MIAMI – Lifting the lower face using minimally invasive barbed sutures can yield rejuvenation results that last 12-18 months, providing an option for patients who do not wish to undergo full facelift surgery, according to a presentation at ODAC 2017.

“We have something new in our toolbox. The Silhouette InstaLift is a “good new thing to consider adding to your practice. It works really nice for me in combination with other facial rejuvenation strategies,” said Susan Weinkle, MD, a private practice Mohs surgeon and aesthetic dermatologist in Bradenton, Fla.

“Now we can reposition the skin. It works quite nicely in skin of color also,” Dr. Weinkle said during a lecture and live demonstration at the Orlando Dermatology Aesthetic and Clinical Conference.
 

Procedure tips

Begin by marking where on the patient’s face you intend to place the sutures. The proper vector is a straight lift back toward the upper ear in many cases. Also, take a photo before you start, so you know the location of the sutures in case the patient comes back for more, Dr. Weinkle recommended.

“What I like to do next is to sit the patient up and look at them head-on,” Dr. Weinkle said. “It helps to tweak the placement of the suture markings.” If a patient’s face appears asymmetrical, the dermatologist can place more sutures on one side than the other. Also, when there are neck issues, you can put an exit point for the sutures 1.5 cm below the mandible, she added.

Be patient after you anesthetize the entry and exit points because the epinephrine does not work immediately, Dr. Weinkle advised.

She does not anesthetize along the entire suture tract because the aim is to thread the sutures through the subcutaneous tissue. “You do not want to anesthetize the tract area between entry and exit points. If the patient feels it, you’re probably too superficial and you’re in the dermis.”

The next step is using an 18G needle to form an entry point for the 23G needle. “Pinch the skin, insert and stretch the skin just a bit. If you don’t pinch at the entry point, the cones can be difficult to pop in.” Dr. Weinkle said. Also, if you establish all entry points before inserting the sutures, it can save time.

Dr. Weinkle generally uses a number 8 InstaLift suture, but it also comes in sizes 12 and 16. After you open the package, gently pull the suture to tighten the knots between the cones. “Don’t pull hard from both ends – you can break the suture.”

When inserting the long needle to place the suture, it’s “almost like playing the violin with a bow.” As the clinician advances along tract line, he or she should run the needle between thumb and forefinger to check the positioning. Once the suture is placed and the needle removed, pull medially on the suture until the cones audibly “pop” – they are self anchoring. “I’ve seen some people break the sutures. You can pull them out and start again,” she noted.

“InstaLift is a bit of a misnomer,” Dr. Weinkle said. “Fibroblast stimulation and collagen improves final result over the next 2-3 months.” Improvements can last 12-18 months – it’s not permanent. “I think I would make a great candidate,” she joked. “Unfortunately, this is one thing I cannot do myself.”

There is minimal bruising after the procedure in Dr. Weinkle’s experience. Potential complications include swelling, dimpling at entry points, misplacement, and ecchymosis.

Dr. Weinkle is a consultant and principal investigator for Sinclair Pharma, manufacturer of InstaLift.

 

MIAMI – Lifting the lower face using minimally invasive barbed sutures can yield rejuvenation results that last 12-18 months, providing an option for patients who do not wish to undergo full facelift surgery, according to a presentation at ODAC 2017.

“We have something new in our toolbox. The Silhouette InstaLift is a “good new thing to consider adding to your practice. It works really nice for me in combination with other facial rejuvenation strategies,” said Susan Weinkle, MD, a private practice Mohs surgeon and aesthetic dermatologist in Bradenton, Fla.

“Now we can reposition the skin. It works quite nicely in skin of color also,” Dr. Weinkle said during a lecture and live demonstration at the Orlando Dermatology Aesthetic and Clinical Conference.
 

Procedure tips

Begin by marking where on the patient’s face you intend to place the sutures. The proper vector is a straight lift back toward the upper ear in many cases. Also, take a photo before you start, so you know the location of the sutures in case the patient comes back for more, Dr. Weinkle recommended.

“What I like to do next is to sit the patient up and look at them head-on,” Dr. Weinkle said. “It helps to tweak the placement of the suture markings.” If a patient’s face appears asymmetrical, the dermatologist can place more sutures on one side than the other. Also, when there are neck issues, you can put an exit point for the sutures 1.5 cm below the mandible, she added.

Be patient after you anesthetize the entry and exit points because the epinephrine does not work immediately, Dr. Weinkle advised.

She does not anesthetize along the entire suture tract because the aim is to thread the sutures through the subcutaneous tissue. “You do not want to anesthetize the tract area between entry and exit points. If the patient feels it, you’re probably too superficial and you’re in the dermis.”

The next step is using an 18G needle to form an entry point for the 23G needle. “Pinch the skin, insert and stretch the skin just a bit. If you don’t pinch at the entry point, the cones can be difficult to pop in.” Dr. Weinkle said. Also, if you establish all entry points before inserting the sutures, it can save time.

Dr. Weinkle generally uses a number 8 InstaLift suture, but it also comes in sizes 12 and 16. After you open the package, gently pull the suture to tighten the knots between the cones. “Don’t pull hard from both ends – you can break the suture.”

When inserting the long needle to place the suture, it’s “almost like playing the violin with a bow.” As the clinician advances along tract line, he or she should run the needle between thumb and forefinger to check the positioning. Once the suture is placed and the needle removed, pull medially on the suture until the cones audibly “pop” – they are self anchoring. “I’ve seen some people break the sutures. You can pull them out and start again,” she noted.

“InstaLift is a bit of a misnomer,” Dr. Weinkle said. “Fibroblast stimulation and collagen improves final result over the next 2-3 months.” Improvements can last 12-18 months – it’s not permanent. “I think I would make a great candidate,” she joked. “Unfortunately, this is one thing I cannot do myself.”

There is minimal bruising after the procedure in Dr. Weinkle’s experience. Potential complications include swelling, dimpling at entry points, misplacement, and ecchymosis.

Dr. Weinkle is a consultant and principal investigator for Sinclair Pharma, manufacturer of InstaLift.

 

MIAMI – Lifting the lower face using minimally invasive barbed sutures can yield rejuvenation results that last 12-18 months, providing an option for patients who do not wish to undergo full facelift surgery, according to a presentation at ODAC 2017.

“We have something new in our toolbox. The Silhouette InstaLift is a “good new thing to consider adding to your practice. It works really nice for me in combination with other facial rejuvenation strategies,” said Susan Weinkle, MD, a private practice Mohs surgeon and aesthetic dermatologist in Bradenton, Fla.

“Now we can reposition the skin. It works quite nicely in skin of color also,” Dr. Weinkle said during a lecture and live demonstration at the Orlando Dermatology Aesthetic and Clinical Conference.
 

Procedure tips

Begin by marking where on the patient’s face you intend to place the sutures. The proper vector is a straight lift back toward the upper ear in many cases. Also, take a photo before you start, so you know the location of the sutures in case the patient comes back for more, Dr. Weinkle recommended.

“What I like to do next is to sit the patient up and look at them head-on,” Dr. Weinkle said. “It helps to tweak the placement of the suture markings.” If a patient’s face appears asymmetrical, the dermatologist can place more sutures on one side than the other. Also, when there are neck issues, you can put an exit point for the sutures 1.5 cm below the mandible, she added.

Be patient after you anesthetize the entry and exit points because the epinephrine does not work immediately, Dr. Weinkle advised.

She does not anesthetize along the entire suture tract because the aim is to thread the sutures through the subcutaneous tissue. “You do not want to anesthetize the tract area between entry and exit points. If the patient feels it, you’re probably too superficial and you’re in the dermis.”

The next step is using an 18G needle to form an entry point for the 23G needle. “Pinch the skin, insert and stretch the skin just a bit. If you don’t pinch at the entry point, the cones can be difficult to pop in.” Dr. Weinkle said. Also, if you establish all entry points before inserting the sutures, it can save time.

Dr. Weinkle generally uses a number 8 InstaLift suture, but it also comes in sizes 12 and 16. After you open the package, gently pull the suture to tighten the knots between the cones. “Don’t pull hard from both ends – you can break the suture.”

When inserting the long needle to place the suture, it’s “almost like playing the violin with a bow.” As the clinician advances along tract line, he or she should run the needle between thumb and forefinger to check the positioning. Once the suture is placed and the needle removed, pull medially on the suture until the cones audibly “pop” – they are self anchoring. “I’ve seen some people break the sutures. You can pull them out and start again,” she noted.

“InstaLift is a bit of a misnomer,” Dr. Weinkle said. “Fibroblast stimulation and collagen improves final result over the next 2-3 months.” Improvements can last 12-18 months – it’s not permanent. “I think I would make a great candidate,” she joked. “Unfortunately, this is one thing I cannot do myself.”

There is minimal bruising after the procedure in Dr. Weinkle’s experience. Potential complications include swelling, dimpling at entry points, misplacement, and ecchymosis.

Dr. Weinkle is a consultant and principal investigator for Sinclair Pharma, manufacturer of InstaLift.

 

SAN FRANCISCO – Nivolumab was associated with durable responses in heavily pretreated patients with advanced hepatocellular carcinoma in the dose-escalation and dose-expansion phases of the CheckMate 040 study.

Further, the safety profile of nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), was consistent with that observed in other solid tumors; events were manageable, and no new safety signals were detected, Ignacio Melero, MD, of Clinica Universidad de Navarra, Pamplona, Spain, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and Society of Surgical Oncology.

Sharon Worcester/Frontline Medical News

In all, 262 patients with histologically confirmed advanced disease not amenable to curative resection were treated across the CheckMate 040 dose-escalation phase (phase I), which evaluated 0.1-10 mg/kg of nivolumab given every 2 weeks, and the dose-expansion phase (phase II), which involved nivolumab at a dose of 3 mg/kg every 2 weeks in four cohorts: sorafenib naive/intolerant patients, sorafenib progressors, hepatitis C virus-infected patients, and hepatitis B virus-infected patients.

“Because of the inflammation that often afflicts the liver, we were very afraid of precipitating hyper-acute or fulminant hepatitis in these patients, and that was the reason we undertook a very careful dose escalation,” Dr. Melero said, adding that due to efficacy and safety results in the dose escalation phase, the 3-mg/kg dose used in other clinical trials was expanded to all subjects, including uninfected patients and those with HCV or HBV infection.

In regard to safety and tolerability – the primary endpoint of phase I – grade 3/4 treatment-related adverse events occurred in 20% of patients. No maximum tolerated dose was reached during dose escalation, Dr. Melero said.

The most common reason for treatment discontinuation was disease progression; very few patients discontinued for toxicity, he said, noting that “the safety profile was very consistent with what has been reported in other indications.”

In fact, most grade 3/4 events involved laboratory abnormalities without clinical repercussions, he said.

The safety profile in phase II was consistent with that observed in phase I, and no differences in safety were seen in the three categories of hepatocellular carcinoma patients in the study.

In regard to objective response – the primary endpoint of phase II – the investigator-assessed rates were 16.2% in phase I and 18.6% in phase II, and the rates assessed by blinded independent central review were 18.9% and 14.5% in the phases, respectively. Based on imaging assessed using modified RESIST criteria, the rates were 21.6% and 18.6%, respectively.

The median duration of response was 17.1 months in phase I, and had not yet been reached in phase II, Dr. Melero said, adding that in uninfected patients, an “important number of patients developed stable disease that was durable.”

This also was seen in patients with chronic hepatitis, he noted.

“We believe that stabilization of disease is a driver of survival, because we have seen that in dose escalation, 45% of patients were alive 18 months after treatment onset, and at last data base log [in dose escalation], 71% were alive 9 months after starting treatment,” he said.

Of note, objective response rates were similar in patients treated with sorafenib and in those who received nivolumab as first-line treatment, and they were similar regardless of tumor programmed death-ligand 1 (PD-L1) expression.

Quality of life, as reported by patients via EQ-5D questionnaire, remained stable over time.

Study subjects had a median age of 63 years, and were heavily pretreated – most often by sorafenib.

Hepatocellular carcinoma diagnosed at advanced stages has a poor prognosis, and those who progress on sorafenib – the only systemic therapy option in such patients – have few options, Dr. Melero said.

Nivolumab, which has been shown to restore T-cell–mediated antitumor activity, has demonstrated clinical and survival benefit in a number of tumor types.

The current findings suggest that it also is a promising alternative for advanced hepatocellular carcinoma.

