Attention-deficit/hyperactivity disorder (ADHD) often persists beyond childhood into adulthood. One of the therapeutic challenges of treat­ing ADHD is identifying comorbidities, including underlying mood and anxiety disorders, and ongoing substance abuse. Effective treatment modalities tend to pri­oritize management of substance abuse, but the patient’s age may dictate the overall assessment plan.

So-called 'reward' center
Treating childhood ADHD with stimu­lants might reduce the risk for future drug abuse.¹ It is estimated that approximately 10 million people with ADHD are undiag­nosed in the United States²; characteristic ADHD symptoms—inattention, hyperac­tivity, impulsivity—can persist in adult­hood, and affected persons might not meet societal expectations. Previously uniden­tified attention difficulties may emerge during early adulthood because of increas­ingly complex tasks at school and work.

Persons with undiagnosed ADHD might turn to potentially self-destructive means of placating inner tension. Cocaine has phar­macological properties in common with stimulants such as methylphenidate, which often is prescribed for ADHD. Cocaine and methylphenidate both work on altering brain chemistry with a similar mechanism of action, allowing for increased dopamine in the nucleus accumbens, also known as the “reward center” of the brain.

Adults with ADHD have a 300% higher risk of developing a substance use disorder than adults without ADHD.³ An estimated 15% to 25% of adults with substance abuse have comorbid ADHD. Although these patients abuse of a variety of substances including Cannabis and alcohol, cocaine is one of the most commonly abused substances among this population. These observations could point to a self-medication hypothesis.
 

Why self-medicate?
The self-medication hypothesis, formu­lated by Khantzian in 1985, was based on several clinical observations. Khantzian stated that an abuser’s drug of choice is not selected at random but, rather, by an inherent desire to suppress the attri­butes of the condition that seems to oth­erwise wreak havoc on his (her) life. Almost a century earlier, Freud men­tioned that cocaine is an antidepressant. Among persons with ADHD who have not been given that diagnosis, or treated for the disorder, cocaine is a popular drug. Because of the antidepressant features of cocaine and its ability to produce a rapid increase of dopamine levels that exert a pro-euphoric effect, coupled with a seem­ingly paradoxical calming influence that leads to increased productivity, it is not surprising to find that cocaine is abused. Reportedly, persons who have not been treated because their ADHD is undiag­nosed turn to cocaine because it improves attention, raises self-esteem, and allows users to harness a level of focus that they could not otherwise achieve.⁴

Mechanism of action
Methylphenidate reduces ADHD symp­toms by increasing extracellular dopamine in the brain, acting by means of a mechanism that is similar to that of cocaine.⁵ By block­ing reuptake of dopamine and allowing an extracellular surplus, users continue to experience the pleasurable effect the neuro-transmitter produces. Methylphenidate has been shown to be an even more potent inhibitor of the same autoreceptors. Injecting methylphenidate has been shown to produce a rapid release of dopamine sim­ilar to that of cocaine.⁵

However, methylphenidate causes a much slower increase in dopamine; its effect on the brain has been shown to be similar to that of cocaine without the increased abuse potential. Cocaine use remodels the brain by reconfiguring con­nections that are essential for craving and self-control.⁵ Therefore, substituting meth­ylphenidate for cocaine could help ADHD patients by:
   • improving overall executive functioning
   • decreasing feelings of low self-worth
   • increasing daily functioning
   • minimizing craving and the risk of sub­sequent cocaine abuse.
 

Treatment recommendations
Carefully consider pharmacodynamics and pharmacokinetics when prescribing ADHD medication. In general, children and adolescents with ADHD respond more favorably to stimulants than adults do. In children, the mainstay of treatment is slow-dose stimulants such as methylphenidate; second-line treatments are immediate-release stimulants and atomoxetine, a selec­tive norepinephrine reuptake inhibitor.⁶ Adults with ADHD might benefit from a nonstimulant, in part because of the pres­ence of complex comorbidities.⁶ Modafinil often is prescribed for adults with ADHD.

Atomoxetine readily increases norepi­nephrine and dopamine in the prefrontal cortex as it bypasses the nucleus accum­bens. Although atomoxetine is not a stimu­lant, the efficacy of the drug is based on its ability to increase norepinephrine through selective inhibition of the norepineph­rine transporter. Norepinephrine modu­lates higher cortical functions—attention, executive function, arousal—that lead to a reduction in hyperactivity, inattention, and impulsivity.

Because dopamine is released in the prefrontal cortex—not in the nucleus accumbens—the addiction potential of atomoxetine is low.⁷ The drug might be an effective intervention for patients who are using cocaine to self-medicate. Stimulants such as methylphenidate have proven effective in safely mimicking the mecha­nism of action of cocaine. Nonstimulants, such as atomoxetine and modafinil, lack abuse potential and are excellent options for treating adults with ADHD.

Clinicians generally are advised to treat a patient’s underlying ADHD symptoms before addressing ongoing substance abuse. If a patient abruptly discontinues cocaine use before ADHD symptoms are properly controlled, her (his) condition might deterio­rate further and the treatment plan might fail to progress. Some patients have experienced a reduction in craving for cocaine after they began stimulant therapy; these people no longer felt a need to self-medicate because their symptoms were being addressed.⁴

Attention-deficit/hyperactivity disorder (ADHD) often persists beyond childhood into adulthood. One of the therapeutic challenges of treat­ing ADHD is identifying comorbidities, including underlying mood and anxiety disorders, and ongoing substance abuse. Effective treatment modalities tend to pri­oritize management of substance abuse, but the patient’s age may dictate the overall assessment plan.

So-called 'reward' center
Treating childhood ADHD with stimu­lants might reduce the risk for future drug abuse.¹ It is estimated that approximately 10 million people with ADHD are undiag­nosed in the United States²; characteristic ADHD symptoms—inattention, hyperac­tivity, impulsivity—can persist in adult­hood, and affected persons might not meet societal expectations. Previously uniden­tified attention difficulties may emerge during early adulthood because of increas­ingly complex tasks at school and work.

Persons with undiagnosed ADHD might turn to potentially self-destructive means of placating inner tension. Cocaine has phar­macological properties in common with stimulants such as methylphenidate, which often is prescribed for ADHD. Cocaine and methylphenidate both work on altering brain chemistry with a similar mechanism of action, allowing for increased dopamine in the nucleus accumbens, also known as the “reward center” of the brain.

Adults with ADHD have a 300% higher risk of developing a substance use disorder than adults without ADHD.³ An estimated 15% to 25% of adults with substance abuse have comorbid ADHD. Although these patients abuse of a variety of substances including Cannabis and alcohol, cocaine is one of the most commonly abused substances among this population. These observations could point to a self-medication hypothesis.
 

