DDW 2013

ORLANDO – Guidelines that attempt to predict whether stones have migrated into the common bile duct appear to get it right, said an investigator at the annual Digestive Disease Week.

A prospective study looking at American Society for Gastrointestinal Endoscopy (ASGE) criteria for evaluating patients with choledocholithiais found that the guidelines correctly predicted the presence of a common bile duct (CBD) stone in 75% of patients deemed to be at high risk, and accurately called the shots in 55% of patients at intermediate risk, reported Dr. Andrew Korson of Beth Israel Deaconess Medical Center in Boston.

The ASGE guidelines are intended to help clinicians decide whether and when an invasive procedure may be warranted, based on certain clinical features, Dr. Korson noted.

"In the past decade there has been heightened awareness of the problem of proper patient selection for endoscopic retrograde cholangiography [ERC] in the setting of suspected choledocholithiasis, and to date there has been no single noninvasive test that has been shown to reliably identify these patients," he said.

The ASGE guidelines stratify patients into high-risk (greater than 50% incidence of choledocholithiasis), intermediate-risk (10%-50% incidence), and low-risk (less than 10% incidence) categories based on the presence of specific predictive features.

Very strong predictors of choledocholithiasis are evidence of a CBD stone on transabdominal ultrasound, clinical ascending cholangitis, and a bilirubin level higher than 4 mg/dL. Strong predictors are a dilated CBD on ultrasound (greater than 6 mm with gallbladder in situ) and a bilirubin level from 1.8 to 4 mg/dL. Moderate predictors are an abnormal liver biochemical test other than bilirubin, age older than 55, and clinical gallstone pancreatitis.

High-risk patients under this classification scheme are those with any very strong predictor or both strong predictors. Patients at low risk are those with no predictors present, and those at intermediate risk are everyone in between.

Only some get stones

Dr. Korson and his colleagues looked at the proportion of patients within ASGE risk categories who actually had choledocholithiasis on ERC.

They enrolled 402 consecutive patients referred to the hospital for ERC for suspected choledocholithiasis.

They considered clinical, radiographic, and biochemical data at initial presentation, and used transabdominal ultrasound to measure the CBD diameter and the presence of echodensities suggestive of stones or, if ultrasound was not performed, CT or magnetic resonance cholangiopancreatography (MRCP) to gather evidence for choledocholithiasis.

The authors used the data to prospectively apply ASGE criteria and risk-stratify the patients.

Endoscopy was performed with either sphincterectomy or balloon sweep at the discretion of the attending gastroenterologist, with the endoscopist blinded to the risk category.

Of the 402 patients enrolled, 69 were excluded for anatomical reasons or because of a lack of complete data, leaving 333 for the final analysis.

Of the 243 patients classified as high risk, 183 (75.3%) were found to have a CBD stone, and 60 (24.7%) had no stone. Of the 88 at intermediate risk, 47 (53.4%) were found on ERC to have a stone, and 41 (46.6%) were not. Neither of the two low-risk patients had a stone.

The investigators determined the positive predictive value (PPV) of the ASGE criteria to be 55% for intermediate-risk patients, and 75% for high-risk patients (P for each less than .001).

In both univariate and multivariate analyses, only radiographic evidence of a CBD stone and elevated liver enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) were significant predictors of risk. Ascending cholangitis, a total bilirubin level above 4 mg/dL, dilated common bile duct, age, and gallstone pancreatitis were not significant independent predictors.

The odds ratio (OR) for choledocholithiasis based on CBD stone on radiographic evidence was 3.56 (P less than .001), and for elevated liver biochemical tests, was 2.26 (P = .03).

In a post hoc univariate analysis, each 10-IU/L increase in ALT, AST, and alkaline phosphatase was associated with a respective odds ratio of 1.01 (P = .04), 1.01 (P =.03), and 1.02 (P = .04) for choledocholithiasis.

Dr. Korson noted that based on the heavy weighting of their sample toward high- and intermediate-risk patients, "further evaluation of factors that separate intermediate- from low-risk patients is warranted."

He acknowledged study limitations, including possible referral bias, because all of the cases were evaluated at a tertiary care center, a high-acuity study population was used, and CT or MRCP was used to detect CBD dilation or a stone when ultrasound was unavailable.

The funding source for the study was not disclosed. Dr. Korson reported having no relevant financial disclosures.

ORLANDO – Guidelines that attempt to predict whether stones have migrated into the common bile duct appear to get it right, said an investigator at the annual Digestive Disease Week.

A prospective study looking at American Society for Gastrointestinal Endoscopy (ASGE) criteria for evaluating patients with choledocholithiais found that the guidelines correctly predicted the presence of a common bile duct (CBD) stone in 75% of patients deemed to be at high risk, and accurately called the shots in 55% of patients at intermediate risk, reported Dr. Andrew Korson of Beth Israel Deaconess Medical Center in Boston.

The ASGE guidelines are intended to help clinicians decide whether and when an invasive procedure may be warranted, based on certain clinical features, Dr. Korson noted.

"In the past decade there has been heightened awareness of the problem of proper patient selection for endoscopic retrograde cholangiography [ERC] in the setting of suspected choledocholithiasis, and to date there has been no single noninvasive test that has been shown to reliably identify these patients," he said.

The ASGE guidelines stratify patients into high-risk (greater than 50% incidence of choledocholithiasis), intermediate-risk (10%-50% incidence), and low-risk (less than 10% incidence) categories based on the presence of specific predictive features.

Very strong predictors of choledocholithiasis are evidence of a CBD stone on transabdominal ultrasound, clinical ascending cholangitis, and a bilirubin level higher than 4 mg/dL. Strong predictors are a dilated CBD on ultrasound (greater than 6 mm with gallbladder in situ) and a bilirubin level from 1.8 to 4 mg/dL. Moderate predictors are an abnormal liver biochemical test other than bilirubin, age older than 55, and clinical gallstone pancreatitis.

High-risk patients under this classification scheme are those with any very strong predictor or both strong predictors. Patients at low risk are those with no predictors present, and those at intermediate risk are everyone in between.

Only some get stones

Dr. Korson and his colleagues looked at the proportion of patients within ASGE risk categories who actually had choledocholithiasis on ERC.

They enrolled 402 consecutive patients referred to the hospital for ERC for suspected choledocholithiasis.

They considered clinical, radiographic, and biochemical data at initial presentation, and used transabdominal ultrasound to measure the CBD diameter and the presence of echodensities suggestive of stones or, if ultrasound was not performed, CT or magnetic resonance cholangiopancreatography (MRCP) to gather evidence for choledocholithiasis.

The authors used the data to prospectively apply ASGE criteria and risk-stratify the patients.

Endoscopy was performed with either sphincterectomy or balloon sweep at the discretion of the attending gastroenterologist, with the endoscopist blinded to the risk category.

Of the 402 patients enrolled, 69 were excluded for anatomical reasons or because of a lack of complete data, leaving 333 for the final analysis.

Of the 243 patients classified as high risk, 183 (75.3%) were found to have a CBD stone, and 60 (24.7%) had no stone. Of the 88 at intermediate risk, 47 (53.4%) were found on ERC to have a stone, and 41 (46.6%) were not. Neither of the two low-risk patients had a stone.

The investigators determined the positive predictive value (PPV) of the ASGE criteria to be 55% for intermediate-risk patients, and 75% for high-risk patients (P for each less than .001).

In both univariate and multivariate analyses, only radiographic evidence of a CBD stone and elevated liver enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) were significant predictors of risk. Ascending cholangitis, a total bilirubin level above 4 mg/dL, dilated common bile duct, age, and gallstone pancreatitis were not significant independent predictors.

The odds ratio (OR) for choledocholithiasis based on CBD stone on radiographic evidence was 3.56 (P less than .001), and for elevated liver biochemical tests, was 2.26 (P = .03).

In a post hoc univariate analysis, each 10-IU/L increase in ALT, AST, and alkaline phosphatase was associated with a respective odds ratio of 1.01 (P = .04), 1.01 (P =.03), and 1.02 (P = .04) for choledocholithiasis.

Dr. Korson noted that based on the heavy weighting of their sample toward high- and intermediate-risk patients, "further evaluation of factors that separate intermediate- from low-risk patients is warranted."

He acknowledged study limitations, including possible referral bias, because all of the cases were evaluated at a tertiary care center, a high-acuity study population was used, and CT or MRCP was used to detect CBD dilation or a stone when ultrasound was unavailable.

The funding source for the study was not disclosed. Dr. Korson reported having no relevant financial disclosures.

ORLANDO – Guidelines that attempt to predict whether stones have migrated into the common bile duct appear to get it right, said an investigator at the annual Digestive Disease Week.

A prospective study looking at American Society for Gastrointestinal Endoscopy (ASGE) criteria for evaluating patients with choledocholithiais found that the guidelines correctly predicted the presence of a common bile duct (CBD) stone in 75% of patients deemed to be at high risk, and accurately called the shots in 55% of patients at intermediate risk, reported Dr. Andrew Korson of Beth Israel Deaconess Medical Center in Boston.

The ASGE guidelines are intended to help clinicians decide whether and when an invasive procedure may be warranted, based on certain clinical features, Dr. Korson noted.

"In the past decade there has been heightened awareness of the problem of proper patient selection for endoscopic retrograde cholangiography [ERC] in the setting of suspected choledocholithiasis, and to date there has been no single noninvasive test that has been shown to reliably identify these patients," he said.

The ASGE guidelines stratify patients into high-risk (greater than 50% incidence of choledocholithiasis), intermediate-risk (10%-50% incidence), and low-risk (less than 10% incidence) categories based on the presence of specific predictive features.

