Richard Hyer

CHICAGO — The patient on biologic therapy who must travel and requires immunization with a live attenuated virus or bacteria should be immunized before beginning biologic therapy, according to a case report presented to a symposium that was sponsored by the American College of Rheumatology.

“Think hard about the patient’s life before you put them on biologic therapy, and immunize before you give the medications,” advised Dr. Clifton O. Bingham, who is director of the rheumatology clinics at Johns Hopkins University, Baltimore. However, he acknowledged that this would not always be possible.

The case was a 35-year-old woman with psoriatic arthritis whose work required her to travel to Burkina Faso, a small, landlocked country in West Africa, where yellow fever is endemic. The patient’s skin and articular disease was well controlled with etanercept and methotrexate.

As a practical matter, Dr. Bingham said that the immunomodulators etanercept and methotrexate could be withheld for at least 1 month, and then the patient could be given yellow fever vaccine. He advised waiting 2-3 weeks before restarting the medication. “The disease may flare during that period of time, so that’s the risk you take,” he said.

If the patient was required to travel to the infected area with only 2 weeks’ notice, Dr. Bingham advised providing a letter of medical contraindication to yellow fever vaccination. “That should allow her to enter the country, but you tell her to be really careful.” When a patient is on biological therapy, he said it is important to understand which live vaccinations could potentially reactivate in the setting of immunosuppression.

Vaccines that contain live attenuated viruses or bacteria include: varicella; intranasal influenza/H1N1; measles, mumps, and rubella; yellow fever; oral polio; oral typhoid; vaccinia (smallpox); BCG; and rotavirus.

Disseminated disease has been reported in immunocompromised patients who were immunized with live-virus vaccines. Live viral dissemination has occurred in patients during chemotherapy, and there have been cases of infection in patients receiving immunosuppression for organ transplantation. Live virus dissemination has also been reported in patients with HIV infection. (J. Infect. Dis. 2008;197 [Suppl 2]; Clin. Infect. Dis. 2009;49:1550-6; AIDS Rev.2007;9:173-87).

“So, the recommendation is, with people who are on biologics and people who are immunosuppressed, they should not receive these live vaccinations,” Dr. Bingham said.

Up-to-date vaccine information is available online from the Centers for Disease Control and Prevention (www.cdc.gov/vaccines/pubs/vis/default.htm).

An audience member asked, “Do you think that in some cases it may be a better choice to subject somebody to the risk of an attenuated organism, as opposed to the risk of wild-type disease in an area where the disease may be highly endemic?”

Dr. Bingham said, “The risk of developing yellow fever is about 50 per 100,000 in western Africa, and about 10 per 100,000 in Central and South America. So it is a low risk. But if you delve a little deeper into that information, you find out that many of those patients die. It’s potentially a fatal disease. So you do have to balance the risk.”

Disclosures: Dr. Bingham disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Centocor, Cypress Bioscience, Genentech, Merck, Novartis, Osiris Therapeutics, Procter & Gamble, Roche, Sonosite, Targeted Genetics, UCB, and Wyeth.

CHICAGO — The patient on biologic therapy who must travel and requires immunization with a live attenuated virus or bacteria should be immunized before beginning biologic therapy, according to a case report presented to a symposium that was sponsored by the American College of Rheumatology.

“Think hard about the patient’s life before you put them on biologic therapy, and immunize before you give the medications,” advised Dr. Clifton O. Bingham, who is director of the rheumatology clinics at Johns Hopkins University, Baltimore. However, he acknowledged that this would not always be possible.

The case was a 35-year-old woman with psoriatic arthritis whose work required her to travel to Burkina Faso, a small, landlocked country in West Africa, where yellow fever is endemic. The patient’s skin and articular disease was well controlled with etanercept and methotrexate.

As a practical matter, Dr. Bingham said that the immunomodulators etanercept and methotrexate could be withheld for at least 1 month, and then the patient could be given yellow fever vaccine. He advised waiting 2-3 weeks before restarting the medication. “The disease may flare during that period of time, so that’s the risk you take,” he said.

If the patient was required to travel to the infected area with only 2 weeks’ notice, Dr. Bingham advised providing a letter of medical contraindication to yellow fever vaccination. “That should allow her to enter the country, but you tell her to be really careful.” When a patient is on biological therapy, he said it is important to understand which live vaccinations could potentially reactivate in the setting of immunosuppression.

Vaccines that contain live attenuated viruses or bacteria include: varicella; intranasal influenza/H1N1; measles, mumps, and rubella; yellow fever; oral polio; oral typhoid; vaccinia (smallpox); BCG; and rotavirus.

Disseminated disease has been reported in immunocompromised patients who were immunized with live-virus vaccines. Live viral dissemination has occurred in patients during chemotherapy, and there have been cases of infection in patients receiving immunosuppression for organ transplantation. Live virus dissemination has also been reported in patients with HIV infection. (J. Infect. Dis. 2008;197 [Suppl 2]; Clin. Infect. Dis. 2009;49:1550-6; AIDS Rev.2007;9:173-87).

“So, the recommendation is, with people who are on biologics and people who are immunosuppressed, they should not receive these live vaccinations,” Dr. Bingham said.

Up-to-date vaccine information is available online from the Centers for Disease Control and Prevention (www.cdc.gov/vaccines/pubs/vis/default.htm).

An audience member asked, “Do you think that in some cases it may be a better choice to subject somebody to the risk of an attenuated organism, as opposed to the risk of wild-type disease in an area where the disease may be highly endemic?”

Dr. Bingham said, “The risk of developing yellow fever is about 50 per 100,000 in western Africa, and about 10 per 100,000 in Central and South America. So it is a low risk. But if you delve a little deeper into that information, you find out that many of those patients die. It’s potentially a fatal disease. So you do have to balance the risk.”

Disclosures: Dr. Bingham disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Centocor, Cypress Bioscience, Genentech, Merck, Novartis, Osiris Therapeutics, Procter & Gamble, Roche, Sonosite, Targeted Genetics, UCB, and Wyeth.

CHICAGO — The patient on biologic therapy who must travel and requires immunization with a live attenuated virus or bacteria should be immunized before beginning biologic therapy, according to a case report presented to a symposium that was sponsored by the American College of Rheumatology.

“Think hard about the patient’s life before you put them on biologic therapy, and immunize before you give the medications,” advised Dr. Clifton O. Bingham, who is director of the rheumatology clinics at Johns Hopkins University, Baltimore. However, he acknowledged that this would not always be possible.

The case was a 35-year-old woman with psoriatic arthritis whose work required her to travel to Burkina Faso, a small, landlocked country in West Africa, where yellow fever is endemic. The patient’s skin and articular disease was well controlled with etanercept and methotrexate.

As a practical matter, Dr. Bingham said that the immunomodulators etanercept and methotrexate could be withheld for at least 1 month, and then the patient could be given yellow fever vaccine. He advised waiting 2-3 weeks before restarting the medication. “The disease may flare during that period of time, so that’s the risk you take,” he said.

If the patient was required to travel to the infected area with only 2 weeks’ notice, Dr. Bingham advised providing a letter of medical contraindication to yellow fever vaccination. “That should allow her to enter the country, but you tell her to be really careful.” When a patient is on biological therapy, he said it is important to understand which live vaccinations could potentially reactivate in the setting of immunosuppression.

Vaccines that contain live attenuated viruses or bacteria include: varicella; intranasal influenza/H1N1; measles, mumps, and rubella; yellow fever; oral polio; oral typhoid; vaccinia (smallpox); BCG; and rotavirus.

Disseminated disease has been reported in immunocompromised patients who were immunized with live-virus vaccines. Live viral dissemination has occurred in patients during chemotherapy, and there have been cases of infection in patients receiving immunosuppression for organ transplantation. Live virus dissemination has also been reported in patients with HIV infection. (J. Infect. Dis. 2008;197 [Suppl 2]; Clin. Infect. Dis. 2009;49:1550-6; AIDS Rev.2007;9:173-87).

“So, the recommendation is, with people who are on biologics and people who are immunosuppressed, they should not receive these live vaccinations,” Dr. Bingham said.

Up-to-date vaccine information is available online from the Centers for Disease Control and Prevention (www.cdc.gov/vaccines/pubs/vis/default.htm).

An audience member asked, “Do you think that in some cases it may be a better choice to subject somebody to the risk of an attenuated organism, as opposed to the risk of wild-type disease in an area where the disease may be highly endemic?”

Dr. Bingham said, “The risk of developing yellow fever is about 50 per 100,000 in western Africa, and about 10 per 100,000 in Central and South America. So it is a low risk. But if you delve a little deeper into that information, you find out that many of those patients die. It’s potentially a fatal disease. So you do have to balance the risk.”

Disclosures: Dr. Bingham disclosed financial relationships with Abbott, Amgen, Bristol-Myers Squibb, Centocor, Cypress Bioscience, Genentech, Merck, Novartis, Osiris Therapeutics, Procter & Gamble, Roche, Sonosite, Targeted Genetics, UCB, and Wyeth.

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.

CHICAGO — Redefining the upper limit of serum urate for a diagnosis of gout from 9-10 mg/dL to 6.8-7 mg/dL would better serve patients, said Dr. John S. Sundy of Duke Clinical Research Institute, Chapel Hill, N.C.

Although there is no indication for urate-lowering therapy in patients with asymptomatic uricemia, practice patterns need to be changed and include earlier use of diet to reduce urate levels, he said.

Many patients currently classified as normal are in fact slowly depositing urate crystals in soft tissue, he said, and are therefore at risk for developing gout. Proper diet that limits alcohol and fructose consumption is a key intervention.

Alcohol drinkers who consume more than five drinks daily have a 2.5-fold increased risk for developing gout. A weight gain of 30 pounds since high school doubles the relative risk of developing gout, whereas a weight loss of only 10 pounds actually cuts the risk almost in half, he said.

One can of fructose-sweetened soft drink per day represents a 1.4 increase in relative risk of developing gout, and two or more represent a 1.8 relative risk (BMJ 2008;336:309-12). Fruit juice and high-fructose fruits such as oranges and apples are also significantly associated with gout. “There are clearly metabolic pathways where fructose consumption actually leads to marked elevations in serum urate values, leading to acceleration of deposition of urate crystals in soft tissues. I've really begun to counsel my patients about this and counsel them to reduce their intake of fructose,” said Dr. Sundy.

To manage flares or symptoms, the low-dose colchicine regimen of 1.2 mg at onset of flare followed by 0.6 mg within 1 hour was as effective as high-dose therapy (4.8 mg), but better tolerated, he said. “It shows we can do much lower doses to achieve the same outcome, with far fewer side effects.”

The most important urate-lowering drugs remain allopurinol, febuxostat, and probenecid, said Dr. Sundy, although probenecid is rarely used. He expects the approval of enzyme replacement therapy with polyethylene glycol–modified uricase (PEG-uricase) and expects this to be an IV drug, administered every 2 weeks, for the severe, end-of-spectrum, treatment-failure gout population. “This will be a rheumatologist's drug, maybe a nephrologist's drug, for certain populations.”

At least two new uricosuric agents are on the horizon, he said. The drugs are RDEA594, which he described as “totally experimental,” and Tranilast, a drug already approved in Asia for anti-inflammation.

Moderator Dr. Herbert Baraf, a rheumatologist in private practice in Silver Spring, Md., questioned interleukin-1 inhibition. “Do you think that's realistic, or is that the elephant gun on the mouse?”

“For certain applications, it's realistic,” said Dr. Sundy. “For example for patients who don't respond well and require large doses of corticosteroids to manage a gout flare. For patients in whom there are contraindications to using the nonsteroidal. For example, the brittle diabetic with moderate or severe chronic disease. This is the strategy for the short term. For people with severe disease it could be a corticoteroid-sparing drug.”

