Doug Brunk

Emerging endoluminal techniques and devices intended for weight loss therapy may reduce the risk of morbidity and mortality associated with current bariatric surgery approaches, according to the research findings of Dr. Philip Schauer and his associates.

The use of endoluminal approaches to avoid any type of abdominal incision and, more importantly, any intra-abdominal dissection “may go a long way to further reduce the morbidity of these operations, making them cheaper and safer,” said Dr. Schauer in an interview. “They may expand the access for patients. Only 1% of patients with severe obesity are actually getting access to surgery, which is the only known therapy to be effective for a large percentage of patients.”

Dr. Schauer, director of advanced laparoscopic and bariatric surgery at the bariatric and metabolic institute of the Cleveland Clinic, and his associates categorized the current endoluminal methods for weight loss therapy as presurgical endoluminal therapy, postsurgical endoluminal revision procedures, and primary procedures (Surg. Endosc. 2007;21:347–56).

In the presurgical endoluminal therapy arena, Dr. Michel Gagner and his associates pioneered a two-stage operation consisting of a sleeve gastrectomy followed by a Roux-en-Y gastric bypass (RYGB) or a duodenal switch (Obes. Surg. 2003;13:861–4).

“The rationale is that the first-stage operation, sleeve gastrectomy, is comparatively simple (requiring no anasto- mosis), needs less operative time (1–2 hours), and results in a predictable 40- to 50-kg weight loss,” Dr. Schauer and his associates wrote in their review. “Such weight loss reduces the operative risk for the second-stage procedure, which presumably results in more weight loss and greater durability.”

Dr. Gagner, professor of surgery and chief of bariatric surgery at Cornell University, New York, and his associates were also the first to publish results of an approach using the placement of endoluminal duodenojejunal tube or plastic sleeve to the first part of the duodenum proximal to the ampulla of Vater in pigs as a weight-loss strategy (Obes. Surg. 2006;16:620–6). This study, which demonstrated good weight loss in pigs, was the basis for the first human trial reported by Dr. Leonardo Rodriguez and his associates at the annual meeting of the American Society for Metabolic and Bariatric Surgery (formerly the American Society for Bariatric Surgery) in June 2007.

In the human trial, 12 patients from Chile and Brazil, including four with diabetes, underwent placement of a 61-cm endoluminal duodenojejunal tube or plastic sleeve that was anchored endoscopically in the duodenum and removed after 12 weeks. All of the patients achieved an estimated weight loss of at least 10%, and 10 of the 12 patients lost an estimated 24% of their weight. None of the diabetic patients required hypoglycemic medications.

“By diverting the flow of food from the duodenum and the proximal jejunum, we might be able to change some of the GI hormones that may switch the diabetes to reverse itself,” Dr. Gagner said.

In other studies of presurgical endoluminal therapy, the intragastric balloon developed by BioEnterics Corp. has been used successfully as a first-stage procedure to reduce presurgical weight and perioperative risk in superobese patients, but clinical results are limited.

In the arena of postsurgical endoluminal revision procedures, small studies of C.R. Bard Inc.'s EndoCinch suturing system and endoscopic suturing device have demonstrated promising results.

Dr. Christopher C. Thompson and his associates used the EndoCinch suturing system in eight patients who had undergone RYGB but had regained an average of 24 kg from baseline (Surg. Obes. Relat. Dis. 2005;1:223). At 4 months after undergoing the procedure, six of the eight patients had lost an average of 10 kg, and four reported significant improvements in satiety.

Such suturing procedures hold promise, Dr. Schauer said, because “they emulate gastric restriction, a concept that has been proven over several decades.”

Dr. Schauer disclosed that he is a paid consultant for Bard, Davol, Ethicon Endo-Surgery Inc., Stryker Endoscopy, Baxter International Inc., W.L. Gore & Associates Inc., and Barosense Inc.

Dr. Gagner disclosed that he is a scientific adviser for GI Dynamics Inc. He has also received research grants from Covidien AG, Olympus America Inc., and Bard.

With the flow of food diverted, GI hormones may change enoughto cause the diabetes to reverse itself. DR. GAGNER

Emerging endoluminal techniques and devices intended for weight loss therapy may reduce the risk of morbidity and mortality associated with current bariatric surgery approaches, according to the research findings of Dr. Philip Schauer and his associates.

The use of endoluminal approaches to avoid any type of abdominal incision and, more importantly, any intra-abdominal dissection “may go a long way to further reduce the morbidity of these operations, making them cheaper and safer,” said Dr. Schauer in an interview. “They may expand the access for patients. Only 1% of patients with severe obesity are actually getting access to surgery, which is the only known therapy to be effective for a large percentage of patients.”

Dr. Schauer, director of advanced laparoscopic and bariatric surgery at the bariatric and metabolic institute of the Cleveland Clinic, and his associates categorized the current endoluminal methods for weight loss therapy as presurgical endoluminal therapy, postsurgical endoluminal revision procedures, and primary procedures (Surg. Endosc. 2007;21:347–56).

In the presurgical endoluminal therapy arena, Dr. Michel Gagner and his associates pioneered a two-stage operation consisting of a sleeve gastrectomy followed by a Roux-en-Y gastric bypass (RYGB) or a duodenal switch (Obes. Surg. 2003;13:861–4).

“The rationale is that the first-stage operation, sleeve gastrectomy, is comparatively simple (requiring no anasto- mosis), needs less operative time (1–2 hours), and results in a predictable 40- to 50-kg weight loss,” Dr. Schauer and his associates wrote in their review. “Such weight loss reduces the operative risk for the second-stage procedure, which presumably results in more weight loss and greater durability.”

Dr. Gagner, professor of surgery and chief of bariatric surgery at Cornell University, New York, and his associates were also the first to publish results of an approach using the placement of endoluminal duodenojejunal tube or plastic sleeve to the first part of the duodenum proximal to the ampulla of Vater in pigs as a weight-loss strategy (Obes. Surg. 2006;16:620–6). This study, which demonstrated good weight loss in pigs, was the basis for the first human trial reported by Dr. Leonardo Rodriguez and his associates at the annual meeting of the American Society for Metabolic and Bariatric Surgery (formerly the American Society for Bariatric Surgery) in June 2007.

In the human trial, 12 patients from Chile and Brazil, including four with diabetes, underwent placement of a 61-cm endoluminal duodenojejunal tube or plastic sleeve that was anchored endoscopically in the duodenum and removed after 12 weeks. All of the patients achieved an estimated weight loss of at least 10%, and 10 of the 12 patients lost an estimated 24% of their weight. None of the diabetic patients required hypoglycemic medications.

“By diverting the flow of food from the duodenum and the proximal jejunum, we might be able to change some of the GI hormones that may switch the diabetes to reverse itself,” Dr. Gagner said.

In other studies of presurgical endoluminal therapy, the intragastric balloon developed by BioEnterics Corp. has been used successfully as a first-stage procedure to reduce presurgical weight and perioperative risk in superobese patients, but clinical results are limited.

In the arena of postsurgical endoluminal revision procedures, small studies of C.R. Bard Inc.'s EndoCinch suturing system and endoscopic suturing device have demonstrated promising results.

Dr. Christopher C. Thompson and his associates used the EndoCinch suturing system in eight patients who had undergone RYGB but had regained an average of 24 kg from baseline (Surg. Obes. Relat. Dis. 2005;1:223). At 4 months after undergoing the procedure, six of the eight patients had lost an average of 10 kg, and four reported significant improvements in satiety.

Such suturing procedures hold promise, Dr. Schauer said, because “they emulate gastric restriction, a concept that has been proven over several decades.”

Dr. Schauer disclosed that he is a paid consultant for Bard, Davol, Ethicon Endo-Surgery Inc., Stryker Endoscopy, Baxter International Inc., W.L. Gore & Associates Inc., and Barosense Inc.

Dr. Gagner disclosed that he is a scientific adviser for GI Dynamics Inc. He has also received research grants from Covidien AG, Olympus America Inc., and Bard.

With the flow of food diverted, GI hormones may change enoughto cause the diabetes to reverse itself. DR. GAGNER

Emerging endoluminal techniques and devices intended for weight loss therapy may reduce the risk of morbidity and mortality associated with current bariatric surgery approaches, according to the research findings of Dr. Philip Schauer and his associates.

The use of endoluminal approaches to avoid any type of abdominal incision and, more importantly, any intra-abdominal dissection “may go a long way to further reduce the morbidity of these operations, making them cheaper and safer,” said Dr. Schauer in an interview. “They may expand the access for patients. Only 1% of patients with severe obesity are actually getting access to surgery, which is the only known therapy to be effective for a large percentage of patients.”

Dr. Schauer, director of advanced laparoscopic and bariatric surgery at the bariatric and metabolic institute of the Cleveland Clinic, and his associates categorized the current endoluminal methods for weight loss therapy as presurgical endoluminal therapy, postsurgical endoluminal revision procedures, and primary procedures (Surg. Endosc. 2007;21:347–56).

In the presurgical endoluminal therapy arena, Dr. Michel Gagner and his associates pioneered a two-stage operation consisting of a sleeve gastrectomy followed by a Roux-en-Y gastric bypass (RYGB) or a duodenal switch (Obes. Surg. 2003;13:861–4).

“The rationale is that the first-stage operation, sleeve gastrectomy, is comparatively simple (requiring no anasto- mosis), needs less operative time (1–2 hours), and results in a predictable 40- to 50-kg weight loss,” Dr. Schauer and his associates wrote in their review. “Such weight loss reduces the operative risk for the second-stage procedure, which presumably results in more weight loss and greater durability.”

Dr. Gagner, professor of surgery and chief of bariatric surgery at Cornell University, New York, and his associates were also the first to publish results of an approach using the placement of endoluminal duodenojejunal tube or plastic sleeve to the first part of the duodenum proximal to the ampulla of Vater in pigs as a weight-loss strategy (Obes. Surg. 2006;16:620–6). This study, which demonstrated good weight loss in pigs, was the basis for the first human trial reported by Dr. Leonardo Rodriguez and his associates at the annual meeting of the American Society for Metabolic and Bariatric Surgery (formerly the American Society for Bariatric Surgery) in June 2007.

In the human trial, 12 patients from Chile and Brazil, including four with diabetes, underwent placement of a 61-cm endoluminal duodenojejunal tube or plastic sleeve that was anchored endoscopically in the duodenum and removed after 12 weeks. All of the patients achieved an estimated weight loss of at least 10%, and 10 of the 12 patients lost an estimated 24% of their weight. None of the diabetic patients required hypoglycemic medications.

“By diverting the flow of food from the duodenum and the proximal jejunum, we might be able to change some of the GI hormones that may switch the diabetes to reverse itself,” Dr. Gagner said.

In other studies of presurgical endoluminal therapy, the intragastric balloon developed by BioEnterics Corp. has been used successfully as a first-stage procedure to reduce presurgical weight and perioperative risk in superobese patients, but clinical results are limited.

In the arena of postsurgical endoluminal revision procedures, small studies of C.R. Bard Inc.'s EndoCinch suturing system and endoscopic suturing device have demonstrated promising results.

Dr. Christopher C. Thompson and his associates used the EndoCinch suturing system in eight patients who had undergone RYGB but had regained an average of 24 kg from baseline (Surg. Obes. Relat. Dis. 2005;1:223). At 4 months after undergoing the procedure, six of the eight patients had lost an average of 10 kg, and four reported significant improvements in satiety.

Such suturing procedures hold promise, Dr. Schauer said, because “they emulate gastric restriction, a concept that has been proven over several decades.”

Dr. Schauer disclosed that he is a paid consultant for Bard, Davol, Ethicon Endo-Surgery Inc., Stryker Endoscopy, Baxter International Inc., W.L. Gore & Associates Inc., and Barosense Inc.

Dr. Gagner disclosed that he is a scientific adviser for GI Dynamics Inc. He has also received research grants from Covidien AG, Olympus America Inc., and Bard.

With the flow of food diverted, GI hormones may change enoughto cause the diabetes to reverse itself. DR. GAGNER

A large, long-term study has found there is no overall preventive effect of ascorbic acid, vitamin E, or beta-carotene on cardiovascular events in women at high risk for cardiovascular disease, whether taken alone or in combination.