“Nivolumab demonstrated objective responses and long-term survival in both sorafenib-experienced and sorafenib-naive patients. Nivolumab monotherapy provided early, stable and durable responses when they took place, efficacy was observed irrespective of chronic viral infection by hepatitis viruses, and responses were also observed in PD-L1-negative cases upon examination of biopsies,” he concluded, noting that a randomized phase III trial comparing nivolumab with systemic sorafenib is ongoing.

CheckMate 040 was sponsored by Bristol Myers Squibb. Dr. Melero reported receiving honoraria from and serving as a consultant or adviser for AstraZeneca, Bayer, Bristol-Myers Squibb, Incyte, Merck Serono, MSD, and Roche, and reported research funding to his institution from Alligator Bioscience, Pfizer, and Tusk Therapeutics.

sworcester@frontlinemedcom.com

 

SAN FRANCISCO – Nivolumab was associated with durable responses in heavily pretreated patients with advanced hepatocellular carcinoma in the dose-escalation and dose-expansion phases of the CheckMate 040 study.

Further, the safety profile of nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), was consistent with that observed in other solid tumors; events were manageable, and no new safety signals were detected, Ignacio Melero, MD, of Clinica Universidad de Navarra, Pamplona, Spain, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and Society of Surgical Oncology.

Sharon Worcester/Frontline Medical News

In all, 262 patients with histologically confirmed advanced disease not amenable to curative resection were treated across the CheckMate 040 dose-escalation phase (phase I), which evaluated 0.1-10 mg/kg of nivolumab given every 2 weeks, and the dose-expansion phase (phase II), which involved nivolumab at a dose of 3 mg/kg every 2 weeks in four cohorts: sorafenib naive/intolerant patients, sorafenib progressors, hepatitis C virus-infected patients, and hepatitis B virus-infected patients.

“Because of the inflammation that often afflicts the liver, we were very afraid of precipitating hyper-acute or fulminant hepatitis in these patients, and that was the reason we undertook a very careful dose escalation,” Dr. Melero said, adding that due to efficacy and safety results in the dose escalation phase, the 3-mg/kg dose used in other clinical trials was expanded to all subjects, including uninfected patients and those with HCV or HBV infection.

In regard to safety and tolerability – the primary endpoint of phase I – grade 3/4 treatment-related adverse events occurred in 20% of patients. No maximum tolerated dose was reached during dose escalation, Dr. Melero said.

The most common reason for treatment discontinuation was disease progression; very few patients discontinued for toxicity, he said, noting that “the safety profile was very consistent with what has been reported in other indications.”

In fact, most grade 3/4 events involved laboratory abnormalities without clinical repercussions, he said.

The safety profile in phase II was consistent with that observed in phase I, and no differences in safety were seen in the three categories of hepatocellular carcinoma patients in the study.

In regard to objective response – the primary endpoint of phase II – the investigator-assessed rates were 16.2% in phase I and 18.6% in phase II, and the rates assessed by blinded independent central review were 18.9% and 14.5% in the phases, respectively. Based on imaging assessed using modified RESIST criteria, the rates were 21.6% and 18.6%, respectively.

The median duration of response was 17.1 months in phase I, and had not yet been reached in phase II, Dr. Melero said, adding that in uninfected patients, an “important number of patients developed stable disease that was durable.”

This also was seen in patients with chronic hepatitis, he noted.

“We believe that stabilization of disease is a driver of survival, because we have seen that in dose escalation, 45% of patients were alive 18 months after treatment onset, and at last data base log [in dose escalation], 71% were alive 9 months after starting treatment,” he said.

Of note, objective response rates were similar in patients treated with sorafenib and in those who received nivolumab as first-line treatment, and they were similar regardless of tumor programmed death-ligand 1 (PD-L1) expression.

Quality of life, as reported by patients via EQ-5D questionnaire, remained stable over time.

Study subjects had a median age of 63 years, and were heavily pretreated – most often by sorafenib.

Hepatocellular carcinoma diagnosed at advanced stages has a poor prognosis, and those who progress on sorafenib – the only systemic therapy option in such patients – have few options, Dr. Melero said.

Nivolumab, which has been shown to restore T-cell–mediated antitumor activity, has demonstrated clinical and survival benefit in a number of tumor types.

The current findings suggest that it also is a promising alternative for advanced hepatocellular carcinoma.

“Nivolumab demonstrated objective responses and long-term survival in both sorafenib-experienced and sorafenib-naive patients. Nivolumab monotherapy provided early, stable and durable responses when they took place, efficacy was observed irrespective of chronic viral infection by hepatitis viruses, and responses were also observed in PD-L1-negative cases upon examination of biopsies,” he concluded, noting that a randomized phase III trial comparing nivolumab with systemic sorafenib is ongoing.

CheckMate 040 was sponsored by Bristol Myers Squibb. Dr. Melero reported receiving honoraria from and serving as a consultant or adviser for AstraZeneca, Bayer, Bristol-Myers Squibb, Incyte, Merck Serono, MSD, and Roche, and reported research funding to his institution from Alligator Bioscience, Pfizer, and Tusk Therapeutics.

sworcester@frontlinemedcom.com

 

SAN FRANCISCO – Nivolumab was associated with durable responses in heavily pretreated patients with advanced hepatocellular carcinoma in the dose-escalation and dose-expansion phases of the CheckMate 040 study.

Further, the safety profile of nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1), was consistent with that observed in other solid tumors; events were manageable, and no new safety signals were detected, Ignacio Melero, MD, of Clinica Universidad de Navarra, Pamplona, Spain, reported at the symposium, sponsored by ASCO, ASTRO, the American Gastroenterological Association, and Society of Surgical Oncology.

Sharon Worcester/Frontline Medical News

In all, 262 patients with histologically confirmed advanced disease not amenable to curative resection were treated across the CheckMate 040 dose-escalation phase (phase I), which evaluated 0.1-10 mg/kg of nivolumab given every 2 weeks, and the dose-expansion phase (phase II), which involved nivolumab at a dose of 3 mg/kg every 2 weeks in four cohorts: sorafenib naive/intolerant patients, sorafenib progressors, hepatitis C virus-infected patients, and hepatitis B virus-infected patients.

“Because of the inflammation that often afflicts the liver, we were very afraid of precipitating hyper-acute or fulminant hepatitis in these patients, and that was the reason we undertook a very careful dose escalation,” Dr. Melero said, adding that due to efficacy and safety results in the dose escalation phase, the 3-mg/kg dose used in other clinical trials was expanded to all subjects, including uninfected patients and those with HCV or HBV infection.

In regard to safety and tolerability – the primary endpoint of phase I – grade 3/4 treatment-related adverse events occurred in 20% of patients. No maximum tolerated dose was reached during dose escalation, Dr. Melero said.

The most common reason for treatment discontinuation was disease progression; very few patients discontinued for toxicity, he said, noting that “the safety profile was very consistent with what has been reported in other indications.”

In fact, most grade 3/4 events involved laboratory abnormalities without clinical repercussions, he said.

The safety profile in phase II was consistent with that observed in phase I, and no differences in safety were seen in the three categories of hepatocellular carcinoma patients in the study.

In regard to objective response – the primary endpoint of phase II – the investigator-assessed rates were 16.2% in phase I and 18.6% in phase II, and the rates assessed by blinded independent central review were 18.9% and 14.5% in the phases, respectively. Based on imaging assessed using modified RESIST criteria, the rates were 21.6% and 18.6%, respectively.

The median duration of response was 17.1 months in phase I, and had not yet been reached in phase II, Dr. Melero said, adding that in uninfected patients, an “important number of patients developed stable disease that was durable.”

This also was seen in patients with chronic hepatitis, he noted.

“We believe that stabilization of disease is a driver of survival, because we have seen that in dose escalation, 45% of patients were alive 18 months after treatment onset, and at last data base log [in dose escalation], 71% were alive 9 months after starting treatment,” he said.

Of note, objective response rates were similar in patients treated with sorafenib and in those who received nivolumab as first-line treatment, and they were similar regardless of tumor programmed death-ligand 1 (PD-L1) expression.

Quality of life, as reported by patients via EQ-5D questionnaire, remained stable over time.

Study subjects had a median age of 63 years, and were heavily pretreated – most often by sorafenib.

Hepatocellular carcinoma diagnosed at advanced stages has a poor prognosis, and those who progress on sorafenib – the only systemic therapy option in such patients – have few options, Dr. Melero said.

Nivolumab, which has been shown to restore T-cell–mediated antitumor activity, has demonstrated clinical and survival benefit in a number of tumor types.

The current findings suggest that it also is a promising alternative for advanced hepatocellular carcinoma.

“Nivolumab demonstrated objective responses and long-term survival in both sorafenib-experienced and sorafenib-naive patients. Nivolumab monotherapy provided early, stable and durable responses when they took place, efficacy was observed irrespective of chronic viral infection by hepatitis viruses, and responses were also observed in PD-L1-negative cases upon examination of biopsies,” he concluded, noting that a randomized phase III trial comparing nivolumab with systemic sorafenib is ongoing.

CheckMate 040 was sponsored by Bristol Myers Squibb. Dr. Melero reported receiving honoraria from and serving as a consultant or adviser for AstraZeneca, Bayer, Bristol-Myers Squibb, Incyte, Merck Serono, MSD, and Roche, and reported research funding to his institution from Alligator Bioscience, Pfizer, and Tusk Therapeutics.

sworcester@frontlinemedcom.com

 

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Monochorionic twins should be identified in the first trimester. Chorionicity is a straightforward determination at this time but can be difficult to determine in the second trimester if a single placental mass is all that is visible on an ultrasound. Most important, however, is the need for early surveillance of monochorionic twin pregnancies and the detection of potential problems and complications.

Increased ultrasonographic surveillance recommended for monochorionic twin pregnancies has been outlined in a recent consensus statement from the North American Fetal Therapy Network (Obstet Gynecol. 2015 Jan;125[1]:118-23). Beginning at 16 weeks’ gestation, monochorionic twins should be assessed every 2 weeks using amniotic fluid balance, presence/absence of fluid within the fetal bladder, and with fetal Doppler (umbilical artery, middle cerebral artery, and ductus venosus) studies. Fetal growth should also be assessed at least every 4 weeks.

Since monochorionic twins are at increased risk for congenital heart disease, echocardiography is also performed between 18 and 22 weeks, with surveillance intervals of 2 weeks or shorter if potential complications are identified. Early detection of these and other complications allows for earlier intervention, earlier referral if necessary, and potentially better outcomes.
 

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

 

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

 

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Monochorionic twins should be identified in the first trimester. Chorionicity is a straightforward determination at this time but can be difficult to determine in the second trimester if a single placental mass is all that is visible on an ultrasound. Most important, however, is the need for early surveillance of monochorionic twin pregnancies and the detection of potential problems and complications.

Increased ultrasonographic surveillance recommended for monochorionic twin pregnancies has been outlined in a recent consensus statement from the North American Fetal Therapy Network (Obstet Gynecol. 2015 Jan;125[1]:118-23). Beginning at 16 weeks’ gestation, monochorionic twins should be assessed every 2 weeks using amniotic fluid balance, presence/absence of fluid within the fetal bladder, and with fetal Doppler (umbilical artery, middle cerebral artery, and ductus venosus) studies. Fetal growth should also be assessed at least every 4 weeks.

Since monochorionic twins are at increased risk for congenital heart disease, echocardiography is also performed between 18 and 22 weeks, with surveillance intervals of 2 weeks or shorter if potential complications are identified. Early detection of these and other complications allows for earlier intervention, earlier referral if necessary, and potentially better outcomes.
 

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

 

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

 

Approximately 20% of all twin pregnancies are monochorionic, with the fetuses sharing a single placenta. Although the majority of these pregnancies are uncomplicated, monochorionic twins are significantly more likely than dichorionic twins to incur complications that can threaten the life and health of one or both fetuses.

The death of one monochorionic twin leaves the other twin with a 15% risk of demise. Survival after the loss of a co-twin is also associated with a 25% incidence of neurologic injury, compared with a 2% incidence in dichorionic pregnancies. Additionally, monochorionic pregnancies carry the risk of unique complications such as twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion.

Courtesy University of Maryland School of Medicine

Monochorionic twins should be identified in the first trimester. Chorionicity is a straightforward determination at this time but can be difficult to determine in the second trimester if a single placental mass is all that is visible on an ultrasound. Most important, however, is the need for early surveillance of monochorionic twin pregnancies and the detection of potential problems and complications.