Disclosures: Dr. Sundy disclosed research support from Savient Pharmaceuticals, Genentech, Regeneron Pharmaceuticals, and Ardea Biosciences; consulting to Ardea, Anadys Pharmceuticals, Regeneron, and Savient; and speakers bureau with Takeda Pharmaceuticals. Duke University and Mountain View Pharmaceuticals hold patent rights in pegylated urate oxidase and its use which have been licensed to Savient Pharmaceuticals. He disclosed off-label use of allopurinol and anakinra, and experimental use of pegloticase, rilonacept, canakinumab, and RDEA594. Dr. Baraf disclosed no financial relationships.

CHICAGO — A high degree of concordance of oral human papilloma virus infection between HPV-positive patients with oropharynx cancer and their sexual partners suggests that partners are at high risk for HPV-related disease, according to a study from the University of Texas M.D. Anderson Cancer Center in Houston.

Investigators reported that HPV was transmitted between HPV+ patients with oropharynx cancer and their sexual partners at a rate approaching 70%. Almost 60% of these cases involved HPV 16, a causative agent in head and neck squamous cell carcinoma, specifically tonsil cancer, as well as in most cervical malignant and premalignant conditions.

"There was a high rate of human papilloma virus transmission between oropharynx cancer (OPC) patients with HPV+ mouth swabs and their spouses or partners," commented first author Dr. Vassiliki Papadimitrakopoulou, a professor in the department of thoracic/head and neck medical oncology at M.D. Anderson. The study was presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Human papilloma virus transmission between sexual partners is well documented in cervical cancer, but not in head and neck squamous cell carcinoma. Investigators thought that information on transmission could help define a population that would benefit from heightened cancer screening and vaccination.

"HPV-related OPC occurs in a younger group of patients than does the tobacco-related squamous cell cancer of the head and neck," noted Dr. Anne Tsao, the study's principal investigator from the same department at M.D. Anderson.

The authors used mouth swabs to gather DNA from 454 individuals, comprising 227 pairs of oropharynx cancer patients and their partners. Samples from 200 patient-partner pairs yielded adequate DNA for analysis, and this was the minimum required to meet the study’s planned accrual.

In situ hybridization and/or p16 immunohistochemistry detected HPV in 84 (86%) of 98 patients, for whom complete information on HPV status in tumor tissue was available at the time of the presentation. Not all of these cases resulted in positive mouth swabs, however.

Of the 200 patient-partner pairs, only 39 pairs (20%) had one or both members with a mouth swab testing positive for HPV. In 28 of these 39 pairs (72%), the mouth swab was positive in patients, and in 19 of these 28 (68%) the partners also had positive mouth swabs. The investigators reported 100% concordance for at least one human papilloma virus genotype in these 19 pairs, confirming that the virus had been exchanged between the partners; 58% of transmission cases involved HPV-16.

In 11 of the 39 pairs, the patient with oropharynx cancer tested negative for HPV, whereas the partner tested positive.

Regardless of HPV status as determined by mouth swabs, 30% of female partners but none of the men in the study reported a history of HPV-related disease. The investigators observed that this generates a hypothesis "that HPV affects the cervix at an earlier age than it does the oropharynx, and that gender may have a role in oncogenic susceptibility and/or chronic transmission of the virus." The data "encourage" screening of female partners and HPV+ female patients for cervical abnormalities, they advised.

"We recommend increased screening of partners of human papilloma virus positive patients in general," said Dr. Papadimitrakopoulou. She cautioned, however: "We don't know that the mouth swab is an adequate screening method."

In a discussion of the study, Anil Chaturvedi, D.V.M., Ph.D, an investigator at the National Cancer Institute, observed, "We know that oral HPV infection is a strong cause of a subset of head and neck cancers [but] very little is currently known about the molecular epidemiology of human papilloma virus infections ... [this study] showed that oral human papilloma virus infection was highly concordant among human papilloma virus-positive patients and their partners. The study underscores the partner population as an ideal high-risk population to perhaps investigate the presence of a premalignant lesion."

Dr. Chaturvedi also expressed concern about the low sensitivity of mouth swabs as a test for HPV, however. "I'd like to note a potential limitation of this particular study, which relates to the low sensitivity of mouth swabs in detecting oral HPV infection, as evidenced by the low percent positive agreement between tumor HPV status and the presence of HPV in oral swabs," he said.

The investigators and the discussant disclosed no relevant relationships. The National Cancer Institute funded the study.

CHICAGO — A high degree of concordance of oral human papilloma virus infection between HPV-positive patients with oropharynx cancer and their sexual partners suggests that partners are at high risk for HPV-related disease, according to a study from the University of Texas M.D. Anderson Cancer Center in Houston.

Investigators reported that HPV was transmitted between HPV+ patients with oropharynx cancer and their sexual partners at a rate approaching 70%. Almost 60% of these cases involved HPV 16, a causative agent in head and neck squamous cell carcinoma, specifically tonsil cancer, as well as in most cervical malignant and premalignant conditions.

"There was a high rate of human papilloma virus transmission between oropharynx cancer (OPC) patients with HPV+ mouth swabs and their spouses or partners," commented first author Dr. Vassiliki Papadimitrakopoulou, a professor in the department of thoracic/head and neck medical oncology at M.D. Anderson. The study was presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Human papilloma virus transmission between sexual partners is well documented in cervical cancer, but not in head and neck squamous cell carcinoma. Investigators thought that information on transmission could help define a population that would benefit from heightened cancer screening and vaccination.

"HPV-related OPC occurs in a younger group of patients than does the tobacco-related squamous cell cancer of the head and neck," noted Dr. Anne Tsao, the study's principal investigator from the same department at M.D. Anderson.

The authors used mouth swabs to gather DNA from 454 individuals, comprising 227 pairs of oropharynx cancer patients and their partners. Samples from 200 patient-partner pairs yielded adequate DNA for analysis, and this was the minimum required to meet the study’s planned accrual.

In situ hybridization and/or p16 immunohistochemistry detected HPV in 84 (86%) of 98 patients, for whom complete information on HPV status in tumor tissue was available at the time of the presentation. Not all of these cases resulted in positive mouth swabs, however.

Of the 200 patient-partner pairs, only 39 pairs (20%) had one or both members with a mouth swab testing positive for HPV. In 28 of these 39 pairs (72%), the mouth swab was positive in patients, and in 19 of these 28 (68%) the partners also had positive mouth swabs. The investigators reported 100% concordance for at least one human papilloma virus genotype in these 19 pairs, confirming that the virus had been exchanged between the partners; 58% of transmission cases involved HPV-16.

In 11 of the 39 pairs, the patient with oropharynx cancer tested negative for HPV, whereas the partner tested positive.

Regardless of HPV status as determined by mouth swabs, 30% of female partners but none of the men in the study reported a history of HPV-related disease. The investigators observed that this generates a hypothesis "that HPV affects the cervix at an earlier age than it does the oropharynx, and that gender may have a role in oncogenic susceptibility and/or chronic transmission of the virus." The data "encourage" screening of female partners and HPV+ female patients for cervical abnormalities, they advised.

"We recommend increased screening of partners of human papilloma virus positive patients in general," said Dr. Papadimitrakopoulou. She cautioned, however: "We don't know that the mouth swab is an adequate screening method."

In a discussion of the study, Anil Chaturvedi, D.V.M., Ph.D, an investigator at the National Cancer Institute, observed, "We know that oral HPV infection is a strong cause of a subset of head and neck cancers [but] very little is currently known about the molecular epidemiology of human papilloma virus infections ... [this study] showed that oral human papilloma virus infection was highly concordant among human papilloma virus-positive patients and their partners. The study underscores the partner population as an ideal high-risk population to perhaps investigate the presence of a premalignant lesion."

Dr. Chaturvedi also expressed concern about the low sensitivity of mouth swabs as a test for HPV, however. "I'd like to note a potential limitation of this particular study, which relates to the low sensitivity of mouth swabs in detecting oral HPV infection, as evidenced by the low percent positive agreement between tumor HPV status and the presence of HPV in oral swabs," he said.

The investigators and the discussant disclosed no relevant relationships. The National Cancer Institute funded the study.

CHICAGO — A high degree of concordance of oral human papilloma virus infection between HPV-positive patients with oropharynx cancer and their sexual partners suggests that partners are at high risk for HPV-related disease, according to a study from the University of Texas M.D. Anderson Cancer Center in Houston.

Investigators reported that HPV was transmitted between HPV+ patients with oropharynx cancer and their sexual partners at a rate approaching 70%. Almost 60% of these cases involved HPV 16, a causative agent in head and neck squamous cell carcinoma, specifically tonsil cancer, as well as in most cervical malignant and premalignant conditions.

"There was a high rate of human papilloma virus transmission between oropharynx cancer (OPC) patients with HPV+ mouth swabs and their spouses or partners," commented first author Dr. Vassiliki Papadimitrakopoulou, a professor in the department of thoracic/head and neck medical oncology at M.D. Anderson. The study was presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Human papilloma virus transmission between sexual partners is well documented in cervical cancer, but not in head and neck squamous cell carcinoma. Investigators thought that information on transmission could help define a population that would benefit from heightened cancer screening and vaccination.

"HPV-related OPC occurs in a younger group of patients than does the tobacco-related squamous cell cancer of the head and neck," noted Dr. Anne Tsao, the study's principal investigator from the same department at M.D. Anderson.

The authors used mouth swabs to gather DNA from 454 individuals, comprising 227 pairs of oropharynx cancer patients and their partners. Samples from 200 patient-partner pairs yielded adequate DNA for analysis, and this was the minimum required to meet the study’s planned accrual.

In situ hybridization and/or p16 immunohistochemistry detected HPV in 84 (86%) of 98 patients, for whom complete information on HPV status in tumor tissue was available at the time of the presentation. Not all of these cases resulted in positive mouth swabs, however.

Of the 200 patient-partner pairs, only 39 pairs (20%) had one or both members with a mouth swab testing positive for HPV. In 28 of these 39 pairs (72%), the mouth swab was positive in patients, and in 19 of these 28 (68%) the partners also had positive mouth swabs. The investigators reported 100% concordance for at least one human papilloma virus genotype in these 19 pairs, confirming that the virus had been exchanged between the partners; 58% of transmission cases involved HPV-16.

In 11 of the 39 pairs, the patient with oropharynx cancer tested negative for HPV, whereas the partner tested positive.

Regardless of HPV status as determined by mouth swabs, 30% of female partners but none of the men in the study reported a history of HPV-related disease. The investigators observed that this generates a hypothesis "that HPV affects the cervix at an earlier age than it does the oropharynx, and that gender may have a role in oncogenic susceptibility and/or chronic transmission of the virus." The data "encourage" screening of female partners and HPV+ female patients for cervical abnormalities, they advised.

"We recommend increased screening of partners of human papilloma virus positive patients in general," said Dr. Papadimitrakopoulou. She cautioned, however: "We don't know that the mouth swab is an adequate screening method."

In a discussion of the study, Anil Chaturvedi, D.V.M., Ph.D, an investigator at the National Cancer Institute, observed, "We know that oral HPV infection is a strong cause of a subset of head and neck cancers [but] very little is currently known about the molecular epidemiology of human papilloma virus infections ... [this study] showed that oral human papilloma virus infection was highly concordant among human papilloma virus-positive patients and their partners. The study underscores the partner population as an ideal high-risk population to perhaps investigate the presence of a premalignant lesion."

Dr. Chaturvedi also expressed concern about the low sensitivity of mouth swabs as a test for HPV, however. "I'd like to note a potential limitation of this particular study, which relates to the low sensitivity of mouth swabs in detecting oral HPV infection, as evidenced by the low percent positive agreement between tumor HPV status and the presence of HPV in oral swabs," he said.