Very strong predictors of choledocholithiasis are evidence of a CBD stone on transabdominal ultrasound, clinical ascending cholangitis, and a bilirubin level higher than 4 mg/dL. Strong predictors are a dilated CBD on ultrasound (greater than 6 mm with gallbladder in situ) and a bilirubin level from 1.8 to 4 mg/dL. Moderate predictors are an abnormal liver biochemical test other than bilirubin, age older than 55, and clinical gallstone pancreatitis.

High-risk patients under this classification scheme are those with any very strong predictor or both strong predictors. Patients at low risk are those with no predictors present, and those at intermediate risk are everyone in between.

Only some get stones

Dr. Korson and his colleagues looked at the proportion of patients within ASGE risk categories who actually had choledocholithiasis on ERC.

They enrolled 402 consecutive patients referred to the hospital for ERC for suspected choledocholithiasis.

They considered clinical, radiographic, and biochemical data at initial presentation, and used transabdominal ultrasound to measure the CBD diameter and the presence of echodensities suggestive of stones or, if ultrasound was not performed, CT or magnetic resonance cholangiopancreatography (MRCP) to gather evidence for choledocholithiasis.

The authors used the data to prospectively apply ASGE criteria and risk-stratify the patients.

Endoscopy was performed with either sphincterectomy or balloon sweep at the discretion of the attending gastroenterologist, with the endoscopist blinded to the risk category.

Of the 402 patients enrolled, 69 were excluded for anatomical reasons or because of a lack of complete data, leaving 333 for the final analysis.

Of the 243 patients classified as high risk, 183 (75.3%) were found to have a CBD stone, and 60 (24.7%) had no stone. Of the 88 at intermediate risk, 47 (53.4%) were found on ERC to have a stone, and 41 (46.6%) were not. Neither of the two low-risk patients had a stone.

The investigators determined the positive predictive value (PPV) of the ASGE criteria to be 55% for intermediate-risk patients, and 75% for high-risk patients (P for each less than .001).

In both univariate and multivariate analyses, only radiographic evidence of a CBD stone and elevated liver enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) were significant predictors of risk. Ascending cholangitis, a total bilirubin level above 4 mg/dL, dilated common bile duct, age, and gallstone pancreatitis were not significant independent predictors.

The odds ratio (OR) for choledocholithiasis based on CBD stone on radiographic evidence was 3.56 (P less than .001), and for elevated liver biochemical tests, was 2.26 (P = .03).

In a post hoc univariate analysis, each 10-IU/L increase in ALT, AST, and alkaline phosphatase was associated with a respective odds ratio of 1.01 (P = .04), 1.01 (P =.03), and 1.02 (P = .04) for choledocholithiasis.

Dr. Korson noted that based on the heavy weighting of their sample toward high- and intermediate-risk patients, "further evaluation of factors that separate intermediate- from low-risk patients is warranted."

He acknowledged study limitations, including possible referral bias, because all of the cases were evaluated at a tertiary care center, a high-acuity study population was used, and CT or MRCP was used to detect CBD dilation or a stone when ultrasound was unavailable.

The funding source for the study was not disclosed. Dr. Korson reported having no relevant financial disclosures.

ORLANDO – A novel urinary test differentiates pancreatic cancer from chronic pancreatitis and could ultimately provide a tool for the early detection of pancreatic cancer, according to findings from a prospective multicenter study in Germany.

In an independent validation cohort of 47 patients with pancreatic cancer and 60 patients with chronic pancreatitis, the test – which measures the distribution of 55 peptides shown in a screening cohort to be distinct in malignant vs. benign disease – had an area under the curve (AUC) of 0.89. At the optimum cutoff, sensitivity and specificity of the test were 85% and 91%, respectively, Dr. Bastian Schönemeier reported at the annual Digestive Disease Week.

In 94 healthy controls, specificity was 80%, he said, explaining that the test was designed to compare malignant and benign disease, rather than malignant disease and no disease.

The use of proteomic analysis to identify patterns of multiple peptide markers that may have diagnostic value is an emerging technology that has shown promise in other conditions, as well. For example, Dr. Schönemeier and his colleagues demonstrated in a prior study that a proteomic analysis of urine distinguishes cholangiocarcinoma from other benign biliary disorders.

Given their success, the investigators began to investigate whether certain peptide markers in urine are differentially regulated in pancreatic cancer and chronic pancreatitis. The goal was include the most discriminative peptides in a multimarker model for accurate differentiation of the two conditions.

Peptides with altered excretion levels in a sample of 18 patients with histologically proven, but untreated pancreatic cancer, and 22 patients with chronic pancreatitis were identified using capillary electrophoresis coupled online to mass spectrometry. Those that differed significantly between the groups were included in the model, which was then applied prospectively to the independent cohort and healthy controls.

On amino acid sequencing, fragments of fetuin-a and alpha-1-antitrypsin were among 13 prominent markers for pancreatic cancer. This was verified by enzyme immunoassay and immunohistochemistry.

The findings are intriguing, because the diagnosis of pancreatic cancer – the fifth-most-deadly cancer worldwide, has doubled in incidence during the last 40 years, from 5 to 10 cases per 100,000 persons per year, Dr. Schönemeier said, adding that 5-year survival is less than 5%, because a lack of markers and specific symptoms impedes early diagnosis.

While the urinary test evaluated in this study is promising and clearly is capable of differentiating chronic pancreatitis and pancreatic cancer, further study is needed, he said.

"I’m not saying at all that we can now detect (pancreatic) cancer early, but ... it may be useful for proving pancreatic cancer in unclear cases, and it may be useful for surveillance of patients with chronic pancreatitis, he said.

Longitudinal and larger studies are needed to verify the findings, he noted.

Dr. Schönemeier reported having no disclosures.

ORLANDO – A novel urinary test differentiates pancreatic cancer from chronic pancreatitis and could ultimately provide a tool for the early detection of pancreatic cancer, according to findings from a prospective multicenter study in Germany.

In an independent validation cohort of 47 patients with pancreatic cancer and 60 patients with chronic pancreatitis, the test – which measures the distribution of 55 peptides shown in a screening cohort to be distinct in malignant vs. benign disease – had an area under the curve (AUC) of 0.89. At the optimum cutoff, sensitivity and specificity of the test were 85% and 91%, respectively, Dr. Bastian Schönemeier reported at the annual Digestive Disease Week.

In 94 healthy controls, specificity was 80%, he said, explaining that the test was designed to compare malignant and benign disease, rather than malignant disease and no disease.

The use of proteomic analysis to identify patterns of multiple peptide markers that may have diagnostic value is an emerging technology that has shown promise in other conditions, as well. For example, Dr. Schönemeier and his colleagues demonstrated in a prior study that a proteomic analysis of urine distinguishes cholangiocarcinoma from other benign biliary disorders.

Given their success, the investigators began to investigate whether certain peptide markers in urine are differentially regulated in pancreatic cancer and chronic pancreatitis. The goal was include the most discriminative peptides in a multimarker model for accurate differentiation of the two conditions.

Peptides with altered excretion levels in a sample of 18 patients with histologically proven, but untreated pancreatic cancer, and 22 patients with chronic pancreatitis were identified using capillary electrophoresis coupled online to mass spectrometry. Those that differed significantly between the groups were included in the model, which was then applied prospectively to the independent cohort and healthy controls.

On amino acid sequencing, fragments of fetuin-a and alpha-1-antitrypsin were among 13 prominent markers for pancreatic cancer. This was verified by enzyme immunoassay and immunohistochemistry.

The findings are intriguing, because the diagnosis of pancreatic cancer – the fifth-most-deadly cancer worldwide, has doubled in incidence during the last 40 years, from 5 to 10 cases per 100,000 persons per year, Dr. Schönemeier said, adding that 5-year survival is less than 5%, because a lack of markers and specific symptoms impedes early diagnosis.

While the urinary test evaluated in this study is promising and clearly is capable of differentiating chronic pancreatitis and pancreatic cancer, further study is needed, he said.

"I’m not saying at all that we can now detect (pancreatic) cancer early, but ... it may be useful for proving pancreatic cancer in unclear cases, and it may be useful for surveillance of patients with chronic pancreatitis, he said.

Longitudinal and larger studies are needed to verify the findings, he noted.

Dr. Schönemeier reported having no disclosures.

ORLANDO – A novel urinary test differentiates pancreatic cancer from chronic pancreatitis and could ultimately provide a tool for the early detection of pancreatic cancer, according to findings from a prospective multicenter study in Germany.

In an independent validation cohort of 47 patients with pancreatic cancer and 60 patients with chronic pancreatitis, the test – which measures the distribution of 55 peptides shown in a screening cohort to be distinct in malignant vs. benign disease – had an area under the curve (AUC) of 0.89. At the optimum cutoff, sensitivity and specificity of the test were 85% and 91%, respectively, Dr. Bastian Schönemeier reported at the annual Digestive Disease Week.

In 94 healthy controls, specificity was 80%, he said, explaining that the test was designed to compare malignant and benign disease, rather than malignant disease and no disease.

The use of proteomic analysis to identify patterns of multiple peptide markers that may have diagnostic value is an emerging technology that has shown promise in other conditions, as well. For example, Dr. Schönemeier and his colleagues demonstrated in a prior study that a proteomic analysis of urine distinguishes cholangiocarcinoma from other benign biliary disorders.

Given their success, the investigators began to investigate whether certain peptide markers in urine are differentially regulated in pancreatic cancer and chronic pancreatitis. The goal was include the most discriminative peptides in a multimarker model for accurate differentiation of the two conditions.

Peptides with altered excretion levels in a sample of 18 patients with histologically proven, but untreated pancreatic cancer, and 22 patients with chronic pancreatitis were identified using capillary electrophoresis coupled online to mass spectrometry. Those that differed significantly between the groups were included in the model, which was then applied prospectively to the independent cohort and healthy controls.