For the randomized trial, known as the Women's Antioxidant and Cardiovascular Study, Nancy R. Cook, Sc.D., of the division of preventive medicine at Brigham and Women's Hospital, Boston, and her associates tested the effects of ascorbic acid, vitamin E, and beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death in 8,171 women aged 40 years or older. All had a history of CVD or three or more risk factors for CVD.

The mean age of the 8,171 women was 61 years. Of these, 5,238 had a prior cardiovascular event and 2,933 had three or more CVD risk factors. In a two-by-two-by-two factorial study design, each study participant took 500 mg per day of ascorbic acid (synthetic vitamin C), 600 IU of vitamin E every other day, and 50 mg of beta-carotene every other day. The women took the supplements for a mean of 9.4 years, starting in 1995–1996 and ending on Jan. 31, 2005 (Arch. Intern. Med. 2007;167:1610–8).

Compliance was defined as taking at least two-thirds of the study pills. The researchers relied on patient self-reports for compliance twice during the first year, then annually until the end of the trial.

During a mean 9.4 years of follow-up, 1,450 women had a total of 1,856 CVD events. These included 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 CVD-related deaths. The researchers found no overall effect of ascorbic acid, vitamin E, or beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death among the women. However, a marginally significant reduction in the primary outcome from vitamin E use was observed in a subgroup of women with a history of CVD (relative risk 0.89).

There were no overall effects of the agents on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD-related death. However, a significant reduction in stroke was seen in women taking both ascorbic acid and vitamin E.

The study was supported by a National Heart, Lung, and Blood Institute grant. Cognis supplied the vitamin E and placebo; BASF supplied all other supplements and placebos. Neither had influence on the study design or conduct.

A large, long-term study has found there is no overall preventive effect of ascorbic acid, vitamin E, or beta-carotene on cardiovascular events in women at high risk for cardiovascular disease, whether taken alone or in combination.

For the randomized trial, known as the Women's Antioxidant and Cardiovascular Study, Nancy R. Cook, Sc.D., of the division of preventive medicine at Brigham and Women's Hospital, Boston, and her associates tested the effects of ascorbic acid, vitamin E, and beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death in 8,171 women aged 40 years or older. All had a history of CVD or three or more risk factors for CVD.

The mean age of the 8,171 women was 61 years. Of these, 5,238 had a prior cardiovascular event and 2,933 had three or more CVD risk factors. In a two-by-two-by-two factorial study design, each study participant took 500 mg per day of ascorbic acid (synthetic vitamin C), 600 IU of vitamin E every other day, and 50 mg of beta-carotene every other day. The women took the supplements for a mean of 9.4 years, starting in 1995–1996 and ending on Jan. 31, 2005 (Arch. Intern. Med. 2007;167:1610–8).

Compliance was defined as taking at least two-thirds of the study pills. The researchers relied on patient self-reports for compliance twice during the first year, then annually until the end of the trial.

During a mean 9.4 years of follow-up, 1,450 women had a total of 1,856 CVD events. These included 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 CVD-related deaths. The researchers found no overall effect of ascorbic acid, vitamin E, or beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death among the women. However, a marginally significant reduction in the primary outcome from vitamin E use was observed in a subgroup of women with a history of CVD (relative risk 0.89).

There were no overall effects of the agents on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD-related death. However, a significant reduction in stroke was seen in women taking both ascorbic acid and vitamin E.

The study was supported by a National Heart, Lung, and Blood Institute grant. Cognis supplied the vitamin E and placebo; BASF supplied all other supplements and placebos. Neither had influence on the study design or conduct.

A large, long-term study has found there is no overall preventive effect of ascorbic acid, vitamin E, or beta-carotene on cardiovascular events in women at high risk for cardiovascular disease, whether taken alone or in combination.

For the randomized trial, known as the Women's Antioxidant and Cardiovascular Study, Nancy R. Cook, Sc.D., of the division of preventive medicine at Brigham and Women's Hospital, Boston, and her associates tested the effects of ascorbic acid, vitamin E, and beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death in 8,171 women aged 40 years or older. All had a history of CVD or three or more risk factors for CVD.

The mean age of the 8,171 women was 61 years. Of these, 5,238 had a prior cardiovascular event and 2,933 had three or more CVD risk factors. In a two-by-two-by-two factorial study design, each study participant took 500 mg per day of ascorbic acid (synthetic vitamin C), 600 IU of vitamin E every other day, and 50 mg of beta-carotene every other day. The women took the supplements for a mean of 9.4 years, starting in 1995–1996 and ending on Jan. 31, 2005 (Arch. Intern. Med. 2007;167:1610–8).

Compliance was defined as taking at least two-thirds of the study pills. The researchers relied on patient self-reports for compliance twice during the first year, then annually until the end of the trial.

During a mean 9.4 years of follow-up, 1,450 women had a total of 1,856 CVD events. These included 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 CVD-related deaths. The researchers found no overall effect of ascorbic acid, vitamin E, or beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death among the women. However, a marginally significant reduction in the primary outcome from vitamin E use was observed in a subgroup of women with a history of CVD (relative risk 0.89).

There were no overall effects of the agents on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD-related death. However, a significant reduction in stroke was seen in women taking both ascorbic acid and vitamin E.

The study was supported by a National Heart, Lung, and Blood Institute grant. Cognis supplied the vitamin E and placebo; BASF supplied all other supplements and placebos. Neither had influence on the study design or conduct.

LA JOLLA, CALIF. — Improvements in the short- and long-term survival of hepatocellular carcinoma patients are being realized through liver transplantation, surgical resection, and several new therapies, Dr. Donald J. Hillebrand said at a meeting on chronic liver disease sponsored by Scripps Clinic.

Even so, the incidence of hepatocellular carcinoma (HCC) has increased from 1.4 per 100,000 patients in the mid-1970s to 3.3 per 100,000 in 2000–2002. “This disease is on the rise, which is in contrast to most of the abdominal cancers that we deal with on a day-to-day basis,” said Dr. Hillebrand, medical director of liver transplantation for the Scripps Center for Organ and Cell Transplantation in La Jolla, Calif.

At the same time, the prognosis for patients with HCC remains dismal. An estimated 90% of all patients with the diagnosis succumb to the disease. “Roughly half of these patients will die of the tumor,” he said. “The other half will die from progression of their liver disease. So the more aggressive we are with therapy, the more we push them, but the closer we are to helping them achieve locoregional control.”

Dr. Hillebrand emphasized the need for a multidisciplinary approach to HCC. “It can't be just a liver transplant program, because many individuals will benefit from resection,” he said. “The hallmark in the middle of all this is the role of the hepatologist. I probably see more HCC than our oncologists, because they come to us in the liver clinic. In general we don't send an individual to an oncologist unless we've exhausted all of the other locoregional treatment options.”

The best prognostic group includes patients with a performance status of zero and no constitutional symptoms, Child-Pugh class A cirrhosis, no vascular invasion, and no extrahepatic spread.

Liver transplant “by far achieves the best outcome in patients with decompensated cirrhosis who meet criteria,” Dr. Hillebrand said. “Unfortunately, there is a shortage of organ donors available. We can't transplant everybody with HCC.”

Surgical resection can be effective in patients without cirrhosis if there is no vascular involvement, because they don't have portal hypertension or hepatic insufficiency. Resection can also be effective in patients with cirrhosis and preserved liver function and relatively early-stage liver cancer. Patients with Child-Pugh class A cirrhosis who have a peripherally located single lesion “can do quite well, with 60% long-term survival,” he said.

Dr. Hillebrand noted that candidates for surgical resection should be stratified based on their ability to survive the procedure. “So if the patient has clinically significant portal hypertension or increased serum bilirubin, those are two hallmarks against the ability to tolerate resection,” he said.

Indications for surgical resection in patients with no cirrhosis include tumors of any size, as long as there is no microvascular, lymph node, or extrahepatic spread, and resection is technically feasible.

Indications for surgical resection in patients with cirrhosis include having Child-Pugh class A disease, no clinically significant portal hypertension, and a bilirubin level of less than 1 mg/dL. With these criteria, “probably no more than 5% of the HCC that we see in the Western world would be eligible for resection,” he said.

Some transplant surgeons are performing portal vein embolization ipsilateral to the tumor to promote hypertrophy of the contralateral lobe. Although this procedure is rare, “there are some data that suggest this may improve the resectability of these tumors,” Dr. Hillebrand said. “Usually it's done at major centers that have a tremendous experience with hepatic resection and are more willing to push the envelope.”

He pointed out that 50%–75% of patients who undergo surgical resection for HCC will develop a local recurrence or a second primary tumor.

Dr. Hillebrand went on to highlight the following new therapies for HCC:

▸ Ablative therapies. These include chemically mediated forms, such as percutaneous ethanol injection and acetic acid injection, as well as energy-mediated forms, such as cryoablation, microwave ablation, and radiofrequency ablation.

Ablative therapies “can serve as a bridge to transplant,” while avoiding upper abdominal scarring. They “provide effective control of the tumor for up to 1–2 years while patients wait for a liver transplant,” Dr. Hillebrand said. “For select patients, ablation may offer the same 5-year survival results as surgical resection. The question that hasn't fully been answered yet is, is there initial benefit to tumor reduction, the so-called concept of downstaging?”

▸ Locoregional therapies. These include transarterial chemoembolization, radioactive yttrium-impregnated class microspheres, targeted radiation therapies, laser beam therapies, and cisplatinum gel injection.

One phase II trial of proton beam therapy in 34 patients with HCC and an average tumor size of 5.7 cm demonstrated a 75% local tumor control rate at 2 years (Gastroenterology 2004;127:S189–93).

▸ Systemic therapies. Historically there have been no safe and effective systemic chemotherapy regimens, but two new agents that have been studied are nolatrexed (Thymitaq) and sorafenib (Nexavar).

A recent phase II trial of nolatrexed in 39 patients with advanced HCC showed one partial response for 7 months (Invest. New Drugs 2007;25:85–94). The median overall survival was 32 weeks. “Unfortunately, this was a huge study that turned out to be less than exciting,” Dr. Hillebrand said.

A more promising drug is sorafenib, which is approved for renal cell carcinoma. A phase II study of 137 patients showed partial response in 2.2%, minor response in 5.8%, and a delay in time to disease progression of 4.2 months.

Recently, a phase III trial of sorafenib in 602 patients was terminated early because improvements in overall survival were seen. Results of the SHARP trial are expected to be released later this year.

LA JOLLA, CALIF. — Improvements in the short- and long-term survival of hepatocellular carcinoma patients are being realized through liver transplantation, surgical resection, and several new therapies, Dr. Donald J. Hillebrand said at a meeting on chronic liver disease sponsored by Scripps Clinic.

Even so, the incidence of hepatocellular carcinoma (HCC) has increased from 1.4 per 100,000 patients in the mid-1970s to 3.3 per 100,000 in 2000–2002. “This disease is on the rise, which is in contrast to most of the abdominal cancers that we deal with on a day-to-day basis,” said Dr. Hillebrand, medical director of liver transplantation for the Scripps Center for Organ and Cell Transplantation in La Jolla, Calif.

At the same time, the prognosis for patients with HCC remains dismal. An estimated 90% of all patients with the diagnosis succumb to the disease. “Roughly half of these patients will die of the tumor,” he said. “The other half will die from progression of their liver disease. So the more aggressive we are with therapy, the more we push them, but the closer we are to helping them achieve locoregional control.”

Dr. Hillebrand emphasized the need for a multidisciplinary approach to HCC. “It can't be just a liver transplant program, because many individuals will benefit from resection,” he said. “The hallmark in the middle of all this is the role of the hepatologist. I probably see more HCC than our oncologists, because they come to us in the liver clinic. In general we don't send an individual to an oncologist unless we've exhausted all of the other locoregional treatment options.”

The best prognostic group includes patients with a performance status of zero and no constitutional symptoms, Child-Pugh class A cirrhosis, no vascular invasion, and no extrahepatic spread.

