Michele G. Sullivan

An additional 1,000 women may have died from ovarian cancer linked to hormone therapy during a 15-year period in the United Kingdom, according to results from an enormous, but controversial, epidemiologic study.

After 6.5 million woman-years of follow-up, investigators for the Million Women Study concluded that those taking HT were 20% more likely to develop and die from ovarian cancer than those who had never taken it, but that the risk for women who quit taking HT returned to baseline by 5 years (Lancet 2007 [Epub doi:10.1016/S0140–6736(07)60534–0]).

Hormone therapy accounted for one extra case of ovarian cancer and one extra death per 2,500 users over a 5-year period, wrote Dr. Valerie Beral, lead author for the Million Women Study Collaboration. “If this association is causal, the use of HT since 1991 has resulted in roughly 1,300 extra cases of ovarian cancer and 1,000 extra deaths from the malignancy in the U.K.,” the investigators wrote.

From 1991 to 2001, the study—the largest epidemiologic study of its kind—enrolled 1.3 million women aged 50–64 years. All had been invited to the National Health Service Breast Screening Programme and completed an initial survey about social, demographic, and lifestyle factors, including the use of HT. About 3 years after recruitment, the women received a second questionnaire to secure updated information on HT.

Other researchers have questioned the MWS results since its first publication in 2003, saying that its methodologic problems make its conclusions difficult to interpret or accept.

The MWS ovarian cancer analysis included 948,576 women: 474,682 had never used HT, 186,751 were past users, and 287,143 were current users. The subjects' mean age at last follow-up was 57 years; 56% had used oral contraceptives, and 20% were current smokers.

The women were followed for an average of 5 years to determine ovarian cancer incidence. During that time, 2,273 such cancers were reported to the national registry. Current users were 20% more likely than never-users to develop the cancer—a significant difference. There was no difference in incidence between never-users and past users.

Current users had been taking HT for an average of 8 years at the time of diagnosis, and incidence increased with the duration of HT. Women who had taken hormones for 10 or more years were at a 30% increased risk for disease, compared with never-users.

But the risk of developing ovarian cancer dropped rapidly after ceasing HT. Compared with women who had never used HT, the relative risk for ovarian cancer was 1.01 for women who had been off HT less than 5 years and 0.95 for those who were off HT 5 or more years.

There were no significant differences in the risks between HT preparations (different estrogenic and progestogenic components; oral or transdermal; or between preparations with progestagens). Likewise, the researchers wrote, there were no significant associations with any demographic factor. Adjusting for age, socioeconomic status, body mass index, physical activity, or alcohol and tobacco use did not alter the relative risk for current users by more than 2%.

HT users who had undergone hysterectomy did have a significantly increased risk, compared with those who had not, but the researchers said that was probably because they had been taking HT longer.

The women were followed for an average of 7 years to determine ovarian cancer mortality. During this time, 1,591 deaths were attributed to ovarian cancer. Women who were current users of HT at their last follow-up were 23% more likely to die from the disease than never-users. Past users were at no significantly increased risk of death.

Again, there were no significant differences in risk after the researchers adjusted for demographic characteristics. There were also no significant differences in the risk of death between the different preparations of HT or the mode of administration.

The standardized ovarian cancer incidence rate was 2.2/1,000 women per 5 years among never-users and 2.6/1,000 women per 5 years in current users. The standardized mortality rate was 1.3 deaths/1,000 women per 5 years among never-users and 1.6/1,000 women per 5 years in current users.

But these numbers cannot be viewed in isolation, wrote the authors, whose study has previously examined the incidence of breast and endometrial cancers in these women. “Ovarian, endometrial, and breast cancer account for 39% of all cancers registered in women in the United Kingdom. The total incidence of these three cancers in the study population is 63% higher in current users of HT than in never-users. Thus, when ovarian, endometrial, and breast cancer are taken together, use of HT results in a material increase in the incidence of these common cancers.”

Dr. Steve Narod, of the Women's College Research Institute, Toronto, agreed. “[The risk] might be thought of as small, but enormous numbers of women have been exposed,” he wrote in an accompanying commentary” (Lancet 2007 [Epub doi:10.1016/S0140-6736(07)60535-2]).

Study Controversial From the Start

There's no doubt that the Million Women Study has been directly responsible for the dramatic decrease in British and European hormone therapy prescriptions, experts say. But they also point out that criticism has dogged this enormous epidemiologic study every step of the way. Since 2003, critics have charged that a flawed methodology makes MWs' conclusions almost impossible to accept.

Critical response began with the first MWS publication in 2003. The Lancet published several letters questioning its methodology in the same issue that carried the breast cancer study (Lancet 2003;362:1330–1).

British epidemiologist Richard Farmer is one of several researchers who have repeatedly challenged the investigation's methodology. “Both [the breast cancer and endometrial cancer] studies have the same serious design flaws and there are important aspects of the published reports that are inconsistent,” wrote Dr. Farmer, emeritus professor of epidemiology at the University of Surrey (England) (Climacteric 2005;8:210–3).

Dr. Farmer and his colleague, Dr. M. Whitehead reported in 2004 that the study's design flaws “render the results largely uninterpretable because built-in biases have affected risk estimates” (Endoc. 2004;24:187–93).

Nevertheless, the Million Women Study carried the same national and international impact as did the U.S. Women's Health Initiative. Immediately after the first MWS publication, Britain's drug regulatory agency, the Committee on Safety of Medicines, announced that the data confirmed an HT duration-dependent increase in the risk of breast cancer, and advised counseling patients of that risk.

MWS significantly influenced HT prescribing patterns in the United Kingdom and throughout Europe. In the Netherlands, for instance, the publication of WHI was followed by a modest decrease in prescribing of HT. But after publication of the initial MWS results, rates dropped precipitously (Br. J. Clin. Pharm. 2005;60:641–7).

The study's main flaw is that HT use is based entirely based on recall—a notoriously unreliable source of information, said Dr. James Fiorica, director of gynecologic oncology at Sarasota Memorial Hospital, Fla., and a member of the speakers' board at Wyeth Pharmaceuticals, which manufactures the HT drugs Prempro and Premarin.

“MWS was questionnaire based,” he said in an interview. “This gives you no idea of compliance, or how long these women were really on hormones. It's easy to attribute cancer risk to a drug, but very hard to draw these conclusions based on a questionnaire.”

Dr. Wulf Utian, executive director of the North American Menopause Society, said the MWS ovarian cancer data won't change any of the HT prescribing recommendations included in the group's recent position statement. “The Million Women Study data are absolutely riddled with methodological problems; most serious investigators are not certain how to interpret these data,” Dr. Utian said in an interview. “The only conclusion we can draw from this study is that, clearly, we do not have all the answers. HT carries both potential benefit and potential risk, but in most instances, these absolute risks are rare.”

Treatment decisions should be based on a women's individual risk profile, he said. “If a woman of low risk and high need is prescribed HT she has little to fear. On the other hand, a woman of high risk and weak indication for HT would be better off to concentrate on healthy living and other more appropriate remedies for her problem.”

An additional 1,000 women may have died from ovarian cancer linked to hormone therapy during a 15-year period in the United Kingdom, according to results from an enormous, but controversial, epidemiologic study.

After 6.5 million woman-years of follow-up, investigators for the Million Women Study concluded that those taking HT were 20% more likely to develop and die from ovarian cancer than those who had never taken it, but that the risk for women who quit taking HT returned to baseline by 5 years (Lancet 2007 [Epub doi:10.1016/S0140–6736(07)60534–0]).

Hormone therapy accounted for one extra case of ovarian cancer and one extra death per 2,500 users over a 5-year period, wrote Dr. Valerie Beral, lead author for the Million Women Study Collaboration. “If this association is causal, the use of HT since 1991 has resulted in roughly 1,300 extra cases of ovarian cancer and 1,000 extra deaths from the malignancy in the U.K.,” the investigators wrote.

From 1991 to 2001, the study—the largest epidemiologic study of its kind—enrolled 1.3 million women aged 50–64 years. All had been invited to the National Health Service Breast Screening Programme and completed an initial survey about social, demographic, and lifestyle factors, including the use of HT. About 3 years after recruitment, the women received a second questionnaire to secure updated information on HT.

Other researchers have questioned the MWS results since its first publication in 2003, saying that its methodologic problems make its conclusions difficult to interpret or accept.

The MWS ovarian cancer analysis included 948,576 women: 474,682 had never used HT, 186,751 were past users, and 287,143 were current users. The subjects' mean age at last follow-up was 57 years; 56% had used oral contraceptives, and 20% were current smokers.

The women were followed for an average of 5 years to determine ovarian cancer incidence. During that time, 2,273 such cancers were reported to the national registry. Current users were 20% more likely than never-users to develop the cancer—a significant difference. There was no difference in incidence between never-users and past users.

Current users had been taking HT for an average of 8 years at the time of diagnosis, and incidence increased with the duration of HT. Women who had taken hormones for 10 or more years were at a 30% increased risk for disease, compared with never-users.

But the risk of developing ovarian cancer dropped rapidly after ceasing HT. Compared with women who had never used HT, the relative risk for ovarian cancer was 1.01 for women who had been off HT less than 5 years and 0.95 for those who were off HT 5 or more years.

There were no significant differences in the risks between HT preparations (different estrogenic and progestogenic components; oral or transdermal; or between preparations with progestagens). Likewise, the researchers wrote, there were no significant associations with any demographic factor. Adjusting for age, socioeconomic status, body mass index, physical activity, or alcohol and tobacco use did not alter the relative risk for current users by more than 2%.

HT users who had undergone hysterectomy did have a significantly increased risk, compared with those who had not, but the researchers said that was probably because they had been taking HT longer.

The women were followed for an average of 7 years to determine ovarian cancer mortality. During this time, 1,591 deaths were attributed to ovarian cancer. Women who were current users of HT at their last follow-up were 23% more likely to die from the disease than never-users. Past users were at no significantly increased risk of death.

Again, there were no significant differences in risk after the researchers adjusted for demographic characteristics. There were also no significant differences in the risk of death between the different preparations of HT or the mode of administration.

The standardized ovarian cancer incidence rate was 2.2/1,000 women per 5 years among never-users and 2.6/1,000 women per 5 years in current users. The standardized mortality rate was 1.3 deaths/1,000 women per 5 years among never-users and 1.6/1,000 women per 5 years in current users.

But these numbers cannot be viewed in isolation, wrote the authors, whose study has previously examined the incidence of breast and endometrial cancers in these women. “Ovarian, endometrial, and breast cancer account for 39% of all cancers registered in women in the United Kingdom. The total incidence of these three cancers in the study population is 63% higher in current users of HT than in never-users. Thus, when ovarian, endometrial, and breast cancer are taken together, use of HT results in a material increase in the incidence of these common cancers.”

Dr. Steve Narod, of the Women's College Research Institute, Toronto, agreed. “[The risk] might be thought of as small, but enormous numbers of women have been exposed,” he wrote in an accompanying commentary” (Lancet 2007 [Epub doi:10.1016/S0140-6736(07)60535-2]).

Study Controversial From the Start

There's no doubt that the Million Women Study has been directly responsible for the dramatic decrease in British and European hormone therapy prescriptions, experts say. But they also point out that criticism has dogged this enormous epidemiologic study every step of the way. Since 2003, critics have charged that a flawed methodology makes MWs' conclusions almost impossible to accept.

Critical response began with the first MWS publication in 2003. The Lancet published several letters questioning its methodology in the same issue that carried the breast cancer study (Lancet 2003;362:1330–1).

British epidemiologist Richard Farmer is one of several researchers who have repeatedly challenged the investigation's methodology. “Both [the breast cancer and endometrial cancer] studies have the same serious design flaws and there are important aspects of the published reports that are inconsistent,” wrote Dr. Farmer, emeritus professor of epidemiology at the University of Surrey (England) (Climacteric 2005;8:210–3).

Dr. Farmer and his colleague, Dr. M. Whitehead reported in 2004 that the study's design flaws “render the results largely uninterpretable because built-in biases have affected risk estimates” (Endoc. 2004;24:187–93).

Nevertheless, the Million Women Study carried the same national and international impact as did the U.S. Women's Health Initiative. Immediately after the first MWS publication, Britain's drug regulatory agency, the Committee on Safety of Medicines, announced that the data confirmed an HT duration-dependent increase in the risk of breast cancer, and advised counseling patients of that risk.

MWS significantly influenced HT prescribing patterns in the United Kingdom and throughout Europe. In the Netherlands, for instance, the publication of WHI was followed by a modest decrease in prescribing of HT. But after publication of the initial MWS results, rates dropped precipitously (Br. J. Clin. Pharm. 2005;60:641–7).

The study's main flaw is that HT use is based entirely based on recall—a notoriously unreliable source of information, said Dr. James Fiorica, director of gynecologic oncology at Sarasota Memorial Hospital, Fla., and a member of the speakers' board at Wyeth Pharmaceuticals, which manufactures the HT drugs Prempro and Premarin.

“MWS was questionnaire based,” he said in an interview. “This gives you no idea of compliance, or how long these women were really on hormones. It's easy to attribute cancer risk to a drug, but very hard to draw these conclusions based on a questionnaire.”

Dr. Wulf Utian, executive director of the North American Menopause Society, said the MWS ovarian cancer data won't change any of the HT prescribing recommendations included in the group's recent position statement. “The Million Women Study data are absolutely riddled with methodological problems; most serious investigators are not certain how to interpret these data,” Dr. Utian said in an interview. “The only conclusion we can draw from this study is that, clearly, we do not have all the answers. HT carries both potential benefit and potential risk, but in most instances, these absolute risks are rare.”

Treatment decisions should be based on a women's individual risk profile, he said. “If a woman of low risk and high need is prescribed HT she has little to fear. On the other hand, a woman of high risk and weak indication for HT would be better off to concentrate on healthy living and other more appropriate remedies for her problem.”

An additional 1,000 women may have died from ovarian cancer linked to hormone therapy during a 15-year period in the United Kingdom, according to results from an enormous, but controversial, epidemiologic study.

After 6.5 million woman-years of follow-up, investigators for the Million Women Study concluded that those taking HT were 20% more likely to develop and die from ovarian cancer than those who had never taken it, but that the risk for women who quit taking HT returned to baseline by 5 years (Lancet 2007 [Epub doi:10.1016/S0140–6736(07)60534–0]).