Why self-medicate?
The self-medication hypothesis, formu­lated by Khantzian in 1985, was based on several clinical observations. Khantzian stated that an abuser’s drug of choice is not selected at random but, rather, by an inherent desire to suppress the attri­butes of the condition that seems to oth­erwise wreak havoc on his (her) life. Almost a century earlier, Freud men­tioned that cocaine is an antidepressant. Among persons with ADHD who have not been given that diagnosis, or treated for the disorder, cocaine is a popular drug. Because of the antidepressant features of cocaine and its ability to produce a rapid increase of dopamine levels that exert a pro-euphoric effect, coupled with a seem­ingly paradoxical calming influence that leads to increased productivity, it is not surprising to find that cocaine is abused. Reportedly, persons who have not been treated because their ADHD is undiag­nosed turn to cocaine because it improves attention, raises self-esteem, and allows users to harness a level of focus that they could not otherwise achieve.⁴

Mechanism of action
Methylphenidate reduces ADHD symp­toms by increasing extracellular dopamine in the brain, acting by means of a mechanism that is similar to that of cocaine.⁵ By block­ing reuptake of dopamine and allowing an extracellular surplus, users continue to experience the pleasurable effect the neuro-transmitter produces. Methylphenidate has been shown to be an even more potent inhibitor of the same autoreceptors. Injecting methylphenidate has been shown to produce a rapid release of dopamine sim­ilar to that of cocaine.⁵

However, methylphenidate causes a much slower increase in dopamine; its effect on the brain has been shown to be similar to that of cocaine without the increased abuse potential. Cocaine use remodels the brain by reconfiguring con­nections that are essential for craving and self-control.⁵ Therefore, substituting meth­ylphenidate for cocaine could help ADHD patients by:
   • improving overall executive functioning
   • decreasing feelings of low self-worth
   • increasing daily functioning
   • minimizing craving and the risk of sub­sequent cocaine abuse.
 

Treatment recommendations
Carefully consider pharmacodynamics and pharmacokinetics when prescribing ADHD medication. In general, children and adolescents with ADHD respond more favorably to stimulants than adults do. In children, the mainstay of treatment is slow-dose stimulants such as methylphenidate; second-line treatments are immediate-release stimulants and atomoxetine, a selec­tive norepinephrine reuptake inhibitor.⁶ Adults with ADHD might benefit from a nonstimulant, in part because of the pres­ence of complex comorbidities.⁶ Modafinil often is prescribed for adults with ADHD.

Atomoxetine readily increases norepi­nephrine and dopamine in the prefrontal cortex as it bypasses the nucleus accum­bens. Although atomoxetine is not a stimu­lant, the efficacy of the drug is based on its ability to increase norepinephrine through selective inhibition of the norepineph­rine transporter. Norepinephrine modu­lates higher cortical functions—attention, executive function, arousal—that lead to a reduction in hyperactivity, inattention, and impulsivity.

Because dopamine is released in the prefrontal cortex—not in the nucleus accumbens—the addiction potential of atomoxetine is low.⁷ The drug might be an effective intervention for patients who are using cocaine to self-medicate. Stimulants such as methylphenidate have proven effective in safely mimicking the mecha­nism of action of cocaine. Nonstimulants, such as atomoxetine and modafinil, lack abuse potential and are excellent options for treating adults with ADHD.

Clinicians generally are advised to treat a patient’s underlying ADHD symptoms before addressing ongoing substance abuse. If a patient abruptly discontinues cocaine use before ADHD symptoms are properly controlled, her (his) condition might deterio­rate further and the treatment plan might fail to progress. Some patients have experienced a reduction in craving for cocaine after they began stimulant therapy; these people no longer felt a need to self-medicate because their symptoms were being addressed.⁴

Attention-deficit/hyperactivity disorder (ADHD) often persists beyond childhood into adulthood. One of the therapeutic challenges of treat­ing ADHD is identifying comorbidities, including underlying mood and anxiety disorders, and ongoing substance abuse. Effective treatment modalities tend to pri­oritize management of substance abuse, but the patient’s age may dictate the overall assessment plan.

So-called 'reward' center
Treating childhood ADHD with stimu­lants might reduce the risk for future drug abuse.¹ It is estimated that approximately 10 million people with ADHD are undiag­nosed in the United States²; characteristic ADHD symptoms—inattention, hyperac­tivity, impulsivity—can persist in adult­hood, and affected persons might not meet societal expectations. Previously uniden­tified attention difficulties may emerge during early adulthood because of increas­ingly complex tasks at school and work.

Persons with undiagnosed ADHD might turn to potentially self-destructive means of placating inner tension. Cocaine has phar­macological properties in common with stimulants such as methylphenidate, which often is prescribed for ADHD. Cocaine and methylphenidate both work on altering brain chemistry with a similar mechanism of action, allowing for increased dopamine in the nucleus accumbens, also known as the “reward center” of the brain.

Adults with ADHD have a 300% higher risk of developing a substance use disorder than adults without ADHD.³ An estimated 15% to 25% of adults with substance abuse have comorbid ADHD. Although these patients abuse of a variety of substances including Cannabis and alcohol, cocaine is one of the most commonly abused substances among this population. These observations could point to a self-medication hypothesis.
 

Why self-medicate?
The self-medication hypothesis, formu­lated by Khantzian in 1985, was based on several clinical observations. Khantzian stated that an abuser’s drug of choice is not selected at random but, rather, by an inherent desire to suppress the attri­butes of the condition that seems to oth­erwise wreak havoc on his (her) life. Almost a century earlier, Freud men­tioned that cocaine is an antidepressant. Among persons with ADHD who have not been given that diagnosis, or treated for the disorder, cocaine is a popular drug. Because of the antidepressant features of cocaine and its ability to produce a rapid increase of dopamine levels that exert a pro-euphoric effect, coupled with a seem­ingly paradoxical calming influence that leads to increased productivity, it is not surprising to find that cocaine is abused. Reportedly, persons who have not been treated because their ADHD is undiag­nosed turn to cocaine because it improves attention, raises self-esteem, and allows users to harness a level of focus that they could not otherwise achieve.⁴

Mechanism of action
Methylphenidate reduces ADHD symp­toms by increasing extracellular dopamine in the brain, acting by means of a mechanism that is similar to that of cocaine.⁵ By block­ing reuptake of dopamine and allowing an extracellular surplus, users continue to experience the pleasurable effect the neuro-transmitter produces. Methylphenidate has been shown to be an even more potent inhibitor of the same autoreceptors. Injecting methylphenidate has been shown to produce a rapid release of dopamine sim­ilar to that of cocaine.⁵

However, methylphenidate causes a much slower increase in dopamine; its effect on the brain has been shown to be similar to that of cocaine without the increased abuse potential. Cocaine use remodels the brain by reconfiguring con­nections that are essential for craving and self-control.⁵ Therefore, substituting meth­ylphenidate for cocaine could help ADHD patients by:
   • improving overall executive functioning
   • decreasing feelings of low self-worth
   • increasing daily functioning
   • minimizing craving and the risk of sub­sequent cocaine abuse.
 

Treatment recommendations
Carefully consider pharmacodynamics and pharmacokinetics when prescribing ADHD medication. In general, children and adolescents with ADHD respond more favorably to stimulants than adults do. In children, the mainstay of treatment is slow-dose stimulants such as methylphenidate; second-line treatments are immediate-release stimulants and atomoxetine, a selec­tive norepinephrine reuptake inhibitor.⁶ Adults with ADHD might benefit from a nonstimulant, in part because of the pres­ence of complex comorbidities.⁶ Modafinil often is prescribed for adults with ADHD.

