GENERAL SURGERY NEWS The Independent Monthly Newspaper for the General Surgeon
GeneralSurgeryNews.com
January 2021 • Volume 48 • Number 1
Robotic-Assisted Hernia Repair: What Exactly Are We Arguing About?
Surgery in the Millennial Era: Staying Ahead Of the Curve
Debate Centers on Whether the Robot’s Advantages Can Be Captured By Traditional Peer-Reviewed Research
Embracing Technology, Innovation By KAREN BLUM
By CHRISTINA FRANGOU
Warren, MD, an associate professor of surgery at the University Jeremy South Carolina School of Medicine, Greenville, checks PubMed frequently
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of
cceptance of diversity and technology, and staying current with social media, are skills that surgeons need in the coming years, a panel of experts said during the 2020 annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons, which was held virtually. “Surgical training and surgical practice are very different in 2020 than decades before,” said Kate Lak, MD, FACS, an assistant professor of surgery at the Medical College of Wisconsin, in Milwaukee, and the chair of a session on surgery in the
for new reports on robotic hernia repair. Dr. Warren, a minimally invasive surgery fellowship-trained surgeon and proponent of the robot in hernia repair, has been tracking the literature on the robot for years. A search last December turned up 438 articles, with more than 100 published in the past year. That’s not a lot for a technology that has been around since the late 1990s, and one that grew in proportional use more than 40-fold for inguinal and ventral hernia repairs between 2012 and 2018 (JAMA Netw Open 2020;3[1]:e1918911). The published literature does not reflect what Dr. Warren believes the robot can do. But, he said, the evidence “is coming.” As it stands now, the state of published literature on robotic hernia repair is a hotbutton issue: Some surgeons argue that more research is necessary before this expensive Continued on page 20
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Evidence Grows for Avoiding Biopsy in Hepatocellular Carcinoma
Multimodal Laxatives Speed GI Function After Colorectal Surgery
Antibiotic Therapy For SSIs: Onus on the Surgeon to Get It Right
By KATE O’ROURKE
By CHRISTINA FRANGOU
By CHASE DOYLE
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new study supports exhausting noninvasive methods to diagnose hepatocellular carcinoma (HCC) before attempting biopsy. In an analysis of data from the National Cancer Database, overall survival was lower in HCC patients who underwent preoperative tissue diagnosis compared with clinical diagnosis. The findings were presented at the 2020 annual meeting of the Society of Surgical Oncology (abstract 63).
atients who underwent elective colorectal surgery recovered their gastrointestinal function faster when they received multimodal laxatives as part of an enhanced recovery after surgery protocol, according to a single-center, open-label, randomized controlled trial. The study, which was presented at the American College of Surgeons Clinical Congress 2020, showed no increase in overall complications or leaks associated with laxatives. The trial was designed to address the lack of evidence about readily available laxatives in improving GI function after surgery. Most published research focuses on
hen used appropriately, antibiotics decrease surgical site infections, mortality and cost while improving patient outcomes. When used inappropriately, they can increase infection risk, resistant pathogens, adverse events and mortality. It’s up to surgeons to get it right, according to Addison K. May, MD, a professor and the chief of acute care surgery at Atrium Health and Carolinas Medical Center, in Charlotte, N.C. During the American College of Surgeons Clinical Congress 2020, Dr. May shared several principles
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NE W TECHNOLOG Y
8 New Device Takes Surgical Robotics In Smaller, Simpler Direction S URGEONS’ LOU N G E
14 Operating on Older Patients J OURNAL WATCH
18 Recent Studies That Could Affect Your Practice facebook.com/generalsurgerynews
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IN THE NEWS
JANUARY 2021 / GENERAL SURGERY NEWS
Synthetics, Biologics Compared for Complex Hernia Repairs In Small Randomized Trial, Biologic Mesh Had Almost Twice as Many Infections, Readmissions By CHRISTINA FRANGOU
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iologic mesh was associated with nearly double the rate of surgical site infections, wound dehiscence and readmissions compared with synthetic mesh in a small randomized controlled trial in patients undergoing complex open ventral hernia repair. The results, which were presented at the American College of Surgeons 2020 Clinical Congress, come from a pilot study of 87 adults who were treated at a single institution and have been followed for at least one year after surgery. Study participants had a wide range of hernias; approximately two-thirds had a hernia of CDC wound class 2 to 4. The mean mesh area was 390 cm2 in the biologic group and 383 cm2 in the synthetic group, and component separation was carried out in 32% and 42%, respectively. Fourteen patients (42.4%) in the biologic mesh group developed major complications, including mesh infection, recurrence and reoperation, compared with eight patients (21.6%) in the synthetic mesh group. Although the difference was not statistically significant
(P=0.071), Bayesian analysis demonstrated a 95% probability of an increased risk for major complications with biologic mesh. The analysis showed no differences in rates of seromas, hematomas or ClavienDindo complication grade between mesh groups. Additional randomized controlled trials with longer follow-up are needed, said lead author Oscar A. Olavarria, MD, a surgery resident with McGovern Medical School at UT Health Science Center, in Houston. He noted that this study is underpowered and should be considered hypothesis generating. It is “a guide to surgeons, not the definitive answer,” he said. Based on this trial’s results, “there is no clear advantage of biologic mesh over synthetic mesh during open ventral hernia repair when the mesh is placed in the retromuscular position,” Dr. Olavarria said. Michael J. Rosen, MD, the director of Cleveland Clinic Center for Abdominal Core Health, who is leading another trial examining this question, said: “The results are compelling in that we should
Frederick L. Greene, MD Charlotte, NC
Lauren A. Kosinski, MD Chestertown, MD
Editorial Advisory Board
Marina Kurian, MD New York, NY
Maurice Arregui, MD Indianapolis, IN Philip S. Barie, MD, MBA New York, NY L.D. Britt, MD, MPH Norfolk, VA James Forrest Calland, MD Charlottesville, VA David Earle, MD Lowell, MA Sharmila Dissanaike, MD Lubbock, TX Edward Felix, MD Pismo Beach, CA Robert J. Fitzgibbons Jr., MD Omaha, NE Michael Goldfarb, MD Long Branch, NJ Leo A. Gordon, MD Los Angeles, CA
—Oscar A. Olavarria, MD
at least question the utility of biologic mesh as a whole.” These findings are the first publicly available data from a randomized controlled trial comparing the two types of mesh in open complex ventral hernia repair. Several larger trials are underway, with at least one having completed accrual. The UT Health trial used major complications as the primary outcome, grouping together mesh infection, reoperation and recurrence. Using major
MISSION STATEMENT OF GSN It is the mission of General Surgery News to be an independent and reliable source of news and analysis about the current state of surgery. It strives to provide a venue for discussion and opinions, from all viewpoints, on the issues most important to surgeons.
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Gina Adrales, MD, MPH Baltimore, MD
‘There is no clear advantage of biologic mesh over synthetic mesh during open ventral hernia repair when the mesh is placed in the retromuscular position.’
DISCLAIMER Opinions and statements published in General Surgery
News are of the individual author or speaker and do not represent the views of the editorial advisory board, editorial staff or reporters. DISCLOSURE POLICY We endeavor to obtain relevant financial
Raymond J. Lanzafame, MD, MBA Rochester, NY
disclosures from all interviewees and rely on our sources to accurately provide this information, which we believe can be important in evaluating the research discussed in this publication.
Timothy Lepore, MD Nantucket, MA
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complications as a composite outcome measure increased the number of events for analysis and reduced the number of patients needed to detect a difference between the two groups, said Benjamin Poulose, MD, the chief of the Division of General and Gastrointestinal Surgery and co-director of the Center for Abdominal Core Health at the Ohio State University Wexner Medical Center, in Columbus. “Although having a composite measure in and of itself is not continued on the following page
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OPINION
GENERAL SURGERY NEWS / JANUARY 2021
2021: Managing Expectations By FREDERICK L. GREENE, MD
O
ver the last 25 years, it has been my tradition to offer a few New Year’s resolutions each January for our dedicated General Surgery News readers to ponder. Since 2020 has been very different from any experience in our collective lifetimes, I thought I would depart slightly from this tradition and instead offer “Expectations” for the new year. The following list, while certainly not exhaustive, represents a few of my hopes, anticipations, possibilities and, yes, expectations for 2021. In 2021, I expect: • There will be a SARS-CoV-2 vaccine that is efficacious and safe. • Our hospitals will not have to cancel elective surgical cases due to a pandemic. • We will be able to attend our surgical organizational meetings in person.
• We will see a return of decency and respect in our national politics. • The Boeing 737 Max will be safe to fly. • I will still have weekly Zoom calls with my college buddies. • Schools will be open for in-person learning for all students. • Wearing masks will still be necessary. • The important lessons learned from telehealth services will continue. • General surgeons might not have a 7% reduction in Medicare reimbursement. • Following science will be seen as vital for safe public health. • We will be able to attend live shows and concerts. • Hard lessons learned regarding racism and bigotry will not be forgotten. • We will be able to go to movie theaters safely. • Resident candidates won’t have to have virtual interviews. • MLB will have 162 regular-season games.
I am sure that many of you will come up with your own list of 2021 expectations, and we would enjoy reading them (khorty@mcmahonmed.com). I am also certain that we all have many reasons to be thankful during the past year despite the seemingly never-ending litany of public health and sociopolitical conundrums that we faced. There is no doubt that we all learned a great deal during this past year and will be even more resolute when future challenges ensue. Finally, as we manage our expectations for 2021, hopefully we will do it as a healthier, safer and more unified nation. Happy New Year! ■ —Dr. Greene is a surgeon in Charlotte, N.C.
A Surgeon and His Art
Mesh Trial continued from the previous page
“The Beach at the Breakers”: A Watercolor by Gerald Marks, MD
The Northeastern Society of Colon and Rectal Surgeons (NESCRS), an amalgam of three societies, as a group, discovered the special joy of including families with their scientific meeting. The creativity of Jim Guthrie, may his soul rest in peace, enabled us to meet in the off-season at the iconic Breakers Hotel in Palm Beach, FL, where we met for over a dozen years. Collectively, we learned the meaning of “gracious living” while we enjoyed what everyone agreed were scientifically superb presentations and discussions frequently heralding important new attitudes and procedures, often in conjunction with Dr. Steven Wexner and the Cleveland Clinic Florida, in Weston. A nightly reception and dinner set the stage for a meaningful social interaction that helped define the exceptional soul of the meeting. This painting is dedicated to the memory of those wonderful meetings and all their extraordinary participants.
[a] problem, when it combines different outcomes it can be,” he said. Patients were operated on between March 2017 and January 2019, and were not suitable candidates for a minimally invasive repair. They were randomized in a 1:1 ratio to a repair with biologic or synthetic mesh. Nearly half were ASA physical status class III to IV, and 34% in the biologic group and 23% in the synthetic group had diabetes, while 11% and 7% were smokers, respectively. About 40% of patients had a recurrent hernia. Surgeons performed a posterior fascial closure, with posterior component separation if needed, and placed the mesh in retromuscular fashion with anterior fascial closure. The repairs were performed by surgeons with high volumes of abdominal wall reconstruction, which may limit the generalizability of the findings, the authors said. They plan to complete three- and fiveyear follow-up of patients to assess longterm outcomes. It is possible that biologic mesh has a place in complex open ventral hernia repair, Dr. Olavarria noted. The study did not look at biologic mesh in bridged repairs or in placements other than retromuscular. Mesh in these settings should be studied in randomized controlled trials, he said. The investigators used a porcine acellular dermal matrix mesh and a mid-density, macroporous polypropylene mesh. The study will be published in an ■ upcoming issue of Surgical Infections.
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IN THE NEWS
GENERAL SURGERY NEWS / JANUARY 2021
After Neoadjuvant Chemo for Breast Cancer, Shorter Time To Surgery Better Study Called ‘Practice-Changing’; HER2-Negative Patients Should Have Surgery Within 4 Weeks By KATE O’ROURKE
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ncreasing time to surgery beyond four weeks is a modifiable risk factor for adverse oncologic outcomes after neoadjuvant chemotherapy for breast cancer, according to a new study presented at the 2020 annual meeting of the Society of Surgical Oncology, held virtually (abstract 12). According to Thomas Sutton, MD, a fourth-year general surgery resident in the Department of Surgery at Oregon Health & Science University, in Portland, who presented the data, the impact of length of time to surgery on oncologic outcomes after neoadjuvant chemotherapy in breast cancer patients is unclear. One study of breast cancer patients found reduced overall survival and recurrencefree survival (RFS) with a time to surgery of less than 21 days versus more than 21 days (Eur J Surg Oncol 2017;43[4]:613618). Another study in breast cancer patients found that those with neoadjuvant chemotherapy to surgery intervals of up to eight weeks had equivalent overall survival, RFS and locoregional RFS (Ann Surg Oncol 2016;23[5]:1515-1521). The new study included women with nonmetastatic breast cancer who received neoadjuvant chemotherapy from January 2011 to December 2017 in the Legacy Health System Tumor Registry. The researchers identified 463 patients, with 220 receiving neoadjuvant chemotherapy in four weeks or less, 175 receiving it between four and six weeks, and 68 receiving it in greater than six weeks. No differences in race, ASA (American Society of Anesthesiologists) classification, ECOG (Eastern Cooperative Oncology Group) status, grade of lymphovascular invasion, cancer subtype, chemotherapy regimen received, nature of breast or axillary operation, or adjuvant radiation existed between the groups. A time to surgery greater than six weeks had a greater age and a higher clinical and post-neoadjuvant stage than the other two groups. The median time to surgery was 29 days (range, 11-153 days). The median follow-up was 47 months (range, two to 93 months). On multivariate analysis, which adjusted for clinical stage at diagnosis, lymphovascular invasion, receptor status and residual cancer burden score/ final pathologic stage, time to surgery of four to six weeks was associated with worse RFS (hazard ratio [HR], 1.998;
P<0.01), compared with less than four weeks. Time to surgery of more than six weeks was strongly associated with worse RFS (HR, 4.614; P<0.0001) and overall survival (HR, 2.461; P<0.01), compared with less than four weeks. The mean residual cancer burden score was higher in patients with a time to surgery of more than six weeks, compared with less than four weeks (HR, 2.192 vs. 1.426;
Time to surgery of more than six weeks was strongly associated with worse recurrence-free survival (hazard ratio, 4.614) and overall survival (hazard ratio, 2.461), compared with less than four weeks.
