ACS Surgery News

In women with breast cancer undergoing breast-conserving surgery, accelerated partial breast irradiation (APBI) using multicatheter brachytherapy does not negatively affect quality of life, compared with standard whole breast irradiation, investigators have reported.

Patients reported similar quality of life scores for multicatheter brachytherapy–based APBI and whole breast irradiation in the study by the Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO).

Moreover, breast symptom scores were significantly worse for whole-breast radiation, Rebekka Schäfer, MD, of the department of radiation oncology at the University Hospital Würzburg (Germany) and colleagues reported in Lancet Oncology.

“This trial provides further clinical evidence that APBI with interstitial brachytherapy can be considered as an alternative treatment option after breast-conserving surgery for patients with low-risk breast cancer,” Dr. Schäfer and coauthors wrote.

In several previous studies, APBI has been shown to have clinical outcomes equivalent to those of whole breast irradiation in terms of disease recurrence, survival, and treatment side effects, they added.

The quality of life findings in the present report come from long-term follow-up of a randomized, controlled, phase 3 trial conducted at 16 European centers. This study included 1,184 women with early breast cancer randomly who, after receiving breast-conserving surgery, were assigned either to APBI that used multicatheter brachytherapy or to whole breast irradiation.

Women in the study completed validated quality of life questionnaires right before and right after radiotherapy, as well as during follow-up.

A little more than half of the women in each group completed the quality of life questionnaires after the treatment and again at follow-up, investigators said.

Global health status was stable over time in both groups, investigators reported. In the APBI group, global health status score on a scale of 0-100 was 65.6 right after the procedure and 66.2 at 5 years; similarly, scores in the whole breast irradiation group were 64.6 after radiotherapy and 66.0 at 5 years.

The only quality of life difference between arms that investigators characterized as moderately clinically relevant was in breast symptom scores, which were significantly worse in the whole breast radiation group right after radiotherapy (difference of means, 13.6; 95% CI, 9.7-17.5; P less than .0001) and at 3-month follow-up (difference of means, 12.7; 95% CI, 9.8-15.6; P less than .0001).

Emotional functioning, fatigue, and financial difficulty scores in the APBI group were “slightly better” than in the whole breast radiation group right after radiotherapy and at a 3-month follow-up, investigators reported; however, at 5 year follow-up, there were no significant differences between arms in those measures.

“Our findings show that APBI using multicatheter interstitial brachytherapy does not result in clinically significant deterioration of overall quality of life and that the different domains of quality of life after APBI were not worse in comparison with whole breast irradiation in terms of clinically relevant differences,” Dr. Schäfer and colleagues concluded in their report.

Dr. Schäfer reported no conflicts of interest. Coauthors reported disclosures outside of the submitted work including Nucletron Operations BV, Elekta Company, Merck Serono, Novocure, AstraZeneca, and Bristol-Myers Squibb, among others.

SOURCE: Schäfer R et al. Lancet Oncol. 2018 Apr 22. doi: 10.1016/S1470-2045(18)30195-5.

In women with breast cancer undergoing breast-conserving surgery, accelerated partial breast irradiation (APBI) using multicatheter brachytherapy does not negatively affect quality of life, compared with standard whole breast irradiation, investigators have reported.

Patients reported similar quality of life scores for multicatheter brachytherapy–based APBI and whole breast irradiation in the study by the Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO).

Moreover, breast symptom scores were significantly worse for whole-breast radiation, Rebekka Schäfer, MD, of the department of radiation oncology at the University Hospital Würzburg (Germany) and colleagues reported in Lancet Oncology.

“This trial provides further clinical evidence that APBI with interstitial brachytherapy can be considered as an alternative treatment option after breast-conserving surgery for patients with low-risk breast cancer,” Dr. Schäfer and coauthors wrote.

In several previous studies, APBI has been shown to have clinical outcomes equivalent to those of whole breast irradiation in terms of disease recurrence, survival, and treatment side effects, they added.

The quality of life findings in the present report come from long-term follow-up of a randomized, controlled, phase 3 trial conducted at 16 European centers. This study included 1,184 women with early breast cancer randomly who, after receiving breast-conserving surgery, were assigned either to APBI that used multicatheter brachytherapy or to whole breast irradiation.

Women in the study completed validated quality of life questionnaires right before and right after radiotherapy, as well as during follow-up.

A little more than half of the women in each group completed the quality of life questionnaires after the treatment and again at follow-up, investigators said.

Global health status was stable over time in both groups, investigators reported. In the APBI group, global health status score on a scale of 0-100 was 65.6 right after the procedure and 66.2 at 5 years; similarly, scores in the whole breast irradiation group were 64.6 after radiotherapy and 66.0 at 5 years.

The only quality of life difference between arms that investigators characterized as moderately clinically relevant was in breast symptom scores, which were significantly worse in the whole breast radiation group right after radiotherapy (difference of means, 13.6; 95% CI, 9.7-17.5; P less than .0001) and at 3-month follow-up (difference of means, 12.7; 95% CI, 9.8-15.6; P less than .0001).

Emotional functioning, fatigue, and financial difficulty scores in the APBI group were “slightly better” than in the whole breast radiation group right after radiotherapy and at a 3-month follow-up, investigators reported; however, at 5 year follow-up, there were no significant differences between arms in those measures.

“Our findings show that APBI using multicatheter interstitial brachytherapy does not result in clinically significant deterioration of overall quality of life and that the different domains of quality of life after APBI were not worse in comparison with whole breast irradiation in terms of clinically relevant differences,” Dr. Schäfer and colleagues concluded in their report.

Dr. Schäfer reported no conflicts of interest. Coauthors reported disclosures outside of the submitted work including Nucletron Operations BV, Elekta Company, Merck Serono, Novocure, AstraZeneca, and Bristol-Myers Squibb, among others.

SOURCE: Schäfer R et al. Lancet Oncol. 2018 Apr 22. doi: 10.1016/S1470-2045(18)30195-5.

In women with breast cancer undergoing breast-conserving surgery, accelerated partial breast irradiation (APBI) using multicatheter brachytherapy does not negatively affect quality of life, compared with standard whole breast irradiation, investigators have reported.

Patients reported similar quality of life scores for multicatheter brachytherapy–based APBI and whole breast irradiation in the study by the Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO).

Moreover, breast symptom scores were significantly worse for whole-breast radiation, Rebekka Schäfer, MD, of the department of radiation oncology at the University Hospital Würzburg (Germany) and colleagues reported in Lancet Oncology.

“This trial provides further clinical evidence that APBI with interstitial brachytherapy can be considered as an alternative treatment option after breast-conserving surgery for patients with low-risk breast cancer,” Dr. Schäfer and coauthors wrote.

In several previous studies, APBI has been shown to have clinical outcomes equivalent to those of whole breast irradiation in terms of disease recurrence, survival, and treatment side effects, they added.

The quality of life findings in the present report come from long-term follow-up of a randomized, controlled, phase 3 trial conducted at 16 European centers. This study included 1,184 women with early breast cancer randomly who, after receiving breast-conserving surgery, were assigned either to APBI that used multicatheter brachytherapy or to whole breast irradiation.

Women in the study completed validated quality of life questionnaires right before and right after radiotherapy, as well as during follow-up.

A little more than half of the women in each group completed the quality of life questionnaires after the treatment and again at follow-up, investigators said.

Global health status was stable over time in both groups, investigators reported. In the APBI group, global health status score on a scale of 0-100 was 65.6 right after the procedure and 66.2 at 5 years; similarly, scores in the whole breast irradiation group were 64.6 after radiotherapy and 66.0 at 5 years.

The only quality of life difference between arms that investigators characterized as moderately clinically relevant was in breast symptom scores, which were significantly worse in the whole breast radiation group right after radiotherapy (difference of means, 13.6; 95% CI, 9.7-17.5; P less than .0001) and at 3-month follow-up (difference of means, 12.7; 95% CI, 9.8-15.6; P less than .0001).

