Endoscopy, Pancreas, & Biliary Tract

Early results from a small clinical trial suggest the new oral skin cancer drug vismodegib may be therapeutic in patients receiving chemotherapy for metastatic pancreatic cancer.

Half of 20 patients treated with vismodegib (Erivedge, GDC-0449) and gemcitabine (Gemzar) were progression free at 3 months, investigators reported during a pancreatic cancer conference sponsored by the American Association for Cancer Research. Five patients had partial responses, and five had stable disease.

The study found pretreatment sonic hedgehog expression level was the biological correlate most predictive of therapeutic benefit. Vismodegib, a small molecule drug from Genentech, blocks the Smoothened (SMO) protein in the hedgehog signaling pathway

If validated in additional studies, the combination of vismodegib and gemcitabine "has the potential to change the way we treat pancreatic cancer" lead author Dr. Edward Kim of the University of Michigan Comprehensive Cancer Center in Ann Arbor, said in a press briefing at the meeting in Lake Tahoe, Nev.

In previous research, the investigators determined that specific pancreatic cancer stem cells express significantly elevated levels of sonic hedgehog (Cancer Res. 2007;67:1030-7), which led to successful phase I studies, Dr. Kim said in an interview. Building on that foundation, for the current clinical trial, the researchers incorporated pair core tumor biopsies to prospectively compare the inhibition of the hedgehog pathway in pancreatic cancer before and after vismodegib treatment.

To date, 21 of the study’s planned 25 patients with advanced pancreatic cancer have been enrolled. Data from 20 of the patients with paired biopsies who had completed three treatment cycles were reported at the meeting.

All of the patients had previously untreated metastatic pancreatic cancer, for which the protocol initiated daily monotherapy with vismodegib for 4 weeks, followed by combination treatment with vismodegib and gemcitabine on days 1, 8, and 15 of each month in a 3-month cycle, Dr. Kim reported. Each patient underwent two sets of three core biopsies – one set prior to treatment and another set 3 weeks after treatment initiation.

To evaluate the effects of the experimental drug on pancreatic cancer stem cells, the investigators used immunohistochemistry to evaluate expression of sonic hedgehog and Ki-67, a static marker of tumor proliferation.

"After three cycles of therapy, five patients showed evidence of partial disease response [defined as a minimum 30% decrease in the sum of the longest-diameter target lesions relative to baseline, based on RECIST criteria] and five patients had stable disease, yielding 3-month progression-free survival rate of 50%," Dr. Kim stated. Additionally, half of the evaluable patients demonstrated an average 60% reduction in pancreatic cancer stem cells and a 54% decrease in the proliferation index.

Importantly, Dr. Kim noted, "sonic hedgehog expression was more highly expressed in patients who had a partial response or stable disease compared with patients whose disease progressed." Specifically, the mean pretreatment hedgehog expression H-score (intensity times the percentage of positive cells) was 285 in patients with partial response or stable disease compared with 168 in those with progression.

"We are currently conducting further correlative studies to determine the best predictors of which patients stand to benefit from this treatment regimen," he said. The researchers also are continuing to investigate the effect that vismodegib has on hedgehog pathway target genes.

The response rate observed in this study exceeded expectations, according to session moderator Dr. Daniel Von Hoff, chief scientific officer for the Scottsdale Healthcare Research Institute and physician-in-chief at TGen (Translational Genomics Research Institute) in Phoenix. "We usually see about a 5%-9% change of response to gemcitabine by itself, but here it was 25%. The good news is that this drug doesn’t add any toxicities."

The Food and Drug Administration approved vismodegib Jan. 30 for locally advanced or metastatic basal cell carcinoma that cannot be treated with surgery or radiation. It has not been considered for an indication in pancreatic cancer.

Dr. Kim and Dr. Von Hoff disclosed having no relevant financial conflicts of interest.

Early results from a small clinical trial suggest the new oral skin cancer drug vismodegib may be therapeutic in patients receiving chemotherapy for metastatic pancreatic cancer.

Half of 20 patients treated with vismodegib (Erivedge, GDC-0449) and gemcitabine (Gemzar) were progression free at 3 months, investigators reported during a pancreatic cancer conference sponsored by the American Association for Cancer Research. Five patients had partial responses, and five had stable disease.

The study found pretreatment sonic hedgehog expression level was the biological correlate most predictive of therapeutic benefit. Vismodegib, a small molecule drug from Genentech, blocks the Smoothened (SMO) protein in the hedgehog signaling pathway

If validated in additional studies, the combination of vismodegib and gemcitabine "has the potential to change the way we treat pancreatic cancer" lead author Dr. Edward Kim of the University of Michigan Comprehensive Cancer Center in Ann Arbor, said in a press briefing at the meeting in Lake Tahoe, Nev.

In previous research, the investigators determined that specific pancreatic cancer stem cells express significantly elevated levels of sonic hedgehog (Cancer Res. 2007;67:1030-7), which led to successful phase I studies, Dr. Kim said in an interview. Building on that foundation, for the current clinical trial, the researchers incorporated pair core tumor biopsies to prospectively compare the inhibition of the hedgehog pathway in pancreatic cancer before and after vismodegib treatment.

To date, 21 of the study’s planned 25 patients with advanced pancreatic cancer have been enrolled. Data from 20 of the patients with paired biopsies who had completed three treatment cycles were reported at the meeting.

All of the patients had previously untreated metastatic pancreatic cancer, for which the protocol initiated daily monotherapy with vismodegib for 4 weeks, followed by combination treatment with vismodegib and gemcitabine on days 1, 8, and 15 of each month in a 3-month cycle, Dr. Kim reported. Each patient underwent two sets of three core biopsies – one set prior to treatment and another set 3 weeks after treatment initiation.

To evaluate the effects of the experimental drug on pancreatic cancer stem cells, the investigators used immunohistochemistry to evaluate expression of sonic hedgehog and Ki-67, a static marker of tumor proliferation.

"After three cycles of therapy, five patients showed evidence of partial disease response [defined as a minimum 30% decrease in the sum of the longest-diameter target lesions relative to baseline, based on RECIST criteria] and five patients had stable disease, yielding 3-month progression-free survival rate of 50%," Dr. Kim stated. Additionally, half of the evaluable patients demonstrated an average 60% reduction in pancreatic cancer stem cells and a 54% decrease in the proliferation index.

Importantly, Dr. Kim noted, "sonic hedgehog expression was more highly expressed in patients who had a partial response or stable disease compared with patients whose disease progressed." Specifically, the mean pretreatment hedgehog expression H-score (intensity times the percentage of positive cells) was 285 in patients with partial response or stable disease compared with 168 in those with progression.

"We are currently conducting further correlative studies to determine the best predictors of which patients stand to benefit from this treatment regimen," he said. The researchers also are continuing to investigate the effect that vismodegib has on hedgehog pathway target genes.

