Experimental and new investigational drugs for the treatment of uterine fibroids.

INTRODUCTION: Uterine fibroids, the most prevalent benign tumors among reproductive-age women, pose treatment challenges that range from surgical interventions to medical therapies for symptom control. Progestins and estroprogestins effectively manage uterine bleeding by suppressing dysfunctional endometrium over fibroids. While GnRH agonists represent a crucial milestone in symptom treatment, their prolonged use results in menopausal-like symptoms and irreversible bone mineral density loss. Advancements in understanding fibroid pathophysiology have prompted the exploration of new compounds to overcome current therapy limitations. AREAS COVERED: This manuscript offers an updated overview of investigational drugs for symptomatic uterine fibroids. EXPERT OPINION: Despite ulipristal acetate's well-established efficacy as a selective progesterone receptor modulator (SPRM) in fibroid treatment, its prescription has declined due to the rare but severe risk of liver damage. Oral GnRH antagonists, like elagolix, relugolix, and linzagolix, with their novel pharmacodynamic properties, are gaining traction in fibroid management, inducing a dose-dependent reduction in circulating sex hormone levels. Ongoing research on natural compounds, such as vitamin D and epigallocatechin gallate (EGCG), presents emerging options for treating uterine fibroids. This evolving landscape reflects the ongoing efforts to improve therapeutic outcomes for individuals with symptomatic uterine fibroids.

How challenging could be preoperative and intraoperative diagnosis of endometrial cancer?

BACKGROUND: Aim of this study was to rate the misdiagnosis of histological type between preoperative endometrial biopsy and final postoperative pathology focusing on non-endometrioid endometrial cancer (NEEC). Secondary objective is to assess the concordance between intraoperative assessment and final pathology in a subgroup of patients. METHODS: A multicenter retrospective study was conducted in patients with histological diagnosis of endometrial cancer who underwent surgical staging between 2011 and 2016. The concordance rate and the Kappa Cohen coefficient were calculated to assess the correlation concerning the histological type between endometrial biopsy and final pathology, and between intraoperative assessment and final pathology in a subgroup of patients. RESULTS: Two hundred ninety-five patients were enrolled, 226 were endometrioid carcinomas and 61 NEEC at final pathology. The concordance rate between pre-operative and final pathology for NEEC and the Kappa Cohen coefficient were 81.4% and 0.41 (CI 95% 0.3059-0.5122), respectively. 26 out of 61 (42.6%) NEEC were preoperatively misdiagnosed. The frozen section was performed in a subgroup of 86 patients (29.15%): the concordance rate between frozen section and final pathology for NEEC was 80% and the Kappa Cohen coefficient was 0.28 (CI 95% 0.212-0.347). CONCLUSIONS: Preoperative pathological histotype assessment predicts final pathology with a moderate grade of accuracy and the identification of NEEC could be challenging. Efforts should be directed toward molecular characterization of diagnostic samples in order to improve diagnostic accuracy and guide therapeutic decisions.

The effect of a uterine manipulator on the recurrence and mortality of endometrial cancer: a multi-centric study by the Italian Society of Gynecological Endoscopy.

BACKGROUND: Although widely adopted, the use of a uterine manipulator during laparoscopic treatment of endometrial cancer represents a debated issue, and some authors hypothesize that it potentially may cause an increased risk of relapse, particularly at specific sites. OBJECTIVE: Our aim was to evaluate the risk and site of disease recurrence, overall survival, and disease-specific survival in women who had laparoscopic surgery with and without the use of a uterine manipulator. STUDY DESIGN: Data were reviewed from consecutive patients who had laparoscopic surgery for endometrial cancer staging in 7 Italian centers. Subjects were stratified according to whether a uterine manipulator was used during surgery; if so, the type of manipulator was identified. Multivariable analysis to correct for possible confounders and propensity score that matched the minimize selection bias were utilized. The primary outcome was the risk of disease recurrence. Secondary outcomes were disease-specific and overall survival and the site of recurrence, according to the use or no use of the uterine manipulator and to the different types of manipulators used. RESULTS: We included 951 patients: 579 patients in the manipulator group and 372 patients in the no manipulator group. After a median follow-up period of 46 months (range,12-163 months), the rate of recurrence was 13.5% and 11.6% in the manipulator and no manipulator groups, respectively (P=.37). Positive lymph nodes and myometrial invasion of >50% were associated independently with the risk of recurrence after adjustment for possible confounders. The use of a uterine manipulator did not affect the risk of recurrence, both at univariate (odds ratio, 1.18; 95% confidence interval, 0.80-1.77) and multivariable analysis (odds ratio, 1.00; 95% confidence interval, 0.60-1.70). Disease-free, disease-specific, and overall survivals were similar between groups. Propensity-matched analysis confirmed these findings. The site of recurrence was comparable between groups. In addition, the type of uterine manipulator and the presence or not of a balloon at the tip of the device were not associated significantly with the risk of recurrence. CONCLUSION: The use of a uterine manipulator during laparoscopic surgery does not affect the risk of recurrence and has no impact on disease-specific or overall survival and on the site of recurrence in women affected by endometrial cancer.