Liver transplant “by far achieves the best outcome in patients with decompensated cirrhosis who meet criteria,” Dr. Hillebrand said. “Unfortunately, there is a shortage of organ donors available. We can't transplant everybody with HCC.”

Surgical resection can be effective in patients without cirrhosis if there is no vascular involvement, because they don't have portal hypertension or hepatic insufficiency. Resection can also be effective in patients with cirrhosis and preserved liver function and relatively early-stage liver cancer. Patients with Child-Pugh class A cirrhosis who have a peripherally located single lesion “can do quite well, with 60% long-term survival,” he said.

Dr. Hillebrand noted that candidates for surgical resection should be stratified based on their ability to survive the procedure. “So if the patient has clinically significant portal hypertension or increased serum bilirubin, those are two hallmarks against the ability to tolerate resection,” he said.

Indications for surgical resection in patients with no cirrhosis include tumors of any size, as long as there is no microvascular, lymph node, or extrahepatic spread, and resection is technically feasible.

Indications for surgical resection in patients with cirrhosis include having Child-Pugh class A disease, no clinically significant portal hypertension, and a bilirubin level of less than 1 mg/dL. With these criteria, “probably no more than 5% of the HCC that we see in the Western world would be eligible for resection,” he said.

Some transplant surgeons are performing portal vein embolization ipsilateral to the tumor to promote hypertrophy of the contralateral lobe. Although this procedure is rare, “there are some data that suggest this may improve the resectability of these tumors,” Dr. Hillebrand said. “Usually it's done at major centers that have a tremendous experience with hepatic resection and are more willing to push the envelope.”

He pointed out that 50%–75% of patients who undergo surgical resection for HCC will develop a local recurrence or a second primary tumor.

Dr. Hillebrand went on to highlight the following new therapies for HCC:

▸ Ablative therapies. These include chemically mediated forms, such as percutaneous ethanol injection and acetic acid injection, as well as energy-mediated forms, such as cryoablation, microwave ablation, and radiofrequency ablation.

Ablative therapies “can serve as a bridge to transplant,” while avoiding upper abdominal scarring. They “provide effective control of the tumor for up to 1–2 years while patients wait for a liver transplant,” Dr. Hillebrand said. “For select patients, ablation may offer the same 5-year survival results as surgical resection. The question that hasn't fully been answered yet is, is there initial benefit to tumor reduction, the so-called concept of downstaging?”

▸ Locoregional therapies. These include transarterial chemoembolization, radioactive yttrium-impregnated class microspheres, targeted radiation therapies, laser beam therapies, and cisplatinum gel injection.

One phase II trial of proton beam therapy in 34 patients with HCC and an average tumor size of 5.7 cm demonstrated a 75% local tumor control rate at 2 years (Gastroenterology 2004;127:S189–93).

▸ Systemic therapies. Historically there have been no safe and effective systemic chemotherapy regimens, but two new agents that have been studied are nolatrexed (Thymitaq) and sorafenib (Nexavar).

A recent phase II trial of nolatrexed in 39 patients with advanced HCC showed one partial response for 7 months (Invest. New Drugs 2007;25:85–94). The median overall survival was 32 weeks. “Unfortunately, this was a huge study that turned out to be less than exciting,” Dr. Hillebrand said.

A more promising drug is sorafenib, which is approved for renal cell carcinoma. A phase II study of 137 patients showed partial response in 2.2%, minor response in 5.8%, and a delay in time to disease progression of 4.2 months.

Recently, a phase III trial of sorafenib in 602 patients was terminated early because improvements in overall survival were seen. Results of the SHARP trial are expected to be released later this year.

LA JOLLA, CALIF. — Improvements in the short- and long-term survival of hepatocellular carcinoma patients are being realized through liver transplantation, surgical resection, and several new therapies, Dr. Donald J. Hillebrand said at a meeting on chronic liver disease sponsored by Scripps Clinic.

Even so, the incidence of hepatocellular carcinoma (HCC) has increased from 1.4 per 100,000 patients in the mid-1970s to 3.3 per 100,000 in 2000–2002. “This disease is on the rise, which is in contrast to most of the abdominal cancers that we deal with on a day-to-day basis,” said Dr. Hillebrand, medical director of liver transplantation for the Scripps Center for Organ and Cell Transplantation in La Jolla, Calif.

At the same time, the prognosis for patients with HCC remains dismal. An estimated 90% of all patients with the diagnosis succumb to the disease. “Roughly half of these patients will die of the tumor,” he said. “The other half will die from progression of their liver disease. So the more aggressive we are with therapy, the more we push them, but the closer we are to helping them achieve locoregional control.”

Dr. Hillebrand emphasized the need for a multidisciplinary approach to HCC. “It can't be just a liver transplant program, because many individuals will benefit from resection,” he said. “The hallmark in the middle of all this is the role of the hepatologist. I probably see more HCC than our oncologists, because they come to us in the liver clinic. In general we don't send an individual to an oncologist unless we've exhausted all of the other locoregional treatment options.”

The best prognostic group includes patients with a performance status of zero and no constitutional symptoms, Child-Pugh class A cirrhosis, no vascular invasion, and no extrahepatic spread.

Liver transplant “by far achieves the best outcome in patients with decompensated cirrhosis who meet criteria,” Dr. Hillebrand said. “Unfortunately, there is a shortage of organ donors available. We can't transplant everybody with HCC.”

Surgical resection can be effective in patients without cirrhosis if there is no vascular involvement, because they don't have portal hypertension or hepatic insufficiency. Resection can also be effective in patients with cirrhosis and preserved liver function and relatively early-stage liver cancer. Patients with Child-Pugh class A cirrhosis who have a peripherally located single lesion “can do quite well, with 60% long-term survival,” he said.

Dr. Hillebrand noted that candidates for surgical resection should be stratified based on their ability to survive the procedure. “So if the patient has clinically significant portal hypertension or increased serum bilirubin, those are two hallmarks against the ability to tolerate resection,” he said.

Indications for surgical resection in patients with no cirrhosis include tumors of any size, as long as there is no microvascular, lymph node, or extrahepatic spread, and resection is technically feasible.

Indications for surgical resection in patients with cirrhosis include having Child-Pugh class A disease, no clinically significant portal hypertension, and a bilirubin level of less than 1 mg/dL. With these criteria, “probably no more than 5% of the HCC that we see in the Western world would be eligible for resection,” he said.

Some transplant surgeons are performing portal vein embolization ipsilateral to the tumor to promote hypertrophy of the contralateral lobe. Although this procedure is rare, “there are some data that suggest this may improve the resectability of these tumors,” Dr. Hillebrand said. “Usually it's done at major centers that have a tremendous experience with hepatic resection and are more willing to push the envelope.”

He pointed out that 50%–75% of patients who undergo surgical resection for HCC will develop a local recurrence or a second primary tumor.

Dr. Hillebrand went on to highlight the following new therapies for HCC:

▸ Ablative therapies. These include chemically mediated forms, such as percutaneous ethanol injection and acetic acid injection, as well as energy-mediated forms, such as cryoablation, microwave ablation, and radiofrequency ablation.

Ablative therapies “can serve as a bridge to transplant,” while avoiding upper abdominal scarring. They “provide effective control of the tumor for up to 1–2 years while patients wait for a liver transplant,” Dr. Hillebrand said. “For select patients, ablation may offer the same 5-year survival results as surgical resection. The question that hasn't fully been answered yet is, is there initial benefit to tumor reduction, the so-called concept of downstaging?”

▸ Locoregional therapies. These include transarterial chemoembolization, radioactive yttrium-impregnated class microspheres, targeted radiation therapies, laser beam therapies, and cisplatinum gel injection.

One phase II trial of proton beam therapy in 34 patients with HCC and an average tumor size of 5.7 cm demonstrated a 75% local tumor control rate at 2 years (Gastroenterology 2004;127:S189–93).

▸ Systemic therapies. Historically there have been no safe and effective systemic chemotherapy regimens, but two new agents that have been studied are nolatrexed (Thymitaq) and sorafenib (Nexavar).

A recent phase II trial of nolatrexed in 39 patients with advanced HCC showed one partial response for 7 months (Invest. New Drugs 2007;25:85–94). The median overall survival was 32 weeks. “Unfortunately, this was a huge study that turned out to be less than exciting,” Dr. Hillebrand said.

A more promising drug is sorafenib, which is approved for renal cell carcinoma. A phase II study of 137 patients showed partial response in 2.2%, minor response in 5.8%, and a delay in time to disease progression of 4.2 months.

Recently, a phase III trial of sorafenib in 602 patients was terminated early because improvements in overall survival were seen. Results of the SHARP trial are expected to be released later this year.

SAN DIEGO — Obesity-related liver disease may be clinically underrecognized, results from a single-center study showed.

“Our results indicate that a normal liver ultrasound, liver function tests, and gross appearance does not exclude the presence of significant liver disease,” the researchers, led by Dr. Joshua E. Roller, wrote in a poster presented at the annual meeting of the American Society for Bariatric Surgery.

“If certain subgroups of morbidly obese patients can be identified that are at increased risk for liver disease progression, then intervention with bariatric surgery may become especially critical, and should be aggressively pursued,” they wrote.

Dr. Roller and his associate at the Duke Weight Loss Surgery Center at Duke University, Durham, N.C., reviewed the demographic, perioperative, and liver biopsy data from 153 patients who underwent Roux-en-Y gastric bypass for morbid obesity from January 2005 to September 2006.

The mean age of patients was 41 years, their mean body mass index was 48 kg/m

The researchers reported that preoperatively only 7.8% of patients had abnormal liver function tests, and ultrasound detected fatty liver in 35% of patients.

However, 92% of patients had abnormal liver biopsies: Mild steatosis was present in 58.3%, moderate steatosis was found in 21.1%, and 12.6% of patients had severe steatosis.

Fibrosis was present in 12.6% of the liver biopsy specimens.

Intraoperatively, the liver appeared normal by surgeon observation in 65% of patients; the rest of the patients appeared to have a fatty and/or enlarged liver.

The researchers identified nonalcoholic steatohepatitis in 24.5% of patients with steatosis. Of these, 48.6% had mild fibrosis. Nonalcoholic steatohepatitis was significantly more common in men than in women (45.8% vs. 20.5%, respectively) and in whites compared with African Americans (27.9% vs. 9.7%, respectively). Patients aged 50 years and older had higher rates of nonalcoholic steatohepatitis than did their younger counterparts, but the difference was not statistically significant (35% vs. 20.5%, respectively).

Liver fibrosis was significantly more common in whites than in African Americans (16.4% vs. 0%, respectively) and in men compared with women (33.3% vs. 8.5%, respectively).

No associations were detected between the presence of nonalcoholic steatohepatitis or liver fibrosis and preoperative weight loss, weight gain, or body mass index.

“Further prospective, randomized, controlled trials are needed to determine the impact of obesity surgery on nonalcoholic fatty liver disease,” the researchers concluded.

SAN DIEGO — Obesity-related liver disease may be clinically underrecognized, results from a single-center study showed.

“Our results indicate that a normal liver ultrasound, liver function tests, and gross appearance does not exclude the presence of significant liver disease,” the researchers, led by Dr. Joshua E. Roller, wrote in a poster presented at the annual meeting of the American Society for Bariatric Surgery.

“If certain subgroups of morbidly obese patients can be identified that are at increased risk for liver disease progression, then intervention with bariatric surgery may become especially critical, and should be aggressively pursued,” they wrote.

Dr. Roller and his associate at the Duke Weight Loss Surgery Center at Duke University, Durham, N.C., reviewed the demographic, perioperative, and liver biopsy data from 153 patients who underwent Roux-en-Y gastric bypass for morbid obesity from January 2005 to September 2006.

The mean age of patients was 41 years, their mean body mass index was 48 kg/m

The researchers reported that preoperatively only 7.8% of patients had abnormal liver function tests, and ultrasound detected fatty liver in 35% of patients.

However, 92% of patients had abnormal liver biopsies: Mild steatosis was present in 58.3%, moderate steatosis was found in 21.1%, and 12.6% of patients had severe steatosis.