The investigators and the discussant disclosed no relevant relationships. The National Cancer Institute funded the study.

Major Finding: For newly diagnosed GBM patients, median overall survival reached 21.2 months with a regimen incorporating bevacizumab, temozolomide, irinotecan, and radiation.

Data Source: First 75 patients treated with bevacizumab, temozolomide, and radiation followed by bevacizumab, temozolomide, and irinotecan in a phase II trial.

Disclosures: The investigator-sponsored study received support from Genentech Inc. and Schering-Plough. Dr. Vredenburgh said he consults for Genentech.

CHICAGO — A new protocol that adds temozolomide and radiation to bevacizumab and irinotecan for patients with newly diagnosed glioblastoma multiforme has resulted in median overall survival reaching 21.2 months, according to investigators from Duke University.

At 16 months, 65.3% of the first 75 patients in the up-front, phase II trial were still alive, they reported. The 2-year overall survival rate was 45%.

“We were not surprised by the findings. … We had shown that bevacizumab plus irinotecan had good efficacy in glioblastoma,” said principal investigator Dr. James Vredenburgh, a professor of medicine and the medical director of adult clinical services at Duke University Medical Center.

He suggested that the findings will encourage investigators to enroll patients in phase III studies now underway. “I think the phase III studies will change clinical practice,” Dr. Vredenburgh said.

In May 2009, the Food and Drug Administration approved bevacizumab (Avastin) mono-therapy second-line for treatment of glioblastoma that had progressed after first-line treatment. Temozolomide (Temo-dar) was approved in March 2005 as a first-line treatment with radiation and as a maintenance therapy.

The new experimental protocol uses bevacizumab in combination with temozolomide and radiation therapy, followed by bevacizumab, temozolomide, and irinotecan (Camptosar) for newly diagnosed glioblastoma multiforme and gliosarcoma.

The study rationale was that VEGF (vascular endothelial growth factor) is an essential part of glioblastoma biology, and the anti-VEGF monoclonal antibody bevacizumab has demonstrated synergy with radiation and chemotherapy. Irinotecan was thought possibly to have synergy with temozolomide. Bevacizumab with or without irinotecan had shown activity in recurrent disease, and it was thought that using bevacizumab with chemotherapy in newly diagnosed patients might improve survival.

Using previously reported median survival of 15.8 months in resected patients (N. Engl. J. Med. 2005;352:987-96) as a benchmark, the investigators set the primary end point of this trial as the proportion of patients who were alive 16 months after initiation of combination chemoradiotherapy, with a target of more than 60%.

The study was opened on August 15, 2007, and 75 patients were accrued through September 4, 2008, with a median follow-up of 25 months (range, 19–31 months). A second cohort of 50 patients was enrolled from October 30, 2008, to March 26, 2009. These 50 patients are included in the toxicity data, but not in the survival analysis.

The protocol called for all patients to start receiving radiation therapy and temozolomide at 75 mg/m

After radiation therapy, patients received 6-12 monthly cycles of temozolomide at 200 mg/m

Median progression-free survival reached 14.2 months, and the 2-year progression-free survival rate was 13.3% for the first 75 patients, Dr. Vredenburgh reported.

Median overall survival from progression, which was measured in 62 patients, was 5 months; the 2-year overall survival from progression was 8.8%.

Grade 4 hematologic toxicity occurred in 17 of 125 patients, and deep vein thrombosis/pulmonary embolism occurred in 9 patients.

All other toxicities occurred in not more than two patients. There were four toxic deaths (one each from myocardial infarction, DVT/PE, sepsis, and pneumocystis pneumonia).

Findings should encourage patient enrollment in potentially practice-changing phase III trials.

Source DR. VREDENBURGH

Major Finding: For newly diagnosed GBM patients, median overall survival reached 21.2 months with a regimen incorporating bevacizumab, temozolomide, irinotecan, and radiation.

Data Source: First 75 patients treated with bevacizumab, temozolomide, and radiation followed by bevacizumab, temozolomide, and irinotecan in a phase II trial.

Disclosures: The investigator-sponsored study received support from Genentech Inc. and Schering-Plough. Dr. Vredenburgh said he consults for Genentech.

CHICAGO — A new protocol that adds temozolomide and radiation to bevacizumab and irinotecan for patients with newly diagnosed glioblastoma multiforme has resulted in median overall survival reaching 21.2 months, according to investigators from Duke University.

At 16 months, 65.3% of the first 75 patients in the up-front, phase II trial were still alive, they reported. The 2-year overall survival rate was 45%.

“We were not surprised by the findings. … We had shown that bevacizumab plus irinotecan had good efficacy in glioblastoma,” said principal investigator Dr. James Vredenburgh, a professor of medicine and the medical director of adult clinical services at Duke University Medical Center.

He suggested that the findings will encourage investigators to enroll patients in phase III studies now underway. “I think the phase III studies will change clinical practice,” Dr. Vredenburgh said.

In May 2009, the Food and Drug Administration approved bevacizumab (Avastin) mono-therapy second-line for treatment of glioblastoma that had progressed after first-line treatment. Temozolomide (Temo-dar) was approved in March 2005 as a first-line treatment with radiation and as a maintenance therapy.

The new experimental protocol uses bevacizumab in combination with temozolomide and radiation therapy, followed by bevacizumab, temozolomide, and irinotecan (Camptosar) for newly diagnosed glioblastoma multiforme and gliosarcoma.

The study rationale was that VEGF (vascular endothelial growth factor) is an essential part of glioblastoma biology, and the anti-VEGF monoclonal antibody bevacizumab has demonstrated synergy with radiation and chemotherapy. Irinotecan was thought possibly to have synergy with temozolomide. Bevacizumab with or without irinotecan had shown activity in recurrent disease, and it was thought that using bevacizumab with chemotherapy in newly diagnosed patients might improve survival.

Using previously reported median survival of 15.8 months in resected patients (N. Engl. J. Med. 2005;352:987-96) as a benchmark, the investigators set the primary end point of this trial as the proportion of patients who were alive 16 months after initiation of combination chemoradiotherapy, with a target of more than 60%.

The study was opened on August 15, 2007, and 75 patients were accrued through September 4, 2008, with a median follow-up of 25 months (range, 19–31 months). A second cohort of 50 patients was enrolled from October 30, 2008, to March 26, 2009. These 50 patients are included in the toxicity data, but not in the survival analysis.

The protocol called for all patients to start receiving radiation therapy and temozolomide at 75 mg/m

After radiation therapy, patients received 6-12 monthly cycles of temozolomide at 200 mg/m

Median progression-free survival reached 14.2 months, and the 2-year progression-free survival rate was 13.3% for the first 75 patients, Dr. Vredenburgh reported.

Median overall survival from progression, which was measured in 62 patients, was 5 months; the 2-year overall survival from progression was 8.8%.

Grade 4 hematologic toxicity occurred in 17 of 125 patients, and deep vein thrombosis/pulmonary embolism occurred in 9 patients.

All other toxicities occurred in not more than two patients. There were four toxic deaths (one each from myocardial infarction, DVT/PE, sepsis, and pneumocystis pneumonia).

Findings should encourage patient enrollment in potentially practice-changing phase III trials.

Source DR. VREDENBURGH

Major Finding: For newly diagnosed GBM patients, median overall survival reached 21.2 months with a regimen incorporating bevacizumab, temozolomide, irinotecan, and radiation.

Data Source: First 75 patients treated with bevacizumab, temozolomide, and radiation followed by bevacizumab, temozolomide, and irinotecan in a phase II trial.

Disclosures: The investigator-sponsored study received support from Genentech Inc. and Schering-Plough. Dr. Vredenburgh said he consults for Genentech.

CHICAGO — A new protocol that adds temozolomide and radiation to bevacizumab and irinotecan for patients with newly diagnosed glioblastoma multiforme has resulted in median overall survival reaching 21.2 months, according to investigators from Duke University.

At 16 months, 65.3% of the first 75 patients in the up-front, phase II trial were still alive, they reported. The 2-year overall survival rate was 45%.

“We were not surprised by the findings. … We had shown that bevacizumab plus irinotecan had good efficacy in glioblastoma,” said principal investigator Dr. James Vredenburgh, a professor of medicine and the medical director of adult clinical services at Duke University Medical Center.

He suggested that the findings will encourage investigators to enroll patients in phase III studies now underway. “I think the phase III studies will change clinical practice,” Dr. Vredenburgh said.

In May 2009, the Food and Drug Administration approved bevacizumab (Avastin) mono-therapy second-line for treatment of glioblastoma that had progressed after first-line treatment. Temozolomide (Temo-dar) was approved in March 2005 as a first-line treatment with radiation and as a maintenance therapy.

The new experimental protocol uses bevacizumab in combination with temozolomide and radiation therapy, followed by bevacizumab, temozolomide, and irinotecan (Camptosar) for newly diagnosed glioblastoma multiforme and gliosarcoma.

The study rationale was that VEGF (vascular endothelial growth factor) is an essential part of glioblastoma biology, and the anti-VEGF monoclonal antibody bevacizumab has demonstrated synergy with radiation and chemotherapy. Irinotecan was thought possibly to have synergy with temozolomide. Bevacizumab with or without irinotecan had shown activity in recurrent disease, and it was thought that using bevacizumab with chemotherapy in newly diagnosed patients might improve survival.

Using previously reported median survival of 15.8 months in resected patients (N. Engl. J. Med. 2005;352:987-96) as a benchmark, the investigators set the primary end point of this trial as the proportion of patients who were alive 16 months after initiation of combination chemoradiotherapy, with a target of more than 60%.

The study was opened on August 15, 2007, and 75 patients were accrued through September 4, 2008, with a median follow-up of 25 months (range, 19–31 months). A second cohort of 50 patients was enrolled from October 30, 2008, to March 26, 2009. These 50 patients are included in the toxicity data, but not in the survival analysis.

The protocol called for all patients to start receiving radiation therapy and temozolomide at 75 mg/m

After radiation therapy, patients received 6-12 monthly cycles of temozolomide at 200 mg/m

Median progression-free survival reached 14.2 months, and the 2-year progression-free survival rate was 13.3% for the first 75 patients, Dr. Vredenburgh reported.

Median overall survival from progression, which was measured in 62 patients, was 5 months; the 2-year overall survival from progression was 8.8%.

Grade 4 hematologic toxicity occurred in 17 of 125 patients, and deep vein thrombosis/pulmonary embolism occurred in 9 patients.

All other toxicities occurred in not more than two patients. There were four toxic deaths (one each from myocardial infarction, DVT/PE, sepsis, and pneumocystis pneumonia).

Findings should encourage patient enrollment in potentially practice-changing phase III trials.

Source DR. VREDENBURGH

Major Finding: Gleason scores of 7 or higher were twice as common, 44% vs. 22%, in low-risk men who delayed radical prostatectomy compared with men who passed up active surveillance for immediate surgery, but many of the delayed surgeries were ordered after Gleason score reached 7 or higher on surveillance biopsies.

Data Source: 1,120 men who were eligible for active surveillance: 772 who chose the monitoring strategy and 348 who opted for immediate radical prostatectomy.

Disclosures: The investigators and discussant disclosed no conflicts of interest.

CHICAGO — A prospective cohort study comparing immediate radical prostatectomy with delayed surgery in 1,120 men who qualified for active surveillance suggests waiting is a viable option for most patients deemed to be at low risk of developing prostate cancer.

Men in the delayed-surgery group were twice as likely to have a Gleason score of 7 or higher, reported Bruce J. Trock, Ph.D., and his coinvestigators from Johns Hopkins University, Baltimore. The delayed-surgery group also had more tumors that were not organ confined.