Laparoscopic vs. open treatment of endometrial cancer in the elderly and very elderly: An age-stratified multicenter study on 1606 women.

Objective To investigate in depth the effect of increasing age on the peri-operative outcomes of laparoscopic treatment for endometrial cancer, compared to open surgery, with stratification of patients according to the different definitions of elderly age used in the literature. METHODS: Data of consecutive patients who underwent surgery for endometrial cancer staging at six centers were reviewed and analyzed according to surgical approach (laparoscopic or open), different definitions of elderly and very elderly age (≥65years, ≥75years, ≥80years), and class of age (<65; ≥65-<75; ≥75-80; ≥80years). Multivariable analysis to correct for possible confounders and propensity-score matching to minimize selection bias were used. RESULTS: A total of 1606 patients were included: 938 and 668 patients received laparoscopic and open surgery, respectively. With increasing age, fewer patients received laparoscopy (P<0.001 with ANOVA). The percentage of patients who received lymphadenectomy declined significantly in both groups for age ≥80years. Blood transfusions, incidence and severity of post-operative complications, and hospital stay were significantly lower among patients who had laparoscopy both in younger (<65years) and elderly (whether defined as ≥65 or ≥75years) patients, with no effect of age on any of the characteristics analyzed ( ANOVA: P>0.05). The same tendency was observed among very-elderly patients (≥80years). Multivariable and propensity score-matched analysis confirmed these findings. CONCLUSIONS: Laparoscopy for staging endometrial cancer retains its advantages over open surgery even in elderly and very-elderly patients. Our data strongly suggest that minimally-invasive surgery is advantageous even among subjects ≥80years.

Complications after the treatment of endometrial cancer: a prospective study using the French-Italian glossary.

INTRODUCTION: The evaluation of treatment complications is crucial in modern oncology because they heavily influence the every day life of patients. Several authors confirmed the reproducibility of the French-Italian glossary to score the complications in patients with endometrial cancer after radiotherapy (RT), but the treatment of endometrial carcinoma is primarily surgical and chemotherapy is often used for high-risk disease. OBJECTIVES: This study aimed to analyze the incidence of complications in our patients treated for endometrial cancer and to verify whether the glossary is a suitable instrument in the description of complications after surgery, RT, and chemotherapy. METHODS: The data of patients affected by endometrial cancer treated in the Gynecology and Obstetrics Academic Department, Azienda Ospedaliera Mauriziano Umberto I in Turin from 2000 to 2009 (with surgery alone or integrated treatments) were prospectively collected, and complications were described using the glossary. Every patient included in the analyses had a minimum of 18 months follow-up. RESULTS: Of the 271 patients, 68 (25%) experienced at least 1 complication with 87 overall complications. Most of the complications were mild (63%) and were found in the urinary (30%) or cutaneous systems (30%). Forty-four (50%) complications appeared within 1 year after treatment, but 9 (10%) complications appeared after 60 months of follow-up. Patients who were submitted to both surgery and RT showed a trend of higher rate of at least 1 complication (19/58 [32.7%]) if compared with surgery alone (36/135 [26.6%]), even if the difference was not statistically significant (P = 0.09). The incidence of complications in patients treated or not with lymphadenectomy was not statistically different (P = 0.088), whereas patients treated with laparotomy had a higher rate of cutaneous complications if compared with the laparoscopic approach (P = 0.018). The glossary included all observed complications. CONCLUSIONS: One every 4 women treated for endometrial cancer develops a complication. Clinicians should check for complications especially after integrated treatments maintaining surveillance even in the long term. The glossary is a comprehensive instrument to describe the complications of endometrial cancer, regardless of the type of treatment delivered.

Retroperitoneal and retrograde total laparoscopic hysterectomy as a standard treatment in a community hospital.

