Betsy Bates

SAN FRANCISCO — Physicians are using patients' genotypes to determine the type of treatment they receive for rectal carcinoma in a Washington University study, with a more aggressive regimen reserved for patients with “bad-risk” genetic profiles.

The strategy appears to have paid off so far, with significantly improved outcomes for a subgroup of patients predicted to do poorly on the basis of polymorphisms of a pivotal gene, reported Dr. Benjamin R. Tan, a medical oncologist at Washington University in St. Louis.

A total of 86 patients had been enrolled in the study, out of an expected total of 108, prior to Dr. Tan's release of preliminary results at a symposium that was sponsored by the American Society of Clinical Oncology.

Patients were stratified by polymorphisms in the thymidine synthase (TYMS) gene, which encodes for an enzyme that serves as a prime target for 5-fluorouracil (5-FU).

The more triple-repeat patterns identified in a certain region of the gene, the more likely a patient is to be resistant to 5-FU and to face a poor prognosis, Dr. Tan explained.

“If you can identify patients that will have a poor response to 5-FU-only chemoradiation, then the addition of another active agent may improve outcomes,” he said.

A prospective study was therefore designed to selectively add the drug irinotecan to a neoadjuvant chemoradiation protocol in patients with a bad-risk TYMS genetic profile, also known as a triple-triple polymorphism.

All patients in the study also received the standard regimen used to treat Washington University patients with T3 and T4 adenocarcinoma of the rectum: 5-FU-based chemotherapy plus radiation, followed by restaging and resection 6–10 weeks following therapy.

Of the 86 patients, 63 were found to have good-risk genetic profiles. Previous research suggested that 60% of the good-risk patients would be expected to respond so well to the regimen that they could be downstaged at surgery.

Downstaging is associated not only with a better prognosis, but also with a better chance at sphincter preservation during surgery, Dr. Tan noted.

The predicted outlook was less optimistic for the remaining 23 patients.

Previous research suggested just 22% of patients with a bad-risk genetic profile could be downstaged at surgery. Not all of the patients underwent surgery following chemoradiation, but of those who did, 30 of 52 patients (58%) with a good-risk genetic profile were downstaged, just as predicted.

Moreover, 12 of 17 (71%) of the bad-risk patients were downstaged at surgery, far more than expected. Eight of the patients showed a complete pathologic response to chemoradiation.

Among the five bad-risk patients who were not downstaged, four had surgical pathology specimens that showed only microscopic disease.

Of 17 bad-risk patients who were treated with irinotecan, 5-FU, and radiation, 16 “had a very good response to this strategy,” Dr. Tan said at the symposium.

In addition to the American Society of Clinical Oncology, the symposium was co-sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Grades 3 and 4 diarrhea were more prevalent among patients in the bad-risk group who were receiving irinotecan in addition to the standard chemoradiation regimen, he added.

One death occurred in both the bad- and good-risk groups.

Dr. Tan and his associates concluded that “genotype-directed therapies” are feasible for rectal cancer, and may offer significant advantages for patients with bad-risk genetic profiles.

SAN FRANCISCO — Physicians are using patients' genotypes to determine the type of treatment they receive for rectal carcinoma in a Washington University study, with a more aggressive regimen reserved for patients with “bad-risk” genetic profiles.

The strategy appears to have paid off so far, with significantly improved outcomes for a subgroup of patients predicted to do poorly on the basis of polymorphisms of a pivotal gene, reported Dr. Benjamin R. Tan, a medical oncologist at Washington University in St. Louis.

A total of 86 patients had been enrolled in the study, out of an expected total of 108, prior to Dr. Tan's release of preliminary results at a symposium that was sponsored by the American Society of Clinical Oncology.

Patients were stratified by polymorphisms in the thymidine synthase (TYMS) gene, which encodes for an enzyme that serves as a prime target for 5-fluorouracil (5-FU).

The more triple-repeat patterns identified in a certain region of the gene, the more likely a patient is to be resistant to 5-FU and to face a poor prognosis, Dr. Tan explained.

“If you can identify patients that will have a poor response to 5-FU-only chemoradiation, then the addition of another active agent may improve outcomes,” he said.

A prospective study was therefore designed to selectively add the drug irinotecan to a neoadjuvant chemoradiation protocol in patients with a bad-risk TYMS genetic profile, also known as a triple-triple polymorphism.

All patients in the study also received the standard regimen used to treat Washington University patients with T3 and T4 adenocarcinoma of the rectum: 5-FU-based chemotherapy plus radiation, followed by restaging and resection 6–10 weeks following therapy.

Of the 86 patients, 63 were found to have good-risk genetic profiles. Previous research suggested that 60% of the good-risk patients would be expected to respond so well to the regimen that they could be downstaged at surgery.

Downstaging is associated not only with a better prognosis, but also with a better chance at sphincter preservation during surgery, Dr. Tan noted.

The predicted outlook was less optimistic for the remaining 23 patients.

Previous research suggested just 22% of patients with a bad-risk genetic profile could be downstaged at surgery. Not all of the patients underwent surgery following chemoradiation, but of those who did, 30 of 52 patients (58%) with a good-risk genetic profile were downstaged, just as predicted.

Moreover, 12 of 17 (71%) of the bad-risk patients were downstaged at surgery, far more than expected. Eight of the patients showed a complete pathologic response to chemoradiation.

Among the five bad-risk patients who were not downstaged, four had surgical pathology specimens that showed only microscopic disease.

Of 17 bad-risk patients who were treated with irinotecan, 5-FU, and radiation, 16 “had a very good response to this strategy,” Dr. Tan said at the symposium.

In addition to the American Society of Clinical Oncology, the symposium was co-sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Grades 3 and 4 diarrhea were more prevalent among patients in the bad-risk group who were receiving irinotecan in addition to the standard chemoradiation regimen, he added.

One death occurred in both the bad- and good-risk groups.

Dr. Tan and his associates concluded that “genotype-directed therapies” are feasible for rectal cancer, and may offer significant advantages for patients with bad-risk genetic profiles.

SAN FRANCISCO — Physicians are using patients' genotypes to determine the type of treatment they receive for rectal carcinoma in a Washington University study, with a more aggressive regimen reserved for patients with “bad-risk” genetic profiles.

The strategy appears to have paid off so far, with significantly improved outcomes for a subgroup of patients predicted to do poorly on the basis of polymorphisms of a pivotal gene, reported Dr. Benjamin R. Tan, a medical oncologist at Washington University in St. Louis.

A total of 86 patients had been enrolled in the study, out of an expected total of 108, prior to Dr. Tan's release of preliminary results at a symposium that was sponsored by the American Society of Clinical Oncology.

Patients were stratified by polymorphisms in the thymidine synthase (TYMS) gene, which encodes for an enzyme that serves as a prime target for 5-fluorouracil (5-FU).

The more triple-repeat patterns identified in a certain region of the gene, the more likely a patient is to be resistant to 5-FU and to face a poor prognosis, Dr. Tan explained.

“If you can identify patients that will have a poor response to 5-FU-only chemoradiation, then the addition of another active agent may improve outcomes,” he said.

A prospective study was therefore designed to selectively add the drug irinotecan to a neoadjuvant chemoradiation protocol in patients with a bad-risk TYMS genetic profile, also known as a triple-triple polymorphism.

All patients in the study also received the standard regimen used to treat Washington University patients with T3 and T4 adenocarcinoma of the rectum: 5-FU-based chemotherapy plus radiation, followed by restaging and resection 6–10 weeks following therapy.

Of the 86 patients, 63 were found to have good-risk genetic profiles. Previous research suggested that 60% of the good-risk patients would be expected to respond so well to the regimen that they could be downstaged at surgery.

Downstaging is associated not only with a better prognosis, but also with a better chance at sphincter preservation during surgery, Dr. Tan noted.

The predicted outlook was less optimistic for the remaining 23 patients.

Previous research suggested just 22% of patients with a bad-risk genetic profile could be downstaged at surgery. Not all of the patients underwent surgery following chemoradiation, but of those who did, 30 of 52 patients (58%) with a good-risk genetic profile were downstaged, just as predicted.

Moreover, 12 of 17 (71%) of the bad-risk patients were downstaged at surgery, far more than expected. Eight of the patients showed a complete pathologic response to chemoradiation.

Among the five bad-risk patients who were not downstaged, four had surgical pathology specimens that showed only microscopic disease.

Of 17 bad-risk patients who were treated with irinotecan, 5-FU, and radiation, 16 “had a very good response to this strategy,” Dr. Tan said at the symposium.

In addition to the American Society of Clinical Oncology, the symposium was co-sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

Grades 3 and 4 diarrhea were more prevalent among patients in the bad-risk group who were receiving irinotecan in addition to the standard chemoradiation regimen, he added.

One death occurred in both the bad- and good-risk groups.

Dr. Tan and his associates concluded that “genotype-directed therapies” are feasible for rectal cancer, and may offer significant advantages for patients with bad-risk genetic profiles.

SAN FRANCISCO — Nearly a quarter of colorectal cancer patients presented to the emergency department in a Canadian study, and those patients tended to be older and sicker than those diagnosed in a physician's office.

Dr. Alex D. Mitchell, of the department of surgery at Dalhousie University in Halifax, Nova Scotia, studied 455 patients undergoing resection for colorectal cancer during a 2-year period. The initial site of presentation was the emergency department (ED) for 108 patients (24%), Dr. Mitchell reported at a symposium sponsored by the American Society of Clinical Oncology. Obstruction was the most common presentation, found in 43% of ED patients, followed by bleeding and/or anemia in 32%, pain in 23%, and other symptoms in 2%.

The mean age of the patients admitted through the ED was 71 years, significantly older than the mean age of 67 in patients admitted nonemergently. No differences were seen between the two groups in patients' socioeconomic status, area of residence, or education.

An intriguing association was found with weight, however. Among 24 patients with a body mass index (BMI) of 40 kg/m

Dr. Mitchell said that in Canada, as in the United States, morbidly obese patients tend to have lower incomes and are less likely to receive colorectal cancer screening and early diagnosis, compared with patients of normal weight. “At present we can only speculate on reasons why obesity is associated with emergency room presentation,” he said in an interview.

“It is highly unlikely that this is a result of differences in tumor biology in obese individuals. It is more likely that this is related to issues with access to care and patient motivation to access care,” he added.

Dr. Mitchell and his associates, including Dr. Geoffrey A. Porter, interim chief of surgery, also considered the possibility that psychological traits that contribute to morbid obesity might play a role in delaying patients from seeking care at the first sign of colorectal cancer symptoms.

Clearly, patients who did present to the emergency department tended to have later-stage disease. Nearly 40% of stage IV patients presented to the ED, compared with just 7% of patients with stage I disease. (See chart.)

