Radical Extirpation With Intraoperative Radiotherapy for Locally Recurrent Gynecologic Cancer: An Institutional Review.

OBJECTIVE: To report survival outcomes in patients with locally recurrent gynecologic cancers managed with curative-intent radical extirpation, perioperative external beam radiotherapy, and intraoperative radiotherapy (IORT). PATIENTS AND METHODS: We conducted a retrospective cohort analysis of 44 patients with locally recurrent gynecologic cancer treated at a single tertiary-care center (Mayo Clinic in Arizona) over a 15-year period (January 1, 2004, to July 31, 2019). This cohort included patients with uterine (n=21, 47.7%), ovarian (n=3, 6.8%), cervical (n=11, 25.0%), vaginal (n=2, 4.5%), vulvar (n=1, 2.3%), and unknown primary (n=6, 13.6%) cancer. Curative-intent radical extirpation included pelvic exenteration (n=13, 29.5%), laterally extended endopelvic resection (n=22, 50.0%), excision of para-aortic lymph node metastasis (n=8, 18.2%), and radical vaginectomy (n=1, 2.3%). Of the 44 patients in our cohort, 37 (84.1%) received IORT and 7 (15.9%) had intended to receive IORT but did not receive it. RESULTS: The median follow-up for the 44 patients was 12 months (range, 1 to 161 months). For patients who received IORT, the median progression-free survival (PFS) and overall survival (OS) were 13 and 21 months, respectively, and the 3-year cumulative incidence of central, locoregional, and distant recurrence was 27.0% (10 of 37), 40.5% (15 of 37), and 37.8% (14 of 37), respectively. Surgical margins were classified as negative (28 of 44, 63.6%), microscopic (11 of 44, 25.0%), or macroscopic (5 of 44, 11.4%). Negative, microscopic, and macroscopic surgical margins resulted in 3-year PFS of 51.8%, 20.5%, and 0%, respectively (P=.01) and 3-year OS of 62.9%, 20.0%, and 0%, respectively (P=.035). Progression-free survival (P=.69) and OS (P=.88) were not different between patients with negative surgical margins who received (n=21) and did not receive (n=7) IORT. Ten of 37 patients (27.0%) had development of grade 3 or higher toxicities, with 1 death due to sepsis. CONCLUSION: Complete tumor resection at the time of curative-intent radical extirpation achieved higher rates of PFS and OS regardless of IORT administration.

Retro cervical tunneling to ensure correct placement for robotic-assisted transabdominal cerclage.

OBJECTIVE: To demonstrate the step-by-step surgical technique of robotic-assisted transabdominal cerclage, highlighting a new posterior compartment approach. DESIGN: Stepwise explanation of a surgical technique using surgical video. SETTING: The procedure was performed at the Obstetrics and Gynecology Department, Hospital Vall d'Hebron in Barcelona, Spain, a tertiary medical center. The local institutional review board considers that case reports are exempt from research approval. PATIENT(S): A 26-year-old non-pregnant patient, with a history of cervical incompetence, three second-trimester losses, and vaginal cerclage failure during her previous pregnancy. INTERVENTION(S): Robotic-assisted transabdominal cerclage placement was performed. An 8-mm, 30° scope; monopolar scissors; and Maryland bipolar graspers were used. A uterine manipulator was used for better exposure. First, a bladder flap was created, and the uterine vessels were identified and skeletonized. Next, a window between the uterine vessels and the uterine cervix at the level of the cervical-isthmic junction was created bilaterally. At the posterior compartment, the dissection of the root of the uterosacral ligaments was carefully performed. A retrocervical pocket was created with monopolar scissors and sharp dissection. The procedure was finished with the Mersilene tape placement. First, the tape was passed through the window created in the right broad ligament, with a posterior-to-anterior direction, the retro cervical pocket, and finally through the left broad ligament. The knot was placed anteriorly and reperitonization was performed. In addition to this operation, robotic-assisted transabdominal cerclage was successfully performed in another six patients with good surgical and obstetrics outcomes. MAIN OUTCOME MEASURE(S): Intraoperative technique to ensure successful robot-assisted abdominal cerclage placement. RESULT(S): The patient became pregnant six months following the robotic-assisted transabdominal cerclage. Her pregnancy was closely followed up at the High-Risk Obstetric Unit, and she had no complications during pregnancy. An elective cesarean section was performed at 36 weeks with a healthy newborn baby that was discharged with the mother three days after delivery. CONCLUSION(S): The development of a retro cervical pocket during robotic-assisted transabdominal cerclage can be performed safely and effectively. It may help prevent displacement of the Mersilene tape during endoscopic knotting.

