Caroline Helwick

NEW ORLEANS — For Helicobacter pylori infection, a 14-day hybrid therapy that combines sequential and concomitant drug treatments improved the eradication rate, compared with 14-day standard sequential therapy, according to Dr. Ping-I. Hsu.

“Worldwide, the eradication rate with standard triple therapy is less than 80% in intention-to-treat analyses,” Dr. Hsu of Kaohsiung (Taiwan) Veterans General Hospital said at the meeting. Standard triple therapy includes a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole.

“The ideal antimicrobial therapy would have an eradication rate of at least 95% by per-protocol analysis,” which would earn it a grade A score, he said.

In a recent assessment of 15 trials, mean eradication rates were 93% with sequential therapy and less than 95% with concomitant therapy (Gut e-pub June 4, 2010), both of which are grade B results, he noted.

The specific aim of the current study was to investigate whether either extending the duration of sequential therapy to 14 days or a 14-day hybrid regimen that combined sequential and concomitant approaches might increase the eradication rate to at least 95% (grade A) in per-protocol analysis. Subjects had H. pylori infection proven by at least two positive results for the urease test, histology, and urea breath test.

The study was done as two separate pilot studies where 240 patients were randomized to the sequential therapy group, which included esomeprazole 40 mg b.i.d. plus amoxicillin 1 g b.i.d. (EA) for 7 days followed by esomeprazole, clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d. for 7 days, or to hybrid therapy, which included EA for 7 days followed by EA plus clarithromycin and metronidazole for 7 days. Patients were followed to week 8, when they underwent endoscopy with urease testing and histology, or urea breath test.

After excluding patients who had lack of compliance or incomplete follow-up, the final analyses included 115 in the sequential (control) group and 109 in the hybrid therapy group. The groups were similar demographically except for a higher proportion of metronidazole-susceptible patients in the sequential group.

In both the intention-to-treat and per-protocol analysis, the outcomes were superior after hybrid therapy, Dr. Hsu said (see box above).

“The study also showed that simply prolonging the treatment duration of sequential therapy does not achieve a grade A result,” Dr. Hsu pointed out, since a rate of 93% can be achieved with just 10 days of sequential therapy (Clin. Gastroenterol. Hepatol. 2010;8:36–41).

In a univariate analysis of clinical and bacterial factors associated with efficacy, no factors analyzed affected efficacy in the hybrid arm, but the presence of resistant strains reduced the eradication rate in the control arm to 88%.

When patients are resistant to both clarithromycin and metronidazole, 10-day sequential therapy carries only a 33% cure rate, and 14-day sequential therapy has a 75% cure rare; however, with hybrid therapy, amoxicillin administration is prolonged out to 14 days, which can result in a 100% cure rate, he reported.

AstraZeneca provided the study medications, but was not otherwise involved in the study.

The eradication rate was better after hybrid therapy than after standard sequential therapy.

Source DR. HSU

Source Elsevier Global Medical News

NEW ORLEANS — For Helicobacter pylori infection, a 14-day hybrid therapy that combines sequential and concomitant drug treatments improved the eradication rate, compared with 14-day standard sequential therapy, according to Dr. Ping-I. Hsu.

“Worldwide, the eradication rate with standard triple therapy is less than 80% in intention-to-treat analyses,” Dr. Hsu of Kaohsiung (Taiwan) Veterans General Hospital said at the meeting. Standard triple therapy includes a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole.

“The ideal antimicrobial therapy would have an eradication rate of at least 95% by per-protocol analysis,” which would earn it a grade A score, he said.

In a recent assessment of 15 trials, mean eradication rates were 93% with sequential therapy and less than 95% with concomitant therapy (Gut e-pub June 4, 2010), both of which are grade B results, he noted.

The specific aim of the current study was to investigate whether either extending the duration of sequential therapy to 14 days or a 14-day hybrid regimen that combined sequential and concomitant approaches might increase the eradication rate to at least 95% (grade A) in per-protocol analysis. Subjects had H. pylori infection proven by at least two positive results for the urease test, histology, and urea breath test.

The study was done as two separate pilot studies where 240 patients were randomized to the sequential therapy group, which included esomeprazole 40 mg b.i.d. plus amoxicillin 1 g b.i.d. (EA) for 7 days followed by esomeprazole, clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d. for 7 days, or to hybrid therapy, which included EA for 7 days followed by EA plus clarithromycin and metronidazole for 7 days. Patients were followed to week 8, when they underwent endoscopy with urease testing and histology, or urea breath test.

After excluding patients who had lack of compliance or incomplete follow-up, the final analyses included 115 in the sequential (control) group and 109 in the hybrid therapy group. The groups were similar demographically except for a higher proportion of metronidazole-susceptible patients in the sequential group.

In both the intention-to-treat and per-protocol analysis, the outcomes were superior after hybrid therapy, Dr. Hsu said (see box above).

“The study also showed that simply prolonging the treatment duration of sequential therapy does not achieve a grade A result,” Dr. Hsu pointed out, since a rate of 93% can be achieved with just 10 days of sequential therapy (Clin. Gastroenterol. Hepatol. 2010;8:36–41).

In a univariate analysis of clinical and bacterial factors associated with efficacy, no factors analyzed affected efficacy in the hybrid arm, but the presence of resistant strains reduced the eradication rate in the control arm to 88%.

When patients are resistant to both clarithromycin and metronidazole, 10-day sequential therapy carries only a 33% cure rate, and 14-day sequential therapy has a 75% cure rare; however, with hybrid therapy, amoxicillin administration is prolonged out to 14 days, which can result in a 100% cure rate, he reported.

AstraZeneca provided the study medications, but was not otherwise involved in the study.

The eradication rate was better after hybrid therapy than after standard sequential therapy.

Source DR. HSU

Source Elsevier Global Medical News

NEW ORLEANS — For Helicobacter pylori infection, a 14-day hybrid therapy that combines sequential and concomitant drug treatments improved the eradication rate, compared with 14-day standard sequential therapy, according to Dr. Ping-I. Hsu.

“Worldwide, the eradication rate with standard triple therapy is less than 80% in intention-to-treat analyses,” Dr. Hsu of Kaohsiung (Taiwan) Veterans General Hospital said at the meeting. Standard triple therapy includes a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole.

“The ideal antimicrobial therapy would have an eradication rate of at least 95% by per-protocol analysis,” which would earn it a grade A score, he said.

In a recent assessment of 15 trials, mean eradication rates were 93% with sequential therapy and less than 95% with concomitant therapy (Gut e-pub June 4, 2010), both of which are grade B results, he noted.

The specific aim of the current study was to investigate whether either extending the duration of sequential therapy to 14 days or a 14-day hybrid regimen that combined sequential and concomitant approaches might increase the eradication rate to at least 95% (grade A) in per-protocol analysis. Subjects had H. pylori infection proven by at least two positive results for the urease test, histology, and urea breath test.

The study was done as two separate pilot studies where 240 patients were randomized to the sequential therapy group, which included esomeprazole 40 mg b.i.d. plus amoxicillin 1 g b.i.d. (EA) for 7 days followed by esomeprazole, clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d. for 7 days, or to hybrid therapy, which included EA for 7 days followed by EA plus clarithromycin and metronidazole for 7 days. Patients were followed to week 8, when they underwent endoscopy with urease testing and histology, or urea breath test.

After excluding patients who had lack of compliance or incomplete follow-up, the final analyses included 115 in the sequential (control) group and 109 in the hybrid therapy group. The groups were similar demographically except for a higher proportion of metronidazole-susceptible patients in the sequential group.

In both the intention-to-treat and per-protocol analysis, the outcomes were superior after hybrid therapy, Dr. Hsu said (see box above).

“The study also showed that simply prolonging the treatment duration of sequential therapy does not achieve a grade A result,” Dr. Hsu pointed out, since a rate of 93% can be achieved with just 10 days of sequential therapy (Clin. Gastroenterol. Hepatol. 2010;8:36–41).

In a univariate analysis of clinical and bacterial factors associated with efficacy, no factors analyzed affected efficacy in the hybrid arm, but the presence of resistant strains reduced the eradication rate in the control arm to 88%.

When patients are resistant to both clarithromycin and metronidazole, 10-day sequential therapy carries only a 33% cure rate, and 14-day sequential therapy has a 75% cure rare; however, with hybrid therapy, amoxicillin administration is prolonged out to 14 days, which can result in a 100% cure rate, he reported.

AstraZeneca provided the study medications, but was not otherwise involved in the study.

The eradication rate was better after hybrid therapy than after standard sequential therapy.

Source DR. HSU

Source Elsevier Global Medical News

NEW ORLEANS — Adverse effects attributed to proton pump inhibitors, including a risk for adverse interactions with clopidogrel, have probably been overstated.

Dr. Michael F. Vaezi, professor of medicine and clinical director of the division of gastroenterology at Vanderbilt University Medical Center in Nashville, Tenn., told attendees that although there are “interesting epidemiologic associations” that may have “some biologic plausibility,” the associations are weak in magnitude and are based on inconsistent findings from heterogeneous studies with a high potential for confounding.

Issues With Clopidogrel

The potential for an interaction with clopidogrel—that is, whether PPIs (specifically, omeprazole and esomeprazole) inhibit the anticoagulation effect of clopidogrel so that it is less effective in preventing cardiovascular injury—has been a “huge issue,” because cardiologists, or patients themselves, are discontinuing proton pump inhibitors (PPIs) that they were using for reflux disease.

A number of studies have suggested harmful interactions, Dr. Vaezi said. One study showed a reduction in the platelet reactivity index, indicating poor response to clopidogrel, in 61% of patients who received omeprazole vs. 26% of patients in a placebo group, a highly significant difference (J. Am. Coll. Cardiol. 2008;51:256-60). In a retrospective Department of Veterans Affairs cohort study, all-cause mortality was significantly increased in patients on PPIs plus clopidogrel vs. clopidogrel alone (JAMA 2009;301:937-44).

But a recent meta-analysis of 23 studies on this topic, involving 93,278 patients, showed no excess risk for cardiovascular events for PPIs that were used with clopidogrel in observational studies (odds ratio, 1.15) among propensity-matched or randomized-trial participants (Aliment. Pharmacol. Ther. 2010;31:810-23). No significant association was found between PPI use and overall mortality, noted Dr. Vaezi.

“The most recent analysis asked the right question: If you are not on a PPI but are on clopidogrel, what is the risk of bleeding?” he said. A recent study examined a database of more than 20,000 patients (including 7,593 concurrent users of clopidogrel and PPIs) who were hospitalized for gastroduodenal bleeding and serious cardiovascular disease (Ann. Intern. Med. 2010;152:337-45). The adjusted incidence of hospitalization for bleeding in concurrent users was 50% lower than it was in nonusers of PPIs who were taking clopidogrel. For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 per 1,000 person-years, the study found.

The authors concluded that in patients with serious coronary heart disease that was treated with clopidogrel, concurrent PPI use was associated with reduced hospitalizations for gastroduodenal bleeding, and the corresponding point estimate for serious cardiovascular disease was not increased.

“But we are left with the [Food and Drug Administration] warnings about using omeprazole and esomeprazole, though the data are not strong,” Dr. Vaezi maintained. In his practice, he keeps patients on omeprazole and clopidogrel and prefers not to switch to another PPI, having observed that some such patients stop responding to PPIs altogether. It may be prudent, however, to give one drug at night and the other in the morning, he added.

Hip Fracture

PPIs have been associated with a risk for hip fracture, but a nested, case-control study from the U.K. General Practice Research Database, including 13,556 cases and 135,386 controls, showed an odds ratio of approximately 2.0 in the crude analysis, and approximately 1.5 in the adjusted analysis (JAMA 2006;296:2947-53). However, when others analyzed this study and excluded patients with baseline risk factors for fracture, they observed no increased risk among PPI users (Pharmacotherapy 2008;28:951-9).

“If anything, patients who were on PPIs the longest were somewhat protected,” Dr. Vaezi noted. He added that other studies have found that the extended use of PPIs, and also use of H₂ receptor blockers, is associated with reduced risk—which are interesting findings that are inconsistent with the concept of harm from PPIs, he maintained. However, despite the negative association the FDA most recently has decided to revise the warnings and precautions section of the prescription labeling as well as the OTC drug facts label for proton pump inhibitors to warn about the potential increased risk of fractures of hip, wrist and spine.

The most recent study, based on the Manitoba Bone Mineral Density Database, showed that 5 years of PPI use posed no risk for adverse effects to the hip or spine (Tarstroenterology 2010;138:896-904), he said. Analyses of associations with pneumonia and anemia also point to weak effects, he added.

Disclosures: Dr. Vaezi reported receiving research funds and consulting fees from Takeda Pharmaceutical Co., and research funds from AstraZeneca.

NEW ORLEANS — Adverse effects attributed to proton pump inhibitors, including a risk for adverse interactions with clopidogrel, have probably been overstated.

Dr. Michael F. Vaezi, professor of medicine and clinical director of the division of gastroenterology at Vanderbilt University Medical Center in Nashville, Tenn., told attendees that although there are “interesting epidemiologic associations” that may have “some biologic plausibility,” the associations are weak in magnitude and are based on inconsistent findings from heterogeneous studies with a high potential for confounding.

Issues With Clopidogrel

The potential for an interaction with clopidogrel—that is, whether PPIs (specifically, omeprazole and esomeprazole) inhibit the anticoagulation effect of clopidogrel so that it is less effective in preventing cardiovascular injury—has been a “huge issue,” because cardiologists, or patients themselves, are discontinuing proton pump inhibitors (PPIs) that they were using for reflux disease.

A number of studies have suggested harmful interactions, Dr. Vaezi said. One study showed a reduction in the platelet reactivity index, indicating poor response to clopidogrel, in 61% of patients who received omeprazole vs. 26% of patients in a placebo group, a highly significant difference (J. Am. Coll. Cardiol. 2008;51:256-60). In a retrospective Department of Veterans Affairs cohort study, all-cause mortality was significantly increased in patients on PPIs plus clopidogrel vs. clopidogrel alone (JAMA 2009;301:937-44).

But a recent meta-analysis of 23 studies on this topic, involving 93,278 patients, showed no excess risk for cardiovascular events for PPIs that were used with clopidogrel in observational studies (odds ratio, 1.15) among propensity-matched or randomized-trial participants (Aliment. Pharmacol. Ther. 2010;31:810-23). No significant association was found between PPI use and overall mortality, noted Dr. Vaezi.

“The most recent analysis asked the right question: If you are not on a PPI but are on clopidogrel, what is the risk of bleeding?” he said. A recent study examined a database of more than 20,000 patients (including 7,593 concurrent users of clopidogrel and PPIs) who were hospitalized for gastroduodenal bleeding and serious cardiovascular disease (Ann. Intern. Med. 2010;152:337-45). The adjusted incidence of hospitalization for bleeding in concurrent users was 50% lower than it was in nonusers of PPIs who were taking clopidogrel. For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 per 1,000 person-years, the study found.