Hospital stays were longer among patients admitted through the ED (10 days vs. 8 days), and perioperative mortality rates were greater among ED-admitted patients (7.4% vs. 2.3%).

Previous research has shown that colorectal cancer patients who initially present to the ED have greater 30-day mortality rates and worse 5-year survival rates than do patients diagnosed in a physician's office or clinic.

“The known negative prognostic impact of emergency room presentation, combined with the increased perioperative mortality and length of stay, would suggest a potential benefit to targeted strategies aimed at reducing the use of the emergency room in the diagnosis and treatment of colorectal cancer,” Dr. Mitchell and his colleagues concluded in a poster presentation.

The meeting was also sponsored by the American Gastroenterological Association, the American Association for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Nearly a quarter of colorectal cancer patients presented to the emergency department in a Canadian study, and those patients tended to be older and sicker than those diagnosed in a physician's office.

Dr. Alex D. Mitchell, of the department of surgery at Dalhousie University in Halifax, Nova Scotia, studied 455 patients undergoing resection for colorectal cancer during a 2-year period. The initial site of presentation was the emergency department (ED) for 108 patients (24%), Dr. Mitchell reported at a symposium sponsored by the American Society of Clinical Oncology. Obstruction was the most common presentation, found in 43% of ED patients, followed by bleeding and/or anemia in 32%, pain in 23%, and other symptoms in 2%.

The mean age of the patients admitted through the ED was 71 years, significantly older than the mean age of 67 in patients admitted nonemergently. No differences were seen between the two groups in patients' socioeconomic status, area of residence, or education.

An intriguing association was found with weight, however. Among 24 patients with a body mass index (BMI) of 40 kg/m

Dr. Mitchell said that in Canada, as in the United States, morbidly obese patients tend to have lower incomes and are less likely to receive colorectal cancer screening and early diagnosis, compared with patients of normal weight. “At present we can only speculate on reasons why obesity is associated with emergency room presentation,” he said in an interview.

“It is highly unlikely that this is a result of differences in tumor biology in obese individuals. It is more likely that this is related to issues with access to care and patient motivation to access care,” he added.

Dr. Mitchell and his associates, including Dr. Geoffrey A. Porter, interim chief of surgery, also considered the possibility that psychological traits that contribute to morbid obesity might play a role in delaying patients from seeking care at the first sign of colorectal cancer symptoms.

Clearly, patients who did present to the emergency department tended to have later-stage disease. Nearly 40% of stage IV patients presented to the ED, compared with just 7% of patients with stage I disease. (See chart.)

Hospital stays were longer among patients admitted through the ED (10 days vs. 8 days), and perioperative mortality rates were greater among ED-admitted patients (7.4% vs. 2.3%).

Previous research has shown that colorectal cancer patients who initially present to the ED have greater 30-day mortality rates and worse 5-year survival rates than do patients diagnosed in a physician's office or clinic.

“The known negative prognostic impact of emergency room presentation, combined with the increased perioperative mortality and length of stay, would suggest a potential benefit to targeted strategies aimed at reducing the use of the emergency room in the diagnosis and treatment of colorectal cancer,” Dr. Mitchell and his colleagues concluded in a poster presentation.

The meeting was also sponsored by the American Gastroenterological Association, the American Association for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Nearly a quarter of colorectal cancer patients presented to the emergency department in a Canadian study, and those patients tended to be older and sicker than those diagnosed in a physician's office.

Dr. Alex D. Mitchell, of the department of surgery at Dalhousie University in Halifax, Nova Scotia, studied 455 patients undergoing resection for colorectal cancer during a 2-year period. The initial site of presentation was the emergency department (ED) for 108 patients (24%), Dr. Mitchell reported at a symposium sponsored by the American Society of Clinical Oncology. Obstruction was the most common presentation, found in 43% of ED patients, followed by bleeding and/or anemia in 32%, pain in 23%, and other symptoms in 2%.

The mean age of the patients admitted through the ED was 71 years, significantly older than the mean age of 67 in patients admitted nonemergently. No differences were seen between the two groups in patients' socioeconomic status, area of residence, or education.

An intriguing association was found with weight, however. Among 24 patients with a body mass index (BMI) of 40 kg/m

Dr. Mitchell said that in Canada, as in the United States, morbidly obese patients tend to have lower incomes and are less likely to receive colorectal cancer screening and early diagnosis, compared with patients of normal weight. “At present we can only speculate on reasons why obesity is associated with emergency room presentation,” he said in an interview.

“It is highly unlikely that this is a result of differences in tumor biology in obese individuals. It is more likely that this is related to issues with access to care and patient motivation to access care,” he added.

Dr. Mitchell and his associates, including Dr. Geoffrey A. Porter, interim chief of surgery, also considered the possibility that psychological traits that contribute to morbid obesity might play a role in delaying patients from seeking care at the first sign of colorectal cancer symptoms.

Clearly, patients who did present to the emergency department tended to have later-stage disease. Nearly 40% of stage IV patients presented to the ED, compared with just 7% of patients with stage I disease. (See chart.)

Hospital stays were longer among patients admitted through the ED (10 days vs. 8 days), and perioperative mortality rates were greater among ED-admitted patients (7.4% vs. 2.3%).

Previous research has shown that colorectal cancer patients who initially present to the ED have greater 30-day mortality rates and worse 5-year survival rates than do patients diagnosed in a physician's office or clinic.

“The known negative prognostic impact of emergency room presentation, combined with the increased perioperative mortality and length of stay, would suggest a potential benefit to targeted strategies aimed at reducing the use of the emergency room in the diagnosis and treatment of colorectal cancer,” Dr. Mitchell and his colleagues concluded in a poster presentation.

The meeting was also sponsored by the American Gastroenterological Association, the American Association for Therapeutic Radiology and Oncology, and the Society of Surgical Oncology.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Negative-pressure vacuum therapy appears to speed healing and increase the likelihood of complete closure of nonhealing diabetic foot ulcers, Dr. David G. Armstrong said at the annual meeting of the American Academy of Dermatology.

But negative pressure, like any other therapy for nonhealing wounds, should be “married with good common sense” and the critical steps of debridement and pressure offloading.

“In my opinion, what this device does is make complicated wounds [simpler]. Once you get a nice carpet of granulation tissue, then stop,” advised Dr. Armstrong, professor of surgery and chair of research at Rosalind Franklin University of Medicine and Science in North Chicago, Ill.

In negative-pressure wound therapy, subatmospheric pressure is delivered to the wound through a pump attached to a foam dressing. A canister collects exudate wicked from the wound, Dr. Armstrong explained.

Dr. Armstrong recommends that a stoma paste or hydrocolloid be placed around the periphery of the wound to prevent maceration from exudate that is collected during the process.

Although the exact mechanism of action has not been identified, negative-pressure therapy reduces edema, uniformly draws wound edges together, and may promote both cytokine elaboration and angiogenesis.

The therapy can be performed on an outpatient basis, although the set-up is bulky, Dr. Armstrong noted.

At a cost he likened to a moderately priced hotel stay—$70–$100 a day—the therapy is not cheap, but it could reduce the overall cost of healing diabetic foot ulcers if it keeps patients out of the hospital.

Diabetic foot ulcer treatment averages $28,000, and 75% of those costs are related to the hospital stay.

In a recently published randomized trial, Dr. Armstrong and Dr. Lawrence A. Lavery of Scott and White Memorial Hospital in Temple, Tex., found that large, deep diabetic foot wounds secondary to amputation healed faster and more completely when treated with negative-pressure therapy than with standard wound care (Lancet 2005;366:1704–10).

Wounds closed completely in more than half of the patients (43 of 77) receiving continuous treatment with the vacuum-assisted closure (VAC) system for the 112-day study period. Just 33 of 85 patients receiving standard moist wound care healed completely.

“Rapid granulation tissue formation provided a clinical 'wow!' factor,” in the VAC group, Dr. Armstrong said.

There was a trend toward fewer reamputations in patients who received VAC, although the study was not powered to evaluate that end point.

Even though the study was met with some criticism for allowing clinical judgment to guide therapeutic interventions, Dr. Armstrong said that such a study design is necessary for research to have “real world” relevance.

His study enrolled patients with wounds eight times larger than those in previous trials of negative-pressure therapy.

“It may be that in some trials, the less you need [interventions], the better they work,” Dr. Armstrong said.

The study used the VAC therapy system manufactured by Kinetic Concepts Inc., which sponsored the research.

Dr. Armstrong stressed throughout his talk the need for matching wound therapies to the right patients and wounds.

Not every nonhealing wound needs negative-pressure therapy, for example. Referring to the oft-quoted phrase, “Don't just do something, stand there,” Dr. Armstrong noted that physicians are sometimes reluctant to follow that advice.

“You feel like squirting something, spraying something, applying something to the wound. Much of this really helps people, but some of it won't,” Dr. Armstrong commented.

Well-designed trials with appropriately selected patients will point the way to “keeping a few more limbs on a few more bodies,” he added.

SAN FRANCISCO — Negative-pressure vacuum therapy appears to speed healing and increase the likelihood of complete closure of nonhealing diabetic foot ulcers, Dr. David G. Armstrong said at the annual meeting of the American Academy of Dermatology.

But negative pressure, like any other therapy for nonhealing wounds, should be “married with good common sense” and the critical steps of debridement and pressure offloading.

“In my opinion, what this device does is make complicated wounds [simpler]. Once you get a nice carpet of granulation tissue, then stop,” advised Dr. Armstrong, professor of surgery and chair of research at Rosalind Franklin University of Medicine and Science in North Chicago, Ill.

In negative-pressure wound therapy, subatmospheric pressure is delivered to the wound through a pump attached to a foam dressing. A canister collects exudate wicked from the wound, Dr. Armstrong explained.

Dr. Armstrong recommends that a stoma paste or hydrocolloid be placed around the periphery of the wound to prevent maceration from exudate that is collected during the process.

Although the exact mechanism of action has not been identified, negative-pressure therapy reduces edema, uniformly draws wound edges together, and may promote both cytokine elaboration and angiogenesis.

The therapy can be performed on an outpatient basis, although the set-up is bulky, Dr. Armstrong noted.

At a cost he likened to a moderately priced hotel stay—$70–$100 a day—the therapy is not cheap, but it could reduce the overall cost of healing diabetic foot ulcers if it keeps patients out of the hospital.

Diabetic foot ulcer treatment averages $28,000, and 75% of those costs are related to the hospital stay.

In a recently published randomized trial, Dr. Armstrong and Dr. Lawrence A. Lavery of Scott and White Memorial Hospital in Temple, Tex., found that large, deep diabetic foot wounds secondary to amputation healed faster and more completely when treated with negative-pressure therapy than with standard wound care (Lancet 2005;366:1704–10).

Wounds closed completely in more than half of the patients (43 of 77) receiving continuous treatment with the vacuum-assisted closure (VAC) system for the 112-day study period. Just 33 of 85 patients receiving standard moist wound care healed completely.