P<0.0001). On multivariate analysis, time to surgery of more than six weeks was associated with a positive size of effect on a residual cancer burden score of 0.59 (P<0.0001). Also, hormone receptor–positive disease, lymphovascular invasion and clinical stage III disease were associated with a higher residual cancer burden score (size continued on page 8
The Surgeon Orients in the OR for More Accurate Margin Analysis MarginMarker™ Sterile six-color ink kit; the surgeon applies ink to designate each margin for pathology.
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Request a Sample | VectorSurgical.com | +1 (262) 798-7970 Vector Surgical, the Vector Surgical Logo, MarginMarker and CorrectClips are trademarks of Vector Surgical LLC. Reg U.S. Pat & TM Off | © 2021 Vector Surgical LLC | References (1) Molina MA, Snell S, Franceshchi, D, et al. Breast specimen orientation. Ann Surg Oncol. 2009; 16:285-288. (2) Altman AM, Nguyen DD, Johnson B, et al. Intraoperative inking is superior to suture marking for specimen orientation in breast cancer. Breast J. 2019;00:1-7. (3) Singh M, Singh G, Hogan KT, Atkins KA, Schroen AT. The effect of intraoperative specimen inking on lumpectomy re-excision rates. World J Surg Oncol. 2010;8-4. (4) Van Den Bruele AB, Jasra B, Smotherman C, et al. Cost-effectiveness of surgeon performed intraoperative specimen ink in breast conservation surgery. Journal Surgical Research. 208;441-447 | MMCC SPREAD GSN JAN 2021
IN THE NEWS
JANUARY 2021 / GENERAL SURGERY NEWS
Simple Test Can Reveal More Hiatal Hernias By MARCUS A. BANKS
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erforming a 45-degree straight leg raise test on a patient who has experienced multiple rapid swallows detects hiatal hernias that would otherwise be missed during high-resolution esophageal manometry, new research shows. The findings could help clinicians better identify patients with hernias, and might even allow them to do so using telemedicine, according to the
researchers, who presented at the 2020 virtual meeting of the American College of Gastroenterology (poster P0868). “The nice thing about a straight leg raise is that it’s very easy to do at home,” said Mahesh Botejue, MD, a resident at Riverside Community Hospital, in California. “You can have a patient do a straight leg raise with a family member or a friend, and if they feel
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the onset of symptoms that would allow you the ability to determine if they need manometry or evaluation for GERD.” Dr. Botejue, who conducted the study as a medical student at Temple University, in Philadelphia, said a trained clinician should offer guidance to the family member or friend about how to correctly perform the straight leg raise via video. In the new study, the investigators performed high-resolution esophageal manometry (HREM) on 436 patients (283 women; mean age, 54.1±16.1 years). Of those, 216 (49.5%) had a hiatal hernia on baseline HREM. These clearly herniated patients had significantly lower pressure at the lower esophageal sphincter (LES; 5.8±6.6 vs. 13.2±7.7 mm Hg) and more significant heartburn than the others, the researchers reported. That left 220 patients without detected hiatal hernias at baseline HREM. Dr. Botejue and his colleagues performed straight leg raise tests to stimulate reflux in these patients as a way to reveal additional hiatal hernias. Dr. Botejue and his colleagues held both legs of patients at a 45-degree angle for 30 seconds after they had completed multiple rapid swallows. When peristaltic wave occurred, they noted which patients had positive or negative straight leg tests. They then assessed which patients with a positive straight leg test also had hiatal hernias, based on factors such as low LES pressure or high body mass index. For 24 of the 220 patients (10.9%) who completed straight leg raise tests, Dr. Botejue and his colleagues found previously undetected hiatal hernias. “For us, 10% is a substantial number,” he said. Straight leg raises are one of many physical maneuvers that could improve the diagnostic accuracy of HREM, according to Ronnie Fass, MD, a gastroenterologist at MetroHealth Medical System in Cleveland. While improving accuracy is always ideal, Dr. Fass cautioned that increasing the length of the HREM procedure could have diminishing returns. “Adding additional diagnostic maneuvers may prolong the time of an invasive procedure and potentially can affect patients’ tolerance and accuracy of the test,” he said. A diagnosis of hiatal hernia usually occurs during endoscopy, Dr. Fass added, and HREM usually is performed afterward. As a result, most patients who undergo HREM will already know whether they have a hiatal hernia. Thus, adding a straight leg raise to the HREM protocol may only be needed in rare cases, ■ he said.
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GENERAL SURGERY NEWS / JANUARY 2021
New Device Takes Robotics in Smaller, Simpler Direction By MONICA J. SMITH
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e’ve glimpsed a possible future of robotic surgery, and it’s just slightly larger than a bread box. Weighing less than two pounds, the miniaturized in vivo robotic assistant (MIRA) is about the size of a human hand and fits into a patient’s abdomen through a single 2.5- to 3-cm umbilical incision. Assembled together, the robot and a camera extend no more than 24 inches. “When we started our research into robotic surgery, we thought the current iteration on the market—the very large and expensive da Vinci system [Intuitive Surgical]—was probably not the right way to go about it,” said Dmitry Oleynikov, MD, the co-founder and chief medical officer of Virtual Incision, a medical device company that develops miniaturized robotic support systems. “The analogy we use is comparing the big mainframe computers from the 1970s and 1980s to what we have now, in our watches and iPhones.”
‘At this stage in the game, the MIRA is a fantastic concept, and it’s taking surgical robotics in a different direction. I think it will, ultimately, be better.’ —Michael A. Jobst, MD The MIRA features a robotically controlled articulating scope that fits through the center channel of the robot, and two interchangeable instruments; it is designed to create triangulation between the camera and instruments to provide unobstructed visibility and reduce the risk for collisions during surgery. Once the device is placed through the gel port, the surgeon can manipulate it to look at all four quadrants. “If the device needs to be advanced or withdrawn, that can be done with the help of the bedside assistant,” said Dr. Oleynikov, also the chair of surgery at Monmouth Medical Center and a clinical professor of surgery at Robert Wood Johnson Medical School of Rutgers University, in New Brunswick, N.J. The device is still in an investigational stage and not available for sale in the United States, but Dr. Oleynikov anticipates the MIRA will be used for general surgery procedures including colon resection, cholecystectomy, sleeve gastrectomy and hernia repair, pending FDA approval. In Paraguay two years ago, under strict research protocol, Dr. Oleynikov and his colleagues performed two colon resections with a slightly earlier prototype. “Both patients were successfully discharged from the hospital in just a couple of days with no problems or issues,” he said.
Breast Cancer continued from page 6
of effect of +1.02, +0.89 and +0.70, respectively; P<0.0001 for all). Human epidermal growth factor receptor 2 (HER2)-positive disease was associated with a lower residual cancer burden score (size of effect, –0.89; P<0.0001), and on subgroup analysis was the only group not affected by longer time to surgery.
The MIRA’s small size does not require a dedicated space or infrastructure, nor does it need a dedicated setup team, which could give it an advantage over currently available robotic platforms. The system is designed to be used anywhere general surgery is performed—an academic medical center, a community hospital or an ambulatory surgery center. “We anticipate the MIRA will open up access to robotic surgery much more broadly. Virtual Incision is focused on the underserved 80%-plus of the market that needs a smaller and simpler solution,” Dr. Oleynikov said. Feedback from robotic and laparoscopic surgeons regarding ease of use has been promising, he said. “The learning curve for laparoscopic colectomy is around 55 cases. Robotics has reduced that learning curve to 15 to 25 for a colectomy. We expect the MIRA to further reduce the learning curve to five to 10 cases.” The current system has two effectors, a bipolar grasper, monopolar scissors and a surgeon-controlled camera. The robot itself can be reused up to 15 times following sterilization, and the camera can be used up to 50 times. “Our plan would be to recycle the system after it has completed all of its cycles,” Dr. Oleynikov said. Although the company has not yet put a price on the system—it is too early in development to determine— the cost of a procedure conducted with the MIRA is expected to be roughly equivalent to a laparoscopic operation. Virtual Incision is working with the FDA for approval of its initial investigational device exemption trial, on which Michael A. Jobst, MD, will be one of the primary investigators. He has been consulting with Virtual Incision on the MIRA for a few years and has used it in a dry lab, pig models and a cadaver. “I think it’s awesome,” said Dr. Jobst, a colon and rectal surgeon at Surgical Associates, PC, in Lincoln, Neb. “Other surgeons point out that it doesn’t have a vessel sealer or stapling capability, but in 2010, the da Vinci system didn’t have those features, either. At this stage in the game, the MIRA is a fantastic concept, and it’s taking surgical robotics in a different direction. ■ I think it will, ultimately, be better.”
The miniaturized in vivo robot assistant (MIRA) consists of an articulating scope with two miniaturized arms (lower right) and a surgeon console (above and below).
Column Editor: Michael A. Goldfarb, MD, professor of surgery at Drexel University College of Medicine, in Philadelphia. Neither Dr. Goldfarb nor GSN has any financial relationship with Virtual Incision.
“In breast cancer patients receiving neoadjuvant chemotherapy, time to surgery greater than six weeks is independently associated with adverse recurrence and survival outcomes. We also showed that longer time to surgery is an independent predictor or higher residual cancer burden score. These findings may be mediated by tumor regrowth and metastatic seeding during the time to surgery interval,” Dr. Sutton said. “We
recommend that surgery be performed within six weeks following neoadjuvant chemotherapy in the absence of contraindications. Additional considerations should be given to operation within four weeks.” Asked to comment on the study, David Bartlett, MD, the system chair of the Allegheny Health Network Cancer Institute, and an immediate past president of the SSO, said the study was
practice-changing, as it suggests that HER2-negative breast cancer patients should have surgery within four weeks of completion of neoadjuvant therapy. “While timely surgery was previously felt to be important, this study demonstrates the importance of a less than fourweek time line with a potential impact on survival. This result will enhance the practitioners focus on having surgery within four weeks,” Dr. Bartlett said. ■
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IN THE NEWS
GENERAL SURGERY NEWS / JANUARY 2021
Mulitmodal Laxatives continued from page 1
novel therapeutic medications, such as alvimopan. “That’s where our trial comes in,” said lead author Nagendra N. Dudi-Venkata, a PhD candidate and general surgery trainee at Royal Adelaide Hospital, University of Adelaide, in Australia. In the study, 170 patients were randomized to receive the usual enhanced recovery protocol (ERP) or ERP with a multimodal laxative regimen called STIMULAX, consisting of Coloxyl with
senna (one tablet twice daily); macrogol (Movicol, one satchel twice daily) and a once-daily Fleet enema (in patients who had right-sided resections). STIMULAX was started on the day of surgery, except for the enema, which was started on post-op day 1, and continued until bowel action or hospital discharge. The primary outcome was GI-2, a validated composite measure of tolerance of a solid diet and passage of stool. STIMULAX patients achieved GI-2 with a
Outcomes of Multimodal Laxatives After Colorectal Surgery Mulitmodal Laxative Group
Control Group
GI-2 achieved
2 days
3 days
Prolonged post-op ileus
22.4%
37.6%
Length of stay
5 days
6 days
median of two days compared with three for the control arm (P=0.029). They also had a lower incidence of prolonged postoperative ileus (22.4% vs. 37.6%; P=0.030) and required one day less for the first passage of stool (two vs. three days; P<0.001). The 30-day postoperative complications were similar between the STIMULAX and control arms: Anastomotic leaks were reported in 5.6% and 6.5%, respectively (P>0.99). Patients had similar rates of diarrhea and electrolyte derangements. However, there was no significant difference in length of stay: Patients in the STIMULAX group had a median fiveday hospital stay (range, four to eight days) compared with six in the control arm (range, four to nine days) (P=0.171). As a result of the study, the investigators added multimodal laxatives to their standard ERP with one modification: replacing macrogol with magnesium hydroxide because of a reduced risk for vomiting, Dudi-Venkata said. While applauding the randomized trial design, Erin King-Mullins, MD, a colorectal surgeon at Georgia Colon and Rectal Surgical Associates, in Atlanta, questioned the value of the regimen without a measurable decrease in length of stay. “The overall goals of enhanced recovery are centered around getting that early return of bowel function in order to decrease length of stay and cost,” she said. She does not recommend laxatives for patients as part of an ERP based on the lack of current evidence. “I am somewhat concerned about the potential effects on postoperative fluid shifts and electrolyte derangements that may accompany such an aggressive approach to stimulating bowel function in the immediate post-op period, particularly if diarrhea is induced,” she said. The laxative Coloxyl with senna used in this study is not available in the United States, although its components are. Direct hospital costs were $1,300 lower in the STIMULAX group at $26,059, but the cost data do not apply here. Paula M. Termuhlen, MD, the regional campus dean and a professor of surgery continued on page 13
IN THE NEWS
JANUARY 2021 / GENERAL SURGERY NEWS
Evidence Grows for Avoiding Biopsy in Hepatocellular Carcinoma continued from page 1
“Preoperative tissue diagnosis of HCC is associated with decreased overall survival in patients in this national cohort,” said Fadi Dahdaleh, MD, a cancer surgeon and clinical assistant professor of surgery at Edward-Elmhurst Health, in Chicago, who presented the study. A primary hepatic malignancy that typically arises in the setting of chronic liver disease, HCC has a characteristic radiographic appearance on contrastenhanced imaging, with a predominant arterial blood supply that enables noninvasive diagnosis in high-risk subjects. The American College of Radiologists uses the Liver Imaging Reporting and Data System (LI-RADS) for standardized reporting. Specificity of clinical diagnosis using LI-RADS is over 90% in higher-risk patient populations rendering biopsy unnecessary for many. “Tumor dissemination along the needle tract is a well-documented phenomenon, estimated to occur in 2.5% to 10% of cases,” Dr. Dahdaleh said. When seeding occurs, the chest wall and peritoneal recurrences may arise, indicating that tissue diagnosis can convert localized to disseminated disease, he said. In the new study, researchers hypothesized that tissue diagnosis confirming HCC would confer inferior survival. To find out, the investigators conducted a retrospective case–control, propensity score–matched analysis of the National Cancer Database. Patients were included if they were older than 18, had a pathologic diagnosis of HCC, and were treated with major hepatic resection or transplantation. Patients were excluded if they had alternative diagnostic testing such as surgical exploration or open/laparoscopic surgical biopsies, underwent inadequate resections or had missing information about chemotherapy or radiation. The primary outcome was overall survival from the time of HCC diagnosis. Of 172,283 cases identified between 2006 and 2015, 16,366 met the inclusion criteria. The researchers found that 12,100 (73.9%) were men and mean age was 66.8 years. Curative procedures were divided equally between hepatectomies and transplantation (48.4% and 51.6%, respectively). The researchers found that 70.4% of cases had a clinical diagnosis and 29.6% underwent tissue diagnosis. After matching, 4,251 patients were selected from each group. Patients who underwent tissue diagnosis had decreased overall survival compared with the clinical diagnosis group (median, 121.76 vs. 63.38 months, respectively; P<0.001). Similarly, five-year survival was lower in the tissue diagnosis group (median, 68.2% vs. 51.6%; P<0.001). Overall survival advantage with clinical diagnosis persisted after
matching (85.6 vs. 65.5 months; P<0.001) and so did five-year survival (60.9% vs. 47.6%; P<0.001). In a stratified analysis among patients who had transplantation, survival advantage persisted with clinical diagnosis (mean, 89.4 months in the tissue diagnosis group vs. 100.28 months in the clinical diagnosis group; P<0.001). “The effect of tissue diagnosis was maintained after propensity-matching for factors known to impact biopsy method and survival in patients with HCC
including age, Charlson score, tumor size and lymphovascular invasion,” Dr. Dahdaleh said. “Those findings suggest avoiding biopsy whenever possible.” Dr. Dahdaleh said the study was limited in that it was a retrospective analysis, which was inherently susceptible to selection and observational biases, and the National Cancer Database did not include important end points such as recurrence patterns and disease-free survival. “This study is certainly informative for
REPROCESSED VESSEL SEALING DEVICES HAVE VISIBLE CONTAMINATION ON THEM.1,† A study published in Surgical Endoscopy raises questions about the sterility of reprocessed vessel-sealing devices
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clinical practice and reaffirms how many practice,” said Laleh Melstrom, MD, an assistant professor of surgery and immuno-oncology at City of Hope National Medical Center, in Duarte, Calif. “If a lesion meets clinical and imaging characteristics most clinicians that take care of patients with HCC do not pursue a biopsy. This is a well-established tenet of care, and it is excellent that these investigators were able to demonstrate an association ■ with survival.”