The authors concluded that in patients with serious coronary heart disease that was treated with clopidogrel, concurrent PPI use was associated with reduced hospitalizations for gastroduodenal bleeding, and the corresponding point estimate for serious cardiovascular disease was not increased.

“But we are left with the [Food and Drug Administration] warnings about using omeprazole and esomeprazole, though the data are not strong,” Dr. Vaezi maintained. In his practice, he keeps patients on omeprazole and clopidogrel and prefers not to switch to another PPI, having observed that some such patients stop responding to PPIs altogether. It may be prudent, however, to give one drug at night and the other in the morning, he added.

Hip Fracture

PPIs have been associated with a risk for hip fracture, but a nested, case-control study from the U.K. General Practice Research Database, including 13,556 cases and 135,386 controls, showed an odds ratio of approximately 2.0 in the crude analysis, and approximately 1.5 in the adjusted analysis (JAMA 2006;296:2947-53). However, when others analyzed this study and excluded patients with baseline risk factors for fracture, they observed no increased risk among PPI users (Pharmacotherapy 2008;28:951-9).

“If anything, patients who were on PPIs the longest were somewhat protected,” Dr. Vaezi noted. He added that other studies have found that the extended use of PPIs, and also use of H₂ receptor blockers, is associated with reduced risk—which are interesting findings that are inconsistent with the concept of harm from PPIs, he maintained. However, despite the negative association the FDA most recently has decided to revise the warnings and precautions section of the prescription labeling as well as the OTC drug facts label for proton pump inhibitors to warn about the potential increased risk of fractures of hip, wrist and spine.

The most recent study, based on the Manitoba Bone Mineral Density Database, showed that 5 years of PPI use posed no risk for adverse effects to the hip or spine (Tarstroenterology 2010;138:896-904), he said. Analyses of associations with pneumonia and anemia also point to weak effects, he added.

Disclosures: Dr. Vaezi reported receiving research funds and consulting fees from Takeda Pharmaceutical Co., and research funds from AstraZeneca.

NEW ORLEANS — Adverse effects attributed to proton pump inhibitors, including a risk for adverse interactions with clopidogrel, have probably been overstated.

Dr. Michael F. Vaezi, professor of medicine and clinical director of the division of gastroenterology at Vanderbilt University Medical Center in Nashville, Tenn., told attendees that although there are “interesting epidemiologic associations” that may have “some biologic plausibility,” the associations are weak in magnitude and are based on inconsistent findings from heterogeneous studies with a high potential for confounding.

Issues With Clopidogrel

The potential for an interaction with clopidogrel—that is, whether PPIs (specifically, omeprazole and esomeprazole) inhibit the anticoagulation effect of clopidogrel so that it is less effective in preventing cardiovascular injury—has been a “huge issue,” because cardiologists, or patients themselves, are discontinuing proton pump inhibitors (PPIs) that they were using for reflux disease.

A number of studies have suggested harmful interactions, Dr. Vaezi said. One study showed a reduction in the platelet reactivity index, indicating poor response to clopidogrel, in 61% of patients who received omeprazole vs. 26% of patients in a placebo group, a highly significant difference (J. Am. Coll. Cardiol. 2008;51:256-60). In a retrospective Department of Veterans Affairs cohort study, all-cause mortality was significantly increased in patients on PPIs plus clopidogrel vs. clopidogrel alone (JAMA 2009;301:937-44).

But a recent meta-analysis of 23 studies on this topic, involving 93,278 patients, showed no excess risk for cardiovascular events for PPIs that were used with clopidogrel in observational studies (odds ratio, 1.15) among propensity-matched or randomized-trial participants (Aliment. Pharmacol. Ther. 2010;31:810-23). No significant association was found between PPI use and overall mortality, noted Dr. Vaezi.

“The most recent analysis asked the right question: If you are not on a PPI but are on clopidogrel, what is the risk of bleeding?” he said. A recent study examined a database of more than 20,000 patients (including 7,593 concurrent users of clopidogrel and PPIs) who were hospitalized for gastroduodenal bleeding and serious cardiovascular disease (Ann. Intern. Med. 2010;152:337-45). The adjusted incidence of hospitalization for bleeding in concurrent users was 50% lower than it was in nonusers of PPIs who were taking clopidogrel. For patients at highest risk for bleeding, PPI use was associated with an absolute reduction of 28.5 per 1,000 person-years, the study found.

The authors concluded that in patients with serious coronary heart disease that was treated with clopidogrel, concurrent PPI use was associated with reduced hospitalizations for gastroduodenal bleeding, and the corresponding point estimate for serious cardiovascular disease was not increased.

“But we are left with the [Food and Drug Administration] warnings about using omeprazole and esomeprazole, though the data are not strong,” Dr. Vaezi maintained. In his practice, he keeps patients on omeprazole and clopidogrel and prefers not to switch to another PPI, having observed that some such patients stop responding to PPIs altogether. It may be prudent, however, to give one drug at night and the other in the morning, he added.

Hip Fracture

PPIs have been associated with a risk for hip fracture, but a nested, case-control study from the U.K. General Practice Research Database, including 13,556 cases and 135,386 controls, showed an odds ratio of approximately 2.0 in the crude analysis, and approximately 1.5 in the adjusted analysis (JAMA 2006;296:2947-53). However, when others analyzed this study and excluded patients with baseline risk factors for fracture, they observed no increased risk among PPI users (Pharmacotherapy 2008;28:951-9).

“If anything, patients who were on PPIs the longest were somewhat protected,” Dr. Vaezi noted. He added that other studies have found that the extended use of PPIs, and also use of H₂ receptor blockers, is associated with reduced risk—which are interesting findings that are inconsistent with the concept of harm from PPIs, he maintained. However, despite the negative association the FDA most recently has decided to revise the warnings and precautions section of the prescription labeling as well as the OTC drug facts label for proton pump inhibitors to warn about the potential increased risk of fractures of hip, wrist and spine.

The most recent study, based on the Manitoba Bone Mineral Density Database, showed that 5 years of PPI use posed no risk for adverse effects to the hip or spine (Tarstroenterology 2010;138:896-904), he said. Analyses of associations with pneumonia and anemia also point to weak effects, he added.

Disclosures: Dr. Vaezi reported receiving research funds and consulting fees from Takeda Pharmaceutical Co., and research funds from AstraZeneca.

NEW ORLEANS — For the treatment of pediatric brain cancer, more than 25% of radiation oncologists said they would not expect parents to partake in decision making for scenarios with a high risk for neurocognitive impairment, according to a study by Dr. Robert Olson, a resident in radiation oncology at the University of British Columbia in Vancouver.

“Cure rates for pediatric cancers have risen, but at the cost of increased late effects. Historically, physicians have decided on the trade-off between cure and late effects. More recently, patients' right to choose their own risk/benefit ratio has been accepted in adult oncology, but it is less accepted in pediatric oncology, and oncologists' views about joint decision making have not been well evaluated,” Dr. Olson said at the meeting.

The survey, developed by the British Columbia Cancer Agency, collected demographic information, practice patterns, and views on informed consent and joint decision making from 56 oncologists, 84% of whom were radiation oncologists. They primarily practiced in the United States (39%), Canada (30%), and Europe (25%), for a mean of 19 years.

Shared decision making was defined as a process in which the patient and the clinician share information with each other, take steps to participate in the process, and agree on a course of action. Patients can delegate the decision to the physician, but would share in the discussion first, Dr. Olson noted.

Several hypothetical cases were presented to illustrate the difficulty in quantifying the risk/benefit ratio and the complexity of discussions.

The first case involved a 5-year-old boy with metastatic medulloblastoma to the craniospinal axis for which radiation treatment would likely cause severe cognitive impairment. In this scenario, 100% of respondents said they would discuss cognitive side effects with the parents, and 84% said they would find these discussions stressful. The more complicated scenario was case number two, involving a 4-year-old boy with a completely excised medulloblastoma that was confined to the posterior fossa. The treatment choices were radiotherapy with minimally intense chemotherapy, which offered an 80%-90% chance of cure but a high risk of neurocognitive impairment, and high-dose chemotherapy with stem cell rescue, which offered a 40%-70% chance of cure but a low risk for neurocognitive impairment. For treatment, 84% of respondents chose radiotherapy, which could be partly explained by the fact that most responders were radiation oncologists.

For this scenario, 72% of respondents indicated that there was a role for joint decision making with parents, whereas 23% felt there was not. Their answers did not differ significantly according to age, sex, country, years in practice, time spent with patients, and number of new patients per year.

The oncologists' comments for this scenario included: “Parents must have a say and a choice of treatment”; “Clinicians should guide but not burden the parents to decide”; and “It is important not to make the parents the final deciders, as they may well carry significant guilt if there are adverse outcomes.”

“It is worrisome that only [three-quarters or less] of oncologists feel that parents should have a say in these treatment decisions,” Dr. Olson remarked, “but, still, there has been a shift toward shared decision making compared to a time when parents were not often given a say at all.”

NEW ORLEANS — For the treatment of pediatric brain cancer, more than 25% of radiation oncologists said they would not expect parents to partake in decision making for scenarios with a high risk for neurocognitive impairment, according to a study by Dr. Robert Olson, a resident in radiation oncology at the University of British Columbia in Vancouver.

“Cure rates for pediatric cancers have risen, but at the cost of increased late effects. Historically, physicians have decided on the trade-off between cure and late effects. More recently, patients' right to choose their own risk/benefit ratio has been accepted in adult oncology, but it is less accepted in pediatric oncology, and oncologists' views about joint decision making have not been well evaluated,” Dr. Olson said at the meeting.

The survey, developed by the British Columbia Cancer Agency, collected demographic information, practice patterns, and views on informed consent and joint decision making from 56 oncologists, 84% of whom were radiation oncologists. They primarily practiced in the United States (39%), Canada (30%), and Europe (25%), for a mean of 19 years.

Shared decision making was defined as a process in which the patient and the clinician share information with each other, take steps to participate in the process, and agree on a course of action. Patients can delegate the decision to the physician, but would share in the discussion first, Dr. Olson noted.

Several hypothetical cases were presented to illustrate the difficulty in quantifying the risk/benefit ratio and the complexity of discussions.

The first case involved a 5-year-old boy with metastatic medulloblastoma to the craniospinal axis for which radiation treatment would likely cause severe cognitive impairment. In this scenario, 100% of respondents said they would discuss cognitive side effects with the parents, and 84% said they would find these discussions stressful. The more complicated scenario was case number two, involving a 4-year-old boy with a completely excised medulloblastoma that was confined to the posterior fossa. The treatment choices were radiotherapy with minimally intense chemotherapy, which offered an 80%-90% chance of cure but a high risk of neurocognitive impairment, and high-dose chemotherapy with stem cell rescue, which offered a 40%-70% chance of cure but a low risk for neurocognitive impairment. For treatment, 84% of respondents chose radiotherapy, which could be partly explained by the fact that most responders were radiation oncologists.

For this scenario, 72% of respondents indicated that there was a role for joint decision making with parents, whereas 23% felt there was not. Their answers did not differ significantly according to age, sex, country, years in practice, time spent with patients, and number of new patients per year.

The oncologists' comments for this scenario included: “Parents must have a say and a choice of treatment”; “Clinicians should guide but not burden the parents to decide”; and “It is important not to make the parents the final deciders, as they may well carry significant guilt if there are adverse outcomes.”

“It is worrisome that only [three-quarters or less] of oncologists feel that parents should have a say in these treatment decisions,” Dr. Olson remarked, “but, still, there has been a shift toward shared decision making compared to a time when parents were not often given a say at all.”

NEW ORLEANS — For the treatment of pediatric brain cancer, more than 25% of radiation oncologists said they would not expect parents to partake in decision making for scenarios with a high risk for neurocognitive impairment, according to a study by Dr. Robert Olson, a resident in radiation oncology at the University of British Columbia in Vancouver.

“Cure rates for pediatric cancers have risen, but at the cost of increased late effects. Historically, physicians have decided on the trade-off between cure and late effects. More recently, patients' right to choose their own risk/benefit ratio has been accepted in adult oncology, but it is less accepted in pediatric oncology, and oncologists' views about joint decision making have not been well evaluated,” Dr. Olson said at the meeting.

The survey, developed by the British Columbia Cancer Agency, collected demographic information, practice patterns, and views on informed consent and joint decision making from 56 oncologists, 84% of whom were radiation oncologists. They primarily practiced in the United States (39%), Canada (30%), and Europe (25%), for a mean of 19 years.

Shared decision making was defined as a process in which the patient and the clinician share information with each other, take steps to participate in the process, and agree on a course of action. Patients can delegate the decision to the physician, but would share in the discussion first, Dr. Olson noted.

Several hypothetical cases were presented to illustrate the difficulty in quantifying the risk/benefit ratio and the complexity of discussions.

The first case involved a 5-year-old boy with metastatic medulloblastoma to the craniospinal axis for which radiation treatment would likely cause severe cognitive impairment. In this scenario, 100% of respondents said they would discuss cognitive side effects with the parents, and 84% said they would find these discussions stressful. The more complicated scenario was case number two, involving a 4-year-old boy with a completely excised medulloblastoma that was confined to the posterior fossa. The treatment choices were radiotherapy with minimally intense chemotherapy, which offered an 80%-90% chance of cure but a high risk of neurocognitive impairment, and high-dose chemotherapy with stem cell rescue, which offered a 40%-70% chance of cure but a low risk for neurocognitive impairment. For treatment, 84% of respondents chose radiotherapy, which could be partly explained by the fact that most responders were radiation oncologists.

For this scenario, 72% of respondents indicated that there was a role for joint decision making with parents, whereas 23% felt there was not. Their answers did not differ significantly according to age, sex, country, years in practice, time spent with patients, and number of new patients per year.

The oncologists' comments for this scenario included: “Parents must have a say and a choice of treatment”; “Clinicians should guide but not burden the parents to decide”; and “It is important not to make the parents the final deciders, as they may well carry significant guilt if there are adverse outcomes.”

“It is worrisome that only [three-quarters or less] of oncologists feel that parents should have a say in these treatment decisions,” Dr. Olson remarked, “but, still, there has been a shift toward shared decision making compared to a time when parents were not often given a say at all.”

NEW ORLEANS — More than 50 genetic risk factors for ulcerative colitis have now been identified by the International Inflammatory Bowel Disease Genetics Consortium, said John D. Rioux, Ph.D.

“The work of the International IBD Consortium has dramatically increased the number of known UC [ulcerative colitis] loci and is expected to significantly increase our understanding of disease pathogenesis that relates to both shared and UC-specific inflammatory pathways,” said Dr. Rioux of the University of Montreal. The Consortium spans 15 countries and employs over 80 clinical and basic researchers.

Genome-wide association (GWA) studies analyze “hundreds of thousands of genetic variants for thousands of patients and controls” to identify genetic risk factors, he said.

GWA studies have identified genetic risk factors for Crohn's disease.