Comparing the effects of alcohol sclerotherapy with those of surgery on anti-Müllerian hormone and ovarian reserve after endometrioma treatment. A prospective multicenter pilot cohort study.

STUDY OBJECTIVE: To compare the effects of ultrasound-guided aspiration and ethanol sclerotherapy with those of laparoscopic surgery on anti-Müllerian hormone (AMH) levels and ovarian reserve in benign-appearing ovarian endometrioma. DESIGN: A prospective, cohort pilot study. SETTING: Multiple centers, Spain. PATIENTS: Forty patients with a suspected ovarian endometrioma with a maximum diameter of 35-100 mm. Serum hormonal concentrations were analyzed in 26 of these women. INTERVENTIONS: Two groups: one that received US-guided aspiration plus alcohol sclerotherapy (n = 16) and the other that underwent laparoscopic cystectomy (n = 10). MEASUREMENTS AND MAIN RESULTS: We studied serum hormonal concentrations (AMH, FSH and 17-ß-estradiol) and antral follicle counts (AFC) in each patient at baseline, and after the procedures and pregnancies. No differences were found when comparing AMH and FSH concentrations before and after each procedure. 17-ß-estradiol concentrations were significantly increased after alcohol sclerotherapy (p < 0.001). AFC recovery after 6 months seemed to be higher after sclerotherapy than after surgery. Three patients became pregnant in the sclerotherapy group. CONCLUSION: This pilot study indicated that alcohol sclerotherapy preserves fertility in patients with endometriomas better than surgery, with significant increases in serum estradiol concentrations, possible AFC recovery and spontaneous pregnancies observed in the patients after sclerotherapy.

Predictors of Postoperative Urinary Retention in Outpatient Minimally Invasive Hysterectomy.

STUDY OBJECTIVE: To identify risk factors associated with postoperative urinary retention in patients undergoing outpatient minimally invasive hysterectomy. DESIGN: A retrospective cohort study. SETTING: An academic medical center. PATIENTS: All patients undergoing outpatient minimally invasive hysterectomy between January 2013 and July 2018 were considered for inclusion in the study. INTERVENTIONS: Outpatient laparoscopic, vaginal, or robotically assisted laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS: Four hundred forty-four patients met the inclusion criteria. Postoperative urinary retention occurred in 94 patients, and 347 patients successfully passed their voiding trial in the postanesthesia care unit for a pass rate of 79%. Demographic characteristics were similar, except patients who experienced postoperative urinary retention were less likely to be menopausal (23.4% vs 34.7%, p = .038). Those with urinary retention received more perioperative opioids (morphine milligram equivalent of 14.4 mg vs11.2 mg, p = .012), had longer operative times (122.9 ± 55.6 vs 95.7 ± 42.3 minutes, p < .01), and experienced more blood loss (105.3 ± 134.4 vs 78.5 ± 86.8 mL, p = .025). The rate of urinary tract infections was similar. Logistic regression analysis showed that the route of hysterectomy and age were not associated with an increased risk for urinary retention, whereas a longer operative time and higher doses of perioperative opioid use were. CONCLUSION: In patients undergoing minimally invasive outpatient hysterectomy, a longer operative time and increased perioperative narcotic use increases the risk of postoperative urinary retention.

Robotic Excision of Full-thickness Diaphragmatic Endometriosis.