Atomoxetine readily increases norepi­nephrine and dopamine in the prefrontal cortex as it bypasses the nucleus accum­bens. Although atomoxetine is not a stimu­lant, the efficacy of the drug is based on its ability to increase norepinephrine through selective inhibition of the norepineph­rine transporter. Norepinephrine modu­lates higher cortical functions—attention, executive function, arousal—that lead to a reduction in hyperactivity, inattention, and impulsivity.

Because dopamine is released in the prefrontal cortex—not in the nucleus accumbens—the addiction potential of atomoxetine is low.⁷ The drug might be an effective intervention for patients who are using cocaine to self-medicate. Stimulants such as methylphenidate have proven effective in safely mimicking the mecha­nism of action of cocaine. Nonstimulants, such as atomoxetine and modafinil, lack abuse potential and are excellent options for treating adults with ADHD.

Clinicians generally are advised to treat a patient’s underlying ADHD symptoms before addressing ongoing substance abuse. If a patient abruptly discontinues cocaine use before ADHD symptoms are properly controlled, her (his) condition might deterio­rate further and the treatment plan might fail to progress. Some patients have experienced a reduction in craving for cocaine after they began stimulant therapy; these people no longer felt a need to self-medicate because their symptoms were being addressed.⁴

Hookahs in a shop

Credit: Steven Damron

A new study indicates that individuals exposed to hookah smoke have an increase in the uptake of benzene, a substance linked to the development of hematologic malignancies.

Levels of S-phenylmercapturic acid (SPMA), a metabolite of benzene, were more than 4 times higher after study subjects smoked a hookah than before they did.

And non-smoking subjects experienced a nearly 3-fold increase in SPMA levels after they visited a hookah lounge.

Nada Kassem, RN, DrPH, of San Diego State University in California, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.

“Hookah smoking involves the use of burning charcoal that is needed to heat the hookah tobacco to generate the smoke that the smoker inhales,” Dr Kassem explained.

“In addition to inhaling toxicants and carcinogens found in the hookah tobacco smoke, hookah smokers and non-smokers who socialize with hookah smokers also inhale large quantities of charcoal combustion-generated toxic and carcinogenic emissions.”

To gain more insight into the dangers of hookah smoke, Dr Kassem and her colleagues analyzed levels of SPMA in the urine of 105 hookah smokers and 103 non-smokers.

The team obtained urine samples the morning of and the morning after participants attended a hookah-only smoking event at a hookah lounge or a private home.

SPMA levels in hookah smokers increased 4.2-fold after smoking at a hookah lounge (P<0.001) and increased 1.9-fold after smoking in a private home (P=0.003).

Non-smokers’ SPMA levels increased 2.6-fold after attending a social event in a hookah lounge (P=0.055).

However, non-smokers had similarly high levels of SPMA before and after attending hookah events in a private home (P=0.933). This suggests these subjects had chronic exposure to benzene before the study, according to Dr Kassem.

Regardless, she and her colleagues said the study’s results suggest hookah smoke increases the uptake of benzene, which has been linked to a range of hematologic malignancies, particularly acute myeloid leukemia.

“In contrast to what is believed, hookah tobacco smoking is not a safe alternative to smoking other forms of tobacco,” Dr Kassem said.

She and her colleagues noted that there is no safe level of exposure to benzene. And this suggests a need for interventions to reduce or prevent the use of hookahs, limit hookah-related exposure to toxic substances, and include hookah smoking in clean indoor air legislation.

Hookahs in a shop

Credit: Steven Damron

A new study indicates that individuals exposed to hookah smoke have an increase in the uptake of benzene, a substance linked to the development of hematologic malignancies.

Levels of S-phenylmercapturic acid (SPMA), a metabolite of benzene, were more than 4 times higher after study subjects smoked a hookah than before they did.

And non-smoking subjects experienced a nearly 3-fold increase in SPMA levels after they visited a hookah lounge.

Nada Kassem, RN, DrPH, of San Diego State University in California, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.

“Hookah smoking involves the use of burning charcoal that is needed to heat the hookah tobacco to generate the smoke that the smoker inhales,” Dr Kassem explained.

“In addition to inhaling toxicants and carcinogens found in the hookah tobacco smoke, hookah smokers and non-smokers who socialize with hookah smokers also inhale large quantities of charcoal combustion-generated toxic and carcinogenic emissions.”

To gain more insight into the dangers of hookah smoke, Dr Kassem and her colleagues analyzed levels of SPMA in the urine of 105 hookah smokers and 103 non-smokers.

The team obtained urine samples the morning of and the morning after participants attended a hookah-only smoking event at a hookah lounge or a private home.

SPMA levels in hookah smokers increased 4.2-fold after smoking at a hookah lounge (P<0.001) and increased 1.9-fold after smoking in a private home (P=0.003).

Non-smokers’ SPMA levels increased 2.6-fold after attending a social event in a hookah lounge (P=0.055).

However, non-smokers had similarly high levels of SPMA before and after attending hookah events in a private home (P=0.933). This suggests these subjects had chronic exposure to benzene before the study, according to Dr Kassem.

Regardless, she and her colleagues said the study’s results suggest hookah smoke increases the uptake of benzene, which has been linked to a range of hematologic malignancies, particularly acute myeloid leukemia.

“In contrast to what is believed, hookah tobacco smoking is not a safe alternative to smoking other forms of tobacco,” Dr Kassem said.

She and her colleagues noted that there is no safe level of exposure to benzene. And this suggests a need for interventions to reduce or prevent the use of hookahs, limit hookah-related exposure to toxic substances, and include hookah smoking in clean indoor air legislation.

Hookahs in a shop

Credit: Steven Damron

A new study indicates that individuals exposed to hookah smoke have an increase in the uptake of benzene, a substance linked to the development of hematologic malignancies.

Levels of S-phenylmercapturic acid (SPMA), a metabolite of benzene, were more than 4 times higher after study subjects smoked a hookah than before they did.

And non-smoking subjects experienced a nearly 3-fold increase in SPMA levels after they visited a hookah lounge.

Nada Kassem, RN, DrPH, of San Diego State University in California, and her colleagues reported these findings in Cancer Epidemiology, Biomarkers & Prevention.

“Hookah smoking involves the use of burning charcoal that is needed to heat the hookah tobacco to generate the smoke that the smoker inhales,” Dr Kassem explained.

“In addition to inhaling toxicants and carcinogens found in the hookah tobacco smoke, hookah smokers and non-smokers who socialize with hookah smokers also inhale large quantities of charcoal combustion-generated toxic and carcinogenic emissions.”

To gain more insight into the dangers of hookah smoke, Dr Kassem and her colleagues analyzed levels of SPMA in the urine of 105 hookah smokers and 103 non-smokers.

The team obtained urine samples the morning of and the morning after participants attended a hookah-only smoking event at a hookah lounge or a private home.

SPMA levels in hookah smokers increased 4.2-fold after smoking at a hookah lounge (P<0.001) and increased 1.9-fold after smoking in a private home (P=0.003).

Non-smokers’ SPMA levels increased 2.6-fold after attending a social event in a hookah lounge (P=0.055).

