynecologic oncology units in Spain. PATIENTS: Total of 381 women with locally advanced cervical cancer and International Federation of Gynecology and Obstetrics 2018 stage IIIC 1r (radiologic) and higher who received primary treatment with chemoradiotherapy. INTERVENTIONS: Patients underwent pelvic lymph node debulking and para-aortic lymphadenectomy (group 1), only para-aortic lymphadenectomy (group 2), or no lymph node surgical staging (group 3). On the basis of pelvic node histology, group 1 was subdivided as negative (group 1A) or positive (group 1B). MEASUREMENTS AND MAIN RESULTS: False positives and negatives of imaging tests, disease-free survival, overall survival, and postoperative complications were evaluated. In group 1, pelvic lymph node involvement was 43.3% (71 of 164), and aortic involvement was 24.4% (40 of 164). In group 2, aortic nodes were positive in 29.7% (33 of 111). Disease-free survival and overall survival were similar in the 3 groups (p = .95) and in groups 1A and 1B (p = .25). No differences were found between groups 1 and 2 in intraoperative (3.7% vs 2.7%, p = .744), early postoperative (8.0% vs 6.3%, p = .776), or late postoperative complications (6.1% vs 2.7%, p = .252). Fewer early and late complications were attributed to radiotherapy in group 1A than in the others (p = .022). CONCLUSION: Laparoscopic pelvic lymph node debulking during para-aortic staging surgery in patients with locally advanced cervical cancer with suspicious nodes allows for the confirmation of metastatic lymph nodes without affecting survival or increasing surgical complications. This information improves the selection of patients requiring boost irradiation, thus avoiding overtreatment of patients with negative nodes.

Fertility sparing treatment in patients with endometrial cancer (FERT-ENC): a multicentric retrospective study from the Spanish Investigational Network Gynecologic Oncology Group (SPAIN-GOG).

OBJECTIVE: The primary objective was to evaluate the response rate of conservative treatment for endometrial cancer, and the secondary objective was to assess oncological, fertility and obstetric outcomes in patients who underwent fertility preservation treatment. MATERIAL AND METHODS: This multicentre, observational, retrospective study evaluated endometrial cancer patients who underwent fertility-sparing treatment in Spanish centres between January 2010 and January 2020. Seventy-three patients with stage IA endometrioid adenocarcinoma of the uterus were included in the study. RESULTS: The levonorgestrel intrauterine device (LNG-IUD) was the most common fertility-sparing treatment (53.4%), followed by megestrol acetate (20.5%) and medroxyprogesterone acetate (16.4%). During the 24-month follow-up period, the rate of complete response to fertility-sparing management was 74% (n = 54), and 8.2% (n = 6) of patients presented a partial response. Additionally, 13 (17.8%) patients presented with persistent disease and six (8.2%) relapsed after response. The LNG-IUD was associated with a higher complete response rate than the other methods (87.2 vs. 58.8%; p = 0.01). Surgical treatment (at least hysterectomy) was performed in 44 (60.3%) patients as the end of fertility-sparing treatment. Four (5.5%) patients presented relapse after surgery, associated with final FIGO stage III (p = 0.036), myometrial invasion > 50% (p = 0.018) and final tumour grade 2-3 (p = 0.018). The mean follow-up period was 57.8 (range 6-159) months. The 5-year relapse-free survival and overall survival rates were 92.6% [95% CI (81.3, 97.2)] and 93.5% [95% CI (80.7, 97.9)], respectively. During follow-up, three patients (4.1%) died of the disease after completion of surgical treatment. Up to 50.7% of patients included in the study attempted to get pregnant. Of these, the rate of pregnancy was 81.1% (n = 30/37), and reproductive techniques were used for this purpose in 78.4% of cases. CONCLUSIONS: Fertility-sparing management presented a high response rate in patients with endometrial cancer. LNG-IUD was associated with a better response rate compared to the other treatment options. Moreover, in patients using this management method, pregnancy could be achieved using reproductive techniques.

Molecular Management of High-Grade Serous Ovarian Carcinoma.