Emotional functioning, fatigue, and financial difficulty scores in the APBI group were “slightly better” than in the whole breast radiation group right after radiotherapy and at a 3-month follow-up, investigators reported; however, at 5 year follow-up, there were no significant differences between arms in those measures.

“Our findings show that APBI using multicatheter interstitial brachytherapy does not result in clinically significant deterioration of overall quality of life and that the different domains of quality of life after APBI were not worse in comparison with whole breast irradiation in terms of clinically relevant differences,” Dr. Schäfer and colleagues concluded in their report.

Dr. Schäfer reported no conflicts of interest. Coauthors reported disclosures outside of the submitted work including Nucletron Operations BV, Elekta Company, Merck Serono, Novocure, AstraZeneca, and Bristol-Myers Squibb, among others.

SOURCE: Schäfer R et al. Lancet Oncol. 2018 Apr 22. doi: 10.1016/S1470-2045(18)30195-5.

NEW ORLEANS – Gabapentin heads the short list of prescription drugs other than opioids and benzodiazepines with substantial black-market abuse potential, according to Alexander Y. Walley, MD.

“At least in Massachusetts, where I see patients, these are the pills that people are using and trading on the street. Your part of the country might have others,” noted Dr. Walley, director of the addiction medicine fellowship program at Boston Medical Center.

Bruce Jancin/MDedge News

Gabapentinoids

Gabapentin and pregabalin are not addictive in the sense that it’s easy to get laboratory animals or healthy volunteers to self-administer them. However, gabapentinoid use disorder is extremely common among people with opioid use disorder, who report that the combination boosts the euphoric effects of opioids and reduces opioid withdrawal symptoms without causing side effects.

Indeed, a recent systematic review of 106 studies found that gabapentinoid use disorder was present in up to 26% of opioid users (Eur Neuropsychopharmacol. 2017 Dec;27[12]:1185-1215).

Overdoses involving gabapentinoids alone are uncommon because they require consumption at up to 25 times the maximum recommended dose. Moreover, these overdoses are rarely fatal.

“You almost can’t overdose on a gabapentinoid, because you have to take lots and lots of it to do so, and you’ll usually survive. But if you add it to an opioid or other sedative, then you’re really in dangerous territory. That’s where all the deaths are clustered,” Dr. Walley explained.

A recent Canadian/Dutch population-based, nested, case-control study concluded that concomitant prescription of opioids and gabapentin was associated with a 49% greater chance of fatal overdose, compared with opioid prescription alone, in an analysis extensively adjusted for potential confounders. A dose-response effect was noted, such that coprescription of high-dose gabapentin was linked to an adjusted 58% increased risk (PLoS Med. 2017 Oct 3;14[10]:e1002396).

Complicating the picture, however, is solid evidence from a randomized, placebo-controlled, crossover trial that gabapentin and opioids are synergistic for relief from neuropathic pain, which can be notoriously difficult to control (N Engl J Med. 2005 Mar 31;352[13]:1324-34).

“It’s tricky, because you can potentially spare having to use high-dose opioids by adding gabapentin,” Dr. Walley observed. “So, as prescribers, you’re in a difficult position, because there’s a mixed message here: When gabapentin is combined with opioids, that’s when it’s dangerous – but that’s also when they’re potentially more effective for pain.”

Promethazine

This drug has a host of neurobiologic actions, which collectively provide sedative and antiemetic effects. Promethazine jacks up opioid-induced euphoria and alleviates withdrawal symptoms. It’s commonly detected in toxicology testing of patients on prescription opioids for chronic pain or on methadone therapy for opioid use disorder.

National Poison Data System figures show an unwelcome trend: A sharp uptick in promethazine abuse/misuse beginning in 2008, even while the total number of poisoning events of all kinds reported to the system began a steady decline (J Addict Med. 2015 May-Jun;9[3]:233-7).
 

Clonidine

This centrally acting alpha2-adrenoreceptor and imidazoline-receptor agonist is indicated for treatment of hypertension. However, it’s also extensively used off-label to treat anxiety, as well as for alcohol and opioid withdrawal symptoms. The problem is, clonidine boosts opioid-induced euphoria.

A retrospective study of clonidine-overdose patients characterized the clonidine overdose syndrome as marked by sedation, hypotension, bradycardia, and excessive pupillary constriction (Clin Toxicol [Phila]. 2017 Mar;55[3]:187-92).

“The combination of clonidine and opioids is particularly dangerous,” according to Dr. Walley. “Even though it mimics what an opioid overdose looks like, a clonidine overdose is not responsive to naloxone.”
 

Stimulants

One-quarter of patients who are prescribed methylphenidate or amphetamine for ADHD report being asked to divert their medication, and 11%-29% sell or give it to others seeking to use it recreationally or as a performance aid.

It’s common for prescription seekers to misrepresent symptoms of ADHD, and this play-acting is often tough to detect. In contrast, the nonstimulant atomoxetine (Strattera) and the alpha-adrenergic agonists prescribed for ADHD aren’t linked to misuse or diversion (Postgrad Med. 2014 Sep;126[5]:64-81).

Bupropion

This norepinephrine and dopamine reuptake inhibitor is generally assumed to have low abuse potential. That’s usually true – except in jail and prisons.

“In my patient population, where I have a keen eye to what’s being used on the street, bupropion is not one of the medications that I see very often in my patients who are not incarcerated,” Dr. Walley said. “But in incarcerated settings, it does have a street value.”
 

Consider safeguards

None of the prescription drugs on Dr. Walley’s problem list is included in prescription monitoring programs, nor are they detectable with standard toxicology testing. This poses a challenge for prescribing physicians.

Before prescribing any of these potentially abusable medications for a given patient, therefore, Dr. Walley considers the underlying risks. For example, an addiction history is a big red flag. So is coprescription of an opioid or another drug that might have synergistic adverse effects. Dr. Walley makes sure there is a solid indication for the medication, and, having prescribed the drug, he wants to see and document clear functional benefit.

Drug-specific toxicology screening is worthy of consideration as a means of confirming the presence of the prescribed medication, along with the absence of opioids or other drugs that shouldn’t be on board.

“I do this with gabapentin, because I see a lot of diversion,” he explained. “If gabapentin doesn’t show up in the toxicology screen, I stop prescribing it. Or if I detect it and it hasn’t been prescribed, that allows me to have a safety discussion with the patient.”

Dr. Walley reported no financial conflicts of interest regarding his presentation.

[email protected]

NEW ORLEANS – Gabapentin heads the short list of prescription drugs other than opioids and benzodiazepines with substantial black-market abuse potential, according to Alexander Y. Walley, MD.

“At least in Massachusetts, where I see patients, these are the pills that people are using and trading on the street. Your part of the country might have others,” noted Dr. Walley, director of the addiction medicine fellowship program at Boston Medical Center.

Bruce Jancin/MDedge News

Gabapentinoids

Gabapentin and pregabalin are not addictive in the sense that it’s easy to get laboratory animals or healthy volunteers to self-administer them. However, gabapentinoid use disorder is extremely common among people with opioid use disorder, who report that the combination boosts the euphoric effects of opioids and reduces opioid withdrawal symptoms without causing side effects.

Indeed, a recent systematic review of 106 studies found that gabapentinoid use disorder was present in up to 26% of opioid users (Eur Neuropsychopharmacol. 2017 Dec;27[12]:1185-1215).

Overdoses involving gabapentinoids alone are uncommon because they require consumption at up to 25 times the maximum recommended dose. Moreover, these overdoses are rarely fatal.

“You almost can’t overdose on a gabapentinoid, because you have to take lots and lots of it to do so, and you’ll usually survive. But if you add it to an opioid or other sedative, then you’re really in dangerous territory. That’s where all the deaths are clustered,” Dr. Walley explained.