The response rate observed in this study exceeded expectations, according to session moderator Dr. Daniel Von Hoff, chief scientific officer for the Scottsdale Healthcare Research Institute and physician-in-chief at TGen (Translational Genomics Research Institute) in Phoenix. "We usually see about a 5%-9% change of response to gemcitabine by itself, but here it was 25%. The good news is that this drug doesn’t add any toxicities."

The Food and Drug Administration approved vismodegib Jan. 30 for locally advanced or metastatic basal cell carcinoma that cannot be treated with surgery or radiation. It has not been considered for an indication in pancreatic cancer.

Dr. Kim and Dr. Von Hoff disclosed having no relevant financial conflicts of interest.

Early results from a small clinical trial suggest the new oral skin cancer drug vismodegib may be therapeutic in patients receiving chemotherapy for metastatic pancreatic cancer.

Half of 20 patients treated with vismodegib (Erivedge, GDC-0449) and gemcitabine (Gemzar) were progression free at 3 months, investigators reported during a pancreatic cancer conference sponsored by the American Association for Cancer Research. Five patients had partial responses, and five had stable disease.

The study found pretreatment sonic hedgehog expression level was the biological correlate most predictive of therapeutic benefit. Vismodegib, a small molecule drug from Genentech, blocks the Smoothened (SMO) protein in the hedgehog signaling pathway

If validated in additional studies, the combination of vismodegib and gemcitabine "has the potential to change the way we treat pancreatic cancer" lead author Dr. Edward Kim of the University of Michigan Comprehensive Cancer Center in Ann Arbor, said in a press briefing at the meeting in Lake Tahoe, Nev.

In previous research, the investigators determined that specific pancreatic cancer stem cells express significantly elevated levels of sonic hedgehog (Cancer Res. 2007;67:1030-7), which led to successful phase I studies, Dr. Kim said in an interview. Building on that foundation, for the current clinical trial, the researchers incorporated pair core tumor biopsies to prospectively compare the inhibition of the hedgehog pathway in pancreatic cancer before and after vismodegib treatment.

To date, 21 of the study’s planned 25 patients with advanced pancreatic cancer have been enrolled. Data from 20 of the patients with paired biopsies who had completed three treatment cycles were reported at the meeting.

All of the patients had previously untreated metastatic pancreatic cancer, for which the protocol initiated daily monotherapy with vismodegib for 4 weeks, followed by combination treatment with vismodegib and gemcitabine on days 1, 8, and 15 of each month in a 3-month cycle, Dr. Kim reported. Each patient underwent two sets of three core biopsies – one set prior to treatment and another set 3 weeks after treatment initiation.

To evaluate the effects of the experimental drug on pancreatic cancer stem cells, the investigators used immunohistochemistry to evaluate expression of sonic hedgehog and Ki-67, a static marker of tumor proliferation.

"After three cycles of therapy, five patients showed evidence of partial disease response [defined as a minimum 30% decrease in the sum of the longest-diameter target lesions relative to baseline, based on RECIST criteria] and five patients had stable disease, yielding 3-month progression-free survival rate of 50%," Dr. Kim stated. Additionally, half of the evaluable patients demonstrated an average 60% reduction in pancreatic cancer stem cells and a 54% decrease in the proliferation index.

Importantly, Dr. Kim noted, "sonic hedgehog expression was more highly expressed in patients who had a partial response or stable disease compared with patients whose disease progressed." Specifically, the mean pretreatment hedgehog expression H-score (intensity times the percentage of positive cells) was 285 in patients with partial response or stable disease compared with 168 in those with progression.

"We are currently conducting further correlative studies to determine the best predictors of which patients stand to benefit from this treatment regimen," he said. The researchers also are continuing to investigate the effect that vismodegib has on hedgehog pathway target genes.

The response rate observed in this study exceeded expectations, according to session moderator Dr. Daniel Von Hoff, chief scientific officer for the Scottsdale Healthcare Research Institute and physician-in-chief at TGen (Translational Genomics Research Institute) in Phoenix. "We usually see about a 5%-9% change of response to gemcitabine by itself, but here it was 25%. The good news is that this drug doesn’t add any toxicities."

The Food and Drug Administration approved vismodegib Jan. 30 for locally advanced or metastatic basal cell carcinoma that cannot be treated with surgery or radiation. It has not been considered for an indication in pancreatic cancer.

Dr. Kim and Dr. Von Hoff disclosed having no relevant financial conflicts of interest.

SAN DIEGO – A proposed quality measure for pancreatic surgery has the potential to assess performance more thoroughly than current volume and mortality measures, judging by surgeons’ responses to a recent survey.

The 12-item "Quality Scorecard," developed by Dr. Brian T. Kalish of Beth Israel Deaconess Medical Center, Boston, and a team of pancreatic surgeons from multiple academic medical centers, consists of actionable and meaningful measures. The scorecard is aligned with the Institute of Medicine’s health care quality domains: safety, timeliness, effectiveness, patient centeredness, efficiency, and equitability.

"Traditional quality metrics in high-acuity surgery on their own cannot measure or satisfy the [IOM] domains," Dr. Kalish explained in a plenary presentation at the annual Digestive Disease Week. "Our goal was to evaluate the need for broader quality metrics and whether such broader metrics would align to contemporary IOM domains."

"We expect the scorecard to reveal quality to an extent that volume and mortality alone cannot."

Toward this end, the development team worked with a professional market research firm to create a web-based survey and distribute it to expert pancreatic surgeons identified through specialty societies and verified by survey demographics, Dr. Kalish explained. "The survey asked respondents to rank [62] proposed quality metrics on level of importance, from essential to not important, and to align the metric to one or more of the [IOM] quality domains." Points were awarded for level of importance and multidomain alignment, and the two scores for a given quality metric were averaged to render a total quality score that was then normalized to a 100-point scale, he said.

The 21% survey response rate represented 106 surgeons primarily from academic medical centers in North America who perform an average of 43 pancreatic operations per year, said Dr. Kalish. The need for improved quality metrics was indicated by 90% of the respondents, while 81% believed that a "quality scorecard" in pancreatic surgery would probably or definitely be of value, he reported. More than one-third of the proposed metrics aligned to more than one IOM domain, and at least half of the respondents rated these as essential or very important, he said.

Of the 62 metrics, 12 emerged with the highest total quality score. In rank order, they are: multidisciplinary services for pancreatic diseases, major complication rate, perioperative mortality, overall complication rate, incidence of postoperative hemorrhage, venous thromboembolism prophylaxis, patients with malignancy who undergo adjuvant therapy, readmission rates (30 day, 90 day, total), incidence of postoperative pancreatic fistula, timely and appropriate perioperative antibiotics, survival rates (1 year and 5 year), and timing from diagnosis to surgical consultation.

