Michele G. Sullivan

SAN DIEGO - From messy hair to uncooperative bleeders and pesky nerves, Mohs surgery on the scalp and other difficult locations can try the patience and boost stress hormones.

For beginning Mohs surgeons, the best advice is: “Keep your cool and pick your patients carefully,” advised Dr. Carlos Garcia. “There are certain patients you don’t want to have for your first cases, so choose carefully, and save those until you are more experienced.”

Dr. Garcia, director of surgical dermatology at the University of Oklahoma, Norman, dropped another valuable pearl to novice Mohs practitioners: Know when to call in reinforcements. For example, with primary tumors near the lacrimal system or recurrences in the acral area, “be sure to include a plastic surgeon in your plan, because these are not usually going to be beautiful when you finish.”

The scalp is a very common location for skin cancers and presents a unique set of challenges, Dr. Garcia said. As every parent with a rock-throwing child knows, any scalp wound bleeds in apparent excess of its size.

“No matter what you do, the scalp is going to bleed, and you have to be prepared,” he said. “Most of the small vessels are in the dermis, but the bigger ones are in the deeper layers, and you may be getting into those with Mohs.”

Tumescent anesthesia is a fine approach to hemostasis. “Injected into the dermis, it produces a hard surface and after 15 or 20 minutes you can do surgery with minimal bleeding. The other advantage is that it’s going to give more prolonged hemostasis as well as pain control.”

Locking sutures are another good hemostatic technique, he said. “You can use Prolene or nylon and a running or interrupted suture, but you need to lock in the suture, and you’ll get much better hemostasis from the dermal vessels.”

Hair can also increase the risk for complications. “It’s stressful enough with the bleeding on the scalp, but on top of that you have the hair to deal with,” Dr. Garcia said. “Make sure you have lots of things to take care of that – trimmers, hair clips, mousse, and gel. Do whatever you have to do to get it out of the way.”

Elastic bandages are a must for scalp surgery. “Your patient will need to keep these on during the first 24 hours after surgery when bleeding is the greatest. If you don’t have good compression and warn your patients to maintain it, you’re going to get a lot of phone calls.”

It’s not uncommon for a patient to have multiple cancers or precancerous lesions on the scalp. “My rule of thumb is to get rid of the basic component, and then if I get three epidermal layers with actinic keratosis components but no deep component, I stop the Mohs. Note in the chart that there is a small in situ that will be treated during follow-up,” he said.

Some Mohs surgeons will persist with layers even into the periosteum or bone. “I don’t do bone chiseling because technically I’m not trained to do it, and also because I’m very hesitant because there have been reports of air embolism,” Dr. Garcia said. “The veins from the surface connect very easily with the deeper sinusoidal vessels, and if you have the patient waiting for another layer and not positioned correctly, they can get changing pressure. Air can get in and they can get an embolism in the waiting room. So if you ever delve into this area, be aware of this possibility.” (Dermatol. Surg. 2009;35:1414-21).

Because scalp skin is not very pliable, repair can be a challenge. “Many times I leave these to heal by secondary intention.” It’s not a quick process, though. “If the defect goes to the bone, it’s going to take 3-4 weeks for every centimeter of the wound to completely heal.”

Dr Garcia also passed on some tips about other areas that might challenge the Mohs surgeon:

P Temple: In the temple area, hair and bleeders are the biggest issue. “Get the hair out of the way first and have a couple of mosquito clamps loaded with 4-0 or 5-0 Vicryl to tie off vessels. As a general rule, ligate any blood vessel that’s thicker than a 30-gauge needle.”

The temporal branch of the facial nerve may be at risk if the surgery is near its most superficial area – just over the malar arc. “If you transect any of the branches of the nerve ahead or in front of the external canthus, it will regenerate 100% of the time, and the patient will get full movement back. The closer you get to the preauricular area, the less likely regeneration becomes. If transection happens – and it does – the ear, nose, and throat [specialists] usually will wait 3-4 months before trying to do something about it, to see if there is any spontaneous regeneration.”

P Recurrence in grafted skin or previously irradiated areas: Resist the desire to undertake repeated Mohs, he advised. “These can be bad. They can be too extensive, and you will invest some time and money and some very stressful moments if you get into this.”

P Ear: For tumors in the concha, “Pay attention to the size, type, and proximity to the external canal. It’s really hard to do Mohs excisions in the ear canal.”

P Eyelid: The thinnest skin on the body, the eyelid is even more fragile on elderly people. “This is a very difficult area for me to cut in Mohs. Instead of applying a lot of pressure, I use a number 11 or 15 blade and do several rounds. Use light pressure because the epidermis has a tendency to fold and pull, making it hard to cut.” Bevelling is not as important here because the skin is so friable that the technician can easily flatten it on the slide.

Topical anesthetic ocular drops help the patient tolerate the surgery much better, and allow the placement of a plastic eye shield anchored with a couple of small sutures. “The eye shield and sutures are left in place while the patient is waiting – I just cover it with a full eye patch.”

P Nose: For lesions on the ala or alar arch, cotton swabs, dental rolls, or even a finger push the tissue outward and give good support for excision. “Notching of ala before surgery is a bad prognosis,” Dr. Garcia said. “It means advanced cancer, and this may not be something you want to get into.”

Dr. Garcia said he had no financial disclosures.

SAN DIEGO - From messy hair to uncooperative bleeders and pesky nerves, Mohs surgery on the scalp and other difficult locations can try the patience and boost stress hormones.

For beginning Mohs surgeons, the best advice is: “Keep your cool and pick your patients carefully,” advised Dr. Carlos Garcia. “There are certain patients you don’t want to have for your first cases, so choose carefully, and save those until you are more experienced.”

Dr. Garcia, director of surgical dermatology at the University of Oklahoma, Norman, dropped another valuable pearl to novice Mohs practitioners: Know when to call in reinforcements. For example, with primary tumors near the lacrimal system or recurrences in the acral area, “be sure to include a plastic surgeon in your plan, because these are not usually going to be beautiful when you finish.”

The scalp is a very common location for skin cancers and presents a unique set of challenges, Dr. Garcia said. As every parent with a rock-throwing child knows, any scalp wound bleeds in apparent excess of its size.

“No matter what you do, the scalp is going to bleed, and you have to be prepared,” he said. “Most of the small vessels are in the dermis, but the bigger ones are in the deeper layers, and you may be getting into those with Mohs.”

Tumescent anesthesia is a fine approach to hemostasis. “Injected into the dermis, it produces a hard surface and after 15 or 20 minutes you can do surgery with minimal bleeding. The other advantage is that it’s going to give more prolonged hemostasis as well as pain control.”

Locking sutures are another good hemostatic technique, he said. “You can use Prolene or nylon and a running or interrupted suture, but you need to lock in the suture, and you’ll get much better hemostasis from the dermal vessels.”

Hair can also increase the risk for complications. “It’s stressful enough with the bleeding on the scalp, but on top of that you have the hair to deal with,” Dr. Garcia said. “Make sure you have lots of things to take care of that – trimmers, hair clips, mousse, and gel. Do whatever you have to do to get it out of the way.”

Elastic bandages are a must for scalp surgery. “Your patient will need to keep these on during the first 24 hours after surgery when bleeding is the greatest. If you don’t have good compression and warn your patients to maintain it, you’re going to get a lot of phone calls.”

It’s not uncommon for a patient to have multiple cancers or precancerous lesions on the scalp. “My rule of thumb is to get rid of the basic component, and then if I get three epidermal layers with actinic keratosis components but no deep component, I stop the Mohs. Note in the chart that there is a small in situ that will be treated during follow-up,” he said.

Some Mohs surgeons will persist with layers even into the periosteum or bone. “I don’t do bone chiseling because technically I’m not trained to do it, and also because I’m very hesitant because there have been reports of air embolism,” Dr. Garcia said. “The veins from the surface connect very easily with the deeper sinusoidal vessels, and if you have the patient waiting for another layer and not positioned correctly, they can get changing pressure. Air can get in and they can get an embolism in the waiting room. So if you ever delve into this area, be aware of this possibility.” (Dermatol. Surg. 2009;35:1414-21).

Because scalp skin is not very pliable, repair can be a challenge. “Many times I leave these to heal by secondary intention.” It’s not a quick process, though. “If the defect goes to the bone, it’s going to take 3-4 weeks for every centimeter of the wound to completely heal.”

Dr Garcia also passed on some tips about other areas that might challenge the Mohs surgeon:

P Temple: In the temple area, hair and bleeders are the biggest issue. “Get the hair out of the way first and have a couple of mosquito clamps loaded with 4-0 or 5-0 Vicryl to tie off vessels. As a general rule, ligate any blood vessel that’s thicker than a 30-gauge needle.”

The temporal branch of the facial nerve may be at risk if the surgery is near its most superficial area – just over the malar arc. “If you transect any of the branches of the nerve ahead or in front of the external canthus, it will regenerate 100% of the time, and the patient will get full movement back. The closer you get to the preauricular area, the less likely regeneration becomes. If transection happens – and it does – the ear, nose, and throat [specialists] usually will wait 3-4 months before trying to do something about it, to see if there is any spontaneous regeneration.”

P Recurrence in grafted skin or previously irradiated areas: Resist the desire to undertake repeated Mohs, he advised. “These can be bad. They can be too extensive, and you will invest some time and money and some very stressful moments if you get into this.”

P Ear: For tumors in the concha, “Pay attention to the size, type, and proximity to the external canal. It’s really hard to do Mohs excisions in the ear canal.”

P Eyelid: The thinnest skin on the body, the eyelid is even more fragile on elderly people. “This is a very difficult area for me to cut in Mohs. Instead of applying a lot of pressure, I use a number 11 or 15 blade and do several rounds. Use light pressure because the epidermis has a tendency to fold and pull, making it hard to cut.” Bevelling is not as important here because the skin is so friable that the technician can easily flatten it on the slide.

Topical anesthetic ocular drops help the patient tolerate the surgery much better, and allow the placement of a plastic eye shield anchored with a couple of small sutures. “The eye shield and sutures are left in place while the patient is waiting – I just cover it with a full eye patch.”

P Nose: For lesions on the ala or alar arch, cotton swabs, dental rolls, or even a finger push the tissue outward and give good support for excision. “Notching of ala before surgery is a bad prognosis,” Dr. Garcia said. “It means advanced cancer, and this may not be something you want to get into.”

Dr. Garcia said he had no financial disclosures.

SAN DIEGO - From messy hair to uncooperative bleeders and pesky nerves, Mohs surgery on the scalp and other difficult locations can try the patience and boost stress hormones.

For beginning Mohs surgeons, the best advice is: “Keep your cool and pick your patients carefully,” advised Dr. Carlos Garcia. “There are certain patients you don’t want to have for your first cases, so choose carefully, and save those until you are more experienced.”

Dr. Garcia, director of surgical dermatology at the University of Oklahoma, Norman, dropped another valuable pearl to novice Mohs practitioners: Know when to call in reinforcements. For example, with primary tumors near the lacrimal system or recurrences in the acral area, “be sure to include a plastic surgeon in your plan, because these are not usually going to be beautiful when you finish.”

The scalp is a very common location for skin cancers and presents a unique set of challenges, Dr. Garcia said. As every parent with a rock-throwing child knows, any scalp wound bleeds in apparent excess of its size.

“No matter what you do, the scalp is going to bleed, and you have to be prepared,” he said. “Most of the small vessels are in the dermis, but the bigger ones are in the deeper layers, and you may be getting into those with Mohs.”

Tumescent anesthesia is a fine approach to hemostasis. “Injected into the dermis, it produces a hard surface and after 15 or 20 minutes you can do surgery with minimal bleeding. The other advantage is that it’s going to give more prolonged hemostasis as well as pain control.”

Locking sutures are another good hemostatic technique, he said. “You can use Prolene or nylon and a running or interrupted suture, but you need to lock in the suture, and you’ll get much better hemostasis from the dermal vessels.”

Hair can also increase the risk for complications. “It’s stressful enough with the bleeding on the scalp, but on top of that you have the hair to deal with,” Dr. Garcia said. “Make sure you have lots of things to take care of that – trimmers, hair clips, mousse, and gel. Do whatever you have to do to get it out of the way.”

Elastic bandages are a must for scalp surgery. “Your patient will need to keep these on during the first 24 hours after surgery when bleeding is the greatest. If you don’t have good compression and warn your patients to maintain it, you’re going to get a lot of phone calls.”

It’s not uncommon for a patient to have multiple cancers or precancerous lesions on the scalp. “My rule of thumb is to get rid of the basic component, and then if I get three epidermal layers with actinic keratosis components but no deep component, I stop the Mohs. Note in the chart that there is a small in situ that will be treated during follow-up,” he said.

Some Mohs surgeons will persist with layers even into the periosteum or bone. “I don’t do bone chiseling because technically I’m not trained to do it, and also because I’m very hesitant because there have been reports of air embolism,” Dr. Garcia said. “The veins from the surface connect very easily with the deeper sinusoidal vessels, and if you have the patient waiting for another layer and not positioned correctly, they can get changing pressure. Air can get in and they can get an embolism in the waiting room. So if you ever delve into this area, be aware of this possibility.” (Dermatol. Surg. 2009;35:1414-21).

Because scalp skin is not very pliable, repair can be a challenge. “Many times I leave these to heal by secondary intention.” It’s not a quick process, though. “If the defect goes to the bone, it’s going to take 3-4 weeks for every centimeter of the wound to completely heal.”

Dr Garcia also passed on some tips about other areas that might challenge the Mohs surgeon:

P Temple: In the temple area, hair and bleeders are the biggest issue. “Get the hair out of the way first and have a couple of mosquito clamps loaded with 4-0 or 5-0 Vicryl to tie off vessels. As a general rule, ligate any blood vessel that’s thicker than a 30-gauge needle.”

The temporal branch of the facial nerve may be at risk if the surgery is near its most superficial area – just over the malar arc. “If you transect any of the branches of the nerve ahead or in front of the external canthus, it will regenerate 100% of the time, and the patient will get full movement back. The closer you get to the preauricular area, the less likely regeneration becomes. If transection happens – and it does – the ear, nose, and throat [specialists] usually will wait 3-4 months before trying to do something about it, to see if there is any spontaneous regeneration.”