A recent Canadian/Dutch population-based, nested, case-control study concluded that concomitant prescription of opioids and gabapentin was associated with a 49% greater chance of fatal overdose, compared with opioid prescription alone, in an analysis extensively adjusted for potential confounders. A dose-response effect was noted, such that coprescription of high-dose gabapentin was linked to an adjusted 58% increased risk (PLoS Med. 2017 Oct 3;14[10]:e1002396).

Complicating the picture, however, is solid evidence from a randomized, placebo-controlled, crossover trial that gabapentin and opioids are synergistic for relief from neuropathic pain, which can be notoriously difficult to control (N Engl J Med. 2005 Mar 31;352[13]:1324-34).

“It’s tricky, because you can potentially spare having to use high-dose opioids by adding gabapentin,” Dr. Walley observed. “So, as prescribers, you’re in a difficult position, because there’s a mixed message here: When gabapentin is combined with opioids, that’s when it’s dangerous – but that’s also when they’re potentially more effective for pain.”

Promethazine

This drug has a host of neurobiologic actions, which collectively provide sedative and antiemetic effects. Promethazine jacks up opioid-induced euphoria and alleviates withdrawal symptoms. It’s commonly detected in toxicology testing of patients on prescription opioids for chronic pain or on methadone therapy for opioid use disorder.

National Poison Data System figures show an unwelcome trend: A sharp uptick in promethazine abuse/misuse beginning in 2008, even while the total number of poisoning events of all kinds reported to the system began a steady decline (J Addict Med. 2015 May-Jun;9[3]:233-7).
 

Clonidine

This centrally acting alpha2-adrenoreceptor and imidazoline-receptor agonist is indicated for treatment of hypertension. However, it’s also extensively used off-label to treat anxiety, as well as for alcohol and opioid withdrawal symptoms. The problem is, clonidine boosts opioid-induced euphoria.

A retrospective study of clonidine-overdose patients characterized the clonidine overdose syndrome as marked by sedation, hypotension, bradycardia, and excessive pupillary constriction (Clin Toxicol [Phila]. 2017 Mar;55[3]:187-92).

“The combination of clonidine and opioids is particularly dangerous,” according to Dr. Walley. “Even though it mimics what an opioid overdose looks like, a clonidine overdose is not responsive to naloxone.”
 

Stimulants

One-quarter of patients who are prescribed methylphenidate or amphetamine for ADHD report being asked to divert their medication, and 11%-29% sell or give it to others seeking to use it recreationally or as a performance aid.

It’s common for prescription seekers to misrepresent symptoms of ADHD, and this play-acting is often tough to detect. In contrast, the nonstimulant atomoxetine (Strattera) and the alpha-adrenergic agonists prescribed for ADHD aren’t linked to misuse or diversion (Postgrad Med. 2014 Sep;126[5]:64-81).

Bupropion

This norepinephrine and dopamine reuptake inhibitor is generally assumed to have low abuse potential. That’s usually true – except in jail and prisons.

“In my patient population, where I have a keen eye to what’s being used on the street, bupropion is not one of the medications that I see very often in my patients who are not incarcerated,” Dr. Walley said. “But in incarcerated settings, it does have a street value.”
 

Consider safeguards

None of the prescription drugs on Dr. Walley’s problem list is included in prescription monitoring programs, nor are they detectable with standard toxicology testing. This poses a challenge for prescribing physicians.

Before prescribing any of these potentially abusable medications for a given patient, therefore, Dr. Walley considers the underlying risks. For example, an addiction history is a big red flag. So is coprescription of an opioid or another drug that might have synergistic adverse effects. Dr. Walley makes sure there is a solid indication for the medication, and, having prescribed the drug, he wants to see and document clear functional benefit.

Drug-specific toxicology screening is worthy of consideration as a means of confirming the presence of the prescribed medication, along with the absence of opioids or other drugs that shouldn’t be on board.

“I do this with gabapentin, because I see a lot of diversion,” he explained. “If gabapentin doesn’t show up in the toxicology screen, I stop prescribing it. Or if I detect it and it hasn’t been prescribed, that allows me to have a safety discussion with the patient.”

Dr. Walley reported no financial conflicts of interest regarding his presentation.

[email protected]

NEW ORLEANS – Gabapentin heads the short list of prescription drugs other than opioids and benzodiazepines with substantial black-market abuse potential, according to Alexander Y. Walley, MD.

“At least in Massachusetts, where I see patients, these are the pills that people are using and trading on the street. Your part of the country might have others,” noted Dr. Walley, director of the addiction medicine fellowship program at Boston Medical Center.

Bruce Jancin/MDedge News

Gabapentinoids

Gabapentin and pregabalin are not addictive in the sense that it’s easy to get laboratory animals or healthy volunteers to self-administer them. However, gabapentinoid use disorder is extremely common among people with opioid use disorder, who report that the combination boosts the euphoric effects of opioids and reduces opioid withdrawal symptoms without causing side effects.

Indeed, a recent systematic review of 106 studies found that gabapentinoid use disorder was present in up to 26% of opioid users (Eur Neuropsychopharmacol. 2017 Dec;27[12]:1185-1215).

Overdoses involving gabapentinoids alone are uncommon because they require consumption at up to 25 times the maximum recommended dose. Moreover, these overdoses are rarely fatal.

“You almost can’t overdose on a gabapentinoid, because you have to take lots and lots of it to do so, and you’ll usually survive. But if you add it to an opioid or other sedative, then you’re really in dangerous territory. That’s where all the deaths are clustered,” Dr. Walley explained.

A recent Canadian/Dutch population-based, nested, case-control study concluded that concomitant prescription of opioids and gabapentin was associated with a 49% greater chance of fatal overdose, compared with opioid prescription alone, in an analysis extensively adjusted for potential confounders. A dose-response effect was noted, such that coprescription of high-dose gabapentin was linked to an adjusted 58% increased risk (PLoS Med. 2017 Oct 3;14[10]:e1002396).

Complicating the picture, however, is solid evidence from a randomized, placebo-controlled, crossover trial that gabapentin and opioids are synergistic for relief from neuropathic pain, which can be notoriously difficult to control (N Engl J Med. 2005 Mar 31;352[13]:1324-34).

“It’s tricky, because you can potentially spare having to use high-dose opioids by adding gabapentin,” Dr. Walley observed. “So, as prescribers, you’re in a difficult position, because there’s a mixed message here: When gabapentin is combined with opioids, that’s when it’s dangerous – but that’s also when they’re potentially more effective for pain.”

Promethazine

This drug has a host of neurobiologic actions, which collectively provide sedative and antiemetic effects. Promethazine jacks up opioid-induced euphoria and alleviates withdrawal symptoms. It’s commonly detected in toxicology testing of patients on prescription opioids for chronic pain or on methadone therapy for opioid use disorder.

National Poison Data System figures show an unwelcome trend: A sharp uptick in promethazine abuse/misuse beginning in 2008, even while the total number of poisoning events of all kinds reported to the system began a steady decline (J Addict Med. 2015 May-Jun;9[3]:233-7).
 

Clonidine

This centrally acting alpha2-adrenoreceptor and imidazoline-receptor agonist is indicated for treatment of hypertension. However, it’s also extensively used off-label to treat anxiety, as well as for alcohol and opioid withdrawal symptoms. The problem is, clonidine boosts opioid-induced euphoria.

A retrospective study of clonidine-overdose patients characterized the clonidine overdose syndrome as marked by sedation, hypotension, bradycardia, and excessive pupillary constriction (Clin Toxicol [Phila]. 2017 Mar;55[3]:187-92).

“The combination of clonidine and opioids is particularly dangerous,” according to Dr. Walley. “Even though it mimics what an opioid overdose looks like, a clonidine overdose is not responsive to naloxone.”
 

Stimulants

One-quarter of patients who are prescribed methylphenidate or amphetamine for ADHD report being asked to divert their medication, and 11%-29% sell or give it to others seeking to use it recreationally or as a performance aid.