On amino acid sequencing, fragments of fetuin-a and alpha-1-antitrypsin were among 13 prominent markers for pancreatic cancer. This was verified by enzyme immunoassay and immunohistochemistry.

The findings are intriguing, because the diagnosis of pancreatic cancer – the fifth-most-deadly cancer worldwide, has doubled in incidence during the last 40 years, from 5 to 10 cases per 100,000 persons per year, Dr. Schönemeier said, adding that 5-year survival is less than 5%, because a lack of markers and specific symptoms impedes early diagnosis.

While the urinary test evaluated in this study is promising and clearly is capable of differentiating chronic pancreatitis and pancreatic cancer, further study is needed, he said.

"I’m not saying at all that we can now detect (pancreatic) cancer early, but ... it may be useful for proving pancreatic cancer in unclear cases, and it may be useful for surveillance of patients with chronic pancreatitis, he said.

Longitudinal and larger studies are needed to verify the findings, he noted.

Dr. Schönemeier reported having no disclosures.

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – The rates of adjuvant therapy and the use of surgery for resectable stage I and II pancreatic cancer have remained lower than expected, while nonsurgical therapy for the stage II disease has significantly increased, according to an analysis of a national cancer database.

The analysis showed that more patients with stage I and II resectable disease are receiving chemotherapy in addition to surgery, and fewer are undergoing chemoradiation.

But, "despite all the evidence in favor of adjuvant therapy, its use remains unacceptably low," said Siavash Raigani, a second-year medical student at Case Western Reserve University, Cleveland, who presented the abstract at the annual Digestive Disease Week.

Depending on hospital setting and stage, somewhere between one-third and two-thirds of the patients did not receive adjuvant therapy, Mr. Raigani reported.

The analysis also showed that nonsurgical therapy for the disease continues to be used at a high rate, with 43% of stage I and 60% of stage II pancreatic cancer patients undergoing surgery, "which is lower than expected," said Mr. Raigani.

The analysis reflects what previous studies have shown.

In 2007, Dr. Karl Y. Bilimoria and his colleagues analyzed the National Cancer Data Base (NCDB) for the years between 1995 and 2004 and found "the striking underuse of pancreatectomy in the United States. Of early stage pancreatic cancer patients without any identifiable contraindications, 38.2% failed to undergo surgery." (Ann. Surg. 2007;246:173-80).

"What’s more startling is that there has been no improvement in the years since Dr. Bilimoria brought this to our attention several years ago and the authors should be commended for not letting this issue rest," said Dr. John D. Allendorf of Columbia University Medical Center, New York, who called Mr. Raigani’s analysis "impressive."

Mr. Raigani and his colleagues analyzed the NCDB, selecting 47,000 patients diagnosed with stage I and II pancreatic cancer between 2003 and 2010. They analyzed the database on initial treatment – surgery alone, surgery plus chemotherapy, or surgery plus chemoradiation – and collected data on the hospital setting, community hospital or teaching-research hospital.

Results showed that there was no significant change in surgical resection rates for stage I pancreatic cancer during the study period, but there was a significant different between the two hospital settings, with 53% of patients receiving surgery in teaching hospitals, compared with 32% in community hospitals in 2010.

Similarly, the use of surgery for treatment of stage II disease didn’t change significantly over time, but a significant difference remained between teaching hospitals (60%) and community hospitals (52%) in 2010.

One issue in pancreatic cancer keeps coming up over and over again, said Dr. Vic Velanovich, professor of medicine at the University of South Florida, Tampa. "We know who is a resectable candidate based on pathologic criteria, but what we don’t know is should they be getting an operation based on associated comorbidities," he said.

The other issue has to do with where patients are getting these operations done. "The teaching hospitals or high-volume hospitals are all going to have lower mortalities. But the opposite side of that coin is if you’re at a smaller hospital, where your predicted mortality is higher, perhaps by not operating on those patient, you’re actually saving lives, because you’re not subjecting them to postoperative mortality just because of that operation," said Dr. Velanovich, who moderated the abstract session.

Meanwhile, the use of chemotherapy plus surgery for treatment of stage I and II disease increased more than twofold at both types of hospital (P less than .0001). In contrast, use of chemoradiation plus surgery decreased by roughly 30% in both types of hospitals (P less than .05), the authors reported.

The analysis showed that in community hospitals, the rate of chemotherapy for patients with stage I disease receiving surgery increased from 5% to 14%, while the chemoradiation rates decreased from 34% to 19% during the study period. For stage II patients, the rate of chemotherapy increased from 9% to 27%, and chemoradiation rates decreased from 53% to 39% (P less than .0001 for all).

In teaching hospitals, the rate of chemotherapy for stage I patients increased from 6% to 16%, while the chemoradiation rate decreased from 30% to 19% between 2003 and 2010. For stage II patients, the rate of chemotherapy increased from 9% to 32%, while chemoradiation rates decreased from 42% to 30% (P less than .0001 for all).

Mr. Raigani said the increase in the use of chemotherapy concurrent with the decrease in the use of chemoradiation in addition to surgery correlates temporally with the publication of more trials examining chemotherapy only. However, the use of adjuvant chemoradiation was still more common in the United States as of 2010. Among stage I patients, 44% received chemotherapy, compared with 56% receiving chemoradiation. In stage II patients, those rates were 47% and 53%, respectively.

Meanwhile, the use of surgery alone as first-course treatment for stage II pancreatic cancer decreased by nearly 25% at both hospital settings (P less than .0001 for both). There was no significant change in rates of surgery alone in stage I disease.

Nonsurgical treatment of stage II disease was "surprisingly high," the authors reported. It increased from 31% to 36% at teaching-research hospitals and from 41% to 43% at community hospitals (P less than .0001). There was no significant change in the use of nonsurgical therapy for stage I cancer at either hospital setting during the analysis period, although the difference based on hospital setting remained significant (44% in teaching hospitals vs. 63% in community hospitals, P less than .0001).

Mr. Raigani said some of the possible factors leading to nonsurgical therapy – in addition to age, race, and insurance type – are lack of referral because of the pessimistic view on pancreatic cancer survival and an evaluation by a surgeon inexperienced in pancreas surgery.

The analysis had several limitations, according to the authors. The NCDB provides data in aggregate form and not at an individual level, which limits the predictive factor analysis. Also, NDCB does not distinguish between adjuvant and neoadjuvant therapy.

Mr. Raigani and Dr. Velanovich had no disclosures. Dr. Allendorf is a consultant for Covidien.

nmiller@frontlinemedcom.com

On Twitter @NaseemSMiller

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

ORLANDO – Risk-based drug treatment with colonoscopy at 6 months – and treatment step-up for recurrence – was significantly more effective in preventing postoperative recurrence of Crohn’s disease, compared with standard drug therapy alone, based on data from the POCER (Post-Operative Crohn’s Endoscopic Recurrence) study.

At an 18-month follow-up colonoscopy, 49% of patients randomized to a risk-based intervention had endoscopic recurrence, compared with 67% of those in a standard drug therapy arm, Dr. Peter De Cruz reported during a late-breaking abstract session at the annual Digestive Disease Week.

Researchers compared the two recurrence-prevention strategies in 174 subjects who were stratified as high risk or low risk based on smoking status, presence of perforating disease, and previous surgeries. The participants were randomized 2:1 to either active care or standard drug therapy. Approximately one-third of patients in the active care arm showed signs of early recurrence at a 6-month colonoscopy and thus received step-up treatment.

Complete mucosal normality was observed in 22% of those in the risk-based treatment arm, compared with 8% in the standard therapy arm; no significant differences were noted with respect to severe endoscopic recurrence or clinical recurrence, said Dr. De Cruz of St. Vincent’s Hospital, Melbourne, Australia.

Patients in the multicenter POCER study were adults undergoing intestinal resection of all macroscopic disease. The treatment arms were similar in terms of demographics, disease characteristics, and prior drug therapy. Of 122 patients in the risk-based treatment arm, 101 were high-risk, and 21 were low-risk. Of 52 patients in the standard drug therapy arm, 44 were high-risk, and 8 were low-risk.

All patients were treated beginning postoperatively with 3 months of 400 mg metronidazole twice daily. High-risk patients also received 2 mg/kg of azathioprine daily, or 1.5 mg/kg of 6 mercaptopurine. Those intolerant of thiopurine were treated with adalimumab induction, followed by 40 mg every 2 weeks. Low-risk patients received no additional treatment following the 3 months of metronidazole.

For recurrence at 6 months, low-risk patients were stepped up to thiopurine; high-risk patients on thiopurine were stepped up to 40 mg adalimumab every 2 weeks, and high-risk patients on adalimumab every 2 weeks stepped up to weekly adalimumab.

The endoscopic remission rate at 18 months was 25% for the low-risk patients who stepped up to thiopurine 41% for high-risk patients who stepped up to thiopurine, and 50% for those who stepped up to weekly adalimumab.

Overall, 39% of patients who stepped up at 6 months were in remission at 1 year. Notably, 31% of the low-risk patients with endoscopic remission at the 6-month colonoscopy, 46% of the high-risk patients on thiopurine, and 41% of the high-risk patients on adalimumab with endoscopic remission at 6 months had endoscopic recurrence 1 year later.

"We can’t afford to relax," Dr. De Cruz said regarding those patients with remission 6 months postoperatively.

This study also allowed for comparison of the efficacy of adalimumab and thiopurine given immediately postoperatively in the high-risk patients. At 6 months, adalimumab was associated with a nearly 80% endoscopic remission rate, compared with 55% for thiopurine, Dr. De Cruz noted.

At 18 months, there was no significant difference in the recurrence rates between patients treated with adalimumab immediately postoperatively and those stepped up to adalimumab in combination with thiopurine. There was, however, a trend toward reduced recurrence rates among those on immediate postoperative adalimumab.

