Michele G. Sullivan

SAN DIEGO – The risk of discontinuation syndrome is small when antidepressant treatment is suddenly stopped, but the symptoms – though somewhat brief – are still unpleasant for patients, according to Dr. Kurt Kroenke.

Unfortunately, he said, there are no firm data that predict who might develop discontinuation syndrome, which drugs are likely to cause it, or whether medication tapering can avoid it.

"If you just immediately stop an antidepressant, you can expect to have a 5%-15% incidence of discontinuation syndrome," Dr. Kroenke said at the annual meeting of the American College of Physicians. "It usually starts within a few days and stops within a few weeks," but it’s no picnic for patients.

FINISH is the acronym that describes this syndrome, said Dr. Kroenke, an internist at Indiana University, Bloomington. Patients experience flulike symptoms, insomnia, nausea, imbalance, strange sensory dysesthesias, and hyperarousal or anxiety.

The syndrome is probably less likely if a patient is switching to another drug rather than ceasing medication altogether, but no studies have determined the best way to implement either change. "It’s not clear if a long taper is better than a short taper, or even if discontinuation syndrome is something that’s dose related," he said. "If you’re on 200 mg of sertraline and you stop, as opposed to 50 mg, we can’t say the higher dose equals an increased risk."

Some studies seem to suggest that the risk is highest with paroxetine. "Fluoxetine probably has the lowest risk because of its long half-life. Venlafaxine is associated with an intermediate risk and all the others fall somewhere below that," Dr. Kroenke said.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial provides the largest single body of evidence on antidepressant switching (Am. J. Psychiatry 2006;163:1905-17). The methodology in the trial, which involved four levels of treatment and seven antidepressants, was basically simple, Dr. Kroenke said. "You either discontinued one medication and immediately began another or you decreased the first medication while initiating the second at a low dose, doing this taper/titration over 1 week. It doesn’t get much simpler than that." Most investigators in the study chose the first option, he said.

"Having said that, I would probably go for some version of option two, and if the patient is on a higher dose, I might spend a week tapering one while titrating the other."

In a few specific situations, Dr. Kroenke said he strongly favors the taper/titrating method. "I always consider tapering if I’m working with paroxetine or venlafaxine, especially if it’s at a higher dose and has been taken for a long duration," he said. "And definitely if the patient has experienced discontinuation syndrome in the past."

Dr. Kroenke said he has consulted for, and received honoraria from, Eli Lilly and Forest.

SAN DIEGO – The risk of discontinuation syndrome is small when antidepressant treatment is suddenly stopped, but the symptoms – though somewhat brief – are still unpleasant for patients, according to Dr. Kurt Kroenke.

Unfortunately, he said, there are no firm data that predict who might develop discontinuation syndrome, which drugs are likely to cause it, or whether medication tapering can avoid it.

"If you just immediately stop an antidepressant, you can expect to have a 5%-15% incidence of discontinuation syndrome," Dr. Kroenke said at the annual meeting of the American College of Physicians. "It usually starts within a few days and stops within a few weeks," but it’s no picnic for patients.

FINISH is the acronym that describes this syndrome, said Dr. Kroenke, an internist at Indiana University, Bloomington. Patients experience flulike symptoms, insomnia, nausea, imbalance, strange sensory dysesthesias, and hyperarousal or anxiety.

The syndrome is probably less likely if a patient is switching to another drug rather than ceasing medication altogether, but no studies have determined the best way to implement either change. "It’s not clear if a long taper is better than a short taper, or even if discontinuation syndrome is something that’s dose related," he said. "If you’re on 200 mg of sertraline and you stop, as opposed to 50 mg, we can’t say the higher dose equals an increased risk."

Some studies seem to suggest that the risk is highest with paroxetine. "Fluoxetine probably has the lowest risk because of its long half-life. Venlafaxine is associated with an intermediate risk and all the others fall somewhere below that," Dr. Kroenke said.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial provides the largest single body of evidence on antidepressant switching (Am. J. Psychiatry 2006;163:1905-17). The methodology in the trial, which involved four levels of treatment and seven antidepressants, was basically simple, Dr. Kroenke said. "You either discontinued one medication and immediately began another or you decreased the first medication while initiating the second at a low dose, doing this taper/titration over 1 week. It doesn’t get much simpler than that." Most investigators in the study chose the first option, he said.

"Having said that, I would probably go for some version of option two, and if the patient is on a higher dose, I might spend a week tapering one while titrating the other."

In a few specific situations, Dr. Kroenke said he strongly favors the taper/titrating method. "I always consider tapering if I’m working with paroxetine or venlafaxine, especially if it’s at a higher dose and has been taken for a long duration," he said. "And definitely if the patient has experienced discontinuation syndrome in the past."

Dr. Kroenke said he has consulted for, and received honoraria from, Eli Lilly and Forest.

SAN DIEGO – The risk of discontinuation syndrome is small when antidepressant treatment is suddenly stopped, but the symptoms – though somewhat brief – are still unpleasant for patients, according to Dr. Kurt Kroenke.

Unfortunately, he said, there are no firm data that predict who might develop discontinuation syndrome, which drugs are likely to cause it, or whether medication tapering can avoid it.

"If you just immediately stop an antidepressant, you can expect to have a 5%-15% incidence of discontinuation syndrome," Dr. Kroenke said at the annual meeting of the American College of Physicians. "It usually starts within a few days and stops within a few weeks," but it’s no picnic for patients.

FINISH is the acronym that describes this syndrome, said Dr. Kroenke, an internist at Indiana University, Bloomington. Patients experience flulike symptoms, insomnia, nausea, imbalance, strange sensory dysesthesias, and hyperarousal or anxiety.

The syndrome is probably less likely if a patient is switching to another drug rather than ceasing medication altogether, but no studies have determined the best way to implement either change. "It’s not clear if a long taper is better than a short taper, or even if discontinuation syndrome is something that’s dose related," he said. "If you’re on 200 mg of sertraline and you stop, as opposed to 50 mg, we can’t say the higher dose equals an increased risk."

Some studies seem to suggest that the risk is highest with paroxetine. "Fluoxetine probably has the lowest risk because of its long half-life. Venlafaxine is associated with an intermediate risk and all the others fall somewhere below that," Dr. Kroenke said.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial provides the largest single body of evidence on antidepressant switching (Am. J. Psychiatry 2006;163:1905-17). The methodology in the trial, which involved four levels of treatment and seven antidepressants, was basically simple, Dr. Kroenke said. "You either discontinued one medication and immediately began another or you decreased the first medication while initiating the second at a low dose, doing this taper/titration over 1 week. It doesn’t get much simpler than that." Most investigators in the study chose the first option, he said.

"Having said that, I would probably go for some version of option two, and if the patient is on a higher dose, I might spend a week tapering one while titrating the other."

In a few specific situations, Dr. Kroenke said he strongly favors the taper/titrating method. "I always consider tapering if I’m working with paroxetine or venlafaxine, especially if it’s at a higher dose and has been taken for a long duration," he said. "And definitely if the patient has experienced discontinuation syndrome in the past."

Dr. Kroenke said he has consulted for, and received honoraria from, Eli Lilly and Forest.

SAN DIEGO – The risk of discontinuation syndrome is small when antidepressant treatment is suddenly stopped, but the symptoms – though somewhat brief – are still unpleasant for patients, according to Dr. Kurt Kroenke.

Unfortunately, he said, there are no firm data that predict who might develop discontinuation syndrome, which drugs are likely to cause it, or whether medication tapering can avoid it.