It’s common for prescription seekers to misrepresent symptoms of ADHD, and this play-acting is often tough to detect. In contrast, the nonstimulant atomoxetine (Strattera) and the alpha-adrenergic agonists prescribed for ADHD aren’t linked to misuse or diversion (Postgrad Med. 2014 Sep;126[5]:64-81).

Bupropion

This norepinephrine and dopamine reuptake inhibitor is generally assumed to have low abuse potential. That’s usually true – except in jail and prisons.

“In my patient population, where I have a keen eye to what’s being used on the street, bupropion is not one of the medications that I see very often in my patients who are not incarcerated,” Dr. Walley said. “But in incarcerated settings, it does have a street value.”
 

Consider safeguards

None of the prescription drugs on Dr. Walley’s problem list is included in prescription monitoring programs, nor are they detectable with standard toxicology testing. This poses a challenge for prescribing physicians.

Before prescribing any of these potentially abusable medications for a given patient, therefore, Dr. Walley considers the underlying risks. For example, an addiction history is a big red flag. So is coprescription of an opioid or another drug that might have synergistic adverse effects. Dr. Walley makes sure there is a solid indication for the medication, and, having prescribed the drug, he wants to see and document clear functional benefit.

Drug-specific toxicology screening is worthy of consideration as a means of confirming the presence of the prescribed medication, along with the absence of opioids or other drugs that shouldn’t be on board.

“I do this with gabapentin, because I see a lot of diversion,” he explained. “If gabapentin doesn’t show up in the toxicology screen, I stop prescribing it. Or if I detect it and it hasn’t been prescribed, that allows me to have a safety discussion with the patient.”

Dr. Walley reported no financial conflicts of interest regarding his presentation.

[email protected]

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.

The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.

Michele G. Sullivan/MDedge News

The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.

ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.

Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.

Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.

Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.

There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:

• E. coli (thirteen in the routine and one in the ertapenem group).
• Klebsiella species (four and one, respectively).
• Proteus species (one in the ertapenem group).

Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.

In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).

Dr. Nutman made no financial declarations.

[email protected]

SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.

MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.

The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.

Michele G. Sullivan/MDedge News

The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.

ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.

Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.

Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.

Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.

There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:

• E. coli (thirteen in the routine and one in the ertapenem group).
• Klebsiella species (four and one, respectively).
• Proteus species (one in the ertapenem group).

Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.

In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).

Dr. Nutman made no financial declarations.

[email protected]

SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.

MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.

The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.

Michele G. Sullivan/MDedge News

The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.

ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.

Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.

Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.

Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.

There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:

• E. coli (thirteen in the routine and one in the ertapenem group).
• Klebsiella species (four and one, respectively).
• Proteus species (one in the ertapenem group).

Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.

In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).

Dr. Nutman made no financial declarations.

[email protected]

SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.

Registration Now Open for 2018 ACS Quality and Safety Conference

Health care professionals dedicated to raising the bar on the quality of surgical care and patient safety are invited to attend the 2018 American College of Surgeons (ACS) Quality and Safety Conference, July 21–24 at the Hyatt Regency Orlando, FL.

• Trauma Quality Programs, including Pediatrics, Trauma Center Verification, the Trauma Quality Improvement Program, and Performance Improvement and Patient Safety

The conference theme, Partnering for Improvement, will set the tone for the meeting, as presenters and organizers strive to achieve the following:

• Provide a professional forum to discuss and apply the most recent knowledge on quality and safety initiatives in surgery

• Present methods used to analyze data from ACS Quality Programs and demonstrate practical ways to use the data for quality improvement (QI)

• Assist hospitals and providers in managing, analyzing, and interpreting data

• Enhance the learning experience by offering breakout sessions that educate attendees on topic areas of their interest

An additional track will be dedicated to Optimal Resources for Surgical Quality and Safety, the “red book,” which will explore concepts and resources from the manual, information on QI tools, methodology, nomenclature, and organizational design and infrastructure. Other notable sessions will highlight important clinical topics, including efficiency in surgical care, the opioid epidemic, and preoperative optimization.

Keynote speaker Rolf Benirschke, a former placekicker in the NFL, will discuss his experience collapsing on a cross-country team flight while battling ulcerative colitis and subsequently undergoing two emergency operations within six days.

Further details about the conference can be viewed on the Quality and Safety Conference website at www.facs.org/quality-programs/quality-safety-conference.

Registration Now Open for 2018 ACS Quality and Safety Conference

Health care professionals dedicated to raising the bar on the quality of surgical care and patient safety are invited to attend the 2018 American College of Surgeons (ACS) Quality and Safety Conference, July 21–24 at the Hyatt Regency Orlando, FL.

• Trauma Quality Programs, including Pediatrics, Trauma Center Verification, the Trauma Quality Improvement Program, and Performance Improvement and Patient Safety

The conference theme, Partnering for Improvement, will set the tone for the meeting, as presenters and organizers strive to achieve the following:

• Provide a professional forum to discuss and apply the most recent knowledge on quality and safety initiatives in surgery

• Present methods used to analyze data from ACS Quality Programs and demonstrate practical ways to use the data for quality improvement (QI)

• Assist hospitals and providers in managing, analyzing, and interpreting data

• Enhance the learning experience by offering breakout sessions that educate attendees on topic areas of their interest

An additional track will be dedicated to Optimal Resources for Surgical Quality and Safety, the “red book,” which will explore concepts and resources from the manual, information on QI tools, methodology, nomenclature, and organizational design and infrastructure. Other notable sessions will highlight important clinical topics, including efficiency in surgical care, the opioid epidemic, and preoperative optimization.

Keynote speaker Rolf Benirschke, a former placekicker in the NFL, will discuss his experience collapsing on a cross-country team flight while battling ulcerative colitis and subsequently undergoing two emergency operations within six days.

Further details about the conference can be viewed on the Quality and Safety Conference website at www.facs.org/quality-programs/quality-safety-conference.

Registration Now Open for 2018 ACS Quality and Safety Conference

Health care professionals dedicated to raising the bar on the quality of surgical care and patient safety are invited to attend the 2018 American College of Surgeons (ACS) Quality and Safety Conference, July 21–24 at the Hyatt Regency Orlando, FL.

• Trauma Quality Programs, including Pediatrics, Trauma Center Verification, the Trauma Quality Improvement Program, and Performance Improvement and Patient Safety

The conference theme, Partnering for Improvement, will set the tone for the meeting, as presenters and organizers strive to achieve the following:

• Provide a professional forum to discuss and apply the most recent knowledge on quality and safety initiatives in surgery

• Present methods used to analyze data from ACS Quality Programs and demonstrate practical ways to use the data for quality improvement (QI)

• Assist hospitals and providers in managing, analyzing, and interpreting data

• Enhance the learning experience by offering breakout sessions that educate attendees on topic areas of their interest

An additional track will be dedicated to Optimal Resources for Surgical Quality and Safety, the “red book,” which will explore concepts and resources from the manual, information on QI tools, methodology, nomenclature, and organizational design and infrastructure. Other notable sessions will highlight important clinical topics, including efficiency in surgical care, the opioid epidemic, and preoperative optimization.

Keynote speaker Rolf Benirschke, a former placekicker in the NFL, will discuss his experience collapsing on a cross-country team flight while battling ulcerative colitis and subsequently undergoing two emergency operations within six days.

Further details about the conference can be viewed on the Quality and Safety Conference website at www.facs.org/quality-programs/quality-safety-conference.

LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.

At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.

designer491/Thinkstock

All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.

Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.

“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”

In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.

“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.

The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”

Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.

SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.

LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.

At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.

designer491/Thinkstock

All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.

Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.

“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”

In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.

“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.

The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”

Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.

SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.

LOS ANGELES – Women treated surgically and with hormones for endometriosis may continue to experience pain, say investigators, and that pain frequently extends beyond the pelvis.