P Recurrence in grafted skin or previously irradiated areas: Resist the desire to undertake repeated Mohs, he advised. “These can be bad. They can be too extensive, and you will invest some time and money and some very stressful moments if you get into this.”

P Ear: For tumors in the concha, “Pay attention to the size, type, and proximity to the external canal. It’s really hard to do Mohs excisions in the ear canal.”

P Eyelid: The thinnest skin on the body, the eyelid is even more fragile on elderly people. “This is a very difficult area for me to cut in Mohs. Instead of applying a lot of pressure, I use a number 11 or 15 blade and do several rounds. Use light pressure because the epidermis has a tendency to fold and pull, making it hard to cut.” Bevelling is not as important here because the skin is so friable that the technician can easily flatten it on the slide.

Topical anesthetic ocular drops help the patient tolerate the surgery much better, and allow the placement of a plastic eye shield anchored with a couple of small sutures. “The eye shield and sutures are left in place while the patient is waiting – I just cover it with a full eye patch.”

P Nose: For lesions on the ala or alar arch, cotton swabs, dental rolls, or even a finger push the tissue outward and give good support for excision. “Notching of ala before surgery is a bad prognosis,” Dr. Garcia said. “It means advanced cancer, and this may not be something you want to get into.”

Dr. Garcia said he had no financial disclosures.

SILVER SPRING, Md. – A Food and Drug Administration advisory committee voted Jan. 20 against immediate approval of the beta-amyloid imaging agent florbetapir, saying that inter-reader variability and lack of a single reading technique in the existing data must still be addressed.

But after voting 13 to 3 to deny approval, the Peripheral and Central Nervous System Drugs Advisory Committee – in an unusual motion – took an additional stance on the compound. The committee voted unanimously to approve florbetapir if Avid Radiopharmaceuticals Inc., the company developing the compound, would train readers in a consistent technique, and then re-evaluate scans from both a recent phase III and a previous phase II trial. Eli Lilly & Co. acquired Avid in November 2010.

"What we need as the underpinning for approval is a re-read and re-study of these scans based on a training program," said committee member Dr. Peter Herscovitch. "[Without that] we cannot say there is consistency in the reading" of patients with mild cognitive impairment – the population seen as the most likely to utilize florbetapir-PET imaging.

The action of a second vote surprised Capt. Rafel Rieves, director of FDA’s Division of Medical Imaging Products. But he said there was no prohibition against the committee voting on a motion of its own making, as long as it answered FDA’s primary question – whether or not to approve florbetapir based on the existing data.

The committee based its decision partially on Avid’s latest trial, published Jan. 19 (JAMA 2011;305:275-83). The study comprised 35 end-of-life patients, whose brains were also examined at autopsy, and 74 young, healthy controls. It found that florbetapir-PET imaging was 93% sensitive and 100% specific for identifying beta-amyloid plaques in the brain – a finding necessary for a diagnosis of Alzheimer’s disease.

But committee members pointed out that different readers examined the cohorts and used different techniques for each one. The autopsy cohort, read by three radiologists, rated amyloid burden on a scale of 1 to 5. The control cohort, read by three other radiologists, used a binary rating of positive or negative.

Reproducibility seemed good in these patients, who appeared to represent two ends of the amyloid spectrum – young adults almost universally expected to have negative results, and elderly patients close to death, who were much more likely to have positive results. None of the patients in the trial had a "moderate’ amyloid load, although the committee said that these patients would represent the bulk of those evaluated in clinical practice.

Avid’s phase II trial comprised 79 healthy controls, 45 patients with Alzheimer’s disease, and 60 with mild cognitive impairment (MCI). Among this MCI group, reader variability was high, indicating readers’ difficulty in judging the visual cut point of a clinically significant amyloid burden, the committee members said.

Re-evaluating the scans in both groups, with more readers specifically trained in florbetapir imaging techniques, would provide the definitive answers needed for approval, the committee agreed.

Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting, but occasionally the FDA grants a waiver to a panelist with a conflict of interest.

SILVER SPRING, Md. – A Food and Drug Administration advisory committee voted Jan. 20 against immediate approval of the beta-amyloid imaging agent florbetapir, saying that inter-reader variability and lack of a single reading technique in the existing data must still be addressed.

But after voting 13 to 3 to deny approval, the Peripheral and Central Nervous System Drugs Advisory Committee – in an unusual motion – took an additional stance on the compound. The committee voted unanimously to approve florbetapir if Avid Radiopharmaceuticals Inc., the company developing the compound, would train readers in a consistent technique, and then re-evaluate scans from both a recent phase III and a previous phase II trial. Eli Lilly & Co. acquired Avid in November 2010.

"What we need as the underpinning for approval is a re-read and re-study of these scans based on a training program," said committee member Dr. Peter Herscovitch. "[Without that] we cannot say there is consistency in the reading" of patients with mild cognitive impairment – the population seen as the most likely to utilize florbetapir-PET imaging.

The action of a second vote surprised Capt. Rafel Rieves, director of FDA’s Division of Medical Imaging Products. But he said there was no prohibition against the committee voting on a motion of its own making, as long as it answered FDA’s primary question – whether or not to approve florbetapir based on the existing data.

The committee based its decision partially on Avid’s latest trial, published Jan. 19 (JAMA 2011;305:275-83). The study comprised 35 end-of-life patients, whose brains were also examined at autopsy, and 74 young, healthy controls. It found that florbetapir-PET imaging was 93% sensitive and 100% specific for identifying beta-amyloid plaques in the brain – a finding necessary for a diagnosis of Alzheimer’s disease.

But committee members pointed out that different readers examined the cohorts and used different techniques for each one. The autopsy cohort, read by three radiologists, rated amyloid burden on a scale of 1 to 5. The control cohort, read by three other radiologists, used a binary rating of positive or negative.

Reproducibility seemed good in these patients, who appeared to represent two ends of the amyloid spectrum – young adults almost universally expected to have negative results, and elderly patients close to death, who were much more likely to have positive results. None of the patients in the trial had a "moderate’ amyloid load, although the committee said that these patients would represent the bulk of those evaluated in clinical practice.

Avid’s phase II trial comprised 79 healthy controls, 45 patients with Alzheimer’s disease, and 60 with mild cognitive impairment (MCI). Among this MCI group, reader variability was high, indicating readers’ difficulty in judging the visual cut point of a clinically significant amyloid burden, the committee members said.

Re-evaluating the scans in both groups, with more readers specifically trained in florbetapir imaging techniques, would provide the definitive answers needed for approval, the committee agreed.

Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting, but occasionally the FDA grants a waiver to a panelist with a conflict of interest.

SILVER SPRING, Md. – A Food and Drug Administration advisory committee voted Jan. 20 against immediate approval of the beta-amyloid imaging agent florbetapir, saying that inter-reader variability and lack of a single reading technique in the existing data must still be addressed.

But after voting 13 to 3 to deny approval, the Peripheral and Central Nervous System Drugs Advisory Committee – in an unusual motion – took an additional stance on the compound. The committee voted unanimously to approve florbetapir if Avid Radiopharmaceuticals Inc., the company developing the compound, would train readers in a consistent technique, and then re-evaluate scans from both a recent phase III and a previous phase II trial. Eli Lilly & Co. acquired Avid in November 2010.

"What we need as the underpinning for approval is a re-read and re-study of these scans based on a training program," said committee member Dr. Peter Herscovitch. "[Without that] we cannot say there is consistency in the reading" of patients with mild cognitive impairment – the population seen as the most likely to utilize florbetapir-PET imaging.

The action of a second vote surprised Capt. Rafel Rieves, director of FDA’s Division of Medical Imaging Products. But he said there was no prohibition against the committee voting on a motion of its own making, as long as it answered FDA’s primary question – whether or not to approve florbetapir based on the existing data.

The committee based its decision partially on Avid’s latest trial, published Jan. 19 (JAMA 2011;305:275-83). The study comprised 35 end-of-life patients, whose brains were also examined at autopsy, and 74 young, healthy controls. It found that florbetapir-PET imaging was 93% sensitive and 100% specific for identifying beta-amyloid plaques in the brain – a finding necessary for a diagnosis of Alzheimer’s disease.

But committee members pointed out that different readers examined the cohorts and used different techniques for each one. The autopsy cohort, read by three radiologists, rated amyloid burden on a scale of 1 to 5. The control cohort, read by three other radiologists, used a binary rating of positive or negative.

Reproducibility seemed good in these patients, who appeared to represent two ends of the amyloid spectrum – young adults almost universally expected to have negative results, and elderly patients close to death, who were much more likely to have positive results. None of the patients in the trial had a "moderate’ amyloid load, although the committee said that these patients would represent the bulk of those evaluated in clinical practice.

Avid’s phase II trial comprised 79 healthy controls, 45 patients with Alzheimer’s disease, and 60 with mild cognitive impairment (MCI). Among this MCI group, reader variability was high, indicating readers’ difficulty in judging the visual cut point of a clinically significant amyloid burden, the committee members said.

Re-evaluating the scans in both groups, with more readers specifically trained in florbetapir imaging techniques, would provide the definitive answers needed for approval, the committee agreed.

Panel members have been cleared of potential conflicts of interest by the FDA prior to the meeting, but occasionally the FDA grants a waiver to a panelist with a conflict of interest.

PALM BEACH, FLA. – When anatomy and pathology permit, patients reap the greatest benefits from a distal pancreatectomy that spares both the spleen and the splenic vessels.

Blood loss, fistula formation, length of hospital stay, and splenic infarct were all significantly lower in the spleen-sparing, vessel-sparing procedure than in a vessel-ligation procedure, Dr. Henry Pitt said at the annual meeting of the Southern Surgical Association.

"Splenic preservation with vessel ligation really offers no advantages over distal pancreatectomy with splenectomy, so vessel preservation is the preferred procedure for splenic-sparing distal pancreatectomy," said Dr. Pitt, a professor of surgery at Indiana University, Indianapolis.

Dr. Pitt presented a retrospective analysis of 86 spleen-sparing distal pancreatectomies, 45 with ligation and 41 with a vessel-sparing procedure. These were prospectively matched with another 86 patients who had distal pancreatectomy with splenectomy.

There were no significant differences in the patients' baseline characteristics. The average age was 55 years, with an average American Society of Anesthesiologists score of 3. "Pathology was also matched," Dr. Pitt said. The most common diagnosis was intraductal papular mucinous neoplasm, followed by cystic tumors. Other tumors included neuroendocrine and adenocarcinomas. None of the patients had invasive tumors.

Coauthor Dr. Attila Nakeeb described the process by which surgeons decide which path to pursue. Although the preoperative aim may be vessel sparing, "the ability to preserve the spleen is clearly a matter of anatomy and pathology," he said. "The ideal patient is one with a benign neoplasm, and any kind of inflammation is a major problem. The assessment usually depends on several factors, including the preoperative pathology."

The branching of the splenic vessels into the hilum is also important. "If you have a long pancreas with the hilum way up into the spleen and the vessels branching early, it’s much more difficult to do either of the techniques. Most of these patients get a splenectomy. In patients with inflammation, we don’t even make an attempt to preserve the vessels," said Dr. Nakeeb, a professor of surgery at Indiana University.

Intraoperative ultrasound is used in every case to identify the vasculature and trace the branching patterns, especially in patients with excess peripancreatic fat.

"If we make the preoperative decision to preserve the spleen, we also first attempt to preserve the vessels," Dr. Nakeeb said. "If we are unsuccessful in that, we convert to a ligation; if that does not go well, we convert to a splenectomy."

For the vessel-sparing, vessel-ligating, and splenectomy groups, there was no significant difference in operative time. The average time for the spleen-preserving procedures was 3.5 hours; for splenectomy, it was 4 hours.

Blood loss was significantly different. The average loss in the vessel-preserving group was 200 mL; in the ligation group, 500 mL; and in the splenectomy group, 600 mL.

In the spleen-preserving groups, splenic infarcts occurred in 2% (1) of the vessel-preservation group and in 39% (16) of the ligation group.

Pancreatic fistulas occurred in 2% (1) of the vessel-preservation group, 12% (5) of the vessel-ligation group, and 13% (11) of the splenectomy group. One patient in the vessel-preservation group required abscess drainage, compared with 15% of the vessel-ligation group and 16% of the splenectomy group – a significant difference.

The overall postoperative morbidity was 18% in the vessel-preservation group, 39% in the vessel-ligation group, and 38% in the splenectomy group, significantly favoring vessel preservation. The hospital length of stay was also significantly in favor of the vessel-preservation group – 4.5 days – compared with 6 days in the vessel-ligation group and 7 in the splenectomy group.

"Since the vessel-ligation outcomes were so similar to the outcomes in the splenectomy group, there is no real advantage over a distal pancreatectomy with splenectomy," Dr. Pitt said. "Vessel preservation was associated with less blood loss, a lower risk of requiring drainage, lower overall morbidity, shorter length of stay, and fewer infarcts."

Dr. Pitt attributed most of the research in the study to his colleague Dr. Joal Beane, an intern. "He really did all the work," Dr. Pitt said.

Dr. Pitt and Dr. Nakeeb reported no financial conflicts.

PALM BEACH, FLA. – When anatomy and pathology permit, patients reap the greatest benefits from a distal pancreatectomy that spares both the spleen and the splenic vessels.

Blood loss, fistula formation, length of hospital stay, and splenic infarct were all significantly lower in the spleen-sparing, vessel-sparing procedure than in a vessel-ligation procedure, Dr. Henry Pitt said at the annual meeting of the Southern Surgical Association.

"Splenic preservation with vessel ligation really offers no advantages over distal pancreatectomy with splenectomy, so vessel preservation is the preferred procedure for splenic-sparing distal pancreatectomy," said Dr. Pitt, a professor of surgery at Indiana University, Indianapolis.

Dr. Pitt presented a retrospective analysis of 86 spleen-sparing distal pancreatectomies, 45 with ligation and 41 with a vessel-sparing procedure. These were prospectively matched with another 86 patients who had distal pancreatectomy with splenectomy.