"The metrics related to mortality, the rate and severity of complications, and access to multidisciplinary services for pancreatic disease had the highest total quality scores; technical and perioperative metrics had intermediate scores; and metrics related to patient satisfaction with care, costs of care, and patient demographics had the lowest total quality scores," Dr. Kalish observed. With respect to the IOM domains, "the least represented domains were equitability, efficiency, and patient-centeredness," he said.

Although the actual performance thresholds for each of the metrics require further definition and validation, "we expect the scorecard to reveal quality to an extent that volume and mortality alone cannot," Dr. Kalish stated, noting that the development process is ongoing.

Future efforts include the organization of patient focus groups and a formal survey of patients and family members to attain insight into which quality metrics are important to those receiving care, as well as a multicenter prospective validation.

Dr. Kalish reported having no relevant financial conflicts of interest.

SAN DIEGO – A proposed quality measure for pancreatic surgery has the potential to assess performance more thoroughly than current volume and mortality measures, judging by surgeons’ responses to a recent survey.

The 12-item "Quality Scorecard," developed by Dr. Brian T. Kalish of Beth Israel Deaconess Medical Center, Boston, and a team of pancreatic surgeons from multiple academic medical centers, consists of actionable and meaningful measures. The scorecard is aligned with the Institute of Medicine’s health care quality domains: safety, timeliness, effectiveness, patient centeredness, efficiency, and equitability.

"Traditional quality metrics in high-acuity surgery on their own cannot measure or satisfy the [IOM] domains," Dr. Kalish explained in a plenary presentation at the annual Digestive Disease Week. "Our goal was to evaluate the need for broader quality metrics and whether such broader metrics would align to contemporary IOM domains."

"We expect the scorecard to reveal quality to an extent that volume and mortality alone cannot."

Toward this end, the development team worked with a professional market research firm to create a web-based survey and distribute it to expert pancreatic surgeons identified through specialty societies and verified by survey demographics, Dr. Kalish explained. "The survey asked respondents to rank [62] proposed quality metrics on level of importance, from essential to not important, and to align the metric to one or more of the [IOM] quality domains." Points were awarded for level of importance and multidomain alignment, and the two scores for a given quality metric were averaged to render a total quality score that was then normalized to a 100-point scale, he said.

The 21% survey response rate represented 106 surgeons primarily from academic medical centers in North America who perform an average of 43 pancreatic operations per year, said Dr. Kalish. The need for improved quality metrics was indicated by 90% of the respondents, while 81% believed that a "quality scorecard" in pancreatic surgery would probably or definitely be of value, he reported. More than one-third of the proposed metrics aligned to more than one IOM domain, and at least half of the respondents rated these as essential or very important, he said.

Of the 62 metrics, 12 emerged with the highest total quality score. In rank order, they are: multidisciplinary services for pancreatic diseases, major complication rate, perioperative mortality, overall complication rate, incidence of postoperative hemorrhage, venous thromboembolism prophylaxis, patients with malignancy who undergo adjuvant therapy, readmission rates (30 day, 90 day, total), incidence of postoperative pancreatic fistula, timely and appropriate perioperative antibiotics, survival rates (1 year and 5 year), and timing from diagnosis to surgical consultation.

"The metrics related to mortality, the rate and severity of complications, and access to multidisciplinary services for pancreatic disease had the highest total quality scores; technical and perioperative metrics had intermediate scores; and metrics related to patient satisfaction with care, costs of care, and patient demographics had the lowest total quality scores," Dr. Kalish observed. With respect to the IOM domains, "the least represented domains were equitability, efficiency, and patient-centeredness," he said.

Although the actual performance thresholds for each of the metrics require further definition and validation, "we expect the scorecard to reveal quality to an extent that volume and mortality alone cannot," Dr. Kalish stated, noting that the development process is ongoing.

Future efforts include the organization of patient focus groups and a formal survey of patients and family members to attain insight into which quality metrics are important to those receiving care, as well as a multicenter prospective validation.

Dr. Kalish reported having no relevant financial conflicts of interest.

SAN DIEGO – A proposed quality measure for pancreatic surgery has the potential to assess performance more thoroughly than current volume and mortality measures, judging by surgeons’ responses to a recent survey.

The 12-item "Quality Scorecard," developed by Dr. Brian T. Kalish of Beth Israel Deaconess Medical Center, Boston, and a team of pancreatic surgeons from multiple academic medical centers, consists of actionable and meaningful measures. The scorecard is aligned with the Institute of Medicine’s health care quality domains: safety, timeliness, effectiveness, patient centeredness, efficiency, and equitability.

"Traditional quality metrics in high-acuity surgery on their own cannot measure or satisfy the [IOM] domains," Dr. Kalish explained in a plenary presentation at the annual Digestive Disease Week. "Our goal was to evaluate the need for broader quality metrics and whether such broader metrics would align to contemporary IOM domains."

"We expect the scorecard to reveal quality to an extent that volume and mortality alone cannot."

Toward this end, the development team worked with a professional market research firm to create a web-based survey and distribute it to expert pancreatic surgeons identified through specialty societies and verified by survey demographics, Dr. Kalish explained. "The survey asked respondents to rank [62] proposed quality metrics on level of importance, from essential to not important, and to align the metric to one or more of the [IOM] quality domains." Points were awarded for level of importance and multidomain alignment, and the two scores for a given quality metric were averaged to render a total quality score that was then normalized to a 100-point scale, he said.

The 21% survey response rate represented 106 surgeons primarily from academic medical centers in North America who perform an average of 43 pancreatic operations per year, said Dr. Kalish. The need for improved quality metrics was indicated by 90% of the respondents, while 81% believed that a "quality scorecard" in pancreatic surgery would probably or definitely be of value, he reported. More than one-third of the proposed metrics aligned to more than one IOM domain, and at least half of the respondents rated these as essential or very important, he said.

Of the 62 metrics, 12 emerged with the highest total quality score. In rank order, they are: multidisciplinary services for pancreatic diseases, major complication rate, perioperative mortality, overall complication rate, incidence of postoperative hemorrhage, venous thromboembolism prophylaxis, patients with malignancy who undergo adjuvant therapy, readmission rates (30 day, 90 day, total), incidence of postoperative pancreatic fistula, timely and appropriate perioperative antibiotics, survival rates (1 year and 5 year), and timing from diagnosis to surgical consultation.

"The metrics related to mortality, the rate and severity of complications, and access to multidisciplinary services for pancreatic disease had the highest total quality scores; technical and perioperative metrics had intermediate scores; and metrics related to patient satisfaction with care, costs of care, and patient demographics had the lowest total quality scores," Dr. Kalish observed. With respect to the IOM domains, "the least represented domains were equitability, efficiency, and patient-centeredness," he said.