At the annual meeting of the American Academy of Neurology, Barbara Karp, MD, of the National Institute of Neurological Disorders and Stroke, presented results from an ongoing randomized trial of women with endometriosis receiving botulinum toxin to treat endometriosis-related chronic pelvic pain and pelvic spasm.

designer491/Thinkstock

All subjects had myofascial dysfunction. Most reported headaches and half reported orofacial pain, while 13 subjects reported myofascial trigger points in all the 26 spots assessed, which included head and facial muscles, shoulder and back muscles, and muscles in the buttocks, abdomen, and upper legs.

Dr. Karp said her group hypothesized that for patients with endometriosis, the widespread pain seen in the study “probably has some origin in sensitization initiated by pain associated with the endometriosis lesions, and that gives us a mechanism to think about peripheral and central sensitization.” But she noted that such sensitization can be easily missed in the clinic.

“One of the things that’s really underappreciated is how much women with chronic pelvic pain have pain elsewhere. So the neurologist or pain specialist may say, ‘that’s not my body territory, there’s something going on with your pelvis.’ And the gynecologist may be focused on the endometriosis and the endometriosis lesions. So you have these women with really widespread pain problems whose care is being fractionated.”

In another aspect of the study she also presented at the meeting, Dr. Karp, a neurologist who has studied the therapeutic use of neurotoxins such as botulinum for 30 years, showed results from an open-label extension of a randomized trial of botulinum toxin injections to treat pelvic spasm in the same cohort of women with confirmed endometriosis and confirmed pelvic muscle spasm.

“It’s an area of the body neurologists don’t feel comfortable injecting, and I don’t necessarily feel comfortable doing it myself,” Dr. Karp said.

The researchers had to develop their own procedure because at the time they started the research there was almost nothing in the literature on how to inject botulinum toxin for pelvic pain in women. “People in different specialties have been doing it [to relieve pelvic pain] and it’s really widespread, but they’re doing it all different ways,” Dr. Karp said. “We’re hoping to find a best approach.”

Dr. Karp and her colleagues’ research is supported by the NINDS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. OnabotulinumtoxinA for the clinical trial is supplied by Allergan. Dr. Karp has received research support from Allergan and Merz.

SOURCE: Karp B et al. AAN 2018, Abstract P2.096; Karp B et al. AAN 2018, Abstract P2.098.

SEATTLE – Preop thromboelastometry can identify patients who need extra anticoagulation against venous thromboembolism following bariatric surgery, according to a prospective investigation of 40 patients at Conemaugh Memorial Medical Center in Johnstown, Pa.

Enoxaparin 40 mg twice daily just wasn’t enough for people who were hypercoagulable before surgery. The goal of the study was to find the best way to prevent venous thromboembolism (VTE) after weight loss surgery. At present, there’s no consensus on prophylaxis dosing, timing, duration, or even what agent to use for these patients. Conemaugh uses postop enoxaparin, a low-molecular-weight heparin. Among many other options, some hospitals opt for preop dosing with traditional heparin, which is less expensive.

jacoblund/Thinkstock

[email protected]

SOURCE: Urias D et al. World Congress of Endoscopic Surgery hosted by SAGES & CAGS abstract S023.

SEATTLE – Preop thromboelastometry can identify patients who need extra anticoagulation against venous thromboembolism following bariatric surgery, according to a prospective investigation of 40 patients at Conemaugh Memorial Medical Center in Johnstown, Pa.

Enoxaparin 40 mg twice daily just wasn’t enough for people who were hypercoagulable before surgery. The goal of the study was to find the best way to prevent venous thromboembolism (VTE) after weight loss surgery. At present, there’s no consensus on prophylaxis dosing, timing, duration, or even what agent to use for these patients. Conemaugh uses postop enoxaparin, a low-molecular-weight heparin. Among many other options, some hospitals opt for preop dosing with traditional heparin, which is less expensive.

jacoblund/Thinkstock

[email protected]

SOURCE: Urias D et al. World Congress of Endoscopic Surgery hosted by SAGES & CAGS abstract S023.

SEATTLE – Preop thromboelastometry can identify patients who need extra anticoagulation against venous thromboembolism following bariatric surgery, according to a prospective investigation of 40 patients at Conemaugh Memorial Medical Center in Johnstown, Pa.

Enoxaparin 40 mg twice daily just wasn’t enough for people who were hypercoagulable before surgery. The goal of the study was to find the best way to prevent venous thromboembolism (VTE) after weight loss surgery. At present, there’s no consensus on prophylaxis dosing, timing, duration, or even what agent to use for these patients. Conemaugh uses postop enoxaparin, a low-molecular-weight heparin. Among many other options, some hospitals opt for preop dosing with traditional heparin, which is less expensive.

jacoblund/Thinkstock

[email protected]

SOURCE: Urias D et al. World Congress of Endoscopic Surgery hosted by SAGES & CAGS abstract S023.

States continue to battle budget-busting prices of prescription drugs. But a federal court decision could limit the weapons available to them – underscoring the challenge states face as they, in the absence of federal action, go one on one against the powerful drug industry.

The 2-to-1 ruling April 13 by the U.S. 4th Circuit Court of Appeals invalidated a Maryland law meant to limit “price-gouging” by makers of generic drugs. The measure was inspired by cases such as that of former Turing Pharmaceutical CEO Martin Shkreli, who raised one generic’s price 5,000% after buying the company.

Kenishirotie/Thinkstock

“We are evaluating all options with regard to next steps,” said Maryland Attorney General Brian Frosh in a statement. His office would not elaborate further.

The state could appeal to have the case heard “en banc,” meaning by the full 4th Circuit, with jurisdiction over five states.

Such appeals aren’t commonly granted, but this law could be a strong candidate, suggested Aaron S. Kesselheim, MD, an associate professor at Harvard Medical School, Boston, who researches drug-price regulation.

The April 13 ruling looms large as other state legislatures grapple with ever-climbing drug prices.

Similar price-gouging legislation has been introduced in at least 13 states this year, though none of those measures became law, according to the National Conference of State Legislatures (NCSL). Three other bills failed to gain passage.

The NCSL also cited the law in a March advisory for states seeking new approaches to regulating drug prices.

The court’s finding could have a chilling effect on such efforts, especially as more state legislatures wrap up business for 2018.

“A negative court ruling will put a damper or a pause on state activities,” said Richard Cauchi, NCSL’s health program director. “Unless this topic is your No. 1 priority of the year, your legislators are juggling multiple bills, multiple strategies. When bill three gets in trouble, they move to bill four.”

The appeals court held that Maryland’s law overstepped limits on how states can regulate commerce – specifically, a constitutional ban on states controlling business that takes place outside their borders. The majority ruling argues that, since most generics manufacturers and drug wholesalers engage in trade outside Maryland, the state cannot control what prices they charge.

In a dissenting opinion, the panel’s third judge argued Maryland can regulate the drug prices charged within the state since the law is meant to affect only medications being sold to its own residents.

Dr. Kesselheim argued similarly in a JAMA viewpoint (2018;319[9]:865-866).

Regardless, striking down a law on constitutional grounds can be particularly discouraging, suggested Rachel Sachs, an associate law professor at Washington University in St. Louis who researches drug regulations.

“If it had been a rejection on vagueness grounds, that’s something you can cure with a more specific statute,” she said. “But the fact that they said this is unconstitutional poses real concern for other states.”

That’s important. While the federal government has talked a big game on bringing down drug prices, it has done little. Instead, states have taken the lead – spurred by the budget squeeze pricey prescriptions impose on their Medicaid programs and on state employee benefits packages.

But states have far fewer tools at their disposal than does Congress. Most state laws so far tackle only pieces of the problem – targeting a specific drug or particular practice, experts said.

“We’ll get more broad and better evolution on this issue if the federal government decides to take it seriously – which it hasn’t so far,” Dr. Kesselheim said.

To be fair, Maryland’s law is only one of a bevy of approaches.

Other states have focused on price transparency laws. In California, drug companies must disclose in advance if a price might increase by more than a set percent and that they justify the increase. Industry has sued to block the California law.

New York has limited what the state will pay for drugs, establishing a process to review if expensive drugs are priced out of step with their medical value.