High-grade serous ovarian carcinoma (HGSOC) represents the most common form of epithelial ovarian carcinoma. The absence of specific symptoms leads to late-stage diagnosis, making HGSOC one of the gynecological cancers with the worst prognosis. The cellular origin of HGSOC and the role of reproductive hormones, genetic traits (such as alterations in P53 and DNA-repair mechanisms), chromosomal instability, or dysregulation of crucial signaling pathways have been considered when evaluating prognosis and response to therapy in HGSOC patients. However, the detection of HGSOC is still based on traditional methods such as carbohydrate antigen 125 (CA125) detection and ultrasound, and the combined use of these methods has yet to support significant reductions in overall mortality rates. The current paradigm for HGSOC management has moved towards early diagnosis via the non-invasive detection of molecular markers through liquid biopsies. This review presents an integrated view of the relevant cellular and molecular aspects involved in the etiopathogenesis of HGSOC and brings together studies that consider new horizons for the possible early detection of this gynecological cancer.

Integrative Genomic and Transcriptomic Profiling Reveals a Differential Molecular Signature in Uterine Leiomyoma versus Leiomyosarcoma.

The absence of standardized molecular profiling to differentiate uterine leiomyosarcomas versus leiomyomas represents a current diagnostic challenge. In this study, we aimed to search for a differential molecular signature for these myometrial tumors based on artificial intelligence. For this purpose, differential exome and transcriptome-wide research was performed on histologically confirmed leiomyomas (n = 52) and leiomyosarcomas (n = 44) to elucidate differences between and within these two entities. We identified a significantly higher tumor mutation burden in leiomyosarcomas vs. leiomyomas in terms of somatic single-nucleotide variants (171,863 vs. 81,152), indels (9491 vs. 4098), and copy number variants (8390 vs. 5376). Further, we discovered alterations in specific copy number variant regions that affect the expression of some tumor suppressor genes. A transcriptomic analysis revealed 489 differentially expressed genes between these two conditions, as well as structural rearrangements targeting ATRX and RAD51B. These results allowed us to develop a machine learning approach based on 19 differentially expressed genes that differentiate both tumor types with high sensitivity and specificity. Our findings provide a novel molecular signature for the diagnosis of leiomyoma and leiomyosarcoma, which could be helpful to complement the current morphological and immunohistochemical diagnosis and may lay the foundation for the future evaluation of malignancy risk.

Vesicovaginal Fistula Repair by Modified Martius Flap: A Step-by-Step Surgical Technique Video.

BACKGROUND: Fistula repair in the perineal region represents a major challenge for surgeons. It is important for the medical community to facilitate and disclose these techniques. OBJECTIVE: The aim of this article was to show a stepwise approach for a direct repair and use of a Martius flap for a vesicovaginal fistula. METHODS: We show a single case performed in a patient who presented with a vesicovaginal fistula diagnosed after surgery, which did not respond to conservative management. The procedure consists of the following steps: intraoperative cystoscopy, anatomical direct repair of the fistulous tract between the bladder and vagina, and modified Martius flap. CONCLUSIONS: Martius flap is a repair technique used for complex fistula in the perineal region. It is a simple, safe, and reproducible procedure with good long-term functional and esthetic results.

Machine Learning-Based Integration of Prognostic Magnetic Resonance Imaging Biomarkers for Myometrial Invasion Stratification in Endometrial Cancer.

BACKGROUND: Estimation of the depth of myometrial invasion (MI) in endometrial cancer is pivotal in the preoperatively staging. Magnetic resonance (MR) reports suffer from human subjectivity. Multiparametric MR imaging radiomics and parameters may improve the diagnostic accuracy. PURPOSE: To discriminate between patients with MI ≥ 50% using a machine learning-based model combining texture features and descriptors from preoperatively MR images. STUDY TYPE: Retrospective. POPULATION: One hundred forty-three women with endometrial cancer were included. The series was split into training (n = 107, 46 with MI ≥ 50%) and test (n = 36, 16 with MI ≥ 50%) cohorts. FIELD STRENGTH/SEQUENCES: Fast spin echo T2-weighted (T2W), diffusion-weighted (DW), and T1-weighted gradient echo dynamic contrast-enhanced (DCE) sequences were obtained at 1.5 or 3 T magnets. ASSESSMENT: Tumors were manually segmented slice-by-slice. Texture metrics were calculated from T2W and ADC map images. Also, the apparent diffusion coefficient (ADC), wash-in slope, wash-out slope, initial area under the curve at 60 sec and at 90 sec, initial slope, time to peak and peak amplitude maps from DCE sequences were obtained as parameters. MR diagnostic models using single-sequence features and a combination of features and parameters from the three sequences were built to estimate MI using Adaboost methods. The pathological depth of MI was used as gold standard. STATISTICAL TEST: Area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, accuracy, positive predictive value, negative predictive value, precision and recall were computed to assess the Adaboost models performance. RESULTS: The diagnostic model based on the features and parameters combination showed the best performance to depict patient with MI ≥ 50% in the test cohort (accuracy = 86.1% and AUROC = 87.1%). The rest of diagnostic models showed a worse accuracy (accuracy = 41.67%-63.89% and AUROC = 41.43%-63.13%). DATA CONCLUSION: The model combining the texture features from T2W and ADC map images with the semi-quantitative parameters from DW and DCE series allow the preoperative estimation of myometrial invasion. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3.

