Jeff Evans

WASHINGTON — The focus on short-term goals during cancer treatment can overshadow care for diabetes and other endocrine disorders that patients may have or acquire as they undergo treatment.

When cancer patients return to the community after successful treatment at a cancer center, it's easy for their primary care physicians “to lose focus on their other medical problems, because cancer becomes the focus when they're at the cancer center,” Robert F. Gagel, M.D., said at a consensus conference on patient safety and medical system errors in diabetes and endocrinology.

A similar situation can develop when patients receive cancer treatment in the community or at a university hospital where oncology is not a major part of the hospital's services, said Dr. Gagel of the division of internal medicine at the M.D. Anderson Cancer Center, Houston.

Dr. Gagel and his colleagues convinced administrators at the center that intensive control of diabetes was important enough to merit building a diabetes section there. That “is quite an amazing thing if one understands how resources are allocated” in a cancer center, he said.

Patients with impaired glucose tolerance who were in the Second National Health and Nutrition Examination Survey Mortality Study had a higher cumulative mortality from cancer than did patients who had normal glucose tolerance (Am. J. Epidemiol. 2003;157: 1092–100). Similarly, in a study of colon cancer mortality, diabetic patients had lower survival than did nondiabetic patients (J. Clin. Oncol. 2003;21:433–40).

Another study showed that the development of two or more episodes of hyperglycemia (blood glucose level of 200 mg/dL or higher) during the first 30 days of induction chemotherapy for acute lymphocytic leukemia was associated with a significant reduction in the median duration of complete remission and median survival, compared with patients who did not have hyperglycemia (Cancer 2004; 100:1179–85).

The reason for higher mortality among patients with hyperglycemia is unknown, Dr. Gagel noted, although it might be due to higher rates of infection. The hyperglycemic patients in the leukemia study developed sepsis or any complicated infection at higher rates than did patients without hyperglycemia.

Many cancer patients, especially those with breast cancer, have a high risk for osteoporosis. The major contributor to bone loss in patients with breast cancer is hypogonadism in the 50% or more of women who develop ovarian failure after chemotherapy. Of 49 women in a study who had early-stage breast cancer treated with adjuvant chemotherapy, 35 developed ovarian failure and had a rapid progression of bone loss 6 and 12 months later (J. Clin. Oncol. 2001;19:3303–5). About 14% of breast cancer survivors in the Women's Health Initiative study had a fracture during less than 5 years of follow-up.

The introduction of aromatase inhibitors in the last 2 years has contributed to the risk of osteoporosis in breast cancer patients, Dr. Gagel said. Aromatase inhibitors block conversion of androstenedione to estrone, or testosterone to estradiol, thereby lowering estrogen levels further.

In a recent trial comparing the aromatase inhibitor anastrozole (Arimidex) with tamoxifen, anastrozole significantly decreased spinal and hip bone mass after a median follow-up of 33 months, compared with tamoxifen. The rate of fractures also was significantly higher with anastrozole than with tamoxifen (Lancet 2002;359:2131–9). Follow-up at 47 months did not show continued worsening of bone mass or fracture risk (Cancer 2003;98:1802–10).

The conference was cosponsored by the American College of Endocrinology and the American Association of Clinical Endocrinologists.

WASHINGTON — The focus on short-term goals during cancer treatment can overshadow care for diabetes and other endocrine disorders that patients may have or acquire as they undergo treatment.

When cancer patients return to the community after successful treatment at a cancer center, it's easy for their primary care physicians “to lose focus on their other medical problems, because cancer becomes the focus when they're at the cancer center,” Robert F. Gagel, M.D., said at a consensus conference on patient safety and medical system errors in diabetes and endocrinology.

A similar situation can develop when patients receive cancer treatment in the community or at a university hospital where oncology is not a major part of the hospital's services, said Dr. Gagel of the division of internal medicine at the M.D. Anderson Cancer Center, Houston.

Dr. Gagel and his colleagues convinced administrators at the center that intensive control of diabetes was important enough to merit building a diabetes section there. That “is quite an amazing thing if one understands how resources are allocated” in a cancer center, he said.

Patients with impaired glucose tolerance who were in the Second National Health and Nutrition Examination Survey Mortality Study had a higher cumulative mortality from cancer than did patients who had normal glucose tolerance (Am. J. Epidemiol. 2003;157: 1092–100). Similarly, in a study of colon cancer mortality, diabetic patients had lower survival than did nondiabetic patients (J. Clin. Oncol. 2003;21:433–40).

Another study showed that the development of two or more episodes of hyperglycemia (blood glucose level of 200 mg/dL or higher) during the first 30 days of induction chemotherapy for acute lymphocytic leukemia was associated with a significant reduction in the median duration of complete remission and median survival, compared with patients who did not have hyperglycemia (Cancer 2004; 100:1179–85).

The reason for higher mortality among patients with hyperglycemia is unknown, Dr. Gagel noted, although it might be due to higher rates of infection. The hyperglycemic patients in the leukemia study developed sepsis or any complicated infection at higher rates than did patients without hyperglycemia.

Many cancer patients, especially those with breast cancer, have a high risk for osteoporosis. The major contributor to bone loss in patients with breast cancer is hypogonadism in the 50% or more of women who develop ovarian failure after chemotherapy. Of 49 women in a study who had early-stage breast cancer treated with adjuvant chemotherapy, 35 developed ovarian failure and had a rapid progression of bone loss 6 and 12 months later (J. Clin. Oncol. 2001;19:3303–5). About 14% of breast cancer survivors in the Women's Health Initiative study had a fracture during less than 5 years of follow-up.

The introduction of aromatase inhibitors in the last 2 years has contributed to the risk of osteoporosis in breast cancer patients, Dr. Gagel said. Aromatase inhibitors block conversion of androstenedione to estrone, or testosterone to estradiol, thereby lowering estrogen levels further.

In a recent trial comparing the aromatase inhibitor anastrozole (Arimidex) with tamoxifen, anastrozole significantly decreased spinal and hip bone mass after a median follow-up of 33 months, compared with tamoxifen. The rate of fractures also was significantly higher with anastrozole than with tamoxifen (Lancet 2002;359:2131–9). Follow-up at 47 months did not show continued worsening of bone mass or fracture risk (Cancer 2003;98:1802–10).

The conference was cosponsored by the American College of Endocrinology and the American Association of Clinical Endocrinologists.

WASHINGTON — The focus on short-term goals during cancer treatment can overshadow care for diabetes and other endocrine disorders that patients may have or acquire as they undergo treatment.

When cancer patients return to the community after successful treatment at a cancer center, it's easy for their primary care physicians “to lose focus on their other medical problems, because cancer becomes the focus when they're at the cancer center,” Robert F. Gagel, M.D., said at a consensus conference on patient safety and medical system errors in diabetes and endocrinology.

A similar situation can develop when patients receive cancer treatment in the community or at a university hospital where oncology is not a major part of the hospital's services, said Dr. Gagel of the division of internal medicine at the M.D. Anderson Cancer Center, Houston.

Dr. Gagel and his colleagues convinced administrators at the center that intensive control of diabetes was important enough to merit building a diabetes section there. That “is quite an amazing thing if one understands how resources are allocated” in a cancer center, he said.

Patients with impaired glucose tolerance who were in the Second National Health and Nutrition Examination Survey Mortality Study had a higher cumulative mortality from cancer than did patients who had normal glucose tolerance (Am. J. Epidemiol. 2003;157: 1092–100). Similarly, in a study of colon cancer mortality, diabetic patients had lower survival than did nondiabetic patients (J. Clin. Oncol. 2003;21:433–40).

Another study showed that the development of two or more episodes of hyperglycemia (blood glucose level of 200 mg/dL or higher) during the first 30 days of induction chemotherapy for acute lymphocytic leukemia was associated with a significant reduction in the median duration of complete remission and median survival, compared with patients who did not have hyperglycemia (Cancer 2004; 100:1179–85).

The reason for higher mortality among patients with hyperglycemia is unknown, Dr. Gagel noted, although it might be due to higher rates of infection. The hyperglycemic patients in the leukemia study developed sepsis or any complicated infection at higher rates than did patients without hyperglycemia.

Many cancer patients, especially those with breast cancer, have a high risk for osteoporosis. The major contributor to bone loss in patients with breast cancer is hypogonadism in the 50% or more of women who develop ovarian failure after chemotherapy. Of 49 women in a study who had early-stage breast cancer treated with adjuvant chemotherapy, 35 developed ovarian failure and had a rapid progression of bone loss 6 and 12 months later (J. Clin. Oncol. 2001;19:3303–5). About 14% of breast cancer survivors in the Women's Health Initiative study had a fracture during less than 5 years of follow-up.

The introduction of aromatase inhibitors in the last 2 years has contributed to the risk of osteoporosis in breast cancer patients, Dr. Gagel said. Aromatase inhibitors block conversion of androstenedione to estrone, or testosterone to estradiol, thereby lowering estrogen levels further.

In a recent trial comparing the aromatase inhibitor anastrozole (Arimidex) with tamoxifen, anastrozole significantly decreased spinal and hip bone mass after a median follow-up of 33 months, compared with tamoxifen. The rate of fractures also was significantly higher with anastrozole than with tamoxifen (Lancet 2002;359:2131–9). Follow-up at 47 months did not show continued worsening of bone mass or fracture risk (Cancer 2003;98:1802–10).

The conference was cosponsored by the American College of Endocrinology and the American Association of Clinical Endocrinologists.

CAMBRIDGE, MD. — The liver is a dynamic organ during pregnancy, and standard physiologic changes may mimic pregnancy-induced hepatic disease.