A multivariate analysis showed that active smoking was significantly associated with an increased endoscopic recurrence rate at 18 months, whereas the intervention of endoscopy at 6 months was significantly associated with a reduced recurrence risk at 18 months.

Most prior studies of postoperative recurrence prevention in Crohn’s surgery patients have focused on drug therapy compared with placebo; few have focused on risk-based strategies, Dr. De Cruz noted.

The findings indicate that step-up therapy based on endoscopy is a viable postoperative strategy in patients at high risk of recurrence, he said. No unexpected serious adverse events occurred in this study.

Dr. De Cruz warned, however, that remission at 6 months is no guarantee of remission 1 year later.

"Intensifying treatment at 6 months brings about 40% of patients with recurrence into remission, and we found that a small group of patients had recurrent disease despite endoscopic monitoring and intense treatment," he said.

Dr. De Cruz reported having no disclosures. Several study coauthors disclosed relationships with multiple pharmaceutical companies.

ORLANDO – Home monitoring of select patients with mild, nonalcoholic acute interstitial pancreatitis is as safe as in-hospital monitoring, at a cost saving of nearly $15,000, according to a study presented at the annual Digestive Disease Week.

In a randomized controlled trial of 84 patients there were no cases of organ failure or pancreatic necrosis and no deaths within 30 days in patients assigned to either home or hospital monitoring. One patient in the home group and two in the hospital group required readmission within 30 days of discharge, reported Dr. Ali T. Ince of the Bezmialem Vakif University Medical Faculty Hospital in Istanbul, Turkey.

The total tab for home monitoring, including emergency department evaluation, intravenous therapy, and nursing visits, was $7,135, compared with $21,960 for in-hospital care, a savings of $14,825.

"Patients with mild nonalcoholic acute pancreatitis can be safely treated at home with regular visits by a nurse. Widespread adoption of this practice could result in large costs savings," Dr. Ince said.

In 2009, acute pancreatitis cases cost the U.S. health care system about $2.6 billion, for a median per patient charge of $6,096.

"The cost of severe acute pancreatitis is more than the cost of mild acute pancreatitis. However, since only 10%-15% of patients have severe acute pancreatitis, the majority of patients admitted have mild disease," he noted.

To see whether home care of such patients could be safely provided, the investigators enrolled patients admitted to the emergency department for evaluation of acute pancreatitis. Those with an Imrie scoring system value of 5 or lower, a Harmless Acute Pancreatitis Score (HAPS) of 2 or less, and a hematocrit of less than 44% were randomly assigned to either home or hospital monitoring, 42 patients in each group. All patients took nothing by mouth initially and had an oral diet gradually reintroduced.

Hospitalized patients were followed for a mean of 5 days. Home-treated patients received nurse visits on the second, third, and fifth day following discharge from the emergency department. At each home visit, nurses took vital signs, assessed symptoms, and evaluated patients’ general condition and transmitted the data to the attending physician. All patients were asked about their complaints and had physical and laboratory exams on day 7, day 14, and day 30.

Patients with organ failure, signs or symptoms of sepsis, alcoholic acute pancreatitis, prior evidence of a dilated pancreatic duct or pancreatic calcifications, coagulopathies, or comorbidities requiring hospitalization were excluded, Dr. Ince said.

All patients in each group were treated with lactated Ringer’s solution 100-150 mL/hour IV for 3 days, parenteral pantoprazole 40 mg/day, intramuscular diclofenac as needed for pain, and parenteral metoclopramide as needed for nausea, he noted.

In addition, those patients with acute biliary pancreatitis and concurrent cholangitis underwent endoscopic retrograde cholangiopancreatography (ERCP) within 12 hours of admission and received oral amoxicillin/clavulanate 875 mg/125 mg and ciprofloxacin 500 mg; they were monitored as inpatients for up to 24 hours following admission. Patients in this group who remained clinically stable with blood cultures negative for pathogenic organisms within the first 24 hours were then randomized.

All patients with acute biliary pancreatitis and an intact gallbladder underwent cholecystectomy within 6 weeks of the pancreatitis episode.

No home-monitored patients required hospitalization in the 5-7 days after discharge, and, as noted before, only one required readmission within 30 days, Dr. Ince said.

He said that the study was limited by the exclusion of alcoholic pancreatitis, which may make the results less applicable to Western nations where alcohol consumption is heavier than in Turkey. He added, however, that acute biliary pancreatitis has overtaken alcoholic pancreatitis in many Western countries, probably because of rising obesity rates.

The study was sponsored by Bezmialem Vakif University. Dr. Ince reported having no financial disclosures.

ORLANDO – Home monitoring of select patients with mild, nonalcoholic acute interstitial pancreatitis is as safe as in-hospital monitoring, at a cost saving of nearly $15,000, according to a study presented at the annual Digestive Disease Week.

In a randomized controlled trial of 84 patients there were no cases of organ failure or pancreatic necrosis and no deaths within 30 days in patients assigned to either home or hospital monitoring. One patient in the home group and two in the hospital group required readmission within 30 days of discharge, reported Dr. Ali T. Ince of the Bezmialem Vakif University Medical Faculty Hospital in Istanbul, Turkey.

The total tab for home monitoring, including emergency department evaluation, intravenous therapy, and nursing visits, was $7,135, compared with $21,960 for in-hospital care, a savings of $14,825.

"Patients with mild nonalcoholic acute pancreatitis can be safely treated at home with regular visits by a nurse. Widespread adoption of this practice could result in large costs savings," Dr. Ince said.

In 2009, acute pancreatitis cases cost the U.S. health care system about $2.6 billion, for a median per patient charge of $6,096.

"The cost of severe acute pancreatitis is more than the cost of mild acute pancreatitis. However, since only 10%-15% of patients have severe acute pancreatitis, the majority of patients admitted have mild disease," he noted.

To see whether home care of such patients could be safely provided, the investigators enrolled patients admitted to the emergency department for evaluation of acute pancreatitis. Those with an Imrie scoring system value of 5 or lower, a Harmless Acute Pancreatitis Score (HAPS) of 2 or less, and a hematocrit of less than 44% were randomly assigned to either home or hospital monitoring, 42 patients in each group. All patients took nothing by mouth initially and had an oral diet gradually reintroduced.

Hospitalized patients were followed for a mean of 5 days. Home-treated patients received nurse visits on the second, third, and fifth day following discharge from the emergency department. At each home visit, nurses took vital signs, assessed symptoms, and evaluated patients’ general condition and transmitted the data to the attending physician. All patients were asked about their complaints and had physical and laboratory exams on day 7, day 14, and day 30.

Patients with organ failure, signs or symptoms of sepsis, alcoholic acute pancreatitis, prior evidence of a dilated pancreatic duct or pancreatic calcifications, coagulopathies, or comorbidities requiring hospitalization were excluded, Dr. Ince said.

All patients in each group were treated with lactated Ringer’s solution 100-150 mL/hour IV for 3 days, parenteral pantoprazole 40 mg/day, intramuscular diclofenac as needed for pain, and parenteral metoclopramide as needed for nausea, he noted.

In addition, those patients with acute biliary pancreatitis and concurrent cholangitis underwent endoscopic retrograde cholangiopancreatography (ERCP) within 12 hours of admission and received oral amoxicillin/clavulanate 875 mg/125 mg and ciprofloxacin 500 mg; they were monitored as inpatients for up to 24 hours following admission. Patients in this group who remained clinically stable with blood cultures negative for pathogenic organisms within the first 24 hours were then randomized.

All patients with acute biliary pancreatitis and an intact gallbladder underwent cholecystectomy within 6 weeks of the pancreatitis episode.

No home-monitored patients required hospitalization in the 5-7 days after discharge, and, as noted before, only one required readmission within 30 days, Dr. Ince said.

He said that the study was limited by the exclusion of alcoholic pancreatitis, which may make the results less applicable to Western nations where alcohol consumption is heavier than in Turkey. He added, however, that acute biliary pancreatitis has overtaken alcoholic pancreatitis in many Western countries, probably because of rising obesity rates.

The study was sponsored by Bezmialem Vakif University. Dr. Ince reported having no financial disclosures.

ORLANDO – Home monitoring of select patients with mild, nonalcoholic acute interstitial pancreatitis is as safe as in-hospital monitoring, at a cost saving of nearly $15,000, according to a study presented at the annual Digestive Disease Week.

In a randomized controlled trial of 84 patients there were no cases of organ failure or pancreatic necrosis and no deaths within 30 days in patients assigned to either home or hospital monitoring. One patient in the home group and two in the hospital group required readmission within 30 days of discharge, reported Dr. Ali T. Ince of the Bezmialem Vakif University Medical Faculty Hospital in Istanbul, Turkey.

The total tab for home monitoring, including emergency department evaluation, intravenous therapy, and nursing visits, was $7,135, compared with $21,960 for in-hospital care, a savings of $14,825.

"Patients with mild nonalcoholic acute pancreatitis can be safely treated at home with regular visits by a nurse. Widespread adoption of this practice could result in large costs savings," Dr. Ince said.

In 2009, acute pancreatitis cases cost the U.S. health care system about $2.6 billion, for a median per patient charge of $6,096.

"The cost of severe acute pancreatitis is more than the cost of mild acute pancreatitis. However, since only 10%-15% of patients have severe acute pancreatitis, the majority of patients admitted have mild disease," he noted.

To see whether home care of such patients could be safely provided, the investigators enrolled patients admitted to the emergency department for evaluation of acute pancreatitis. Those with an Imrie scoring system value of 5 or lower, a Harmless Acute Pancreatitis Score (HAPS) of 2 or less, and a hematocrit of less than 44% were randomly assigned to either home or hospital monitoring, 42 patients in each group. All patients took nothing by mouth initially and had an oral diet gradually reintroduced.