This appeared to be the result of selection bias, however. Many of the delayed surgeries were ordered after a surveillance biopsy showed the patient had a Gleason score of 7 or higher, explained Dr. Trock, director of the division of epidemiology at the university's Brady Urological Institute. When these men were excluded, surgical pathology was similar in the remaining men who delayed radical prostatectomy and those who opted for immediate surgery.

“So it appears that a missed high-grade tumor at [the initial] biopsy is the predominant risk in the active-surveillance cohort,” Dr. Trock said, suggesting that higher risk was confined to men who had been undergraded in their initial biopsies. The median time to delayed surgery was 23 months, he noted.

The study began in 1995 and compared 772 men in an active-surveillance cohort with 348 men who were eligible for active surveillance but instead elected to have immediate radical prostatectomy.

Eligibility for active surveillance included a prostate-specific antigen density less than 0.15 ng/mL per cc, biopsy Gleason score of 6 or less, two or fewer positive cores, and 50 % or less of any biopsy core involved with tumor.

Progression was considered to occur if the pathology of a follow-up biopsy exceeded these eligibility criteria and triggered a recommendation for treatment. Of the 772 men enrolled in the active-surveillance program, 116 (15%) have since undergone radical prostatectomy: 25 had “no trigger” indicating higher-risk disease but chose surgery anyway, 43 had a biopsy upgrade (Gleason score 7 or higher), and 48 had more than two positive cores or more than 50% of a core involved with tumor.

These 116 patients were frequency matched 1:3 with 348 men who met eligibility for active surveillance but decided on immediate radical prostatectomy.

Looking just at the men who underwent surgery, the study found that 44% of the delayed-surgery group had Gleason 7 or greater at surgery vs. 22 % of the immediate-surgery group. Non–organ confined tumors occurred in 27% of the delayed surgeries vs. 16% of the immediate surgeries.

These differences were even more pronounced when the men upgraded at a surveillance biopsy were compared with the immediate-surgery group: 76% vs. 22%, respectively, for Gleason score of 7 or higher and 34% vs. 16% for non–organ confined disease. Among 67 men who were not upgraded before delayed surgery, 25% had Gleason scores of 7 or higher and 23% had non–organ confined disease. Neither measure was significantly different from the pathology in the immediate-prostatectomy group.

The clinical translation of these findings is that about 15% of men under active surveillance undergo radical prostatectomy within 2-3 years, according to Dr. Trock. Overall, the risk of adverse pathology at radical prostatectomy is low: The chance of a high-grade Gleason score greater than or equal to 7 is 4.5 per 100 person-years, while the risk of non–organ confined pathology is 1.2 per 100 person-years.

Major Finding: Gleason scores of 7 or higher were twice as common, 44% vs. 22%, in low-risk men who delayed radical prostatectomy compared with men who passed up active surveillance for immediate surgery, but many of the delayed surgeries were ordered after Gleason score reached 7 or higher on surveillance biopsies.

Data Source: 1,120 men who were eligible for active surveillance: 772 who chose the monitoring strategy and 348 who opted for immediate radical prostatectomy.

Disclosures: The investigators and discussant disclosed no conflicts of interest.

CHICAGO — A prospective cohort study comparing immediate radical prostatectomy with delayed surgery in 1,120 men who qualified for active surveillance suggests waiting is a viable option for most patients deemed to be at low risk of developing prostate cancer.

Men in the delayed-surgery group were twice as likely to have a Gleason score of 7 or higher, reported Bruce J. Trock, Ph.D., and his coinvestigators from Johns Hopkins University, Baltimore. The delayed-surgery group also had more tumors that were not organ confined.

This appeared to be the result of selection bias, however. Many of the delayed surgeries were ordered after a surveillance biopsy showed the patient had a Gleason score of 7 or higher, explained Dr. Trock, director of the division of epidemiology at the university's Brady Urological Institute. When these men were excluded, surgical pathology was similar in the remaining men who delayed radical prostatectomy and those who opted for immediate surgery.

“So it appears that a missed high-grade tumor at [the initial] biopsy is the predominant risk in the active-surveillance cohort,” Dr. Trock said, suggesting that higher risk was confined to men who had been undergraded in their initial biopsies. The median time to delayed surgery was 23 months, he noted.

The study began in 1995 and compared 772 men in an active-surveillance cohort with 348 men who were eligible for active surveillance but instead elected to have immediate radical prostatectomy.

Eligibility for active surveillance included a prostate-specific antigen density less than 0.15 ng/mL per cc, biopsy Gleason score of 6 or less, two or fewer positive cores, and 50 % or less of any biopsy core involved with tumor.

Progression was considered to occur if the pathology of a follow-up biopsy exceeded these eligibility criteria and triggered a recommendation for treatment. Of the 772 men enrolled in the active-surveillance program, 116 (15%) have since undergone radical prostatectomy: 25 had “no trigger” indicating higher-risk disease but chose surgery anyway, 43 had a biopsy upgrade (Gleason score 7 or higher), and 48 had more than two positive cores or more than 50% of a core involved with tumor.

These 116 patients were frequency matched 1:3 with 348 men who met eligibility for active surveillance but decided on immediate radical prostatectomy.

Looking just at the men who underwent surgery, the study found that 44% of the delayed-surgery group had Gleason 7 or greater at surgery vs. 22 % of the immediate-surgery group. Non–organ confined tumors occurred in 27% of the delayed surgeries vs. 16% of the immediate surgeries.

These differences were even more pronounced when the men upgraded at a surveillance biopsy were compared with the immediate-surgery group: 76% vs. 22%, respectively, for Gleason score of 7 or higher and 34% vs. 16% for non–organ confined disease. Among 67 men who were not upgraded before delayed surgery, 25% had Gleason scores of 7 or higher and 23% had non–organ confined disease. Neither measure was significantly different from the pathology in the immediate-prostatectomy group.

The clinical translation of these findings is that about 15% of men under active surveillance undergo radical prostatectomy within 2-3 years, according to Dr. Trock. Overall, the risk of adverse pathology at radical prostatectomy is low: The chance of a high-grade Gleason score greater than or equal to 7 is 4.5 per 100 person-years, while the risk of non–organ confined pathology is 1.2 per 100 person-years.

Major Finding: Gleason scores of 7 or higher were twice as common, 44% vs. 22%, in low-risk men who delayed radical prostatectomy compared with men who passed up active surveillance for immediate surgery, but many of the delayed surgeries were ordered after Gleason score reached 7 or higher on surveillance biopsies.

Data Source: 1,120 men who were eligible for active surveillance: 772 who chose the monitoring strategy and 348 who opted for immediate radical prostatectomy.

Disclosures: The investigators and discussant disclosed no conflicts of interest.

CHICAGO — A prospective cohort study comparing immediate radical prostatectomy with delayed surgery in 1,120 men who qualified for active surveillance suggests waiting is a viable option for most patients deemed to be at low risk of developing prostate cancer.

Men in the delayed-surgery group were twice as likely to have a Gleason score of 7 or higher, reported Bruce J. Trock, Ph.D., and his coinvestigators from Johns Hopkins University, Baltimore. The delayed-surgery group also had more tumors that were not organ confined.

This appeared to be the result of selection bias, however. Many of the delayed surgeries were ordered after a surveillance biopsy showed the patient had a Gleason score of 7 or higher, explained Dr. Trock, director of the division of epidemiology at the university's Brady Urological Institute. When these men were excluded, surgical pathology was similar in the remaining men who delayed radical prostatectomy and those who opted for immediate surgery.

“So it appears that a missed high-grade tumor at [the initial] biopsy is the predominant risk in the active-surveillance cohort,” Dr. Trock said, suggesting that higher risk was confined to men who had been undergraded in their initial biopsies. The median time to delayed surgery was 23 months, he noted.

The study began in 1995 and compared 772 men in an active-surveillance cohort with 348 men who were eligible for active surveillance but instead elected to have immediate radical prostatectomy.

Eligibility for active surveillance included a prostate-specific antigen density less than 0.15 ng/mL per cc, biopsy Gleason score of 6 or less, two or fewer positive cores, and 50 % or less of any biopsy core involved with tumor.

Progression was considered to occur if the pathology of a follow-up biopsy exceeded these eligibility criteria and triggered a recommendation for treatment. Of the 772 men enrolled in the active-surveillance program, 116 (15%) have since undergone radical prostatectomy: 25 had “no trigger” indicating higher-risk disease but chose surgery anyway, 43 had a biopsy upgrade (Gleason score 7 or higher), and 48 had more than two positive cores or more than 50% of a core involved with tumor.

These 116 patients were frequency matched 1:3 with 348 men who met eligibility for active surveillance but decided on immediate radical prostatectomy.

Looking just at the men who underwent surgery, the study found that 44% of the delayed-surgery group had Gleason 7 or greater at surgery vs. 22 % of the immediate-surgery group. Non–organ confined tumors occurred in 27% of the delayed surgeries vs. 16% of the immediate surgeries.

These differences were even more pronounced when the men upgraded at a surveillance biopsy were compared with the immediate-surgery group: 76% vs. 22%, respectively, for Gleason score of 7 or higher and 34% vs. 16% for non–organ confined disease. Among 67 men who were not upgraded before delayed surgery, 25% had Gleason scores of 7 or higher and 23% had non–organ confined disease. Neither measure was significantly different from the pathology in the immediate-prostatectomy group.

The clinical translation of these findings is that about 15% of men under active surveillance undergo radical prostatectomy within 2-3 years, according to Dr. Trock. Overall, the risk of adverse pathology at radical prostatectomy is low: The chance of a high-grade Gleason score greater than or equal to 7 is 4.5 per 100 person-years, while the risk of non–organ confined pathology is 1.2 per 100 person-years.

CHICAGO — A new online resource will help seriously ill patients and their physicians request expanded access to investigational therapies when they have exhausted all other treatment options and the patients are not eligible for a clinical trial, it was announced June 4 at a joint news conference of the American Society of Clinical Oncology and the Food and Drug Administration.

"Most clinical trials have quite stringent eligibility criteria, and many patients are not eligible to enroll," said ASCO President-Elect George W. Sledge Jr., of Indiana University Simon Cancer Center, Indianapolis.

"In those instances when preliminary scientific evidence suggests that treatment with an unapproved therapy might be beneficial, the FDA's expanded access regulations allow physicians to request access to an investigational agent, outside of the clinical trial setting, for seriously ill patients," he said.

Expanded access has been allowed since the 1970s, but many physicians have been uncertain about how to request it, what regulations apply, and the legal ramifications. All of these issues are clarified in the new Web site.

"It's been clear to the agency that there was room for progress," said FDA Principal Deputy Commissioner Dr. Joshua M. Sharfstein, addressing the press conference on the opening day of ASCO's annual meeting.

"This is about the opportunity for the FDA to work with a medical specialty society, in this case ASCO, in what really should be a model for the agency - and work together to develop a program to reach out to clinicians and help them understand something that can be a little confusing at first," he said.

The new resources are available immediately to all patients and physicians, free of charge, through ASCO's physician education Web site, ASCO University.  

The material is presented in three online modules, which introduce the expanded access regulations, outline the process for requesting expanded access, and explain the physicians' legal responsibilities for treating patients with an investigational agent outside of a clinical trial.

The modules also contain resources such as a glossary, an expanded access request checklist, and various templates (letter to manufacturer, consent form, etc.) to help physicians with the paperwork.

In August 2009, the FDA issued updated regulations and attempted to clarify the rules in two publications, "Expanded Access to Investigational Drugs for Treatment Use," and "Charging for Investigational Drugs." The new Web site goes a step further.

To clarify the new rules for patients and the medical community, ASCO consulted the main stakeholders, including representatives from patient advocacy groups, manufacturers, institutional review boards, and the FDA, as well as physicians.

Although these tools were made with the oncology community in mind, these resources should be helpful to doctors from other medical specialties as well.

