Volume 70 - 2007 - Fasc.2 - Original articles
Immunogenicity of infliximab : how to handle the problem ?
Background : The introduction of infliximab has greatly advanced the therapeutic armamentarium of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Although the benefit/risk ratio for infliximab is positive, of partic- ular concern has been the problem of immunogenicity ascribed to the chimeric properties of the drug. Antibody formation is associ- ated with allergic reactions and loss of response.
Aims and methods : A literature search was undertaken on the magnitude of the problem of immunogenicity and on the clinical consequences. A survey was conducted about the clinical practice and management of acute and delayed allergic reactions to inflix- imab in different centres in Belgium. For this, a questionnaire was sent to all members of the Belgian IBD research group (n = 38 belonging to 29 centers).
Results and conclusion: Infusion reactions are important immunologic events induced by the presence of a substantial con- centration of antibodies against infliximab (ATI) in the serum. Concomitant immunosuppressive treatment may optimize response to infliximab by preventing the formation of antibodies. Steroid administration prior to an infliximab infusion can further reduce the immunogenicity. Probably the most effective strategy to optimize treatment and avoid immunogenicity is maintenance therapy. If infliximab therapy can be discontinued is yet unclear but when treatment goals have been reached, we feel this should be attempted. In the case of relapse, infliximab should be restarted as maintenance long term. Practical guidelines on how to handle the problem of immunogenicity to infliximab are important for clini- cians treating patients with IBD. (Acta gastroenterol. belg., 2007, 70, 163-170).
Endoscopic sphincterotomy for acute relapsing pancreatitis associated with peri- ampullary diverticula : a long-term follow-up
Background and study aims : Periampullary diverticula (PAD) are extraluminal outpouchings of the duodenum arising within a radius of 2-3 cm from the ampulla of Vater. Data concerning the association of PAD with biliopancreatic disease are inconsistent, but an association between acute pancreatitis and PAD has been reported. The aim of this retrospective study was to evaluate the outcome of endoscopic sphincterotomy (ES) in a Greek cohort of patients with acute relapsing pancreatitis associated with PAD.
Patients and methods : A total of 344 patients who had under- gone ERCP between 1994 and 2005 for investigation of acute pan- creatitis were retrospectively entered into a database. Of these patients, 11 (3.19% ; median age : 69 years ; range : 58-78 ; 3 men, 8 women) were found to have acute relapsing pancreatitis associ- ated with PAD. All patients underwent ES and were followed for new episodes of acute pancreatitis or other complications.
Results : No further episodes of acute pancreatitis occurred after ES, during a long-term follow-up (median : 4.3 years, range : 1.9-10.4). Two patients (18.2%) presented post-procedure mild pancreatitis and one patient (9.1%) post-ES stenosis with two small common bile duct stones and was treated with ES and extraction of stones.
Conclusion : ES is the treatment of choice for patients with acute relapsing pancreatitis associated with PAD. (Acta gastro- enterol. belg., 2007, 70, 163-166).
Percutaneous and surgical radiofrequency ablation of liver malignancies: a single institutional experience
Background : the purpose of this study was to report a single academic institution's experience with radiofrequency ablation (RFA) of liver malignancies
Methods : Sixty-five patients underwent RFA technique through a percutaneous (Group I : 33 patients) or a surgical approach (Group II : 32 patients). The two groups were different according to type of disease selection (more hepatocellular carcinoma in Group I and liver metastases in Group II) and tumour features (smaller size but greater number of lesions in Group II). In Group II, RFA was associated to liver resection in 23 patients (72%).
Results : The 2-month postoperative mortality and complication rates were low in both groups. The postoperative hospital stay was longer in Group II. During a median follow-up of 24 months in Group I and 21 months in Group II, the local "in-situ" recurrence rate was 41.4% and 9.1%, respectively. For RFA-treated tumours < 30 mm in size, the local "in-situ" recurrence rate was 40.5% in Group I and 0% in Group II. Multivariate statistical analysis demonstrated that larger tumour and a percutaneous approach for RFA were independent predictive factors of local "in-situ" liver tumour recurrence.
Conclusions : RFA appears to be a safe technique for treating liver malignancies by both approaches. Tumour size and type of RFA approach are predictive factors of in-situ liver tumour recur- rence. (Acta gastroenterol. belg., 2007, 70, 167-173).
Appropriate management of symptomatic GORD in primary care : has expert opinion changed between 2001 and 2005 ?
Objective : To determine current opinions of clinical experts on the appropriate management of symptomatic GORD in primary care, and to compare these opinions with those from a similar study conducted in 2001.