OF THE TIME.1 †Contamination was found following disassembly of the devices and jaws. The study found that 52% of reprocessed devices studied had visible contamination. The remaining 48% did not have contamination that was visible to the naked eye. ‡The combination of failed tests included visual inspection, optical and scanning electron microscopy, hemoglobin detection, and sterility testing. §Sterility assurance level of 10-6 accepted by the FDA as laid out in the Association for the Advancement of Medical Instrumentation (AAMI) standards ST67 and TIR 12 for devices contacting normally sterile tissue.
1. Chivukula, S.R., Lammers, S. & Wagner, J. Assessing organic material on single-use vessel sealing devices: a comparative study of reprocessed and new LigaSure™ devices. Surg Endosc (2020). https://doi.org/10.1007/s00464020-07969-8.
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IN THE NEWS
Surgery in the Millennial Age continued from page 1
millennial era. “Training in this modern environment has handed our trainees challenges and new opportunities. Likewise, entering and thriving in surgical practice in 2020 entails embracing a staggering volume of new innovation.” Surgeons in 2020 can look very diverse based on their backgrounds, training, use of technology, practice environment and patient mix, said Yalini Vigneswaran, MD, MPH, an assistant professor of surgery at the University of Chicago Pritzker School of Medicine. But there is still room for growth. About 21% of general surgeons in the United States are female, Dr. Vigneswaran said, citing 2017 data from the American Medical Association, not far ahead of gastroenterology, with 18% women. Underrepresented minorities also remain underrepresented in general surgery residency programs, accounting for up to 20% of trainees depending on ethnicity, according to 2014 data from the Accreditation Council for Graduate Medical Education. “This year, there’s been a lot of emphasis on diversity and inclusion,” Dr. Vigneswaran said. “Societies understand this is a priority that we are still behind, and need to make active efforts to grow diversity in the field.” In surgery, it’s important to think about inclusion not just in traditional ways but also in the technical aspects, she said. “One thing that has always bothered me as a female surgeon is a lot of the design of laparoscopy has not been remodeled,” she noted. “It’s been based upon man’s glove size 7 1/2 to 8, and a lot of this has not been redesigned. Several works have shown females and surgeons with smaller hands are more prone to injuries,” likely due to instrument design and training. She urged viewers to consider how to be more inclusive of other sizes and shapes of surgeons. Telemedicine and technology, especially in the COVID-19 pandemic, are revolutionizing how health care is developing, Dr. Vigneswaran added: “It’s becoming more clear telemedicine will not go away, even as we have better control of the pandemic.” Patients who are used to ordering packages on Amazon or ride shares through Uber also like being “one click away from immediate engagement and convenience,” she said. More facets of care, including evaluations and patient communications, are being done using technology. Technology can also be used for remote coaching and “telementoring” by more experienced surgeons, said Dimitrios Stefanidis, MD, PhD, FACS, FASMBS, a professor and the vice chair of education at Indiana University School of Medicine, in Indianapolis. This capability can be particularly beneficial for surgeons
seeking more help who live in rural areas or remote locations, he said. In addition, surgical technology has been increasing rapidly over the past decades, said Abel Bello, MD, FACS, FASBMS, a bariatric surgeon with MIB Surgery in Plantation, Fla., leaving some health care practitioners struggling to keep on top of new information. Always bear in mind, he said, that not all new technologies turn out to be beneficial or lasting. There are several ways to stay current
‘A surgeon’s skill and ability to perform a procedure well is unimportant, in fact irrelevant, if the procedure should not be done in the first place.’ —Abel Bello, MD
IN COMPLEX HERNIA REPAIR, PATIENT RISK FACTORS AND POSTOPERATIVE WOUND COMPLICATIONS CAN CONTRIBUTE TO THE PERIL OF HERNIA RECURRENCE
INDICATIONS STRATTICE™ Reconstructive Tissue Matrix (RTM), STRATTICE™ RTM Perforated, STRATTICE™ RTM Extra Thick, and STRATTICE™ RTM Laparoscopic are intended for use as soft tissue patches to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue membranes. Indications for use of these products include the repair of hernias and/or body wall defects which require the use of reinforcing or bridging material to obtain the desired surgical outcome. STRATTICE™ RTM Laparoscopic is indicated for such uses in open or laparoscopic procedures. These products are supplied sterile and are intended for single patient one-time use only. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS These products should not be used in patients with a known sensitivity to porcine material and/or Polysorbate 20. WARNINGS Do not resterilize. Discard all open and unused portions of these devices. Do not use if the package is opened or damaged. Do not use if seal is broken or compromised. After use, handle and dispose of all unused product and packaging in accordance with accepted medical practice and applicable local, state, and federal laws and regulations. Do not reuse once the surgical mesh has been removed from the packaging and/or is in contact with a patient. This increases risk of patient-to-patient contamination and subsequent infection. For STRATTICE™ RTM Extra Thick, do not use if the temperature monitoring device does not display “OK.” PRECAUTIONS Discard these products if mishandling has caused possible damage or contamination, or the products are past their expiration date. Ensure these products are placed in a sterile basin and covered with room temperature sterile saline or room temperature sterile lactated Ringer’s solution for a minimum of 2 minutes prior to implantation in the body. Place these products in maximum possible contact with healthy, well-vascularized tissue to promote cell ingrowth and tissue remodeling. These products should be hydrated and moist when the package is opened. If the surgical mesh is dry, do not use.
IN THE NEWS
JANUARY 2021 / GENERAL SURGERY NEWS
with surgical developments, Dr. Bello said. Communicate with your patients and peers; follow innovators in the field or join surgery groups on social media; read journals; join professional organizations and attend conferences; and note new product announcements, he advised. Be sure that any new technology has solid evidence of its efficacy and superiority over alternatives before you incorporate it into your practice, Dr. Bello said. “A surgeon’s skill and ability to perform a procedure well is unimportant, in fact irrelevant, if the procedure should not be done in the first place.” When deciding whether to adopt a new
surgical technology, consider if the technology will improve the quality of clinical care; if you have the financial, human and infrastructural resources to use it; and if you have evaluated all known or potential barriers to adoption, he said. Attend live courses and training seminars for the new equipment; remember there is a learning curve; and commit to small changes at a time, gradually increasing as you improve and experience better outcomes. Facebook has a number of private groups for surgeons, such as the International Hernia Collaboration and International Bariatric Club, and eight groups
for SAGES itself. Through these, practitioners can post surgical videos, share thoughts on journal articles, or ask professional colleagues for advice regarding challenging cases, said Omar Ghanem, MD, a bariatric surgeon at Mayo Clinic in Rochester, Minn. Surgeons also can make good use of other social media platforms, following innovators or sharing their research on Twitter, watching surgical videos on YouTube, or using Facebook pages or Instagram accounts to market their practices, posting photos or blog posts, said Neil Floch, MD, FACS, the section chief of
general surgery and director of bariatric surgery at Norwalk Hospital, in Connecticut. Be original and entertaining, he said, because people like new information. “It’s important that you participate,” Dr. Floch said. “Having your marketing team do it is not as significant as you, because your influence, reputation and visibility are key to promoting you as a surgeon, your practice and what you do.” ■ Dr. Bello reported consulting for Ethicon Endo-Surgery. The other speakers reported no relevant financial disclosures.
Multimodal GI continued from page 10
STRATTICE™ RTM, a 100% biologic mesh, is a durable solution for abdominal wall reconstruction based on the long-term outcomes of low hernia recurrence rates across multiple published clinical studies1-5 In a recent retrospective evaluation, biologic meshes were shown to have a
CUMULATIVE HERNIA RECURRENCE RATE OF
8.3
% AT
7 YEARS POST-OP1,*
*Includes po porc rcin inee annd bo bovi v ne ace cellul ular dermall matrices (ADMs) (n = 157). Bridged re reppair ir andd human ADM wer e e excluded from the study grou o p.
TO LEARN MORE ABOUT STRATTICE™ RTM, SPEAK TO YOUR ALLERGAN REPRESENTATIVE
at the University of Minnesota Medical School in Duluth, said a larger multiinstitutional study would help American surgeons become more comfortable with this protocol. Even so, the results may help surgeons who are looking for ways to enable patients to tolerate a regular diet faster and recover their energy, she said. “This is an important study because it helps us identify one way to assist patients with regaining their bowel function after intestinal surgery,” said Dr. Termuhlen, who moderated the session. In the journal American Surgeon (2020 Oct 7. [Epub ahead of print]), Dr. DudiVenkata and his colleagues reported results from a propensity score–matched analysis of 173 patients, of whom 67 had laxatives prescribed from day 1 after elective bowel resection, stoma reversal or formation of stoma, for any indication. The study, which was underpowered, showed a trend toward shorter GI-2 and days to passage of stool in favor of the laxative group, but the difference was not statistically significant. ■
COMING IN MARCH PRECAUTIONS (Continued) Certain considerations should be used when performing surgical procedures using a surgical mesh product. Consider the risk/benefit balance of use in patients with significant co-morbidities; including but not limited to, obesity, smoking, diabetes, immunosuppression, malnourishment, poor tissue oxygenation (such as COPD), and pre- or post-operative radiation. Bioburden-reducing techniques should be utilized in significantly contaminated or infected cases to minimize contamination levels at the surgical site, including, but not limited to, appropriate drainage, debridement, negative pressure therapy, and/or antimicrobial therapy prior and in addition to implantation of the surgical mesh. In large abdominal wall defect cases where midline fascial closure cannot be obtained, with or without separation of components techniques, utilization of the surgical mesh in a bridged fashion is associated with a higher risk of hernia recurrence than when used to reinforce fascial closure. For STRATTICE™ RTM Perforated, if a tissue punch-out piece is visible, remove using aseptic technique before implantation. For STRATTICE™ RTM Laparoscopic, refrain from using excessive force if inserting the mesh through the trocar. STRATTICE™ RTM, STRATTICE™ RTM Perforated, STRATTICE™ RTM Extra Thick, and STRATTICE™ RTM Laparoscopic are available by prescription only. For more information, please see the Instructions for Use (IFU) for all STRATTICE™ RTM products available at www.allergan.com/StratticeIFU or call 1.800.678.1605. To report an adverse reaction, please call Allergan at 1.800.367.5737. For more information, please call Allergan Customer Service at 1.800.367.5737, or visit www.StratticeTissueMatrix.com/hcp. References: 1. Garvey PB, Giordano SA, Baumann DP, Liu J, Butler CE. Long-term outcomes after abdominal wall reconstruction with acellular dermal matrix. J Am Coll Surg. 2017;224(3):341-350. 2. Golla D, Russo CC. Outcomes following placement of non-cross-linked porcine-derived acellular dermal matrix in complex ventral hernia repair. Int Surg. 2014;99(3):235-240. 3. Liang MK, Berger RL, Nguyen MT, Hicks SC, Li LT, Leong M. Outcomes with porcine acellular dermal matrix versus synthetic mesh and suture in complicated open ventral hernia repair. Surg Infect (Larchmt). 2014;15(5):506512. 4. Booth JH, Garvey PB, Baumann DP, et al. Primary fascial closure with mesh reinforcement is superior to bridged mesh repair for abdominal wall reconstruction. J Am Coll Surg. 2013;217(6):9991009. 5. Richmond B, Ubert A, Judhan R, et al. Component separation with porcine acellular dermal reinforcement is superior to traditional bridged mesh repairs in the open repair of significant midline ventral hernia defects. Am Surg. 2014;80(8):725-731. Allergan® and its design are trademarks of Allergan, Inc. STRATTICE™ and its design are trademarks of LifeCell Corporation, an Allergan affiliate. © 2019 Allergan. All rights reserved. STM122131 03/19
Extended Wound Care Coverage Articles planned for the March issue include … • On the Spot: Experts Debate the Most Controversial Issues in Wound Care • Clinical Review: Classification of Wounds • The Value of Early Adoption of Negative Pressure Wound Therapy • Biophysical Treatment of Wounds: Shockwave and Plasma on the Horizon
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GENERAL SURGERY NEWS / JANUARY 2021
Happy New Year, and welcome to the January issue of The Surgeons’ Lounge. In this issue, Abraham Betancourt, MD, FACS, a general surgery specialist in Weston, Fla., discusses the specific issues of operating on older patients. Also, in the section “The Instrument, the Name,” we explore the history of medical face masks. This is very timely as we all continue to go through the COVID-19 pandemic. Hoping all our readers stay safe! We look forward to our readers’ questions, Samuel Szomstein, MD, FACS S comments and interesting cases to present. Editor, The Surgeons’ Lounge e Szomsts@ccf.org g
Operating on Older Patients QUESTION for Dr. Betancourt From Joel S. Friede, MD, PGY-1 general surgery resident, Cleveland Clinic Florida, Weston
As general surgeons in minimally invasive times, we often have patients present to our office asking for surgical resolution of long-standing surgical disease. Sometimes a surgical approach may be challenging, as some of these patients have more burden than just anatomic disruption. Each patient we encounter in our office, the emergency department or as a consult has different demographics and comorbidities. We would like for you to discuss one particular demographic characteristic: the extremes of age, particularly the elderly patient. Please comment on the following:
• Can you tell us about the oldest patient you have operated on and what surgery you performed? • How did old age affect your surgical approach and decision making? • Was age a determinant factor on intra- and/or postoperative outcomes? • What does the most recent literature mention on this topic? Would you agree based on your experience?
