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VIDEO: Newer MRI hardware, software significantly better at detecting pancreatic cysts
As magnetic resonance imaging technology continues to advance year after year, so does MRI’s ability to accurately detect pancreatic cysts, according to a new study published in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.08.038).
“To our knowledge, this is the first study to analyze the relationship between the technical improvements in imaging techniques (specifically, MRI) and the presence of incidentally found PCLs [pancreatic cystic lesions],” said the study authors, led by Dr. Michael B. Wallace of the Mayo Clinic in Jacksonville, Fla.
Dr. Wallace and his coinvestigators launched this retrospective descriptive study selecting the first 50 consecutive abdominal MRI patients at the Jacksonville Mayo Clinic during January and February of each year from 2005 through 2014, for a total of 500 cases who met inclusion criteria included in the study. Patients were excluded if they had preexisting symptomatic or asymptomatic pancreatitis, either acute or chronic, pancreatic masses, pancreatic cysts, pancreatic surgery, pancreatic symptoms, or any pancreas-related indications found by MRI.
The clinic underwent periodic MRI updates over the course of the 10-year study, along with requisite software updates to “take advantage of the new hardware technology,” the study explains. Major hardware improvements, provided by Siemens Medical Solutions USA, were Symphony/Sonata, Espree/Avanto, and Aera/Skyra, while software updates corresponding to each hardware update were VA, VB, and VD, respectively.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Furthermore, each software update had other, smaller upgrades, leading to a total of 20 combinations of MRI hardware and software on which MRIs were performed over the 10 years. Every MRI taken included “an axial and a coronal T2-weighted single-shot (HASTE) pulse sequence [with] TR 1400-1500 ms, TE 82-99 ms, and slice thickness 5-7 mm (gap, 0.5-0.7 mm).” Each MRI was analyzed by a pancreatic MRI specialist to find incidental cysts.
The number of patients found with pancreatic cysts increased incrementally from 2005 to 2014, with 2010 being the year with the highest number. A total of 208 subjects (41.6%) were found to have incidental cysts, but only 44 of these cases were discovered in the original MRI. The presence of cysts was associated with older age in patients who had them; only 20% of all subjects under 50 years of age had cysts, compared to 32.4% of those between 50 and 60 years, 54.9% of those between 60 and 70 years, and 61.5% of those over the age of 70 years (P less than .01).
Additionally, 56.4% of all subjects with diabetes (P less than .01), 59.0% of subjects with nonmelanoma skin cancer (P less than .03), and 58.1% of those with hepatocarcinoma (P less than .02) were also found to have cysts. Most striking, however, is that newer hardware and software permutations were able to detect cysts in 56.3% (Skyra) of patients who had them, compared with only 30.3% (Symphony) of patients who underwent MRI on older technology.
“The variable field strength” (1.5 T vs. 3 T) was not significantly related to the presence of PCLs,” Dr. Wallace and his coauthors concluded. “We believe this may be secondary to the lack of power of the analysis, because only 6% of the examinations were 3-T studies. Therefore, we speculate that this relationship may be confirmed if the number of 3-T studies increased.”
Males and females each made up roughly 50% of the study population, with a median age of 60 years and 85% being white. Additionally, 4% of subjects had a family history of pancreatic cancer, 12% had a personal history of solid organ transplant, and 53% had a personal history of smoking.
This study was funded by the Mayo Clinic. Dr. Wallace disclosed that he has received grant funding from Olympus, Boston Scientific, and Cosmo Pharmaceuticals, and travel support from Olympus. No other authors reported any financial disclosures.
The increasing prevalence of pancreatic cystic lesions on MRI scanning may provide an important opportunity for detection of early precursors of pancreatic cancer – or may represent just another insignificant incidental finding. What is the implication of a small asymptomatic cyst?
MRI scanning of the pancreas has revolutionized our ability to detect early cystic neoplasms of the pancreas. Pancreatic cysts appear as well-defined, small, round fluid-filled structures within the pancreas. The inner structures – such as septations, nodules, and adjacent masses – offer clues as to the type of cyst and the risk of malignancy. But the real strength of pancreatic MRI scanning is the ability to detect and portray small cysts and the adjacent main pancreatic duct.
The size, number, and distribution of cysts over time can be tracked with MRI surveillance. By tracking the diameter of cysts and calculating the rate of growth of cysts, clinicians may be able to predict the development of malignancy in intraductal papillary mucinous neoplasms.
How should these patients be managed clinically? Once a cyst has been identified, are clinicians obligated to notify the patient, monitor the cyst with an established surveillance program, or biopsy the cyst? If the cyst is very small and benign appearing, can the clinician ignore the finding and perhaps not notify the patient?
Once again, we are watching dilemmas unfold as technology outstrips our understanding of diseases and their management. We are going to need some good correlations between imaging and tissue of pancreatic cystic lesions. In the meantime, it is important to reserve the use of pancreatic MRI scanning to high-risk patients or patients with CT scan abnormalities.
Dr. William R. Brugge, AGAF, is professor of medicine, Harvard Medical School, and director, Pancreas Biliary Center, Massachusetts General Hospital, both in Boston. He is a consultant with Boston Scientific.