Although the actual performance thresholds for each of the metrics require further definition and validation, "we expect the scorecard to reveal quality to an extent that volume and mortality alone cannot," Dr. Kalish stated, noting that the development process is ongoing.

Future efforts include the organization of patient focus groups and a formal survey of patients and family members to attain insight into which quality metrics are important to those receiving care, as well as a multicenter prospective validation.

Dr. Kalish reported having no relevant financial conflicts of interest.

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

Patients with severe diabetes but only mild obesity see a dramatic benefit after gastric bypass surgery, a new study has found, with 88% experiencing durable disease remission within 6 months, along with major reductions in 10-year cardiovascular risk.

No mortality, major surgical complications, excessive weight loss, or malnutrition was seen among the 66 patients in the study, all of whom underwent laparoscopic Roux-en-Y gastric bypass (RYGB) surgery, according to the findings published in the July issue of Diabetes Care (2012;35:1420-8) and presented at the annual scientific sessions of the American Diabetes Association in Philadelphia.

Bariatric surgery is currently recommended by the National Institutes of Health only for people with a body mass index (BMI) of 40 kg/m² or higher, or above 35 for people with comorbidities such as severe diabetes. Very obese patients with diabetes have seen dramatic reductions in disease activity after RYGB surgery, with an estimated 80%-85% experiencing durable remission. There is increasing evidence that the procedure triggers hormonal and metabolic antidiabetes responses independent of weight loss (Annu. Rev. Med. 2010;61:393-411; Int. J. Obes. 2009;33:S33-S40; Endocrinology 2009;150:2518-25).

People with mild obesity and diabetes constitute a larger group than the very obese, yet they do not currently qualify for bariatric surgery.

Dr. Ricardo V. Cohen of Oswaldo Cruz Hospital and Marcia Maria Braido Hospital, both in São Paulo, Brazil, and his colleagues sought to investigate whether people with a lower BMI and poorly controlled diabetes also would see significant benefit. More than one-fourth of people in the United States with diabetes have class I obesity, or a BMI of 30-35 (Int. J. Clin. Pract. 2007;61:737-47).

For their research, Dr. Cohen and his colleagues recruited 40 men and 26 women. All were white and ranged in age from 31 to 63 years, and had a BMI of 30.0-34.9 and diabetes lasting 7 years or more at the time of surgery. The mean HbA_1c level was 9.7% at the time of surgery, despite the use of insulin and/or oral diabetes medications (n = 7 on insulin). Follow-up on the cohort was 100%, for a median 5 years.

Within 26 weeks after surgery, 88% of patients were able to discontinue their diabetes medications and maintain an HbA_1c level of less than 6.5% without resuming diabetes medications in the follow-up period.

Improvement without remission was seen in 11% of patients, who were able to withdraw insulin and/or reduce dosages of oral medications between 3 and 14 weeks after surgery. One patient showed no improvement in glycemic control, but was able to withdraw insulin and achieve diabetes control with oral medications 7 months post surgery.

Mean HbA_1c for the entire cohort fell progressively throughout the study, from 9.7% to 5.9% (P less than .001). Fasting plasma glucose (FPG) fell from 156 mg/dL to 97 mg/dL (P less than .001). Most of these changes occurred within the first 6 months.

All patients saw progressive reductions in waist circumference and total body weight, although the magnitude of weight loss was not seen as corresponding with decreases in either FPG or HbA_1c until after 5 years post surgery, when the investigators saw significant correlations between weight loss and decrease in FPG. No correlations were seen between weight loss and decrease in HbA_1c. Also, while the ratio of change in C-peptide to change in glucose increased significantly in the postoperative period, there was no correlation seen between the magnitude of the increase and weight lost. All these findings suggest that the surgery induces mechanisms of antidiabetes action independent of weight loss.

The predicted 10-year risk of cardiovascular disease fell after surgery in the cohort, with a 71% decrease in coronary heart disease (CHD, P = .001), 84% decrease in fatal CHD (P = .001), 50% decrease in stroke (P = .01), and 57% decrease in fatal stroke (P = .009). Hypertension and dyslipidemia were also seen to have improved, with hypertension resolving in 15 of the 26 (58%) patients who had it at baseline, hypercholesterolemia resolving in 21 of 33 (64%) patients, and hypertriglyceridemia resolving in 18 of 31 (58%), in the follow-up period.

Importantly, none of the subjects lost excessive weight or showed evidence of malnutrition. The lowest BMI observed in the follow-up period was 23.6.

The findings, Dr. Cohen and his colleagues wrote in their analysis, have broad implications for health policy, as they "indicate that RYGB is a safe, effective procedure to ameliorate type 2 diabetes and associated comorbidities, thereby reducing predicted cardiovascular disease risk, in patients with a BMI of 30–35 kg/m²."

While randomized controlled trial data are required to confirm that the procedure can be recommended in these patients, the investigators wrote, "our favorable findings from a relatively large, long-term study help justify such trials to clarify whether standard indications for RYGB should be broadened and whether this operation might be viewed primarily as ‘metabolic,’ rather than ‘bariatric,’ surgery."

Dr. Cohen and colleagues’ study was funded by the Municipal Health Authority and Marcia Maria Braido Hospital in São Paulo, Brazil. Dr. Cohen disclosed that he received previous study funding from Covidien, and one of his coauthors, Dr. David E. Cummings of the University of Washington, Seattle, disclosed receiving past funding from Ethicon Endo-Surgery. The other authors said they had no relevant financial disclosures.

SAN DIEGO – Researchers have taken a major step toward eliminating the need for routine pathology on every polyp removed during colonoscopy.

Use of a high-definition, dual-focus colonoscope allowed endoscopists to perform "significantly more accurate, high-confidence endoscopic diagnosis of diminutive polyps," Dr. Tonya Kaltenbach said at the annual Digestive Disease Week.

"In many hospitals, about 20%-25% of all pathology samples are small colon polyps, almost all of which are benign. This is a lot of money that can be saved," said Dr. Kaltenbach in a written statement. About 80% of all polyps found during screening colonoscopy are diminutive, 5 mm in diameter or less, and the current standard of care is to do a pathology analysis on each of these polyps.

As used by five gastroenterologists who participated in the study at three U.S. centers to assess 530 polyps in 277 people, the high-definition scope produced a 95.9% agreement in polyp assignment for follow-up surveillance, compared with pathology-laboratory analysis of the same polyps, and a 96.4% negative predictive value for adenomas, said Dr. Kaltenbach, a gastroenterologist at the VA Medical Center in Palo Alto, Calif.

These performance levels surpassed the greater than 90% targets for colonoscopic assessment of diminutive polyps set last year by a committee organized by the American Society of Gastrointestinal Endoscopy (Gastrointest. Endosc. 2011;73:419-22). Notably, the 90% threshold for assignment of postpolypectomy surveillance accuracy and negative predictive value was set by the ASGE committee before dual-focus colonoscopies like the one used in the current study were in widespread use, said Dr. Roy Soetikno, chief of endoscopy at the Palo Alto VA and senior investigator on the study.