Hormone therapy accounted for one extra case of ovarian cancer and one extra death per 2,500 users over a 5-year period, wrote Dr. Valerie Beral, lead author for the Million Women Study Collaboration. “If this association is causal, the use of HT since 1991 has resulted in roughly 1,300 extra cases of ovarian cancer and 1,000 extra deaths from the malignancy in the U.K.,” the investigators wrote.

From 1991 to 2001, the study—the largest epidemiologic study of its kind—enrolled 1.3 million women aged 50–64 years. All had been invited to the National Health Service Breast Screening Programme and completed an initial survey about social, demographic, and lifestyle factors, including the use of HT. About 3 years after recruitment, the women received a second questionnaire to secure updated information on HT.

Other researchers have questioned the MWS results since its first publication in 2003, saying that its methodologic problems make its conclusions difficult to interpret or accept.

The MWS ovarian cancer analysis included 948,576 women: 474,682 had never used HT, 186,751 were past users, and 287,143 were current users. The subjects' mean age at last follow-up was 57 years; 56% had used oral contraceptives, and 20% were current smokers.

The women were followed for an average of 5 years to determine ovarian cancer incidence. During that time, 2,273 such cancers were reported to the national registry. Current users were 20% more likely than never-users to develop the cancer—a significant difference. There was no difference in incidence between never-users and past users.

Current users had been taking HT for an average of 8 years at the time of diagnosis, and incidence increased with the duration of HT. Women who had taken hormones for 10 or more years were at a 30% increased risk for disease, compared with never-users.

But the risk of developing ovarian cancer dropped rapidly after ceasing HT. Compared with women who had never used HT, the relative risk for ovarian cancer was 1.01 for women who had been off HT less than 5 years and 0.95 for those who were off HT 5 or more years.

There were no significant differences in the risks between HT preparations (different estrogenic and progestogenic components; oral or transdermal; or between preparations with progestagens). Likewise, the researchers wrote, there were no significant associations with any demographic factor. Adjusting for age, socioeconomic status, body mass index, physical activity, or alcohol and tobacco use did not alter the relative risk for current users by more than 2%.

HT users who had undergone hysterectomy did have a significantly increased risk, compared with those who had not, but the researchers said that was probably because they had been taking HT longer.

The women were followed for an average of 7 years to determine ovarian cancer mortality. During this time, 1,591 deaths were attributed to ovarian cancer. Women who were current users of HT at their last follow-up were 23% more likely to die from the disease than never-users. Past users were at no significantly increased risk of death.

Again, there were no significant differences in risk after the researchers adjusted for demographic characteristics. There were also no significant differences in the risk of death between the different preparations of HT or the mode of administration.

The standardized ovarian cancer incidence rate was 2.2/1,000 women per 5 years among never-users and 2.6/1,000 women per 5 years in current users. The standardized mortality rate was 1.3 deaths/1,000 women per 5 years among never-users and 1.6/1,000 women per 5 years in current users.

But these numbers cannot be viewed in isolation, wrote the authors, whose study has previously examined the incidence of breast and endometrial cancers in these women. “Ovarian, endometrial, and breast cancer account for 39% of all cancers registered in women in the United Kingdom. The total incidence of these three cancers in the study population is 63% higher in current users of HT than in never-users. Thus, when ovarian, endometrial, and breast cancer are taken together, use of HT results in a material increase in the incidence of these common cancers.”

Dr. Steve Narod, of the Women's College Research Institute, Toronto, agreed. “[The risk] might be thought of as small, but enormous numbers of women have been exposed,” he wrote in an accompanying commentary” (Lancet 2007 [Epub doi:10.1016/S0140-6736(07)60535-2]).

Study Controversial From the Start

There's no doubt that the Million Women Study has been directly responsible for the dramatic decrease in British and European hormone therapy prescriptions, experts say. But they also point out that criticism has dogged this enormous epidemiologic study every step of the way. Since 2003, critics have charged that a flawed methodology makes MWs' conclusions almost impossible to accept.

Critical response began with the first MWS publication in 2003. The Lancet published several letters questioning its methodology in the same issue that carried the breast cancer study (Lancet 2003;362:1330–1).

British epidemiologist Richard Farmer is one of several researchers who have repeatedly challenged the investigation's methodology. “Both [the breast cancer and endometrial cancer] studies have the same serious design flaws and there are important aspects of the published reports that are inconsistent,” wrote Dr. Farmer, emeritus professor of epidemiology at the University of Surrey (England) (Climacteric 2005;8:210–3).

Dr. Farmer and his colleague, Dr. M. Whitehead reported in 2004 that the study's design flaws “render the results largely uninterpretable because built-in biases have affected risk estimates” (Endoc. 2004;24:187–93).

Nevertheless, the Million Women Study carried the same national and international impact as did the U.S. Women's Health Initiative. Immediately after the first MWS publication, Britain's drug regulatory agency, the Committee on Safety of Medicines, announced that the data confirmed an HT duration-dependent increase in the risk of breast cancer, and advised counseling patients of that risk.

MWS significantly influenced HT prescribing patterns in the United Kingdom and throughout Europe. In the Netherlands, for instance, the publication of WHI was followed by a modest decrease in prescribing of HT. But after publication of the initial MWS results, rates dropped precipitously (Br. J. Clin. Pharm. 2005;60:641–7).

The study's main flaw is that HT use is based entirely based on recall—a notoriously unreliable source of information, said Dr. James Fiorica, director of gynecologic oncology at Sarasota Memorial Hospital, Fla., and a member of the speakers' board at Wyeth Pharmaceuticals, which manufactures the HT drugs Prempro and Premarin.

“MWS was questionnaire based,” he said in an interview. “This gives you no idea of compliance, or how long these women were really on hormones. It's easy to attribute cancer risk to a drug, but very hard to draw these conclusions based on a questionnaire.”

Dr. Wulf Utian, executive director of the North American Menopause Society, said the MWS ovarian cancer data won't change any of the HT prescribing recommendations included in the group's recent position statement. “The Million Women Study data are absolutely riddled with methodological problems; most serious investigators are not certain how to interpret these data,” Dr. Utian said in an interview. “The only conclusion we can draw from this study is that, clearly, we do not have all the answers. HT carries both potential benefit and potential risk, but in most instances, these absolute risks are rare.”

Treatment decisions should be based on a women's individual risk profile, he said. “If a woman of low risk and high need is prescribed HT she has little to fear. On the other hand, a woman of high risk and weak indication for HT would be better off to concentrate on healthy living and other more appropriate remedies for her problem.”

HOT SPRINGS, VA. — Total vaginal hysterectomy may be an appropriate therapy for patients with endometrial cancers whose medical comorbidities put them at increased risk of complications with standard surgery, Dr. Susan Smith said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

She presented a retrospective review of 63 patients who underwent vaginal hysterectomy for proven or presumed endometrial cancer. Their average age was 62 years; 70% were obese, with an average weight of 235 pounds. Most (80%) had at least two comorbidities that put them at increased risk of intra- or postoperative complications, including hypertension (75%), cardiovascular disease (40%), diabetes (40%), or pulmonary disease (27%), as well as obesity. About half of the group had three or more coexisting factors, said Dr. Smith of the University of South Florida, Tampa.

The average operating time was 119 minutes, with an average blood loss of 330 cc. Only two patients (3%) had to be converted to a laparotomy during the surgery.

There were no perioperative deaths, and more than half of the patients (57%) had no postoperative complications. The most common complications were fever (16%), blood transfusion (11%), and prolonged hospital stay (6%). Fewer than 5% of patients had a postoperative infection (cuff cellulitis, pneumonia, or urinary tract infection).

Follow-up ranging from 6 months to 7 years was available for 44% of the patients. None of these had any evidence of disease at their last visit, but five had needed adjuvant therapy.

“More patients did need additional therapy, but their records were not available for review in this study,” Dr. Smith said.

“Careful screening and a frank, informed discussion of this nontraditional approach and its implications” are necessary before proceeding with this treatment track, she said.

A hysterectomy by laparotomy is the preferred method of treating endometrial cancer in women who have a good surgical risk-benefit ratio, Dr. Matthew Burrell, a gynecologic oncologist from Atlanta, noted in discussing the report.

HOT SPRINGS, VA. — Total vaginal hysterectomy may be an appropriate therapy for patients with endometrial cancers whose medical comorbidities put them at increased risk of complications with standard surgery, Dr. Susan Smith said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

She presented a retrospective review of 63 patients who underwent vaginal hysterectomy for proven or presumed endometrial cancer. Their average age was 62 years; 70% were obese, with an average weight of 235 pounds. Most (80%) had at least two comorbidities that put them at increased risk of intra- or postoperative complications, including hypertension (75%), cardiovascular disease (40%), diabetes (40%), or pulmonary disease (27%), as well as obesity. About half of the group had three or more coexisting factors, said Dr. Smith of the University of South Florida, Tampa.

The average operating time was 119 minutes, with an average blood loss of 330 cc. Only two patients (3%) had to be converted to a laparotomy during the surgery.

There were no perioperative deaths, and more than half of the patients (57%) had no postoperative complications. The most common complications were fever (16%), blood transfusion (11%), and prolonged hospital stay (6%). Fewer than 5% of patients had a postoperative infection (cuff cellulitis, pneumonia, or urinary tract infection).

Follow-up ranging from 6 months to 7 years was available for 44% of the patients. None of these had any evidence of disease at their last visit, but five had needed adjuvant therapy.

“More patients did need additional therapy, but their records were not available for review in this study,” Dr. Smith said.

“Careful screening and a frank, informed discussion of this nontraditional approach and its implications” are necessary before proceeding with this treatment track, she said.

A hysterectomy by laparotomy is the preferred method of treating endometrial cancer in women who have a good surgical risk-benefit ratio, Dr. Matthew Burrell, a gynecologic oncologist from Atlanta, noted in discussing the report.

HOT SPRINGS, VA. — Total vaginal hysterectomy may be an appropriate therapy for patients with endometrial cancers whose medical comorbidities put them at increased risk of complications with standard surgery, Dr. Susan Smith said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

She presented a retrospective review of 63 patients who underwent vaginal hysterectomy for proven or presumed endometrial cancer. Their average age was 62 years; 70% were obese, with an average weight of 235 pounds. Most (80%) had at least two comorbidities that put them at increased risk of intra- or postoperative complications, including hypertension (75%), cardiovascular disease (40%), diabetes (40%), or pulmonary disease (27%), as well as obesity. About half of the group had three or more coexisting factors, said Dr. Smith of the University of South Florida, Tampa.

The average operating time was 119 minutes, with an average blood loss of 330 cc. Only two patients (3%) had to be converted to a laparotomy during the surgery.

There were no perioperative deaths, and more than half of the patients (57%) had no postoperative complications. The most common complications were fever (16%), blood transfusion (11%), and prolonged hospital stay (6%). Fewer than 5% of patients had a postoperative infection (cuff cellulitis, pneumonia, or urinary tract infection).

Follow-up ranging from 6 months to 7 years was available for 44% of the patients. None of these had any evidence of disease at their last visit, but five had needed adjuvant therapy.

“More patients did need additional therapy, but their records were not available for review in this study,” Dr. Smith said.

“Careful screening and a frank, informed discussion of this nontraditional approach and its implications” are necessary before proceeding with this treatment track, she said.

A hysterectomy by laparotomy is the preferred method of treating endometrial cancer in women who have a good surgical risk-benefit ratio, Dr. Matthew Burrell, a gynecologic oncologist from Atlanta, noted in discussing the report.

PHILADELPHIA — Infections caused by methicillin-resistant Staphylococcus aureus occur in a bimodal pattern in the first year of life, with peaks in the first 5 months and again shortly before the first birthday. The peaks reflect two separate reservoirs of methicillin-resistant S. aureus (MRSA)—the first possibly from a maternal source and the latter from the community, Dr. Ana Krishnan and Dr. Karen Carpenter said in a poster presentation at a meeting of the Eastern Society for Pediatric Research.

The physicians conducted a 10-year retrospective review of MRSA among children less than age 12 months treated in a large Northern Virginia birthing center. The review identified 85 MRSA-positive cultures, which occurred with increasing frequency as the years progressed. Only two cases were identified in 1997, the first year of the study. Cases remained infrequent, between 1 and 8 per year, until 2004, when they doubled to 15. Infections have continued to rise each year since then, with 25 cases recorded by the end of 2006.

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old, said Dr. Krishnan, a pediatric resident at Inova Fairfax Hospital for Children, Falls Church, Va.

“In the first 30-60 days of life, there are more [hospital-acquired] than community-acquired MRSA infections,” she said in an interview. “This correlates with the greater number of babies in the neonatal intensive care unit. About 50% of the babies who had the infections in the first 60 days were in the [neonatal] ICU.”

The ratio of hospital-acquired (HA) and community-acquired (CA) infections began to change after the patients reached about 2 months of age, she said. “At this point, we found a shift toward more infections being acquired in the community. But this difference disappears toward the end of the first year.” In months 11 and 12, there are about equal numbers of community- and hospital-acquired infections.

She also noted that a second peak of infection occurred just before the first birthday, with the highest incidence (71%) during the fall and winter months. Additionally, most patients in this age group (73%) presented with a concurrent upper respiratory infection. “This apparent association needs further investigation,” Dr. Krishnan said at the meeting, which was cosponsored by Children's Hospital of Philadelphia.

CA-MRSA also was significantly more likely than HA-MRSA to cause pustulosis (28% vs. 13%) and abscesses requiring drainage (33% vs. 10%). Invasive infections were similar between the groups (22% and 26%), but among invasive infections, bacteremia was more common in HA-MRSA (18% vs. 7%) and nonbacteremic invasive infections more common in CA-MRSA (17% vs. 8%).

The two types of MRSA infections display distinct antibiotic susceptibilities, Dr. Krishnan said. Most CA-MRSA infections were susceptible to clindamycin (76%), with none of the tested cultures displaying inducible resistance. Only 37% of HA-MRSA cultures were sensitive to clindamycin, however, and 25% of those tested did display inducible resistance.

The researchers plan additional studies to explore the possible relationship between early-infancy infections and a maternal reservoir of MRSA, Dr. Krishnan said. “We plan a prospective study looking at mother-infant couplets. We want to culture mothers before delivery, identify those with MRSA, and follow the pairs for a year to assess MRSA colonization and disease.”

