Betsy Bates

SAN FRANCISCO — Perioperative mortality associated with pancreatectomy in pancreatic cancer patients is improving, Dr. James T. McPhee reported at a symposium sponsored by the American Society of Clinical Oncology.

In 1998, 7.7% of patients died before leaving the hospital following pancreatectomy for neoplasm. That figure dropped to 4.4% by 2003, according to a retrospective analysis of 6,024 patients tracked through the National Inpatient Sample, a representative database of 994 hospitals in 37 states.

“Pancreatic resection remains the only curative intervention for pancreatic cancer,” noted Dr. McPhee, a surgeon at the University of Massachusetts Memorial Medical Center in Worcester. Mortality was considerably lower in hospitals with a high volume of the difficult surgeries, Dr. McPhee said at the symposium.

By 2003, the in-hospital mortality rate at hospitals performing more than 13 pancreatectomies per year was 2%, down from 2.8% in 1998. That compared with 8.3% in 2003 and 14% in 1998 at low-volume hospitals, defined as those performing fewer than four of the procedures a year.

Perioperative mortality at centers that did 4–13 cases per year fell into the midrange between the high- and low-volume hospitals. The overall in-hospital mortality rate for all hospitals over the 6-year period was 5.8%.

A multivariate regression analysis determined that surgical volume was the most powerful independent variable linked to mortality. Other negative predictors included advanced age, male gender, and, to a lesser degree, the year of the surgery.

“Could the decrease in mortality over time reflect a paradigm shift whereby a higher percentage of pancreatic resections are being performed at high-volume surgical centers?” Dr. McPhee asked.

A look at total cases and potential confounders “lends some credence,” to that theory, he said. Certainly, more cancer patients are undergoing pancreatectomy at high-volume centers: 40% in 2003, compared with 32% in 1998.

Furthermore, high-volume centers do not appear to be doing less complex cases, which could serve as a possible explanation for the mortality disparity, he said.

Although data were not available on every patient's race or socioeconomic status, two important potential confounders—age and gender—appeared well balanced between high- and low-volume centers, Dr. McPhee and his associates found.

The gastrointestinal cancer symposium was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiation and Oncology, and the Society of Surgical Oncology.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Perioperative mortality associated with pancreatectomy in pancreatic cancer patients is improving, Dr. James T. McPhee reported at a symposium sponsored by the American Society of Clinical Oncology.

In 1998, 7.7% of patients died before leaving the hospital following pancreatectomy for neoplasm. That figure dropped to 4.4% by 2003, according to a retrospective analysis of 6,024 patients tracked through the National Inpatient Sample, a representative database of 994 hospitals in 37 states.

“Pancreatic resection remains the only curative intervention for pancreatic cancer,” noted Dr. McPhee, a surgeon at the University of Massachusetts Memorial Medical Center in Worcester. Mortality was considerably lower in hospitals with a high volume of the difficult surgeries, Dr. McPhee said at the symposium.

By 2003, the in-hospital mortality rate at hospitals performing more than 13 pancreatectomies per year was 2%, down from 2.8% in 1998. That compared with 8.3% in 2003 and 14% in 1998 at low-volume hospitals, defined as those performing fewer than four of the procedures a year.

Perioperative mortality at centers that did 4–13 cases per year fell into the midrange between the high- and low-volume hospitals. The overall in-hospital mortality rate for all hospitals over the 6-year period was 5.8%.

A multivariate regression analysis determined that surgical volume was the most powerful independent variable linked to mortality. Other negative predictors included advanced age, male gender, and, to a lesser degree, the year of the surgery.

“Could the decrease in mortality over time reflect a paradigm shift whereby a higher percentage of pancreatic resections are being performed at high-volume surgical centers?” Dr. McPhee asked.

A look at total cases and potential confounders “lends some credence,” to that theory, he said. Certainly, more cancer patients are undergoing pancreatectomy at high-volume centers: 40% in 2003, compared with 32% in 1998.

Furthermore, high-volume centers do not appear to be doing less complex cases, which could serve as a possible explanation for the mortality disparity, he said.

Although data were not available on every patient's race or socioeconomic status, two important potential confounders—age and gender—appeared well balanced between high- and low-volume centers, Dr. McPhee and his associates found.

The gastrointestinal cancer symposium was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiation and Oncology, and the Society of Surgical Oncology.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Perioperative mortality associated with pancreatectomy in pancreatic cancer patients is improving, Dr. James T. McPhee reported at a symposium sponsored by the American Society of Clinical Oncology.

In 1998, 7.7% of patients died before leaving the hospital following pancreatectomy for neoplasm. That figure dropped to 4.4% by 2003, according to a retrospective analysis of 6,024 patients tracked through the National Inpatient Sample, a representative database of 994 hospitals in 37 states.

“Pancreatic resection remains the only curative intervention for pancreatic cancer,” noted Dr. McPhee, a surgeon at the University of Massachusetts Memorial Medical Center in Worcester. Mortality was considerably lower in hospitals with a high volume of the difficult surgeries, Dr. McPhee said at the symposium.

By 2003, the in-hospital mortality rate at hospitals performing more than 13 pancreatectomies per year was 2%, down from 2.8% in 1998. That compared with 8.3% in 2003 and 14% in 1998 at low-volume hospitals, defined as those performing fewer than four of the procedures a year.

Perioperative mortality at centers that did 4–13 cases per year fell into the midrange between the high- and low-volume hospitals. The overall in-hospital mortality rate for all hospitals over the 6-year period was 5.8%.

A multivariate regression analysis determined that surgical volume was the most powerful independent variable linked to mortality. Other negative predictors included advanced age, male gender, and, to a lesser degree, the year of the surgery.

“Could the decrease in mortality over time reflect a paradigm shift whereby a higher percentage of pancreatic resections are being performed at high-volume surgical centers?” Dr. McPhee asked.

A look at total cases and potential confounders “lends some credence,” to that theory, he said. Certainly, more cancer patients are undergoing pancreatectomy at high-volume centers: 40% in 2003, compared with 32% in 1998.

Furthermore, high-volume centers do not appear to be doing less complex cases, which could serve as a possible explanation for the mortality disparity, he said.

Although data were not available on every patient's race or socioeconomic status, two important potential confounders—age and gender—appeared well balanced between high- and low-volume centers, Dr. McPhee and his associates found.

The gastrointestinal cancer symposium was also sponsored by the American Gastroenterological Association, the American Society for Therapeutic Radiation and Oncology, and the Society of Surgical Oncology.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — A majority of patients with chronic pancreatitis experienced pain relief and many were spared a lifetime of insulin-dependent diabetes when total pancreatectomy was followed by autotransplantation of islet cells in a University of Minnesota study.

Dr. Tun Jie and Dr. David E. Sutherland, both of the University of Minnesota, Minneapolis, reported results of the dual procedure in 136 patients at the annual clinical congress of the American College of Surgeons. Their retrospective clinical review represents the largest collection of cases presented to date.

An estimated 80,000 patients per year suffer pancreatitis, at a cost of $63.8 million, Dr. Jie said.

In some patients, the disease becomes chronic, resulting in intractable pain, malabsorption, and weight loss despite interim surgical procedures such as dilation of the pancreatic duct. For these patients, pain control often is achieved only by total pancreatectomy, he explained. However, the surgery propels patients into diabetes by removing the gland that makes insulin.

Since 1977, the University of Minnesota has been using various techniques to isolate and process patients' islet of Langerhans cells from their diseased pancreases and transplant them back into the patients following pancreatectomy.

Among 105 patients who completed a pain questionnaire following the dual procedure, 68 reported complete resolution of pain and another 22 said their pain had lessened. Just 15 patients said their pain was unchanged, and none reported worsened pain following pancreatectomy.

Insulin independence was achieved in patients who received the most pancreatic islet cells, with a threshold of 2,000 islet equivalents per kilogram required to prevent the need for regular insulin injections.

Of the 51 patients who did receive 2,000 or more islet cells, 37 required only intermittent insulin or none at all during long-term follow-up.

The investigators found a clear link between previous surgery and islet cell yield. Patients with no previous pancreatic surgery had a mean yield of about 4,000 islet equivalents per kilogram, compared with about 3,700 for patients with a previous pancreatic resection. Patients with a history of a Puestow procedure (lateral pancreaticojejunostomy) had a much lower mean yield, about 1,531 islet equivalents per kilogram.

Because extensive surgery impacts islet cell yield, pancreatectomy and autotransplantation should be performed early in the course of the disease, Dr. Jie recommended.

Over the years, the surgical team refined the procedure, eventually concluding that complete pancreatectomy was preferable to near-total pancreatectomy or distal pancreatectomy, since patients undergoing the latter procedures often required reoperation.

The method of islet processing and infusion also varied, with results representing eight different distribution options. The preferred approach is always a portal infusion, said Dr. Jie, but portal pressure variability sometimes necessitates the use of a kidney capsule or peritoneal infusion.

The mean operating time of 10 hours included 2–4 hours for islet isolation in some cases. (Today, infusion of islet cells is sometimes done post operatively.) The estimated blood loss was 1,500 cc.

The mean length of hospital stay was 22 days; however, some patients remained hospitalized for an extended period only for completion of metabolic studies.

There were two deaths in the series, one due to sepsis following colon perforation and one due to pulmonary embolism on postoperative day 2.

Complications among the 136 patients included 42 infections, 12 bleeding episodes requiring reoperation, and 6 biliary complications.

Pediatric patients included in the series “are the group doing the best,” Dr. Jie said.

Patient selection reflected referral patterns to the University of Minnesota and therefore a relatively low number of patients whose chronic pancreatitis was due to alcohol abuse.

“I can tell you that alcoholic patients in our population actually have done the worst. Part of that involves lifestyle [issues] such as trauma unrelated to the surgery itself, and not taking medical advice as they should,” he continued.

Dr. Jeffrey B. Matthews, a University of Cincinnati surgeon who has performed numerous pancreatectomy/islet cell autotransplants, raised the troubling issue of patients in intractable visceral pain whose lengthy medical histories fail to document a clear history of pancreatitis.

Dr. Sutherland agreed that these patients pose a dilemma, but said that the surgery is often their only option and noted that they do well.

Another thorny issue is narcotic-induced hyperalgesia syndrome in patients treated for years with powerful painkillers prior to the surgery.

Dr. Sutherland said that although these patients get some relief from pancreatitis pain, simple intestinal gas remains very painful for them.

Malabsorption and maldigestion are common problems following the surgery, and Dr. Sutherland said he increasingly believes colectomy should be performed in conjunction with total pancreatectomy in patients who already have extreme colon dysfunction.

SAN FRANCISCO — A majority of patients with chronic pancreatitis experienced pain relief and many were spared a lifetime of insulin-dependent diabetes when total pancreatectomy was followed by autotransplantation of islet cells in a University of Minnesota study.

Dr. Tun Jie and Dr. David E. Sutherland, both of the University of Minnesota, Minneapolis, reported results of the dual procedure in 136 patients at the annual clinical congress of the American College of Surgeons. Their retrospective clinical review represents the largest collection of cases presented to date.

An estimated 80,000 patients per year suffer pancreatitis, at a cost of $63.8 million, Dr. Jie said.