The clinical challenge of distinguishing the normal from abnormal liver during pregnancy was addressed by Ayman Koteish, M.D., of Johns Hopkins University, Baltimore.

For example, a clinician may detect spider angiomata and palmar erythema, which are associated with liver diseases, during a physical examination of a pregnant woman, but these signs are to be expected in pregnancy and do not indicate liver disease. These two signs are thought to result from a high-estrogen state, he said.

On the other hand, a palpable liver in pregnancy, especially in late pregnancy, is not to be ignored, he said at a hepatobiliary update sponsored by the university.

Laboratory results during pregnancy commonly show decreases in albumin of 1 g/dL. Alkaline phosphatase may rise to levels two to four times normal, and increases in total bile acids to 11 μmol/L or less are common. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may rise a little, but stay within the normal range.

Hyperemesis gravidarum

The nausea and vomiting that characterize this condition in 2% of pregnant women may lead to dehydration and malnutrition. Some women develop a transient hyperthyroidism that eventually gets better as hyperemesis gravidarum resolves.

Liver histology is not warranted to diagnose the condition, but AST and ALT levels may be increased to less than three times the normal values and bilirubin can be mildly elevated. Physicians normally give supportive treatment, including antiemetics such as phenothiazines or 5-HT3 antagonists such as ondansetron; dexamethasone can be used for severe cases.

Preeclampsia and eclampsia

About 25% of patients with preeclampsia and 90% of those with eclampsia will have AST and ALT values anywhere from 5 to 100 times normal and a bilirubin level less than 5 μmol/L. Jaundice, if present, is usually mild; it won't be clinically evident if the bilirubin level is less than 3 μmol/L, Dr. Koteish pointed out.

HELLP syndrome

This is the most severe form of preeclampsia, consisting of hemolysis, elevated liver enzymes, and low platelets. Most women (80%) who experience HELLP develop it during the third trimester, but 15% have the condition before week 27. Proteinuria and hypertension develop in up to 85% of patients. A liver biopsy is not needed to make the diagnosis.

The deterioration of patients with HELLP is unpredictable and can include subcapsular hematoma, infarction, renal failure, maternal death in 1%–3% of patients, prematurity or intrauterine growth restriction in about one-third of fetuses, and perinatal mortality rates of 7%–60%.

Patients with the HELLP syndrome need an “expeditious delivery,” Dr. Koteish said. Delivery eliminates any fetal liver dysfunction or thrombocytopenia, as well as maternal chronic liver dysfunction. Most patients recover within 72 hours after delivery, but 4%–27% can have a recurrence of the syndrome in future pregnancies.

Intrahepatic cholestasis of pregnancy

ICP occurs in the second half of pregnancy, with intractable pruritus that is worse at night on the palms and soles without specific skin findings except scratch marks.

The rate of ICP is only 0.5%–1.5% in the United States and Europe, but is as high as 15% in Chile. Between 45% and 70% of women with ICP have a recurrence in future pregnancies. They carry a predisposition to develop cholesterol stones. Women who have had a cholecystectomy or multiple pregnancies are at higher risk for ICP.

The diagnosis of ICP is usually made with a serum bile acid level greater than 11 μmol/L and a high bilirubin level in about 20% of patients. The ratio of cholic acid to chenodeoxycholic acid has been reported to be significantly higher in ICP pregnancies than in normal pregnancies (4 to 1 vs. 1.5 to 1). Liver biopsies are not warranted to obtain the diagnosis because no sequelae follow in the liver, and the condition generally lasts until delivery and is reversible.

“If pruritus lasts beyond 2 weeks after delivery, an alternative diagnosis such as primary sclerosing cholangitis or primary biliary cirrhosis should be entertained,” Dr. Koteish advised.

For treating ICP, ursodeoxycholic acid at 10–15 mg/kg per day has been shown to be safe and effective; 20–25 mg/kg per day may be more effective, he noted.

Acute fatty liver of pregnancy

This type of liver dysfunction develops in only 1 out of every 7,000 to 16,000 pregnant women, but carries a 70% maternal mortality and a 90% fetal mortality because of acute liver failure and coagulopathy. It usually strikes between 30 and 38 weeks, about half the time along with preeclampsia. In general, hypertension is absent, and there is a prolonged prothrombin time and low fibrinogen.

Some of the complications of acute fatty liver of pregnancy include diabetes insipidus, disseminated intravascular coagulopathy, spontaneous labor, and postpartum hemorrhage.

The disease has been associated with a deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD). The fetus is usually homozygous for the mutation while the mother is heterozygous. Long-chain fatty acids accumulate on the fetal side and then transfer to the mother's circulation, Dr. Koteish said.

He advised performing genetic tests on the mother, father, and infant for the various mutations that can occur to the LCHAD gene, because the infant is at risk of sudden death, cardiomyopathy, and neuromyopathy.

Diseases coincidental with pregnancy

Patients with hepatitis B or C virus infections that occur coincidentally with pregnancy do not need therapy, Dr. Koteish advised. HBV infection is transmitted to the fetus 90% of the time when the mother is positive for hepatitis B e antigen. However, hepatitis B vaccine given at birth provides protection against transmission.

HCV transmission to the fetus occurs 6%–10% or more of the time, depending on the mother's viremic load.

Once the disease activity of women with autoimmune hepatitis or Wilson's disease becomes stable, fertility returns. These patients may conceive but should continue therapy.

Herpes simplex virus hepatitis represents a threat to the fetus. Visceral dissemination of HSV, though normally rare, occurs more commonly in pregnancy, typically in the second or third trimester. The symptoms and signs of HSV hepatitis include a flulike prodrome, vesicles in about half of patients, and high ALT and AST levels. A biopsy and serology or culture are enough to make the diagnosis. Once the infection is under control with acyclovir, delivery can occur with less risk of transmission to the infant.

Hepatitis E virus infection is possible on trips to endemic areas, such as tropical and subtropical countries including India and Mexico. The virus normally has a fecal-oral route of transmission, but vertical transmission has been reported. A self-limited illness develops in about 80% of women, but up to 20% progress to liver failure; the disease can lead to high fetal complication rates as well as an increasing risk of fatality as term approaches.

Fertility is reduced in cirrhosis, making pregnancy rare, but pregnancy is more common in women with noncirrhotic portal hypertension. Little data exist on the risks involved in pregnancy with noncirrhotic portal hypertension, but reports have documented rates of fetal wastage in 8%–20%, spontaneous abortion in 15%–20%, and perinatal mortality in 11%–18%. Maternal complications develop in 30%–50% of women, but these tend to be less common and less severe if the woman is diagnosed and undergoes decompression before conception.

If a woman has received a liver transplant, pregnancy does not seem to affect the functioning of the graft. However, conception needs to be delayed for at least 6 months after the transplant surgery because of the risk of cytomegalovirus infection. Immunosuppressive drugs should be continued throughout the pregnancy.

CAMBRIDGE, MD. — The liver is a dynamic organ during pregnancy, and standard physiologic changes may mimic pregnancy-induced hepatic disease.

The clinical challenge of distinguishing the normal from abnormal liver during pregnancy was addressed by Ayman Koteish, M.D., of Johns Hopkins University, Baltimore.

For example, a clinician may detect spider angiomata and palmar erythema, which are associated with liver diseases, during a physical examination of a pregnant woman, but these signs are to be expected in pregnancy and do not indicate liver disease. These two signs are thought to result from a high-estrogen state, he said.

On the other hand, a palpable liver in pregnancy, especially in late pregnancy, is not to be ignored, he said at a hepatobiliary update sponsored by the university.

Laboratory results during pregnancy commonly show decreases in albumin of 1 g/dL. Alkaline phosphatase may rise to levels two to four times normal, and increases in total bile acids to 11 μmol/L or less are common. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may rise a little, but stay within the normal range.

Hyperemesis gravidarum

The nausea and vomiting that characterize this condition in 2% of pregnant women may lead to dehydration and malnutrition. Some women develop a transient hyperthyroidism that eventually gets better as hyperemesis gravidarum resolves.

Liver histology is not warranted to diagnose the condition, but AST and ALT levels may be increased to less than three times the normal values and bilirubin can be mildly elevated. Physicians normally give supportive treatment, including antiemetics such as phenothiazines or 5-HT3 antagonists such as ondansetron; dexamethasone can be used for severe cases.

Preeclampsia and eclampsia

About 25% of patients with preeclampsia and 90% of those with eclampsia will have AST and ALT values anywhere from 5 to 100 times normal and a bilirubin level less than 5 μmol/L. Jaundice, if present, is usually mild; it won't be clinically evident if the bilirubin level is less than 3 μmol/L, Dr. Koteish pointed out.

HELLP syndrome

This is the most severe form of preeclampsia, consisting of hemolysis, elevated liver enzymes, and low platelets. Most women (80%) who experience HELLP develop it during the third trimester, but 15% have the condition before week 27. Proteinuria and hypertension develop in up to 85% of patients. A liver biopsy is not needed to make the diagnosis.

The deterioration of patients with HELLP is unpredictable and can include subcapsular hematoma, infarction, renal failure, maternal death in 1%–3% of patients, prematurity or intrauterine growth restriction in about one-third of fetuses, and perinatal mortality rates of 7%–60%.

Patients with the HELLP syndrome need an “expeditious delivery,” Dr. Koteish said. Delivery eliminates any fetal liver dysfunction or thrombocytopenia, as well as maternal chronic liver dysfunction. Most patients recover within 72 hours after delivery, but 4%–27% can have a recurrence of the syndrome in future pregnancies.

