Originally published by our sister publication General Surgery News
CHARLOTTE, N.C.—Randomized controlled trials traditionally require a tremendous amount of resources to cover cost and effort; embedding these trials in the Abdominal Core Health Quality Collaborative has allowed the data registry to facilitate RCTs on hernia surgical outcomes without prohibitive investment.
“As a field, we have an increasing need for high-quality data in hernia and abdominal core health. It’s unlike oncology or transplant surgery, which often have a lot of well-funded trials to help guide patient decisions on what surgery to offer and to whom. We’re trying to change that,” said Benjamin Poulose, MD, MPH, a professor of surgery at The Ohio State University Wexner Medical Center, in Columbus, and the director of the Abdominal Core Health Quality Collaborative (ACHQC) Quality and Outcomes.
“Now that we’re able to embed RCTs within the infrastructure of our quality collaborative, it’s much easier and less costly to perform these high-quality trials,” Dr. Poulose said.
At the 2022 meeting of the American Hernia Society, presenters summarized several registry-embedded RCTs attempting to answer some of the field’s most pressing clinical questions.
The Open Versus Robotic Retromuscular Hernia Repair RCT
Standing in for his colleague Jeremy Warren, MD, M. Wes Love, MD, a minimally invasive surgeon with Prisma Health, in Greenville, S.C., discussed the results of the long-anticipated ORREO (Open Versus Robotic Retromuscular Hernia Repair) trial, which attempted to establish whether minimally invasive abdominal wall reconstruction results in clinical outcomes that are superior to open repair.
Other than reduced length of stay, they found no significant advantages. While patients undergoing a robotic repair had an average hospital stay one day shorter than those who had an open repair, there was no statistically significant difference in the primary composite end point of surgical site infection, surgical site occurrence (ssO), an ssO requiring procedural intervention, readmission or recurrence.
“This was originally powered with the assumption that we would have a bit higher enrollment. There were still concerns that we would be underpowered by looking at just a single outcome metric, so rather than looking at just one end point, like ssI, we developed a composite end point,” Dr. Love said.
The trial included adults over 18 years of age with a hernia between 7 and 15 cm in size and at least one comorbidity known to affect hernia repair: a body mass index 30 kg/m2 or greater, diabetes, chronic obstructive pulmonary disease or smoking. With the initial power analysis indicating they’d need 46 patients in each arm, the researchers enrolled a total of 100 patients, for 50 in each arm.
“It was an intention-to-treat analysis, which was sort of the fly in the ointment. From a research standpoint, an intention-to-treat analysis makes very reliable data. The problem for us is that compounded with what was ultimately an underpowered study, five patients converted from robotic to open; then their outcomes were included in the robotic arm, which is the intention-to-treat analysis purpose, but they drag down the outcomes for your run-of-the-mill, everything-went-well robotic repair,” Dr. Love said.
Three of those five patients each had an ssO. “Sixty percent of them had something go wrong, which in a per-protocol analysis would have belonged to the open group, not the robotic group. If we did this again, I think we would set it up as a per-protocol analysis instead of intention to treat,” Dr. Love said.
The researchers are waiting to collect patient-reported outcomes and the two-year recurrence rate to cap off the study, “but we kind of know where this is heading. It was underpowered, and recruitment was surprisingly difficult,” Dr. Love said, noting that a surprising number of patients were strongly averse to a robotic repair.
Ultimately, what was originally planned to be an overpowered analysis that would require two years for enrollment and yield plenty of data to demonstrate significance turned into an underpowered analysis that took four years of recruitment due to patient reluctance.
“I think we learned a lot about how we could have designed this trial better, and there’s already interest in revamping it a bit,” Dr. Love said.
Antibiotic Irrigation to Reduce Wound Morbidity: The RINSE Trial
Dr. Love also reported on the RINSE trial, which attempted to determine whether antibiotic irrigation reduces the rate of ssIs in ventral hernia repair (VHR), which antibiotic is preferable and what technique (timing, pulse lavage, duration) is best.
“There’s a lot of good retrospective data on this, and a bit of RCT data, but from the colorectal literature—not the ventral hernia literature—and I’ll explain why that matters,” Dr. Love said.
This trial, also the brainchild of Dr. Warren, randomized 210 patients undergoing retromuscular VHR with polypropylene mesh to clindamycin-gentamicin or saline irrigation; the subgroup analysis considered whether they received a transversus abdominis muscle release and clean, clean-contaminated and contaminated cases.
At 30 days, 11 (10%) patients in the control arm and 10 (9%) in the antibiotic arm experienced an ssI (P=0.836); ssIs requiring procedural intervention were reported in eight patients in both arms (P=0.985). Outcomes were similarly equivalent for 30-day ssO and ssO requiring procedural intervention.
“It was a pretty decent sample size, but in the end, we were unable to demonstrate significant difference in ssI,” Dr. Love said.
“This brings me to the point about the RCTs in the colorectal literature and our study design. By definition, all of the colorectal cases were clean-contaminated. When we did our power analysis, we were estimating at least 60% clean-contaminated cases, but 80% were clean. I think what this study tells us is that antibiotic irrigation probably doesn’t make a difference in clean cases.”
After his presentation, a number of people voiced an interest in repeating the study, focusing on higher risk populations. “It’s there anecdotally; everybody believes in it. We just need again to tailor the study specifically to answer the question we’re trying to answer instead of casting such a wide net,” Dr. Love said.