The increasing prevalence of pancreatic cystic lesions on MRI scanning may provide an important opportunity for detection of early precursors of pancreatic cancer – or may represent just another insignificant incidental finding. What is the implication of a small asymptomatic cyst?
MRI scanning of the pancreas has revolutionized our ability to detect early cystic neoplasms of the pancreas. Pancreatic cysts appear as well-defined, small, round fluid-filled structures within the pancreas. The inner structures – such as septations, nodules, and adjacent masses – offer clues as to the type of cyst and the risk of malignancy. But the real strength of pancreatic MRI scanning is the ability to detect and portray small cysts and the adjacent main pancreatic duct.
The size, number, and distribution of cysts over time can be tracked with MRI surveillance. By tracking the diameter of cysts and calculating the rate of growth of cysts, clinicians may be able to predict the development of malignancy in intraductal papillary mucinous neoplasms.
How should these patients be managed clinically? Once a cyst has been identified, are clinicians obligated to notify the patient, monitor the cyst with an established surveillance program, or biopsy the cyst? If the cyst is very small and benign appearing, can the clinician ignore the finding and perhaps not notify the patient?
Once again, we are watching dilemmas unfold as technology outstrips our understanding of diseases and their management. We are going to need some good correlations between imaging and tissue of pancreatic cystic lesions. In the meantime, it is important to reserve the use of pancreatic MRI scanning to high-risk patients or patients with CT scan abnormalities.
Dr. William R. Brugge, AGAF, is professor of medicine, Harvard Medical School, and director, Pancreas Biliary Center, Massachusetts General Hospital, both in Boston. He is a consultant with Boston Scientific.
The increasing prevalence of pancreatic cystic lesions on MRI scanning may provide an important opportunity for detection of early precursors of pancreatic cancer – or may represent just another insignificant incidental finding. What is the implication of a small asymptomatic cyst?
MRI scanning of the pancreas has revolutionized our ability to detect early cystic neoplasms of the pancreas. Pancreatic cysts appear as well-defined, small, round fluid-filled structures within the pancreas. The inner structures – such as septations, nodules, and adjacent masses – offer clues as to the type of cyst and the risk of malignancy. But the real strength of pancreatic MRI scanning is the ability to detect and portray small cysts and the adjacent main pancreatic duct.
The size, number, and distribution of cysts over time can be tracked with MRI surveillance. By tracking the diameter of cysts and calculating the rate of growth of cysts, clinicians may be able to predict the development of malignancy in intraductal papillary mucinous neoplasms.
How should these patients be managed clinically? Once a cyst has been identified, are clinicians obligated to notify the patient, monitor the cyst with an established surveillance program, or biopsy the cyst? If the cyst is very small and benign appearing, can the clinician ignore the finding and perhaps not notify the patient?
Once again, we are watching dilemmas unfold as technology outstrips our understanding of diseases and their management. We are going to need some good correlations between imaging and tissue of pancreatic cystic lesions. In the meantime, it is important to reserve the use of pancreatic MRI scanning to high-risk patients or patients with CT scan abnormalities.
Dr. William R. Brugge, AGAF, is professor of medicine, Harvard Medical School, and director, Pancreas Biliary Center, Massachusetts General Hospital, both in Boston. He is a consultant with Boston Scientific.
As magnetic resonance imaging technology continues to advance year after year, so does MRI’s ability to accurately detect pancreatic cysts, according to a new study published in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.08.038).
“To our knowledge, this is the first study to analyze the relationship between the technical improvements in imaging techniques (specifically, MRI) and the presence of incidentally found PCLs [pancreatic cystic lesions],” said the study authors, led by Dr. Michael B. Wallace of the Mayo Clinic in Jacksonville, Fla.
Dr. Wallace and his coinvestigators launched this retrospective descriptive study selecting the first 50 consecutive abdominal MRI patients at the Jacksonville Mayo Clinic during January and February of each year from 2005 through 2014, for a total of 500 cases who met inclusion criteria included in the study. Patients were excluded if they had preexisting symptomatic or asymptomatic pancreatitis, either acute or chronic, pancreatic masses, pancreatic cysts, pancreatic surgery, pancreatic symptoms, or any pancreas-related indications found by MRI.
The clinic underwent periodic MRI updates over the course of the 10-year study, along with requisite software updates to “take advantage of the new hardware technology,” the study explains. Major hardware improvements, provided by Siemens Medical Solutions USA, were Symphony/Sonata, Espree/Avanto, and Aera/Skyra, while software updates corresponding to each hardware update were VA, VB, and VD, respectively.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Furthermore, each software update had other, smaller upgrades, leading to a total of 20 combinations of MRI hardware and software on which MRIs were performed over the 10 years. Every MRI taken included “an axial and a coronal T2-weighted single-shot (HASTE) pulse sequence [with] TR 1400-1500 ms, TE 82-99 ms, and slice thickness 5-7 mm (gap, 0.5-0.7 mm).” Each MRI was analyzed by a pancreatic MRI specialist to find incidental cysts.