Intrahepatic cholestasis of pregnancy

ICP occurs in the second half of pregnancy, with intractable pruritus that is worse at night on the palms and soles without specific skin findings except scratch marks.

The rate of ICP is only 0.5%–1.5% in the United States and Europe, but is as high as 15% in Chile. Between 45% and 70% of women with ICP have a recurrence in future pregnancies. They carry a predisposition to develop cholesterol stones. Women who have had a cholecystectomy or multiple pregnancies are at higher risk for ICP.

The diagnosis of ICP is usually made with a serum bile acid level greater than 11 μmol/L and a high bilirubin level in about 20% of patients. The ratio of cholic acid to chenodeoxycholic acid has been reported to be significantly higher in ICP pregnancies than in normal pregnancies (4 to 1 vs. 1.5 to 1). Liver biopsies are not warranted to obtain the diagnosis because no sequelae follow in the liver, and the condition generally lasts until delivery and is reversible.

“If pruritus lasts beyond 2 weeks after delivery, an alternative diagnosis such as primary sclerosing cholangitis or primary biliary cirrhosis should be entertained,” Dr. Koteish advised.

For treating ICP, ursodeoxycholic acid at 10–15 mg/kg per day has been shown to be safe and effective; 20–25 mg/kg per day may be more effective, he noted.

Acute fatty liver of pregnancy

This type of liver dysfunction develops in only 1 out of every 7,000 to 16,000 pregnant women, but carries a 70% maternal mortality and a 90% fetal mortality because of acute liver failure and coagulopathy. It usually strikes between 30 and 38 weeks, about half the time along with preeclampsia. In general, hypertension is absent, and there is a prolonged prothrombin time and low fibrinogen.

Some of the complications of acute fatty liver of pregnancy include diabetes insipidus, disseminated intravascular coagulopathy, spontaneous labor, and postpartum hemorrhage.

The disease has been associated with a deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD). The fetus is usually homozygous for the mutation while the mother is heterozygous. Long-chain fatty acids accumulate on the fetal side and then transfer to the mother's circulation, Dr. Koteish said.

He advised performing genetic tests on the mother, father, and infant for the various mutations that can occur to the LCHAD gene, because the infant is at risk of sudden death, cardiomyopathy, and neuromyopathy.

Diseases coincidental with pregnancy

Patients with hepatitis B or C virus infections that occur coincidentally with pregnancy do not need therapy, Dr. Koteish advised. HBV infection is transmitted to the fetus 90% of the time when the mother is positive for hepatitis B e antigen. However, hepatitis B vaccine given at birth provides protection against transmission.

HCV transmission to the fetus occurs 6%–10% or more of the time, depending on the mother's viremic load.

Once the disease activity of women with autoimmune hepatitis or Wilson's disease becomes stable, fertility returns. These patients may conceive but should continue therapy.

Herpes simplex virus hepatitis represents a threat to the fetus. Visceral dissemination of HSV, though normally rare, occurs more commonly in pregnancy, typically in the second or third trimester. The symptoms and signs of HSV hepatitis include a flulike prodrome, vesicles in about half of patients, and high ALT and AST levels. A biopsy and serology or culture are enough to make the diagnosis. Once the infection is under control with acyclovir, delivery can occur with less risk of transmission to the infant.

Hepatitis E virus infection is possible on trips to endemic areas, such as tropical and subtropical countries including India and Mexico. The virus normally has a fecal-oral route of transmission, but vertical transmission has been reported. A self-limited illness develops in about 80% of women, but up to 20% progress to liver failure; the disease can lead to high fetal complication rates as well as an increasing risk of fatality as term approaches.

Fertility is reduced in cirrhosis, making pregnancy rare, but pregnancy is more common in women with noncirrhotic portal hypertension. Little data exist on the risks involved in pregnancy with noncirrhotic portal hypertension, but reports have documented rates of fetal wastage in 8%–20%, spontaneous abortion in 15%–20%, and perinatal mortality in 11%–18%. Maternal complications develop in 30%–50% of women, but these tend to be less common and less severe if the woman is diagnosed and undergoes decompression before conception.

If a woman has received a liver transplant, pregnancy does not seem to affect the functioning of the graft. However, conception needs to be delayed for at least 6 months after the transplant surgery because of the risk of cytomegalovirus infection. Immunosuppressive drugs should be continued throughout the pregnancy.

CAMBRIDGE, MD. — The liver is a dynamic organ during pregnancy, and standard physiologic changes may mimic pregnancy-induced hepatic disease.

The clinical challenge of distinguishing the normal from abnormal liver during pregnancy was addressed by Ayman Koteish, M.D., of Johns Hopkins University, Baltimore.

For example, a clinician may detect spider angiomata and palmar erythema, which are associated with liver diseases, during a physical examination of a pregnant woman, but these signs are to be expected in pregnancy and do not indicate liver disease. These two signs are thought to result from a high-estrogen state, he said.

On the other hand, a palpable liver in pregnancy, especially in late pregnancy, is not to be ignored, he said at a hepatobiliary update sponsored by the university.

Laboratory results during pregnancy commonly show decreases in albumin of 1 g/dL. Alkaline phosphatase may rise to levels two to four times normal, and increases in total bile acids to 11 μmol/L or less are common. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels may rise a little, but stay within the normal range.

Hyperemesis gravidarum

The nausea and vomiting that characterize this condition in 2% of pregnant women may lead to dehydration and malnutrition. Some women develop a transient hyperthyroidism that eventually gets better as hyperemesis gravidarum resolves.

Liver histology is not warranted to diagnose the condition, but AST and ALT levels may be increased to less than three times the normal values and bilirubin can be mildly elevated. Physicians normally give supportive treatment, including antiemetics such as phenothiazines or 5-HT3 antagonists such as ondansetron; dexamethasone can be used for severe cases.

Preeclampsia and eclampsia

About 25% of patients with preeclampsia and 90% of those with eclampsia will have AST and ALT values anywhere from 5 to 100 times normal and a bilirubin level less than 5 μmol/L. Jaundice, if present, is usually mild; it won't be clinically evident if the bilirubin level is less than 3 μmol/L, Dr. Koteish pointed out.

HELLP syndrome

This is the most severe form of preeclampsia, consisting of hemolysis, elevated liver enzymes, and low platelets. Most women (80%) who experience HELLP develop it during the third trimester, but 15% have the condition before week 27. Proteinuria and hypertension develop in up to 85% of patients. A liver biopsy is not needed to make the diagnosis.

The deterioration of patients with HELLP is unpredictable and can include subcapsular hematoma, infarction, renal failure, maternal death in 1%–3% of patients, prematurity or intrauterine growth restriction in about one-third of fetuses, and perinatal mortality rates of 7%–60%.

Patients with the HELLP syndrome need an “expeditious delivery,” Dr. Koteish said. Delivery eliminates any fetal liver dysfunction or thrombocytopenia, as well as maternal chronic liver dysfunction. Most patients recover within 72 hours after delivery, but 4%–27% can have a recurrence of the syndrome in future pregnancies.

Intrahepatic cholestasis of pregnancy

ICP occurs in the second half of pregnancy, with intractable pruritus that is worse at night on the palms and soles without specific skin findings except scratch marks.

The rate of ICP is only 0.5%–1.5% in the United States and Europe, but is as high as 15% in Chile. Between 45% and 70% of women with ICP have a recurrence in future pregnancies. They carry a predisposition to develop cholesterol stones. Women who have had a cholecystectomy or multiple pregnancies are at higher risk for ICP.

The diagnosis of ICP is usually made with a serum bile acid level greater than 11 μmol/L and a high bilirubin level in about 20% of patients. The ratio of cholic acid to chenodeoxycholic acid has been reported to be significantly higher in ICP pregnancies than in normal pregnancies (4 to 1 vs. 1.5 to 1). Liver biopsies are not warranted to obtain the diagnosis because no sequelae follow in the liver, and the condition generally lasts until delivery and is reversible.

“If pruritus lasts beyond 2 weeks after delivery, an alternative diagnosis such as primary sclerosing cholangitis or primary biliary cirrhosis should be entertained,” Dr. Koteish advised.

For treating ICP, ursodeoxycholic acid at 10–15 mg/kg per day has been shown to be safe and effective; 20–25 mg/kg per day may be more effective, he noted.

Acute fatty liver of pregnancy

This type of liver dysfunction develops in only 1 out of every 7,000 to 16,000 pregnant women, but carries a 70% maternal mortality and a 90% fetal mortality because of acute liver failure and coagulopathy. It usually strikes between 30 and 38 weeks, about half the time along with preeclampsia. In general, hypertension is absent, and there is a prolonged prothrombin time and low fibrinogen.

Some of the complications of acute fatty liver of pregnancy include diabetes insipidus, disseminated intravascular coagulopathy, spontaneous labor, and postpartum hemorrhage.

The disease has been associated with a deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD). The fetus is usually homozygous for the mutation while the mother is heterozygous. Long-chain fatty acids accumulate on the fetal side and then transfer to the mother's circulation, Dr. Koteish said.

He advised performing genetic tests on the mother, father, and infant for the various mutations that can occur to the LCHAD gene, because the infant is at risk of sudden death, cardiomyopathy, and neuromyopathy.

Diseases coincidental with pregnancy

Patients with hepatitis B or C virus infections that occur coincidentally with pregnancy do not need therapy, Dr. Koteish advised. HBV infection is transmitted to the fetus 90% of the time when the mother is positive for hepatitis B e antigen. However, hepatitis B vaccine given at birth provides protection against transmission.