While individual studies have been successful, the statistical power for gene discovery is limited by sample size.

The larger the sample size, the greater the number of genetic risk factors identified, he noted.

Previously, the Consortium performed one of the first studies to combine GWA results, and identified more than 30 risk factors for Crohn's disease.

“At that time, much less was known about the genetics of UC, with only the MHC and the IL23R gene having confirmed associations.

In the last year, multiple GWAs of UC have been done and have produced 18 independent new associations.

“These studies provided a unique opportunity to identify a much more complete catalog of genetic risk factors,” he said.

In the current study, results from six GWA studies of UC were combined in a meta-analysis.

Data from 6,433 patients with UC and 20,999 population controls from North America and Europe were combined into a dataset.

“Out of nearly millions of polymorphisms examined,” the tests ultimately revealed 75 independent genomic regions significantly associated with UC.

In preliminary investigations, the meta-analysis has confirmed 18 known UC loci, 21 novel loci, and 4 nominally significant loci (which investigators expect to become significant upon further analyses), for a total of 43 genetic risk factors to date.

Another 26 genetic risk factors are being studied but have not yet been replicated.

“Many of the UC genetic risk factors are shared with Crohn's disease—nearly 50%—as well as other inflammatory diseases,” he noted.

The other inflammatory diseases include psoriasis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, and others.

“We predict there are at least 52 loci associated with UC, about 50% of which are shared with Crohn's disease and about 25% with other inflammatory diagnoses.

“The remainder appear to be UC-specific,” he said.

“The research into the genetics of ulcerative colitis has highlighted the similarities and differences between ulcerative colitis and Crohn's disease, said Dr. María T. Abreu in an interview.

“It shows us some of the explanations for why patients with ulcerative colitis who have a J-pouch [also called an ileal pouch–anal anastomosis] may ultimately develop Crohn's disease,” said Dr. Abreu, professor of medicine and chief, division of gastroenterology, University of Miami.

The Consortium is currently testing all novel loci in an independent set of 10,000 UC patients and a similar number of population controls to confirm these findings, but even the preliminary results provide “convincing evidence,” he said, of associations to genes of biological significance to disease pathogenesis: TNFRSF14, JAK2, CARD9 and others.

An analysis of the literature suggests that novel UC genes pinpoint potential molecular mechanisms.

“In other words, each new UC gene contributes to the puzzle,” he said.

For example, ETS1 on chromosome 11 has a profound impact on Th1 immune responses. DAP (death-associated protein) on chromosome 5 modulates mTOR (mammalian target of rapamycin) activity. WSB1 on chromosome 17 is a hedgehog-inducible ubiquitin ligase, and its loss results in spontaneous intestinal inflammation.

“We can begin to put these into biological pathways.

Many genes in these pathways protect or predispose to disease and we can identify novel targets and appropriate genetic testing within the context of clinical trials and patient selection,” he said.

“Our work,” he added, “has just begun.”

'We predict there are at least 52 loci associated with UC.'

Source DR. RIOUX

NEW ORLEANS — More than 50 genetic risk factors for ulcerative colitis have now been identified by the International Inflammatory Bowel Disease Genetics Consortium, said John D. Rioux, Ph.D.

“The work of the International IBD Consortium has dramatically increased the number of known UC [ulcerative colitis] loci and is expected to significantly increase our understanding of disease pathogenesis that relates to both shared and UC-specific inflammatory pathways,” said Dr. Rioux of the University of Montreal. The Consortium spans 15 countries and employs over 80 clinical and basic researchers.

Genome-wide association (GWA) studies analyze “hundreds of thousands of genetic variants for thousands of patients and controls” to identify genetic risk factors, he said.

GWA studies have identified genetic risk factors for Crohn's disease.

While individual studies have been successful, the statistical power for gene discovery is limited by sample size.

The larger the sample size, the greater the number of genetic risk factors identified, he noted.

Previously, the Consortium performed one of the first studies to combine GWA results, and identified more than 30 risk factors for Crohn's disease.

“At that time, much less was known about the genetics of UC, with only the MHC and the IL23R gene having confirmed associations.

In the last year, multiple GWAs of UC have been done and have produced 18 independent new associations.

“These studies provided a unique opportunity to identify a much more complete catalog of genetic risk factors,” he said.

In the current study, results from six GWA studies of UC were combined in a meta-analysis.

Data from 6,433 patients with UC and 20,999 population controls from North America and Europe were combined into a dataset.

“Out of nearly millions of polymorphisms examined,” the tests ultimately revealed 75 independent genomic regions significantly associated with UC.

In preliminary investigations, the meta-analysis has confirmed 18 known UC loci, 21 novel loci, and 4 nominally significant loci (which investigators expect to become significant upon further analyses), for a total of 43 genetic risk factors to date.

Another 26 genetic risk factors are being studied but have not yet been replicated.

“Many of the UC genetic risk factors are shared with Crohn's disease—nearly 50%—as well as other inflammatory diseases,” he noted.

The other inflammatory diseases include psoriasis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, and others.

“We predict there are at least 52 loci associated with UC, about 50% of which are shared with Crohn's disease and about 25% with other inflammatory diagnoses.

“The remainder appear to be UC-specific,” he said.

“The research into the genetics of ulcerative colitis has highlighted the similarities and differences between ulcerative colitis and Crohn's disease, said Dr. María T. Abreu in an interview.

“It shows us some of the explanations for why patients with ulcerative colitis who have a J-pouch [also called an ileal pouch–anal anastomosis] may ultimately develop Crohn's disease,” said Dr. Abreu, professor of medicine and chief, division of gastroenterology, University of Miami.

The Consortium is currently testing all novel loci in an independent set of 10,000 UC patients and a similar number of population controls to confirm these findings, but even the preliminary results provide “convincing evidence,” he said, of associations to genes of biological significance to disease pathogenesis: TNFRSF14, JAK2, CARD9 and others.

An analysis of the literature suggests that novel UC genes pinpoint potential molecular mechanisms.

“In other words, each new UC gene contributes to the puzzle,” he said.

For example, ETS1 on chromosome 11 has a profound impact on Th1 immune responses. DAP (death-associated protein) on chromosome 5 modulates mTOR (mammalian target of rapamycin) activity. WSB1 on chromosome 17 is a hedgehog-inducible ubiquitin ligase, and its loss results in spontaneous intestinal inflammation.

“We can begin to put these into biological pathways.

Many genes in these pathways protect or predispose to disease and we can identify novel targets and appropriate genetic testing within the context of clinical trials and patient selection,” he said.

“Our work,” he added, “has just begun.”

'We predict there are at least 52 loci associated with UC.'

Source DR. RIOUX

NEW ORLEANS — More than 50 genetic risk factors for ulcerative colitis have now been identified by the International Inflammatory Bowel Disease Genetics Consortium, said John D. Rioux, Ph.D.

“The work of the International IBD Consortium has dramatically increased the number of known UC [ulcerative colitis] loci and is expected to significantly increase our understanding of disease pathogenesis that relates to both shared and UC-specific inflammatory pathways,” said Dr. Rioux of the University of Montreal. The Consortium spans 15 countries and employs over 80 clinical and basic researchers.

Genome-wide association (GWA) studies analyze “hundreds of thousands of genetic variants for thousands of patients and controls” to identify genetic risk factors, he said.

GWA studies have identified genetic risk factors for Crohn's disease.

While individual studies have been successful, the statistical power for gene discovery is limited by sample size.

The larger the sample size, the greater the number of genetic risk factors identified, he noted.

Previously, the Consortium performed one of the first studies to combine GWA results, and identified more than 30 risk factors for Crohn's disease.

“At that time, much less was known about the genetics of UC, with only the MHC and the IL23R gene having confirmed associations.

In the last year, multiple GWAs of UC have been done and have produced 18 independent new associations.

“These studies provided a unique opportunity to identify a much more complete catalog of genetic risk factors,” he said.

In the current study, results from six GWA studies of UC were combined in a meta-analysis.

Data from 6,433 patients with UC and 20,999 population controls from North America and Europe were combined into a dataset.

“Out of nearly millions of polymorphisms examined,” the tests ultimately revealed 75 independent genomic regions significantly associated with UC.

In preliminary investigations, the meta-analysis has confirmed 18 known UC loci, 21 novel loci, and 4 nominally significant loci (which investigators expect to become significant upon further analyses), for a total of 43 genetic risk factors to date.

Another 26 genetic risk factors are being studied but have not yet been replicated.

“Many of the UC genetic risk factors are shared with Crohn's disease—nearly 50%—as well as other inflammatory diseases,” he noted.

The other inflammatory diseases include psoriasis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, and others.

“We predict there are at least 52 loci associated with UC, about 50% of which are shared with Crohn's disease and about 25% with other inflammatory diagnoses.

“The remainder appear to be UC-specific,” he said.

“The research into the genetics of ulcerative colitis has highlighted the similarities and differences between ulcerative colitis and Crohn's disease, said Dr. María T. Abreu in an interview.

“It shows us some of the explanations for why patients with ulcerative colitis who have a J-pouch [also called an ileal pouch–anal anastomosis] may ultimately develop Crohn's disease,” said Dr. Abreu, professor of medicine and chief, division of gastroenterology, University of Miami.

The Consortium is currently testing all novel loci in an independent set of 10,000 UC patients and a similar number of population controls to confirm these findings, but even the preliminary results provide “convincing evidence,” he said, of associations to genes of biological significance to disease pathogenesis: TNFRSF14, JAK2, CARD9 and others.

An analysis of the literature suggests that novel UC genes pinpoint potential molecular mechanisms.

“In other words, each new UC gene contributes to the puzzle,” he said.

For example, ETS1 on chromosome 11 has a profound impact on Th1 immune responses. DAP (death-associated protein) on chromosome 5 modulates mTOR (mammalian target of rapamycin) activity. WSB1 on chromosome 17 is a hedgehog-inducible ubiquitin ligase, and its loss results in spontaneous intestinal inflammation.

“We can begin to put these into biological pathways.

Many genes in these pathways protect or predispose to disease and we can identify novel targets and appropriate genetic testing within the context of clinical trials and patient selection,” he said.

“Our work,” he added, “has just begun.”

'We predict there are at least 52 loci associated with UC.'

Source DR. RIOUX

Major Finding: Of 76 patients who had unverified indications for a PPI, 11 were able to discontinue therapy without recurrence of symptoms during the 6 months of follow-up.

Data Source: A standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark.

Disclosures: Dr. Bytzer is a speaker or consultant for AstraZeneca Pharmaceuticals, Nycomed, and Orexo. Dr. Reimer has received grant support from and is a consultant to AstraZeneca Pharmaceuticals.

NEW ORLEANS — Patients with gastroesophageal reflux disease are very difficult to wean off proton pump inhibitors, and there is evidence that patients essentially become “addicted” to acid suppression, findings of large study suggest.

Dr. Peter Bytzer of Copenhagen University and Køge (Denmark) Hospital, and Dr. Christina Reimer, also of the university, reported study findings that indicate proton pump inhibitors (PPIs) are nearly impossible to discontinue, even for patients who lack a formal indication for their use.

“We found that discontinuing long-term PPI therapy was possible in only a minority of patients and that the majority experiencing symptom relapse after discontinuing the drug had no abnormal endoscopic findings,” Dr. Reimer said in a poster presentation. “Rapid recurrence of typical reflux symptoms was the main reason for restarting therapy, and 7 days of esomeprazole was helpful, despite the normal endoscopic findings.”

Dr. Bytzer and Dr. Reimer conducted a standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark. They identified 901 long-term users (at least 120 tablets), of whom 525 had an endoscopically verified diagnosis of esophagitis, Barrett's esophagus, or peptic stricture or had abnormal pH on monitoring, and therefore were categorized as having an indication for long-term treatment.

The remaining 376 patients were considered to have an unverified indication for a PPI and 76 of them agreed to attempt discontinue the drug. If symptoms recurred within 6 months after PPI withdrawal, patients underwent endoscopy. Those without abnormal findings were then randomized to 7 days of PPI therapy with esomeprazole 40 mg/day or placebo.

Of the 76 patients, 53 (63%) had symptom recurrence within the first week of discontinuing the PPI. The main symptoms were heartburn/acid regurgitation (48%) and dyspepsia (42%), Dr. Reimer reported at a DDW poster session.

On endoscopy, 31 (59%) had no abnormal findings.

Only 11 (14%) discontinued therapy without recurrence of symptoms during the 6 months of follow-up.

The 53 patients asked to restart therapy and were randomized to a PPI or placebo for 7 days; 80% of those taking esomeprazole had treatment success, compared with 13% receiving placebo.

Prescriptions for PPIs have essentially quadrupled in the past 10 years, according to data from the Danish Medicines Agency, Dr. Bytzer noted in a separate presentation at the meeting. “The increase in PPI use is explained by an increase long-term use.”

This hypothesis is supported by evidence of an increased prevalence in acid-related conditions, more liberal prescribing habits—including empirical PPI therapy for unspecific dyspepsia—and PPI “dependency” as a result of acid rebound that requires more and more suppression, he said.

Ironically, studies have suggested that PPIs can actually stimulate acid secretion in healthy volunteers. In a 2007 systemic review, Hunfeld et al. concluded “there is evidence from uncontrolled trials for an increased capacity to secrete acid in [Helicobacter pylori]–negative subjects after 8 weeks of treatment” and “there is no strong evidence for a clinically relevant increased acid production after withdrawal of proton pump inhibitor therapy” (Aliment. Pharmacol. Ther. 2007;25:39-46).

“In other words, once you remove the PPI you get an increased capacity to secrete acid. But is this clinically relevant? Will rebound acid hypersecretion lead to acid-related symptoms?” he questioned.

Apparently, it can. In a blinded withdrawal study conducted by Dr. Bytzer's group, 120 healthy volunteers were randomized to esomeprazole 40 mg or placebo for 8 weeks, after which the esomeprazole group crossed over to placebo for 4 weeks (Gastroenterol. 2009;137:80-7).

After crossing over, these patients experienced a significant increase in dyspepsia, heartburn, and regurgitation at weeks 10, 11, and 12.

These subjects had not had symptoms prior the study and were never on acid reducers. They were unaware of the shift to placebo. After the start of a PPI, gastrin significantly increased, and 44% got significant acid-related symptoms, he reported.

Other investigators have found increases in reflux laryngitis, heartburn, and dyspepsia after discontinuation of PPIs, he added.

To discontinue PPI therapy in long-term users, patients can slowly taper down doses over 3 weeks or so, he suggested, however, he said it remains difficult to discontinue PPI therapy, especially in patients with GERD.

Major Finding: Of 76 patients who had unverified indications for a PPI, 11 were able to discontinue therapy without recurrence of symptoms during the 6 months of follow-up.

Data Source: A standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark.

Disclosures: Dr. Bytzer is a speaker or consultant for AstraZeneca Pharmaceuticals, Nycomed, and Orexo. Dr. Reimer has received grant support from and is a consultant to AstraZeneca Pharmaceuticals.