There were no significant differences in the patients' baseline characteristics. The average age was 55 years, with an average American Society of Anesthesiologists score of 3. "Pathology was also matched," Dr. Pitt said. The most common diagnosis was intraductal papular mucinous neoplasm, followed by cystic tumors. Other tumors included neuroendocrine and adenocarcinomas. None of the patients had invasive tumors.

Coauthor Dr. Attila Nakeeb described the process by which surgeons decide which path to pursue. Although the preoperative aim may be vessel sparing, "the ability to preserve the spleen is clearly a matter of anatomy and pathology," he said. "The ideal patient is one with a benign neoplasm, and any kind of inflammation is a major problem. The assessment usually depends on several factors, including the preoperative pathology."

The branching of the splenic vessels into the hilum is also important. "If you have a long pancreas with the hilum way up into the spleen and the vessels branching early, it’s much more difficult to do either of the techniques. Most of these patients get a splenectomy. In patients with inflammation, we don’t even make an attempt to preserve the vessels," said Dr. Nakeeb, a professor of surgery at Indiana University.

Intraoperative ultrasound is used in every case to identify the vasculature and trace the branching patterns, especially in patients with excess peripancreatic fat.

"If we make the preoperative decision to preserve the spleen, we also first attempt to preserve the vessels," Dr. Nakeeb said. "If we are unsuccessful in that, we convert to a ligation; if that does not go well, we convert to a splenectomy."

For the vessel-sparing, vessel-ligating, and splenectomy groups, there was no significant difference in operative time. The average time for the spleen-preserving procedures was 3.5 hours; for splenectomy, it was 4 hours.

Blood loss was significantly different. The average loss in the vessel-preserving group was 200 mL; in the ligation group, 500 mL; and in the splenectomy group, 600 mL.

In the spleen-preserving groups, splenic infarcts occurred in 2% (1) of the vessel-preservation group and in 39% (16) of the ligation group.

Pancreatic fistulas occurred in 2% (1) of the vessel-preservation group, 12% (5) of the vessel-ligation group, and 13% (11) of the splenectomy group. One patient in the vessel-preservation group required abscess drainage, compared with 15% of the vessel-ligation group and 16% of the splenectomy group – a significant difference.

The overall postoperative morbidity was 18% in the vessel-preservation group, 39% in the vessel-ligation group, and 38% in the splenectomy group, significantly favoring vessel preservation. The hospital length of stay was also significantly in favor of the vessel-preservation group – 4.5 days – compared with 6 days in the vessel-ligation group and 7 in the splenectomy group.

"Since the vessel-ligation outcomes were so similar to the outcomes in the splenectomy group, there is no real advantage over a distal pancreatectomy with splenectomy," Dr. Pitt said. "Vessel preservation was associated with less blood loss, a lower risk of requiring drainage, lower overall morbidity, shorter length of stay, and fewer infarcts."

Dr. Pitt attributed most of the research in the study to his colleague Dr. Joal Beane, an intern. "He really did all the work," Dr. Pitt said.

Dr. Pitt and Dr. Nakeeb reported no financial conflicts.

PALM BEACH, FLA. – When anatomy and pathology permit, patients reap the greatest benefits from a distal pancreatectomy that spares both the spleen and the splenic vessels.

Blood loss, fistula formation, length of hospital stay, and splenic infarct were all significantly lower in the spleen-sparing, vessel-sparing procedure than in a vessel-ligation procedure, Dr. Henry Pitt said at the annual meeting of the Southern Surgical Association.

"Splenic preservation with vessel ligation really offers no advantages over distal pancreatectomy with splenectomy, so vessel preservation is the preferred procedure for splenic-sparing distal pancreatectomy," said Dr. Pitt, a professor of surgery at Indiana University, Indianapolis.

Dr. Pitt presented a retrospective analysis of 86 spleen-sparing distal pancreatectomies, 45 with ligation and 41 with a vessel-sparing procedure. These were prospectively matched with another 86 patients who had distal pancreatectomy with splenectomy.

There were no significant differences in the patients' baseline characteristics. The average age was 55 years, with an average American Society of Anesthesiologists score of 3. "Pathology was also matched," Dr. Pitt said. The most common diagnosis was intraductal papular mucinous neoplasm, followed by cystic tumors. Other tumors included neuroendocrine and adenocarcinomas. None of the patients had invasive tumors.

Coauthor Dr. Attila Nakeeb described the process by which surgeons decide which path to pursue. Although the preoperative aim may be vessel sparing, "the ability to preserve the spleen is clearly a matter of anatomy and pathology," he said. "The ideal patient is one with a benign neoplasm, and any kind of inflammation is a major problem. The assessment usually depends on several factors, including the preoperative pathology."

The branching of the splenic vessels into the hilum is also important. "If you have a long pancreas with the hilum way up into the spleen and the vessels branching early, it’s much more difficult to do either of the techniques. Most of these patients get a splenectomy. In patients with inflammation, we don’t even make an attempt to preserve the vessels," said Dr. Nakeeb, a professor of surgery at Indiana University.

Intraoperative ultrasound is used in every case to identify the vasculature and trace the branching patterns, especially in patients with excess peripancreatic fat.

"If we make the preoperative decision to preserve the spleen, we also first attempt to preserve the vessels," Dr. Nakeeb said. "If we are unsuccessful in that, we convert to a ligation; if that does not go well, we convert to a splenectomy."

For the vessel-sparing, vessel-ligating, and splenectomy groups, there was no significant difference in operative time. The average time for the spleen-preserving procedures was 3.5 hours; for splenectomy, it was 4 hours.

Blood loss was significantly different. The average loss in the vessel-preserving group was 200 mL; in the ligation group, 500 mL; and in the splenectomy group, 600 mL.

In the spleen-preserving groups, splenic infarcts occurred in 2% (1) of the vessel-preservation group and in 39% (16) of the ligation group.

Pancreatic fistulas occurred in 2% (1) of the vessel-preservation group, 12% (5) of the vessel-ligation group, and 13% (11) of the splenectomy group. One patient in the vessel-preservation group required abscess drainage, compared with 15% of the vessel-ligation group and 16% of the splenectomy group – a significant difference.

The overall postoperative morbidity was 18% in the vessel-preservation group, 39% in the vessel-ligation group, and 38% in the splenectomy group, significantly favoring vessel preservation. The hospital length of stay was also significantly in favor of the vessel-preservation group – 4.5 days – compared with 6 days in the vessel-ligation group and 7 in the splenectomy group.

"Since the vessel-ligation outcomes were so similar to the outcomes in the splenectomy group, there is no real advantage over a distal pancreatectomy with splenectomy," Dr. Pitt said. "Vessel preservation was associated with less blood loss, a lower risk of requiring drainage, lower overall morbidity, shorter length of stay, and fewer infarcts."

Dr. Pitt attributed most of the research in the study to his colleague Dr. Joal Beane, an intern. "He really did all the work," Dr. Pitt said.

Dr. Pitt and Dr. Nakeeb reported no financial conflicts.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote in the Jan. 25 issue of the Journal of the American College of Cardiology (2011;57:418-23).

"Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life," wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, these patients’ mean age was 57 years; most (70%) were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Among the heart failure symptoms assessed were plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower left ventricular ejection fractions, and higher NT-proBNP levels, and were less likely to be taking nitrates. A multivariate analysis showed that only NT-proBNP and ejection fraction were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

In a multivariate model, significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) experienced a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3 point or more increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Patients whose BDI was 3 points lower than baseline (indicating an improvement in depression) showed a proportional risk reduction, compared with those with a 2 or less point change (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure. "Exploratory analyses ... suggest that worsening symptoms of depression in heart failure patients may be of particular concern," the authors said. However, they noted, "It is important to note that the observational data reported in the present study do not lend themselves to causal inferences nor to insights into the potential effects of interventions designed to modify symptoms of depression."

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O’Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote in the Jan. 25 issue of the Journal of the American College of Cardiology (2011;57:418-23).

"Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life," wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, these patients’ mean age was 57 years; most (70%) were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Among the heart failure symptoms assessed were plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower left ventricular ejection fractions, and higher NT-proBNP levels, and were less likely to be taking nitrates. A multivariate analysis showed that only NT-proBNP and ejection fraction were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

In a multivariate model, significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) experienced a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3 point or more increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Patients whose BDI was 3 points lower than baseline (indicating an improvement in depression) showed a proportional risk reduction, compared with those with a 2 or less point change (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure. "Exploratory analyses ... suggest that worsening symptoms of depression in heart failure patients may be of particular concern," the authors said. However, they noted, "It is important to note that the observational data reported in the present study do not lend themselves to causal inferences nor to insights into the potential effects of interventions designed to modify symptoms of depression."

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O’Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote in the Jan. 25 issue of the Journal of the American College of Cardiology (2011;57:418-23).

"Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life," wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, these patients’ mean age was 57 years; most (70%) were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Among the heart failure symptoms assessed were plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower left ventricular ejection fractions, and higher NT-proBNP levels, and were less likely to be taking nitrates. A multivariate analysis showed that only NT-proBNP and ejection fraction were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

In a multivariate model, significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) experienced a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3 point or more increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Patients whose BDI was 3 points lower than baseline (indicating an improvement in depression) showed a proportional risk reduction, compared with those with a 2 or less point change (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure. "Exploratory analyses ... suggest that worsening symptoms of depression in heart failure patients may be of particular concern," the authors said. However, they noted, "It is important to note that the observational data reported in the present study do not lend themselves to causal inferences nor to insights into the potential effects of interventions designed to modify symptoms of depression."

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O’Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote in the Jan. 25 issue of the Journal of the American College of Cardiology (2011;57:418-23).

"Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life," wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, these patients’ mean age was 57 years; most (70%) were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Among the heart failure symptoms assessed were plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower left ventricular ejection fractions, and higher NT-proBNP levels, and were less likely to be taking nitrates. A multivariate analysis showed that only NT-proBNP and ejection fraction were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

In a multivariate model, significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) experienced a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3 point or more increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Patients whose BDI was 3 points lower than baseline (indicating an improvement in depression) showed a proportional risk reduction, compared with those with a 2 or less point change (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure. "Exploratory analyses ... suggest that worsening symptoms of depression in heart failure patients may be of particular concern," the authors said. However, they noted, "It is important to note that the observational data reported in the present study do not lend themselves to causal inferences nor to insights into the potential effects of interventions designed to modify symptoms of depression."

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O’Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote in the Jan. 25 issue of the Journal of the American College of Cardiology (2011;57:418-23).

"Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life," wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, these patients’ mean age was 57 years; most (70%) were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Among the heart failure symptoms assessed were plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower left ventricular ejection fractions, and higher NT-proBNP levels, and were less likely to be taking nitrates. A multivariate analysis showed that only NT-proBNP and ejection fraction were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

In a multivariate model, significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) experienced a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3 point or more increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Patients whose BDI was 3 points lower than baseline (indicating an improvement in depression) showed a proportional risk reduction, compared with those with a 2 or less point change (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure. "Exploratory analyses ... suggest that worsening symptoms of depression in heart failure patients may be of particular concern," the authors said. However, they noted, "It is important to note that the observational data reported in the present study do not lend themselves to causal inferences nor to insights into the potential effects of interventions designed to modify symptoms of depression."

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O’Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

Worsening depression is associated with a doubling in the risk of cardiac-related hospitalization or death.

The significant increase in poor cardiovascular outcomes was seen regardless of any changes in the status of heart failure, suggesting that depression exerted the biggest influence on the increased risk, Andrew Sherwood, Ph.D., and his colleagues wrote in the Jan. 25 issue of the Journal of the American College of Cardiology (2011;57:418-23).

"Our findings support the recent American Heart Association position encouraging depression screening, and further suggest that it may be prudent for clinicians to reassess symptoms of depression routinely in heart failure patients who are at increased risk for adverse clinical outcomes and impaired quality of life," wrote Dr. Sherwood of Duke University Medical Center, Durham, N.C., and his coauthors.

The prospective study examined a cohort of 204 outpatients with confirmed heart failure; 27 died during the first year and 30 were unavailable for follow-up. Therefore, 147 were followed for a mean of 5 years. At baseline, these patients’ mean age was 57 years; most (70%) were men. Most had a New York Heart Association functional class of II (69%) or III (37%). The most common baseline medications were beta-blockers (88%) and ACE inhibitors (86%). Antidepressant use occurred in 20% of patients at baseline.

The study was unique among similar investigations because it assessed several clinical aspects of heart failure and depression at baseline and in each of the follow-up years. Among the heart failure symptoms assessed were plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP; mean baseline measure 1,159 pg/mL) and left ventricular ejection fraction (baseline mean 32%).

At baseline, the average score on the Beck Depression Inventory was 10, a level considered clinically significant for depressive symptoms.

Patients who died during the first year had significantly higher resting heart rates, lower left ventricular ejection fractions, and higher NT-proBNP levels, and were less likely to be taking nitrates. A multivariate analysis showed that only NT-proBNP and ejection fraction were significantly associated with early death.

Among the group of 147 followed through 5 years, 127 (86%) either died or were hospitalized (53). Of the deaths, 40 were from cardiac conditions and 15 occurred before any hospitalization.

In a multivariate model, significant risks for cardiac hospitalization or death included cardiac ischemia (hazard ratio 1.84), NT-proBNP increase of 1,000 pg/mL (HR 1.17), and hospitalization within the first year (HR 2.4).

Over the follow-up period, 65 patients (44%) experienced a 2-point change or less in either direction from their baseline BDI score; 43 (29%) showed an increase of 3 or more points in the BDI and 39 (27%) showed a decrease of 3 or more points.

Compared with those whose BDI changed 2 or fewer points, those with a 3 point or more increase were twice as likely to experience cardiac hospitalization or death (HR 2.12), a significant difference. Patients whose BDI was 3 points lower than baseline (indicating an improvement in depression) showed a proportional risk reduction, compared with those with a 2 or less point change (HR 0.87), but this was not a significant association.

The extent of depression at baseline was significantly related to the risk of cardiovascular hospitalization or death, with a 6% increase in risk for every 1-point increase in BDI. The 5-year change in BDI was also significantly related to the poor cardiovascular outcomes, with a 7% increased risk for every 1-point increase in the scale.