Today, some of the scopes used in routine U.S. practice have the high-definition, dual focus features of the one used in the study, and within the next 5 years essentially all U.S. colonoscopies will have these performance characteristics, he said in an interview.

Although the new study results showed that endoscopists can surpass the thresholds set by the ASGE for visual assessment, widespread use of the method will require further validation, Dr. Soetikno said. "We need to develop programs to teach gastroenterologists and incorporate them into fellowship programs. We also need a way to store the images so that people can document their diagnoses. But [our study] is the beginning," he said.

Dr. Soetikno also noted that the idea of visual assessment of potentially cancerous or precancerous lesions is not new, as the same approach is routinely used in dermatology. With new technologies, gastroenterologists "may be able to do the same thing. We can save our resources, and not spend money on evaluating polyps of no consequence."

Dr. Soetikno, Dr. Kaltenbach, and their associates designed the Veterans Affairs Colorectal Lesion Interpretation and Diagnosis (VALID) study to test the hypothesis that colonoscopy using a high-definition, narrow-band imaging, dual focus colonoscope could increase the rate of accurate, high-confidence histology predictions of diminutive polyps. Five endoscopists working at three VA Medical Centers randomized 558 patients scheduled to undergo routine colonoscopy. The patients averaged 63 years old, 95% were men, and about 80% were white. Roughly 38% underwent colonoscopy for screening, 44% for surveillance following a history of polyps, and for 19% the examination was symptom driven (total is 101% due to rounding).

The protocol randomized 277 people to high-definition colonoscopy with an Olympus model CF-HQ190, and 281 people to examination with an older model without dual-focus capability, the Olympus CF-H180. Examination of the people in the dual-focus group found 710 polyps, including 530 diminutive lesions; the control group had 599 polyps, including 445 that were 5 mm or less.

The endoscopists made accurate, high-confidence endoscopic predictions on 75% of the diminutive polyps that they saw using the dual-focus device, compared with a 63% when they used the less advanced endoscope, a statistically significant difference. When compared with the pathologic assessments, 95.9% of the high-confidence, dual-focus diagnoses produced correct surveillance-interval recommendations, compared with a 95.2% rate using the standard-focus device. Negative predictive value was 96.4% using the dual-focus scope and 92.0% for the more conventional scope. In addition, the dual-focus scope produced no misdiagnoses of advanced histology as non-neoplasia, and use of this scope did not result in any meaningful increase in examination time, nor did it produce any bleeding or perforation.

The VALID study received partial funding from Olympus America, the company that markets the dual-focus, high-definition colonoscope tested. Dr. Soetikno said that he has been a consultant to Olympus. Dr. Kaltenbach and Dr. Kochman said they had no disclosures.

SAN DIEGO – Researchers have taken a major step toward eliminating the need for routine pathology on every polyp removed during colonoscopy.

Use of a high-definition, dual-focus colonoscope allowed endoscopists to perform "significantly more accurate, high-confidence endoscopic diagnosis of diminutive polyps," Dr. Tonya Kaltenbach said at the annual Digestive Disease Week.

"In many hospitals, about 20%-25% of all pathology samples are small colon polyps, almost all of which are benign. This is a lot of money that can be saved," said Dr. Kaltenbach in a written statement. About 80% of all polyps found during screening colonoscopy are diminutive, 5 mm in diameter or less, and the current standard of care is to do a pathology analysis on each of these polyps.

As used by five gastroenterologists who participated in the study at three U.S. centers to assess 530 polyps in 277 people, the high-definition scope produced a 95.9% agreement in polyp assignment for follow-up surveillance, compared with pathology-laboratory analysis of the same polyps, and a 96.4% negative predictive value for adenomas, said Dr. Kaltenbach, a gastroenterologist at the VA Medical Center in Palo Alto, Calif.

These performance levels surpassed the greater than 90% targets for colonoscopic assessment of diminutive polyps set last year by a committee organized by the American Society of Gastrointestinal Endoscopy (Gastrointest. Endosc. 2011;73:419-22). Notably, the 90% threshold for assignment of postpolypectomy surveillance accuracy and negative predictive value was set by the ASGE committee before dual-focus colonoscopies like the one used in the current study were in widespread use, said Dr. Roy Soetikno, chief of endoscopy at the Palo Alto VA and senior investigator on the study.

Today, some of the scopes used in routine U.S. practice have the high-definition, dual focus features of the one used in the study, and within the next 5 years essentially all U.S. colonoscopies will have these performance characteristics, he said in an interview.

Although the new study results showed that endoscopists can surpass the thresholds set by the ASGE for visual assessment, widespread use of the method will require further validation, Dr. Soetikno said. "We need to develop programs to teach gastroenterologists and incorporate them into fellowship programs. We also need a way to store the images so that people can document their diagnoses. But [our study] is the beginning," he said.

Dr. Soetikno also noted that the idea of visual assessment of potentially cancerous or precancerous lesions is not new, as the same approach is routinely used in dermatology. With new technologies, gastroenterologists "may be able to do the same thing. We can save our resources, and not spend money on evaluating polyps of no consequence."

Dr. Soetikno, Dr. Kaltenbach, and their associates designed the Veterans Affairs Colorectal Lesion Interpretation and Diagnosis (VALID) study to test the hypothesis that colonoscopy using a high-definition, narrow-band imaging, dual focus colonoscope could increase the rate of accurate, high-confidence histology predictions of diminutive polyps. Five endoscopists working at three VA Medical Centers randomized 558 patients scheduled to undergo routine colonoscopy. The patients averaged 63 years old, 95% were men, and about 80% were white. Roughly 38% underwent colonoscopy for screening, 44% for surveillance following a history of polyps, and for 19% the examination was symptom driven (total is 101% due to rounding).

The protocol randomized 277 people to high-definition colonoscopy with an Olympus model CF-HQ190, and 281 people to examination with an older model without dual-focus capability, the Olympus CF-H180. Examination of the people in the dual-focus group found 710 polyps, including 530 diminutive lesions; the control group had 599 polyps, including 445 that were 5 mm or less.

The endoscopists made accurate, high-confidence endoscopic predictions on 75% of the diminutive polyps that they saw using the dual-focus device, compared with a 63% when they used the less advanced endoscope, a statistically significant difference. When compared with the pathologic assessments, 95.9% of the high-confidence, dual-focus diagnoses produced correct surveillance-interval recommendations, compared with a 95.2% rate using the standard-focus device. Negative predictive value was 96.4% using the dual-focus scope and 92.0% for the more conventional scope. In addition, the dual-focus scope produced no misdiagnoses of advanced histology as non-neoplasia, and use of this scope did not result in any meaningful increase in examination time, nor did it produce any bleeding or perforation.