The number of patients found with pancreatic cysts increased incrementally from 2005 to 2014, with 2010 being the year with the highest number. A total of 208 subjects (41.6%) were found to have incidental cysts, but only 44 of these cases were discovered in the original MRI. The presence of cysts was associated with older age in patients who had them; only 20% of all subjects under 50 years of age had cysts, compared to 32.4% of those between 50 and 60 years, 54.9% of those between 60 and 70 years, and 61.5% of those over the age of 70 years (P less than .01).
Additionally, 56.4% of all subjects with diabetes (P less than .01), 59.0% of subjects with nonmelanoma skin cancer (P less than .03), and 58.1% of those with hepatocarcinoma (P less than .02) were also found to have cysts. Most striking, however, is that newer hardware and software permutations were able to detect cysts in 56.3% (Skyra) of patients who had them, compared with only 30.3% (Symphony) of patients who underwent MRI on older technology.
“The variable field strength” (1.5 T vs. 3 T) was not significantly related to the presence of PCLs,” Dr. Wallace and his coauthors concluded. “We believe this may be secondary to the lack of power of the analysis, because only 6% of the examinations were 3-T studies. Therefore, we speculate that this relationship may be confirmed if the number of 3-T studies increased.”
Males and females each made up roughly 50% of the study population, with a median age of 60 years and 85% being white. Additionally, 4% of subjects had a family history of pancreatic cancer, 12% had a personal history of solid organ transplant, and 53% had a personal history of smoking.
This study was funded by the Mayo Clinic. Dr. Wallace disclosed that he has received grant funding from Olympus, Boston Scientific, and Cosmo Pharmaceuticals, and travel support from Olympus. No other authors reported any financial disclosures.
As magnetic resonance imaging technology continues to advance year after year, so does MRI’s ability to accurately detect pancreatic cysts, according to a new study published in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2015.08.038).
“To our knowledge, this is the first study to analyze the relationship between the technical improvements in imaging techniques (specifically, MRI) and the presence of incidentally found PCLs [pancreatic cystic lesions],” said the study authors, led by Dr. Michael B. Wallace of the Mayo Clinic in Jacksonville, Fla.
Dr. Wallace and his coinvestigators launched this retrospective descriptive study selecting the first 50 consecutive abdominal MRI patients at the Jacksonville Mayo Clinic during January and February of each year from 2005 through 2014, for a total of 500 cases who met inclusion criteria included in the study. Patients were excluded if they had preexisting symptomatic or asymptomatic pancreatitis, either acute or chronic, pancreatic masses, pancreatic cysts, pancreatic surgery, pancreatic symptoms, or any pancreas-related indications found by MRI.
The clinic underwent periodic MRI updates over the course of the 10-year study, along with requisite software updates to “take advantage of the new hardware technology,” the study explains. Major hardware improvements, provided by Siemens Medical Solutions USA, were Symphony/Sonata, Espree/Avanto, and Aera/Skyra, while software updates corresponding to each hardware update were VA, VB, and VD, respectively.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Furthermore, each software update had other, smaller upgrades, leading to a total of 20 combinations of MRI hardware and software on which MRIs were performed over the 10 years. Every MRI taken included “an axial and a coronal T2-weighted single-shot (HASTE) pulse sequence [with] TR 1400-1500 ms, TE 82-99 ms, and slice thickness 5-7 mm (gap, 0.5-0.7 mm).” Each MRI was analyzed by a pancreatic MRI specialist to find incidental cysts.
The number of patients found with pancreatic cysts increased incrementally from 2005 to 2014, with 2010 being the year with the highest number. A total of 208 subjects (41.6%) were found to have incidental cysts, but only 44 of these cases were discovered in the original MRI. The presence of cysts was associated with older age in patients who had them; only 20% of all subjects under 50 years of age had cysts, compared to 32.4% of those between 50 and 60 years, 54.9% of those between 60 and 70 years, and 61.5% of those over the age of 70 years (P less than .01).
Additionally, 56.4% of all subjects with diabetes (P less than .01), 59.0% of subjects with nonmelanoma skin cancer (P less than .03), and 58.1% of those with hepatocarcinoma (P less than .02) were also found to have cysts. Most striking, however, is that newer hardware and software permutations were able to detect cysts in 56.3% (Skyra) of patients who had them, compared with only 30.3% (Symphony) of patients who underwent MRI on older technology.
“The variable field strength” (1.5 T vs. 3 T) was not significantly related to the presence of PCLs,” Dr. Wallace and his coauthors concluded. “We believe this may be secondary to the lack of power of the analysis, because only 6% of the examinations were 3-T studies. Therefore, we speculate that this relationship may be confirmed if the number of 3-T studies increased.”
Males and females each made up roughly 50% of the study population, with a median age of 60 years and 85% being white. Additionally, 4% of subjects had a family history of pancreatic cancer, 12% had a personal history of solid organ transplant, and 53% had a personal history of smoking.