Dr. Betancourt’s REPLY Can you tell us about the oldest patient you’ve operated on and what surgery you performed? It was a 100-year-old female patient for whom we were consulted by the ER. She presented with an acute abdomen and, after workup, was found to have a perforated gastric ulcer. We took her to the OR, and she underwent open repair with a modified Graham patch and abdominal washout. How did old age affect your surgical approach and decision making? The patient’s age should always be taken in consideration in order to choose the best approach, especially in acute care surgery. For this particular patient presenting with an acute abdomen, I wanted to address the situation without any delay given the fact that there were signs suggestive of sepsis, and that is precisely what I mean when I say good judgment must prevail in such acute cases. This was a very frail patient with prior operations, and she was very thin with a likely decreased cardiovascular reserve given her age. I knew a small supraumbilical incision would be a quick and effective solution and a good middle ground between an extensive midline laparotomy and a minimally invasive approach, and so avoiding the unnecessary stress from the pneumoperitoneum required for a laparoscopic approach but also with a small to midsized incision carrying less postoperative morbidity than an extensive laparotomy. Was age a determining factor on intra- and/or postoperative outcomes? It definitely was. Geriatric patients have a higher risk for complications and mortality given their frail nature. It is well known that physically, cognitively and nutritionally, this group of patients is depleted, so they have to be approached in a very unique way, which varies on a patient-to-patient basis. Intraoperatively, judicious fluid management with strict intake/output is certainly a must if we are to avoid any fluid overload. It is my personal experience that this age group does better with restrictive IV fluid strategies than fixed-volume strategies, which can cause fluid overload. Once surgery is done, special attention must be turned to the cognitive aspect of the patient. We must be very wary and avoid medications that might cause delirium or deteriorate the patient’s mentation. To do so, we must very accurately assess and document the patient’s baseline preoperatively, as any changes in mentation may be critical to postoperative outcomes in this age group. Also, nutritional status shouldn’t be neglected, both pre- and postoperatively. Every surgical team should assess and correct any nutritional deficiencies without delay, in order to improve wound healing. Last but not least, aggressive physical/occupational therapy
should be addressed. Most of the time you will note some baseline physical impairment in this group of patients, which can jeopardize their recovery. For this reason, we should tackle these issues sooner rather than later, and it might even be beneficial to begin preoperatively. Nowadays everything seems to be more standardized for postoperative management. For example, most institutions across the United States have implemented the enhanced recovery after surgery protocols in order to expedite patient recovery, but I want to highlight that, in this age group, a standardized automated approach for postoperative recovery should not be taken. We need to take our time and very thoroughly assess these patients and review their chart and history, as they need to be addressed in a detailed and comprehensive manner in order to offer the best chance for an uneventful recovery.
In order to provide optimal care for older surgical patients, a thorough assessment of the individual’s baseline health status is essential. What does the most recent literature mention on this topic? Would you agree based on your experience? Adults aged 65 years and older are the fastest-growing population in the United States, and their number is expected to double to 89 million between 2010 and 2050. Older surgical patients often require a different level of care than younger patients during the perioperative period. They are prone to developing postoperative complications, functional decline, loss of independence and other untoward outcomes. In order to provide optimal care for older surgical patients, a thorough assessment of the individual’s baseline health status is essential. Independent from the literature that we review and on which we base our care, I definitely agree that special attention must be paid when caring for this particular group of patients, and perhaps specialized care is more beneficial than standardized protocols. Protocols already exist that are directed toward postoperative geriatric care. In my daily practice, I use the guidelines for geriatric patients recommended by the American College of Surgeons, and strongly encourage readers to review them before taking any extreme age patient to the OR (https://bit.ly/3gN6a3u).
Suggested Reading Chow WB, Rosenthal RA, Merkow RP, et al. Optimal preoperative assessment of the geriatric surgical patient: a best practices guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. J Am Coll Surg. 2012;215(4):453-466.
SURGEONS’ LOUNGE
JANUARY 2021 / GENERAL SURGERY NEWS
15
The Instrument, the Name
Uncovering the History of Medical Face Masks in the Time of COVID-19 By Lisandro Montorfano, MD, and Mileydis Alonso, DO, Cleveland Clinic Florida, Weston
M
uch attention has been given to the role of the surgical mask in helping control the COVID-19 pandemic. The concept of universal masking has been debated at length since the early phases of the COVID-19 pandemic. The World Health Organization recommends that every person should wear a mask. Also, The New York Times has published several articles regarding surgical face mask usage in the general population. Although masks have become a symbol of our times, they have been around for many years. It is difficult to determine exactly when they were first used for preventing the spread of airborne infections.
droplet infections from spreading to the patients. However, it was not until 1910 that the use of face masks became common in hospitals and surgery (Figure). In 1915, Meltzer advised the use of a fine-mesh gauze mask to cover the faces of patients with infantile paralysis and the health care personnel caring for them. In 1918, Dr. George H. Weaver from the Durand Hospital in
MORE THAN
7 MILLION PATIENTS
Chicago described his two-year experience treating patients with diphtheria and showed that the incidence of diphtheria infections among attendants who wore a mask of double-thickness gauze was zero. Dr. Weaver was one of the first physicians who recommended sterilizing masks after the first use, replacing moist masks with sterile ones, and avoiding touching masks when in contact
with sick patients. That same year during World War I, Dr. Joseph A. Capps, a Major in the U.S. army, established that there was 95% effectiveness in protecting health care workers caring for patients with contagious diseases as well as for protecting patients against cross infections in military hospitals when wearing a three- to four-layer face mask. continued on the following page
HAVE RECEIVED
EXPAREL SINCE 20121
BUILT TO WEATHER POSTSURGICAL PAIN Figure. Illustration from the manuscript Matuschek C, Moll F, Fangerau H, et al. The history and value of face masks. Eur J Med Res. 2020;25(1):23.
In 1897, Dr. Carl Georg Friedrich Wilhelm Flügge, a famous bacteriologist and hygienist from Germany, developed the droplet theory of infection. His theory revolved around the idea that microorganisms in droplets expelled from the respiratory tract are a means of transmission. That same year, Dr. Johann Freiherr von Mikulicz-Radecki, a Polish surgeon, proposed that one layer of gauze could serve as what is now known as a surgical mask. In 1898, Dr. W. Huebner recommended masks made of two layers of gauze to be worn during operations, stating this mask was more efficient. Over the last century, medical researchers have continued to experiment with designs and materials. In 1905, Dr. Alice Hamilton, an American physician, published a manuscript wherein she suggested that scarlet fever was transmitted through respiratory droplets. She was an advocate of the use of face masks. Dr. Hamilton claimed that masks should be worn by nurses handling sterile dressings and doctors during operations to prevent
Non-opioid EXPAREL, powered by DepoFoam® technology, delivers precise pain control for the critical first few days after surgery to enable enhanced recovery.
In laparoscopic colorectal surgery, ERAS and multimodal protocols with EXPAREL improved clinical and economic outcomes2: FEWER OPIOIDS % over 3 days*†
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2.96 days vs 3.93 days (P=0.003)
Learn more at: www.EXPAREL.com ERAS=enhanced recovery after surgery; PACU=post-anesthesia care unit; LOS=length of stay. *The clinical benefit of the decrease in opioid consumption was not demonstrated in pivotal trials. † A retrospective observational study of 140 patients who underwent laparoscopic colon surgery, comparing local infiltration with EXPAREL 266 mg/20 mL expanded with 20 mL normal saline and 20 mL of 0.25% bupivacaine HCl to a historical matched control group for postsurgical pain, opioid use, and length of stay. Opioid utilization was measured using the World Health Organization’s defined daily dose (DDD), converting each opioid used into the respective DDD (intravenous fentanyl [1 DDD = 100 mcg], intravenous dilaudid [1 DDD = 2 mg], oral dilaudid [1 DDD = 4 mg], oral oxycodone [1 DDD = 20 mg], and hydrocodone [1 DDD = 10 mg]). ‡ Pain was measured using a visual analog scale (0 to 10). Indication EXPAREL is indicated for single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia. Safety and efficacy have not been established in other nerve blocks. Important Safety Information EXPAREL is contraindicated in obstetrical paracervical block anesthesia. Adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via infiltration were nausea, constipation, and vomiting; adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via interscalene brachial plexus nerve block were nausea, pyrexia, and constipation. If EXPAREL and other non-bupivacaine local anesthetics, including lidocaine, are administered at the same site, there may be an immediate release of bupivacaine from EXPAREL. Therefore, EXPAREL may be administered to the same site 20 minutes after injecting lidocaine. EXPAREL is not recommended to be used in the following patient population: patients <18 years old and/or pregnant patients. Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Warnings and Precautions Specific to EXPAREL Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL. EXPAREL is not recommended for the following types or routes of administration: epidural, intrathecal, regional nerve blocks other than interscalene brachial plexus nerve block, or intravascular or intra-articular use. The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered and may last for up to 5 days, as seen in clinical trials.
neurologic reactions with the use of local anesthetics. These include persistent anesthesia and paresthesia. CNS reactions are characterized by excitation and/or depression. Cardiovascular System Reactions: Toxic blood concentrations depress cardiac conductivity and excitability which may lead to dysrhythmias, sometimes leading to death. Allergic Reactions: Allergic-type reactions (eg, anaphylaxis and angioedema) are rare and may occur as a result of hypersensitivity to the local anesthetic or to other formulation ingredients. Chondrolysis: There have been reports of chondrolysis (mostly in the shoulder joint) following intra-articular infusion of local anesthetics, which is an unapproved use. Methemoglobinemia: Cases of methemoglobinemia have been reported with local anesthetic use. Please refer to brief summary of Prescribing Information on adjacent page. For more information, please visit www.EXPAREL.com or call 1-855-793-9727. References: 1. Data on File. 6306. Parsippany, NJ: Pacira BioSciences, Inc.; July 2020. 2. Keller DS, Pedraza R, Tahilramani RN, Flores-Gonzalez JR, Ibarra S. Impact of long-acting local anesthesia on clinical and financial outcomes in laparoscopic colorectal surgery. Am J Surg. 2017;214(1):53-58.