A number of states have since 2017 passed laws regulating pharmacy benefit managers – the contractors who negotiate discounted drug coverage for insurance plans, but who rarely reveal what level of discount they actually pass on to consumers.

Experts expect that activity to continue, especially as escalating drug prices show little sign of letting up.

“The states are going to keep trying and experimenting,” Ms. Sachs added. “This is a problem that isn’t going away.”

Even efforts such as Maryland’s – which targeted price-gouging – will likely remain at the forefront.

“I don’t think this is the end of states trying to do something on price gouging,” said Ellen Albritton, a senior policy analyst at the left-leaning advocacy group Families USA who consults with states on drug-pricing policy. “It’s such an issue that offends people’s sensibilities. It’s crazy people can do this.”

KHN’s coverage of prescription drug development, costs, and pricing is supported by the Laura and John Arnold Foundation. Kaiser Health News is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

States continue to battle budget-busting prices of prescription drugs. But a federal court decision could limit the weapons available to them – underscoring the challenge states face as they, in the absence of federal action, go one on one against the powerful drug industry.

The 2-to-1 ruling April 13 by the U.S. 4th Circuit Court of Appeals invalidated a Maryland law meant to limit “price-gouging” by makers of generic drugs. The measure was inspired by cases such as that of former Turing Pharmaceutical CEO Martin Shkreli, who raised one generic’s price 5,000% after buying the company.

Kenishirotie/Thinkstock

“We are evaluating all options with regard to next steps,” said Maryland Attorney General Brian Frosh in a statement. His office would not elaborate further.

The state could appeal to have the case heard “en banc,” meaning by the full 4th Circuit, with jurisdiction over five states.

Such appeals aren’t commonly granted, but this law could be a strong candidate, suggested Aaron S. Kesselheim, MD, an associate professor at Harvard Medical School, Boston, who researches drug-price regulation.

The April 13 ruling looms large as other state legislatures grapple with ever-climbing drug prices.

Similar price-gouging legislation has been introduced in at least 13 states this year, though none of those measures became law, according to the National Conference of State Legislatures (NCSL). Three other bills failed to gain passage.

The NCSL also cited the law in a March advisory for states seeking new approaches to regulating drug prices.

The court’s finding could have a chilling effect on such efforts, especially as more state legislatures wrap up business for 2018.

“A negative court ruling will put a damper or a pause on state activities,” said Richard Cauchi, NCSL’s health program director. “Unless this topic is your No. 1 priority of the year, your legislators are juggling multiple bills, multiple strategies. When bill three gets in trouble, they move to bill four.”

The appeals court held that Maryland’s law overstepped limits on how states can regulate commerce – specifically, a constitutional ban on states controlling business that takes place outside their borders. The majority ruling argues that, since most generics manufacturers and drug wholesalers engage in trade outside Maryland, the state cannot control what prices they charge.

In a dissenting opinion, the panel’s third judge argued Maryland can regulate the drug prices charged within the state since the law is meant to affect only medications being sold to its own residents.

Dr. Kesselheim argued similarly in a JAMA viewpoint (2018;319[9]:865-866).

Regardless, striking down a law on constitutional grounds can be particularly discouraging, suggested Rachel Sachs, an associate law professor at Washington University in St. Louis who researches drug regulations.

“If it had been a rejection on vagueness grounds, that’s something you can cure with a more specific statute,” she said. “But the fact that they said this is unconstitutional poses real concern for other states.”

That’s important. While the federal government has talked a big game on bringing down drug prices, it has done little. Instead, states have taken the lead – spurred by the budget squeeze pricey prescriptions impose on their Medicaid programs and on state employee benefits packages.

But states have far fewer tools at their disposal than does Congress. Most state laws so far tackle only pieces of the problem – targeting a specific drug or particular practice, experts said.

“We’ll get more broad and better evolution on this issue if the federal government decides to take it seriously – which it hasn’t so far,” Dr. Kesselheim said.

To be fair, Maryland’s law is only one of a bevy of approaches.

Other states have focused on price transparency laws. In California, drug companies must disclose in advance if a price might increase by more than a set percent and that they justify the increase. Industry has sued to block the California law.

New York has limited what the state will pay for drugs, establishing a process to review if expensive drugs are priced out of step with their medical value.

A number of states have since 2017 passed laws regulating pharmacy benefit managers – the contractors who negotiate discounted drug coverage for insurance plans, but who rarely reveal what level of discount they actually pass on to consumers.

Experts expect that activity to continue, especially as escalating drug prices show little sign of letting up.

“The states are going to keep trying and experimenting,” Ms. Sachs added. “This is a problem that isn’t going away.”

Even efforts such as Maryland’s – which targeted price-gouging – will likely remain at the forefront.

“I don’t think this is the end of states trying to do something on price gouging,” said Ellen Albritton, a senior policy analyst at the left-leaning advocacy group Families USA who consults with states on drug-pricing policy. “It’s such an issue that offends people’s sensibilities. It’s crazy people can do this.”

KHN’s coverage of prescription drug development, costs, and pricing is supported by the Laura and John Arnold Foundation. Kaiser Health News is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

States continue to battle budget-busting prices of prescription drugs. But a federal court decision could limit the weapons available to them – underscoring the challenge states face as they, in the absence of federal action, go one on one against the powerful drug industry.

The 2-to-1 ruling April 13 by the U.S. 4th Circuit Court of Appeals invalidated a Maryland law meant to limit “price-gouging” by makers of generic drugs. The measure was inspired by cases such as that of former Turing Pharmaceutical CEO Martin Shkreli, who raised one generic’s price 5,000% after buying the company.

Kenishirotie/Thinkstock

“We are evaluating all options with regard to next steps,” said Maryland Attorney General Brian Frosh in a statement. His office would not elaborate further.

The state could appeal to have the case heard “en banc,” meaning by the full 4th Circuit, with jurisdiction over five states.

Such appeals aren’t commonly granted, but this law could be a strong candidate, suggested Aaron S. Kesselheim, MD, an associate professor at Harvard Medical School, Boston, who researches drug-price regulation.

The April 13 ruling looms large as other state legislatures grapple with ever-climbing drug prices.

Similar price-gouging legislation has been introduced in at least 13 states this year, though none of those measures became law, according to the National Conference of State Legislatures (NCSL). Three other bills failed to gain passage.

The NCSL also cited the law in a March advisory for states seeking new approaches to regulating drug prices.

The court’s finding could have a chilling effect on such efforts, especially as more state legislatures wrap up business for 2018.

“A negative court ruling will put a damper or a pause on state activities,” said Richard Cauchi, NCSL’s health program director. “Unless this topic is your No. 1 priority of the year, your legislators are juggling multiple bills, multiple strategies. When bill three gets in trouble, they move to bill four.”

The appeals court held that Maryland’s law overstepped limits on how states can regulate commerce – specifically, a constitutional ban on states controlling business that takes place outside their borders. The majority ruling argues that, since most generics manufacturers and drug wholesalers engage in trade outside Maryland, the state cannot control what prices they charge.

In a dissenting opinion, the panel’s third judge argued Maryland can regulate the drug prices charged within the state since the law is meant to affect only medications being sold to its own residents.

Dr. Kesselheim argued similarly in a JAMA viewpoint (2018;319[9]:865-866).

Regardless, striking down a law on constitutional grounds can be particularly discouraging, suggested Rachel Sachs, an associate law professor at Washington University in St. Louis who researches drug regulations.

“If it had been a rejection on vagueness grounds, that’s something you can cure with a more specific statute,” she said. “But the fact that they said this is unconstitutional poses real concern for other states.”

That’s important. While the federal government has talked a big game on bringing down drug prices, it has done little. Instead, states have taken the lead – spurred by the budget squeeze pricey prescriptions impose on their Medicaid programs and on state employee benefits packages.

But states have far fewer tools at their disposal than does Congress. Most state laws so far tackle only pieces of the problem – targeting a specific drug or particular practice, experts said.