"If you just immediately stop an antidepressant, you can expect to have a 5%-15% incidence of discontinuation syndrome," Dr. Kroenke said at the annual meeting of the American College of Physicians. "It usually starts within a few days and stops within a few weeks," but it’s no picnic for patients.

FINISH is the acronym that describes this syndrome, said Dr. Kroenke, an internist at Indiana University, Bloomington. Patients experience flulike symptoms, insomnia, nausea, imbalance, strange sensory dysesthesias, and hyperarousal or anxiety.

The syndrome is probably less likely if a patient is switching to another drug rather than ceasing medication altogether, but no studies have determined the best way to implement either change. "It’s not clear if a long taper is better than a short taper, or even if discontinuation syndrome is something that’s dose related," he said. "If you’re on 200 mg of sertraline and you stop, as opposed to 50 mg, we can’t say the higher dose equals an increased risk."

Some studies seem to suggest that the risk is highest with paroxetine. "Fluoxetine probably has the lowest risk because of its long half-life. Venlafaxine is associated with an intermediate risk and all the others fall somewhere below that," Dr. Kroenke said.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial provides the largest single body of evidence on antidepressant switching (Am. J. Psychiatry 2006;163:1905-17). The methodology in the trial, which involved four levels of treatment and seven antidepressants, was basically simple, Dr. Kroenke said. "You either discontinued one medication and immediately began another or you decreased the first medication while initiating the second at a low dose, doing this taper/titration over 1 week. It doesn’t get much simpler than that." Most investigators in the study chose the first option, he said.

"Having said that, I would probably go for some version of option two, and if the patient is on a higher dose, I might spend a week tapering one while titrating the other."

In a few specific situations, Dr. Kroenke said he strongly favors the taper/titrating method. "I always consider tapering if I’m working with paroxetine or venlafaxine, especially if it’s at a higher dose and has been taken for a long duration," he said. "And definitely if the patient has experienced discontinuation syndrome in the past."

Dr. Kroenke said he has consulted for, and received honoraria from, Eli Lilly and Forest.

SAN DIEGO – The risk of discontinuation syndrome is small when antidepressant treatment is suddenly stopped, but the symptoms – though somewhat brief – are still unpleasant for patients, according to Dr. Kurt Kroenke.

Unfortunately, he said, there are no firm data that predict who might develop discontinuation syndrome, which drugs are likely to cause it, or whether medication tapering can avoid it.

"If you just immediately stop an antidepressant, you can expect to have a 5%-15% incidence of discontinuation syndrome," Dr. Kroenke said at the annual meeting of the American College of Physicians. "It usually starts within a few days and stops within a few weeks," but it’s no picnic for patients.

FINISH is the acronym that describes this syndrome, said Dr. Kroenke, an internist at Indiana University, Bloomington. Patients experience flulike symptoms, insomnia, nausea, imbalance, strange sensory dysesthesias, and hyperarousal or anxiety.

The syndrome is probably less likely if a patient is switching to another drug rather than ceasing medication altogether, but no studies have determined the best way to implement either change. "It’s not clear if a long taper is better than a short taper, or even if discontinuation syndrome is something that’s dose related," he said. "If you’re on 200 mg of sertraline and you stop, as opposed to 50 mg, we can’t say the higher dose equals an increased risk."

Some studies seem to suggest that the risk is highest with paroxetine. "Fluoxetine probably has the lowest risk because of its long half-life. Venlafaxine is associated with an intermediate risk and all the others fall somewhere below that," Dr. Kroenke said.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial provides the largest single body of evidence on antidepressant switching (Am. J. Psychiatry 2006;163:1905-17). The methodology in the trial, which involved four levels of treatment and seven antidepressants, was basically simple, Dr. Kroenke said. "You either discontinued one medication and immediately began another or you decreased the first medication while initiating the second at a low dose, doing this taper/titration over 1 week. It doesn’t get much simpler than that." Most investigators in the study chose the first option, he said.

"Having said that, I would probably go for some version of option two, and if the patient is on a higher dose, I might spend a week tapering one while titrating the other."

In a few specific situations, Dr. Kroenke said he strongly favors the taper/titrating method. "I always consider tapering if I’m working with paroxetine or venlafaxine, especially if it’s at a higher dose and has been taken for a long duration," he said. "And definitely if the patient has experienced discontinuation syndrome in the past."

Dr. Kroenke said he has consulted for, and received honoraria from, Eli Lilly and Forest.

SAN DIEGO – The risk of discontinuation syndrome is small when antidepressant treatment is suddenly stopped, but the symptoms – though somewhat brief – are still unpleasant for patients, according to Dr. Kurt Kroenke.

Unfortunately, he said, there are no firm data that predict who might develop discontinuation syndrome, which drugs are likely to cause it, or whether medication tapering can avoid it.

"If you just immediately stop an antidepressant, you can expect to have a 5%-15% incidence of discontinuation syndrome," Dr. Kroenke said at the annual meeting of the American College of Physicians. "It usually starts within a few days and stops within a few weeks," but it’s no picnic for patients.

FINISH is the acronym that describes this syndrome, said Dr. Kroenke, an internist at Indiana University, Bloomington. Patients experience flulike symptoms, insomnia, nausea, imbalance, strange sensory dysesthesias, and hyperarousal or anxiety.

The syndrome is probably less likely if a patient is switching to another drug rather than ceasing medication altogether, but no studies have determined the best way to implement either change. "It’s not clear if a long taper is better than a short taper, or even if discontinuation syndrome is something that’s dose related," he said. "If you’re on 200 mg of sertraline and you stop, as opposed to 50 mg, we can’t say the higher dose equals an increased risk."

Some studies seem to suggest that the risk is highest with paroxetine. "Fluoxetine probably has the lowest risk because of its long half-life. Venlafaxine is associated with an intermediate risk and all the others fall somewhere below that," Dr. Kroenke said.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial provides the largest single body of evidence on antidepressant switching (Am. J. Psychiatry 2006;163:1905-17). The methodology in the trial, which involved four levels of treatment and seven antidepressants, was basically simple, Dr. Kroenke said. "You either discontinued one medication and immediately began another or you decreased the first medication while initiating the second at a low dose, doing this taper/titration over 1 week. It doesn’t get much simpler than that." Most investigators in the study chose the first option, he said.

"Having said that, I would probably go for some version of option two, and if the patient is on a higher dose, I might spend a week tapering one while titrating the other."

In a few specific situations, Dr. Kroenke said he strongly favors the taper/titrating method. "I always consider tapering if I’m working with paroxetine or venlafaxine, especially if it’s at a higher dose and has been taken for a long duration," he said. "And definitely if the patient has experienced discontinuation syndrome in the past."

Dr. Kroenke said he has consulted for, and received honoraria from, Eli Lilly and Forest.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

A minimally invasive esophagectomy resulted in improved postoperative outcomes and a complete resection rate (R0) that was just as high as with open surgery, plus a significantly greater harvest of lymph nodes.

Compared with those who had open surgery, patients who underwent the minimally invasive surgery had significantly less blood loss, shorter hospital stays, and fewer major complications, said Dr. Adam C. Berger at the annual meeting of the Southern Surgical Association.

Although further studies are needed to confirm the benefits of such an approach, "Our current practice is to attempt minimally invasive esophagectomies in all patients," said Dr. Berger of the Kimmel Cancer Center at the Thomas Jefferson University Hospital in Philadelphia.

He and his colleagues presented a retrospective study comparing surgical and oncologic outcomes in two groups of patients with esophageal cancer. This comprised 65 patients who underwent esophagectomy with a thoracoscopic component (11 thoracoscopy/laparotomy, 2 Ivor-Lewis thoracoscopy/laparoscopy, and 52 three-hole thoracoscopy/laparoscopy) compared with 53 patients who underwent open surgery (15 Ivor-Lewis and 38 three-hole esophagectomy) during the same time period.