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old. DR. KRISHNAN

PHILADELPHIA — Infections caused by methicillin-resistant Staphylococcus aureus occur in a bimodal pattern in the first year of life, with peaks in the first 5 months and again shortly before the first birthday. The peaks reflect two separate reservoirs of methicillin-resistant S. aureus (MRSA)—the first possibly from a maternal source and the latter from the community, Dr. Ana Krishnan and Dr. Karen Carpenter said in a poster presentation at a meeting of the Eastern Society for Pediatric Research.

The physicians conducted a 10-year retrospective review of MRSA among children less than age 12 months treated in a large Northern Virginia birthing center. The review identified 85 MRSA-positive cultures, which occurred with increasing frequency as the years progressed. Only two cases were identified in 1997, the first year of the study. Cases remained infrequent, between 1 and 8 per year, until 2004, when they doubled to 15. Infections have continued to rise each year since then, with 25 cases recorded by the end of 2006.

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old, said Dr. Krishnan, a pediatric resident at Inova Fairfax Hospital for Children, Falls Church, Va.

“In the first 30-60 days of life, there are more [hospital-acquired] than community-acquired MRSA infections,” she said in an interview. “This correlates with the greater number of babies in the neonatal intensive care unit. About 50% of the babies who had the infections in the first 60 days were in the [neonatal] ICU.”

The ratio of hospital-acquired (HA) and community-acquired (CA) infections began to change after the patients reached about 2 months of age, she said. “At this point, we found a shift toward more infections being acquired in the community. But this difference disappears toward the end of the first year.” In months 11 and 12, there are about equal numbers of community- and hospital-acquired infections.

She also noted that a second peak of infection occurred just before the first birthday, with the highest incidence (71%) during the fall and winter months. Additionally, most patients in this age group (73%) presented with a concurrent upper respiratory infection. “This apparent association needs further investigation,” Dr. Krishnan said at the meeting, which was cosponsored by Children's Hospital of Philadelphia.

CA-MRSA also was significantly more likely than HA-MRSA to cause pustulosis (28% vs. 13%) and abscesses requiring drainage (33% vs. 10%). Invasive infections were similar between the groups (22% and 26%), but among invasive infections, bacteremia was more common in HA-MRSA (18% vs. 7%) and nonbacteremic invasive infections more common in CA-MRSA (17% vs. 8%).

The two types of MRSA infections display distinct antibiotic susceptibilities, Dr. Krishnan said. Most CA-MRSA infections were susceptible to clindamycin (76%), with none of the tested cultures displaying inducible resistance. Only 37% of HA-MRSA cultures were sensitive to clindamycin, however, and 25% of those tested did display inducible resistance.

The researchers plan additional studies to explore the possible relationship between early-infancy infections and a maternal reservoir of MRSA, Dr. Krishnan said. “We plan a prospective study looking at mother-infant couplets. We want to culture mothers before delivery, identify those with MRSA, and follow the pairs for a year to assess MRSA colonization and disease.”

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old. DR. KRISHNAN

PHILADELPHIA — Infections caused by methicillin-resistant Staphylococcus aureus occur in a bimodal pattern in the first year of life, with peaks in the first 5 months and again shortly before the first birthday. The peaks reflect two separate reservoirs of methicillin-resistant S. aureus (MRSA)—the first possibly from a maternal source and the latter from the community, Dr. Ana Krishnan and Dr. Karen Carpenter said in a poster presentation at a meeting of the Eastern Society for Pediatric Research.

The physicians conducted a 10-year retrospective review of MRSA among children less than age 12 months treated in a large Northern Virginia birthing center. The review identified 85 MRSA-positive cultures, which occurred with increasing frequency as the years progressed. Only two cases were identified in 1997, the first year of the study. Cases remained infrequent, between 1 and 8 per year, until 2004, when they doubled to 15. Infections have continued to rise each year since then, with 25 cases recorded by the end of 2006.

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old, said Dr. Krishnan, a pediatric resident at Inova Fairfax Hospital for Children, Falls Church, Va.

“In the first 30-60 days of life, there are more [hospital-acquired] than community-acquired MRSA infections,” she said in an interview. “This correlates with the greater number of babies in the neonatal intensive care unit. About 50% of the babies who had the infections in the first 60 days were in the [neonatal] ICU.”

The ratio of hospital-acquired (HA) and community-acquired (CA) infections began to change after the patients reached about 2 months of age, she said. “At this point, we found a shift toward more infections being acquired in the community. But this difference disappears toward the end of the first year.” In months 11 and 12, there are about equal numbers of community- and hospital-acquired infections.

She also noted that a second peak of infection occurred just before the first birthday, with the highest incidence (71%) during the fall and winter months. Additionally, most patients in this age group (73%) presented with a concurrent upper respiratory infection. “This apparent association needs further investigation,” Dr. Krishnan said at the meeting, which was cosponsored by Children's Hospital of Philadelphia.

CA-MRSA also was significantly more likely than HA-MRSA to cause pustulosis (28% vs. 13%) and abscesses requiring drainage (33% vs. 10%). Invasive infections were similar between the groups (22% and 26%), but among invasive infections, bacteremia was more common in HA-MRSA (18% vs. 7%) and nonbacteremic invasive infections more common in CA-MRSA (17% vs. 8%).

The two types of MRSA infections display distinct antibiotic susceptibilities, Dr. Krishnan said. Most CA-MRSA infections were susceptible to clindamycin (76%), with none of the tested cultures displaying inducible resistance. Only 37% of HA-MRSA cultures were sensitive to clindamycin, however, and 25% of those tested did display inducible resistance.

The researchers plan additional studies to explore the possible relationship between early-infancy infections and a maternal reservoir of MRSA, Dr. Krishnan said. “We plan a prospective study looking at mother-infant couplets. We want to culture mothers before delivery, identify those with MRSA, and follow the pairs for a year to assess MRSA colonization and disease.”

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old. DR. KRISHNAN

PHILADELPHIA — Infections caused by methicillin-resistant Staphylococcus aureus occurred in a bimodal pattern in the first year of life, with peaks in the first 5 months and again shortly before the first birthday.

The peaks reflect two separate reservoirs of methicillin-resistant S. aureus (MRSA)—the first possibly from a maternal source and the latter from the community, Dr. Ana Krishnan and Dr. Karen Carpenter said in a poster presentation at a meeting of the Eastern Society for Pediatric Research.

The physicians conducted a 10-year retrospective review of MRSA among children under the age of 12 months who were treated in a large Northern Virginia birthing center.

The review identified 85 MRSA-positive cultures, which occurred with increasing frequency as the years progressed. Only two cases were identified in 1997, the first year of the study.

Cases remained infrequent, between 1 and 8 per year, until 2004, when they doubled to 15. Infections have continued to rise each year since then, with 25 cases recorded by the end of 2006.

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old, said Dr. Krishnan, a pediatric resident at Inova Fairfax Hospital for Children, Falls Church, Va.

“In the first 30–60 days of life, there are more [hospital-acquired] than community-acquired MRSA infections,” she said in an interview.

“This correlates with the greater number of babies in the neonatal intensive care unit. About 50% of the babies who had the infections in the first 60 days were in the [neonatal] ICU.”

The ratio of hospital-acquired (HA) and community-acquired (CA) infections began to change after the patients reached about 2 months of age, she said. “At this point, we found a shift toward more infections being acquired in the community. But this difference disappears toward the end of the first year.”

In months 11 and 12, there are about equal numbers of community- and hospital-acquired infections.

She also noted that a second peak of infection occurred just before the first birthday, with the highest incidence (71%) during the fall and winter months. Additionally, most patients in this age group (73%) presented with a concurrent upper respiratory infection.

“This apparent association needs further investigation,” Dr. Krishnan said at the meeting, cosponsored by Children's Hospital of Philadelphia.

CA-MRSA also was significantly more likely than HA-MRSA to cause pustulosis (28% vs. 13%) and abscesses requiring drainage (33% vs. 10%).

Invasive infections were similar between the groups (22% and 26%), but among invasive infections, bacteremia was more common in HA-MRSA (18% vs. 7%) and nonbacteremic invasive infections more common in CA-MRSA (17% vs. 8%).

The two types of MRSA infections display distinct antibiotic susceptibilities, Dr. Krishnan said.

Most CA-MRSA infections were susceptible to clindamycin (76%), with none of the tested cultures displaying inducible resistance.

Only 37% of HA-MRSA cultures were sensitive to clindamycin, however, and 25% of those tested did display inducible resistance.

The researchers plan additional studies to explore the possible relationship between early-infancy infections and a maternal reservoir of MRSA, Dr. Krishnan said.

“We plan a prospective study looking at mother-infant couplets. We want to culture mothers before delivery, identify those with MRSA, and follow the pairs for a year to assess MRSA colonization and disease.”

A second peak of infection occurred just before the first birthday, 71% of cases during the fall and winter. DR. KRISHNAN

PHILADELPHIA — Infections caused by methicillin-resistant Staphylococcus aureus occurred in a bimodal pattern in the first year of life, with peaks in the first 5 months and again shortly before the first birthday.

The peaks reflect two separate reservoirs of methicillin-resistant S. aureus (MRSA)—the first possibly from a maternal source and the latter from the community, Dr. Ana Krishnan and Dr. Karen Carpenter said in a poster presentation at a meeting of the Eastern Society for Pediatric Research.

The physicians conducted a 10-year retrospective review of MRSA among children under the age of 12 months who were treated in a large Northern Virginia birthing center.

The review identified 85 MRSA-positive cultures, which occurred with increasing frequency as the years progressed. Only two cases were identified in 1997, the first year of the study.

Cases remained infrequent, between 1 and 8 per year, until 2004, when they doubled to 15. Infections have continued to rise each year since then, with 25 cases recorded by the end of 2006.

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old, said Dr. Krishnan, a pediatric resident at Inova Fairfax Hospital for Children, Falls Church, Va.

“In the first 30–60 days of life, there are more [hospital-acquired] than community-acquired MRSA infections,” she said in an interview.

“This correlates with the greater number of babies in the neonatal intensive care unit. About 50% of the babies who had the infections in the first 60 days were in the [neonatal] ICU.”

The ratio of hospital-acquired (HA) and community-acquired (CA) infections began to change after the patients reached about 2 months of age, she said. “At this point, we found a shift toward more infections being acquired in the community. But this difference disappears toward the end of the first year.”

In months 11 and 12, there are about equal numbers of community- and hospital-acquired infections.

She also noted that a second peak of infection occurred just before the first birthday, with the highest incidence (71%) during the fall and winter months. Additionally, most patients in this age group (73%) presented with a concurrent upper respiratory infection.

“This apparent association needs further investigation,” Dr. Krishnan said at the meeting, cosponsored by Children's Hospital of Philadelphia.

CA-MRSA also was significantly more likely than HA-MRSA to cause pustulosis (28% vs. 13%) and abscesses requiring drainage (33% vs. 10%).

Invasive infections were similar between the groups (22% and 26%), but among invasive infections, bacteremia was more common in HA-MRSA (18% vs. 7%) and nonbacteremic invasive infections more common in CA-MRSA (17% vs. 8%).

The two types of MRSA infections display distinct antibiotic susceptibilities, Dr. Krishnan said.

Most CA-MRSA infections were susceptible to clindamycin (76%), with none of the tested cultures displaying inducible resistance.

Only 37% of HA-MRSA cultures were sensitive to clindamycin, however, and 25% of those tested did display inducible resistance.

The researchers plan additional studies to explore the possible relationship between early-infancy infections and a maternal reservoir of MRSA, Dr. Krishnan said.

“We plan a prospective study looking at mother-infant couplets. We want to culture mothers before delivery, identify those with MRSA, and follow the pairs for a year to assess MRSA colonization and disease.”

A second peak of infection occurred just before the first birthday, 71% of cases during the fall and winter. DR. KRISHNAN

PHILADELPHIA — Infections caused by methicillin-resistant Staphylococcus aureus occurred in a bimodal pattern in the first year of life, with peaks in the first 5 months and again shortly before the first birthday.

The peaks reflect two separate reservoirs of methicillin-resistant S. aureus (MRSA)—the first possibly from a maternal source and the latter from the community, Dr. Ana Krishnan and Dr. Karen Carpenter said in a poster presentation at a meeting of the Eastern Society for Pediatric Research.

The physicians conducted a 10-year retrospective review of MRSA among children under the age of 12 months who were treated in a large Northern Virginia birthing center.

The review identified 85 MRSA-positive cultures, which occurred with increasing frequency as the years progressed. Only two cases were identified in 1997, the first year of the study.

Cases remained infrequent, between 1 and 8 per year, until 2004, when they doubled to 15. Infections have continued to rise each year since then, with 25 cases recorded by the end of 2006.

Most infections (64%) occurred in infants less than 5 months old, with 25% occurring in children less than 1 month old, said Dr. Krishnan, a pediatric resident at Inova Fairfax Hospital for Children, Falls Church, Va.

“In the first 30–60 days of life, there are more [hospital-acquired] than community-acquired MRSA infections,” she said in an interview.

“This correlates with the greater number of babies in the neonatal intensive care unit. About 50% of the babies who had the infections in the first 60 days were in the [neonatal] ICU.”

The ratio of hospital-acquired (HA) and community-acquired (CA) infections began to change after the patients reached about 2 months of age, she said. “At this point, we found a shift toward more infections being acquired in the community. But this difference disappears toward the end of the first year.”

In months 11 and 12, there are about equal numbers of community- and hospital-acquired infections.

She also noted that a second peak of infection occurred just before the first birthday, with the highest incidence (71%) during the fall and winter months. Additionally, most patients in this age group (73%) presented with a concurrent upper respiratory infection.

“This apparent association needs further investigation,” Dr. Krishnan said at the meeting, cosponsored by Children's Hospital of Philadelphia.

CA-MRSA also was significantly more likely than HA-MRSA to cause pustulosis (28% vs. 13%) and abscesses requiring drainage (33% vs. 10%).

Invasive infections were similar between the groups (22% and 26%), but among invasive infections, bacteremia was more common in HA-MRSA (18% vs. 7%) and nonbacteremic invasive infections more common in CA-MRSA (17% vs. 8%).

The two types of MRSA infections display distinct antibiotic susceptibilities, Dr. Krishnan said.

Most CA-MRSA infections were susceptible to clindamycin (76%), with none of the tested cultures displaying inducible resistance.

