Steerable DROP-IN radioguidance during minimal-invasive non-robotic cervical and endometrial sentinel lymph node surgery.

PURPOSE: The recently introduced tethered DROP-IN gamma probe has revolutionized the way robotic radioguided surgery is performed, fully exploiting the nature of steerable robotic instruments. Given this success, the current first-in-human study investigates if the DROP-IN can also provide benefit in combination with steerable non-robotic instruments during conventional laparoscopic surgery, showing equivalence or even benefit over a traditional rigid gamma probe. METHODS: The evaluation was performed in ten patients during laparoscopic cervical (n = 4) and endometrial (n = 6) cancer sentinel lymph node (SLN) procedures. Surgical guidance was provided using the hybrid, or bi-modal, SLN tracer ICG-99mTc-nanocolloid. SLN detection was compared between the traditional rigid laparoscopic gamma probe, the combination of a DROP-IN gamma probe and a steerable laparoscopic instrument (LaproFlex), and fluorescence imaging. RESULTS: The gynecologists experienced an enlarged freedom of movement when using the DROP-IN + LaproFlex combination compared to the rigid laparoscopic probe, making it possible to better isolate the SLN signal from background signals. This did not translate into a change in the SLN find rate yet. In both cervical and endometrial cancer combined, the rigid probe and DROP-IN + LaproFlex combination provided an equivalent detection rate of 96%, while fluorescence provided 85%. CONCLUSION: We have successfully demonstrated the in-human use of steerable DROP-IN radioguidance during laparoscopic cervical and endometrial cancer SLN procedures, expanding the utility beyond robotic procedures. Indicating an improved surgical experience, these findings encourage further investigation and consideration on a path towards routine clinical practice and improved patient outcome. TRIAL REGISTRATION: HCB/2021/0777 and NCT04492995; https://clinicaltrials.gov/study/NCT04492995.

Mapping sentinel lymph nodes in early-stage ovarian cancer (MELISA) trial - a further step towards lymphadenectomy replacement.

OBJECTIVE: Sistematic pelvic and para-aortic lymphadenectomy is part of the staging surgery for early-stage epithelial ovarian cancer, with no therapeutic value. The Mapping Sentinel Lymph Nodes In Early-Stage Ovarian Cancer (MELISA) trial prospectively assessed the SLN detection rate and the diagnostic accuracy of the SLN mapping technique in patients with early-stage epithelial ovarian cancer. METHODS: This prospective, single-arm study included patients diagnosed with early-stage epithelial ovarian cancer (FIGO stages I and II), via either primary surgery or re-staging surgery. SLN mapping was performed by injecting 0.2 mL of 37-mBq 99mTc-nanocoloid albumin and 2 mL of 2.5 mg/mL indocyanine green into the infundibulopelvic and utero-ovarian ligaments. After removal of SLNs, a complete systematic pelvic and para-aortic lymphadenectomy was performed. SLN Ultrastaging analysis was applied. The primary outcome was the overall SLN detection rate, either with one or both tracers. Secondary outcomes were the diagnostic accuracy of detecting lymph node metastases and factors that may influence SLN detection. RESULTS: Thirty patients were included. SLNs were identified in 27 patients (90%). Detection rates in primary and re-staging surgery were 89% and 92%, respectively. Para-aortic drainage was the predominant lymphatic spread, observed in 26 of 27 patients. Ultrastaging pathologic reports listed 1 SLN with macrometastasis, 1 with micrometastasis, and 5 with isolated tumor cells; the sensitivity of SLN mapping was 100%, with a false-negative rate of 0%. Univariate analysis showed a nonsignificant higher proportion of patients with uterine fibroids, adenomyosis, and endometriosis (100%, 67%, 67%, respectively) in patients in whom SLNs were not detected. CONCLUSION: SLN mapping has a high detection rate (90%) and is an accurate technique for detecting lymph node involvement in early-stage epithelial ovarian cancer. SLN mapping is a potential alternative to systematic lymphadenectomy to reduce associated morbidity, but further research is needed to evaluate the impact of SLN mapping on oncologic outcomes and its cost-effectiveness.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer.

OBJECTIVE: To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. METHODS: In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. RESULTS: A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. CONCLUSIONS: Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

Feasibility of a Multimodal Prehabilitation Programme in Patients Undergoing Cytoreductive Surgery for Advanced Ovarian Cancer: A Pilot Study.

INTRODUCTION: Treatment for advanced ovarian cancer (AOC) comprises cytoreductive surgery combined with chemotherapy. Multimodal prehabilitation programmes before surgery have demonstrated efficacy in postoperative outcomes in non-gynaecological surgeries. However, the viability and effects of these programmes on patients with AOC are unknown. We aimed to evaluate the feasibility and postoperative impact of a multimodal prehabilitation programme in AOC patients undergoing surgery. METHODS: This single-centre, before-and-after intervention pilot study included 34 patients in two cohorts: the prehabilitation cohort prospectively included 15 patients receiving supervised exercise, nutritional optimisation, and psychological preparation from December 2019 to January 2021; the control cohort included 19 consecutive patients between January 2018 and November 2019. Enhanced Recovery After Surgery guidelines were followed. RESULTS: The overall adherence to the multimodal prehabilitation programme was 80%, with 86.7% adherence to exercise training, 100% adherence to nutritional optimisation, and 80% adherence to psychological preparation. The median hospital stay was shorter in the prehabilitation cohort (5 (IQR, 4-6) vs. 7 days (IQR, 5-9) in the control cohort, p = 0.04). Differences in postoperative complications using the comprehensive complication index (CCI) were not significant (CCI score: 9.3 (SD 12.12) in the prehabilitation cohort vs. 16.61 (SD 16.89) in the control cohort, p = 0.08). The median time to starting chemotherapy was shorter in the prehabilitation cohort (25 (IQR, 23-25) vs. 35 days (IQR, 28-45) in the control cohort, p = 0.03). CONCLUSIONS: A multimodal prehabilitation programme before cytoreductive surgery is feasible in AOC patients with no major adverse effects, and results in significantly shorter hospital stays and time to starting chemotherapy.

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.

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.

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.

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).