This study was funded by the Mayo Clinic. Dr. Wallace disclosed that he has received grant funding from Olympus, Boston Scientific, and Cosmo Pharmaceuticals, and travel support from Olympus. No other authors reported any financial disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Newer MRI technology is more effective at detecting pancreatic cysts, particularly in patients with diabetes or advanced age.
Major finding: Newer MRI hardware and software detected pancreatic cysts in 56.3% of patients, compared with only 30.3% on older MRI hardware and software.
Data source: Retrospective, descriptive study of 500 patients undergoing MRI for nonpancreatic indications during January and February of 2005-2014.
Disclosures: Study funded by the Mayo Clinic. Dr. Michael B. Wallace disclosed relationships with Olympus, Boston Scientific, and Cosmo Pharmaceuticals.
Increased prevalence of pancreatic cysts due to MRI improvements
The apparent increase in the prevalence of incidental pancreatic cysts in recent years may be tied to improvements in MRI scanning technology, results of a study suggest.
Researchers conducted a retrospective analysis of data from 500 patients who underwent an MRI for nonpancreatic indications at a single center between 2005 and 2014; 50 were sampled from each year in chronological order.
A total of 208 patients (41.6%) were found to have an incidental cyst, of which less than a quarter were described in the original MRI report, according to a paper published online in Clinical Gastroenterology and Hepatology.
Analysis showed a very strong association between the type of imaging hardware and software, and the presence of cysts; older hardware found pancreatic cysts in 30.3% of patients and the newest hardware found cysts in 56.3% of patients.
However, MRI field strength was not associated with the frequency of lesion discovery (Clin Gastro Hepatol. 2015 Sep 11. doi: 10.1016/j.cgh.2015.08.038).
Most cysts were relatively small, with a median size of 4 mm. Nearly half of the patients with a cyst only had one described.
Nearly two-thirds of these cysts (62%) had an uncertain diagnosis, but 35% of patients were diagnosed with an intraductal papillary mucinous neoplasm, and one patient showed radiologic evidence of subacute pancreatitis.
When compared to the rest of the cohort, individuals with pancreatic cysts were more likely to be older, have diabetes mellitus, or have a personal history of cancer, particularly nonmelanoma skin cancer and hepatocellular carcinoma.
“Our study demonstrates the relationship between the higher trend of incidental pancreatic cysts observed in the recent years and the improvements in the technical features of MRIs,” wrote Dr. Maria Moris and colleagues from the Mayo Clinic, Jacksonville.
The authors said the real prevalence of pancreatic cystic lesions is estimated to range from 0.2% to 44.7%.
Their finding of a prevalence of 41.6% was higher than that found in similar imaging studies, but the authors suggested some of this may be due to the lack of a size cutoff in their study, as opposed to a 5-mm cutoff used in one earlier study that found a prevalence of 10%.
“Moreover, we believe that we may have even underestimated the real prevalence because of the absence of magnetic resonance cholangiopancreatography sequences (only 19% of the examinations), and the lack of 3-T studies (6% of the MRIs),” they wrote.
The median size of the lesions was lower than those found in previous studies.
“This smaller size was unexpected because, as a result of the exclusion criteria applied, the technical features of the MRIs were not the most specific for [pancreatic cystic lesion] PCL visualization,” the authors wrote, suggesting that this may have been due to the radiologist’s experience in this field.
The study was funded by the Joyce E. Baker Foundation for Research at Mayo Clinic in Jacksonville. One author disclosed grants or travel support from Olympus, Boston Scientific, and Cosmo Pharmaceuticals. There were no other conflicts of interest declared.
AGA Resource
Review the AGA guideline on the management of asymptomatic pancreatic neoplastic cysts at http://www.gastro.org/guidelines/2015/5/29/pancreatic-cysts.
The apparent increase in the prevalence of incidental pancreatic cysts in recent years may be tied to improvements in MRI scanning technology, results of a study suggest.
Researchers conducted a retrospective analysis of data from 500 patients who underwent an MRI for nonpancreatic indications at a single center between 2005 and 2014; 50 were sampled from each year in chronological order.
A total of 208 patients (41.6%) were found to have an incidental cyst, of which less than a quarter were described in the original MRI report, according to a paper published online in Clinical Gastroenterology and Hepatology.
Analysis showed a very strong association between the type of imaging hardware and software, and the presence of cysts; older hardware found pancreatic cysts in 30.3% of patients and the newest hardware found cysts in 56.3% of patients.
However, MRI field strength was not associated with the frequency of lesion discovery (Clin Gastro Hepatol. 2015 Sep 11. doi: 10.1016/j.cgh.2015.08.038).
Most cysts were relatively small, with a median size of 4 mm. Nearly half of the patients with a cyst only had one described.
Nearly two-thirds of these cysts (62%) had an uncertain diagnosis, but 35% of patients were diagnosed with an intraductal papillary mucinous neoplasm, and one patient showed radiologic evidence of subacute pancreatitis.
When compared to the rest of the cohort, individuals with pancreatic cysts were more likely to be older, have diabetes mellitus, or have a personal history of cancer, particularly nonmelanoma skin cancer and hepatocellular carcinoma.