Only 37% of HA-MRSA cultures were sensitive to clindamycin, however, and 25% of those tested did display inducible resistance.

The researchers plan additional studies to explore the possible relationship between early-infancy infections and a maternal reservoir of MRSA, Dr. Krishnan said.

“We plan a prospective study looking at mother-infant couplets. We want to culture mothers before delivery, identify those with MRSA, and follow the pairs for a year to assess MRSA colonization and disease.”

A second peak of infection occurred just before the first birthday, 71% of cases during the fall and winter. DR. KRISHNAN

The rates of new acute hepatitis A and B infections in the United States have plummeted to the lowest levels ever recorded, and may herald the eventual elimination of the diseases in this country.

New infections from both viruses declined in 2005 to more than 80% below the previously recorded nadir, according to a new report issued by the Centers for Disease Control and Prevention.

The incidence of hepatitis A for 2005—the latest year for which full data are available—was just 1.5/100,000, and the incidence of hepatitis B was only 1.8/100,000. Both were the lowest rates ever recorded in the United States, the report noted (MMWR 2007;56:[No. SS-3]).

“The trend has been very impressive,” Dr. Emmet B. Keeffe, professor of medicine and chief of hepatology at Stanford (Calif.) University Medical Center, told this news organization. “We are having a significant impact on this disease in the United States, and we could see its eradication.”

Dr. Hua Chen of University of Houston agreed. “I'm very optimistic about it. I really believe these diseases could be eliminated within 10 or 20 years,” said Dr. Chen, an expert on hepatitis vaccine research.

CDC epidemiologist Annemarie Wasley, Sc.D., who prepared the report, expressed a more cautious outlook, but said the numbers illustrate the beneficial impact of a national vaccine strategy aimed at eradicating hepatitis.

“While it's difficult to predict the future, we feel that if we keep applying these recommendations, strengthening them where they are weak, and reaching out to high-risk groups, we can continue this downward trend to an even lower incidence of new infection,” she said in an interview.

The decrease in new infections is related directly to recent expansions in the recommendations for routine hepatitis A vaccination in young children and to ongoing hepatitis B vaccination strategies, Dr. Wasley said. “The significant progress we're seeing in the reduction of new infections is concentrated primarily in younger age groups, and most probably reflects the impact of our universal vaccination strategies.”

Only 4,488 acute symptomatic cases of hepatitis A were reported to the National Notifiable Diseases Surveillance System in 2005, according to the report. The disease incidence peaked in 1995, when more than 31,500 cases (12/100,000) were reported.

Rates have declined steadily since then, reflecting the 1996 recommendation to vaccinate those at increased risk of infection (international travelers, men who have sex with men, drug users, and children living in communities with high rates of disease). A 1999 recommendation to implement routine vaccination for children in 11 states with high infection rates contributed to the effect: New infections dropped from more than 17,000 in 1999 to fewer than 9,000 in 2002.

The 2005 recommendation to include hepatitis A as part of the routine childhood vaccination schedule probably will help to perpetuate the downward trend. That recommendation will “provide the foundation for eventual consideration of elimination of indigenous hepatitis A virus transmission in the U.S.,” the report noted.

Hepatitis A has shown a cyclical pattern in the United States since record keeping began in 1966, the report said. The 2005 rate of new infection is more than 80% lower than any previously recorded low in that cycle.

Hepatitis B also showed a similarly dramatic decline in 2005, with 5,494 acute symptomatic cases. This amounted to an 80% decline since 1991, when more than 24,000 cases were reported.

The decline in this disease is associated with the national four-step program to eliminate transmission of hepatitis B, launched in 1991.

The key elements of that program were universal vaccination of all newborns, routine screening of all pregnant women with prenatal treatment of those infected, routine vaccination of all unvaccinated children and adolescents, and vaccination of all at-risk adults.

In addition to the dramatic declines in hepatitis A and B, the report notes a significant decline in hepatitis C. This finding is probably because of risk-reduction behaviors and the decline in needle sharing among injectable drug users, Dr. Wasley said.

Hepatitis C continued the decline it has shown since its peak in 1985, when almost 27,000 new cases occurred. In 2005, only 671 cases were reported, for an overall national rate of just 0.2/100,000.

But despite the good news, challenges remain. Unfortunately, Dr. Wasley said, rates of hepatitis B among 24- to 44-year-olds remain unacceptably high. Most of the occurrences in this age group are associated with high-risk behaviors, including intravenous drug use, male/male sex, and multiple sexual partners.

“The vaccine has always been recommended for people with these risk factors, but the challenge is getting it to them—and that's one of the things we need to focus on in the future.”

Her recent review of more than 6,000 respondents to the National Health and Nutrition Examination Survey examined factors affecting hepatitis vaccination rates (Curr. Med. Res. Opin. 2006;22:2489–96). Among those with high-risk behaviors, being single, male, and uninsured had significant negative associations with hepatitis vaccination. “The people who need it most are the ones who don't have it,” said Dr. Chen.

Dr. Keeffe agreed. “These are hard populations to penetrate and elicit compliance from. Doctors who work in these environments, such as STD clinics or inner cities with large indigent populations, need to try and increase the delivery of vaccine to these patients.”

But even if new hepatitis infections become a relic of the past, Dr. Wasley said, physicians will be dealing with the existing chronic infections for years and years to come. “We can't forget that there are more than 3 million people in this country who have chronic hepatitis, and that is an enormous health care burden.”

ELSEVIER GLOBAL MEDICAL NEWS

The rates of new acute hepatitis A and B infections in the United States have plummeted to the lowest levels ever recorded, and may herald the eventual elimination of the diseases in this country.

New infections from both viruses declined in 2005 to more than 80% below the previously recorded nadir, according to a new report issued by the Centers for Disease Control and Prevention.

The incidence of hepatitis A for 2005—the latest year for which full data are available—was just 1.5/100,000, and the incidence of hepatitis B was only 1.8/100,000. Both were the lowest rates ever recorded in the United States, the report noted (MMWR 2007;56:[No. SS-3]).

“The trend has been very impressive,” Dr. Emmet B. Keeffe, professor of medicine and chief of hepatology at Stanford (Calif.) University Medical Center, told this news organization. “We are having a significant impact on this disease in the United States, and we could see its eradication.”

Dr. Hua Chen of University of Houston agreed. “I'm very optimistic about it. I really believe these diseases could be eliminated within 10 or 20 years,” said Dr. Chen, an expert on hepatitis vaccine research.

CDC epidemiologist Annemarie Wasley, Sc.D., who prepared the report, expressed a more cautious outlook, but said the numbers illustrate the beneficial impact of a national vaccine strategy aimed at eradicating hepatitis.

“While it's difficult to predict the future, we feel that if we keep applying these recommendations, strengthening them where they are weak, and reaching out to high-risk groups, we can continue this downward trend to an even lower incidence of new infection,” she said in an interview.

The decrease in new infections is related directly to recent expansions in the recommendations for routine hepatitis A vaccination in young children and to ongoing hepatitis B vaccination strategies, Dr. Wasley said. “The significant progress we're seeing in the reduction of new infections is concentrated primarily in younger age groups, and most probably reflects the impact of our universal vaccination strategies.”

Only 4,488 acute symptomatic cases of hepatitis A were reported to the National Notifiable Diseases Surveillance System in 2005, according to the report. The disease incidence peaked in 1995, when more than 31,500 cases (12/100,000) were reported.

Rates have declined steadily since then, reflecting the 1996 recommendation to vaccinate those at increased risk of infection (international travelers, men who have sex with men, drug users, and children living in communities with high rates of disease). A 1999 recommendation to implement routine vaccination for children in 11 states with high infection rates contributed to the effect: New infections dropped from more than 17,000 in 1999 to fewer than 9,000 in 2002.

The 2005 recommendation to include hepatitis A as part of the routine childhood vaccination schedule probably will help to perpetuate the downward trend. That recommendation will “provide the foundation for eventual consideration of elimination of indigenous hepatitis A virus transmission in the U.S.,” the report noted.

Hepatitis A has shown a cyclical pattern in the United States since record keeping began in 1966, the report said. The 2005 rate of new infection is more than 80% lower than any previously recorded low in that cycle.

Hepatitis B also showed a similarly dramatic decline in 2005, with 5,494 acute symptomatic cases. This amounted to an 80% decline since 1991, when more than 24,000 cases were reported.

The decline in this disease is associated with the national four-step program to eliminate transmission of hepatitis B, launched in 1991.

The key elements of that program were universal vaccination of all newborns, routine screening of all pregnant women with prenatal treatment of those infected, routine vaccination of all unvaccinated children and adolescents, and vaccination of all at-risk adults.

In addition to the dramatic declines in hepatitis A and B, the report notes a significant decline in hepatitis C. This finding is probably because of risk-reduction behaviors and the decline in needle sharing among injectable drug users, Dr. Wasley said.

Hepatitis C continued the decline it has shown since its peak in 1985, when almost 27,000 new cases occurred. In 2005, only 671 cases were reported, for an overall national rate of just 0.2/100,000.

But despite the good news, challenges remain. Unfortunately, Dr. Wasley said, rates of hepatitis B among 24- to 44-year-olds remain unacceptably high. Most of the occurrences in this age group are associated with high-risk behaviors, including intravenous drug use, male/male sex, and multiple sexual partners.

“The vaccine has always been recommended for people with these risk factors, but the challenge is getting it to them—and that's one of the things we need to focus on in the future.”

Her recent review of more than 6,000 respondents to the National Health and Nutrition Examination Survey examined factors affecting hepatitis vaccination rates (Curr. Med. Res. Opin. 2006;22:2489–96). Among those with high-risk behaviors, being single, male, and uninsured had significant negative associations with hepatitis vaccination. “The people who need it most are the ones who don't have it,” said Dr. Chen.

Dr. Keeffe agreed. “These are hard populations to penetrate and elicit compliance from. Doctors who work in these environments, such as STD clinics or inner cities with large indigent populations, need to try and increase the delivery of vaccine to these patients.”

But even if new hepatitis infections become a relic of the past, Dr. Wasley said, physicians will be dealing with the existing chronic infections for years and years to come. “We can't forget that there are more than 3 million people in this country who have chronic hepatitis, and that is an enormous health care burden.”

ELSEVIER GLOBAL MEDICAL NEWS

The rates of new acute hepatitis A and B infections in the United States have plummeted to the lowest levels ever recorded, and may herald the eventual elimination of the diseases in this country.

New infections from both viruses declined in 2005 to more than 80% below the previously recorded nadir, according to a new report issued by the Centers for Disease Control and Prevention.

The incidence of hepatitis A for 2005—the latest year for which full data are available—was just 1.5/100,000, and the incidence of hepatitis B was only 1.8/100,000. Both were the lowest rates ever recorded in the United States, the report noted (MMWR 2007;56:[No. SS-3]).

“The trend has been very impressive,” Dr. Emmet B. Keeffe, professor of medicine and chief of hepatology at Stanford (Calif.) University Medical Center, told this news organization. “We are having a significant impact on this disease in the United States, and we could see its eradication.”

Dr. Hua Chen of University of Houston agreed. “I'm very optimistic about it. I really believe these diseases could be eliminated within 10 or 20 years,” said Dr. Chen, an expert on hepatitis vaccine research.

CDC epidemiologist Annemarie Wasley, Sc.D., who prepared the report, expressed a more cautious outlook, but said the numbers illustrate the beneficial impact of a national vaccine strategy aimed at eradicating hepatitis.

“While it's difficult to predict the future, we feel that if we keep applying these recommendations, strengthening them where they are weak, and reaching out to high-risk groups, we can continue this downward trend to an even lower incidence of new infection,” she said in an interview.

The decrease in new infections is related directly to recent expansions in the recommendations for routine hepatitis A vaccination in young children and to ongoing hepatitis B vaccination strategies, Dr. Wasley said. “The significant progress we're seeing in the reduction of new infections is concentrated primarily in younger age groups, and most probably reflects the impact of our universal vaccination strategies.”

Only 4,488 acute symptomatic cases of hepatitis A were reported to the National Notifiable Diseases Surveillance System in 2005, according to the report. The disease incidence peaked in 1995, when more than 31,500 cases (12/100,000) were reported.

Rates have declined steadily since then, reflecting the 1996 recommendation to vaccinate those at increased risk of infection (international travelers, men who have sex with men, drug users, and children living in communities with high rates of disease). A 1999 recommendation to implement routine vaccination for children in 11 states with high infection rates contributed to the effect: New infections dropped from more than 17,000 in 1999 to fewer than 9,000 in 2002.

The 2005 recommendation to include hepatitis A as part of the routine childhood vaccination schedule probably will help to perpetuate the downward trend. That recommendation will “provide the foundation for eventual consideration of elimination of indigenous hepatitis A virus transmission in the U.S.,” the report noted.

Hepatitis A has shown a cyclical pattern in the United States since record keeping began in 1966, the report said. The 2005 rate of new infection is more than 80% lower than any previously recorded low in that cycle.

Hepatitis B also showed a similarly dramatic decline in 2005, with 5,494 acute symptomatic cases. This amounted to an 80% decline since 1991, when more than 24,000 cases were reported.

The decline in this disease is associated with the national four-step program to eliminate transmission of hepatitis B, launched in 1991.

The key elements of that program were universal vaccination of all newborns, routine screening of all pregnant women with prenatal treatment of those infected, routine vaccination of all unvaccinated children and adolescents, and vaccination of all at-risk adults.

In addition to the dramatic declines in hepatitis A and B, the report notes a significant decline in hepatitis C. This finding is probably because of risk-reduction behaviors and the decline in needle sharing among injectable drug users, Dr. Wasley said.

Hepatitis C continued the decline it has shown since its peak in 1985, when almost 27,000 new cases occurred. In 2005, only 671 cases were reported, for an overall national rate of just 0.2/100,000.

But despite the good news, challenges remain. Unfortunately, Dr. Wasley said, rates of hepatitis B among 24- to 44-year-olds remain unacceptably high. Most of the occurrences in this age group are associated with high-risk behaviors, including intravenous drug use, male/male sex, and multiple sexual partners.

“The vaccine has always been recommended for people with these risk factors, but the challenge is getting it to them—and that's one of the things we need to focus on in the future.”