Ultrastaging protocol in sentinel lymph node for apparent early stage ovarian cancer.

OBJECTIVE: The objective of the present study is to determine the role of sentinel lymph node (SLN) ultrastaging in apparent early-stage ovarian cancer. METHODS: We previously demonstrated the feasibility of SLN in early-stage ovarian cancer in a pilot study and in a clinical trial (NCT03452982). The SLN of the 30 patients involved in both were processed following an ultrastaging protocol. The cost of ultrastaging processing was also reported. RESULTS: A SLN was detected in up to 91.3% and 90% in the pelvic and para-aortic region, respectively. In all cases, a SLN was detected at least in one field, pelvic or para-aortic. The mean time from injection to SLN resection was 53.3 ± 20.3 min. Two of 30 (6.6%) patients had a contralateral SLN in the para-aortic field, but no patients had contralateral SLN within the pelvic field after injection. The mean number of harvested SLN was 2.1 ± 1.4 (range: 0-5) and 2.7 ± 1.5 (range: 0-7) in the pelvic and para-aortic region, respectively. Two patients were upgraded to stage IIIA1 because of lymph node metastasis. In the first case, based on single sections and haematoxylin and eosin (H&E) examination, a pelvic SLN micrometastasis (1 mm) was found on the first H&E section. By using the ultrastaging protocol, the size of the metastasis was increased to 2.1 mm (macrometastasis). In the same patient, the ultrastaging study of the inframesenteric para-cava SLNs found isolated tumour cells in the subcapsular and interfollicular lymph nodes sinus in one of the two SLN harvested (in one of the sections at the fourth and fifth ultrastage levels). The other upstaged case was a para-aortic macrometastasis in a patient in whom the SLN was not identified in the para-aortic field because of the absence of migration from the infundibulo-pelvic stump injection. The cost of ultrastaging in each patient depended on the total number of SLN retrieved, averaging 96.8 € (range: 0-230.5) and 124.5 € (range: 0-322.7€) for pelvic and para-aortic SLN, respectively. CONCLUSIONS: A uniform protocol for ultrastaging is essential for lower-volume metastasis detection and to provide reproducible information between upcoming studies, as evidence about SLN in ovarian cancer is growing.

Combined use of ICG and technetium does not improve sentinel lymph node detection in endometrial cancer: Results of the COMBITEC study.

OBJECTIVE: There is scarce evidence available about the benefit of combining technetium (99mTc) and indocyanine green (ICG) for sentinel lymph node (SLN) biopsy in endometrial cancer. The aim of this study was to compare the overall and bilateral pelvic detection rates of SLNs in two retrospective cohorts: ICG exclusive vs. combined ICG+99mTc. METHODS: The COMBITEC study (COMBined ICG and Technetium for SLN detection in Endometrial Cancer) consisted of a multicentre retrospective study (February 2015-June 2020) including patients diagnosed with endometrial atypical hyperplasia or early-stage endometrial carcinoma who underwent SLN biopsy by cervical injection of ICG with or without 99mTc in four different referral centers in Spain. RESULTS: A total of 180 patients were included, 51% (n = 92) in ICG group and 49% (n = 88) in ICG+99mTc group. Eighty-seven percent of the patients presented endometrioid histology, and over 99% of the procedures were performed by a minimally invasive approach. Both groups were comparable regarding their basal characteristics, except for a higher body mass index in ICG+99mTc group and a bigger proportion of robotic-assisted procedures in ICG group. Overall detection rate was 92.8% without significant differences between groups (ICG: 94.6% vs ICG+99mTc: 90.9%, p = .34). No significant differences were observed neither in bilateral pelvic nor aortic mapping rate. When 99mTc was used, surgical procedures were significantly longer. In 7.3% of mapped patients, at least one positive SLN was found (ICG: 10.3% vs ICG+99mTc: 3.9%, p = .109). Empty node packet rates and number of SLNs retrieved per patient were also similar between cohorts. CONCLUSION: Combining preoperative 99mTc to intraoperative ICG did not improve SLN detection in endometrial cancer, but resulted in longer procedures.