However, non-smokers had similarly high levels of SPMA before and after attending hookah events in a private home (P=0.933). This suggests these subjects had chronic exposure to benzene before the study, according to Dr Kassem.

Regardless, she and her colleagues said the study’s results suggest hookah smoke increases the uptake of benzene, which has been linked to a range of hematologic malignancies, particularly acute myeloid leukemia.

“In contrast to what is believed, hookah tobacco smoking is not a safe alternative to smoking other forms of tobacco,” Dr Kassem said.

She and her colleagues noted that there is no safe level of exposure to benzene. And this suggests a need for interventions to reduce or prevent the use of hookahs, limit hookah-related exposure to toxic substances, and include hookah smoking in clean indoor air legislation.

Frederick Roth, PhD

Credit: Mount Sinai Hospital

Researchers say they’ve created the largest-scale map of direct interactions between proteins encoded by the human genome, and this has revealed dozens of genes that may be involved in cancers.

This human interactome map describes about 14,000 direct interactions between proteins.

The map is about 30% larger than previous maps and contains more high-quality interactions than have come from all previous studies combined, according to the researchers.

Frederick Roth, PhD, of the University of Toronto and Mount Sinai Hospital in Ontario, Canada, and his colleagues described their map in Cell.

First, the researchers identified protein interactions via lab experiments. Then, they used computer modelling to zoom in on proteins that connect to one or more other cancer proteins.

“We show, really for the first time, that cancer proteins are more likely to interconnect with one another than they are to connect to randomly chosen non-cancer proteins,” Dr Roth said.

“Once you see that proteins associated to the same disease are more likely to connect to each other, now you can use this network of interactions as a prediction tool to find new cancer proteins and the genes they encode.”

For example, two known cancer genes encoded two proteins that interacted with CTBP2, a protein encoded at a location tied to prostate cancer, which can spread to nearby lymph nodes. These two proteins are implicated in lymphoid tumors, suggesting that CTBP2 plays a role in the development of lymphoid tumors.

Using their predictive method, the researchers found that 60 of their predicted cancer genes fit into a known cancer pathway.

The study also revealed that the network of protein interactions in humans covers a much broader range of genes than some past research has suggested.

Dr Roth said studies often focus on “popular” proteins that have already been linked to disease or are interesting for other reasons, and this has created a bias in our understanding of protein interactions.

“One major conclusion of the paper is that when you look systematically for interactions, you find them everywhere,” he said.

He and his colleagues believe that knowledge of protein interactions is likely to inform worldwide efforts to sequence and interpret cancer genomes.

Frederick Roth, PhD

Credit: Mount Sinai Hospital

Researchers say they’ve created the largest-scale map of direct interactions between proteins encoded by the human genome, and this has revealed dozens of genes that may be involved in cancers.

This human interactome map describes about 14,000 direct interactions between proteins.

The map is about 30% larger than previous maps and contains more high-quality interactions than have come from all previous studies combined, according to the researchers.

Frederick Roth, PhD, of the University of Toronto and Mount Sinai Hospital in Ontario, Canada, and his colleagues described their map in Cell.

First, the researchers identified protein interactions via lab experiments. Then, they used computer modelling to zoom in on proteins that connect to one or more other cancer proteins.

“We show, really for the first time, that cancer proteins are more likely to interconnect with one another than they are to connect to randomly chosen non-cancer proteins,” Dr Roth said.

“Once you see that proteins associated to the same disease are more likely to connect to each other, now you can use this network of interactions as a prediction tool to find new cancer proteins and the genes they encode.”

For example, two known cancer genes encoded two proteins that interacted with CTBP2, a protein encoded at a location tied to prostate cancer, which can spread to nearby lymph nodes. These two proteins are implicated in lymphoid tumors, suggesting that CTBP2 plays a role in the development of lymphoid tumors.

Using their predictive method, the researchers found that 60 of their predicted cancer genes fit into a known cancer pathway.

The study also revealed that the network of protein interactions in humans covers a much broader range of genes than some past research has suggested.

Dr Roth said studies often focus on “popular” proteins that have already been linked to disease or are interesting for other reasons, and this has created a bias in our understanding of protein interactions.

“One major conclusion of the paper is that when you look systematically for interactions, you find them everywhere,” he said.

He and his colleagues believe that knowledge of protein interactions is likely to inform worldwide efforts to sequence and interpret cancer genomes.

Frederick Roth, PhD

Credit: Mount Sinai Hospital

Researchers say they’ve created the largest-scale map of direct interactions between proteins encoded by the human genome, and this has revealed dozens of genes that may be involved in cancers.

This human interactome map describes about 14,000 direct interactions between proteins.

The map is about 30% larger than previous maps and contains more high-quality interactions than have come from all previous studies combined, according to the researchers.

Frederick Roth, PhD, of the University of Toronto and Mount Sinai Hospital in Ontario, Canada, and his colleagues described their map in Cell.

First, the researchers identified protein interactions via lab experiments. Then, they used computer modelling to zoom in on proteins that connect to one or more other cancer proteins.

“We show, really for the first time, that cancer proteins are more likely to interconnect with one another than they are to connect to randomly chosen non-cancer proteins,” Dr Roth said.

“Once you see that proteins associated to the same disease are more likely to connect to each other, now you can use this network of interactions as a prediction tool to find new cancer proteins and the genes they encode.”

For example, two known cancer genes encoded two proteins that interacted with CTBP2, a protein encoded at a location tied to prostate cancer, which can spread to nearby lymph nodes. These two proteins are implicated in lymphoid tumors, suggesting that CTBP2 plays a role in the development of lymphoid tumors.

Using their predictive method, the researchers found that 60 of their predicted cancer genes fit into a known cancer pathway.

The study also revealed that the network of protein interactions in humans covers a much broader range of genes than some past research has suggested.

Dr Roth said studies often focus on “popular” proteins that have already been linked to disease or are interesting for other reasons, and this has created a bias in our understanding of protein interactions.

“One major conclusion of the paper is that when you look systematically for interactions, you find them everywhere,” he said.

He and his colleagues believe that knowledge of protein interactions is likely to inform worldwide efforts to sequence and interpret cancer genomes.

With no consensus regarding the normal endometrial thickness in postmenopausal women without vaginal bleeding, there are no guidelines for clinicians to follow on when to biopsy, if at all, in an older patient presenting with pelvic pain but no bleeding.

To determine at what endometrial thickness biopsy would be optimal, Michelle Louie, MD, and colleagues from Magee Women’s Hospital in Pittsburgh, Pennsylvania, performed a retrospective cohort analysis of postmenopausal women aged 50 or older who underwent transvaginal ultrasound (TVUS) for indications other than vaginal bleeding. They presented their findings in an abstract at the 43rd AAGL Global Congress in Vancouver, Canada.

Details of the study

Patients were included if they had an endometrial lining of 4 mm or greater and excluded if they had a history of tamoxifen use, hormone replacement, endometrial ablation, hereditary cancer syndrome, or no available pathology results.

Of 462 biopsies, 435 (94.2%) had benign pathology, nine (2.0%) had carcinoma, and seven (1.5%) had atypical hyperplasia.