In some patients, the disease becomes chronic, resulting in intractable pain, malabsorption, and weight loss despite interim surgical procedures such as dilation of the pancreatic duct. For these patients, pain control often is achieved only by total pancreatectomy, he explained. However, the surgery propels patients into diabetes by removing the gland that makes insulin.

Since 1977, the University of Minnesota has been using various techniques to isolate and process patients' islet of Langerhans cells from their diseased pancreases and transplant them back into the patients following pancreatectomy.

Among 105 patients who completed a pain questionnaire following the dual procedure, 68 reported complete resolution of pain and another 22 said their pain had lessened. Just 15 patients said their pain was unchanged, and none reported worsened pain following pancreatectomy.

Insulin independence was achieved in patients who received the most pancreatic islet cells, with a threshold of 2,000 islet equivalents per kilogram required to prevent the need for regular insulin injections.

Of the 51 patients who did receive 2,000 or more islet cells, 37 required only intermittent insulin or none at all during long-term follow-up.

The investigators found a clear link between previous surgery and islet cell yield. Patients with no previous pancreatic surgery had a mean yield of about 4,000 islet equivalents per kilogram, compared with about 3,700 for patients with a previous pancreatic resection. Patients with a history of a Puestow procedure (lateral pancreaticojejunostomy) had a much lower mean yield, about 1,531 islet equivalents per kilogram.

Because extensive surgery impacts islet cell yield, pancreatectomy and autotransplantation should be performed early in the course of the disease, Dr. Jie recommended.

Over the years, the surgical team refined the procedure, eventually concluding that complete pancreatectomy was preferable to near-total pancreatectomy or distal pancreatectomy, since patients undergoing the latter procedures often required reoperation.

The method of islet processing and infusion also varied, with results representing eight different distribution options. The preferred approach is always a portal infusion, said Dr. Jie, but portal pressure variability sometimes necessitates the use of a kidney capsule or peritoneal infusion.

The mean operating time of 10 hours included 2–4 hours for islet isolation in some cases. (Today, infusion of islet cells is sometimes done post operatively.) The estimated blood loss was 1,500 cc.

The mean length of hospital stay was 22 days; however, some patients remained hospitalized for an extended period only for completion of metabolic studies.

There were two deaths in the series, one due to sepsis following colon perforation and one due to pulmonary embolism on postoperative day 2.

Complications among the 136 patients included 42 infections, 12 bleeding episodes requiring reoperation, and 6 biliary complications.

Pediatric patients included in the series “are the group doing the best,” Dr. Jie said.

Patient selection reflected referral patterns to the University of Minnesota and therefore a relatively low number of patients whose chronic pancreatitis was due to alcohol abuse.

“I can tell you that alcoholic patients in our population actually have done the worst. Part of that involves lifestyle [issues] such as trauma unrelated to the surgery itself, and not taking medical advice as they should,” he continued.

Dr. Jeffrey B. Matthews, a University of Cincinnati surgeon who has performed numerous pancreatectomy/islet cell autotransplants, raised the troubling issue of patients in intractable visceral pain whose lengthy medical histories fail to document a clear history of pancreatitis.

Dr. Sutherland agreed that these patients pose a dilemma, but said that the surgery is often their only option and noted that they do well.

Another thorny issue is narcotic-induced hyperalgesia syndrome in patients treated for years with powerful painkillers prior to the surgery.

Dr. Sutherland said that although these patients get some relief from pancreatitis pain, simple intestinal gas remains very painful for them.

Malabsorption and maldigestion are common problems following the surgery, and Dr. Sutherland said he increasingly believes colectomy should be performed in conjunction with total pancreatectomy in patients who already have extreme colon dysfunction.

SAN FRANCISCO — A majority of patients with chronic pancreatitis experienced pain relief and many were spared a lifetime of insulin-dependent diabetes when total pancreatectomy was followed by autotransplantation of islet cells in a University of Minnesota study.

Dr. Tun Jie and Dr. David E. Sutherland, both of the University of Minnesota, Minneapolis, reported results of the dual procedure in 136 patients at the annual clinical congress of the American College of Surgeons. Their retrospective clinical review represents the largest collection of cases presented to date.

An estimated 80,000 patients per year suffer pancreatitis, at a cost of $63.8 million, Dr. Jie said.

In some patients, the disease becomes chronic, resulting in intractable pain, malabsorption, and weight loss despite interim surgical procedures such as dilation of the pancreatic duct. For these patients, pain control often is achieved only by total pancreatectomy, he explained. However, the surgery propels patients into diabetes by removing the gland that makes insulin.

Since 1977, the University of Minnesota has been using various techniques to isolate and process patients' islet of Langerhans cells from their diseased pancreases and transplant them back into the patients following pancreatectomy.

Among 105 patients who completed a pain questionnaire following the dual procedure, 68 reported complete resolution of pain and another 22 said their pain had lessened. Just 15 patients said their pain was unchanged, and none reported worsened pain following pancreatectomy.

Insulin independence was achieved in patients who received the most pancreatic islet cells, with a threshold of 2,000 islet equivalents per kilogram required to prevent the need for regular insulin injections.

Of the 51 patients who did receive 2,000 or more islet cells, 37 required only intermittent insulin or none at all during long-term follow-up.

The investigators found a clear link between previous surgery and islet cell yield. Patients with no previous pancreatic surgery had a mean yield of about 4,000 islet equivalents per kilogram, compared with about 3,700 for patients with a previous pancreatic resection. Patients with a history of a Puestow procedure (lateral pancreaticojejunostomy) had a much lower mean yield, about 1,531 islet equivalents per kilogram.

Because extensive surgery impacts islet cell yield, pancreatectomy and autotransplantation should be performed early in the course of the disease, Dr. Jie recommended.

Over the years, the surgical team refined the procedure, eventually concluding that complete pancreatectomy was preferable to near-total pancreatectomy or distal pancreatectomy, since patients undergoing the latter procedures often required reoperation.

The method of islet processing and infusion also varied, with results representing eight different distribution options. The preferred approach is always a portal infusion, said Dr. Jie, but portal pressure variability sometimes necessitates the use of a kidney capsule or peritoneal infusion.

The mean operating time of 10 hours included 2–4 hours for islet isolation in some cases. (Today, infusion of islet cells is sometimes done post operatively.) The estimated blood loss was 1,500 cc.

The mean length of hospital stay was 22 days; however, some patients remained hospitalized for an extended period only for completion of metabolic studies.

There were two deaths in the series, one due to sepsis following colon perforation and one due to pulmonary embolism on postoperative day 2.

Complications among the 136 patients included 42 infections, 12 bleeding episodes requiring reoperation, and 6 biliary complications.

Pediatric patients included in the series “are the group doing the best,” Dr. Jie said.

Patient selection reflected referral patterns to the University of Minnesota and therefore a relatively low number of patients whose chronic pancreatitis was due to alcohol abuse.

“I can tell you that alcoholic patients in our population actually have done the worst. Part of that involves lifestyle [issues] such as trauma unrelated to the surgery itself, and not taking medical advice as they should,” he continued.

Dr. Jeffrey B. Matthews, a University of Cincinnati surgeon who has performed numerous pancreatectomy/islet cell autotransplants, raised the troubling issue of patients in intractable visceral pain whose lengthy medical histories fail to document a clear history of pancreatitis.

Dr. Sutherland agreed that these patients pose a dilemma, but said that the surgery is often their only option and noted that they do well.

Another thorny issue is narcotic-induced hyperalgesia syndrome in patients treated for years with powerful painkillers prior to the surgery.

Dr. Sutherland said that although these patients get some relief from pancreatitis pain, simple intestinal gas remains very painful for them.

Malabsorption and maldigestion are common problems following the surgery, and Dr. Sutherland said he increasingly believes colectomy should be performed in conjunction with total pancreatectomy in patients who already have extreme colon dysfunction.

PASADENA, CALIF. — The conundrum of whether tubal disease should be treated before moving on to assisted reproductive technologies has persisted for nearly 3 decades—since in vitro fertilization was first developed to compensate for tubal dysfunction.

During a recent talk at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California, Dr. Michael P. Diamond, director of reproductive endocrinology and infertility at Detroit Medical Center and Wayne State University in Michigan, offered his recommendations concerning the following three forms of tuboperitoneal disease:

Endometriosis

A number of relatively small studies and a metaanalysis suggest that significant diminishment of success rates for assisted reproductive technologies seems to occur mostly in women with stage III or IV endometriosis and particularly in those with large endometriomas, but not so much in women with less severe endometrial disease.

Early studies pointing to impaired pregnancy outcomes may be reflective of difficulties in laparoscopic oocyte retrieval, rather than success of the assisted reproductive technologies (ART) process itself. Dr. Diamond therefore recommends prior treatment of late-stage endometriosis with GnRH analog and possibly surgery when there is hope of reducing endometriomas, improving the environment for ART, and reducing toxicity associated with extensive endometriosis. The jury is still out with regard to treating stage I-II endometriosis before moving forward with ART, he said.

Hydrosalpinges

Hydrosalpinx has the potential of reducing fertility via a number of mechanisms, including deprivation of embryos of nutrients in the endometrial cavity and embryonic toxicity associated with exposure to hydrosalpinx fluid.

Hydrosalpinx can also impair endometrial receptivity through altered integrin expression, interleukins, progesterone receptors, and other factors.

It may interfere with normal endometrial peristalsis, and finally, in “a very mechanistic process,” it can cause embryos to literally wash out of the fallopian tube.

A Cochrane Database review shows that pregnancy and live birth rates were significantly improved if salpingectomy was performed prior to ART for patients with true hydrosalpinges (Cochrane Database Syst. Rev. 3:CD002125, 2001, update 2004).

However, “that's not the whole story. That's not how all of these patients present,” he said. There is no evidence in the literature that surgery improves ART outcomes for patients with mild tubal disease.

It is also unclear what the best course of treatment is for patients who have no evidence of hydrosalpinges on ultrasound, but who develop filling of the tube during a diagnostic hysterosalpingogram.

Pelvic Adhesions

If a patient is going to undergo ART for infertility, will adhesions around her ovaries and fallopian tubes have any deleterious effect on the procedure?

In fact, there have been papers that suggest that is the case, he said. Japanese researchers have demonstrated that periovarian adhesions interfere with diffusion of gonadotropins into the follicular fluid during IVF treatment, affecting both the follicular human chorionic gonadotropin (hCG) concentration and the ratio between follicular hCG and serum hCG concentration (Hum. Reprod. 1998;13:2072–6).

Very early studies by Dr. Diamond and associates were able to document the presence of adhesions over time when oocyte retrieval was achieved through laparoscopy (Fertil. Steril. 1988;49:100–3).

These studies found that although the number of follicles was not affected by periovarian adhesions, the number of oocytes retrieved was reduced by about a third, he said. The bottom line is that oocytes can still be obtained in patients with periovarian adhesions, and surgery offers no assurance of cure. Indeed, several studies suggest more extensive adhesion formation following surgery.

“While the data are mixed, I think there is good evidence you can get very reasonable ovarian response to gonadotropin stimulation even in the presence of pelvic adhesions and even if they're extensive around the ovary,” he said adding that surgery for adhesions “probably would not justify the expense and morbidity of a surgical procedure.”