“We’ll get more broad and better evolution on this issue if the federal government decides to take it seriously – which it hasn’t so far,” Dr. Kesselheim said.

To be fair, Maryland’s law is only one of a bevy of approaches.

Other states have focused on price transparency laws. In California, drug companies must disclose in advance if a price might increase by more than a set percent and that they justify the increase. Industry has sued to block the California law.

New York has limited what the state will pay for drugs, establishing a process to review if expensive drugs are priced out of step with their medical value.

A number of states have since 2017 passed laws regulating pharmacy benefit managers – the contractors who negotiate discounted drug coverage for insurance plans, but who rarely reveal what level of discount they actually pass on to consumers.

Experts expect that activity to continue, especially as escalating drug prices show little sign of letting up.

“The states are going to keep trying and experimenting,” Ms. Sachs added. “This is a problem that isn’t going away.”

Even efforts such as Maryland’s – which targeted price-gouging – will likely remain at the forefront.

“I don’t think this is the end of states trying to do something on price gouging,” said Ellen Albritton, a senior policy analyst at the left-leaning advocacy group Families USA who consults with states on drug-pricing policy. “It’s such an issue that offends people’s sensibilities. It’s crazy people can do this.”

KHN’s coverage of prescription drug development, costs, and pricing is supported by the Laura and John Arnold Foundation. Kaiser Health News is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.

CMS is turning to patients to help drive health information technology toward greater interoperability, accessibility, and usability – elusive goals that have not been reached by working with health care professionals and IT vendors alone.

“MyHealthEData makes it clear that patients should have access and control to share their data with whomever they want, making the patient the center of our health system,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said at the annual HIMSS conference. “Patients need to be able to control their information and know that it is secure and private. Having access to their medical information will help them make decisions about their care and have a better understanding of their health.”

She added that “once information is freely flowing from the patient to the provider, the advances in coordinated, value-based care and patient-centric care will be even greater than anything we can imagine today.”

The agency’s vision “is to empower patients by giving them direct access and control over their claims and EHR data. Patients could share their data with applications designed to help them make more informed health care decisions of with their providers and caregivers to help better manage their care,” Ms. Verma said in an interview.

For example, the initiative could lead to the development of products such as the following:

• Mobile apps to help patients manage medications and medical appointments.
• Simple processes that carry patients’ data when they switch providers or health insurance plans.
• Wearables, such as step trackers or glucose monitors, that are linked to patients’ clinical record.

To get to this future health IT nirvana, CMS will need to address the ongoing interoperability issues that continue to plague EHRs. And that’s where CMS is turning its efforts back to helping clinicians.

The agency “will be announcing a complete overhaul of the meaningful use program for hospitals and the advancing care information performance category of the Quality Payment Program,” Ms. Verma announced at HIMSS.

[email protected]

CMS is turning to patients to help drive health information technology toward greater interoperability, accessibility, and usability – elusive goals that have not been reached by working with health care professionals and IT vendors alone.

“MyHealthEData makes it clear that patients should have access and control to share their data with whomever they want, making the patient the center of our health system,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said at the annual HIMSS conference. “Patients need to be able to control their information and know that it is secure and private. Having access to their medical information will help them make decisions about their care and have a better understanding of their health.”

She added that “once information is freely flowing from the patient to the provider, the advances in coordinated, value-based care and patient-centric care will be even greater than anything we can imagine today.”

The agency’s vision “is to empower patients by giving them direct access and control over their claims and EHR data. Patients could share their data with applications designed to help them make more informed health care decisions of with their providers and caregivers to help better manage their care,” Ms. Verma said in an interview.

For example, the initiative could lead to the development of products such as the following:

• Mobile apps to help patients manage medications and medical appointments.
• Simple processes that carry patients’ data when they switch providers or health insurance plans.
• Wearables, such as step trackers or glucose monitors, that are linked to patients’ clinical record.

To get to this future health IT nirvana, CMS will need to address the ongoing interoperability issues that continue to plague EHRs. And that’s where CMS is turning its efforts back to helping clinicians.

The agency “will be announcing a complete overhaul of the meaningful use program for hospitals and the advancing care information performance category of the Quality Payment Program,” Ms. Verma announced at HIMSS.

[email protected]

CMS is turning to patients to help drive health information technology toward greater interoperability, accessibility, and usability – elusive goals that have not been reached by working with health care professionals and IT vendors alone.

“MyHealthEData makes it clear that patients should have access and control to share their data with whomever they want, making the patient the center of our health system,” Seema Verma, administrator of the Centers for Medicare & Medicaid Services, said at the annual HIMSS conference. “Patients need to be able to control their information and know that it is secure and private. Having access to their medical information will help them make decisions about their care and have a better understanding of their health.”

She added that “once information is freely flowing from the patient to the provider, the advances in coordinated, value-based care and patient-centric care will be even greater than anything we can imagine today.”

The agency’s vision “is to empower patients by giving them direct access and control over their claims and EHR data. Patients could share their data with applications designed to help them make more informed health care decisions of with their providers and caregivers to help better manage their care,” Ms. Verma said in an interview.

For example, the initiative could lead to the development of products such as the following:

• Mobile apps to help patients manage medications and medical appointments.
• Simple processes that carry patients’ data when they switch providers or health insurance plans.
• Wearables, such as step trackers or glucose monitors, that are linked to patients’ clinical record.

To get to this future health IT nirvana, CMS will need to address the ongoing interoperability issues that continue to plague EHRs. And that’s where CMS is turning its efforts back to helping clinicians.

The agency “will be announcing a complete overhaul of the meaningful use program for hospitals and the advancing care information performance category of the Quality Payment Program,” Ms. Verma announced at HIMSS.

[email protected]

Ovarian cancer most commonly follows a pattern of intraperitoneal spread, and even in the setting of bulky extra-ovarian disease, it can be thought of as being largely localized to the peritoneal compartment. This forms some of the rationale for performing extensive cytoreductive surgery (CRS) on ovarian cancer metastatic within the peritoneal cavity, and also some of the rationale for delivery of cytotoxic therapy directly to this compartment (intraperitoneal or “IP” chemotherapy). To be most effective, IP chemotherapy should be able to contact all peritoneal surfaces and be exposed to very low volume tumors (ideally no thicker than 2-mm implants).

There is a large body of evidence demonstrating the benefits of conventional IP chemotherapy in women who have received complete or “optimal” CRS to disease measuring less than 1 cm³.¹ However, IP chemotherapy is complicated by difficult administration and can be difficult for patients to tolerate. It is associated with significant toxicity, more so than what is seen from intravenous chemotherapy, and this toxicity is drawn out over the 18 (or more) weeks of therapy. It requires placement of an intraperitoneal port, and there are many problems associated with this foreign body including infection, malposition, and even erosions into underlying visceral structures. There are also concerns regarding the ability of the intraperitoneal infusions to reach all peritoneal surfaces when postoperative adhesions may have formed to pocket-off areas of the peritoneal cavity.

Hyperthermic intraperitoneal chemotherapy (HIPEC), at the time of CRS, is a strategy that has been explored to overcome some of these challenges.² HIPEC has the most history as an adjunct to the surgical management of gastrointestinal cancers (particularly appendiceal and colorectal). The technique first described by Dr. Paul H. Sugarbaker for gastrointestinal tumors remains similar to that performed in ovarian cancer.³ Patients first undergo extensive CRS until there is no macroscopic residual disease. Immediately following cytoreduction, catheters are placed into the peritoneal cavity, the main incision is temporarily closed (to prevent spillage), and an infusion of cytotoxic agents (commonly cisplatin, often with a second agent such as mitomycin C or doxorubicin) is warmed and then distilled into the peritoneal cavity until it is “moderately distended.” The patient’s body is then rolled back and forth to “wash” down the entire peritoneal cavity. All peritoneal surfaces can be touched by the agent as this procedure is happening intraoperatively prior to adhesion formation.

