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Taking the pain out of pancreatitis
Vol. 96, No. 11, 2001 ISSN 0002-9270/01/$20.00
WHAT’S NEW IN GI EDITOR
The Subtle Side of Celiac
Jon S. Thompson, M.D., F.A.C.S. GASTROENTEROLOGY
Randall E. Brand Rene´e L. Young John K. DiBaise Hemant K. Roy Timothy M. McCashland RADIOLOGY
Aurelio Matamoros, Jr.
PATHOLOGY
James L. Wisecarver
LIVER STUDY UNIT
Carol A. Casey PEDIATRIC GASTROENTEROLOGY
David R. Mack University of Nebraska Medical Center Omaha, Nebraska
Goldstein NS, Underhill J. Morphologic features suggestive of gluten sensitivity in architecturally normal duodenal biopsy specimens. Am J Clin Pathol 2001;116:63–71. Goldstein and Underhill compared the histological features from small bowel biopsy specimens from a group of 78 study patients with findings from biopsies collected from an ageand sex-matched group of 24 control patients. The control group consisted of patients without symptoms of gluten sensitivity (GS) who had documented gastroesophageal reflux disease on accompanying esophageal biopsies. The study group consisted of patients who had undergone small bowel biopsy and also had an antigliadin serum antibody test ordered, presumably to rule out GS. The patients were observed clinically for 15 months, including determination of IgA antigliadin and IgA antiendomysium antibody titers and repeat biopsy. Twelve of the 78 study patients were ultimately confirmed to have GS based on laboratory studies, trial dietary adjustments, and subsequent biopsies showing classic signs of celiac disease with marked mucosal flattening. Examination of the initial nondiagnostic biopsies revealed an increase in the number of intraepithelial lymphocytes on the tips of the villi that extended down the sides. The authors suggest that an average of 12 or more intraepithelial lymphocytes in the tips of the villi and extending down the sides of the villi in an even distribution are suggestive of GS. Close clinical observation with repeat biopsy or, possibly, a trial dietary modification may then provide the necessary diagnostic information. James Wisecarver, M.D., Ph.D.
Taking the Pain Out of Pancreatitis Nealon WH, Matin S. Analysis of surgical success in preventing recurrent acute exacerbations in chronic pancreatitis. Ann Surg 2001;233:793–800. Abdominal pain is the most prominent symptom of chronic pancreatitis and may lead to narcotic dependence. Surgical procedures, both resection and decompression, provide pain relief in approximately 80% of patients with chronic, unrelenting pain and the appropriate structural defects. Many patients with chronic pancreatitis experience severe acute exacerbations of pain, often leading to hospitalization. Nealon and Matin investigated whether surgical intervention would reduce the incidence and severity of these acute attacks. One hundred eighty-five of 259 patients observed prospectively in a pancreatic clinic underwent operative procedures for chronic pancreatitis and its complications. Ninety-two percent had chronic ethanol abuse. One hundred four patients had chronic pain only, 71 had chronic pain with acute exacerbations, and 84 had acute exacerbations only. Decompressive procedures were performed in 124 patients and resection in 75. Postoperative pain relief was achieved in 83% of patients overall and was similar for different operations. No further acute exacerbations occurred in 66% and 82% of patients with chronic pain plus exacerbation and acute exacerbation only with a mean follow-up of 81 months. Longitudinal decompression was more effective than distal pancreatectomy for preventing exacerbations. The authors were not able to make an association between ethanal use and acute exacerbations. The authors conclude that
WHAT’S NEW IN GI
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2001 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
3060
What’s New in GI
surgical intervention prevents recurrent acute exacerbations. Thus, prevention of acute pain exacerbations should be considered an indication for operation, particularly when longitudinal pancreaticojejunostomy is feasible. Jon S. Thompson, M.D.