Increased ultrasonographic surveillance recommended for monochorionic twin pregnancies has been outlined in a recent consensus statement from the North American Fetal Therapy Network (Obstet Gynecol. 2015 Jan;125[1]:118-23). Beginning at 16 weeks’ gestation, monochorionic twins should be assessed every 2 weeks using amniotic fluid balance, presence/absence of fluid within the fetal bladder, and with fetal Doppler (umbilical artery, middle cerebral artery, and ductus venosus) studies. Fetal growth should also be assessed at least every 4 weeks.

Since monochorionic twins are at increased risk for congenital heart disease, echocardiography is also performed between 18 and 22 weeks, with surveillance intervals of 2 weeks or shorter if potential complications are identified. Early detection of these and other complications allows for earlier intervention, earlier referral if necessary, and potentially better outcomes.
 

Twin-to-twin transfusion syndrome

Twin-to-twin transfusion syndrome (TTTS) is one of the most common and most serious complications, affecting approximately 10% of monochorionic pregnancies. Significant imbalances in blood-flow exchange lead to progressive cardiovascular decompensation that causes one twin to become a “donor” of blood volume, and the other twin to become a “recipient.” Without proper treatment between 16 and 26 weeks’ gestation, the perinatal mortality rate has been estimated to be 70% or higher.

Disease severity is classified according to the Quintero staging system. Stage I is characterized by amniotic fluid discordance. In stage II, the bladder of the donor twin is no longer visible sonographically. Stage III is marked by critically abnormal Doppler waveforms in either twin (absent/reverse end-diastolic velocity in the umbilical artery, reverse flow in the ductus venosus, or pulsatile flow in the umbilical vein). In stage IV, one of the twins has developed hydrops, and stage V is characterized by the death of one or both of the twins.

Amnioreduction to decrease intra-amniotic pressure had been the treatment of choice until a randomized controlled trial, published in 2004, demonstrated that fetoscopic laser coagulation of anastomoses was superior as a first-line treatment for severe TTTS that is diagnosed before 26 weeks. Perinatal mortality and morbidity were significantly lower after the laser treatment (N Engl J Med. 2004 Jul 8;351[2]:136-44).

Outcomes were further improved over the next decade as the laser surgery technique was modified to cover the entire vascular equator rather than selective components of the vasculature. In an open-label randomized controlled trial comparing the two approaches for severe TTTS, fetoscopic laser coagulation of the vascular equator (known as the Solomon technique) reduced the risk of twin anemia polycythemia sequence and recurrence of TTTS – the two main postoperative complications associated with residual anastomoses after selective coagulation (Lancet. 2014 Jun 21;383[9935]:2144-51).

The procedure has many challenges and can be impacted by one’s inability to see the entire vascular equator because of poor access, by the patient’s history of other interventions, and by the stage of TTTS.

Laser coagulation is regarded as the standard treatment for Quintero stage II-IV disease, and it is offered in some cases of stage I disease, such as those involving severe polyhydramnios and shortened cervix. Research currently underway is examining the outcomes of treatment for stage I disease, but data thus far suggest that intervening at stage I is generally better than expectant management.

With laser coagulation treatment, the survival rate in pregnancies complicated by TTTS is about 85%-90% for one fetus, and about 70% for both. TTTS sometimes causes one twin, particularly the recipient, to develop pulmonary valve stenosis, but this is generally a functional problem that resolves when the syndrome is treated.

After treatment, it is important to monitor for the development of twin anemia-polycythemia sequence, which may still occur if full visualization of the vascular equator was not possible or if a fine vessel was missed. Such monitoring involves weekly ultrasound surveillance with middle cerebral artery peak systolic velocity measurements.

Patients should also be monitored for abnormal neurologic development, ventriculomegaly, and other signs of abnormal brain development. Even “perfect” laser treatment with seemingly complete placental separation has been associated with abnormal neurologic development in about 10%-15% of cases.

Maternal complications with TTTS include placental abruption and preterm membrane rupture, the latter of which occurs about 15%-20% of the time.

Currently under much discussion is fetoscopic laser coagulation of TTTS placentas that have “proximate cord insertions.” The surgery in these cases – where the cords are less than 4 cm apart – is much more challenging because of technical difficulties in visualizing the vascular equator, and outcomes are being studied. Some centers will not perform laser surgery on placentas with proximate cord insertions, which fortunately are uncommon. However, the surgery is possible; I have completed three cases thus far, each with dual survival.

 

Selective fetal growth restriction

Selective fetal growth restriction (sFGR) stems from unequal placental sharing and affects approximately 15%-20% of all monochorionic pregnancies, making it a bit more common than TTTS. Diagnostic criteria vary, but the North American Fetal Therapy Network recommends using either an estimated fetal weight below the 10th percentile, with or without significant growth discordance (greater than 25%), or just growth discordance greater than 25%. Either provides an acceptable definition of sFGR.

With sFGR, in general, the normally growing twin has normal fluid and the growth-restricted twin has less fluid. This makes it different from TTTS, in which the twins may have different sizes but fluid discordance is always present. Also in TTTS, there is a finding of polyhydramnios in the recipient.

There are three types of sFGR, based on umbilical artery Doppler findings. In type I there is no cardiovascular imbalance, and management typically involves weekly monitoring with Doppler ultrasound. If Doppler findings remain normal for some time, monitoring every 2-4 weeks will suffice. Elective delivery is generally set for 35 or 36 weeks.

Type II sFGR involves cardiovascular compromise early in pregnancy, with umbilical artery Doppler showing persistent reversed or absent end-diastolic flow. Treatment options include monitoring closely and, in general, delivering by 32 weeks. In these cases, prematurity may jeopardize the life or health of the normally growing twin while saving the life of the growth-restricted twin.

When type II sFGR is diagnosed early, selective termination of the growth-restricted fetus may be another option. This is a relatively safe procedure overall but it carries risks such as ruptured membrane and damage to the normal twin (10%-35% risk).

Type III sFGR is uniquely unpredictable, with intermittently absent or reversed flow stemming from a large artery-artery anastomosis. The direction of blood flow may suddenly change; in fact, the diagnosis is made by placing the Doppler caliper close to the placenta cord insertion and watching the end-diastolic flow. Present, absent, and reverse flow within a minute of observation demonstrates the presence of a large artery-artery anastomosis.

The risk of unexpected fetal death with severe sFGR is estimated to be 15% or higher, and the spontaneous death of the poorly growing twin threatens both the survival and the neurologic health of the co-twin. The risk of a parenchymal lesion for the co-twin is about 20%-40%.

Management decisions can be extremely difficult. As with type II, one could manage expectantly and generally deliver by 32 weeks. Fetoscopic laser coagulation to achieve complete dichorionization, as done with TTTS, could also be discussed; this approach could save the life of one twin in the event that the co-twin dies. Finally, selective termination may again be an option. None is a perfect treatment, and parents must be thoroughly counseled and supported in understanding the options and risks.

Twin anemia polycythemia sequence

Unlike TTTS, twin anemia polycythemia sequence (TAPS) does not involve a fluid shift. Rather, red blood cells shift from one fetus to the other through extremely small-caliber vessels, leading to severe anemia of one fetus and polycythemia of the other. The chronic and unbalanced transfusion occurs in about 5% of monochorionic twins, generally after 26 weeks’ gestation.

TAPS also occurs after laser treatment for TTTS in about 10%-15% of cases (generally within 4 weeks of treatment), though this incidence is significantly reduced when complete dichorionization is achieved using the Solomon technique for fetoscopic laser coagulation. Diagnosis is made when the middle cerebral artery peak systolic velocity of the red blood cell donor is greater than 1.5 MoM and the peak systolic velocity of the recipient is less than 1.0 MoM, without amniotic fluid discordance.

There are no established preferred treatments, but fetoscopic laser coagulation is an option for some patients. Visibility can be extremely poor when TAPS occurs after a laser treatment and vessels can be difficult to identify, but in selected cases it is possible with an experienced team. When performed, treatment can be followed by delivery or by intrauterine transfusion of the anemic fetus. Intrauterine transfusion has been studied as a primary treatment, but it generally is problematic because the small vessels at the root of TAPS continue to exist.

Twin reversed arterial perfusion

In about 1% of monochorionic pregnancies, an arterial incident prevents one of the twins from developing a heart and upper body. Some research has suggested that the condition is associated with trisomies in about 10% of the cases.

The viable, structurally normal co-twin therefore acts like a pump, continually perfusing the nonviable twin through an abnormal vascular circuit that allows arterial blood to flow in a reverse direction. In the process, the normal twin, or “pump twin,” can develop heart failure and hydrops. Mortality appears to be about 55%.

Diagnosis is straightforward, but it has been challenging to determine which pregnancies will require intervention. Some research has suggested that the risk of hydrops and mortality increases significantly – and favors intervention – when the weight difference is greater than 70%. On the other hand, if the difference is less than 50%, survival of the pump twin approaches 80% and continuing surveillance may be most appropriate.

Radiofrequency ablation of the cord of the nonviable twin is one of the treatment methods and has about an 80% success rate. Another option is coagulation of the blood supply in the abnormal twin using a laser fiber via a fine needle during the first trimester. An ongoing European trial of the procedure is showing success rates of approximately 70%.
 

 

Dr. Turan is director of fetal therapy and complex obstetric surgery, and an associate professor of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, Baltimore. He reported having no relevant financial disclosures.

 

Editor’s Note: This is the second installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte Inc. The series will cover issues in reproductive endocrinology and infertility, maternal-fetal medicine, gynecologic oncology, and female pelvic medicine, as well as general test-taking and study tips. This month’s edition of the Board Corner focuses on Zika virus.

In 2016, The American Board of Obstetricians and Gynecologists assigned four maintenance of certification (MOC) articles dealing with Zika virus:

Zika Virus and Pregnancy: What Obstetric Health Care Providers Need to Know¹

Estimating Contraceptive Needs and Increasing Access to Contraception in Response to the Zika Virus Disease Outbreak – Puerto Rico, 2016²

Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure – United States, 2016³

Interim Guidelines for Pregnant Women During a Zika Virus Outbreak – United States, 2016⁴

The diagnosis and management of Zika virus in pregnancy is a hot topic that should be reviewed before any Obstetrics and Gynecology board exam. This month’s Board Corner will review the key elements for ob.gyns.

Let’s begin with a possible medical board question: Which of the following is LEAST LIKELY to be associated with congenital Zika virus infection?

A. Omphalocele

B. Microcephaly

C. Ventriculomegaly

D. Cataract

E. Intracranial calcifications



The correct answer is A.

Omphalocele has not been observed to be associated with Zika virus infection. Answers B-E are incorrect because reported fetal and neonatal abnormalities associated with Zika virus include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Key points

The key points to remember are:

Transmission of Zika virus to humans most commonly occurs from the bite of an infected mosquito. Other modes of transmission have been reported, such as sexual transmission, maternal-fetal transmission, and transmission through blood transfusion.

Infection with Zika virus and maternal-fetal transmission have been documented in all trimesters of pregnancy. Reported fetal and neonatal sequelae include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness. For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation.

Literature summary

Zika virus is a mosquito-borne virus that is most commonly transmitted by the Aedes aegypti mosquito. This species of mosquito is also known to transmit dengue, yellow fever, and chikungunya viruses. Initial data suggest that the incubation period for Zika virus is a few days up to 2 weeks. Acute onset of fever, maculopapular rash, conjunctivitis, and arthralgia are the most common symptoms of Zika infection. Symptoms generally only last up to 7 days and are typically mild. Only about 20% of people infected with the virus become ill. There is currently no specific antiviral treatment available for Zika virus disease.

Testing for Zika virus can include detection of viral RNA, Zika antigen, or antibodies. Reverse transcription–polymerase chain reaction (RT-PCR) can be performed on serum, amniotic fluid, and tissue (such as placenta). It is recommended that RT-PCR testing of serum be performed within 7 days of the onset of symptoms. Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness.

Though fetal microcephaly can be detected ultrasonographically at 18-20 weeks gestation, the diagnosis can be challenging because there is no standard definition of fetal microcephaly. Because other intracranial abnormalities have been detected in association with congenital Zika infection, a complete ultrasound examination should be performed to assess the fetal neuroanatomy.

For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation. RT-PCR can be used to test for the presence of Zika virus RNA in the amniotic fluid. Patients should be referred to a maternal-fetal medicine specialist for serial ultrasounds to assess fetal anatomy and monitor fetal growth every 3-4 weeks.