HCV transmission to the fetus occurs 6%–10% or more of the time, depending on the mother's viremic load.

Once the disease activity of women with autoimmune hepatitis or Wilson's disease becomes stable, fertility returns. These patients may conceive but should continue therapy.

Herpes simplex virus hepatitis represents a threat to the fetus. Visceral dissemination of HSV, though normally rare, occurs more commonly in pregnancy, typically in the second or third trimester. The symptoms and signs of HSV hepatitis include a flulike prodrome, vesicles in about half of patients, and high ALT and AST levels. A biopsy and serology or culture are enough to make the diagnosis. Once the infection is under control with acyclovir, delivery can occur with less risk of transmission to the infant.

Hepatitis E virus infection is possible on trips to endemic areas, such as tropical and subtropical countries including India and Mexico. The virus normally has a fecal-oral route of transmission, but vertical transmission has been reported. A self-limited illness develops in about 80% of women, but up to 20% progress to liver failure; the disease can lead to high fetal complication rates as well as an increasing risk of fatality as term approaches.

Fertility is reduced in cirrhosis, making pregnancy rare, but pregnancy is more common in women with noncirrhotic portal hypertension. Little data exist on the risks involved in pregnancy with noncirrhotic portal hypertension, but reports have documented rates of fetal wastage in 8%–20%, spontaneous abortion in 15%–20%, and perinatal mortality in 11%–18%. Maternal complications develop in 30%–50% of women, but these tend to be less common and less severe if the woman is diagnosed and undergoes decompression before conception.

If a woman has received a liver transplant, pregnancy does not seem to affect the functioning of the graft. However, conception needs to be delayed for at least 6 months after the transplant surgery because of the risk of cytomegalovirus infection. Immunosuppressive drugs should be continued throughout the pregnancy.

ORLANDO, FLA. — Hemodialysis patients with end-stage renal disease have a high risk for colorectal cancer, compared with the general population, Jonathan M. Koff, M.D., reported at the annual meeting of the American College of Gastroenterology.

Patients on dialysis already are known to have an increased risk for hematologic, thyroid, cervical, bladder, kidney, and skin malignancies.

In three separate studies, nephrologists have concluded that colorectal cancer screening is not cost effective in dialysis patients, Dr. Koff said, but that perception could change based on evidence of a high risk of colorectal cancer in such patients, along with growth in the number of patients with end-stage renal disease (ESRD).

In 2001, 96,000 new patients developed ESRD. At that time, about three-fourths of the 406,000 patients who received renal replacement therapy were on dialysis, while the other one-fourth had kidney transplants. The diabetes and metabolic syndrome epidemics may increase the number of patients who receive renal replacement therapy to more than an estimated 2.2 million by 2030, said Dr. Koff of Walter Reed Army Medical Center, Washington.

He and his colleagues conducted a retrospective cohort study of 272,024 patients in the United States Renal Data System, which is managed by the National Institute of Diabetes and Digestive and Kidney Diseases. These patients began dialysis therapy for ESRD between 1995 and 1999 with Medicare as their primary payer.

During the study period, 1.1% of dialysis patients developed colorectal cancer. Dialysis patients had an 82% higher risk of colorectal cancer, compared with age-matched rates in the general population in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database on cancer statistics.

The risk for developing colorectal cancer declined with increasing age; patients aged 30–39 years had the highest risk—more than eightfold higher than the risk for people of the same age in the SEER database.

In a multivariate analysis, advanced age, other malignancy, hemodialysis (rather than peritoneal dialysis), and low hemoglobin and albumin levels were associated independently with an increased risk of colorectal cancer.

Dr. Koff pointed out that he could not independently confirm the diagnoses of colorectal cancer or determine if any of the patients were screened for colorectal cancer before or during the study period.

Only 32% of dialysis patients with colorectal cancer survived 1 year after being diagnosed with cancer; 10% lived 5 years after the diagnosis.

Several different mechanisms could contribute to the increased incidence of colorectal cancer in dialysis patients. Uremia may contribute by causing “functional immunosuppression or decreased tumor surveillance,” Dr. Koff said.

Patients with ESRD may have a lower prevalence of nonsteroidal anti-inflammatory drug use than other patients, according to one study, perhaps providing less chemoprevention, he suggested. Another recent study found that patients with type 2 diabetes who take insulin have a higher risk of colorectal cancer than do similar patients who don't take insulin (INTERNAL MEDICINE NEWS, Nov. 15, 2004, p. 60).

ORLANDO, FLA. — Hemodialysis patients with end-stage renal disease have a high risk for colorectal cancer, compared with the general population, Jonathan M. Koff, M.D., reported at the annual meeting of the American College of Gastroenterology.

Patients on dialysis already are known to have an increased risk for hematologic, thyroid, cervical, bladder, kidney, and skin malignancies.

In three separate studies, nephrologists have concluded that colorectal cancer screening is not cost effective in dialysis patients, Dr. Koff said, but that perception could change based on evidence of a high risk of colorectal cancer in such patients, along with growth in the number of patients with end-stage renal disease (ESRD).

In 2001, 96,000 new patients developed ESRD. At that time, about three-fourths of the 406,000 patients who received renal replacement therapy were on dialysis, while the other one-fourth had kidney transplants. The diabetes and metabolic syndrome epidemics may increase the number of patients who receive renal replacement therapy to more than an estimated 2.2 million by 2030, said Dr. Koff of Walter Reed Army Medical Center, Washington.

He and his colleagues conducted a retrospective cohort study of 272,024 patients in the United States Renal Data System, which is managed by the National Institute of Diabetes and Digestive and Kidney Diseases. These patients began dialysis therapy for ESRD between 1995 and 1999 with Medicare as their primary payer.

During the study period, 1.1% of dialysis patients developed colorectal cancer. Dialysis patients had an 82% higher risk of colorectal cancer, compared with age-matched rates in the general population in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database on cancer statistics.

The risk for developing colorectal cancer declined with increasing age; patients aged 30–39 years had the highest risk—more than eightfold higher than the risk for people of the same age in the SEER database.

In a multivariate analysis, advanced age, other malignancy, hemodialysis (rather than peritoneal dialysis), and low hemoglobin and albumin levels were associated independently with an increased risk of colorectal cancer.

Dr. Koff pointed out that he could not independently confirm the diagnoses of colorectal cancer or determine if any of the patients were screened for colorectal cancer before or during the study period.

Only 32% of dialysis patients with colorectal cancer survived 1 year after being diagnosed with cancer; 10% lived 5 years after the diagnosis.

Several different mechanisms could contribute to the increased incidence of colorectal cancer in dialysis patients. Uremia may contribute by causing “functional immunosuppression or decreased tumor surveillance,” Dr. Koff said.

Patients with ESRD may have a lower prevalence of nonsteroidal anti-inflammatory drug use than other patients, according to one study, perhaps providing less chemoprevention, he suggested. Another recent study found that patients with type 2 diabetes who take insulin have a higher risk of colorectal cancer than do similar patients who don't take insulin (INTERNAL MEDICINE NEWS, Nov. 15, 2004, p. 60).

ORLANDO, FLA. — Hemodialysis patients with end-stage renal disease have a high risk for colorectal cancer, compared with the general population, Jonathan M. Koff, M.D., reported at the annual meeting of the American College of Gastroenterology.

Patients on dialysis already are known to have an increased risk for hematologic, thyroid, cervical, bladder, kidney, and skin malignancies.

In three separate studies, nephrologists have concluded that colorectal cancer screening is not cost effective in dialysis patients, Dr. Koff said, but that perception could change based on evidence of a high risk of colorectal cancer in such patients, along with growth in the number of patients with end-stage renal disease (ESRD).

In 2001, 96,000 new patients developed ESRD. At that time, about three-fourths of the 406,000 patients who received renal replacement therapy were on dialysis, while the other one-fourth had kidney transplants. The diabetes and metabolic syndrome epidemics may increase the number of patients who receive renal replacement therapy to more than an estimated 2.2 million by 2030, said Dr. Koff of Walter Reed Army Medical Center, Washington.

He and his colleagues conducted a retrospective cohort study of 272,024 patients in the United States Renal Data System, which is managed by the National Institute of Diabetes and Digestive and Kidney Diseases. These patients began dialysis therapy for ESRD between 1995 and 1999 with Medicare as their primary payer.

During the study period, 1.1% of dialysis patients developed colorectal cancer. Dialysis patients had an 82% higher risk of colorectal cancer, compared with age-matched rates in the general population in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database on cancer statistics.

The risk for developing colorectal cancer declined with increasing age; patients aged 30–39 years had the highest risk—more than eightfold higher than the risk for people of the same age in the SEER database.

In a multivariate analysis, advanced age, other malignancy, hemodialysis (rather than peritoneal dialysis), and low hemoglobin and albumin levels were associated independently with an increased risk of colorectal cancer.

Dr. Koff pointed out that he could not independently confirm the diagnoses of colorectal cancer or determine if any of the patients were screened for colorectal cancer before or during the study period.

Only 32% of dialysis patients with colorectal cancer survived 1 year after being diagnosed with cancer; 10% lived 5 years after the diagnosis.

Several different mechanisms could contribute to the increased incidence of colorectal cancer in dialysis patients. Uremia may contribute by causing “functional immunosuppression or decreased tumor surveillance,” Dr. Koff said.