A Stimulating Approach to Treat Fecal Incontinence Ganio E, Luc AR, Clerico G, Trompetto M. Sacral nerve stimulation for treatment of fecal incontinence: A novel approach for intractable fecal incontinence. Dis Colon Rectum 2001;44:619 –31. Currently, sacral nerve stimulation (SNS) has been used successfully in clinical practice to control intractable urinary incontinence. The clinical application of such stimulation for anorectal dysfunction, and fecal incontinence in particular, is still in its infancy. The concept would seem to be to recruit residual function of the muscles involved in maintaining continence by electrically stimulating their peripheral nerve supply. This may occur by transforming the muscle phenotype to a more fatigue-resistant type. Additional mechanisms may also play a role, based on the fact that the target nerve carries not only efferent motor but also afferent sensory and autonomic nerves. Ganio et al. evaluated the effects of temporary percutaneous and permanently implanted SNS in 23 and five patients, respectively, with a variety of causes of intractable fecal incontinence but structurally intact external and internal sphincters. Baseline anorectal manovolumetry, pudendal nerve terminal motor latency measurements, and anal ultrasound were performed. Symptom response and manometry were reassessed on the final day of temporary SNS and again at 1 and 4 months in those with permanent im-
AJG – Vol. 96, No. 11, 2001
plants. Temporary percutaneous SNS was performed for a minimum of 7 days. A ⬎50% reduction in incontinence occurred in 89%, whereas continence was achieved in 74%. Significant changes noted on repeated manometry included an increase in resting pressure and voluntary squeeze, a reduction in the pressure for first sensation and urge to defecate, and a reduction in the rectal volume for urge sensation. Similar clinical benefits were seen in the five patients who received a permanent implant at a median follow-up of 19.2 months. There were no complications of this therapy. Interestingly, some patients with concomitant urinary voiding abnormalities and chronic pelvic pain also noted considerable improvement in those symptoms after temporary and permanent SNS. Ganio and colleagues have shown that temporary SNS is feasible, can have a beneficial effect on refractory fecal incontinence, and may be a useful test to determine which patients may benefit from a permanent implant. Larger controlled studies will be necessary to determine the efficacy and safety of SNS and clarify its mechanism of action. J. K. DiBaise, M.D.
Peripheral NMDA Receptors and Visceral Pain McRoberts JA, Coutinho SV, Marvizon JCG, et al. Role of peripheral N-methyl-D-aspartate (NMDA) receptors in visceral nociception in rats. Gastroenterology 2001;120:1737– 48. Functional GI syndromes are commonly encountered in clinical practice. Visceral hypersensitivity has been proposed to explain some of the symptoms occurring in these syndromes, at least in some patients. Although several mechanisms underlying peripheral sensitization in the context of tissue injury or inflammation have been identified, the role that
these mechanisms play in noninflammatory peripheral sensitization, such as occurs in the functional bowel disorders, remains unknown. N-MethylD-aspartate (NMDA) receptors play an important role in long term potentiation and memory processing in the central nervous system. Available evidence suggests that the roles of NMDA receptors differ with respect to the processing of visceral and somatic pain. These authors hypothesized that NMDA receptors are expressed in the peripheral nervous system and are involved in mediating pain responses in the noninflamed gut. In an elegant series of experiments, adult rats were shown to express NMDA receptors on the cell bodies and primary afferent nerves innervating the colon. Activation of these receptors resulted in calcium-dependent release of proinflammatory peptides. Using a well-characterized model of visceral pain perception, McRoberts et al. also showed that behavioral pain responses to noxious mechanical stimulation were inhibited by i.v. administration of a noncompetitive antagonist of the NMDA receptor. Finally, administration of the same antagonist inhibited colorectal distension responsive afferent nerve activity in single fiber recordings of decentralized pelvic nerves. The authors conclude that NMDA receptors are present in peripheral visceral nerves and may be important in visceral pain processing in the absence of inflammation, thus providing a novel mechanism for development of peripheral sensitization and visceral hyperalgesia. These observations suggest a fundamental difference in the role of NMDA receptors in the processing of visceral and somatic pain and imply that peripheral NMDA receptor antagonists may be useful in the treatment of visceral pain associated with functional bowel disorders. Given the current lack of effective therapies for these disorders, studies with such agents in humans are eagerly awaited. J. K. DiBaise, M.D.