The extent of depression at baseline also significantly increased the risk of all-cause hospitalization or mortality, with a 9% increase in risk for every 1-point increase in BDI. The 5-year change in BDI increased the risk of all-cause hospitalization or mortality by 6% for every 1-point increase in BDI.

The relationship between increasing depression and adverse outcome remained significant, even after controlling for the severity of heart failure. "Exploratory analyses ... suggest that worsening symptoms of depression in heart failure patients may be of particular concern," the authors said. However, they noted, "It is important to note that the observational data reported in the present study do not lend themselves to causal inferences nor to insights into the potential effects of interventions designed to modify symptoms of depression."

The study was sponsored by the National Institutes of Health. Dr. Sherwood had no financial declarations, but a coauthor, Dr. Christopher O’Connor, also of Duke University, declared relationships with Merck, Medtronic, Forest, GE Healthcare, Amgen, Medpace, Roche, Actelion, Johnson & Johnson, Novella, and Trevena.

Fluoxetine, in combination with physical rehabilitation, appears to boost motor recovery in patients who have had an acute ischemic stroke.

The mechanism of the benefit isn’t entirely clear and it should not be assumed that all selective serotonin-reuptake inhibitors would exert the same effect, Dr. Francois Chollet and his colleagues reported Jan. 10 in the Lancet Neurology.

"Selective serotonin-reuptake inhibitors are not a uniform category of drugs and further basic science and pharmacology studies will also be needed to increase understanding of their mechanisms of action," wrote Dr. Chollet of the Centre Hospitalier Universitaire de Toulouse (France) and his coauthors (Lancet Neurol. 2011 Jan. 10 [doi:10.1016/S1474-4422(10)70314-8]).

The FLAME trial randomized 118 patients with acute ischemic stroke to either placebo or 20 mg fluoxetine once daily for 3 months. All patients received standard-of-care physical rehabilitation treatment.

The primary end point was a change in the Fugl-Meyer Motor Scale (FMMS), a 100-point scale that rates post-stroke motor recovery, with 0 being flaccid hemiplegia and 100 being normal movement.

Secondary end points included the National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS) and the Montgomery Asberg depression rating scale (MADRS).

The patients’ average age was 66 years. Men and women were similarly represented. The most common comorbidities were hypertension, dyslipidemia, smoking, prior cardiac disease, and diabetes. Stroke location was in the carotid territory in more than 80% of patients. More than half of the group had severe post-stroke disability as measured by the mRS.

There was good study retention in the trial, with two drop-outs in the fluoxetine group and four in the placebo group.

By the end of 90 days, the mean total improvement in FMMS scores in the active group was significantly greater than in the placebo group (36 vs. 22). The difference remained significant after researchers controlled for treatment center, age, stroke history, and baseline FMMS score. Upper and lower limb scores made similar improvements.

When the investigators analyzed the results of 76 patients who did not get thrombolytic therapy after their stroke, the mean improvement in FMMS scores still was significantly higher in the active group (38 vs. 24).

At the end of follow-up, the total NIHSS score was not significantly different between the treatment groups, but the motor component was significantly better in the active group. The mRS improved in both treatment groups but, after adjustment, the between-group difference was not significant.

After 90 days, the mean change in MADRS scores was significantly lower in patients who received fluoxetine than in those who received placebo. The frequency of clinical depression also was significantly lower in the active group (7% vs. 29%). However, the authors pointed out, this probably was not caused by the drug’s antidepressant effects alone. "In a previous study, a single dose of fluoxetine improved hand motor function and increased activity in the motor cortex, compared with placebo in patients recovering from stroke, showing a specific motor effect, whereas a mood effect is unlikely after a single dose."

Adverse events included one death in each group; each was related to the stroke. Other adverse events found in each group were hyponatremia, gastrointestinal symptoms, liver enzyme abnormalities, and psychiatric disorders. There were two serious adverse events in the fluoxetine group (hyponatremia and partial seizure). No patient discontinued therapy because of an adverse event.

Exactly how the antidepressant may benefit stroke patients remains unclear, the authors noted. Studies indicate that animals with a brain injury experience better functional recovery when treated with drugs that affect neurotransmitters. There is even evidence that such drugs might induce structural and physiologic brain changes after the insult. "One hypothesis is that a primary function of the brain serotoninergic system is to facilitate motor output, which emphasizes that the drug intake would be more efficient when paired with [physical] training," the authors wrote.

The study was sponsored by the French Ministry of Health. None of the authors declared any financial conflict.

Fluoxetine, in combination with physical rehabilitation, appears to boost motor recovery in patients who have had an acute ischemic stroke.

The mechanism of the benefit isn’t entirely clear and it should not be assumed that all selective serotonin-reuptake inhibitors would exert the same effect, Dr. Francois Chollet and his colleagues reported Jan. 10 in the Lancet Neurology.

"Selective serotonin-reuptake inhibitors are not a uniform category of drugs and further basic science and pharmacology studies will also be needed to increase understanding of their mechanisms of action," wrote Dr. Chollet of the Centre Hospitalier Universitaire de Toulouse (France) and his coauthors (Lancet Neurol. 2011 Jan. 10 [doi:10.1016/S1474-4422(10)70314-8]).

The FLAME trial randomized 118 patients with acute ischemic stroke to either placebo or 20 mg fluoxetine once daily for 3 months. All patients received standard-of-care physical rehabilitation treatment.

The primary end point was a change in the Fugl-Meyer Motor Scale (FMMS), a 100-point scale that rates post-stroke motor recovery, with 0 being flaccid hemiplegia and 100 being normal movement.

Secondary end points included the National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS) and the Montgomery Asberg depression rating scale (MADRS).

The patients’ average age was 66 years. Men and women were similarly represented. The most common comorbidities were hypertension, dyslipidemia, smoking, prior cardiac disease, and diabetes. Stroke location was in the carotid territory in more than 80% of patients. More than half of the group had severe post-stroke disability as measured by the mRS.

There was good study retention in the trial, with two drop-outs in the fluoxetine group and four in the placebo group.

By the end of 90 days, the mean total improvement in FMMS scores in the active group was significantly greater than in the placebo group (36 vs. 22). The difference remained significant after researchers controlled for treatment center, age, stroke history, and baseline FMMS score. Upper and lower limb scores made similar improvements.

When the investigators analyzed the results of 76 patients who did not get thrombolytic therapy after their stroke, the mean improvement in FMMS scores still was significantly higher in the active group (38 vs. 24).

At the end of follow-up, the total NIHSS score was not significantly different between the treatment groups, but the motor component was significantly better in the active group. The mRS improved in both treatment groups but, after adjustment, the between-group difference was not significant.

After 90 days, the mean change in MADRS scores was significantly lower in patients who received fluoxetine than in those who received placebo. The frequency of clinical depression also was significantly lower in the active group (7% vs. 29%). However, the authors pointed out, this probably was not caused by the drug’s antidepressant effects alone. "In a previous study, a single dose of fluoxetine improved hand motor function and increased activity in the motor cortex, compared with placebo in patients recovering from stroke, showing a specific motor effect, whereas a mood effect is unlikely after a single dose."

Adverse events included one death in each group; each was related to the stroke. Other adverse events found in each group were hyponatremia, gastrointestinal symptoms, liver enzyme abnormalities, and psychiatric disorders. There were two serious adverse events in the fluoxetine group (hyponatremia and partial seizure). No patient discontinued therapy because of an adverse event.

Exactly how the antidepressant may benefit stroke patients remains unclear, the authors noted. Studies indicate that animals with a brain injury experience better functional recovery when treated with drugs that affect neurotransmitters. There is even evidence that such drugs might induce structural and physiologic brain changes after the insult. "One hypothesis is that a primary function of the brain serotoninergic system is to facilitate motor output, which emphasizes that the drug intake would be more efficient when paired with [physical] training," the authors wrote.

The study was sponsored by the French Ministry of Health. None of the authors declared any financial conflict.

Fluoxetine, in combination with physical rehabilitation, appears to boost motor recovery in patients who have had an acute ischemic stroke.

The mechanism of the benefit isn’t entirely clear and it should not be assumed that all selective serotonin-reuptake inhibitors would exert the same effect, Dr. Francois Chollet and his colleagues reported Jan. 10 in the Lancet Neurology.

"Selective serotonin-reuptake inhibitors are not a uniform category of drugs and further basic science and pharmacology studies will also be needed to increase understanding of their mechanisms of action," wrote Dr. Chollet of the Centre Hospitalier Universitaire de Toulouse (France) and his coauthors (Lancet Neurol. 2011 Jan. 10 [doi:10.1016/S1474-4422(10)70314-8]).

The FLAME trial randomized 118 patients with acute ischemic stroke to either placebo or 20 mg fluoxetine once daily for 3 months. All patients received standard-of-care physical rehabilitation treatment.

The primary end point was a change in the Fugl-Meyer Motor Scale (FMMS), a 100-point scale that rates post-stroke motor recovery, with 0 being flaccid hemiplegia and 100 being normal movement.

Secondary end points included the National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS) and the Montgomery Asberg depression rating scale (MADRS).

The patients’ average age was 66 years. Men and women were similarly represented. The most common comorbidities were hypertension, dyslipidemia, smoking, prior cardiac disease, and diabetes. Stroke location was in the carotid territory in more than 80% of patients. More than half of the group had severe post-stroke disability as measured by the mRS.

There was good study retention in the trial, with two drop-outs in the fluoxetine group and four in the placebo group.

By the end of 90 days, the mean total improvement in FMMS scores in the active group was significantly greater than in the placebo group (36 vs. 22). The difference remained significant after researchers controlled for treatment center, age, stroke history, and baseline FMMS score. Upper and lower limb scores made similar improvements.

When the investigators analyzed the results of 76 patients who did not get thrombolytic therapy after their stroke, the mean improvement in FMMS scores still was significantly higher in the active group (38 vs. 24).

At the end of follow-up, the total NIHSS score was not significantly different between the treatment groups, but the motor component was significantly better in the active group. The mRS improved in both treatment groups but, after adjustment, the between-group difference was not significant.

After 90 days, the mean change in MADRS scores was significantly lower in patients who received fluoxetine than in those who received placebo. The frequency of clinical depression also was significantly lower in the active group (7% vs. 29%). However, the authors pointed out, this probably was not caused by the drug’s antidepressant effects alone. "In a previous study, a single dose of fluoxetine improved hand motor function and increased activity in the motor cortex, compared with placebo in patients recovering from stroke, showing a specific motor effect, whereas a mood effect is unlikely after a single dose."

Adverse events included one death in each group; each was related to the stroke. Other adverse events found in each group were hyponatremia, gastrointestinal symptoms, liver enzyme abnormalities, and psychiatric disorders. There were two serious adverse events in the fluoxetine group (hyponatremia and partial seizure). No patient discontinued therapy because of an adverse event.

Exactly how the antidepressant may benefit stroke patients remains unclear, the authors noted. Studies indicate that animals with a brain injury experience better functional recovery when treated with drugs that affect neurotransmitters. There is even evidence that such drugs might induce structural and physiologic brain changes after the insult. "One hypothesis is that a primary function of the brain serotoninergic system is to facilitate motor output, which emphasizes that the drug intake would be more efficient when paired with [physical] training," the authors wrote.

The study was sponsored by the French Ministry of Health. None of the authors declared any financial conflict.

A new law calls for the creation of a national strategic plan to address Alzheimer’s disease and halt the avalanche of new cases that could overwhelm the federal health care system within the next 50 years.

Photo Credit: Wikimedia Commons

Unanimously passed by both the Senate and the House before Christmas, the National Alzheimer’s Project Act (S. 3036) was signed by President Obama Jan. 4.

Under the new law, the Office of the National Alzheimer’s Project will be created within the Health and Human Services department. President Obama will appoint the director, who is to work with an advisory council "to promote research efforts into mechanisms to slow and stop the development of Alzheimer’s for those at risk of developing the disease."

HHS Secretary Kathleen Sebelius expressed her support for the bill on Dec. 15, as it entered its final legislative stages. "I applaud Congress for passing the National Alzheimer’s Project Act with bipartisan support," she said in a statement. "We ... recognize the devastating impact Alzheimer’s has on America’s seniors, families and our health care system. The passage of this act will help to ensure we confront this challenge with an aggressive and coordinated national strategy."

The new advisory council will be tasked with assessing how to address Alzheimer’s on multiple fronts including research, advocacy, patient care, and caregiver support, according to Harry Johns, president of the Alzheimer’s Association.

"The Alzheimer’s Association is pleased that a much-needed plan will now be put into place to address the challenges of Alzheimer’s disease," he said in a statement. "Given the devastation experienced by millions of families because of this disease and the staggering economic costs, particularly to Medicare and Medicaid, we must have an effective strategy now. The fact that Alzheimer’s is the only one of the top 10 causes of death without a way to prevent, cure, or even slow it underscores the critical need for the swift, aggressive implementation of this legislation."

The advisory council will comprise eight federal appointees – including the Surgeon General – as well as 12 expert nonfederal members: two patient advocates, two caregivers, two health care providers, two state health department representatives, two researchers, and two volunteer association representatives.

The council is to meet quarterly and provide Congress with an annual report evaluating all nationally and federally funded efforts in Alzheimer’s research, clinical care, institutional, and home- and community-based programs and their outcomes. The council is also required to provide an annually updated national Alzheimer’s response plan.

The annual reporting requirement might be what sets this plan apart from other similar laws, according to Robert Egge, vice president of public policy and advocacy for the Alzheimer’s Association.

"Some [laws such as this] have mattered very little and some have made very large impacts," he said in an interview. "We think all the elements are here to make this a meaningful piece of legislation. One very important element is the requirement of annual reporting to Congress. This will create an ongoing dialogue we have never had about Alzheimer’s disease, what we are doing about it, and how we are progressing."

Mr. Egge pointed out that the new law may help direct how federal dollars are spent on Alzheimer’s care and research.

"We are already spending an awful lot on this disease - $172 billion per year – but most of that is in a reactive, not proactive way. What this task force will wrestle with is how to spend money in the best, most strategic ways – which will lead to great opportunities for proactive strategies."