Patients with ESRD may have a lower prevalence of nonsteroidal anti-inflammatory drug use than other patients, according to one study, perhaps providing less chemoprevention, he suggested. Another recent study found that patients with type 2 diabetes who take insulin have a higher risk of colorectal cancer than do similar patients who don't take insulin (INTERNAL MEDICINE NEWS, Nov. 15, 2004, p. 60).

Racial Differences in Cancer Surgery

Black patients with locoregional esophageal cancer are less likely to be evaluated for surgery than are white patients, and they receive surgery less often than white patients even when they are surgically evaluated, reported Ewout W. Steyerberg, M.D., of Erasmus MC, Rotterdam, the Netherlands, and associates.

An analysis of patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results database found that surgeons assessed a significantly smaller percentage of black patients (70% [258 of 367]), compared with white patients (78% [2,307 of 2,946]). The percentage of black patients who actually underwent surgery after being assessed by a surgeon (35% [90 of 258]) was significantly lower than that of white patients (59% [1,351 of 2,307]). Overall, significantly more white patients than black patients had surgery (46% vs. 25%) (J. Clin. Oncol. 2005;23:510–7).

Neither medically relevant factors nor nonmedical factors explained the differences involving surgical evaluation or surgery performed in the observational study. Significantly fewer black patients survived than did white patients at follow-up of 6 months (58% vs. 64%), 1 year (39% vs. 43%), 2 years (18% vs. 25%), and 5 years (8% vs. 11%). The type of treatment received, rather than nonmedical factors, explained most of the higher mortality in black patients.

Chromoendoscopy Detects Barrett's

Chromoendoscopy with crystal violet detects short-segment Barrett's esophagus with greater sensitivity and specificity than does chromoendoscopy with methylene blue, based on the results of a prospective study.

Yuji Amano, M.D., and colleagues at Shimane University, Izumo, Japan, found that chromoendoscopy with 0.05% crystal violet detected Barrett's epithelium with 89% sensitivity, 86% specificity, and 88% diagnostic accuracy in 100 patients with suspected short-segment Barrett's esophagus. These results were significantly better than those obtained with 0.1% crystal violet, 0.5% methylene blue, or 1% methylene blue in 300 patients (Am. J. Gastroenterol. 2005;100:21–6).

In patients who had nondysplastic and dysplastic Barrett's epithelium stained, 0.05% crystal violet detected the mucosal pit pattern—important for making a histological diagnosis—at the highest rate (93%) of all methods.

Hepatitis C Virus Persists After Tx

Hepatitis C virus RNA persists and appears to replicate at low levels in patients years after they had a sustained virologic response to treatment, according to Marek Radkowski, M.D., of the Mayo Clinic Scottsdale (Ariz.) and colleagues.

In 17 patients who had a sustained virologic response that had lasted for 40 to 109 months prior to the study, 15 had hepatitis C virus (HCV) RNA detected in a liver biopsy, serum, peripheral blood mononuclear cells, or cultures of lymphocytes or macrophages. The investigators detected HCV RNA-negative strand in lymphocytes in two patients and in macrophages from four other patients. HCV RNA-negative strand is a replicative intermediate in the viral life cycle and is generally accepted as evidence of ongoing HCV replication (Hepatology 2005;41:106–14).

“This continuous presence of HCV RNA could explain the phenomenon of relatively common persistence of humoral and cellular immunity for many years after supposed viral clearance and could present a potential risk for transmission or infection reactivation,” the researchers said.

Prognosis of Acetaminophen Liver Injury

Measurement of alpha-fetoprotein levels along with other established criteria may aid in determining the prognosis of acetaminophen-induced fulminant hepatic failure, reported Lars E. Schmidt, M.D., and Kim Dalhoff, M.D., of Rigshospitalet, Copenhagen.

An increase of alpha-fetoprotein higher than 3.9 mcg/L on the day after the peak level of alanine aminotransferase predicted survival from severe acetaminophen-induced liver injury with 100% sensitivity in 239 patients seen at Copenhagen University Hospital during 1999–2002. Dr. Schmidt and Dr. Dalhoff suggested that in marginal or protracted cases of acetaminophen-induced fulminant hepatic failure, measurements of alpha-fetoprotein could supplement the King's College Hospital criteria to identify patients who are likely to die as a consequence of their fulminant hepatic failure. The King's criteria include the prognostic variables of etiology, age, serum bilirubin, serum creatinine, degree of encephalopathy, and arterial pH (Hepatology 2005;41:26–31).

“It must be stressed that these models will aid, but not replace, clinical judgment,” James Neuberger, M.D., said in an editorial (Hepatology 2005;41:19–22).

Racial Differences in Cancer Surgery

Black patients with locoregional esophageal cancer are less likely to be evaluated for surgery than are white patients, and they receive surgery less often than white patients even when they are surgically evaluated, reported Ewout W. Steyerberg, M.D., of Erasmus MC, Rotterdam, the Netherlands, and associates.

An analysis of patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results database found that surgeons assessed a significantly smaller percentage of black patients (70% [258 of 367]), compared with white patients (78% [2,307 of 2,946]). The percentage of black patients who actually underwent surgery after being assessed by a surgeon (35% [90 of 258]) was significantly lower than that of white patients (59% [1,351 of 2,307]). Overall, significantly more white patients than black patients had surgery (46% vs. 25%) (J. Clin. Oncol. 2005;23:510–7).

Neither medically relevant factors nor nonmedical factors explained the differences involving surgical evaluation or surgery performed in the observational study. Significantly fewer black patients survived than did white patients at follow-up of 6 months (58% vs. 64%), 1 year (39% vs. 43%), 2 years (18% vs. 25%), and 5 years (8% vs. 11%). The type of treatment received, rather than nonmedical factors, explained most of the higher mortality in black patients.

Chromoendoscopy Detects Barrett's

Chromoendoscopy with crystal violet detects short-segment Barrett's esophagus with greater sensitivity and specificity than does chromoendoscopy with methylene blue, based on the results of a prospective study.

Yuji Amano, M.D., and colleagues at Shimane University, Izumo, Japan, found that chromoendoscopy with 0.05% crystal violet detected Barrett's epithelium with 89% sensitivity, 86% specificity, and 88% diagnostic accuracy in 100 patients with suspected short-segment Barrett's esophagus. These results were significantly better than those obtained with 0.1% crystal violet, 0.5% methylene blue, or 1% methylene blue in 300 patients (Am. J. Gastroenterol. 2005;100:21–6).

In patients who had nondysplastic and dysplastic Barrett's epithelium stained, 0.05% crystal violet detected the mucosal pit pattern—important for making a histological diagnosis—at the highest rate (93%) of all methods.

Hepatitis C Virus Persists After Tx

Hepatitis C virus RNA persists and appears to replicate at low levels in patients years after they had a sustained virologic response to treatment, according to Marek Radkowski, M.D., of the Mayo Clinic Scottsdale (Ariz.) and colleagues.

In 17 patients who had a sustained virologic response that had lasted for 40 to 109 months prior to the study, 15 had hepatitis C virus (HCV) RNA detected in a liver biopsy, serum, peripheral blood mononuclear cells, or cultures of lymphocytes or macrophages. The investigators detected HCV RNA-negative strand in lymphocytes in two patients and in macrophages from four other patients. HCV RNA-negative strand is a replicative intermediate in the viral life cycle and is generally accepted as evidence of ongoing HCV replication (Hepatology 2005;41:106–14).

“This continuous presence of HCV RNA could explain the phenomenon of relatively common persistence of humoral and cellular immunity for many years after supposed viral clearance and could present a potential risk for transmission or infection reactivation,” the researchers said.

Prognosis of Acetaminophen Liver Injury

Measurement of alpha-fetoprotein levels along with other established criteria may aid in determining the prognosis of acetaminophen-induced fulminant hepatic failure, reported Lars E. Schmidt, M.D., and Kim Dalhoff, M.D., of Rigshospitalet, Copenhagen.

An increase of alpha-fetoprotein higher than 3.9 mcg/L on the day after the peak level of alanine aminotransferase predicted survival from severe acetaminophen-induced liver injury with 100% sensitivity in 239 patients seen at Copenhagen University Hospital during 1999–2002. Dr. Schmidt and Dr. Dalhoff suggested that in marginal or protracted cases of acetaminophen-induced fulminant hepatic failure, measurements of alpha-fetoprotein could supplement the King's College Hospital criteria to identify patients who are likely to die as a consequence of their fulminant hepatic failure. The King's criteria include the prognostic variables of etiology, age, serum bilirubin, serum creatinine, degree of encephalopathy, and arterial pH (Hepatology 2005;41:26–31).

“It must be stressed that these models will aid, but not replace, clinical judgment,” James Neuberger, M.D., said in an editorial (Hepatology 2005;41:19–22).

Racial Differences in Cancer Surgery

Black patients with locoregional esophageal cancer are less likely to be evaluated for surgery than are white patients, and they receive surgery less often than white patients even when they are surgically evaluated, reported Ewout W. Steyerberg, M.D., of Erasmus MC, Rotterdam, the Netherlands, and associates.

An analysis of patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results database found that surgeons assessed a significantly smaller percentage of black patients (70% [258 of 367]), compared with white patients (78% [2,307 of 2,946]). The percentage of black patients who actually underwent surgery after being assessed by a surgeon (35% [90 of 258]) was significantly lower than that of white patients (59% [1,351 of 2,307]). Overall, significantly more white patients than black patients had surgery (46% vs. 25%) (J. Clin. Oncol. 2005;23:510–7).