Her recent review of more than 6,000 respondents to the National Health and Nutrition Examination Survey examined factors affecting hepatitis vaccination rates (Curr. Med. Res. Opin. 2006;22:2489–96). Among those with high-risk behaviors, being single, male, and uninsured had significant negative associations with hepatitis vaccination. “The people who need it most are the ones who don't have it,” said Dr. Chen.

Dr. Keeffe agreed. “These are hard populations to penetrate and elicit compliance from. Doctors who work in these environments, such as STD clinics or inner cities with large indigent populations, need to try and increase the delivery of vaccine to these patients.”

But even if new hepatitis infections become a relic of the past, Dr. Wasley said, physicians will be dealing with the existing chronic infections for years and years to come. “We can't forget that there are more than 3 million people in this country who have chronic hepatitis, and that is an enormous health care burden.”

ELSEVIER GLOBAL MEDICAL NEWS

ORLANDO — Laparoscopic Nissen fundoplication is a feasible option for some patients with medically refractory gastroesophageal reflux disease, Dr. Ignazio M. Civello said at a meeting on laparoscopy and minimally invasive surgery sponsored by the Society of Laparoendoscopic Surgeons.

“We used to do this procedure much more often than we do now,” said Dr. Civello, director of surgery at the Università Cattolica del Sacro Cuore Policlinico Gemelli, Rome. “But it still may be an option for patients who experience symptoms despite adequate medical therapy or for those who don't wish to embark on long-term medication.”

He presented a 5-year case series of 150 patients (mean age 55 years) who underwent the surgery. All of them had gastroesophageal reflux symptoms, including heartburn (95 patients), dysphagia (62), epigastric pain (65), and chest pain (35).

Preoperatively, all of the patients underwent barium x-ray, endoscopy, esophageal motility testing, and 24-hour pH monitoring, Dr. Civello said.

Of the 150 patients, 147 had severe acid reflux on pH monitoring. Endoscopic evidence of esophagitis was seen in 68, and 55 also had hiatal hernia with defective lower esophageal sphincter.

The entire group underwent laparoscopic Nissen fundoplication with no division of the short gastric vessels, and a concomitant crural repair.

The mean operative time was 90 minutes. There were two conversions: one because of splenic injuries that were not repairable by laparoscopy, and one caused by a large gastric fundus perforation during the flap construction maneuver.

The average hospital stay was 3 days. There was no postoperative morbidity or mortality. Follow-up of 6–18 months was available for 135 patients.

The outcomes were assessed by using a structured questionnaire and repeat 24-hour pH monitoring.

All of the patients had resolution of their acid reflux. Functional results were excellent in 85%, good in 10%, fair in 3%, and poor in 2%.

Persistent dysphagia occurred in 15 patients, and 20 had gas and bloating—a transient postoperative phenomenon that usually resolves within 12 months of surgery, Dr. Civello said.

ORLANDO — Laparoscopic Nissen fundoplication is a feasible option for some patients with medically refractory gastroesophageal reflux disease, Dr. Ignazio M. Civello said at a meeting on laparoscopy and minimally invasive surgery sponsored by the Society of Laparoendoscopic Surgeons.

“We used to do this procedure much more often than we do now,” said Dr. Civello, director of surgery at the Università Cattolica del Sacro Cuore Policlinico Gemelli, Rome. “But it still may be an option for patients who experience symptoms despite adequate medical therapy or for those who don't wish to embark on long-term medication.”

He presented a 5-year case series of 150 patients (mean age 55 years) who underwent the surgery. All of them had gastroesophageal reflux symptoms, including heartburn (95 patients), dysphagia (62), epigastric pain (65), and chest pain (35).

Preoperatively, all of the patients underwent barium x-ray, endoscopy, esophageal motility testing, and 24-hour pH monitoring, Dr. Civello said.

Of the 150 patients, 147 had severe acid reflux on pH monitoring. Endoscopic evidence of esophagitis was seen in 68, and 55 also had hiatal hernia with defective lower esophageal sphincter.

The entire group underwent laparoscopic Nissen fundoplication with no division of the short gastric vessels, and a concomitant crural repair.

The mean operative time was 90 minutes. There were two conversions: one because of splenic injuries that were not repairable by laparoscopy, and one caused by a large gastric fundus perforation during the flap construction maneuver.

The average hospital stay was 3 days. There was no postoperative morbidity or mortality. Follow-up of 6–18 months was available for 135 patients.

The outcomes were assessed by using a structured questionnaire and repeat 24-hour pH monitoring.

All of the patients had resolution of their acid reflux. Functional results were excellent in 85%, good in 10%, fair in 3%, and poor in 2%.

Persistent dysphagia occurred in 15 patients, and 20 had gas and bloating—a transient postoperative phenomenon that usually resolves within 12 months of surgery, Dr. Civello said.

ORLANDO — Laparoscopic Nissen fundoplication is a feasible option for some patients with medically refractory gastroesophageal reflux disease, Dr. Ignazio M. Civello said at a meeting on laparoscopy and minimally invasive surgery sponsored by the Society of Laparoendoscopic Surgeons.

“We used to do this procedure much more often than we do now,” said Dr. Civello, director of surgery at the Università Cattolica del Sacro Cuore Policlinico Gemelli, Rome. “But it still may be an option for patients who experience symptoms despite adequate medical therapy or for those who don't wish to embark on long-term medication.”

He presented a 5-year case series of 150 patients (mean age 55 years) who underwent the surgery. All of them had gastroesophageal reflux symptoms, including heartburn (95 patients), dysphagia (62), epigastric pain (65), and chest pain (35).

Preoperatively, all of the patients underwent barium x-ray, endoscopy, esophageal motility testing, and 24-hour pH monitoring, Dr. Civello said.

Of the 150 patients, 147 had severe acid reflux on pH monitoring. Endoscopic evidence of esophagitis was seen in 68, and 55 also had hiatal hernia with defective lower esophageal sphincter.

The entire group underwent laparoscopic Nissen fundoplication with no division of the short gastric vessels, and a concomitant crural repair.

The mean operative time was 90 minutes. There were two conversions: one because of splenic injuries that were not repairable by laparoscopy, and one caused by a large gastric fundus perforation during the flap construction maneuver.

The average hospital stay was 3 days. There was no postoperative morbidity or mortality. Follow-up of 6–18 months was available for 135 patients.

The outcomes were assessed by using a structured questionnaire and repeat 24-hour pH monitoring.

All of the patients had resolution of their acid reflux. Functional results were excellent in 85%, good in 10%, fair in 3%, and poor in 2%.

Persistent dysphagia occurred in 15 patients, and 20 had gas and bloating—a transient postoperative phenomenon that usually resolves within 12 months of surgery, Dr. Civello said.

ORLANDO — Light may soon take a place in the diagnostic and surgical armamentarium for breast cancer.

Researchers at the Technical University of Munich, Germany, have developed and are currently evaluating the world's first autofluorescence ductoscope, which has the potential to diagnose the earliest forms of intraductal breast cancer and guide surgical treatment, Dr. Volker Jacobs said at a meeting on laparoscopy and minimally invasive surgery.

The prototype chosen for study uses a 300-watt xenon lamp that emits white light; a foot switch adds a blue filter to change it to a fluorescent excitation light. Under this spectrum, healthy tissue shines brightly, reflecting 100% of the light, while dysplastic tissue reflects a reduced amount, or even none, and fades into blackness, said Dr. Jacobs, a research and clinical consultant in obstetrics and gynecology at the university.

This picture isn't optimal for diagnostic evaluation, however, he said in an interview. “We needed a more sophisticated way of viewing the information. So a complex data processing was performed to invert the picture [healthy areas diminish and suspicious areas are highlighted], and then we overlay it with an image from the red-violet spectrum to improve detection of potential lesions.” In this final image, suspicious areas and potential intraductal lesions appear blue-violet.

The journal Clinical Breast Cancer has accepted Dr. Jacobs' technical feasibility study for publication. The paper describes five patients examined intraoperatively with this technique. All had either histologically confirmed ductal carcinoma in situ or papilloma that had been discovered with other imaging methods or fine-needle biopsies.

Diagnostic and autofluorescence ductoscopy were performed before segment or duct excision or lumpectomy. The additional time required for the ductoscopy was minimal, ranging from 5 to 15 minutes, and there were no associated complications. Since the procedure uses only light, there was no need for intravenous administration of any contrast agent.

The paper notes that areas of suspicion reflected distinctly different light values than did normal tissue. “The degree of blue-violet color appears to be proportional to the degree of alteration in this tissue, just as it is in bronchoscopy,” Dr. Jacobs said at the meeting, sponsored by the Society of Laparoendoscopic Surgeons. “The more light we see, the more dysplastic the tissue should be.”

This observation, if confirmed in prospective trials, could open the door to an impressive array of applications for autofluorescent ductoscopy, he said. “It could lead us to be able to intraoperatively differentiate between benign and nonbenign lesions, and maybe even to have semiquantitative visual differentiation that would allow us to make some instant conclusions about the lesion. This could really improve the diagnostic value of the procedure and might even allow earlier therapeutic intervention.”

Similarly, he said, these color gradations could someday benefit women at high risk of breast cancer. “We might be able to develop this into an early screening procedure for these patients,” Dr. Jacobs said. “This is hypothetical at this stage, but we are convinced it can be done.”

Since the initial feasibility study included only five patients, there weren't enough data to characterize ductal lesions according to imaging color. But Dr. Jacobs hopes to publish a larger case series within a year; this study will include more data on color gradations, and compare the autofluorescent imaging to standard imaging techniques.

The most immediate application of autofluorescent ductal imaging would probably be surgical, he said. “If we could take a biopsy under autofluorescent visualization, we might be able to use the color as a guide to getting clear margins. This might cut down on the number of R1 resections, and also reduce the need for consecutive operations to ensure clear tumor margins.”

In fact, Dr. Jacobs said, autofluorescent diagnostic ductoscopy would combine very well with interventional ductoscopy. The color gradations would guide the surgeon to the suspicious area, which could be treated endoscopically.

This type of interventional ductoscopy is under investigation in Europe. Miniature instruments only 0.8–0.4 mm in diameter are used in the procedures, passing through an additional working channel of the ductoscope.

Instruments include cytology brushes, microforceps, and a titanium basket for grabbing and removing intraductal papillomas. “All of these devices are either already in clinical use or are being investigated in Europe,” Dr. Jacobs said. “But interventional ductoscopy is still an experimental procedure. We do not yet know, for example, if the removal of a papilloma by this means is as effective as the removal by traditional surgery. This needs further evaluation in trials.”

The instrument combines an autofluorescence light source and camera already approved in Europe for diagnostic bronchoscopy with a 1.3-mm diameter ductoscope. Like autofluorescence bronchoscopy, it operates on the principle that healthy and dysplastic tissues reflect different percentages of light, Dr. Jacobs said.

Light-induced fluorescence bronchoscopy has been used for several years to identify early lung lesions: A helium cadmium blue laser stimulates the lining of the bronchi to autofluoresce in a range of colors. Normal, healthy tissue is shown as being bright green, and suspicious tissue looks reddish-brown.

A summary of studies with this technique concluded that it can increase the detection rate of premalignant lesions by up to six times, compared with conventional, white-light bronchoscopy (Lung Cancer 2004;45[suppl. 2]:S29–37). “We wondered if we could use a similar technique to identify early breast lesions,” Dr. Jacobs said.

In 2003, he and Dr. Stefan Paepke began investigating the scientific and clinical potential of autofluorescence ductoscopy. “Transferring this technology from large-lumen bronchoscopy to small-lumen endoscopy seemed technically feasible. We were soon able to get our first prototypes developed and start a clinical evaluation,” he said.

Neither investigator claims a financial interest in either the procedure or the unit.

Although many of autofluorescence ductoscopy's benefits are still theoretical, some are immediate and proven, Dr. Jacobs said. The procedure can be done on an outpatient basis. It's relatively inexpensive (about 10 times cheaper than an open biopsy in Germany), minimally invasive, and eliminates the need for sedation or contrast agents—all important considerations for a procedure with the potential to enter into widespread use.

“Its long-term clinical impact is still unproven at the present time,” he said. “It's a target on the horizon. But we are convinced it's a target we can reach.”

Dr. Volker Jacobs displays images obtained with his prototype autofluorescence ductoscope. Courtesy Dr. Volker R. Jacobs

ORLANDO — Light may soon take a place in the diagnostic and surgical armamentarium for breast cancer.

Researchers at the Technical University of Munich, Germany, have developed and are currently evaluating the world's first autofluorescence ductoscope, which has the potential to diagnose the earliest forms of intraductal breast cancer and guide surgical treatment, Dr. Volker Jacobs said at a meeting on laparoscopy and minimally invasive surgery.

The prototype chosen for study uses a 300-watt xenon lamp that emits white light; a foot switch adds a blue filter to change it to a fluorescent excitation light. Under this spectrum, healthy tissue shines brightly, reflecting 100% of the light, while dysplastic tissue reflects a reduced amount, or even none, and fades into blackness, said Dr. Jacobs, a research and clinical consultant in obstetrics and gynecology at the university.

This picture isn't optimal for diagnostic evaluation, however, he said in an interview. “We needed a more sophisticated way of viewing the information. So a complex data processing was performed to invert the picture [healthy areas diminish and suspicious areas are highlighted], and then we overlay it with an image from the red-violet spectrum to improve detection of potential lesions.” In this final image, suspicious areas and potential intraductal lesions appear blue-violet.

The journal Clinical Breast Cancer has accepted Dr. Jacobs' technical feasibility study for publication. The paper describes five patients examined intraoperatively with this technique. All had either histologically confirmed ductal carcinoma in situ or papilloma that had been discovered with other imaging methods or fine-needle biopsies.

Diagnostic and autofluorescence ductoscopy were performed before segment or duct excision or lumpectomy. The additional time required for the ductoscopy was minimal, ranging from 5 to 15 minutes, and there were no associated complications. Since the procedure uses only light, there was no need for intravenous administration of any contrast agent.

The paper notes that areas of suspicion reflected distinctly different light values than did normal tissue. “The degree of blue-violet color appears to be proportional to the degree of alteration in this tissue, just as it is in bronchoscopy,” Dr. Jacobs said at the meeting, sponsored by the Society of Laparoendoscopic Surgeons. “The more light we see, the more dysplastic the tissue should be.”

