FDA granted permission to an Irish company to market the “PneumoLiner,” a first-of-its-kind containment system indicated for isolating and containing uterine tissue during a minimally invasive hysterectomy or myomectomy. The agency announced its action April 7.
Gynecologists will soon be able to use the containment system—designed to prevent dissemination of potentially cancerous tissue—with specific models of power morcellators to conduct laparoscopic surgery in a limited population of women.
The device consists of a containment bag and a tube-like plunger, which has been proven to be impermeable to substances that were “similar in molecular size to tissues, cells and body fluids,” the agency said.
The power morcellation procedure, which until recently was performed in an estimated 100,000 women annually in the U.S., is the focal point of a two-year debate that has divided the surgical field. When a previously undiagnosed malignant tumor—usually a sarcoma—is present, the procedure spreads the cancerous tissue, upstaging the disease. To date, there isn’t a reliable method to determine whether or not a uterine tumor is malignant before it has been removed and fully examined.
Critics say the procedure is avoidable and is a violation of basic principles in surgery, while proponents argue that the majority of women stand to benefit from the minimally invasive procedure, which allows for faster recovery and is safer than the attendant complications of open surgery.
Hooman Noorchashm, a cardiothoracic surgeon who led an aggressive campaign against power morcellation, said FDA’s decision is “unacceptable.”
“FDA ought to have classified this as a [high-risk] Class III device and taken it through the Premarket Approval process,” Noorchashm, wrote in an email to Peter Lurie, the FDA associate commissioner for public health strategy and analysis. “Or, even better would have been to take the device to the FDA’s Office of Hematology and Oncology Products for evaluation and input, given the well-established oncological hazard.
“I find it incredible that FDA physicians and leaders are OK with the concept of not knowing the exact oncological risk, yet they release the device into the marketplace to be unleashed on women,” wrote Noorchashm, formerly a Brigham & Women’s Hospital physician. “Do they expect women to be used as guinea pigs for a device whose oncological hazard is indeterminate, as they fully admit?
“Or is it that they have faith in ‘personal responsibility’ on the part of a specialty that suppressed clear information from the FDA for over 20 years?”
It’s not publicly known whether FDA units besides the Center for Devices and Radiological Health played a role in the decision to grant this permission.
“This new device does not change our position on the risks associated with power morcellation,” William Maisel, CDRH deputy director for science and chief scientist, said in a statement. “We are continuing to warn against the use of power morcellators for the vast majority of women undergoing removal of the uterus or uterine fibroids.
“The PneumoLiner is intended to contain morcellated tissue in the very limited patient population for whom power morcellation may be an appropriate therapeutic option—and only if patients have been appropriately informed of the risks.”
In a recently published prospective cohort study that treated 76 women, researchers identified seven instances—9.2 percent of the cases—in which leaks and spills occurred when containment systems were used with power morcellators. The study, published February 2016 in the American Journal of Obstetrics and Gynecology, does not identify PneumoLiner as one of the devices used.
FDA: No Data on Risk of Spreading Cancer
FDA classifies the PneumoLiner as a Class II moderate-risk device that is intended for use only in:
- Women without uterine fibroids undergoing hysterectomy, and
- Some pre-menopausal women with fibroids who want to maintain their fertility.
The containment system is manufactured by Advanced Surgical Concepts Ltd. of Bray, Ireland.
The company doesn’t manufacture power morcellators, Class II devices that use spinning blades to pulverize tissue into fragments that are then removed through small incisions.
While FDA has approved analogous devices for use in laparoscopic procedures, this is the first time the agency has allowed containment bags to be used with power morcellators.
The announcement comes over a year after the agency’s November 2014 guidance on power morcellators, which declared the devices as contraindicated for removal of tissue containing fibroids in the vast majority of women (The Cancer Letter, Nov. 26, 2014).
In April 2014, an FDA advisory discouraged the use of power morcellation, finding that one in 350 women who are undergoing hysterectomy or myomectomy for fibroids is found to have an unsuspected uterine sarcoma.