'You can get a very reasonable ovarian response to gonadotropin stimulation even in the presence of pelvic adhesions.' DR. DIAMOND

PASADENA, CALIF. — The conundrum of whether tubal disease should be treated before moving on to assisted reproductive technologies has persisted for nearly 3 decades—since in vitro fertilization was first developed to compensate for tubal dysfunction.

During a recent talk at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California, Dr. Michael P. Diamond, director of reproductive endocrinology and infertility at Detroit Medical Center and Wayne State University in Michigan, offered his recommendations concerning the following three forms of tuboperitoneal disease:

Endometriosis

A number of relatively small studies and a metaanalysis suggest that significant diminishment of success rates for assisted reproductive technologies seems to occur mostly in women with stage III or IV endometriosis and particularly in those with large endometriomas, but not so much in women with less severe endometrial disease.

Early studies pointing to impaired pregnancy outcomes may be reflective of difficulties in laparoscopic oocyte retrieval, rather than success of the assisted reproductive technologies (ART) process itself. Dr. Diamond therefore recommends prior treatment of late-stage endometriosis with GnRH analog and possibly surgery when there is hope of reducing endometriomas, improving the environment for ART, and reducing toxicity associated with extensive endometriosis. The jury is still out with regard to treating stage I-II endometriosis before moving forward with ART, he said.

Hydrosalpinges

Hydrosalpinx has the potential of reducing fertility via a number of mechanisms, including deprivation of embryos of nutrients in the endometrial cavity and embryonic toxicity associated with exposure to hydrosalpinx fluid.

Hydrosalpinx can also impair endometrial receptivity through altered integrin expression, interleukins, progesterone receptors, and other factors.

It may interfere with normal endometrial peristalsis, and finally, in “a very mechanistic process,” it can cause embryos to literally wash out of the fallopian tube.

A Cochrane Database review shows that pregnancy and live birth rates were significantly improved if salpingectomy was performed prior to ART for patients with true hydrosalpinges (Cochrane Database Syst. Rev. 3:CD002125, 2001, update 2004).

However, “that's not the whole story. That's not how all of these patients present,” he said. There is no evidence in the literature that surgery improves ART outcomes for patients with mild tubal disease.

It is also unclear what the best course of treatment is for patients who have no evidence of hydrosalpinges on ultrasound, but who develop filling of the tube during a diagnostic hysterosalpingogram.

Pelvic Adhesions

If a patient is going to undergo ART for infertility, will adhesions around her ovaries and fallopian tubes have any deleterious effect on the procedure?

In fact, there have been papers that suggest that is the case, he said. Japanese researchers have demonstrated that periovarian adhesions interfere with diffusion of gonadotropins into the follicular fluid during IVF treatment, affecting both the follicular human chorionic gonadotropin (hCG) concentration and the ratio between follicular hCG and serum hCG concentration (Hum. Reprod. 1998;13:2072–6).

Very early studies by Dr. Diamond and associates were able to document the presence of adhesions over time when oocyte retrieval was achieved through laparoscopy (Fertil. Steril. 1988;49:100–3).

These studies found that although the number of follicles was not affected by periovarian adhesions, the number of oocytes retrieved was reduced by about a third, he said. The bottom line is that oocytes can still be obtained in patients with periovarian adhesions, and surgery offers no assurance of cure. Indeed, several studies suggest more extensive adhesion formation following surgery.

“While the data are mixed, I think there is good evidence you can get very reasonable ovarian response to gonadotropin stimulation even in the presence of pelvic adhesions and even if they're extensive around the ovary,” he said adding that surgery for adhesions “probably would not justify the expense and morbidity of a surgical procedure.”

'You can get a very reasonable ovarian response to gonadotropin stimulation even in the presence of pelvic adhesions.' DR. DIAMOND

PASADENA, CALIF. — The conundrum of whether tubal disease should be treated before moving on to assisted reproductive technologies has persisted for nearly 3 decades—since in vitro fertilization was first developed to compensate for tubal dysfunction.

During a recent talk at the annual meeting of the Obstetrical and Gynecological Assembly of Southern California, Dr. Michael P. Diamond, director of reproductive endocrinology and infertility at Detroit Medical Center and Wayne State University in Michigan, offered his recommendations concerning the following three forms of tuboperitoneal disease:

Endometriosis

A number of relatively small studies and a metaanalysis suggest that significant diminishment of success rates for assisted reproductive technologies seems to occur mostly in women with stage III or IV endometriosis and particularly in those with large endometriomas, but not so much in women with less severe endometrial disease.

Early studies pointing to impaired pregnancy outcomes may be reflective of difficulties in laparoscopic oocyte retrieval, rather than success of the assisted reproductive technologies (ART) process itself. Dr. Diamond therefore recommends prior treatment of late-stage endometriosis with GnRH analog and possibly surgery when there is hope of reducing endometriomas, improving the environment for ART, and reducing toxicity associated with extensive endometriosis. The jury is still out with regard to treating stage I-II endometriosis before moving forward with ART, he said.

Hydrosalpinges

Hydrosalpinx has the potential of reducing fertility via a number of mechanisms, including deprivation of embryos of nutrients in the endometrial cavity and embryonic toxicity associated with exposure to hydrosalpinx fluid.

Hydrosalpinx can also impair endometrial receptivity through altered integrin expression, interleukins, progesterone receptors, and other factors.

It may interfere with normal endometrial peristalsis, and finally, in “a very mechanistic process,” it can cause embryos to literally wash out of the fallopian tube.

A Cochrane Database review shows that pregnancy and live birth rates were significantly improved if salpingectomy was performed prior to ART for patients with true hydrosalpinges (Cochrane Database Syst. Rev. 3:CD002125, 2001, update 2004).

However, “that's not the whole story. That's not how all of these patients present,” he said. There is no evidence in the literature that surgery improves ART outcomes for patients with mild tubal disease.

It is also unclear what the best course of treatment is for patients who have no evidence of hydrosalpinges on ultrasound, but who develop filling of the tube during a diagnostic hysterosalpingogram.

Pelvic Adhesions

If a patient is going to undergo ART for infertility, will adhesions around her ovaries and fallopian tubes have any deleterious effect on the procedure?

In fact, there have been papers that suggest that is the case, he said. Japanese researchers have demonstrated that periovarian adhesions interfere with diffusion of gonadotropins into the follicular fluid during IVF treatment, affecting both the follicular human chorionic gonadotropin (hCG) concentration and the ratio between follicular hCG and serum hCG concentration (Hum. Reprod. 1998;13:2072–6).

Very early studies by Dr. Diamond and associates were able to document the presence of adhesions over time when oocyte retrieval was achieved through laparoscopy (Fertil. Steril. 1988;49:100–3).

These studies found that although the number of follicles was not affected by periovarian adhesions, the number of oocytes retrieved was reduced by about a third, he said. The bottom line is that oocytes can still be obtained in patients with periovarian adhesions, and surgery offers no assurance of cure. Indeed, several studies suggest more extensive adhesion formation following surgery.

“While the data are mixed, I think there is good evidence you can get very reasonable ovarian response to gonadotropin stimulation even in the presence of pelvic adhesions and even if they're extensive around the ovary,” he said adding that surgery for adhesions “probably would not justify the expense and morbidity of a surgical procedure.”

'You can get a very reasonable ovarian response to gonadotropin stimulation even in the presence of pelvic adhesions.' DR. DIAMOND

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

But early diagnosis and prompt surgery can mean the difference between life and death for the mother and the fetus, said Dr. J. Gerald Quirk, 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 said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

About 1 in 1,000 pregnancies are complicated by appendicitis, and appendectomy confirms the disease in two-thirds to three-fourths of patients.

Perforation is not an uncommon result of delay, with dire consequences. Fetal death results from unperforated appendicitis in 3%–5% of cases; a perforated appendix is associated with a 20%–30% fetal mortality rate. Maternal mortality, seen in about 0.1% of cases of unperforated appendicitis, rises 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, since many 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 can help but is not always reliable. In any case, do a surgical consult immediately and promptly decide to operate or not. Perioperative antibiotics should be administered.

General anesthesia is usually well tolerated in pregnancy; laparoscopy and laparotomy appear 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 should be minimized. Some institutions advocate external fetal monitoring.

Post 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.

'What you're doing is just increasing the risks [of appendiceal perforation] … by waiting.' DR. QUIRK

Differential Dx of Appendicitis

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 be exquisitely difficult in a nonpregnant patient. Pregnancy only makes the task more daunting.

But early diagnosis and prompt surgery can mean the difference between life and death for the mother and the fetus, said Dr. J. Gerald Quirk, 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 said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

About 1 in 1,000 pregnancies are complicated by appendicitis, and appendectomy confirms the disease in two-thirds to three-fourths of patients.

Perforation is not an uncommon result of delay, with dire consequences. Fetal death results from unperforated appendicitis in 3%–5% of cases; a perforated appendix is associated with a 20%–30% fetal mortality rate. Maternal mortality, seen in about 0.1% of cases of unperforated appendicitis, rises 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, since many 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 can help but is not always reliable. In any case, do a surgical consult immediately and promptly decide to operate or not. Perioperative antibiotics should be administered.

General anesthesia is usually well tolerated in pregnancy; laparoscopy and laparotomy appear 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 should be minimized. Some institutions advocate external fetal monitoring.

Post 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.

'What you're doing is just increasing the risks [of appendiceal perforation] … by waiting.' DR. QUIRK

Differential Dx of Appendicitis

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 be exquisitely difficult in a nonpregnant patient. Pregnancy only makes the task more daunting.

But early diagnosis and prompt surgery can mean the difference between life and death for the mother and the fetus, said Dr. J. Gerald Quirk, 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 said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

About 1 in 1,000 pregnancies are complicated by appendicitis, and appendectomy confirms the disease in two-thirds to three-fourths of patients.

Perforation is not an uncommon result of delay, with dire consequences. Fetal death results from unperforated appendicitis in 3%–5% of cases; a perforated appendix is associated with a 20%–30% fetal mortality rate. Maternal mortality, seen in about 0.1% of cases of unperforated appendicitis, rises 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, since many 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 can help but is not always reliable. In any case, do a surgical consult immediately and promptly decide to operate or not. Perioperative antibiotics should be administered.

General anesthesia is usually well tolerated in pregnancy; laparoscopy and laparotomy appear 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 should be minimized. Some institutions advocate external fetal monitoring.

Post 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.

'What you're doing is just increasing the risks [of appendiceal perforation] … by waiting.' DR. QUIRK

Differential Dx of Appendicitis

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

SAN FRANCISCO — A new, multitargeted biologic therapy halted gastrointestinal tumor progression so dramatically, a phase III study was unblinded early so that patients assigned to placebo could immediately receive the drug, researchers reported at a symposium sponsored by the American Society of Clinical Oncology.

The drug, sunitinib, underwent expedited review at the Food and Drug Administration and received approval during the meeting for the treatment of gastrointestinal stromal tumors (GIST) resistant to the first-line drug imatinib, and for treatment of advanced kidney cancer.

Dr. George D. Demetri used a Certs analogy of “two mints in one” to describe the multipronged way in which sunitinib targets tumors: blocking mutated signaling enzymes that permit uncontrolled cell growth, while cutting off growth factors to blood vessels that feed tumors.