Hospitalized patients were followed for a mean of 5 days. Home-treated patients received nurse visits on the second, third, and fifth day following discharge from the emergency department. At each home visit, nurses took vital signs, assessed symptoms, and evaluated patients’ general condition and transmitted the data to the attending physician. All patients were asked about their complaints and had physical and laboratory exams on day 7, day 14, and day 30.

Patients with organ failure, signs or symptoms of sepsis, alcoholic acute pancreatitis, prior evidence of a dilated pancreatic duct or pancreatic calcifications, coagulopathies, or comorbidities requiring hospitalization were excluded, Dr. Ince said.

All patients in each group were treated with lactated Ringer’s solution 100-150 mL/hour IV for 3 days, parenteral pantoprazole 40 mg/day, intramuscular diclofenac as needed for pain, and parenteral metoclopramide as needed for nausea, he noted.

In addition, those patients with acute biliary pancreatitis and concurrent cholangitis underwent endoscopic retrograde cholangiopancreatography (ERCP) within 12 hours of admission and received oral amoxicillin/clavulanate 875 mg/125 mg and ciprofloxacin 500 mg; they were monitored as inpatients for up to 24 hours following admission. Patients in this group who remained clinically stable with blood cultures negative for pathogenic organisms within the first 24 hours were then randomized.

All patients with acute biliary pancreatitis and an intact gallbladder underwent cholecystectomy within 6 weeks of the pancreatitis episode.

No home-monitored patients required hospitalization in the 5-7 days after discharge, and, as noted before, only one required readmission within 30 days, Dr. Ince said.

He said that the study was limited by the exclusion of alcoholic pancreatitis, which may make the results less applicable to Western nations where alcohol consumption is heavier than in Turkey. He added, however, that acute biliary pancreatitis has overtaken alcoholic pancreatitis in many Western countries, probably because of rising obesity rates.

The study was sponsored by Bezmialem Vakif University. Dr. Ince reported having no financial disclosures.

ORLANDO – Cold snare polypectomy is clearly superior to double biopsy cold forceps polypectomy for the complete removal of small colorectal polyps, according to findings from a single-center, prospective, randomized controlled study involving 54 patients.

The rates of both visual polyp eradication and complete histologic eradication were significantly higher in patients randomized to the cold snare polypectomy (CSP) group than in those randomized to the cold forceps polypectomy (CFP) group (91.5% vs. 78.3%, and 93.2% vs. 75.9%, respectively), Dr. Chang Kyun Lee reported at the annual Digestive Disease Week.

Additional analysis in the CFP group showed a histologic eradication rate of 92% for 1- to 3-mm polyps, and 50% for 4- to 5-mm polyps.

On logistic regression analysis, CFP and polyp size of 4 mm or larger were associated with incomplete polyp eradication (odds ratios 4.75 and 4.38, respectively), whereas lesion location and histologic diagnosis were not, said Dr. Lee of Kyung Hee University, Seoul, Republic of Korea.

The 54 study subjects were adults (mean age, 53.7 years) and a total of 115 1- to 5-mm polyps. Most polyps (88%) were 0-IIa type, and most (70.1%) were tubular adenomas. The mean polyp size was 3.66 mm.

The treatment groups did not differ significantly with respect to sex, age, indication for colonoscopy, or procedure time, and no differences were noted in the size, location, and diagnosis of polyps.

Only one polyp with advanced histologic features was identified. The 5-mm lesion – a tubular adenoma – was located in the proximal colon and was removed completely via CFP.

CSP was performed using a minisnare, and CFP was performed using standard large-capacity forceps and a double biopsy technique (two "bites" per forceps pass). Polyp removal time was significantly shorter with CSP than with CFP (14.29 vs. 22.03 seconds), though this difference was not clinically meaningful. The rate of successful retrieval of polypectomy samples was lower in the CSP group (93.2% vs. 100% for CFP), Dr. Lee noted.

While cold techniques are widely used in clinical practice, few studies have directly compared outcomes with different techniques. These findings indicate that choice of technique is clinically important to the endoscopic removal of diminutive polyps, he said.

"Based on the findings, we recommend that cold snaring be considered as the primary method for endoscopic treatment of polyps in the 4- to 5-mm size range. However, given the incomplete polypectomy rate in this study – about 15% – further technical refinements and instrumental innovations are required for future studies," Dr. Lee concluded.

Dr. Lee reported having no disclosures.

ORLANDO – Cold snare polypectomy is clearly superior to double biopsy cold forceps polypectomy for the complete removal of small colorectal polyps, according to findings from a single-center, prospective, randomized controlled study involving 54 patients.

The rates of both visual polyp eradication and complete histologic eradication were significantly higher in patients randomized to the cold snare polypectomy (CSP) group than in those randomized to the cold forceps polypectomy (CFP) group (91.5% vs. 78.3%, and 93.2% vs. 75.9%, respectively), Dr. Chang Kyun Lee reported at the annual Digestive Disease Week.

Additional analysis in the CFP group showed a histologic eradication rate of 92% for 1- to 3-mm polyps, and 50% for 4- to 5-mm polyps.

On logistic regression analysis, CFP and polyp size of 4 mm or larger were associated with incomplete polyp eradication (odds ratios 4.75 and 4.38, respectively), whereas lesion location and histologic diagnosis were not, said Dr. Lee of Kyung Hee University, Seoul, Republic of Korea.

The 54 study subjects were adults (mean age, 53.7 years) and a total of 115 1- to 5-mm polyps. Most polyps (88%) were 0-IIa type, and most (70.1%) were tubular adenomas. The mean polyp size was 3.66 mm.

The treatment groups did not differ significantly with respect to sex, age, indication for colonoscopy, or procedure time, and no differences were noted in the size, location, and diagnosis of polyps.

Only one polyp with advanced histologic features was identified. The 5-mm lesion – a tubular adenoma – was located in the proximal colon and was removed completely via CFP.

CSP was performed using a minisnare, and CFP was performed using standard large-capacity forceps and a double biopsy technique (two "bites" per forceps pass). Polyp removal time was significantly shorter with CSP than with CFP (14.29 vs. 22.03 seconds), though this difference was not clinically meaningful. The rate of successful retrieval of polypectomy samples was lower in the CSP group (93.2% vs. 100% for CFP), Dr. Lee noted.

While cold techniques are widely used in clinical practice, few studies have directly compared outcomes with different techniques. These findings indicate that choice of technique is clinically important to the endoscopic removal of diminutive polyps, he said.

"Based on the findings, we recommend that cold snaring be considered as the primary method for endoscopic treatment of polyps in the 4- to 5-mm size range. However, given the incomplete polypectomy rate in this study – about 15% – further technical refinements and instrumental innovations are required for future studies," Dr. Lee concluded.

Dr. Lee reported having no disclosures.

ORLANDO – Cold snare polypectomy is clearly superior to double biopsy cold forceps polypectomy for the complete removal of small colorectal polyps, according to findings from a single-center, prospective, randomized controlled study involving 54 patients.

The rates of both visual polyp eradication and complete histologic eradication were significantly higher in patients randomized to the cold snare polypectomy (CSP) group than in those randomized to the cold forceps polypectomy (CFP) group (91.5% vs. 78.3%, and 93.2% vs. 75.9%, respectively), Dr. Chang Kyun Lee reported at the annual Digestive Disease Week.

Additional analysis in the CFP group showed a histologic eradication rate of 92% for 1- to 3-mm polyps, and 50% for 4- to 5-mm polyps.

On logistic regression analysis, CFP and polyp size of 4 mm or larger were associated with incomplete polyp eradication (odds ratios 4.75 and 4.38, respectively), whereas lesion location and histologic diagnosis were not, said Dr. Lee of Kyung Hee University, Seoul, Republic of Korea.

The 54 study subjects were adults (mean age, 53.7 years) and a total of 115 1- to 5-mm polyps. Most polyps (88%) were 0-IIa type, and most (70.1%) were tubular adenomas. The mean polyp size was 3.66 mm.

The treatment groups did not differ significantly with respect to sex, age, indication for colonoscopy, or procedure time, and no differences were noted in the size, location, and diagnosis of polyps.

Only one polyp with advanced histologic features was identified. The 5-mm lesion – a tubular adenoma – was located in the proximal colon and was removed completely via CFP.

CSP was performed using a minisnare, and CFP was performed using standard large-capacity forceps and a double biopsy technique (two "bites" per forceps pass). Polyp removal time was significantly shorter with CSP than with CFP (14.29 vs. 22.03 seconds), though this difference was not clinically meaningful. The rate of successful retrieval of polypectomy samples was lower in the CSP group (93.2% vs. 100% for CFP), Dr. Lee noted.

While cold techniques are widely used in clinical practice, few studies have directly compared outcomes with different techniques. These findings indicate that choice of technique is clinically important to the endoscopic removal of diminutive polyps, he said.

"Based on the findings, we recommend that cold snaring be considered as the primary method for endoscopic treatment of polyps in the 4- to 5-mm size range. However, given the incomplete polypectomy rate in this study – about 15% – further technical refinements and instrumental innovations are required for future studies," Dr. Lee concluded.

Dr. Lee reported having no disclosures.

ORLANDO – A systemwide medical error disclosure program that successfully reduced the rate of claims and improved claim resolution time for a large university health system had similar effects on gastroenterology-specific claims, a retrospective study has shown.

The findings suggest that error disclosure programs can benefit even procedure-based specialties like gastroenterology, Dr. Megan A. Adams reported at the annual Digestive Disease Week.