This observation, if confirmed in prospective trials, could open the door to an impressive array of applications for autofluorescent ductoscopy, he said. “It could lead us to be able to intraoperatively differentiate between benign and nonbenign lesions, and maybe even to have semiquantitative visual differentiation that would allow us to make some instant conclusions about the lesion. This could really improve the diagnostic value of the procedure and might even allow earlier therapeutic intervention.”

Similarly, he said, these color gradations could someday benefit women at high risk of breast cancer. “We might be able to develop this into an early screening procedure for these patients,” Dr. Jacobs said. “This is hypothetical at this stage, but we are convinced it can be done.”

Since the initial feasibility study included only five patients, there weren't enough data to characterize ductal lesions according to imaging color. But Dr. Jacobs hopes to publish a larger case series within a year; this study will include more data on color gradations, and compare the autofluorescent imaging to standard imaging techniques.

The most immediate application of autofluorescent ductal imaging would probably be surgical, he said. “If we could take a biopsy under autofluorescent visualization, we might be able to use the color as a guide to getting clear margins. This might cut down on the number of R1 resections, and also reduce the need for consecutive operations to ensure clear tumor margins.”

In fact, Dr. Jacobs said, autofluorescent diagnostic ductoscopy would combine very well with interventional ductoscopy. The color gradations would guide the surgeon to the suspicious area, which could be treated endoscopically.

This type of interventional ductoscopy is under investigation in Europe. Miniature instruments only 0.8–0.4 mm in diameter are used in the procedures, passing through an additional working channel of the ductoscope.

Instruments include cytology brushes, microforceps, and a titanium basket for grabbing and removing intraductal papillomas. “All of these devices are either already in clinical use or are being investigated in Europe,” Dr. Jacobs said. “But interventional ductoscopy is still an experimental procedure. We do not yet know, for example, if the removal of a papilloma by this means is as effective as the removal by traditional surgery. This needs further evaluation in trials.”

The instrument combines an autofluorescence light source and camera already approved in Europe for diagnostic bronchoscopy with a 1.3-mm diameter ductoscope. Like autofluorescence bronchoscopy, it operates on the principle that healthy and dysplastic tissues reflect different percentages of light, Dr. Jacobs said.

Light-induced fluorescence bronchoscopy has been used for several years to identify early lung lesions: A helium cadmium blue laser stimulates the lining of the bronchi to autofluoresce in a range of colors. Normal, healthy tissue is shown as being bright green, and suspicious tissue looks reddish-brown.

A summary of studies with this technique concluded that it can increase the detection rate of premalignant lesions by up to six times, compared with conventional, white-light bronchoscopy (Lung Cancer 2004;45[suppl. 2]:S29–37). “We wondered if we could use a similar technique to identify early breast lesions,” Dr. Jacobs said.

In 2003, he and Dr. Stefan Paepke began investigating the scientific and clinical potential of autofluorescence ductoscopy. “Transferring this technology from large-lumen bronchoscopy to small-lumen endoscopy seemed technically feasible. We were soon able to get our first prototypes developed and start a clinical evaluation,” he said.

Neither investigator claims a financial interest in either the procedure or the unit.

Although many of autofluorescence ductoscopy's benefits are still theoretical, some are immediate and proven, Dr. Jacobs said. The procedure can be done on an outpatient basis. It's relatively inexpensive (about 10 times cheaper than an open biopsy in Germany), minimally invasive, and eliminates the need for sedation or contrast agents—all important considerations for a procedure with the potential to enter into widespread use.

“Its long-term clinical impact is still unproven at the present time,” he said. “It's a target on the horizon. But we are convinced it's a target we can reach.”

Dr. Volker Jacobs displays images obtained with his prototype autofluorescence ductoscope. Courtesy Dr. Volker R. Jacobs

ORLANDO — Light may soon take a place in the diagnostic and surgical armamentarium for breast cancer.

Researchers at the Technical University of Munich, Germany, have developed and are currently evaluating the world's first autofluorescence ductoscope, which has the potential to diagnose the earliest forms of intraductal breast cancer and guide surgical treatment, Dr. Volker Jacobs said at a meeting on laparoscopy and minimally invasive surgery.

The prototype chosen for study uses a 300-watt xenon lamp that emits white light; a foot switch adds a blue filter to change it to a fluorescent excitation light. Under this spectrum, healthy tissue shines brightly, reflecting 100% of the light, while dysplastic tissue reflects a reduced amount, or even none, and fades into blackness, said Dr. Jacobs, a research and clinical consultant in obstetrics and gynecology at the university.

This picture isn't optimal for diagnostic evaluation, however, he said in an interview. “We needed a more sophisticated way of viewing the information. So a complex data processing was performed to invert the picture [healthy areas diminish and suspicious areas are highlighted], and then we overlay it with an image from the red-violet spectrum to improve detection of potential lesions.” In this final image, suspicious areas and potential intraductal lesions appear blue-violet.

The journal Clinical Breast Cancer has accepted Dr. Jacobs' technical feasibility study for publication. The paper describes five patients examined intraoperatively with this technique. All had either histologically confirmed ductal carcinoma in situ or papilloma that had been discovered with other imaging methods or fine-needle biopsies.

Diagnostic and autofluorescence ductoscopy were performed before segment or duct excision or lumpectomy. The additional time required for the ductoscopy was minimal, ranging from 5 to 15 minutes, and there were no associated complications. Since the procedure uses only light, there was no need for intravenous administration of any contrast agent.

The paper notes that areas of suspicion reflected distinctly different light values than did normal tissue. “The degree of blue-violet color appears to be proportional to the degree of alteration in this tissue, just as it is in bronchoscopy,” Dr. Jacobs said at the meeting, sponsored by the Society of Laparoendoscopic Surgeons. “The more light we see, the more dysplastic the tissue should be.”

This observation, if confirmed in prospective trials, could open the door to an impressive array of applications for autofluorescent ductoscopy, he said. “It could lead us to be able to intraoperatively differentiate between benign and nonbenign lesions, and maybe even to have semiquantitative visual differentiation that would allow us to make some instant conclusions about the lesion. This could really improve the diagnostic value of the procedure and might even allow earlier therapeutic intervention.”

Similarly, he said, these color gradations could someday benefit women at high risk of breast cancer. “We might be able to develop this into an early screening procedure for these patients,” Dr. Jacobs said. “This is hypothetical at this stage, but we are convinced it can be done.”

Since the initial feasibility study included only five patients, there weren't enough data to characterize ductal lesions according to imaging color. But Dr. Jacobs hopes to publish a larger case series within a year; this study will include more data on color gradations, and compare the autofluorescent imaging to standard imaging techniques.

The most immediate application of autofluorescent ductal imaging would probably be surgical, he said. “If we could take a biopsy under autofluorescent visualization, we might be able to use the color as a guide to getting clear margins. This might cut down on the number of R1 resections, and also reduce the need for consecutive operations to ensure clear tumor margins.”

In fact, Dr. Jacobs said, autofluorescent diagnostic ductoscopy would combine very well with interventional ductoscopy. The color gradations would guide the surgeon to the suspicious area, which could be treated endoscopically.

This type of interventional ductoscopy is under investigation in Europe. Miniature instruments only 0.8–0.4 mm in diameter are used in the procedures, passing through an additional working channel of the ductoscope.

Instruments include cytology brushes, microforceps, and a titanium basket for grabbing and removing intraductal papillomas. “All of these devices are either already in clinical use or are being investigated in Europe,” Dr. Jacobs said. “But interventional ductoscopy is still an experimental procedure. We do not yet know, for example, if the removal of a papilloma by this means is as effective as the removal by traditional surgery. This needs further evaluation in trials.”

The instrument combines an autofluorescence light source and camera already approved in Europe for diagnostic bronchoscopy with a 1.3-mm diameter ductoscope. Like autofluorescence bronchoscopy, it operates on the principle that healthy and dysplastic tissues reflect different percentages of light, Dr. Jacobs said.

Light-induced fluorescence bronchoscopy has been used for several years to identify early lung lesions: A helium cadmium blue laser stimulates the lining of the bronchi to autofluoresce in a range of colors. Normal, healthy tissue is shown as being bright green, and suspicious tissue looks reddish-brown.

A summary of studies with this technique concluded that it can increase the detection rate of premalignant lesions by up to six times, compared with conventional, white-light bronchoscopy (Lung Cancer 2004;45[suppl. 2]:S29–37). “We wondered if we could use a similar technique to identify early breast lesions,” Dr. Jacobs said.

In 2003, he and Dr. Stefan Paepke began investigating the scientific and clinical potential of autofluorescence ductoscopy. “Transferring this technology from large-lumen bronchoscopy to small-lumen endoscopy seemed technically feasible. We were soon able to get our first prototypes developed and start a clinical evaluation,” he said.

Neither investigator claims a financial interest in either the procedure or the unit.

Although many of autofluorescence ductoscopy's benefits are still theoretical, some are immediate and proven, Dr. Jacobs said. The procedure can be done on an outpatient basis. It's relatively inexpensive (about 10 times cheaper than an open biopsy in Germany), minimally invasive, and eliminates the need for sedation or contrast agents—all important considerations for a procedure with the potential to enter into widespread use.

“Its long-term clinical impact is still unproven at the present time,” he said. “It's a target on the horizon. But we are convinced it's a target we can reach.”

Dr. Volker Jacobs displays images obtained with his prototype autofluorescence ductoscope. Courtesy Dr. Volker R. Jacobs

PHILADELPHIA — Universal prenatal screening of maternal blood lead levels significantly increases the identification rate of women with abnormal levels, allowing earlier identification of infants born at risk, Dr. Tatyana Gabinsky said at the annual meeting of the Eastern Society for Pediatric Research.

Dr. Gabinsky of Elmhurst (N.Y.) Hospital Center, presented a 4-year retrospective study (2002–2006) of more than 20,000 women who received blood lead screenings during their first prenatal visits.

Before 2002, her institution followed the Centers for Disease Control and Prevention recommendation for screening only women identified by questionnaire as being at increased risk for elevated lead levels. Beginning in 2004, the hospital began screening all women as part of routine care.

In all, 20,263 women were screened. The blood lead level was at least 5 mcg/dL in 6% and 7–10 mcg/dL in 5%.

About 1% of the women had extremely high levels (median 17 mcg/dL; range 11–56 mcg/dL).

With the selective screen, the identification rate of women with levels in the 5- to 10-mcg/dL range was 2.2%, and only 0.28% in those with a level greater than 10 mcg/dL.

With universal screening, those identification rates increased to 7% in women in the 5- to 10-mcg/dL range and 1.6% in women with a level greater than 10 mcg/dL.

Universal screening also allowed staff to increase their identification rate of infants born with elevated blood lead levels (2%–11%), Dr. Gabinsky said.

Most (91%) of the women with elevated blood lead levels were foreign born, she added. The most common nationalities were Mexican (35%), Bangladeshi (21%), and Pakistani (16%).

She is conducting a follow-up study of infants born to mothers with a blood lead level greater than 10 mcg/dL. Infants with a newborn level greater than 10 mcg/dL are retested on a monthly basis, while those with a newborn level of 5- to 10-mcg/dL are tested every 2–3 months. Most of them are able to clear the lead by 1 year of age, she said.

“By the time they are 12 months old, the majority are almost normal. Even in babies with a level as high as 42 mcg/dL, by 12 months they are only at 5 mcg/dL,” said Dr. Gabinsky.

PHILADELPHIA — Universal prenatal screening of maternal blood lead levels significantly increases the identification rate of women with abnormal levels, allowing earlier identification of infants born at risk, Dr. Tatyana Gabinsky said at the annual meeting of the Eastern Society for Pediatric Research.

Dr. Gabinsky of Elmhurst (N.Y.) Hospital Center, presented a 4-year retrospective study (2002–2006) of more than 20,000 women who received blood lead screenings during their first prenatal visits.

Before 2002, her institution followed the Centers for Disease Control and Prevention recommendation for screening only women identified by questionnaire as being at increased risk for elevated lead levels. Beginning in 2004, the hospital began screening all women as part of routine care.

In all, 20,263 women were screened. The blood lead level was at least 5 mcg/dL in 6% and 7–10 mcg/dL in 5%.

About 1% of the women had extremely high levels (median 17 mcg/dL; range 11–56 mcg/dL).

With the selective screen, the identification rate of women with levels in the 5- to 10-mcg/dL range was 2.2%, and only 0.28% in those with a level greater than 10 mcg/dL.

With universal screening, those identification rates increased to 7% in women in the 5- to 10-mcg/dL range and 1.6% in women with a level greater than 10 mcg/dL.

Universal screening also allowed staff to increase their identification rate of infants born with elevated blood lead levels (2%–11%), Dr. Gabinsky said.

Most (91%) of the women with elevated blood lead levels were foreign born, she added. The most common nationalities were Mexican (35%), Bangladeshi (21%), and Pakistani (16%).

She is conducting a follow-up study of infants born to mothers with a blood lead level greater than 10 mcg/dL. Infants with a newborn level greater than 10 mcg/dL are retested on a monthly basis, while those with a newborn level of 5- to 10-mcg/dL are tested every 2–3 months. Most of them are able to clear the lead by 1 year of age, she said.

“By the time they are 12 months old, the majority are almost normal. Even in babies with a level as high as 42 mcg/dL, by 12 months they are only at 5 mcg/dL,” said Dr. Gabinsky.

PHILADELPHIA — Universal prenatal screening of maternal blood lead levels significantly increases the identification rate of women with abnormal levels, allowing earlier identification of infants born at risk, Dr. Tatyana Gabinsky said at the annual meeting of the Eastern Society for Pediatric Research.

Dr. Gabinsky of Elmhurst (N.Y.) Hospital Center, presented a 4-year retrospective study (2002–2006) of more than 20,000 women who received blood lead screenings during their first prenatal visits.

Before 2002, her institution followed the Centers for Disease Control and Prevention recommendation for screening only women identified by questionnaire as being at increased risk for elevated lead levels. Beginning in 2004, the hospital began screening all women as part of routine care.

In all, 20,263 women were screened. The blood lead level was at least 5 mcg/dL in 6% and 7–10 mcg/dL in 5%.

About 1% of the women had extremely high levels (median 17 mcg/dL; range 11–56 mcg/dL).

With the selective screen, the identification rate of women with levels in the 5- to 10-mcg/dL range was 2.2%, and only 0.28% in those with a level greater than 10 mcg/dL.