Endometrial thickness of 14 mm or greater was associated with atypical hyperplasia (odds ratio [OR], 4.29; P = .02), with a negative predictive value of 98.3%. A thickness of 15 mm or greater was associated with carcinoma (OR, 4.53; P = .03), with a negative predictive value of 98.5%.

Under 14 mm, the risk of hyperplasia was low, the authors found, at 0.08%. Below 15 mm, the risk of cancer was 0.06%.

They found no significant associations between endometrial lining TVUS appearance, age, parity, body mass index, diabetes, hypertension, hyperlipidemia, and carcinoma or atypical hyperplasia.

When biopsy might not be necessary

Therefore, regardless of conventional risk factors for endometrial cancer, if a postmenopausal woman reports pelvic pain without vaginal bleeding, and is found to have a thickened endometrial lining of less than 14 mm on TVUS, biopsy might not be warranted, conclude the study authors.  

With no consensus regarding the normal endometrial thickness in postmenopausal women without vaginal bleeding, there are no guidelines for clinicians to follow on when to biopsy, if at all, in an older patient presenting with pelvic pain but no bleeding.

To determine at what endometrial thickness biopsy would be optimal, Michelle Louie, MD, and colleagues from Magee Women’s Hospital in Pittsburgh, Pennsylvania, performed a retrospective cohort analysis of postmenopausal women aged 50 or older who underwent transvaginal ultrasound (TVUS) for indications other than vaginal bleeding. They presented their findings in an abstract at the 43rd AAGL Global Congress in Vancouver, Canada.

Details of the study

Patients were included if they had an endometrial lining of 4 mm or greater and excluded if they had a history of tamoxifen use, hormone replacement, endometrial ablation, hereditary cancer syndrome, or no available pathology results.

Of 462 biopsies, 435 (94.2%) had benign pathology, nine (2.0%) had carcinoma, and seven (1.5%) had atypical hyperplasia.

Endometrial thickness of 14 mm or greater was associated with atypical hyperplasia (odds ratio [OR], 4.29; P = .02), with a negative predictive value of 98.3%. A thickness of 15 mm or greater was associated with carcinoma (OR, 4.53; P = .03), with a negative predictive value of 98.5%.

Under 14 mm, the risk of hyperplasia was low, the authors found, at 0.08%. Below 15 mm, the risk of cancer was 0.06%.

They found no significant associations between endometrial lining TVUS appearance, age, parity, body mass index, diabetes, hypertension, hyperlipidemia, and carcinoma or atypical hyperplasia.

When biopsy might not be necessary

Therefore, regardless of conventional risk factors for endometrial cancer, if a postmenopausal woman reports pelvic pain without vaginal bleeding, and is found to have a thickened endometrial lining of less than 14 mm on TVUS, biopsy might not be warranted, conclude the study authors.  

With no consensus regarding the normal endometrial thickness in postmenopausal women without vaginal bleeding, there are no guidelines for clinicians to follow on when to biopsy, if at all, in an older patient presenting with pelvic pain but no bleeding.

To determine at what endometrial thickness biopsy would be optimal, Michelle Louie, MD, and colleagues from Magee Women’s Hospital in Pittsburgh, Pennsylvania, performed a retrospective cohort analysis of postmenopausal women aged 50 or older who underwent transvaginal ultrasound (TVUS) for indications other than vaginal bleeding. They presented their findings in an abstract at the 43rd AAGL Global Congress in Vancouver, Canada.

Details of the study

Patients were included if they had an endometrial lining of 4 mm or greater and excluded if they had a history of tamoxifen use, hormone replacement, endometrial ablation, hereditary cancer syndrome, or no available pathology results.

Of 462 biopsies, 435 (94.2%) had benign pathology, nine (2.0%) had carcinoma, and seven (1.5%) had atypical hyperplasia.

Endometrial thickness of 14 mm or greater was associated with atypical hyperplasia (odds ratio [OR], 4.29; P = .02), with a negative predictive value of 98.3%. A thickness of 15 mm or greater was associated with carcinoma (OR, 4.53; P = .03), with a negative predictive value of 98.5%.

Under 14 mm, the risk of hyperplasia was low, the authors found, at 0.08%. Below 15 mm, the risk of cancer was 0.06%.

They found no significant associations between endometrial lining TVUS appearance, age, parity, body mass index, diabetes, hypertension, hyperlipidemia, and carcinoma or atypical hyperplasia.

When biopsy might not be necessary

Therefore, regardless of conventional risk factors for endometrial cancer, if a postmenopausal woman reports pelvic pain without vaginal bleeding, and is found to have a thickened endometrial lining of less than 14 mm on TVUS, biopsy might not be warranted, conclude the study authors.  

Plasma for transfusion

Credit: Cristina Granados

The US Food and Drug Administration (FDA) has accepted a clinical protocol to make the INTERCEPT Blood System available to treat plasma collected from Ebola survivors.

Transfusion of blood or plasma from recovered Ebola patients can be of benefit in patients with acute Ebola infections, but recovered patients may carry undetected pathogens such as malaria, which is where the INTERCEPT Blood System for plasma comes in.

The system is used for the preparation and storage of whole blood-derived and apheresis plasma (fresh or recently thawed). It can inactivate a range of viruses, bacteria, and parasites to reduce the risk of transmission via transfusion.

“The INTERCEPT pathogen inactivation process can diminish the risk of other pathogens that may contaminate the plasma of valuable Ebola convalescent donors and will provide a new therapeutic resource for patients with Ebola,” said Laurence Corash, MD, senior vice president and chief medical officer of Cerus Corporation, the company developing the INTERCEPT system.

The INTERCEPT Blood System for plasma does not have FDA approval. The agency has approved use of the system via an investigational device exemption (IDE). This allows for early access to a device not yet approved in the US when no satisfactory alternative is available to treat patients with serious or life-threatening conditions.

Under this IDE, investigators at Emory University will collect Ebola convalescent plasma from recovered patients and use the INTERCEPT system for onsite pathogen inactivation.

Following testing for Ebola antibodies at the Centers for Disease Control and Prevention, the treated plasma will be stored at Emory for use with future patients. If needed, Emory will also supply the treated plasma for use at other Ebola treatment centers, such as the University of Nebraska Medical Center.

To further increase the availability of convalescent plasma, Cerus and the trial investigators are collaborating with the American Red Cross and America’s Blood Centers to create a national network of plasma collection sites to access recovered Ebola patients.

“Having a supply of convalescent plasma that has been through pathogen inactivation is critical to making this therapy readily available as new Ebola patients are diagnosed and urgently require treatment,” said Anne Winkler, MD, principal investigator for the study and an assistant professor at the Emory University School of Medicine in Atlanta, Georgia.

The World Health Organization recently identified convalescent plasma as a potentially promising experimental approach to treat Ebola, issuing interim guidance suggesting how the plasma should be sourced and supplied.

The Bill & Melinda Gates Foundation recently announced a $5.7 million commitment to support efforts in Guinea and other Ebola-affected countries to scale up the production and evaluation of potential therapies for people infected with the Ebola virus, including convalescent plasma treated with pathogen inactivation.