NEW ORLEANS — Patients with gastroesophageal reflux disease are very difficult to wean off proton pump inhibitors, and there is evidence that patients essentially become “addicted” to acid suppression, findings of large study suggest.

Dr. Peter Bytzer of Copenhagen University and Køge (Denmark) Hospital, and Dr. Christina Reimer, also of the university, reported study findings that indicate proton pump inhibitors (PPIs) are nearly impossible to discontinue, even for patients who lack a formal indication for their use.

“We found that discontinuing long-term PPI therapy was possible in only a minority of patients and that the majority experiencing symptom relapse after discontinuing the drug had no abnormal endoscopic findings,” Dr. Reimer said in a poster presentation. “Rapid recurrence of typical reflux symptoms was the main reason for restarting therapy, and 7 days of esomeprazole was helpful, despite the normal endoscopic findings.”

Dr. Bytzer and Dr. Reimer conducted a standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark. They identified 901 long-term users (at least 120 tablets), of whom 525 had an endoscopically verified diagnosis of esophagitis, Barrett's esophagus, or peptic stricture or had abnormal pH on monitoring, and therefore were categorized as having an indication for long-term treatment.

The remaining 376 patients were considered to have an unverified indication for a PPI and 76 of them agreed to attempt discontinue the drug. If symptoms recurred within 6 months after PPI withdrawal, patients underwent endoscopy. Those without abnormal findings were then randomized to 7 days of PPI therapy with esomeprazole 40 mg/day or placebo.

Of the 76 patients, 53 (63%) had symptom recurrence within the first week of discontinuing the PPI. The main symptoms were heartburn/acid regurgitation (48%) and dyspepsia (42%), Dr. Reimer reported at a DDW poster session.

On endoscopy, 31 (59%) had no abnormal findings.

Only 11 (14%) discontinued therapy without recurrence of symptoms during the 6 months of follow-up.

The 53 patients asked to restart therapy and were randomized to a PPI or placebo for 7 days; 80% of those taking esomeprazole had treatment success, compared with 13% receiving placebo.

Prescriptions for PPIs have essentially quadrupled in the past 10 years, according to data from the Danish Medicines Agency, Dr. Bytzer noted in a separate presentation at the meeting. “The increase in PPI use is explained by an increase long-term use.”

This hypothesis is supported by evidence of an increased prevalence in acid-related conditions, more liberal prescribing habits—including empirical PPI therapy for unspecific dyspepsia—and PPI “dependency” as a result of acid rebound that requires more and more suppression, he said.

Ironically, studies have suggested that PPIs can actually stimulate acid secretion in healthy volunteers. In a 2007 systemic review, Hunfeld et al. concluded “there is evidence from uncontrolled trials for an increased capacity to secrete acid in [Helicobacter pylori]–negative subjects after 8 weeks of treatment” and “there is no strong evidence for a clinically relevant increased acid production after withdrawal of proton pump inhibitor therapy” (Aliment. Pharmacol. Ther. 2007;25:39-46).

“In other words, once you remove the PPI you get an increased capacity to secrete acid. But is this clinically relevant? Will rebound acid hypersecretion lead to acid-related symptoms?” he questioned.

Apparently, it can. In a blinded withdrawal study conducted by Dr. Bytzer's group, 120 healthy volunteers were randomized to esomeprazole 40 mg or placebo for 8 weeks, after which the esomeprazole group crossed over to placebo for 4 weeks (Gastroenterol. 2009;137:80-7).

After crossing over, these patients experienced a significant increase in dyspepsia, heartburn, and regurgitation at weeks 10, 11, and 12.

These subjects had not had symptoms prior the study and were never on acid reducers. They were unaware of the shift to placebo. After the start of a PPI, gastrin significantly increased, and 44% got significant acid-related symptoms, he reported.

Other investigators have found increases in reflux laryngitis, heartburn, and dyspepsia after discontinuation of PPIs, he added.

To discontinue PPI therapy in long-term users, patients can slowly taper down doses over 3 weeks or so, he suggested, however, he said it remains difficult to discontinue PPI therapy, especially in patients with GERD.

Major Finding: Of 76 patients who had unverified indications for a PPI, 11 were able to discontinue therapy without recurrence of symptoms during the 6 months of follow-up.

Data Source: A standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark.

Disclosures: Dr. Bytzer is a speaker or consultant for AstraZeneca Pharmaceuticals, Nycomed, and Orexo. Dr. Reimer has received grant support from and is a consultant to AstraZeneca Pharmaceuticals.

NEW ORLEANS — Patients with gastroesophageal reflux disease are very difficult to wean off proton pump inhibitors, and there is evidence that patients essentially become “addicted” to acid suppression, findings of large study suggest.

Dr. Peter Bytzer of Copenhagen University and Køge (Denmark) Hospital, and Dr. Christina Reimer, also of the university, reported study findings that indicate proton pump inhibitors (PPIs) are nearly impossible to discontinue, even for patients who lack a formal indication for their use.

“We found that discontinuing long-term PPI therapy was possible in only a minority of patients and that the majority experiencing symptom relapse after discontinuing the drug had no abnormal endoscopic findings,” Dr. Reimer said in a poster presentation. “Rapid recurrence of typical reflux symptoms was the main reason for restarting therapy, and 7 days of esomeprazole was helpful, despite the normal endoscopic findings.”

Dr. Bytzer and Dr. Reimer conducted a standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark. They identified 901 long-term users (at least 120 tablets), of whom 525 had an endoscopically verified diagnosis of esophagitis, Barrett's esophagus, or peptic stricture or had abnormal pH on monitoring, and therefore were categorized as having an indication for long-term treatment.

The remaining 376 patients were considered to have an unverified indication for a PPI and 76 of them agreed to attempt discontinue the drug. If symptoms recurred within 6 months after PPI withdrawal, patients underwent endoscopy. Those without abnormal findings were then randomized to 7 days of PPI therapy with esomeprazole 40 mg/day or placebo.

Of the 76 patients, 53 (63%) had symptom recurrence within the first week of discontinuing the PPI. The main symptoms were heartburn/acid regurgitation (48%) and dyspepsia (42%), Dr. Reimer reported at a DDW poster session.

On endoscopy, 31 (59%) had no abnormal findings.

Only 11 (14%) discontinued therapy without recurrence of symptoms during the 6 months of follow-up.

The 53 patients asked to restart therapy and were randomized to a PPI or placebo for 7 days; 80% of those taking esomeprazole had treatment success, compared with 13% receiving placebo.

Prescriptions for PPIs have essentially quadrupled in the past 10 years, according to data from the Danish Medicines Agency, Dr. Bytzer noted in a separate presentation at the meeting. “The increase in PPI use is explained by an increase long-term use.”

This hypothesis is supported by evidence of an increased prevalence in acid-related conditions, more liberal prescribing habits—including empirical PPI therapy for unspecific dyspepsia—and PPI “dependency” as a result of acid rebound that requires more and more suppression, he said.

Ironically, studies have suggested that PPIs can actually stimulate acid secretion in healthy volunteers. In a 2007 systemic review, Hunfeld et al. concluded “there is evidence from uncontrolled trials for an increased capacity to secrete acid in [Helicobacter pylori]–negative subjects after 8 weeks of treatment” and “there is no strong evidence for a clinically relevant increased acid production after withdrawal of proton pump inhibitor therapy” (Aliment. Pharmacol. Ther. 2007;25:39-46).

“In other words, once you remove the PPI you get an increased capacity to secrete acid. But is this clinically relevant? Will rebound acid hypersecretion lead to acid-related symptoms?” he questioned.

Apparently, it can. In a blinded withdrawal study conducted by Dr. Bytzer's group, 120 healthy volunteers were randomized to esomeprazole 40 mg or placebo for 8 weeks, after which the esomeprazole group crossed over to placebo for 4 weeks (Gastroenterol. 2009;137:80-7).

After crossing over, these patients experienced a significant increase in dyspepsia, heartburn, and regurgitation at weeks 10, 11, and 12.

These subjects had not had symptoms prior the study and were never on acid reducers. They were unaware of the shift to placebo. After the start of a PPI, gastrin significantly increased, and 44% got significant acid-related symptoms, he reported.

Other investigators have found increases in reflux laryngitis, heartburn, and dyspepsia after discontinuation of PPIs, he added.

To discontinue PPI therapy in long-term users, patients can slowly taper down doses over 3 weeks or so, he suggested, however, he said it remains difficult to discontinue PPI therapy, especially in patients with GERD.

NEW ORLEANS — More than 50 genetic risk factors for ulcerative colitis have now been identified by the International Inflammatory Bowel Disease Genetics Consortium, John D. Rioux, Ph.D., said at the meeting.

“The work of the International IBD Consortium has dramatically increased the number of known UC [ulcerative colitis] loci and is expected to significantly increase our understanding of disease pathogenesis that relates to both shared and UC-specific inflammatory pathways,” said Dr. Rioux of the University of Montreal. The Consortium spans 15 countries and employs more than 80 clinical and basic researchers.

Genome-wide association (GWA) studies analyze “hundreds of thousands of genetic variants for thousands of patients and controls” to identify genetic risk factors, he said.

GWA studies have identified genetic risk factors for Crohn's disease. While individual studies have been successful, the statistical power for gene discovery is limited by sample size. The larger the sample size, the greater the number of genetic risk factors identified, he noted.

Previously, the Consortium performed one of the first studies to combine GWA results, and identified more than 30 risk factors for Crohn's disease.

“At that time, much less was known about the genetics of UC, with only the MHC and the IL23R gene having confirmed associations. In the last year, multiple GWAs of UC have been done and have produced 18 independent new associations. These studies provided a unique opportunity to identify a much more complete catalog of genetic risk factors,” he said.

In the current study, results from six GWA studies of UC were combined in a meta-analysis. Data from 6,433 patients with UC and 20,999 population controls from North America and Europe were combined into a dataset.

“Out of nearly millions of polymorphisms examined,” the tests ultimately revealed 75 independent genomic regions significantly associated with UC.

In preliminary investigations, the meta-analysis has confirmed 18 known ulcerative colitis loci, 21 novel loci, and 4 nominally significant loci (which investigators expect to become significant upon further analyses), for a total of 43 genetic risk factors to date. Another 26 are being studied but have not yet been replicated.

“Many of the UC genetic risk factors are shared with Crohn's disease—nearly 50%—as well as other inflammatory diseases,” Dr. Rioux suggested. The other inflammatory diseases include psoriasis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, and others.

“We predict there are at least 52 loci associated with UC, about 50% of which are shared with Crohn's disease and about 25% with other inflammatory diagnoses. The remainder appear to be UC-specific,” he said.

“The research into the genetics of ulcerative colitis has highlighted the similarities and differences between ulcerative colitis and Crohn's disease, said Dr. María T. Abreu in an interview. “It shows us some of the explanations for why patients with ulcerative colitis who have a J-pouch [also called an ileal pouch–anal anastomosis] may ultimately develop Crohn's disease,” said Dr. Abreu, professor of medicine and chief, division of gastroenterology, University of Miami.

The Consortium is currently testing all novel loci in an independent set of 10,000 UC patients and a similar number of population controls to confirm these findings, but even the preliminary results provide “convincing evidence,” he said, of associations to genes of biological significance to disease pathogenesis: TNFRSF14, JAK2, CARD9 and others.

An analysis of the literature suggests that novel UC genes pinpoint potential molecular mechanisms. “In other words, each new UC gene contributes to the puzzle,” he said.

For example, ETS1 on chromosome 11 has a profound impact on Th1 immune responses. DAP (death-associated protein) on chromosome 5 modulates mTOR (mammalian target of rapamycin) activity. WSB1 on chromosome 17 is a hedgehog-inducible ubiquitin ligase, and its loss results in spontaneous intestinal inflammation.

“We can begin to put these into biological pathways. Many genes in these pathways protect or predispose to disease, and we can identify novel targets and appropriate genetic testing within the context of clinical trials and patient selection. Our work,” he added, “has just begun.”

These studies provided a unique opportunity to identify a more complete catalog of genetic risk factors.

Source DR. RIOUX

NEW ORLEANS — More than 50 genetic risk factors for ulcerative colitis have now been identified by the International Inflammatory Bowel Disease Genetics Consortium, John D. Rioux, Ph.D., said at the meeting.

“The work of the International IBD Consortium has dramatically increased the number of known UC [ulcerative colitis] loci and is expected to significantly increase our understanding of disease pathogenesis that relates to both shared and UC-specific inflammatory pathways,” said Dr. Rioux of the University of Montreal. The Consortium spans 15 countries and employs more than 80 clinical and basic researchers.

Genome-wide association (GWA) studies analyze “hundreds of thousands of genetic variants for thousands of patients and controls” to identify genetic risk factors, he said.

GWA studies have identified genetic risk factors for Crohn's disease. While individual studies have been successful, the statistical power for gene discovery is limited by sample size. The larger the sample size, the greater the number of genetic risk factors identified, he noted.

Previously, the Consortium performed one of the first studies to combine GWA results, and identified more than 30 risk factors for Crohn's disease.

“At that time, much less was known about the genetics of UC, with only the MHC and the IL23R gene having confirmed associations. In the last year, multiple GWAs of UC have been done and have produced 18 independent new associations. These studies provided a unique opportunity to identify a much more complete catalog of genetic risk factors,” he said.

In the current study, results from six GWA studies of UC were combined in a meta-analysis. Data from 6,433 patients with UC and 20,999 population controls from North America and Europe were combined into a dataset.

“Out of nearly millions of polymorphisms examined,” the tests ultimately revealed 75 independent genomic regions significantly associated with UC.

In preliminary investigations, the meta-analysis has confirmed 18 known ulcerative colitis loci, 21 novel loci, and 4 nominally significant loci (which investigators expect to become significant upon further analyses), for a total of 43 genetic risk factors to date. Another 26 are being studied but have not yet been replicated.

“Many of the UC genetic risk factors are shared with Crohn's disease—nearly 50%—as well as other inflammatory diseases,” Dr. Rioux suggested. The other inflammatory diseases include psoriasis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, and others.

“We predict there are at least 52 loci associated with UC, about 50% of which are shared with Crohn's disease and about 25% with other inflammatory diagnoses. The remainder appear to be UC-specific,” he said.

“The research into the genetics of ulcerative colitis has highlighted the similarities and differences between ulcerative colitis and Crohn's disease, said Dr. María T. Abreu in an interview. “It shows us some of the explanations for why patients with ulcerative colitis who have a J-pouch [also called an ileal pouch–anal anastomosis] may ultimately develop Crohn's disease,” said Dr. Abreu, professor of medicine and chief, division of gastroenterology, University of Miami.

The Consortium is currently testing all novel loci in an independent set of 10,000 UC patients and a similar number of population controls to confirm these findings, but even the preliminary results provide “convincing evidence,” he said, of associations to genes of biological significance to disease pathogenesis: TNFRSF14, JAK2, CARD9 and others.

