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Highlights From the American Society Of Colon and Rectal Surgeons
All Articles by CHRISTINA FRANGOU
The American Society of Colon and Rectal Surgeons (ASCRS) held its 2021 meeting virtually this spring. Here, General Surgery News presents some of the top papers from the meeting.
The TINGLE Trial: TAP Block With Liposomal Bupivacaine Not Supported
A liposomal bupivacaine block does not provide superior or extended analgesia for minimally invasive colorectal surgery, according to results from the first randomized trial comparing liposomal bupivacaine with bupivacaine plus epinephrine and dexamethasone for transversus abdominis plane blocks.
“While the ideal TAP block medication isn’t known, the very expensive liposomal bupivacaine [Exparel, Pacira] doesn’t seem to offer any benefits above our recommended mixture of bupivacaine, epinephrine and dexamethasone, which is highly effective, cheap and readily available,” said author Adam Truong, MD, the chief surgical resident at Cedars-Sinai Medical Center, in Los Angeles.
The study is published in Diseases of the Colon & Rectum (2021;64[7]:888-898).
In the single-center trial, 102 adult patients undergoing minimally invasive colorectal surgery were randomized 1:1 to receive a laparoscopic TAP block with liposomal bupivacaine or bupivacaine with epinephrine and dexamethasone.
There was no difference in the primary end point of total oral morphine equivalents administered within 48 hours after surgery. Patients received 69 mg in the liposomal bupivacaine group and 47 mg in the group with bupivacaine plus epinephrine and dexamethasone (difference in median 95% CI, –17 to 49 mg; P=0.60).
Emily Carter Paulson, MD, an associate professor of clinical surgery at the University of Pennsylvania, in Philadelphia, noted that the difference in postoperative morphine use could be clinically significant, even though it was not statistically significant. “It seems that a 50% difference in opioid usage is pretty significant,” she said.
The study had 84% power to detect a 15-mg mean difference in 48-hour morphine requirement, Dr. Truong said.
There were no significant differences in pain scores, time to ambulation, time to diet tolerance or bowel movement, length of stay, overall complications or readmission rates between the two groups.
The average wholesale price of liposomal bupivacaine is $336.22 compared with $5.47 for a TAP block with bupivacaine plus epinephrine and dexamethasone.
Dr. Truong said the study could not be conducted in a double-blind fashion, as the investigators were required to document the administered TAP block medication into the medication administration record. In order to conceal the treatment assignment, the team performed several methods, such as employing a single investigator who was not part of the treatment team to manage randomization and handling of medications.
The paper was first presented at the ASCRS in 2020 and received the New England Society of Colon & Rectal Surgeons Award. It was presented this spring as part of the “best of 2020” session.
Male surgeons perform more highly remunerated procedures in colorectal surgery than their female counterparts, contributing to a gender wage gap in colorectal surgery, according to an analysis of Medicare claims data.
Investigators examined nearly 63,000 Medicare claims submitted by board-certified colorectal surgeons between 2013 and 2017. Of these, only 16.9% were from female surgeons—a rate that increased annually, reaching 22.7% in 2017.
Analysis showed that, every year, male surgeons submitted more claims, submitted more highly reimbursed claims and used a greater number of procedural codes than female surgeons. Men and women were remunerated the same amount for performing the same procedures, but mean submitted charges per female surgeon in 2017 were $2,562 less than that for male surgeons ($16,614 vs. $19,176; P<0.0001). The same year, the average reimbursement for female surgeons was $4,193 compared with $4,962 for male surgeons, for a difference of $1,105 (P<0.0001).
At $689 per procedure, therapeutic endoscopy was the highest remunerated claim. Half of male surgeons who submitted Medicare claims performed therapeutic endoscopies, compared with only one-third of female surgeons (P<0.001). In 2017, male surgeons submitted claims for 675 polypectomies, the most commonly performed therapeutic endoscopic procedure; female surgeons submitted 107.
In comparison, 41.8% of female surgeons obtained the majority of their income from outpatient clinic procedures. These are the lowest remunerated procedures at $189.
The study also showed that male surgeons utilize a higher proportion of procedural codes compared with female surgeons (98% vs. 46%; P<0.0001). Of the 147 unique codes used in 2017, 77 were used only by male surgeons compared with three that were used only by female surgeons.
The study did not look at private practice wage contributions, rank, and seniority of surgeons or academic and educational pursuits.