Still, the law does not earmark funding for patients, caregivers, support organizations, or research. As such, its intent seems more to draw federal and public attention to the looming Alzheimer’s crisis, rather than directly boost research funding, said Dr. Marwan N. Sabbagh, director of the Cleo Roberts Alzheimer’s and Movement Disorder Clinic at Banner Sun Health Research Institute, Sun City, Ariz.

"Signing the National Alzheimer’s Project Act into law provides an important first step toward developing a framework in which the medical and scientific community, as well as legislators and activists, can tackle this growing epidemic," he said in an interview. "Presently, research in Alzheimer’s is underfunded and current treatment options are limited. This act will increase awareness that address this disease. More needs to be done, however, including a major increase in research funds and emphasis on participation in research studies."

r. Steven T. DeKosky, an Alzheimer’s researcher and medical school dean at the University of Virginia, Charlottesville, agreed – at least in part.

"There is no money in this to do things," he said in an interview. "But research is only one part of what we need. We now know that it’s going to take a lot longer than we thought to find a cure for this and, in the meantime, we have to prepare to take care of a lot of people who are going to develop it."

Building national awareness is probably the first step toward increasing financial support for the disease in any area, said Dr. Richard J. Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz.

"The main thing this does is elevate Alzheimer’s to a visible national debate, and one that also puts it on our social agenda that may catalyze more progressive change," he said in an interview. "And if that means more funding for research, clinical, and community programs, then even better."

A new law calls for the creation of a national strategic plan to address Alzheimer’s disease and halt the avalanche of new cases that could overwhelm the federal health care system within the next 50 years.

Photo Credit: Wikimedia Commons

Unanimously passed by both the Senate and the House before Christmas, the National Alzheimer’s Project Act (S. 3036) was signed by President Obama Jan. 4.

Under the new law, the Office of the National Alzheimer’s Project will be created within the Health and Human Services department. President Obama will appoint the director, who is to work with an advisory council "to promote research efforts into mechanisms to slow and stop the development of Alzheimer’s for those at risk of developing the disease."

HHS Secretary Kathleen Sebelius expressed her support for the bill on Dec. 15, as it entered its final legislative stages. "I applaud Congress for passing the National Alzheimer’s Project Act with bipartisan support," she said in a statement. "We ... recognize the devastating impact Alzheimer’s has on America’s seniors, families and our health care system. The passage of this act will help to ensure we confront this challenge with an aggressive and coordinated national strategy."

The new advisory council will be tasked with assessing how to address Alzheimer’s on multiple fronts including research, advocacy, patient care, and caregiver support, according to Harry Johns, president of the Alzheimer’s Association.

"The Alzheimer’s Association is pleased that a much-needed plan will now be put into place to address the challenges of Alzheimer’s disease," he said in a statement. "Given the devastation experienced by millions of families because of this disease and the staggering economic costs, particularly to Medicare and Medicaid, we must have an effective strategy now. The fact that Alzheimer’s is the only one of the top 10 causes of death without a way to prevent, cure, or even slow it underscores the critical need for the swift, aggressive implementation of this legislation."

The advisory council will comprise eight federal appointees – including the Surgeon General – as well as 12 expert nonfederal members: two patient advocates, two caregivers, two health care providers, two state health department representatives, two researchers, and two volunteer association representatives.

The council is to meet quarterly and provide Congress with an annual report evaluating all nationally and federally funded efforts in Alzheimer’s research, clinical care, institutional, and home- and community-based programs and their outcomes. The council is also required to provide an annually updated national Alzheimer’s response plan.

The annual reporting requirement might be what sets this plan apart from other similar laws, according to Robert Egge, vice president of public policy and advocacy for the Alzheimer’s Association.

"Some [laws such as this] have mattered very little and some have made very large impacts," he said in an interview. "We think all the elements are here to make this a meaningful piece of legislation. One very important element is the requirement of annual reporting to Congress. This will create an ongoing dialogue we have never had about Alzheimer’s disease, what we are doing about it, and how we are progressing."

Mr. Egge pointed out that the new law may help direct how federal dollars are spent on Alzheimer’s care and research.

"We are already spending an awful lot on this disease - $172 billion per year – but most of that is in a reactive, not proactive way. What this task force will wrestle with is how to spend money in the best, most strategic ways – which will lead to great opportunities for proactive strategies."

Still, the law does not earmark funding for patients, caregivers, support organizations, or research. As such, its intent seems more to draw federal and public attention to the looming Alzheimer’s crisis, rather than directly boost research funding, said Dr. Marwan N. Sabbagh, director of the Cleo Roberts Alzheimer’s and Movement Disorder Clinic at Banner Sun Health Research Institute, Sun City, Ariz.

"Signing the National Alzheimer’s Project Act into law provides an important first step toward developing a framework in which the medical and scientific community, as well as legislators and activists, can tackle this growing epidemic," he said in an interview. "Presently, research in Alzheimer’s is underfunded and current treatment options are limited. This act will increase awareness that address this disease. More needs to be done, however, including a major increase in research funds and emphasis on participation in research studies."

r. Steven T. DeKosky, an Alzheimer’s researcher and medical school dean at the University of Virginia, Charlottesville, agreed – at least in part.

"There is no money in this to do things," he said in an interview. "But research is only one part of what we need. We now know that it’s going to take a lot longer than we thought to find a cure for this and, in the meantime, we have to prepare to take care of a lot of people who are going to develop it."

Building national awareness is probably the first step toward increasing financial support for the disease in any area, said Dr. Richard J. Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz.

"The main thing this does is elevate Alzheimer’s to a visible national debate, and one that also puts it on our social agenda that may catalyze more progressive change," he said in an interview. "And if that means more funding for research, clinical, and community programs, then even better."

A new law calls for the creation of a national strategic plan to address Alzheimer’s disease and halt the avalanche of new cases that could overwhelm the federal health care system within the next 50 years.

Photo Credit: Wikimedia Commons

Unanimously passed by both the Senate and the House before Christmas, the National Alzheimer’s Project Act (S. 3036) was signed by President Obama Jan. 4.

Under the new law, the Office of the National Alzheimer’s Project will be created within the Health and Human Services department. President Obama will appoint the director, who is to work with an advisory council "to promote research efforts into mechanisms to slow and stop the development of Alzheimer’s for those at risk of developing the disease."

HHS Secretary Kathleen Sebelius expressed her support for the bill on Dec. 15, as it entered its final legislative stages. "I applaud Congress for passing the National Alzheimer’s Project Act with bipartisan support," she said in a statement. "We ... recognize the devastating impact Alzheimer’s has on America’s seniors, families and our health care system. The passage of this act will help to ensure we confront this challenge with an aggressive and coordinated national strategy."

The new advisory council will be tasked with assessing how to address Alzheimer’s on multiple fronts including research, advocacy, patient care, and caregiver support, according to Harry Johns, president of the Alzheimer’s Association.

"The Alzheimer’s Association is pleased that a much-needed plan will now be put into place to address the challenges of Alzheimer’s disease," he said in a statement. "Given the devastation experienced by millions of families because of this disease and the staggering economic costs, particularly to Medicare and Medicaid, we must have an effective strategy now. The fact that Alzheimer’s is the only one of the top 10 causes of death without a way to prevent, cure, or even slow it underscores the critical need for the swift, aggressive implementation of this legislation."

The advisory council will comprise eight federal appointees – including the Surgeon General – as well as 12 expert nonfederal members: two patient advocates, two caregivers, two health care providers, two state health department representatives, two researchers, and two volunteer association representatives.

The council is to meet quarterly and provide Congress with an annual report evaluating all nationally and federally funded efforts in Alzheimer’s research, clinical care, institutional, and home- and community-based programs and their outcomes. The council is also required to provide an annually updated national Alzheimer’s response plan.

The annual reporting requirement might be what sets this plan apart from other similar laws, according to Robert Egge, vice president of public policy and advocacy for the Alzheimer’s Association.

"Some [laws such as this] have mattered very little and some have made very large impacts," he said in an interview. "We think all the elements are here to make this a meaningful piece of legislation. One very important element is the requirement of annual reporting to Congress. This will create an ongoing dialogue we have never had about Alzheimer’s disease, what we are doing about it, and how we are progressing."

Mr. Egge pointed out that the new law may help direct how federal dollars are spent on Alzheimer’s care and research.

"We are already spending an awful lot on this disease - $172 billion per year – but most of that is in a reactive, not proactive way. What this task force will wrestle with is how to spend money in the best, most strategic ways – which will lead to great opportunities for proactive strategies."

Still, the law does not earmark funding for patients, caregivers, support organizations, or research. As such, its intent seems more to draw federal and public attention to the looming Alzheimer’s crisis, rather than directly boost research funding, said Dr. Marwan N. Sabbagh, director of the Cleo Roberts Alzheimer’s and Movement Disorder Clinic at Banner Sun Health Research Institute, Sun City, Ariz.

"Signing the National Alzheimer’s Project Act into law provides an important first step toward developing a framework in which the medical and scientific community, as well as legislators and activists, can tackle this growing epidemic," he said in an interview. "Presently, research in Alzheimer’s is underfunded and current treatment options are limited. This act will increase awareness that address this disease. More needs to be done, however, including a major increase in research funds and emphasis on participation in research studies."

r. Steven T. DeKosky, an Alzheimer’s researcher and medical school dean at the University of Virginia, Charlottesville, agreed – at least in part.

"There is no money in this to do things," he said in an interview. "But research is only one part of what we need. We now know that it’s going to take a lot longer than we thought to find a cure for this and, in the meantime, we have to prepare to take care of a lot of people who are going to develop it."

Building national awareness is probably the first step toward increasing financial support for the disease in any area, said Dr. Richard J. Caselli, professor of neurology at the Mayo Clinic, Scottsdale, Ariz.

"The main thing this does is elevate Alzheimer’s to a visible national debate, and one that also puts it on our social agenda that may catalyze more progressive change," he said in an interview. "And if that means more funding for research, clinical, and community programs, then even better."

SAN DIEGO - Train them well, pay them well, appreciate them well – and they will provide years of reliable service.

Those are the simple secrets that allow Mohs surgeons to retain their right-hand man or woman: the Mohs technician, Alexander Lutz said at a meeting sponsored by the American Society of Mohs Surgeons.

Paying careful attention to the details that keep a Mohs technician professionally satisfied and secure will pay off in a big way, said Mr. Lutz, the owner of Travel Tech Mohs Services, Carson, Calif. "It’s important to hold on to your technician – because once they get trained, once they get good – they are going to be in high demand. There is always a need for good Mohs techs."

The Mohs surgeon–technician relationship is a unique one in medicine – a symbiotic relationship not seen in other areas. "It’s a rare relationship between and physician and nonphysician, even more so than a surgeon with his surgical nurse or tech," said Mr. Lutz. "The nurse might be helping the surgeon, but you aren’t depending on them to complete the surgery. With a Mohs technician, you are."

No Mohs surgeon, however talented, can perform good Mohs surgery without precise slides as a guide. The technician brings the key element to the table for success in every case. "What happens if you lose your tech to a competitor? Not only are you not doing any Mohs, your competitor is doing more," he said.

Hiring

There are three ways to hire a technician, Mr. Lutz said: Hire and train an in-house full- or part-time person; borrow a technician from a nearby lab or hospital and either pay that person or pay the lab for that person’s time; or use a travelling service to hire a tech for only the days Mohs occurs at the office.

"Probably the most popular way is to hire and train the person in your office," Mr Lutz said. In every state except New York and Rhode Island, the trainee does not have to be a certified histotechnician. "It can be someone you already have on staff – even your office manager."

The "borrowing" technique only works well if the physician is located near a lab or is already affiliated with a hospital. The "mobile tech" option works for physicians who do the surgery occasionally, but this service isn’t available in all states – California and Florida are probably the best-supplied, he said.

The hiring process should be exacting and include several interviews. "One consideration – though it’s not necessary – is whether they already have Mohs experience. Even if you are considering an experienced histotechnician, they might not be familiar with Mohs. They might be more used to bread-loafing a specimen and looking for tumor, rather than the concept of slicing horizontally and getting underneath it."

Interviewing

Key points to consider when interviewing are whether the individual has good manual dexterity, good communication skills, and "a perfectionist personality," he said. "In my experience, good Mohs techs have a couple of things in common. They are all manually dextrous and perfectionists. I always ask if they have a hobby that shows dexterity, like knitting, musical instruments, or even juggling."

It’s hard to overstate the importance of good communication skills, Mr. Lutz stressed. "This is critical. And it’s one reason why I suggest that you do the interviewing yourself. Don’t delegate it to your practice manager. This person will be working with you every day, and it helps unbelievably if you have good communication, if you like the person, if you believe them to be ethical."

Communication is also important because, as a Mohs surgeon, you will be liable for the technician’s errors. "The Clinical Laboratory Improvement Amendments see you as the lab director, so you are inheriting [the technician’s] mistakes, and their liability is your liability.’

If the interviewee is experienced in Mohs, find out what cryostat he or she is most familiar with, or if the person is cross-trained on several." You want someone who is competent on your cryostat or can learn it quickly."

Physical limitations must be taken into account, even though interviewers are not allowed to ask about them on an application. "The way to deal with this is to put it in the job description," Mr. Lutz said. "They need to be able to lift 30 pounds. They need to be able to stand for at least 30 minutes at a time and to do repetitive tasks. If they sign off on all these things, they’re telling you they are able to do them. Then, if it turns out they can’t, this makes it easier to let them go."

Don’t forget the background check, he added. "I’m always amazed at how many people will hire without doing a background check."

Wage and Benefits

To attract and maintain the best person, the physician has to be prepared to offer a competitive wage, an attractive benefits package with health care and retirement, and the promise of continuous training. "An intensive 4-day course is fine, but even the best is not enough to go back and start cutting good slides. Find somewhere to get hold of pig skin – a pig’s foot from a market is fine and will last a whole day – and let the person practice cutting and sectioning 40 hours a week for a couple of weeks. If you let them take one course and expect to start surgery the next week, I can tell you the stress on both of you is going to be unimaginable."