An interim analysis of an international study found that sunitinib made a “truly dramatic difference” in the time it took tumors to progress in patients with GIST. Among 207 patients randomly assigned to receive sunitinib, time to progression was 27.3 weeks, compared with 6.4 weeks in 105 patients receiving placebo.

The difference equated to a 70% reduction in the risk of progression in the study patients, all of whom had developed either intolerance or resistance to imatinib (Gleevec), which Dr. Demetri called the “poster child drug for selectively inhibiting … kinase signaling enzymes.”

The study also found a 51% reduction in the relative risk of death among patients taking sunitinib, reported Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute, Boston.

The trial was unblinded after patients had been on the drug for 6–8 months, when an interim analysis demonstrated “strongly positive” efficacy. At the time of the American Society of Clinical Oncology's gastrointestinal symposium, median survival had not been reached in either treatment group.

Beyond offering hope for patients with imatinib-resistant GIST tumors, sunitinib's success may offer a blueprint for how to develop drugs quickly based on customized genetic tumor profiles.

Dr. Demetri described an analysis of how well compounds selectively bind to signaling enzymes—kinases—that are known to spur the growth of cancer cells. In this case, sunitinib was shown to potently bind not only to KIT—a tyrosine kinase and an imatinib target—but also to many other signaling enzymes.

“We can [now] look for mutations that cause resistance, much as you would analyze bacteria for resistance to antibiotics,” he explained. “This gives us a tool to move very quickly from laboratory compounds to new effective things that can be tested for helping patients in the clinic.

Sunitinib was generally well tolerated, even among patients who could not tolerate imatinib due to that agent's side effects, which can include a life-threatening rash.

The most common side effects associated with sunitinib were fatigue, diarrhea, nausea, mouth sores, and skin discoloration.

Dr. Demetri said the new agent will provide oncologists with a therapeutic option for patients whose tumors become resistant to imatinib, a problem that generally develops after 18 months to 2 years of therapy.

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

PET images of gastrointestinal stromal tumors in the liver show how multitargeted biologic therapy can halt growth. Photos courtesy Dr. Annick D. Van den Abbeele and Dr. George D. Demetri/Dana-Farber Cancer Institute

SAN FRANCISCO — A new, multitargeted biologic therapy halted gastrointestinal tumor progression so dramatically, a phase III study was unblinded early so that patients assigned to placebo could immediately receive the drug, researchers reported at a symposium sponsored by the American Society of Clinical Oncology.

The drug, sunitinib, underwent expedited review at the Food and Drug Administration and received approval during the meeting for the treatment of gastrointestinal stromal tumors (GIST) resistant to the first-line drug imatinib, and for treatment of advanced kidney cancer.

Dr. George D. Demetri used a Certs analogy of “two mints in one” to describe the multipronged way in which sunitinib targets tumors: blocking mutated signaling enzymes that permit uncontrolled cell growth, while cutting off growth factors to blood vessels that feed tumors.

An interim analysis of an international study found that sunitinib made a “truly dramatic difference” in the time it took tumors to progress in patients with GIST. Among 207 patients randomly assigned to receive sunitinib, time to progression was 27.3 weeks, compared with 6.4 weeks in 105 patients receiving placebo.

The difference equated to a 70% reduction in the risk of progression in the study patients, all of whom had developed either intolerance or resistance to imatinib (Gleevec), which Dr. Demetri called the “poster child drug for selectively inhibiting … kinase signaling enzymes.”

The study also found a 51% reduction in the relative risk of death among patients taking sunitinib, reported Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute, Boston.

The trial was unblinded after patients had been on the drug for 6–8 months, when an interim analysis demonstrated “strongly positive” efficacy. At the time of the American Society of Clinical Oncology's gastrointestinal symposium, median survival had not been reached in either treatment group.

Beyond offering hope for patients with imatinib-resistant GIST tumors, sunitinib's success may offer a blueprint for how to develop drugs quickly based on customized genetic tumor profiles.

Dr. Demetri described an analysis of how well compounds selectively bind to signaling enzymes—kinases—that are known to spur the growth of cancer cells. In this case, sunitinib was shown to potently bind not only to KIT—a tyrosine kinase and an imatinib target—but also to many other signaling enzymes.

“We can [now] look for mutations that cause resistance, much as you would analyze bacteria for resistance to antibiotics,” he explained. “This gives us a tool to move very quickly from laboratory compounds to new effective things that can be tested for helping patients in the clinic.

Sunitinib was generally well tolerated, even among patients who could not tolerate imatinib due to that agent's side effects, which can include a life-threatening rash.

The most common side effects associated with sunitinib were fatigue, diarrhea, nausea, mouth sores, and skin discoloration.

Dr. Demetri said the new agent will provide oncologists with a therapeutic option for patients whose tumors become resistant to imatinib, a problem that generally develops after 18 months to 2 years of therapy.

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

PET images of gastrointestinal stromal tumors in the liver show how multitargeted biologic therapy can halt growth. Photos courtesy Dr. Annick D. Van den Abbeele and Dr. George D. Demetri/Dana-Farber Cancer Institute

SAN FRANCISCO — A new, multitargeted biologic therapy halted gastrointestinal tumor progression so dramatically, a phase III study was unblinded early so that patients assigned to placebo could immediately receive the drug, researchers reported at a symposium sponsored by the American Society of Clinical Oncology.

The drug, sunitinib, underwent expedited review at the Food and Drug Administration and received approval during the meeting for the treatment of gastrointestinal stromal tumors (GIST) resistant to the first-line drug imatinib, and for treatment of advanced kidney cancer.

Dr. George D. Demetri used a Certs analogy of “two mints in one” to describe the multipronged way in which sunitinib targets tumors: blocking mutated signaling enzymes that permit uncontrolled cell growth, while cutting off growth factors to blood vessels that feed tumors.

An interim analysis of an international study found that sunitinib made a “truly dramatic difference” in the time it took tumors to progress in patients with GIST. Among 207 patients randomly assigned to receive sunitinib, time to progression was 27.3 weeks, compared with 6.4 weeks in 105 patients receiving placebo.

The difference equated to a 70% reduction in the risk of progression in the study patients, all of whom had developed either intolerance or resistance to imatinib (Gleevec), which Dr. Demetri called the “poster child drug for selectively inhibiting … kinase signaling enzymes.”

The study also found a 51% reduction in the relative risk of death among patients taking sunitinib, reported Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute, Boston.

The trial was unblinded after patients had been on the drug for 6–8 months, when an interim analysis demonstrated “strongly positive” efficacy. At the time of the American Society of Clinical Oncology's gastrointestinal symposium, median survival had not been reached in either treatment group.

Beyond offering hope for patients with imatinib-resistant GIST tumors, sunitinib's success may offer a blueprint for how to develop drugs quickly based on customized genetic tumor profiles.

Dr. Demetri described an analysis of how well compounds selectively bind to signaling enzymes—kinases—that are known to spur the growth of cancer cells. In this case, sunitinib was shown to potently bind not only to KIT—a tyrosine kinase and an imatinib target—but also to many other signaling enzymes.

“We can [now] look for mutations that cause resistance, much as you would analyze bacteria for resistance to antibiotics,” he explained. “This gives us a tool to move very quickly from laboratory compounds to new effective things that can be tested for helping patients in the clinic.

Sunitinib was generally well tolerated, even among patients who could not tolerate imatinib due to that agent's side effects, which can include a life-threatening rash.

The most common side effects associated with sunitinib were fatigue, diarrhea, nausea, mouth sores, and skin discoloration.

Dr. Demetri said the new agent will provide oncologists with a therapeutic option for patients whose tumors become resistant to imatinib, a problem that generally develops after 18 months to 2 years of therapy.

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

PET images of gastrointestinal stromal tumors in the liver show how multitargeted biologic therapy can halt growth. Photos courtesy Dr. Annick D. Van den Abbeele and Dr. George D. Demetri/Dana-Farber Cancer Institute

SAN FRANCISCO — A new, multitargeted biologic therapy halted gastrointestinal tumor progression so dramatically, a phase III study was unblinded early so that patients assigned to placebo could immediately receive the drug, researchers reported at a symposium sponsored by the American Society of Clinical Oncology.

The drug, sunitinib, underwent expedited review at the Food and Drug Administration and received approval during the meeting for the treatment of gastrointestinal stromal tumors (GIST) resistant to the first-line drug imatinib, and for treatment of advanced kidney cancer.

Dr. George D. Demetri used a Certs analogy of “two mints in one” to describe the multipronged way in which sunitinib targets tumors: blocking mutated signaling enzymes that permit uncontrolled cell growth, while cutting off growth factors to blood vessels that feed tumors.

An interim analysis of an international study found that sunitinib made a “truly dramatic difference” in the time it took tumors to progress in patients with GIST. Among 207 patients randomly assigned to receive sunitinib, time to progression was 27.3 weeks. Among the 105 patients who were receiving placebo, the time was just 6.4 weeks.

The difference equated to a 70% reduction in the risk of progression in the study patients, all of whom had developed either intolerance or resistance to imatinib (Gleevec), which Dr. Demetri called the “poster child drug for selectively inhibiting … kinase signaling enzymes.”

The study also found a 51% reduction in the relative risk of death among patients taking sunitinib, reported Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute, Boston.

The trial was unblinded after patients had been receiving the drug for 6–8 months, when an interim analysis demonstrated “strongly positive” efficacy.

At the time of the American Society of Clinical Oncology's gastrointestinal symposium, median survival had not been reached in either treatment group.

Beyond offering hope for patients with imatinib-resistant GIST tumors, sunitinib's success may offer a blueprint for how to develop drugs quickly based on customized genetic tumor profiles.

Dr. Demetri described an analysis of how well compounds selectively bind to signaling enzymes—kinases—that are known to spur the growth of cancer cells. In this case, sunitinib was shown to potently bind not only to KIT—a tyrosine kinase and an imatinib target—but also to many other signaling enzymes.

“We can [now] look for mutations that cause resistance, much as you would analyze bacteria for resistance to antibiotics. This gives us a tool to move very quickly from laboratory compounds to new effective things that can be tested for helping patients in the clinic,” Dr. Demetri said.

Sunitinib was generally well tolerated, even among those patients who were not able to tolerate imatinib because of that agent's side effects, which can include a life-threatening rash. The most common side effects observed with sunitinib treatment were fatigue, diarrhea, nausea, mouth sores, and skin discoloration.

Dr. Demetri said the new agent will provide oncologists with a therapeutic option for patients whose tumors become resistant to imatinib, a problem that generally develops after 18 months to 2 years of therapy.

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

SAN FRANCISCO — A new, multitargeted biologic therapy halted gastrointestinal tumor progression so dramatically, a phase III study was unblinded early so that patients assigned to placebo could immediately receive the drug, researchers reported at a symposium sponsored by the American Society of Clinical Oncology.

The drug, sunitinib, underwent expedited review at the Food and Drug Administration and received approval during the meeting for the treatment of gastrointestinal stromal tumors (GIST) resistant to the first-line drug imatinib, and for treatment of advanced kidney cancer.

Dr. George D. Demetri used a Certs analogy of “two mints in one” to describe the multipronged way in which sunitinib targets tumors: blocking mutated signaling enzymes that permit uncontrolled cell growth, while cutting off growth factors to blood vessels that feed tumors.

