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Making gluten easier to stomach
AJG – February, 2003
Restorative Proctocolectomy and Portal Vein Thrombosis Remzi FH, Fazio VW, Oncel M, et al. Portal vein thrombi after restorative proctectomy. Surgery 2002;132:655– 62. Portal vein thrombosis is a common condition which has been associated with a variety of factors including cirrhosis, malignancy and hypercoagulable states. There has also been an association reported between inflammatory bowel disease and, more recently, the surgical treatment of this condition with procedures such as the restorative proctocolectomy. The incidence and significance of this finding has not been clarified. Remzi and colleagues at the Cleveland clinic reported 702 patients undergoing restorative proctocolectomy and found that 94 had undergone a CT scan in the early postoperative period based on clinical symptoms. They found that portal vein thrombosis was present in 42 of 94 patients for an incidence of 45%. A significant proportion, particularly of non-occlusive thrombi, were not highlighted during the initial radiologic review. Twenty of 45 patients undergoing CT scan because of septic complications of restorative proctocolectomy had portal vein thrombosis. Another 22 patients were found to have thrombosis without any evidence of a septic source. The occurrence of portal vein thrombosis in both symptomatic and asymptomatic patients could not be predicted based on preoperative characteristics, hospital stay or technical factors. They did find that patients who were steroid-dependent and those who had not received perioperative heparin therapy had an increased risk of portal vein thrombosis. Only
What’s New in GI
two patients in their study had been diagnosed with a hypercoagulable state preoperatively. They concluded that there is a high chance of finding portal vein thrombosis in patients undergoing CT scan after restorative proctocolectomy. This is often a subtle finding and treated patients commonly recover completely. Portal vein thrombosis, particularly when only partially occlusive, appears to be a common but subtle finding detected on CT patients after an ileoanal pullthrough. Obviously there are a number of factors that may predispose to this condition related to the underlying disease, the operation itself and perioperative care. Fortunately, anticoagulation and time will allow this to resolve without sequelae in most patients. Jon S. Thompson, M.D.
Making Gluten Easier to Stomach Shan L, Molberg O, Parrot I, et al. Structural basis for gluten intolerance in celiac sprue. Science 2002;297: 2275–79. Celiac sprue is exceedingly common with estimates of 3– 4/1000 of the Caucasian population. The clinical manifestations vary widely from the asymptomatic to those with severe malabsorption. Moreover, celiac sprue engenders a significant increased risk of malignancies (approximately 30%), especially nonHodgkin’s lymphoma. Adherence to a gluten-free diet can mitigate the symptoms and also decrease the cancer risk. However, this diet is onerous making compliance suboptimal. Attempts to detoxify gluten has been confounded by the large number of
249
potential targets in gluten. The immunogenicity of these epitopes are believed to be potentiated through deamidation by small bowel mucosa tissue transglutamalse (tTG). Shan and colleagues used pancreatic and gastric enzymes to digest the 266 amino acid ␣2-gliadin in order to isolate a 33 amino acid region. This unique peptide appeared to be remarkably stable, being able to withstand a 15 h incubation with small intestinal brush border membranes (as opposed to other gluten-related peptides which were rapidly degraded). Moreover, this 33 amino acid peptide was an excellent substrate for tTG, and the deamidated peptide had a much higher affinity for HLA DQ2, consonant with the prediction for a sprue-inducing antigen. To further support the importance of this peptide, it was incubated with T-cell clones from sprue patients and demonstrated a marked increase in lymphocyte proliferation. This epitope was found in foods toxic to sprue patients such as wheat, barley and rye, but not “safe” foods such as oats, rice and maize. Finally, digestion of the peptide with a bacterial propyl endopeptidase (PEP) mitigated its T-cell stimulatory response. This elegant study may have important clinical ramifications. For instance, identification of the culprit in gluten may lead to more accurate detection of foods that are unsafe for sprue patients. Furthermore, this may lead to new strategies or detoxifying gluten, either by proteolytic digestion or through elimination of this epitope by genetic engineering. In the future, the benefits of a gluten free diet (decreased symptoms and malignancy) may become more palatable for patients. Hermant K. Roy, M.D.