Mean patient age was 61 years. Neoadjuvant therapy was administered in 28 (43%) of the minimally invasive esophagectomy (MIE) group and 43 (81%) of the open surgery group. Adenocarcinoma was present in most patients (85% MIE and 74% open). Squamous cell carcinoma occurred in 6% of the MIE group and 26% of the open group; there were five cases (8%) of high-grade dysplasia in the MIE group. One patient had MIE for esophageal melanoma.

During the thoracoscopy, Dr. Berger uses 10-mm ports in the anterior axillary line at the fourth and eighth intercostal spaces and at the posterior axillary line. "A 5-mm port is placed at the tip of the scapula, and a suction port can be placed between the ports in the anterior axillary line," he said. "Finally, a suture is placed in the tendinous portion of the diaphragm to maintain retraction."

He uses a Penrose drain to encircle and retract the esophagus. The azygous vein is divided, and the aortic branches are divided or clipped. "The subcarinal lymph node package is dissected under direct vision and removed, and paraesophageal lymph nodes and tissue dissected up with the specimen."

During the subsequent laparoscopy, he places a 5-mm port in the right lateral subcostal area to accommodate a liver retractor, a 12-mm port in the umbilicus for the camera, an additional 12-mm working port in the right subcostal region, and a 5-mm port in the left subcostal region. "Once the gastric mobilization is complete, we often enlarge the 12-mm right subcostal port to about 5 cm and place a Lap Disk."

After dissecting the neck, he isolates and divides the esophagus. The completed reconstruction involves sewing the tip of the gastric tube to the chest tube and pulling that tube back up into the neck for a side-to-side esophagectomy. Anastomosis is in the neck with the gastric tube in the posterior mediastinum.

Mortality was similar in both groups of patients (8%). While the overall rate of complications was not significantly different (48% MIE vs. 60% open), the rate of major complications was (20% vs. 41%). Respiratory failure or acute respiratory distress syndrome occurred in a significantly smaller percentage of MIE patients (8% vs. 21%). There were also fewer cases of pneumonia among the MIE patients, but this was not a significant difference (8% vs. 18%). "Interestingly, there was a significant increase in the number of patients with a deep venous thrombosis or pulmonary embolism in the open group (2% vs. 11%)," Dr. Berger said. "This may have something to do with earlier postoperative mobilization for patients with MIE."

MIE patients also fared significantly better in terms of blood loss (182 mL vs. 619 mL) and median length of stay (9 vs. 16 days). Oncologic outcomes were as good as, or better than, those seen in open surgery. "There was no difference in R0 resection rates," Dr. Berger pointed out (97% MIE vs. 94% open). "We also saw a more than doubling of the number of examined lymph nodes in the MIE group, which was highly significant (20 vs. 9; P less than .0001)."

Dr. Berger pointed out a major limitation of the study. Because his group attempts the MIE approach in all patients, "It's impossible to find a concurrent group of patients who had open surgery for comparison." Also, he noted, "Pathology standards have changed and, thus, the importance of lymph nodes has become more recognized. Higher node yields are shown to be an important prognostic factor for survival. Therefore, our pathologists are now more diligent in finding the lymph nodes in the specimen."

Dr. Berger had no disclosures.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Poor sleep in early pregnancy might be one significant driver of depression in later pregnancy, an Australian prospective study has found.

"This finding suggests the need for clinicians to not just screen for depressive symptoms during pregnancy (which is the trend now), but to consider other potentially important problems, like the quality of sleep and severe physical symptoms during early pregnancy," Helen Skouteris, Ph.D., said at the World Conference on Women’s Mental Health. "These issues may very well contribute to the development of – or maintain – depression throughout pregnancy."

Dr. Skouteris, an expert in developmental psychology at Deakin University in Burwood, Victoria, presented the results of a prospective study of 257 pregnant women in Australia who were recruited at 15-23 weeks’ gestation. The study consisted of two self-reported questionnaires that assessed physical symptoms of pregnancy, sleep quality, and mood during early pregnancy and during the last trimester.

At recruitment, the women’s mean age was 32 years. Almost half (48%) were first-time mothers and most (77%) were married. Most of the women (73%) also had at least some college education, and 57% had an annual household income of more than 75,000 Australian dollars ($77,500). "This is typical of the women who volunteer for our research programs," Dr. Skouteris noted.

At the time of the first survey, the women had been pregnant for a mean of 18 weeks; the mean gestation at the time of the second survey was 34 weeks.

Both packets, which were mailed to the subjects, contained the self-administered Beck Depression Inventory, the Pittsburgh Sleep Quality Index, and a physical symptoms questionnaire that listed 29 common symptoms of pregnancy. Women were asked to rate these symptoms on a 0-3 scale (with 0 as "not at all" and 3 as "very much") regarding discomfort from the symptoms, their frequency, and their general effect on life. Sleep was reported for the prior 4 weeks, physical symptoms for the prior 8 weeks, and mood at the time of the interview.

A previous study by Dr. Skouteris and her colleagues concluded that physical symptoms were the main driver of maternal depression (J. Affect. Disord. 2010;123:317-20). "In that study, we showed that physical symptoms in early pregnancy were predictive of greater depression scores in late pregnancy," Dr. Skouteris said at the conference. However, that study did not find that sleep quality early on was associated with later physical symptoms, she added.

The current unpublished data, based on three regression analyses, show that poor sleep is the missing link between early physical symptoms and late depression. Fatigue was the most commonly reported physical symptom at both the early and later interviews (94% and 92%, respectively).

"The path seems to travel from severe physical symptoms early to poor sleep throughout, and then to depression later in pregnancy. Clearly, these results show that physical symptoms early in pregnancy might be a key risk factor for depression later on in pregnancy. Now we must consider other moderators in this relationship; there might be other things that contribute to this equation."

She also mentioned that 15% of the women in the study rated very high on the anxiety measure.

"These women were very anxious about the delivery and what it might mean to their education, career, and general way of life," Dr. Skouteris said. "We’re now exploring these subjective ways a woman feels about her pregnancy, and their possible relationship between stress, anxiety, and depression throughout pregnancy and into the postnatal period." This study will provide more data about these links, since the women will be assessed monthly instead of twice.

The Australian Research Council supported the study. Dr. Skouteris had no potential conflicts of interest.

MADRID – Neonatal outcomes were generally worse among pregnant women who take antipsychotics than among those in the general population, but the rates of birth defects were not significantly altered, with an incidence of 5% compared with 4% in the general population.

Outcomes varied with the type of medication, Heather Gilbert, R.N., said at the World Conference on Women’s Mental Health.* The infants of women taking clozapine were most at risk, with two of the six babies born to these mothers (33%) exhibiting a congenital malformation. These infants also had a higher rate of neonatal complications, including premature birth, respiratory distress, and admission to the neonatal intensive care unit, according to Australia’s National Register of Antipsychotic Medications in Pregnancy. The incidence of gestational diabetes also was higher than among the general population (16% vs. 4%).

It was not surprising that clozapine proved particularly troublesome for babies exposed in utero, primary investigator Dr. Jayashri Kulkarni said in an interview. "The clozapine babies did have the worst outcomes, but this was not unexpected, because that is the most difficult medication to manage. But even in that worst group, the adverse issues were not catastrophic."