An analysis of the literature suggests that novel UC genes pinpoint potential molecular mechanisms. “In other words, each new UC gene contributes to the puzzle,” he said.

For example, ETS1 on chromosome 11 has a profound impact on Th1 immune responses. DAP (death-associated protein) on chromosome 5 modulates mTOR (mammalian target of rapamycin) activity. WSB1 on chromosome 17 is a hedgehog-inducible ubiquitin ligase, and its loss results in spontaneous intestinal inflammation.

“We can begin to put these into biological pathways. Many genes in these pathways protect or predispose to disease, and we can identify novel targets and appropriate genetic testing within the context of clinical trials and patient selection. Our work,” he added, “has just begun.”

These studies provided a unique opportunity to identify a more complete catalog of genetic risk factors.

Source DR. RIOUX

NEW ORLEANS — More than 50 genetic risk factors for ulcerative colitis have now been identified by the International Inflammatory Bowel Disease Genetics Consortium, John D. Rioux, Ph.D., said at the meeting.

“The work of the International IBD Consortium has dramatically increased the number of known UC [ulcerative colitis] loci and is expected to significantly increase our understanding of disease pathogenesis that relates to both shared and UC-specific inflammatory pathways,” said Dr. Rioux of the University of Montreal. The Consortium spans 15 countries and employs more than 80 clinical and basic researchers.

Genome-wide association (GWA) studies analyze “hundreds of thousands of genetic variants for thousands of patients and controls” to identify genetic risk factors, he said.

GWA studies have identified genetic risk factors for Crohn's disease. While individual studies have been successful, the statistical power for gene discovery is limited by sample size. The larger the sample size, the greater the number of genetic risk factors identified, he noted.

Previously, the Consortium performed one of the first studies to combine GWA results, and identified more than 30 risk factors for Crohn's disease.

“At that time, much less was known about the genetics of UC, with only the MHC and the IL23R gene having confirmed associations. In the last year, multiple GWAs of UC have been done and have produced 18 independent new associations. These studies provided a unique opportunity to identify a much more complete catalog of genetic risk factors,” he said.

In the current study, results from six GWA studies of UC were combined in a meta-analysis. Data from 6,433 patients with UC and 20,999 population controls from North America and Europe were combined into a dataset.

“Out of nearly millions of polymorphisms examined,” the tests ultimately revealed 75 independent genomic regions significantly associated with UC.

In preliminary investigations, the meta-analysis has confirmed 18 known ulcerative colitis loci, 21 novel loci, and 4 nominally significant loci (which investigators expect to become significant upon further analyses), for a total of 43 genetic risk factors to date. Another 26 are being studied but have not yet been replicated.

“Many of the UC genetic risk factors are shared with Crohn's disease—nearly 50%—as well as other inflammatory diseases,” Dr. Rioux suggested. The other inflammatory diseases include psoriasis, celiac disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, and others.

“We predict there are at least 52 loci associated with UC, about 50% of which are shared with Crohn's disease and about 25% with other inflammatory diagnoses. The remainder appear to be UC-specific,” he said.

“The research into the genetics of ulcerative colitis has highlighted the similarities and differences between ulcerative colitis and Crohn's disease, said Dr. María T. Abreu in an interview. “It shows us some of the explanations for why patients with ulcerative colitis who have a J-pouch [also called an ileal pouch–anal anastomosis] may ultimately develop Crohn's disease,” said Dr. Abreu, professor of medicine and chief, division of gastroenterology, University of Miami.

The Consortium is currently testing all novel loci in an independent set of 10,000 UC patients and a similar number of population controls to confirm these findings, but even the preliminary results provide “convincing evidence,” he said, of associations to genes of biological significance to disease pathogenesis: TNFRSF14, JAK2, CARD9 and others.

An analysis of the literature suggests that novel UC genes pinpoint potential molecular mechanisms. “In other words, each new UC gene contributes to the puzzle,” he said.

For example, ETS1 on chromosome 11 has a profound impact on Th1 immune responses. DAP (death-associated protein) on chromosome 5 modulates mTOR (mammalian target of rapamycin) activity. WSB1 on chromosome 17 is a hedgehog-inducible ubiquitin ligase, and its loss results in spontaneous intestinal inflammation.

“We can begin to put these into biological pathways. Many genes in these pathways protect or predispose to disease, and we can identify novel targets and appropriate genetic testing within the context of clinical trials and patient selection. Our work,” he added, “has just begun.”

These studies provided a unique opportunity to identify a more complete catalog of genetic risk factors.

Source DR. RIOUX

NEW ORLEANS — For eradication of Helicobacter pylori infection, a 14-day hybrid therapy that combines sequential and concomitant drug treatments improved the eradication rate, compared with 14-day standard sequential therapy, investigators reported.

“Worldwide, the eradication rate with standard triple therapy is less than 80% in intention-to-treat analyses,” said Dr. Ping-I. Hsu of Kaohsiung (Taiwan) Veterans General Hospital, who presented the findings. Standard triple therapy includes a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole.

“The ideal antimicrobial therapy would have an eradication rate of at least 95% by per-protocol analysis,” which would earn it a grade A score, he said.

In a recent assessment of 15 trials, mean eradication rates were 93% with sequential therapy and less than 95% with concomitant therapy (Gut 2010 June 4,[doi:10.1136/gut.2009.192757]), both of which are grade B results, he noted.

“We questioned whether prolonging the treatment duration of sequential therapy or continuing the amoxicillin throughout the treatment course might increase the eradication rate,” he said. The specific aim of the study was to investigate whether either extending the duration of sequential therapy to 14 days or a 14-day hybrid regimen that combined sequential and concomitant approaches might increase the eradication rate to at least 95% (grade A) in per-protocol analysis. Subjects had H. pylori infection proven by at least two positive results for the urease test, histology, and urea breath test.

The study was done as two separate pilot studies where 240 patients were randomized to the sequential therapy group, which included esomeprazole 40 mg b.i.d. plus amoxicillin 1 g b.i.d. (EA) for 7 days followed by esomeprazole, clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d. for 7 days, or to hybrid therapy, which included EA for 7 days followed by EA plus clarithromycin and metronidazole for 7 days. Patients were followed to week 8, when they underwent endoscopy with urease testing and histology, or urea breath test.

After excluding patients who had lack of compliance or incomplete follow-up, the final analyses included 115 in the sequential (control) group and 109 in the hybrid therapy group. The groups were similar demographically except for a higher proportion of metronidazole-susceptible patients in the sequential group.

In both the intention-to-treat and per-protocol analysis, the outcomes were superior after hybrid therapy, Dr. Hsu reported (see chart).

“The study also showed that simply prolonging the treatment duration of sequential therapy does not achieve a grade A result,” Dr. Hsu pointed out, since a rate of 93% can be achieved with just 10 days of sequential therapy (Clin. Gastroenterol. Hepatol. 2010;8:36-41).

In a univariate analysis of clinical and bacterial factors associated with efficacy, no factors analyzed affected efficacy in the hybrid arm, but the presence of resistant strains reduced the eradication rate in the control arm to 88%.

The investigators received the medications from AstraZeneca, which was otherwise not involved in the planning, analysis, or writing of the paper.

Source Elsevier Global Medical News

NEW ORLEANS — For eradication of Helicobacter pylori infection, a 14-day hybrid therapy that combines sequential and concomitant drug treatments improved the eradication rate, compared with 14-day standard sequential therapy, investigators reported.

“Worldwide, the eradication rate with standard triple therapy is less than 80% in intention-to-treat analyses,” said Dr. Ping-I. Hsu of Kaohsiung (Taiwan) Veterans General Hospital, who presented the findings. Standard triple therapy includes a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole.

“The ideal antimicrobial therapy would have an eradication rate of at least 95% by per-protocol analysis,” which would earn it a grade A score, he said.

In a recent assessment of 15 trials, mean eradication rates were 93% with sequential therapy and less than 95% with concomitant therapy (Gut 2010 June 4,[doi:10.1136/gut.2009.192757]), both of which are grade B results, he noted.

“We questioned whether prolonging the treatment duration of sequential therapy or continuing the amoxicillin throughout the treatment course might increase the eradication rate,” he said. The specific aim of the study was to investigate whether either extending the duration of sequential therapy to 14 days or a 14-day hybrid regimen that combined sequential and concomitant approaches might increase the eradication rate to at least 95% (grade A) in per-protocol analysis. Subjects had H. pylori infection proven by at least two positive results for the urease test, histology, and urea breath test.

The study was done as two separate pilot studies where 240 patients were randomized to the sequential therapy group, which included esomeprazole 40 mg b.i.d. plus amoxicillin 1 g b.i.d. (EA) for 7 days followed by esomeprazole, clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d. for 7 days, or to hybrid therapy, which included EA for 7 days followed by EA plus clarithromycin and metronidazole for 7 days. Patients were followed to week 8, when they underwent endoscopy with urease testing and histology, or urea breath test.

After excluding patients who had lack of compliance or incomplete follow-up, the final analyses included 115 in the sequential (control) group and 109 in the hybrid therapy group. The groups were similar demographically except for a higher proportion of metronidazole-susceptible patients in the sequential group.

In both the intention-to-treat and per-protocol analysis, the outcomes were superior after hybrid therapy, Dr. Hsu reported (see chart).

“The study also showed that simply prolonging the treatment duration of sequential therapy does not achieve a grade A result,” Dr. Hsu pointed out, since a rate of 93% can be achieved with just 10 days of sequential therapy (Clin. Gastroenterol. Hepatol. 2010;8:36-41).

In a univariate analysis of clinical and bacterial factors associated with efficacy, no factors analyzed affected efficacy in the hybrid arm, but the presence of resistant strains reduced the eradication rate in the control arm to 88%.

The investigators received the medications from AstraZeneca, which was otherwise not involved in the planning, analysis, or writing of the paper.

Source Elsevier Global Medical News

NEW ORLEANS — For eradication of Helicobacter pylori infection, a 14-day hybrid therapy that combines sequential and concomitant drug treatments improved the eradication rate, compared with 14-day standard sequential therapy, investigators reported.

“Worldwide, the eradication rate with standard triple therapy is less than 80% in intention-to-treat analyses,” said Dr. Ping-I. Hsu of Kaohsiung (Taiwan) Veterans General Hospital, who presented the findings. Standard triple therapy includes a proton pump inhibitor (PPI), clarithromycin, and either amoxicillin or metronidazole.

“The ideal antimicrobial therapy would have an eradication rate of at least 95% by per-protocol analysis,” which would earn it a grade A score, he said.

In a recent assessment of 15 trials, mean eradication rates were 93% with sequential therapy and less than 95% with concomitant therapy (Gut 2010 June 4,[doi:10.1136/gut.2009.192757]), both of which are grade B results, he noted.

“We questioned whether prolonging the treatment duration of sequential therapy or continuing the amoxicillin throughout the treatment course might increase the eradication rate,” he said. The specific aim of the study was to investigate whether either extending the duration of sequential therapy to 14 days or a 14-day hybrid regimen that combined sequential and concomitant approaches might increase the eradication rate to at least 95% (grade A) in per-protocol analysis. Subjects had H. pylori infection proven by at least two positive results for the urease test, histology, and urea breath test.

The study was done as two separate pilot studies where 240 patients were randomized to the sequential therapy group, which included esomeprazole 40 mg b.i.d. plus amoxicillin 1 g b.i.d. (EA) for 7 days followed by esomeprazole, clarithromycin 500 mg b.i.d., and metronidazole 500 mg b.i.d. for 7 days, or to hybrid therapy, which included EA for 7 days followed by EA plus clarithromycin and metronidazole for 7 days. Patients were followed to week 8, when they underwent endoscopy with urease testing and histology, or urea breath test.

After excluding patients who had lack of compliance or incomplete follow-up, the final analyses included 115 in the sequential (control) group and 109 in the hybrid therapy group. The groups were similar demographically except for a higher proportion of metronidazole-susceptible patients in the sequential group.

In both the intention-to-treat and per-protocol analysis, the outcomes were superior after hybrid therapy, Dr. Hsu reported (see chart).

“The study also showed that simply prolonging the treatment duration of sequential therapy does not achieve a grade A result,” Dr. Hsu pointed out, since a rate of 93% can be achieved with just 10 days of sequential therapy (Clin. Gastroenterol. Hepatol. 2010;8:36-41).

In a univariate analysis of clinical and bacterial factors associated with efficacy, no factors analyzed affected efficacy in the hybrid arm, but the presence of resistant strains reduced the eradication rate in the control arm to 88%.

The investigators received the medications from AstraZeneca, which was otherwise not involved in the planning, analysis, or writing of the paper.

Source Elsevier Global Medical News

NEW ORLEANS — Diminutive polyps have a very low risk of advanced histology and virtually no risk of cancer, and therefore clinicians should balance the small potential benefit of removing them against potential harms posed by polypectomy, Dr. Thomas F. Imperiale said.

In an invited lecture on the management of diminutive polyps, Dr. Imperiale acknowledged that endoscopists often elect to remove these polyps, but he said they should consider several factors first.

Diminutive polyps (less than or equal to 5 mm) constitute at least 80% of all colorectal polyps and have been identified in 44% of persons undergoing colonoscopy for any indication, he said.

Nearly half occur in the sigmoid colon and rectum, and the remainder are fairly evenly distributed throughout the colon. Diminutive polyps are neoplastic in 35%–50% of cases, with the risk of neoplasia increasing in accordance with polyp size. The highest risk occurs in the ascending colon and cecum, said Dr. Imperiale, professor of medicine, Indiana University Medical Center, Indianapolis.

The clinical importance of diminutive polyps is not great, as cancer is uncommon (less than 1%). In a recent systematic review of four studies involving more than 20,000 patients, the frequency of advanced lesions among patients whose largest polyp was diminutive was 0.9%, but it rose dramatically to 73.5% when the polyp was 10 mm or larger (Aliment. Pharmacol. Ther. 2010;31:210–7).

Furthermore, these lesions grow slowly, generally less than 0.5 mm per year. Hyperplastic polyps appear to have an even slower rate of growth, he added.

Like the cancer risk, the benefit of removing polyps is proportional to their size. The number needed to resect to prevent one advanced adenoma or colorectal cancer, therefore, varies widely.

“The prevention of one cancer in a person with a diminutive polyp is associated with a cost-effectiveness ratio that is 5–10 times the established cost-effectiveness threshold,” he pointed out. “For large polyps, however, resection is cost saving.”

Polypectomy is probably overutilized for diminutive polyps and conveys more harm than benefit, he maintained, noting that it increases the risk for major complication and, when incompletely performed, is responsible for 30% of interval cancers.

In vivo histologic assessment has a potential role in the management of diminutive polyps. With this, the clinician can avoid removing non–neoplastic polyps, especially distal ones, thus reducing costs and risks; can resect and discard small adenomas, reducing pathology costs; and can identify cancer via real-time histology, which improves treatment selection, Dr. Imperiale said.