Restorative Proctocolectomy and Portal Vein Thrombosis Remzi FH, Fazio VW, Oncel M, et al. Portal vein thrombi after restorative proctectomy. Surgery 2002;132:655– 62. Portal vein thrombosis is a common condition which has been associated with a variety of factors including cirrhosis, malignancy and hypercoagulable states. There has also been an association reported between inflammatory bowel disease and, more recently, the surgical treatment of this condition with procedures such as the restorative proctocolectomy. The incidence and significance of this finding has not been clarified. Remzi and colleagues at the Cleveland clinic reported 702 patients undergoing restorative proctocolectomy and found that 94 had undergone a CT scan in the early postoperative period based on clinical symptoms. They found that portal vein thrombosis was present in 42 of 94 patients for an incidence of 45%. A significant proportion, particularly of non-occlusive thrombi, were not highlighted during the initial radiologic review. Twenty of 45 patients undergoing CT scan because of septic complications of restorative proctocolectomy had portal vein thrombosis. Another 22 patients were found to have thrombosis without any evidence of a septic source. The occurrence of portal vein thrombosis in both symptomatic and asymptomatic patients could not be predicted based on preoperative characteristics, hospital stay or technical factors. They did find that patients who were steroid-dependent and those who had not received perioperative heparin therapy had an increased risk of portal vein thrombosis. Only
What’s New in GI
two patients in their study had been diagnosed with a hypercoagulable state preoperatively. They concluded that there is a high chance of finding portal vein thrombosis in patients undergoing CT scan after restorative proctocolectomy. This is often a subtle finding and treated patients commonly recover completely. Portal vein thrombosis, particularly when only partially occlusive, appears to be a common but subtle finding detected on CT patients after an ileoanal pullthrough. Obviously there are a number of factors that may predispose to this condition related to the underlying disease, the operation itself and perioperative care. Fortunately, anticoagulation and time will allow this to resolve without sequelae in most patients. Jon S. Thompson, M.D.
Making Gluten Easier to Stomach Shan L, Molberg O, Parrot I, et al. Structural basis for gluten intolerance in celiac sprue. Science 2002;297: 2275–79. Celiac sprue is exceedingly common with estimates of 3– 4/1000 of the Caucasian population. The clinical manifestations vary widely from the asymptomatic to those with severe malabsorption. Moreover, celiac sprue engenders a significant increased risk of malignancies (approximately 30%), especially nonHodgkin’s lymphoma. Adherence to a gluten-free diet can mitigate the symptoms and also decrease the cancer risk. However, this diet is onerous making compliance suboptimal. Attempts to detoxify gluten has been confounded by the large number of
249
potential targets in gluten. The immunogenicity of these epitopes are believed to be potentiated through deamidation by small bowel mucosa tissue transglutamalse (tTG). Shan and colleagues used pancreatic and gastric enzymes to digest the 266 amino acid ␣2-gliadin in order to isolate a 33 amino acid region. This unique peptide appeared to be remarkably stable, being able to withstand a 15 h incubation with small intestinal brush border membranes (as opposed to other gluten-related peptides which were rapidly degraded). Moreover, this 33 amino acid peptide was an excellent substrate for tTG, and the deamidated peptide had a much higher affinity for HLA DQ2, consonant with the prediction for a sprue-inducing antigen. To further support the importance of this peptide, it was incubated with T-cell clones from sprue patients and demonstrated a marked increase in lymphocyte proliferation. This epitope was found in foods toxic to sprue patients such as wheat, barley and rye, but not “safe” foods such as oats, rice and maize. Finally, digestion of the peptide with a bacterial propyl endopeptidase (PEP) mitigated its T-cell stimulatory response. This elegant study may have important clinical ramifications. For instance, identification of the culprit in gluten may lead to more accurate detection of foods that are unsafe for sprue patients. Furthermore, this may lead to new strategies or detoxifying gluten, either by proteolytic digestion or through elimination of this epitope by genetic engineering. In the future, the benefits of a gluten free diet (decreased symptoms and malignancy) may become more palatable for patients. Hermant K. Roy, M.D.