The PneumoLiner containment system was reviewed through FDA’s de novo classification process. Since new and novel devices without a predicate device automatically receive a high-risk Class III designation, the de novo pathway allows the agency to reclassify devices considered appropriate for the low and moderate-risk Classes I and II.
By classifying the PneumoLiner as Class II, FDA has determined that general controls and special controls provide reasonable assurance of the safety and effectiveness of the device for its intended use with power morcellators. This means the agency decided that the risk posed by the device, and the level of controls needed to mitigate those risks, aren’t high enough to warrant a Class III designation, which would have called for more rigorous premarket testing. A randomized clinical trial would likely have been required.
The full list of special controls, which includes labeling requirements and demonstration of impermeability and non-spillage, is published in FDA’s granting order to the company, available here.
“The PneumoLiner is compatible with bipolar or electromechanical laparoscopic power morcellators that are between 15 mm and 18 mm in shaft outer diameter and 135 mm and 180 mm in shaft working length and which have an external component that allows for the proper orientation of the laparoscope to perform a contained morcellation,” FDA’s granting order states.
According to FDA, the PneumoLiner bag’s mechanical strength demonstrated that the device could withstand forces in excess of those expected to occur in actual clinical use.
“Other testing determined that the inflated bag provided adequate space for surgeons to perform morcellation with good visualization,” the agency said.
However, FDA requires the manufacturer to warn patients and health care providers that the containment system has not been proven to reduce the risk of spreading cancer during power morcellation.
“We want to be clear that, although the device has been shown to successfully contain morcellated tissue, it has not been proven to reduce the risk of cancer spread during surgery,” Maisel said in a statement.
Risks associated with the PneumoLiner device include dissemination of morcellated tissue, injury to surrounding tissues or organs, infections and a prolongation of the surgical procedure.
Also, FDA requires the label to state that only physicians who have successfully completed the company’s validated training program can use the device in a clinical setting.
The data used to guide FDA’s decision aren’t publicly available at this time—most companies choose to withhold raw data, and information from relevant studies may be published in the de novo summary. The agency usually publishes the summary a few weeks after the granting order and is considered confidential until the manufacturer has had a chance to review it.
The PneumoLiner is a registered trademark (serial no. 86646099) as of Jan. 26, 2016, but it appears no U.S. patents have been issued for the device. There is no public information on the design or make of the device and how it specifically meets FDA’s special controls—it is likely that a patent application is in the works; the pre-grant publication of the application takes up to 18 months from the earliest filing date.
The American Congress of Obstetricians and Gynecologists, a professional association representing 58,000 specialists, declined to comment on the FDA announcement.
“We have not had a chance to review the evidence, so it’s not appropriate for us to comment until we do,” an ACOG spokesperson said to The Cancer Letter. The American Association of Gynecologic Laparoscopists also declined to comment, citing a short timeline.
Jubilee Brown, a board member of the Fellowship in Minimally Invasive Gynecologic Surgery and director of gynecologic oncology at The Woman’s Hospital of Texas, said FDA’s support for advances in technology that may improve outcomes of women undergoing minimally invasive surgery is “encouraging.”
“The PneumoLiner may provide a way to potentially improve the process of morcellation,” Brown, a professor in the Department of Gynecologic Oncology and Reproductive Medicine and chair-elect of the faculty senate at MD Anderson Cancer Center, said to The Cancer Letter. “Of course, continued outcomes research and optimal training for minimally invasive gynecologic surgeons is essential. I remain convinced that minimally invasive surgery continues to offer significant advantages to open surgery for appropriately selected women.”
Company: PneumoLiner is Safe
The use of containment systems with morcellators dates back to June 1990, when Ralph Clayman—now emeritus dean of the Department of Urology at University of California, Irvine—performed the first laparoscopic power morcellation procedure on a diseased kidney at Barnes Hospital, Washington University in St. Louis (BMJ, Volume 307, Dec. 4, 1993).