An interim analysis of an international study found that sunitinib made a “truly dramatic difference” in the time it took tumors to progress in patients with GIST. Among 207 patients randomly assigned to receive sunitinib, time to progression was 27.3 weeks. Among the 105 patients who were receiving placebo, the time was just 6.4 weeks.

The difference equated to a 70% reduction in the risk of progression in the study patients, all of whom had developed either intolerance or resistance to imatinib (Gleevec), which Dr. Demetri called the “poster child drug for selectively inhibiting … kinase signaling enzymes.”

The study also found a 51% reduction in the relative risk of death among patients taking sunitinib, reported Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute, Boston.

The trial was unblinded after patients had been receiving the drug for 6–8 months, when an interim analysis demonstrated “strongly positive” efficacy.

At the time of the American Society of Clinical Oncology's gastrointestinal symposium, median survival had not been reached in either treatment group.

Beyond offering hope for patients with imatinib-resistant GIST tumors, sunitinib's success may offer a blueprint for how to develop drugs quickly based on customized genetic tumor profiles.

Dr. Demetri described an analysis of how well compounds selectively bind to signaling enzymes—kinases—that are known to spur the growth of cancer cells. In this case, sunitinib was shown to potently bind not only to KIT—a tyrosine kinase and an imatinib target—but also to many other signaling enzymes.

“We can [now] look for mutations that cause resistance, much as you would analyze bacteria for resistance to antibiotics. This gives us a tool to move very quickly from laboratory compounds to new effective things that can be tested for helping patients in the clinic,” Dr. Demetri said.

Sunitinib was generally well tolerated, even among those patients who were not able to tolerate imatinib because of that agent's side effects, which can include a life-threatening rash. The most common side effects observed with sunitinib treatment were fatigue, diarrhea, nausea, mouth sores, and skin discoloration.

Dr. Demetri said the new agent will provide oncologists with a therapeutic option for patients whose tumors become resistant to imatinib, a problem that generally develops after 18 months to 2 years of therapy.

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

SAN FRANCISCO — A new, multitargeted biologic therapy halted gastrointestinal tumor progression so dramatically, a phase III study was unblinded early so that patients assigned to placebo could immediately receive the drug, researchers reported at a symposium sponsored by the American Society of Clinical Oncology.

The drug, sunitinib, underwent expedited review at the Food and Drug Administration and received approval during the meeting for the treatment of gastrointestinal stromal tumors (GIST) resistant to the first-line drug imatinib, and for treatment of advanced kidney cancer.

Dr. George D. Demetri used a Certs analogy of “two mints in one” to describe the multipronged way in which sunitinib targets tumors: blocking mutated signaling enzymes that permit uncontrolled cell growth, while cutting off growth factors to blood vessels that feed tumors.

An interim analysis of an international study found that sunitinib made a “truly dramatic difference” in the time it took tumors to progress in patients with GIST. Among 207 patients randomly assigned to receive sunitinib, time to progression was 27.3 weeks. Among the 105 patients who were receiving placebo, the time was just 6.4 weeks.

The difference equated to a 70% reduction in the risk of progression in the study patients, all of whom had developed either intolerance or resistance to imatinib (Gleevec), which Dr. Demetri called the “poster child drug for selectively inhibiting … kinase signaling enzymes.”

The study also found a 51% reduction in the relative risk of death among patients taking sunitinib, reported Dr. Demetri, director of the Center for Sarcoma and Bone Oncology at the Dana-Farber Cancer Institute, Boston.

The trial was unblinded after patients had been receiving the drug for 6–8 months, when an interim analysis demonstrated “strongly positive” efficacy.

At the time of the American Society of Clinical Oncology's gastrointestinal symposium, median survival had not been reached in either treatment group.

Beyond offering hope for patients with imatinib-resistant GIST tumors, sunitinib's success may offer a blueprint for how to develop drugs quickly based on customized genetic tumor profiles.

Dr. Demetri described an analysis of how well compounds selectively bind to signaling enzymes—kinases—that are known to spur the growth of cancer cells. In this case, sunitinib was shown to potently bind not only to KIT—a tyrosine kinase and an imatinib target—but also to many other signaling enzymes.

“We can [now] look for mutations that cause resistance, much as you would analyze bacteria for resistance to antibiotics. This gives us a tool to move very quickly from laboratory compounds to new effective things that can be tested for helping patients in the clinic,” Dr. Demetri said.

Sunitinib was generally well tolerated, even among those patients who were not able to tolerate imatinib because of that agent's side effects, which can include a life-threatening rash. The most common side effects observed with sunitinib treatment were fatigue, diarrhea, nausea, mouth sores, and skin discoloration.

Dr. Demetri said the new agent will provide oncologists with a therapeutic option for patients whose tumors become resistant to imatinib, a problem that generally develops after 18 months to 2 years of therapy.

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

SAN DIEGO – Obsessive or impulsive reward-based behavior was reported by nearly 6 in 10 patients with Parkinson's disease answering an anonymous survey, adding to the suspicion that dopaminergic medications may influence impulse control.

Patients who had suffered from Parkinson's disease for more than 5 years, as well as those taking certain combinations of medications, were most likely to report such behaviors as obsessive or recurrent thoughts, the need to repeatedly check or organize, or impulsive eating, shopping, or gambling.

Dr. Jennifer S. Hui and her associates at the movement disorders center of the University of Southern California, Los Angeles, distributed anonymous questionnaires to 161 patients with Parkinson's disease. Among the 97 patients who returned surveys, 57 acknowledged engaging in at least one reward-based behavior, 34 respondents reported two such behaviors, and 20 acknowledged three or more.

The most commonly reported behaviors were obsessive or recurrent thoughts (25 patients); the urge to repeatedly check or organize (21 patients); the urge to go shopping (15); feeling the need to eat or starve (13); the urge to gamble (12); and an increased interest in sex (10).

In smaller numbers, patients endorsed a wide range of behaviors–including an increased interest in pornography, a change in usual sexual practices, the desire to increase the dose of medications for enhanced mood, and the need to “live on the edge”–and even reported compulsive bridge playing.

Nearly half of patients felt these behaviors represented a “distinct change in their personalities,” Dr. Hui reported in a poster presented at the annual meeting of the American Neurological Association.

Patients reporting reward-based behaviors were more likely than were others to be taking combinations of medications, especially Sinemet (carbidopa/levodopa) and Mirapex (pramipexole dihydrochloride). In the survey, 16 of 19 patients taking that combination of drugs acknowledged obsessive or impulsive behavior. Nine of 14 patients taking Sinemet (carbidopa/levodopa) and Requip (ropinirole) also reported such behaviors.

Some have theorized that dopamine agonists may contribute to reward-based behaviors because of their effect on the dopaminergic mesolimbic reward circuit. Other factors, such as personality, genetic susceptibility, and brain changes associated with the disease itself, may be involved as well, Dr. Hui said in an interview.

Although the science is far from clear, class action suits were filed in the United States and Canada last year alleging that Mirapex, manufactured by Boehringer Ingelheim, was responsible for their gambling addiction.

Dr. Hui said several prospective studies are underway to further clarify the issue, including one that will follow patients from the time they begin taking dopamine agonists, to examine the effect of personality, medication, and comorbid depression on the expression of reward-based behaviors.

“We have just started to enroll, but already two patients have described a distinct change in their behavior (hypersexuality and rearranging/shopping) within weeks of starting the agonist,” she noted.

On the other hand, 6 of 15 patients in the study presented at the meeting were not taking any of the three listed dopamine agonist medications, and yet they said they, too, suffered from impulse-control behaviors.

The likely explanation, then, is that combinations of factors probably contribute to the behaviors, although drugs theoretically could certainly play a key role.

“The dopaminergic mesolimbic mesocortical system is the core circuit underlying subjective pleasure produced by food, sex, and pathological addictions. Recent positron emission tomography (PET) studies have indicated the dopaminergic reward circuitry is deficient in Parkinson's disease,” Dr. Hui and her coinvestigators concluded.

“The effect of exogenous dopamine on this altered reward system may explain behavioral abnormalities in Parkinson's disease patients.”

SAN DIEGO – Obsessive or impulsive reward-based behavior was reported by nearly 6 in 10 patients with Parkinson's disease answering an anonymous survey, adding to the suspicion that dopaminergic medications may influence impulse control.

Patients who had suffered from Parkinson's disease for more than 5 years, as well as those taking certain combinations of medications, were most likely to report such behaviors as obsessive or recurrent thoughts, the need to repeatedly check or organize, or impulsive eating, shopping, or gambling.

Dr. Jennifer S. Hui and her associates at the movement disorders center of the University of Southern California, Los Angeles, distributed anonymous questionnaires to 161 patients with Parkinson's disease. Among the 97 patients who returned surveys, 57 acknowledged engaging in at least one reward-based behavior, 34 respondents reported two such behaviors, and 20 acknowledged three or more.

The most commonly reported behaviors were obsessive or recurrent thoughts (25 patients); the urge to repeatedly check or organize (21 patients); the urge to go shopping (15); feeling the need to eat or starve (13); the urge to gamble (12); and an increased interest in sex (10).

In smaller numbers, patients endorsed a wide range of behaviors–including an increased interest in pornography, a change in usual sexual practices, the desire to increase the dose of medications for enhanced mood, and the need to “live on the edge”–and even reported compulsive bridge playing.

Nearly half of patients felt these behaviors represented a “distinct change in their personalities,” Dr. Hui reported in a poster presented at the annual meeting of the American Neurological Association.

Patients reporting reward-based behaviors were more likely than were others to be taking combinations of medications, especially Sinemet (carbidopa/levodopa) and Mirapex (pramipexole dihydrochloride). In the survey, 16 of 19 patients taking that combination of drugs acknowledged obsessive or impulsive behavior. Nine of 14 patients taking Sinemet (carbidopa/levodopa) and Requip (ropinirole) also reported such behaviors.

Some have theorized that dopamine agonists may contribute to reward-based behaviors because of their effect on the dopaminergic mesolimbic reward circuit. Other factors, such as personality, genetic susceptibility, and brain changes associated with the disease itself, may be involved as well, Dr. Hui said in an interview.

Although the science is far from clear, class action suits were filed in the United States and Canada last year alleging that Mirapex, manufactured by Boehringer Ingelheim, was responsible for their gambling addiction.

Dr. Hui said several prospective studies are underway to further clarify the issue, including one that will follow patients from the time they begin taking dopamine agonists, to examine the effect of personality, medication, and comorbid depression on the expression of reward-based behaviors.

“We have just started to enroll, but already two patients have described a distinct change in their behavior (hypersexuality and rearranging/shopping) within weeks of starting the agonist,” she noted.

On the other hand, 6 of 15 patients in the study presented at the meeting were not taking any of the three listed dopamine agonist medications, and yet they said they, too, suffered from impulse-control behaviors.

The likely explanation, then, is that combinations of factors probably contribute to the behaviors, although drugs theoretically could certainly play a key role.

“The dopaminergic mesolimbic mesocortical system is the core circuit underlying subjective pleasure produced by food, sex, and pathological addictions. Recent positron emission tomography (PET) studies have indicated the dopaminergic reward circuitry is deficient in Parkinson's disease,” Dr. Hui and her coinvestigators concluded.