Although in vivo histology could be used to avoid the removal of non–neoplastic polyps, it also means that adenomas are left intact and the surveillance interval could prove to be too long (which raises the risk of cancer) or too short (which increases risk from needless polypectomy), he said.

Several recent studies have evaluated the effect of optical diagnosis without pathology on surveillance intervals, essentially concluding that adenomatous and hyperplastic polyps can be adequately identified and that this approach might be acceptable for diminutive targets.

Before such techniques are implemented, he said, “we need more real-time data. We need to identify optimal techniques. And we need to quantify the effects on surveillance and estimate the downstream effects, which would be the incidence of colorectal cancer, complications, and costs.”

Disclosures: Dr. Imperiale has no relevant financial disclosures.

NEW ORLEANS — Diminutive polyps have a very low risk of advanced histology and virtually no risk of cancer, and therefore clinicians should balance the small potential benefit of removing them against potential harms posed by polypectomy, Dr. Thomas F. Imperiale said.

In an invited lecture on the management of diminutive polyps, Dr. Imperiale acknowledged that endoscopists often elect to remove these polyps, but he said they should consider several factors first.

Diminutive polyps (less than or equal to 5 mm) constitute at least 80% of all colorectal polyps and have been identified in 44% of persons undergoing colonoscopy for any indication, he said.

Nearly half occur in the sigmoid colon and rectum, and the remainder are fairly evenly distributed throughout the colon. Diminutive polyps are neoplastic in 35%–50% of cases, with the risk of neoplasia increasing in accordance with polyp size. The highest risk occurs in the ascending colon and cecum, said Dr. Imperiale, professor of medicine, Indiana University Medical Center, Indianapolis.

The clinical importance of diminutive polyps is not great, as cancer is uncommon (less than 1%). In a recent systematic review of four studies involving more than 20,000 patients, the frequency of advanced lesions among patients whose largest polyp was diminutive was 0.9%, but it rose dramatically to 73.5% when the polyp was 10 mm or larger (Aliment. Pharmacol. Ther. 2010;31:210–7).

Furthermore, these lesions grow slowly, generally less than 0.5 mm per year. Hyperplastic polyps appear to have an even slower rate of growth, he added.

Like the cancer risk, the benefit of removing polyps is proportional to their size. The number needed to resect to prevent one advanced adenoma or colorectal cancer, therefore, varies widely.

“The prevention of one cancer in a person with a diminutive polyp is associated with a cost-effectiveness ratio that is 5–10 times the established cost-effectiveness threshold,” he pointed out. “For large polyps, however, resection is cost saving.”

Polypectomy is probably overutilized for diminutive polyps and conveys more harm than benefit, he maintained, noting that it increases the risk for major complication and, when incompletely performed, is responsible for 30% of interval cancers.

In vivo histologic assessment has a potential role in the management of diminutive polyps. With this, the clinician can avoid removing non–neoplastic polyps, especially distal ones, thus reducing costs and risks; can resect and discard small adenomas, reducing pathology costs; and can identify cancer via real-time histology, which improves treatment selection, Dr. Imperiale said.

Although in vivo histology could be used to avoid the removal of non–neoplastic polyps, it also means that adenomas are left intact and the surveillance interval could prove to be too long (which raises the risk of cancer) or too short (which increases risk from needless polypectomy), he said.

Several recent studies have evaluated the effect of optical diagnosis without pathology on surveillance intervals, essentially concluding that adenomatous and hyperplastic polyps can be adequately identified and that this approach might be acceptable for diminutive targets.

Before such techniques are implemented, he said, “we need more real-time data. We need to identify optimal techniques. And we need to quantify the effects on surveillance and estimate the downstream effects, which would be the incidence of colorectal cancer, complications, and costs.”

Disclosures: Dr. Imperiale has no relevant financial disclosures.

NEW ORLEANS — Diminutive polyps have a very low risk of advanced histology and virtually no risk of cancer, and therefore clinicians should balance the small potential benefit of removing them against potential harms posed by polypectomy, Dr. Thomas F. Imperiale said.

In an invited lecture on the management of diminutive polyps, Dr. Imperiale acknowledged that endoscopists often elect to remove these polyps, but he said they should consider several factors first.

Diminutive polyps (less than or equal to 5 mm) constitute at least 80% of all colorectal polyps and have been identified in 44% of persons undergoing colonoscopy for any indication, he said.

Nearly half occur in the sigmoid colon and rectum, and the remainder are fairly evenly distributed throughout the colon. Diminutive polyps are neoplastic in 35%–50% of cases, with the risk of neoplasia increasing in accordance with polyp size. The highest risk occurs in the ascending colon and cecum, said Dr. Imperiale, professor of medicine, Indiana University Medical Center, Indianapolis.

The clinical importance of diminutive polyps is not great, as cancer is uncommon (less than 1%). In a recent systematic review of four studies involving more than 20,000 patients, the frequency of advanced lesions among patients whose largest polyp was diminutive was 0.9%, but it rose dramatically to 73.5% when the polyp was 10 mm or larger (Aliment. Pharmacol. Ther. 2010;31:210–7).

Furthermore, these lesions grow slowly, generally less than 0.5 mm per year. Hyperplastic polyps appear to have an even slower rate of growth, he added.

Like the cancer risk, the benefit of removing polyps is proportional to their size. The number needed to resect to prevent one advanced adenoma or colorectal cancer, therefore, varies widely.

“The prevention of one cancer in a person with a diminutive polyp is associated with a cost-effectiveness ratio that is 5–10 times the established cost-effectiveness threshold,” he pointed out. “For large polyps, however, resection is cost saving.”

Polypectomy is probably overutilized for diminutive polyps and conveys more harm than benefit, he maintained, noting that it increases the risk for major complication and, when incompletely performed, is responsible for 30% of interval cancers.

In vivo histologic assessment has a potential role in the management of diminutive polyps. With this, the clinician can avoid removing non–neoplastic polyps, especially distal ones, thus reducing costs and risks; can resect and discard small adenomas, reducing pathology costs; and can identify cancer via real-time histology, which improves treatment selection, Dr. Imperiale said.

Although in vivo histology could be used to avoid the removal of non–neoplastic polyps, it also means that adenomas are left intact and the surveillance interval could prove to be too long (which raises the risk of cancer) or too short (which increases risk from needless polypectomy), he said.

Several recent studies have evaluated the effect of optical diagnosis without pathology on surveillance intervals, essentially concluding that adenomatous and hyperplastic polyps can be adequately identified and that this approach might be acceptable for diminutive targets.

Before such techniques are implemented, he said, “we need more real-time data. We need to identify optimal techniques. And we need to quantify the effects on surveillance and estimate the downstream effects, which would be the incidence of colorectal cancer, complications, and costs.”

Disclosures: Dr. Imperiale has no relevant financial disclosures.

Major Finding: Of 76 patients who had unverified indications for a PPI, 11 were able to discontinue therapy without recurrence of symptoms during 6 months of follow-up.

Data Source: A standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark.

Disclosures: Dr. Bytzer is a speaker or consultant for AstraZeneca Pharmaceuticals, Nycomed, and Orexo. Dr. Reimer has received grant support from and is a consultant to AstraZeneca Pharmaceuticals.

NEW ORLEANS — Patients with gastroesophageal reflux disease are very difficult to wean off proton pump inhibitors, and there is evidence that patients essentially become “addicted” to acid suppression, findings of large study suggest.

Dr. Peter Bytzer, of Copenhagen University and Køge (Denmark) Hospital, and Dr. Christina Reimer, also of the university, reported study findings that indicate proton pump inhibitors (PPIs) are nearly impossible to discontinue, even for patients who lack a formal indication for their use.

“We found that discontinuing long-term PPI therapy was possible in only a minority of patients, and that the majority experiencing symptom relapse after discontinuing the drug had no abnormal endoscopic findings,” Dr. Reimer said in a poster presentation. “Rapid recurrence of typical reflux symptoms was the main reason for restarting therapy, and 7 days of esomeprazole was helpful, despite the normal endoscopic findings.”

Dr. Bytzer and Dr. Reimer conducted a standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark. They identified 901 long-term users (at least 120 tablets), of whom 525 had an endoscopically verified diagnosis of esophagitis, Barrett's esophagus, or peptic stricture or had abnormal pH on monitoring and therefore were categorized as having an indication for long-term treatment.

The remaining 376 patients were considered to have an unverified indication for a PPI, and 76 of them agreed to attempt to discontinue the drug. If symptoms recurred within 6 months after PPI withdrawal, patients underwent endoscopy.

Those without abnormal findings were then randomized to 7 days of PPI therapy with esomeprazole 40 mg/day or placebo.

Of the 76 patients, 53 (63%) had symptom recurrence within the first week of discontinuing the PPI. The main symptoms were heartburn/acid regurgitation (48%) and dyspepsia (42%), Dr. Reimer said.

On endoscopy, 31 (59%) had no abnormal findings.

Only 11 (14%) discontinued therapy without recurrence of symptoms during the 6 months of follow-up.

The 53 patients with recurrence were randomized to a PPI or placebo for 7 days; 80% of those taking esomeprazole had treatment success, compared with 13% receiving placebo.

There is evidence of an increased prevalence in acid-related conditions, more liberal prescribing habits—including empirical PPI therapy for unspecific dyspepsia—and PPI “dependency” as a result of acid rebound that requires more and more suppression, Dr. Bytzer said.

Ironically, studies have suggested that PPIs can actually stimulate acid secretion in healthy volunteers. A 2007 systemic review concluded “there is evidence from uncontrolled trials for an increased capacity to secrete acid in [Helicobacter pylori]–negative subjects after 8 weeks of treatment” (Aliment. Pharmacol. Ther. 2007;25:39–46).

“In other words, once you remove the PPI you get an increased capacity to secrete acid. But is this clinically relevant? Will rebound acid hypersecretion lead to acid-related symptoms?” Dr. Bytzer asked.

Apparently, it can. In a blinded withdrawal study conducted by Dr. Bytzer's group, 120 healthy volunteers were randomized to esomeprazole 40 mg or placebo for 8 weeks, after which the esomeprazole group crossed over to placebo for 4 weeks (Gastroenterol. 2009;137:80–7). After crossing over, these patients experienced a significant increase in dyspepsia, heartburn, and regurgitation at weeks 10–12.

“These subjects had not had symptoms prior the study and were never on acid reducers. They were unaware of the shift to placebo. After starting a PPI, gastrin significantly increased, and 44% got significant acid-related symptoms,” he reported.

Other investigators have found increases in reflux laryngitis, heartburn, and dyspepsia after discontinuation of PPIs, he added.

Recently, in a double-blind placebo-controlled trial in 48 H. pylori–negative volunteers, dyspeptic symptoms developed after discontinuation of pantoprazole (Am. J. Gastroenterol. 2010 March 23; doi:10.1038/ajg.2010.81). A total of 11 out of 25 (44%) subjects in the pantoprazole group developed dyspepsia, compared with 2 out of 23 (9%) in the placebo group. During the first week after discontinuation, the pantoprazole group had a mean symptom score of 5.7 versus 0.74 in the placebo group, but these scores progressively declined over 3 weeks.

“We can conclude that PPI therapy induces acid-related symptoms in around 44% of previously asymptomatic subjects, and this rebound acid hypersecretion is probably clinically relevant,” Dr. Bytzer said. “It seems that we may be inducing reflux disease when we give PPIs for non–acid-related symptoms.”

When attempting to discontinue PPI therapy in long-term users, patients can slowly taper down doses over 3 weeks or so, he suggested. However, he said it remains difficult to discontinue PPI therapy, especially in patients with GERD.

Major Finding: Of 76 patients who had unverified indications for a PPI, 11 were able to discontinue therapy without recurrence of symptoms during 6 months of follow-up.

Data Source: A standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark.

Disclosures: Dr. Bytzer is a speaker or consultant for AstraZeneca Pharmaceuticals, Nycomed, and Orexo. Dr. Reimer has received grant support from and is a consultant to AstraZeneca Pharmaceuticals.

NEW ORLEANS — Patients with gastroesophageal reflux disease are very difficult to wean off proton pump inhibitors, and there is evidence that patients essentially become “addicted” to acid suppression, findings of large study suggest.

Dr. Peter Bytzer, of Copenhagen University and Køge (Denmark) Hospital, and Dr. Christina Reimer, also of the university, reported study findings that indicate proton pump inhibitors (PPIs) are nearly impossible to discontinue, even for patients who lack a formal indication for their use.

“We found that discontinuing long-term PPI therapy was possible in only a minority of patients, and that the majority experiencing symptom relapse after discontinuing the drug had no abnormal endoscopic findings,” Dr. Reimer said in a poster presentation. “Rapid recurrence of typical reflux symptoms was the main reason for restarting therapy, and 7 days of esomeprazole was helpful, despite the normal endoscopic findings.”

Dr. Bytzer and Dr. Reimer conducted a standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark. They identified 901 long-term users (at least 120 tablets), of whom 525 had an endoscopically verified diagnosis of esophagitis, Barrett's esophagus, or peptic stricture or had abnormal pH on monitoring and therefore were categorized as having an indication for long-term treatment.

The remaining 376 patients were considered to have an unverified indication for a PPI, and 76 of them agreed to attempt to discontinue the drug. If symptoms recurred within 6 months after PPI withdrawal, patients underwent endoscopy.

Those without abnormal findings were then randomized to 7 days of PPI therapy with esomeprazole 40 mg/day or placebo.

Of the 76 patients, 53 (63%) had symptom recurrence within the first week of discontinuing the PPI. The main symptoms were heartburn/acid regurgitation (48%) and dyspepsia (42%), Dr. Reimer said.

On endoscopy, 31 (59%) had no abnormal findings.

Only 11 (14%) discontinued therapy without recurrence of symptoms during the 6 months of follow-up.

The 53 patients with recurrence were randomized to a PPI or placebo for 7 days; 80% of those taking esomeprazole had treatment success, compared with 13% receiving placebo.

There is evidence of an increased prevalence in acid-related conditions, more liberal prescribing habits—including empirical PPI therapy for unspecific dyspepsia—and PPI “dependency” as a result of acid rebound that requires more and more suppression, Dr. Bytzer said.

Ironically, studies have suggested that PPIs can actually stimulate acid secretion in healthy volunteers. A 2007 systemic review concluded “there is evidence from uncontrolled trials for an increased capacity to secrete acid in [Helicobacter pylori]–negative subjects after 8 weeks of treatment” (Aliment. Pharmacol. Ther. 2007;25:39–46).

“In other words, once you remove the PPI you get an increased capacity to secrete acid. But is this clinically relevant? Will rebound acid hypersecretion lead to acid-related symptoms?” Dr. Bytzer asked.

Apparently, it can. In a blinded withdrawal study conducted by Dr. Bytzer's group, 120 healthy volunteers were randomized to esomeprazole 40 mg or placebo for 8 weeks, after which the esomeprazole group crossed over to placebo for 4 weeks (Gastroenterol. 2009;137:80–7). After crossing over, these patients experienced a significant increase in dyspepsia, heartburn, and regurgitation at weeks 10–12.