OBJECTIVE: To report our experience with a modified procedure for total laparoscopic hysterectomy based on a retrograde and retroperitoneal technique. This surgical approach is analyzed on a consecutive series of patients in a community hospital and theoretical educational advantages are proposed. STUDY DESIGN: All patients undergoing hysterectomy from January 2012 to April 2013 were included in the study. A detailed description of the technique is given. As main outcome measures we evaluated: the number and rate of patients excluded from laparoscopic approach, the rate of late complications need readmission, the rate of transfusions, the rate of conversion to laparotomy and the number of minor complications. The main concern of the study was ureteral complications. RESULTS: Overall 174 patients underwent hysterectomy in our unit. The rate of patients submitted to laparoscopic hysterectomy was 97.5%. The number of complications needing re-admission was three (2%). The rate of conversion was 2.7%. In the study period, two (1.2%) ureteral complications were observed (late fistulae). There were four bladder lesions but the patients were released on the same day as the patients with no lesion. CONCLUSIONS: Opening the retroperitoneum allows rapid control of the main uterine vessels by coagulation, and constant checks on the ureter. Difficult benign situations can be managed. Even in a non-referral center about 94% of hysterectomies can be performed by laparoscopic surgery. This approach is helpful and may be reproducible in gynecological procedures.

Suspecting malignancy in endometrial polyps: value of hysteroscopy.

AIMS AND BACKGROUND: Hysteroscopic polypectomy is the gold standard to treat endometrial polyps and obtain specimens for histological evaluation. There is continuing debate as to when to offer hysteroscopic polypectomy, especially in asymptomatic women with incidental lesions. The aims of this study were to assess the accuracy of hysteroscopy and Vabra sampling in diagnosing atypical hyperplasia and cancer growing on the surface of endometrial polyps and to investigate the association between atypical endometrial polyps and some potential clinical risk factors. METHODS AND STUDY DESIGN: This was a retrospective study. We assessed 1039 hysteroscopies and we identified 345 women with endometrial polyps. All patients with endometrial polyps underwent hysteroscopic polypectomy. Data about age, menopausal status, abnormal uterine bleeding (AUB), hormone replacement therapy and tamoxifen use were collected. Hysteroscopic, histological and clinical data were analyzed. RESULTS: The incidence of endometrial hyperplasia or cancer growing on the surface of endometrial polyps was significantly low (1.7%). Hysteroscopy correctly excluded (negative predictive value: 100%) and accurately predicted (positive predictive value: 85.7%) preneoplastic or neoplastic lesions growing within the epithelial layer of endometrial polyps. Vabra sampling was inadequate for the histological diagnosis in 38.5% of cases. Age over 60 years and postmenopausal AUB were associated with an 8.3-fold ( P = 0.022) and 8.8-fold (P = 0.020) increased risk, respectively, of preneoplastic and neoplastic lesions growing on the surface of endometrial polyps. CONCLUSIONS: Diagnostic hysteroscopy is a good tool to predict malignancy of the epithelial layer of endometrial polyps. Age over 60 years and AUB are associated with an increased risk of malignant polyps. Few suspicious endometrial polyps should undergo surgical resection.

Laparoscopic sacropexy and obstructed defecation syndrome: an anatomoclinical study.

INTRODUCTION AND HYPOTHESIS: Laparoscopic sacropexy (LSP) is associated with obstructed defecation syndrome (ODS) in 10-50% of cases. An anatomoclinical study was carried out to investigate whether there is any correlation between iatrogenic denervation during LSP and ODS. METHODS: Five female cadavers were dissected to identify possible sites of nerve injury during LSP. Subsequently, the videos of 18 LSP were blindly reviewed to assess the location of sacral dissection and tacks, the position and depth of the peritoneal tunnel, and another 4 variables. An anatomical triangle was defined on the right lumbosacral spine so as to clearly describe the sites of the surgical variables, which were then statistically correlated with the patients' postoperative outcome. RESULTS: The only variable associated with postsurgical ODS was dissection in the 90° angle of the anatomical triangle, where the superior hypogastric plexus was observed in all cadavers. CONCLUSIONS: Medial and midline dissection over the sacral promontory might be associated with postoperative ODS.

Ovarian lymphoma and hydronephrosis.