Lead author Nathalie Sela, MD, an abdominal transplant surgery fellow at the University of Nebraska Medical Center, in Omaha, said the study could not account for factors driving this wage gap. Other studies have shown that female surgeons receive fewer referrals and are quicker to lose referrals after a single negative outcome. They’re also more likely to have smaller clinical networks (Am J Surg 2020;220[1]:69-75).
“Understanding this unique gender equity will allow current surgeons to offer greater support and mentorship for future generations,” Dr. Sela said.
High-Risk Features in Stage II Colon Cancer Portend Worse Survival Than Stage III Disease
A new analysis suggests that patients with multiple high-risk features in the presence of stage II colon cancer have worse survival than patients with stage III disease.
High-risk features “have a cumulative effect in stage II colon cancer,” said study author Brian Herritt, MD, a fifthyear resident in general surgery at Louisiana State University Health Sciences Center New Orleans.
These features include T4 lesions, perineural invasion, poor lymph node sampling of 12 nodes or fewer, and poor histologic differentiation.
Using the SEER*Stat database, Dr. Herritt and his colleagues compared the
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overall and relative survival in five-year intervals of patients with stage II disease who were low risk, had one high-risk feature, or had two or more high-risk features, as well as patients with stage III disease. The study included 65,828 patients.
As expected, patients with low-risk stage II disease had the highest five-year relative survival at 90%. This dropped to 82% among stage II patients with one high-risk feature. But stage II patients with multiple high-risk features had a marked drop in five-year relative survival—down to 59%—faring worse than stage III patients who had a relative survival of 68% at five years.
“I think this fairly definitely demonstrates that patients with stage II disease and high-risk features warrant additional treatment after surgery with curative intent,” Dr. Herritt said.
No single high-risk feature approached the mortality associated with multiple features. However, the worst survival in the study population for a single highrisk feature was inadequate nodal sampling at 62%.
Dr. Herritt said more research is needed to delineate the role that chemotherapy will play in patients with high-risk stage II disease. Right now, there is no consensus on use of chemotherapy in stage II disease. Multiple regimens have been proposed based on an individual’s risk factors, but there is no agreed-upon strategy.
Dr. Herritt said specific databases should be created to collect data on individual risk factors, clinical and genetic information, and patient outcomes.
The study was recognized with the General Surgery Forum Best Paper Award.
Medicaid Expansion Improved Early Diagnosis of Colon Cancer
The adoption of Medicaid expansion led to earlier diagnoses of colon cancer for Medicaid patients, lessening one key cancer disparity between insured and uninsured Americans, according to a new study.
The finding comes from an analysis of the American College of Surgeons’ National Cancer Database for the years 2010 to 2017. Midway through the study period, on Jan. 1, 2014, states had the option to expand Medicaid by increasing eligibility to residents with household incomes up to 138% of the federal poverty level.
During the eight years studied, 162,805 patients between the ages of 18 to 65 years who had private or Medicaid insurance were diagnosed with colon cancer and registered with the database.
Investigators ranked hospitals into low-, medium- or high-adoption categories based on the percentage of states in each U.S. Census Bureau division that adopted Medicaid expansion.
In areas with a high-adoption rate of Medicaid expansion, the percentage of late-stage colon cancer diagnoses declined, while there was no change in late-stage diagnosis in areas with low rates of Medicaid expansion. The low-adoption rate category consistently showed the highest percentage of latestage diagnoses, averaging over 60%.
Over the same period, people with private insurance were increasingly likely to have a late-stage colon cancer diagnosis, rising from 47% in 2010 to 52% in 2017.
Analysis was performed to compare Medicaid patients with those with private insurance by eight factors: age, sex, Medicaid expansion, Medicaid adoption rate by division, race, income quartile, facility type and facility setting.
Multivariate analysis showed insurance type was the most significant factor affecting late-stage diagnosis, with an almost 30% increased odds of late-stage colon cancer diagnosis for patients with Medicaid insurance.
“We identified race, socioeconomic status and the rural setting to be factors that lead to disparities in patient care, despite adjusting for Medicaid expansion,” said study author Mayin Lin, DO, MPH, a colon and rectal surgeon at MercyOne Des Moines Surgical Group, in Iowa.
She called on physicians and surgeons to promote access to care and preventive services for patients. “We can improve colon cancer stage diagnosis by promoting cancer screenings and surveillance,” she said.