“Rapid granulation tissue formation provided a clinical 'wow!' factor,” in the VAC group, Dr. Armstrong said.

There was a trend toward fewer reamputations in patients who received VAC, although the study was not powered to evaluate that end point.

Even though the study was met with some criticism for allowing clinical judgment to guide therapeutic interventions, Dr. Armstrong said that such a study design is necessary for research to have “real world” relevance.

His study enrolled patients with wounds eight times larger than those in previous trials of negative-pressure therapy.

“It may be that in some trials, the less you need [interventions], the better they work,” Dr. Armstrong said.

The study used the VAC therapy system manufactured by Kinetic Concepts Inc., which sponsored the research.

Dr. Armstrong stressed throughout his talk the need for matching wound therapies to the right patients and wounds.

Not every nonhealing wound needs negative-pressure therapy, for example. Referring to the oft-quoted phrase, “Don't just do something, stand there,” Dr. Armstrong noted that physicians are sometimes reluctant to follow that advice.

“You feel like squirting something, spraying something, applying something to the wound. Much of this really helps people, but some of it won't,” Dr. Armstrong commented.

Well-designed trials with appropriately selected patients will point the way to “keeping a few more limbs on a few more bodies,” he added.

SAN FRANCISCO — Negative-pressure vacuum therapy appears to speed healing and increase the likelihood of complete closure of nonhealing diabetic foot ulcers, Dr. David G. Armstrong said at the annual meeting of the American Academy of Dermatology.

But negative pressure, like any other therapy for nonhealing wounds, should be “married with good common sense” and the critical steps of debridement and pressure offloading.

“In my opinion, what this device does is make complicated wounds [simpler]. Once you get a nice carpet of granulation tissue, then stop,” advised Dr. Armstrong, professor of surgery and chair of research at Rosalind Franklin University of Medicine and Science in North Chicago, Ill.

In negative-pressure wound therapy, subatmospheric pressure is delivered to the wound through a pump attached to a foam dressing. A canister collects exudate wicked from the wound, Dr. Armstrong explained.

Dr. Armstrong recommends that a stoma paste or hydrocolloid be placed around the periphery of the wound to prevent maceration from exudate that is collected during the process.

Although the exact mechanism of action has not been identified, negative-pressure therapy reduces edema, uniformly draws wound edges together, and may promote both cytokine elaboration and angiogenesis.

The therapy can be performed on an outpatient basis, although the set-up is bulky, Dr. Armstrong noted.

At a cost he likened to a moderately priced hotel stay—$70–$100 a day—the therapy is not cheap, but it could reduce the overall cost of healing diabetic foot ulcers if it keeps patients out of the hospital.

Diabetic foot ulcer treatment averages $28,000, and 75% of those costs are related to the hospital stay.

In a recently published randomized trial, Dr. Armstrong and Dr. Lawrence A. Lavery of Scott and White Memorial Hospital in Temple, Tex., found that large, deep diabetic foot wounds secondary to amputation healed faster and more completely when treated with negative-pressure therapy than with standard wound care (Lancet 2005;366:1704–10).

Wounds closed completely in more than half of the patients (43 of 77) receiving continuous treatment with the vacuum-assisted closure (VAC) system for the 112-day study period. Just 33 of 85 patients receiving standard moist wound care healed completely.

“Rapid granulation tissue formation provided a clinical 'wow!' factor,” in the VAC group, Dr. Armstrong said.

There was a trend toward fewer reamputations in patients who received VAC, although the study was not powered to evaluate that end point.

Even though the study was met with some criticism for allowing clinical judgment to guide therapeutic interventions, Dr. Armstrong said that such a study design is necessary for research to have “real world” relevance.

His study enrolled patients with wounds eight times larger than those in previous trials of negative-pressure therapy.

“It may be that in some trials, the less you need [interventions], the better they work,” Dr. Armstrong said.

The study used the VAC therapy system manufactured by Kinetic Concepts Inc., which sponsored the research.

Dr. Armstrong stressed throughout his talk the need for matching wound therapies to the right patients and wounds.

Not every nonhealing wound needs negative-pressure therapy, for example. Referring to the oft-quoted phrase, “Don't just do something, stand there,” Dr. Armstrong noted that physicians are sometimes reluctant to follow that advice.

“You feel like squirting something, spraying something, applying something to the wound. Much of this really helps people, but some of it won't,” Dr. Armstrong commented.

Well-designed trials with appropriately selected patients will point the way to “keeping a few more limbs on a few more bodies,” he added.

SAN FRANCISCO — A single, patient-initiated dose of famciclovir cut short recurrent outbreaks of herpes labialis by 2 days, Dr. Marcus Conant said at the annual meeting of the American Academy of Dermatology.

Viral replication of herpes simplex virus type 1 lasts 8 hours. Famciclovir remains in a cell for 10 hours, he explained. Given this “window of opportunity … you ought to be able to treat the patient with high-dose famciclovir if it's initiated early in the course of an outbreak,” he said. “That was the idea behind this study.”

Patients recruited from sites in the United States, Canada, and Australia had healthy immune function and a history of prodromal symptoms and vesicle formation associated with at least half of their previous facial herpes outbreaks. Of the 1,376 subjects, 477 experienced symptoms, initiated therapy within an hour, and developed vesicles.

The time to healing of primary vesicular lesions was 4.4 days in 152 patients randomized to receive 1,500 mg of famciclovir in a single dose, 4 days in 157 patients who took 2 doses of 750 mg each on the first day, and 6.2 days in 168 patients on placebo. The time to healing of all vesicular lesions was 4.5 days and 4.1 days in the single- and split-dose treatment groups and 6.6 days with placebo. Resolution of pain and tenderness was more rapid in patients taking the single-dose of famciclovir than in those taking a split dose, starting with 750 mg at the first prodromic sign and 750 mg later that day.

Adverse events included headache and nausea, but were similar in the active treatment and placebo arms.

The magnitude of benefit was significantly greater than that seen in studies of topical treatments, noted Dr. Spotswood Spruance of the University of Utah in a poster further detailing the findings. Acyclovir cream shortens outbreaks by 0.5–0.6 day; penciclovir cream by 0.7–1 day; and docosanol cream by 18 hours.

Still unclear is how efficient patient-initiated therapy was in aborting outbreaks altogether. There was no significant difference in the proportion of patients in the placebo and active treatment groups in progression to a full outbreak. “The problem is, when you say you're having a prodrome, are you really having an eruption or not? You can't really tell that,” said Dr. Conant, professor of dermatology at the University of California, San Francisco.

The challenge for physicians is to convince patients to keep 1,500 mg of famciclovir with them at all times so they can take it immediately. Women tend to keep the 3-tablet 1,500-mg dose in their purses, but men tend to think it will be fine if they wait until they get home, Dr. Conant said.

“Herpes is like a punch in the nose. If someone is going to hit you and you step aside, you're not going to have a black eye. If you don't move away, you're going to have a black eye for about a week,” he said.

A second Novartis-sponsored study showed that genital herpes lesions could be halted at the papule stage in about one of every four patients taking 1,000 mg of famciclovir in divided doses during the first day they recognized prodromal symptoms.

In that study, led by Dr. Stephen Tyring of the University of Texas Health Science Center in Houston, patient-initiated therapy reduced by 2 days the healing time of lesions in 163 patients receiving active drug, compared with 166 receiving placebo.

More than 30% of subjects in the active treatment arm developed no lesions or only papules after initiating therapy, vs. about 10% of patients in the placebo group.

In this study, patients obtained skin samples for polymerase chain reaction testing and visited the clinic for 3 consecutive days following symptoms and up to 14 days or total healing if lesions developed. The researchers concluded that famciclovir could reduce healing time as well as prevent development and/or progression of lesions in some patients with a history of recurrent genital herpes outbreaks.

The challenge for physicians is to convince patients to keep famciclovir with them so they can take it immediately. DR. CONANT

SAN FRANCISCO — A single, patient-initiated dose of famciclovir cut short recurrent outbreaks of herpes labialis by 2 days, Dr. Marcus Conant said at the annual meeting of the American Academy of Dermatology.

Viral replication of herpes simplex virus type 1 lasts 8 hours. Famciclovir remains in a cell for 10 hours, he explained. Given this “window of opportunity … you ought to be able to treat the patient with high-dose famciclovir if it's initiated early in the course of an outbreak,” he said. “That was the idea behind this study.”

Patients recruited from sites in the United States, Canada, and Australia had healthy immune function and a history of prodromal symptoms and vesicle formation associated with at least half of their previous facial herpes outbreaks. Of the 1,376 subjects, 477 experienced symptoms, initiated therapy within an hour, and developed vesicles.

The time to healing of primary vesicular lesions was 4.4 days in 152 patients randomized to receive 1,500 mg of famciclovir in a single dose, 4 days in 157 patients who took 2 doses of 750 mg each on the first day, and 6.2 days in 168 patients on placebo. The time to healing of all vesicular lesions was 4.5 days and 4.1 days in the single- and split-dose treatment groups and 6.6 days with placebo. Resolution of pain and tenderness was more rapid in patients taking the single-dose of famciclovir than in those taking a split dose, starting with 750 mg at the first prodromic sign and 750 mg later that day.

Adverse events included headache and nausea, but were similar in the active treatment and placebo arms.

The magnitude of benefit was significantly greater than that seen in studies of topical treatments, noted Dr. Spotswood Spruance of the University of Utah in a poster further detailing the findings. Acyclovir cream shortens outbreaks by 0.5–0.6 day; penciclovir cream by 0.7–1 day; and docosanol cream by 18 hours.

Still unclear is how efficient patient-initiated therapy was in aborting outbreaks altogether. There was no significant difference in the proportion of patients in the placebo and active treatment groups in progression to a full outbreak. “The problem is, when you say you're having a prodrome, are you really having an eruption or not? You can't really tell that,” said Dr. Conant, professor of dermatology at the University of California, San Francisco.

The challenge for physicians is to convince patients to keep 1,500 mg of famciclovir with them at all times so they can take it immediately. Women tend to keep the 3-tablet 1,500-mg dose in their purses, but men tend to think it will be fine if they wait until they get home, Dr. Conant said.

“Herpes is like a punch in the nose. If someone is going to hit you and you step aside, you're not going to have a black eye. If you don't move away, you're going to have a black eye for about a week,” he said.

A second Novartis-sponsored study showed that genital herpes lesions could be halted at the papule stage in about one of every four patients taking 1,000 mg of famciclovir in divided doses during the first day they recognized prodromal symptoms.

In that study, led by Dr. Stephen Tyring of the University of Texas Health Science Center in Houston, patient-initiated therapy reduced by 2 days the healing time of lesions in 163 patients receiving active drug, compared with 166 receiving placebo.