STUDY OBJECTIVE: To describe a robotic approach to excision of full-thickness diaphragmatic endometriosis. DESIGN: Surgical technique demonstration. SETTING: Symptomatic diaphragmatic endometriosis is commonly associated with lesions that are deeply invasive. In the presence of symptomatic diaphragmatic endometriosis, the posterior diaphragm should be explored. INTERVENTIONS: This video presents a systematic robotic approach to the excision of diaphragmatic endometriosis, highlighting key anatomic landmarks and technical considerations to complete the procedure safely and effectively. Resection of hepatic ligaments, use of a 30° endoscope, and right lateral access can be used to visualize this anatomic area [1]. The phrenic nerve is rarely identified during laparoscopy, if at all, and an inability to identify this structure during hemidiaphragm resection does not seem to result in significant patient morbidity. After diaphragm resection, the pleural cavity and lung should be systematically inspected to rule out the presence of additional endometriotic lesions. If the long axis of the diaphragmatic defect is parallel to the posterior chest wall and can be closed tension-free, then mesh is not necessary [1]. Insertion of a red rubber catheter into the thorax along with the use of negative pressure suction at the end of closure of the diaphragmatic defect may avoid use of a postoperative chest tube. CONCLUSION: The use of robotic assistance for resection of diaphragmatic endometriosis makes this procedure easy and safe to perform. Compared with ablative procedures, complete surgical excision offers higher rates of symptom improvement and resolution in patients with diaphragmatic endometriosis.

Mortality Rates in Benign Laparoscopic and Robotic Gynecologic Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: To review mortality rates in benign gynecologic minimally invasive laparoscopic and robotic surgery (MIS) and the rates associated with commonly performed MIS procedures. DATA SOURCES: An electronic-based search was performed on PubMed, Embase, Scopus, Web of Science, and Cochrane Database for articles published in the last 10 years in English, French, German, Spanish, and Italian. METHODS OF STUDY SELECTION: All MIS articles in benign gynecology reporting operative mortality (within 30 days) were reviewed. TABULATION, INTEGRATION, AND RESULTS: The articles identified through the aforementioned search criteria were independently evaluated by the first 2 authors. The Newcastle-Ottawa scale for observational studies and Cochrane risk-of-bias assessment tool for randomized controlled trials were used to assess the risk of bias. Meta-analysis was applied to calculate pooled mortality rates using the inverse-variance method. Twenty-one articles (124 216 patients) were included. Operative mortality from any benign MIS (laparoscopy and robotics) procedure was 1:6456 (95% confidence interval [CI]: 1:3946-1:10 562). Studies were then grouped based on the surgical procedure. The mortality rate for hysterectomy (119 721 patients), sacrocolpopexy, and adnexal surgery and diagnostic laparoscopy was 1:6814 (95% CI: 1:4119-1:11 275), 1:1246 (95% CI: 1:36-1:44 700), and 1:2245 (95% CI: 1:45-1:113 372), respectively. Eighteen articles reported operative mortality for laparoscopic surgery and 4 for robotic surgery. CONCLUSION: Operative mortality in benign minimally invasive gynecologic surgery is low, and mortality for laparoscopic and robotic approaches appears to be similar.

Mortality Rates in Laparoscopic and Robotic Gynecologic Oncology Surgery: A Systemic Review and Meta-analysis.