The study received the Southern California Society of Colon & Rectal Surgeons Award. ■
YOU KNOW THAT FACE. YOU KNOW WHAT IT’S TELLING YOU. AND NOW YOU HAVE A PROVEN OPTION. NOW AVAILABLE
Barhemsys® is the first and only antiemetic approved for rescue treatment of PONV despite prophylaxis.1 Learn more at Barhemsys.com
Indications
Barhemsys is a selective dopamine-2 (D2) and dopamine-3 (D3) receptor antagonist indicated in adults for: • prevention of postoperative nausea and vomiting (PONV), either alone or in combination with an antiemetic of a different class • treatment of PONV in patients who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis
Select Important Safety Information
Contraindication: Barhemsys is contraindicated in patients with known hypersensitivity to amisulpride. QT Prolongation: Barhemsys causes dose- and concentration-dependent prolongation of the QT interval. The recommended dosage is 5 mg or 10 mg as a single intravenous (IV) dose infused over 1 to 2 minutes. Avoid Barhemsys in patients with congenital long QT syndrome and in patients taking droperidol. Electrocardiogram (ECG) monitoring is recommended in patients with pre-existing arrhythmias/cardiac conduction disorders, electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, and in patients taking other medicinal products (e.g., ondansetron) or with other medical conditions known to prolong the QT interval. Adverse Reactions: Common adverse reactions reported in ≥ 2% of adult patients who received Barhemsys 5 mg (N=748) and at a higher rate than placebo (N=741) in clinical trials for the prevention of PONV were: chills (4% vs. 3%), hypokalemia (4% vs. 2%), procedural hypotension (3% vs. 2%), and abdominal distention (2% vs. 1%). Serum prolactin concentrations were measured in one prophylaxis study where 5% (9/176) of Barhemsys-treated patients had increased blood prolactin reported as an adverse reaction compared with 1% (1/166) of placebo-treated patients. The most common adverse reaction, reported in ≥ 2% of adult patients who received Barhemsys 10 mg (N=418) and at a higher rate than placebo (N=416), in clinical trials for the treatment of PONV was infusion site pain (6% vs. 4%).
Please see the Brief Summary of Prescribing Information for Barhemsys on next page.
1. Barhemsys [Prescribing Information], Indianapolis, IN. Acacia Pharma; 2020. Model used for illustrative purposes only.
AI for Surgeons: Current Realities, Future Possibilities
By VICTORIA STERN
In 2012, a patient arrived at Stanford University Medical Center with a large wound on his foot. The man had been walking on it for a month before coming in for care.
Elsie Gyang Ross, MD, quickly recognized the patient had a circulatory condition known as peripheral artery disease (PAD), in which vessels narrow and restrict or block blood flow to the limbs. The condition affects an estimated 8 million to 12 million Americans but often goes undiagnosed. If left untreated, PAD can increase the risk for stroke and myocardial infarction or, in this case, lead to a wound that doesn’t heal.
Dr. Ross’ patient had wet gangrene of the foot and, even after antibiotics, debridement and revascularization, he ultimately required a below-knee amputation.
“But a lot can be done to treat patients before we need to consider surgery, such as coronary angiography,” Dr. Ross, an assistant professor of surgery and medicine at the Stanford University School of Medicine, in California, told General Surgery News.