References

1. Obstet Gynecol. 2016 Apr;127(4):642-8.

2. Morb Mortal Wkly Rep. 2016;65:311-4.

3. Morb Mortal Wkly Rep. 2016;65:315-22.

4. Morb Mortal Wkly Rep. 2016;65:30-3.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

 

Editor’s Note: This is the second installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte Inc. The series will cover issues in reproductive endocrinology and infertility, maternal-fetal medicine, gynecologic oncology, and female pelvic medicine, as well as general test-taking and study tips. This month’s edition of the Board Corner focuses on Zika virus.

In 2016, The American Board of Obstetricians and Gynecologists assigned four maintenance of certification (MOC) articles dealing with Zika virus:

Zika Virus and Pregnancy: What Obstetric Health Care Providers Need to Know¹

Estimating Contraceptive Needs and Increasing Access to Contraception in Response to the Zika Virus Disease Outbreak – Puerto Rico, 2016²

Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure – United States, 2016³

Interim Guidelines for Pregnant Women During a Zika Virus Outbreak – United States, 2016⁴

The diagnosis and management of Zika virus in pregnancy is a hot topic that should be reviewed before any Obstetrics and Gynecology board exam. This month’s Board Corner will review the key elements for ob.gyns.

Let’s begin with a possible medical board question: Which of the following is LEAST LIKELY to be associated with congenital Zika virus infection?

A. Omphalocele

B. Microcephaly

C. Ventriculomegaly

D. Cataract

E. Intracranial calcifications



The correct answer is A.

Omphalocele has not been observed to be associated with Zika virus infection. Answers B-E are incorrect because reported fetal and neonatal abnormalities associated with Zika virus include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Key points

The key points to remember are:

Transmission of Zika virus to humans most commonly occurs from the bite of an infected mosquito. Other modes of transmission have been reported, such as sexual transmission, maternal-fetal transmission, and transmission through blood transfusion.

Infection with Zika virus and maternal-fetal transmission have been documented in all trimesters of pregnancy. Reported fetal and neonatal sequelae include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness. For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation.

Literature summary

Zika virus is a mosquito-borne virus that is most commonly transmitted by the Aedes aegypti mosquito. This species of mosquito is also known to transmit dengue, yellow fever, and chikungunya viruses. Initial data suggest that the incubation period for Zika virus is a few days up to 2 weeks. Acute onset of fever, maculopapular rash, conjunctivitis, and arthralgia are the most common symptoms of Zika infection. Symptoms generally only last up to 7 days and are typically mild. Only about 20% of people infected with the virus become ill. There is currently no specific antiviral treatment available for Zika virus disease.

Testing for Zika virus can include detection of viral RNA, Zika antigen, or antibodies. Reverse transcription–polymerase chain reaction (RT-PCR) can be performed on serum, amniotic fluid, and tissue (such as placenta). It is recommended that RT-PCR testing of serum be performed within 7 days of the onset of symptoms. Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness.

Though fetal microcephaly can be detected ultrasonographically at 18-20 weeks gestation, the diagnosis can be challenging because there is no standard definition of fetal microcephaly. Because other intracranial abnormalities have been detected in association with congenital Zika infection, a complete ultrasound examination should be performed to assess the fetal neuroanatomy.

For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation. RT-PCR can be used to test for the presence of Zika virus RNA in the amniotic fluid. Patients should be referred to a maternal-fetal medicine specialist for serial ultrasounds to assess fetal anatomy and monitor fetal growth every 3-4 weeks.

References

1. Obstet Gynecol. 2016 Apr;127(4):642-8.

2. Morb Mortal Wkly Rep. 2016;65:311-4.

3. Morb Mortal Wkly Rep. 2016;65:315-22.

4. Morb Mortal Wkly Rep. 2016;65:30-3.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

 

Editor’s Note: This is the second installment of a six-part series that will review key concepts and articles that ob.gyns. can use to prepare for the American Board of Obstetrics and Gynecology Maintenance of Certification examination. The series is adapted from Ob/Gyn Board Master (obgynboardmaster.com), an online board review course created by Erudyte Inc. The series will cover issues in reproductive endocrinology and infertility, maternal-fetal medicine, gynecologic oncology, and female pelvic medicine, as well as general test-taking and study tips. This month’s edition of the Board Corner focuses on Zika virus.

In 2016, The American Board of Obstetricians and Gynecologists assigned four maintenance of certification (MOC) articles dealing with Zika virus:

Zika Virus and Pregnancy: What Obstetric Health Care Providers Need to Know¹

Estimating Contraceptive Needs and Increasing Access to Contraception in Response to the Zika Virus Disease Outbreak – Puerto Rico, 2016²

Update: Interim Guidance for Health Care Providers Caring for Women of Reproductive Age with Possible Zika Virus Exposure – United States, 2016³

Interim Guidelines for Pregnant Women During a Zika Virus Outbreak – United States, 2016⁴

The diagnosis and management of Zika virus in pregnancy is a hot topic that should be reviewed before any Obstetrics and Gynecology board exam. This month’s Board Corner will review the key elements for ob.gyns.

Let’s begin with a possible medical board question: Which of the following is LEAST LIKELY to be associated with congenital Zika virus infection?

A. Omphalocele

B. Microcephaly

C. Ventriculomegaly

D. Cataract

E. Intracranial calcifications



The correct answer is A.

Omphalocele has not been observed to be associated with Zika virus infection. Answers B-E are incorrect because reported fetal and neonatal abnormalities associated with Zika virus include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Key points

The key points to remember are:

Transmission of Zika virus to humans most commonly occurs from the bite of an infected mosquito. Other modes of transmission have been reported, such as sexual transmission, maternal-fetal transmission, and transmission through blood transfusion.

Infection with Zika virus and maternal-fetal transmission have been documented in all trimesters of pregnancy. Reported fetal and neonatal sequelae include microcephaly, ventriculomegaly, intracranial calcifications, brain atrophy, and cataracts.

Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness. For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation.

Literature summary

Zika virus is a mosquito-borne virus that is most commonly transmitted by the Aedes aegypti mosquito. This species of mosquito is also known to transmit dengue, yellow fever, and chikungunya viruses. Initial data suggest that the incubation period for Zika virus is a few days up to 2 weeks. Acute onset of fever, maculopapular rash, conjunctivitis, and arthralgia are the most common symptoms of Zika infection. Symptoms generally only last up to 7 days and are typically mild. Only about 20% of people infected with the virus become ill. There is currently no specific antiviral treatment available for Zika virus disease.

Testing for Zika virus can include detection of viral RNA, Zika antigen, or antibodies. Reverse transcription–polymerase chain reaction (RT-PCR) can be performed on serum, amniotic fluid, and tissue (such as placenta). It is recommended that RT-PCR testing of serum be performed within 7 days of the onset of symptoms. Immunoglobulin M (IgM) can also be detected as early as 4 days after the onset of illness.

Though fetal microcephaly can be detected ultrasonographically at 18-20 weeks gestation, the diagnosis can be challenging because there is no standard definition of fetal microcephaly. Because other intracranial abnormalities have been detected in association with congenital Zika infection, a complete ultrasound examination should be performed to assess the fetal neuroanatomy.

For those women who have laboratory-confirmed Zika virus infection during pregnancy, amniocentesis should be offered after 15 weeks gestation. RT-PCR can be used to test for the presence of Zika virus RNA in the amniotic fluid. Patients should be referred to a maternal-fetal medicine specialist for serial ultrasounds to assess fetal anatomy and monitor fetal growth every 3-4 weeks.

References

1. Obstet Gynecol. 2016 Apr;127(4):642-8.

2. Morb Mortal Wkly Rep. 2016;65:311-4.

3. Morb Mortal Wkly Rep. 2016;65:315-22.

4. Morb Mortal Wkly Rep. 2016;65:30-3.

Dr. Siddighi is editor-in-chief of the Ob/Gyn Board Master and director of female pelvic medicine and reconstructive surgery and director of grand rounds at Loma Linda University Health in California. Ob.Gyn. News and Ob/Gyn Board Master are owned by the same parent company, Frontline Medical Communications.

 

Imagine this scenario: A couple goes on a Caribbean cruise with an all-you-can-eat buffet and an open bar. During the trip, they engage in 2 or 3 days of binge-style drinking, which is considered about four drinks in a single sitting. A few weeks after the trip, the woman finds out that she’s pregnant and calls your office wondering if there will be any harm to the fetus.

This is not a theoretical question. I have received many of these calls over the years, and in some cases the fear of adverse effects on the baby has led the couple to terminate the pregnancy. When we consider the general rise in binge drinking in North America and the fact that about half of all pregnancies are unplanned, this is a very real concern.

The first step is to find out whether the binging occurred during the “none or all period” before implantation, or whether it happened after implantation, reaching the embryo, where the teratogenic risk becomes more tangible.

Unfortunately, the literature has not been clear on the long-term impact of binge drinking in pregnancy. Animal studies suggest that it is the peak in the alcohol level created by binge drinking that causes damage to the fetus, rather than a sustained level of alcohol (although that obviously carries risk as well). The literature in humans has been controversial.

One of the most recent studies is a prospective cohort study of more than 1,600 women and their children sampled from the Danish National Birth Cohort. The investigators collected information on maternal alcohol use in early pregnancy and examined children at age 5 years using the Strengths and Difficulties Questionnaire (SDQ) completed by the mothers and a preschool teacher. It found no statistically significant association between binge drinking in early pregnancy and child behavior at age 5 years (BJOG. 2013 Aug;120[9]:1042-50).

In this study, the investigators corrected for parental education, maternal IQ, prenatal maternal smoking and postnatal parental smoking, the child’s age at testing, the child’s gender, maternal age, parity, marital status, family-home environment, prepregnancy maternal body mass index, and the child’s health status. After adjusting for confounders, they found no association between binge drinking and scores on the SDQ (odds ratio, 1.2; 95% confidence interval, 0.8-1.7 for behavioral scores and OR, 0.8; 95% CI, 0.6-1.2 for total difficulties scores). Additionally, the investigators analyzed low to moderate weekly alcohol consumption in early pregnancy and also could not find a significant effect (OR, 1.1; 95% CI, 0.5-2.3 for behavioral scores and OR, 1.1; 95% CI, 0.6-2.1 for the total difficulties scores).

This finding received a lot of press attention at the time, but it’s not the only study that has shown a lack of effect from binge drinking in contrast to the conventional wisdom on this subject.

A meta-analysis published in early 2014 further adds to the literature on this topic (Alcohol Clin Exp Res. 2014 Jan;38[1]:214-26).

The meta-analysis showed a small, but statistically significant effect on child’s cognition associated with binge drinking in pregnancy (Cohen’s d [a standardized mean difference score] −0.13; 95% CI, −0.21, −0.05). It did not include the 2013 Danish study.

The meta-analysis examined other levels of drinking in pregnancy, not just binging. Out of more than 1,500 papers that were examined, 34 studies met the criteria for inclusion, and just eight were included in the binge drinking analysis. The eight studies comprised more than 10,000 children who were tested from ages 6 months to 14 years. The researchers analyzed eight functional domains: academic performance, attention, behavior, cognition, memory, language and verbal development, executive function, and visual and motor development.

The researchers also separated the studies based on quality. When they analyzed the results for only high-quality studies, the cognition effect was not significant and no other associations were found with other child neuropsychological outcomes.

Several other studies have examined different endpoints, particularly hyperactivity and externalizing behaviors. While several studies show a trend toward those effects, mothers who binge drink also tend to be more externalizing in their own behavior.

An examination of the literature shows just how difficult it is to produce clear results that inform clinical practice. Adjusting for confounding factors from marital status to maternal IQ is just one hurdle. Another area that plagues researchers is that knowledge of drinking in early pregnancy is based on self-reports, and it is nearly impossible to know for sure if the reports of binging are accurate and also if there has been chronic alcohol use.

So what does all of this mean when it comes to advising women? There is no question that women should be advised not to drink when they are pregnant or planning a pregnancy. For a woman who engaged in binge drinking before she knew she was pregnant, it’s difficult to say that there is no effect. Instead, the collective evidence suggests there may be a small effect on cognition. In cases where binge drinking has occurred, children should be monitored as early as possible for any potential developmental effects.
 

 

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. He reported having no relevant financial disclosures. Email him at obnews@frontlinemedcom.com.

 

Imagine this scenario: A couple goes on a Caribbean cruise with an all-you-can-eat buffet and an open bar. During the trip, they engage in 2 or 3 days of binge-style drinking, which is considered about four drinks in a single sitting. A few weeks after the trip, the woman finds out that she’s pregnant and calls your office wondering if there will be any harm to the fetus.