“The effect of exogenous dopamine on this altered reward system may explain behavioral abnormalities in Parkinson's disease patients.”

SAN DIEGO – Obsessive or impulsive reward-based behavior was reported by nearly 6 in 10 patients with Parkinson's disease answering an anonymous survey, adding to the suspicion that dopaminergic medications may influence impulse control.

Patients who had suffered from Parkinson's disease for more than 5 years, as well as those taking certain combinations of medications, were most likely to report such behaviors as obsessive or recurrent thoughts, the need to repeatedly check or organize, or impulsive eating, shopping, or gambling.

Dr. Jennifer S. Hui and her associates at the movement disorders center of the University of Southern California, Los Angeles, distributed anonymous questionnaires to 161 patients with Parkinson's disease. Among the 97 patients who returned surveys, 57 acknowledged engaging in at least one reward-based behavior, 34 respondents reported two such behaviors, and 20 acknowledged three or more.

The most commonly reported behaviors were obsessive or recurrent thoughts (25 patients); the urge to repeatedly check or organize (21 patients); the urge to go shopping (15); feeling the need to eat or starve (13); the urge to gamble (12); and an increased interest in sex (10).

In smaller numbers, patients endorsed a wide range of behaviors–including an increased interest in pornography, a change in usual sexual practices, the desire to increase the dose of medications for enhanced mood, and the need to “live on the edge”–and even reported compulsive bridge playing.

Nearly half of patients felt these behaviors represented a “distinct change in their personalities,” Dr. Hui reported in a poster presented at the annual meeting of the American Neurological Association.

Patients reporting reward-based behaviors were more likely than were others to be taking combinations of medications, especially Sinemet (carbidopa/levodopa) and Mirapex (pramipexole dihydrochloride). In the survey, 16 of 19 patients taking that combination of drugs acknowledged obsessive or impulsive behavior. Nine of 14 patients taking Sinemet (carbidopa/levodopa) and Requip (ropinirole) also reported such behaviors.

Some have theorized that dopamine agonists may contribute to reward-based behaviors because of their effect on the dopaminergic mesolimbic reward circuit. Other factors, such as personality, genetic susceptibility, and brain changes associated with the disease itself, may be involved as well, Dr. Hui said in an interview.

Although the science is far from clear, class action suits were filed in the United States and Canada last year alleging that Mirapex, manufactured by Boehringer Ingelheim, was responsible for their gambling addiction.

Dr. Hui said several prospective studies are underway to further clarify the issue, including one that will follow patients from the time they begin taking dopamine agonists, to examine the effect of personality, medication, and comorbid depression on the expression of reward-based behaviors.

“We have just started to enroll, but already two patients have described a distinct change in their behavior (hypersexuality and rearranging/shopping) within weeks of starting the agonist,” she noted.

On the other hand, 6 of 15 patients in the study presented at the meeting were not taking any of the three listed dopamine agonist medications, and yet they said they, too, suffered from impulse-control behaviors.

The likely explanation, then, is that combinations of factors probably contribute to the behaviors, although drugs theoretically could certainly play a key role.

“The dopaminergic mesolimbic mesocortical system is the core circuit underlying subjective pleasure produced by food, sex, and pathological addictions. Recent positron emission tomography (PET) studies have indicated the dopaminergic reward circuitry is deficient in Parkinson's disease,” Dr. Hui and her coinvestigators concluded.

“The effect of exogenous dopamine on this altered reward system may explain behavioral abnormalities in Parkinson's disease patients.”

LOS CABOS, MEXICO — Dr. Mitchel P. Goldman doesn't accept insurance and says he believes that his cash-only acne patients get more for their money with one to three photodynamic therapy sessions than they do with years of prescriptions for medications, he said at the annual meeting of the Noah Worcester Dermatological Society.

Although he says he knows it sounds heretical—"and maybe you'll strip me of my derm boards"—he has been using the photosensitizing agent 5-aminolevulinic acid (ALA) followed by exposure to a blue-light laser for nearly 4 years and he thinks that there is nothing better for acne. "As soon as insurance companies wake up and realize it's a hell of a lot cheaper to do this than prescribe Accutane—they'll cover it," said Dr. Goldman, a dermatologist in private practice in La Jolla, Calif.

In the meantime, his patients pay $500-$600 for a treatment session that consists of a salicylic acid prep, microdermabrasion of the affected area, a scrub with acetone, 1-hour exposure to ALA (Levulan Kerastik, DUSA Pharmaceuticals), and 10–15 minutes' exposure to a blue light that is approved for the treatment of acne (BLU-U Photodynamic Therapy Illuminator, DUSA Pharmaceuticals Inc.), as well as long-pulse dye laser to individual acne lesions.

He said that he sees at least a 30% improvement in inflammatory acne after each treatment, spaced about 4 weeks apart. He has never done more than three treatments on a patient and he has never seen a patient's acne rebound, even years after a final treatment.

"Have I done controlled studies? No," he admitted. "It definitely lasts a long time."

Dr. Goldman explained that he is reassured by animal data, which show that exposure to photodynamic therapy (PDT) actually reduced, and did not increase, the risk of skin cancer ("Photodynamic Therapy" [London: Elsevier, 2005], pp. 53–64).

He says he has biopsied patients and seen a 90% decrease in the size of sebaceous glands after PDT.

He's read the studies that show that ALA-PDT kills bacteria and appears to normalize follicular shedding, and has participated in a study comparing blue light therapy with topical 1% clindamycin solution for inflammatory acne, in which lesions were reduced 34% after blue light therapy, compared with 14% with clindamycin (J. Drugs Dermatol. 2005;4:64–70).

"This is something the pharmaceutical companies do not want us to investigate, because they're going to lose a few billion dollars in acne treatment," he said.

Dr. Goldman disclosed that he has served as a consultant to DUSA Pharmaceuticals, the manufacturer of Levulan Kerastik (ALA) and the BLU-U light source.

LOS CABOS, MEXICO — Dr. Mitchel P. Goldman doesn't accept insurance and says he believes that his cash-only acne patients get more for their money with one to three photodynamic therapy sessions than they do with years of prescriptions for medications, he said at the annual meeting of the Noah Worcester Dermatological Society.

Although he says he knows it sounds heretical—"and maybe you'll strip me of my derm boards"—he has been using the photosensitizing agent 5-aminolevulinic acid (ALA) followed by exposure to a blue-light laser for nearly 4 years and he thinks that there is nothing better for acne. "As soon as insurance companies wake up and realize it's a hell of a lot cheaper to do this than prescribe Accutane—they'll cover it," said Dr. Goldman, a dermatologist in private practice in La Jolla, Calif.

In the meantime, his patients pay $500-$600 for a treatment session that consists of a salicylic acid prep, microdermabrasion of the affected area, a scrub with acetone, 1-hour exposure to ALA (Levulan Kerastik, DUSA Pharmaceuticals), and 10–15 minutes' exposure to a blue light that is approved for the treatment of acne (BLU-U Photodynamic Therapy Illuminator, DUSA Pharmaceuticals Inc.), as well as long-pulse dye laser to individual acne lesions.

He said that he sees at least a 30% improvement in inflammatory acne after each treatment, spaced about 4 weeks apart. He has never done more than three treatments on a patient and he has never seen a patient's acne rebound, even years after a final treatment.

"Have I done controlled studies? No," he admitted. "It definitely lasts a long time."

Dr. Goldman explained that he is reassured by animal data, which show that exposure to photodynamic therapy (PDT) actually reduced, and did not increase, the risk of skin cancer ("Photodynamic Therapy" [London: Elsevier, 2005], pp. 53–64).

He says he has biopsied patients and seen a 90% decrease in the size of sebaceous glands after PDT.

He's read the studies that show that ALA-PDT kills bacteria and appears to normalize follicular shedding, and has participated in a study comparing blue light therapy with topical 1% clindamycin solution for inflammatory acne, in which lesions were reduced 34% after blue light therapy, compared with 14% with clindamycin (J. Drugs Dermatol. 2005;4:64–70).

"This is something the pharmaceutical companies do not want us to investigate, because they're going to lose a few billion dollars in acne treatment," he said.

Dr. Goldman disclosed that he has served as a consultant to DUSA Pharmaceuticals, the manufacturer of Levulan Kerastik (ALA) and the BLU-U light source.

LOS CABOS, MEXICO — Dr. Mitchel P. Goldman doesn't accept insurance and says he believes that his cash-only acne patients get more for their money with one to three photodynamic therapy sessions than they do with years of prescriptions for medications, he said at the annual meeting of the Noah Worcester Dermatological Society.

Although he says he knows it sounds heretical—"and maybe you'll strip me of my derm boards"—he has been using the photosensitizing agent 5-aminolevulinic acid (ALA) followed by exposure to a blue-light laser for nearly 4 years and he thinks that there is nothing better for acne. "As soon as insurance companies wake up and realize it's a hell of a lot cheaper to do this than prescribe Accutane—they'll cover it," said Dr. Goldman, a dermatologist in private practice in La Jolla, Calif.

In the meantime, his patients pay $500-$600 for a treatment session that consists of a salicylic acid prep, microdermabrasion of the affected area, a scrub with acetone, 1-hour exposure to ALA (Levulan Kerastik, DUSA Pharmaceuticals), and 10–15 minutes' exposure to a blue light that is approved for the treatment of acne (BLU-U Photodynamic Therapy Illuminator, DUSA Pharmaceuticals Inc.), as well as long-pulse dye laser to individual acne lesions.

He said that he sees at least a 30% improvement in inflammatory acne after each treatment, spaced about 4 weeks apart. He has never done more than three treatments on a patient and he has never seen a patient's acne rebound, even years after a final treatment.

"Have I done controlled studies? No," he admitted. "It definitely lasts a long time."

Dr. Goldman explained that he is reassured by animal data, which show that exposure to photodynamic therapy (PDT) actually reduced, and did not increase, the risk of skin cancer ("Photodynamic Therapy" [London: Elsevier, 2005], pp. 53–64).

He says he has biopsied patients and seen a 90% decrease in the size of sebaceous glands after PDT.

He's read the studies that show that ALA-PDT kills bacteria and appears to normalize follicular shedding, and has participated in a study comparing blue light therapy with topical 1% clindamycin solution for inflammatory acne, in which lesions were reduced 34% after blue light therapy, compared with 14% with clindamycin (J. Drugs Dermatol. 2005;4:64–70).

"This is something the pharmaceutical companies do not want us to investigate, because they're going to lose a few billion dollars in acne treatment," he said.

Dr. Goldman disclosed that he has served as a consultant to DUSA Pharmaceuticals, the manufacturer of Levulan Kerastik (ALA) and the BLU-U light source.

LOS CABOS, MEXICO — Advances in photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) have led dermatologists to increasingly extol its virtues as a practical, versatile, and highly effective therapy for actinic keratoses, nonmelanoma skin cancer, acne, and photorejuvenation.

For example, at the annual meeting of the Noah Worcester Dermatological Society, several dermatologists described ALA-PDT with a degree of enthusiasm pointedly absent from presentations concerning many new lasers, skin smoothers, and nonablative, all-purpose devices.