More than 30% of subjects in the active treatment arm developed no lesions or only papules after initiating therapy, vs. about 10% of patients in the placebo group.

In this study, patients obtained skin samples for polymerase chain reaction testing and visited the clinic for 3 consecutive days following symptoms and up to 14 days or total healing if lesions developed. The researchers concluded that famciclovir could reduce healing time as well as prevent development and/or progression of lesions in some patients with a history of recurrent genital herpes outbreaks.

The challenge for physicians is to convince patients to keep famciclovir with them so they can take it immediately. DR. CONANT

SAN FRANCISCO — A single, patient-initiated dose of famciclovir cut short recurrent outbreaks of herpes labialis by 2 days, Dr. Marcus Conant said at the annual meeting of the American Academy of Dermatology.

Viral replication of herpes simplex virus type 1 lasts 8 hours. Famciclovir remains in a cell for 10 hours, he explained. Given this “window of opportunity … you ought to be able to treat the patient with high-dose famciclovir if it's initiated early in the course of an outbreak,” he said. “That was the idea behind this study.”

Patients recruited from sites in the United States, Canada, and Australia had healthy immune function and a history of prodromal symptoms and vesicle formation associated with at least half of their previous facial herpes outbreaks. Of the 1,376 subjects, 477 experienced symptoms, initiated therapy within an hour, and developed vesicles.

The time to healing of primary vesicular lesions was 4.4 days in 152 patients randomized to receive 1,500 mg of famciclovir in a single dose, 4 days in 157 patients who took 2 doses of 750 mg each on the first day, and 6.2 days in 168 patients on placebo. The time to healing of all vesicular lesions was 4.5 days and 4.1 days in the single- and split-dose treatment groups and 6.6 days with placebo. Resolution of pain and tenderness was more rapid in patients taking the single-dose of famciclovir than in those taking a split dose, starting with 750 mg at the first prodromic sign and 750 mg later that day.

Adverse events included headache and nausea, but were similar in the active treatment and placebo arms.

The magnitude of benefit was significantly greater than that seen in studies of topical treatments, noted Dr. Spotswood Spruance of the University of Utah in a poster further detailing the findings. Acyclovir cream shortens outbreaks by 0.5–0.6 day; penciclovir cream by 0.7–1 day; and docosanol cream by 18 hours.

Still unclear is how efficient patient-initiated therapy was in aborting outbreaks altogether. There was no significant difference in the proportion of patients in the placebo and active treatment groups in progression to a full outbreak. “The problem is, when you say you're having a prodrome, are you really having an eruption or not? You can't really tell that,” said Dr. Conant, professor of dermatology at the University of California, San Francisco.

The challenge for physicians is to convince patients to keep 1,500 mg of famciclovir with them at all times so they can take it immediately. Women tend to keep the 3-tablet 1,500-mg dose in their purses, but men tend to think it will be fine if they wait until they get home, Dr. Conant said.

“Herpes is like a punch in the nose. If someone is going to hit you and you step aside, you're not going to have a black eye. If you don't move away, you're going to have a black eye for about a week,” he said.

A second Novartis-sponsored study showed that genital herpes lesions could be halted at the papule stage in about one of every four patients taking 1,000 mg of famciclovir in divided doses during the first day they recognized prodromal symptoms.

In that study, led by Dr. Stephen Tyring of the University of Texas Health Science Center in Houston, patient-initiated therapy reduced by 2 days the healing time of lesions in 163 patients receiving active drug, compared with 166 receiving placebo.

More than 30% of subjects in the active treatment arm developed no lesions or only papules after initiating therapy, vs. about 10% of patients in the placebo group.

In this study, patients obtained skin samples for polymerase chain reaction testing and visited the clinic for 3 consecutive days following symptoms and up to 14 days or total healing if lesions developed. The researchers concluded that famciclovir could reduce healing time as well as prevent development and/or progression of lesions in some patients with a history of recurrent genital herpes outbreaks.

The challenge for physicians is to convince patients to keep famciclovir with them so they can take it immediately. DR. CONANT

PASADENA, CALIF. — Adhesion formation probably occurs within the first 3–5 days following surgery, when hypoxia triggers a cascade of cytokines, growth factors, and clotting factors that form a fibrinous, clotlike mass, Dr. Michael P. Diamond said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Unless a high level of tissue plasminogen activator (TPA) in relation to plasminogen activator inhibitor-1 (PAI-1) can break up the mass, conditions become ripe for uniquely equipped fibroblasts to proliferate and amass at the site of injury.

Angiogenesis follows, and resilient adhesive bands of tissue are formed that are exceedingly difficult to permanently eradicate through adhesiolysis.

The scenario, based on years of research into the unique properties of adhesion tissue, explains why adhesions are so likely to recur after they are lysed. It also offers guidance in the quest for antiadhesion barriers or medications, since these evidently require only short-term action to prevent long-term problems, said Dr. Diamond, professor and associate chair of obstetrics and gynecology at Wayne State University in Detroit.

The fibroblasts in adhesion tissue and fibroblasts in normal peritoneal tissue differ in fundamental ways. Those differences are exaggerated in the face of hypoxia, Dr. Diamond said. “Years later, there are still molecular and biological differences in these tissues that predispose [patients with adhesions] to further adhesion formation.”

Adhesions form after about 60%–80% of laparotomies or laparoscopies, with no meaningful differences seen between the two. “They are not something unique to the work we do as obstetrician gynecologists. Name a surgical specialty and they will have a problem with adhesions,” said Dr. Diamond, who also directs the division of reproductive endocrinology and infertility at his university.

Compared with normal tissue, fibroblasts in adhesions have higher basal levels of collagen, fibronectin, transforming growth factor (TGF)-β1, TGF-β2, and PAI-1. Hypoxia—a result of tissue injury during surgery—heightens the disparity in most of these cytokines. Basal TPA levels, critical to breaking up early adhesion formation, are higher in fibroblasts in normal tissue. In adhesion tissue, they plummet to near zero with hypoxia.

Furthermore, fewer cytokines involved in programmed cell death are produced in adhesion tissue. “These cells are in a revved-up position to heal,” said Dr. Diamond.

In the face of further injury, such as adhesiolysis, the cells are preprogrammed to heal again, with even more vigor than when they first evolved in response to hypoxia.

Dr. Diamond said these studies may shed light on why patients with chronic pelvic pain may obtain significant pain relief following adhesiolysis, but often find that their pain returns to near-baseline levels within several months.

Roughly 10%–20% of patients do experience lasting pain relief following adhesiolysis, but no one has been able to distinguish them from other patients, he said.

Still other questions persist about the connection between adhesions and chronic pelvic pain. For example, Dr. Diamond noted that men develop adhesions at the same or higher rates as women after surgery, trauma, hemorrhage, and other hypoxic events. But the literature contains no studies about adhesions causing pelvic pain in men. He noted that the two approved products designed to prevent adhesions—Interceed and Seprafilm—consistently reduce adhesion formation about half the time. “Each of these help, but neither is a panacea,” he said. Importantly, neither device is approved for use in laparoscopic surgery.

Because hypoxia seems inexorably tied to adhesion formation, any surgical tool that causes injury—scalpel, laser, or coagulation device—is as likely as the others to cause adhesions, according to Dr. Diamond.

More promising than new adhesiolysis techniques may be new preventive agents, perhaps barriers infused with medications, liquids, or gels designed to stay in place at the site of injury for the 3–5 critical days after surgery. One intriguing possibility might be the use of cyclooxygenase-2 (COX-2) inhibitors, since COX-2 is expressed only in the context of hypoxia in fibroblast tissue, he said.

PASADENA, CALIF. — Adhesion formation probably occurs within the first 3–5 days following surgery, when hypoxia triggers a cascade of cytokines, growth factors, and clotting factors that form a fibrinous, clotlike mass, Dr. Michael P. Diamond said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Unless a high level of tissue plasminogen activator (TPA) in relation to plasminogen activator inhibitor-1 (PAI-1) can break up the mass, conditions become ripe for uniquely equipped fibroblasts to proliferate and amass at the site of injury.

Angiogenesis follows, and resilient adhesive bands of tissue are formed that are exceedingly difficult to permanently eradicate through adhesiolysis.

The scenario, based on years of research into the unique properties of adhesion tissue, explains why adhesions are so likely to recur after they are lysed. It also offers guidance in the quest for antiadhesion barriers or medications, since these evidently require only short-term action to prevent long-term problems, said Dr. Diamond, professor and associate chair of obstetrics and gynecology at Wayne State University in Detroit.

The fibroblasts in adhesion tissue and fibroblasts in normal peritoneal tissue differ in fundamental ways. Those differences are exaggerated in the face of hypoxia, Dr. Diamond said. “Years later, there are still molecular and biological differences in these tissues that predispose [patients with adhesions] to further adhesion formation.”

Adhesions form after about 60%–80% of laparotomies or laparoscopies, with no meaningful differences seen between the two. “They are not something unique to the work we do as obstetrician gynecologists. Name a surgical specialty and they will have a problem with adhesions,” said Dr. Diamond, who also directs the division of reproductive endocrinology and infertility at his university.

Compared with normal tissue, fibroblasts in adhesions have higher basal levels of collagen, fibronectin, transforming growth factor (TGF)-β1, TGF-β2, and PAI-1. Hypoxia—a result of tissue injury during surgery—heightens the disparity in most of these cytokines. Basal TPA levels, critical to breaking up early adhesion formation, are higher in fibroblasts in normal tissue. In adhesion tissue, they plummet to near zero with hypoxia.

Furthermore, fewer cytokines involved in programmed cell death are produced in adhesion tissue. “These cells are in a revved-up position to heal,” said Dr. Diamond.

In the face of further injury, such as adhesiolysis, the cells are preprogrammed to heal again, with even more vigor than when they first evolved in response to hypoxia.

Dr. Diamond said these studies may shed light on why patients with chronic pelvic pain may obtain significant pain relief following adhesiolysis, but often find that their pain returns to near-baseline levels within several months.

Roughly 10%–20% of patients do experience lasting pain relief following adhesiolysis, but no one has been able to distinguish them from other patients, he said.

Still other questions persist about the connection between adhesions and chronic pelvic pain. For example, Dr. Diamond noted that men develop adhesions at the same or higher rates as women after surgery, trauma, hemorrhage, and other hypoxic events. But the literature contains no studies about adhesions causing pelvic pain in men. He noted that the two approved products designed to prevent adhesions—Interceed and Seprafilm—consistently reduce adhesion formation about half the time. “Each of these help, but neither is a panacea,” he said. Importantly, neither device is approved for use in laparoscopic surgery.

Because hypoxia seems inexorably tied to adhesion formation, any surgical tool that causes injury—scalpel, laser, or coagulation device—is as likely as the others to cause adhesions, according to Dr. Diamond.