This is not a theoretical question. I have received many of these calls over the years, and in some cases the fear of adverse effects on the baby has led the couple to terminate the pregnancy. When we consider the general rise in binge drinking in North America and the fact that about half of all pregnancies are unplanned, this is a very real concern.

The first step is to find out whether the binging occurred during the “none or all period” before implantation, or whether it happened after implantation, reaching the embryo, where the teratogenic risk becomes more tangible.

Unfortunately, the literature has not been clear on the long-term impact of binge drinking in pregnancy. Animal studies suggest that it is the peak in the alcohol level created by binge drinking that causes damage to the fetus, rather than a sustained level of alcohol (although that obviously carries risk as well). The literature in humans has been controversial.

One of the most recent studies is a prospective cohort study of more than 1,600 women and their children sampled from the Danish National Birth Cohort. The investigators collected information on maternal alcohol use in early pregnancy and examined children at age 5 years using the Strengths and Difficulties Questionnaire (SDQ) completed by the mothers and a preschool teacher. It found no statistically significant association between binge drinking in early pregnancy and child behavior at age 5 years (BJOG. 2013 Aug;120[9]:1042-50).

In this study, the investigators corrected for parental education, maternal IQ, prenatal maternal smoking and postnatal parental smoking, the child’s age at testing, the child’s gender, maternal age, parity, marital status, family-home environment, prepregnancy maternal body mass index, and the child’s health status. After adjusting for confounders, they found no association between binge drinking and scores on the SDQ (odds ratio, 1.2; 95% confidence interval, 0.8-1.7 for behavioral scores and OR, 0.8; 95% CI, 0.6-1.2 for total difficulties scores). Additionally, the investigators analyzed low to moderate weekly alcohol consumption in early pregnancy and also could not find a significant effect (OR, 1.1; 95% CI, 0.5-2.3 for behavioral scores and OR, 1.1; 95% CI, 0.6-2.1 for the total difficulties scores).

This finding received a lot of press attention at the time, but it’s not the only study that has shown a lack of effect from binge drinking in contrast to the conventional wisdom on this subject.

A meta-analysis published in early 2014 further adds to the literature on this topic (Alcohol Clin Exp Res. 2014 Jan;38[1]:214-26).

The meta-analysis showed a small, but statistically significant effect on child’s cognition associated with binge drinking in pregnancy (Cohen’s d [a standardized mean difference score] −0.13; 95% CI, −0.21, −0.05). It did not include the 2013 Danish study.

The meta-analysis examined other levels of drinking in pregnancy, not just binging. Out of more than 1,500 papers that were examined, 34 studies met the criteria for inclusion, and just eight were included in the binge drinking analysis. The eight studies comprised more than 10,000 children who were tested from ages 6 months to 14 years. The researchers analyzed eight functional domains: academic performance, attention, behavior, cognition, memory, language and verbal development, executive function, and visual and motor development.

The researchers also separated the studies based on quality. When they analyzed the results for only high-quality studies, the cognition effect was not significant and no other associations were found with other child neuropsychological outcomes.

Several other studies have examined different endpoints, particularly hyperactivity and externalizing behaviors. While several studies show a trend toward those effects, mothers who binge drink also tend to be more externalizing in their own behavior.

An examination of the literature shows just how difficult it is to produce clear results that inform clinical practice. Adjusting for confounding factors from marital status to maternal IQ is just one hurdle. Another area that plagues researchers is that knowledge of drinking in early pregnancy is based on self-reports, and it is nearly impossible to know for sure if the reports of binging are accurate and also if there has been chronic alcohol use.

So what does all of this mean when it comes to advising women? There is no question that women should be advised not to drink when they are pregnant or planning a pregnancy. For a woman who engaged in binge drinking before she knew she was pregnant, it’s difficult to say that there is no effect. Instead, the collective evidence suggests there may be a small effect on cognition. In cases where binge drinking has occurred, children should be monitored as early as possible for any potential developmental effects.
 

 

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. He reported having no relevant financial disclosures. Email him at obnews@frontlinemedcom.com.

 

Imagine this scenario: A couple goes on a Caribbean cruise with an all-you-can-eat buffet and an open bar. During the trip, they engage in 2 or 3 days of binge-style drinking, which is considered about four drinks in a single sitting. A few weeks after the trip, the woman finds out that she’s pregnant and calls your office wondering if there will be any harm to the fetus.

This is not a theoretical question. I have received many of these calls over the years, and in some cases the fear of adverse effects on the baby has led the couple to terminate the pregnancy. When we consider the general rise in binge drinking in North America and the fact that about half of all pregnancies are unplanned, this is a very real concern.

The first step is to find out whether the binging occurred during the “none or all period” before implantation, or whether it happened after implantation, reaching the embryo, where the teratogenic risk becomes more tangible.

Unfortunately, the literature has not been clear on the long-term impact of binge drinking in pregnancy. Animal studies suggest that it is the peak in the alcohol level created by binge drinking that causes damage to the fetus, rather than a sustained level of alcohol (although that obviously carries risk as well). The literature in humans has been controversial.

One of the most recent studies is a prospective cohort study of more than 1,600 women and their children sampled from the Danish National Birth Cohort. The investigators collected information on maternal alcohol use in early pregnancy and examined children at age 5 years using the Strengths and Difficulties Questionnaire (SDQ) completed by the mothers and a preschool teacher. It found no statistically significant association between binge drinking in early pregnancy and child behavior at age 5 years (BJOG. 2013 Aug;120[9]:1042-50).

In this study, the investigators corrected for parental education, maternal IQ, prenatal maternal smoking and postnatal parental smoking, the child’s age at testing, the child’s gender, maternal age, parity, marital status, family-home environment, prepregnancy maternal body mass index, and the child’s health status. After adjusting for confounders, they found no association between binge drinking and scores on the SDQ (odds ratio, 1.2; 95% confidence interval, 0.8-1.7 for behavioral scores and OR, 0.8; 95% CI, 0.6-1.2 for total difficulties scores). Additionally, the investigators analyzed low to moderate weekly alcohol consumption in early pregnancy and also could not find a significant effect (OR, 1.1; 95% CI, 0.5-2.3 for behavioral scores and OR, 1.1; 95% CI, 0.6-2.1 for the total difficulties scores).

This finding received a lot of press attention at the time, but it’s not the only study that has shown a lack of effect from binge drinking in contrast to the conventional wisdom on this subject.

A meta-analysis published in early 2014 further adds to the literature on this topic (Alcohol Clin Exp Res. 2014 Jan;38[1]:214-26).

The meta-analysis showed a small, but statistically significant effect on child’s cognition associated with binge drinking in pregnancy (Cohen’s d [a standardized mean difference score] −0.13; 95% CI, −0.21, −0.05). It did not include the 2013 Danish study.

The meta-analysis examined other levels of drinking in pregnancy, not just binging. Out of more than 1,500 papers that were examined, 34 studies met the criteria for inclusion, and just eight were included in the binge drinking analysis. The eight studies comprised more than 10,000 children who were tested from ages 6 months to 14 years. The researchers analyzed eight functional domains: academic performance, attention, behavior, cognition, memory, language and verbal development, executive function, and visual and motor development.

The researchers also separated the studies based on quality. When they analyzed the results for only high-quality studies, the cognition effect was not significant and no other associations were found with other child neuropsychological outcomes.

Several other studies have examined different endpoints, particularly hyperactivity and externalizing behaviors. While several studies show a trend toward those effects, mothers who binge drink also tend to be more externalizing in their own behavior.

An examination of the literature shows just how difficult it is to produce clear results that inform clinical practice. Adjusting for confounding factors from marital status to maternal IQ is just one hurdle. Another area that plagues researchers is that knowledge of drinking in early pregnancy is based on self-reports, and it is nearly impossible to know for sure if the reports of binging are accurate and also if there has been chronic alcohol use.

So what does all of this mean when it comes to advising women? There is no question that women should be advised not to drink when they are pregnant or planning a pregnancy. For a woman who engaged in binge drinking before she knew she was pregnant, it’s difficult to say that there is no effect. Instead, the collective evidence suggests there may be a small effect on cognition. In cases where binge drinking has occurred, children should be monitored as early as possible for any potential developmental effects.
 

 

Dr. Koren is professor of physiology/pharmacology and pediatrics at Western University in Ontario. He is the founder of the Motherisk Program. He reported having no relevant financial disclosures. Email him at obnews@frontlinemedcom.com.

Ovarian cancer remains the most deadly gynecologic malignancy in the United States with more than 14,000 deaths in 2016. Yet, the prevalence remains low with approximately 22,000 cases in 2016. Stage at diagnosis is one of the strongest predictors of overall survival. The 5-year overall survival is more than 90% with stage I disease; this drops to 25% for those with distant metastases. Unfortunately, three-quarters of patients have disease spread beyond the ovary at the time ovarian cancer is clinically identified.

In this update, we will review:

• The fundamentals of ovarian cancer screening.

• How to identify patients who would benefit from surveillance.

• The usefulness of tumor markers.

• The results from recent large ovarian cancer screening trials.

Screening is a critical part of secondary prevention through early disease detection, when patients are asymptomatic and treatment can stop progression. Core principles of a good screening test are that the test is noninvasive, tolerable to the patient, and not costly. The disease should pose a major health threat and be detected at a stage at which intervention can impart a survival advantage. Most critically, the test should be sensitive and specific (i.e., detect disease when it is truly present and rarely be positive in the absence of disease).

The likelihood that a screening test accurately diagnoses the disease is referred to as the positive or negative predictive value. For example, the positive predictive value refers to the probability that a patient has ovarian cancer when the test is positive. These predictive values rely strongly on the prevalence of the disease in the test population. Herein lies the major challenge with ovarian cancer screening: The average lifetime risk of developing ovarian cancer is low, approximately 1 in 70. Even a clinical test with 100% sensitivity and 99% specificity would have a positive predictive value of just 4.8%.^1.

A further challenge for ovarian cancer screening is that the confirmatory test requires a major surgical procedure – oophorectomy or ovarian cystectomy – with its own potential risk and harm. Currently, all North American expert groups, including the U.S. Preventive Services Task Force and the Society of Gynecologic Oncology, recommend against screening patients who are at average risk for ovarian cancer.

Screening vs. case finding

A significant distinction should be made between average-risk patients and high-risk patients. Ob.gyns. frequently encounter high-risk patients who would benefit from regular surveillance or case finding (for example, patients with BRCA deleterious mutations or with Lynch syndrome). There are multiple risk factors for ovarian cancer, but the strongest known is family history, which is present in 15% of ovarian cancer patients. Having one relative with ovarian cancer increases the lifetime risk of ovarian cancer up to 5%. When a patient reports having one or more family members with ovarian cancer, it is important to differentiate between a common sporadic presentation and a rare familial cancer syndrome. ACOG Practice Bulletin 103 provides excellent guidance on which patients warrant formal genetic risk assessments by a genetic counselor.²

Tumor markers

During the last 25 years, screening for ovarian cancer in an average-risk population has been evaluated in multiple large prospective studies using serum tumor markers (i.e., CA 125) and ultrasound results.

CA 125 and HE4 tumor markers are frequently elevated in ovarian cancer and have been studied in ovarian cancer screening. However, while having a high sensitivity for detecting disease, they are nonspecific because they are also elevated in numerous benign conditions and therefore have not proven to be a useful screening tool in the average-risk population. There are clinically available tumor marker panels that are not intended for screening. Rather, they clarify the uncertainty of the presurgical adnexal mass evaluation by providing a risk score. High risk scores are generally managed in conjunction with a gynecologic oncology referral.

Multimodal screening

Combined assessment of both ultrasound findings and tumor marker levels shows more promise with respect to prediction of ovarian cancer. However, a systematic review of 25 ovarian cancer screening studies concluded that screening low-risk populations should not be included in clinical practice until randomized trials assessed the effect on mortality and the risk of adverse events. Three large randomized controlled trials have been completed to date.^3,4,5

The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) results appear promising. However, the revealing analysis was post hoc since the original study design did not take into account the inherent delayed effect in screening studies. While these results may provide a basis for future successful screening for ovarian cancer, confirmatory further analysis is pending, using additional data over a period of the next 3 years.

Ultimately, we are all excited about the possibility of effective screening protocols for ovarian cancer and await completed analyses of UKCTOCS. Until their benefits are confirmed, screening and preventive measures should be limited to those at high risk for ovarian cancer.