CHICAGO — A new online resource will help seriously ill patients and their physicians request expanded access to investigational therapies when they have exhausted all other treatment options and the patients are not eligible for a clinical trial, it was announced June 4 at a joint news conference of the American Society of Clinical Oncology and the Food and Drug Administration.

"Most clinical trials have quite stringent eligibility criteria, and many patients are not eligible to enroll," said ASCO President-Elect George W. Sledge Jr., of Indiana University Simon Cancer Center, Indianapolis.

"In those instances when preliminary scientific evidence suggests that treatment with an unapproved therapy might be beneficial, the FDA's expanded access regulations allow physicians to request access to an investigational agent, outside of the clinical trial setting, for seriously ill patients," he said.

Expanded access has been allowed since the 1970s, but many physicians have been uncertain about how to request it, what regulations apply, and the legal ramifications. All of these issues are clarified in the new Web site.

"It's been clear to the agency that there was room for progress," said FDA Principal Deputy Commissioner Dr. Joshua M. Sharfstein, addressing the press conference on the opening day of ASCO's annual meeting.

"This is about the opportunity for the FDA to work with a medical specialty society, in this case ASCO, in what really should be a model for the agency - and work together to develop a program to reach out to clinicians and help them understand something that can be a little confusing at first," he said.

The new resources are available immediately to all patients and physicians, free of charge, through ASCO's physician education Web site, ASCO University.  

The material is presented in three online modules, which introduce the expanded access regulations, outline the process for requesting expanded access, and explain the physicians' legal responsibilities for treating patients with an investigational agent outside of a clinical trial.

The modules also contain resources such as a glossary, an expanded access request checklist, and various templates (letter to manufacturer, consent form, etc.) to help physicians with the paperwork.

In August 2009, the FDA issued updated regulations and attempted to clarify the rules in two publications, "Expanded Access to Investigational Drugs for Treatment Use," and "Charging for Investigational Drugs." The new Web site goes a step further.

To clarify the new rules for patients and the medical community, ASCO consulted the main stakeholders, including representatives from patient advocacy groups, manufacturers, institutional review boards, and the FDA, as well as physicians.

Although these tools were made with the oncology community in mind, these resources should be helpful to doctors from other medical specialties as well.

CHICAGO — A new online resource will help seriously ill patients and their physicians request expanded access to investigational therapies when they have exhausted all other treatment options and the patients are not eligible for a clinical trial, it was announced June 4 at a joint news conference of the American Society of Clinical Oncology and the Food and Drug Administration.

"Most clinical trials have quite stringent eligibility criteria, and many patients are not eligible to enroll," said ASCO President-Elect George W. Sledge Jr., of Indiana University Simon Cancer Center, Indianapolis.

"In those instances when preliminary scientific evidence suggests that treatment with an unapproved therapy might be beneficial, the FDA's expanded access regulations allow physicians to request access to an investigational agent, outside of the clinical trial setting, for seriously ill patients," he said.

Expanded access has been allowed since the 1970s, but many physicians have been uncertain about how to request it, what regulations apply, and the legal ramifications. All of these issues are clarified in the new Web site.

"It's been clear to the agency that there was room for progress," said FDA Principal Deputy Commissioner Dr. Joshua M. Sharfstein, addressing the press conference on the opening day of ASCO's annual meeting.

"This is about the opportunity for the FDA to work with a medical specialty society, in this case ASCO, in what really should be a model for the agency - and work together to develop a program to reach out to clinicians and help them understand something that can be a little confusing at first," he said.

The new resources are available immediately to all patients and physicians, free of charge, through ASCO's physician education Web site, ASCO University.  

The material is presented in three online modules, which introduce the expanded access regulations, outline the process for requesting expanded access, and explain the physicians' legal responsibilities for treating patients with an investigational agent outside of a clinical trial.

The modules also contain resources such as a glossary, an expanded access request checklist, and various templates (letter to manufacturer, consent form, etc.) to help physicians with the paperwork.

In August 2009, the FDA issued updated regulations and attempted to clarify the rules in two publications, "Expanded Access to Investigational Drugs for Treatment Use," and "Charging for Investigational Drugs." The new Web site goes a step further.

To clarify the new rules for patients and the medical community, ASCO consulted the main stakeholders, including representatives from patient advocacy groups, manufacturers, institutional review boards, and the FDA, as well as physicians.

Although these tools were made with the oncology community in mind, these resources should be helpful to doctors from other medical specialties as well.

CHICAGO — Health care disparity in rheumatic disease stems from multiple sources, not just the patient's race or the physician's bias.

Disease incidence and prevalence, access to care, choice of provider and health system, and individual patient preferences can all contribute to disparity, said Dr. Agustin Escalante, professor of medicine and clinical immunology at the University of Texas Health Science Center in San Antonio. Besides, concepts of race are often invalid.

“The traditional concept of race assumes or proposes a small number of defined groups (whites, blacks, Asians, among others) but in fact you don't have the discrete groups the traditional concept assumes,” said Dr. Escalante.

Hispanics, for example, may have European, Asian, or African ancestry, with disease consequences. A 2003 study found the risk of systemic lupus erythematosus in a Caribbean population to be associated with West African admixture (Hum. Genet. 2003;112:310-8).

As to physician bias, “nobody goes into medical school to set up an apartheid system in their clinics,” said Dr. Escalante. But bias can still creep in.

A 1999 study used actors of different races and sexes to portray patients with cardiac and noncardiac chest pain and found that women and African-Americans were less likely than white males to be referred for catheterization (N. Engl. J. Med. 1999;340:618-26).

Alternatively, health disparity can simply be a matter of access to care. If a local physician does not accept Medicaid, the patient may have to travel a distance to find one who does. Insurance may likewise have an impact. A study of patients with rheumatoid arthritis found that those in an HMO were significantly less likely to receive anti–tumor necrosis factor agents than were those who had fee-for-service policies (Arthritis Rheum. 2005;53:423-30).

Language may also have an impact on disparity. A study of pain in the emergency department found that Hispanics were much less likely to receive analgesics than were whites after long-bone fractures (Pain Manag. Nurs. 2008;9:26-32).

“If the patient doesn't speak English and the doctor is uncertain what's going on with them, it will take longer to decide,” said Dr. Escalante.

But the main source of health disparity, according to Dr. Escalante, is patient preference and willingness or unwillingness to receive treatment. A 1995 study found that blacks were half as likely to receive hip replacements as were whites, and Hispanics were one-seventh as likely, despite all patients' being insured with Medicaid (Ann. Rheum. Dis. 1995;54:107-10). A study of referrals found that patients were referred irrespective of race (Arthritis Rheum. 2009;61:1677-85).

A study of preferences for joint replacement for knee arthritis found that for those with severe arthritis, more whites and Hispanics chose total knee arthroplasty than did blacks, by far (J. Clin. Epidemiol. 2006;59:1078-86).

Knowledge was not necessarily a factor: When asked whether they had heard of the procedure before, 100% of whites said yes, compared with 90% of blacks and 80% of Hispanics (Arch. Intern. Med. 2005;165:1117-24).

“Studies have shown that African-Americans tend to be more fearful of the complications of total knee replacement, and they tend to underestimate the benefits,” said Dr. Escalante.

Dr. Escalante concluded by saying that the simplest way to think about cultural competency is language. Symposium chair Dr. John J. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Houston, asked what one bit of advice he would give the audience.

“Everybody could learn Spanish,” said Dr. Escalante.

Disclosures: Dr. Escalante reported no relevant financial interests. The study was sponsored by the University of Texas Health Science Center at San Antonio. Dr. Cush disclosed consulting fees or other remuneration from Centocor Inc., Abbott Laboratories, UCB, Pfizer Inc., Wyeth/Amgen Inc., and Roche, and research grants from Genentech Inc., Pfizer, UCB, Roche, and Celgene Corp.

CHICAGO — Health care disparity in rheumatic disease stems from multiple sources, not just the patient's race or the physician's bias.

Disease incidence and prevalence, access to care, choice of provider and health system, and individual patient preferences can all contribute to disparity, said Dr. Agustin Escalante, professor of medicine and clinical immunology at the University of Texas Health Science Center in San Antonio. Besides, concepts of race are often invalid.

“The traditional concept of race assumes or proposes a small number of defined groups (whites, blacks, Asians, among others) but in fact you don't have the discrete groups the traditional concept assumes,” said Dr. Escalante.

Hispanics, for example, may have European, Asian, or African ancestry, with disease consequences. A 2003 study found the risk of systemic lupus erythematosus in a Caribbean population to be associated with West African admixture (Hum. Genet. 2003;112:310-8).

As to physician bias, “nobody goes into medical school to set up an apartheid system in their clinics,” said Dr. Escalante. But bias can still creep in.

A 1999 study used actors of different races and sexes to portray patients with cardiac and noncardiac chest pain and found that women and African-Americans were less likely than white males to be referred for catheterization (N. Engl. J. Med. 1999;340:618-26).

Alternatively, health disparity can simply be a matter of access to care. If a local physician does not accept Medicaid, the patient may have to travel a distance to find one who does. Insurance may likewise have an impact. A study of patients with rheumatoid arthritis found that those in an HMO were significantly less likely to receive anti–tumor necrosis factor agents than were those who had fee-for-service policies (Arthritis Rheum. 2005;53:423-30).

Language may also have an impact on disparity. A study of pain in the emergency department found that Hispanics were much less likely to receive analgesics than were whites after long-bone fractures (Pain Manag. Nurs. 2008;9:26-32).

“If the patient doesn't speak English and the doctor is uncertain what's going on with them, it will take longer to decide,” said Dr. Escalante.

But the main source of health disparity, according to Dr. Escalante, is patient preference and willingness or unwillingness to receive treatment. A 1995 study found that blacks were half as likely to receive hip replacements as were whites, and Hispanics were one-seventh as likely, despite all patients' being insured with Medicaid (Ann. Rheum. Dis. 1995;54:107-10). A study of referrals found that patients were referred irrespective of race (Arthritis Rheum. 2009;61:1677-85).

A study of preferences for joint replacement for knee arthritis found that for those with severe arthritis, more whites and Hispanics chose total knee arthroplasty than did blacks, by far (J. Clin. Epidemiol. 2006;59:1078-86).

Knowledge was not necessarily a factor: When asked whether they had heard of the procedure before, 100% of whites said yes, compared with 90% of blacks and 80% of Hispanics (Arch. Intern. Med. 2005;165:1117-24).

“Studies have shown that African-Americans tend to be more fearful of the complications of total knee replacement, and they tend to underestimate the benefits,” said Dr. Escalante.

Dr. Escalante concluded by saying that the simplest way to think about cultural competency is language. Symposium chair Dr. John J. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Houston, asked what one bit of advice he would give the audience.

“Everybody could learn Spanish,” said Dr. Escalante.

Disclosures: Dr. Escalante reported no relevant financial interests. The study was sponsored by the University of Texas Health Science Center at San Antonio. Dr. Cush disclosed consulting fees or other remuneration from Centocor Inc., Abbott Laboratories, UCB, Pfizer Inc., Wyeth/Amgen Inc., and Roche, and research grants from Genentech Inc., Pfizer, UCB, Roche, and Celgene Corp.

CHICAGO — Health care disparity in rheumatic disease stems from multiple sources, not just the patient's race or the physician's bias.

Disease incidence and prevalence, access to care, choice of provider and health system, and individual patient preferences can all contribute to disparity, said Dr. Agustin Escalante, professor of medicine and clinical immunology at the University of Texas Health Science Center in San Antonio. Besides, concepts of race are often invalid.

“The traditional concept of race assumes or proposes a small number of defined groups (whites, blacks, Asians, among others) but in fact you don't have the discrete groups the traditional concept assumes,” said Dr. Escalante.

Hispanics, for example, may have European, Asian, or African ancestry, with disease consequences. A 2003 study found the risk of systemic lupus erythematosus in a Caribbean population to be associated with West African admixture (Hum. Genet. 2003;112:310-8).