"[It has] … changed the way I practice," Dr. C. William Hanke said at the meeting.

Dr. Hanke said he recalled hearing about ALA-PDT at an American Academy of Dermatology meeting 5 years ago. His impression of the therapy then was "how terrible it was. There was a lot of hand-holding … because the patient needed it."

Still, it seemed to work pretty well in eradicating actinic keratoses (AKs), and a 2003 study showed that it had the potential to be equal to 5-fluorouracil in efficacy and was preferred by most patients, despite the painful recovery required after a 14− to 18-hour ALA incubation period and subsequent exposure to a specialized light source (J. Drugs Dermatol. 2003;2:629–35).

Since then, ALA-PDT has changed dramatically in the following ways:

▸ Short-contact ALA-PDT is now standard. ALA remains on the skin just 15–60 minutes, profoundly affecting the side-effect profile and reducing pain. Instead of enduring a week of raw skin, erosions, and inflammation, most patients today note only minor stinging, erythema, and scaling that resolve within a few days. Many studies show that short-contact ALA-PDT does not reduce its effectiveness.

▸ Numerous light sources are being used. Although blue light emits a wavelength (405–420 nm) that conforms precisely to the absorption peak for ALA (marketed as the Levulan Kerastick by DUSA Pharmaceuticals Inc.), intense pulsed light (IPL), pulsed dye lasers, and other light sources also are proving effective.

▸ The versatility of ALA-PDT is expanding. Approved for nonhyperkeratotic AKs of the face and scalp, it also is being used on the trunk and extremities for AKs, nonmelanoma skin cancer, pigmented lesions, rosacea, and, especially, acne.

▸ Competition is on the horizon. An American launch is imminent for the photosensitizer methyl aminolevulinate, marketed as Metvix by the Norwegian company PhotoCure ASA. Widely used in Europe, Metvix is incubated for 3 hours under occlusion and activated by red light (630–660 nm) from a diode laser. Besides treating AKs and nonmelanoma skin cancer, the system is used to treat psoriasis.

Dr. Neil S. Sadick voiced a common complaint when he noted that nonablative therapies have now been used for 5 years to treat everything from rosacea to scars, "and we're still not sure [they're] effective or worth it."

In contrast, he said that IPL, which targets chromophores, has become a mainstay in his practice, "providing the greatest amount of clinical satisfaction, consistently, for [the] patients."

When he's treating more than telangiectasias, age spots, and minimal actinic damage, Dr. Sadick said he relies on ALA to amplify the impact of IPL.

"I can decrease five treatments to two [or] three treatments with IPL … for significant actinic damage. It's not nonablative; I would call it microablative," said Dr. Sadick, who practices in New York City and Great Neck, N.Y.

Dr. Mitchel P. Goldman said short-contact ALA-PDT using IPL is "incredibly impressive" for acne and a convenient and "very mildly painful" option for patients with actinic keratoses, telangiectasias, and skin texture problems. He even used the modality to treat his own facial squamous cell carcinoma.

He uses a pulsed dye laser rather than IPL on hair-bearing areas because IPL can remove hair.

Like Dr. Sadick, Dr. Goldman uses ALA-PDT to "boost" the effectiveness of IPL, reducing the number of treatments required.

After one or two treatments of ALA-PDT with IPL for actinic keratoses, "I think that's when you need to biopsy," said Dr. Goldman, who is in private practice in La Jolla, Calif.

Dr. Hanke, director of a dermatologic surgery practice in Carmel, Ind., says that ALA-PDT has become ever more useful in his practice over time, for cosmetic as well as medical dermatology.

If a patient's goal is to have smoother, clearer skin, with less blotchiness and redness, "we can do that," he said.

There are conditions, such as wrinkles, that do not respond well to ALA-PDT, the speakers agreed. In addition, Dr. Hanke said he was unimpressed by its results in a renal transplant patient with extreme sun damage that included a history of skin cancers and many keratoses.

It also doesn't work for disseminated superficial actinic porokeratosis or granulomatous rosacea, he concluded.

Its record in treating warts is erratic, he said, although he has had luck sometimes by paring the wart down, applying several coats of ALA, and then occluding the wart overnight prior to exposure to a light source.

Dr. Hanke has conducted clinical trials for DUSA Pharmaceuticals. Dr. Goldman has been a consultant for DUSA and for the Luminis LightSheer diode laser system, which can be used for phototherapy. Dr. Sadick has conducted research and/or consulted with Syneron, Thermage Inc., and Omnilux Inc., companies that manufacture lasers and light sources that can be used in phototherapy.

Getting the Most from PDT

The following steps can maximize the effects of ALA-PDT:

1Discontinue topical retinoids several weeks before treatment with 5-aminolevulinic acid photodynamic therapy (ALA-PDT).

2Prepare the skin using gentle microdermabrasion or acetone (to maximize the PDT reaction), or isopropyl alcohol (to minimize the PDT reaction).

3 Use a fresh ampule of Levulan Kerastick (ALA). The drug becomes inactive 4 hours after being opened.

4Apply two coats of ALA with a cotton swab. Take extra care to avoid getting the solution in the patient's eyes.

5Adjust exposure to ALA and to the light or laser source according to the patient's condition and severity. For example, the photosensitizer should remain on the skin 60 minutes prior to PDT for treatment of photoaging. Exposure time will vary: 22–25 minutes for an intense pulsed light source or 16 minutes and 40 seconds for a blue light source.

6Use cool airflow, rest periods, and, possibly, topical anesthesia or diazepam (5–10 mg) for pain management.

7Observe the patient post phototherapy, and wash the area thoroughly with soap and water to ensure that all of the photosensitizer has been removed. Apply sunscreen in the office.

8Be adamant in instructing the patient to avoid sun exposure altogether for 24 hours and to wear heavy sunscreen for 3–4 days. Patients can have extreme reactions to sun exposure in the days following phototherapy.

Source: Dr. Hanke

LOS CABOS, MEXICO — Advances in photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) have led dermatologists to increasingly extol its virtues as a practical, versatile, and highly effective therapy for actinic keratoses, nonmelanoma skin cancer, acne, and photorejuvenation.

For example, at the annual meeting of the Noah Worcester Dermatological Society, several dermatologists described ALA-PDT with a degree of enthusiasm pointedly absent from presentations concerning many new lasers, skin smoothers, and nonablative, all-purpose devices.

"[It has] … changed the way I practice," Dr. C. William Hanke said at the meeting.

Dr. Hanke said he recalled hearing about ALA-PDT at an American Academy of Dermatology meeting 5 years ago. His impression of the therapy then was "how terrible it was. There was a lot of hand-holding … because the patient needed it."

Still, it seemed to work pretty well in eradicating actinic keratoses (AKs), and a 2003 study showed that it had the potential to be equal to 5-fluorouracil in efficacy and was preferred by most patients, despite the painful recovery required after a 14− to 18-hour ALA incubation period and subsequent exposure to a specialized light source (J. Drugs Dermatol. 2003;2:629–35).

Since then, ALA-PDT has changed dramatically in the following ways:

▸ Short-contact ALA-PDT is now standard. ALA remains on the skin just 15–60 minutes, profoundly affecting the side-effect profile and reducing pain. Instead of enduring a week of raw skin, erosions, and inflammation, most patients today note only minor stinging, erythema, and scaling that resolve within a few days. Many studies show that short-contact ALA-PDT does not reduce its effectiveness.

▸ Numerous light sources are being used. Although blue light emits a wavelength (405–420 nm) that conforms precisely to the absorption peak for ALA (marketed as the Levulan Kerastick by DUSA Pharmaceuticals Inc.), intense pulsed light (IPL), pulsed dye lasers, and other light sources also are proving effective.

▸ The versatility of ALA-PDT is expanding. Approved for nonhyperkeratotic AKs of the face and scalp, it also is being used on the trunk and extremities for AKs, nonmelanoma skin cancer, pigmented lesions, rosacea, and, especially, acne.

▸ Competition is on the horizon. An American launch is imminent for the photosensitizer methyl aminolevulinate, marketed as Metvix by the Norwegian company PhotoCure ASA. Widely used in Europe, Metvix is incubated for 3 hours under occlusion and activated by red light (630–660 nm) from a diode laser. Besides treating AKs and nonmelanoma skin cancer, the system is used to treat psoriasis.

Dr. Neil S. Sadick voiced a common complaint when he noted that nonablative therapies have now been used for 5 years to treat everything from rosacea to scars, "and we're still not sure [they're] effective or worth it."

In contrast, he said that IPL, which targets chromophores, has become a mainstay in his practice, "providing the greatest amount of clinical satisfaction, consistently, for [the] patients."

When he's treating more than telangiectasias, age spots, and minimal actinic damage, Dr. Sadick said he relies on ALA to amplify the impact of IPL.

"I can decrease five treatments to two [or] three treatments with IPL … for significant actinic damage. It's not nonablative; I would call it microablative," said Dr. Sadick, who practices in New York City and Great Neck, N.Y.

Dr. Mitchel P. Goldman said short-contact ALA-PDT using IPL is "incredibly impressive" for acne and a convenient and "very mildly painful" option for patients with actinic keratoses, telangiectasias, and skin texture problems. He even used the modality to treat his own facial squamous cell carcinoma.

He uses a pulsed dye laser rather than IPL on hair-bearing areas because IPL can remove hair.

Like Dr. Sadick, Dr. Goldman uses ALA-PDT to "boost" the effectiveness of IPL, reducing the number of treatments required.

After one or two treatments of ALA-PDT with IPL for actinic keratoses, "I think that's when you need to biopsy," said Dr. Goldman, who is in private practice in La Jolla, Calif.

Dr. Hanke, director of a dermatologic surgery practice in Carmel, Ind., says that ALA-PDT has become ever more useful in his practice over time, for cosmetic as well as medical dermatology.

If a patient's goal is to have smoother, clearer skin, with less blotchiness and redness, "we can do that," he said.

There are conditions, such as wrinkles, that do not respond well to ALA-PDT, the speakers agreed. In addition, Dr. Hanke said he was unimpressed by its results in a renal transplant patient with extreme sun damage that included a history of skin cancers and many keratoses.

It also doesn't work for disseminated superficial actinic porokeratosis or granulomatous rosacea, he concluded.

Its record in treating warts is erratic, he said, although he has had luck sometimes by paring the wart down, applying several coats of ALA, and then occluding the wart overnight prior to exposure to a light source.

Dr. Hanke has conducted clinical trials for DUSA Pharmaceuticals. Dr. Goldman has been a consultant for DUSA and for the Luminis LightSheer diode laser system, which can be used for phototherapy. Dr. Sadick has conducted research and/or consulted with Syneron, Thermage Inc., and Omnilux Inc., companies that manufacture lasers and light sources that can be used in phototherapy.

Getting the Most from PDT

The following steps can maximize the effects of ALA-PDT:

1Discontinue topical retinoids several weeks before treatment with 5-aminolevulinic acid photodynamic therapy (ALA-PDT).

2Prepare the skin using gentle microdermabrasion or acetone (to maximize the PDT reaction), or isopropyl alcohol (to minimize the PDT reaction).