With universal screening, those identification rates increased to 7% in women in the 5- to 10-mcg/dL range and 1.6% in women with a level greater than 10 mcg/dL.

Universal screening also allowed staff to increase their identification rate of infants born with elevated blood lead levels (2%–11%), Dr. Gabinsky said.

Most (91%) of the women with elevated blood lead levels were foreign born, she added. The most common nationalities were Mexican (35%), Bangladeshi (21%), and Pakistani (16%).

She is conducting a follow-up study of infants born to mothers with a blood lead level greater than 10 mcg/dL. Infants with a newborn level greater than 10 mcg/dL are retested on a monthly basis, while those with a newborn level of 5- to 10-mcg/dL are tested every 2–3 months. Most of them are able to clear the lead by 1 year of age, she said.

“By the time they are 12 months old, the majority are almost normal. Even in babies with a level as high as 42 mcg/dL, by 12 months they are only at 5 mcg/dL,” said Dr. Gabinsky.

The continued decrease in new cases of colorectal cancer represents only a tantalizing peek at what could be achieved if more people took advantage of colon cancer screening, experts say.

National surveys conclude that about half of U.S. citizens eligible for screening undergo the test each year. But despite the steady declines in new colon cancer diagnoses and mortality, a 50% screening rate just isn't good enough, said Dr. Bernard Levin, vice president for cancer prevention and population science at the M.D. Anderson Cancer Center, Houston.

“Although it's high, it's not at the optimal level,” Dr. Levin said in an interview. “What is outstandingly obvious is that we could do so much more.”

According to the American Cancer Society's latest report on cancer trends in the United States, about 112,000 new cases of colorectal cancer will be diagnosed in 2007. That's a 2% decrease from the 2004 report, and a continuation of the decrease that's been in evidence since 1985.

But colorectal cancer is still a killer, ranking third in both prevalence and mortality in men as well as women, according to the report. A concentrated push to increase screening to 80%–-the rate now seen with mammography—could cut by half the 52,000 colorectal cancer deaths expected this year, Dr. Levin said.

Dr. Sidney Winawer, a gastroenterologist at Memorial Sloan Kettering Cancer Center, New York, agreed. “We don't have anything in colorectal cancer like the educational outreach that we see for breast cancer screening. They get their message out consistently, repeatedly, and to many different groups. That's what we need to do—not just talk about screening once a year in March [National Colorectal Cancer Awareness Month.]”

The problem of education is one that must be “attacked on multiple fronts,” said Dr. Winawer, who is also the director of the World Health Organization's Collaborating Center for the Prevention of Colorectal Cancer. “Patient education is only one part of our task. We also need to educate providers— gastroenterologists, primary care physicians, nurses, and health maintenance organizations.”

“We have to emphasize that the risks are equal for men and women; right now, women still don't look upon it as a disease of women. It is an equal-opportunity killer.”

People with a family history of polyps or colorectal cancer are at significantly increased risk of developing the disease; they need to understand that screening is even more important for them, and should begin at a younger age.

“And we simply have to address the fear component of this,” Dr. Winawer said. “People shouldn't be afraid to be screened. The tests are much more comfortable than they were, sedation is much better, we are more experienced, and the instruments are much better.” In addition, he said, most patients don't need to be afraid of what the scope might see, since most colonoscopy findings are easily removed polyps or very early, highly curable cancers.

Because screening picks up these early lesions, it has also contributed to the significant decrease in colorectal cancer mortality noted in the ACS report—about 5,000 fewer deaths are expected this year than were expected according to the 2004 report.

Advances in treatment also play a very strong role, said Dr. Alfred Neugut, head of cancer prevention and control at Herbert Irving Comprehensive Cancer Center, New York. “Colorectal cancer has seen some huge advances in treatment in the last few years, some of the most dramatic treatment changes seen in any cancer. We went from having just one active drug, 5-fluorouracil, to having six or seven.”

Advances in adjuvant therapy for regionally advanced colon cancer have also had a significant impact on mortality. “There has also been an improvement, although less dramatic, in treating metastatic colon cancer,” Dr. Neugut said.

Lifestyle changes have probably also played a part, said Dr. Neugut. “People are more health conscious with regard to diet and exercising.”

Hormone therapy in postmenopausal women might also be exerting a small protective effect, Dr. Levin added. “Women who take hormone therapy have [a] lower incidence of colon cancer, so we may be seeing some of that. And there may be some small effect of the very widespread use of nonsteroidal anti-inflammatories, which are known to reduce both colon polyps and cancer.”

Still, the experts agreed, screening is the area that deserves the most emphasis. “I think we are in an exciting time with regard to developing options for screening,” Dr. Winawer said. “Soon we're going to see better stool screening methods, including a DNA mutation test and an immunochemical test, both of which may be much more accurate than fecal occult blood.”

In the longer term, he said, nurses and technicians will be able to use self-propelling colonoscopes; an endoscopist will only get involved if the imaging reveals polyps that need attention. And computed tomographic colonography, also known as virtual colonoscopy, will make imaging studies much more acceptable to a wider pool of patients.

Computed tomographic colonography employs standard CT scanning to created 3-D images similar to those seen through a colonoscope. The colon is inflated with air during the study, which takes only 10–20 minutes and requires no sedation.

“Both the DNA test and virtual colonoscopy will become options for screening, and perhaps very soon,” Dr. Winawer said. “They are both being used on an ad hoc basis at a number of institutions and may get into the screening guidelines at some point.”

There are also demographic disparities to address, Dr. Levin said. “African Americans have a higher incidence and a higher mortality from colorectal cancer. It may be a mix of biology—the cancers themselves may be different—and access to medical care. There is evidence that screening rates are not as good in underserved populations, and that adjuvant therapy might not be given as aggressively to minority populations.”

Again, he said, education of patients and physicians is key. While it's unreasonable to expect every primary care physician to spend 5 minutes discussing the importance of screening with every eligible patient, “It's not unreasonable to take 7 seconds and give a simple message: 'Don't die of embarrassment. Get screened.'”

ELSEVIER GLOBAL MEDICAL NEWS

Trends in Other Cancers Get Noticed

The decline in colorectal cancer grabbed the most attention in the American Cancer Society's 2007 report, but the paper also highlighted some interesting trends in other gastrointestinal cancers.

Gastric cancer decreased slightly, continuing its dramatic 60-year decline, said Dr. Alfred Neugut. “Gastric cancer was the No. 1 cancer in the U.S. for years. Now it's almost negligible. The reasons probably are dietary, reflecting refrigeration and the increase in the consumption of fresh foods, rather than smoked and cured foods that contained cancer-causing nitrates and nitrites.”

There is also some speculation that the widespread use of antibiotics in childhood has decreased the prevalence of Helicobacter pylori, leading to decreased rates of gastric cancer in adults.

This cancer is still on the rise worldwide, however, said Dr. Sidney Winawer. “This is especially true in China, and probably is related to the prevalence of H. pylori.” American physicians may see more stomach cancer as immigration increases, he added.

There have been no significant improvements in pancreatic cancer incidence or mortality, the report noted. It is not as common as other cancers (it ranks last in incidence for males and doesn't rank in the top 10 for women), but is a virulent killer, ranking fourth in mortality for both genders. The report predicts 33,000 deaths, equally divided between the genders, for 2007.

“These numbers [show] that we don't know much about pancreatic cancer,” said Dr. Neugut. The small declines that have occurred are probably related to a general decrease in smoking.

But there is reason for hope, Dr. Winawer noted. International studies are looking at the best methods of screening for the disease in familial pancreatic cancer. “The protocols include multiple tumor markers, CT scanning, and endoscopic ultrasound,” Dr. Winawer said. “Once we figure out how to detect it in these families, we may be able to apply those techniques to the general population.”

There have been a very few minor advances in treating the disease, but the expense is enormous and the payoff, minimal, said Dr. Bernard Levin. “We are measuring gains in weeks of survival.”

Overall esophageal cancer rates are steady, but this trend masks changes within the disease, said Dr. Neugut. “Adenocarcinoma continues to increase, but squamous cell carcinomas are decreasing, and they are really compensating for each other in terms of the overall incidence.” Increasing obesity and untreated gastroesophageal reflux disease leading to Barrett's are probably the driving forces behind the rise in esophageal adenocarcinoma. The decrease in squamous cell cancer is probably related to the decline in smoking, he said.

The ACS report estimates more than 19,000 new cases of liver cancer for 2007, the majority of which will occur in men. Liver cancer had been increasing up until about 1999, the report said, but now seems to be stabilizing. The incidence of the disease is directly related to the prevalence of hepatitis C infections, Dr. Neugut said.

The continued decrease in new cases of colorectal cancer represents only a tantalizing peek at what could be achieved if more people took advantage of colon cancer screening, experts say.

National surveys conclude that about half of U.S. citizens eligible for screening undergo the test each year. But despite the steady declines in new colon cancer diagnoses and mortality, a 50% screening rate just isn't good enough, said Dr. Bernard Levin, vice president for cancer prevention and population science at the M.D. Anderson Cancer Center, Houston.

“Although it's high, it's not at the optimal level,” Dr. Levin said in an interview. “What is outstandingly obvious is that we could do so much more.”

According to the American Cancer Society's latest report on cancer trends in the United States, about 112,000 new cases of colorectal cancer will be diagnosed in 2007. That's a 2% decrease from the 2004 report, and a continuation of the decrease that's been in evidence since 1985.

But colorectal cancer is still a killer, ranking third in both prevalence and mortality in men as well as women, according to the report. A concentrated push to increase screening to 80%–-the rate now seen with mammography—could cut by half the 52,000 colorectal cancer deaths expected this year, Dr. Levin said.

Dr. Sidney Winawer, a gastroenterologist at Memorial Sloan Kettering Cancer Center, New York, agreed. “We don't have anything in colorectal cancer like the educational outreach that we see for breast cancer screening. They get their message out consistently, repeatedly, and to many different groups. That's what we need to do—not just talk about screening once a year in March [National Colorectal Cancer Awareness Month.]”

The problem of education is one that must be “attacked on multiple fronts,” said Dr. Winawer, who is also the director of the World Health Organization's Collaborating Center for the Prevention of Colorectal Cancer. “Patient education is only one part of our task. We also need to educate providers— gastroenterologists, primary care physicians, nurses, and health maintenance organizations.”

“We have to emphasize that the risks are equal for men and women; right now, women still don't look upon it as a disease of women. It is an equal-opportunity killer.”

People with a family history of polyps or colorectal cancer are at significantly increased risk of developing the disease; they need to understand that screening is even more important for them, and should begin at a younger age.

“And we simply have to address the fear component of this,” Dr. Winawer said. “People shouldn't be afraid to be screened. The tests are much more comfortable than they were, sedation is much better, we are more experienced, and the instruments are much better.” In addition, he said, most patients don't need to be afraid of what the scope might see, since most colonoscopy findings are easily removed polyps or very early, highly curable cancers.

Because screening picks up these early lesions, it has also contributed to the significant decrease in colorectal cancer mortality noted in the ACS report—about 5,000 fewer deaths are expected this year than were expected according to the 2004 report.

Advances in treatment also play a very strong role, said Dr. Alfred Neugut, head of cancer prevention and control at Herbert Irving Comprehensive Cancer Center, New York. “Colorectal cancer has seen some huge advances in treatment in the last few years, some of the most dramatic treatment changes seen in any cancer. We went from having just one active drug, 5-fluorouracil, to having six or seven.”

Advances in adjuvant therapy for regionally advanced colon cancer have also had a significant impact on mortality. “There has also been an improvement, although less dramatic, in treating metastatic colon cancer,” Dr. Neugut said.

Lifestyle changes have probably also played a part, said Dr. Neugut. “People are more health conscious with regard to diet and exercising.”

Hormone therapy in postmenopausal women might also be exerting a small protective effect, Dr. Levin added. “Women who take hormone therapy have [a] lower incidence of colon cancer, so we may be seeing some of that. And there may be some small effect of the very widespread use of nonsteroidal anti-inflammatories, which are known to reduce both colon polyps and cancer.”

Still, the experts agreed, screening is the area that deserves the most emphasis. “I think we are in an exciting time with regard to developing options for screening,” Dr. Winawer said. “Soon we're going to see better stool screening methods, including a DNA mutation test and an immunochemical test, both of which may be much more accurate than fecal occult blood.”

In the longer term, he said, nurses and technicians will be able to use self-propelling colonoscopes; an endoscopist will only get involved if the imaging reveals polyps that need attention. And computed tomographic colonography, also known as virtual colonoscopy, will make imaging studies much more acceptable to a wider pool of patients.

Computed tomographic colonography employs standard CT scanning to created 3-D images similar to those seen through a colonoscope. The colon is inflated with air during the study, which takes only 10–20 minutes and requires no sedation.

“Both the DNA test and virtual colonoscopy will become options for screening, and perhaps very soon,” Dr. Winawer said. “They are both being used on an ad hoc basis at a number of institutions and may get into the screening guidelines at some point.”

There are also demographic disparities to address, Dr. Levin said. “African Americans have a higher incidence and a higher mortality from colorectal cancer. It may be a mix of biology—the cancers themselves may be different—and access to medical care. There is evidence that screening rates are not as good in underserved populations, and that adjuvant therapy might not be given as aggressively to minority populations.”

Again, he said, education of patients and physicians is key. While it's unreasonable to expect every primary care physician to spend 5 minutes discussing the importance of screening with every eligible patient, “It's not unreasonable to take 7 seconds and give a simple message: 'Don't die of embarrassment. Get screened.'”

ELSEVIER GLOBAL MEDICAL NEWS

Trends in Other Cancers Get Noticed

The decline in colorectal cancer grabbed the most attention in the American Cancer Society's 2007 report, but the paper also highlighted some interesting trends in other gastrointestinal cancers.

Gastric cancer decreased slightly, continuing its dramatic 60-year decline, said Dr. Alfred Neugut. “Gastric cancer was the No. 1 cancer in the U.S. for years. Now it's almost negligible. The reasons probably are dietary, reflecting refrigeration and the increase in the consumption of fresh foods, rather than smoked and cured foods that contained cancer-causing nitrates and nitrites.”

There is also some speculation that the widespread use of antibiotics in childhood has decreased the prevalence of Helicobacter pylori, leading to decreased rates of gastric cancer in adults.