Funding is being provided to Clinical Research Management, Inc., and an array of private sector partners to study Ebola convalescent plasma that will be collected through mobile donation units fully equipped with apheresis plasma collection systems and the INTERCEPT Blood System for plasma.

The INTERCEPT platelet and plasma systems have been approved for use in Europe for 8 years and are used in 20 countries. License applications for the systems are under FDA review, with an approval decision expected in 2015.

The FDA recently accepted Cerus’s clinical protocol to make the INTERCEPT Blood System for platelets available under an IDE to regions in the US and its territories with outbreaks of Chikungunya and dengue virus.

Plasma for transfusion

Credit: Cristina Granados

The US Food and Drug Administration (FDA) has accepted a clinical protocol to make the INTERCEPT Blood System available to treat plasma collected from Ebola survivors.

Transfusion of blood or plasma from recovered Ebola patients can be of benefit in patients with acute Ebola infections, but recovered patients may carry undetected pathogens such as malaria, which is where the INTERCEPT Blood System for plasma comes in.

The system is used for the preparation and storage of whole blood-derived and apheresis plasma (fresh or recently thawed). It can inactivate a range of viruses, bacteria, and parasites to reduce the risk of transmission via transfusion.

“The INTERCEPT pathogen inactivation process can diminish the risk of other pathogens that may contaminate the plasma of valuable Ebola convalescent donors and will provide a new therapeutic resource for patients with Ebola,” said Laurence Corash, MD, senior vice president and chief medical officer of Cerus Corporation, the company developing the INTERCEPT system.

The INTERCEPT Blood System for plasma does not have FDA approval. The agency has approved use of the system via an investigational device exemption (IDE). This allows for early access to a device not yet approved in the US when no satisfactory alternative is available to treat patients with serious or life-threatening conditions.

Under this IDE, investigators at Emory University will collect Ebola convalescent plasma from recovered patients and use the INTERCEPT system for onsite pathogen inactivation.

Following testing for Ebola antibodies at the Centers for Disease Control and Prevention, the treated plasma will be stored at Emory for use with future patients. If needed, Emory will also supply the treated plasma for use at other Ebola treatment centers, such as the University of Nebraska Medical Center.

To further increase the availability of convalescent plasma, Cerus and the trial investigators are collaborating with the American Red Cross and America’s Blood Centers to create a national network of plasma collection sites to access recovered Ebola patients.

“Having a supply of convalescent plasma that has been through pathogen inactivation is critical to making this therapy readily available as new Ebola patients are diagnosed and urgently require treatment,” said Anne Winkler, MD, principal investigator for the study and an assistant professor at the Emory University School of Medicine in Atlanta, Georgia.

The World Health Organization recently identified convalescent plasma as a potentially promising experimental approach to treat Ebola, issuing interim guidance suggesting how the plasma should be sourced and supplied.

The Bill & Melinda Gates Foundation recently announced a $5.7 million commitment to support efforts in Guinea and other Ebola-affected countries to scale up the production and evaluation of potential therapies for people infected with the Ebola virus, including convalescent plasma treated with pathogen inactivation.

Funding is being provided to Clinical Research Management, Inc., and an array of private sector partners to study Ebola convalescent plasma that will be collected through mobile donation units fully equipped with apheresis plasma collection systems and the INTERCEPT Blood System for plasma.

The INTERCEPT platelet and plasma systems have been approved for use in Europe for 8 years and are used in 20 countries. License applications for the systems are under FDA review, with an approval decision expected in 2015.

The FDA recently accepted Cerus’s clinical protocol to make the INTERCEPT Blood System for platelets available under an IDE to regions in the US and its territories with outbreaks of Chikungunya and dengue virus.

Plasma for transfusion

Credit: Cristina Granados

The US Food and Drug Administration (FDA) has accepted a clinical protocol to make the INTERCEPT Blood System available to treat plasma collected from Ebola survivors.

Transfusion of blood or plasma from recovered Ebola patients can be of benefit in patients with acute Ebola infections, but recovered patients may carry undetected pathogens such as malaria, which is where the INTERCEPT Blood System for plasma comes in.

The system is used for the preparation and storage of whole blood-derived and apheresis plasma (fresh or recently thawed). It can inactivate a range of viruses, bacteria, and parasites to reduce the risk of transmission via transfusion.

“The INTERCEPT pathogen inactivation process can diminish the risk of other pathogens that may contaminate the plasma of valuable Ebola convalescent donors and will provide a new therapeutic resource for patients with Ebola,” said Laurence Corash, MD, senior vice president and chief medical officer of Cerus Corporation, the company developing the INTERCEPT system.

The INTERCEPT Blood System for plasma does not have FDA approval. The agency has approved use of the system via an investigational device exemption (IDE). This allows for early access to a device not yet approved in the US when no satisfactory alternative is available to treat patients with serious or life-threatening conditions.

Under this IDE, investigators at Emory University will collect Ebola convalescent plasma from recovered patients and use the INTERCEPT system for onsite pathogen inactivation.

Following testing for Ebola antibodies at the Centers for Disease Control and Prevention, the treated plasma will be stored at Emory for use with future patients. If needed, Emory will also supply the treated plasma for use at other Ebola treatment centers, such as the University of Nebraska Medical Center.

To further increase the availability of convalescent plasma, Cerus and the trial investigators are collaborating with the American Red Cross and America’s Blood Centers to create a national network of plasma collection sites to access recovered Ebola patients.

“Having a supply of convalescent plasma that has been through pathogen inactivation is critical to making this therapy readily available as new Ebola patients are diagnosed and urgently require treatment,” said Anne Winkler, MD, principal investigator for the study and an assistant professor at the Emory University School of Medicine in Atlanta, Georgia.

The World Health Organization recently identified convalescent plasma as a potentially promising experimental approach to treat Ebola, issuing interim guidance suggesting how the plasma should be sourced and supplied.

The Bill & Melinda Gates Foundation recently announced a $5.7 million commitment to support efforts in Guinea and other Ebola-affected countries to scale up the production and evaluation of potential therapies for people infected with the Ebola virus, including convalescent plasma treated with pathogen inactivation.

Funding is being provided to Clinical Research Management, Inc., and an array of private sector partners to study Ebola convalescent plasma that will be collected through mobile donation units fully equipped with apheresis plasma collection systems and the INTERCEPT Blood System for plasma.

The INTERCEPT platelet and plasma systems have been approved for use in Europe for 8 years and are used in 20 countries. License applications for the systems are under FDA review, with an approval decision expected in 2015.

The FDA recently accepted Cerus’s clinical protocol to make the INTERCEPT Blood System for platelets available under an IDE to regions in the US and its territories with outbreaks of Chikungunya and dengue virus.

Researcher in the lab

Credit: NIH

A newly identified class of compounds recognize a key target in the Ras signaling pathway and could therefore prove useful in treating a range of malignancies, according to research published in Chemistry & Biology.

The lead compound, NSC-658497, targeted the catalytic activation of Ras by an enzyme called SOS1.

NSC-658497 blocked SOS1-mediated molecular signaling in the Ras pathway that causes rapid cell proliferation, tumor development, and cancer.