Thus, she said, the registry is "essentially a good-news story. "Most of the babies born were pretty healthy. We saw that the use of these medications did not lead to miscarriages and stillbirths," said Dr. Kulkarni, director of the Monash Alfred Psychiatry Research Centre in Melbourne. "What is important, from our standpoint, is that if a patient is doing well on a medication, it’s important to keep that medication going during pregnancy and not let her mental health deteriorate."

In fact, the tragic story of a patient who did stop her antipsychotic drugs during pregnancy inspired Dr. Kulkarni to begin the project.

The National Registry of Psychotic Medications in Pregnancy (NRAMP) obtained ethical approval from 42 boards across Australia before beginning to recruit patients. All women who register undergo a psychiatric evaluation at baseline, which includes the PANSS (Positive and Negative Syndrome Scale). Information about the pregnancy and outcomes is supplied by the clinicians attending the mother. The mother/infant pair is followed for 1 year, with six to eight postnatal interviews using the maternal assessment scales. The baby is assessed for developmental milestones at 6 and 12 weeks and at 6 and 12 months.

Because the registry is not a randomized controlled trial, Dr. Kulkarni has met with some skepticism from clinicians, who say that the data are not a reliable method of judging drug safety. "Ethically, a randomized trial is not something that we could do," she said. "We have to cope with people saying the data are messy," at least until the registry accumulates a much larger number of mother/infant pairs.

The participants’ mean age at recruitment was 32 years; the mean baseline PANSS score was 37. Diagnoses included bipolar affective disorder (40 patients), schizophrenia (28), schizoaffective disorder (8), unspecified psychotic disorder (8), depression (6), anxiety disorder (3), schizophreniform disorder (2), and borderline personality disorder (1). Diagnostic data were missing in four participants.

The largest proportion of the 100 women in the registry thus far took quetiapine during their pregnancy (43); the next most commonly used drug was olanzapine (14). Other medications were risperidone (6), clozapine (6), aripiprazole (4), haloperidol (4), long-acting injectable risperidone (Consta; 3), flupenthixol (2) and ziprasidone (1). In all, 12 women registered but did not receive antipsychotic treatment, and there are missing data on 5.

Pregnancy outcomes were somewhat better than those seen in the general population, with a 2% rate of stillbirth and miscarriage, compared with a 7% rate in the general population. There were two miscarriages (one exposed to quetiapine and one to clozapine) and one stillbirth (quetiapine).

Premature births occurred in 15% of the registry infants, compared with 8% of the general population. This occurred in nine infants exposed to quetiapine (21%), one exposed to risperidone (17%), one to flupenthixol (50%) and in the one exposed to ziprasidone.

Respiratory distress occurred in 27% of the registry infants, compared with 7% of the general population. It was seen in 14 babies exposed to quetiapine (32%), 5 exposed to olanzapine (36%), 1 exposed to risperidone (17%), 2 exposed to clozapine (33%), 1 exposed to haloperidol (24%), 2 exposed to Consta (66%) and in the single baby exposed to ziprasidone.

Medication withdrawal occurred in seven babies who were exposed to quetiapine (16%), and one exposed to olanzapine (7%).

Admission to the neonatal intensive care unit was highest among those exposed to clozapine (three patients; 50%) and flupenthixol (one; 50%). Birth weight below the 10th percentile occurred in babies exposed to quetiapine (four; 9%), olanzapine (one; 7%), risperidone (two; 33%), clozapine (one; 17%), and flupenthixol (one; 50%)

NICU admission also occurred in seven babies who were exposed to quetiapine (16%), one exposed to olanzapine (19%), three exposed to clozapine (50%), two exposed to Consta (66%), and one exposed to flupenthixol (50%).

Large-for-gestational-age babies (greater than the 90% percentile) occurred in eight who were exposed to quetiapine (19%), one exposed to olanzapine (7%), one exposed to aripiprazole (25%), one exposed to haloperidol (25%), and in the single baby exposed to ziprasidone.

Five infants were born with congenital anomalies. One infant who was exposed to clozapine had craniosynostosis and hypertelorism; the mother took 350-750 m/day throughout the pregnancy. The baby’s skull deformity had a partial surgical correction and resulted in a developmental delay at 12 months.

The second infant had gastroschisis and a horseshoe kidney. The mother took 400 mg of clozapine daily throughout pregnancy. The gastroschisis had a surgical correction, whereas the kidney is being managed conservatively and the baby is progressing well.

Congenital malformations occurred in 2 of the 14 babies who were exposed to quetiapine. One baby had an atrial-septal defect; the mother took 1,110 mg/day of quetiapine throughout pregnancy as well as 1,000 mg/day of zuclopenthixol. The defect was resolving spontaneously by 12 months with conservative management.

The second baby who was exposed to quetiapine had a cleft lip and palate, as well as hydrocephalus. The mother took 600 mg/day well throughout the pregnancy. The clefts were surgically repaired and excess cephalic fluid was drained. The baby is progressing and being monitored.

[Sidebar: Removing Antipsychotic Medications in Pregnancy: A Case in Point]

One anomaly occurred in a baby exposed to risperidone: This infant had an abnormal renal collecting tubule and bilateral talipes. The mother took 2 mg/day risperidone up to 36 weeks’ gestation. The abnormal collecting tubule is functioning well, and the talipes underwent surgical repair and braces, with a good result.

Gestational diabetes accounted for most of the maternal complications. "We are seeing a lot of gestational diabetes in the moms – higher than the general population. Maybe this is because they were already overweight, or the drugs contributed to weight gain and insulin intolerance. But clinicians should be aware of this heightened risk, look diligently for signs of it, and give this information to their patients."

The disorder occurred in 16 of the 100 women, including 6 who were taking quetiapine (14%), 4 taking olanzapine (28%), 1 taking risperidone (17%), 4 taking clozapine (67%), and 1 taking Consta (33%). Preeclampsia occurred in one patient who was taking quetiapine (2%).

The registry also tracked smoking, as well as alcohol and substance abuse, but did not control for these factors in any multivariate analysis. Antenatally, smoking was noted in 31% of registry women, compared with 16% of the general population. But antenatal alcohol consumption among registry participants was lower than that in the general population (12% vs. 60%). Substance abuse incidence was about 12% in the registry participants, compared with 7% in the general population. "We have lots of stories from women who smoked a lot of cigarettes and drank a lot, and decreased this during pregnancy. That protective instinct of the mother for the fetus is alive and well, and kicked in among these women."

Managing antipsychotic medications during pregnancy is a new concept to most clinicians in Australia, who continue to assume that the drugs will tip the risk:benefit ratio to the pit of endangering the developing baby, Dr. Kulkarni said. This has led to many recommendations that women with serious mental disorders avoid ever bearing children. She has even received calls from physicians who are angry that the registry seems to support childbearing in this group, "asking me why I’m allowing the gene pool to be polluted."

In her daily work, Dr. Kulkarni deals with significant regrets from women who were told that their mental illness and medication should preclude any childbearing. "I see a number of women in their 50s, approaching menopause, who were given the advice many years back never to have children because of the drug dangers," she said. "Now, they are grieving and experiencing depression over what could have been. The medical profession does not play God. We can only provide information and advice, but not take the role of driving the decision about having children or not."

Dr. Kulkarni said that the registry’s results are interesting, but until many more women are enrolled, it’s difficult to use it as a clinical guideline about what drug is safest for both mother and baby. "We need to accumulate a lot more data, and in the future, we hope to expand the program to sites all over the world."

The NRAMP project data are online; clinicians can register to participate or get more information about setting up similar programs. Physicians interested in obtaining more information about the registry can also e-mail Dr. Kulkarni or Gilbert, the project’s research nurse.

The project is funded by Astra-Zeneca, Janssen-Cilag, Mayne Pharmaceuticals, and the Australian Rotary Health Research Fund. Dr. Kulkarni had no financial disclosures.