Neither medically relevant factors nor nonmedical factors explained the differences involving surgical evaluation or surgery performed in the observational study. Significantly fewer black patients survived than did white patients at follow-up of 6 months (58% vs. 64%), 1 year (39% vs. 43%), 2 years (18% vs. 25%), and 5 years (8% vs. 11%). The type of treatment received, rather than nonmedical factors, explained most of the higher mortality in black patients.

Chromoendoscopy Detects Barrett's

Chromoendoscopy with crystal violet detects short-segment Barrett's esophagus with greater sensitivity and specificity than does chromoendoscopy with methylene blue, based on the results of a prospective study.

Yuji Amano, M.D., and colleagues at Shimane University, Izumo, Japan, found that chromoendoscopy with 0.05% crystal violet detected Barrett's epithelium with 89% sensitivity, 86% specificity, and 88% diagnostic accuracy in 100 patients with suspected short-segment Barrett's esophagus. These results were significantly better than those obtained with 0.1% crystal violet, 0.5% methylene blue, or 1% methylene blue in 300 patients (Am. J. Gastroenterol. 2005;100:21–6).

In patients who had nondysplastic and dysplastic Barrett's epithelium stained, 0.05% crystal violet detected the mucosal pit pattern—important for making a histological diagnosis—at the highest rate (93%) of all methods.

Hepatitis C Virus Persists After Tx

Hepatitis C virus RNA persists and appears to replicate at low levels in patients years after they had a sustained virologic response to treatment, according to Marek Radkowski, M.D., of the Mayo Clinic Scottsdale (Ariz.) and colleagues.

In 17 patients who had a sustained virologic response that had lasted for 40 to 109 months prior to the study, 15 had hepatitis C virus (HCV) RNA detected in a liver biopsy, serum, peripheral blood mononuclear cells, or cultures of lymphocytes or macrophages. The investigators detected HCV RNA-negative strand in lymphocytes in two patients and in macrophages from four other patients. HCV RNA-negative strand is a replicative intermediate in the viral life cycle and is generally accepted as evidence of ongoing HCV replication (Hepatology 2005;41:106–14).

“This continuous presence of HCV RNA could explain the phenomenon of relatively common persistence of humoral and cellular immunity for many years after supposed viral clearance and could present a potential risk for transmission or infection reactivation,” the researchers said.

Prognosis of Acetaminophen Liver Injury

Measurement of alpha-fetoprotein levels along with other established criteria may aid in determining the prognosis of acetaminophen-induced fulminant hepatic failure, reported Lars E. Schmidt, M.D., and Kim Dalhoff, M.D., of Rigshospitalet, Copenhagen.

An increase of alpha-fetoprotein higher than 3.9 mcg/L on the day after the peak level of alanine aminotransferase predicted survival from severe acetaminophen-induced liver injury with 100% sensitivity in 239 patients seen at Copenhagen University Hospital during 1999–2002. Dr. Schmidt and Dr. Dalhoff suggested that in marginal or protracted cases of acetaminophen-induced fulminant hepatic failure, measurements of alpha-fetoprotein could supplement the King's College Hospital criteria to identify patients who are likely to die as a consequence of their fulminant hepatic failure. The King's criteria include the prognostic variables of etiology, age, serum bilirubin, serum creatinine, degree of encephalopathy, and arterial pH (Hepatology 2005;41:26–31).

“It must be stressed that these models will aid, but not replace, clinical judgment,” James Neuberger, M.D., said in an editorial (Hepatology 2005;41:19–22).

ORLANDO, FLA. — A combination of endoscopic and medical treatment of bleeding peptic ulcers with adherent clots results in a significantly lower rebleeding rate than does medical therapy alone, according to findings from a metaanalysis of randomized clinical trials.

Peptic ulcers with adherent clots are problematic because of highly variable rebleeding rates that range from 8% to 36%, Charles J. Kahi, M.D., said at the annual meeting of the American College of Gastroenterology.

In the metaanalysis, patients who received combination therapy had about a 60% lower risk of rebleeding than did those who received medical therapy alone.

During a search of four databases (Medline, Embase, Thomson Biosis, and Brown University Cochrane Center's Central) for trials published during 1966–2003, Dr. Kahi and his colleagues located six randomized trials that compared the combination of endoscopic and medical therapies with medical therapy alone for bleeding peptic ulcers with adherent clots. They contacted the primary authors of the studies, obtained the raw data from each of the trials, and combined all the data into one database.

Four studies were fully published reports, and two were published in abstract form. The six studies included a total of 240 patients.

Overall, three of the trials found no difference in rebleeding rates, whereas the remaining three trials found that the combination treatment gave a significantly lower rebleeding rate than did medical therapy alone, said Dr. Kahi of Indiana University, Indianapolis.

In the four fully published studies, rebleeding occurred in significantly fewer patients (8% [5 of 61 patients]) who received endoscopic plus medical therapy than in those who received medical therapy alone (25% [21 of 85 patients]).

The two groups did not differ in their length of hospital stay, number of transfusions, or mortality.

In each of the studies, endoscopic therapy consisted of clot removal and treatment of the underlying lesion with thermal energy, electrocoagulation, and/or injection of sclerosing agents. Medical therapy included supportive care, ICU monitoring, and acid suppressive medications, such as histamine-2 receptor antagonists or proton-pump inhibitors.

Dr. Kahi cautioned that the metaanalysis might include publication bias because reports of negative studies might not have been published. He also noted that the trials included patients from the United States, Hong Kong, Spain, and South Korea, who may have different responses to medical therapy because of genetic differences.

ORLANDO, FLA. — A combination of endoscopic and medical treatment of bleeding peptic ulcers with adherent clots results in a significantly lower rebleeding rate than does medical therapy alone, according to findings from a metaanalysis of randomized clinical trials.

Peptic ulcers with adherent clots are problematic because of highly variable rebleeding rates that range from 8% to 36%, Charles J. Kahi, M.D., said at the annual meeting of the American College of Gastroenterology.

In the metaanalysis, patients who received combination therapy had about a 60% lower risk of rebleeding than did those who received medical therapy alone.

During a search of four databases (Medline, Embase, Thomson Biosis, and Brown University Cochrane Center's Central) for trials published during 1966–2003, Dr. Kahi and his colleagues located six randomized trials that compared the combination of endoscopic and medical therapies with medical therapy alone for bleeding peptic ulcers with adherent clots. They contacted the primary authors of the studies, obtained the raw data from each of the trials, and combined all the data into one database.

Four studies were fully published reports, and two were published in abstract form. The six studies included a total of 240 patients.

Overall, three of the trials found no difference in rebleeding rates, whereas the remaining three trials found that the combination treatment gave a significantly lower rebleeding rate than did medical therapy alone, said Dr. Kahi of Indiana University, Indianapolis.

In the four fully published studies, rebleeding occurred in significantly fewer patients (8% [5 of 61 patients]) who received endoscopic plus medical therapy than in those who received medical therapy alone (25% [21 of 85 patients]).

The two groups did not differ in their length of hospital stay, number of transfusions, or mortality.

In each of the studies, endoscopic therapy consisted of clot removal and treatment of the underlying lesion with thermal energy, electrocoagulation, and/or injection of sclerosing agents. Medical therapy included supportive care, ICU monitoring, and acid suppressive medications, such as histamine-2 receptor antagonists or proton-pump inhibitors.

Dr. Kahi cautioned that the metaanalysis might include publication bias because reports of negative studies might not have been published. He also noted that the trials included patients from the United States, Hong Kong, Spain, and South Korea, who may have different responses to medical therapy because of genetic differences.

ORLANDO, FLA. — A combination of endoscopic and medical treatment of bleeding peptic ulcers with adherent clots results in a significantly lower rebleeding rate than does medical therapy alone, according to findings from a metaanalysis of randomized clinical trials.

Peptic ulcers with adherent clots are problematic because of highly variable rebleeding rates that range from 8% to 36%, Charles J. Kahi, M.D., said at the annual meeting of the American College of Gastroenterology.

In the metaanalysis, patients who received combination therapy had about a 60% lower risk of rebleeding than did those who received medical therapy alone.

During a search of four databases (Medline, Embase, Thomson Biosis, and Brown University Cochrane Center's Central) for trials published during 1966–2003, Dr. Kahi and his colleagues located six randomized trials that compared the combination of endoscopic and medical therapies with medical therapy alone for bleeding peptic ulcers with adherent clots. They contacted the primary authors of the studies, obtained the raw data from each of the trials, and combined all the data into one database.

Four studies were fully published reports, and two were published in abstract form. The six studies included a total of 240 patients.

Overall, three of the trials found no difference in rebleeding rates, whereas the remaining three trials found that the combination treatment gave a significantly lower rebleeding rate than did medical therapy alone, said Dr. Kahi of Indiana University, Indianapolis.

In the four fully published studies, rebleeding occurred in significantly fewer patients (8% [5 of 61 patients]) who received endoscopic plus medical therapy than in those who received medical therapy alone (25% [21 of 85 patients]).

The two groups did not differ in their length of hospital stay, number of transfusions, or mortality.

In each of the studies, endoscopic therapy consisted of clot removal and treatment of the underlying lesion with thermal energy, electrocoagulation, and/or injection of sclerosing agents. Medical therapy included supportive care, ICU monitoring, and acid suppressive medications, such as histamine-2 receptor antagonists or proton-pump inhibitors.

Dr. Kahi cautioned that the metaanalysis might include publication bias because reports of negative studies might not have been published. He also noted that the trials included patients from the United States, Hong Kong, Spain, and South Korea, who may have different responses to medical therapy because of genetic differences.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of this agent in pregnancy, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus. Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy.

In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

The drug also was not linked to any unusual side effects in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children. “I think we can ensure that at such a low level there is no risk,” Dr. Piette said.