More promising than new adhesiolysis techniques may be new preventive agents, perhaps barriers infused with medications, liquids, or gels designed to stay in place at the site of injury for the 3–5 critical days after surgery. One intriguing possibility might be the use of cyclooxygenase-2 (COX-2) inhibitors, since COX-2 is expressed only in the context of hypoxia in fibroblast tissue, he said.

PASADENA, CALIF. — Adhesion formation probably occurs within the first 3–5 days following surgery, when hypoxia triggers a cascade of cytokines, growth factors, and clotting factors that form a fibrinous, clotlike mass, Dr. Michael P. Diamond said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Unless a high level of tissue plasminogen activator (TPA) in relation to plasminogen activator inhibitor-1 (PAI-1) can break up the mass, conditions become ripe for uniquely equipped fibroblasts to proliferate and amass at the site of injury.

Angiogenesis follows, and resilient adhesive bands of tissue are formed that are exceedingly difficult to permanently eradicate through adhesiolysis.

The scenario, based on years of research into the unique properties of adhesion tissue, explains why adhesions are so likely to recur after they are lysed. It also offers guidance in the quest for antiadhesion barriers or medications, since these evidently require only short-term action to prevent long-term problems, said Dr. Diamond, professor and associate chair of obstetrics and gynecology at Wayne State University in Detroit.

The fibroblasts in adhesion tissue and fibroblasts in normal peritoneal tissue differ in fundamental ways. Those differences are exaggerated in the face of hypoxia, Dr. Diamond said. “Years later, there are still molecular and biological differences in these tissues that predispose [patients with adhesions] to further adhesion formation.”

Adhesions form after about 60%–80% of laparotomies or laparoscopies, with no meaningful differences seen between the two. “They are not something unique to the work we do as obstetrician gynecologists. Name a surgical specialty and they will have a problem with adhesions,” said Dr. Diamond, who also directs the division of reproductive endocrinology and infertility at his university.

Compared with normal tissue, fibroblasts in adhesions have higher basal levels of collagen, fibronectin, transforming growth factor (TGF)-β1, TGF-β2, and PAI-1. Hypoxia—a result of tissue injury during surgery—heightens the disparity in most of these cytokines. Basal TPA levels, critical to breaking up early adhesion formation, are higher in fibroblasts in normal tissue. In adhesion tissue, they plummet to near zero with hypoxia.

Furthermore, fewer cytokines involved in programmed cell death are produced in adhesion tissue. “These cells are in a revved-up position to heal,” said Dr. Diamond.

In the face of further injury, such as adhesiolysis, the cells are preprogrammed to heal again, with even more vigor than when they first evolved in response to hypoxia.

Dr. Diamond said these studies may shed light on why patients with chronic pelvic pain may obtain significant pain relief following adhesiolysis, but often find that their pain returns to near-baseline levels within several months.

Roughly 10%–20% of patients do experience lasting pain relief following adhesiolysis, but no one has been able to distinguish them from other patients, he said.

Still other questions persist about the connection between adhesions and chronic pelvic pain. For example, Dr. Diamond noted that men develop adhesions at the same or higher rates as women after surgery, trauma, hemorrhage, and other hypoxic events. But the literature contains no studies about adhesions causing pelvic pain in men. He noted that the two approved products designed to prevent adhesions—Interceed and Seprafilm—consistently reduce adhesion formation about half the time. “Each of these help, but neither is a panacea,” he said. Importantly, neither device is approved for use in laparoscopic surgery.

Because hypoxia seems inexorably tied to adhesion formation, any surgical tool that causes injury—scalpel, laser, or coagulation device—is as likely as the others to cause adhesions, according to Dr. Diamond.

More promising than new adhesiolysis techniques may be new preventive agents, perhaps barriers infused with medications, liquids, or gels designed to stay in place at the site of injury for the 3–5 critical days after surgery. One intriguing possibility might be the use of cyclooxygenase-2 (COX-2) inhibitors, since COX-2 is expressed only in the context of hypoxia in fibroblast tissue, he said.

PASADENA, CALIF. — Imaging for gynecologic cancer has been greatly improved with fusion techniques that combine the structural and anatomic information from ultrasound, MRI, and CT with metabolic clues highlighted by PET scans.

“This is really the wave of the future,” Dr. Robin Farias-Eisner, professor and chief of gynecology at the University of California, Los Angeles, said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Advances in traditional imaging techniques over the past 2 decades have been “great, but not good enough,” in terms of their overall sensitivity, specificity, and accuracy, Dr. Farias-Eisner said.

A major problem has been the difficulty of identifying microscopic disease in lymph nodes using modalities that depict anatomy and structure. Lymph node metastases not only have an impact on survival, they also dictate treatment, particularly in cervical cancer.

It is here, said Dr. Farias-Eisner, that positron emission tomography with

He displayed a magnetic resonance image of a 63-year-old woman with stage IIB uterine cervical carcinoma that appeared to show lymphadenopathy. A transaxial PET scan of the same patient showed abnormally high uptake of the FDG isomer, and a fusion scan of the images superimposed on each other demonstrated high uptake in both internal iliac lymph nodes, as well as in the sigmoid colon.

In case after case, the fused image completed the picture, demonstrating metabolic tumor activity in a precise location.

Another advantage of incorporating FDG-PET into the work-up is that it provides an evaluation of the whole body.

Finally, it can point to disease in patients whose normal anatomic landmarks have been lost to surgery or radiation.

Dr. Farias-Eisner also expressed enthusiasm about lymphoscintigraphy, in which technetium is injected to help localize the sentinel lymph node in cervical, endometrial, and vulvar cancers.

Advances in ultrasonography are also being studied internationally, including the use of a microbubble contrast agent that enhances the intensity of malignant tissue, when compared with benign tissue, Dr. Farias-Eisner said.

PASADENA, CALIF. — Imaging for gynecologic cancer has been greatly improved with fusion techniques that combine the structural and anatomic information from ultrasound, MRI, and CT with metabolic clues highlighted by PET scans.

“This is really the wave of the future,” Dr. Robin Farias-Eisner, professor and chief of gynecology at the University of California, Los Angeles, said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Advances in traditional imaging techniques over the past 2 decades have been “great, but not good enough,” in terms of their overall sensitivity, specificity, and accuracy, Dr. Farias-Eisner said.

A major problem has been the difficulty of identifying microscopic disease in lymph nodes using modalities that depict anatomy and structure. Lymph node metastases not only have an impact on survival, they also dictate treatment, particularly in cervical cancer.

It is here, said Dr. Farias-Eisner, that positron emission tomography with

He displayed a magnetic resonance image of a 63-year-old woman with stage IIB uterine cervical carcinoma that appeared to show lymphadenopathy. A transaxial PET scan of the same patient showed abnormally high uptake of the FDG isomer, and a fusion scan of the images superimposed on each other demonstrated high uptake in both internal iliac lymph nodes, as well as in the sigmoid colon.

In case after case, the fused image completed the picture, demonstrating metabolic tumor activity in a precise location.

Another advantage of incorporating FDG-PET into the work-up is that it provides an evaluation of the whole body.

Finally, it can point to disease in patients whose normal anatomic landmarks have been lost to surgery or radiation.

Dr. Farias-Eisner also expressed enthusiasm about lymphoscintigraphy, in which technetium is injected to help localize the sentinel lymph node in cervical, endometrial, and vulvar cancers.

Advances in ultrasonography are also being studied internationally, including the use of a microbubble contrast agent that enhances the intensity of malignant tissue, when compared with benign tissue, Dr. Farias-Eisner said.

PASADENA, CALIF. — Imaging for gynecologic cancer has been greatly improved with fusion techniques that combine the structural and anatomic information from ultrasound, MRI, and CT with metabolic clues highlighted by PET scans.

“This is really the wave of the future,” Dr. Robin Farias-Eisner, professor and chief of gynecology at the University of California, Los Angeles, said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Advances in traditional imaging techniques over the past 2 decades have been “great, but not good enough,” in terms of their overall sensitivity, specificity, and accuracy, Dr. Farias-Eisner said.

A major problem has been the difficulty of identifying microscopic disease in lymph nodes using modalities that depict anatomy and structure. Lymph node metastases not only have an impact on survival, they also dictate treatment, particularly in cervical cancer.

It is here, said Dr. Farias-Eisner, that positron emission tomography with

He displayed a magnetic resonance image of a 63-year-old woman with stage IIB uterine cervical carcinoma that appeared to show lymphadenopathy. A transaxial PET scan of the same patient showed abnormally high uptake of the FDG isomer, and a fusion scan of the images superimposed on each other demonstrated high uptake in both internal iliac lymph nodes, as well as in the sigmoid colon.

In case after case, the fused image completed the picture, demonstrating metabolic tumor activity in a precise location.

Another advantage of incorporating FDG-PET into the work-up is that it provides an evaluation of the whole body.

Finally, it can point to disease in patients whose normal anatomic landmarks have been lost to surgery or radiation.

Dr. Farias-Eisner also expressed enthusiasm about lymphoscintigraphy, in which technetium is injected to help localize the sentinel lymph node in cervical, endometrial, and vulvar cancers.

Advances in ultrasonography are also being studied internationally, including the use of a microbubble contrast agent that enhances the intensity of malignant tissue, when compared with benign tissue, Dr. Farias-Eisner said.

PASADENA, CALIF. — Get a pregnant woman with cardiac arrest to the operating room.

That is where the best hope lies for her survival and that of her fetus, said Dr. J. Gerald Quirk at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California.

“A cesarean section by you in the emergency room 2 minutes after a patient is brought in by ambulance is no better than a C-section by the side of the road by EMTs [emergency medical technicians],” said Dr. Quirk, professor and chairman of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook.

Potentially reversible causes of cardiac arrest during pregnancy include hemorrhage, trauma, hypoxia, hypothermia, hyper- and hypokalemia, myocardial infarction, metabolic acidosis, and iatrogenic factors such as medication or anesthesia errors. But complex physiologic and metabolic changes of pregnancy can complicate resuscitation.

“Remember, pregnancy is a high flow, low resistance state,” he said.

Cardiac output is high, and 30% of cardiac output perfuses the uterus. Systemic vascular resistance is low. Airway management may be difficult. Left uterine displacement is necessary, as is application of cricoid pressure to avoid aspiration.

There is a need for increased chest wall compression force, “but it can be hard to know what that force is,” said Dr. Quirk. “The patient is a risk for fractured ribs and pneumothorax.”

In applicable cases, the patient may require aggressive restoration of circulatory volume as well.

The most critical issue is time, he stressed. “If you're going to attempt resuscitation, the best rule of thumb is to do it with the uterus intact for 4–5 minutes,” he said.

In the face of declining oxygen saturation—in short, “if things are not going well”—urgent preparations should be made for the operative delivery of the fetus. The OR offers three things: bright lights, the proper instruments, and an anesthesia cart. “In most hospitals, it's a very short sprint from ER to some operating room,” he said.