Fibrosis was present in 12.6% of the liver biopsy specimens.

Intraoperatively, the liver appeared normal by surgeon observation in 65% of patients; the rest of the patients appeared to have a fatty and/or enlarged liver.

The researchers identified nonalcoholic steatohepatitis in 24.5% of patients with steatosis. Of these, 48.6% had mild fibrosis. Nonalcoholic steatohepatitis was significantly more common in men than in women (45.8% vs. 20.5%, respectively) and in whites compared with African Americans (27.9% vs. 9.7%, respectively). Patients aged 50 years and older had higher rates of nonalcoholic steatohepatitis than did their younger counterparts, but the difference was not statistically significant (35% vs. 20.5%, respectively).

Liver fibrosis was significantly more common in whites than in African Americans (16.4% vs. 0%, respectively) and in men compared with women (33.3% vs. 8.5%, respectively).

No associations were detected between the presence of nonalcoholic steatohepatitis or liver fibrosis and preoperative weight loss, weight gain, or body mass index.

“Further prospective, randomized, controlled trials are needed to determine the impact of obesity surgery on nonalcoholic fatty liver disease,” the researchers concluded.

SAN DIEGO — Obesity-related liver disease may be clinically underrecognized, results from a single-center study showed.

“Our results indicate that a normal liver ultrasound, liver function tests, and gross appearance does not exclude the presence of significant liver disease,” the researchers, led by Dr. Joshua E. Roller, wrote in a poster presented at the annual meeting of the American Society for Bariatric Surgery.

“If certain subgroups of morbidly obese patients can be identified that are at increased risk for liver disease progression, then intervention with bariatric surgery may become especially critical, and should be aggressively pursued,” they wrote.

Dr. Roller and his associate at the Duke Weight Loss Surgery Center at Duke University, Durham, N.C., reviewed the demographic, perioperative, and liver biopsy data from 153 patients who underwent Roux-en-Y gastric bypass for morbid obesity from January 2005 to September 2006.

The mean age of patients was 41 years, their mean body mass index was 48 kg/m

The researchers reported that preoperatively only 7.8% of patients had abnormal liver function tests, and ultrasound detected fatty liver in 35% of patients.

However, 92% of patients had abnormal liver biopsies: Mild steatosis was present in 58.3%, moderate steatosis was found in 21.1%, and 12.6% of patients had severe steatosis.

Fibrosis was present in 12.6% of the liver biopsy specimens.

Intraoperatively, the liver appeared normal by surgeon observation in 65% of patients; the rest of the patients appeared to have a fatty and/or enlarged liver.

The researchers identified nonalcoholic steatohepatitis in 24.5% of patients with steatosis. Of these, 48.6% had mild fibrosis. Nonalcoholic steatohepatitis was significantly more common in men than in women (45.8% vs. 20.5%, respectively) and in whites compared with African Americans (27.9% vs. 9.7%, respectively). Patients aged 50 years and older had higher rates of nonalcoholic steatohepatitis than did their younger counterparts, but the difference was not statistically significant (35% vs. 20.5%, respectively).

Liver fibrosis was significantly more common in whites than in African Americans (16.4% vs. 0%, respectively) and in men compared with women (33.3% vs. 8.5%, respectively).

No associations were detected between the presence of nonalcoholic steatohepatitis or liver fibrosis and preoperative weight loss, weight gain, or body mass index.

“Further prospective, randomized, controlled trials are needed to determine the impact of obesity surgery on nonalcoholic fatty liver disease,” the researchers concluded.

A large, randomized international trial assessing the benefits of giving blood pressure-lowering medications to hypertensive patients aged 80 and older has been halted early because treatment significantly reduced the incidence of stroke and mortality, compared with those who did not receive treatment.

Launched in 2001, the double-blind, placebo-controlled study, known as the Hypertension in the Very Elderly Trial (HYVET), enrolled 3,845 patients with high blood pressure aged 80 and older. Patients took either the placebo or indapamide 1.5 mg and perindopril once a day.

“It was not clear prior to our study whether the over-80s would benefit from blood pressure-lowering medication in the same way as younger people,” the study's primary investigator, Dr. Chris Bulpitt, professor of geriatric medicine at Imperial College London, said in a prepared statement. “Our results are great news for people in this age group because they suggest … such treatment can cut their chances of dying as well as stroke.”

Specific data from the trial have not been released but are expected to appear in the peer-reviewed medical literature. In the meantime, study participants who were on the trial medication will have the option to switch to active indapamide 1.5 mg SR at their final visit.

The British Heart Foundation and the Institut de Recherches Internationales Servier funded the study, which is the largest of its kind.

A large, randomized international trial assessing the benefits of giving blood pressure-lowering medications to hypertensive patients aged 80 and older has been halted early because treatment significantly reduced the incidence of stroke and mortality, compared with those who did not receive treatment.

Launched in 2001, the double-blind, placebo-controlled study, known as the Hypertension in the Very Elderly Trial (HYVET), enrolled 3,845 patients with high blood pressure aged 80 and older. Patients took either the placebo or indapamide 1.5 mg and perindopril once a day.

“It was not clear prior to our study whether the over-80s would benefit from blood pressure-lowering medication in the same way as younger people,” the study's primary investigator, Dr. Chris Bulpitt, professor of geriatric medicine at Imperial College London, said in a prepared statement. “Our results are great news for people in this age group because they suggest … such treatment can cut their chances of dying as well as stroke.”

Specific data from the trial have not been released but are expected to appear in the peer-reviewed medical literature. In the meantime, study participants who were on the trial medication will have the option to switch to active indapamide 1.5 mg SR at their final visit.

The British Heart Foundation and the Institut de Recherches Internationales Servier funded the study, which is the largest of its kind.

A large, randomized international trial assessing the benefits of giving blood pressure-lowering medications to hypertensive patients aged 80 and older has been halted early because treatment significantly reduced the incidence of stroke and mortality, compared with those who did not receive treatment.

Launched in 2001, the double-blind, placebo-controlled study, known as the Hypertension in the Very Elderly Trial (HYVET), enrolled 3,845 patients with high blood pressure aged 80 and older. Patients took either the placebo or indapamide 1.5 mg and perindopril once a day.

“It was not clear prior to our study whether the over-80s would benefit from blood pressure-lowering medication in the same way as younger people,” the study's primary investigator, Dr. Chris Bulpitt, professor of geriatric medicine at Imperial College London, said in a prepared statement. “Our results are great news for people in this age group because they suggest … such treatment can cut their chances of dying as well as stroke.”

Specific data from the trial have not been released but are expected to appear in the peer-reviewed medical literature. In the meantime, study participants who were on the trial medication will have the option to switch to active indapamide 1.5 mg SR at their final visit.

The British Heart Foundation and the Institut de Recherches Internationales Servier funded the study, which is the largest of its kind.

Women at high risk for cardiovascular disease who take ascorbic acid, vitamin E, and beta-carotene in hopes of preventing cardiovascular events may want to rethink that strategy.

A large, long-term study found that there is no overall preventive effect of ascorbic acid, vitamin E, or beta-carotene on cardiovascular events among women at high risk for cardiovascular disease, whether taken alone or in combination.

“While additional research into combinations of agents, particularly for stroke, may be of interest, widespread use of these individual agents for cardiovascular protection does not appear to be warranted,” wrote the researchers, who were led by Nancy R. Cook, Sc.D., of the division of preventive medicine at Brigham and Women's Hospital, Boston.

For the randomized trial, known as the Women's Antioxidant and Cardiovascular Study, Dr. Cook and her associates tested the effects of ascorbic acid, vitamin E, and beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death in 8,171 women aged 40 years or older. All had a history of cardiovascular disease or three or more risk factors for CVD.

The mean age of the 8,171 women was 61 years. Of these, 5,238 (64%) had a prior cardiovascular event and 2,933 (36%) had three or more CVD risk factors.

In a two-by-two-by-two factorial study design, each study participant took 500 mg per day of ascorbic acid (synthetic vitamin C), 600 IU of vitamin E every other day, and 50 mg of beta-carotene every other day. The women took the supplements for a mean of 9.4 years, starting in 1995–1996 and ending on Jan. 31, 2005 (Arch. Intern. Med. 2007; 167:1610–8).

Compliance was defined as taking at least two-thirds of the study pills. The researchers relied on patient self-reports for compliance twice during the first year, then annually until the end of the trial.

Dr. Cook and her associates reported that during a mean 9.4 years of follow-up, 1,450 women had a total of 1,856 cardiovascular disease events. These included 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 cardiovascular disease-related deaths.

The researchers found no overall effect of ascorbic acid, vitamin E, or beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death among women in the study. However, a marginally significant reduction in the primary outcome from vitamin E use was observed in a subgroup of women with a history of CVD (relative risk 0.89).

There were no overall effects of the agents on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD-related death. However, a significant reduction in stroke was seen among women taking both ascorbic acid and vitamin E, compared with those in the placebo group for both agents (RR 0.69), suggesting a two-way interaction.

On average, the reported compliance for each antioxidant was 76% at 4 years and 68% at 8 years of follow-up, which is one limitation of the study. In addition, the researchers wrote that “mortality information follow-up was virtually complete through 2003 and then 93% complete for the remaining two years.”

The study was supported by a grant from the National Heart, Lung, and Blood Institute.

Cognis supplied the vitamin E and its placebo, while BASF supplied all other supplements and their placebos. Neither company had influence on the design or conduct of the study.

Women at high risk for cardiovascular disease who take ascorbic acid, vitamin E, and beta-carotene in hopes of preventing cardiovascular events may want to rethink that strategy.

A large, long-term study found that there is no overall preventive effect of ascorbic acid, vitamin E, or beta-carotene on cardiovascular events among women at high risk for cardiovascular disease, whether taken alone or in combination.

“While additional research into combinations of agents, particularly for stroke, may be of interest, widespread use of these individual agents for cardiovascular protection does not appear to be warranted,” wrote the researchers, who were led by Nancy R. Cook, Sc.D., of the division of preventive medicine at Brigham and Women's Hospital, Boston.

For the randomized trial, known as the Women's Antioxidant and Cardiovascular Study, Dr. Cook and her associates tested the effects of ascorbic acid, vitamin E, and beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death in 8,171 women aged 40 years or older. All had a history of cardiovascular disease or three or more risk factors for CVD.

The mean age of the 8,171 women was 61 years. Of these, 5,238 (64%) had a prior cardiovascular event and 2,933 (36%) had three or more CVD risk factors.

In a two-by-two-by-two factorial study design, each study participant took 500 mg per day of ascorbic acid (synthetic vitamin C), 600 IU of vitamin E every other day, and 50 mg of beta-carotene every other day. The women took the supplements for a mean of 9.4 years, starting in 1995–1996 and ending on Jan. 31, 2005 (Arch. Intern. Med. 2007; 167:1610–8).

Compliance was defined as taking at least two-thirds of the study pills. The researchers relied on patient self-reports for compliance twice during the first year, then annually until the end of the trial.

Dr. Cook and her associates reported that during a mean 9.4 years of follow-up, 1,450 women had a total of 1,856 cardiovascular disease events. These included 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 cardiovascular disease-related deaths.

The researchers found no overall effect of ascorbic acid, vitamin E, or beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death among women in the study. However, a marginally significant reduction in the primary outcome from vitamin E use was observed in a subgroup of women with a history of CVD (relative risk 0.89).

There were no overall effects of the agents on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD-related death. However, a significant reduction in stroke was seen among women taking both ascorbic acid and vitamin E, compared with those in the placebo group for both agents (RR 0.69), suggesting a two-way interaction.

On average, the reported compliance for each antioxidant was 76% at 4 years and 68% at 8 years of follow-up, which is one limitation of the study. In addition, the researchers wrote that “mortality information follow-up was virtually complete through 2003 and then 93% complete for the remaining two years.”

The study was supported by a grant from the National Heart, Lung, and Blood Institute.

Cognis supplied the vitamin E and its placebo, while BASF supplied all other supplements and their placebos. Neither company had influence on the design or conduct of the study.