“Our study demonstrates the relationship between the higher trend of incidental pancreatic cysts observed in the recent years and the improvements in the technical features of MRIs,” wrote Dr. Maria Moris and colleagues from the Mayo Clinic, Jacksonville.
The authors said the real prevalence of pancreatic cystic lesions is estimated to range from 0.2% to 44.7%.
Their finding of a prevalence of 41.6% was higher than that found in similar imaging studies, but the authors suggested some of this may be due to the lack of a size cutoff in their study, as opposed to a 5-mm cutoff used in one earlier study that found a prevalence of 10%.
“Moreover, we believe that we may have even underestimated the real prevalence because of the absence of magnetic resonance cholangiopancreatography sequences (only 19% of the examinations), and the lack of 3-T studies (6% of the MRIs),” they wrote.
The median size of the lesions was lower than those found in previous studies.
“This smaller size was unexpected because, as a result of the exclusion criteria applied, the technical features of the MRIs were not the most specific for [pancreatic cystic lesion] PCL visualization,” the authors wrote, suggesting that this may have been due to the radiologist’s experience in this field.
The study was funded by the Joyce E. Baker Foundation for Research at Mayo Clinic in Jacksonville. One author disclosed grants or travel support from Olympus, Boston Scientific, and Cosmo Pharmaceuticals. There were no other conflicts of interest declared.
AGA Resource
Review the AGA guideline on the management of asymptomatic pancreatic neoplastic cysts at http://www.gastro.org/guidelines/2015/5/29/pancreatic-cysts.
The apparent increase in the prevalence of incidental pancreatic cysts in recent years may be tied to improvements in MRI scanning technology, results of a study suggest.
Researchers conducted a retrospective analysis of data from 500 patients who underwent an MRI for nonpancreatic indications at a single center between 2005 and 2014; 50 were sampled from each year in chronological order.
A total of 208 patients (41.6%) were found to have an incidental cyst, of which less than a quarter were described in the original MRI report, according to a paper published online in Clinical Gastroenterology and Hepatology.
Analysis showed a very strong association between the type of imaging hardware and software, and the presence of cysts; older hardware found pancreatic cysts in 30.3% of patients and the newest hardware found cysts in 56.3% of patients.
However, MRI field strength was not associated with the frequency of lesion discovery (Clin Gastro Hepatol. 2015 Sep 11. doi: 10.1016/j.cgh.2015.08.038).
Most cysts were relatively small, with a median size of 4 mm. Nearly half of the patients with a cyst only had one described.
Nearly two-thirds of these cysts (62%) had an uncertain diagnosis, but 35% of patients were diagnosed with an intraductal papillary mucinous neoplasm, and one patient showed radiologic evidence of subacute pancreatitis.
When compared to the rest of the cohort, individuals with pancreatic cysts were more likely to be older, have diabetes mellitus, or have a personal history of cancer, particularly nonmelanoma skin cancer and hepatocellular carcinoma.
“Our study demonstrates the relationship between the higher trend of incidental pancreatic cysts observed in the recent years and the improvements in the technical features of MRIs,” wrote Dr. Maria Moris and colleagues from the Mayo Clinic, Jacksonville.
The authors said the real prevalence of pancreatic cystic lesions is estimated to range from 0.2% to 44.7%.
Their finding of a prevalence of 41.6% was higher than that found in similar imaging studies, but the authors suggested some of this may be due to the lack of a size cutoff in their study, as opposed to a 5-mm cutoff used in one earlier study that found a prevalence of 10%.
“Moreover, we believe that we may have even underestimated the real prevalence because of the absence of magnetic resonance cholangiopancreatography sequences (only 19% of the examinations), and the lack of 3-T studies (6% of the MRIs),” they wrote.
The median size of the lesions was lower than those found in previous studies.
“This smaller size was unexpected because, as a result of the exclusion criteria applied, the technical features of the MRIs were not the most specific for [pancreatic cystic lesion] PCL visualization,” the authors wrote, suggesting that this may have been due to the radiologist’s experience in this field.
The study was funded by the Joyce E. Baker Foundation for Research at Mayo Clinic in Jacksonville. One author disclosed grants or travel support from Olympus, Boston Scientific, and Cosmo Pharmaceuticals. There were no other conflicts of interest declared.
AGA Resource
Review the AGA guideline on the management of asymptomatic pancreatic neoplastic cysts at http://www.gastro.org/guidelines/2015/5/29/pancreatic-cysts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The apparent increase of the prevalence of incidental pancreatic cysts in recent years may be tied to improvements in MRI scanning technology.
Major finding: Older MRI hardware found pancreatic cysts in 30.3% of patients and the newest hardware found cysts in 56.3% of patients.
Data source: A retrospective analysis of data from 500 patients who underwent an MRI for nonpancreatic indications.
Disclosures: The study was funded by the Joyce E. Baker Foundation for Research at Mayo Clinic in Jacksonville, Fla. One author disclosed grants or travel support from Olympus, Boston Scientific, and Cosmo Pharmaceuticals. There were no other conflicts of interest declared.