In the time it takes to get the patient there, an anesthesiologist and several scrub nurses are likely to be available.

If resuscitative efforts result in restoration of sinus rhythm, “you can always decide not to deliver,” said Dr. Quirk.

The imperative to perform a rapid C-section on a mother in cardiac arrest evolved after a pivotal 1982 case in which a 27-year-old primigravida of 37 weeks' gestation failed to respond to advanced cardiopulmonary resuscitation efforts following massive hemoptysis. An effort was made to save the fetus via C-section. Within moments of the delivery, the mother's pulse was detected and both the mother and infant survived without neurologic sequelae.

Several other case reports led to a “strong push” to do emergency C-sections in such patients. However, the setting is important, said Dr. Quirk.

“If one is going to entertain a perimortem C-section in hopes of salvaging both the mother and the fetus, one must first think of salvaging the mother.”

“If you're going to undertake a C-section in the emergency room, the [mother's] going to die,” he stated. “How are you going to staunch the hemorrhage?”

When the mother cannot be saved, there is still hope for the fetus, but only for a brief time.

Survival of a fetus postmortem, although the stuff of Roman lore, Greek myth, and Shakespeare, has never been actually documented until modern times. Dozens of cases have now been described, but survival of a neurologically intact infant appears to depend on a narrow window of opportunity, with a “break point” of about 15 minutes. Studies suggest that after that point, surviving infants without severe neurologic sequelae are very rare.

The OR offers three things: bright lights, the proper instruments, an anesthesia cart. DR. QUIRK

PASADENA, CALIF. — Get a pregnant woman with cardiac arrest to the operating room.

That is where the best hope lies for her survival and that of her fetus, said Dr. J. Gerald Quirk at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California.

“A cesarean section by you in the emergency room 2 minutes after a patient is brought in by ambulance is no better than a C-section by the side of the road by EMTs [emergency medical technicians],” said Dr. Quirk, professor and chairman of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook.

Potentially reversible causes of cardiac arrest during pregnancy include hemorrhage, trauma, hypoxia, hypothermia, hyper- and hypokalemia, myocardial infarction, metabolic acidosis, and iatrogenic factors such as medication or anesthesia errors. But complex physiologic and metabolic changes of pregnancy can complicate resuscitation.

“Remember, pregnancy is a high flow, low resistance state,” he said.

Cardiac output is high, and 30% of cardiac output perfuses the uterus. Systemic vascular resistance is low. Airway management may be difficult. Left uterine displacement is necessary, as is application of cricoid pressure to avoid aspiration.

There is a need for increased chest wall compression force, “but it can be hard to know what that force is,” said Dr. Quirk. “The patient is a risk for fractured ribs and pneumothorax.”

In applicable cases, the patient may require aggressive restoration of circulatory volume as well.

The most critical issue is time, he stressed. “If you're going to attempt resuscitation, the best rule of thumb is to do it with the uterus intact for 4–5 minutes,” he said.

In the face of declining oxygen saturation—in short, “if things are not going well”—urgent preparations should be made for the operative delivery of the fetus. The OR offers three things: bright lights, the proper instruments, and an anesthesia cart. “In most hospitals, it's a very short sprint from ER to some operating room,” he said.

In the time it takes to get the patient there, an anesthesiologist and several scrub nurses are likely to be available.

If resuscitative efforts result in restoration of sinus rhythm, “you can always decide not to deliver,” said Dr. Quirk.

The imperative to perform a rapid C-section on a mother in cardiac arrest evolved after a pivotal 1982 case in which a 27-year-old primigravida of 37 weeks' gestation failed to respond to advanced cardiopulmonary resuscitation efforts following massive hemoptysis. An effort was made to save the fetus via C-section. Within moments of the delivery, the mother's pulse was detected and both the mother and infant survived without neurologic sequelae.

Several other case reports led to a “strong push” to do emergency C-sections in such patients. However, the setting is important, said Dr. Quirk.

“If one is going to entertain a perimortem C-section in hopes of salvaging both the mother and the fetus, one must first think of salvaging the mother.”

“If you're going to undertake a C-section in the emergency room, the [mother's] going to die,” he stated. “How are you going to staunch the hemorrhage?”

When the mother cannot be saved, there is still hope for the fetus, but only for a brief time.

Survival of a fetus postmortem, although the stuff of Roman lore, Greek myth, and Shakespeare, has never been actually documented until modern times. Dozens of cases have now been described, but survival of a neurologically intact infant appears to depend on a narrow window of opportunity, with a “break point” of about 15 minutes. Studies suggest that after that point, surviving infants without severe neurologic sequelae are very rare.

The OR offers three things: bright lights, the proper instruments, an anesthesia cart. DR. QUIRK

PASADENA, CALIF. — Get a pregnant woman with cardiac arrest to the operating room.

That is where the best hope lies for her survival and that of her fetus, said Dr. J. Gerald Quirk at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California.

“A cesarean section by you in the emergency room 2 minutes after a patient is brought in by ambulance is no better than a C-section by the side of the road by EMTs [emergency medical technicians],” said Dr. Quirk, professor and chairman of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook.

Potentially reversible causes of cardiac arrest during pregnancy include hemorrhage, trauma, hypoxia, hypothermia, hyper- and hypokalemia, myocardial infarction, metabolic acidosis, and iatrogenic factors such as medication or anesthesia errors. But complex physiologic and metabolic changes of pregnancy can complicate resuscitation.

“Remember, pregnancy is a high flow, low resistance state,” he said.

Cardiac output is high, and 30% of cardiac output perfuses the uterus. Systemic vascular resistance is low. Airway management may be difficult. Left uterine displacement is necessary, as is application of cricoid pressure to avoid aspiration.

There is a need for increased chest wall compression force, “but it can be hard to know what that force is,” said Dr. Quirk. “The patient is a risk for fractured ribs and pneumothorax.”

In applicable cases, the patient may require aggressive restoration of circulatory volume as well.

The most critical issue is time, he stressed. “If you're going to attempt resuscitation, the best rule of thumb is to do it with the uterus intact for 4–5 minutes,” he said.

In the face of declining oxygen saturation—in short, “if things are not going well”—urgent preparations should be made for the operative delivery of the fetus. The OR offers three things: bright lights, the proper instruments, and an anesthesia cart. “In most hospitals, it's a very short sprint from ER to some operating room,” he said.

In the time it takes to get the patient there, an anesthesiologist and several scrub nurses are likely to be available.

If resuscitative efforts result in restoration of sinus rhythm, “you can always decide not to deliver,” said Dr. Quirk.

The imperative to perform a rapid C-section on a mother in cardiac arrest evolved after a pivotal 1982 case in which a 27-year-old primigravida of 37 weeks' gestation failed to respond to advanced cardiopulmonary resuscitation efforts following massive hemoptysis. An effort was made to save the fetus via C-section. Within moments of the delivery, the mother's pulse was detected and both the mother and infant survived without neurologic sequelae.

Several other case reports led to a “strong push” to do emergency C-sections in such patients. However, the setting is important, said Dr. Quirk.

“If one is going to entertain a perimortem C-section in hopes of salvaging both the mother and the fetus, one must first think of salvaging the mother.”

“If you're going to undertake a C-section in the emergency room, the [mother's] going to die,” he stated. “How are you going to staunch the hemorrhage?”

When the mother cannot be saved, there is still hope for the fetus, but only for a brief time.

Survival of a fetus postmortem, although the stuff of Roman lore, Greek myth, and Shakespeare, has never been actually documented until modern times. Dozens of cases have now been described, but survival of a neurologically intact infant appears to depend on a narrow window of opportunity, with a “break point” of about 15 minutes. Studies suggest that after that point, surviving infants without severe neurologic sequelae are very rare.

The OR offers three things: bright lights, the proper instruments, an anesthesia cart. DR. QUIRK

PASADENA, CALIF. — The Heimlich maneuver becomes unwieldy during the late stages of pregnancy, requiring adaptations, Dr. J. Gerald Quirk said at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California.

Breast enlargement, diaphragm displacement, and the size and weight of a pregnant woman all contribute to difficulty in performing the traditional emergency maneuver to prevent choking during late pregnancy.

First described in 1974 by Dr. Henry Heimlich, a thoracic surgeon, the Heimlich maneuver involves standing behind a choking victim and placing a fist, thumb side in, underneath the diaphragm.

Using the other hand to push against the fist, a series of abrupt upward thrusts can usually dislodge a piece of food from the airway.

Not only is it difficult to hold a woman in this position during late pregnancy, it is also hard to exert the force necessary to perform the maneuver correctly, said Dr. Quirk, professor and chair of obstetrics, gynecology, and reproductive medicine at Stony Brook (N.Y.) University.

“The best thing to do is lay her on the floor and press down on the lower part of the sternum,” he said.

The woman should be tilted slightly to one side to prevent aortocaval compression.

Dr. Quirk said several case reports suggest that this adaptation is effective in late pregnancy.

PASADENA, CALIF. — The Heimlich maneuver becomes unwieldy during the late stages of pregnancy, requiring adaptations, Dr. J. Gerald Quirk said at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California.

Breast enlargement, diaphragm displacement, and the size and weight of a pregnant woman all contribute to difficulty in performing the traditional emergency maneuver to prevent choking during late pregnancy.

First described in 1974 by Dr. Henry Heimlich, a thoracic surgeon, the Heimlich maneuver involves standing behind a choking victim and placing a fist, thumb side in, underneath the diaphragm.

Using the other hand to push against the fist, a series of abrupt upward thrusts can usually dislodge a piece of food from the airway.

Not only is it difficult to hold a woman in this position during late pregnancy, it is also hard to exert the force necessary to perform the maneuver correctly, said Dr. Quirk, professor and chair of obstetrics, gynecology, and reproductive medicine at Stony Brook (N.Y.) University.

“The best thing to do is lay her on the floor and press down on the lower part of the sternum,” he said.

The woman should be tilted slightly to one side to prevent aortocaval compression.

Dr. Quirk said several case reports suggest that this adaptation is effective in late pregnancy.

PASADENA, CALIF. — The Heimlich maneuver becomes unwieldy during the late stages of pregnancy, requiring adaptations, Dr. J. Gerald Quirk said at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California.

Breast enlargement, diaphragm displacement, and the size and weight of a pregnant woman all contribute to difficulty in performing the traditional emergency maneuver to prevent choking during late pregnancy.

First described in 1974 by Dr. Henry Heimlich, a thoracic surgeon, the Heimlich maneuver involves standing behind a choking victim and placing a fist, thumb side in, underneath the diaphragm.

Using the other hand to push against the fist, a series of abrupt upward thrusts can usually dislodge a piece of food from the airway.