“These subjects had not had symptoms prior the study and were never on acid reducers. They were unaware of the shift to placebo. After starting a PPI, gastrin significantly increased, and 44% got significant acid-related symptoms,” he reported.

Other investigators have found increases in reflux laryngitis, heartburn, and dyspepsia after discontinuation of PPIs, he added.

Recently, in a double-blind placebo-controlled trial in 48 H. pylori–negative volunteers, dyspeptic symptoms developed after discontinuation of pantoprazole (Am. J. Gastroenterol. 2010 March 23; doi:10.1038/ajg.2010.81). A total of 11 out of 25 (44%) subjects in the pantoprazole group developed dyspepsia, compared with 2 out of 23 (9%) in the placebo group. During the first week after discontinuation, the pantoprazole group had a mean symptom score of 5.7 versus 0.74 in the placebo group, but these scores progressively declined over 3 weeks.

“We can conclude that PPI therapy induces acid-related symptoms in around 44% of previously asymptomatic subjects, and this rebound acid hypersecretion is probably clinically relevant,” Dr. Bytzer said. “It seems that we may be inducing reflux disease when we give PPIs for non–acid-related symptoms.”

When attempting to discontinue PPI therapy in long-term users, patients can slowly taper down doses over 3 weeks or so, he suggested. However, he said it remains difficult to discontinue PPI therapy, especially in patients with GERD.

Major Finding: Of 76 patients who had unverified indications for a PPI, 11 were able to discontinue therapy without recurrence of symptoms during 6 months of follow-up.

Data Source: A standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark.

Disclosures: Dr. Bytzer is a speaker or consultant for AstraZeneca Pharmaceuticals, Nycomed, and Orexo. Dr. Reimer has received grant support from and is a consultant to AstraZeneca Pharmaceuticals.

NEW ORLEANS — Patients with gastroesophageal reflux disease are very difficult to wean off proton pump inhibitors, and there is evidence that patients essentially become “addicted” to acid suppression, findings of large study suggest.

Dr. Peter Bytzer, of Copenhagen University and Køge (Denmark) Hospital, and Dr. Christina Reimer, also of the university, reported study findings that indicate proton pump inhibitors (PPIs) are nearly impossible to discontinue, even for patients who lack a formal indication for their use.

“We found that discontinuing long-term PPI therapy was possible in only a minority of patients, and that the majority experiencing symptom relapse after discontinuing the drug had no abnormal endoscopic findings,” Dr. Reimer said in a poster presentation. “Rapid recurrence of typical reflux symptoms was the main reason for restarting therapy, and 7 days of esomeprazole was helpful, despite the normal endoscopic findings.”

Dr. Bytzer and Dr. Reimer conducted a standardized search of patients prescribed PPIs by primary care physicians in the previous 12 months in Denmark. They identified 901 long-term users (at least 120 tablets), of whom 525 had an endoscopically verified diagnosis of esophagitis, Barrett's esophagus, or peptic stricture or had abnormal pH on monitoring and therefore were categorized as having an indication for long-term treatment.

The remaining 376 patients were considered to have an unverified indication for a PPI, and 76 of them agreed to attempt to discontinue the drug. If symptoms recurred within 6 months after PPI withdrawal, patients underwent endoscopy.

Those without abnormal findings were then randomized to 7 days of PPI therapy with esomeprazole 40 mg/day or placebo.

Of the 76 patients, 53 (63%) had symptom recurrence within the first week of discontinuing the PPI. The main symptoms were heartburn/acid regurgitation (48%) and dyspepsia (42%), Dr. Reimer said.

On endoscopy, 31 (59%) had no abnormal findings.

Only 11 (14%) discontinued therapy without recurrence of symptoms during the 6 months of follow-up.

The 53 patients with recurrence were randomized to a PPI or placebo for 7 days; 80% of those taking esomeprazole had treatment success, compared with 13% receiving placebo.

There is evidence of an increased prevalence in acid-related conditions, more liberal prescribing habits—including empirical PPI therapy for unspecific dyspepsia—and PPI “dependency” as a result of acid rebound that requires more and more suppression, Dr. Bytzer said.

Ironically, studies have suggested that PPIs can actually stimulate acid secretion in healthy volunteers. A 2007 systemic review concluded “there is evidence from uncontrolled trials for an increased capacity to secrete acid in [Helicobacter pylori]–negative subjects after 8 weeks of treatment” (Aliment. Pharmacol. Ther. 2007;25:39–46).

“In other words, once you remove the PPI you get an increased capacity to secrete acid. But is this clinically relevant? Will rebound acid hypersecretion lead to acid-related symptoms?” Dr. Bytzer asked.

Apparently, it can. In a blinded withdrawal study conducted by Dr. Bytzer's group, 120 healthy volunteers were randomized to esomeprazole 40 mg or placebo for 8 weeks, after which the esomeprazole group crossed over to placebo for 4 weeks (Gastroenterol. 2009;137:80–7). After crossing over, these patients experienced a significant increase in dyspepsia, heartburn, and regurgitation at weeks 10–12.

“These subjects had not had symptoms prior the study and were never on acid reducers. They were unaware of the shift to placebo. After starting a PPI, gastrin significantly increased, and 44% got significant acid-related symptoms,” he reported.

Other investigators have found increases in reflux laryngitis, heartburn, and dyspepsia after discontinuation of PPIs, he added.

Recently, in a double-blind placebo-controlled trial in 48 H. pylori–negative volunteers, dyspeptic symptoms developed after discontinuation of pantoprazole (Am. J. Gastroenterol. 2010 March 23; doi:10.1038/ajg.2010.81). A total of 11 out of 25 (44%) subjects in the pantoprazole group developed dyspepsia, compared with 2 out of 23 (9%) in the placebo group. During the first week after discontinuation, the pantoprazole group had a mean symptom score of 5.7 versus 0.74 in the placebo group, but these scores progressively declined over 3 weeks.

“We can conclude that PPI therapy induces acid-related symptoms in around 44% of previously asymptomatic subjects, and this rebound acid hypersecretion is probably clinically relevant,” Dr. Bytzer said. “It seems that we may be inducing reflux disease when we give PPIs for non–acid-related symptoms.”

When attempting to discontinue PPI therapy in long-term users, patients can slowly taper down doses over 3 weeks or so, he suggested. However, he said it remains difficult to discontinue PPI therapy, especially in patients with GERD.

NEW ORLEANS – Hope plays an important role in the experience of cancer patients, especially those with poor prognoses, and it often follows an unexpected trajectory.

These were the findings of several studies presented at the annual conference of the American Psychosocial Oncology Society.

“While patients have a hard time defining hope, they almost always know exactly what it means to them, and they usually define its opposite as 'giving up,'” said Amy Pearson of the Lung Cancer Alliance in Washington. Her study was conducted with the National Brain Tumor Society and the Pancreatic Cancer Action Network.

Meredith Cammarata and colleagues from Mount Sinai Hospital in New York added that hope has been described as the ability to acquire belief in one's ability to control one's circumstances, a positive expectation for goal attainment, belief in possibilities for the future, and belief that one's present situation can be modified–that there is a way out of difficulties.

Others have suggested that hope is an experiential process; a relational process; a rational process; or a spiritual and transcendent process that might be determined by one's faith and belief or one's life experiences, her poster noted.

Studies further indicate that hope exists along a continuum, with goals ranging from cure to comfortable death; that hope is fluid and changes throughout the course of the illness; and that hope is dynamic, beginning with one's reaction to a diagnosis, according to Ms. Pearson's study, which examined this “hope trajectory” in 15 long-term survivors of lung, brain, and pancreatic cancers.

Although the 5-year survival rates for these cancers are approximately 30%, 15%, and 5%, respectively, the subjects in the study had survival that was double the median survival time for their tumor type. Therefore, the lung cancer survivors were required to live at least 34 months, but actually lived 4-12 years; the brain tumor survivors were required to live at least 30 months, but lived 8-21 years; and the pancreatic cancer survivors were required live at least 1 year, but actually lived 3-14 years. “We sought to better understand the meaning of hope, the role hope plays, and what contributes to hope or takes it away from these patients,” she said.

The research was based on semistructured 1-hour interviews. Patients also completed an online version of the Herth Hope Index, a validated 12-item scale. From their analysis, three major themes emerged: taking control, having faith, and finding meaning.

All of the patients took at least one action involving treatment decision making. Ten sought second opinions, five researched clinical trials (and three participated), three insisted on off-label treatment, and two performed research to confirm protocols and doctors' decisions. Several continued to work and take other measures to “normalize” their lives. They protected themselves through avoidance of “negative people” and avoidance of negative information. Some made healthy lifestyle changes, which they later attributed to saving their lives.

Family, Faith Are the Main Sources

One-third identified faith as the most important factor in finding hope and in coping, and the majority called faith important. Ten said that their diagnosis had changed their lives for the better or for “a reason.” Virtually all became part of a peer-support network to engender hope in other patients.

The most frequently mentioned sources of hope were family members, church and/or faith, and the medical personnel who treated them. Things that seemed to “take hope away” included dismal research statistics, negative medical personnel, death of other survivors, and setbacks in disease status.

The study validated that patients want to maintain hope–and can do so, especially when the oncology team understands the individual patient's beliefs and helps foster that patient's version of hope. (See box below.)

Other investigators illustrated how the patient's “trajectory of hope” does not necessarily correspond with their prognosis or treatment response.

Strong religious affiliation, a supportive family, cancer prognosis, and treatment plan are “not always associated with hope in the manner in which we would expect them to be,” said Ms. Cammarata. She and her colleagues presented the following cases to illustrate:

▸ Patient No. 1 had acute myeloid leukemia and expressed minimal hope from the time of diagnosis. “Instead of focusing on getting better, she ruminated on her symptoms and the possibility of relapse,” the researchers noted. As the treatment plan and bone marrow transplant team became positive about her diagnosis, she remained hopeless. Even in remission, she refused to leave the house and obsessed over relapse. Despite having a loving support system, she was unable to accept and benefit from their support.” The hope trajectory, which plotted the patient's expression of hope against the treatment course, showed that her hope plummeted continuously from baseline, with the curve continuing to fall even when the transplant appeared to be working.

▸ Patient No. 2 had acute lymphoblastic leukemia. Although she underwent an allogeneic transplant from her HLA-matched sister, she relapsed and died 1 year later. Her experience of hope closely matched her treatment plan, with the curve of her hope trajectory paralleling her treatment's ups and downs. “Because of the match, she was hopeful for a good response, but when she experienced chemotherapy side effects, she became depressed and difficult to engage. After the transplant, she enjoyed a brief state of remission and felt hopeful about regaining a normal life, but she began to be continuously fatigued, and along with this came the fear that she would never feel better. She relapsed within 3 months and was offered a second transplant, but a slim chance for prolonged survival.

“She refused the transplant and chose to live her precious last days as positively as she could, surrounded by family and friends, even giving herself a going-away party,” Ms. Cammarata and colleagues reported. “Her hope trajectory completely mirrored her disease and, surprisingly, the curve even rose as she approached death and treatments failed.”

▸ Patient No. 3 expressed “endless hope,” in spite of a poor prognosis, the death of a friend who also had leukemia, and ultimately his debilitating graft-vs.-host disease. “He had a tremendous amount of optimism from the time of diagnosis,” the authors wrote in the poster. “He felt the transplant made him a better person, and he became closer than ever with his family.” In this case, the trajectory of hope was higher than one would expect, and remained high even in the face of life-threatening complications.

Multiple aspects of hope can be fostered, the investigators suggested, not only for the patient but for the medical team and family. These can influence the already complex and confusing role that hope plays in the mind of a bone marrow transplant patient.

Go Carefully With Informed Consent

Dr. Carl G. Kardinal of the University of Missouri in Columbia suggested that Phase II trials offer patients with advanced disease hope that might not otherwise be available. He and his colleagues evaluated the hope trajectory of 50 consecutive patients who consented to participate in phase II cooperative trials. Patients were interviewed by a psychiatric social worker who was not directly involved in their care.

All 50 patients stated that hope of therapeutic benefit, however small, was their primary motivation to join the trial. Other motivating factors were altruism (29), avoidance of regret that later they should have participated (19), lack of other treatment alternatives (14), and trust that their oncologist thinks this trial might help (10), Dr. Kardinal reported.

He pointed out that this is a vulnerable patient population for whom “truly informed consent” might not be possible. He further maintained that the current informed-consent process is too cumbersome and should be simplified.

“Hope of a treatment response is the overwhelming motivation of cancer patients to participate in phase II trials. This places an even greater responsibility on the physician-investigator to protect these human subjects,” he said.

Physicians Can Create a Space for Hope

Health care providers can foster hope in the following ways:

▸ Even in cancers of poor prognosis, patients can survive. When physicians deliver the diagnosis, they can create a space for hope.

▸ “What can I control?” is an important question for patients. Assess what level of information the patient wants, and communicate accordingly. For patients who believe that a healthy lifestyle might make a difference, foster this behavior.

▸ Psychosocial and support resources might have a positive impact. Inform patients about support resources and peer support programs. Connecting with other patients might help survivors find meaning.

▸ Cancer is an existential crisis. Some patients search for the meaning of it while their faith, spirituality, and personal beliefs might be challenged. If the patient uses faith or spirituality to gain hope, find ways to support this tool. If the patient's questioning of his or her faith results in a loss of hope, consider helping the patient connect with a spiritual community or adviser.

Source: Ms. Pearson

My Take

Seeing the Future as Half Full

A diagnosis like cancer calls the future into question and causes us to peer anxiously ahead. Hope is a way of seeing our future as half full, rather than half empty. Unrealistic hope can be a form of denial, and many cancer patients find themselves caught in the “prison of positive thinking,” urged to be upbeat and positive no matter how bad their prognosis. On the other hand, hopelessness is a symptom of depression, and a uniformly down-beat view is demoralizing to patient, family, and medical staff. The real question is: Hope for what?” Even a very short future can be more than half full.

Dr. David Spiegel is the Jack, Lulu and Sam Willson-professor in the School of Medicine at Stanford (Calif.) University. He also serves as associate chair of psychiatry and behavioral sciences at the university.

NEW ORLEANS – Hope plays an important role in the experience of cancer patients, especially those with poor prognoses, and it often follows an unexpected trajectory.

These were the findings of several studies presented at the annual conference of the American Psychosocial Oncology Society.

“While patients have a hard time defining hope, they almost always know exactly what it means to them, and they usually define its opposite as 'giving up,'” said Amy Pearson of the Lung Cancer Alliance in Washington. Her study was conducted with the National Brain Tumor Society and the Pancreatic Cancer Action Network.

Meredith Cammarata and colleagues from Mount Sinai Hospital in New York added that hope has been described as the ability to acquire belief in one's ability to control one's circumstances, a positive expectation for goal attainment, belief in possibilities for the future, and belief that one's present situation can be modified–that there is a way out of difficulties.