The VALID study received partial funding from Olympus America, the company that markets the dual-focus, high-definition colonoscope tested. Dr. Soetikno said that he has been a consultant to Olympus. Dr. Kaltenbach and Dr. Kochman said they had no disclosures.

SAN DIEGO – Researchers have taken a major step toward eliminating the need for routine pathology on every polyp removed during colonoscopy.

Use of a high-definition, dual-focus colonoscope allowed endoscopists to perform "significantly more accurate, high-confidence endoscopic diagnosis of diminutive polyps," Dr. Tonya Kaltenbach said at the annual Digestive Disease Week.

"In many hospitals, about 20%-25% of all pathology samples are small colon polyps, almost all of which are benign. This is a lot of money that can be saved," said Dr. Kaltenbach in a written statement. About 80% of all polyps found during screening colonoscopy are diminutive, 5 mm in diameter or less, and the current standard of care is to do a pathology analysis on each of these polyps.

As used by five gastroenterologists who participated in the study at three U.S. centers to assess 530 polyps in 277 people, the high-definition scope produced a 95.9% agreement in polyp assignment for follow-up surveillance, compared with pathology-laboratory analysis of the same polyps, and a 96.4% negative predictive value for adenomas, said Dr. Kaltenbach, a gastroenterologist at the VA Medical Center in Palo Alto, Calif.

These performance levels surpassed the greater than 90% targets for colonoscopic assessment of diminutive polyps set last year by a committee organized by the American Society of Gastrointestinal Endoscopy (Gastrointest. Endosc. 2011;73:419-22). Notably, the 90% threshold for assignment of postpolypectomy surveillance accuracy and negative predictive value was set by the ASGE committee before dual-focus colonoscopies like the one used in the current study were in widespread use, said Dr. Roy Soetikno, chief of endoscopy at the Palo Alto VA and senior investigator on the study.

Today, some of the scopes used in routine U.S. practice have the high-definition, dual focus features of the one used in the study, and within the next 5 years essentially all U.S. colonoscopies will have these performance characteristics, he said in an interview.

Although the new study results showed that endoscopists can surpass the thresholds set by the ASGE for visual assessment, widespread use of the method will require further validation, Dr. Soetikno said. "We need to develop programs to teach gastroenterologists and incorporate them into fellowship programs. We also need a way to store the images so that people can document their diagnoses. But [our study] is the beginning," he said.

Dr. Soetikno also noted that the idea of visual assessment of potentially cancerous or precancerous lesions is not new, as the same approach is routinely used in dermatology. With new technologies, gastroenterologists "may be able to do the same thing. We can save our resources, and not spend money on evaluating polyps of no consequence."

Dr. Soetikno, Dr. Kaltenbach, and their associates designed the Veterans Affairs Colorectal Lesion Interpretation and Diagnosis (VALID) study to test the hypothesis that colonoscopy using a high-definition, narrow-band imaging, dual focus colonoscope could increase the rate of accurate, high-confidence histology predictions of diminutive polyps. Five endoscopists working at three VA Medical Centers randomized 558 patients scheduled to undergo routine colonoscopy. The patients averaged 63 years old, 95% were men, and about 80% were white. Roughly 38% underwent colonoscopy for screening, 44% for surveillance following a history of polyps, and for 19% the examination was symptom driven (total is 101% due to rounding).

The protocol randomized 277 people to high-definition colonoscopy with an Olympus model CF-HQ190, and 281 people to examination with an older model without dual-focus capability, the Olympus CF-H180. Examination of the people in the dual-focus group found 710 polyps, including 530 diminutive lesions; the control group had 599 polyps, including 445 that were 5 mm or less.

The endoscopists made accurate, high-confidence endoscopic predictions on 75% of the diminutive polyps that they saw using the dual-focus device, compared with a 63% when they used the less advanced endoscope, a statistically significant difference. When compared with the pathologic assessments, 95.9% of the high-confidence, dual-focus diagnoses produced correct surveillance-interval recommendations, compared with a 95.2% rate using the standard-focus device. Negative predictive value was 96.4% using the dual-focus scope and 92.0% for the more conventional scope. In addition, the dual-focus scope produced no misdiagnoses of advanced histology as non-neoplasia, and use of this scope did not result in any meaningful increase in examination time, nor did it produce any bleeding or perforation.

The VALID study received partial funding from Olympus America, the company that markets the dual-focus, high-definition colonoscope tested. Dr. Soetikno said that he has been a consultant to Olympus. Dr. Kaltenbach and Dr. Kochman said they had no disclosures.

MIAMI – Physicians can optimize quality of life and health for children and adolescents with cystic fibrosis by helping them overcome some considerable nutritional challenges, according to a pediatric gastroenterologist.

Following a diagnosis of cystic fibrosis (which can come as early as the newborn period, with a failure to thrive), "nutritional issues are very common. They are the cornerstone of the deficiencies," Dr. William I. Muinos said.

Parents and patients will need your help to comply with a high-fat diet, for example, or to dose the right amount of pancreatic enzyme therapy as the infant grows through childhood and beyond.

Supporting an appropriate diet is the simplest and most obvious intervention, Dr. Muinos said. However, compliance with a diet in which 35%-40% of total calories come from dietary fat can be challenging. "It sounds easy: Eat more fat! But try to get a picky toddler to comply. He may not want to eat in the hypermetabolic state."

Even with dietary supplements and calorie-dense foods, "it is very difficult, especially in growing children, to consume this amount of dietary fat," Dr. Muinos said at a pediatric update sponsored by Miami Children’s Hospital.

A hypermetabolic state adds to the difficulty. "Think of a long-distance runner trying to eat a Whopper and french fries and drink a milk shake while he’s running a 5-minute mile for 26 miles, and trying to do the work to absorb this food while he’s running. It’s very difficult to do that," he said.

Ideally, nutritional deficiencies should be addressed before they contribute to significant morbidity. Cystic fibrosis adversely affects multiple systems, including many gastrointestinal organs. The high-fat dietary requirements stem in part from deficiencies in pancreatic enzymes that break down fat in the intestine, combined with malabsorption along many portions of the GI tract.

"Manifestations in the gastrointestinal tract are what I deal with on a day-to-day basis," said Dr. Muinos, a pediatric gastroenterologist at Miami Children’s Hospital.

Pancreatic enzyme therapy, therefore, is a cornerstone of cystic fibrosis treatment. Primary care physicians can help families because it can be very difficult to calculate the amount a growing infant, child, or teenager should receive. In general, patients will need 500-4,000 lipase units per gram of fat ingested per day, Dr. Muinos said.

"Children and parents are asked to figure out how many enzymes to give, based on how much fat they are ingesting." Both weight-based and age-based dosing regimens are challenging, he added.