Women at high risk for cardiovascular disease who take ascorbic acid, vitamin E, and beta-carotene in hopes of preventing cardiovascular events may want to rethink that strategy.

A large, long-term study found that there is no overall preventive effect of ascorbic acid, vitamin E, or beta-carotene on cardiovascular events among women at high risk for cardiovascular disease, whether taken alone or in combination.

“While additional research into combinations of agents, particularly for stroke, may be of interest, widespread use of these individual agents for cardiovascular protection does not appear to be warranted,” wrote the researchers, who were led by Nancy R. Cook, Sc.D., of the division of preventive medicine at Brigham and Women's Hospital, Boston.

For the randomized trial, known as the Women's Antioxidant and Cardiovascular Study, Dr. Cook and her associates tested the effects of ascorbic acid, vitamin E, and beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death in 8,171 women aged 40 years or older. All had a history of cardiovascular disease or three or more risk factors for CVD.

The mean age of the 8,171 women was 61 years. Of these, 5,238 (64%) had a prior cardiovascular event and 2,933 (36%) had three or more CVD risk factors.

In a two-by-two-by-two factorial study design, each study participant took 500 mg per day of ascorbic acid (synthetic vitamin C), 600 IU of vitamin E every other day, and 50 mg of beta-carotene every other day. The women took the supplements for a mean of 9.4 years, starting in 1995–1996 and ending on Jan. 31, 2005 (Arch. Intern. Med. 2007; 167:1610–8).

Compliance was defined as taking at least two-thirds of the study pills. The researchers relied on patient self-reports for compliance twice during the first year, then annually until the end of the trial.

Dr. Cook and her associates reported that during a mean 9.4 years of follow-up, 1,450 women had a total of 1,856 cardiovascular disease events. These included 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 cardiovascular disease-related deaths.

The researchers found no overall effect of ascorbic acid, vitamin E, or beta-carotene on the combined primary outcome of myocardial infarction, stroke, coronary revascularization, or CVD-related death among women in the study. However, a marginally significant reduction in the primary outcome from vitamin E use was observed in a subgroup of women with a history of CVD (relative risk 0.89).

There were no overall effects of the agents on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD-related death. However, a significant reduction in stroke was seen among women taking both ascorbic acid and vitamin E, compared with those in the placebo group for both agents (RR 0.69), suggesting a two-way interaction.

On average, the reported compliance for each antioxidant was 76% at 4 years and 68% at 8 years of follow-up, which is one limitation of the study. In addition, the researchers wrote that “mortality information follow-up was virtually complete through 2003 and then 93% complete for the remaining two years.”

The study was supported by a grant from the National Heart, Lung, and Blood Institute.

Cognis supplied the vitamin E and its placebo, while BASF supplied all other supplements and their placebos. Neither company had influence on the design or conduct of the study.

Emerging endoluminal techniques and devices intended for weight loss therapy may reduce the risk of morbidity and mortality associated with current bariatric surgery approaches, according to the research findings of Dr. Philip Schauer and his associates.

The use of endoluminal approaches to avoid any type of abdominal incision and, more importantly, any intra-abdominal dissection “may go a long way to further reduce the morbidity of these operations, making them cheaper and safer,” said Dr. Schauer in an interview. “Potentially, they may expand the access for patients. Only 1% of patients with severe obesity are actually getting access to surgery, which is the only known therapy to be effective for a large percentage of patients.”

Dr. Schauer, director of advanced laparoscopic and bariatric surgery at the bariatric and metabolic institute of the Cleveland Clinic, and his associates categorized the current endoluminal methods for weight loss therapy as presurgical endoluminal therapy, postsurgical endoluminal revision procedures, and primary procedures (Surg. Endosc. 2007;21:347–56).

In the arena of presurgical endoluminal therapy, Dr. Michel Gagner and his associates pioneered a two-stage operation consisting of a sleeve gastrectomy followed by a Roux-en-Y gastric bypass (RYGB) or a duodenal switch (Obes. Surg. 2003;13:861–4).

“The rationale is that the first-stage operation, sleeve gastrectomy, is comparatively simple (requiring no anastomosis), needs less operative time (1–2 hours), and results in a predictable 40- to 50-kg weight loss,” Dr. Schauer and his associates wrote in their review. “Such weight loss reduces the operative risk for the second-stage procedure, which presumably results in more weight loss and greater durability.”

Dr. Gagner, professor of surgery and chief of bariatric surgery at Cornell University, New York, and his associates were also the first to publish results of an approach using the placement of endoluminal duodenojejunal tube or plastic sleeve to the first part of the duodenum proximal to the ampulla of Vater in pigs as a weight-loss strategy (Obes. Surg. 2006;16:620–6). This study, which demonstrated good weight loss in pigs, was the basis for the first human trial reported recently by Dr. Leonardo Rodriguez and his associates at the annual meeting of the American Society for Metabolic and Bariatric Surgery (formerly the American Society for Bariatric Surgery).

In the human trial, 12 patients from Chile and Brazil, including four with diabetes, underwent placement of a 61-cm endoluminal duodenojejunal tube or plastic sleeve that was anchored endoscopically in the duodenum and removed after 12 weeks.

All patients achieved an estimated weight loss of at least 10%, and 10 of the 12 patients lost an estimated 24% of their weight. All of the diabetic patients completed the study without the need for hypoglycemic medications.

“By diverting the flow of food from the duodenum and the proximal jejunum, we might be able to change some of the GI hormones that may switch the diabetes to reverse itself,” Dr. Gagner said in an interview. “I think we will see more and more of that technology being developed, and we'll see variants like different materials, different lengths [of sleeves], et cetera.”

Dr. Gagner was not affiliated with the study.

In other studies of presurgical endoluminal therapy, the intragastric balloon developed by BioEnterics Corp. has been used successfully as a first-stage procedure to reduce presurgical weight and perioperative risk in superobese patients, but clinical results are limited.

In the arena of postsurgical endoluminal revision procedures, small studies of C.R. Bard Inc.'s EndoCinch suturing system and endoscopic suturing device have demonstrated promising results.

Dr. Christopher C. Thompson and his associates used the EndoCinch suturing system in eight patients who had undergone RYGB but had regained an average of 24 kg from baseline (Surg. Obe. Relat. Dis. 2005;1:223).

They placed plications at the rim of the anastomosis, thereby reducing the anastomotic aperture. At 4 months after undergoing the procedure, six of the eight patients had lost an average of 10 kg, and four reported significant improvements in satiety.

In another study, Dr. Michael Schweitzer and his associates used the endoscopic suturing device in four patients who regained weight after RYGB surgery (J. Laparoendosc. Adv. Surg. Tech. A 2004;14:223–6). The study did not include long-term results, but noted that all four patients reported improvements in early weight loss and satiety.

At the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons in April 2007, Dr. Roberto Fogel of Caracas, Venezuela, reported that an endoluminal vertical gastroplasty procedure produced an average excess weight loss of 46% in patients 3 months after surgery. In this procedure, an interrupted suture pattern was used in 31 patients with a mean body mass index (kg/m

Such suturing procedures hold particular promise, Dr. Schauer said, because “they emulate gastric restriction, a concept that has been proven over several decades in bariatric surgery.”

Dr. Schauer is one of the clinicians participating in the phase III RESTORe (Randomized Evaluation of Endoscopic Suturing Transorally for Anastomotic Outlet Reduction) trial for patients with inadequate weight loss following RYGB. The purpose of the trial, which is supported by Bard and Davol Inc., is to evaluate weight loss and other clinical outcomes following application of transoral reduction of a dilated gastrojejunostomy anastomosis in 220 patients who have inadequate weight loss following RYGB. The expected completion date of the trial is July 2008.

The use of endoluminal techniques for the primary treatment of obesity is in its infancy, Dr. Schauer said. One investigational device that has been studied in small trials of patients outside the United States is the transoral gastroplasty (TOGa) system, developed by Satiety Inc. In this procedure, an endoscopic stapling device is inserted through the mouth to the stomach to create a small restrictive pouch.

Dr. Schauer called the development of endoluminal techniques for obesity “another potential great leap forward in reducing the risk of these procedures. We already know that going from open procedures to laparoscopic procedures was one of the major factors that propelled bariatric surgery from a very low niche field [15,000 cases per year] across the United States, to 200,000 procedures per year. What really drove that was the reduction in complications and recovery.”

Dr. Schauer disclosed that he is a paid consultant for Bard, Davol, Ethicon Endo-Surgery Inc., Stryker Endoscopy, Baxter International Inc., W.L. Gore & Associates Inc., and Barosense Inc.

Dr. Gagner disclosed that he is a scientific adviser for GI Dynamics Inc. He has also received research grants from Covidien AG, Olympus America Inc., and Bard.

'We might be able to change some of the GI hormones that may switch the diabetes to reverse itself.' DR. GAGNER

Emerging endoluminal techniques and devices intended for weight loss therapy may reduce the risk of morbidity and mortality associated with current bariatric surgery approaches, according to the research findings of Dr. Philip Schauer and his associates.

The use of endoluminal approaches to avoid any type of abdominal incision and, more importantly, any intra-abdominal dissection “may go a long way to further reduce the morbidity of these operations, making them cheaper and safer,” said Dr. Schauer in an interview. “Potentially, they may expand the access for patients. Only 1% of patients with severe obesity are actually getting access to surgery, which is the only known therapy to be effective for a large percentage of patients.”

Dr. Schauer, director of advanced laparoscopic and bariatric surgery at the bariatric and metabolic institute of the Cleveland Clinic, and his associates categorized the current endoluminal methods for weight loss therapy as presurgical endoluminal therapy, postsurgical endoluminal revision procedures, and primary procedures (Surg. Endosc. 2007;21:347–56).

In the arena of presurgical endoluminal therapy, Dr. Michel Gagner and his associates pioneered a two-stage operation consisting of a sleeve gastrectomy followed by a Roux-en-Y gastric bypass (RYGB) or a duodenal switch (Obes. Surg. 2003;13:861–4).

“The rationale is that the first-stage operation, sleeve gastrectomy, is comparatively simple (requiring no anastomosis), needs less operative time (1–2 hours), and results in a predictable 40- to 50-kg weight loss,” Dr. Schauer and his associates wrote in their review. “Such weight loss reduces the operative risk for the second-stage procedure, which presumably results in more weight loss and greater durability.”

Dr. Gagner, professor of surgery and chief of bariatric surgery at Cornell University, New York, and his associates were also the first to publish results of an approach using the placement of endoluminal duodenojejunal tube or plastic sleeve to the first part of the duodenum proximal to the ampulla of Vater in pigs as a weight-loss strategy (Obes. Surg. 2006;16:620–6). This study, which demonstrated good weight loss in pigs, was the basis for the first human trial reported recently by Dr. Leonardo Rodriguez and his associates at the annual meeting of the American Society for Metabolic and Bariatric Surgery (formerly the American Society for Bariatric Surgery).

In the human trial, 12 patients from Chile and Brazil, including four with diabetes, underwent placement of a 61-cm endoluminal duodenojejunal tube or plastic sleeve that was anchored endoscopically in the duodenum and removed after 12 weeks.

All patients achieved an estimated weight loss of at least 10%, and 10 of the 12 patients lost an estimated 24% of their weight. All of the diabetic patients completed the study without the need for hypoglycemic medications.

“By diverting the flow of food from the duodenum and the proximal jejunum, we might be able to change some of the GI hormones that may switch the diabetes to reverse itself,” Dr. Gagner said in an interview. “I think we will see more and more of that technology being developed, and we'll see variants like different materials, different lengths [of sleeves], et cetera.”

Dr. Gagner was not affiliated with the study.

In other studies of presurgical endoluminal therapy, the intragastric balloon developed by BioEnterics Corp. has been used successfully as a first-stage procedure to reduce presurgical weight and perioperative risk in superobese patients, but clinical results are limited.

In the arena of postsurgical endoluminal revision procedures, small studies of C.R. Bard Inc.'s EndoCinch suturing system and endoscopic suturing device have demonstrated promising results.

Dr. Christopher C. Thompson and his associates used the EndoCinch suturing system in eight patients who had undergone RYGB but had regained an average of 24 kg from baseline (Surg. Obe. Relat. Dis. 2005;1:223).