M-TRAP: Safety and performance of metastatic tumor cell trap device in advanced ovarian cancer patients.

OBJECTIVE: Despite radical surgery and chemotherapy, most patients with ovarian cancer die due to disease progression. M-Trap is an implantable medical device designed to capture peritoneal disseminated tumor cells with the aim to focalize the disease. This trial analyzed the safety and performance of the device. METHODS: This first-in-human prospective, multi-center, non-blinded, single-arm study enrolled 23 women with high-grade serous advanced ovarian cancer. After primary or interval debulking surgery, 3 M-Trap devices were placed in the peritoneum of the abdominal cavity. 18-months post-implantation or at disease progression, devices were initially removed by laparoscopy. The primary safety endpoint was freedom from device and procedure-related major adverse events (MAEs) through 6-months post-implantation compared to an historical control. The primary performance endpoint was histopathologic evidence of tumor cells capture. RESULTS: Only one major adverse event was attributable to the device. 18 women were free of device and procedure related MAEs (78.3%). However, the primary safety endpoint was not achieved (p = 0.131), primarily attributable to the greater surgical complexity of the M-Trap patient population. 62% of recurrent patients demonstrated tumor cell capture in at least one device with a minimal tumor cell infiltration. No other long-term device-related adverse events were reported. The secondary performance endpoint demonstrated a lack of disease focalization. CONCLUSIONS: The M-Trap technology failed to meet its primary safety objective, although when adjusted for surgical complexity, the study approved it. Likewise, the devices did not demonstrate the anticipated benefits in terms of tumor cell capture and disease focalization in recurrent ovarian cancer.

Impact of uterine manipulator on oncological outcome in endometrial cancer surgery.

BACKGROUND: There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. OBJECTIVE: To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. STUDY DESIGN: We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. RESULTS: A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27-4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] I-II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57-0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07-2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63). CONCLUSION: In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I-II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results.

Protective Maneuver to Avoid Tumor Spillage during Laparoscopic Radical Hysterectomy: Vaginal Cuff Closure.

OBJECTIVE: To demonstrate the feasibility of a protective maneuver to avoid tumor exposure during laparoscopic radical hysterectomy. DESIGN: This video illustrates the vaginal cuff closure technique in cervical cancer surgery. SETTING: The Oncologic Gynecology Department at the University Hospital La Fe. INTERVENTIONS: After the Laparoscopic Approach to Cervical Cancer trial [1], the laparoscopic approach to the surgical treatment of cervical cancer has been questioned: laparotomic surgery has been associated with a better cancer outcome. This publication has changed the current approach recommendation for performing radical hysterectomy from minimally invasive surgery to open surgery. There are some theories that might justify these findings. In minimally invasive surgery, the use of a uterine manipulator can condition the spread owing to erosion and friction caused on the tumor, even leading to the perforation of the tumor. In addition, intraperitoneal colpotomy can lead to pelvic peritoneum contamination by the tumor. To close the gap between laparoscopy and laparotomy, some protective maneuvers, such as vaginal cuff closure, have been proposed [2,3]. These strategies aim to reduce the possibility of manipulation or exposure of the tumor to the pelvis during colpotomy in laparoscopic radical hysterectomy. These protective maneuvers have been shown to decrease the relapse rate in retrospective studies [4]. However, prospective trials are needed to elucidate and confirm these findings. In this video, we explain step-by-step the technique of vaginal cuff closure before a radical hysterectomy performance for uterine cervical cancer. First, the nodal status is established by laparoscopic sentinel lymph node dissection and frozen section study. Bilateral pelvic lymphadenectomy is completed according to the size of the tumor. In the case of negative nodal status, the vaginal cuff is closed: Approximately 2 to 3 cm from the tumor (depending on its size), a circumferential incision of the vaginal mucosa is performed, followed by the dissection of the vaginal wall, which should be sufficient to allow a tension-free vaginal closure. The vaginal cuff is then closed with a running suture. A laparoscopic radical hysterectomy is then completed, and the surgical specimen is removed without any manipulation of the tumor. CONCLUSION: Avoiding manipulation of the tumor during cancer surgery is crucial. A vaginal cuff closure technique appears to be an easy protective maneuver that prevents tumor exposure and manipulation during laparoscopic radical hysterectomy.