WHAT’S NEW IN GI EDITOR
The Subtle Side of Celiac
Jon S. Thompson, M.D., F.A.C.S. GASTROENTEROLOGY
Randall E. Brand Rene´e L. Young John K. DiBaise Hemant K. Roy Timothy M. McCashland RADIOLOGY
Aurelio Matamoros, Jr.
PATHOLOGY
James L. Wisecarver
LIVER STUDY UNIT
Carol A. Casey PEDIATRIC GASTROENTEROLOGY
David R. Mack University of Nebraska Medical Center Omaha, Nebraska
Goldstein NS, Underhill J. Morphologic features suggestive of gluten sensitivity in architecturally normal duodenal biopsy specimens. Am J Clin Pathol 2001;116:63–71. Goldstein and Underhill compared the histological features from small bowel biopsy specimens from a group of 78 study patients with findings from biopsies collected from an ageand sex-matched group of 24 control patients. The control group consisted of patients without symptoms of gluten sensitivity (GS) who had documented gastroesophageal reflux disease on accompanying esophageal biopsies. The study group consisted of patients who had undergone small bowel biopsy and also had an antigliadin serum antibody test ordered, presumably to rule out GS. The patients were observed clinically for 15 months, including determination of IgA antigliadin and IgA antiendomysium antibody titers and repeat biopsy. Twelve of the 78 study patients were ultimately confirmed to have GS based on laboratory studies, trial dietary adjustments, and subsequent biopsies showing classic signs of celiac disease with marked mucosal flattening. Examination of the initial nondiagnostic biopsies revealed an increase in the number of intraepithelial lymphocytes on the tips of the villi that extended down the sides. The authors suggest that an average of 12 or more intraepithelial lymphocytes in the tips of the villi and extending down the sides of the villi in an even distribution are suggestive of GS. Close clinical observation with repeat biopsy or, possibly, a trial dietary modification may then provide the necessary diagnostic information. James Wisecarver, M.D., Ph.D.
Taking the Pain Out of Pancreatitis Nealon WH, Matin S. Analysis of surgical success in preventing recurrent acute exacerbations in chronic pancreatitis. Ann Surg 2001;233:793–800. Abdominal pain is the most prominent symptom of chronic pancreatitis and may lead to narcotic dependence. Surgical procedures, both resection and decompression, provide pain relief in approximately 80% of patients with chronic, unrelenting pain and the appropriate structural defects. Many patients with chronic pancreatitis experience severe acute exacerbations of pain, often leading to hospitalization. Nealon and Matin investigated whether surgical intervention would reduce the incidence and severity of these acute attacks. One hundred eighty-five of 259 patients observed prospectively in a pancreatic clinic underwent operative procedures for chronic pancreatitis and its complications. Ninety-two percent had chronic ethanol abuse. One hundred four patients had chronic pain only, 71 had chronic pain with acute exacerbations, and 84 had acute exacerbations only. Decompressive procedures were performed in 124 patients and resection in 75. Postoperative pain relief was achieved in 83% of patients overall and was similar for different operations. No further acute exacerbations occurred in 66% and 82% of patients with chronic pain plus exacerbation and acute exacerbation only with a mean follow-up of 81 months. Longitudinal decompression was more effective than distal pancreatectomy for preventing exacerbations. The authors were not able to make an association between ethanal use and acute exacerbations. The authors conclude that
WHAT’S NEW IN GI
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2001 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
3060
What’s New in GI
surgical intervention prevents recurrent acute exacerbations. Thus, prevention of acute pain exacerbations should be considered an indication for operation, particularly when longitudinal pancreaticojejunostomy is feasible. Jon S. Thompson, M.D.