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Warnings and Precautions for Bupivacaine-Containing Products Central Nervous System (CNS) Reactions: There have been reports of adverse ©2020 Pacira BioSciences, Inc. Parsippany, NJ 07054 PP-EX-US-6100 10/20
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SURGEONS’ LOUNGE
Medical Masks continued from the previous page
Several studies were conducted over the next few years trying to determine which type of gauze mask was the most effective. The most well-known study was conducted by Dr. Brewster C. Doust and Dr. Arthur B. Lyon (JAMA 1918;71[15]:1216-1219). They tested three types of masks: coarse gauze, medium gauze and butter cloth. They concluded that the coarse gauze was ineffective and that finer gauze provided better results in terms of microorganism
Brief Summary (For full prescribing information refer to package insert) INDICATIONS AND USAGE EXPAREL is indicated for single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia. Limitation of Use: Safety and efficacy has not been established in other nerve blocks. CONTRAINDICATIONS EXPAREL is contraindicated in obstetrical paracervical block anesthesia. While EXPAREL has not been tested with this technique, the use of bupivacaine HCl with this technique has resulted in fetal bradycardia and death. WARNINGS AND PRECAUTIONS Warnings and Precautions Specific for EXPAREL As there is a potential risk of severe life-threatening adverse effects associated with the administration of bupivacaine, EXPAREL should be administered in a setting where trained personnel and equipment are available to promptly treat patients who show evidence of neurological or cardiac toxicity. Caution should be taken to avoid accidental intravascular injection of EXPAREL. Convulsions and cardiac arrest have occurred following accidental intravascular injection of bupivacaine and other amide-containing products. Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL. EXPAREL has not been evaluated for the following uses and, therefore, is not recommended for these types of analgesia or routes of administration. • epidural • intrathecal • regional nerve blocks other than interscalene brachial plexus nerve block • intravascular or intra-articular use EXPAREL has not been evaluated for use in the following patient population and, therefore, it is not recommended for administration to these groups. • patients younger than 18 years old • pregnant patients The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered and may last for up to 5 days as seen in clinical trials. ADVERSE REACTIONS Clinical Trial Experience Adverse Reactions Reported in Local Infiltration Clinical Studies The safety of EXPAREL was evaluated in 10 randomized, double-blind, local administration into the surgical site clinical studies involving 823 patients undergoing various surgical procedures. Patients were administered a dose ranging from 66 to 532 mg of EXPAREL. In these studies, the most common adverse reactions (incidence greater than or equal to 10%) following EXPAREL administration were nausea, constipation, and vomiting. The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following EXPAREL administration were pyrexia, dizziness, edema peripheral, anemia, hypotension, pruritus, tachycardia, headache, insomnia, anemia postoperative, muscle spasms, hemorrhagic anemia, back pain, somnolence, and procedural pain. Adverse Reactions Reported in Nerve Block Clinical Studies The safety of EXPAREL was evaluated in four randomized, double-blind, placebocontrolled nerve block clinical studies involving 469 patients undergoing various surgical procedures. Patients were administered a dose of either 133 or 266 mg of EXPAREL. In these studies, the most common adverse reactions (incidence greater than or equal to 10%) following EXPAREL administration were nausea, pyrexia, and constipation. The common adverse reactions (incidence greater than or equal to 2% to less than 10%) following EXPAREL administration as a nerve block were muscle twitching, dysgeusia, urinary retention, fatigue, headache, confusional state, hypotension, hypertension, hypoesthesia oral, pruritus generalized, hyperhidrosis, tachycardia, sinus tachycardia, anxiety, fall, body temperature increased, edema peripheral, sensory loss, hepatic enzyme increased, hiccups, hypoxia, post-procedural hematoma. Postmarketing Experience These adverse reactions are consistent with those observed in clinical studies and most commonly involve the following system organ classes (SOCs): Injury, Poisoning, and Procedural Complications (e.g., drug-drug interaction, procedural pain), Nervous System Disorders (e.g., palsy, seizure), General Disorders And Administration Site Conditions (e.g., lack of efficacy, pain), Skin and Subcutaneous Tissue Disorders (e.g., erythema, rash), and Cardiac Disorders (e.g., bradycardia, cardiac arrest). DRUG INTERACTIONS The toxic effects of local anesthetics are additive and their co-administration should be used with caution including monitoring for neurologic and cardiovascular effects related to local anesthetic systemic toxicity. Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL. Patients who are administered local anesthetics may be at increased risk of developing methemoglobinemia when concurrently exposed to the following drugs, which could include other local anesthetics: Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic cyclophosphamide, flutamide, hydroxyurea, ifosfamide, agents rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine Bupivacaine Bupivacaine HCl administered together with EXPAREL may impact the pharmacokinetic and/or physicochemical properties of EXPAREL, and this effect is concentration dependent. Therefore, bupivacaine HCl and EXPAREL may be administered simultaneously in the same syringe, and bupivacaine HCl may be injected immediately before EXPAREL as long as the ratio of the milligram dose of bupivacaine HCl solution to EXPAREL does not exceed 1:2. Non-bupivacaine Local Anesthetics EXPAREL should not be admixed with local anesthetics other than bupivacaine. Nonbupivacaine based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. There are no data to support administration of other local anesthetics prior to administration of EXPAREL.
GENERAL SURGERY NEWS / JANUARY 2021
transmission prevention. Those findings were later confirmed by Drs. G.H. Weaver and H.M. Leete in 1919. Surgical masks were widely used by the late 1920s. Further studies confirming the efficacy of surgical masks in preventing surgical wound infectious were published by Dr. I.J. Walker in 1930, Dr. Meleney in 1935, and Drs. D. Hart and J.F. Davis in 1937. In the 1940s, with the advent of antibiotics, attention to surgical masks decreased dramatically. There were no major publications or new improvements. However, over time, physicians realized
Other than bupivacaine as noted above, EXPAREL should not be admixed with other drugs prior to administration. Water and Hypotonic Agents Do not dilute EXPAREL with water or other hypotonic agents, as it will result in disruption of the liposomal particles USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary There are no studies conducted with EXPAREL in pregnant women. In animal reproduction studies, embryo-fetal deaths were observed with subcutaneous administration of bupivacaine to rabbits during organogenesis at a dose equivalent to 1.6 times the maximum recommended human dose (MRHD) of 266 mg. Subcutaneous administration of bupivacaine to rats from implantation through weaning produced decreased pup survival at a dose equivalent to 1.5 times the MRHD [see Data]. Based on animal data, advise pregnant women of the potential risks to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. Clinical Considerations Labor or Delivery Bupivacaine is contraindicated for obstetrical paracervical block anesthesia. While EXPAREL has not been studied with this technique, the use of bupivacaine for obstetrical paracervical block anesthesia has resulted in fetal bradycardia and death. Bupivacaine can rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity. The incidence and degree of toxicity depend upon the procedure performed, the type, and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus, and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function. Data Animal Data Bupivacaine hydrochloride was administered subcutaneously to rats and rabbits during the period of organogenesis (implantation to closure of the hard plate). Rat doses were 4.4, 13.3, and 40 mg/kg/day (equivalent to 0.2, 0.5 and 1.5 times the MRHD, respectively, based on the BSA comparisons and a 60 kg human weight) and rabbit doses were 1.3, 5.8, and 22.2 mg/kg/day (equivalent to 0.1, 0.4 and 1.6 times the MRHD, respectively, based on the BSA comparisons and a 60 kg human weight). No embryo-fetal effects were observed in rats at the doses tested with the high dose causing increased maternal lethality. An increase in embryo-fetal deaths was observed in rabbits at the high dose in the absence of maternal toxicity. Decreased pup survival was noted at 1.5 times the MRHD in a rat pre- and post-natal development study when pregnant animals were administered subcutaneous doses of 4.4, 13.3, and 40 mg/kg/day buprenorphine hydrochloride (equivalent to 0.2, 0.5 and 1.5 times the MRHD, respectively, based on the BSA comparisons and a 60 kg human weight) from implantation through weaning (during pregnancy and lactation). Lactation Risk Summary Limited published literature reports that bupivacaine and its metabolite, pipecoloxylidide, are present in human milk at low levels. There is no available information on effects of the drug in the breastfed infant or effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EXPAREL and any potential adverse effects on the breastfed infant from EXPAREL or from the underlying maternal condition. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use Of the total number of patients in the EXPAREL local infiltration clinical studies (N=823), 171 patients were greater than or equal to 65 years of age and 47 patients were greater than or equal to 75 years of age. Of the total number of patients in the EXPAREL nerve block clinical studies (N=531), 241 patients were greater than or equal to 65 years of age and 60 patients were greater than or equal to 75 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients. Clinical experience with EXPAREL has not identified differences in efficacy or safety between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Hepatic Impairment Amide-type local anesthetics, such as bupivacaine, are metabolized by the liver. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations, and potentially local anesthetic systemic toxicity. Therefore, consider increased monitoring for local anesthetic systemic toxicity in subjects with moderate to severe hepatic disease. Renal Impairment Bupivacaine is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. This should be considered when performing dose selection of EXPAREL. OVERDOSAGE Clinical Presentation Acute emergencies from local anesthetics are generally related to high plasma concentrations encountered during therapeutic use of local anesthetics or to unintended intravascular injection of local anesthetic solution. Signs and symptoms of overdose include CNS symptoms (perioral paresthesia, dizziness, dysarthria, confusion, mental obtundation, sensory and visual disturbances and eventually convulsions) and cardiovascular effects (that range from hypertension and tachycardia to myocardial depression, hypotension, bradycardia and asystole). Plasma levels of bupivacaine associated with toxicity can vary. Although concentrations of 2,500 to 4,000 ng/mL have been reported to elicit early subjective CNS symptoms of bupivacaine toxicity, symptoms of toxicity have been reported at levels as low as 800 ng/mL. Management of Local Anesthetic Overdose At the first sign of change, oxygen should be administered. The first step in the management of convulsions, as well as underventilation or apnea, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously. The clinician should be familiar, prior to the use of anesthetics, with these anticonvulsant drugs. Supportive treatment of
circulatory depression may require administration of intravenous fluids and, when appropriate, a vasopressor dictated by the clinical situation (such as ephedrine to enhance myocardial contractile force). If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted. Endotracheal intubation, employing drugs and techniques familiar to the clinician, maybe indicated, after initial administration of oxygen by mask, if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated. DOSAGE AND ADMINISTRATION Important Dosage and Administration Information • EXPAREL is intended for single-dose administration only. • Different formulations of bupivacaine are not bioequivalent even if the milligram strength is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to EXPAREL. • DO NOT dilute EXPAREL with water for injection or other hypotonic agents, as it will result in disruption of the liposomal particles. • Use suspensions of EXPAREL diluted with preservative-free normal (0.9%) saline for injection or lactated Ringer’s solution within 4 hours of preparation in a syringe. • Do not administer EXPAREL if it is suspected that the vial has been frozen or exposed to high temperature (greater than 40°C or 104°F) for an extended period. • Inspect EXPAREL visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer EXPAREL if the product is discolored. Recommended Dosing in Adults Local Analgesia via Infiltration The recommended dose of EXPAREL for local infiltration in adults is up to a maximum dose of 266mg (20 mL), and is based on the following factors: • Size of the surgical site • Volume required to cover the area • Individual patient factors that may impact the safety of an amide local anesthetic As general guidance in selecting the proper dosing, two examples of infiltration dosing are provided: • In patients undergoing bunionectomy, a total of 106 mg (8 mL) of EXPAREL was administered with 7 mL infiltrated into the tissues surrounding the osteotomy, and 1 mL infiltrated into the subcutaneous tissue. • In patients undergoing hemorrhoidectomy, a total of 266 mg (20 mL) of EXPAREL was diluted with 10 mL of saline, for a total of 30 mL, divided into six 5 mL aliquots, injected by visualizing the anal sphincter as a clock face and slowly infiltrating one aliquot to each of the even numbers to produce a field block. Regional Analgesia via Interscalene Brachial Plexus Nerve Block The recommended dose of EXPAREL for interscalene brachial plexus nerve block in adults is 133 mg (10 mL), and is based upon one study of patients undergoing either total shoulder arthroplasty or rotator cuff repair. Compatibility Considerations Admixing EXPAREL with drugs other than bupivacaine HCl prior to administration is not recommended. • Non-bupivacaine based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. • Bupivacaine HCl administered together with EXPAREL may impact the pharmacokinetic and/or physicochemical properties of EXPAREL, and this effect is concentration dependent. Therefore, bupivacaine HCl and EXPAREL may be administered simultaneously in the same syringe, and bupivacaine HCl may be injected immediately before EXPAREL as long as the ratio of the milligram dose of bupivacaine HCl solution to EXPAREL does not exceed 1:2. The toxic effects of these drugs are additive and their administration should be used with caution including monitoring for neurologic and cardiovascular effects related to local anesthetic systemic toxicity. • When a topical antiseptic such as povidone iodine (e.g., Betadine®) is applied, the site should be allowed to dry before EXPAREL is administered into the surgical site. EXPAREL should not be allowed to come into contact with antiseptics such as povidone iodine in solution. Studies conducted with EXPAREL demonstrated that the most common implantable materials (polypropylene, PTFE, silicone, stainless steel, and titanium) are not affected by the presence of EXPAREL any more than they are by saline. None of the materials studied had an adverse effect on EXPAREL. Non-Interchangeability with Other Formulations of Bupivacaine Different formulations of bupivacaine are not bioequivalent even if the milligram dosage is the same. Therefore, it is not possible to convert dosing from any other formulations of bupivacaine to EXPAREL and vice versa. Liposomal encapsulation or incorporation in a lipid complex can substantially affect a drug’s functional properties relative to those of the unencapsulated or nonlipid-associated drug. In addition, different liposomal or lipid-complexed products with a common active ingredient may vary from one another in the chemical composition and physical form of the lipid component. Such differences may affect functional properties of these drug products. Do not substitute. CLINICAL PHARMACOLOGY Pharmacokinetics Administration of EXPAREL results in significant systemic plasma levels of bupivacaine which can persist for 96 hours after local infiltration and 120 hours after interscalene brachial plexus nerve block. In general, peripheral nerve blocks have shown systemic plasma levels of bupivacaine for extended duration when compared to local infiltration. Systemic plasma levels of bupivacaine following administration of EXPAREL are not correlated with local efficacy. PATIENT COUNSELING Inform patients that use of local anesthetics may cause methemoglobinemia, a serious condition that must be treated promptly. Advise patients or caregivers to seek immediate medical attention if they or someone in their care experience the following signs or symptoms: pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue.