 

References

1. Hippokratia. 2007 Apr;11(2):63-6.

2. Obstet Gynecol. 2009 Apr;113(4):957-66.

3. Am J Obstet Gynecol. 2005 Nov;193(5):1630-9.

4. Int J Gynecol Cancer. 2008 May-Jun;18(3):414-20.

5. Lancet. 2016 Mar 5;387(10022):945-56.

Dr. Pierce is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no relevant financial disclosures.

Ovarian cancer remains the most deadly gynecologic malignancy in the United States with more than 14,000 deaths in 2016. Yet, the prevalence remains low with approximately 22,000 cases in 2016. Stage at diagnosis is one of the strongest predictors of overall survival. The 5-year overall survival is more than 90% with stage I disease; this drops to 25% for those with distant metastases. Unfortunately, three-quarters of patients have disease spread beyond the ovary at the time ovarian cancer is clinically identified.

In this update, we will review:

• The fundamentals of ovarian cancer screening.

• How to identify patients who would benefit from surveillance.

• The usefulness of tumor markers.

• The results from recent large ovarian cancer screening trials.

Screening is a critical part of secondary prevention through early disease detection, when patients are asymptomatic and treatment can stop progression. Core principles of a good screening test are that the test is noninvasive, tolerable to the patient, and not costly. The disease should pose a major health threat and be detected at a stage at which intervention can impart a survival advantage. Most critically, the test should be sensitive and specific (i.e., detect disease when it is truly present and rarely be positive in the absence of disease).

The likelihood that a screening test accurately diagnoses the disease is referred to as the positive or negative predictive value. For example, the positive predictive value refers to the probability that a patient has ovarian cancer when the test is positive. These predictive values rely strongly on the prevalence of the disease in the test population. Herein lies the major challenge with ovarian cancer screening: The average lifetime risk of developing ovarian cancer is low, approximately 1 in 70. Even a clinical test with 100% sensitivity and 99% specificity would have a positive predictive value of just 4.8%.^1.

A further challenge for ovarian cancer screening is that the confirmatory test requires a major surgical procedure – oophorectomy or ovarian cystectomy – with its own potential risk and harm. Currently, all North American expert groups, including the U.S. Preventive Services Task Force and the Society of Gynecologic Oncology, recommend against screening patients who are at average risk for ovarian cancer.

Screening vs. case finding

A significant distinction should be made between average-risk patients and high-risk patients. Ob.gyns. frequently encounter high-risk patients who would benefit from regular surveillance or case finding (for example, patients with BRCA deleterious mutations or with Lynch syndrome). There are multiple risk factors for ovarian cancer, but the strongest known is family history, which is present in 15% of ovarian cancer patients. Having one relative with ovarian cancer increases the lifetime risk of ovarian cancer up to 5%. When a patient reports having one or more family members with ovarian cancer, it is important to differentiate between a common sporadic presentation and a rare familial cancer syndrome. ACOG Practice Bulletin 103 provides excellent guidance on which patients warrant formal genetic risk assessments by a genetic counselor.²

Tumor markers

During the last 25 years, screening for ovarian cancer in an average-risk population has been evaluated in multiple large prospective studies using serum tumor markers (i.e., CA 125) and ultrasound results.

CA 125 and HE4 tumor markers are frequently elevated in ovarian cancer and have been studied in ovarian cancer screening. However, while having a high sensitivity for detecting disease, they are nonspecific because they are also elevated in numerous benign conditions and therefore have not proven to be a useful screening tool in the average-risk population. There are clinically available tumor marker panels that are not intended for screening. Rather, they clarify the uncertainty of the presurgical adnexal mass evaluation by providing a risk score. High risk scores are generally managed in conjunction with a gynecologic oncology referral.

Multimodal screening

Combined assessment of both ultrasound findings and tumor marker levels shows more promise with respect to prediction of ovarian cancer. However, a systematic review of 25 ovarian cancer screening studies concluded that screening low-risk populations should not be included in clinical practice until randomized trials assessed the effect on mortality and the risk of adverse events. Three large randomized controlled trials have been completed to date.^3,4,5

The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) results appear promising. However, the revealing analysis was post hoc since the original study design did not take into account the inherent delayed effect in screening studies. While these results may provide a basis for future successful screening for ovarian cancer, confirmatory further analysis is pending, using additional data over a period of the next 3 years.

Ultimately, we are all excited about the possibility of effective screening protocols for ovarian cancer and await completed analyses of UKCTOCS. Until their benefits are confirmed, screening and preventive measures should be limited to those at high risk for ovarian cancer.

 

References

1. Hippokratia. 2007 Apr;11(2):63-6.

2. Obstet Gynecol. 2009 Apr;113(4):957-66.

3. Am J Obstet Gynecol. 2005 Nov;193(5):1630-9.

4. Int J Gynecol Cancer. 2008 May-Jun;18(3):414-20.

5. Lancet. 2016 Mar 5;387(10022):945-56.

Dr. Pierce is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no relevant financial disclosures.

Ovarian cancer remains the most deadly gynecologic malignancy in the United States with more than 14,000 deaths in 2016. Yet, the prevalence remains low with approximately 22,000 cases in 2016. Stage at diagnosis is one of the strongest predictors of overall survival. The 5-year overall survival is more than 90% with stage I disease; this drops to 25% for those with distant metastases. Unfortunately, three-quarters of patients have disease spread beyond the ovary at the time ovarian cancer is clinically identified.

In this update, we will review:

• The fundamentals of ovarian cancer screening.

• How to identify patients who would benefit from surveillance.

• The usefulness of tumor markers.

• The results from recent large ovarian cancer screening trials.

Screening is a critical part of secondary prevention through early disease detection, when patients are asymptomatic and treatment can stop progression. Core principles of a good screening test are that the test is noninvasive, tolerable to the patient, and not costly. The disease should pose a major health threat and be detected at a stage at which intervention can impart a survival advantage. Most critically, the test should be sensitive and specific (i.e., detect disease when it is truly present and rarely be positive in the absence of disease).

The likelihood that a screening test accurately diagnoses the disease is referred to as the positive or negative predictive value. For example, the positive predictive value refers to the probability that a patient has ovarian cancer when the test is positive. These predictive values rely strongly on the prevalence of the disease in the test population. Herein lies the major challenge with ovarian cancer screening: The average lifetime risk of developing ovarian cancer is low, approximately 1 in 70. Even a clinical test with 100% sensitivity and 99% specificity would have a positive predictive value of just 4.8%.^1.

A further challenge for ovarian cancer screening is that the confirmatory test requires a major surgical procedure – oophorectomy or ovarian cystectomy – with its own potential risk and harm. Currently, all North American expert groups, including the U.S. Preventive Services Task Force and the Society of Gynecologic Oncology, recommend against screening patients who are at average risk for ovarian cancer.

Screening vs. case finding

A significant distinction should be made between average-risk patients and high-risk patients. Ob.gyns. frequently encounter high-risk patients who would benefit from regular surveillance or case finding (for example, patients with BRCA deleterious mutations or with Lynch syndrome). There are multiple risk factors for ovarian cancer, but the strongest known is family history, which is present in 15% of ovarian cancer patients. Having one relative with ovarian cancer increases the lifetime risk of ovarian cancer up to 5%. When a patient reports having one or more family members with ovarian cancer, it is important to differentiate between a common sporadic presentation and a rare familial cancer syndrome. ACOG Practice Bulletin 103 provides excellent guidance on which patients warrant formal genetic risk assessments by a genetic counselor.²

Tumor markers

During the last 25 years, screening for ovarian cancer in an average-risk population has been evaluated in multiple large prospective studies using serum tumor markers (i.e., CA 125) and ultrasound results.

CA 125 and HE4 tumor markers are frequently elevated in ovarian cancer and have been studied in ovarian cancer screening. However, while having a high sensitivity for detecting disease, they are nonspecific because they are also elevated in numerous benign conditions and therefore have not proven to be a useful screening tool in the average-risk population. There are clinically available tumor marker panels that are not intended for screening. Rather, they clarify the uncertainty of the presurgical adnexal mass evaluation by providing a risk score. High risk scores are generally managed in conjunction with a gynecologic oncology referral.

Multimodal screening

Combined assessment of both ultrasound findings and tumor marker levels shows more promise with respect to prediction of ovarian cancer. However, a systematic review of 25 ovarian cancer screening studies concluded that screening low-risk populations should not be included in clinical practice until randomized trials assessed the effect on mortality and the risk of adverse events. Three large randomized controlled trials have been completed to date.^3,4,5

The U.K. Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) results appear promising. However, the revealing analysis was post hoc since the original study design did not take into account the inherent delayed effect in screening studies. While these results may provide a basis for future successful screening for ovarian cancer, confirmatory further analysis is pending, using additional data over a period of the next 3 years.

Ultimately, we are all excited about the possibility of effective screening protocols for ovarian cancer and await completed analyses of UKCTOCS. Until their benefits are confirmed, screening and preventive measures should be limited to those at high risk for ovarian cancer.

 

References

1. Hippokratia. 2007 Apr;11(2):63-6.

2. Obstet Gynecol. 2009 Apr;113(4):957-66.

3. Am J Obstet Gynecol. 2005 Nov;193(5):1630-9.

4. Int J Gynecol Cancer. 2008 May-Jun;18(3):414-20.

5. Lancet. 2016 Mar 5;387(10022):945-56.

Dr. Pierce is a gynecologic oncology fellow in the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill. Dr. Rossi is an assistant professor in the division of gynecologic oncology at UNC–Chapel Hill. They reported having no relevant financial disclosures.

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

 

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

 

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”

SAN FRANCISCO—Patients with refractory peripheral T-cell lymphoma (PTCL) have significantly worse overall survival (OS) than patients with relapsed PTCL, according to data from the COMPLETE registry.

The data also showed that patients treated with a curative intent had significantly better OS than patients who received palliative care.

However, there was no significant difference in OS according to disease subtype or between patients who received conventional chemotherapy and those who received novel agents.

Frederick Lansigan, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, presented these data at the 9th Annual T-cell Lymphoma Forum. Data were also presented at the 2016 ASH Annual Meeting (abstract 4150).

Dr Lansigan and his colleagues analyzed COMPLETE data on patients with mature T-cell lymphomas, focusing on patients in first relapse and those with primary refractory disease.

Refractory disease was defined as no response to initial treatment or disease progression during or within 1 month of completing front-line therapy.

Relapsed disease was defined as progression more than 1 month after completing induction therapy in patients who initially achieved a complete response (CR) or partial response (PR).

Patients

There were 138 patients in the analysis—58 with relapsed disease and 80 with refractory disease.

The median time from informed consent to diagnosis of relapsed disease was 11.4 months, and the time to diagnosis of refractory disease was 2.2 months.

Disease subtypes included:

• PTCL not otherwise specified (NOS)—35% of relapsed and 28% of refractory patients
• Angioimmunoblastic T-cell lymphoma—22% and 16%
• ALK- anaplastic large-cell lymphoma (ALCL)—10% and 14%
• ALK+ ALCL—3% and 4%
• Natural killer/T-cell lymphoma, nasal type—9% and 8%
• Enteropathy-associated T-cell lymphoma—5% and 3%
• Hepatosplenic T-cell lymphoma—3% and 5%
• Adult T-cell leukemia/lymphoma—2% and 5%
• Transformed mycosis fungoides—0% and 10%
• “Other”—10% and 9%.

Treatment

Most patients received combination regimens as front-line therapy—81% in the relapsed group and 68% in the refractory group. Nineteen and 32%, respectively, received single-agent treatment.

A majority of patients in both groups received chemotherapy or novel agents as second-line therapy—65% in the relapsed group and 71% in the refractory group. (Novel agents include histone deacetylase inhibitors, monoclonal antibodies, immunoconjugates, pralatrexate, bendamustine, denileukin diftitox, alisertib, and lenalidomide.)

Fifteen percent of relapsed patients and 16% of refractory patients received palliative care/best supportive care/observation as second-line therapy. Fifteen percent and 7%, respectively, had a transplant. Four percent and 6%, respectively, received chemotherapy and radiotherapy.

Of the patients who received systemic therapy second-line, 53% of relapsed patients received novel therapies, and 47% received conventional chemotherapy. Twenty-five percent of the refractory patients received novel therapies, and 75% received chemotherapy (P=0.005 for relapsed/refractory comparison of novel vs traditional therapy).

Most patients with relapsed disease received single agents (74%) rather than multi-agent regimens (26%) as second-line therapy. However, single-agent treatment was about as common as multi-agent regimens for refractory patients—53% and 47%, respectively (P=0.03 for relapsed/refractory comparison).