“This practice [of contained morcellation] was largely abandoned for open abdominal morcellation, which has led to the dilemma we face today,” Frank Bonadio, CEO of Advanced Surgical Concepts, said at an advisory meeting of the FDA Obstetrics and Gynecological Medical Device Advisory Committee July 10, 2014.
The panel was convened in response to mounting evidence that power morcellation—at the time considered a standard of care surgical procedure in gynecology—posed a public health threat to a large population of women.
The panel expressed low confidence in power morcellation as a treatment for uterine fibroids, and focused on alternative procedures, concluding that there was insufficient data on whether the dissemination risk can be reduced using containment systems (The Cancer Letter, July 25, 2014).
In his presentation to the panel, Bonadio described how the PneumoLiner provides total containment.
“In 2011, Dr. Tony Shibley had the idea to take a containment bag in the same way Dr. Clayman did, but make one simple methodological change,” Bonadio said. “ASC has been working with Dr. Shibley to develop a product that is easy to deploy, easily encapsulates the uterus, and establishes insufflation pressure allowing vision and a larger working space and, most significantly, complete containment.”
Shibley, an obstetrics and gynecology specialist at Fairview Physician Associates in Minnesota, described a contained morcellation procedure performed in 2014 on a 56-year-old woman with no detectable malignancy.
“On April 18th of this year, she underwent a primary procedure by my partner using my contained morcellation technique,” Shibley said to the advisory panel members. “The patient had a supracervical hysterectomy, meaning, the uterus was amputated from the cervix, placed within the containment bag, the bag was insufflated, and morcellation was carried out. The pathology report surprisingly and unsuspectingly was leiomyosarcoma.”
It is not publicly known whether, at the time, Shibley received an Investigational Device Exemption, FDA’s license that allows testing of devices that have not been approved for a potentially high-risk indication.
After diagnosis of malignancy, Shibley’s patient underwent a secondary surgery on June 2, 2014, to ascertain whether any dissemination occurred and to reduce the risk of upstaging the disease if the integrity of the containment bag had been compromised.
“This surgery included removing the cervix, taking biopsies from throughout the abdomen, obtaining pelvic fluid, and abdominal washings from throughout the abdomen,” Shibley said. “All of those findings were negative for any malignant cells.”
This means that the containment system was successful, Shibley said.
“This confirms that contained morcellation within an insufflated bag does not increase the patient’s risk and in fact gives many benefits for our patients, including allowing them to continue to receive the benefits of minimally invasive surgery, but adding the safety features,” Shibley said. “I think this is the natural progression in medicine, if we’re doing medicine right.”
Brigham Trial: 9.2 percent of Cases Had Leakage
Manufacturers of power morcellators and minimally invasive gynecologists had been aware of the hazards of “open” unbagged morcellation years before two high-profile cases—Amy Reed and Erika Kaitz—at Brigham & Women’s Hospital drew FDA’s attention to the issue (The Cancer Letter, Dec. 18, 2015).
Brigham is a member institution of Partners HealthCare, a Harvard hospital network.
Johnson & Johnson subsidiary Ethicon—the largest manufacturer of the devices—said it didn’t know of the dangers of power morcellators prior to December 2013, when Reed and her husband Noorchashm filed a Medical Device Report to FDA. Whistleblower Robert Lamparter, a retired pathologist from central Pennsylvania, disagreed, and produced documents from 2006 proving that he had reported to J&J a near-miss case as well as risk estimates similar to FDA’s numbers (The Cancer Letter, Nov. 20, 2015).
In November 2014, The Cancer Letter first reported on Brigham’s role in upstaging Erica Kaitz’s leiomyosarcoma via power morcellation performed in 2012. Kaitz died on Dec. 7, 2013, nearly two months after Reed received her cancer diagnosis at Brigham (The Cancer Letter, Nov. 21, 2014).