As to physician bias, “nobody goes into medical school to set up an apartheid system in their clinics,” said Dr. Escalante. But bias can still creep in.

A 1999 study used actors of different races and sexes to portray patients with cardiac and noncardiac chest pain and found that women and African-Americans were less likely than white males to be referred for catheterization (N. Engl. J. Med. 1999;340:618-26).

Alternatively, health disparity can simply be a matter of access to care. If a local physician does not accept Medicaid, the patient may have to travel a distance to find one who does. Insurance may likewise have an impact. A study of patients with rheumatoid arthritis found that those in an HMO were significantly less likely to receive anti–tumor necrosis factor agents than were those who had fee-for-service policies (Arthritis Rheum. 2005;53:423-30).

Language may also have an impact on disparity. A study of pain in the emergency department found that Hispanics were much less likely to receive analgesics than were whites after long-bone fractures (Pain Manag. Nurs. 2008;9:26-32).

“If the patient doesn't speak English and the doctor is uncertain what's going on with them, it will take longer to decide,” said Dr. Escalante.

But the main source of health disparity, according to Dr. Escalante, is patient preference and willingness or unwillingness to receive treatment. A 1995 study found that blacks were half as likely to receive hip replacements as were whites, and Hispanics were one-seventh as likely, despite all patients' being insured with Medicaid (Ann. Rheum. Dis. 1995;54:107-10). A study of referrals found that patients were referred irrespective of race (Arthritis Rheum. 2009;61:1677-85).

A study of preferences for joint replacement for knee arthritis found that for those with severe arthritis, more whites and Hispanics chose total knee arthroplasty than did blacks, by far (J. Clin. Epidemiol. 2006;59:1078-86).

Knowledge was not necessarily a factor: When asked whether they had heard of the procedure before, 100% of whites said yes, compared with 90% of blacks and 80% of Hispanics (Arch. Intern. Med. 2005;165:1117-24).

“Studies have shown that African-Americans tend to be more fearful of the complications of total knee replacement, and they tend to underestimate the benefits,” said Dr. Escalante.

Dr. Escalante concluded by saying that the simplest way to think about cultural competency is language. Symposium chair Dr. John J. Cush, professor of medicine and rheumatology at Baylor University Medical Center, Houston, asked what one bit of advice he would give the audience.

“Everybody could learn Spanish,” said Dr. Escalante.

Disclosures: Dr. Escalante reported no relevant financial interests. The study was sponsored by the University of Texas Health Science Center at San Antonio. Dr. Cush disclosed consulting fees or other remuneration from Centocor Inc., Abbott Laboratories, UCB, Pfizer Inc., Wyeth/Amgen Inc., and Roche, and research grants from Genentech Inc., Pfizer, UCB, Roche, and Celgene Corp.

CHICAGO — On balance, the news about joint replacement innovations for people with rheumatoid arthritis is good.

New lumbar artificial disks, new ankle implants, customized patient instrumentation, and computer-assisted surgical planning offer options that patients with RA-destroyed joints lacked even a decade ago. The unfortunate flip sides of these advances are aggressive and sometimes misleading direct-to-consumer marketing, and occasional unfavorable biological responses to even the newest implant materials.

The field of orthopedic surgery has benefited from “a lot of great science,” said presenter Dr. William Bugbee, an orthopedic surgeon with the Scripps Institute in La Jolla, Calif. Robust innovation has lead to “constant introduction of new technology.”

In the half century since British orthopedic surgeon Sir John Charnley pioneered modern total hip replacement, joint replacement has become one of the most common and successful interventions for arthritis, said Dr. Bugbee. Joint-specific arthroplasty is now available for hips, knees, shoulders, ankles, elbows, the small joints of the feet and hands, and the lumbar and cervical spines.

Spinal disk replacement is now an alternative to spinal fusion, although its efficacy is unproven, said Dr. Bugbee. The objective is to preserve motion, particularly in the cervical spine; for every level that is fused, the patient loses about 15% of motion. The levels above and below also come under greater stress and tend to degenerate.

Shoulder arthroplasties are often performed on patients with RA. The functional outcomes are acceptable and provide pain relief, but fall short of restoring normal shoulder function, said Dr. Bugbee. “Few people can play tennis” following shoulder arthroplasty, he said. The results depend on the integrity of the rotator cuff. A recent innovation is the reverse shoulder arthroplasty, which accommodates a deficient rotator cuff to allow better function of the shoulder after replacement.

Ankle arthroplasty remains the most common operation for arthritis, and is another area of new design. It presents a particular design challenge because the biological ankle has only 9 cm

Arthroplasties of the hip and/or knee have become common and successful surgical interventions for arthritis, and the need for them is growing with the population. It has been estimated that by 2030, the U.S. population will need 2.3 million knee replacements per year. “There's not enough manpower to do all that work,” said Dr. Bugbee. Technical skill is the single most important factor in success.

The appropriate patient age for joint replacement now ranges from the 40s through the 90s said Dr. Bugbee. Although the intervention was originally conceived to relieve pain for elderly, low-demand patients, it is now expected to bring both pain relief and functional improvement. But it is not without risk: Dr. Bugbee estimated that 90-day mortality after surgery is less than 1%, but deep vein thrombosis occurs in 10%-40% of cases. Dislocation rates are 0%-10% because of larger ball and socket joints. Dr. Bugbee estimated that infection occurs in 0.3%-3% of operations.

There are also functional limitations after joint replacement. “A good hip replacement is tantamount to a normal joint,” said Dr. Bugbee. “Unfortunately, the knee is not the same. It is a much more complex joint.”

One area of concern is biological response to implant materials. Microscopic wear debris can be shed by the articulating surfaces. The polyethylene plastic in some implants can cause a granulomatous response, and an osteolytic response in the bone. In metal-on-metal joints, a tiny amount of wear debris may cause severe early osteoarthritis. Ceramic-to-ceramic hip joints have a wear rate about 50 times less than that of conventional polyethylene joints, but they may squeak.

Direct-to-consumer advertising campaigns have promoted minimally invasive surgery, but smaller incisions are not correlated with better outcome, said Dr. Bugbee. They may even have a higher complication rate.

“The next innovation is so-called customized patient instrumentation,” said Dr. Bugbee. The surgery can actually be computer modeled in advance, and can incorporate instruments that are custom built to fit the individual patient's joints. The surgery is then more accelerated and more precise.

Moderator Dr. John J. Cush of Baylor University Medical Center in Dallas, asked, “When patients have bilateral knees, or right and left knees, one of the things I've noticed over the years [is that] they'll always say, 'My right (or my left) is the best one.' They always have an ipsilateral evaluation and a preference. Is there a good reason for that?”

“No. I've seen the same thing. I cannot for the life of me figure it out,” said Dr. Bugbee.

Disclosures: Dr. Bugbee disclosed research grants from Zimmer Inc., Smith & Nephew Inc., and Depuy Inc. Dr. Cush disclosed consulting fees or other remuneration from Centocor Inc., Abbott Laboratories, UCB, Pfizer Inc., Wyeth/Amgen, and Roche, and research grants from Genentech Inc., Pfizer, UCB, Roche, and Celgene Corp.

CHICAGO — On balance, the news about joint replacement innovations for people with rheumatoid arthritis is good.

New lumbar artificial disks, new ankle implants, customized patient instrumentation, and computer-assisted surgical planning offer options that patients with RA-destroyed joints lacked even a decade ago. The unfortunate flip sides of these advances are aggressive and sometimes misleading direct-to-consumer marketing, and occasional unfavorable biological responses to even the newest implant materials.

The field of orthopedic surgery has benefited from “a lot of great science,” said presenter Dr. William Bugbee, an orthopedic surgeon with the Scripps Institute in La Jolla, Calif. Robust innovation has lead to “constant introduction of new technology.”

In the half century since British orthopedic surgeon Sir John Charnley pioneered modern total hip replacement, joint replacement has become one of the most common and successful interventions for arthritis, said Dr. Bugbee. Joint-specific arthroplasty is now available for hips, knees, shoulders, ankles, elbows, the small joints of the feet and hands, and the lumbar and cervical spines.

Spinal disk replacement is now an alternative to spinal fusion, although its efficacy is unproven, said Dr. Bugbee. The objective is to preserve motion, particularly in the cervical spine; for every level that is fused, the patient loses about 15% of motion. The levels above and below also come under greater stress and tend to degenerate.

Shoulder arthroplasties are often performed on patients with RA. The functional outcomes are acceptable and provide pain relief, but fall short of restoring normal shoulder function, said Dr. Bugbee. “Few people can play tennis” following shoulder arthroplasty, he said. The results depend on the integrity of the rotator cuff. A recent innovation is the reverse shoulder arthroplasty, which accommodates a deficient rotator cuff to allow better function of the shoulder after replacement.

Ankle arthroplasty remains the most common operation for arthritis, and is another area of new design. It presents a particular design challenge because the biological ankle has only 9 cm

Arthroplasties of the hip and/or knee have become common and successful surgical interventions for arthritis, and the need for them is growing with the population. It has been estimated that by 2030, the U.S. population will need 2.3 million knee replacements per year. “There's not enough manpower to do all that work,” said Dr. Bugbee. Technical skill is the single most important factor in success.

The appropriate patient age for joint replacement now ranges from the 40s through the 90s said Dr. Bugbee. Although the intervention was originally conceived to relieve pain for elderly, low-demand patients, it is now expected to bring both pain relief and functional improvement. But it is not without risk: Dr. Bugbee estimated that 90-day mortality after surgery is less than 1%, but deep vein thrombosis occurs in 10%-40% of cases. Dislocation rates are 0%-10% because of larger ball and socket joints. Dr. Bugbee estimated that infection occurs in 0.3%-3% of operations.

There are also functional limitations after joint replacement. “A good hip replacement is tantamount to a normal joint,” said Dr. Bugbee. “Unfortunately, the knee is not the same. It is a much more complex joint.”

One area of concern is biological response to implant materials. Microscopic wear debris can be shed by the articulating surfaces. The polyethylene plastic in some implants can cause a granulomatous response, and an osteolytic response in the bone. In metal-on-metal joints, a tiny amount of wear debris may cause severe early osteoarthritis. Ceramic-to-ceramic hip joints have a wear rate about 50 times less than that of conventional polyethylene joints, but they may squeak.

Direct-to-consumer advertising campaigns have promoted minimally invasive surgery, but smaller incisions are not correlated with better outcome, said Dr. Bugbee. They may even have a higher complication rate.

“The next innovation is so-called customized patient instrumentation,” said Dr. Bugbee. The surgery can actually be computer modeled in advance, and can incorporate instruments that are custom built to fit the individual patient's joints. The surgery is then more accelerated and more precise.

Moderator Dr. John J. Cush of Baylor University Medical Center in Dallas, asked, “When patients have bilateral knees, or right and left knees, one of the things I've noticed over the years [is that] they'll always say, 'My right (or my left) is the best one.' They always have an ipsilateral evaluation and a preference. Is there a good reason for that?”

“No. I've seen the same thing. I cannot for the life of me figure it out,” said Dr. Bugbee.

Disclosures: Dr. Bugbee disclosed research grants from Zimmer Inc., Smith & Nephew Inc., and Depuy Inc. Dr. Cush disclosed consulting fees or other remuneration from Centocor Inc., Abbott Laboratories, UCB, Pfizer Inc., Wyeth/Amgen, and Roche, and research grants from Genentech Inc., Pfizer, UCB, Roche, and Celgene Corp.

CHICAGO — On balance, the news about joint replacement innovations for people with rheumatoid arthritis is good.