P2X7 receptor implicated in visceral pain caused by chronic pancreatitis
A subtype of purinergic receptor on spinal microglial cells mediated visceral pain hypersensitivity in rats with chronic pancreatitis, and pharmacologic or genetic inhibition of this receptor improved hyperalgesia, according to a report in the November issue of Cellular and Molecular Gastroenterology and Hepatology.
“Our study may be the first to identify that P2X7 receptors in spinal microglia are upregulated in chronic pancreatitis, and that this upregulation is associated with the development of visceral hyperalgesia,” said Dr. Pei-Yi Liu at National Yang-Ming University in Taipei, Taiwan, and her associates. A common laboratory dye known as brilliant blue G, which is an antagonist of P2X7R, “not only attenuated but also prevented CP-related chronic visceral hyperalgesia,” the researchers reported.
Chronic pancreatitis causes intense, recurrent epigastric pain that is “difficult and frustrating” to control and can lead to malnutrition, narcotic analgesic addiction, and social and financial problems, said the researchers. Previously, they had linked visceral pain in murine CP to activation of spinal microglia, the main effector immune cells in the central nervous system. The molecular pathways remained unclear, but some research had implicated extracellular adenosine triphosphate (ATP) as well as purinergic receptors in the CNS. Because a purine receptor subtype known as P2X7 had been linked to neuropathic and inflammatory pain, the researchers wondered if it also facilitated visceral pain (Cell Mol Gastroenterol Hepatol. 2015 Jul 22. doi: 10.1016/j.jcmgh.2015.07.008). To explore that question, they created a CP model by injecting 2% trinitrobenzene sulfonic acid into the pancreatic ducts of male rats. They measured behavioral responses to mechanical and electrical stimulation and quantified spinal cord P2X7R levels with the help of standard laboratory assays. They also watched for changes in pain-related behaviors after blocking spinal cord P2X7R with brilliant blue G or knocking it down with short interfering RNA (siRNA).
Spinal P2X7R expression rose significantly after CP induction, as did levels of the OX-42 microglial marker in the dorsal horn of the spinal cord, said the investigators. Brilliant blue G and genetic knock down suppressed P2X7R expression, inhibited activation of spinal microglia, and “significantly attenuated” nociceptive behaviors, they added.
The researchers also pretreated some rats with brilliant blue G before inducing CP and saw that these rats exhibited significantly lower pain responses to mechanical and electrical stimuli compared with other CP rats. In fact, the nociceptive responses of the pretreated CP rats resembled those of non-CP control rats, the investigators said. Spinal tissue from pretreated rats also lacked signs of P2X7R upregulation, they noted.
Taken together, the data “indicate a critical role of P2X7R expressed in the spinal cord in the development of chronic visceral pain in CP,” concluded the researchers. Brilliant blue G inhibits voltage-gated sodium channels, which are known to contribute to chronic visceral pain, and “may represent an effective drug for the treatment of chronic pain in chronic pancreatitis patients,” they added.
The study was funded by Taipei Veterans General Hospital, National Science Council of Taiwan, and the Taiwan Ministry of Education Aim for Top University Grant. The investigators declared no competing interests.
The traditional approach to treating pain in chronic pancreatitis is as if it were a “plumbing” problem – problems with ductal drainage. More recently, the emphasis has been on sensitization of the sensorineural system (“wiring”), in which the pain responses are greatly exaggerated. An additional consideration is whether this sensitization occurs in peripheral nerves that directly innervate the pancreas, or in the central nervous system, or both. This is clinically important because treatments directed at the periphery, e.g., pancreatectomy, may not be effective in patients in whom central sensitization is dominant.
 |
Dr. Pankaj Jay Pasricha |
The findings of Dr. Lui and colleagues show that spinal (hence central) sensitization is important in chronic pancreatitis pain, and that this may be mediated by nonneuronal cells (microglia) in the spinal cord via P2X7R, a nucleotide receptor. This is not surprising, given that this signaling system has shown to be important in other forms of chronic pain. However, some questions remain – is peripheral sensitization driving these changes?
Clearly the “drug” they have used (BBG) is relatively harmless, but it is not practical because it may not be safe in humans (apart from coloring them blue). BBG also affects other channels, notably neuronal voltage-dependent sodium channels. Nevertheless, this study does offer new insight into the pathogenesis of pain in chronic pancreatitis and by itself is an important cautionary message for the growing enthusiasm for total pancreatectomy. It also identifies potential new therapeutic targets for treatment of pain and will, it is hoped, stimulate engagement from the pharmaceutical industry that is developing drugs directed toward glial activation and in particular the P2X7 receptor.
Dr. Pankaj Jay Pasricha, AGAF, is professor of medicine, Johns Hopkins University School of Medicine, director of Johns Hopkins Center for Motility Disorders and Digestive Diseases, and professor of innovation management, The Carey Business School, Johns Hopkins University, Baltimore. He has no conflicts of interest.