Eco-efficiency evaluation in wastewater treatment plants considering greenhouse gas emissions through the data envelopment analysis-tolerance model.

The eco-efficiency evaluation in wastewater treatment plants (WWTPs) is used to know and improve the environmental and economic efficiency of these processes, systems, products, and services. The eco-efficiency evaluations in WWTP contemplate the inputs to be minimized, the desirable results to be maximized, and the undesired results to be minimized. Data envelopment analysis (DEA) is a widely used method to evaluate the eco-efficiency of WWTPs; integrating several approaches in a single index, traditional DEA models do not take into account the uncertainty in the data. This study evaluates the eco-efficiency of a sample of Catalan WWTPs, considering the uncertainty of the data (DEA tolerance model), and it is for the first time that together with CO2, other greenhouse gas (GHG) such as CH4 and N2O are considered as part of the process outputs. GHG emissions were quantified using methods reported in the literature. Seven hundred twenty-nine eco-efficiency scores were estimated for each WWTP instead of a single score like conventional DEA models, analyzing optimistic and pessimistic scenarios. The WWTPs were classified according to the estimated eco-efficiency scores, accounting for the uncertainty in each of the scenarios, and demonstrating the changes in the performance of the WWTPs in the different scenarios. Only two WWTPs were eco-efficient in all the scenarios evaluated. This approach provides essential information to improve efficiency and innovation in the wastewater sector.

Prognostic Value and Therapeutic Implication of Laparoscopic Extraperitoneal Paraaortic Staging in Locally Advanced Cervical Cancer: A Spanish Multicenter Study.

PURPOSE: To assess the impact of laparoscopic extraperitoneal paraaortic staging in therapeutic planning and prognosis of patients with locally advanced cervical cancer (LACC) as compared with imaging staging. METHODS: Retrospective multicenter study of stage IB2 and IIA2 to IVA (FIGO 2009) LACC patients who were candidates for primary chemoradiotherapy. The study (surgical) group included 634 patients undergoing laparoscopic/robotic extraperitoneal paraaortic staging treated with extended-field radiotherapy (EFRT) if lymph node involvement was confirmed. The control (imaging) group included 288 patients treated with EFRT when lymph node involvement was suspected on positron emission tomography-computed tomography scans and/or magnetic resonance imaging. RESULTS: In the study group, a median of 13 (range 9-17) lymph nodes were removed, with a rate of positive paraaortic nodes of 18%, with metastatic size ≤ 5 mm in 20.4% of cases. Paraaortic EFRT was administered to 18% of patients in the study group and in 58% of controls. In 34% of patients from the surgical group, EFRT was modified according to surgical findings with respect to imaging staging. The median follow-up in the study and control groups was 3.7 and 4.8 years, respectively. In both groups, the overall survival and cancer-specific disease-free survival were similar. The time interval between diagnosis and starting EFRT was 18 days longer in the study group, without differences in overall survival as compared with controls (hazard ratio 1.00, 95% confidence interval 0.998-1.005; p = 0.307). CONCLUSIONS: Laparoscopic extraperitoneal paraaortic staging in LACC patients is safe and modified therapeutic planning, allowing better selection of candidates for EFRT.

Sentinel lymph node technique in early-stage ovarian cancer (SENTOV): a phase II clinical trial.