Some reports have noted teratogenicity with high-dose chloroquine; one case occurred in a pregnant woman with lupus. These have included a few cases of ear or eye toxicity. Dr. Piette said that he recommends contraception in patients who receive chloroquine.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of this agent in pregnancy, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus. Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy.

In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

The drug also was not linked to any unusual side effects in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children. “I think we can ensure that at such a low level there is no risk,” Dr. Piette said.

Some reports have noted teratogenicity with high-dose chloroquine; one case occurred in a pregnant woman with lupus. These have included a few cases of ear or eye toxicity. Dr. Piette said that he recommends contraception in patients who receive chloroquine.

DÜSSELDORF, GERMANY — The anti-inflammatory compound hydroxychloroquine appears to be relatively safe during pregnancy, according to a small number of studies totaling about 250 patients.

But these studies have not provided overwhelming evidence proving the safety of this agent in pregnancy, Jean-Charles Piette, M.D., said at an international conference on cutaneous lupus erythematosus. Until 1995, nearly all physicians stopped hydroxychloroquine (Plaquenil) when a patient with lupus erythematosus (LE) became pregnant because there were no data on whether the drug was safe during pregnancy, said Dr. Piette of Hôpital Pitié-Salpétrière, Paris.

Now, many physicians who treat about four to five pregnant women with connective tissue disorder each year regularly prescribe antimalarials to such patients despite a lack of evidence officially establishing the safety of the drugs during pregnancy.

In fact, 69% of 52 physicians who responded to a survey about the use of antimalarials during pregnancy said they continued antimalarials in pregnancy sometimes, often, or always (J. Rheumatol. 2002;29:700–6).

Hydroxychloroquine (HCQ) is known to cross the placenta and is present in similar concentrations in blood from the umbilical cord and the mother (Arthritis Rheum. 2002;46:1123–4).

In one study, 33 women with LE who were exposed to HCQ during 36 pregnancies had similar obstetric outcomes and levels of lupus activity, compared with 53 unexposed pregnant women with LE from the same lupus pregnancy center (Ann. Rheum. Dis. 1996;55:486–8). The investigators in the trial concluded that the continuation of HCQ “is probably safe during pregnancy,” Dr. Piette noted.

In a separate study, HCQ did not cause any disease flares in a group of eight women with systemic LE and two with discoid LE, whereas three patients had flare-ups in a placebo group of nine patients with systemic LE and one with discoid LE. None of the infants born to women taking HCQ had congenital abnormalities, and all of them had normal auditory and neuroophthalmologic evaluations at 1.5–3 years of age (Lupus 2001;10:401–4).

The drug also was not linked to any unusual side effects in another series of 53 pregnancies in women with LE that resulted in live births.

A study conducted by Dr. Piette and his colleagues compared 133 consecutive pregnancies in 90 women with connective tissue disease who took HCQ with 70 consecutive pregnancies in 53 control women with similar disorders who did not take HCQ. Of the pregnancies in women who received HCQ, 122 were exposed to 400 mg/day, and the remaining 11 received 200 mg/day.

Three malformations occurred in exposed infants, while four developed in the infants of control women. One child died as a result of prematurity in each group.

After the last follow-up of children at a mean age of 26 months (age ranging from 12 to 108 months), none of the children exposed to HCQ had visual, hearing, growth, or developmental abnormalities (Arthritis Rheum. 2003;48:3207–11).

Despite data that show no teratogenicity with HCQ, the Physicians' Desk Reference Web site for patients advises pregnant patients to avoid HCQ except in the suppression or treatment of malaria when the benefit outweighs any possible hazards.

HCQ exists at low levels in breast milk—344 ng/mL and 1,424 ng/mL in a report on two mothers—and is delivered in extremely low levels to breast-feeding children. “I think we can ensure that at such a low level there is no risk,” Dr. Piette said.

Some reports have noted teratogenicity with high-dose chloroquine; one case occurred in a pregnant woman with lupus. These have included a few cases of ear or eye toxicity. Dr. Piette said that he recommends contraception in patients who receive chloroquine.

The call for research asks investigators to determine the functional significance of any genes or gene variants identified during analysis of larger data sets.

Federal health agencies have teamed up with private organizations and government health agencies in Canada and Ireland to provide funding for research into the genetic basis of susceptibility to autistic spectrum disorders.

The coalition, headed by the National Institute of Mental Health, has made $21 million available to researchers and requested grant applications titled “Identifying Autism Susceptibility Genes.”

Rather than fund the collection of new data sets on autism spectrum disorders, the coalition wants researchers to submit applications that focus on using large data sets of more than 1,000 pedigrees that already have been assembled. These data sets should have adequate statistical power to detect autism susceptibility loci, according to the NIMH.

Studies have located several chromosomal regions associated with autism, but few specific genes have been identified.

The call for more research asks investigators to determine the functional significance of any genes or gene variants that are identified during the analysis of the large data sets.

The identification of new genes or gene variants may help researchers to subdivide the autism spectrum disorders into distinct disorders with different molecular mechanisms.

Some of the grant applications also may address the possibility that not all heritable traits of autism directly involve alterations in the genetic code.

Heritable changes that do not alter the DNA sequence include epigenetic mechanisms such as imprinting, DNA methylation, and changes in chromatin or protein conformations; they could potentially regulate gene expression and play an important etiologic role in the disorder.

The coalition consists of four other institutes in the National Institutes of Health besides the NIMH, as well as the Canadian Institutes of Health Research, the Health Research Board (Ireland), the Southwest Autism Research and Resource Center, Cure Autism Now, and the National Alliance for Autism Research.

The coalition expects to fund two to three organizations to participate during the 5-year project.

For more information or to request applications, go to http://grants1.nih.gov/grants/guide/rfa-files/RFA-MH-05-007.html

The call for research asks investigators to determine the functional significance of any genes or gene variants identified during analysis of larger data sets.

Federal health agencies have teamed up with private organizations and government health agencies in Canada and Ireland to provide funding for research into the genetic basis of susceptibility to autistic spectrum disorders.

The coalition, headed by the National Institute of Mental Health, has made $21 million available to researchers and requested grant applications titled “Identifying Autism Susceptibility Genes.”

Rather than fund the collection of new data sets on autism spectrum disorders, the coalition wants researchers to submit applications that focus on using large data sets of more than 1,000 pedigrees that already have been assembled. These data sets should have adequate statistical power to detect autism susceptibility loci, according to the NIMH.

Studies have located several chromosomal regions associated with autism, but few specific genes have been identified.

The call for more research asks investigators to determine the functional significance of any genes or gene variants that are identified during the analysis of the large data sets.

The identification of new genes or gene variants may help researchers to subdivide the autism spectrum disorders into distinct disorders with different molecular mechanisms.

Some of the grant applications also may address the possibility that not all heritable traits of autism directly involve alterations in the genetic code.

Heritable changes that do not alter the DNA sequence include epigenetic mechanisms such as imprinting, DNA methylation, and changes in chromatin or protein conformations; they could potentially regulate gene expression and play an important etiologic role in the disorder.

The coalition consists of four other institutes in the National Institutes of Health besides the NIMH, as well as the Canadian Institutes of Health Research, the Health Research Board (Ireland), the Southwest Autism Research and Resource Center, Cure Autism Now, and the National Alliance for Autism Research.

The coalition expects to fund two to three organizations to participate during the 5-year project.

For more information or to request applications, go to http://grants1.nih.gov/grants/guide/rfa-files/RFA-MH-05-007.html

The call for research asks investigators to determine the functional significance of any genes or gene variants identified during analysis of larger data sets.

Federal health agencies have teamed up with private organizations and government health agencies in Canada and Ireland to provide funding for research into the genetic basis of susceptibility to autistic spectrum disorders.

The coalition, headed by the National Institute of Mental Health, has made $21 million available to researchers and requested grant applications titled “Identifying Autism Susceptibility Genes.”

Rather than fund the collection of new data sets on autism spectrum disorders, the coalition wants researchers to submit applications that focus on using large data sets of more than 1,000 pedigrees that already have been assembled. These data sets should have adequate statistical power to detect autism susceptibility loci, according to the NIMH.

Studies have located several chromosomal regions associated with autism, but few specific genes have been identified.

The call for more research asks investigators to determine the functional significance of any genes or gene variants that are identified during the analysis of the large data sets.

The identification of new genes or gene variants may help researchers to subdivide the autism spectrum disorders into distinct disorders with different molecular mechanisms.

Some of the grant applications also may address the possibility that not all heritable traits of autism directly involve alterations in the genetic code.

Heritable changes that do not alter the DNA sequence include epigenetic mechanisms such as imprinting, DNA methylation, and changes in chromatin or protein conformations; they could potentially regulate gene expression and play an important etiologic role in the disorder.

The coalition consists of four other institutes in the National Institutes of Health besides the NIMH, as well as the Canadian Institutes of Health Research, the Health Research Board (Ireland), the Southwest Autism Research and Resource Center, Cure Autism Now, and the National Alliance for Autism Research.

The coalition expects to fund two to three organizations to participate during the 5-year project.

For more information or to request applications, go to http://grants1.nih.gov/grants/guide/rfa-files/RFA-MH-05-007.html

ORLANDO, FLA. — Colorectal cancer occurs at a high enough rate in African Americans and Hispanics under 50 years of age to warrant screening starting at age 40, according to Jaydutt Vadgama, Ph.D., of the Charles R. Drew University of Medicine and Science, Los Angeles.