The objective response rates to second-line therapy were 61% for relapsed patients and 37% for refractory patients (P=0.02). The CR rates were 37% and 12%, respectively (P=0.003).

Survival

The median OS was significantly better for patients with relapsed PTCL—15.7 months, compared to 6.1 months for refractory patients (P=0.0237).

OS was also significantly better for patients who achieved a CR. The median OS was not reached for patients with a CR, 14.6 months for those with a PR, 13.7 months for those with stable disease, and 3.2 months for those who progressed (P<0.0001).

There was no significant difference in median OS for patients who received novel agents and those who received traditional chemotherapy—14.6 months and 11.1 months, respectively (P=0.2362).

 

Disease subtype

There was no significant difference in OS between patients who had PTCL-NOS, ALCL, or another PTCL subtype.

For relapsed patients, the median OS was 26 months for those with ALCL, 34 months for those with PTCL-NOS, and 35 months for those with other subtypes (P=0.82).

For refractory patients, the median OS was 31 months for those with ALCL, 7 months for those with PTCL-NOS, and 11 months for those with other subtypes (P=0.36).

Treatment intent

There was a significant difference in OS according to the intent of treatment.

Among relapsed patients, the median OS was not reached for those treated with curative intent and was 17 months for those who received palliative care (P=0.001).

Among refractory patients, the median OS was 15 months for those treated with curative intent and 5 months for those who received palliative care (P=0.005).

Dr Lansigan noted that the better outcomes in patients treated with curative intent may reflect a host of things, such as performance status, fitness for treatment, and transplant eligibility.

Treatment type

In relapsed patients, there was no significant difference in median OS between patients who underwent a transplant (not reached), those who received chemotherapy (24.4 months), and those who received best supportive care (20.9 months).

In refractory patients, the differences were significant. The median OS was not reached in patients who underwent a transplant, 11.6 months in those who received chemotherapy, and 3.5 months in those who received best supportive care (P=0.001).

In closing, Dr Lansigan noted that, in addition to showing a difference in OS between patients with relapsed and refractory PTCL, the COMPLETE registry highlights differences in practice patterns.

“The refractory group was treated more aggressively with traditional combination salvage regimens, but this does not appear to be better than single-agent chemo,” he said. “Of course, selection bias does play a role here, but this is hypothesis-generating.”

“In the relapsed PTCL group, novel, single-agent chemo was used more often, with good effect, with high response rates and long-term survival outcomes. So novel single agents can be considered as salvage therapy for both relapsed and refractory PTCL. Clinical trials are needed to improve outcomes in this poor-risk subgroup.”

The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted SGX301 (synthetic hypericin) Promising Innovative Medicine (PIM) designation for the treatment of cutaneous T-cell lymphoma (CTCL).

The PIM designation is the first step toward inclusion in the Early Access to Medicines Scheme (EAMS). 

EAMS provides early access to new medicines for patients with life-threatening and seriously debilitating conditions.

PIM status is awarded following an assessment of early nonclinical and clinical data by the MHRA.

PIM designation has been created as an early signal to companies that a product’s development plan is appropriate and indicates that a product could be a candidate for the second phase of the EAMS scheme once further development work has been conducted. 

In the second phase, the product is made available to UK patients before a marketing authorization is approved.

The requirements for PIM designation are:

1. The condition should be life-threatening or seriously debilitating with a high unmet medical need (ie, there is no method of treatment, diagnosis, or prevention available, or existing methods have serious limitations).
2. The medicinal product is likely to offer a major advantage over methods currently used in the UK.
3. The potential adverse effects of the medicinal product are likely to be outweighed by the benefits, allowing for the reasonable expectation of a positive benefit-risk balance. A positive benefit-risk balance should be based on preliminary scientific evidence, as justified by the applicant.

About SGX301

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later. 

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is currently recruiting patients. SGX301 is under development by Soligenix, Inc.

The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted SGX301 (synthetic hypericin) Promising Innovative Medicine (PIM) designation for the treatment of cutaneous T-cell lymphoma (CTCL).

The PIM designation is the first step toward inclusion in the Early Access to Medicines Scheme (EAMS). 

EAMS provides early access to new medicines for patients with life-threatening and seriously debilitating conditions.

PIM status is awarded following an assessment of early nonclinical and clinical data by the MHRA.

PIM designation has been created as an early signal to companies that a product’s development plan is appropriate and indicates that a product could be a candidate for the second phase of the EAMS scheme once further development work has been conducted. 

In the second phase, the product is made available to UK patients before a marketing authorization is approved.

The requirements for PIM designation are:

1. The condition should be life-threatening or seriously debilitating with a high unmet medical need (ie, there is no method of treatment, diagnosis, or prevention available, or existing methods have serious limitations).
2. The medicinal product is likely to offer a major advantage over methods currently used in the UK.
3. The potential adverse effects of the medicinal product are likely to be outweighed by the benefits, allowing for the reasonable expectation of a positive benefit-risk balance. A positive benefit-risk balance should be based on preliminary scientific evidence, as justified by the applicant.

About SGX301

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later. 

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is currently recruiting patients. SGX301 is under development by Soligenix, Inc.

The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has granted SGX301 (synthetic hypericin) Promising Innovative Medicine (PIM) designation for the treatment of cutaneous T-cell lymphoma (CTCL).

The PIM designation is the first step toward inclusion in the Early Access to Medicines Scheme (EAMS). 

EAMS provides early access to new medicines for patients with life-threatening and seriously debilitating conditions.

PIM status is awarded following an assessment of early nonclinical and clinical data by the MHRA.

PIM designation has been created as an early signal to companies that a product’s development plan is appropriate and indicates that a product could be a candidate for the second phase of the EAMS scheme once further development work has been conducted. 

In the second phase, the product is made available to UK patients before a marketing authorization is approved.

The requirements for PIM designation are:

1. The condition should be life-threatening or seriously debilitating with a high unmet medical need (ie, there is no method of treatment, diagnosis, or prevention available, or existing methods have serious limitations).
2. The medicinal product is likely to offer a major advantage over methods currently used in the UK.
3. The potential adverse effects of the medicinal product are likely to be outweighed by the benefits, allowing for the reasonable expectation of a positive benefit-risk balance. A positive benefit-risk balance should be based on preliminary scientific evidence, as justified by the applicant.

About SGX301

SGX301 is a photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a photosensitizer that is applied to skin lesions and then activated by fluorescent light 16 to 24 hours later. 

Combined with photoactivation, hypericin has demonstrated significant antiproliferative effects on activated, normal human lymphoid cells and inhibited the growth of malignant T cells isolated from CTCL patients. Topical hypericin has also proven safe in a phase 1 study of healthy volunteers.

In a phase 2 trial of patients with CTCL (mycosis fungoides only) or psoriasis, topical hypericin conferred a significant improvement over placebo. Among CTCL patients, the treatment prompted a response rate of 58.3%, compared to an 8.3% response rate for placebo (P≤0.04).

Topical hypericin was also well tolerated in this trial. There were no deaths or serious adverse events related to the treatment. However, there were reports of mild to moderate burning, itching, erythema, and pruritus at the application site.

A phase 3 trial of SGX301 is currently recruiting patients. SGX301 is under development by Soligenix, Inc.

In a survey of 200 adults with hemophilia A, most were not aware that factor VIII (FVIII) products can be stored at room temperature.

A majority of patients surveyed thought FVIII products must be stored in the refrigerator at all times.

The minority of

patients who did store FVIII at room temperature felt significantly

more satisfied with their treatment and less restricted in their daily

lives than patients who refrigerated FVIII.

“People living with hemophilia A can feel restricted in their daily life based on the misconception that all FVIII treatments must be stored in the refrigerator,” said Mariasanta Napolitano, MD, of the University of Palermo in Italy.

“It is important that healthcare professionals communicate to patients that some FVIII products can be used portably and at room temperature, to enable them to go about their daily lives as actively as they wish.”

Dr Napolitano and her colleagues presented the results of this survey at the 10th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD, poster P024).

The researchers conducted the survey in adults with hemophilia A in 7 countries. Face-to-face surveys were conducted with 90 people in the European Union (France, Italy, and UK) and 90 people in Latin America (Argentina, Brazil, and Mexico). Online surveys were conducted with 20 people in Japan.

The questionnaire covered current use of FVIII products, patient satisfaction, and restrictions in daily life using verbalized rating scales (eg, “not restricted at all / somewhat restricted / restricted / strongly restricted”).

Seventy-four percent of patients used FVII as prophylaxis, and 26% used on-demand treatment. Sixty-seven percent used recombinant FVIII, and 33% used plasma-derived FVIII.

Storage

Most patients—85%—stored their FVIII product in the refrigerator, with 15% storing their treatment at room temperature.

Of those storing FVIII in the refrigerator, 88% said FVIII must be stored in the refrigerator at all times. Seventy-nine percent of patients said they worry about the temperature at which FVIII is stored.

Seventy-four percent said they wait for their FVIII product to reach room temperature before mixing and injecting it. The median wait time was 10 minutes.

Sixty-two percent of patients said an injection with cold FVIII is more unpleasant than an injection with room temperature FVIII.

Satisfaction

Patients storing FVIII at room temperature were significantly more likely than those storing FVIII in the refrigerator to report overall satisfaction with their FVIII product (52% vs 28%, P<0.05).

Patients storing FVIII at room temperature were also significantly more likely to report satisfaction with:

• Product efficacy (61% vs 43%, P<0.05)
• The procedure of mixing the product before injection (39% vs 22%, P<0.05)
• The flexibility of storage depending on the patients’ needs (55% vs 18%, P<0.05)
• The length of time the product can be stored outside the refrigerator (45% vs 19%, P<0.05)
• The size of vials (42% vs 18%, P<0.05)
• Storage temperature (39% vs 15%, P<0.05).

Daily life

Patients storing FVIII at room temperature travelled significantly more often—16 times per year vs 9 times per year (P<0.01).

Nineteen percent of these patients felt that storing, preparing, and mixing FVIII is disruptive to the normal course of the day, compared to 35% of patients who store FVIII in the refrigerator (P<0.05).

Significantly fewer patients in the room-temperature group said they feel restricted when it comes to sports activities, traveling, and their evening routine (P<0.05).

Forty-eight percent of patients storing FVIII at room temperature said they feel relaxed using FVIII in their daily life, compared to 20% of patients storing FVIII in the refrigerator (P<0.05).

In a survey of 200 adults with hemophilia A, most were not aware that factor VIII (FVIII) products can be stored at room temperature.

A majority of patients surveyed thought FVIII products must be stored in the refrigerator at all times.

The minority of

patients who did store FVIII at room temperature felt significantly

more satisfied with their treatment and less restricted in their daily

lives than patients who refrigerated FVIII.

“People living with hemophilia A can feel restricted in their daily life based on the misconception that all FVIII treatments must be stored in the refrigerator,” said Mariasanta Napolitano, MD, of the University of Palermo in Italy.

“It is important that healthcare professionals communicate to patients that some FVIII products can be used portably and at room temperature, to enable them to go about their daily lives as actively as they wish.”

Dr Napolitano and her colleagues presented the results of this survey at the 10th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD, poster P024).

The researchers conducted the survey in adults with hemophilia A in 7 countries. Face-to-face surveys were conducted with 90 people in the European Union (France, Italy, and UK) and 90 people in Latin America (Argentina, Brazil, and Mexico). Online surveys were conducted with 20 people in Japan.

The questionnaire covered current use of FVIII products, patient satisfaction, and restrictions in daily life using verbalized rating scales (eg, “not restricted at all / somewhat restricted / restricted / strongly restricted”).

Seventy-four percent of patients used FVII as prophylaxis, and 26% used on-demand treatment. Sixty-seven percent used recombinant FVIII, and 33% used plasma-derived FVIII.

Storage

Most patients—85%—stored their FVIII product in the refrigerator, with 15% storing their treatment at room temperature.

Of those storing FVIII in the refrigerator, 88% said FVIII must be stored in the refrigerator at all times. Seventy-nine percent of patients said they worry about the temperature at which FVIII is stored.

Seventy-four percent said they wait for their FVIII product to reach room temperature before mixing and injecting it. The median wait time was 10 minutes.

Sixty-two percent of patients said an injection with cold FVIII is more unpleasant than an injection with room temperature FVIII.

Satisfaction

Patients storing FVIII at room temperature were significantly more likely than those storing FVIII in the refrigerator to report overall satisfaction with their FVIII product (52% vs 28%, P<0.05).