* CORRECTION, 5/10/2011: The original version of this article misspelled Heather Gilbert's last name. This version has been corrected.

MADRID – Neonatal outcomes were generally worse among pregnant women who take antipsychotics than among those in the general population, but the rates of birth defects were not significantly altered, with an incidence of 5% compared with 4% in the general population.

Outcomes varied with the type of medication, Heather Gilbert, R.N., said at the World Conference on Women’s Mental Health.* The infants of women taking clozapine were most at risk, with two of the six babies born to these mothers (33%) exhibiting a congenital malformation. These infants also had a higher rate of neonatal complications, including premature birth, respiratory distress, and admission to the neonatal intensive care unit, according to Australia’s National Register of Antipsychotic Medications in Pregnancy. The incidence of gestational diabetes also was higher than among the general population (16% vs. 4%).

It was not surprising that clozapine proved particularly troublesome for babies exposed in utero, primary investigator Dr. Jayashri Kulkarni said in an interview. "The clozapine babies did have the worst outcomes, but this was not unexpected, because that is the most difficult medication to manage. But even in that worst group, the adverse issues were not catastrophic."

Thus, she said, the registry is "essentially a good-news story. "Most of the babies born were pretty healthy. We saw that the use of these medications did not lead to miscarriages and stillbirths," said Dr. Kulkarni, director of the Monash Alfred Psychiatry Research Centre in Melbourne. "What is important, from our standpoint, is that if a patient is doing well on a medication, it’s important to keep that medication going during pregnancy and not let her mental health deteriorate."

In fact, the tragic story of a patient who did stop her antipsychotic drugs during pregnancy inspired Dr. Kulkarni to begin the project.

The National Registry of Psychotic Medications in Pregnancy (NRAMP) obtained ethical approval from 42 boards across Australia before beginning to recruit patients. All women who register undergo a psychiatric evaluation at baseline, which includes the PANSS (Positive and Negative Syndrome Scale). Information about the pregnancy and outcomes is supplied by the clinicians attending the mother. The mother/infant pair is followed for 1 year, with six to eight postnatal interviews using the maternal assessment scales. The baby is assessed for developmental milestones at 6 and 12 weeks and at 6 and 12 months.

Because the registry is not a randomized controlled trial, Dr. Kulkarni has met with some skepticism from clinicians, who say that the data are not a reliable method of judging drug safety. "Ethically, a randomized trial is not something that we could do," she said. "We have to cope with people saying the data are messy," at least until the registry accumulates a much larger number of mother/infant pairs.

The participants’ mean age at recruitment was 32 years; the mean baseline PANSS score was 37. Diagnoses included bipolar affective disorder (40 patients), schizophrenia (28), schizoaffective disorder (8), unspecified psychotic disorder (8), depression (6), anxiety disorder (3), schizophreniform disorder (2), and borderline personality disorder (1). Diagnostic data were missing in four participants.

The largest proportion of the 100 women in the registry thus far took quetiapine during their pregnancy (43); the next most commonly used drug was olanzapine (14). Other medications were risperidone (6), clozapine (6), aripiprazole (4), haloperidol (4), long-acting injectable risperidone (Consta; 3), flupenthixol (2) and ziprasidone (1). In all, 12 women registered but did not receive antipsychotic treatment, and there are missing data on 5.

Pregnancy outcomes were somewhat better than those seen in the general population, with a 2% rate of stillbirth and miscarriage, compared with a 7% rate in the general population. There were two miscarriages (one exposed to quetiapine and one to clozapine) and one stillbirth (quetiapine).

Premature births occurred in 15% of the registry infants, compared with 8% of the general population. This occurred in nine infants exposed to quetiapine (21%), one exposed to risperidone (17%), one to flupenthixol (50%) and in the one exposed to ziprasidone.

Respiratory distress occurred in 27% of the registry infants, compared with 7% of the general population. It was seen in 14 babies exposed to quetiapine (32%), 5 exposed to olanzapine (36%), 1 exposed to risperidone (17%), 2 exposed to clozapine (33%), 1 exposed to haloperidol (24%), 2 exposed to Consta (66%) and in the single baby exposed to ziprasidone.

Medication withdrawal occurred in seven babies who were exposed to quetiapine (16%), and one exposed to olanzapine (7%).

Admission to the neonatal intensive care unit was highest among those exposed to clozapine (three patients; 50%) and flupenthixol (one; 50%). Birth weight below the 10th percentile occurred in babies exposed to quetiapine (four; 9%), olanzapine (one; 7%), risperidone (two; 33%), clozapine (one; 17%), and flupenthixol (one; 50%)

NICU admission also occurred in seven babies who were exposed to quetiapine (16%), one exposed to olanzapine (19%), three exposed to clozapine (50%), two exposed to Consta (66%), and one exposed to flupenthixol (50%).

Large-for-gestational-age babies (greater than the 90% percentile) occurred in eight who were exposed to quetiapine (19%), one exposed to olanzapine (7%), one exposed to aripiprazole (25%), one exposed to haloperidol (25%), and in the single baby exposed to ziprasidone.

Five infants were born with congenital anomalies. One infant who was exposed to clozapine had craniosynostosis and hypertelorism; the mother took 350-750 m/day throughout the pregnancy. The baby’s skull deformity had a partial surgical correction and resulted in a developmental delay at 12 months.

The second infant had gastroschisis and a horseshoe kidney. The mother took 400 mg of clozapine daily throughout pregnancy. The gastroschisis had a surgical correction, whereas the kidney is being managed conservatively and the baby is progressing well.

Congenital malformations occurred in 2 of the 14 babies who were exposed to quetiapine. One baby had an atrial-septal defect; the mother took 1,110 mg/day of quetiapine throughout pregnancy as well as 1,000 mg/day of zuclopenthixol. The defect was resolving spontaneously by 12 months with conservative management.

The second baby who was exposed to quetiapine had a cleft lip and palate, as well as hydrocephalus. The mother took 600 mg/day well throughout the pregnancy. The clefts were surgically repaired and excess cephalic fluid was drained. The baby is progressing and being monitored.

[Sidebar: Removing Antipsychotic Medications in Pregnancy: A Case in Point]

One anomaly occurred in a baby exposed to risperidone: This infant had an abnormal renal collecting tubule and bilateral talipes. The mother took 2 mg/day risperidone up to 36 weeks’ gestation. The abnormal collecting tubule is functioning well, and the talipes underwent surgical repair and braces, with a good result.

Gestational diabetes accounted for most of the maternal complications. "We are seeing a lot of gestational diabetes in the moms – higher than the general population. Maybe this is because they were already overweight, or the drugs contributed to weight gain and insulin intolerance. But clinicians should be aware of this heightened risk, look diligently for signs of it, and give this information to their patients."

The disorder occurred in 16 of the 100 women, including 6 who were taking quetiapine (14%), 4 taking olanzapine (28%), 1 taking risperidone (17%), 4 taking clozapine (67%), and 1 taking Consta (33%). Preeclampsia occurred in one patient who was taking quetiapine (2%).

The registry also tracked smoking, as well as alcohol and substance abuse, but did not control for these factors in any multivariate analysis. Antenatally, smoking was noted in 31% of registry women, compared with 16% of the general population. But antenatal alcohol consumption among registry participants was lower than that in the general population (12% vs. 60%). Substance abuse incidence was about 12% in the registry participants, compared with 7% in the general population. "We have lots of stories from women who smoked a lot of cigarettes and drank a lot, and decreased this during pregnancy. That protective instinct of the mother for the fetus is alive and well, and kicked in among these women."