New lumbar artificial disks, new ankle implants, customized patient instrumentation, and computer-assisted surgical planning offer options that patients with RA-destroyed joints lacked even a decade ago. The unfortunate flip sides of these advances are aggressive and sometimes misleading direct-to-consumer marketing, and occasional unfavorable biological responses to even the newest implant materials.

The field of orthopedic surgery has benefited from “a lot of great science,” said presenter Dr. William Bugbee, an orthopedic surgeon with the Scripps Institute in La Jolla, Calif. Robust innovation has lead to “constant introduction of new technology.”

In the half century since British orthopedic surgeon Sir John Charnley pioneered modern total hip replacement, joint replacement has become one of the most common and successful interventions for arthritis, said Dr. Bugbee. Joint-specific arthroplasty is now available for hips, knees, shoulders, ankles, elbows, the small joints of the feet and hands, and the lumbar and cervical spines.

Spinal disk replacement is now an alternative to spinal fusion, although its efficacy is unproven, said Dr. Bugbee. The objective is to preserve motion, particularly in the cervical spine; for every level that is fused, the patient loses about 15% of motion. The levels above and below also come under greater stress and tend to degenerate.

Shoulder arthroplasties are often performed on patients with RA. The functional outcomes are acceptable and provide pain relief, but fall short of restoring normal shoulder function, said Dr. Bugbee. “Few people can play tennis” following shoulder arthroplasty, he said. The results depend on the integrity of the rotator cuff. A recent innovation is the reverse shoulder arthroplasty, which accommodates a deficient rotator cuff to allow better function of the shoulder after replacement.

Ankle arthroplasty remains the most common operation for arthritis, and is another area of new design. It presents a particular design challenge because the biological ankle has only 9 cm

Arthroplasties of the hip and/or knee have become common and successful surgical interventions for arthritis, and the need for them is growing with the population. It has been estimated that by 2030, the U.S. population will need 2.3 million knee replacements per year. “There's not enough manpower to do all that work,” said Dr. Bugbee. Technical skill is the single most important factor in success.

The appropriate patient age for joint replacement now ranges from the 40s through the 90s said Dr. Bugbee. Although the intervention was originally conceived to relieve pain for elderly, low-demand patients, it is now expected to bring both pain relief and functional improvement. But it is not without risk: Dr. Bugbee estimated that 90-day mortality after surgery is less than 1%, but deep vein thrombosis occurs in 10%-40% of cases. Dislocation rates are 0%-10% because of larger ball and socket joints. Dr. Bugbee estimated that infection occurs in 0.3%-3% of operations.

There are also functional limitations after joint replacement. “A good hip replacement is tantamount to a normal joint,” said Dr. Bugbee. “Unfortunately, the knee is not the same. It is a much more complex joint.”

One area of concern is biological response to implant materials. Microscopic wear debris can be shed by the articulating surfaces. The polyethylene plastic in some implants can cause a granulomatous response, and an osteolytic response in the bone. In metal-on-metal joints, a tiny amount of wear debris may cause severe early osteoarthritis. Ceramic-to-ceramic hip joints have a wear rate about 50 times less than that of conventional polyethylene joints, but they may squeak.

Direct-to-consumer advertising campaigns have promoted minimally invasive surgery, but smaller incisions are not correlated with better outcome, said Dr. Bugbee. They may even have a higher complication rate.

“The next innovation is so-called customized patient instrumentation,” said Dr. Bugbee. The surgery can actually be computer modeled in advance, and can incorporate instruments that are custom built to fit the individual patient's joints. The surgery is then more accelerated and more precise.

Moderator Dr. John J. Cush of Baylor University Medical Center in Dallas, asked, “When patients have bilateral knees, or right and left knees, one of the things I've noticed over the years [is that] they'll always say, 'My right (or my left) is the best one.' They always have an ipsilateral evaluation and a preference. Is there a good reason for that?”

“No. I've seen the same thing. I cannot for the life of me figure it out,” said Dr. Bugbee.

Disclosures: Dr. Bugbee disclosed research grants from Zimmer Inc., Smith & Nephew Inc., and Depuy Inc. Dr. Cush disclosed consulting fees or other remuneration from Centocor Inc., Abbott Laboratories, UCB, Pfizer Inc., Wyeth/Amgen, and Roche, and research grants from Genentech Inc., Pfizer, UCB, Roche, and Celgene Corp.

CHICAGO — Increasing rates of traumatic intracranial hemorrhage in elderly patients appeared to be linked with the use of antiplatelet agents in a retrospective study of two different time periods.

The rise in traumatic intracranial hemorrhage (TICH) occurred without significant increases in diagnosis of atrial fibrillation or in warfarin (Coumadin) use, and overall mortality remained unchanged, Dr. Jeffrey J. Siracuse said at the meeting.

“Increased life expectancy and the rising prevalence of risk factors have led to [the use of] increased atrial fibrillation nationwide,” said Dr. Siracuse of Beth Israel Deaconess Medical Center, Boston. “Patients with atrial fibrillation are at high risk for stroke and may also be at high risk for bleeding complications.” They often are treated with anticoagulants based on their CHADS₂scores, which are used to estimate risk of thromboembolism in cases of atrial fibrillation, he said. This scoring system emphasizes warfarin prophylaxis. However, these patients also are likely to be taking antiplatelet agents.

The review of the hospital's trauma registry database of 5,371 subjects examined records for all 526 patients admitted with intracranial hemorrhage during 1999–2000 (139 patients) and 2007–2008 (387 patients). Intracranial hemorrhages were considered traumatic if they were secondary to an identified external injury.

Patient records were reviewed for preexisting anticoagulation, international normalized ratio (INR), mechanism of trauma, atrial fibrillation, mortality, and length of stay in the hospital or ICU. CHADS₂ scores were recorded for both groups.

In both time periods, the mean age of patients was 77 years, and half were male. The principal cause of trauma in both groups was a simple fall from the standing position. In the 1999–2000 group, 6.2% of all trauma admissions were TICH patients, but this number doubled to 12.3% in the 2007–2008 group, a significant difference.

The study found little increase in warfarin use in either group over the two periods. However, the use of “strong antiplatelet agents, specifically clopidogrel and Aggrenox, increased fivefold between the two periods,” said Dr. Siracuse. He also said that in the earlier period, 27% of TICH patients were on aspirin, but by the later period, 48% were on aspirin, a significant difference.

The prevalence of atrial fibrillation in patients with TICH did not increase (20% vs. 23%), nor did the average CHADS₂ scores for all trauma patients with atrial fibrillation taking warfarin (2.4 vs. 2.3, a nonsignificant difference).

“Those figures suggested that we had in our area a mature, well-served population where anticoagulation for atrial fibrillation was fully implemented before the development and widespread use of the CHADS₂ scoring system,” said Dr. Siracuse.

Overall, the mortality of patients with TICH was unchanged between the two periods (12.4% vs. 12.2%), and patients showed no difference in the mean numbers of either hospital- or ICU-free days.

“We did not see a large increase, as we thought we would, in atrial fibrillation or in Coumadin use in our TICH population. This could perhaps reflect [the fact] that Massachusetts has the highest patient/physician primary care patient ratio in the country,” said Dr. Siracuse. He said this suggested that medical conditions were identified early and treated aggressively.

The vast majority of patients were injured by simple falls from standing, he said, and many patients on anticoagulation because of high risk for thromboembolism were also at high risk for falls. Therefore, he concluded, increasing rates of TICH appeared to be associated with the use of strong antiplatelet agents rather than with increased warfarin use.

Dr. Siracuse reported no relevant financial interests. The study was sponsored by Beth Israel Deaconess.

CHICAGO — Increasing rates of traumatic intracranial hemorrhage in elderly patients appeared to be linked with the use of antiplatelet agents in a retrospective study of two different time periods.

The rise in traumatic intracranial hemorrhage (TICH) occurred without significant increases in diagnosis of atrial fibrillation or in warfarin (Coumadin) use, and overall mortality remained unchanged, Dr. Jeffrey J. Siracuse said at the meeting.

“Increased life expectancy and the rising prevalence of risk factors have led to [the use of] increased atrial fibrillation nationwide,” said Dr. Siracuse of Beth Israel Deaconess Medical Center, Boston. “Patients with atrial fibrillation are at high risk for stroke and may also be at high risk for bleeding complications.” They often are treated with anticoagulants based on their CHADS₂scores, which are used to estimate risk of thromboembolism in cases of atrial fibrillation, he said. This scoring system emphasizes warfarin prophylaxis. However, these patients also are likely to be taking antiplatelet agents.

The review of the hospital's trauma registry database of 5,371 subjects examined records for all 526 patients admitted with intracranial hemorrhage during 1999–2000 (139 patients) and 2007–2008 (387 patients). Intracranial hemorrhages were considered traumatic if they were secondary to an identified external injury.

Patient records were reviewed for preexisting anticoagulation, international normalized ratio (INR), mechanism of trauma, atrial fibrillation, mortality, and length of stay in the hospital or ICU. CHADS₂ scores were recorded for both groups.

In both time periods, the mean age of patients was 77 years, and half were male. The principal cause of trauma in both groups was a simple fall from the standing position. In the 1999–2000 group, 6.2% of all trauma admissions were TICH patients, but this number doubled to 12.3% in the 2007–2008 group, a significant difference.

The study found little increase in warfarin use in either group over the two periods. However, the use of “strong antiplatelet agents, specifically clopidogrel and Aggrenox, increased fivefold between the two periods,” said Dr. Siracuse. He also said that in the earlier period, 27% of TICH patients were on aspirin, but by the later period, 48% were on aspirin, a significant difference.

The prevalence of atrial fibrillation in patients with TICH did not increase (20% vs. 23%), nor did the average CHADS₂ scores for all trauma patients with atrial fibrillation taking warfarin (2.4 vs. 2.3, a nonsignificant difference).

“Those figures suggested that we had in our area a mature, well-served population where anticoagulation for atrial fibrillation was fully implemented before the development and widespread use of the CHADS₂ scoring system,” said Dr. Siracuse.

Overall, the mortality of patients with TICH was unchanged between the two periods (12.4% vs. 12.2%), and patients showed no difference in the mean numbers of either hospital- or ICU-free days.

“We did not see a large increase, as we thought we would, in atrial fibrillation or in Coumadin use in our TICH population. This could perhaps reflect [the fact] that Massachusetts has the highest patient/physician primary care patient ratio in the country,” said Dr. Siracuse. He said this suggested that medical conditions were identified early and treated aggressively.

The vast majority of patients were injured by simple falls from standing, he said, and many patients on anticoagulation because of high risk for thromboembolism were also at high risk for falls. Therefore, he concluded, increasing rates of TICH appeared to be associated with the use of strong antiplatelet agents rather than with increased warfarin use.

Dr. Siracuse reported no relevant financial interests. The study was sponsored by Beth Israel Deaconess.

CHICAGO — Increasing rates of traumatic intracranial hemorrhage in elderly patients appeared to be linked with the use of antiplatelet agents in a retrospective study of two different time periods.

The rise in traumatic intracranial hemorrhage (TICH) occurred without significant increases in diagnosis of atrial fibrillation or in warfarin (Coumadin) use, and overall mortality remained unchanged, Dr. Jeffrey J. Siracuse said at the meeting.

“Increased life expectancy and the rising prevalence of risk factors have led to [the use of] increased atrial fibrillation nationwide,” said Dr. Siracuse of Beth Israel Deaconess Medical Center, Boston. “Patients with atrial fibrillation are at high risk for stroke and may also be at high risk for bleeding complications.” They often are treated with anticoagulants based on their CHADS₂scores, which are used to estimate risk of thromboembolism in cases of atrial fibrillation, he said. This scoring system emphasizes warfarin prophylaxis. However, these patients also are likely to be taking antiplatelet agents.