“While Ras pathway activation is a dominant event happening in many diseases, so far, the immediate signaling module of the Ras pathway has been difficult to target,” said study author Yi Zheng, PhD, of Cincinnati Children’s Hospital in Ohio.

“Most strategies for treatment have been geared toward hitting molecular effectors that are farther downstream. In this study, we have identified synthetic compounds that specifically recognize the catalytic pocket of SOS1 and demonstrated that they are effective inhibitors of Ras signaling in cells. This establishes a novel targeting approach for cancers and Rasopathies that is useful in developing therapeutics.”

Rasopathies include a group of 9 developmental syndromes that are caused by mutations in the Ras pathway (Noonan, LEOPARD, hereditary Gingival fibromatosis type 1, Capillary malformation-AV malformation, Neurofibromatosis type 1, Legius, Costello, Cardio-facio-cutaneous, and autoimmune lymphoproliferative syndromes).

Dysregulation of the Ras pathway (including its SOS1 catalytic activator) is also linked to a number of malignancies, such as breast, pancreatic, and cervical cancers, as well as leukemia.

To find compounds that could target the Ras pathway, Dr Zheng and his colleagues tested 30,000 synthetic molecular compounds in a database maintained by the National Cancer Institute.

The researchers looked for the compounds’ ability to dock with the catalytic site of SOS1, which led them to identify NSC-658497 and derivatives as lead candidates for the development of a prospective drug.

The team then tested NSC-658497 in cell lines of mouse fibroblasts and prostate cancer. These experiments showed the compound successfully blocked SOS1-to-Ras signaling and the proliferation of cancer cells.

Dr Zheng said one of the researchers’ next steps is to transform NSC-658497 into a drug that can be administered to a living organism so the team can begin testing the inhibitor in mouse models of different Rasopathies and cancers.

One of the targeted approaches the researchers plan to explore is whether NSC-658497 might be most promising in individuals who have a subset of disease in which SOS1 is significantly overexpressed or mutated.

Researcher in the lab

Credit: NIH

A newly identified class of compounds recognize a key target in the Ras signaling pathway and could therefore prove useful in treating a range of malignancies, according to research published in Chemistry & Biology.

The lead compound, NSC-658497, targeted the catalytic activation of Ras by an enzyme called SOS1.

NSC-658497 blocked SOS1-mediated molecular signaling in the Ras pathway that causes rapid cell proliferation, tumor development, and cancer.

“While Ras pathway activation is a dominant event happening in many diseases, so far, the immediate signaling module of the Ras pathway has been difficult to target,” said study author Yi Zheng, PhD, of Cincinnati Children’s Hospital in Ohio.

“Most strategies for treatment have been geared toward hitting molecular effectors that are farther downstream. In this study, we have identified synthetic compounds that specifically recognize the catalytic pocket of SOS1 and demonstrated that they are effective inhibitors of Ras signaling in cells. This establishes a novel targeting approach for cancers and Rasopathies that is useful in developing therapeutics.”

Rasopathies include a group of 9 developmental syndromes that are caused by mutations in the Ras pathway (Noonan, LEOPARD, hereditary Gingival fibromatosis type 1, Capillary malformation-AV malformation, Neurofibromatosis type 1, Legius, Costello, Cardio-facio-cutaneous, and autoimmune lymphoproliferative syndromes).

Dysregulation of the Ras pathway (including its SOS1 catalytic activator) is also linked to a number of malignancies, such as breast, pancreatic, and cervical cancers, as well as leukemia.

To find compounds that could target the Ras pathway, Dr Zheng and his colleagues tested 30,000 synthetic molecular compounds in a database maintained by the National Cancer Institute.

The researchers looked for the compounds’ ability to dock with the catalytic site of SOS1, which led them to identify NSC-658497 and derivatives as lead candidates for the development of a prospective drug.

The team then tested NSC-658497 in cell lines of mouse fibroblasts and prostate cancer. These experiments showed the compound successfully blocked SOS1-to-Ras signaling and the proliferation of cancer cells.

Dr Zheng said one of the researchers’ next steps is to transform NSC-658497 into a drug that can be administered to a living organism so the team can begin testing the inhibitor in mouse models of different Rasopathies and cancers.

One of the targeted approaches the researchers plan to explore is whether NSC-658497 might be most promising in individuals who have a subset of disease in which SOS1 is significantly overexpressed or mutated.

Researcher in the lab

Credit: NIH

A newly identified class of compounds recognize a key target in the Ras signaling pathway and could therefore prove useful in treating a range of malignancies, according to research published in Chemistry & Biology.

The lead compound, NSC-658497, targeted the catalytic activation of Ras by an enzyme called SOS1.

NSC-658497 blocked SOS1-mediated molecular signaling in the Ras pathway that causes rapid cell proliferation, tumor development, and cancer.

“While Ras pathway activation is a dominant event happening in many diseases, so far, the immediate signaling module of the Ras pathway has been difficult to target,” said study author Yi Zheng, PhD, of Cincinnati Children’s Hospital in Ohio.

“Most strategies for treatment have been geared toward hitting molecular effectors that are farther downstream. In this study, we have identified synthetic compounds that specifically recognize the catalytic pocket of SOS1 and demonstrated that they are effective inhibitors of Ras signaling in cells. This establishes a novel targeting approach for cancers and Rasopathies that is useful in developing therapeutics.”

Rasopathies include a group of 9 developmental syndromes that are caused by mutations in the Ras pathway (Noonan, LEOPARD, hereditary Gingival fibromatosis type 1, Capillary malformation-AV malformation, Neurofibromatosis type 1, Legius, Costello, Cardio-facio-cutaneous, and autoimmune lymphoproliferative syndromes).

Dysregulation of the Ras pathway (including its SOS1 catalytic activator) is also linked to a number of malignancies, such as breast, pancreatic, and cervical cancers, as well as leukemia.

To find compounds that could target the Ras pathway, Dr Zheng and his colleagues tested 30,000 synthetic molecular compounds in a database maintained by the National Cancer Institute.

The researchers looked for the compounds’ ability to dock with the catalytic site of SOS1, which led them to identify NSC-658497 and derivatives as lead candidates for the development of a prospective drug.

The team then tested NSC-658497 in cell lines of mouse fibroblasts and prostate cancer. These experiments showed the compound successfully blocked SOS1-to-Ras signaling and the proliferation of cancer cells.

Dr Zheng said one of the researchers’ next steps is to transform NSC-658497 into a drug that can be administered to a living organism so the team can begin testing the inhibitor in mouse models of different Rasopathies and cancers.

One of the targeted approaches the researchers plan to explore is whether NSC-658497 might be most promising in individuals who have a subset of disease in which SOS1 is significantly overexpressed or mutated.

During the 43rd AAGL Global Congress, held November 17–21 in Vancouver, British Columbia, Sarah L. Cohen, MD, MPH, of Brigham and Women’s Hospital in Boston, Massachusetts, stepped attendees through diagnosis and surgical management of adnexal masses in pregnancy, noting the approaches backed by the highest-quality data.

The incidence of adnexal masses in pregnancy is 1 in every 600 live births. A mass can be benign or malignant. Among benign masses found in pregnancy are functional cysts, teratomas, and the corpus luteum.

