METHODS: Asian women received dienogest (2 mg/daily) and were followed for 24 months. The effectiveness of dienogest to improve HRQoL and endometriosis-associated pelvic pain (EAPP) was assessed by patient-reported outcomes. HRQoL, especially the "pain" domain as primary endpoint, was evaluated with the Endometriosis Health Profile-30 (EHP-30) questionnaire. The numeric rating scale served to determine changes in the severity of EAPP. Within the presented interim analysis (data cut-off: 2017-11-27), the mean changes in EHP-30 and EAPP scores from baseline to 6 months upon availability of the data were evaluated. Treatment-emergent adverse events (TEAEs) and bleeding profiles were documented.
RESULTS: Dienogest therapy decreased EHP-30 scores in all assessed domains (score 0-100, lower scores indicate better HRQoL). Primarily, the "pain" domain was improved in 78.4% of patients. EAPP was reduced (score 0-10, lower scores reflect less pain), highlighted by a mean reduction of the pain score by - 4.5 points. Patients with a higher EAPP score at baseline had an increased response to dienogest (- 6.2 points mean change) compared to patients with low baseline EAPP severity (- 1.4 points mean change). Both surgically and clinically diagnosed patients described comparable pain reduction, as well as women with or without prior treatment. Drug-related TEAEs were documented for 31.5% of patients, with amenorrhoea (5.9%) and metrorrhagia (5.1%) being the most common events. The bleeding pattern was changed upon dienogest, characterized by decreased normal bleeding (84.2 to 28.8%) and increased amenorrhea (3.2 to 42.9%) at 6 months.
CONCLUSION: The data indicate an amelioration of HRQoL and EAPP upon dienogest therapy. No new safety signals were observed. Therefore, its use as first-line therapy for long-term management of debilitating and chronic endometriosis-associated pain represents an interesting option that remains to be further investigated.
TRIAL REGISTRATION: Name of registry: Clinical Trials Clinicaltrials.gov registration number: NCT02425462 Registration date: 2015-04-24. Registration timing: prospective.
DESIGN: Excision of bladder endometriosis by first delineating the tumor via cystoscopy and simultaneously excising the nodule laparoscopically SETTING: Mahkota Medical Centre, Melaka, Malaysia.
INTERVENTION: Here we describe a simultaneous cystoscopic and laparoscopic excision of bladder endometriosis. The patient was first seen in 2005 at age 19 years with an endometrioma. She was single (virgo intacta) at that time. She underwent a laparoscopic cystectomy. Postoperatively, she received 3 doses of monthly gonadotropin-releasing hormone (GnRH) analogue injection. She was last seen in 2006 and was well. She conceived spontaneously after that and delivered 2 babies spontaneously in 2007 and 2010 in another city. She consulted me again in April 2016 complaining of dysuria, dysmenorrhea, and inability to hold her urine. She had consulted a urologist 6 months earlier. Cystoscopy performed by the urologist showed bladder endometriosis. No further surgery was performed, and she was given GnRH analogues for 6 months. However, her symptoms persisted after completion of the GnRH analogue. Examination and ultrasound showed a large bladder nodule measuring 4.17 × 2.80 cm. Intravenous urogram showed stricture in the upper right ureter. She underwent a combined urology and gynecology surgery to excise the bladder nodule. Informed consent was obtained from the patient, and the local institutional board provided the approval. The surgery was performed with the patient in the dorsosacral position. A Verres needle was inserted into the abdomen at the umbilicus, and carbon dioxide insufflation was performed. A 10-mm trocar was inserted in the umbilicus, and a 3-dimensional laparoscope (Aesculup-BBraun Einstein Vision; BBraun, Melsungen AG, Germany) was inserted to view the pelvis. Three 5-mm trocars were inserted, 1 on the right side and 2 on the left side of the abdomen. A RUMI (CooperSurgical, Trumbull, CT) uterine manipulator was placed into the uterine cavity. Laparoscopy showed no adhesions in the upper and mid-abdomen. The appendix and the intestines looked normal. Both the ovaries and fallopian tubes were normal. Uterine insufflation with methylene blue showed that both tubes were patent. There was dense endometriosis between the bladder and fundus of the uterus. The omentum was also adherent to the site of the endometriosis. There were endometriotic nodules on the left uterosacral ligaments and the peritoneum in the wall in the pouch of Douglas. The omentum was released, and laparoscopic adhesiolysis was performed. Both the paravesical spaces lateral to the nodule were dissected out. The bladder was released from the uterus with some difficulty. The peritoneal endometriosis in the Pouch of Douglas and the nodules in the left uterosacral ligament were excised. Cystoscopy was performed and stents were first placed in both ureters. The nodule was found to be in the central position, and the margins were about 2 cm from both the ureteral orifices. The nodule was seen protruding into the bladder containing bluish lesions. Demarcation of the bladder endometriosis was done using a resectoscope. Using a needle electrode, a deep circular incision was made around the bladder nodule and into the detrusor muscle. Cystoscopic perforation of the bladder was done and was seen laparoscopically. The bladder endometriotic nodule was completely excised laparoscopically after the demarcation line created via the cystoscopy. Stay sutures were first placed at the superior and inferior edges of the defect. The bladder was repaired continuously in 1 layer using polyglactin 3-0 sutures. The nodule was placed in a bag cut into smaller pieces and removed through the umbilical incision. At the end of the surgery a cystoscopy was perform to check the integrity of the suture. The pelvis was then washed. A bladder catheter was placed. The trocars were then removed under vision, and the rectus sheath was closed using polyglactin 1 suture. The skin incisions were closed. The operation time was 2 hours. The patient received antibiotics for 10 days. She was discharged with a catheter in place on day 3. She underwent a cystogram on day 10 of the surgery, and the bladder was found to be intact. The catheter was then removed. She was seen 6 weeks after the surgery and was well without any symptoms. The ureteric catheters were removed. Histopathology confirmed bladder endometriosis. Five months later she conceived spontaneously and delivered her third child naturally in June 2017. She was seen after her delivery and was advised to take oral contraceptive pills continuously or an intrauterine contraceptive device to prevent recurrence of the endometriosis. She took the oral contraceptive pills for 3 months and then refused any further treatment. She was last seen in February 2019 and was well without any symptoms.
CONCLUSION: In bladder endometriosis a combined approach with the urologist can assist in safely excising deep bladder endometriosis without removal of normal bladder tissue. Stents placed in the ureter assist in avoiding injury to the ureters. Demarcating the endometriotic nodule by the urologist through the bladder and excising the bladder nodule laparoscopically is both safe and effective.