Patients storing FVIII at room temperature were also significantly more likely to report satisfaction with:

• Product efficacy (61% vs 43%, P<0.05)
• The procedure of mixing the product before injection (39% vs 22%, P<0.05)
• The flexibility of storage depending on the patients’ needs (55% vs 18%, P<0.05)
• The length of time the product can be stored outside the refrigerator (45% vs 19%, P<0.05)
• The size of vials (42% vs 18%, P<0.05)
• Storage temperature (39% vs 15%, P<0.05).

Daily life

Patients storing FVIII at room temperature travelled significantly more often—16 times per year vs 9 times per year (P<0.01).

Nineteen percent of these patients felt that storing, preparing, and mixing FVIII is disruptive to the normal course of the day, compared to 35% of patients who store FVIII in the refrigerator (P<0.05).

Significantly fewer patients in the room-temperature group said they feel restricted when it comes to sports activities, traveling, and their evening routine (P<0.05).

Forty-eight percent of patients storing FVIII at room temperature said they feel relaxed using FVIII in their daily life, compared to 20% of patients storing FVIII in the refrigerator (P<0.05).

In a survey of 200 adults with hemophilia A, most were not aware that factor VIII (FVIII) products can be stored at room temperature.

A majority of patients surveyed thought FVIII products must be stored in the refrigerator at all times.

The minority of

patients who did store FVIII at room temperature felt significantly

more satisfied with their treatment and less restricted in their daily

lives than patients who refrigerated FVIII.

“People living with hemophilia A can feel restricted in their daily life based on the misconception that all FVIII treatments must be stored in the refrigerator,” said Mariasanta Napolitano, MD, of the University of Palermo in Italy.

“It is important that healthcare professionals communicate to patients that some FVIII products can be used portably and at room temperature, to enable them to go about their daily lives as actively as they wish.”

Dr Napolitano and her colleagues presented the results of this survey at the 10th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD, poster P024).

The researchers conducted the survey in adults with hemophilia A in 7 countries. Face-to-face surveys were conducted with 90 people in the European Union (France, Italy, and UK) and 90 people in Latin America (Argentina, Brazil, and Mexico). Online surveys were conducted with 20 people in Japan.

The questionnaire covered current use of FVIII products, patient satisfaction, and restrictions in daily life using verbalized rating scales (eg, “not restricted at all / somewhat restricted / restricted / strongly restricted”).

Seventy-four percent of patients used FVII as prophylaxis, and 26% used on-demand treatment. Sixty-seven percent used recombinant FVIII, and 33% used plasma-derived FVIII.

Storage

Most patients—85%—stored their FVIII product in the refrigerator, with 15% storing their treatment at room temperature.

Of those storing FVIII in the refrigerator, 88% said FVIII must be stored in the refrigerator at all times. Seventy-nine percent of patients said they worry about the temperature at which FVIII is stored.

Seventy-four percent said they wait for their FVIII product to reach room temperature before mixing and injecting it. The median wait time was 10 minutes.

Sixty-two percent of patients said an injection with cold FVIII is more unpleasant than an injection with room temperature FVIII.

Satisfaction

Patients storing FVIII at room temperature were significantly more likely than those storing FVIII in the refrigerator to report overall satisfaction with their FVIII product (52% vs 28%, P<0.05).

Patients storing FVIII at room temperature were also significantly more likely to report satisfaction with:

• Product efficacy (61% vs 43%, P<0.05)
• The procedure of mixing the product before injection (39% vs 22%, P<0.05)
• The flexibility of storage depending on the patients’ needs (55% vs 18%, P<0.05)
• The length of time the product can be stored outside the refrigerator (45% vs 19%, P<0.05)
• The size of vials (42% vs 18%, P<0.05)
• Storage temperature (39% vs 15%, P<0.05).

Daily life

Patients storing FVIII at room temperature travelled significantly more often—16 times per year vs 9 times per year (P<0.01).

Nineteen percent of these patients felt that storing, preparing, and mixing FVIII is disruptive to the normal course of the day, compared to 35% of patients who store FVIII in the refrigerator (P<0.05).

Significantly fewer patients in the room-temperature group said they feel restricted when it comes to sports activities, traveling, and their evening routine (P<0.05).

Forty-eight percent of patients storing FVIII at room temperature said they feel relaxed using FVIII in their daily life, compared to 20% of patients storing FVIII in the refrigerator (P<0.05).

New research published in Blood suggests young patients with acute lymphoblastic leukemia (ALL)—and their parents—are likely to over-report treatment adherence.

In a study of 416 pediatric ALL patients, 84% of patients or their parents said the patients took more 6-mercaptopurine (6MP) than they actually did.

6MP is prescribed for 2 years after chemotherapy with the goal of producing durable remissions, but studies show that over 95% of the prescribed doses must be taken for the medication to be effective.

“Because this therapy is administered orally every day, we cannot supervise our patients to make sure they are taking their pills,” said study author Smita Bhatia, MD, of the University of Alabama at Birmingham.

“Findings from this study suggest that we need better ways to monitor intake of medications as prescribed.”

This study included 416 pediatric ALL patients followed over 4 months. Patients received prescription pill bottles for their 6MP that contained a microprocessor chip in the cap to log the date and time the bottle was opened.

The logs were compared to self-report questionnaires completed by patients or their parents and provided to physicians at monthly check-ups.

Patients were classified as:

• Perfect reporters—self-report corresponded to data from the Medication Event Monitoring System (MEMS)
• Over-reporters—self-report was greater than MEMS data by more than 5 days per month for more than 50% of the study months
• Others—all patients not meeting criteria for perfect- or over-reporter.

Twelve percent of patients were classified as perfect reporters, 23.6% were over-reporters, 0.5% were under-reporters, and 63.9% were classified as “others.”

Self-reported 6MP intake exceeded MEMS data at least some of the time in 84% of patients.

“We observed that there was an inverse relationship between over-reporting and the extent of non-adherence,” Dr Bhatia noted.

Of the patients who adhered to their regimens (defined as taking their prescribed dose 95% of the time), a small percentage (8%) over-reported their intake.

However, among those found to be non-adherent, a substantially larger percent (47%) over-reported.

In order to find out why patients were not taking their prescribed medication, study author Wendy Landier, PhD, RN, also of the University of Alabama at Birmingham, organized interviews with patients and their parents.

In these interviews, Dr Landier noted that forgetfulness was the primary reason for non-adherence.

“We found that partnering with a parent was very conducive to our patients’ adherence, playing a key role in combatting forgetfulness,” she said.

Recognizing the importance of parental involvement in patient adherence, the researchers were inspired to conduct further research to make parents more involved.

In a trial that builds on this study, physicians send personalized text messages to both patients and their parents at a prescribed time reminding them to take their medicine. Both patient and parent then report back, via text, that the indicated dose was taken.

“Our first study showed that non-adherence was prevalent, increasing the risk of relapse,” Dr Bhatia said. “We then found that parental vigilance was an important facilitator to adherence, while forgetting to take the medication was the most commonly reported barrier.”

“We used these findings to inform the intervention trial to help families improve adherence to treatment. We hope that this will be a real step in improving outcomes in children with leukemia.”

New research published in Blood suggests young patients with acute lymphoblastic leukemia (ALL)—and their parents—are likely to over-report treatment adherence.

In a study of 416 pediatric ALL patients, 84% of patients or their parents said the patients took more 6-mercaptopurine (6MP) than they actually did.

6MP is prescribed for 2 years after chemotherapy with the goal of producing durable remissions, but studies show that over 95% of the prescribed doses must be taken for the medication to be effective.

“Because this therapy is administered orally every day, we cannot supervise our patients to make sure they are taking their pills,” said study author Smita Bhatia, MD, of the University of Alabama at Birmingham.

“Findings from this study suggest that we need better ways to monitor intake of medications as prescribed.”

This study included 416 pediatric ALL patients followed over 4 months. Patients received prescription pill bottles for their 6MP that contained a microprocessor chip in the cap to log the date and time the bottle was opened.

The logs were compared to self-report questionnaires completed by patients or their parents and provided to physicians at monthly check-ups.

Patients were classified as:

• Perfect reporters—self-report corresponded to data from the Medication Event Monitoring System (MEMS)
• Over-reporters—self-report was greater than MEMS data by more than 5 days per month for more than 50% of the study months
• Others—all patients not meeting criteria for perfect- or over-reporter.

Twelve percent of patients were classified as perfect reporters, 23.6% were over-reporters, 0.5% were under-reporters, and 63.9% were classified as “others.”

Self-reported 6MP intake exceeded MEMS data at least some of the time in 84% of patients.

“We observed that there was an inverse relationship between over-reporting and the extent of non-adherence,” Dr Bhatia noted.

Of the patients who adhered to their regimens (defined as taking their prescribed dose 95% of the time), a small percentage (8%) over-reported their intake.

However, among those found to be non-adherent, a substantially larger percent (47%) over-reported.

In order to find out why patients were not taking their prescribed medication, study author Wendy Landier, PhD, RN, also of the University of Alabama at Birmingham, organized interviews with patients and their parents.

In these interviews, Dr Landier noted that forgetfulness was the primary reason for non-adherence.

“We found that partnering with a parent was very conducive to our patients’ adherence, playing a key role in combatting forgetfulness,” she said.

Recognizing the importance of parental involvement in patient adherence, the researchers were inspired to conduct further research to make parents more involved.

In a trial that builds on this study, physicians send personalized text messages to both patients and their parents at a prescribed time reminding them to take their medicine. Both patient and parent then report back, via text, that the indicated dose was taken.

“Our first study showed that non-adherence was prevalent, increasing the risk of relapse,” Dr Bhatia said. “We then found that parental vigilance was an important facilitator to adherence, while forgetting to take the medication was the most commonly reported barrier.”

“We used these findings to inform the intervention trial to help families improve adherence to treatment. We hope that this will be a real step in improving outcomes in children with leukemia.”

New research published in Blood suggests young patients with acute lymphoblastic leukemia (ALL)—and their parents—are likely to over-report treatment adherence.

In a study of 416 pediatric ALL patients, 84% of patients or their parents said the patients took more 6-mercaptopurine (6MP) than they actually did.

6MP is prescribed for 2 years after chemotherapy with the goal of producing durable remissions, but studies show that over 95% of the prescribed doses must be taken for the medication to be effective.

“Because this therapy is administered orally every day, we cannot supervise our patients to make sure they are taking their pills,” said study author Smita Bhatia, MD, of the University of Alabama at Birmingham.

“Findings from this study suggest that we need better ways to monitor intake of medications as prescribed.”

This study included 416 pediatric ALL patients followed over 4 months. Patients received prescription pill bottles for their 6MP that contained a microprocessor chip in the cap to log the date and time the bottle was opened.

The logs were compared to self-report questionnaires completed by patients or their parents and provided to physicians at monthly check-ups.

Patients were classified as:

• Perfect reporters—self-report corresponded to data from the Medication Event Monitoring System (MEMS)
• Over-reporters—self-report was greater than MEMS data by more than 5 days per month for more than 50% of the study months
• Others—all patients not meeting criteria for perfect- or over-reporter.

Twelve percent of patients were classified as perfect reporters, 23.6% were over-reporters, 0.5% were under-reporters, and 63.9% were classified as “others.”

Self-reported 6MP intake exceeded MEMS data at least some of the time in 84% of patients.

“We observed that there was an inverse relationship between over-reporting and the extent of non-adherence,” Dr Bhatia noted.

Of the patients who adhered to their regimens (defined as taking their prescribed dose 95% of the time), a small percentage (8%) over-reported their intake.

However, among those found to be non-adherent, a substantially larger percent (47%) over-reported.

In order to find out why patients were not taking their prescribed medication, study author Wendy Landier, PhD, RN, also of the University of Alabama at Birmingham, organized interviews with patients and their parents.

In these interviews, Dr Landier noted that forgetfulness was the primary reason for non-adherence.

“We found that partnering with a parent was very conducive to our patients’ adherence, playing a key role in combatting forgetfulness,” she said.

Recognizing the importance of parental involvement in patient adherence, the researchers were inspired to conduct further research to make parents more involved.

In a trial that builds on this study, physicians send personalized text messages to both patients and their parents at a prescribed time reminding them to take their medicine. Both patient and parent then report back, via text, that the indicated dose was taken.

“Our first study showed that non-adherence was prevalent, increasing the risk of relapse,” Dr Bhatia said. “We then found that parental vigilance was an important facilitator to adherence, while forgetting to take the medication was the most commonly reported barrier.”

“We used these findings to inform the intervention trial to help families improve adherence to treatment. We hope that this will be a real step in improving outcomes in children with leukemia.”