Communication

Good communication is the foundation of success, he said. "This bears repeating. You want to speak diligently to the tech about what’s happening in surgery, and have that person in the surgical suite with you if possible. If you’re doing anything out of the norm of what they usually see – eyelid with a conjunctival margin, ear wedge with cartilage – you have to let them know, or they can mess up the slides."

Don’t expect a tech to make a silk purse out of a sow’s ear, he said. "They need good sections to make the kind of slides you need for diagnosis. Give them sections with complete margins, with beveled edges and clean cuts and at least 1-2 mm of epidermal rim. Specimens with jagged epidermal edges are difficult to lay flat and tend to pull out of the medium much more than a nice circular or oval cut with a 30- to 45-degree bevel."

Training

Pay a lot of attention to training. "Send them to courses as much as possible so they can hone their skills." Included in training should be courses on cryostat maintenance and adjustment. "Let your techs adjust the cryostat themselves. Don’t be afraid to let the tech learn to do that, to recondition the microtome. That way if there’s a maintenance issue, you won’t be dead in the water. Get them the education they need so if there is a problem, they know what to do to solve it."

Finally, he said, as soon as the new tech is competent, have him or her train another person in the office. This might make some people nervous about job security, but it’s a matter of practicality for everyone. "If that person ever wants to go on vacation, he’ll need someone good to cover for him."

SAN DIEGO - Train them well, pay them well, appreciate them well – and they will provide years of reliable service.

Those are the simple secrets that allow Mohs surgeons to retain their right-hand man or woman: the Mohs technician, Alexander Lutz said at a meeting sponsored by the American Society of Mohs Surgeons.

Paying careful attention to the details that keep a Mohs technician professionally satisfied and secure will pay off in a big way, said Mr. Lutz, the owner of Travel Tech Mohs Services, Carson, Calif. "It’s important to hold on to your technician – because once they get trained, once they get good – they are going to be in high demand. There is always a need for good Mohs techs."

The Mohs surgeon–technician relationship is a unique one in medicine – a symbiotic relationship not seen in other areas. "It’s a rare relationship between and physician and nonphysician, even more so than a surgeon with his surgical nurse or tech," said Mr. Lutz. "The nurse might be helping the surgeon, but you aren’t depending on them to complete the surgery. With a Mohs technician, you are."

No Mohs surgeon, however talented, can perform good Mohs surgery without precise slides as a guide. The technician brings the key element to the table for success in every case. "What happens if you lose your tech to a competitor? Not only are you not doing any Mohs, your competitor is doing more," he said.

Hiring

There are three ways to hire a technician, Mr. Lutz said: Hire and train an in-house full- or part-time person; borrow a technician from a nearby lab or hospital and either pay that person or pay the lab for that person’s time; or use a travelling service to hire a tech for only the days Mohs occurs at the office.

"Probably the most popular way is to hire and train the person in your office," Mr Lutz said. In every state except New York and Rhode Island, the trainee does not have to be a certified histotechnician. "It can be someone you already have on staff – even your office manager."

The "borrowing" technique only works well if the physician is located near a lab or is already affiliated with a hospital. The "mobile tech" option works for physicians who do the surgery occasionally, but this service isn’t available in all states – California and Florida are probably the best-supplied, he said.

The hiring process should be exacting and include several interviews. "One consideration – though it’s not necessary – is whether they already have Mohs experience. Even if you are considering an experienced histotechnician, they might not be familiar with Mohs. They might be more used to bread-loafing a specimen and looking for tumor, rather than the concept of slicing horizontally and getting underneath it."

Interviewing

Key points to consider when interviewing are whether the individual has good manual dexterity, good communication skills, and "a perfectionist personality," he said. "In my experience, good Mohs techs have a couple of things in common. They are all manually dextrous and perfectionists. I always ask if they have a hobby that shows dexterity, like knitting, musical instruments, or even juggling."

It’s hard to overstate the importance of good communication skills, Mr. Lutz stressed. "This is critical. And it’s one reason why I suggest that you do the interviewing yourself. Don’t delegate it to your practice manager. This person will be working with you every day, and it helps unbelievably if you have good communication, if you like the person, if you believe them to be ethical."

Communication is also important because, as a Mohs surgeon, you will be liable for the technician’s errors. "The Clinical Laboratory Improvement Amendments see you as the lab director, so you are inheriting [the technician’s] mistakes, and their liability is your liability.’

If the interviewee is experienced in Mohs, find out what cryostat he or she is most familiar with, or if the person is cross-trained on several." You want someone who is competent on your cryostat or can learn it quickly."

Physical limitations must be taken into account, even though interviewers are not allowed to ask about them on an application. "The way to deal with this is to put it in the job description," Mr. Lutz said. "They need to be able to lift 30 pounds. They need to be able to stand for at least 30 minutes at a time and to do repetitive tasks. If they sign off on all these things, they’re telling you they are able to do them. Then, if it turns out they can’t, this makes it easier to let them go."

Don’t forget the background check, he added. "I’m always amazed at how many people will hire without doing a background check."

Wage and Benefits

To attract and maintain the best person, the physician has to be prepared to offer a competitive wage, an attractive benefits package with health care and retirement, and the promise of continuous training. "An intensive 4-day course is fine, but even the best is not enough to go back and start cutting good slides. Find somewhere to get hold of pig skin – a pig’s foot from a market is fine and will last a whole day – and let the person practice cutting and sectioning 40 hours a week for a couple of weeks. If you let them take one course and expect to start surgery the next week, I can tell you the stress on both of you is going to be unimaginable."

Communication

Good communication is the foundation of success, he said. "This bears repeating. You want to speak diligently to the tech about what’s happening in surgery, and have that person in the surgical suite with you if possible. If you’re doing anything out of the norm of what they usually see – eyelid with a conjunctival margin, ear wedge with cartilage – you have to let them know, or they can mess up the slides."

Don’t expect a tech to make a silk purse out of a sow’s ear, he said. "They need good sections to make the kind of slides you need for diagnosis. Give them sections with complete margins, with beveled edges and clean cuts and at least 1-2 mm of epidermal rim. Specimens with jagged epidermal edges are difficult to lay flat and tend to pull out of the medium much more than a nice circular or oval cut with a 30- to 45-degree bevel."

Training

Pay a lot of attention to training. "Send them to courses as much as possible so they can hone their skills." Included in training should be courses on cryostat maintenance and adjustment. "Let your techs adjust the cryostat themselves. Don’t be afraid to let the tech learn to do that, to recondition the microtome. That way if there’s a maintenance issue, you won’t be dead in the water. Get them the education they need so if there is a problem, they know what to do to solve it."

Finally, he said, as soon as the new tech is competent, have him or her train another person in the office. This might make some people nervous about job security, but it’s a matter of practicality for everyone. "If that person ever wants to go on vacation, he’ll need someone good to cover for him."

SAN DIEGO - Train them well, pay them well, appreciate them well – and they will provide years of reliable service.

Those are the simple secrets that allow Mohs surgeons to retain their right-hand man or woman: the Mohs technician, Alexander Lutz said at a meeting sponsored by the American Society of Mohs Surgeons.

Paying careful attention to the details that keep a Mohs technician professionally satisfied and secure will pay off in a big way, said Mr. Lutz, the owner of Travel Tech Mohs Services, Carson, Calif. "It’s important to hold on to your technician – because once they get trained, once they get good – they are going to be in high demand. There is always a need for good Mohs techs."

The Mohs surgeon–technician relationship is a unique one in medicine – a symbiotic relationship not seen in other areas. "It’s a rare relationship between and physician and nonphysician, even more so than a surgeon with his surgical nurse or tech," said Mr. Lutz. "The nurse might be helping the surgeon, but you aren’t depending on them to complete the surgery. With a Mohs technician, you are."

No Mohs surgeon, however talented, can perform good Mohs surgery without precise slides as a guide. The technician brings the key element to the table for success in every case. "What happens if you lose your tech to a competitor? Not only are you not doing any Mohs, your competitor is doing more," he said.

Hiring

There are three ways to hire a technician, Mr. Lutz said: Hire and train an in-house full- or part-time person; borrow a technician from a nearby lab or hospital and either pay that person or pay the lab for that person’s time; or use a travelling service to hire a tech for only the days Mohs occurs at the office.

"Probably the most popular way is to hire and train the person in your office," Mr Lutz said. In every state except New York and Rhode Island, the trainee does not have to be a certified histotechnician. "It can be someone you already have on staff – even your office manager."

The "borrowing" technique only works well if the physician is located near a lab or is already affiliated with a hospital. The "mobile tech" option works for physicians who do the surgery occasionally, but this service isn’t available in all states – California and Florida are probably the best-supplied, he said.

The hiring process should be exacting and include several interviews. "One consideration – though it’s not necessary – is whether they already have Mohs experience. Even if you are considering an experienced histotechnician, they might not be familiar with Mohs. They might be more used to bread-loafing a specimen and looking for tumor, rather than the concept of slicing horizontally and getting underneath it."

Interviewing

Key points to consider when interviewing are whether the individual has good manual dexterity, good communication skills, and "a perfectionist personality," he said. "In my experience, good Mohs techs have a couple of things in common. They are all manually dextrous and perfectionists. I always ask if they have a hobby that shows dexterity, like knitting, musical instruments, or even juggling."

It’s hard to overstate the importance of good communication skills, Mr. Lutz stressed. "This is critical. And it’s one reason why I suggest that you do the interviewing yourself. Don’t delegate it to your practice manager. This person will be working with you every day, and it helps unbelievably if you have good communication, if you like the person, if you believe them to be ethical."

Communication is also important because, as a Mohs surgeon, you will be liable for the technician’s errors. "The Clinical Laboratory Improvement Amendments see you as the lab director, so you are inheriting [the technician’s] mistakes, and their liability is your liability.’

If the interviewee is experienced in Mohs, find out what cryostat he or she is most familiar with, or if the person is cross-trained on several." You want someone who is competent on your cryostat or can learn it quickly."

Physical limitations must be taken into account, even though interviewers are not allowed to ask about them on an application. "The way to deal with this is to put it in the job description," Mr. Lutz said. "They need to be able to lift 30 pounds. They need to be able to stand for at least 30 minutes at a time and to do repetitive tasks. If they sign off on all these things, they’re telling you they are able to do them. Then, if it turns out they can’t, this makes it easier to let them go."

Don’t forget the background check, he added. "I’m always amazed at how many people will hire without doing a background check."

Wage and Benefits

To attract and maintain the best person, the physician has to be prepared to offer a competitive wage, an attractive benefits package with health care and retirement, and the promise of continuous training. "An intensive 4-day course is fine, but even the best is not enough to go back and start cutting good slides. Find somewhere to get hold of pig skin – a pig’s foot from a market is fine and will last a whole day – and let the person practice cutting and sectioning 40 hours a week for a couple of weeks. If you let them take one course and expect to start surgery the next week, I can tell you the stress on both of you is going to be unimaginable."

Communication

Good communication is the foundation of success, he said. "This bears repeating. You want to speak diligently to the tech about what’s happening in surgery, and have that person in the surgical suite with you if possible. If you’re doing anything out of the norm of what they usually see – eyelid with a conjunctival margin, ear wedge with cartilage – you have to let them know, or they can mess up the slides."

Don’t expect a tech to make a silk purse out of a sow’s ear, he said. "They need good sections to make the kind of slides you need for diagnosis. Give them sections with complete margins, with beveled edges and clean cuts and at least 1-2 mm of epidermal rim. Specimens with jagged epidermal edges are difficult to lay flat and tend to pull out of the medium much more than a nice circular or oval cut with a 30- to 45-degree bevel."

Training

Pay a lot of attention to training. "Send them to courses as much as possible so they can hone their skills." Included in training should be courses on cryostat maintenance and adjustment. "Let your techs adjust the cryostat themselves. Don’t be afraid to let the tech learn to do that, to recondition the microtome. That way if there’s a maintenance issue, you won’t be dead in the water. Get them the education they need so if there is a problem, they know what to do to solve it."

Finally, he said, as soon as the new tech is competent, have him or her train another person in the office. This might make some people nervous about job security, but it’s a matter of practicality for everyone. "If that person ever wants to go on vacation, he’ll need someone good to cover for him."

PALM BEACH, Fla. – Isolated chemotherapy made some nonresectable tumors amenable to surgery and relieved pain in those who were not surgical candidates in a series of 75 patients with advanced pelvic carcinomas.

Nearly a third of the patients (22 of 75) responded to the therapy and were able to undergo surgery – adding months to their lives – and those who had the therapy for palliation reported significant pain relief, Dr. Harold Wanebo said at the annual meeting of the Southern Surgical Association.

"Isolated pelvic chemoperfusion (IPP) provides high tissue drug exposure without systemic toxicity, so it gives an excellent opportunity to induce regression of chemoresistant pelvic cancer without severe toxic side effects," he said in an interview.

Dr. Wanebo of the Landmark Medical Center in Woonsocket, R.I., and his colleagues described the results of 134 perfusions performed in 75 patients with advanced pelvic carcinomas. Of those, 59 received the chemoperfusion as neoadjuvant therapy for potentially resectable tumors, and 16 who had nonresectable cancers were given the therapy for palliation of pain.

The therapy is relatively simple, Dr. Wanebo said at the meeting. It starts with an arteriography, during which both balloon-occlusion and infusion catheters are placed into the inferior vena cava through the saphenous femoral vein and into the aorta. Tourniquets around both the upper thighs maintain a high level of chemotherapy agents within the pelvis. Fluoroscopic imaging is used to confirm patency of the catheters, which are then attached to start the infusion.

Patients typically received two treatments, about 30 days apart. Depending on the tumor type, the following agents were administered:

• Paclitaxel 40 mg/m2 plus 5-fluorouracil 1,500-2,000 mg/m2.

• Cisplatin 100 mg/m2 or oxaliplatin 150 mg/m2, with mitomycin (10-20 mg/m2) for epithelial cancers (adenocarcinoma from rectal cancer, squamous cancer of anal canal).

• Paclitaxel (60 mg/m2) and cisplatin (150 mg/m2) for gynecologic cancer (endometrial, ovarian, and bladder cancer).

• Other agents, including doxorubicin, ifosfamide, and phenylalanine mustard (PAM), for melanoma and sarcoma.