Managing antipsychotic medications during pregnancy is a new concept to most clinicians in Australia, who continue to assume that the drugs will tip the risk:benefit ratio to the pit of endangering the developing baby, Dr. Kulkarni said. This has led to many recommendations that women with serious mental disorders avoid ever bearing children. She has even received calls from physicians who are angry that the registry seems to support childbearing in this group, "asking me why I’m allowing the gene pool to be polluted."

In her daily work, Dr. Kulkarni deals with significant regrets from women who were told that their mental illness and medication should preclude any childbearing. "I see a number of women in their 50s, approaching menopause, who were given the advice many years back never to have children because of the drug dangers," she said. "Now, they are grieving and experiencing depression over what could have been. The medical profession does not play God. We can only provide information and advice, but not take the role of driving the decision about having children or not."

Dr. Kulkarni said that the registry’s results are interesting, but until many more women are enrolled, it’s difficult to use it as a clinical guideline about what drug is safest for both mother and baby. "We need to accumulate a lot more data, and in the future, we hope to expand the program to sites all over the world."

The NRAMP project data are online; clinicians can register to participate or get more information about setting up similar programs. Physicians interested in obtaining more information about the registry can also e-mail Dr. Kulkarni or Gilbert, the project’s research nurse.

The project is funded by Astra-Zeneca, Janssen-Cilag, Mayne Pharmaceuticals, and the Australian Rotary Health Research Fund. Dr. Kulkarni had no financial disclosures.

* CORRECTION, 5/10/2011: The original version of this article misspelled Heather Gilbert's last name. This version has been corrected.

MADRID – Neonatal outcomes were generally worse among pregnant women who take antipsychotics than among those in the general population, but the rates of birth defects were not significantly altered, with an incidence of 5% compared with 4% in the general population.

Outcomes varied with the type of medication, Heather Gilbert, R.N., said at the World Conference on Women’s Mental Health.* The infants of women taking clozapine were most at risk, with two of the six babies born to these mothers (33%) exhibiting a congenital malformation. These infants also had a higher rate of neonatal complications, including premature birth, respiratory distress, and admission to the neonatal intensive care unit, according to Australia’s National Register of Antipsychotic Medications in Pregnancy. The incidence of gestational diabetes also was higher than among the general population (16% vs. 4%).

It was not surprising that clozapine proved particularly troublesome for babies exposed in utero, primary investigator Dr. Jayashri Kulkarni said in an interview. "The clozapine babies did have the worst outcomes, but this was not unexpected, because that is the most difficult medication to manage. But even in that worst group, the adverse issues were not catastrophic."

Thus, she said, the registry is "essentially a good-news story. "Most of the babies born were pretty healthy. We saw that the use of these medications did not lead to miscarriages and stillbirths," said Dr. Kulkarni, director of the Monash Alfred Psychiatry Research Centre in Melbourne. "What is important, from our standpoint, is that if a patient is doing well on a medication, it’s important to keep that medication going during pregnancy and not let her mental health deteriorate."

In fact, the tragic story of a patient who did stop her antipsychotic drugs during pregnancy inspired Dr. Kulkarni to begin the project.

The National Registry of Psychotic Medications in Pregnancy (NRAMP) obtained ethical approval from 42 boards across Australia before beginning to recruit patients. All women who register undergo a psychiatric evaluation at baseline, which includes the PANSS (Positive and Negative Syndrome Scale). Information about the pregnancy and outcomes is supplied by the clinicians attending the mother. The mother/infant pair is followed for 1 year, with six to eight postnatal interviews using the maternal assessment scales. The baby is assessed for developmental milestones at 6 and 12 weeks and at 6 and 12 months.

Because the registry is not a randomized controlled trial, Dr. Kulkarni has met with some skepticism from clinicians, who say that the data are not a reliable method of judging drug safety. "Ethically, a randomized trial is not something that we could do," she said. "We have to cope with people saying the data are messy," at least until the registry accumulates a much larger number of mother/infant pairs.

The participants’ mean age at recruitment was 32 years; the mean baseline PANSS score was 37. Diagnoses included bipolar affective disorder (40 patients), schizophrenia (28), schizoaffective disorder (8), unspecified psychotic disorder (8), depression (6), anxiety disorder (3), schizophreniform disorder (2), and borderline personality disorder (1). Diagnostic data were missing in four participants.

The largest proportion of the 100 women in the registry thus far took quetiapine during their pregnancy (43); the next most commonly used drug was olanzapine (14). Other medications were risperidone (6), clozapine (6), aripiprazole (4), haloperidol (4), long-acting injectable risperidone (Consta; 3), flupenthixol (2) and ziprasidone (1). In all, 12 women registered but did not receive antipsychotic treatment, and there are missing data on 5.

Pregnancy outcomes were somewhat better than those seen in the general population, with a 2% rate of stillbirth and miscarriage, compared with a 7% rate in the general population. There were two miscarriages (one exposed to quetiapine and one to clozapine) and one stillbirth (quetiapine).

Premature births occurred in 15% of the registry infants, compared with 8% of the general population. This occurred in nine infants exposed to quetiapine (21%), one exposed to risperidone (17%), one to flupenthixol (50%) and in the one exposed to ziprasidone.

Respiratory distress occurred in 27% of the registry infants, compared with 7% of the general population. It was seen in 14 babies exposed to quetiapine (32%), 5 exposed to olanzapine (36%), 1 exposed to risperidone (17%), 2 exposed to clozapine (33%), 1 exposed to haloperidol (24%), 2 exposed to Consta (66%) and in the single baby exposed to ziprasidone.

Medication withdrawal occurred in seven babies who were exposed to quetiapine (16%), and one exposed to olanzapine (7%).

Admission to the neonatal intensive care unit was highest among those exposed to clozapine (three patients; 50%) and flupenthixol (one; 50%). Birth weight below the 10th percentile occurred in babies exposed to quetiapine (four; 9%), olanzapine (one; 7%), risperidone (two; 33%), clozapine (one; 17%), and flupenthixol (one; 50%)

NICU admission also occurred in seven babies who were exposed to quetiapine (16%), one exposed to olanzapine (19%), three exposed to clozapine (50%), two exposed to Consta (66%), and one exposed to flupenthixol (50%).

Large-for-gestational-age babies (greater than the 90% percentile) occurred in eight who were exposed to quetiapine (19%), one exposed to olanzapine (7%), one exposed to aripiprazole (25%), one exposed to haloperidol (25%), and in the single baby exposed to ziprasidone.

Five infants were born with congenital anomalies. One infant who was exposed to clozapine had craniosynostosis and hypertelorism; the mother took 350-750 m/day throughout the pregnancy. The baby’s skull deformity had a partial surgical correction and resulted in a developmental delay at 12 months.

The second infant had gastroschisis and a horseshoe kidney. The mother took 400 mg of clozapine daily throughout pregnancy. The gastroschisis had a surgical correction, whereas the kidney is being managed conservatively and the baby is progressing well.

Congenital malformations occurred in 2 of the 14 babies who were exposed to quetiapine. One baby had an atrial-septal defect; the mother took 1,110 mg/day of quetiapine throughout pregnancy as well as 1,000 mg/day of zuclopenthixol. The defect was resolving spontaneously by 12 months with conservative management.

The second baby who was exposed to quetiapine had a cleft lip and palate, as well as hydrocephalus. The mother took 600 mg/day well throughout the pregnancy. The clefts were surgically repaired and excess cephalic fluid was drained. The baby is progressing and being monitored.