In a retrospective study, Dr. Vadgama found that of 148 patients who had been diagnosed with colorectal cancer at the Martin Luther King/Drew Medical Center during 1996–2004, 38 (26%) were younger than 50 years of age. At diagnosis, the 38 patients had a median age of 42 years. Half of the patients under age 50 had a family history of colorectal cancer.

During 1993–1997, 46% of the 11,615 cases of colorectal cancer in African Americans and Hispanics in California occurred in patients younger than 50 years.

“Colorectal cancer screening should be considered in African Americans and Hispanics beginning at age 40 regardless of family history,” the researchers suggested in a poster presentation at the annual meeting of the American College of Gastroenterology.

The college's guidelines on colorectal cancer screening, published in 2000, recommend that patients at higher than average risk for colorectal cancer should be screened by colonoscopy at an age of 40 years or 10 years younger than the age of the youngest affected relative at diagnosis, whichever is earlier.

ORLANDO, FLA. — Colorectal cancer occurs at a high enough rate in African Americans and Hispanics under 50 years of age to warrant screening starting at age 40, according to Jaydutt Vadgama, Ph.D., of the Charles R. Drew University of Medicine and Science, Los Angeles.

In a retrospective study, Dr. Vadgama found that of 148 patients who had been diagnosed with colorectal cancer at the Martin Luther King/Drew Medical Center during 1996–2004, 38 (26%) were younger than 50 years of age. At diagnosis, the 38 patients had a median age of 42 years. Half of the patients under age 50 had a family history of colorectal cancer.

During 1993–1997, 46% of the 11,615 cases of colorectal cancer in African Americans and Hispanics in California occurred in patients younger than 50 years.

“Colorectal cancer screening should be considered in African Americans and Hispanics beginning at age 40 regardless of family history,” the researchers suggested in a poster presentation at the annual meeting of the American College of Gastroenterology.

The college's guidelines on colorectal cancer screening, published in 2000, recommend that patients at higher than average risk for colorectal cancer should be screened by colonoscopy at an age of 40 years or 10 years younger than the age of the youngest affected relative at diagnosis, whichever is earlier.

ORLANDO, FLA. — Colorectal cancer occurs at a high enough rate in African Americans and Hispanics under 50 years of age to warrant screening starting at age 40, according to Jaydutt Vadgama, Ph.D., of the Charles R. Drew University of Medicine and Science, Los Angeles.

In a retrospective study, Dr. Vadgama found that of 148 patients who had been diagnosed with colorectal cancer at the Martin Luther King/Drew Medical Center during 1996–2004, 38 (26%) were younger than 50 years of age. At diagnosis, the 38 patients had a median age of 42 years. Half of the patients under age 50 had a family history of colorectal cancer.

During 1993–1997, 46% of the 11,615 cases of colorectal cancer in African Americans and Hispanics in California occurred in patients younger than 50 years.

“Colorectal cancer screening should be considered in African Americans and Hispanics beginning at age 40 regardless of family history,” the researchers suggested in a poster presentation at the annual meeting of the American College of Gastroenterology.

The college's guidelines on colorectal cancer screening, published in 2000, recommend that patients at higher than average risk for colorectal cancer should be screened by colonoscopy at an age of 40 years or 10 years younger than the age of the youngest affected relative at diagnosis, whichever is earlier.

ORLANDO, FLA. — Daily intake of a lactobacilli-fermented milk may help prevent antibiotic-associated diarrhea in hospitalized patients, Natalie A. Fortier reported at the annual meeting of the American College of Gastroenterology.

Few of the published studies on the use of probiotics to prevent antibiotic-associated diarrhea have had a strong randomized, placebo-controlled design, said Ms. Fortier of the University of Montreal.

The daily drink, which contained 50 billion colony-forming units of live Lactobacillus acidophilus and L. casei, was associated with significantly fewer cases of antibiotic-associated diarrhea (7 of 41 patients) than was a placebo drink composed of lactoserum devoid of any microorganisms (16 of 43 patients).

Ms. Fortier and her colleagues at the university defined antibiotic-associated diarrhea as three or more liquid stools in a 24-hour period in the randomized, double-blind trial.

The researchers provided the active treatment or placebo daily to adult patients with an average age of 70 years on the 7–10 days that they were taking antibiotics and obtained follow-up from the patients for 21 days after they stopped taking antibiotics.

The patients began prophylactic treatment in the first 48 hours after starting antibiotics, which were primarily for upper respiratory tract infections.

Those with active diarrhea, GI bleeding, inflammatory bowel disease, Clostridium difficile infection in the last 3 months, a high risk of an immunocompromised state, lactose intolerance, or a regular intake of probiotics were excluded from the trial.

Diarrhea associated with C. difficile occurred less often in patients who received the active treatment (1 of 41) than in placebo patients (7 of 43), although the difference did not reach statistical significance.

Actively treated patients had a significantly shorter median length of stay in the hospital, compared with patients who received placebo (8 days vs. 10 days).

Ms. Fortier and her associates obtained their results from a multivariate analysis after controlling for risk factors for antibiotic-associated diarrhea and C. difficile-associated diarrhea as well for the fact that significantly more placebo patients received β-lactam antibiotics (67%) than did actively treated patients (41%).

Side effects—mostly of a GI nature—occurred in nearly half of patients in each group, she said.

The active and placebo preparations were provided by Bio-K+ International Inc., Laval, Que., which manufactures and markets the active treatment.

ORLANDO, FLA. — Daily intake of a lactobacilli-fermented milk may help prevent antibiotic-associated diarrhea in hospitalized patients, Natalie A. Fortier reported at the annual meeting of the American College of Gastroenterology.

Few of the published studies on the use of probiotics to prevent antibiotic-associated diarrhea have had a strong randomized, placebo-controlled design, said Ms. Fortier of the University of Montreal.

The daily drink, which contained 50 billion colony-forming units of live Lactobacillus acidophilus and L. casei, was associated with significantly fewer cases of antibiotic-associated diarrhea (7 of 41 patients) than was a placebo drink composed of lactoserum devoid of any microorganisms (16 of 43 patients).

Ms. Fortier and her colleagues at the university defined antibiotic-associated diarrhea as three or more liquid stools in a 24-hour period in the randomized, double-blind trial.

The researchers provided the active treatment or placebo daily to adult patients with an average age of 70 years on the 7–10 days that they were taking antibiotics and obtained follow-up from the patients for 21 days after they stopped taking antibiotics.

The patients began prophylactic treatment in the first 48 hours after starting antibiotics, which were primarily for upper respiratory tract infections.

Those with active diarrhea, GI bleeding, inflammatory bowel disease, Clostridium difficile infection in the last 3 months, a high risk of an immunocompromised state, lactose intolerance, or a regular intake of probiotics were excluded from the trial.

Diarrhea associated with C. difficile occurred less often in patients who received the active treatment (1 of 41) than in placebo patients (7 of 43), although the difference did not reach statistical significance.

Actively treated patients had a significantly shorter median length of stay in the hospital, compared with patients who received placebo (8 days vs. 10 days).

Ms. Fortier and her associates obtained their results from a multivariate analysis after controlling for risk factors for antibiotic-associated diarrhea and C. difficile-associated diarrhea as well for the fact that significantly more placebo patients received β-lactam antibiotics (67%) than did actively treated patients (41%).

Side effects—mostly of a GI nature—occurred in nearly half of patients in each group, she said.

The active and placebo preparations were provided by Bio-K+ International Inc., Laval, Que., which manufactures and markets the active treatment.

ORLANDO, FLA. — Daily intake of a lactobacilli-fermented milk may help prevent antibiotic-associated diarrhea in hospitalized patients, Natalie A. Fortier reported at the annual meeting of the American College of Gastroenterology.

Few of the published studies on the use of probiotics to prevent antibiotic-associated diarrhea have had a strong randomized, placebo-controlled design, said Ms. Fortier of the University of Montreal.

The daily drink, which contained 50 billion colony-forming units of live Lactobacillus acidophilus and L. casei, was associated with significantly fewer cases of antibiotic-associated diarrhea (7 of 41 patients) than was a placebo drink composed of lactoserum devoid of any microorganisms (16 of 43 patients).

Ms. Fortier and her colleagues at the university defined antibiotic-associated diarrhea as three or more liquid stools in a 24-hour period in the randomized, double-blind trial.

The researchers provided the active treatment or placebo daily to adult patients with an average age of 70 years on the 7–10 days that they were taking antibiotics and obtained follow-up from the patients for 21 days after they stopped taking antibiotics.

The patients began prophylactic treatment in the first 48 hours after starting antibiotics, which were primarily for upper respiratory tract infections.

Those with active diarrhea, GI bleeding, inflammatory bowel disease, Clostridium difficile infection in the last 3 months, a high risk of an immunocompromised state, lactose intolerance, or a regular intake of probiotics were excluded from the trial.

Diarrhea associated with C. difficile occurred less often in patients who received the active treatment (1 of 41) than in placebo patients (7 of 43), although the difference did not reach statistical significance.

Actively treated patients had a significantly shorter median length of stay in the hospital, compared with patients who received placebo (8 days vs. 10 days).

Ms. Fortier and her associates obtained their results from a multivariate analysis after controlling for risk factors for antibiotic-associated diarrhea and C. difficile-associated diarrhea as well for the fact that significantly more placebo patients received β-lactam antibiotics (67%) than did actively treated patients (41%).

Side effects—mostly of a GI nature—occurred in nearly half of patients in each group, she said.

The active and placebo preparations were provided by Bio-K+ International Inc., Laval, Que., which manufactures and markets the active treatment.