Not only is it difficult to hold a woman in this position during late pregnancy, it is also hard to exert the force necessary to perform the maneuver correctly, said Dr. Quirk, professor and chair of obstetrics, gynecology, and reproductive medicine at Stony Brook (N.Y.) University.

“The best thing to do is lay her on the floor and press down on the lower part of the sternum,” he said.

The woman should be tilted slightly to one side to prevent aortocaval compression.

Dr. Quirk said several case reports suggest that this adaptation is effective in late pregnancy.

PASADENA, CALIF. — The diagnosis of appendicitis can, of course, be exquisitely difficult in a nonpregnant patient. Pregnancy only makes the task more daunting.

However, the challenge must be met because early diagnosis and prompt surgery may mean the difference between life and death for both the mother and the fetus, said Dr. J. Gerald Quirk, who is professor and chairman of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook.

“The risks of temporizing appendicitis in pregnant women are quite grave,” he warned at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Approximately 1 in 1,000 pregnancies are complicated by appendicitis, noted Dr. Quirk. Appendectomy confirms the disease in two-thirds to three-fourths of patients.

Unfortunately, perforation is not an uncommon result of delay, with dire consequences. While fetal mortality occurs as a result of unperforated appendicitis in 3%–5% of cases, a perforated appendix is associated with the much higher fetal mortality rate of 20%–30%.

Maternal mortality, seen in approximately 0.1% of cases of unperforated appendicitis, rises precipitously to 4% with perforation.

The threshold for surgery should therefore be low, and increasingly so as the pregnancy progresses, since perforation is twice as common in the third trimester as it is in the first or second. “What you're doing is just increasing the risks … by waiting.”

And still, in part out of reluctance to operate unnecessarily, “We are loathe to make the diagnosis and a lot of surgeons are loathe to act on the diagnosis,” he said.

In fact, when special accommodations are made for physiologic changes associated with pregnancy, uncomplicated surgery and anesthesiology are not thought to be linked to adverse perinatal outcomes, said Dr. Quirk.

“In most cases, I think one can be assured that what's best for mom is best for the fetus.”

It is not surgery that poses the greatest risk, but, in the words of Dr. E.A. Babler in 1908, “[the mortality of appendicitis is] the mortality of delay.”

Uncertainty drives that delay, inasmuch as many of the classic signs and symptoms may not be present or may be confusing in the pregnant patient, and the differential diagnosis of appendicitis is long and complex. (See box.)

The location of the appendix varies during different stages of pregnancy. “What we do know is that it moves around,” he said.

Direct abdominal tenderness is a fairly reliable sign of appendicitis during pregnancy, but rebound tenderness is much less reliable, because the enlarged uterus shields the abdominal wall. Rectal tenderness is frequently absent, said Dr. Quirk.

Anorexia, present in nearly all nonpregnant patients with appendicitis, occurred in only one- to two-thirds of pregnant patients in a 1975 study from Parkland Hospital in Dallas, he noted. In early pregnancy, anorexia may be associated with morning sickness, further complicating its usefulness as a contributor to a diagnosis of appendicitis.

Dr. Quirk said a urinalysis showing many white cells but no bacteria may reinforce the diagnosis of appendicitis in a pregnant woman, because periureteritis can develop over the right ureter.

Ultrasound or spiral CT imaging may be helpful, but imaging is not always reliable. In any case, a surgical consult should be obtained immediately and the decision to operate made promptly. Also, perioperative antibiotics should be administered.

General anesthesia is generally well-tolerated in pregnancy; laparoscopy or laparotomy appear to be equally safe. The incision generally is made over the point of maximal tenderness, or at the midline if the diagnosis is seriously in doubt or if diffuse peritonitis might be present.

The table should be tilted 30 degrees to the left, and uterine manipulation minimized. Some institutions advocate external fetal monitoring.

Following surgery, Dr. Quirk recommends monitoring the uterus for contractions. The mother should ambulate early and be kept well hydrated. During rest, the patient should maintain the tilt position.

Because the diagnosis is so difficult, negative appendectomies can be expected. Acceptable rates are considered to be 25%–35% in early pregnancy and more than 40% in the second and third trimesters, “as the consequences of delay are so severe,” he said.

Differential Diagnosis

Nonobstetric Conditions

Urinary calculi

Cholelithiasis

Cholecystitis

Bowel obstruction

Gastroenteritis

Mesenteric adenitis

Colonic carcinoma

Rectus hematoma

Acute intermittent porphyria

Perforated duodenal ulcer

Pneumonia

Meckel's diverticulum

Obstetric Conditions

Preterm labor

Abruptio placentae

Chorioamnionitis

Adnexal torsion

Ectopic pregnancy

Pelvic inflammatory disease

Round ligament pain

Uteroovarian vein rupture

Carneous degeneration of myomas

Uterine rupture (placenta percreta; rudimentary horn)

Source: Dr. Quirk

PASADENA, CALIF. — The diagnosis of appendicitis can, of course, be exquisitely difficult in a nonpregnant patient. Pregnancy only makes the task more daunting.

However, the challenge must be met because early diagnosis and prompt surgery may mean the difference between life and death for both the mother and the fetus, said Dr. J. Gerald Quirk, who is professor and chairman of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook.

“The risks of temporizing appendicitis in pregnant women are quite grave,” he warned at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Approximately 1 in 1,000 pregnancies are complicated by appendicitis, noted Dr. Quirk. Appendectomy confirms the disease in two-thirds to three-fourths of patients.

Unfortunately, perforation is not an uncommon result of delay, with dire consequences. While fetal mortality occurs as a result of unperforated appendicitis in 3%–5% of cases, a perforated appendix is associated with the much higher fetal mortality rate of 20%–30%.

Maternal mortality, seen in approximately 0.1% of cases of unperforated appendicitis, rises precipitously to 4% with perforation.

The threshold for surgery should therefore be low, and increasingly so as the pregnancy progresses, since perforation is twice as common in the third trimester as it is in the first or second. “What you're doing is just increasing the risks … by waiting.”

And still, in part out of reluctance to operate unnecessarily, “We are loathe to make the diagnosis and a lot of surgeons are loathe to act on the diagnosis,” he said.

In fact, when special accommodations are made for physiologic changes associated with pregnancy, uncomplicated surgery and anesthesiology are not thought to be linked to adverse perinatal outcomes, said Dr. Quirk.

“In most cases, I think one can be assured that what's best for mom is best for the fetus.”

It is not surgery that poses the greatest risk, but, in the words of Dr. E.A. Babler in 1908, “[the mortality of appendicitis is] the mortality of delay.”

Uncertainty drives that delay, inasmuch as many of the classic signs and symptoms may not be present or may be confusing in the pregnant patient, and the differential diagnosis of appendicitis is long and complex. (See box.)

The location of the appendix varies during different stages of pregnancy. “What we do know is that it moves around,” he said.

Direct abdominal tenderness is a fairly reliable sign of appendicitis during pregnancy, but rebound tenderness is much less reliable, because the enlarged uterus shields the abdominal wall. Rectal tenderness is frequently absent, said Dr. Quirk.

Anorexia, present in nearly all nonpregnant patients with appendicitis, occurred in only one- to two-thirds of pregnant patients in a 1975 study from Parkland Hospital in Dallas, he noted. In early pregnancy, anorexia may be associated with morning sickness, further complicating its usefulness as a contributor to a diagnosis of appendicitis.

Dr. Quirk said a urinalysis showing many white cells but no bacteria may reinforce the diagnosis of appendicitis in a pregnant woman, because periureteritis can develop over the right ureter.

Ultrasound or spiral CT imaging may be helpful, but imaging is not always reliable. In any case, a surgical consult should be obtained immediately and the decision to operate made promptly. Also, perioperative antibiotics should be administered.

General anesthesia is generally well-tolerated in pregnancy; laparoscopy or laparotomy appear to be equally safe. The incision generally is made over the point of maximal tenderness, or at the midline if the diagnosis is seriously in doubt or if diffuse peritonitis might be present.

The table should be tilted 30 degrees to the left, and uterine manipulation minimized. Some institutions advocate external fetal monitoring.

Following surgery, Dr. Quirk recommends monitoring the uterus for contractions. The mother should ambulate early and be kept well hydrated. During rest, the patient should maintain the tilt position.

Because the diagnosis is so difficult, negative appendectomies can be expected. Acceptable rates are considered to be 25%–35% in early pregnancy and more than 40% in the second and third trimesters, “as the consequences of delay are so severe,” he said.

Differential Diagnosis

Nonobstetric Conditions

Urinary calculi

Cholelithiasis

Cholecystitis

Bowel obstruction

Gastroenteritis

Mesenteric adenitis

Colonic carcinoma

Rectus hematoma

Acute intermittent porphyria

Perforated duodenal ulcer

Pneumonia

Meckel's diverticulum

Obstetric Conditions

Preterm labor

Abruptio placentae

Chorioamnionitis

Adnexal torsion

Ectopic pregnancy

Pelvic inflammatory disease

Round ligament pain

Uteroovarian vein rupture

Carneous degeneration of myomas

Uterine rupture (placenta percreta; rudimentary horn)

Source: Dr. Quirk

PASADENA, CALIF. — The diagnosis of appendicitis can, of course, be exquisitely difficult in a nonpregnant patient. Pregnancy only makes the task more daunting.

However, the challenge must be met because early diagnosis and prompt surgery may mean the difference between life and death for both the mother and the fetus, said Dr. J. Gerald Quirk, who is professor and chairman of obstetrics, gynecology, and reproductive medicine at the State University of New York at Stony Brook.

“The risks of temporizing appendicitis in pregnant women are quite grave,” he warned at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Approximately 1 in 1,000 pregnancies are complicated by appendicitis, noted Dr. Quirk. Appendectomy confirms the disease in two-thirds to three-fourths of patients.

Unfortunately, perforation is not an uncommon result of delay, with dire consequences. While fetal mortality occurs as a result of unperforated appendicitis in 3%–5% of cases, a perforated appendix is associated with the much higher fetal mortality rate of 20%–30%.

Maternal mortality, seen in approximately 0.1% of cases of unperforated appendicitis, rises precipitously to 4% with perforation.

The threshold for surgery should therefore be low, and increasingly so as the pregnancy progresses, since perforation is twice as common in the third trimester as it is in the first or second. “What you're doing is just increasing the risks … by waiting.”

And still, in part out of reluctance to operate unnecessarily, “We are loathe to make the diagnosis and a lot of surgeons are loathe to act on the diagnosis,” he said.

In fact, when special accommodations are made for physiologic changes associated with pregnancy, uncomplicated surgery and anesthesiology are not thought to be linked to adverse perinatal outcomes, said Dr. Quirk.

“In most cases, I think one can be assured that what's best for mom is best for the fetus.”