Methods : In 2001, a panel of 6 Belgian general practitioners and 6 gastroenterologists assessed the appropriateness of referral versus short-term anti-secretory medication for 768 different patient profiles, using the RAND/UCLA method. Applying a simi- lar methodology, the same panel repeated these assessments in 2005. In addition, panellists were asked to indicate the preferred type of medication for all patient profiles.
Results : Agreement between the results of 2001 and 2005 was high. Appropriateness ratings on referral versus medication were similar in 79% of patient profiles (weighted kappa value 0.77). Higher age and use of NSAIDs remained the dominant factors in favour of referral.
Medication preference (not measured in 2001) showed marked differences between general practitioners and gastroenterologists. Gastroenterologists showed a higher preference for PPI high dose, whereas general practitioners more frequently chose for PPI low dose. H2-receptor antagonists were preferred in only few cases.
Conclusions : This study showed that expert opinion on the appropriateness of referral for endoscopy in patients with symp- tomatic GORD has only slightly changed over the past few years. Preferences for low and high dose PPIs varied between the two groups of physicians, which is most likely to be ascribed to the dif- ferent patient populations seen in either primary or specialised care. (Acta gastroenterol. belg., 2007, 70, 171-176).
A health economic model to assess the cost-effectiveness of pegylated interferon a-2a and ribavirin in patients with moderate chronic hepatitis C and persistent- ly normal alanine aminotransferase levels
Background and study aims : The treatment of patients with moderate chronic hepatitis C and persistently normal alanine aminotransferase levels is still under discussion and the cost-effec- tiveness of such strategy is unknown. The objective of this study was to estimate the cost-effectiveness of their treatment in com- parison with no treatment.
Patients and methods : The assessed treatment is composed of pegylated interferon a-2a and ribavirin, which is the current stan- dard treatment. Two groups were studied : patients with genotype 1 and patients with genotypes 2-3. At the beginning of the study, patients were aged of 45.
Long-term economic and clinical outcomes over a 30 year peri- od were predicted using a Markov simulation model. A health care payer perspective was chosen. Data were obtained from published literature. Variations of uncertainty parameters were assessed through a sensitivity analysis.
Results : The incremental cost-effectiveness ratios (ICERs) were € 5,338/QALY for genotype 1 and € 1,080/QALY for genotypes 2- 3. In the sensitivity analysis, ratios remained lower than € 20,00O.A Monte Carlo simulation with 1,000 iterations gives a 95% con- fidence interval for the ICER of € 3,199 to € 8,972 for genotype 1 and € 56 to € 1,981 for genotypes 2-3.
Conclusion : Even though the treatment of these patients gener- ates a cost, it has the advantage that in comparison with no treat- ment, a great number of people are cured, complications are less frequent and patients gain more quality-adjusted life-year (QALY), which involves an ICER considered as acceptable for the European society (< € 20,000). (Acta gastroenterol. belg., 2007, 70, 177-187).
Endoscopic Retrogade Cholangiopangreatography is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians
Background and aim : Diagnosis and treatment of pancreatic and biliary diseases represents a special problem in old patients who often suffer from one or more concomitant diseases. The aim of this study was to evaluate the safety and the efficacy of ERCP in very old patients (octogenarians).
Patients and methods : Patients 80 years or older who under- went ERCP from October 2001 to December 2005 were studied retrospectively.
Results : A total of 209 patients (121 women, 88 men), with a mean age 86 ± 4.4 years old (80-102) underwent 251 ERCPs. All but three patients tolerated the procedure well. Three procedures were not completed due to patients' discomfort (1.4%). Two of these patients underwent percutaneous transhepatic cholangiog- raphy and the other one was treated conservatively. A cholan- giogram was obtained in 193 cases (92.3%), although in 7 patients an additional attempt was required. The main endoscopic findings were common bile duct stones in 51.8% (100/193) and cancer in 28% (54/193) of patients. Based on the diagnostic findings, a ther- apeutic intervention was indicated in 189 patients (90.4%) and was achieved in 181 of them (95.8%). Complications were observed in 9.6% of ERCPs (24/251). Post - ERCP mild pancre- atitis was the more frequent complication in 11 procedures (4.4%). No severe pancreatitis was observed. Six procedures were compli- cated by cholangitis (2.4%) and two by cholecystitis (0.8%). Early surgical intervention was required in 2 cases because of oesophageal perforation and retroperitoneal perforation respec- tively. Two patients died (0.8%) ; one patient with pancreatic can- cer died due to septic shock after inadequate biliary drainage and the other one died after operation for retroperitoneal perforation.
Conclusions : In conclusion, ERCP is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians despite the high comorbidity in this group of patients. (Acta gastroenterol. belg., 2007, 70, 174-177).
