Ureterolysis in Laparoscopic Total Hysterectomy: Routine Approach; A Parallel Multicenter Randomized Controlled Trial. (ULTRA) Mega Trial
Ureterolysis in Laparoscopic Total Hysterectomy: Routine Approach; A Parallel Multicenter Randomized Controlled Trial. (ULTRA) Mega Trial
This randomized controlled trial will compare routine bilateral ureterolysis with selective ureterolysis during total laparoscopic hysterectomy for benign gynecological conditions. Participants will be allocated to either routine ureter identification and dissection before uterine vessel ligation or selective ureterolysis performed only when predefined intraoperative safety triggers are present. The primary outcome will be the incidence of recognized and unrecognized ureteric injury, while secondary outcomes will include operative time, blood loss, other perioperative complications, conversion to laparotomy, length of hospital stay, and postoperative recovery.
Total laparoscopic hysterectomy (TLH) is an established minimally invasive approach for benign gynaecological disease, offering less postoperative pain, shorter hospitalization, faster recovery, and fewer wound-related complications than open abdominal hysterectomy. The updated 2023 Cochrane review included 28 randomized controlled trials involving 3,431 women in the comparison of laparoscopic versus abdominal hysterectomy. Laparoscopic hysterectomy was associated with a mean 13.0-day earlier return to normal activities; however, it was also associated with a higher risk of urinary tract injury (odds ratio 2.16, 95% confidence interval 1.19-3.93).[1] As minimally invasive surgical expertise has expanded, TLH has increasingly been used in patients with large fibroids, endometriosis, adhesions, previous pelvic surgery, and other causes of distorted pelvic anatomy.[2,3] Despite its overall favourable safety profile, ureteric injury remains one of the most serious complications of TLH. Contemporary estimates vary according to the surgical indication, operative complexity, surgeon experience, method of injury detection, and duration of follow-up. A systematic review of benign gynaecological laparoscopy involving 140,444 procedures reported an overall lower urinary tract injury rate of 0.33% and a pooled ureteric injury rate of approximately 0.08%; laparoscopic hysterectomy was among the procedures associated with the highest risk.[2] A more recent systematic review covering approximately 1.7 million caesarean sections and hysterectomies confirmed that injury rates vary substantially by hysterectomy route and clinical indication.[3] Population-based data from England similarly demonstrated that ureteric injury is uncommon but clinically important, occurring in 1,792 of 377,073 hysterectomies overall, with marked variation according to the indication and surgical approach.[4] Conversely, a contemporary series of 2,345 laparoscopic hysterectomies performed by high-volume fellowship-trained minimally invasive surgeons reported only one ureteric injury (0.04%), illustrating the potential influence of surgeon training and procedural volume.[5] The clinical consequences of ureteric injury may be substantial. Injuries may be recognized during surgery or present postoperatively with flank pain, urinary leakage, ureterovaginal fistula, urinary obstruction, infection, urinoma, loss of renal function, or the need for radiological, endoscopic, or reconstructive intervention. Ureteric injuries are more frequently missed intraoperatively than bladder injuries; a systematic review found that approximately 60% were diagnosed only after surgery.[2] Delayed recognition is associated with greater morbidity, more secondary procedures, prolonged treatment, and increased healthcare utilization compared with injuries identified intraoperatively.[6] Ureteric injuries following hysterectomy are also an important source of claims for patient compensation and medico-legal concern.[7] Several mechanisms may contribute to ureteric injury during TLH. Laparoscopic surgery lacks direct tactile feedback and depends predominantly on visual identification of anatomy. With conventional two-dimensional imaging, depth perception may be reduced. The ureter may be injured through transection, ligation, suturing, crushing, excessive traction, devascularization, or thermal spread from electrosurgical or ultrasonic instruments.[2,6] The risk may increase during the surgical learning curve and in the presence of endometriosis, adhesions, previous surgery, a large uterus, cervical or broad-ligament fibroids, pelvic organ prolapse, malignancy, or intraoperative haemorrhage.[4,5,8] The ureter is particularly vulnerable at several points along its pelvic course: where it crosses the iliac vessels at the pelvic brim, where it passes beneath the uterine artery lateral to the cervix, and where the distal ureter approaches the bladder and vaginal fornix. Identification of the ureter at the pelvic brim alone may be insufficient because it does not ensure visualization of the distal segment near the uterine vessels and bladder, where many hysterectomy-related injuries occur.[8,9] Distorted anatomy and anatomical variation can further alter the relationship between the ureter, uterine artery, cervix, and operative field.
