Cathepsin Protease Inhibition Reduces Endometriosis Lesion Establishment.

Endometriosis is a gynecologic disease characterized by the ectopic presence of endometrial tissue on organs within the peritoneal cavity, causing debilitating abdominal pain and infertility. Current treatments alleviate moderate pain symptoms associated with the disorder but exhibit limited ability to prevent new or recurring lesion establishment and growth. Retrograde menstruation has been implicated for introducing endometrial tissue into the peritoneal cavity, but molecular mechanisms underlying attachment and invasion are not fully understood. We hypothesize that cysteine cathepsins, a group of powerful extracellular matrix proteases, facilitate endometrial tissue invasion and endometriosis lesion establishment in the peritoneal wall and inhibiting this activity would decrease endometriosis lesion implantation. To test this, we used an immunocompetent endometriosis mouse model and found that endometriotic lesions exhibited a greater than 5-fold increase in active cathepsins compared to tissue from peritoneal wall or eutopic endometrium, with cathepsins L and K specifically implicated. Human endometriosis lesions also exhibited greater cathepsin activity than adjacent peritoneum tissue, supporting the mouse results. Finally, we tested the hypothesis that inhibiting cathepsin activity could block endometriosis lesion attachment and implantation in vivo. Intraperitoneal injection of the broad cysteine cathepsin inhibitor, E-64, significantly reduced the number of attached endometriosis lesions in our murine model compared to vehicle-treated controls demonstrating that cathepsin proteases contribute to endometriosis lesion establishment, and their inhibition may provide a novel, nonhormonal therapy for endometriosis.

Novel port placement and 5-mm instrumentation for robotic-assisted hysterectomy.

BACKGROUND AND OBJECTIVES: The value of robotic surgery for gynecologic procedures has been critically evaluated over the past few years. Its drawbacks have been noted as larger port size, location of port placement, limited instrumentation, and cost. In this study, we describe a novel technique for robotic-assisted laparoscopic hysterectomy (RALH) with 3 important improvements: (1) more aesthetic triangular laparoscopic port configuration, (2) use of 5-mm robotic cannulas and instruments, and (3) improved access around the robotic arms for the bedside assistant with the use of pediatric-length laparoscopic instruments. METHODS: We reviewed a series of 44 women who underwent a novel RALH technique and concomitant procedures for benign hysterectomy between January 2008 and September 2011. RESULTS: The novel RALH technique and concomitant procedures were completed in all of the cases without conversion to larger ports, laparotomy, or video-assisted laparoscopy. Mean age was 49.9 years (SD 8.8, range 33-70), mean body mass index was 26.1 (SD 5.1, range 18.9-40.3), mean uterine weight was 168.2 g (SD 212.7, range 60-1405), mean estimated blood loss was 69.7 mL (SD 146.9, range 20-1000), and median length of stay was <1 day (SD 0.6, range 0-2.5). There were no major and 3 minor peri- and postoperative complications, including 2 urinary tract infections and 1 case of intravenous site thrombophlebitis. Mean follow-up time was 40.0 months (SD 13.6, range 15-59). CONCLUSION: Use of the triangular gynecology laparoscopic port placement and 5-mm robotic instruments for RALH is safe and feasible and does not impede the surgeon's ability to perform the procedures or affect patient outcomes.

Office visceral slide test compared with two perioperative tests for predicting periumbilical adhesions.

OBJECTIVE: To determine whether the office visceral slide test is an effective screening test for predicting obliterating periumbilical adhesions compared with two ultrasound tests performed in the operating room. METHODS: Women undergoing benign laparoscopic gynecologic surgery between July 2012 and August 2013 were invited to participate. All participants had an office-based ultrasound test at their preoperative visit (the office visceral slide test), two operating room ultrasound tests (the preoperative examination with visceral slide and the periumbilical ultrasound-guided saline infusion test), and then their scheduled laparoscopic procedure. We measured the ability of the three screening tests to detect obliterating periumbilical adhesions. RESULTS: Eighty-two women completed the study; 12 women were excluded because they had no history of surgery and 70 women with a history of abdominal and pelvic surgery were analyzed in the study group. The study group (n=70) had a median of two (range, 1-6) previous abdominal surgeries. The median number of previous laparotomies was 0 (range, 0-5). The median number of previous laparoscopies was 1 (range, 0-6). At laparoscopy, 6 of 70 women (8.6%) had periumbilical adhesions diagnosed; 18 of 70 women (25.7%) had any adhesions located in the abdomen or pelvis. The office visceral slide test had a sensitivity of 83.3%, specificity of 100%, positive predictive value of 100%, negative predictive value of 98.5% and diagnostic accuracy of 98.6%. CONCLUSION: The office visceral slide test is a simple and reliable test for detecting obliterating periumbilical adhesions in the outpatient setting. LEVEL OF EVIDENCE: II.