A Stimulating Approach to Treat Fecal Incontinence Ganio E, Luc AR, Clerico G, Trompetto M. Sacral nerve stimulation for treatment of fecal incontinence: A novel approach for intractable fecal incontinence. Dis Colon Rectum 2001;44:619 –31. Currently, sacral nerve stimulation (SNS) has been used successfully in clinical practice to control intractable urinary incontinence. The clinical application of such stimulation for anorectal dysfunction, and fecal incontinence in particular, is still in its infancy. The concept would seem to be to recruit residual function of the muscles involved in maintaining continence by electrically stimulating their peripheral nerve supply. This may occur by transforming the muscle phenotype to a more fatigue-resistant type. Additional mechanisms may also play a role, based on the fact that the target nerve carries not only efferent motor but also afferent sensory and autonomic nerves. Ganio et al. evaluated the effects of temporary percutaneous and permanently implanted SNS in 23 and five patients, respectively, with a variety of causes of intractable fecal incontinence but structurally intact external and internal sphincters. Baseline anorectal manovolumetry, pudendal nerve terminal motor latency measurements, and anal ultrasound were performed. Symptom response and manometry were reassessed on the final day of temporary SNS and again at 1 and 4 months in those with permanent im-
AJG – Vol. 96, No. 11, 2001
plants. Temporary percutaneous SNS was performed for a minimum of 7 days. A ⬎50% reduction in incontinence occurred in 89%, whereas continence was achieved in 74%. Significant changes noted on repeated manometry included an increase in resting pressure and voluntary squeeze, a reduction in the pressure for first sensation and urge to defecate, and a reduction in the rectal volume for urge sensation. Similar clinical benefits were seen in the five patients who received a permanent implant at a median follow-up of 19.2 months. There were no complications of this therapy. Interestingly, some patients with concomitant urinary voiding abnormalities and chronic pelvic pain also noted considerable improvement in those symptoms after temporary and permanent SNS. Ganio and colleagues have shown that temporary SNS is feasible, can have a beneficial effect on refractory fecal incontinence, and may be a useful test to determine which patients may benefit from a permanent implant. Larger controlled studies will be necessary to determine the efficacy and safety of SNS and clarify its mechanism of action. J. K. DiBaise, M.D.
Peripheral NMDA Receptors and Visceral Pain McRoberts JA, Coutinho SV, Marvizon JCG, et al. Role of peripheral N-methyl-D-aspartate (NMDA) receptors in visceral nociception in rats. Gastroenterology 2001;120:1737– 48. Functional GI syndromes are commonly encountered in clinical practice. Visceral hypersensitivity has been proposed to explain some of the symptoms occurring in these syndromes, at least in some patients. Although several mechanisms underlying peripheral sensitization in the context of tissue injury or inflammation have been identified, the role that
these mechanisms play in noninflammatory peripheral sensitization, such as occurs in the functional bowel disorders, remains unknown. N-MethylD-aspartate (NMDA) receptors play an important role in long term potentiation and memory processing in the central nervous system. Available evidence suggests that the roles of NMDA receptors differ with respect to the processing of visceral and somatic pain. These authors hypothesized that NMDA receptors are expressed in the peripheral nervous system and are involved in mediating pain responses in the noninflamed gut. In an elegant series of experiments, adult rats were shown to express NMDA receptors on the cell bodies and primary afferent nerves innervating the colon. Activation of these receptors resulted in calcium-dependent release of proinflammatory peptides. Using a well-characterized model of visceral pain perception, McRoberts et al. also showed that behavioral pain responses to noxious mechanical stimulation were inhibited by i.v. administration of a noncompetitive antagonist of the NMDA receptor. Finally, administration of the same antagonist inhibited colorectal distension responsive afferent nerve activity in single fiber recordings of decentralized pelvic nerves. The authors conclude that NMDA receptors are present in peripheral visceral nerves and may be important in visceral pain processing in the absence of inflammation, thus providing a novel mechanism for development of peripheral sensitization and visceral hyperalgesia. These observations suggest a fundamental difference in the role of NMDA receptors in the processing of visceral and somatic pain and imply that peripheral NMDA receptor antagonists may be useful in the treatment of visceral pain associated with functional bowel disorders. Given the current lack of effective therapies for these disorders, studies with such agents in humans are eagerly awaited. J. K. DiBaise, M.D.