[Sidebar: Removing Antipsychotic Medications in Pregnancy: A Case in Point]

One anomaly occurred in a baby exposed to risperidone: This infant had an abnormal renal collecting tubule and bilateral talipes. The mother took 2 mg/day risperidone up to 36 weeks’ gestation. The abnormal collecting tubule is functioning well, and the talipes underwent surgical repair and braces, with a good result.

Gestational diabetes accounted for most of the maternal complications. "We are seeing a lot of gestational diabetes in the moms – higher than the general population. Maybe this is because they were already overweight, or the drugs contributed to weight gain and insulin intolerance. But clinicians should be aware of this heightened risk, look diligently for signs of it, and give this information to their patients."

The disorder occurred in 16 of the 100 women, including 6 who were taking quetiapine (14%), 4 taking olanzapine (28%), 1 taking risperidone (17%), 4 taking clozapine (67%), and 1 taking Consta (33%). Preeclampsia occurred in one patient who was taking quetiapine (2%).

The registry also tracked smoking, as well as alcohol and substance abuse, but did not control for these factors in any multivariate analysis. Antenatally, smoking was noted in 31% of registry women, compared with 16% of the general population. But antenatal alcohol consumption among registry participants was lower than that in the general population (12% vs. 60%). Substance abuse incidence was about 12% in the registry participants, compared with 7% in the general population. "We have lots of stories from women who smoked a lot of cigarettes and drank a lot, and decreased this during pregnancy. That protective instinct of the mother for the fetus is alive and well, and kicked in among these women."

Managing antipsychotic medications during pregnancy is a new concept to most clinicians in Australia, who continue to assume that the drugs will tip the risk:benefit ratio to the pit of endangering the developing baby, Dr. Kulkarni said. This has led to many recommendations that women with serious mental disorders avoid ever bearing children. She has even received calls from physicians who are angry that the registry seems to support childbearing in this group, "asking me why I’m allowing the gene pool to be polluted."

In her daily work, Dr. Kulkarni deals with significant regrets from women who were told that their mental illness and medication should preclude any childbearing. "I see a number of women in their 50s, approaching menopause, who were given the advice many years back never to have children because of the drug dangers," she said. "Now, they are grieving and experiencing depression over what could have been. The medical profession does not play God. We can only provide information and advice, but not take the role of driving the decision about having children or not."

Dr. Kulkarni said that the registry’s results are interesting, but until many more women are enrolled, it’s difficult to use it as a clinical guideline about what drug is safest for both mother and baby. "We need to accumulate a lot more data, and in the future, we hope to expand the program to sites all over the world."

The NRAMP project data are online; clinicians can register to participate or get more information about setting up similar programs. Physicians interested in obtaining more information about the registry can also e-mail Dr. Kulkarni or Gilbert, the project’s research nurse.

The project is funded by Astra-Zeneca, Janssen-Cilag, Mayne Pharmaceuticals, and the Australian Rotary Health Research Fund. Dr. Kulkarni had no financial disclosures.

* CORRECTION, 5/10/2011: The original version of this article misspelled Heather Gilbert's last name. This version has been corrected.

BARCELONA – Severe hyposmia may be associated with a deficiency of striatal dopamine transporter protein and slight cognitive decline – characteristics that could identify people with an increased risk of developing Parkinson’s disease, according to preliminary findings from the Parkinson’s Associated Risk Study.

"This is an interesting observation: [Cognitive] decline may be occurring well in advance of motor symptoms," Dr. Kenneth Marek said at the International Conference on Alzheimer’s and Parkinson’s Diseases. "This might be something we could use to predict who will develop dopamine transporter deficiency and, eventually, symptomatic Parkinson’s."

The prospective PARS (Parkinson’s Associated Risk Study) aims to test the effectiveness of two biomarkers – sense of smell and dopamine transporter imaging – in identifying subjects who are at risk of developing the disease. First-degree relatives of Parkinson’s disease patients and control subjects will be followed for 2 years to determine whether a deficiency in striatal dopamine transporter (DAT) increases their disease risk.

Dr. Marek and his coinvestigators recruited subjects by a mass mailing of the UPSIT (University of Pennsylvania Smell Identification Test); those scoring in the 15th percentile and lower are invited to participate. So far, 9,400 tests have been mailed out, half to relatives of patients and half to subjects recruited by community notices. About 5,000 have sent the test back.

"We have identified 650 people who were hyposmic below this 15th percentile," said Dr. Marek, president and senior scientist at the Institute for Neurodegenerative Disorders in New Haven, Conn. "This is considered rather severe hyposmia and, interestingly, only about a third of these folks noticed that they even had this symptom."

He presented data on 303 participants (203 hyposmic, 100 normosmic) who had undergone the baseline evaluation. Tests included a neuropsychological test battery, early Parkinson’s symptom score, and SPECT (single-photon emission CT) brain imaging of striatal DAT binding with the imaging compound iodine-123–beta-CIT. The study is grouping participants according to their striatal DAT levels: Greater than 80% is considered normal, 65%-80% is considered indeterminate, and less than 65% is considered a deficiency consistent with Parkinson’s disease.

Of the 203 hyposmic subjects, 11% had a DAT level less than 65%, compared with 1% of the normosmic group, a significant difference. "That one person in the normosmic group also has a REM sleep behavior disorder," Dr. Marek noted.

Indeterminate DAT levels were seen in 17% of the hyposmic and in 7% of the normosmic groups, and normal levels were seen in 71% of the hyposmic and 92% of the normosmic groups. (Percentages in the hyposmic group do not equal 100% because of rounding.)

Bowel habits also varied significantly between the groups. Nearly half (48%) of those with the lowest DAT density reported fewer than one bowel movement per day, compared with 21% of the normal-level group. Conversely, 13% of the lowest-level group reported one or more bowel movements per day, compared with 51% of the normal-level group.

"Similarly, [the lowest DAT-level group was] much more likely to endorse questions related to REM sleep behavior disorder," Dr. Marek said. "And when we used another tool – a nine-item symptom rating scale that assesses early Parkinson’s – those individuals in the lowest DAT group were more likely to endorse the symptoms."

Taking these data into account, he said it seems as if "these individuals express a number of features that we might call ‘premotor Parkinsonism.’ "

The researchers have completed cognitive testing on 131 participants (17 with decreased DAT levels and 114 with normal levels). Mean age was the same (68 years) in both groups and their educational levels were not significantly different.

"Even in this group, [in which all the] subjects were entirely cognitively normal, it was possible to distinguish individuals based on their cognitive function related to whether they had this early DAT deficit or not," Dr. Marek said. "I would not call them cognitively impaired, because they were not, but they were different and easily distinguished, based on their scores and imaging outcomes."

Finally, he said, when the global cognitive scores of individuals in all three DAT levels were compared, "we got some sense that there is a relationship between the extent of DAT deficit and the likelihood of seeing these cognitive changes."

The PARS study is being sponsored by the U.S. Department of Defense, the Michael J. Fox Foundation for Parkinson’s Research, and the National Parkinson Foundation. As an employee of the Institute for Neurodegenerative Disorders, Dr. Marek participates in multiple clinical studies, some of which are funded by drug companies.

BARCELONA – Severe hyposmia may be associated with a deficiency of striatal dopamine transporter protein and slight cognitive decline – characteristics that could identify people with an increased risk of developing Parkinson’s disease, according to preliminary findings from the Parkinson’s Associated Risk Study.

"This is an interesting observation: [Cognitive] decline may be occurring well in advance of motor symptoms," Dr. Kenneth Marek said at the International Conference on Alzheimer’s and Parkinson’s Diseases. "This might be something we could use to predict who will develop dopamine transporter deficiency and, eventually, symptomatic Parkinson’s."