INTRODUCTION: Ovarian lymphoma is a rare entity, and hydronephrosis from lymphoma is even rarer. Most reports describe a laparoscopic approach to the disease, but we report a case of hydroureteronephrosis associated with ovarian lymphoma managed completely by miniinvasive techniques. CASE REPORT: A 51-year-old woman was referred to us for back pain and renal colic and computed tomography scan findings of right hydroureteronephrosis and a mass in the right mesorectum and uterosacral ligament. After magnetic resonance imaging was performed, the patient underwent laparoscopic adnexectomy and ureterolysis after ureteroscopy and stenting. Histology results showed diffuse B-cell lymphoma of the ovary occluding the ureter without infiltration. The patient has undergone 6 cycles of chemotherapy. DISCUSSION: This is the first report to describe ovarian lymphoma and hydroureteronephrosis managed completely by laparoscopic surgery and endoscopy. Frequency in clinical practice, differential diagnosis, and endoscopic approach are discussed. The advantages of a multidisciplinary endoscopic team are underlined.

The retrograde and retroperitoneal totally laparoscopic hysterectomy for endometrial cancer.

Introduction. We retrospectively report our experience with the utilization of an original procedure for total laparoscopic hysterectomy based on completely retrograde and retroperitoneal technique for surgical staging and treatment of the endometrial cancer. The surgical, financial, and oncological advantages are here discussed. Methods. The technique used here has been based on a combination of a retroperitoneal approach with a retrograde and lateral dissection of the bladder and retrograde culdotomy with variable resection of parametrium. No disposable instruments and no uterine manipulator were utilized. Results. Intraoperative and postoperative complications were observed in 10% of the cases overall. Operative time length and mean haemoglobin drop value results were 129 min and 125 mL, respectively. Most patients were dismissed on days 3-5 from the hospital. Seventy-eight percent of the patients were alive with no evidence of disease at mean followup of 49 months. Conclusions. Our original laparoscopic technique is based on a retroperitoneal approach in order to rapidly control main uterine vessels coagulation, constantly check the ureter, and eventually decide type and site of lymph nodes removal. This procedure has important cost saving implications and the avoidance of uterine manipulator is of matter in case such as these of uterine malignancy.

Laparoscopic bipolar coagulation of hypogastric artery in postpartum haemorrhage: a case report.

Background. Postpartum haemorrhage (PPH) is a significant contributor to worldwide maternal morbidity and mortality. When PPH continues despite aggressive medical treatment, early consideration should be given to surgical intervention. Various surgical interventions may be used but conservative interventions are recommended primarily. Case. This case report describes laparoscopic coagulation of hypogastric artery technique in a patient with PPH. Conclusions. Laparoscopic ligature of the hypogastric artery for PPH treatment can be a valid alternative to laparotomy in patients with vaginal delivery.

A comparison of urinary complications following total laparoscopic radical hysterectomy and laparoscopic pelvic lymphadenectomy to open abdominal surgery.

OBJECTIVE: The objective of this study was to compare total laparoscopic radical hysterectomy (TLRH) and laparoscopic pelvic lymphadenectomy (LPS) to total abdominal radical hysterectomy (TARH) and pelvic lymphadenectomy (LPT) in terms of urinary tract lesions and postoperative urinary retention. METHODS: Starting in 2004, we treated all early stage cervical cancer patients with TLRH and LPS. The control group for this analysis was a historical cohort of patients treated with TARH+LPT. Within the TLRH+LPS group, we assessed whether the width of parametrial tissue removed was a risk factor for urinary tract injuries or postoperative urinary retention. RESULTS: Fifty women were included in the TLRH+LPS group and forty-eight were included in the TARH+LPT group. There were no conversions from laparoscopy to laparotomy. There was no statistically significant difference in intraoperative urinary complications between the groups. Four (8%) intraoperative urinary tract injuries in the LPS (3 cystotomies and 1 ureteral lesions all repaired laparoscopically) and 2 (4.2%) in the LPT group (2 cystotomies) occurred (p=0.68). Similarly, there was no statistically significant difference in postoperative urinary complications between groups. Urinary postoperative complications were: 1 (2%) ureterovaginal and 1 vesicovaginal fistulas, 1 delayed ureteric fistula in LPS group vs. 0 in LPT group (p=0.24). Urinary retention was complained by 7 (14%) and 7 (14.6%) patients in LPS and LPT groups respectively (p=1.00). The average width of parametrial tissue removed in the LPS group was 32.2+14.0 mm in patients with vs. 39.5+13.6 mm in patients without urinary complications (p=0.11). CONCLUSIONS: A laparoscopic approach is comparable to the laparotomy in terms of urinary lesions and postoperative retention. The width of parametrium removed does not affect the risk of urinary lesions or postoperative retention.

Surgicopathologic outcome of laparoscopic versus open radical hysterectomy.

