Laparoscopic-Assisted Vaginal Hysterectomy With Dense Bladder Adhesions and Absent Cervix: A Case Report With a Descriptive Video of the Entire Procedure.

Hysterectomy is one of the most frequently performed surgical procedures in the United States. Hysterectomy for benign gynecological reasons can be performed through several approaches: abdominal, laparoscopic, laparoscopically assisted vaginal, robotic-assisted, and vaginal natural orifice hysterectomy. The choice of approach is strongly influenced by factors such as previous procedures, safety, and recovery process. Currently, vaginal hysterectomy, laparoscopic-assisted vaginal hysterectomy (LAVH), assisted vaginal hysterectomy, and robotic-assisted vaginal hysterectomy are considered minimally invasive approaches with multiple benefits to the patient such as less trauma, shorter operative time, and shorter postoperative period. However, in patients with pelvic adhesions, adhesions within the abdominal cavity, especially omental adhesions to the abdominal wall, and adhesions between the uterus and the bladder caused by multiple cesarian sections or prior surgery on the cervix, these minimally invasive approaches are problematic. In this report, we describe in detail our approach to LAVH in a patient with severe abdominal adhesions and an absent cervix. We believe that our approach is safe and relatively fast compared to an open abdominal procedure and, therefore, it may help gynecologic surgeons-in-training nationwide.

Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer.

High-grade serous ovarian cancer (HGSOC) is often sensitive to initial treatment with platinum and taxane combination chemotherapy, but most patients relapse with chemotherapy-resistant disease. To systematically identify genes modulating chemotherapy response, we performed pooled functional genomic screens in HGSOC cell lines treated with cisplatin, paclitaxel, or cisplatin plus paclitaxel. Genes in the intrinsic pathway of apoptosis were among the top candidate resistance genes in both gain-of-function and loss-of-function screens. In an open reading frame overexpression screen, followed by a mini-pool secondary screen, anti-apoptotic genes including BCL2L1 (BCL-XL) and BCL2L2 (BCL-W) were associated with chemotherapy resistance. In a CRISPR-Cas9 knockout screen, loss of BCL2L1 decreased cell survival whereas loss of proapoptotic genes promoted resistance. To dissect the role of individual anti-apoptotic proteins in HGSOC chemotherapy response, we evaluated overexpression or inhibition of BCL-2, BCL-XL, BCL-W, and MCL1 in HGSOC cell lines. Overexpression of anti-apoptotic proteins decreased apoptosis and modestly increased cell viability upon cisplatin or paclitaxel treatment. Conversely, specific inhibitors of BCL-XL, MCL1, or BCL-XL/BCL-2, but not BCL-2 alone, enhanced cell death when combined with cisplatin or paclitaxel. Anti-apoptotic protein inhibitors also sensitized HGSOC cells to the poly (ADP-ribose) polymerase inhibitor olaparib. These unbiased screens highlight anti-apoptotic proteins as mediators of chemotherapy resistance in HGSOC, and support inhibition of BCL-XL and MCL1, alone or combined with chemotherapy or targeted agents, in treatment of primary and recurrent HGSOC. IMPLICATIONS: Anti-apoptotic proteins modulate drug resistance in ovarian cancer, and inhibitors of BCL-XL or MCL1 promote cell death in combination with chemotherapy.