Others have suggested that hope is an experiential process; a relational process; a rational process; or a spiritual and transcendent process that might be determined by one's faith and belief or one's life experiences, her poster noted.

Studies further indicate that hope exists along a continuum, with goals ranging from cure to comfortable death; that hope is fluid and changes throughout the course of the illness; and that hope is dynamic, beginning with one's reaction to a diagnosis, according to Ms. Pearson's study, which examined this “hope trajectory” in 15 long-term survivors of lung, brain, and pancreatic cancers.

Although the 5-year survival rates for these cancers are approximately 30%, 15%, and 5%, respectively, the subjects in the study had survival that was double the median survival time for their tumor type. Therefore, the lung cancer survivors were required to live at least 34 months, but actually lived 4-12 years; the brain tumor survivors were required to live at least 30 months, but lived 8-21 years; and the pancreatic cancer survivors were required live at least 1 year, but actually lived 3-14 years. “We sought to better understand the meaning of hope, the role hope plays, and what contributes to hope or takes it away from these patients,” she said.

The research was based on semistructured 1-hour interviews. Patients also completed an online version of the Herth Hope Index, a validated 12-item scale. From their analysis, three major themes emerged: taking control, having faith, and finding meaning.

All of the patients took at least one action involving treatment decision making. Ten sought second opinions, five researched clinical trials (and three participated), three insisted on off-label treatment, and two performed research to confirm protocols and doctors' decisions. Several continued to work and take other measures to “normalize” their lives. They protected themselves through avoidance of “negative people” and avoidance of negative information. Some made healthy lifestyle changes, which they later attributed to saving their lives.

Family, Faith Are the Main Sources

One-third identified faith as the most important factor in finding hope and in coping, and the majority called faith important. Ten said that their diagnosis had changed their lives for the better or for “a reason.” Virtually all became part of a peer-support network to engender hope in other patients.

The most frequently mentioned sources of hope were family members, church and/or faith, and the medical personnel who treated them. Things that seemed to “take hope away” included dismal research statistics, negative medical personnel, death of other survivors, and setbacks in disease status.

The study validated that patients want to maintain hope–and can do so, especially when the oncology team understands the individual patient's beliefs and helps foster that patient's version of hope. (See box below.)

Other investigators illustrated how the patient's “trajectory of hope” does not necessarily correspond with their prognosis or treatment response.

Strong religious affiliation, a supportive family, cancer prognosis, and treatment plan are “not always associated with hope in the manner in which we would expect them to be,” said Ms. Cammarata. She and her colleagues presented the following cases to illustrate:

▸ Patient No. 1 had acute myeloid leukemia and expressed minimal hope from the time of diagnosis. “Instead of focusing on getting better, she ruminated on her symptoms and the possibility of relapse,” the researchers noted. As the treatment plan and bone marrow transplant team became positive about her diagnosis, she remained hopeless. Even in remission, she refused to leave the house and obsessed over relapse. Despite having a loving support system, she was unable to accept and benefit from their support.” The hope trajectory, which plotted the patient's expression of hope against the treatment course, showed that her hope plummeted continuously from baseline, with the curve continuing to fall even when the transplant appeared to be working.

▸ Patient No. 2 had acute lymphoblastic leukemia. Although she underwent an allogeneic transplant from her HLA-matched sister, she relapsed and died 1 year later. Her experience of hope closely matched her treatment plan, with the curve of her hope trajectory paralleling her treatment's ups and downs. “Because of the match, she was hopeful for a good response, but when she experienced chemotherapy side effects, she became depressed and difficult to engage. After the transplant, she enjoyed a brief state of remission and felt hopeful about regaining a normal life, but she began to be continuously fatigued, and along with this came the fear that she would never feel better. She relapsed within 3 months and was offered a second transplant, but a slim chance for prolonged survival.

“She refused the transplant and chose to live her precious last days as positively as she could, surrounded by family and friends, even giving herself a going-away party,” Ms. Cammarata and colleagues reported. “Her hope trajectory completely mirrored her disease and, surprisingly, the curve even rose as she approached death and treatments failed.”

▸ Patient No. 3 expressed “endless hope,” in spite of a poor prognosis, the death of a friend who also had leukemia, and ultimately his debilitating graft-vs.-host disease. “He had a tremendous amount of optimism from the time of diagnosis,” the authors wrote in the poster. “He felt the transplant made him a better person, and he became closer than ever with his family.” In this case, the trajectory of hope was higher than one would expect, and remained high even in the face of life-threatening complications.

Multiple aspects of hope can be fostered, the investigators suggested, not only for the patient but for the medical team and family. These can influence the already complex and confusing role that hope plays in the mind of a bone marrow transplant patient.

Go Carefully With Informed Consent

Dr. Carl G. Kardinal of the University of Missouri in Columbia suggested that Phase II trials offer patients with advanced disease hope that might not otherwise be available. He and his colleagues evaluated the hope trajectory of 50 consecutive patients who consented to participate in phase II cooperative trials. Patients were interviewed by a psychiatric social worker who was not directly involved in their care.

All 50 patients stated that hope of therapeutic benefit, however small, was their primary motivation to join the trial. Other motivating factors were altruism (29), avoidance of regret that later they should have participated (19), lack of other treatment alternatives (14), and trust that their oncologist thinks this trial might help (10), Dr. Kardinal reported.

He pointed out that this is a vulnerable patient population for whom “truly informed consent” might not be possible. He further maintained that the current informed-consent process is too cumbersome and should be simplified.

“Hope of a treatment response is the overwhelming motivation of cancer patients to participate in phase II trials. This places an even greater responsibility on the physician-investigator to protect these human subjects,” he said.

Physicians Can Create a Space for Hope

Health care providers can foster hope in the following ways:

▸ Even in cancers of poor prognosis, patients can survive. When physicians deliver the diagnosis, they can create a space for hope.

▸ “What can I control?” is an important question for patients. Assess what level of information the patient wants, and communicate accordingly. For patients who believe that a healthy lifestyle might make a difference, foster this behavior.

▸ Psychosocial and support resources might have a positive impact. Inform patients about support resources and peer support programs. Connecting with other patients might help survivors find meaning.

▸ Cancer is an existential crisis. Some patients search for the meaning of it while their faith, spirituality, and personal beliefs might be challenged. If the patient uses faith or spirituality to gain hope, find ways to support this tool. If the patient's questioning of his or her faith results in a loss of hope, consider helping the patient connect with a spiritual community or adviser.

Source: Ms. Pearson

My Take

Seeing the Future as Half Full

A diagnosis like cancer calls the future into question and causes us to peer anxiously ahead. Hope is a way of seeing our future as half full, rather than half empty. Unrealistic hope can be a form of denial, and many cancer patients find themselves caught in the “prison of positive thinking,” urged to be upbeat and positive no matter how bad their prognosis. On the other hand, hopelessness is a symptom of depression, and a uniformly down-beat view is demoralizing to patient, family, and medical staff. The real question is: Hope for what?” Even a very short future can be more than half full.

Dr. David Spiegel is the Jack, Lulu and Sam Willson-professor in the School of Medicine at Stanford (Calif.) University. He also serves as associate chair of psychiatry and behavioral sciences at the university.

NEW ORLEANS – Hope plays an important role in the experience of cancer patients, especially those with poor prognoses, and it often follows an unexpected trajectory.

These were the findings of several studies presented at the annual conference of the American Psychosocial Oncology Society.

“While patients have a hard time defining hope, they almost always know exactly what it means to them, and they usually define its opposite as 'giving up,'” said Amy Pearson of the Lung Cancer Alliance in Washington. Her study was conducted with the National Brain Tumor Society and the Pancreatic Cancer Action Network.

Meredith Cammarata and colleagues from Mount Sinai Hospital in New York added that hope has been described as the ability to acquire belief in one's ability to control one's circumstances, a positive expectation for goal attainment, belief in possibilities for the future, and belief that one's present situation can be modified–that there is a way out of difficulties.

Others have suggested that hope is an experiential process; a relational process; a rational process; or a spiritual and transcendent process that might be determined by one's faith and belief or one's life experiences, her poster noted.

Studies further indicate that hope exists along a continuum, with goals ranging from cure to comfortable death; that hope is fluid and changes throughout the course of the illness; and that hope is dynamic, beginning with one's reaction to a diagnosis, according to Ms. Pearson's study, which examined this “hope trajectory” in 15 long-term survivors of lung, brain, and pancreatic cancers.

Although the 5-year survival rates for these cancers are approximately 30%, 15%, and 5%, respectively, the subjects in the study had survival that was double the median survival time for their tumor type. Therefore, the lung cancer survivors were required to live at least 34 months, but actually lived 4-12 years; the brain tumor survivors were required to live at least 30 months, but lived 8-21 years; and the pancreatic cancer survivors were required live at least 1 year, but actually lived 3-14 years. “We sought to better understand the meaning of hope, the role hope plays, and what contributes to hope or takes it away from these patients,” she said.

The research was based on semistructured 1-hour interviews. Patients also completed an online version of the Herth Hope Index, a validated 12-item scale. From their analysis, three major themes emerged: taking control, having faith, and finding meaning.

All of the patients took at least one action involving treatment decision making. Ten sought second opinions, five researched clinical trials (and three participated), three insisted on off-label treatment, and two performed research to confirm protocols and doctors' decisions. Several continued to work and take other measures to “normalize” their lives. They protected themselves through avoidance of “negative people” and avoidance of negative information. Some made healthy lifestyle changes, which they later attributed to saving their lives.

Family, Faith Are the Main Sources

One-third identified faith as the most important factor in finding hope and in coping, and the majority called faith important. Ten said that their diagnosis had changed their lives for the better or for “a reason.” Virtually all became part of a peer-support network to engender hope in other patients.

The most frequently mentioned sources of hope were family members, church and/or faith, and the medical personnel who treated them. Things that seemed to “take hope away” included dismal research statistics, negative medical personnel, death of other survivors, and setbacks in disease status.

The study validated that patients want to maintain hope–and can do so, especially when the oncology team understands the individual patient's beliefs and helps foster that patient's version of hope. (See box below.)

Other investigators illustrated how the patient's “trajectory of hope” does not necessarily correspond with their prognosis or treatment response.

Strong religious affiliation, a supportive family, cancer prognosis, and treatment plan are “not always associated with hope in the manner in which we would expect them to be,” said Ms. Cammarata. She and her colleagues presented the following cases to illustrate:

▸ Patient No. 1 had acute myeloid leukemia and expressed minimal hope from the time of diagnosis. “Instead of focusing on getting better, she ruminated on her symptoms and the possibility of relapse,” the researchers noted. As the treatment plan and bone marrow transplant team became positive about her diagnosis, she remained hopeless. Even in remission, she refused to leave the house and obsessed over relapse. Despite having a loving support system, she was unable to accept and benefit from their support.” The hope trajectory, which plotted the patient's expression of hope against the treatment course, showed that her hope plummeted continuously from baseline, with the curve continuing to fall even when the transplant appeared to be working.

▸ Patient No. 2 had acute lymphoblastic leukemia. Although she underwent an allogeneic transplant from her HLA-matched sister, she relapsed and died 1 year later. Her experience of hope closely matched her treatment plan, with the curve of her hope trajectory paralleling her treatment's ups and downs. “Because of the match, she was hopeful for a good response, but when she experienced chemotherapy side effects, she became depressed and difficult to engage. After the transplant, she enjoyed a brief state of remission and felt hopeful about regaining a normal life, but she began to be continuously fatigued, and along with this came the fear that she would never feel better. She relapsed within 3 months and was offered a second transplant, but a slim chance for prolonged survival.

“She refused the transplant and chose to live her precious last days as positively as she could, surrounded by family and friends, even giving herself a going-away party,” Ms. Cammarata and colleagues reported. “Her hope trajectory completely mirrored her disease and, surprisingly, the curve even rose as she approached death and treatments failed.”

▸ Patient No. 3 expressed “endless hope,” in spite of a poor prognosis, the death of a friend who also had leukemia, and ultimately his debilitating graft-vs.-host disease. “He had a tremendous amount of optimism from the time of diagnosis,” the authors wrote in the poster. “He felt the transplant made him a better person, and he became closer than ever with his family.” In this case, the trajectory of hope was higher than one would expect, and remained high even in the face of life-threatening complications.

Multiple aspects of hope can be fostered, the investigators suggested, not only for the patient but for the medical team and family. These can influence the already complex and confusing role that hope plays in the mind of a bone marrow transplant patient.

Go Carefully With Informed Consent

Dr. Carl G. Kardinal of the University of Missouri in Columbia suggested that Phase II trials offer patients with advanced disease hope that might not otherwise be available. He and his colleagues evaluated the hope trajectory of 50 consecutive patients who consented to participate in phase II cooperative trials. Patients were interviewed by a psychiatric social worker who was not directly involved in their care.

All 50 patients stated that hope of therapeutic benefit, however small, was their primary motivation to join the trial. Other motivating factors were altruism (29), avoidance of regret that later they should have participated (19), lack of other treatment alternatives (14), and trust that their oncologist thinks this trial might help (10), Dr. Kardinal reported.

He pointed out that this is a vulnerable patient population for whom “truly informed consent” might not be possible. He further maintained that the current informed-consent process is too cumbersome and should be simplified.

“Hope of a treatment response is the overwhelming motivation of cancer patients to participate in phase II trials. This places an even greater responsibility on the physician-investigator to protect these human subjects,” he said.

Physicians Can Create a Space for Hope

Health care providers can foster hope in the following ways:

▸ Even in cancers of poor prognosis, patients can survive. When physicians deliver the diagnosis, they can create a space for hope.

▸ “What can I control?” is an important question for patients. Assess what level of information the patient wants, and communicate accordingly. For patients who believe that a healthy lifestyle might make a difference, foster this behavior.

▸ Psychosocial and support resources might have a positive impact. Inform patients about support resources and peer support programs. Connecting with other patients might help survivors find meaning.

▸ Cancer is an existential crisis. Some patients search for the meaning of it while their faith, spirituality, and personal beliefs might be challenged. If the patient uses faith or spirituality to gain hope, find ways to support this tool. If the patient's questioning of his or her faith results in a loss of hope, consider helping the patient connect with a spiritual community or adviser.

Source: Ms. Pearson

My Take

Seeing the Future as Half Full

A diagnosis like cancer calls the future into question and causes us to peer anxiously ahead. Hope is a way of seeing our future as half full, rather than half empty. Unrealistic hope can be a form of denial, and many cancer patients find themselves caught in the “prison of positive thinking,” urged to be upbeat and positive no matter how bad their prognosis. On the other hand, hopelessness is a symptom of depression, and a uniformly down-beat view is demoralizing to patient, family, and medical staff. The real question is: Hope for what?” Even a very short future can be more than half full.

Dr. David Spiegel is the Jack, Lulu and Sam Willson-professor in the School of Medicine at Stanford (Calif.) University. He also serves as associate chair of psychiatry and behavioral sciences at the university.