They placed plications at the rim of the anastomosis, thereby reducing the anastomotic aperture. At 4 months after undergoing the procedure, six of the eight patients had lost an average of 10 kg, and four reported significant improvements in satiety.

In another study, Dr. Michael Schweitzer and his associates used the endoscopic suturing device in four patients who regained weight after RYGB surgery (J. Laparoendosc. Adv. Surg. Tech. A 2004;14:223–6). The study did not include long-term results, but noted that all four patients reported improvements in early weight loss and satiety.

At the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons in April 2007, Dr. Roberto Fogel of Caracas, Venezuela, reported that an endoluminal vertical gastroplasty procedure produced an average excess weight loss of 46% in patients 3 months after surgery. In this procedure, an interrupted suture pattern was used in 31 patients with a mean body mass index (kg/m

Such suturing procedures hold particular promise, Dr. Schauer said, because “they emulate gastric restriction, a concept that has been proven over several decades in bariatric surgery.”

Dr. Schauer is one of the clinicians participating in the phase III RESTORe (Randomized Evaluation of Endoscopic Suturing Transorally for Anastomotic Outlet Reduction) trial for patients with inadequate weight loss following RYGB. The purpose of the trial, which is supported by Bard and Davol Inc., is to evaluate weight loss and other clinical outcomes following application of transoral reduction of a dilated gastrojejunostomy anastomosis in 220 patients who have inadequate weight loss following RYGB. The expected completion date of the trial is July 2008.

The use of endoluminal techniques for the primary treatment of obesity is in its infancy, Dr. Schauer said. One investigational device that has been studied in small trials of patients outside the United States is the transoral gastroplasty (TOGa) system, developed by Satiety Inc. In this procedure, an endoscopic stapling device is inserted through the mouth to the stomach to create a small restrictive pouch.

Dr. Schauer called the development of endoluminal techniques for obesity “another potential great leap forward in reducing the risk of these procedures. We already know that going from open procedures to laparoscopic procedures was one of the major factors that propelled bariatric surgery from a very low niche field [15,000 cases per year] across the United States, to 200,000 procedures per year. What really drove that was the reduction in complications and recovery.”

Dr. Schauer disclosed that he is a paid consultant for Bard, Davol, Ethicon Endo-Surgery Inc., Stryker Endoscopy, Baxter International Inc., W.L. Gore & Associates Inc., and Barosense Inc.

Dr. Gagner disclosed that he is a scientific adviser for GI Dynamics Inc. He has also received research grants from Covidien AG, Olympus America Inc., and Bard.

'We might be able to change some of the GI hormones that may switch the diabetes to reverse itself.' DR. GAGNER

Emerging endoluminal techniques and devices intended for weight loss therapy may reduce the risk of morbidity and mortality associated with current bariatric surgery approaches, according to the research findings of Dr. Philip Schauer and his associates.

The use of endoluminal approaches to avoid any type of abdominal incision and, more importantly, any intra-abdominal dissection “may go a long way to further reduce the morbidity of these operations, making them cheaper and safer,” said Dr. Schauer in an interview. “Potentially, they may expand the access for patients. Only 1% of patients with severe obesity are actually getting access to surgery, which is the only known therapy to be effective for a large percentage of patients.”

Dr. Schauer, director of advanced laparoscopic and bariatric surgery at the bariatric and metabolic institute of the Cleveland Clinic, and his associates categorized the current endoluminal methods for weight loss therapy as presurgical endoluminal therapy, postsurgical endoluminal revision procedures, and primary procedures (Surg. Endosc. 2007;21:347–56).

In the arena of presurgical endoluminal therapy, Dr. Michel Gagner and his associates pioneered a two-stage operation consisting of a sleeve gastrectomy followed by a Roux-en-Y gastric bypass (RYGB) or a duodenal switch (Obes. Surg. 2003;13:861–4).

“The rationale is that the first-stage operation, sleeve gastrectomy, is comparatively simple (requiring no anastomosis), needs less operative time (1–2 hours), and results in a predictable 40- to 50-kg weight loss,” Dr. Schauer and his associates wrote in their review. “Such weight loss reduces the operative risk for the second-stage procedure, which presumably results in more weight loss and greater durability.”

Dr. Gagner, professor of surgery and chief of bariatric surgery at Cornell University, New York, and his associates were also the first to publish results of an approach using the placement of endoluminal duodenojejunal tube or plastic sleeve to the first part of the duodenum proximal to the ampulla of Vater in pigs as a weight-loss strategy (Obes. Surg. 2006;16:620–6). This study, which demonstrated good weight loss in pigs, was the basis for the first human trial reported recently by Dr. Leonardo Rodriguez and his associates at the annual meeting of the American Society for Metabolic and Bariatric Surgery (formerly the American Society for Bariatric Surgery).

In the human trial, 12 patients from Chile and Brazil, including four with diabetes, underwent placement of a 61-cm endoluminal duodenojejunal tube or plastic sleeve that was anchored endoscopically in the duodenum and removed after 12 weeks.

All patients achieved an estimated weight loss of at least 10%, and 10 of the 12 patients lost an estimated 24% of their weight. All of the diabetic patients completed the study without the need for hypoglycemic medications.

“By diverting the flow of food from the duodenum and the proximal jejunum, we might be able to change some of the GI hormones that may switch the diabetes to reverse itself,” Dr. Gagner said in an interview. “I think we will see more and more of that technology being developed, and we'll see variants like different materials, different lengths [of sleeves], et cetera.”

Dr. Gagner was not affiliated with the study.

In other studies of presurgical endoluminal therapy, the intragastric balloon developed by BioEnterics Corp. has been used successfully as a first-stage procedure to reduce presurgical weight and perioperative risk in superobese patients, but clinical results are limited.

In the arena of postsurgical endoluminal revision procedures, small studies of C.R. Bard Inc.'s EndoCinch suturing system and endoscopic suturing device have demonstrated promising results.

Dr. Christopher C. Thompson and his associates used the EndoCinch suturing system in eight patients who had undergone RYGB but had regained an average of 24 kg from baseline (Surg. Obe. Relat. Dis. 2005;1:223).

They placed plications at the rim of the anastomosis, thereby reducing the anastomotic aperture. At 4 months after undergoing the procedure, six of the eight patients had lost an average of 10 kg, and four reported significant improvements in satiety.

In another study, Dr. Michael Schweitzer and his associates used the endoscopic suturing device in four patients who regained weight after RYGB surgery (J. Laparoendosc. Adv. Surg. Tech. A 2004;14:223–6). The study did not include long-term results, but noted that all four patients reported improvements in early weight loss and satiety.

At the annual meeting of the Society of American Gastrointestinal Endoscopic Surgeons in April 2007, Dr. Roberto Fogel of Caracas, Venezuela, reported that an endoluminal vertical gastroplasty procedure produced an average excess weight loss of 46% in patients 3 months after surgery. In this procedure, an interrupted suture pattern was used in 31 patients with a mean body mass index (kg/m

Such suturing procedures hold particular promise, Dr. Schauer said, because “they emulate gastric restriction, a concept that has been proven over several decades in bariatric surgery.”

Dr. Schauer is one of the clinicians participating in the phase III RESTORe (Randomized Evaluation of Endoscopic Suturing Transorally for Anastomotic Outlet Reduction) trial for patients with inadequate weight loss following RYGB. The purpose of the trial, which is supported by Bard and Davol Inc., is to evaluate weight loss and other clinical outcomes following application of transoral reduction of a dilated gastrojejunostomy anastomosis in 220 patients who have inadequate weight loss following RYGB. The expected completion date of the trial is July 2008.

The use of endoluminal techniques for the primary treatment of obesity is in its infancy, Dr. Schauer said. One investigational device that has been studied in small trials of patients outside the United States is the transoral gastroplasty (TOGa) system, developed by Satiety Inc. In this procedure, an endoscopic stapling device is inserted through the mouth to the stomach to create a small restrictive pouch.

Dr. Schauer called the development of endoluminal techniques for obesity “another potential great leap forward in reducing the risk of these procedures. We already know that going from open procedures to laparoscopic procedures was one of the major factors that propelled bariatric surgery from a very low niche field [15,000 cases per year] across the United States, to 200,000 procedures per year. What really drove that was the reduction in complications and recovery.”

Dr. Schauer disclosed that he is a paid consultant for Bard, Davol, Ethicon Endo-Surgery Inc., Stryker Endoscopy, Baxter International Inc., W.L. Gore & Associates Inc., and Barosense Inc.

Dr. Gagner disclosed that he is a scientific adviser for GI Dynamics Inc. He has also received research grants from Covidien AG, Olympus America Inc., and Bard.

'We might be able to change some of the GI hormones that may switch the diabetes to reverse itself.' DR. GAGNER

LONG BEACH, CALIF. – So little is known about effective interventions for delirium that efforts to help elderly patients with the condition leave many clinicians, well, delirious.

The goal of treating delirium is not just to control agitation or hallucinations, but to reverse the delirium and thereby mitigate associated morbidity and mortality risks, Dr. Jay S. Luxenberg said at the annual meeting of the California Association of Long Term Care Medicine.

“The modern concepts of delirium emphasize that delirium can be a persistent issue for a given patient, persisting months and even years,” said Dr. Luxenberg, an internist and geriatrician who is medical director of the Jewish Home in San Francisco. “It may actually reflect a current decline in cognitive functions.”

Another emerging concept about delirium is that it markedly and independently affects patient outcomes such as length of stay, functional decline, and loss of independent living.

“What we need to be thinking of is baseline vulnerability to delirium: what pushes people over the edge,” said Dr. Luxenberg, also of the University of California, San Francisco. “Ultimately, the precipitating factor is just that: the precipitating factor. Of course if they have a urinary tract infection, we're going to treat it. If they have bronchitis, we're going to treat it.”

The exact incidence of delirium among the elderly is not known, but Dr. Luxenberg said that it is surely higher than the national average of 2% reported by Medicare for the period of July 1, 2006, through Dec. 31, 2006. “It isn't being identified as clearly as it should be,” he asserted.

He recommended being specific about delirium symptoms of risk factors during admission assessments. “On your problem list, identify things explicitly because the people who do the [Minimum Data Set] look for written data from the doctor,” he said.

“Anytime a patient is on a lot of medications we should list polypharmacy as one of their problems, even if they need every one of those drugs. Similarly, if the person has delirium, we should write it, not imply it.”

In a study of 2,158 patients with an average age of 84, admitted to a skilled nursing facility from a hospital, 16% had delirium as defined by the Confusion Assessment Method (J. Gerontol. A Biol. Sci. Med. Sci. 2003;58:M441–5). In addition, about 13% of patients had two or more symptoms of delirium and about 40% had one symptom of delirium.

Unresolved, delirium can have significant impact on mortality. One study of 393 postacute care patients (with an average age of 84 years) found that functional recovery differed significantly by delirium resolution status (J. Gerontol. A Biol. Sci. Med. Sci. 2006;61:204–8).

Specifically, patients who resolved their delirium within 2 weeks without recurrence regained 100% of their prehospital functional level, while those who did not retained less than 50% of their prehospital functional level.

In a more recent study, researchers used the Memorial Delirium Assessment Scale to assess psychomotor activity in 457 newly admitted delirious postacute care patients (J. Gerontol. A Biol. Sci. Med. Sci. 2007;62:174–9). The patients were classified as hyperactive, hypoactive, mixed, or normal. Hypoactive patients were 1.6 times more likely to die during 1 year of follow-up compared with patients who had normal psychomotor activity, a difference that was statistically significant.

Patients with the hyperactive and mixed subtypes had an increased risk of dying during 1 year of follow-up compared with patients who had normal psychomotor activity, but the elevations were not statistically significant.

The current data on treatment options for delirium “makes you yearn for more data and better studies,” he said.

A Cochrane review that Dr. Luxenberg helped assemble on the use of antipsychotics for delirium found only three studies suitable for inclusion (Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005594. DOI:10.1002/14651858. CD005594.pub2.). Meta-analysis was only possible in comparing risperidone (Risperdal) vs. haloperidol (Haldol) and olanzapine (Zyprexa) vs. haloperidol.