The prospective PARS (Parkinson’s Associated Risk Study) aims to test the effectiveness of two biomarkers – sense of smell and dopamine transporter imaging – in identifying subjects who are at risk of developing the disease. First-degree relatives of Parkinson’s disease patients and control subjects will be followed for 2 years to determine whether a deficiency in striatal dopamine transporter (DAT) increases their disease risk.

Dr. Marek and his coinvestigators recruited subjects by a mass mailing of the UPSIT (University of Pennsylvania Smell Identification Test); those scoring in the 15th percentile and lower are invited to participate. So far, 9,400 tests have been mailed out, half to relatives of patients and half to subjects recruited by community notices. About 5,000 have sent the test back.

"We have identified 650 people who were hyposmic below this 15th percentile," said Dr. Marek, president and senior scientist at the Institute for Neurodegenerative Disorders in New Haven, Conn. "This is considered rather severe hyposmia and, interestingly, only about a third of these folks noticed that they even had this symptom."

He presented data on 303 participants (203 hyposmic, 100 normosmic) who had undergone the baseline evaluation. Tests included a neuropsychological test battery, early Parkinson’s symptom score, and SPECT (single-photon emission CT) brain imaging of striatal DAT binding with the imaging compound iodine-123–beta-CIT. The study is grouping participants according to their striatal DAT levels: Greater than 80% is considered normal, 65%-80% is considered indeterminate, and less than 65% is considered a deficiency consistent with Parkinson’s disease.

Of the 203 hyposmic subjects, 11% had a DAT level less than 65%, compared with 1% of the normosmic group, a significant difference. "That one person in the normosmic group also has a REM sleep behavior disorder," Dr. Marek noted.

Indeterminate DAT levels were seen in 17% of the hyposmic and in 7% of the normosmic groups, and normal levels were seen in 71% of the hyposmic and 92% of the normosmic groups. (Percentages in the hyposmic group do not equal 100% because of rounding.)

Bowel habits also varied significantly between the groups. Nearly half (48%) of those with the lowest DAT density reported fewer than one bowel movement per day, compared with 21% of the normal-level group. Conversely, 13% of the lowest-level group reported one or more bowel movements per day, compared with 51% of the normal-level group.

"Similarly, [the lowest DAT-level group was] much more likely to endorse questions related to REM sleep behavior disorder," Dr. Marek said. "And when we used another tool – a nine-item symptom rating scale that assesses early Parkinson’s – those individuals in the lowest DAT group were more likely to endorse the symptoms."

Taking these data into account, he said it seems as if "these individuals express a number of features that we might call ‘premotor Parkinsonism.’ "

The researchers have completed cognitive testing on 131 participants (17 with decreased DAT levels and 114 with normal levels). Mean age was the same (68 years) in both groups and their educational levels were not significantly different.

"Even in this group, [in which all the] subjects were entirely cognitively normal, it was possible to distinguish individuals based on their cognitive function related to whether they had this early DAT deficit or not," Dr. Marek said. "I would not call them cognitively impaired, because they were not, but they were different and easily distinguished, based on their scores and imaging outcomes."

Finally, he said, when the global cognitive scores of individuals in all three DAT levels were compared, "we got some sense that there is a relationship between the extent of DAT deficit and the likelihood of seeing these cognitive changes."

The PARS study is being sponsored by the U.S. Department of Defense, the Michael J. Fox Foundation for Parkinson’s Research, and the National Parkinson Foundation. As an employee of the Institute for Neurodegenerative Disorders, Dr. Marek participates in multiple clinical studies, some of which are funded by drug companies.

BARCELONA – Severe hyposmia may be associated with a deficiency of striatal dopamine transporter protein and slight cognitive decline – characteristics that could identify people with an increased risk of developing Parkinson’s disease, according to preliminary findings from the Parkinson’s Associated Risk Study.

"This is an interesting observation: [Cognitive] decline may be occurring well in advance of motor symptoms," Dr. Kenneth Marek said at the International Conference on Alzheimer’s and Parkinson’s Diseases. "This might be something we could use to predict who will develop dopamine transporter deficiency and, eventually, symptomatic Parkinson’s."

The prospective PARS (Parkinson’s Associated Risk Study) aims to test the effectiveness of two biomarkers – sense of smell and dopamine transporter imaging – in identifying subjects who are at risk of developing the disease. First-degree relatives of Parkinson’s disease patients and control subjects will be followed for 2 years to determine whether a deficiency in striatal dopamine transporter (DAT) increases their disease risk.

Dr. Marek and his coinvestigators recruited subjects by a mass mailing of the UPSIT (University of Pennsylvania Smell Identification Test); those scoring in the 15th percentile and lower are invited to participate. So far, 9,400 tests have been mailed out, half to relatives of patients and half to subjects recruited by community notices. About 5,000 have sent the test back.

"We have identified 650 people who were hyposmic below this 15th percentile," said Dr. Marek, president and senior scientist at the Institute for Neurodegenerative Disorders in New Haven, Conn. "This is considered rather severe hyposmia and, interestingly, only about a third of these folks noticed that they even had this symptom."

He presented data on 303 participants (203 hyposmic, 100 normosmic) who had undergone the baseline evaluation. Tests included a neuropsychological test battery, early Parkinson’s symptom score, and SPECT (single-photon emission CT) brain imaging of striatal DAT binding with the imaging compound iodine-123–beta-CIT. The study is grouping participants according to their striatal DAT levels: Greater than 80% is considered normal, 65%-80% is considered indeterminate, and less than 65% is considered a deficiency consistent with Parkinson’s disease.

Of the 203 hyposmic subjects, 11% had a DAT level less than 65%, compared with 1% of the normosmic group, a significant difference. "That one person in the normosmic group also has a REM sleep behavior disorder," Dr. Marek noted.

Indeterminate DAT levels were seen in 17% of the hyposmic and in 7% of the normosmic groups, and normal levels were seen in 71% of the hyposmic and 92% of the normosmic groups. (Percentages in the hyposmic group do not equal 100% because of rounding.)

Bowel habits also varied significantly between the groups. Nearly half (48%) of those with the lowest DAT density reported fewer than one bowel movement per day, compared with 21% of the normal-level group. Conversely, 13% of the lowest-level group reported one or more bowel movements per day, compared with 51% of the normal-level group.

"Similarly, [the lowest DAT-level group was] much more likely to endorse questions related to REM sleep behavior disorder," Dr. Marek said. "And when we used another tool – a nine-item symptom rating scale that assesses early Parkinson’s – those individuals in the lowest DAT group were more likely to endorse the symptoms."

Taking these data into account, he said it seems as if "these individuals express a number of features that we might call ‘premotor Parkinsonism.’ "

The researchers have completed cognitive testing on 131 participants (17 with decreased DAT levels and 114 with normal levels). Mean age was the same (68 years) in both groups and their educational levels were not significantly different.

"Even in this group, [in which all the] subjects were entirely cognitively normal, it was possible to distinguish individuals based on their cognitive function related to whether they had this early DAT deficit or not," Dr. Marek said. "I would not call them cognitively impaired, because they were not, but they were different and easily distinguished, based on their scores and imaging outcomes."

Finally, he said, when the global cognitive scores of individuals in all three DAT levels were compared, "we got some sense that there is a relationship between the extent of DAT deficit and the likelihood of seeing these cognitive changes."

The PARS study is being sponsored by the U.S. Department of Defense, the Michael J. Fox Foundation for Parkinson’s Research, and the National Parkinson Foundation. As an employee of the Institute for Neurodegenerative Disorders, Dr. Marek participates in multiple clinical studies, some of which are funded by drug companies.