OBJECTIVE: Early-stage ovarian cancer might represent an ideal disease scenario for sentinel lymph node application. Nevertheless, the published experience seems to be limited. Our objective was to assess the feasibility and safety concerns of sentinel lymph node biopsy in patients with clinical stage I-II ovarian cancer. METHODS: We conducted a prospective cohort study of 20 patients with histologically confirmed ovarian cancer. 99mTc and indocyanine green were injected into both the utero-ovarian and infundibulopelvic ligament stump, if they were present, during surgical staging. An intraoperative gamma probe and near-infrared fluorescence imaging were used to detect the sentinel lymph nodes. Inclusion criteria included: >18 years of age, suspicious adnexal mass (unilateral or bilateral) at ultrasound and CT imaging or confirmed ovarian tumor after previous surgery (unilateral or bilateral salpingo-oophorectomy with or without hysterectomy). Adverse events were recorded through postoperative day 30. The primary trial end point was to report adverse events related to the technique, including the use of 99mTc and ICG intraperitoneally, as well as the feasibility of the technique. RESULTS: A total of 20 patients were included in the analysis. Sentinel lymph nodes were detected in 14/15 (93%) pelvic and all 20 (100%) para-aortic regions. Five patients did not have utero-ovarian injection because of prior hysterectomy. The mean time from injection to sentinel lymph node resection was 53±15 min (range; 30-80). The mean number of harvested sentinel lymph nodes was 2.2±1.5 (range; 0-5) lymph nodes in the pelvis and 3.3±1.8 (range; 1-7) lymph nodes in the para-aortic region. There were no adverse intraoperative events, nor any within the 30 days of follow-up related with the technique. CONCLUSION: Sentinel lymph node mapping in early-stage ovarian cancer is feasible without major intraoperative or < 30 days safety concerns. (NCT03452982). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03452982.

Sentinel Lymph Node Technique in Apparent Early Ovarian Cancer: Laparoscopic Technique.

STUDY OBJECTIVE: To demonstrate the feasibility of laparoscopic sentinel lymph node technique in presumed early-stage ovarian cancer. DESIGN: Video illustrating the laparoscopic performance of the sentinel lymph node technique in ovarian cancer. SETTING: The Oncologic Gynecology Department at the University Hospital La Fe. PATIENTS: Candidates for the technique presented an apparent early stage ovarian cancer. The technique was performed in the context of a clinical trial called SENTOV (NCT03452982). INTERVENTIONS: To date, lymphadenectomy is recommended after the diagnosis of apparent early-stage ovarian cancer as part of the surgical staging. Minimally invasive surgery can be considered for the purpose of restaging [1]. Up to 14% of the patients are upstaged because of positive lymph nodes after pelvic and para-aortic lymphadenectomy [2]. Regarding low-grade tumors, a lower rate of lymph node involvement has been reported [3]. Sentinel lymph node technique has been reported to be feasible in a recent pilot study [4]. Two clinical trials (Sentinel Lymph Node in Early Ovarian Cancer and Sentine Lymph Node in Early Ovarian Cancer) are currently ongoing to clarify the use of sentinel lymph node technique in early ovarian cancer. The injection points were at the infundibulopelvic and ovarian ligament stumps. Two hundred microliters of saline solution containing 37 MBq of technetium-99m nanocolloid followed by 0.5 mL of indocyanine green (ICG) was injected subperitoneally. We used a 27 G needle at each injection point. Immediately after injection and also at 15 and 30 minutes after injection, the operative field was checked guided by the acoustic signal of the gamma probe and the near-infrared camera. We performed a minimum dissection looking for the sentinel lymph node or nodes in the pelvic and para-aortic region. Any lymph node with a remarkable radioactivity count as high as 10 times the background and/or dyed with ICG was considered a sentinel lymph node and was harvested separately. A systematic surgical staging was performed after the sentinel lymph node procedure was completed. Because of its small size, the ICG molecule is not caught in the lymph node valve system and keeps migrating when performing lymphography. An exhaustive direct view of the dye path is required to avoid misleading detection of the real sentinel lymph node. This theoretical problem is resolved by the use of the 99mTC-nanocolloid. This tracer gets trapped into the lymph node valve system because of its molecular size and does not keep migrating as does ICG. As such, a combination of both methods is proposed. CONCLUSION: Laparoscopic performance of sentinel lymph node technique in ovarian cancer seems to achievable. Between 2017 and 2019, this procedure was performed in 30 patients (13 laparoscopic), in the context of our pilot experience [4] and the Sentinel Lymph Node in Early Ovarian Cancer clinical trial (NCT03452982).