The results showed no significant difference in overall effect on delirium with olanzapine or risperidone compared with haloperidol.

Data on the use of cholinesterase inhibitors and benzodiazepines for delirium are even more sparse.

One controlled study of haloperidol as a delirium prophylaxis in hip surgery patients found that while there was no effect on the postoperative incidence of acute confusion, patients in the haloperidol arm had earlier improvement of delirium scores and had less severe delirium compared with patients who did not take the drug. The average age of study participants was 79 years (J. Am. Geriatr. Soc. 2005;53:1658–66).

“Somebody should do this study again,” Dr. Luxenberg said. “This is potentially interesting.”

Until more is known about medical interventions for delirium, other approaches are worthy of consideration, including the use of bright or blue light for circadian rhythm disturbances, complementary and alternative medicine, and minimizing the need for restraints by using clysis and by using intramuscular injections instead of intravenous injections, he said.

“Deemphasize the idea that you have to search for an underlying cause of delirium, such as [ordering] a CT scan to look for intra-abdominal abscesses,” he said. “Looking for the common things–the drugs, the [urinary tract infections]–suffices. If the patients aren't coughing, they're not short of breath, and their oxygen saturation is fine, they probably don't need a chest CT to look for occult pneumonia as the cause of their delirium.”

'What we need to be thinking of is baseline vulnerability to delirium.' DR. LUXENBERG

LONG BEACH, CALIF. – So little is known about effective interventions for delirium that efforts to help elderly patients with the condition leave many clinicians, well, delirious.

The goal of treating delirium is not just to control agitation or hallucinations, but to reverse the delirium and thereby mitigate associated morbidity and mortality risks, Dr. Jay S. Luxenberg said at the annual meeting of the California Association of Long Term Care Medicine.

“The modern concepts of delirium emphasize that delirium can be a persistent issue for a given patient, persisting months and even years,” said Dr. Luxenberg, an internist and geriatrician who is medical director of the Jewish Home in San Francisco. “It may actually reflect a current decline in cognitive functions.”

Another emerging concept about delirium is that it markedly and independently affects patient outcomes such as length of stay, functional decline, and loss of independent living.

“What we need to be thinking of is baseline vulnerability to delirium: what pushes people over the edge,” said Dr. Luxenberg, also of the University of California, San Francisco. “Ultimately, the precipitating factor is just that: the precipitating factor. Of course if they have a urinary tract infection, we're going to treat it. If they have bronchitis, we're going to treat it.”

The exact incidence of delirium among the elderly is not known, but Dr. Luxenberg said that it is surely higher than the national average of 2% reported by Medicare for the period of July 1, 2006, through Dec. 31, 2006. “It isn't being identified as clearly as it should be,” he asserted.

He recommended being specific about delirium symptoms of risk factors during admission assessments. “On your problem list, identify things explicitly because the people who do the [Minimum Data Set] look for written data from the doctor,” he said.

“Anytime a patient is on a lot of medications we should list polypharmacy as one of their problems, even if they need every one of those drugs. Similarly, if the person has delirium, we should write it, not imply it.”

In a study of 2,158 patients with an average age of 84, admitted to a skilled nursing facility from a hospital, 16% had delirium as defined by the Confusion Assessment Method (J. Gerontol. A Biol. Sci. Med. Sci. 2003;58:M441–5). In addition, about 13% of patients had two or more symptoms of delirium and about 40% had one symptom of delirium.

Unresolved, delirium can have significant impact on mortality. One study of 393 postacute care patients (with an average age of 84 years) found that functional recovery differed significantly by delirium resolution status (J. Gerontol. A Biol. Sci. Med. Sci. 2006;61:204–8).

Specifically, patients who resolved their delirium within 2 weeks without recurrence regained 100% of their prehospital functional level, while those who did not retained less than 50% of their prehospital functional level.

In a more recent study, researchers used the Memorial Delirium Assessment Scale to assess psychomotor activity in 457 newly admitted delirious postacute care patients (J. Gerontol. A Biol. Sci. Med. Sci. 2007;62:174–9). The patients were classified as hyperactive, hypoactive, mixed, or normal. Hypoactive patients were 1.6 times more likely to die during 1 year of follow-up compared with patients who had normal psychomotor activity, a difference that was statistically significant.

Patients with the hyperactive and mixed subtypes had an increased risk of dying during 1 year of follow-up compared with patients who had normal psychomotor activity, but the elevations were not statistically significant.

The current data on treatment options for delirium “makes you yearn for more data and better studies,” he said.

A Cochrane review that Dr. Luxenberg helped assemble on the use of antipsychotics for delirium found only three studies suitable for inclusion (Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005594. DOI:10.1002/14651858. CD005594.pub2.). Meta-analysis was only possible in comparing risperidone (Risperdal) vs. haloperidol (Haldol) and olanzapine (Zyprexa) vs. haloperidol.

The results showed no significant difference in overall effect on delirium with olanzapine or risperidone compared with haloperidol.

Data on the use of cholinesterase inhibitors and benzodiazepines for delirium are even more sparse.

One controlled study of haloperidol as a delirium prophylaxis in hip surgery patients found that while there was no effect on the postoperative incidence of acute confusion, patients in the haloperidol arm had earlier improvement of delirium scores and had less severe delirium compared with patients who did not take the drug. The average age of study participants was 79 years (J. Am. Geriatr. Soc. 2005;53:1658–66).

“Somebody should do this study again,” Dr. Luxenberg said. “This is potentially interesting.”

Until more is known about medical interventions for delirium, other approaches are worthy of consideration, including the use of bright or blue light for circadian rhythm disturbances, complementary and alternative medicine, and minimizing the need for restraints by using clysis and by using intramuscular injections instead of intravenous injections, he said.

“Deemphasize the idea that you have to search for an underlying cause of delirium, such as [ordering] a CT scan to look for intra-abdominal abscesses,” he said. “Looking for the common things–the drugs, the [urinary tract infections]–suffices. If the patients aren't coughing, they're not short of breath, and their oxygen saturation is fine, they probably don't need a chest CT to look for occult pneumonia as the cause of their delirium.”

'What we need to be thinking of is baseline vulnerability to delirium.' DR. LUXENBERG

LONG BEACH, CALIF. – So little is known about effective interventions for delirium that efforts to help elderly patients with the condition leave many clinicians, well, delirious.

The goal of treating delirium is not just to control agitation or hallucinations, but to reverse the delirium and thereby mitigate associated morbidity and mortality risks, Dr. Jay S. Luxenberg said at the annual meeting of the California Association of Long Term Care Medicine.

“The modern concepts of delirium emphasize that delirium can be a persistent issue for a given patient, persisting months and even years,” said Dr. Luxenberg, an internist and geriatrician who is medical director of the Jewish Home in San Francisco. “It may actually reflect a current decline in cognitive functions.”

Another emerging concept about delirium is that it markedly and independently affects patient outcomes such as length of stay, functional decline, and loss of independent living.

“What we need to be thinking of is baseline vulnerability to delirium: what pushes people over the edge,” said Dr. Luxenberg, also of the University of California, San Francisco. “Ultimately, the precipitating factor is just that: the precipitating factor. Of course if they have a urinary tract infection, we're going to treat it. If they have bronchitis, we're going to treat it.”

The exact incidence of delirium among the elderly is not known, but Dr. Luxenberg said that it is surely higher than the national average of 2% reported by Medicare for the period of July 1, 2006, through Dec. 31, 2006. “It isn't being identified as clearly as it should be,” he asserted.

He recommended being specific about delirium symptoms of risk factors during admission assessments. “On your problem list, identify things explicitly because the people who do the [Minimum Data Set] look for written data from the doctor,” he said.

“Anytime a patient is on a lot of medications we should list polypharmacy as one of their problems, even if they need every one of those drugs. Similarly, if the person has delirium, we should write it, not imply it.”

In a study of 2,158 patients with an average age of 84, admitted to a skilled nursing facility from a hospital, 16% had delirium as defined by the Confusion Assessment Method (J. Gerontol. A Biol. Sci. Med. Sci. 2003;58:M441–5). In addition, about 13% of patients had two or more symptoms of delirium and about 40% had one symptom of delirium.

Unresolved, delirium can have significant impact on mortality. One study of 393 postacute care patients (with an average age of 84 years) found that functional recovery differed significantly by delirium resolution status (J. Gerontol. A Biol. Sci. Med. Sci. 2006;61:204–8).

Specifically, patients who resolved their delirium within 2 weeks without recurrence regained 100% of their prehospital functional level, while those who did not retained less than 50% of their prehospital functional level.

In a more recent study, researchers used the Memorial Delirium Assessment Scale to assess psychomotor activity in 457 newly admitted delirious postacute care patients (J. Gerontol. A Biol. Sci. Med. Sci. 2007;62:174–9). The patients were classified as hyperactive, hypoactive, mixed, or normal. Hypoactive patients were 1.6 times more likely to die during 1 year of follow-up compared with patients who had normal psychomotor activity, a difference that was statistically significant.

Patients with the hyperactive and mixed subtypes had an increased risk of dying during 1 year of follow-up compared with patients who had normal psychomotor activity, but the elevations were not statistically significant.

The current data on treatment options for delirium “makes you yearn for more data and better studies,” he said.

A Cochrane review that Dr. Luxenberg helped assemble on the use of antipsychotics for delirium found only three studies suitable for inclusion (Cochrane Database of Systematic Reviews 2007, Issue 2. Art. No.: CD005594. DOI:10.1002/14651858. CD005594.pub2.). Meta-analysis was only possible in comparing risperidone (Risperdal) vs. haloperidol (Haldol) and olanzapine (Zyprexa) vs. haloperidol.

The results showed no significant difference in overall effect on delirium with olanzapine or risperidone compared with haloperidol.

Data on the use of cholinesterase inhibitors and benzodiazepines for delirium are even more sparse.

One controlled study of haloperidol as a delirium prophylaxis in hip surgery patients found that while there was no effect on the postoperative incidence of acute confusion, patients in the haloperidol arm had earlier improvement of delirium scores and had less severe delirium compared with patients who did not take the drug. The average age of study participants was 79 years (J. Am. Geriatr. Soc. 2005;53:1658–66).

“Somebody should do this study again,” Dr. Luxenberg said. “This is potentially interesting.”

Until more is known about medical interventions for delirium, other approaches are worthy of consideration, including the use of bright or blue light for circadian rhythm disturbances, complementary and alternative medicine, and minimizing the need for restraints by using clysis and by using intramuscular injections instead of intravenous injections, he said.

“Deemphasize the idea that you have to search for an underlying cause of delirium, such as [ordering] a CT scan to look for intra-abdominal abscesses,” he said. “Looking for the common things–the drugs, the [urinary tract infections]–suffices. If the patients aren't coughing, they're not short of breath, and their oxygen saturation is fine, they probably don't need a chest CT to look for occult pneumonia as the cause of their delirium.”

'What we need to be thinking of is baseline vulnerability to delirium.' DR. LUXENBERG

SAN DIEGO — Celiac disease affects an estimated 1% of people in the United States, yet only about 3% of people with the disease are being diagnosed, Dr. Peter H.R. Green said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Reasons for the poor rate of diagnosis are multifactorial, said Dr. Green, who directs Columbia University's Celiac Disease Center in New York. They include:

▸ A shift to the silent form of celiac disease. “The patients and the doctors are on the wrong pages in the [medical] textbooks,” he said. “The patients got it wrong in that they forgot to get diarrhea, and the doctors got it wrong in that they thought that all patients with celiac disease had to have diarrhea.” In fact, he explained, only about half of celiac disease patients present with diarrhea.

So-called silent modes of presentation include bone disease, weight loss, dermatitis herpetiformis, psoriasis, chronic urticaria, and anemia, including iron-deficiency anemia.

“There are increased rates of atopy and there are oral manifestations [in the form of] dental enamel defects such as yellow spots, white spots, and brown spots,” he added.

High-risk groups that Dr. Green screens include patients with a family history of celiac disease, patients with type 1 diabetes, and those with primary biliary sclerosis and Sjögren's syndrome.