Work-up
Ultrasound imaging is a valuable component of the work-up, owing to its risk-free nature. Magnetic resonance imaging may be appropriate in selected cases, but gadolinium contrast should be avoided.

In pregnancy, the aim is to limit ionizing radiation to less than 5 to 10 rads to minimize the risk of childhood malignancy/leukemia, with no single imaging study exceeding 5 rads.

Tumor markers may be helpful, but careful interpretation is critical, taking into account the effects of pregnancy itself on CA-125 (which peaks in the first trimester), human chorionic gonadotropin, alpha fetoprotein, inhibin A, and lactate dehydrogenase.

When expectant management may be appropriate
Watchful waiting may be considered for simple cysts less than 6 cm in size, provided the patient is asymptomatic with no signs of malignancy.

Surgery is indicated when the patient is symptomatic, when there is a concern for malignancy, and when a persistent mass exceeds 10 cm in size.

As always, elective surgery is preferable, as emergent surgery in pregnancy is associated with a risk of preterm labor of 22% to 35%.

Optimal timing of surgery
Surgery can be performed safely in any trimester, provided the gynecologist is aware of special concerns. For example, in the first trimester, organogenesis is under way and the corpus luteum is still present. If the corpus luteum is removed, progesterone supplementation is necessary.

When surgery can be postponed to the second trimester, it allows time for possible resolution of the mass.

Mode of surgery
Laparoscopy allows for faster recovery, less pain (and, therefore, lower narcotic exposure to the fetus), and improved maternal ventilation.

Prophylaxis for venous thromboembolism is indicated through the use of pneumatic compression devices and, when appropriate, heparin.

Initial port placement can be performed using a Hassan technique, Veress needle, or optical trocar.

Insufflation pressures of 10 to 15 mm Hg are safe, with intraoperative monitoring of carbon dioxide. 

Availability of guidelines
Surgeons should make use of guidelines, when feasible, to guide surgery. For example, the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) publishes guidelines on surgery during pregnancy. The American College of Obstetricians and Gynecologists also offers guidelines.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

During the 43rd AAGL Global Congress, held November 17–21 in Vancouver, British Columbia, Sarah L. Cohen, MD, MPH, of Brigham and Women’s Hospital in Boston, Massachusetts, stepped attendees through diagnosis and surgical management of adnexal masses in pregnancy, noting the approaches backed by the highest-quality data.

The incidence of adnexal masses in pregnancy is 1 in every 600 live births. A mass can be benign or malignant. Among benign masses found in pregnancy are functional cysts, teratomas, and the corpus luteum.

Work-up
Ultrasound imaging is a valuable component of the work-up, owing to its risk-free nature. Magnetic resonance imaging may be appropriate in selected cases, but gadolinium contrast should be avoided.

In pregnancy, the aim is to limit ionizing radiation to less than 5 to 10 rads to minimize the risk of childhood malignancy/leukemia, with no single imaging study exceeding 5 rads.

Tumor markers may be helpful, but careful interpretation is critical, taking into account the effects of pregnancy itself on CA-125 (which peaks in the first trimester), human chorionic gonadotropin, alpha fetoprotein, inhibin A, and lactate dehydrogenase.

When expectant management may be appropriate
Watchful waiting may be considered for simple cysts less than 6 cm in size, provided the patient is asymptomatic with no signs of malignancy.

Surgery is indicated when the patient is symptomatic, when there is a concern for malignancy, and when a persistent mass exceeds 10 cm in size.

As always, elective surgery is preferable, as emergent surgery in pregnancy is associated with a risk of preterm labor of 22% to 35%.

Optimal timing of surgery
Surgery can be performed safely in any trimester, provided the gynecologist is aware of special concerns. For example, in the first trimester, organogenesis is under way and the corpus luteum is still present. If the corpus luteum is removed, progesterone supplementation is necessary.

When surgery can be postponed to the second trimester, it allows time for possible resolution of the mass.

Mode of surgery
Laparoscopy allows for faster recovery, less pain (and, therefore, lower narcotic exposure to the fetus), and improved maternal ventilation.

Prophylaxis for venous thromboembolism is indicated through the use of pneumatic compression devices and, when appropriate, heparin.

Initial port placement can be performed using a Hassan technique, Veress needle, or optical trocar.

Insufflation pressures of 10 to 15 mm Hg are safe, with intraoperative monitoring of carbon dioxide. 

Availability of guidelines
Surgeons should make use of guidelines, when feasible, to guide surgery. For example, the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) publishes guidelines on surgery during pregnancy. The American College of Obstetricians and Gynecologists also offers guidelines.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

During the 43rd AAGL Global Congress, held November 17–21 in Vancouver, British Columbia, Sarah L. Cohen, MD, MPH, of Brigham and Women’s Hospital in Boston, Massachusetts, stepped attendees through diagnosis and surgical management of adnexal masses in pregnancy, noting the approaches backed by the highest-quality data.

The incidence of adnexal masses in pregnancy is 1 in every 600 live births. A mass can be benign or malignant. Among benign masses found in pregnancy are functional cysts, teratomas, and the corpus luteum.

Work-up
Ultrasound imaging is a valuable component of the work-up, owing to its risk-free nature. Magnetic resonance imaging may be appropriate in selected cases, but gadolinium contrast should be avoided.

In pregnancy, the aim is to limit ionizing radiation to less than 5 to 10 rads to minimize the risk of childhood malignancy/leukemia, with no single imaging study exceeding 5 rads.

Tumor markers may be helpful, but careful interpretation is critical, taking into account the effects of pregnancy itself on CA-125 (which peaks in the first trimester), human chorionic gonadotropin, alpha fetoprotein, inhibin A, and lactate dehydrogenase.

When expectant management may be appropriate
Watchful waiting may be considered for simple cysts less than 6 cm in size, provided the patient is asymptomatic with no signs of malignancy.

Surgery is indicated when the patient is symptomatic, when there is a concern for malignancy, and when a persistent mass exceeds 10 cm in size.

As always, elective surgery is preferable, as emergent surgery in pregnancy is associated with a risk of preterm labor of 22% to 35%.

Optimal timing of surgery
Surgery can be performed safely in any trimester, provided the gynecologist is aware of special concerns. For example, in the first trimester, organogenesis is under way and the corpus luteum is still present. If the corpus luteum is removed, progesterone supplementation is necessary.

When surgery can be postponed to the second trimester, it allows time for possible resolution of the mass.

Mode of surgery
Laparoscopy allows for faster recovery, less pain (and, therefore, lower narcotic exposure to the fetus), and improved maternal ventilation.

Prophylaxis for venous thromboembolism is indicated through the use of pneumatic compression devices and, when appropriate, heparin.

Initial port placement can be performed using a Hassan technique, Veress needle, or optical trocar.

Insufflation pressures of 10 to 15 mm Hg are safe, with intraoperative monitoring of carbon dioxide. 

Availability of guidelines
Surgeons should make use of guidelines, when feasible, to guide surgery. For example, the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) publishes guidelines on surgery during pregnancy. The American College of Obstetricians and Gynecologists also offers guidelines.

Share your thoughts on this article! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.