OBJECTIVE: To compare the surgicopathologic outcome of total laparoscopic radical hysterectomy (LRH) with that of abdominal radical hysterectomy (ARH) for the treatment of early-stage cervical cancer. METHODS: Radical hysterectomy specimens of sequential patients undergoing LRH (N=50) were compared with those of historical controls selected from consecutive women who have had conventional ARH (N=48), and who met the same criteria for eligibility as the cases. To evaluate the extent of parametrial resection, parametrial tissues were systematically measured at their widest dimensions before tissue processing. RESULTS: No difference was found in demographics, histologic type, tumor stage and grade between the two groups. The parametrial width was similar between LRH and ARH in both type II (right parametrium: 2.4 cm (1-3) vs. 2.3 (1.8-4.0), p=0.28; left parametrium: 2.3 cm (1.8-4) vs. 2.2 (1.2-3.0), p=0.54) and type III radical hysterectomy (right parametrium: 3.8 cm (2.3-6.5) vs. 3.4 (1.7-7.0), p=0.59; left parametrium: 3.6 cm (2-6) vs. 3.5 (1.5-6.5), p=0.82). There were no significant differences between the two groups with regard to lymph nodes yield and likelihood of identifying positive margins or metastatic disease. CONCLUSION: Our results suggest that laparoscopically managed patients with cervical cancer undergo a similar extent of surgery as those treated with the traditional ARH, as judged by objective pathologic criteria.

Laparoscopic treatment of endometrial cancer: feasibility and results.

OBJECTIVE: The aim of this study was to compare laparoscopic and abdominal approach in the treatment of endometrial cancer in our department. STUDY DESIGN: From January 1999 to November 2002, 77 patients underwent surgery for stages I-III endometrial cancer. The first group of 36 patients had abdominal hysterectomy as well as salpingo-oophorectomy, with or without lymphadenectomy. The remaining 41 patients received laparoscopic assisted vaginal hysterectomy as well as salpingo-oophorectomy, with or without lymphadenectomy. In this retrospective study, we have compared the surgical results, the short- and long-term morbidity and the outcome of the two patient groups. RESULTS: Body mass index (BMI) was significantly higher in the laparoscopic group (27.3 versus 24.6; p=0.009). The average time for surgery was significantly longer for the laparoscopic group (143.6 min versus 109.7 min; p=0.0001), but lymphadenectomy was performed in more patients (63.4% versus 25%; p=0.001). Postoperative hospital stay was significantly longer in patients undergoing the abdominal approach (4.59 days versus 3.18 days; p<0.0001). No blood transfusions were performed and the rates of complications were similar in the two groups. No differences were found in recurrence and survival rate. CONCLUSIONS: In our experience, laparoscopic and abdominal surgery can achieve similar results in the treatment of endometrial cancer. In our series, even with the BMI and the number of lymphadenectomies being higher in the laparoscopic group, the rates of complications were similar in the two groups.

Laparoscopic neurolysis of the pelvic sciatic nerve in a case of catamenial footdrop.

Isolated cases of cyclic sciatica associated with endometriosis have been reported since the 1940s. Surgical intervention, either by laparoscopy for lesions within the pelvis or by open procedures for extrapelvic lesions, has usually been performed. A 37-year-old woman with catamenial footdrop and pain of the right thigh came to our observation. Previously, she underwent laparoscopy for bilateral ovarian endometriomas. In a second laparoscopy, we removed her uterosacral right ligament and recto-vaginal endometriotic nodules. After a temporary improvement, a third surgical procedure was necessary: laparoscopic neurolysis to free the sciatic nerve from fibrotic tissue. Then the patient was treated with gonadotropin-releasing hormone analogs for 6 months, and she is free of symptoms 2 years after last surgery. This is the first described case of laparoscopic neurolysis of the proximal sciatic nerve. The procedure has been successful in treating a patient with endometriosis in whom the cause of the syndrome was probably due to entrapment of the nerve in fibrous tissue.

Genital and peritoneal tuberculosis: potential role of laparoscopy in diagnosis and management.

Genital and peritoneal tuberculosis are rare in developed countries and can mimic ovarian cancer. We report two different cases that came to our attention, both in a month. The first patient was referred to us for an asymptomatic pelvic mass. The second patient came to us because of weight loss, abdominal swelling, and ascites. Unfortunately, the imaging findings were misleading, and the laboratory analyses were not helpful. Only the laparoscopic approach was useful for final diagnosis. We conclude that the symptoms of abdominal tuberculosis vary greatly, and laparoscopy can be essential for its diagnosis and management.