The medical error disclosure program, which included incident reporting and disclosure, internal investigation of all claims, an offer of apology and compensation for all reasonable claims, and vigorous defense of all unreasonable claims, was adopted at the University of Michigan Health System (UMHS) in 2001 following a 1999 Institute of Medicine report calling for efforts to reduce medical errors. The program was developed in light of an increasing realization that traditional "deny-and-defend" approaches to claims were failing to achieve the goal of improving patient care.

A hospitalwide analysis published in 2010 showed a statistically significant 36% decrease in the average monthly rate of new claims per patient encounter, 30% decrease in the median time from claim reporting to resolution, and 44% decrease in the average cost per lawsuit following program implementation (Ann. Intern. Med. 2010;153:213-21).

"But the question remained: ‘Can we apply these systemwide findings to gastroenterology?’ First, we have a procedure-based specialty. We also do many open-access procedures where we have no preexisting or established relationship with our patients. And, finally, we treat gastrointestinal-specific diseases, such as [those in] patients with functional bowel disorders, who represent a complex patient population," said Dr. Adams of the University of Michigan Medical Center, Ann Arbor.

A review of gastroenterology-specific claims in the UMHS Risk Management database from 1990 to 2010 showed that despite a 72% increase in encounters in the 10 years after implementation, compared with the 10 years prior (412,000 vs. 240,000 encounters), only 28 claims were made after, versus 38 before, implementation.

The rate of claims declined significantly from 0.16% to 0.068% per 1,000 patient encounters. Moreover, after adjustment for inflation, total settlement dollars decreased by 54%, overall claims-related costs decreased by 94%, mean total liability per claim decreased by 52%, and time to claim resolution decreased by 50%.

Although the findings are limited by the small number of claims and an inability to determine causality, and did not consider statewide or national trends in the filing of claims, the results do demonstrate that the systemwide findings at UMHS were "reproduced in a dramatic way in the procedure-based specialty of gastroenterology," Dr. Adams said.

"When properly implemented as part of a systemwide quality improvement effort, medical error disclosure programs help to foster a culture of transparency, and in doing so, strengthen patients’ trust in the health care system. They also help to promote ongoing medical error prevention in a way that does not lead to increased medical liability," she said, adding that further research looking at the generalizability of these findings to other health systems is warranted.

Dr. Adams reported having no relevant financial disclosures.

ORLANDO – A systemwide medical error disclosure program that successfully reduced the rate of claims and improved claim resolution time for a large university health system had similar effects on gastroenterology-specific claims, a retrospective study has shown.

The findings suggest that error disclosure programs can benefit even procedure-based specialties like gastroenterology, Dr. Megan A. Adams reported at the annual Digestive Disease Week.

The medical error disclosure program, which included incident reporting and disclosure, internal investigation of all claims, an offer of apology and compensation for all reasonable claims, and vigorous defense of all unreasonable claims, was adopted at the University of Michigan Health System (UMHS) in 2001 following a 1999 Institute of Medicine report calling for efforts to reduce medical errors. The program was developed in light of an increasing realization that traditional "deny-and-defend" approaches to claims were failing to achieve the goal of improving patient care.

A hospitalwide analysis published in 2010 showed a statistically significant 36% decrease in the average monthly rate of new claims per patient encounter, 30% decrease in the median time from claim reporting to resolution, and 44% decrease in the average cost per lawsuit following program implementation (Ann. Intern. Med. 2010;153:213-21).

"But the question remained: ‘Can we apply these systemwide findings to gastroenterology?’ First, we have a procedure-based specialty. We also do many open-access procedures where we have no preexisting or established relationship with our patients. And, finally, we treat gastrointestinal-specific diseases, such as [those in] patients with functional bowel disorders, who represent a complex patient population," said Dr. Adams of the University of Michigan Medical Center, Ann Arbor.

A review of gastroenterology-specific claims in the UMHS Risk Management database from 1990 to 2010 showed that despite a 72% increase in encounters in the 10 years after implementation, compared with the 10 years prior (412,000 vs. 240,000 encounters), only 28 claims were made after, versus 38 before, implementation.

The rate of claims declined significantly from 0.16% to 0.068% per 1,000 patient encounters. Moreover, after adjustment for inflation, total settlement dollars decreased by 54%, overall claims-related costs decreased by 94%, mean total liability per claim decreased by 52%, and time to claim resolution decreased by 50%.

Although the findings are limited by the small number of claims and an inability to determine causality, and did not consider statewide or national trends in the filing of claims, the results do demonstrate that the systemwide findings at UMHS were "reproduced in a dramatic way in the procedure-based specialty of gastroenterology," Dr. Adams said.

"When properly implemented as part of a systemwide quality improvement effort, medical error disclosure programs help to foster a culture of transparency, and in doing so, strengthen patients’ trust in the health care system. They also help to promote ongoing medical error prevention in a way that does not lead to increased medical liability," she said, adding that further research looking at the generalizability of these findings to other health systems is warranted.

Dr. Adams reported having no relevant financial disclosures.

ORLANDO – A systemwide medical error disclosure program that successfully reduced the rate of claims and improved claim resolution time for a large university health system had similar effects on gastroenterology-specific claims, a retrospective study has shown.

The findings suggest that error disclosure programs can benefit even procedure-based specialties like gastroenterology, Dr. Megan A. Adams reported at the annual Digestive Disease Week.

The medical error disclosure program, which included incident reporting and disclosure, internal investigation of all claims, an offer of apology and compensation for all reasonable claims, and vigorous defense of all unreasonable claims, was adopted at the University of Michigan Health System (UMHS) in 2001 following a 1999 Institute of Medicine report calling for efforts to reduce medical errors. The program was developed in light of an increasing realization that traditional "deny-and-defend" approaches to claims were failing to achieve the goal of improving patient care.

A hospitalwide analysis published in 2010 showed a statistically significant 36% decrease in the average monthly rate of new claims per patient encounter, 30% decrease in the median time from claim reporting to resolution, and 44% decrease in the average cost per lawsuit following program implementation (Ann. Intern. Med. 2010;153:213-21).

"But the question remained: ‘Can we apply these systemwide findings to gastroenterology?’ First, we have a procedure-based specialty. We also do many open-access procedures where we have no preexisting or established relationship with our patients. And, finally, we treat gastrointestinal-specific diseases, such as [those in] patients with functional bowel disorders, who represent a complex patient population," said Dr. Adams of the University of Michigan Medical Center, Ann Arbor.

A review of gastroenterology-specific claims in the UMHS Risk Management database from 1990 to 2010 showed that despite a 72% increase in encounters in the 10 years after implementation, compared with the 10 years prior (412,000 vs. 240,000 encounters), only 28 claims were made after, versus 38 before, implementation.

The rate of claims declined significantly from 0.16% to 0.068% per 1,000 patient encounters. Moreover, after adjustment for inflation, total settlement dollars decreased by 54%, overall claims-related costs decreased by 94%, mean total liability per claim decreased by 52%, and time to claim resolution decreased by 50%.

Although the findings are limited by the small number of claims and an inability to determine causality, and did not consider statewide or national trends in the filing of claims, the results do demonstrate that the systemwide findings at UMHS were "reproduced in a dramatic way in the procedure-based specialty of gastroenterology," Dr. Adams said.

"When properly implemented as part of a systemwide quality improvement effort, medical error disclosure programs help to foster a culture of transparency, and in doing so, strengthen patients’ trust in the health care system. They also help to promote ongoing medical error prevention in a way that does not lead to increased medical liability," she said, adding that further research looking at the generalizability of these findings to other health systems is warranted.

Dr. Adams reported having no relevant financial disclosures.

ORLANDO – Immunoablation and hematopoietic stem cell transplantation is highly effective – but also risky – for patients with intractable Crohn’s disease, according to interim findings from the randomized controlled ASTIC (Autologous Stem Cell Transplantation International Crohn’s Disease) trial.

At 1-year follow-up in the 5-year study, the treatment was associated with significant improvements as measured by the Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD), Dr. Christopher J. Hawkey reported at the annual Digestive Disease Week. However, patients experienced more than three serious adverse events per person, and one death occurred 2 weeks after transplantation, he said.

Of 45 patients with impaired quality of life due to moderate to severe Crohn’s disease activity despite treatment with at least three immunosuppressive agents, all underwent stem cell mobilization treatment and were then randomized to receive either immediate or delayed immunoablation and hematopoietic stem cell transplantation (HSCT). The delayed-treatment group served as a control group.

In 22 patients who received immediate treatment and survived until 1-year follow-up, the CDAI score was halved to a median value of 162, compared with only about a 50-point drop in 13 patients in the control group who continued in the study (9 patients withdrew early – mainly because of disease worsening – and some went on to early HSCT). Furthermore, an "encouraging number" of patients in the treatment group were able to discontinue all immunosuppressive drugs and steroids (about two-thirds of patients, compared with 15% in the control group), said Dr. Hawkey of the University of Nottingham, England.

Almost half of the patients in the treatment group achieved a CDAI score of 150 or less, signaling clinical remission.

"Strikingly, most of these patients were not taking any drugs at the time, either," Dr. Hawkey said.

The SES-CD score also decreased markedly in the treatment group, falling from a mean of 13 to 4 points, with four patients achieving complete absence of any evidence of involvement or ulceration, compared with no patients in the control group.

Complete mucosal healing, defined as lack of erosions or ulcerations on endoscopy, occurred in 40% of treatment-group patients, compared with only 15% of control-group patients, but several of these patients were still taking anti–tumor necrosis factor (anti-TNF) drugs or steroids, Dr. Hawkey said.

"Nevertheless, these are quite substantial findings," he said.

Patients included in the trial were adults who had undergone up to 12 surgeries each but who still had disease-related impairments to quality of life.

"For such an extreme technique, we wanted to enroll the most resistant patients," Dr. Hawkey said.