Hospital stays ranged from 3 to 4 days. Neutropenia precautions required extended stays (7-12 days).

Advanced rectal cancer was present in 50 patients. Of these, 26 had the procedure as neoadjuvant therapy before a planned pelvic resection; 8 received it for palliation before surgery, and 16 as palliation only after a previous conventional resection. Of the 26 patients, 15 responded with tumors that became locally resectable, and 7 were resected with curative intent. Four required additional surgery to get clear margins. The other 11 patients did not respond to the chemoperfusion therapy; of those, 2 were treated with an implanted infusion device and for 9, the treatment was palliative.

Eight of the 26 patients had an anorectal squamous cell cancer. Of those, five became eligible for surgery and underwent resection, which resulted in a median survival of 15 months and a mean survival of 31 months; one patient was living without disease at 119 months.

Eight of the 26 patients developed resectable tumors but were not resected. Of those, one with sacral invasion had a pathological complete response; the posttreatment biopsy was negative and the planned resection was aborted. Two patients were medically inoperable; three refused the abdominal sacral resection; and two developed pelvic metastases that precluded resection.

Those who had resections survived for a median of 30 months, and those who had treatment for palliation only survived a median of 8 months.

Complications in a small number of patients included a vascular-arterial intraoperative repair, locoregional edema, scrotal edema, ileus with small bowel obstruction, groin hematoma, bladder dysfunction, hematuria, and incontinence. A larger number of patients experienced hematologic problems such as anemia, neutropenia, and thrombocytopenia. Systemic complications included temporary extremity weakness, bronchospasm, and venous thrombosis.

One patient with advanced endometrial cancer died on postprocedure day 7, and two with recurrent rectal cancer died postoperatively on days 8 and 10 after experiencing symptoms such as fever, sepsis, and neutropenia. "This emphasizes need to carefully monitor patients for 9-11 days after IPP to ensure against neutropenia, which can be fatal if not treated properly," Dr. Wanebo said.

Some cancers – such as recurrent rectal cancer, anorectal squamous cell cancers, gynecologic cancers, and melanoma – seemed to respond better to the treatment, Dr. Wanebo said. Patients with sarcoma did not respond as well.

All of the patients who were perfused for palliation experienced significant pain relief lasting for up to 4 months, including 11 of the 14 whose pain had been narcotic resistant. This was probably because the perfusion therapy halted or regressed perineural invasions.

"In these resection specimens, you often see tumor invasion of the nerve roots," Dr. Wanebo said. "It’s really not clear whether the IPP affects this invasion, or somehow disturbs the neural signaling, but the pain relief is significant," he said, adding that the importance of pain relief for patients with advanced cancers can’t be overstated.

Dr. Wanebo had no financial disclosures.

PALM BEACH, Fla. – Isolated chemotherapy made some nonresectable tumors amenable to surgery and relieved pain in those who were not surgical candidates in a series of 75 patients with advanced pelvic carcinomas.

Nearly a third of the patients (22 of 75) responded to the therapy and were able to undergo surgery – adding months to their lives – and those who had the therapy for palliation reported significant pain relief, Dr. Harold Wanebo said at the annual meeting of the Southern Surgical Association.

"Isolated pelvic chemoperfusion (IPP) provides high tissue drug exposure without systemic toxicity, so it gives an excellent opportunity to induce regression of chemoresistant pelvic cancer without severe toxic side effects," he said in an interview.

Dr. Wanebo of the Landmark Medical Center in Woonsocket, R.I., and his colleagues described the results of 134 perfusions performed in 75 patients with advanced pelvic carcinomas. Of those, 59 received the chemoperfusion as neoadjuvant therapy for potentially resectable tumors, and 16 who had nonresectable cancers were given the therapy for palliation of pain.

The therapy is relatively simple, Dr. Wanebo said at the meeting. It starts with an arteriography, during which both balloon-occlusion and infusion catheters are placed into the inferior vena cava through the saphenous femoral vein and into the aorta. Tourniquets around both the upper thighs maintain a high level of chemotherapy agents within the pelvis. Fluoroscopic imaging is used to confirm patency of the catheters, which are then attached to start the infusion.

Patients typically received two treatments, about 30 days apart. Depending on the tumor type, the following agents were administered:

• Paclitaxel 40 mg/m2 plus 5-fluorouracil 1,500-2,000 mg/m2.

• Cisplatin 100 mg/m2 or oxaliplatin 150 mg/m2, with mitomycin (10-20 mg/m2) for epithelial cancers (adenocarcinoma from rectal cancer, squamous cancer of anal canal).

• Paclitaxel (60 mg/m2) and cisplatin (150 mg/m2) for gynecologic cancer (endometrial, ovarian, and bladder cancer).

• Other agents, including doxorubicin, ifosfamide, and phenylalanine mustard (PAM), for melanoma and sarcoma.

Hospital stays ranged from 3 to 4 days. Neutropenia precautions required extended stays (7-12 days).

Advanced rectal cancer was present in 50 patients. Of these, 26 had the procedure as neoadjuvant therapy before a planned pelvic resection; 8 received it for palliation before surgery, and 16 as palliation only after a previous conventional resection. Of the 26 patients, 15 responded with tumors that became locally resectable, and 7 were resected with curative intent. Four required additional surgery to get clear margins. The other 11 patients did not respond to the chemoperfusion therapy; of those, 2 were treated with an implanted infusion device and for 9, the treatment was palliative.

Eight of the 26 patients had an anorectal squamous cell cancer. Of those, five became eligible for surgery and underwent resection, which resulted in a median survival of 15 months and a mean survival of 31 months; one patient was living without disease at 119 months.

Eight of the 26 patients developed resectable tumors but were not resected. Of those, one with sacral invasion had a pathological complete response; the posttreatment biopsy was negative and the planned resection was aborted. Two patients were medically inoperable; three refused the abdominal sacral resection; and two developed pelvic metastases that precluded resection.

Those who had resections survived for a median of 30 months, and those who had treatment for palliation only survived a median of 8 months.

Complications in a small number of patients included a vascular-arterial intraoperative repair, locoregional edema, scrotal edema, ileus with small bowel obstruction, groin hematoma, bladder dysfunction, hematuria, and incontinence. A larger number of patients experienced hematologic problems such as anemia, neutropenia, and thrombocytopenia. Systemic complications included temporary extremity weakness, bronchospasm, and venous thrombosis.

One patient with advanced endometrial cancer died on postprocedure day 7, and two with recurrent rectal cancer died postoperatively on days 8 and 10 after experiencing symptoms such as fever, sepsis, and neutropenia. "This emphasizes need to carefully monitor patients for 9-11 days after IPP to ensure against neutropenia, which can be fatal if not treated properly," Dr. Wanebo said.

Some cancers – such as recurrent rectal cancer, anorectal squamous cell cancers, gynecologic cancers, and melanoma – seemed to respond better to the treatment, Dr. Wanebo said. Patients with sarcoma did not respond as well.

All of the patients who were perfused for palliation experienced significant pain relief lasting for up to 4 months, including 11 of the 14 whose pain had been narcotic resistant. This was probably because the perfusion therapy halted or regressed perineural invasions.

"In these resection specimens, you often see tumor invasion of the nerve roots," Dr. Wanebo said. "It’s really not clear whether the IPP affects this invasion, or somehow disturbs the neural signaling, but the pain relief is significant," he said, adding that the importance of pain relief for patients with advanced cancers can’t be overstated.

Dr. Wanebo had no financial disclosures.

PALM BEACH, Fla. – Isolated chemotherapy made some nonresectable tumors amenable to surgery and relieved pain in those who were not surgical candidates in a series of 75 patients with advanced pelvic carcinomas.

Nearly a third of the patients (22 of 75) responded to the therapy and were able to undergo surgery – adding months to their lives – and those who had the therapy for palliation reported significant pain relief, Dr. Harold Wanebo said at the annual meeting of the Southern Surgical Association.

"Isolated pelvic chemoperfusion (IPP) provides high tissue drug exposure without systemic toxicity, so it gives an excellent opportunity to induce regression of chemoresistant pelvic cancer without severe toxic side effects," he said in an interview.

Dr. Wanebo of the Landmark Medical Center in Woonsocket, R.I., and his colleagues described the results of 134 perfusions performed in 75 patients with advanced pelvic carcinomas. Of those, 59 received the chemoperfusion as neoadjuvant therapy for potentially resectable tumors, and 16 who had nonresectable cancers were given the therapy for palliation of pain.

The therapy is relatively simple, Dr. Wanebo said at the meeting. It starts with an arteriography, during which both balloon-occlusion and infusion catheters are placed into the inferior vena cava through the saphenous femoral vein and into the aorta. Tourniquets around both the upper thighs maintain a high level of chemotherapy agents within the pelvis. Fluoroscopic imaging is used to confirm patency of the catheters, which are then attached to start the infusion.

Patients typically received two treatments, about 30 days apart. Depending on the tumor type, the following agents were administered:

• Paclitaxel 40 mg/m2 plus 5-fluorouracil 1,500-2,000 mg/m2.

• Cisplatin 100 mg/m2 or oxaliplatin 150 mg/m2, with mitomycin (10-20 mg/m2) for epithelial cancers (adenocarcinoma from rectal cancer, squamous cancer of anal canal).

• Paclitaxel (60 mg/m2) and cisplatin (150 mg/m2) for gynecologic cancer (endometrial, ovarian, and bladder cancer).

• Other agents, including doxorubicin, ifosfamide, and phenylalanine mustard (PAM), for melanoma and sarcoma.

Hospital stays ranged from 3 to 4 days. Neutropenia precautions required extended stays (7-12 days).

Advanced rectal cancer was present in 50 patients. Of these, 26 had the procedure as neoadjuvant therapy before a planned pelvic resection; 8 received it for palliation before surgery, and 16 as palliation only after a previous conventional resection. Of the 26 patients, 15 responded with tumors that became locally resectable, and 7 were resected with curative intent. Four required additional surgery to get clear margins. The other 11 patients did not respond to the chemoperfusion therapy; of those, 2 were treated with an implanted infusion device and for 9, the treatment was palliative.

Eight of the 26 patients had an anorectal squamous cell cancer. Of those, five became eligible for surgery and underwent resection, which resulted in a median survival of 15 months and a mean survival of 31 months; one patient was living without disease at 119 months.

Eight of the 26 patients developed resectable tumors but were not resected. Of those, one with sacral invasion had a pathological complete response; the posttreatment biopsy was negative and the planned resection was aborted. Two patients were medically inoperable; three refused the abdominal sacral resection; and two developed pelvic metastases that precluded resection.

Those who had resections survived for a median of 30 months, and those who had treatment for palliation only survived a median of 8 months.

Complications in a small number of patients included a vascular-arterial intraoperative repair, locoregional edema, scrotal edema, ileus with small bowel obstruction, groin hematoma, bladder dysfunction, hematuria, and incontinence. A larger number of patients experienced hematologic problems such as anemia, neutropenia, and thrombocytopenia. Systemic complications included temporary extremity weakness, bronchospasm, and venous thrombosis.

One patient with advanced endometrial cancer died on postprocedure day 7, and two with recurrent rectal cancer died postoperatively on days 8 and 10 after experiencing symptoms such as fever, sepsis, and neutropenia. "This emphasizes need to carefully monitor patients for 9-11 days after IPP to ensure against neutropenia, which can be fatal if not treated properly," Dr. Wanebo said.

Some cancers – such as recurrent rectal cancer, anorectal squamous cell cancers, gynecologic cancers, and melanoma – seemed to respond better to the treatment, Dr. Wanebo said. Patients with sarcoma did not respond as well.

All of the patients who were perfused for palliation experienced significant pain relief lasting for up to 4 months, including 11 of the 14 whose pain had been narcotic resistant. This was probably because the perfusion therapy halted or regressed perineural invasions.

"In these resection specimens, you often see tumor invasion of the nerve roots," Dr. Wanebo said. "It’s really not clear whether the IPP affects this invasion, or somehow disturbs the neural signaling, but the pain relief is significant," he said, adding that the importance of pain relief for patients with advanced cancers can’t be overstated.

Dr. Wanebo had no financial disclosures.

A 2-week course of rifaximin was associated with adequate relief of irritable bowel syndrome symptoms for the first 4 weeks after completion of therapy in 41% of patients who had IBS without constipation.

The results of two identical phase III placebo-controlled studies, TARGET 1 and TARGET 2, were similar overall, Dr. Mark Pimentel and his colleagues wrote in the Jan. 6 issue of the New England Journal of Medicine (2011;364:22-32).

TARGET 1 found that 41% of those taking rifaximin reported adequate relief of their global IBS symptoms, compared with 31% of those taking placebo (P = .01), for at least 2 of the first 4 weeks after treatment ended. In TARGET 2, those numbers were 41% vs. 32% (P = .03), and for the two studies combined the results were also 41% vs. 32%, respectively (P less than .001).

Rifaximin, a poorly absorbed broad-spectrum antibiotic, may work by controlling bacterial overgrowth in the gut, wrote Dr. Pimentel of the Cedars–Sinai Medical Center, Los Angeles, and his colleagues. However, the authors explained, "Some patients in both of our studies did not have a response to treatment, a finding that is consistent with the results of other placebo-controlled clinical trials involving patients with IBS and that may reflect differences in the underlying cause of the symptoms."

Both studies were funded by Salix Pharmaceuticals, the drug’s manufacturer. They included a total of 1,260 patients (623 in TARGET 1 and 637 in TARGET 2). All patients were randomized to 14 days of either placebo or 550 mg rifaximin three times daily and were followed weekly for 10 additional weeks. Study retention was high, with 90% completing the entire trial. Last-results carried forward were used in a secondary analysis.

The patients’ average age was 46 years in each group. Overall, most patients (about 72%) were female, and 91% were white. All had IBS without constipation, with an average duration of 11-12 years.

Patients eligible for the study rated their IBS symptoms of abdominal pain and bloating as a 2-4.5 on a 7-point Likert scale (where 0 = not at all, and 6 = a very great deal). Most patients (82%) reported daily stool urgency.