OBJECTIVE: To review early operative mortality (<30 days) for minimally invasive surgery (MIS), laparoscopic and robotic, in gynecologic oncology. DATA SOURCES: An electronic-based search was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Database in the last 10 years. METHODS OF STUDY SELECTION: All MIS studies in gynecologic oncology reporting operative mortality from any cause (within 30 days) were included. Studies were excluded if mortality was not reported for MIS or included benign gynecology. TABULATION, INTEGRATION, AND RESULTS: Meta-analysis was applied to calculate pooled mortality rates using the inverse-variance method. The relative risks and their corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method. Sixty-five studies were included (39 183 patients) for an operative mortality of 1:381 (95% CI, 1:306-1:474). Studies were subselected and analyzed by procedures, malignancy, and surgical approach. Of 39 183 patients, 38 619 underwent any type of hysterectomy for a mortality of 1:379 (95% CI, 1:304-1:472). The mortality was 1:281 (95% CI, 1:169-1:469) for a laparoscopic approach and 1:476 (95% CI, 1:365-1:620) for a robotic approach. There were 3369 patients with early cervical cancer undergoing radical hysterectomy with a mortality of 1:2049 (95% CI, 1:356-1:11 832). There were 3501 patients with endometrial cancer undergoing hysterectomy with lymph node dissection with a mortality of 1:195 (95% CI, 1:109-1:349). There were 418 patients with ovarian cancer undergoing MIS procedures with a mortality of 1 in 685 (95% CI, 1:44-1:10971). Eleven studies with 4037 patients compared mortality of gynecologic oncology surgery of any type (laparoscopic [1:626] vs robotic [1:716] for a relative risk of 1.12 [95% CI, 0.35-3.49]). CONCLUSION: The overall operative mortality for minimally invasive surgery in gynecologic oncology is 1 in 381 (95% CI, 1:306-1:474). For patients with early cervical cancer, it is 1:2049 (95% CI, 1:356-1: 11832), for endometrial cancer with node dissection it is 1:195 (95% CI, 1:109-1:349), and for ovarian cancer it is 1 in 685 (95% CI, 1:44-1:10 971). There is no difference between the type of MIS approach for patients undergoing any type of gynecologic oncology surgery.

Robotic Complete Excision of Sacrocolpopexy Mesh: Standardized Technique.

STUDY OBJECTIVE: To describe a standardized technique for robotic complete excision of sacrocolpopexy mesh. DESIGN: A step by step video demonstration of the technique. SETTING: A tertiary care academic hospital. PATIENTS: Three patients with persistent pain after sacrocolpopexy mesh insertion. Although exposure can usually be controlled with partial mesh removal, complete excision may be required for patients with persistent pain, exposure, or severe infection. Because of the inherent inflammation, fibrosis, and distortion of tissue planes with mesh augmentation, removal should be performed in a methodical fashion, preparing for possible visceral injury. INTERVENTION: Robotic-assisted sacrocolpopexy mesh removal. MEASUREMENTS AND MAIN RESULTS: This video (Video 1) presents a systematic, minimally invasive approach to sacrocolpopexy mesh removal, highlighting the technical and anatomic aspects that can facilitate the procedure. Retroperitoneal dissection along with identification of the anatomic landmarks, such as the sacral promontory, iliac vessels, right ureter, bladder, and rectum, are critical. Backfilling the bladder and the use of vaginal and rectal probes can also optimize difficult tissue planes. In each compartment, identifying the whole mesh before starting its removal may prevent leaving mesh fragments. The caudal to cranial and lateral to medial approach facilitates the extraction of the synthetic tissue. Removing the sacral mesh last allows the attachment to be used as a point of traction. Superior dissection of the mesh requires careful dissection and recognition of great vessels along with autonomic nervous structures such as the superior hypogastric plexus. CONCLUSION: Minimally invasive removal of sacrocolpopexy mesh can be standardized using this step by step approach.

Lgr5 Does Not Vary Throughout the Menstrual Cycle in Endometriotic Human Eutopic Endometrium.

Endometriosis is characterized by the abnormal presence of endometrium outside of the uterus, resulting in pelvic pain and infertility. The leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has been postulated to be a marker of stem cells in the endometrium. However, LGR5⁺ cells have a macrophage-like phenotype in this tissue, so it is unclear what role LGR5⁺ cells actually play in the endometrium. Macrophages serve an important function in the endometrium to maintain fertility, while LGR5⁺ cells generally have a role in tumor progression and are involved in invasion in some cancers. We sought to determine whether LGR5⁺ cells vary across the menstrual cycle in women with endometriosis and whether there are implications for LGR5 in the aggressiveness of endometriosis and reproductive outcomes. We performed immunofluorescence, flow cytometry, and primary culture in vitro experiments on eutopic and ectopic endometrium from healthy and endometriosis patients and observed that neither LGR5⁺ cells nor LGR5 expression varied throughout the cycle. Interestingly, we observed that LGR5⁺ cell percentage overexpressing CD163 (anti-inflammatory marker) was higher in healthy endometrium, suggesting that in endometriosis, endometrium presents a more pro-inflammatory phenotype that likely leads to poor obstetric outcomes. We also observed higher levels of LGR5⁺ cells in ectopic lesions compared to eutopic endometrium and specifically in deep infiltrating endometriosis, indicating that LGR5 could be involved in progression and aggressiveness of the disease.