Another issue is that most parents do not know all the fat content in the food," Dr. Muinos said. "How many of you know how much fat was in the doughnut you ate this morning?"

Enzyme therapy also presents some practical hurdles that vary by age. "Infants might spit them up. Toddlers are toddlers and might refuse to take them. Older kids don’t want to be different; they don’t want to take the enzymes in front of their friends."

Watch for adverse events. Colonic strictures, for example, have been reported with high-dose enzyme therapy. Refer the patient to a gastroenterology specialist if adverse effects or symptoms of nutritional malabsorption persist, Dr. Muinos said.

Because of the fat metabolism and absorption challenges, clinical deficiencies in vitamins A, D, E, and K are common. "The high incidence of fat-soluble vitamin deficiencies contribute to the significant morbidity and mortality for our patients," Dr. Muinos said. For example, vitamin A deficiencies can lead to blindness; vitamin D deficiency can cause immune system dysfunction; vitamin E deficiency can cause truncal ataxia; and vitamin K deficiency can significantly affect coagulation factors.

This means the child will be taking more pills, Dr. Muinos said. In addition to the enzyme pills, they have to take fat-soluble vitamins on a daily basis.

"If things fail, we always have tubes in gastroenterology." Tube feeding can address high energy requirements, poor absorption, and/or poor intake. Tube feeding is generally indicated for children with cystic fibrosis whose height is below the 85th percentile and who demonstrates no weight gain for 2-3 months (if aged younger than 5 years) or no weight gain for 6 months or weight loss for 2-3 months (if aged 5 years or older).

"The challenges in treating these patients are incredible," Dr. Muinos said. He added that the only way to truly improve quality of life and outcomes for these patients is to find a cure.

Dr. Muinos reported that he had no relevant financial disclosures.

MIAMI – Physicians can optimize quality of life and health for children and adolescents with cystic fibrosis by helping them overcome some considerable nutritional challenges, according to a pediatric gastroenterologist.

Following a diagnosis of cystic fibrosis (which can come as early as the newborn period, with a failure to thrive), "nutritional issues are very common. They are the cornerstone of the deficiencies," Dr. William I. Muinos said.

Parents and patients will need your help to comply with a high-fat diet, for example, or to dose the right amount of pancreatic enzyme therapy as the infant grows through childhood and beyond.

Supporting an appropriate diet is the simplest and most obvious intervention, Dr. Muinos said. However, compliance with a diet in which 35%-40% of total calories come from dietary fat can be challenging. "It sounds easy: Eat more fat! But try to get a picky toddler to comply. He may not want to eat in the hypermetabolic state."

Even with dietary supplements and calorie-dense foods, "it is very difficult, especially in growing children, to consume this amount of dietary fat," Dr. Muinos said at a pediatric update sponsored by Miami Children’s Hospital.

A hypermetabolic state adds to the difficulty. "Think of a long-distance runner trying to eat a Whopper and french fries and drink a milk shake while he’s running a 5-minute mile for 26 miles, and trying to do the work to absorb this food while he’s running. It’s very difficult to do that," he said.

Ideally, nutritional deficiencies should be addressed before they contribute to significant morbidity. Cystic fibrosis adversely affects multiple systems, including many gastrointestinal organs. The high-fat dietary requirements stem in part from deficiencies in pancreatic enzymes that break down fat in the intestine, combined with malabsorption along many portions of the GI tract.

"Manifestations in the gastrointestinal tract are what I deal with on a day-to-day basis," said Dr. Muinos, a pediatric gastroenterologist at Miami Children’s Hospital.

Pancreatic enzyme therapy, therefore, is a cornerstone of cystic fibrosis treatment. Primary care physicians can help families because it can be very difficult to calculate the amount a growing infant, child, or teenager should receive. In general, patients will need 500-4,000 lipase units per gram of fat ingested per day, Dr. Muinos said.

"Children and parents are asked to figure out how many enzymes to give, based on how much fat they are ingesting." Both weight-based and age-based dosing regimens are challenging, he added.

Another issue is that most parents do not know all the fat content in the food," Dr. Muinos said. "How many of you know how much fat was in the doughnut you ate this morning?"

Enzyme therapy also presents some practical hurdles that vary by age. "Infants might spit them up. Toddlers are toddlers and might refuse to take them. Older kids don’t want to be different; they don’t want to take the enzymes in front of their friends."

Watch for adverse events. Colonic strictures, for example, have been reported with high-dose enzyme therapy. Refer the patient to a gastroenterology specialist if adverse effects or symptoms of nutritional malabsorption persist, Dr. Muinos said.

Because of the fat metabolism and absorption challenges, clinical deficiencies in vitamins A, D, E, and K are common. "The high incidence of fat-soluble vitamin deficiencies contribute to the significant morbidity and mortality for our patients," Dr. Muinos said. For example, vitamin A deficiencies can lead to blindness; vitamin D deficiency can cause immune system dysfunction; vitamin E deficiency can cause truncal ataxia; and vitamin K deficiency can significantly affect coagulation factors.

This means the child will be taking more pills, Dr. Muinos said. In addition to the enzyme pills, they have to take fat-soluble vitamins on a daily basis.

"If things fail, we always have tubes in gastroenterology." Tube feeding can address high energy requirements, poor absorption, and/or poor intake. Tube feeding is generally indicated for children with cystic fibrosis whose height is below the 85th percentile and who demonstrates no weight gain for 2-3 months (if aged younger than 5 years) or no weight gain for 6 months or weight loss for 2-3 months (if aged 5 years or older).

"The challenges in treating these patients are incredible," Dr. Muinos said. He added that the only way to truly improve quality of life and outcomes for these patients is to find a cure.

Dr. Muinos reported that he had no relevant financial disclosures.

MIAMI – Physicians can optimize quality of life and health for children and adolescents with cystic fibrosis by helping them overcome some considerable nutritional challenges, according to a pediatric gastroenterologist.

Following a diagnosis of cystic fibrosis (which can come as early as the newborn period, with a failure to thrive), "nutritional issues are very common. They are the cornerstone of the deficiencies," Dr. William I. Muinos said.

Parents and patients will need your help to comply with a high-fat diet, for example, or to dose the right amount of pancreatic enzyme therapy as the infant grows through childhood and beyond.

Supporting an appropriate diet is the simplest and most obvious intervention, Dr. Muinos said. However, compliance with a diet in which 35%-40% of total calories come from dietary fat can be challenging. "It sounds easy: Eat more fat! But try to get a picky toddler to comply. He may not want to eat in the hypermetabolic state."

Even with dietary supplements and calorie-dense foods, "it is very difficult, especially in growing children, to consume this amount of dietary fat," Dr. Muinos said at a pediatric update sponsored by Miami Children’s Hospital.