The primary end point was adequate relief of global IBS symptoms, which patients answered with "yes" or "no." The authors prospectively determined the threshold of "adequate relief" as a score of 0 or 1 for at least 50% of days in a given week and 1 or 2 for 100% of the days in a given week. Additionally, patients were asked to rate relief of bloating, abdominal pain and discomfort, and daily stool consistency.

Overall, significantly more patients in the active group than the placebo group met the primary end point (41% vs. 32%). The secondary analysis with last observation carried forward yielded similar results.

In the two studies combined, significantly more patients in the active group than the placebo group reported adequate relief of bloating for at least 2 of the first 4 weeks after treatment (40% vs. 30%; P less than .001). For the composite end point of abdominal pain or discomfort and loose or watery stools during this time period, significantly more patients treated with rifaximin had relief, compared with placebo-group patients (TARGET 1: 47% vs. 39%, P = .04; TARGET 2: 47% vs. 36%, P = .008).

In an analysis of durability of response based on a weekly assessment, "more patients in the rifaximin group than in the placebo group in both studies had adequate relief of global IBS symptoms within the first month, with continued relief during the first 2 months and during all 3 months in both studies," the authors wrote, noting that the difference was significant at P less than .001 for both studies combined, for relief during all 3 months.

The authors provided a supplementary appendix containing graphs showing that the percentage of patients with adequate relief of global IBS symptoms declined in both groups, in both studies, during the 10 weeks after treatment.

Two patients in the rifaximin group and five in the placebo group had serious adverse events. The incidence of infections was similar in the two groups. There were no cases of ischemic colitis and no deaths.

Regarding the mechanism of action, the authors noted several possible pathways. Besides altering the balance of the gut flora, the drug might also decrease gas associated with bacterial activity, reduce local inflammatory response to bacteria, or alter both the bacteria and host response.

"Whatever the final pathway, the durable effects suggest that rifaximin is affecting an underlying cause of IBS that is linked to an alteration in the intestinal microbiota," they said.

In an accompanying editorial, Dr. Jan Tack of the University of Leuven, Belgium, noted the declining durability of rifaximin’s effect and the relatively small difference between the active and placebo responses. "The therapeutic gain, with the rates of response to treatment (i.e., adequate relief) ranging between 9 and 12% more with rifaximin than with placebo, is in the lower spectrum of what is considered to be clinically relevant," he wrote. Dr. Tack also noted that since IBS is a chronic disorder, the follow-up period was relatively short (N. Eng. J. Med. 2011;364:81-2).

Despite the studies’ positive findings, including the favorable safety profile, he wrote that, "clinicians should proceed with caution." Although "rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents that are available to treat IBS," he also wrote that, "taking into account the high prevalence of IBS in the general population, the effect that larger-scale use of poorly absorbed antibiotics may have on antibiotic-resistance profiles should be taken into account."

Until researchers are able to identify a subgroup of patients that might respond well to the drug, "It seems prudent to restrict the use of nonabsorbable antibiotics to patients in whom small-intestine bacterial overgrowth has been confirmed, or to single treatment cycles in patients who have IBS without constipation and who have not had a response to currently available symptom-directed therapies," Dr. Tack wrote.

All of the paper’s authors reported financial relationships with Salix, either in the form of grants, payment for producing educational materials, travel expenses, speakers fees, company stock, or company employment. Cedars–Sinai Medical Center, employer of Dr. Pimentel, holds patents licensed by Salix Pharmaceuticals. Dr. Tack reported no financial relationship with Salix.

A 2-week course of rifaximin was associated with adequate relief of irritable bowel syndrome symptoms for the first 4 weeks after completion of therapy in 41% of patients who had IBS without constipation.

The results of two identical phase III placebo-controlled studies, TARGET 1 and TARGET 2, were similar overall, Dr. Mark Pimentel and his colleagues wrote in the Jan. 6 issue of the New England Journal of Medicine (2011;364:22-32).

TARGET 1 found that 41% of those taking rifaximin reported adequate relief of their global IBS symptoms, compared with 31% of those taking placebo (P = .01), for at least 2 of the first 4 weeks after treatment ended. In TARGET 2, those numbers were 41% vs. 32% (P = .03), and for the two studies combined the results were also 41% vs. 32%, respectively (P less than .001).

Rifaximin, a poorly absorbed broad-spectrum antibiotic, may work by controlling bacterial overgrowth in the gut, wrote Dr. Pimentel of the Cedars–Sinai Medical Center, Los Angeles, and his colleagues. However, the authors explained, "Some patients in both of our studies did not have a response to treatment, a finding that is consistent with the results of other placebo-controlled clinical trials involving patients with IBS and that may reflect differences in the underlying cause of the symptoms."

Both studies were funded by Salix Pharmaceuticals, the drug’s manufacturer. They included a total of 1,260 patients (623 in TARGET 1 and 637 in TARGET 2). All patients were randomized to 14 days of either placebo or 550 mg rifaximin three times daily and were followed weekly for 10 additional weeks. Study retention was high, with 90% completing the entire trial. Last-results carried forward were used in a secondary analysis.

The patients’ average age was 46 years in each group. Overall, most patients (about 72%) were female, and 91% were white. All had IBS without constipation, with an average duration of 11-12 years.

Patients eligible for the study rated their IBS symptoms of abdominal pain and bloating as a 2-4.5 on a 7-point Likert scale (where 0 = not at all, and 6 = a very great deal). Most patients (82%) reported daily stool urgency.

The primary end point was adequate relief of global IBS symptoms, which patients answered with "yes" or "no." The authors prospectively determined the threshold of "adequate relief" as a score of 0 or 1 for at least 50% of days in a given week and 1 or 2 for 100% of the days in a given week. Additionally, patients were asked to rate relief of bloating, abdominal pain and discomfort, and daily stool consistency.

Overall, significantly more patients in the active group than the placebo group met the primary end point (41% vs. 32%). The secondary analysis with last observation carried forward yielded similar results.

In the two studies combined, significantly more patients in the active group than the placebo group reported adequate relief of bloating for at least 2 of the first 4 weeks after treatment (40% vs. 30%; P less than .001). For the composite end point of abdominal pain or discomfort and loose or watery stools during this time period, significantly more patients treated with rifaximin had relief, compared with placebo-group patients (TARGET 1: 47% vs. 39%, P = .04; TARGET 2: 47% vs. 36%, P = .008).

In an analysis of durability of response based on a weekly assessment, "more patients in the rifaximin group than in the placebo group in both studies had adequate relief of global IBS symptoms within the first month, with continued relief during the first 2 months and during all 3 months in both studies," the authors wrote, noting that the difference was significant at P less than .001 for both studies combined, for relief during all 3 months.

The authors provided a supplementary appendix containing graphs showing that the percentage of patients with adequate relief of global IBS symptoms declined in both groups, in both studies, during the 10 weeks after treatment.

Two patients in the rifaximin group and five in the placebo group had serious adverse events. The incidence of infections was similar in the two groups. There were no cases of ischemic colitis and no deaths.

Regarding the mechanism of action, the authors noted several possible pathways. Besides altering the balance of the gut flora, the drug might also decrease gas associated with bacterial activity, reduce local inflammatory response to bacteria, or alter both the bacteria and host response.

"Whatever the final pathway, the durable effects suggest that rifaximin is affecting an underlying cause of IBS that is linked to an alteration in the intestinal microbiota," they said.

In an accompanying editorial, Dr. Jan Tack of the University of Leuven, Belgium, noted the declining durability of rifaximin’s effect and the relatively small difference between the active and placebo responses. "The therapeutic gain, with the rates of response to treatment (i.e., adequate relief) ranging between 9 and 12% more with rifaximin than with placebo, is in the lower spectrum of what is considered to be clinically relevant," he wrote. Dr. Tack also noted that since IBS is a chronic disorder, the follow-up period was relatively short (N. Eng. J. Med. 2011;364:81-2).

Despite the studies’ positive findings, including the favorable safety profile, he wrote that, "clinicians should proceed with caution." Although "rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents that are available to treat IBS," he also wrote that, "taking into account the high prevalence of IBS in the general population, the effect that larger-scale use of poorly absorbed antibiotics may have on antibiotic-resistance profiles should be taken into account."

Until researchers are able to identify a subgroup of patients that might respond well to the drug, "It seems prudent to restrict the use of nonabsorbable antibiotics to patients in whom small-intestine bacterial overgrowth has been confirmed, or to single treatment cycles in patients who have IBS without constipation and who have not had a response to currently available symptom-directed therapies," Dr. Tack wrote.

All of the paper’s authors reported financial relationships with Salix, either in the form of grants, payment for producing educational materials, travel expenses, speakers fees, company stock, or company employment. Cedars–Sinai Medical Center, employer of Dr. Pimentel, holds patents licensed by Salix Pharmaceuticals. Dr. Tack reported no financial relationship with Salix.

A 2-week course of rifaximin was associated with adequate relief of irritable bowel syndrome symptoms for the first 4 weeks after completion of therapy in 41% of patients who had IBS without constipation.

The results of two identical phase III placebo-controlled studies, TARGET 1 and TARGET 2, were similar overall, Dr. Mark Pimentel and his colleagues wrote in the Jan. 6 issue of the New England Journal of Medicine (2011;364:22-32).

TARGET 1 found that 41% of those taking rifaximin reported adequate relief of their global IBS symptoms, compared with 31% of those taking placebo (P = .01), for at least 2 of the first 4 weeks after treatment ended. In TARGET 2, those numbers were 41% vs. 32% (P = .03), and for the two studies combined the results were also 41% vs. 32%, respectively (P less than .001).

Rifaximin, a poorly absorbed broad-spectrum antibiotic, may work by controlling bacterial overgrowth in the gut, wrote Dr. Pimentel of the Cedars–Sinai Medical Center, Los Angeles, and his colleagues. However, the authors explained, "Some patients in both of our studies did not have a response to treatment, a finding that is consistent with the results of other placebo-controlled clinical trials involving patients with IBS and that may reflect differences in the underlying cause of the symptoms."

Both studies were funded by Salix Pharmaceuticals, the drug’s manufacturer. They included a total of 1,260 patients (623 in TARGET 1 and 637 in TARGET 2). All patients were randomized to 14 days of either placebo or 550 mg rifaximin three times daily and were followed weekly for 10 additional weeks. Study retention was high, with 90% completing the entire trial. Last-results carried forward were used in a secondary analysis.

The patients’ average age was 46 years in each group. Overall, most patients (about 72%) were female, and 91% were white. All had IBS without constipation, with an average duration of 11-12 years.

Patients eligible for the study rated their IBS symptoms of abdominal pain and bloating as a 2-4.5 on a 7-point Likert scale (where 0 = not at all, and 6 = a very great deal). Most patients (82%) reported daily stool urgency.

The primary end point was adequate relief of global IBS symptoms, which patients answered with "yes" or "no." The authors prospectively determined the threshold of "adequate relief" as a score of 0 or 1 for at least 50% of days in a given week and 1 or 2 for 100% of the days in a given week. Additionally, patients were asked to rate relief of bloating, abdominal pain and discomfort, and daily stool consistency.

Overall, significantly more patients in the active group than the placebo group met the primary end point (41% vs. 32%). The secondary analysis with last observation carried forward yielded similar results.

In the two studies combined, significantly more patients in the active group than the placebo group reported adequate relief of bloating for at least 2 of the first 4 weeks after treatment (40% vs. 30%; P less than .001). For the composite end point of abdominal pain or discomfort and loose or watery stools during this time period, significantly more patients treated with rifaximin had relief, compared with placebo-group patients (TARGET 1: 47% vs. 39%, P = .04; TARGET 2: 47% vs. 36%, P = .008).

In an analysis of durability of response based on a weekly assessment, "more patients in the rifaximin group than in the placebo group in both studies had adequate relief of global IBS symptoms within the first month, with continued relief during the first 2 months and during all 3 months in both studies," the authors wrote, noting that the difference was significant at P less than .001 for both studies combined, for relief during all 3 months.

The authors provided a supplementary appendix containing graphs showing that the percentage of patients with adequate relief of global IBS symptoms declined in both groups, in both studies, during the 10 weeks after treatment.

Two patients in the rifaximin group and five in the placebo group had serious adverse events. The incidence of infections was similar in the two groups. There were no cases of ischemic colitis and no deaths.

Regarding the mechanism of action, the authors noted several possible pathways. Besides altering the balance of the gut flora, the drug might also decrease gas associated with bacterial activity, reduce local inflammatory response to bacteria, or alter both the bacteria and host response.

"Whatever the final pathway, the durable effects suggest that rifaximin is affecting an underlying cause of IBS that is linked to an alteration in the intestinal microbiota," they said.

In an accompanying editorial, Dr. Jan Tack of the University of Leuven, Belgium, noted the declining durability of rifaximin’s effect and the relatively small difference between the active and placebo responses. "The therapeutic gain, with the rates of response to treatment (i.e., adequate relief) ranging between 9 and 12% more with rifaximin than with placebo, is in the lower spectrum of what is considered to be clinically relevant," he wrote. Dr. Tack also noted that since IBS is a chronic disorder, the follow-up period was relatively short (N. Eng. J. Med. 2011;364:81-2).

Despite the studies’ positive findings, including the favorable safety profile, he wrote that, "clinicians should proceed with caution." Although "rifaximin has the potential to provide a welcome addition to the limited armamentarium of agents that are available to treat IBS," he also wrote that, "taking into account the high prevalence of IBS in the general population, the effect that larger-scale use of poorly absorbed antibiotics may have on antibiotic-resistance profiles should be taken into account."

Until researchers are able to identify a subgroup of patients that might respond well to the drug, "It seems prudent to restrict the use of nonabsorbable antibiotics to patients in whom small-intestine bacterial overgrowth has been confirmed, or to single treatment cycles in patients who have IBS without constipation and who have not had a response to currently available symptom-directed therapies," Dr. Tack wrote.

All of the paper’s authors reported financial relationships with Salix, either in the form of grants, payment for producing educational materials, travel expenses, speakers fees, company stock, or company employment. Cedars–Sinai Medical Center, employer of Dr. Pimentel, holds patents licensed by Salix Pharmaceuticals. Dr. Tack reported no financial relationship with Salix.