Pacira Pharmaceuticals, Inc. San Diego, CA 92121 USA Patent Numbers: 6,132,766 5,891,467 5,766,627 8,182,835 Trademark of Pacira Pharmaceuticals, Inc. For additional information call 1-855-RX-EXPAREL (1-855-793-9727) Rx only November 2018
antibiotics were not a replacement for careful attention to sterile techniques. In the 1950s, aseptic surgical technique became extremely important, and the whole concept included the use of surgical scrubs, gloves, proper gowning, capping and sterile drapes, among other measures. In 1958, Drs. J.C. Kiser and C.R. Hitchcock designed a mask that combined the properties of filtration and deflection. Dr. R. Adams evaluated this mask and concluded that a fitted filter mask was more efficient than gauze masks. In 1961, Dr. M.M. Musselman described a new fitted mask intended to be used only once and then discarded. In the 1970s, the first N95 masks were created by 3M using a melt-blown process. It was initially designed for industrial use, but it became a health care standard following the virus-blocking technology developed by Professor Peter Tsai at the University of Tennessee. Today, the COVID-19 pandemic has brought a huge surge in the number of patients, shortage of health care personnel, and limited bed space, and the contribution of an efficient surgical mask plays a crucial role in helping to prevent COVID-19 transmission. Surgical masks not only help protect ourselves and others by reducing overall viral transmission, but they function as a visual aide-mémoire to intensify diligent hand hygiene and social distancing. Surgical masks also represent an act of solidarity, displaying that the citizens of the world are on board with the preventive measures needed to control COVID-19 contagion. ■
Suggested Reading Bowman E. N95 mask shortage brings inventor out of retirement in search of safe reuse method [transcript]. Morning Edition. National Public Radio. April 17, 2020. Matuschek C, Moll F, Fangerau H, et al. The history and value of face masks. Eur J Med Res. 2020;25(1):23. Rockwood CA, O’Donoghue DH. The surgical mask: its development, usage, and efficiency: a review of the literature, and new experimental studies. AMA Arch Surg. 1960;80(6):963-971. Spooner JL. History of surgical mouth masks. AORN J. 1967;5:76-80. Tirupathi R, Bharathidasan K, Palabindala V, et al. Comprehensive review of mask utility and challenges during the COVID19 pandemic. Infez Med. 2020;28(suppl 1):57-63. University of Tennessee Research Foundation. UT researcher’s nonwoven fabrics protect the health of more than a billion people. August 27, 2019. Accessed July 24, 2020. https://utrf.tennessee.edu/ut-researchersnonwoven-fabrics-protect-the-health-ofmore-than-a-billion-people/ Wilson M. The untold origin story of the N95 mask. Fast Company. March 24, 2020. Accessed July 24, 2020. http://fastcompany.com
IN THE NEWS
JANUARY 2021 / GENERAL SURGERY NEWS
Antibiotic Stewardship for SSIs continued from page 1
of antibiotic stewardship, which attempts to maximize the benefits of these agents while minimizing risk. “As the patient’s surgeon, you are best positioned to influence the decisions regarding indication for antibiotic exposure and achieving adequate source control,” Dr. May said. “Decisions that you make, or at least that you influence, have very significant implications for your patient. Getting antibiotics right is your responsibility.” As Dr. May reported, the first death in the United States from a pan-resistant pathogen occurred in January 2017. The surgical patient, who died of sepsis from an incompletely drained seroma following a femur fracture, had been treated with multiple rounds of antibiotics and had Klebsiella pneumoniae isolated that was resistant to all 26 available antibiotics for gram-negative bacteria, including aminoglycoside and polymyxin classes. However, according to Dr. May, this complication was preventable.
have adequate information to indicate their benefit. “Getting the coverage and timing of antibiotic therapy right makes a big difference, but so does using antibiotics when they are not needed,” said Dr. May, who noted that excessive antibiotic use is associated with an increased risk for subsequent infectious complications in both prophylactic and therapeutic settings. As Dr. May reported, results of a randomized trial of one versus five days of
antibiotics following penetrating abdominal trauma showed that patients receiving the longer course of therapy had nearly twice the infection risk. This also holds true for other prophylactic settings in patients who are critically ill, Dr. May said, including those with head and neck cancer, pneumonia, candidemia, and extraabdominal infections when treating intraabdominal processes.
Antibiotic-Resistant Infections Antibiotic exposure is also the single biggest risk factor for subsequent antibiotic-resistant bacterial infections. This is
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true across all classes, Dr. May said, but is more strongly associated with some classes than others, particularly second- and third-generation cephalosporins and fluoroquinolones for gram-negative bacteria. According to Dr. May, the risk for subsequent resistant infections increases with excessive use in both the prophylactic and therapeutic settings, and increases with each day of antibiotic exposure. A study of over 6,000 patients, for example, showed a 2.8% increased risk for antibiotic-resistant infection with each day of exposure to broad-spectrum antibiotic therapy. This continued on page 22
‘Getting the coverage and timing of antibiotic therapy right makes a big difference, but so does using antibiotics when they are not needed.’ —Addison K. May, MD Dr. May outlined six important concepts regarding antibiotic use: Adequate spectrum of empirical antibiotic therapy and prophylaxis. Adequate empirical therapy, which is defined as covering all the involved pathogens, is strongly associated with increased survival across all sites as well as all pathogens. Optimal timing of initial antibiotic therapy and prophylaxis. The time to initial antibiotic therapy is strongly associated with outcome, particularly for patients who are severely ill. In a study of patients with septic shock, every hour delay from hypotension to initiating antibiotics was associated with a 12% increase in the risk for death. This association is true across all pathogens and all settings. Appropriate pharmacokinetic dosing. Appropriate dosing is required to achieve adequate levels of antibiotics at the tissue site. Deescalation of empirical antibiotic therapy. Once the pathogen is known, deescalation of empirical antibiotics limits exposure to broad-spectrum antibiotics. Duration of antibiotic prophylaxis and therapy. Not using antibiotics beyond their proven benefit will limit antibiotic exposure. Avoidance of unnecessary antibiotic therapy. Use antibiotics only when you
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Management News The Independent Source of News for Operating Room Managers, Supply Chain Professionals & C Suite
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GENERAL SURGERY NEWS / JANUARY 2021
n this installment of Journal Watch, we welcome guest columnist Shannelle Campbell, MD, MPH, a general surgeon and an assistant professor at UNC Chapel Hill, in North Carolina. We will be evaluating two recent articles from the British Journal of Surgery: one that looks at mesh weight and chronic groin pain, and the other comparing treatment of diverticulitis with either primary anastomosis or Hartmann’s procedure. We also review findings from the recently published PROVE-IT trial, comparing minimally invasive ventral hernia repair techniques. The hope is readers will find these worthwhile topics relevant to the scope of a general surgeon’s expertise and be able to use the findings to alter and/or reinforce current practice.
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No Association Found Between Mesh Weight and Chronic Pain in Study In the British Journal of Surgery, Melkemichel et al published the results of a prospective, patient-reported outcomes study that identified the presence of chronic pain after open anterior inguinal hernia repair based on mesh weight (2020;107[12]:1659-1666). Using the Swedish Hernia Registry, male patients aged at least 15 years who underwent unilateral Lichtenstein repair of an inguinal hernia between 2012 and 2016 were asked to complete a questionnaire assessing the presence of pain one year after surgery. The questions were taken from the validated Inguinal Pain Questionnaire, specifically developed for groin hernia repairs. Exclusion criteria included female patients, femoral hernias, nonsutured mesh, mesh fixated with absorbable sutures (repairs involving plugs/patches/Prolene Hernia System or UltraPro Hernia System [Ethicon]), an open posterior approach, emergency hernia repairs and bilateral hernia repairs. Clinically important variables were analyzed, such as age, American Society of Anesthesiologists (ASA) status, type of hernia, hernia recurrence, nerve management and grade of surgeon. The primary end point of the study was significant patient-reported chronic pain one year after hernia repair. The questionnaire asked respondents to grade their pain on a scale of 1 to 7, with 1 being no pain and 7 being pain present with prompt medical advice sought. Levels 1 to 3 indicated no pain and levels 4 to 7 represented pain, with a level of at least 4 indicating significant persistent pain. Three mesh types were analyzed: heavyweight standard polypropylene (≥50 g/m2); regular lightweight polypropylene (<50 g/m2); and composite lightweight polypropylene with absorbable monofilament poliglecaprone-25 fibers (weight <30 g/m2). A total of 43,303 open anterior mesh groin hernia repairs were performed during the time frame. The response rate to the pain questionnaire at one year after surgery was 70.6%. After exclusions, 23,259 hernia repairs were available for analysis. Of these, 3,690 patients (15.9%) reported persistent pain one year after surgery. Severe pain was reported by 6.9% of the study population. The proportions of hernia repairs using heavyweight, lightweight and composite lightweight mesh were similar among the groups that did or did not develop chronic pain. Other hernia-related characteristics were comparable. The pain group had a higher proportion of younger patients (17% vs. 13.3% in the no-pain group). Logistic regression analyses showed no significant difference in chronic pain between regular lightweight or composite lightweight versus heavyweight mesh. Young age was the strongest risk factor for developing chronic pain (19.4% among patients <50 years of age); a subgroup analysis showed no significant difference in the risk for chronic pain between lightweight and lightweight composite versus heavyweight mesh. Other associations with the development of chronic
pain include direct hernia repairs, ASA grades III to IV and lack of iliohypogastric nerve identification. In this prospective study, the authors found no association between chronic pain and mesh weight after open anterior inguinal hernia repair. Study limitations include the absence of validation using patient-related factors (smoking, body mass index, medications, postoperative complications), which were difficult to assess due to missing data. Data on different types of mesh were grouped together, which could lead to misclassification bias. Mesh properties other than weight were not studied. Maybe, most importantly, there was no information regarding preoperative pain among patients, which may have confounded the study results. Also, the study population consisted of only Swedish male patients, which may limit generalizability. However, this study’s strengths include satisfactory response rate to the questionnaire and the availability of data on loss to follow-up, which allowed comparisons of responders and nonresponders.
Cost-Effectiveness of Primary Anastomosis Versus Hartmann’s Procedure for Perforated Diverticulitis In the British Journal of Surgery, Lambrichts et al published the results of a cost-effectiveness analysis of the DIVA arm of the Ladies trial, which explored sigmoid resection with primary anastomosis (PA) or end colostomy (2020;107[12]:1686-1694). The Ladies trial was a multicenter, randomized, openlabel, superiority trial performed in Belgium, Italy and the Netherlands to assess outcomes of the surgical management of perforated diverticulitis. The DIVA arm of this trial compared sigmoid resection with PA, with or without diverting ileostomy, with Hartmann’s procedure (HP) in patients with Hinchey III or IV perforated diverticulitis. Patients were included if they were 18 to 85 years of age, hemodynamically stable and immunocompetent. Exclusion criteria included patients with dementia, a history of sigmoidectomy or pelvic radiation therapy, chronic steroid treatment, or preoperative shock requiring inotropic support. The primary end point of the DIVA arm was 12-month stoma-free survival; secondary outcomes of morbidity and readmissions also were recorded. Recent studies suggested that the benefits of PA include lower morbidity rates, a higher rate of stoma-free survival, shorter time to stoma reversal and a shorter post-reversal hospital stay, which may reduce associated costs, but no cost-effectiveness studies comparing the two approaches have been done. Therefore, this study aimed to assess the cost-effectiveness and cost utility of HP compared with PA during the first 12 months after the index procedure. This was performed from the societal perspective. Data on resource use were collected prospectively through clinical record forms and study questionnaires completed at one, three, six, nine and 12 months after the index procedure. Direct medical costs (e.g., costs of index and reversal operations, reinterventions,
Arielle Perez, MD, MPH, MS Director of UNC Health Hernia Center and Assistant Professor of Surgery in the Division of General, Acute Care, and Trauma Surgery at the University of North Carolina at Chapel Hill School of Medicine Column Editor
Shannelle Campbell, MD, MPH Guest Columnist
diagnostic imaging, readmissions, outpatient visits, emergency department visits and stoma care) and direct nonmedical costs, associated with home care and travel expenses, were evaluated. Indirect nonmedical costs resulting from work absence or decreased productivity were determined by using the Short Form Health and Labour Questionnaire. Total costs per patient were calculated by multiplying resources used by associated unit costs. Unit costs were calculated in euros and adjusted to 2018 by the Dutch consumer price index. Health-related quality of life (QOL) and quality-adjusted life-years (QALYs) were derived from the EuroQoL-5D threelevel questionnaire (EQ-5D) at two weeks, four weeks, and three, six and 12 months after the index procedure. Outcomes were scored from 0 to 1, with 1 being optimal QOL. Patients were analyzed according to the modified intention-to-treat principle. Missing data on the EQ-5D and on indirect costs were imputed by means of multiple imputation. Sensitivity analyses were performed by varying unit costs to determine the robustness of calculated costs. Incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were calculated by dividing the incremental costs by the incremental probability of being stoma-free and incremental QALYs, respectively. A total of 130 patients were included, with 66 in the HP group and 64 in the PA group. Stoma-related costs and total costs were higher in the HP group, with a mean difference in costs of –8,126 euros (–$9,966.42) in favor of PA. The mean probability of being stomafree at the end of 12 months was 86% for the PA group and 65% for the HP group. The ICER was –39,094 euros (–$47,961.89), indicating that PA was more costeffective than HP. The accompanying ICER plane shows that PA is dominant. The mean value QALYs during 12-month follow-up were 0.72 in the PA group and 0.64 in the HP group, resulting in an ICUR of –101,435 euros (–$124,444.01). Unit costs for specified cost groups were increased and decreased by 20% and 50%, while those for other cost groups were not changed for the sensitivity analyses. The results of the sensitivity analyses showed that PA was associated with lower costs, with cost differences ranging from –7,263 euros (–$8,910.50) to –8,932 euros (–$10,958.09). Overall, this study demonstrates that PA is more cost-effective with a higher likelihood of being stomafree in the first year. However, this study’s results may not be generalizable, as the majority of patients in the study were Dutch, and unit costs and calculations were based on the Dutch health care system. Also, the results should be interpreted within the context of the inclusion and exclusion criteria of the DIVA arm. Another limitation is the small sample size of this study, as a result of early termination of enrollment due to slow accrual. The response rate to the questionnaires sent out during follow-up was 47% to 64%; multiple imputation techniques were used to handle missing data and reduce the influence of attrition bias. Nevertheless, this study is
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based on a multicenter randomized trial with prospective cost data collected from a societal perspective—taking into account indirect nonmedical costs—which is a strength. Also, unit costs were derived from hospital ledgers and the Dutch costing manual, allowing for more granular reflection of clinical practice, compared with costs being derived from diagnosis-related group data.