The traditional approach to treating pain in chronic pancreatitis is as if it were a “plumbing” problem – problems with ductal drainage. More recently, the emphasis has been on sensitization of the sensorineural system (“wiring”), in which the pain responses are greatly exaggerated. An additional consideration is whether this sensitization occurs in peripheral nerves that directly innervate the pancreas, or in the central nervous system, or both. This is clinically important because treatments directed at the periphery, e.g., pancreatectomy, may not be effective in patients in whom central sensitization is dominant.
|
Dr. Pankaj Jay Pasricha |
The findings of Dr. Lui and colleagues show that spinal (hence central) sensitization is important in chronic pancreatitis pain, and that this may be mediated by nonneuronal cells (microglia) in the spinal cord via P2X7R, a nucleotide receptor. This is not surprising, given that this signaling system has shown to be important in other forms of chronic pain. However, some questions remain – is peripheral sensitization driving these changes?
Clearly the “drug” they have used (BBG) is relatively harmless, but it is not practical because it may not be safe in humans (apart from coloring them blue). BBG also affects other channels, notably neuronal voltage-dependent sodium channels. Nevertheless, this study does offer new insight into the pathogenesis of pain in chronic pancreatitis and by itself is an important cautionary message for the growing enthusiasm for total pancreatectomy. It also identifies potential new therapeutic targets for treatment of pain and will, it is hoped, stimulate engagement from the pharmaceutical industry that is developing drugs directed toward glial activation and in particular the P2X7 receptor.
Dr. Pankaj Jay Pasricha, AGAF, is professor of medicine, Johns Hopkins University School of Medicine, director of Johns Hopkins Center for Motility Disorders and Digestive Diseases, and professor of innovation management, The Carey Business School, Johns Hopkins University, Baltimore. He has no conflicts of interest.
The traditional approach to treating pain in chronic pancreatitis is as if it were a “plumbing” problem – problems with ductal drainage. More recently, the emphasis has been on sensitization of the sensorineural system (“wiring”), in which the pain responses are greatly exaggerated. An additional consideration is whether this sensitization occurs in peripheral nerves that directly innervate the pancreas, or in the central nervous system, or both. This is clinically important because treatments directed at the periphery, e.g., pancreatectomy, may not be effective in patients in whom central sensitization is dominant.
|
Dr. Pankaj Jay Pasricha |
The findings of Dr. Lui and colleagues show that spinal (hence central) sensitization is important in chronic pancreatitis pain, and that this may be mediated by nonneuronal cells (microglia) in the spinal cord via P2X7R, a nucleotide receptor. This is not surprising, given that this signaling system has shown to be important in other forms of chronic pain. However, some questions remain – is peripheral sensitization driving these changes?
Clearly the “drug” they have used (BBG) is relatively harmless, but it is not practical because it may not be safe in humans (apart from coloring them blue). BBG also affects other channels, notably neuronal voltage-dependent sodium channels. Nevertheless, this study does offer new insight into the pathogenesis of pain in chronic pancreatitis and by itself is an important cautionary message for the growing enthusiasm for total pancreatectomy. It also identifies potential new therapeutic targets for treatment of pain and will, it is hoped, stimulate engagement from the pharmaceutical industry that is developing drugs directed toward glial activation and in particular the P2X7 receptor.
Dr. Pankaj Jay Pasricha, AGAF, is professor of medicine, Johns Hopkins University School of Medicine, director of Johns Hopkins Center for Motility Disorders and Digestive Diseases, and professor of innovation management, The Carey Business School, Johns Hopkins University, Baltimore. He has no conflicts of interest.
A subtype of purinergic receptor on spinal microglial cells mediated visceral pain hypersensitivity in rats with chronic pancreatitis, and pharmacologic or genetic inhibition of this receptor improved hyperalgesia, according to a report in the November issue of Cellular and Molecular Gastroenterology and Hepatology.
“Our study may be the first to identify that P2X7 receptors in spinal microglia are upregulated in chronic pancreatitis, and that this upregulation is associated with the development of visceral hyperalgesia,” said Dr. Pei-Yi Liu at National Yang-Ming University in Taipei, Taiwan, and her associates. A common laboratory dye known as brilliant blue G, which is an antagonist of P2X7R, “not only attenuated but also prevented CP-related chronic visceral hyperalgesia,” the researchers reported.
Chronic pancreatitis causes intense, recurrent epigastric pain that is “difficult and frustrating” to control and can lead to malnutrition, narcotic analgesic addiction, and social and financial problems, said the researchers. Previously, they had linked visceral pain in murine CP to activation of spinal microglia, the main effector immune cells in the central nervous system. The molecular pathways remained unclear, but some research had implicated extracellular adenosine triphosphate (ATP) as well as purinergic receptors in the CNS. Because a purine receptor subtype known as P2X7 had been linked to neuropathic and inflammatory pain, the researchers wondered if it also facilitated visceral pain (Cell Mol Gastroenterol Hepatol. 2015 Jul 22. doi: 10.1016/j.jcmgh.2015.07.008). To explore that question, they created a CP model by injecting 2% trinitrobenzene sulfonic acid into the pancreatic ducts of male rats. They measured behavioral responses to mechanical and electrical stimulation and quantified spinal cord P2X7R levels with the help of standard laboratory assays. They also watched for changes in pain-related behaviors after blocking spinal cord P2X7R with brilliant blue G or knocking it down with short interfering RNA (siRNA).