The treatment and control groups were well matched with respect to major demographics as well as CDAI and SES-CD scores, and patients were relatively young, having been diagnosed with Crohn’s disease at an early age, he noted.

Stem cell mobilization was achieved using 4 g/m² of intravenous cyclophosphamide delivered over 2 days, followed by 10 mcg/kg filgrastim daily until randomization. The conditioning regimen in the treatment group was 50 mg/kg per day of intravenous cyclophosphamide for 4 days, 2.5 mg/kg per day of antithymocyte globulin, and 1 mg/kg of methyl prednisolone on days 3-5. The bone marrow was reconstituted by infusion of an unselected graft of 3-8 × 10⁶ CD34-positive cells/kg.

One patient in the treatment group died 2 weeks after HSCT due to sepsis, and a significantly greater number of serious adverse events – usually infectious – occurred during follow-up in the treatment group than in the control group (an average of 3.3 per person).

The findings could have important implications for the treatment of Crohn’s disease.

"Immunoablation and repopulation of the bone marrow by uncommitted stem cells has excited a lot of interest in Crohn’s disease lately, and some of the case reports are undoubtedly so dramatic that it’s reasonable to talk about a cure in those patients," Dr. Hawkey said.

HSCT has been shown in controlled clinical trials to be effective – albeit with major toxicities – in systemic sclerosis and multiple sclerosis, but this is the first randomized controlled trial to evaluate the technique in Crohn’s disease.

"Our goal was quite an ambitious one. If we could achieve clinical remission, and patients were off drugs, that would be something of a game-changer," he said.

Indeed, the findings thus far suggest that stem cell transplantation is highly effective for patients with resistant Crohn’s disease, but in most cases, there is evidence of disease persistence.

"So this is seldom a cure, although sometimes it clearly is," he said, adding that given the significant number of serious adverse events, weighing the risks and benefits will be the key to successful clinical use in the future.

Outcomes following HSCT in the delayed-treatment group will be presented at a later date, he said.

Dr. Hawkey serves on advisory committees or review panels for Atlantic Healthcare, Bayer AG, GlaxoSmithKline, Novartis Pharmaceuticals, Boehringer Ingelheim, and Takeda Pharmaceuticals.

ORLANDO – Immunoablation and hematopoietic stem cell transplantation is highly effective – but also risky – for patients with intractable Crohn’s disease, according to interim findings from the randomized controlled ASTIC (Autologous Stem Cell Transplantation International Crohn’s Disease) trial.

At 1-year follow-up in the 5-year study, the treatment was associated with significant improvements as measured by the Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD), Dr. Christopher J. Hawkey reported at the annual Digestive Disease Week. However, patients experienced more than three serious adverse events per person, and one death occurred 2 weeks after transplantation, he said.

Of 45 patients with impaired quality of life due to moderate to severe Crohn’s disease activity despite treatment with at least three immunosuppressive agents, all underwent stem cell mobilization treatment and were then randomized to receive either immediate or delayed immunoablation and hematopoietic stem cell transplantation (HSCT). The delayed-treatment group served as a control group.

In 22 patients who received immediate treatment and survived until 1-year follow-up, the CDAI score was halved to a median value of 162, compared with only about a 50-point drop in 13 patients in the control group who continued in the study (9 patients withdrew early – mainly because of disease worsening – and some went on to early HSCT). Furthermore, an "encouraging number" of patients in the treatment group were able to discontinue all immunosuppressive drugs and steroids (about two-thirds of patients, compared with 15% in the control group), said Dr. Hawkey of the University of Nottingham, England.

Almost half of the patients in the treatment group achieved a CDAI score of 150 or less, signaling clinical remission.

"Strikingly, most of these patients were not taking any drugs at the time, either," Dr. Hawkey said.

The SES-CD score also decreased markedly in the treatment group, falling from a mean of 13 to 4 points, with four patients achieving complete absence of any evidence of involvement or ulceration, compared with no patients in the control group.

Complete mucosal healing, defined as lack of erosions or ulcerations on endoscopy, occurred in 40% of treatment-group patients, compared with only 15% of control-group patients, but several of these patients were still taking anti–tumor necrosis factor (anti-TNF) drugs or steroids, Dr. Hawkey said.

"Nevertheless, these are quite substantial findings," he said.

Patients included in the trial were adults who had undergone up to 12 surgeries each but who still had disease-related impairments to quality of life.

"For such an extreme technique, we wanted to enroll the most resistant patients," Dr. Hawkey said.

The treatment and control groups were well matched with respect to major demographics as well as CDAI and SES-CD scores, and patients were relatively young, having been diagnosed with Crohn’s disease at an early age, he noted.

Stem cell mobilization was achieved using 4 g/m² of intravenous cyclophosphamide delivered over 2 days, followed by 10 mcg/kg filgrastim daily until randomization. The conditioning regimen in the treatment group was 50 mg/kg per day of intravenous cyclophosphamide for 4 days, 2.5 mg/kg per day of antithymocyte globulin, and 1 mg/kg of methyl prednisolone on days 3-5. The bone marrow was reconstituted by infusion of an unselected graft of 3-8 × 10⁶ CD34-positive cells/kg.

One patient in the treatment group died 2 weeks after HSCT due to sepsis, and a significantly greater number of serious adverse events – usually infectious – occurred during follow-up in the treatment group than in the control group (an average of 3.3 per person).

The findings could have important implications for the treatment of Crohn’s disease.

"Immunoablation and repopulation of the bone marrow by uncommitted stem cells has excited a lot of interest in Crohn’s disease lately, and some of the case reports are undoubtedly so dramatic that it’s reasonable to talk about a cure in those patients," Dr. Hawkey said.

HSCT has been shown in controlled clinical trials to be effective – albeit with major toxicities – in systemic sclerosis and multiple sclerosis, but this is the first randomized controlled trial to evaluate the technique in Crohn’s disease.

"Our goal was quite an ambitious one. If we could achieve clinical remission, and patients were off drugs, that would be something of a game-changer," he said.

Indeed, the findings thus far suggest that stem cell transplantation is highly effective for patients with resistant Crohn’s disease, but in most cases, there is evidence of disease persistence.

"So this is seldom a cure, although sometimes it clearly is," he said, adding that given the significant number of serious adverse events, weighing the risks and benefits will be the key to successful clinical use in the future.

Outcomes following HSCT in the delayed-treatment group will be presented at a later date, he said.

Dr. Hawkey serves on advisory committees or review panels for Atlantic Healthcare, Bayer AG, GlaxoSmithKline, Novartis Pharmaceuticals, Boehringer Ingelheim, and Takeda Pharmaceuticals.

ORLANDO – Immunoablation and hematopoietic stem cell transplantation is highly effective – but also risky – for patients with intractable Crohn’s disease, according to interim findings from the randomized controlled ASTIC (Autologous Stem Cell Transplantation International Crohn’s Disease) trial.

At 1-year follow-up in the 5-year study, the treatment was associated with significant improvements as measured by the Crohn’s Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD), Dr. Christopher J. Hawkey reported at the annual Digestive Disease Week. However, patients experienced more than three serious adverse events per person, and one death occurred 2 weeks after transplantation, he said.

Of 45 patients with impaired quality of life due to moderate to severe Crohn’s disease activity despite treatment with at least three immunosuppressive agents, all underwent stem cell mobilization treatment and were then randomized to receive either immediate or delayed immunoablation and hematopoietic stem cell transplantation (HSCT). The delayed-treatment group served as a control group.

In 22 patients who received immediate treatment and survived until 1-year follow-up, the CDAI score was halved to a median value of 162, compared with only about a 50-point drop in 13 patients in the control group who continued in the study (9 patients withdrew early – mainly because of disease worsening – and some went on to early HSCT). Furthermore, an "encouraging number" of patients in the treatment group were able to discontinue all immunosuppressive drugs and steroids (about two-thirds of patients, compared with 15% in the control group), said Dr. Hawkey of the University of Nottingham, England.

Almost half of the patients in the treatment group achieved a CDAI score of 150 or less, signaling clinical remission.

"Strikingly, most of these patients were not taking any drugs at the time, either," Dr. Hawkey said.

The SES-CD score also decreased markedly in the treatment group, falling from a mean of 13 to 4 points, with four patients achieving complete absence of any evidence of involvement or ulceration, compared with no patients in the control group.

Complete mucosal healing, defined as lack of erosions or ulcerations on endoscopy, occurred in 40% of treatment-group patients, compared with only 15% of control-group patients, but several of these patients were still taking anti–tumor necrosis factor (anti-TNF) drugs or steroids, Dr. Hawkey said.

"Nevertheless, these are quite substantial findings," he said.

Patients included in the trial were adults who had undergone up to 12 surgeries each but who still had disease-related impairments to quality of life.

"For such an extreme technique, we wanted to enroll the most resistant patients," Dr. Hawkey said.

The treatment and control groups were well matched with respect to major demographics as well as CDAI and SES-CD scores, and patients were relatively young, having been diagnosed with Crohn’s disease at an early age, he noted.

Stem cell mobilization was achieved using 4 g/m² of intravenous cyclophosphamide delivered over 2 days, followed by 10 mcg/kg filgrastim daily until randomization. The conditioning regimen in the treatment group was 50 mg/kg per day of intravenous cyclophosphamide for 4 days, 2.5 mg/kg per day of antithymocyte globulin, and 1 mg/kg of methyl prednisolone on days 3-5. The bone marrow was reconstituted by infusion of an unselected graft of 3-8 × 10⁶ CD34-positive cells/kg.

One patient in the treatment group died 2 weeks after HSCT due to sepsis, and a significantly greater number of serious adverse events – usually infectious – occurred during follow-up in the treatment group than in the control group (an average of 3.3 per person).

The findings could have important implications for the treatment of Crohn’s disease.