3 Use a fresh ampule of Levulan Kerastick (ALA). The drug becomes inactive 4 hours after being opened.

4Apply two coats of ALA with a cotton swab. Take extra care to avoid getting the solution in the patient's eyes.

5Adjust exposure to ALA and to the light or laser source according to the patient's condition and severity. For example, the photosensitizer should remain on the skin 60 minutes prior to PDT for treatment of photoaging. Exposure time will vary: 22–25 minutes for an intense pulsed light source or 16 minutes and 40 seconds for a blue light source.

6Use cool airflow, rest periods, and, possibly, topical anesthesia or diazepam (5–10 mg) for pain management.

7Observe the patient post phototherapy, and wash the area thoroughly with soap and water to ensure that all of the photosensitizer has been removed. Apply sunscreen in the office.

8Be adamant in instructing the patient to avoid sun exposure altogether for 24 hours and to wear heavy sunscreen for 3–4 days. Patients can have extreme reactions to sun exposure in the days following phototherapy.

Source: Dr. Hanke

LOS CABOS, MEXICO — Advances in photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) have led dermatologists to increasingly extol its virtues as a practical, versatile, and highly effective therapy for actinic keratoses, nonmelanoma skin cancer, acne, and photorejuvenation.

For example, at the annual meeting of the Noah Worcester Dermatological Society, several dermatologists described ALA-PDT with a degree of enthusiasm pointedly absent from presentations concerning many new lasers, skin smoothers, and nonablative, all-purpose devices.

"[It has] … changed the way I practice," Dr. C. William Hanke said at the meeting.

Dr. Hanke said he recalled hearing about ALA-PDT at an American Academy of Dermatology meeting 5 years ago. His impression of the therapy then was "how terrible it was. There was a lot of hand-holding … because the patient needed it."

Still, it seemed to work pretty well in eradicating actinic keratoses (AKs), and a 2003 study showed that it had the potential to be equal to 5-fluorouracil in efficacy and was preferred by most patients, despite the painful recovery required after a 14− to 18-hour ALA incubation period and subsequent exposure to a specialized light source (J. Drugs Dermatol. 2003;2:629–35).

Since then, ALA-PDT has changed dramatically in the following ways:

▸ Short-contact ALA-PDT is now standard. ALA remains on the skin just 15–60 minutes, profoundly affecting the side-effect profile and reducing pain. Instead of enduring a week of raw skin, erosions, and inflammation, most patients today note only minor stinging, erythema, and scaling that resolve within a few days. Many studies show that short-contact ALA-PDT does not reduce its effectiveness.

▸ Numerous light sources are being used. Although blue light emits a wavelength (405–420 nm) that conforms precisely to the absorption peak for ALA (marketed as the Levulan Kerastick by DUSA Pharmaceuticals Inc.), intense pulsed light (IPL), pulsed dye lasers, and other light sources also are proving effective.

▸ The versatility of ALA-PDT is expanding. Approved for nonhyperkeratotic AKs of the face and scalp, it also is being used on the trunk and extremities for AKs, nonmelanoma skin cancer, pigmented lesions, rosacea, and, especially, acne.

▸ Competition is on the horizon. An American launch is imminent for the photosensitizer methyl aminolevulinate, marketed as Metvix by the Norwegian company PhotoCure ASA. Widely used in Europe, Metvix is incubated for 3 hours under occlusion and activated by red light (630–660 nm) from a diode laser. Besides treating AKs and nonmelanoma skin cancer, the system is used to treat psoriasis.

Dr. Neil S. Sadick voiced a common complaint when he noted that nonablative therapies have now been used for 5 years to treat everything from rosacea to scars, "and we're still not sure [they're] effective or worth it."

In contrast, he said that IPL, which targets chromophores, has become a mainstay in his practice, "providing the greatest amount of clinical satisfaction, consistently, for [the] patients."

When he's treating more than telangiectasias, age spots, and minimal actinic damage, Dr. Sadick said he relies on ALA to amplify the impact of IPL.

"I can decrease five treatments to two [or] three treatments with IPL … for significant actinic damage. It's not nonablative; I would call it microablative," said Dr. Sadick, who practices in New York City and Great Neck, N.Y.

Dr. Mitchel P. Goldman said short-contact ALA-PDT using IPL is "incredibly impressive" for acne and a convenient and "very mildly painful" option for patients with actinic keratoses, telangiectasias, and skin texture problems. He even used the modality to treat his own facial squamous cell carcinoma.

He uses a pulsed dye laser rather than IPL on hair-bearing areas because IPL can remove hair.

Like Dr. Sadick, Dr. Goldman uses ALA-PDT to "boost" the effectiveness of IPL, reducing the number of treatments required.

After one or two treatments of ALA-PDT with IPL for actinic keratoses, "I think that's when you need to biopsy," said Dr. Goldman, who is in private practice in La Jolla, Calif.

Dr. Hanke, director of a dermatologic surgery practice in Carmel, Ind., says that ALA-PDT has become ever more useful in his practice over time, for cosmetic as well as medical dermatology.

If a patient's goal is to have smoother, clearer skin, with less blotchiness and redness, "we can do that," he said.

There are conditions, such as wrinkles, that do not respond well to ALA-PDT, the speakers agreed. In addition, Dr. Hanke said he was unimpressed by its results in a renal transplant patient with extreme sun damage that included a history of skin cancers and many keratoses.

It also doesn't work for disseminated superficial actinic porokeratosis or granulomatous rosacea, he concluded.

Its record in treating warts is erratic, he said, although he has had luck sometimes by paring the wart down, applying several coats of ALA, and then occluding the wart overnight prior to exposure to a light source.

Dr. Hanke has conducted clinical trials for DUSA Pharmaceuticals. Dr. Goldman has been a consultant for DUSA and for the Luminis LightSheer diode laser system, which can be used for phototherapy. Dr. Sadick has conducted research and/or consulted with Syneron, Thermage Inc., and Omnilux Inc., companies that manufacture lasers and light sources that can be used in phototherapy.

Getting the Most from PDT

The following steps can maximize the effects of ALA-PDT:

1Discontinue topical retinoids several weeks before treatment with 5-aminolevulinic acid photodynamic therapy (ALA-PDT).

2Prepare the skin using gentle microdermabrasion or acetone (to maximize the PDT reaction), or isopropyl alcohol (to minimize the PDT reaction).

3 Use a fresh ampule of Levulan Kerastick (ALA). The drug becomes inactive 4 hours after being opened.

4Apply two coats of ALA with a cotton swab. Take extra care to avoid getting the solution in the patient's eyes.

5Adjust exposure to ALA and to the light or laser source according to the patient's condition and severity. For example, the photosensitizer should remain on the skin 60 minutes prior to PDT for treatment of photoaging. Exposure time will vary: 22–25 minutes for an intense pulsed light source or 16 minutes and 40 seconds for a blue light source.

6Use cool airflow, rest periods, and, possibly, topical anesthesia or diazepam (5–10 mg) for pain management.

7Observe the patient post phototherapy, and wash the area thoroughly with soap and water to ensure that all of the photosensitizer has been removed. Apply sunscreen in the office.

8Be adamant in instructing the patient to avoid sun exposure altogether for 24 hours and to wear heavy sunscreen for 3–4 days. Patients can have extreme reactions to sun exposure in the days following phototherapy.

Source: Dr. Hanke

SANTA BARBARA, CALIF. — Secondary primary melanomas occur in 2.3% of patients, compared with a 1% incidence of primary melanoma in the white population.

That difference is high enough to justify annual skin examinations throughout life for any patient with a history of melanoma, said Dr. June K. Robinson, chief of dermatology at Dartmouth-Hitchcock Medical Center, Hanover, N.H.

The checks should be at shorter intervals in the years immediately following a melanoma diagnosis, she explained at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Patients with stage IA melanoma should receive a history and physical every 6 months for 2 years, then annually, she said. Those with stage IB through stage III should receive a history and physical, chest x-ray, and lactic dehydrogenase (LDH) screen every 3–6 months for 3 years, then every 6–12 months for 2 years, and then annually.

The timing of the examinations is admittedly guesswork, Dr. Robinson said. “More than anything else, you're hand-holding. You're a stable presence for them,” Dr. Robinson said.

An overlooked benefit of follow-up examinations is the opportunity to identify and educate family members who often do not realize that they need to protect themselves and perform regular skin self-examinations.

If a family member accompanies a melanoma survivor to an appointment, Dr. Robinson speaks directly about elevated risk in family members and preventive steps that can be taken.

Patients who come alone can be counseled to speak with their siblings, children, and grandchildren about melanoma risk, tanning booths, sun protection, and the importance of skin self-examination and regular screening, she said.

SANTA BARBARA, CALIF. — Secondary primary melanomas occur in 2.3% of patients, compared with a 1% incidence of primary melanoma in the white population.

That difference is high enough to justify annual skin examinations throughout life for any patient with a history of melanoma, said Dr. June K. Robinson, chief of dermatology at Dartmouth-Hitchcock Medical Center, Hanover, N.H.

The checks should be at shorter intervals in the years immediately following a melanoma diagnosis, she explained at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Patients with stage IA melanoma should receive a history and physical every 6 months for 2 years, then annually, she said. Those with stage IB through stage III should receive a history and physical, chest x-ray, and lactic dehydrogenase (LDH) screen every 3–6 months for 3 years, then every 6–12 months for 2 years, and then annually.

The timing of the examinations is admittedly guesswork, Dr. Robinson said. “More than anything else, you're hand-holding. You're a stable presence for them,” Dr. Robinson said.

An overlooked benefit of follow-up examinations is the opportunity to identify and educate family members who often do not realize that they need to protect themselves and perform regular skin self-examinations.

If a family member accompanies a melanoma survivor to an appointment, Dr. Robinson speaks directly about elevated risk in family members and preventive steps that can be taken.

Patients who come alone can be counseled to speak with their siblings, children, and grandchildren about melanoma risk, tanning booths, sun protection, and the importance of skin self-examination and regular screening, she said.

SANTA BARBARA, CALIF. — Secondary primary melanomas occur in 2.3% of patients, compared with a 1% incidence of primary melanoma in the white population.

That difference is high enough to justify annual skin examinations throughout life for any patient with a history of melanoma, said Dr. June K. Robinson, chief of dermatology at Dartmouth-Hitchcock Medical Center, Hanover, N.H.

The checks should be at shorter intervals in the years immediately following a melanoma diagnosis, she explained at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.

Patients with stage IA melanoma should receive a history and physical every 6 months for 2 years, then annually, she said. Those with stage IB through stage III should receive a history and physical, chest x-ray, and lactic dehydrogenase (LDH) screen every 3–6 months for 3 years, then every 6–12 months for 2 years, and then annually.

The timing of the examinations is admittedly guesswork, Dr. Robinson said. “More than anything else, you're hand-holding. You're a stable presence for them,” Dr. Robinson said.

An overlooked benefit of follow-up examinations is the opportunity to identify and educate family members who often do not realize that they need to protect themselves and perform regular skin self-examinations.

If a family member accompanies a melanoma survivor to an appointment, Dr. Robinson speaks directly about elevated risk in family members and preventive steps that can be taken.

Patients who come alone can be counseled to speak with their siblings, children, and grandchildren about melanoma risk, tanning booths, sun protection, and the importance of skin self-examination and regular screening, she said.