▸ Physicians' failure to recognize celiac disease. Physicians “are taught that it's a rare condition,” he said, when in fact it is not and the clinical manifestations vary widely. “That's one of the reasons why there is such a low rate of diagnosis, because no one set of doctors [is] looking at all of those patients.”

▸ Lack of support from the pharmaceutical industry. “We know that over 80% of medical research is financed by the pharmaceutical industry, and by far the bulk of postgraduate education is financed by the pharmaceutical industry,” said Dr. Green, who is also a professor of medicine at Columbia.

The major sources of referrals to Columbia's Celiac Disease Center are neurologists. Other common sources of referral include gynecologists, endocrinologists, and rheumatologists.

In patients with suspected celiac disease, Dr. Green and his associates consider a panel of tests that include the tissue transglutaminase 2 (tTG)-IgA, the tTG-IgG, the IgA endomysial antibody (EMA), and total IgA level. “The best test is probably tTG-IgA, and throw in the tTG-IgG,” he said. “The IgA endomysial antibody need not be done routinely, but it's of value in difficult cases.”

The accepted standard for diagnosis is a biopsy of the descending duodenum. Most celiac disease patients (90%) will have a Marsh III lesion on biopsy, which includes partial, subtotal, and total villous atrophy.

Patients with celiac disease face a 10-fold increased risk of having at least one other autoimmune disease.

Various malignancies have also been linked to having celiac disease, including esophageal and head and neck squamous cell carcinoma, small intestinal carcinoma, and non-Hodgkin's lymphomas.

The management of celiac disease is a lifelong gluten-free diet, which Dr. Green said is difficult to follow in the United States. He recalled seeing gluten-free options on the menu at an ice cream store in Buenos Aires. In Argentina, he said, “there's a lot of celiac disease, and people have very good services.”

Dr. Green predicted that more people will be diagnosed with celiac disease as physicians learn about the wide variability of clinical presentation and the availability of sensitive and specific tests. “As more people become diagnosed, there will be greater awareness, and then people with celiac disease will get a better deal in this country.”

Physicians 'are taught that it's a rare condition,' when in fact it is not and the clinical manifestations vary widely. DR. GREEN

SAN DIEGO — Celiac disease affects an estimated 1% of people in the United States, yet only about 3% of people with the disease are being diagnosed, Dr. Peter H.R. Green said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Reasons for the poor rate of diagnosis are multifactorial, said Dr. Green, who directs Columbia University's Celiac Disease Center in New York. They include:

▸ A shift to the silent form of celiac disease. “The patients and the doctors are on the wrong pages in the [medical] textbooks,” he said. “The patients got it wrong in that they forgot to get diarrhea, and the doctors got it wrong in that they thought that all patients with celiac disease had to have diarrhea.” In fact, he explained, only about half of celiac disease patients present with diarrhea.

So-called silent modes of presentation include bone disease, weight loss, dermatitis herpetiformis, psoriasis, chronic urticaria, and anemia, including iron-deficiency anemia.

“There are increased rates of atopy and there are oral manifestations [in the form of] dental enamel defects such as yellow spots, white spots, and brown spots,” he added.

High-risk groups that Dr. Green screens include patients with a family history of celiac disease, patients with type 1 diabetes, and those with primary biliary sclerosis and Sjögren's syndrome.

▸ Physicians' failure to recognize celiac disease. Physicians “are taught that it's a rare condition,” he said, when in fact it is not and the clinical manifestations vary widely. “That's one of the reasons why there is such a low rate of diagnosis, because no one set of doctors [is] looking at all of those patients.”

▸ Lack of support from the pharmaceutical industry. “We know that over 80% of medical research is financed by the pharmaceutical industry, and by far the bulk of postgraduate education is financed by the pharmaceutical industry,” said Dr. Green, who is also a professor of medicine at Columbia.

The major sources of referrals to Columbia's Celiac Disease Center are neurologists. Other common sources of referral include gynecologists, endocrinologists, and rheumatologists.

In patients with suspected celiac disease, Dr. Green and his associates consider a panel of tests that include the tissue transglutaminase 2 (tTG)-IgA, the tTG-IgG, the IgA endomysial antibody (EMA), and total IgA level. “The best test is probably tTG-IgA, and throw in the tTG-IgG,” he said. “The IgA endomysial antibody need not be done routinely, but it's of value in difficult cases.”

The accepted standard for diagnosis is a biopsy of the descending duodenum. Most celiac disease patients (90%) will have a Marsh III lesion on biopsy, which includes partial, subtotal, and total villous atrophy.

Patients with celiac disease face a 10-fold increased risk of having at least one other autoimmune disease.

Various malignancies have also been linked to having celiac disease, including esophageal and head and neck squamous cell carcinoma, small intestinal carcinoma, and non-Hodgkin's lymphomas.

The management of celiac disease is a lifelong gluten-free diet, which Dr. Green said is difficult to follow in the United States. He recalled seeing gluten-free options on the menu at an ice cream store in Buenos Aires. In Argentina, he said, “there's a lot of celiac disease, and people have very good services.”

Dr. Green predicted that more people will be diagnosed with celiac disease as physicians learn about the wide variability of clinical presentation and the availability of sensitive and specific tests. “As more people become diagnosed, there will be greater awareness, and then people with celiac disease will get a better deal in this country.”

Physicians 'are taught that it's a rare condition,' when in fact it is not and the clinical manifestations vary widely. DR. GREEN

SAN DIEGO — Celiac disease affects an estimated 1% of people in the United States, yet only about 3% of people with the disease are being diagnosed, Dr. Peter H.R. Green said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Reasons for the poor rate of diagnosis are multifactorial, said Dr. Green, who directs Columbia University's Celiac Disease Center in New York. They include:

▸ A shift to the silent form of celiac disease. “The patients and the doctors are on the wrong pages in the [medical] textbooks,” he said. “The patients got it wrong in that they forgot to get diarrhea, and the doctors got it wrong in that they thought that all patients with celiac disease had to have diarrhea.” In fact, he explained, only about half of celiac disease patients present with diarrhea.

So-called silent modes of presentation include bone disease, weight loss, dermatitis herpetiformis, psoriasis, chronic urticaria, and anemia, including iron-deficiency anemia.

“There are increased rates of atopy and there are oral manifestations [in the form of] dental enamel defects such as yellow spots, white spots, and brown spots,” he added.

High-risk groups that Dr. Green screens include patients with a family history of celiac disease, patients with type 1 diabetes, and those with primary biliary sclerosis and Sjögren's syndrome.

▸ Physicians' failure to recognize celiac disease. Physicians “are taught that it's a rare condition,” he said, when in fact it is not and the clinical manifestations vary widely. “That's one of the reasons why there is such a low rate of diagnosis, because no one set of doctors [is] looking at all of those patients.”

▸ Lack of support from the pharmaceutical industry. “We know that over 80% of medical research is financed by the pharmaceutical industry, and by far the bulk of postgraduate education is financed by the pharmaceutical industry,” said Dr. Green, who is also a professor of medicine at Columbia.

The major sources of referrals to Columbia's Celiac Disease Center are neurologists. Other common sources of referral include gynecologists, endocrinologists, and rheumatologists.

In patients with suspected celiac disease, Dr. Green and his associates consider a panel of tests that include the tissue transglutaminase 2 (tTG)-IgA, the tTG-IgG, the IgA endomysial antibody (EMA), and total IgA level. “The best test is probably tTG-IgA, and throw in the tTG-IgG,” he said. “The IgA endomysial antibody need not be done routinely, but it's of value in difficult cases.”

The accepted standard for diagnosis is a biopsy of the descending duodenum. Most celiac disease patients (90%) will have a Marsh III lesion on biopsy, which includes partial, subtotal, and total villous atrophy.

Patients with celiac disease face a 10-fold increased risk of having at least one other autoimmune disease.

Various malignancies have also been linked to having celiac disease, including esophageal and head and neck squamous cell carcinoma, small intestinal carcinoma, and non-Hodgkin's lymphomas.

The management of celiac disease is a lifelong gluten-free diet, which Dr. Green said is difficult to follow in the United States. He recalled seeing gluten-free options on the menu at an ice cream store in Buenos Aires. In Argentina, he said, “there's a lot of celiac disease, and people have very good services.”

Dr. Green predicted that more people will be diagnosed with celiac disease as physicians learn about the wide variability of clinical presentation and the availability of sensitive and specific tests. “As more people become diagnosed, there will be greater awareness, and then people with celiac disease will get a better deal in this country.”

Physicians 'are taught that it's a rare condition,' when in fact it is not and the clinical manifestations vary widely. DR. GREEN

SAN DIEGO – Thirteen percent of patients who underwent laparoscopic adjustable gastric banding required a major reoperation, results from a long-term single-center study showed.

“We see complications, even many years after surgery,” Dr. Vincenzo Bacci said at the annual meeting of the American Society for Bariatric Surgery. “[These patients need] lifelong management and surveillance.”

He and his associates studied the rate and causes of reoperation in 448 patients who underwent laparoscopic adjustable gastric banding in the surgery department at La Sapienza University in Rome, between 1996 and 2006. In 2002, the perigastric technique was replaced by the pars flaccida approach. Of the 448 patients, 83% were women and their average body mass index was 43 kg/m

Of the total, 59 patients (13%) required a major reoperation for band repositioning/removal or revision, and 29 patients (6%) required a minor reoperation for port complications. Patients with a BMI of greater than 50 kg/m

The main reasons for major reoperation were dilatation, erosion of the band, lack of weight loss, psychological problems, and slippage. Minor reoperations were necessitated by infections of the port site, a twist of the port, or breakage. The rate of major reoperation in a subset of patients followed for longer than 5 years was 24%, chiefly because they had undergone gastric banding with the perigastric technique.

SAN DIEGO – Thirteen percent of patients who underwent laparoscopic adjustable gastric banding required a major reoperation, results from a long-term single-center study showed.

“We see complications, even many years after surgery,” Dr. Vincenzo Bacci said at the annual meeting of the American Society for Bariatric Surgery. “[These patients need] lifelong management and surveillance.”

He and his associates studied the rate and causes of reoperation in 448 patients who underwent laparoscopic adjustable gastric banding in the surgery department at La Sapienza University in Rome, between 1996 and 2006. In 2002, the perigastric technique was replaced by the pars flaccida approach. Of the 448 patients, 83% were women and their average body mass index was 43 kg/m

Of the total, 59 patients (13%) required a major reoperation for band repositioning/removal or revision, and 29 patients (6%) required a minor reoperation for port complications. Patients with a BMI of greater than 50 kg/m

The main reasons for major reoperation were dilatation, erosion of the band, lack of weight loss, psychological problems, and slippage. Minor reoperations were necessitated by infections of the port site, a twist of the port, or breakage. The rate of major reoperation in a subset of patients followed for longer than 5 years was 24%, chiefly because they had undergone gastric banding with the perigastric technique.

SAN DIEGO – Thirteen percent of patients who underwent laparoscopic adjustable gastric banding required a major reoperation, results from a long-term single-center study showed.

“We see complications, even many years after surgery,” Dr. Vincenzo Bacci said at the annual meeting of the American Society for Bariatric Surgery. “[These patients need] lifelong management and surveillance.”

He and his associates studied the rate and causes of reoperation in 448 patients who underwent laparoscopic adjustable gastric banding in the surgery department at La Sapienza University in Rome, between 1996 and 2006. In 2002, the perigastric technique was replaced by the pars flaccida approach. Of the 448 patients, 83% were women and their average body mass index was 43 kg/m

Of the total, 59 patients (13%) required a major reoperation for band repositioning/removal or revision, and 29 patients (6%) required a minor reoperation for port complications. Patients with a BMI of greater than 50 kg/m

The main reasons for major reoperation were dilatation, erosion of the band, lack of weight loss, psychological problems, and slippage. Minor reoperations were necessitated by infections of the port site, a twist of the port, or breakage. The rate of major reoperation in a subset of patients followed for longer than 5 years was 24%, chiefly because they had undergone gastric banding with the perigastric technique.