"Immunoablation and repopulation of the bone marrow by uncommitted stem cells has excited a lot of interest in Crohn’s disease lately, and some of the case reports are undoubtedly so dramatic that it’s reasonable to talk about a cure in those patients," Dr. Hawkey said.

HSCT has been shown in controlled clinical trials to be effective – albeit with major toxicities – in systemic sclerosis and multiple sclerosis, but this is the first randomized controlled trial to evaluate the technique in Crohn’s disease.

"Our goal was quite an ambitious one. If we could achieve clinical remission, and patients were off drugs, that would be something of a game-changer," he said.

Indeed, the findings thus far suggest that stem cell transplantation is highly effective for patients with resistant Crohn’s disease, but in most cases, there is evidence of disease persistence.

"So this is seldom a cure, although sometimes it clearly is," he said, adding that given the significant number of serious adverse events, weighing the risks and benefits will be the key to successful clinical use in the future.

Outcomes following HSCT in the delayed-treatment group will be presented at a later date, he said.

Dr. Hawkey serves on advisory committees or review panels for Atlantic Healthcare, Bayer AG, GlaxoSmithKline, Novartis Pharmaceuticals, Boehringer Ingelheim, and Takeda Pharmaceuticals.

ORLANDO – Researchers have identified a novel genetic marker for increased pancreatic cancer risk.

The marker, a single nucleotide polymorphism (SNP) of the cholecystokinin-B (CCK-B) receptor, could serve as a screening test for high-risk subjects, Dr. Jill P. Smith reported at the annual Digestive Disease Week.

The CCK-B receptor is a G-protein coupled receptor through which the effects of the peptide gastrin – which regulates pancreatic cancer growth – are mediated. Both gastrin and the CCK-B receptor are overexpressed in pancreatic cancer.

Dr. Smith and her colleagues discovered a splice variant of the CCK-B receptor, known as the CCK-C receptor, which results from retention of the fourth intron on the CCK-B receptor and the insertion of 69 amino acids to the third intracellular loop, she explained.

This change increases the affinity to gastrin and is associated with a more aggressive pancreatic cancer phenotype.

"So we hypothesized that the missplicing of the fourth intron of the CCK-B receptor was the result of a genetic mutation. We also felt that the translation of the additional 69 amino acids in the third intracellular loop of the CCK-B receptor would then contribute to the aggressive phenotype that we know of as pancreatic cancer," said Dr. Smith of the National Institutes of Health.

The investigators analyzed DNA extracted from blood or surgical cancer tissue specimens of 962 pancreatic cancer patients with ductal adenocarcinoma who were treated at three major medical centers, as well as from samples of normal pancreas tissue. The analysis confirmed that the etiology of the misspliced receptor was due to a SNP (involving a transition from C to A) at position 32 of the fourth intron that corresponded to the known SNP rs1800843. The newly identified SNP was not previously identified in genomewide association studies due to its location within an intron, rather than an exon, she noted.

The frequency of the A allele was significantly greater among those with pancreatic cancer than among controls (odds ratio, 1.57).

In addition, survival was significantly reduced in subjects who had the A allele (either AA or AC), compared with subjects with the CC genotype: Survival was about 14 months for patients with AA and 17 months for those with AC, compared with nearly 20 months for CC, Dr. Smith said.

The reduced survival was not a result of more advanced disease state at diagnosis, as the mean stage of subjects with two A alleles (AA) was slightly lower than in those with the CC genotype, she noted.

The findings are notable given that survival from pancreatic cancer has not improved over the past several decades, and that no test exists to diagnose pancreatic cancer in the early stages; more than 90% of patients have advanced disease at the time of diagnosis. Also, no screening tests without radiation are available for high-risk patients, Dr. Smith said.

"The finding of a germline mutation linked to a phenotype that’s significantly increased in patients with pancreatic cancer makes the CCK-B receptor relevant for clinical screening in high-risk subjects or families. Use of this new genetic marker may lead to early detection or even prevention of pancreatic cancer," she concluded.

This study was supported by a National Institutes of Health grant. Dr. Smith disclosed that she is a TNI Biotech stock shareholder.

ORLANDO – Researchers have identified a novel genetic marker for increased pancreatic cancer risk.

The marker, a single nucleotide polymorphism (SNP) of the cholecystokinin-B (CCK-B) receptor, could serve as a screening test for high-risk subjects, Dr. Jill P. Smith reported at the annual Digestive Disease Week.

The CCK-B receptor is a G-protein coupled receptor through which the effects of the peptide gastrin – which regulates pancreatic cancer growth – are mediated. Both gastrin and the CCK-B receptor are overexpressed in pancreatic cancer.

Dr. Smith and her colleagues discovered a splice variant of the CCK-B receptor, known as the CCK-C receptor, which results from retention of the fourth intron on the CCK-B receptor and the insertion of 69 amino acids to the third intracellular loop, she explained.

This change increases the affinity to gastrin and is associated with a more aggressive pancreatic cancer phenotype.

"So we hypothesized that the missplicing of the fourth intron of the CCK-B receptor was the result of a genetic mutation. We also felt that the translation of the additional 69 amino acids in the third intracellular loop of the CCK-B receptor would then contribute to the aggressive phenotype that we know of as pancreatic cancer," said Dr. Smith of the National Institutes of Health.

The investigators analyzed DNA extracted from blood or surgical cancer tissue specimens of 962 pancreatic cancer patients with ductal adenocarcinoma who were treated at three major medical centers, as well as from samples of normal pancreas tissue. The analysis confirmed that the etiology of the misspliced receptor was due to a SNP (involving a transition from C to A) at position 32 of the fourth intron that corresponded to the known SNP rs1800843. The newly identified SNP was not previously identified in genomewide association studies due to its location within an intron, rather than an exon, she noted.

The frequency of the A allele was significantly greater among those with pancreatic cancer than among controls (odds ratio, 1.57).

In addition, survival was significantly reduced in subjects who had the A allele (either AA or AC), compared with subjects with the CC genotype: Survival was about 14 months for patients with AA and 17 months for those with AC, compared with nearly 20 months for CC, Dr. Smith said.

The reduced survival was not a result of more advanced disease state at diagnosis, as the mean stage of subjects with two A alleles (AA) was slightly lower than in those with the CC genotype, she noted.

The findings are notable given that survival from pancreatic cancer has not improved over the past several decades, and that no test exists to diagnose pancreatic cancer in the early stages; more than 90% of patients have advanced disease at the time of diagnosis. Also, no screening tests without radiation are available for high-risk patients, Dr. Smith said.

"The finding of a germline mutation linked to a phenotype that’s significantly increased in patients with pancreatic cancer makes the CCK-B receptor relevant for clinical screening in high-risk subjects or families. Use of this new genetic marker may lead to early detection or even prevention of pancreatic cancer," she concluded.

This study was supported by a National Institutes of Health grant. Dr. Smith disclosed that she is a TNI Biotech stock shareholder.

ORLANDO – Researchers have identified a novel genetic marker for increased pancreatic cancer risk.

The marker, a single nucleotide polymorphism (SNP) of the cholecystokinin-B (CCK-B) receptor, could serve as a screening test for high-risk subjects, Dr. Jill P. Smith reported at the annual Digestive Disease Week.

The CCK-B receptor is a G-protein coupled receptor through which the effects of the peptide gastrin – which regulates pancreatic cancer growth – are mediated. Both gastrin and the CCK-B receptor are overexpressed in pancreatic cancer.

Dr. Smith and her colleagues discovered a splice variant of the CCK-B receptor, known as the CCK-C receptor, which results from retention of the fourth intron on the CCK-B receptor and the insertion of 69 amino acids to the third intracellular loop, she explained.

This change increases the affinity to gastrin and is associated with a more aggressive pancreatic cancer phenotype.

"So we hypothesized that the missplicing of the fourth intron of the CCK-B receptor was the result of a genetic mutation. We also felt that the translation of the additional 69 amino acids in the third intracellular loop of the CCK-B receptor would then contribute to the aggressive phenotype that we know of as pancreatic cancer," said Dr. Smith of the National Institutes of Health.

The investigators analyzed DNA extracted from blood or surgical cancer tissue specimens of 962 pancreatic cancer patients with ductal adenocarcinoma who were treated at three major medical centers, as well as from samples of normal pancreas tissue. The analysis confirmed that the etiology of the misspliced receptor was due to a SNP (involving a transition from C to A) at position 32 of the fourth intron that corresponded to the known SNP rs1800843. The newly identified SNP was not previously identified in genomewide association studies due to its location within an intron, rather than an exon, she noted.

The frequency of the A allele was significantly greater among those with pancreatic cancer than among controls (odds ratio, 1.57).

In addition, survival was significantly reduced in subjects who had the A allele (either AA or AC), compared with subjects with the CC genotype: Survival was about 14 months for patients with AA and 17 months for those with AC, compared with nearly 20 months for CC, Dr. Smith said.

The reduced survival was not a result of more advanced disease state at diagnosis, as the mean stage of subjects with two A alleles (AA) was slightly lower than in those with the CC genotype, she noted.

The findings are notable given that survival from pancreatic cancer has not improved over the past several decades, and that no test exists to diagnose pancreatic cancer in the early stages; more than 90% of patients have advanced disease at the time of diagnosis. Also, no screening tests without radiation are available for high-risk patients, Dr. Smith said.

"The finding of a germline mutation linked to a phenotype that’s significantly increased in patients with pancreatic cancer makes the CCK-B receptor relevant for clinical screening in high-risk subjects or families. Use of this new genetic marker may lead to early detection or even prevention of pancreatic cancer," she concluded.

This study was supported by a National Institutes of Health grant. Dr. Smith disclosed that she is a TNI Biotech stock shareholder.