It is not surgery that poses the greatest risk, but, in the words of Dr. E.A. Babler in 1908, “[the mortality of appendicitis is] the mortality of delay.”

Uncertainty drives that delay, inasmuch as many of the classic signs and symptoms may not be present or may be confusing in the pregnant patient, and the differential diagnosis of appendicitis is long and complex. (See box.)

The location of the appendix varies during different stages of pregnancy. “What we do know is that it moves around,” he said.

Direct abdominal tenderness is a fairly reliable sign of appendicitis during pregnancy, but rebound tenderness is much less reliable, because the enlarged uterus shields the abdominal wall. Rectal tenderness is frequently absent, said Dr. Quirk.

Anorexia, present in nearly all nonpregnant patients with appendicitis, occurred in only one- to two-thirds of pregnant patients in a 1975 study from Parkland Hospital in Dallas, he noted. In early pregnancy, anorexia may be associated with morning sickness, further complicating its usefulness as a contributor to a diagnosis of appendicitis.

Dr. Quirk said a urinalysis showing many white cells but no bacteria may reinforce the diagnosis of appendicitis in a pregnant woman, because periureteritis can develop over the right ureter.

Ultrasound or spiral CT imaging may be helpful, but imaging is not always reliable. In any case, a surgical consult should be obtained immediately and the decision to operate made promptly. Also, perioperative antibiotics should be administered.

General anesthesia is generally well-tolerated in pregnancy; laparoscopy or laparotomy appear to be equally safe. The incision generally is made over the point of maximal tenderness, or at the midline if the diagnosis is seriously in doubt or if diffuse peritonitis might be present.

The table should be tilted 30 degrees to the left, and uterine manipulation minimized. Some institutions advocate external fetal monitoring.

Following surgery, Dr. Quirk recommends monitoring the uterus for contractions. The mother should ambulate early and be kept well hydrated. During rest, the patient should maintain the tilt position.

Because the diagnosis is so difficult, negative appendectomies can be expected. Acceptable rates are considered to be 25%–35% in early pregnancy and more than 40% in the second and third trimesters, “as the consequences of delay are so severe,” he said.

Differential Diagnosis

Nonobstetric Conditions

Urinary calculi

Cholelithiasis

Cholecystitis

Bowel obstruction

Gastroenteritis

Mesenteric adenitis

Colonic carcinoma

Rectus hematoma

Acute intermittent porphyria

Perforated duodenal ulcer

Pneumonia

Meckel's diverticulum

Obstetric Conditions

Preterm labor

Abruptio placentae

Chorioamnionitis

Adnexal torsion

Ectopic pregnancy

Pelvic inflammatory disease

Round ligament pain

Uteroovarian vein rupture

Carneous degeneration of myomas

Uterine rupture (placenta percreta; rudimentary horn)

Source: Dr. Quirk

VANCOUVER, B.C. — A biopsy from the scalp of this 88-year-old patient revealed a deep and diffuse lymphoid infiltrate extending into fat.

The histopathology of this lesion resembled a follicle from a lymph node, and it contained a germinal center, a mantle zone, and a surrounding marginal zone.

“Of note, there was a grenz zone, a sparing of the papillary dermis, which is characteristic of B-cell lymphoma,” commented Jenny Murase, M.D., a dermatology resident at the University of California, Irvine, who presented the case at the annual meeting of the Pacific Dermatologic Association.

Immunohistochemical stains were performed, with CD20 and CD79 marking nodular aggregates. “These are present in malignant B cells,” she said.

CD3, CD7, and CD43 marked smaller background lymphocytes, which are T-cell markers.

Also relevant was positive CD- 30 (Ki-1) staining, consistent with a diagnosis of follicular B-cell lymphoma, recently renamed follicle center cell lymphoma by the World Health Organization.

“Interestingly, CD10 staining was negative, although it is usually positive in follicle center lymphoma,” Dr. Murase said.

The patient's positive BCL-2 gene findings helped to clinch the diagnosis.

Dr. Murase explained several features that can aid in differentiating progressive transformation of germinal centers from lymphoma.

“Germinal centers have significant mitoses as compared to neoplasms,” she said. In addition, tingible body macrophages contain “ingested nuclear debris, which represents lymphocytes that have been selected to be destroyed in reactive follicles.

“This selection process will not occur in neoplasms,” she said.

Follicular B-cell lymphoma, or follicle center cell lymphoma, represents about 30% of cases of non-Hodgkin's lymphoma. Its incidence has been rising by 3%–5% per year for 20 years.

The median age at diagnosis is 60–65 years.

An indolent clinical course is common. Median survival is 5–10 years, and the survival rate is 75%.

“This tumor is very radiosensitive,” Dr. Murase said.

Recent studies have suggested that rituximab (Rituxan) and fludarabine (Fludara) have a greater chemotherapeutic effect on this cancer than commonly used multidrug combinations.

Dr. Murase's patient had a normal blood chemistry panel and CT scan. However, a PET scan revealed activity in the lower left anterior cervical region and bilateral pulmonary hila involvement. A bone marrow biopsy showed extensive disease, and the patient was staged as IVA.

He received a 6-week course of 375 mg of infused rituximab which he tolerated well and which led to a resolution of his pruritus. He remains alive with his disease.

Dr. Murase said the case demonstrates the need to biopsy and work up a patient who is not responding to traditional therapy for a seemingly simple problem.

Moreover, “I feel this case demonstrates that very subtle skin findings can have potentially serious implications. In this case, a patient's pruritic scalp led us to his bone marrow involvement,” she said.

VANCOUVER, B.C. — A biopsy from the scalp of this 88-year-old patient revealed a deep and diffuse lymphoid infiltrate extending into fat.

The histopathology of this lesion resembled a follicle from a lymph node, and it contained a germinal center, a mantle zone, and a surrounding marginal zone.

“Of note, there was a grenz zone, a sparing of the papillary dermis, which is characteristic of B-cell lymphoma,” commented Jenny Murase, M.D., a dermatology resident at the University of California, Irvine, who presented the case at the annual meeting of the Pacific Dermatologic Association.

Immunohistochemical stains were performed, with CD20 and CD79 marking nodular aggregates. “These are present in malignant B cells,” she said.

CD3, CD7, and CD43 marked smaller background lymphocytes, which are T-cell markers.

Also relevant was positive CD- 30 (Ki-1) staining, consistent with a diagnosis of follicular B-cell lymphoma, recently renamed follicle center cell lymphoma by the World Health Organization.

“Interestingly, CD10 staining was negative, although it is usually positive in follicle center lymphoma,” Dr. Murase said.

The patient's positive BCL-2 gene findings helped to clinch the diagnosis.

Dr. Murase explained several features that can aid in differentiating progressive transformation of germinal centers from lymphoma.

“Germinal centers have significant mitoses as compared to neoplasms,” she said. In addition, tingible body macrophages contain “ingested nuclear debris, which represents lymphocytes that have been selected to be destroyed in reactive follicles.

“This selection process will not occur in neoplasms,” she said.

Follicular B-cell lymphoma, or follicle center cell lymphoma, represents about 30% of cases of non-Hodgkin's lymphoma. Its incidence has been rising by 3%–5% per year for 20 years.

The median age at diagnosis is 60–65 years.

An indolent clinical course is common. Median survival is 5–10 years, and the survival rate is 75%.

“This tumor is very radiosensitive,” Dr. Murase said.

Recent studies have suggested that rituximab (Rituxan) and fludarabine (Fludara) have a greater chemotherapeutic effect on this cancer than commonly used multidrug combinations.

Dr. Murase's patient had a normal blood chemistry panel and CT scan. However, a PET scan revealed activity in the lower left anterior cervical region and bilateral pulmonary hila involvement. A bone marrow biopsy showed extensive disease, and the patient was staged as IVA.

He received a 6-week course of 375 mg of infused rituximab which he tolerated well and which led to a resolution of his pruritus. He remains alive with his disease.

Dr. Murase said the case demonstrates the need to biopsy and work up a patient who is not responding to traditional therapy for a seemingly simple problem.

Moreover, “I feel this case demonstrates that very subtle skin findings can have potentially serious implications. In this case, a patient's pruritic scalp led us to his bone marrow involvement,” she said.

VANCOUVER, B.C. — A biopsy from the scalp of this 88-year-old patient revealed a deep and diffuse lymphoid infiltrate extending into fat.

The histopathology of this lesion resembled a follicle from a lymph node, and it contained a germinal center, a mantle zone, and a surrounding marginal zone.

“Of note, there was a grenz zone, a sparing of the papillary dermis, which is characteristic of B-cell lymphoma,” commented Jenny Murase, M.D., a dermatology resident at the University of California, Irvine, who presented the case at the annual meeting of the Pacific Dermatologic Association.

Immunohistochemical stains were performed, with CD20 and CD79 marking nodular aggregates. “These are present in malignant B cells,” she said.

CD3, CD7, and CD43 marked smaller background lymphocytes, which are T-cell markers.

Also relevant was positive CD- 30 (Ki-1) staining, consistent with a diagnosis of follicular B-cell lymphoma, recently renamed follicle center cell lymphoma by the World Health Organization.

“Interestingly, CD10 staining was negative, although it is usually positive in follicle center lymphoma,” Dr. Murase said.

The patient's positive BCL-2 gene findings helped to clinch the diagnosis.

Dr. Murase explained several features that can aid in differentiating progressive transformation of germinal centers from lymphoma.

“Germinal centers have significant mitoses as compared to neoplasms,” she said. In addition, tingible body macrophages contain “ingested nuclear debris, which represents lymphocytes that have been selected to be destroyed in reactive follicles.

“This selection process will not occur in neoplasms,” she said.

Follicular B-cell lymphoma, or follicle center cell lymphoma, represents about 30% of cases of non-Hodgkin's lymphoma. Its incidence has been rising by 3%–5% per year for 20 years.

The median age at diagnosis is 60–65 years.

An indolent clinical course is common. Median survival is 5–10 years, and the survival rate is 75%.

“This tumor is very radiosensitive,” Dr. Murase said.

Recent studies have suggested that rituximab (Rituxan) and fludarabine (Fludara) have a greater chemotherapeutic effect on this cancer than commonly used multidrug combinations.

Dr. Murase's patient had a normal blood chemistry panel and CT scan. However, a PET scan revealed activity in the lower left anterior cervical region and bilateral pulmonary hila involvement. A bone marrow biopsy showed extensive disease, and the patient was staged as IVA.

He received a 6-week course of 375 mg of infused rituximab which he tolerated well and which led to a resolution of his pruritus. He remains alive with his disease.

Dr. Murase said the case demonstrates the need to biopsy and work up a patient who is not responding to traditional therapy for a seemingly simple problem.

Moreover, “I feel this case demonstrates that very subtle skin findings can have potentially serious implications. In this case, a patient's pruritic scalp led us to his bone marrow involvement,” she said.