A hypermetabolic state adds to the difficulty. "Think of a long-distance runner trying to eat a Whopper and french fries and drink a milk shake while he’s running a 5-minute mile for 26 miles, and trying to do the work to absorb this food while he’s running. It’s very difficult to do that," he said.

Ideally, nutritional deficiencies should be addressed before they contribute to significant morbidity. Cystic fibrosis adversely affects multiple systems, including many gastrointestinal organs. The high-fat dietary requirements stem in part from deficiencies in pancreatic enzymes that break down fat in the intestine, combined with malabsorption along many portions of the GI tract.

"Manifestations in the gastrointestinal tract are what I deal with on a day-to-day basis," said Dr. Muinos, a pediatric gastroenterologist at Miami Children’s Hospital.

Pancreatic enzyme therapy, therefore, is a cornerstone of cystic fibrosis treatment. Primary care physicians can help families because it can be very difficult to calculate the amount a growing infant, child, or teenager should receive. In general, patients will need 500-4,000 lipase units per gram of fat ingested per day, Dr. Muinos said.

"Children and parents are asked to figure out how many enzymes to give, based on how much fat they are ingesting." Both weight-based and age-based dosing regimens are challenging, he added.

Another issue is that most parents do not know all the fat content in the food," Dr. Muinos said. "How many of you know how much fat was in the doughnut you ate this morning?"

Enzyme therapy also presents some practical hurdles that vary by age. "Infants might spit them up. Toddlers are toddlers and might refuse to take them. Older kids don’t want to be different; they don’t want to take the enzymes in front of their friends."

Watch for adverse events. Colonic strictures, for example, have been reported with high-dose enzyme therapy. Refer the patient to a gastroenterology specialist if adverse effects or symptoms of nutritional malabsorption persist, Dr. Muinos said.

Because of the fat metabolism and absorption challenges, clinical deficiencies in vitamins A, D, E, and K are common. "The high incidence of fat-soluble vitamin deficiencies contribute to the significant morbidity and mortality for our patients," Dr. Muinos said. For example, vitamin A deficiencies can lead to blindness; vitamin D deficiency can cause immune system dysfunction; vitamin E deficiency can cause truncal ataxia; and vitamin K deficiency can significantly affect coagulation factors.

This means the child will be taking more pills, Dr. Muinos said. In addition to the enzyme pills, they have to take fat-soluble vitamins on a daily basis.

"If things fail, we always have tubes in gastroenterology." Tube feeding can address high energy requirements, poor absorption, and/or poor intake. Tube feeding is generally indicated for children with cystic fibrosis whose height is below the 85th percentile and who demonstrates no weight gain for 2-3 months (if aged younger than 5 years) or no weight gain for 6 months or weight loss for 2-3 months (if aged 5 years or older).

"The challenges in treating these patients are incredible," Dr. Muinos said. He added that the only way to truly improve quality of life and outcomes for these patients is to find a cure.

Dr. Muinos reported that he had no relevant financial disclosures.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.

NEW YORK – In a chart review of 264 patients who underwent bariatric surgery, near-complete resolution of osteoarthritis knee pain was reported by many patients.

Specifically, 71% of those who underwent roux-en-Y gastric bypass (RYGB) reported resolution of knee pain associated with osteoarthritis (OA), as did 63% of those who underwent laparoscopic sleeve gastrectomy (LSG) and 51% of those who underwent laparoscopic adjustable gastric banding (LAGB), according to coauthor Dr. Steven B. Abramson, who reported the findings at a rheumatology meeting sponsored by New York University.

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis," said Dr. Abramson, professor of medicine and pathology and senior vice president and vice dean for education, faculty, and academic affairs and director of the division of rheumatology at NYU Langone Medical Center.

The study was originally presented by James X. Lui, a medical student at New York University, at the 2011 World Congress of the Osteoarthritis Research Society International (OARSI) (Abst. 17).

Patients underwent bariatric surgery at Bellevue Hospital Center between January 2008 and March 2010. The average age was 42.5 years, 92% were female, and the average presurgical body mass index was 44.2 kg/m². Of the 264 patients, LAGB was performed in 192, RYGB in 53, and LSG in 19. OA was present in 88% of the patients, making it the most common obesity-related comorbidity.

At a mean 17.2 months’ follow-up, patients lost 28.4% of excess weight. Significant differences in weight loss was seen among the three types of surgeries (P less than .001), with those undergoing RYGB losing 43.6% of excess weight, compared with 37.4% in those undergoing LSG and 23.3% in those who underwent LAGB.

The investigators used the Assessment of Obesity-Related Comorbidities (AORC) to rate 10 comorbid conditions. For OA, the severity was rated as ranging from 0 (pain not present) to 5 (awaiting or has undergone joint replacement). There was no difference in preoperative AORC mean scores between surgical groups.

The three bariatric surgeries produced statistically significant resolution of all obesity-related comorbidities (P less than .001). Scores on the AORC decreased the most overall in patients who underwent RYGB (66%) versus 60% for LSG and 44% for LAGB, respectively.

Comparing postoperative to preoperative scores, OA improved following all three types of surgeries. The greatest change was seen in those who underwent RYGB (2 points), compared with those who underwent LSG (1.6 point change) or LAGB (1.2 point change).

"I predict bariatric surgery will become increasingly used as a treatment for osteoarthritis."

The highest proportion of patients who had marked improvement of OA symptoms (postsurgical score of 0 on the AORC) was found in the RYGB group (71%), although good outcomes were also seen for 63% of the LSG and 51% of the LAGB groups.

Bariatric surgery lessened other comorbidities as well. For instance, resolution of hypertension was seen in 57% of the RYGB group, 29% of the LSG group, and 23% of the LAGB group. The effects on diabetes were less pronounced, with between 29% and 43% of patients reaching resolution, depending on the type of surgery.

Dr. Abramson suggests that the threshold for BMI as an indication for bariatric surgery could drop from BMI greater than 35 to BMI greater than 30 if there are comorbid conditions. "This includes a substantial percentage of U.S. patients with symptomatic knee OA who could become potential candidates for LAGB surgery if our preliminary studies were validated by prospective clinical trials," said Dr. Abramson.

Dr. Abramson also discussed the results of a study by Dr. Pascal Richette of the University of Paris who studied 140 obese patients with painful knee OA undergoing bariatric surgery (Ann. Rheum. Dis. 2011;70:139-44). As expected, a significant decrease in BMI resulted from surgery, as did a decrease in knee pain on the Western Ontario and McMaster Universities Osteoarthritis Index. Changes in levels of joint biomarkers, such as a significant increase of the N-terminal propeptide of type IIA collagen levels (a biomarker of cartilage synthesis) and a significant decrease in cartilage oligomeric protein (COMP) (a biomarker of cartilage degradation) suggests that structural effects on cartilage result from weight loss.

Dr. Abramson reported no relevant financial relationships.