The review of the hospital's trauma registry database of 5,371 subjects examined records for all 526 patients admitted with intracranial hemorrhage during 1999–2000 (139 patients) and 2007–2008 (387 patients). Intracranial hemorrhages were considered traumatic if they were secondary to an identified external injury.

Patient records were reviewed for preexisting anticoagulation, international normalized ratio (INR), mechanism of trauma, atrial fibrillation, mortality, and length of stay in the hospital or ICU. CHADS₂ scores were recorded for both groups.

In both time periods, the mean age of patients was 77 years, and half were male. The principal cause of trauma in both groups was a simple fall from the standing position. In the 1999–2000 group, 6.2% of all trauma admissions were TICH patients, but this number doubled to 12.3% in the 2007–2008 group, a significant difference.

The study found little increase in warfarin use in either group over the two periods. However, the use of “strong antiplatelet agents, specifically clopidogrel and Aggrenox, increased fivefold between the two periods,” said Dr. Siracuse. He also said that in the earlier period, 27% of TICH patients were on aspirin, but by the later period, 48% were on aspirin, a significant difference.

The prevalence of atrial fibrillation in patients with TICH did not increase (20% vs. 23%), nor did the average CHADS₂ scores for all trauma patients with atrial fibrillation taking warfarin (2.4 vs. 2.3, a nonsignificant difference).

“Those figures suggested that we had in our area a mature, well-served population where anticoagulation for atrial fibrillation was fully implemented before the development and widespread use of the CHADS₂ scoring system,” said Dr. Siracuse.

Overall, the mortality of patients with TICH was unchanged between the two periods (12.4% vs. 12.2%), and patients showed no difference in the mean numbers of either hospital- or ICU-free days.

“We did not see a large increase, as we thought we would, in atrial fibrillation or in Coumadin use in our TICH population. This could perhaps reflect [the fact] that Massachusetts has the highest patient/physician primary care patient ratio in the country,” said Dr. Siracuse. He said this suggested that medical conditions were identified early and treated aggressively.

The vast majority of patients were injured by simple falls from standing, he said, and many patients on anticoagulation because of high risk for thromboembolism were also at high risk for falls. Therefore, he concluded, increasing rates of TICH appeared to be associated with the use of strong antiplatelet agents rather than with increased warfarin use.

Dr. Siracuse reported no relevant financial interests. The study was sponsored by Beth Israel Deaconess.

CHICAGO — A modified gold nanoparticle vector has been used successfully to transfect pancreatic islets in a murine model, reversing type 1 diabetes in vivo, according to research conducted at the University of Illinois at Chicago.

The vector also reversed type 1 diabetes in vitro in human and mouse islet cells.

“This work shows for the first time efficient and nontoxic transfection of islets at a very high rate of over 98%, and with good homogeneous intracellular distribution,” Rafael A. Vega, Ph.D., said at the annual meeting of the Central Surgical Association.

The distribution of the nanoparticle vector was nearly identical in rodent and human islet cores. “Characterization of the islet function demonstrated biocompatibility, and no functional compromise was observed with untransfected or transfected islets,” said Dr. Vega, lead investigator of the study.

He and his colleagues isolated mouse pancreatic islet cells and human islet cells, transfected them with the vector, and transplanted them into a murine model (four mice). An oligonucleotide-modified gold nanoparticle (AuNP) was used as the vector, and was chemically conjugated with a marker to quantify distribution.

Flow cytometry demonstrated 98% transfection. The vector was not found to be toxic, and no functional compromise was observed for three key parameters: mitochondrial membrane potential, glucose and KCl-stimulated Ca

Normal function was preserved in the AuNP-transfected islets. The mice maintained steady body weight as efficiently as the untransfected control mice, and all mice returned to euglycemic status, demonstrating that reversal of diabetes can be preserved even with transfected gold nanoparticles. No toxicity was observed post transplantation. AuNP-transfected human islets were found to have graft function similar to that of untransfected control islets, as confirmed by intraperitoneal glucose tolerance testing.

“Essentially, we were able to demonstrate that in vivo functions remain intact,” said Dr. Vega. He expressed interest in related uses of the nanoparticle vector, such as for direct manipulation of post-transplant factors including inflammation, apoptosis, amyloid formation, oxidative stress, and immunologic response.

Dr. Vega said that pancreatic islet cell transplantation is an attractive therapy for type 1 diabetes, because recipients may achieve euglycemia. There are significant obstacles, however, including the availability of donor cells and the potential for rejection post transplant.

“One of the problems of pancreatic islet cell transplantation is the effective delivery of molecular therapeutic cargos into islets,” said Dr. Vega. “It is actually difficult to achieve intracellular penetration when using a vector,” at least in part because of the islet's complex multicellular architecture. The AuNP vector shows some promise for solving this problem.

The vector was found to reduce enzymatic degradation of the nucleic acid cargo and to have a strong binding affinity with complementary targets, with little or no observed toxicity, said Dr. Vega.

Dr. Dixon Kaufman, a professor of surgeryat Northwestern University, Chicago, cho attended the presentation, said, “You're onto something that's efficient and safe, and looks extremely promising.”

Dr. Kaufman asked about the fate of the nanoparticles over time. “If it diffuses very efficiently, how long is it retained? Does it diffuse out of the islets as well?”

“As far as where in the cells they go, it's in the cytoplasm,” said Dr. Vega. The gold nanoparticles stay in the cell, he said. “The data that we're looking at shows no functional compromise or toxicity with them in there.”

The study was funded by the Chicago Diabetes Project and the University of Illinois at Chicago. Dr. Vega reported no relevant financial interests.

CHICAGO — A modified gold nanoparticle vector has been used successfully to transfect pancreatic islets in a murine model, reversing type 1 diabetes in vivo, according to research conducted at the University of Illinois at Chicago.

The vector also reversed type 1 diabetes in vitro in human and mouse islet cells.

“This work shows for the first time efficient and nontoxic transfection of islets at a very high rate of over 98%, and with good homogeneous intracellular distribution,” Rafael A. Vega, Ph.D., said at the annual meeting of the Central Surgical Association.

The distribution of the nanoparticle vector was nearly identical in rodent and human islet cores. “Characterization of the islet function demonstrated biocompatibility, and no functional compromise was observed with untransfected or transfected islets,” said Dr. Vega, lead investigator of the study.

He and his colleagues isolated mouse pancreatic islet cells and human islet cells, transfected them with the vector, and transplanted them into a murine model (four mice). An oligonucleotide-modified gold nanoparticle (AuNP) was used as the vector, and was chemically conjugated with a marker to quantify distribution.

Flow cytometry demonstrated 98% transfection. The vector was not found to be toxic, and no functional compromise was observed for three key parameters: mitochondrial membrane potential, glucose and KCl-stimulated Ca

Normal function was preserved in the AuNP-transfected islets. The mice maintained steady body weight as efficiently as the untransfected control mice, and all mice returned to euglycemic status, demonstrating that reversal of diabetes can be preserved even with transfected gold nanoparticles. No toxicity was observed post transplantation. AuNP-transfected human islets were found to have graft function similar to that of untransfected control islets, as confirmed by intraperitoneal glucose tolerance testing.

“Essentially, we were able to demonstrate that in vivo functions remain intact,” said Dr. Vega. He expressed interest in related uses of the nanoparticle vector, such as for direct manipulation of post-transplant factors including inflammation, apoptosis, amyloid formation, oxidative stress, and immunologic response.

Dr. Vega said that pancreatic islet cell transplantation is an attractive therapy for type 1 diabetes, because recipients may achieve euglycemia. There are significant obstacles, however, including the availability of donor cells and the potential for rejection post transplant.

“One of the problems of pancreatic islet cell transplantation is the effective delivery of molecular therapeutic cargos into islets,” said Dr. Vega. “It is actually difficult to achieve intracellular penetration when using a vector,” at least in part because of the islet's complex multicellular architecture. The AuNP vector shows some promise for solving this problem.

The vector was found to reduce enzymatic degradation of the nucleic acid cargo and to have a strong binding affinity with complementary targets, with little or no observed toxicity, said Dr. Vega.

Dr. Dixon Kaufman, a professor of surgeryat Northwestern University, Chicago, cho attended the presentation, said, “You're onto something that's efficient and safe, and looks extremely promising.”

Dr. Kaufman asked about the fate of the nanoparticles over time. “If it diffuses very efficiently, how long is it retained? Does it diffuse out of the islets as well?”

“As far as where in the cells they go, it's in the cytoplasm,” said Dr. Vega. The gold nanoparticles stay in the cell, he said. “The data that we're looking at shows no functional compromise or toxicity with them in there.”

The study was funded by the Chicago Diabetes Project and the University of Illinois at Chicago. Dr. Vega reported no relevant financial interests.

CHICAGO — A modified gold nanoparticle vector has been used successfully to transfect pancreatic islets in a murine model, reversing type 1 diabetes in vivo, according to research conducted at the University of Illinois at Chicago.

The vector also reversed type 1 diabetes in vitro in human and mouse islet cells.

“This work shows for the first time efficient and nontoxic transfection of islets at a very high rate of over 98%, and with good homogeneous intracellular distribution,” Rafael A. Vega, Ph.D., said at the annual meeting of the Central Surgical Association.

The distribution of the nanoparticle vector was nearly identical in rodent and human islet cores. “Characterization of the islet function demonstrated biocompatibility, and no functional compromise was observed with untransfected or transfected islets,” said Dr. Vega, lead investigator of the study.

He and his colleagues isolated mouse pancreatic islet cells and human islet cells, transfected them with the vector, and transplanted them into a murine model (four mice). An oligonucleotide-modified gold nanoparticle (AuNP) was used as the vector, and was chemically conjugated with a marker to quantify distribution.

Flow cytometry demonstrated 98% transfection. The vector was not found to be toxic, and no functional compromise was observed for three key parameters: mitochondrial membrane potential, glucose and KCl-stimulated Ca

Normal function was preserved in the AuNP-transfected islets. The mice maintained steady body weight as efficiently as the untransfected control mice, and all mice returned to euglycemic status, demonstrating that reversal of diabetes can be preserved even with transfected gold nanoparticles. No toxicity was observed post transplantation. AuNP-transfected human islets were found to have graft function similar to that of untransfected control islets, as confirmed by intraperitoneal glucose tolerance testing.

“Essentially, we were able to demonstrate that in vivo functions remain intact,” said Dr. Vega. He expressed interest in related uses of the nanoparticle vector, such as for direct manipulation of post-transplant factors including inflammation, apoptosis, amyloid formation, oxidative stress, and immunologic response.

Dr. Vega said that pancreatic islet cell transplantation is an attractive therapy for type 1 diabetes, because recipients may achieve euglycemia. There are significant obstacles, however, including the availability of donor cells and the potential for rejection post transplant.

“One of the problems of pancreatic islet cell transplantation is the effective delivery of molecular therapeutic cargos into islets,” said Dr. Vega. “It is actually difficult to achieve intracellular penetration when using a vector,” at least in part because of the islet's complex multicellular architecture. The AuNP vector shows some promise for solving this problem.

The vector was found to reduce enzymatic degradation of the nucleic acid cargo and to have a strong binding affinity with complementary targets, with little or no observed toxicity, said Dr. Vega.

Dr. Dixon Kaufman, a professor of surgeryat Northwestern University, Chicago, cho attended the presentation, said, “You're onto something that's efficient and safe, and looks extremely promising.”

Dr. Kaufman asked about the fate of the nanoparticles over time. “If it diffuses very efficiently, how long is it retained? Does it diffuse out of the islets as well?”

“As far as where in the cells they go, it's in the cytoplasm,” said Dr. Vega. The gold nanoparticles stay in the cell, he said. “The data that we're looking at shows no functional compromise or toxicity with them in there.”

The study was funded by the Chicago Diabetes Project and the University of Illinois at Chicago. Dr. Vega reported no relevant financial interests.