PROVE-IT Trial: Laparoscopic Versus Robot-Assisted for Ventral Hernia Repair In JAMA Surgery, Petro et al discuss the results from the PROVE-IT trial, which evaluated patient-reported outcomes of robotic versus laparoscopic ventral hernia repair (VHR) with intraperitoneal mesh (2020 Oct 21. [Epub ahead of print]). This randomized trial evaluated minimally invasive VHR performed by two surgeons from 2017 to 2020 at Cleveland Clinic. Inclusion criteria for the study were elective patients aged 18 years or older with a primary or incisional midline ventral hernia of 7 cm or less, amenable to minimally invasive repair. Both laparoscopic and robotic surgery were initiated by gaining laparoscopic intraabdominal access based on surgeon preference and then placing additional trocars. Reduction of hernia contents with subsequent adhesiolysis to allow for 5-cm mesh overlap past the defect was performed before mesh placement. For patients undergoing robotic repair, adhesiolysis method—robotic or laparoscopic—was left to surgeon
preference. Defect closure was performed using serial figure-of-eight 0 monofilament permanent suture and a transfascial suture passer using a shoelacing technique, as previously described by Orenstein et al for laparoscopic repairs (Surg Endosc 2011;25[5]:1452-1457; Table), and a running 0 permanent self-locking suture for robotic repairs. A barrier-coated monofilament polypropylene mesh was then secured as an intraperitoneal onlay mesh (IPOM) using four permanent transfascial sutures at four cardinal points, and then a double-crown fixation of permanent tacks for the laparoscopic repair and a circumferential 3-0 self-locking suture for the robotic repair. The primary outcome measurement was patientreported pain scores, measured by the 0-to-10 Numerical Rating Scale (NRS-11), on postoperative day 1. NRS-11 scores were also collected preoperatively, in the PACU, and days 1, 7, 30 and 365 after surgery. Secondary outcome measurements included pain as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity - Short Form 3a and abdominal wall–specific QOL using the HerniaRelated QOL Survey (HerQLes), OR time, PACU opioid consumption, rates of same-day discharge, hospital length of stay, surgical site infection, surgical site occurrence, surgical site occurrence requiring a procedural intervention, ventral hernia recurrence and cost. In total, 81 patients were randomized, with 39 in each arm. Three patients in each group were excluded due to conversion to open repair, with two other patients in
the robotic arm being converted to laparoscopic repair (one due to a bed malfunction making robot docking unsafe and one due to limited intraperitoneal space making intracorporeal suturing difficult). Both groups were similar in regard to patient demographics, medical comorbidities and hernia characteristics, except for the laparoscopic arm, which had a lower BMI (31 vs. 35 kg/ m2; P=0.02). Further analysis to account for the difference in BMI showed no difference. Laparoscopic repairs had significantly shorter median operative times compared with robotic VHR (94 vs. 146 minutes; P<0.001), with both surgeons having comparable times on both platforms. Postoperative NRS-11 scores on postoperative day 1 were the same, as well as additional NRS-11 scores. Hospital LOS, opioid consumption in the PACU and rates of same-day discharge were similar. PROMIS pain and HerQLes QOL score changes were similar between the two groups. Although the laparoscopic group demonstrated a statistically significant improvement in PROMIS 3a pain scores (–3 vs. 0; P=0.3), this difference has been shown to be clinically insignificant. The cost ratio was significantly less for the laparoscopic group and attributed to the difference in OR time, with similar findings of disposable/reusable item costs. The PROVE-IT trial is the latest randomized controlled trial evaluating robotics versus laparoscopy, from some of the same authors as the RIVAL trial, which evaluated inguinal hernia repair, and is the first to continued on page 22
Article
Journal
Study Design
Key Takeaways
Words of Caution
Useful Related Articles
Patient-reported chronic pain after open inguinal hernia repair with lightweight or heavyweight mesh: a prospective, patient-reported outcomes study
Melkemichel M, Bringman S, Nilsson H, et al. Br J Surg. 2020;107(12):16591666
Prospective cohort (patientreported outcomes study)
• Patient-reported chronic pain one year after open mesh repair of inguinal hernia is common, particularly in young men
• Study population of only Swedish male patients may not be applicable to other populations
Uzzaman MM, Ratnasingham K, Ashraf N. Hernia. 2012;16(5):505-518
• Confounding variables of patient-related factors (smoking, BMI, medications, postoperative complications) were not assessed
Sajid MS, Leaver C, Baig MK, et al. Br J Surg. 2012;99(1):29-37
• Risk for developing chronic pain was not influenced by type of mesh
• Data on different types of heavyweight and regular lightweight mesh were grouped together; mesh properties other than weight could not be studied in this cohort • Baseline preoperative pain was not assessed • Use of self-fixating mesh and absorbable fixation were not assessed
Cost-effectiveness of sigmoid resection with primary anastomosis or end colostomy for perforated diverticulitis: an analysis of the randomized Ladies trial
Lambrichts DPV, van Dieren S, Bemelman WA, et al. Br J Surg. 2020;107(12):16861694
Costeffectiveness analysis of multicenter, parallel-group, randomized, open-label superiority trial (DIVA arm of the Ladies trial)
• Total costs were lower for primary anastomosis than for Hartmann’s procedure • Higher probability of being stomafree at end of 12 months after primary anastomosis compared with Hartmann’s procedure • Incremental cost-effectiveness was –39,094 euros (–$47,961.89), indicating that primary anastomosis is more cost-effective than Hartmann’s procedure
• Study results may not be generalizable to all populations (study population mostly Dutch, and all hemodynamically stable, immunocompetent patients <85 years of age); unit costs and calculations are all based on Dutch health care system
Lambrichts DPV, Vennix S, Musters GD, et al. Lancet Gastroenterol Hepatol. 2019;4(8):599-610
• Small sample size; enrollment into study was terminated early due to slow accrual
• Higher quality-adjusted life-years during 12-month follow-up with primary anastomosis than with Hartmann’s procedure Patient-reported outcomes of robotic vs laparoscopic ventral hernia repair with intraperitoneal mesh: The PROVEIT randomized clinical trial
Petro CC, Zolin S, Krpata D, et al. JAMA Surg. 2020 Oct 21. [Epub ahead of print]
Randomized controlled trial
• No difference in 30-day pain scores, hospital length of stay, complications or quality of life with robotic or laparoscopic intraperitoneal onlay mesh (IPOM) repair • Robotic IPOM repair has a longer operative time and higher cost when compared with laparoscopic IPOM repair • Long-term follow-up is imperative of all surgeons to ensure evaluation
• Increased cost was due to difference in operative time; with increased efficiency and reduced disposable costs, overall costs may offset • Robotic IPOM, as discussed by the authors, may be a bridge to more complex robotic hernia repairs, which show benefit with costs, length of stay, pain, etc.
Orenstein SB, Dumeer JL, Monteagudo J, et al. Surg Endosc. 2011;25(5):1452-1457 Bittner JG IV, Alrefai S, Vy M, et al. Surg Endosc. 2018;32(2):727-734 Kudsi OY, Gokcal F, Chang K. Am J Surg. 2020;220(4):837-844 Martin-Del-Campo LA, Weltz AS, Belyansky I, et al. Surg Endosc. 2018;32(2):840-845
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Robotic Hernia Repair: What Exactly Are We Arguing About? continued from page 1
technology becomes more widely adopted, whereas others claim that the traditional system of presenting and publishing data—especially in the form of randomized controlled trials (RCTs)—is not designed to pick up the nuances offered by this technology. Supporters of robotic surgery say the literature does not demonstrate the advantages they see in their practices. Conrad Ballecer, MD, a surgeon in Arizona and a vocal educator in robotic surgery, said, “For the overwhelming majority of surgeons who have incorporated robotics into their practice, they don’t need peer-reviewed publications to legitimize what they do.” The debate on robotic hernia repair splinters along the private versus academic divide in surgery, Dr. Ballecer said. Scientific publications belong to the world
‘For the overwhelming majority of surgeons who have incorporated robotics into their practice, they don’t need peer-reviewed publications to legitimize what they do.’ —Conrad Ballecer, MD
‘We’ve never accepted, in most realms of medicine, to just throw your hands in the air and say, “Well, I guess we’re just not going to evaluate these techniques.” That's not how it works.’
—Clayton Petro, MD
‘I can’t ethically look at my patients and say, “I’m going do this procedure one way or the other; I don’t know which one is better,” when I do know.’ —Yuri Novitsky, MD
‘I do think [contributing data] is part of your responsibility, particularly if that's something you want to keep offering to patients.’
—Ajita Prabhu, MD
of academia, but private practice surgeons are driving the robotic movement in hernia repair and have amassed some of the largest series in the world, he said. Most don’t publish their results or participate in trials, he added. Instead, they tend to share their experiences through training programs or on social media, which accelerates knowledge sharing compared with traditional publishing. Dr. Ballecer said these forums provide critical information about robotic hernia repair. “I don’t think it’s an obligation that surgeons publish. It’s our obligation to follow up our patients and track our own data,” he said. “At the end of the day, people are going to do what works in their practice.”
State of the Evidence Most of the studies of robotic inguinal or ventral hernia repair are case series or retrospective comparative studies, along with some registry-based reports from the Abdominal Core Health Quality Collaborative (formerly the Americas Hernia Society Quality Collaborative). Three published reports from RCTs compare robotic and laparoscopic repairs. The multicenter RIVAL (Robotic Inguinal vs Transabdominal Laparoscopic Inguinal Hernia Repair) trial of inguinal hernia repair—in which Dr. Warren participated—compared a robotic approach with a transabdominal laparoscopic approach; the authors found showed no clinical benefit for patients and, contrary to expectations, no ergonomic advantages for the participating surgeons (JAMA Surg 2020;155[5]:380-387). The authors reported higher costs, longer operative time and additional surgeon frustration using the robotic approach. A multicenter trial of 124 patients in Houston demonstrated that robotic ventral repairs increased operative duration and health care costs, but did not reduce 90-day postoperative hospital days (BMJ 2020;370:m2457). In addition, last October, surgeons from Cleveland Clinic reported results from the PROVE-IT randomized trial comparing the patient-reported outcomes of 75 patients who underwent robotic or laparoscopic ventral hernia repair (JAMA Surg [Epub Oct 21, 2020]. doi: 10.1001/jamasurg.2020.4569). Two surgeons performed all the repairs; both completed fellowships with training in advanced laparoscopy and complex abdominal wall reconstruction, and both had robotic training and credentialing in line with requirements from their department and Intuitive Surgical (the maker of the da Vinci system). One of the enrolling surgeons had several years of robotic experience and the other was in the first year of clinical practice. They found the two approaches resulted in similar outcomes, with no differences in postoperative pain, complication rates, quality of life and hospital length of stay. The robotic approach increased the median operative time by 52 minutes, with robotic procedures taking a median of 146 minutes. This incurred additional cost, which the authors said was not offset by a measurable clinical benefit. They concluded that “the need for randomized trials evaluating these robotic techniques now grows more important than ever. … Owing to the increased operative time and associated cost, there is currently no measurable benefit to justify the robotic approach.” Ajita Prabhu, MD, and Clayton C. Petro, MD, surgeons from Cleveland Clinic, led the PROVE-IT trial, and Dr. Prabhu also participated in the RIVAL trial.
Dr. Prabhu said they expected the PROVE-IT trial to demonstrate that patients who underwent robotic repair experienced less pain; it did not. “It is true that we did not find a clinical benefit for the patient with one approach over the other,” she said. “However, this does not suffice to say that this is evidence of the absence of clinical benefit. We’re going to need a lot more data from surgeons from other centers with long-term follow-up.” She added that although the study is small, there is value in publishing the experiences of two minimally invasive surgery‒trained surgeons who compared the two approaches in a randomized fashion. Drs. Prabhu and Petro also looked at the question of fixation of the mesh prosthesis in intraperitoneal onlay mesh procedures. The robotic platform makes it possible to do intracorporeal suturing and peritoneal mesh fixation with a running stitch. But the PROVE-IT study suggested patients did not have less pain if their mesh was sewn in place robotically instead of fixed with tacks and transfascial sutures laparoscopically. In an invited commentary, surgeons Ann M. Defnet, MD, and S. Scott Davis Jr., MD, noted that it is “valuable to know that sewing the mesh may not adequately address the problem of postoperative pain.” They predicted the study would be criticized because the investigating surgeons were not expert robotic surgeons and called on “robotic protagonists to demonstrate the benefits with higher level evidence to support widespread adoption.” Since then, other surgeons have taken issue with the authors’ conclusions. Yuri Novitsky, MD, the director of the Comprehensive Hernia Center at Columbia University, in New York City, said the PROVE-IT study had methodological flaws. The authors did not record the pain medications used by patients and did not collect pain data at a standardized point, he said. He added that at least one of the enrolling surgeons was still in their learning curve. He is concerned that the authors came to negative, sweeping conclusions about the robot and suggested this could have harmful consequences for other surgeons’ practices. “The way this study is concluded, the way it’s designed, it may impede robotic access and utilization by those who have learned to rely on it,” Dr. Novitsky said. He said he worries that hospital administrators and insurance companies may be influenced by the study’s conclusions. Robotic inguinal hernia repair and intraperitoneal mesh placement for ventral hernias are often regarded as techniques that surgeons should be comfortable with before moving to more advanced robotic techniques, the PROVE-IT authors said. However, if future studies fail to show a clinical benefit of the robot in advanced procedures, then use of the robot in more basic techniques becomes “a bridge to nowhere,” they wrote. Sean Orenstein, MD, an associate professor of surgery at Oregon Health & Science University, in Portland, disagreed. He uses the robot in complex cases where he would struggle with regular laparoscopy, having first trained on the robot with simpler cases. “It is a bridge to somewhere, and an important bridge,” he said. “But how do you measure that in a study?”
The Role of RCTs in Assessing the Robot It will be challenging to tease out the benefits of robotic repairs through small RCTs, said surgeons on both sides of the debate. For inguinal hernia repair, patient outcomes tend to be continued on page 22
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Robotic Hernia Repair continued from page 20
good whether it is performed robotically or laparoscopically, so to discern a measurable difference would require large numbers of patients. For ventral hernia repairs, the issue is more complicated. For one, the robotic approach makes it easier for surgeons to transition from performing open repairs to minimally invasive surgery. The visualization is better, and it can be easier to identify specific tissue planes and manipulate tissue. “To me, it’s still laparoscopy but a heightened version of it,” Dr. Orenstein said. The robot allows a surgeon to keep mesh out of the peritoneal cavity. For robotic transversus abdominis release or extended totally extraperitoneal repair, there isn’t necessarily a laparoscopic alternative. “If you’re someone who feels like it’s very important to get mesh out of the peritoneal cavity, then the robot is great because it allows you to do that,” Dr. Petro noted. “The trouble is that to elucidate that in a clinical trial isn’t necessarily practical. It takes years and years to come to fruition.” Dr. Petro added that RCTs are excellent at answering a single specific question, but the results of one trial cannot be used to call for an end to robotic hernia repairs. “A negative conclusion doesn’t mean that a trial is anti-robot. It just means that the answer to one question did not favor the robot,” he said. A randomized trial requires equipoise; investigators must believe that it’s ethical to randomly assign patients to either treatment arm. Surgeons who are more facile with one approach over the other feel it’s unfair to subject their patients to randomization. “I can’t ethically look at my patients and say, ‘I’m going do this procedure one way or the other; I don’t know which one is better,’ when I do know,” Dr. Novitsky said. Many published studies of robotic surgery in hernia and other general surgery fields use operating time as an outcome. In many of these studies, robotic cases take longer, particularly when a surgeon is early in their learning curve. The added time in the OR is not always offset by shorter lengths of stay or clinical benefits. But operating times may be a misleading variable, given inherent differences in the techniques used and the experience of surgeons in the study, Dr. Warren said.