A health economic model to assess the cost-effectiveness of pegylated interferon a-2a and ribavirin in patients with moderate chronic hepatitis C and persistent- ly normal alanine aminotransferase levels
Background and study aims : The treatment of patients with moderate chronic hepatitis C and persistently normal alanine aminotransferase levels is still under discussion and the cost-effec- tiveness of such strategy is unknown. The objective of this study was to estimate the cost-effectiveness of their treatment in com- parison with no treatment.
Patients and methods : The assessed treatment is composed of pegylated interferon a-2a and ribavirin, which is the current stan- dard treatment. Two groups were studied : patients with genotype 1 and patients with genotypes 2-3. At the beginning of the study, patients were aged of 45.
Long-term economic and clinical outcomes over a 30 year peri- od were predicted using a Markov simulation model. A health care payer perspective was chosen. Data were obtained from published literature. Variations of uncertainty parameters were assessed through a sensitivity analysis.
Results : The incremental cost-effectiveness ratios (ICERs) were € 5,338/QALY for genotype 1 and € 1,080/QALY for genotypes 2- 3. In the sensitivity analysis, ratios remained lower than € 20,00O.A Monte Carlo simulation with 1,000 iterations gives a 95% con- fidence interval for the ICER of € 3,199 to € 8,972 for genotype 1 and € 56 to € 1,981 for genotypes 2-3.
Conclusion : Even though the treatment of these patients gener- ates a cost, it has the advantage that in comparison with no treat- ment, a great number of people are cured, complications are less frequent and patients gain more quality-adjusted life-year (QALY), which involves an ICER considered as acceptable for the European society (< € 20,000). (Acta gastroenterol. belg., 2007, 70, 178-188).
Percutaneous and surgical radiofrequency ablation of liver malignancies: a single institutional experience
Background : the purpose of this study was to report a single academic institution's experience with radiofrequency ablation (RFA) of liver malignancies
Methods : Sixty-five patients underwent RFA technique through a percutaneous (Group I : 33 patients) or a surgical approach (Group II : 32 patients). The two groups were different according to type of disease selection (more hepatocellular carcinoma in Group I and liver metastases in Group II) and tumour features (smaller size but greater number of lesions in Group II). In Group II, RFA was associated to liver resection in 23 patients (72%).
Results : The 2-month postoperative mortality and complication rates were low in both groups. The postoperative hospital stay was longer in Group II. During a median follow-up of 24 months in Group I and 21 months in Group II, the local "in-situ" recurrence rate was 41.4% and 9.1%, respectively. For RFA-treated tumours < 30 mm in size, the local "in-situ" recurrence rate was 40.5% in Group I and 0% in Group II. Multivariate statistical analysis demonstrated that larger tumour and a percutaneous approach for RFA were independent predictive factors of local "in-situ" liver tumour recurrence.
Conclusions : RFA appears to be a safe technique for treating liver malignancies by both approaches. Tumour size and type of RFA approach are predictive factors of in-situ liver tumour recur- rence. (Acta gastroenterol. belg., 2007, 70, 188-194).
Endoscopic sphincterotomy for acute relapsing pancreatitis associated with peri- ampullary diverticula : a long-term follow-up
Background and study aims : Periampullary diverticula (PAD) are extraluminal outpouchings of the duodenum arising within a radius of 2-3 cm from the ampulla of Vater. Data concerning the association of PAD with biliopancreatic disease are inconsistent, but an association between acute pancreatitis and PAD has been reported. The aim of this retrospective study was to evaluate the outcome of endoscopic sphincterotomy (ES) in a Greek cohort of patients with acute relapsing pancreatitis associated with PAD.
Patients and methods : A total of 344 patients who had under- gone ERCP between 1994 and 2005 for investigation of acute pan- creatitis were retrospectively entered into a database. Of these patients, 11 (3.19% ; median age : 69 years ; range : 58-78 ; 3 men, 8 women) were found to have acute relapsing pancreatitis associ- ated with PAD. All patients underwent ES and were followed for new episodes of acute pancreatitis or other complications.
Results : No further episodes of acute pancreatitis occurred after ES, during a long-term follow-up (median : 4.3 years, range : 1.9-10.4). Two patients (18.2%) presented post-procedure mild pancreatitis and one patient (9.1%) post-ES stenosis with two small common bile duct stones and was treated with ES and extraction of stones.
Conclusion : ES is the treatment of choice for patients with acute relapsing pancreatitis associated with PAD. (Acta gastro- enterol. belg., 2007, 70, 195-198).
Appropriate management of symptomatic GORD in primary care : has expert opinion changed between 2001 and 2005 ?