Fixation Versus No Fixation for Open Retromuscular VHR: Long-Term Results
Ajita Prabhu, MD, an associate professor of surgery at Cleveland Clinic, reported on the long-term results of an RCT investigating the utility of using transfascial sutures to fixate mesh in patients undergoing retromuscular VHR.
“This is something we were all taught to do in training because it was thought to take the tension off the midline and help the mesh lay flat so that it will properly incorporate into the abdominal wall. The downside is that transfascial sutures could potentially contribute to short-term and/or long-term chronic pain even though we’ve typically used slow-absorbing sutures,” Dr. Prabhu said.
With a primary outcome of hernia recurrence at one year, Dr. Prabhu and her colleagues hypothesized that patients who did not receive transfascial fixation would be noninferior to those who did.
“The reason we picked noninferiority is that if patients who don’t receive fixation have much less pain, then no fixation would be the way to go. But it’s possible they would have a higher rate of recurrence, in which case, who cares about pain. We wanted to demonstrate that no fixation is no worse in terms of recurrence,” Dr. Prabhu said.
Assuming a recurrence rate of 5% in those who received transfascial suture fixation, the investigators set a noninferiority margin of 10% recurrence in patients not receiving fixation. Their secondary outcome was pain reported at 30 days and one year using validated survey tools.
The trial included 325 patients, 163 who did not receive fixation and 162 of whom received a minimum of eight transfascial sutures. The patients were well matched in terms of demographic and clinical characteristics; most cases were clean; fascial closure was achieved in 100% of cases; and operating time and operative complications were similar.
Hernia recurrence was 7.4% in the fixation group and 9.2% in the no-fixation group. “It didn’t even trend toward statistical significance,” Dr. Prabhu said.
While the no-fixation group reported slightly less pain at 30 days than the fixation group, it did not reach statistical significance, and at one year both groups had similar pain scores.
With so little difference in outcomes between the two groups, the researchers concluded that fascial sutures for mesh fixation could safely be abandoned in this patient population. Dr. Prabhu said many of her colleagues have already stopped using fascial sutures in these types of cases.
“I think these findings just might reinforce what people are doing anyway. But I also think it’s important to have data that supports these changes that so often happen anecdotally, to show us we really are doing the right thing,” she said.
“There has to be some evidence behind these changes, otherwise we’re just running amok with anecdotes.”
Robotic eTEP Versus IPOM Evaluation: The REVEAL RCT
Clayton C. Petro, MD, an abdominal wall reconstructive surgeon at the Cleveland Clinic Foundation, and his colleagues hypothesized that the avoidance of mesh fixation in a robotic enhanced-view totally extraperitoneal repair (eTEP) would leave patients in less early postoperative pain than a robotic intraperitoneal onlay mesh (rIPOM) repair (Surg Endosc 2022 Nov 2; doi:0.1007/s00464-022-09722-9).
But that’s not what happened.
“Most general surgeons appreciate that the rIPOM technique is notoriously painful, so we thought the newer technique, where you lay the mesh in between the muscles, would cause less pain, but it didn’t,” Dr. Petro said.
To investigate pain associated with either procedure, five surgeons at three institutions randomized 100 patients with midline ventral hernias 7 cm or smaller to eTEP or rIPOM, with a primary outcome of pain measured on a scale of 0 to 10 on day 1 post-procedure.
“We chose pain on the first day because I think it’s within those first 24 hours that you have an opportunity to make an impact on what proportion of patients go home the same day and how much opioid medication they need,” Dr. Petro said.
Both groups reported a pain score of 5 on the first day after surgery; likewise, there were no pain differences reported immediately post-procedure, at day 7 or 30. Other measures, such as same-day discharge, narcotic use and quality of life were also similar.
“There is some retrospective data suggesting a repair without mesh fixation is a little less painful, but for the eTEP we have to dissect the muscles apart and it’s a pretty big dissection. I think that dissection hurts just as much as a piece of mesh sewn to the underside of the muscle. For those types of hernias, pain just comes with the territory,” Dr. Petro said.
Critics of the study might contend that whether or not there is a difference in pain, intraperitoneal mesh should be avoided, Dr. Petro said, “but the idea that intraperitoneal mesh is bad is hard to prove in the context of a RCT, since those events are rare and often occur many years later. I think proponents of eTEP will continue to hang their hats on their concern about intraperitoneal mesh.”
Personally, Dr. Petro believes that fears of intraperitoneal mesh may be overblown, or should at least be appropriately compared with the complications associated with trying to get mesh outside the peritoneal cavity, such as a breakdown of the posterior sheath or complications that might occur by dissecting in the wrong plane.
“I think there are pros and cons associated with each technique that have to be weighed against each other,” Dr. Petro said.
He emphasized that the RCTs are capable of answering only one question, in this case whether there is a pain benefit associated with eTEP. “Any other results we glean, even in the one-year results we’re putting together now, are all exploratory. People will be interested in the pain outcome, but I think the true divide is a mostly philosophical one: whether the mesh needs to be outside the peritoneal cavity for these small hernias, and whether it’s worth the extra time of doing that dissection. That’s just not going to be an easy question to answer in the context of a RCT.”
Drs. Love and Petro reported no relevant financial disclosures. Dr. Poulose receives salary support from ACHQC, and research support from Advanced Medical Solutions and BD. Dr. Prabhu is a speaker for and receives research support from Intuitive Surgical, is on the advisory board for CMR Surgical and Surgimatix, and is a consultant to Verb Surgical.