This cancer is still on the rise worldwide, however, said Dr. Sidney Winawer. “This is especially true in China, and probably is related to the prevalence of H. pylori.” American physicians may see more stomach cancer as immigration increases, he added.

There have been no significant improvements in pancreatic cancer incidence or mortality, the report noted. It is not as common as other cancers (it ranks last in incidence for males and doesn't rank in the top 10 for women), but is a virulent killer, ranking fourth in mortality for both genders. The report predicts 33,000 deaths, equally divided between the genders, for 2007.

“These numbers [show] that we don't know much about pancreatic cancer,” said Dr. Neugut. The small declines that have occurred are probably related to a general decrease in smoking.

But there is reason for hope, Dr. Winawer noted. International studies are looking at the best methods of screening for the disease in familial pancreatic cancer. “The protocols include multiple tumor markers, CT scanning, and endoscopic ultrasound,” Dr. Winawer said. “Once we figure out how to detect it in these families, we may be able to apply those techniques to the general population.”

There have been a very few minor advances in treating the disease, but the expense is enormous and the payoff, minimal, said Dr. Bernard Levin. “We are measuring gains in weeks of survival.”

Overall esophageal cancer rates are steady, but this trend masks changes within the disease, said Dr. Neugut. “Adenocarcinoma continues to increase, but squamous cell carcinomas are decreasing, and they are really compensating for each other in terms of the overall incidence.” Increasing obesity and untreated gastroesophageal reflux disease leading to Barrett's are probably the driving forces behind the rise in esophageal adenocarcinoma. The decrease in squamous cell cancer is probably related to the decline in smoking, he said.

The ACS report estimates more than 19,000 new cases of liver cancer for 2007, the majority of which will occur in men. Liver cancer had been increasing up until about 1999, the report said, but now seems to be stabilizing. The incidence of the disease is directly related to the prevalence of hepatitis C infections, Dr. Neugut said.

The continued decrease in new cases of colorectal cancer represents only a tantalizing peek at what could be achieved if more people took advantage of colon cancer screening, experts say.

National surveys conclude that about half of U.S. citizens eligible for screening undergo the test each year. But despite the steady declines in new colon cancer diagnoses and mortality, a 50% screening rate just isn't good enough, said Dr. Bernard Levin, vice president for cancer prevention and population science at the M.D. Anderson Cancer Center, Houston.

“Although it's high, it's not at the optimal level,” Dr. Levin said in an interview. “What is outstandingly obvious is that we could do so much more.”

According to the American Cancer Society's latest report on cancer trends in the United States, about 112,000 new cases of colorectal cancer will be diagnosed in 2007. That's a 2% decrease from the 2004 report, and a continuation of the decrease that's been in evidence since 1985.

But colorectal cancer is still a killer, ranking third in both prevalence and mortality in men as well as women, according to the report. A concentrated push to increase screening to 80%–-the rate now seen with mammography—could cut by half the 52,000 colorectal cancer deaths expected this year, Dr. Levin said.

Dr. Sidney Winawer, a gastroenterologist at Memorial Sloan Kettering Cancer Center, New York, agreed. “We don't have anything in colorectal cancer like the educational outreach that we see for breast cancer screening. They get their message out consistently, repeatedly, and to many different groups. That's what we need to do—not just talk about screening once a year in March [National Colorectal Cancer Awareness Month.]”

The problem of education is one that must be “attacked on multiple fronts,” said Dr. Winawer, who is also the director of the World Health Organization's Collaborating Center for the Prevention of Colorectal Cancer. “Patient education is only one part of our task. We also need to educate providers— gastroenterologists, primary care physicians, nurses, and health maintenance organizations.”

“We have to emphasize that the risks are equal for men and women; right now, women still don't look upon it as a disease of women. It is an equal-opportunity killer.”

People with a family history of polyps or colorectal cancer are at significantly increased risk of developing the disease; they need to understand that screening is even more important for them, and should begin at a younger age.

“And we simply have to address the fear component of this,” Dr. Winawer said. “People shouldn't be afraid to be screened. The tests are much more comfortable than they were, sedation is much better, we are more experienced, and the instruments are much better.” In addition, he said, most patients don't need to be afraid of what the scope might see, since most colonoscopy findings are easily removed polyps or very early, highly curable cancers.

Because screening picks up these early lesions, it has also contributed to the significant decrease in colorectal cancer mortality noted in the ACS report—about 5,000 fewer deaths are expected this year than were expected according to the 2004 report.

Advances in treatment also play a very strong role, said Dr. Alfred Neugut, head of cancer prevention and control at Herbert Irving Comprehensive Cancer Center, New York. “Colorectal cancer has seen some huge advances in treatment in the last few years, some of the most dramatic treatment changes seen in any cancer. We went from having just one active drug, 5-fluorouracil, to having six or seven.”

Advances in adjuvant therapy for regionally advanced colon cancer have also had a significant impact on mortality. “There has also been an improvement, although less dramatic, in treating metastatic colon cancer,” Dr. Neugut said.

Lifestyle changes have probably also played a part, said Dr. Neugut. “People are more health conscious with regard to diet and exercising.”

Hormone therapy in postmenopausal women might also be exerting a small protective effect, Dr. Levin added. “Women who take hormone therapy have [a] lower incidence of colon cancer, so we may be seeing some of that. And there may be some small effect of the very widespread use of nonsteroidal anti-inflammatories, which are known to reduce both colon polyps and cancer.”

Still, the experts agreed, screening is the area that deserves the most emphasis. “I think we are in an exciting time with regard to developing options for screening,” Dr. Winawer said. “Soon we're going to see better stool screening methods, including a DNA mutation test and an immunochemical test, both of which may be much more accurate than fecal occult blood.”

In the longer term, he said, nurses and technicians will be able to use self-propelling colonoscopes; an endoscopist will only get involved if the imaging reveals polyps that need attention. And computed tomographic colonography, also known as virtual colonoscopy, will make imaging studies much more acceptable to a wider pool of patients.

Computed tomographic colonography employs standard CT scanning to created 3-D images similar to those seen through a colonoscope. The colon is inflated with air during the study, which takes only 10–20 minutes and requires no sedation.

“Both the DNA test and virtual colonoscopy will become options for screening, and perhaps very soon,” Dr. Winawer said. “They are both being used on an ad hoc basis at a number of institutions and may get into the screening guidelines at some point.”

There are also demographic disparities to address, Dr. Levin said. “African Americans have a higher incidence and a higher mortality from colorectal cancer. It may be a mix of biology—the cancers themselves may be different—and access to medical care. There is evidence that screening rates are not as good in underserved populations, and that adjuvant therapy might not be given as aggressively to minority populations.”

Again, he said, education of patients and physicians is key. While it's unreasonable to expect every primary care physician to spend 5 minutes discussing the importance of screening with every eligible patient, “It's not unreasonable to take 7 seconds and give a simple message: 'Don't die of embarrassment. Get screened.'”

ELSEVIER GLOBAL MEDICAL NEWS

Trends in Other Cancers Get Noticed

The decline in colorectal cancer grabbed the most attention in the American Cancer Society's 2007 report, but the paper also highlighted some interesting trends in other gastrointestinal cancers.

Gastric cancer decreased slightly, continuing its dramatic 60-year decline, said Dr. Alfred Neugut. “Gastric cancer was the No. 1 cancer in the U.S. for years. Now it's almost negligible. The reasons probably are dietary, reflecting refrigeration and the increase in the consumption of fresh foods, rather than smoked and cured foods that contained cancer-causing nitrates and nitrites.”

There is also some speculation that the widespread use of antibiotics in childhood has decreased the prevalence of Helicobacter pylori, leading to decreased rates of gastric cancer in adults.

This cancer is still on the rise worldwide, however, said Dr. Sidney Winawer. “This is especially true in China, and probably is related to the prevalence of H. pylori.” American physicians may see more stomach cancer as immigration increases, he added.

There have been no significant improvements in pancreatic cancer incidence or mortality, the report noted. It is not as common as other cancers (it ranks last in incidence for males and doesn't rank in the top 10 for women), but is a virulent killer, ranking fourth in mortality for both genders. The report predicts 33,000 deaths, equally divided between the genders, for 2007.

“These numbers [show] that we don't know much about pancreatic cancer,” said Dr. Neugut. The small declines that have occurred are probably related to a general decrease in smoking.

But there is reason for hope, Dr. Winawer noted. International studies are looking at the best methods of screening for the disease in familial pancreatic cancer. “The protocols include multiple tumor markers, CT scanning, and endoscopic ultrasound,” Dr. Winawer said. “Once we figure out how to detect it in these families, we may be able to apply those techniques to the general population.”

There have been a very few minor advances in treating the disease, but the expense is enormous and the payoff, minimal, said Dr. Bernard Levin. “We are measuring gains in weeks of survival.”

Overall esophageal cancer rates are steady, but this trend masks changes within the disease, said Dr. Neugut. “Adenocarcinoma continues to increase, but squamous cell carcinomas are decreasing, and they are really compensating for each other in terms of the overall incidence.” Increasing obesity and untreated gastroesophageal reflux disease leading to Barrett's are probably the driving forces behind the rise in esophageal adenocarcinoma. The decrease in squamous cell cancer is probably related to the decline in smoking, he said.

The ACS report estimates more than 19,000 new cases of liver cancer for 2007, the majority of which will occur in men. Liver cancer had been increasing up until about 1999, the report said, but now seems to be stabilizing. The incidence of the disease is directly related to the prevalence of hepatitis C infections, Dr. Neugut said.

HOT SPRINGS, VA. — Patients with ovarian cancer who have a hypersensitivity reaction to carboplatin can be successfully treated with cisplatin without a lengthy desensitization procedure, Dr. Megan Callahan said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

She presented a review of 24 women with ovarian cancer who received cisplatin after an allergic reaction to carboplatin. It is the largest case series to date.

Carboplatin hypersensitivity is correlated with the number of treatment cycles experienced, said Dr. Callahan of the University of Virginia, Charlottesville. “The cumulative risk increases from 0.92% for less than five cycles to 6.5% for six cycles, and up to 19% for eight cycles,” she said. Her patients' reactions occurred at a median of 10 cycles. None of the reactions was life threatening.

All of the patients were rechallenged with cisplatin in a subsequent treatment cycle. The drug was given at a standard infusion rate over 1.5 hours. None of the patients received desensitization with steroids or antihistamines.

Most (18) were able to tolerate the full number of cisplatin treatment cycles without a hypersensitivity reaction. Only one of the six who reacted to cisplatin did so in the first cycle. The rest were able to tolerate 1–6 cycles before having a reaction. All of the cisplatin reactions were managed conservatively on an outpatient basis.

Dr. Callahan's 24 patients bring the total reported in the literature to 57. Among these patients, only seven had cisplatin reactions, and one died. “This results in an 86% success rate for cisplatin rechallenge.”

She added that she has not been able to identify any predisposing factors that might predict which patients would react to either drug. “We looked at past medical history, reported allergies, and concurrent medications, and we couldn't identify anything.” The severity of the initial carboplatin reaction also did not help predict which patients would later experience a cisplatin reaction.

HOT SPRINGS, VA. — Patients with ovarian cancer who have a hypersensitivity reaction to carboplatin can be successfully treated with cisplatin without a lengthy desensitization procedure, Dr. Megan Callahan said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

She presented a review of 24 women with ovarian cancer who received cisplatin after an allergic reaction to carboplatin. It is the largest case series to date.

Carboplatin hypersensitivity is correlated with the number of treatment cycles experienced, said Dr. Callahan of the University of Virginia, Charlottesville. “The cumulative risk increases from 0.92% for less than five cycles to 6.5% for six cycles, and up to 19% for eight cycles,” she said. Her patients' reactions occurred at a median of 10 cycles. None of the reactions was life threatening.

All of the patients were rechallenged with cisplatin in a subsequent treatment cycle. The drug was given at a standard infusion rate over 1.5 hours. None of the patients received desensitization with steroids or antihistamines.

Most (18) were able to tolerate the full number of cisplatin treatment cycles without a hypersensitivity reaction. Only one of the six who reacted to cisplatin did so in the first cycle. The rest were able to tolerate 1–6 cycles before having a reaction. All of the cisplatin reactions were managed conservatively on an outpatient basis.

Dr. Callahan's 24 patients bring the total reported in the literature to 57. Among these patients, only seven had cisplatin reactions, and one died. “This results in an 86% success rate for cisplatin rechallenge.”

She added that she has not been able to identify any predisposing factors that might predict which patients would react to either drug. “We looked at past medical history, reported allergies, and concurrent medications, and we couldn't identify anything.” The severity of the initial carboplatin reaction also did not help predict which patients would later experience a cisplatin reaction.

HOT SPRINGS, VA. — Patients with ovarian cancer who have a hypersensitivity reaction to carboplatin can be successfully treated with cisplatin without a lengthy desensitization procedure, Dr. Megan Callahan said at the annual meeting of the South Atlantic Association of Obstetricians and Gynecologists.

She presented a review of 24 women with ovarian cancer who received cisplatin after an allergic reaction to carboplatin. It is the largest case series to date.

Carboplatin hypersensitivity is correlated with the number of treatment cycles experienced, said Dr. Callahan of the University of Virginia, Charlottesville. “The cumulative risk increases from 0.92% for less than five cycles to 6.5% for six cycles, and up to 19% for eight cycles,” she said. Her patients' reactions occurred at a median of 10 cycles. None of the reactions was life threatening.

All of the patients were rechallenged with cisplatin in a subsequent treatment cycle. The drug was given at a standard infusion rate over 1.5 hours. None of the patients received desensitization with steroids or antihistamines.

Most (18) were able to tolerate the full number of cisplatin treatment cycles without a hypersensitivity reaction. Only one of the six who reacted to cisplatin did so in the first cycle. The rest were able to tolerate 1–6 cycles before having a reaction. All of the cisplatin reactions were managed conservatively on an outpatient basis.

Dr. Callahan's 24 patients bring the total reported in the literature to 57. Among these patients, only seven had cisplatin reactions, and one died. “This results in an 86% success rate for cisplatin rechallenge.”

She added that she has not been able to identify any predisposing factors that might predict which patients would react to either drug. “We looked at past medical history, reported allergies, and concurrent medications, and we couldn't identify anything.” The severity of the initial carboplatin reaction also did not help predict which patients would later experience a cisplatin reaction.