Objective : To determine current opinions of clinical experts on the appropriate management of symptomatic GORD in primary care, and to compare these opinions with those from a similar study conducted in 2001.
Methods : In 2001, a panel of 6 Belgian general practitioners and 6 gastroenterologists assessed the appropriateness of referral versus short-term anti-secretory medication for 768 different patient profiles, using the RAND/UCLA method. Applying a simi- lar methodology, the same panel repeated these assessments in 2005. In addition, panellists were asked to indicate the preferred type of medication for all patient profiles.
Results : Agreement between the results of 2001 and 2005 was high. Appropriateness ratings on referral versus medication were similar in 79% of patient profiles (weighted kappa value 0.77). Higher age and use of NSAIDs remained the dominant factors in favour of referral.
Medication preference (not measured in 2001) showed marked differences between general practitioners and gastroenterologists. Gastroenterologists showed a higher preference for PPI high dose, whereas general practitioners more frequently chose for PPI low dose. H2-receptor antagonists were preferred in only few cases.
Conclusions : This study showed that expert opinion on the appropriateness of referral for endoscopy in patients with symp- tomatic GORD has only slightly changed over the past few years. Preferences for low and high dose PPIs varied between the two groups of physicians, which is most likely to be ascribed to the dif- ferent patient populations seen in either primary or specialised care. (Acta gastroenterol. belg., 2007, 70, 189-194).
Immunogenicity of infliximab : how to handle the problem ?
Background : The introduction of infliximab has greatly advanced the therapeutic armamentarium of the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Although the benefit/risk ratio for infliximab is positive, of partic- ular concern has been the problem of immunogenicity ascribed to the chimeric properties of the drug. Antibody formation is associ- ated with allergic reactions and loss of response.
Aims and methods : A literature search was undertaken on the magnitude of the problem of immunogenicity and on the clinical consequences. A survey was conducted about the clinical practice and management of acute and delayed allergic reactions to inflix- imab in different centres in Belgium. For this, a questionnaire was sent to all members of the Belgian IBD research group (n = 38 belonging to 29 centers).
Results and conclusion: Infusion reactions are important immunologic events induced by the presence of a substantial con- centration of antibodies against infliximab (ATI) in the serum. Concomitant immunosuppressive treatment may optimize response to infliximab by preventing the formation of antibodies. Steroid administration prior to an infliximab infusion can further reduce the immunogenicity. Probably the most effective strategy to optimize treatment and avoid immunogenicity is maintenance therapy. If infliximab therapy can be discontinued is yet unclear but when treatment goals have been reached, we feel this should be attempted. In the case of relapse, infliximab should be restarted as maintenance long term. Practical guidelines on how to handle the problem of immunogenicity to infliximab are important for clini- cians treating patients with IBD. (Acta gastroenterol. belg., 2007, 70, 195-202).
Endoscopic retrogade cholangiopancreatography is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians
Background and aim : Diagnosis and treatment of pancreatic and biliary diseases represents a special problem in old patients who often suffer from one or more concomitant diseases. The aim of this study was to evaluate the safety and efficacy of ERCP in very old patients (octogenarians).
Patients and methods : Patients 80 years or older who under- went ERCP from October 2001 to December 2005 were studied retrospectively.
Results : A total of 209 patients (121 women, 88 men), with a mean age 86 ± 4.4 years old (80-102) underwent 251 ERCPs. All but three patients tolerated the procedure well. Three procedures were not completed due to patients' discomfort (1.4%). Two of these patients underwent percutaneous transhepatic cholangiog- raphy and the other one was treated conservatively. A cholan- giogram was obtained in 193 cases (92.3%), although in 7 patients an additional attempt was required. The main endoscopic findings were common bile duct stones in 51.8% (100/193) and cancer in 28% (54/193) of patients. Based on the diagnostic findings, a ther- apeutic intervention was indicated in 189 patients (90.4%) and was achieved in 181 of them (95.8%). Complications were observed in 9.6% of ERCPs (24/251). Post - ERCP mild pancre- atitis was the more frequent complication in 11 procedures (4.4%). No severe pancreatitis was observed. Six procedures were compli- cated by cholangitis (2.4%) and two by cholecystitis (0.8%). Early surgical intervention was required in 2 cases because of oesophageal perforation and retroperitoneal perforation respec- tively. Two patients died (0.8%) ; one patient with pancreatic can- cer died due to septic shock after inadequate biliary drainage and the other one died after operation for retroperitoneal perforation.
Conclusions : In conclusion, ERCP is safe and effective method for diagnosis and treatment of biliary and pancreatic disorders in octogenarians despite the high comorbidity in this group of patients. (Acta gastroenterol. belg., 2007, 70, 199-202).