In particular, Dr. Ross said, what if clinicians could use artificial intelligence to diagnose patients sooner or predict who
Delivers when it matters most ™
Brief Summary of Prescribing Information for Barhemsys® (amisulpride) injection
See package insert for full Prescribing Information
Indications: Barhemsys is a selective dopamine-2 (D2) and dopamine-3 (D3) receptor antagonist indicated in adults for: • prevention of postoperative nausea and vomiting (PONV), either alone or in combination with an antiemetic of a different class • treatment of PONV in patients who have received antiemetic prophylaxis with an agent of a different class or have not received prophylaxis Dosage & Administration: The recommended adult dosage of Barhemsys: • Prevention of PONV, either alone or in combination with another antiemetic: 5 mg as a single intravenous dose infused over 1 to 2 minutes at the time of induction of anesthesia. • Treatment of PONV: 10 mg as a single intravenous dose infused over 1 to 2 minutes in the event of nausea and/or vomiting after a surgical procedure. Protect from light. Barhemsys is subject to photodegradation. Administer Barhemsys within 12 hours of removal of the vial from the protective carton. See full prescribing information for preparation and administration instructions. Dosage Forms and Strength: Injection: 5 mg/2 mL (2.5 mg/mL) as a clear, colorless sterile solution in a single-dose vial. Contraindication: Barhemsys is contraindicated in patients with known hypersensitivity to amisulpride. QT Prolongation: Barhemsys causes dose- and concentration-dependent prolongation of the QT interval. The recommended dosage is 5 mg or 10 mg as a single intravenous (IV) dose infused over 1 to 2 minutes. Avoid Barhemsys in patients with congenital long QT syndrome and in patients taking droperidol. Electrocardiogram (ECG) monitoring is recommended in patients with pre-existing arrhythmias/cardiac conduction disorders, electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, and in patients taking other medicinal products (e.g., ondansetron) or with other medical conditions known to prolong the QT interval. Adverse Reactions: Common adverse reactions reported in ≥ 2% of adult patients who received Barhemsys 5 mg (N=748) and at a higher rate than placebo (N=741) in clinical trials for the prevention of PONV were: chills (4% vs. 3%), hypokalemia (4% vs. 2%), procedural hypotension (3% vs. 2%), and abdominal distention (2% vs. 1%). Serum prolactin concentrations were measured in one prophylaxis study where 5% (9/176) of Barhemsys-treated patients had increased blood prolactin reported as an adverse reaction compared with 1% (1/166) of placebo-treated patients. The most common adverse reaction, reported in ≥ 2% of adult patients who received Barhemsys 10 mg (N=418) and at a higher rate than placebo (N=416), in clinical trials for the treatment of PONV was infusion site pain (6% vs. 4%).
Drug Interactions:
• Barhemsys causes dose- and concentration-dependent QT prolongation. To avoid potential additive effects, avoid use of Barhemsys in patients taking droperidol. • ECG monitoring is recommended in patients taking other drugs known to prolong the QT interval (e.g., ondansetron). • Reciprocal antagonism of effects occurs between dopamine agonists (e.g., levodopa) and Barhemsys. Avoid using levodopa with Barhemsys. Postmarketing Experience: The following adverse reactions have been identified during postapproval chronic oral use of amisulpride outside of the United States (Barhemsys is not approved for oral dosing or chronic use). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Blood and Lymphatic System Disorders: agranulocytosis; Cardiac Disorders: bradycardia, torsades de pointes, ventricular tachycardia, prolonged QT by electrocardiogram; General Disorders: neuroleptic malignant syndrome; Immune System Disorders: angioedema, hypersensitivity, urticaria; Hepatic Disorders: increased hepatic enzymes; Nervous System Disorders: agitation, anxiety, dystonia, extrapyramidal disorder, seizure; Psychiatric Disorders: confusional state, insomnia, somnolence; Vascular Disorders: hypotension. Use in Specific Populations: Pregnancy—Risk Summary: Available data with amisulpride use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, there were no adverse developmental effects observed with oral administration of amisulpride in rats and rabbits during the period of organogenesis at exposures about 43 and 645 times, respectively, the exposure delivered by the highest recommended human dose (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data—Animal Data: Reproduction studies of amisulpride were conducted in pregnant rats administered oral doses up to 160 mg/kg/day (43 times the exposure based on area under the curve (AUC) at the highest recommended dose of 10 mg) throughout the period of organogenesis. No adverse embryo-fetal developmental effects were observed at any dose level. Maternal animals exhibited a dose-related decrease in overall mean body weight gain. In rabbits administered amisulpride throughout the period of organogenesis, oral doses up to 210 mg/kg/day (645 times the exposure based on AUC at the highest recommended dose of 10 mg) had no adverse developmental effects on the fetus. Maternal animals exhibited reduced mean body weight gain at doses of 100 and 210 mg/kg/day and reduced food intake was observed at 210 mg/kg/day. The pre- and post-natal developmental effects of amisulpride were assessed in rats administered oral doses of 60, 100 or 160 mg/kg/day during the periods of organogenesis and lactation. At 160 mg/kg/day (43 times the exposure based on AUC at the highest recommended