The “H” in HIPEC stands for hyperthermic, which is a key differentiator from traditional intraperitoneal and intravenous chemotherapy administration. Some chemotherapy agents, such as cisplatin, have a synergistic effect with hyperthermia. Some of these effects include increased oxygen free radical formation, increased cellular uptake of drug, reversal of mechanisms of drug resistance, and increases in DNA damage. The ideal range of hyperthermia is between 41° C and 44° C. At higher temperatures, infusions rates can be faster; however, higher temperatures are associated with more toxicity, particularly of the small bowel.⁴

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Armstrong DK et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34-43.

2. Helm CW et al. Hyperthermic intraperitoneal chemotherapy with and without cytoreductive surgery for epithelial ovarian cancer. J Surg Oncol. 2008;98(4):283-90.

3. Glehen O et al. Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of perfusion. J Surg Oncol. 2008;98(4):242-6.

4. Kusamura S et al. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008;98(4):247-52.

5. Kusamura S et al. Impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on systemic toxicity. Ann Surg Oncol. 2007;14(9):2550-8.

6. van Driel WJ et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan;378(3):230-240.

Ovarian cancer most commonly follows a pattern of intraperitoneal spread, and even in the setting of bulky extra-ovarian disease, it can be thought of as being largely localized to the peritoneal compartment. This forms some of the rationale for performing extensive cytoreductive surgery (CRS) on ovarian cancer metastatic within the peritoneal cavity, and also some of the rationale for delivery of cytotoxic therapy directly to this compartment (intraperitoneal or “IP” chemotherapy). To be most effective, IP chemotherapy should be able to contact all peritoneal surfaces and be exposed to very low volume tumors (ideally no thicker than 2-mm implants).

There is a large body of evidence demonstrating the benefits of conventional IP chemotherapy in women who have received complete or “optimal” CRS to disease measuring less than 1 cm³.¹ However, IP chemotherapy is complicated by difficult administration and can be difficult for patients to tolerate. It is associated with significant toxicity, more so than what is seen from intravenous chemotherapy, and this toxicity is drawn out over the 18 (or more) weeks of therapy. It requires placement of an intraperitoneal port, and there are many problems associated with this foreign body including infection, malposition, and even erosions into underlying visceral structures. There are also concerns regarding the ability of the intraperitoneal infusions to reach all peritoneal surfaces when postoperative adhesions may have formed to pocket-off areas of the peritoneal cavity.

Hyperthermic intraperitoneal chemotherapy (HIPEC), at the time of CRS, is a strategy that has been explored to overcome some of these challenges.² HIPEC has the most history as an adjunct to the surgical management of gastrointestinal cancers (particularly appendiceal and colorectal). The technique first described by Dr. Paul H. Sugarbaker for gastrointestinal tumors remains similar to that performed in ovarian cancer.³ Patients first undergo extensive CRS until there is no macroscopic residual disease. Immediately following cytoreduction, catheters are placed into the peritoneal cavity, the main incision is temporarily closed (to prevent spillage), and an infusion of cytotoxic agents (commonly cisplatin, often with a second agent such as mitomycin C or doxorubicin) is warmed and then distilled into the peritoneal cavity until it is “moderately distended.” The patient’s body is then rolled back and forth to “wash” down the entire peritoneal cavity. All peritoneal surfaces can be touched by the agent as this procedure is happening intraoperatively prior to adhesion formation.

The “H” in HIPEC stands for hyperthermic, which is a key differentiator from traditional intraperitoneal and intravenous chemotherapy administration. Some chemotherapy agents, such as cisplatin, have a synergistic effect with hyperthermia. Some of these effects include increased oxygen free radical formation, increased cellular uptake of drug, reversal of mechanisms of drug resistance, and increases in DNA damage. The ideal range of hyperthermia is between 41° C and 44° C. At higher temperatures, infusions rates can be faster; however, higher temperatures are associated with more toxicity, particularly of the small bowel.⁴

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Armstrong DK et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34-43.

2. Helm CW et al. Hyperthermic intraperitoneal chemotherapy with and without cytoreductive surgery for epithelial ovarian cancer. J Surg Oncol. 2008;98(4):283-90.

3. Glehen O et al. Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of perfusion. J Surg Oncol. 2008;98(4):242-6.

4. Kusamura S et al. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008;98(4):247-52.

5. Kusamura S et al. Impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on systemic toxicity. Ann Surg Oncol. 2007;14(9):2550-8.

6. van Driel WJ et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan;378(3):230-240.

Ovarian cancer most commonly follows a pattern of intraperitoneal spread, and even in the setting of bulky extra-ovarian disease, it can be thought of as being largely localized to the peritoneal compartment. This forms some of the rationale for performing extensive cytoreductive surgery (CRS) on ovarian cancer metastatic within the peritoneal cavity, and also some of the rationale for delivery of cytotoxic therapy directly to this compartment (intraperitoneal or “IP” chemotherapy). To be most effective, IP chemotherapy should be able to contact all peritoneal surfaces and be exposed to very low volume tumors (ideally no thicker than 2-mm implants).

There is a large body of evidence demonstrating the benefits of conventional IP chemotherapy in women who have received complete or “optimal” CRS to disease measuring less than 1 cm³.¹ However, IP chemotherapy is complicated by difficult administration and can be difficult for patients to tolerate. It is associated with significant toxicity, more so than what is seen from intravenous chemotherapy, and this toxicity is drawn out over the 18 (or more) weeks of therapy. It requires placement of an intraperitoneal port, and there are many problems associated with this foreign body including infection, malposition, and even erosions into underlying visceral structures. There are also concerns regarding the ability of the intraperitoneal infusions to reach all peritoneal surfaces when postoperative adhesions may have formed to pocket-off areas of the peritoneal cavity.

Hyperthermic intraperitoneal chemotherapy (HIPEC), at the time of CRS, is a strategy that has been explored to overcome some of these challenges.² HIPEC has the most history as an adjunct to the surgical management of gastrointestinal cancers (particularly appendiceal and colorectal). The technique first described by Dr. Paul H. Sugarbaker for gastrointestinal tumors remains similar to that performed in ovarian cancer.³ Patients first undergo extensive CRS until there is no macroscopic residual disease. Immediately following cytoreduction, catheters are placed into the peritoneal cavity, the main incision is temporarily closed (to prevent spillage), and an infusion of cytotoxic agents (commonly cisplatin, often with a second agent such as mitomycin C or doxorubicin) is warmed and then distilled into the peritoneal cavity until it is “moderately distended.” The patient’s body is then rolled back and forth to “wash” down the entire peritoneal cavity. All peritoneal surfaces can be touched by the agent as this procedure is happening intraoperatively prior to adhesion formation.

The “H” in HIPEC stands for hyperthermic, which is a key differentiator from traditional intraperitoneal and intravenous chemotherapy administration. Some chemotherapy agents, such as cisplatin, have a synergistic effect with hyperthermia. Some of these effects include increased oxygen free radical formation, increased cellular uptake of drug, reversal of mechanisms of drug resistance, and increases in DNA damage. The ideal range of hyperthermia is between 41° C and 44° C. At higher temperatures, infusions rates can be faster; however, higher temperatures are associated with more toxicity, particularly of the small bowel.⁴

Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Armstrong DK et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34-43.

2. Helm CW et al. Hyperthermic intraperitoneal chemotherapy with and without cytoreductive surgery for epithelial ovarian cancer. J Surg Oncol. 2008;98(4):283-90.

3. Glehen O et al. Hyperthermic intraperitoneal chemotherapy: nomenclature and modalities of perfusion. J Surg Oncol. 2008;98(4):242-6.

4. Kusamura S et al. Drugs, carrier solutions and temperature in hyperthermic intraperitoneal chemotherapy. J Surg Oncol. 2008;98(4):247-52.

5. Kusamura S et al. Impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on systemic toxicity. Ann Surg Oncol. 2007;14(9):2550-8.

6. van Driel WJ et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N Engl J Med. 2018 Jan;378(3):230-240.