FDA said it did not receive any reports of adverse outcomes from manufacturers and hospitals prior to December 2013—this has become the focus of probes by FBI, Government Accountability Office, and Congress (The Cancer Letter, Dec. 18, 2015).
In a study by Brigham physicians Michael Muto and Michael Seidman published November 2012 in PLOS ONE, the authors identify four patients—out of 1,091 patients—who showed evidence of peritoneal dissemination of leiomyosarcoma after undergoing power morcellation. Three of the four patients died, with an average post-diagnosis survival of 24.3 months.
It is not publicly known where the four patients were treated.
In 2013, Muto, director of the Gynecologic Oncology Fellowship Program at Brigham and an associate professor of obstetric, gynecology and reproductive biology at Harvard Medical School, referred Reed for a minimally invasive operation which he knew would likely involve power morcellation in 2013, according to Noorchashm.
Reed, at the time an anesthesiologist at Beth Israel Deaconess Medical Center, signed a consent form, which does not mention morcellation or the accompanying risk of dissemination of occult sarcoma. The form can be downloaded here.
In 2014, Brigham conducted a prospective study focused on using power morcellators inside containment bags. Jon Einarsson, chief of the Division of Minimally Invasive Gynecology at Brigham, was the lead investigator for the single-arm study, which was designed to enroll 400 patients across several partner institutions. Einarsson is the Brigham surgeon who performed the unbagged version of the procedure on Kaitz.
The study was suspended in November 2014, after The Cancer Letter reported that Brigham did not apply for an Investigational Device Exemption to obtain permission from FDA to conduct the high-risk study (The Cancer Letter, Nov. 26, 2014).
It is not publicly known whether the study was resumed under an IDE, but the results of the study were published February 2016 in the American Journal of Obstetrics and Gynecology.
The study enrolled 89 patients from Brigham, Faulkner Hospital, Massachusetts General Hospital, Newton-Wellesley Hospital, and Lahey Hospital and Medical Center. The paper doesn’t specify whether the patients were treated before or after the suspension.
Brigham officials did not respond to questions about the study from The Cancer Letter.
Of the 76 patients that successfully underwent the contained power morcellation protocol, there were seven observed instances of fluid or tissue leakage—9.2 percent, or a nearly 1 in 10 rate.
“Given the lack of existing data on the incidence of leakage with contained tissue extraction, a formal power analysis was not performed,” the authors wrote. “The enrollment goal was set at 400 patients in an attempt to comprehensively evaluate this technique, with plans for interim analyses.
“Specifically, a plan was outlined to halt the study at the time of interim analysis if any complications related to the use of the containment bags were noted or if blue dye leakage was observed in greater than 5 percent of cases.”
However, the containment bags were visually intact, and the final pathological diagnosis was benign in all cases, the authors note. The PneumoLiner containment system is not identified as being used in this study.
“Specimen containment bags used for this purpose included the following: EcoSac (Espiner Medical, North Somerset, United Kingdom), 50 x 50 cm isolation bag (3, St Paul, MN), Anchor tissue retrieval system (Anchor Products Co, Addison, IL), and Endocatch (Covidien, Minneapolis, MN),” the authors wrote. “These containment bag options were chosen from among hospital stock, and the use of a particular bag type was based on surgeon preference.”
It is unclear whether the tissue and fluid leakage observed in the study—seven of 76 patients—is clinically significant, the authors wrote.
“These instances do represent potential opportunities for tissue dissemination,” the authors wrote. “Even in cases of open surgery and intact specimen extirpation, there may be uterine tissue disruption and fluid spread, particularly in cases of supracervical hysterectomy or myomectomy.
“Regardless, the authors decided to close the study at the time of interim analysis to allow for further refinements in technique, which may minimize such concerns and enhance reproducibility.
“Despite the instances of tissue or fluid leakage that were observed in this study, our results provide additional support for the feasibility of contained tissue extraction and justify continued efforts toward improving such a system. Further refinements of the technique and equipment available for this process will afford additional advantages in efficiency and system integrity.”