Laparoscopic Isthmocele Repair with Hysteroscopic Assistance.

OBJECTIVE: To demonstrate our experience with hysteroscopic assistance in the laparoscopic repair of an isthmocele. DESIGN: Surgical video article (Canadian Task Force classification III). SETTING: University hospital. INTERVENTION: A 42-year-old woman with a history of previous caesarean section presented as an emergency with a large, seriously infected isthmocele. Once the infection was cured with antibiotics, sonography revealed a 23 × 14-mm isthmocele with 1.4-mm residual myometrium thickness. She reported postmenstrual spotting and dysmenorrhea of several years duration, as well as previous dyspareunia that had worsened after her cesarean section. Given her symptomatic isthmocele with thin residual myometrium and desire for childbearing, laparoscopic repair was offered. First, the bladder was dissected to expose the isthmus. Uterine arteries were dissected. Hysteroscopic guidance and transillumination revealed the edges of the defect. The isthmocele and fibrotic tissue were excised with cold scissors, minimizing cauterization. A hysterometer was placed in the uterine cavity to respect the cervical canal and posterior uterine wall, and the myometrium was then closed in 2 layers. The total surgical time was 120 minutes. The postoperative period was uneventful. At 2 months after surgery, sonography confirmed restoration, with a myometrium thickness of 8.3 mm. The patient was asymptomatic, except for dyspareunia. At 6 months after surgery, hysteroscopic examination was normal. We recommended that the patient avoid attempting pregnancy for 9 months. CONCLUSION: Hysteroscopic simultaneous assistance during laparoscopic isthmocele repair can be of great help in identifying the edges of the defect, especially in large cavities and in first cases, in which edges might not be clear otherwise. Resecting all of the fibrotic tissue while respecting healthy myometrium is essential. Excessive cauterization and ischemic suturing could prevent proper healing of the myometrium.

Aberrant expression of epithelial leucine-rich repeat containing G protein-coupled receptor 5-positive cells in the eutopic endometrium in endometriosis and implications in deep-infiltrating endometriosis.

OBJECTIVE: To characterize leucine-rich repeat containing G protein-coupled receptor 5-positive (LGR5+) cells from the endometrium of women with endometriosis. DESIGN: Prospective experimental study. SETTING: University hospital/fertility clinic. PATIENT(S): Twenty-seven women with endometriosis who underwent surgery and 12 healthy egg donors, together comprising 39 endometrial samples. INTERVENTION(S): Obtaining of uterine aspirates by using a Cornier Pipelle. MAIN OUTCOMES MEASURE(S): Immunofluorescence in formalin-fixed paraffin-embedded tissue from mice and healthy and pathologic human endometrium using antibodies against LGR5, E-cadherin, and cytokeratin, and epithelial and stromal LGR5+ cells isolated from healthy and pathologic human eutopic endometrium by fluorescence-activated cell sorting and transcriptomic characterization by RNA high sequencing. RESULT(S): Immunofluorescence showed that LGR5+ cells colocalized with epithelial markers in the stroma of the endometrium only in endometriotic patients. The results from RNA high sequencing of LGR5+ cells from epithelium and stroma did not show any statistically significant differences between them. The LGR5+ versus LGR5- cells in pathologic endometrium showed 394 differentially expressed genes. The LGR5+ cells in deep-infiltrating endometriosis expressed inflammatory markers not present in the other types of the disease. CONCLUSION(S): Our results revealed the presence of aberrantly located LGR5+ cells coexpressing epithelial markers in the stromal compartment of women with endometriosis. These cells have a statistically significantly different expression profile in deep-infiltrating endometriosis in comparison with other types of endometriosis, independent of the menstrual cycle phase. Further studies are needed to elucidate their role and influence in reproductive outcomes.