Ureterolysis involves deliberate identification and dissection of the ureter to define its course and separate it from structures being coagulated, divided, or sutured. Nevertheless, the optimal strategy for its use during TLH remains uncertain. Under a selective strategy, ureterolysis is performed only when predefined risk factors or intraoperative concerns are present, such as poor visualization, distorted anatomy, large or cervical fibroids, moderate-to-severe endometriosis, dense adhesions, active bleeding, or surgeon concern regarding ureteric safety. This approach limits retroperitoneal dissection in uncomplicated cases but depends on reliable recognition of risk before an injury occurs.
In contrast, routine bilateral ureterolysis involves systematic identification and mobilization of both ureters before uterine vessel ligation in every TLH. Routine dissection could improve anatomical orientation, maintain the ureters outside the operative field, and reduce inadvertent mechanical or thermal injury. However, it may also increase operative time and introduce harms related to additional dissection, including bleeding, direct ureteric trauma, devascularization, and thermal damage. Technical publications emphasize that ureterolysis requires careful handling, preservation of the periureteric tissue and blood supply, and limited use of energy near the ureter.[8,9] Current hysterectomy guidance supports the use of minimally invasive routes when appropriate and emphasizes the importance of anatomical identification and prevention of urinary tract injury.[10] However, existing guidelines do not establish routine bilateral ureterolysis as a standard component of every TLH. Consequently, practice remains variable and is influenced by patient characteristics, operative findings, surgeon experience, training, and institutional practice.
To our knowledge, no adequately powered randomized controlled trial has directly compared routine bilateral ureterolysis with a standardized selective ureterolysis strategy during TLH for benign disease. The available literature consists principally of retrospective cohorts, case series, technical reports, and expert recommendations.[4,5,8,9] These studies are highly vulnerable to confounding by indication because surgeons are more likely to perform ureterolysis in difficult procedures that already carry a greater baseline risk of injury. Observational comparisons may therefore incorrectly associate ureterolysis with either increased injury, because it is used in complex cases, or improved safety, because it is performed by more experienced surgeons.
A definitive evaluation presents an important methodological challenge because ureteric injury is a rare outcome. For example, assuming an injury rate of 0.4% in the selective group, a conventional trial would require many thousands of participants to detect even a substantial relative reduction with adequate statistical power. A single-centre study would therefore be unlikely to recruit a sufficient number of participants within a reasonable period. Furthermore, restricting recruitment to a small number of expert surgeons could limit external validity and underestimate injury rates in routine practice.
A large, pragmatic, multicentre randomized mega-trial is therefore required. Participation by diverse hospitals and surgeons would provide the sample size necessary to evaluate a rare but clinically serious outcome while improving the generalizability of the findings. Randomization should be stratified by centre and important prognostic factors, with standardized definitions of routine and selective ureterolysis, surgeon credentialing, documentation of protocol adherence, and systematic surveillance for both recognized and unrecognized postoperative ureteric injuries. Because the intervention cannot be concealed from operating surgeons, postoperative outcome assessment and adjudication should be performed by assessors blinded to treatment allocation.
The primary outcome should include all confirmed ureteric injuries within a prespecified postoperative period, irrespective of whether they are recognized intraoperatively or diagnosed after surgery. Important secondary outcomes should include bladder and other urinary tract injuries, operative time, blood loss, conversion to laparotomy, thermal injury, reoperation, readmission, postoperative imaging or urological intervention, length of hospital stay, quality of life, healthcare costs, and other surgical complications. Subgroup analyses may determine whether the effect differs according to endometriosis, previous surgery, uterine size, distorted anatomy, surgeon experience, and institutional surgical volume.
The proposed trial will address a clinically important and unresolved question by determining whether routine bilateral ureterolysis reduces ureteric injury compared with a clearly defined selective strategy during TLH for benign gynaecological conditions. Its findings could standardize surgical practice, inform professional guidelines and training, identify patients most likely to benefit, and reduce preventable morbidity and healthcare utilization without exposing patients to unnecessary retroperitoneal dissection.
Inclusion Criteria:
Exclusion Criteria:
kelsetohy@kasralainy.edu.eg01110006946
kelsetohy@kasralainy.edu.eg01110006946