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matters, Dr. May said, because multidrug-resistant pathogens are associated with increased mortality. “Prolonged antibiotic therapy cannot replace source control,” Dr. May concluded. “Extending antibiotics if they haven’t worked over a short period is rarely effective over a longer period.” Robert G. Sawyer, MD, the chair of the Department of Surgery at Western Michigan University, in Kalamazoo, noted that infection with an antibiotic-resistant organism is a product of a seriously disordered host microbiome, and exposure to antibiotics is by far the most significant event that disrupts the host microbiome. According to Dr. Sawyer, many other risk factors for infections with resistant organisms are merely
“Operating times vary so much from surgeon to surgeon and practice to practice.” Just because randomized trials are challenging does not mean they should not be done, Dr. Petro noted. “We’ve never accepted, in most realms of medicine, to just throw your hands in the air and say, ‘Well, I guess we’re just not going to critically evaluate these techniques.’ That’s not how it works,” he said, adding that if only experts do trials, the results may not be applicable to real-world practice.
Dr. Orenstein said a paradigm shift has occurred in modern medicine, moving away from traditional publishing to more hands-on learning. Industry-sponsored courses are essential for developing advanced surgical skills for new techniques and technology. “They’re becoming more popular,” he said, acknowledging that there is a potential for bias because courses are industry sponsored. “But I think surgeons make a concerted effort to be up front and honest with our surgical education and teaching,” he said.
Does Conflict of Interest Matter?
Surgeons Tracking Their Outcomes
Surgeons who educate, lecture and publish about robotic repairs often do so with financial support from the industry. Dr. Warren said he believes surgeons who receive industry support are too often “dismissed out of hand” for working with industry. He receives funding from Intuitive Surgical, but feels it should not be used to undermine his publications if he is transparent about reporting it. “It can be insulting because I want to educate others, and the best way to do that is via industryassisted tools. It doesn’t mean I’m not genuine in my evaluation of and use of the robot.” Surgeons are not always forthcoming about industry support, even though it is required. In a 2018 analysis published in Annals of Surgery, investigators reported that the authors of robotic surgery studies did not consistently report payments from Intuitive Surgical in published articles, based on a comparison with the Open Payments database (Ann Surg 2018;268[1]:86-92). “As long as people are open about industry support, I think it’s fine. But they need to be open about it,” Dr. Petro said. Industry support is critical for the development of new technologies and the training of surgeons, said Edward Felix, MD, a retired private practice surgeon in California. An early adopter of laparoscopy for hernia repair, he has become convinced of the robot’s value after initially criticizing the technology. Industry-supported training in robotic surgery has led to welltrained surgeons and prevented some of the errors of the laparoscopic era, he said. “In the early days of laparoscopy, there was no real mentoring and there were no restraints. That’s why I think it took 25 years for laparoscopic hernia repair to take off,” he said.
Dr. Prabhu believes surgeons need to track, present and publish their experiences with new technology. If they don’t want to participate in RCTs, they should contribute to registries, which can help demonstrate where the robot has value, she said. She noted that sharing information on social media is not enough. “I do think [contributing data] is part of your responsibility, particularly if that’s something that you want to keep offering to patients,” she said. “The best thing that we can do is educate ourselves as to what’s out there, critically appraise it and decide how to use it.” Dr. Warren believes it is only a matter of time before the published literature reflects what surgeons claim the robot can do. He said as more surgeons gain experience with the robot and publish more results, the advantages will become evident. However, that won’t occur without more data from surgeons about what is happening in their practices, Dr. Warren cautioned. “Those of us who are out there preaching the robotic technique and the benefits of this new approach, we have an obligation to review our results, talk about our results, track those results, and hopefully to publish those results,” he said. ■
markers for possible prior antibiotic exposure, such as age, diabetes and institutionalization. Therefore, he said, the most important data to decide on altering empirical therapy are history of prior infections, colonization or antibiotic use. “Antibiotic resistance is really, really important,” said Dr. Sawyer, who noted that appropriate empirical therapy never overrides source control. “Pervasive resistant bacteria in the community are rare, but may become more important in the United States someday. “I usually follow guidelines, unless there is documented history of infection or colonization with a resistant organism or a recent course of antibiotics,” Dr. Sawyer added. “Act quickly when you see these patients, choose your antibiotics wisely, reassess frequently and then don’t overdo it with ■ your antibiotics.”
Dr. Ballecer is a consultant for Intuitive Surgical and Medtronic. Dr. Felix receives speaking fees from Medtronic. Dr. Novitsky is a consultant and proctor for Intuitive Surgical; a consultant for BD Interventional; and has received grants from Intuitive Surgical. Dr. Orenstein is an instructor and consultant and serves on the advisory board of BD Bard; an instructor for Intuitive Surgical; an instructor and consultant for LifeCell/Allergan; and a consultant for Polynovo. Dr. Petro is the recipient of a 2020 SAGES Robotic Research Grant. Dr. Prahbu has received consulting fees from CMR Surgical and Verb Surgical, as well as speaker fees and research support to the Cleveland Clinic from Intuitive Surgical. Dr. Warren has received honoraria from Intuitive Surgical for speaking and teaching.
Journal Watch continued from page 19
evaluate VHR with intraperitoneal mesh. The study found no difference in pain, complications, LOS or QOL with laparoscopic or robotic IPOM VHR. The most salient finding of this study was the increased OR time and cost with robotic repair. The authors do a good job addressing arguments that can be posed by robot enthusiasts and other critics of the study’s methodology, as well as evaluating the limitations of the report. Although the robotic platform appears to take longer and be more costly, it appears that with increased efficiency and reduced cost of disposables—realized with the recently launched Intuitive Extended Use Program—the cost difference may become a moot point. Also, the level and consistency of the OR staff during these cases is unclear and may affect OR times; in surgery, especially robotic surgery, a knowledgeable OR team
can play a critical role in time to dock and exchange instruments. The IPOM technique evaluated in this study is often, as acknowledged by the authors, considered a basic procedure, and is a means of safely learning the robotic techniques and then expanding into more advanced procedures for complex hernia repair and abdominal wall reconstruction. These more advanced procedures have been shown in other studies to have benefit when performed on the robot compared with open or laparoscopic techniques. The results from the PROVE-IT and RIVAL trials demonstrate the costliness of robotics in more basic hernia repair. The value of the robotic platform for use in more advanced cases may be of great benefit, as argued by robotic adopters, or potentially may be a “bridge to nowhere,” as posed by the authors. It is for this reason that surgeons must ensure long-term outcomes evaluation and continued high-quality evi■ dence in the form of studies.
Important Safety Information (continued) Kcentra is contraindicated in patients with known anaphylactic or severe systemic reactions to Kcentra or any of its components (including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin). Kcentra is also contraindicated in patients with disseminated intravascular coagulation. Because Kcentra contains heparin, it is contraindicated in patients with heparin-induced thrombocytopenia (HIT). Hypersensitivity reactions to Kcentra may occur. If patient experiences severe allergic or anaphylactic type reactions, discontinue administration and institute appropriate treatment. In clinical trials, the most frequent (≥2.8%) adverse reactions observed in subjects receiving Kcentra were headache, nausea/vomiting, hypotension, and anemia. The most serious adverse reactions were thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis. Kcentra is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), cannot be completely eliminated. To report SUSPECTED ADVERSE REACTIONS, contact the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
KCENTRA® (Prothrombin Complex Concentrate [Human]) For Intravenous Use, Lyophilized Powder for Reconstitution Initial U.S. Approval: 2013
• Administer reconstituted Kcentra at a rate of 0.12 mL/kg/min (~3 units/kg/min) up to a maximum rate of 8.4 mL/min (~210 units/min). Pre-treatment INR
BRIEF SUMMARY OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Kcentra safely and effectively. See full prescribing information for Kcentra. WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS Patients being treated with Vitamin K antagonists (VKA) therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the potential risks of thromboembolic events, especially in patients with the history of a thromboembolic event. Resumption of anticoagulation should be carefully considered as soon as the risk of thromboembolic events outweighs the risk of acute bleeding. • Both fatal and non-fatal arterial and venous thromboembolic complications have been reported with Kcentra in clinical trials and post marketing surveillance. Monitor patients receiving Kcentra for signs and symptoms of thromboembolic events. • Kcentra was not studied in subjects who had a thromboembolic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the prior 3 months. Kcentra may not be suitable in patients with thromboembolic events in the prior 3 months. ------------------------------------INDICATIONS AND USAGE---------------------------------Kcentra, Prothrombin Complex Concentrate (Human), is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients with: • acute major bleeding or • need for an urgent surgery/invasive procedure. -----------------------------DOSAGE AND ADMINISTRATION--------------------------------For intravenous use after reconstitution only. • Kcentra dosing should be individualized based on the patient’s baseline International Normalized Ratio (INR) value, and body weight. • Administer Vitamin K concurrently to patients receiving Kcentra to maintain factor levels once the effects of Kcentra have diminished. • The safety and effectiveness of repeat dosing have not been established and it is not recommended.
Dose* of Kcentra (units† of Factor IX) / kg body weight Maximum dose‡ (units of Factor IX) *
† ‡
2–< 4
4–6
>6
25
35
50
Not to exceed 2500
Not to exceed 3500
Not to exceed 5000
Dosing is based on body weight. Dose based on actual potency is stated on the vial, which will vary from 2031 Factor IX units/mL after reconstitution. The actual potency for 500 vial ranges from 400-620 units/vial. The actual potency for 1000 unit vial ranges from 800-1240 units/vial. Units refer to International Units. Dose is based on body weight up to but not exceeding 100 kg. For patients weighing more than 100 kg, maximum dose should not be exceeded.
---------------------------------DOSAGE FORMS AND STRENGTHS-------------------------• Kcentra is available as a white or slightly colored lyophilized concentrate in a single-use vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S. --------------------------------------CONTRAINDICATIONS -----------------------------------Kcentra is contraindicated in patients with: • Known anaphylactic or severe systemic reactions to Kcentra or any components in Kcentra including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin. • Disseminated intravascular coagulation. • Known heparin-induced thrombocytopenia. Kcentra contains heparin. ----------------------------------WARNINGS AND PRECAUTIONS---------------------------• Hypersensitivity reactions may occur. If necessary, discontinue administration and institute appropriate treatment. • Arterial and venous thromboembolic complications have been reported in patients receiving Kcentra. Monitor patients receiving Kcentra for signs and symptoms of thromboembolic events. Kcentra was not studied in subjects who had a thrombotic or thromboembolic (TE) event within the prior 3 months. Kcentra may not be suitable in patients with thromboembolic events in the prior 3 months. • Kcentra is made from human blood and may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. -----------------------------------ADVERSE REACTIONS---------------------------------------• The most common adverse reactions (ARs) (frequency * 2.8%) observed in subjects receiving Kcentra were headache, nausea/vomiting, hypotension, and anemia. (6) • The most serious ARs were thromboembolic events including stroke, pulmonary embolism, and deep vein thrombosis. To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring at 1-866-9156958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Revised: October 2018
KCT-0320 Kcentra Journal Ad Re-Size General Surgery News.indd 2
8/14/20 3:43 PM
You can't freeze time waiting for plasma to thaw
Choose Kcentra for fast and sustained urgent warfarin reversal vs plasma* FASTER ACTING† Superior INR reduction at 30 minutes after end of infusion vs plasma
FASTER ADMINISTRATION, LOWER VOLUME • Mean infusion time is under 25 minutes • ~85% less volume vs plasma
SUSTAINED INR REDUCTION‡ Statistically significant INR reduction sustained ≤1.3 for up to 8 or 12 hours vs plasma
When time is essential, it’s time for Kcentra
Learn more at www.Kcentra.com
*Effective hemostasis measured up to 24 hours for the Acute Major Bleeding trial and until the end of procedure (up to 24 hours) for the Urgent Surgery/Invasive Procedures trial. Rapid INR reduction to ≤1.3 at 0.5 hours after end of infusion. †In 2 head-to-head trials, Kcentra demonstrated superiority to plasma in 3 of 4 efficacy endpoints. Superior hemostatic efficacy in the Urgent Surgery/Invasive Procedures trial and equally effective hemostasis in the Acute Major Bleeding trial. Faster INR reduction (to ≤1.3 at 30 minutes after end of infusion) in both head-to-head trials. ‡8 hours for Urgent Surgery/Invasive Procedures trial and 12 hours for Acute Major Bleeding trial. Administer vitamin K concurrently to patients receiving Kcentra. Vitamin K is administered to maintain vitamin K-dependent clotting factor levels once the effects of Kcentra have diminished.
Important Safety Information Kcentra is a blood coagulation factor replacement indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA—eg, warfarin) therapy in adult patients with acute major bleeding or the need for urgent surgery or other invasive procedure. Kcentra is for intravenous use only. WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS Patients being treated with Vitamin K antagonist therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the risk of thromboembolic events, especially in patients with history of such events. Resumption of anticoagulation therapy should be carefully considered once the risk of thromboembolic events outweighs the risk of acute bleeding. Both fatal and nonfatal arterial and venous thromboembolic complications have been reported in clinical trials and postmarketing surveillance. Monitor patients receiving Kcentra, and inform them of signs and symptoms of thromboembolic events. Kcentra was not studied in subjects who had a thromboembolic event, myocardial infarction, disseminated intravascular coagulation, cerebral vascular accident, transient ischemic attack, unstable angina pectoris, or severe peripheral vascular disease within the prior 3 months. Kcentra might not be suitable for patients with thromboembolic events in the prior 3 months. Please see additional Important Safety Information and the brief summary of full prescribing information on adjacent page.
Kcentra is manufactured by CSL Behring GmbH and distributed by CSL Behring LLC. Kcentra® is a registered trademark of CSL Behring GmbH. Biotherapies for Life® is a registered trademark of CSL Behring LLC. ©2020 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA www.CSLBehring.com www.Kcentra.com KCT-0320-AUG20