The NOVEL trial: natural orifice versus laparoscopic cholecystectomy—a prospective, randomized evaluation

Steven D. Schwaitzberg, Kurt Roberts, John R. Romanelli, David J. Desilets, David Earle, Santiago Horgan, Lee Swanstrom, Eric Hungness, Nathaniel Soper, Michael L. Kochman, on behalf of the Natural Orifice Surgery Consortium for Assessment and Research® (NOSCAR®) Clinical Trial Group

The evolution of Natural Orifice Translumenal Endoscopic Surgery® (NOTES®) represents a case study in surgical procedural evolution. Beginning in 2004 with preclinical feasibility studies, and followed by the creation of the NOSCAR® collaboration between The Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Gastrointestinal Endoscopy, procedural development followed a stepwise incremental pathway. The work of this consortium has included white paper analyses, obtaining outside independent funding for basic science and procedural development, and, ultimately, the initiation of a prospective randomized clinical trial comparing NOTES® cholecystectomy as an alternative procedure to laparoscopic cholecystectomy. Ninety patients were randomized into a randomized clinical trial with the primary objective of demonstrating non-inferiority of the transvaginal and transgastric arms to the laparoscopic arm. In the original trial design, there were both transgastric and transvaginal groups to be compared to the laparoscopic control group. However, after enrollment and randomization of 6 laparoscopic controls and 4 transgastric cases into the transgastric group, this arm was ultimately deemed not practical due to lagging enrollment, and the arm was closed. Three transgastric via the transgastric approach were performed in total with 9 laparoscopic control cases enrolled through the TG arm. Overall a total of 41 transvaginal and their 39 laparoscopic cholecystectomy controls were randomized into the study with 37 transvaginal and 33 laparoscopic cholecystectomies being ultimately performed. Overall total operating time was statistically longer in the NOTES® group: 96.9 (64.97) minutes versus 52.1 (19.91) minutes. There were no major adverse events such as common bile duct injury or return to the operating room for hemorrhage. Intraoperative blood loss, length of stay, and total medication given in the PACU were not statistically different. There were no conversions in the NOTES® group to a laparoscopic or open procedure, nor were there any injuries, bile leaks, hemorrhagic complications, wound infections, or wound dehiscence in either group. There were no readmissions. Visual Analogue Scale (VAS) pain scores were 3.4 (CI 2.82) in the laparoscopic group and 2.9 (CI 1.96) in the transvaginal group (p = 0.41). The clinical assessment on cosmesis scores was not statistically different when recorded by clinical observers for most characteristics measured when the transvaginal group was compared to the laparoscopic group. Taken as a whole, the results slightly favor the transvaginal group. SF-12 scores were not statistically different at all postoperative time points except for the SF-12 mental component which was superior in the transvaginal group at all time points (p < 0.05). The safety profile for transvaginal cholecystectomy demonstrates that this approach is safe and produces at least non-inferior clinical results with superior cosmesis, with a transient reduction in discomfort. The transvaginal approach to cholecystectomy should no longer be considered experimental. As a model for intersociety collaboration, the study demonstrated the ultimate feasibility and success of partnership as a model for basic research, procedural development, fundraising, and clinical trial execution for novel interventional concepts, regardless of physician board certification.