dose of 10 mg), maternal animals exhibited a reduction in mean body weight gain and decrease in food intake during lactation. Amisulpride had no effect on maternal pregnancy parameters, litter survival or pup growth, development or maturation at any dose tested. Lactation—Risk Summary: Based on case reports in published literature, amisulpride is present in human milk at concentrations that are 11- to 20-fold higher than human plasma in patients taking multiple oral doses of amisulpride (200 to 400 mg/day). The estimated infant daily dose ranged from 5% to 11% of the maternal dose. There are ways to minimize drug exposure to a breastfed infant (see Clinical Considerations). There are no reports of adverse effects on the breastfed child and no information on the effects of amisulpride on milk production. The pharmacological action of amisulpride, a dopamine-2 (D2) receptor antagonist, may result in an increase in serum prolactin levels, which may lead to a reversible increase in maternal milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Barhemsys and any potential adverse effects on the breastfed child from Barhemsys or from the underlying maternal condition. Clinical Considerations: A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for 48 hours after Barhemsys administration to minimize drug exposure to a breastfed infant. Females and Males of Reproductive Potential—Infertility: In animal fertility studies, administration of repeated doses of amisulpride over a 10-day period to female rats resulted in infertility that was reversible. Pediatric Use—Safety and effectiveness in pediatric patients have not been established. Geriatric Use—No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Renal Impairment—Avoid Barhemsys in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2). The pharmacokinetics of amisulpride in patients with severe renal impairment have not been adequately studied in clinical trials. Amisulpride is known to be substantially excreted by the kidneys, and patients with severe renal impairment may have increased systemic exposure and an increased risk of adverse reactions. No dosage adjustment is necessary in patients with mild to moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m2). Overdosage: Doses of oral amisulpride (Barhemsys is not approved for oral dosing) above 1200 mg/day have been associated with adverse reactions related to dopamine-2 (D2) antagonism, in particular: • cardiovascular adverse reactions (e.g., prolongation of the QT interval, torsades de pointes, bradycardia and hypotension). • neuropsychiatric adverse reactions (e.g., sedation, coma, seizures, and dystonic and extrapyramidal reactions). There is no specific antidote for amisulpride overdose. Management includes cardiac monitoring and treatment of severe extrapyramidal symptoms. Since amisulpride is weakly dialyzed, hemodialysis should not be used to eliminate the drug. How Supplied/Storage and Handling: Barhemsys is supplied as follows: Package of 10 cartons (NDC 71390-125-20). Each carton (NDC 71390-125-21) contains one singledose vial of clear, colorless, sterile solution of Barhemsys, 5 mg in 2 mL (2.5 mg/mL). Store vials at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Patient Counseling Information: QT Prolongation—Instruct patients to contact their healthcare provider immediately if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode. Drug Interactions—Advise patients to report to their healthcare provider if they are taking drugs which prolong the QT interval. Lactation—Women may consider reducing infant exposure through pumping and discarding breastmilk for 48 hours after Barhemsys administration. ‘AI is there to make us better. It should run quietly in the background, catching our blind spots and helping us make more informed decisions about patient care.’
—Elsie Gyang Ross, MD
would develop PAD so patients can begin treatment earlier and avoid surgery?
In 2014, Dr. Ross, along with her colleagues at Stanford University’s Center for Biomedical Informatics Research, began evaluating machine learning algorithms to identify patients at risk for PAD. Machine learning algorithms— mathematical tools that help make sense of data—learn from experience. In other words, the more data fed into the algorithm, the more accurate the diagnosis or prediction becomes.
A 2016 analysis described the process of constructing machine learning models using data from 1,755 patients who had undergone elective coronary angiography but whose PAD status was unknown. Dr. Ross and his team found that the machine learning algorithms could recognize PAD and predict mortality better than standard linear regression models (J Vasc Surg 2016;64[5]:1515-1522.e3). A 2019 study that included 7,686 patients with PAD and incorporated almost 1,000 variables from electronic health records reported that the machine learning models could accurately forecast which PAD patients would develop major cardiac and cerebrovascular events (Circulat Cardiovasc Qual Outcomes 2019;12).
The goal of these models and others, Dr. Ross explained, is not for machine learning or its operationalized counterpart, AI, to take over care or make decisions for surgeons. “AI is there to make us better,” she said. “It should run quietly in the background, catching our blind spots and helping us make more informed decisions about patient care.”
Developing and validating AI and machine learning models takes time and an enormous amount of data before they can be integrated into clinical practice. However, interest in AI technology has ballooned in the past few years, with approvals by the FDA increasing from just two at the end of 2017 to more than