Spinal P2X7R expression rose significantly after CP induction, as did levels of the OX-42 microglial marker in the dorsal horn of the spinal cord, said the investigators. Brilliant blue G and genetic knock down suppressed P2X7R expression, inhibited activation of spinal microglia, and “significantly attenuated” nociceptive behaviors, they added.
The researchers also pretreated some rats with brilliant blue G before inducing CP and saw that these rats exhibited significantly lower pain responses to mechanical and electrical stimuli compared with other CP rats. In fact, the nociceptive responses of the pretreated CP rats resembled those of non-CP control rats, the investigators said. Spinal tissue from pretreated rats also lacked signs of P2X7R upregulation, they noted.
Taken together, the data “indicate a critical role of P2X7R expressed in the spinal cord in the development of chronic visceral pain in CP,” concluded the researchers. Brilliant blue G inhibits voltage-gated sodium channels, which are known to contribute to chronic visceral pain, and “may represent an effective drug for the treatment of chronic pain in chronic pancreatitis patients,” they added.
The study was funded by Taipei Veterans General Hospital, National Science Council of Taiwan, and the Taiwan Ministry of Education Aim for Top University Grant. The investigators declared no competing interests.
A subtype of purinergic receptor on spinal microglial cells mediated visceral pain hypersensitivity in rats with chronic pancreatitis, and pharmacologic or genetic inhibition of this receptor improved hyperalgesia, according to a report in the November issue of Cellular and Molecular Gastroenterology and Hepatology.
“Our study may be the first to identify that P2X7 receptors in spinal microglia are upregulated in chronic pancreatitis, and that this upregulation is associated with the development of visceral hyperalgesia,” said Dr. Pei-Yi Liu at National Yang-Ming University in Taipei, Taiwan, and her associates. A common laboratory dye known as brilliant blue G, which is an antagonist of P2X7R, “not only attenuated but also prevented CP-related chronic visceral hyperalgesia,” the researchers reported.
Chronic pancreatitis causes intense, recurrent epigastric pain that is “difficult and frustrating” to control and can lead to malnutrition, narcotic analgesic addiction, and social and financial problems, said the researchers. Previously, they had linked visceral pain in murine CP to activation of spinal microglia, the main effector immune cells in the central nervous system. The molecular pathways remained unclear, but some research had implicated extracellular adenosine triphosphate (ATP) as well as purinergic receptors in the CNS. Because a purine receptor subtype known as P2X7 had been linked to neuropathic and inflammatory pain, the researchers wondered if it also facilitated visceral pain (Cell Mol Gastroenterol Hepatol. 2015 Jul 22. doi: 10.1016/j.jcmgh.2015.07.008). To explore that question, they created a CP model by injecting 2% trinitrobenzene sulfonic acid into the pancreatic ducts of male rats. They measured behavioral responses to mechanical and electrical stimulation and quantified spinal cord P2X7R levels with the help of standard laboratory assays. They also watched for changes in pain-related behaviors after blocking spinal cord P2X7R with brilliant blue G or knocking it down with short interfering RNA (siRNA).
Spinal P2X7R expression rose significantly after CP induction, as did levels of the OX-42 microglial marker in the dorsal horn of the spinal cord, said the investigators. Brilliant blue G and genetic knock down suppressed P2X7R expression, inhibited activation of spinal microglia, and “significantly attenuated” nociceptive behaviors, they added.
The researchers also pretreated some rats with brilliant blue G before inducing CP and saw that these rats exhibited significantly lower pain responses to mechanical and electrical stimuli compared with other CP rats. In fact, the nociceptive responses of the pretreated CP rats resembled those of non-CP control rats, the investigators said. Spinal tissue from pretreated rats also lacked signs of P2X7R upregulation, they noted.
Taken together, the data “indicate a critical role of P2X7R expressed in the spinal cord in the development of chronic visceral pain in CP,” concluded the researchers. Brilliant blue G inhibits voltage-gated sodium channels, which are known to contribute to chronic visceral pain, and “may represent an effective drug for the treatment of chronic pain in chronic pancreatitis patients,” they added.
The study was funded by Taipei Veterans General Hospital, National Science Council of Taiwan, and the Taiwan Ministry of Education Aim for Top University Grant. The investigators declared no competing interests.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: A subtype of purinergic receptor on spinal microglial cells mediated visceral pain hypersensitivity in rats with chronic pancreatitis.
Major finding: Spinal P2X7R expression rose significantly after CP induction, and pharmacologic inhibition and genetic knock down inhibited activation of spinal microglia and “significantly attenuated” nociceptive behaviors.
Data source: Controlled, prospective, molecular and behavioral study of rats with chemically induced chronic pancreatitis.
Disclosures: The study was funded by Taipei Veterans General Hospital, National Science Council of Taiwan, and the Taiwan Ministry of Education Aim for Top University Grant. The investigators declared no competing interests.
