Role of antispasmodics in the treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.

Epidemiologic characteristics of Helicobacter pylori infection in southeast Hungary

BACKGROUND Epidemiologic studies have revealed a decrease in the prevalence of Helicobacter pylori(H.pylori)infection in Western Europe.AIM To obtain data regarding the prevalence of H.pylori in Csongrád and Békés Counties in Hungary,evaluate the differences in its prevalence between urban and rural areas,and establish factors associated with positive seroprevalence.METHODS One-thousand and one healthy blood donors[male/female:501/500,mean age:40(19–65)years]were enrolled in this study.Subjects were tested for H.pylori IgG antibody positivity via enzyme-linked immunosorbent assay.Subgroup analysis by age,gender,smoking habits,alcohol consumption,and urban vs nonurban residence was also performed.RESULTS The overall seropositivity of H.pylori was 32%.It was higher in males(34.93%vs 29.2%,P=0.0521)and in rural areas(36.2%vs 27.94%,P=0.0051).Agricultural/industrial workers were more likely to be positive for infection than office workers(38.35%vs 30.11%,P=0.0095)and rural subjects in Békés County than those in Csongrád County(43.36%vs 33.33%,P=0.0015).CONCLUSION Although the prevalence of H.pylori infection decreased in recent decades in Southeast Hungary,it remains high in middle-aged rural populations.Generally accepted risk factors for H.pylori positivity appeared to be valid for the studied population.

Diagnostic role of secretin-enhanced MRCP in patients with unsuccessful ERCP

AIM:To evaluate the value of MR cholangiopancreatography (MRCP)in patients in whom endoscopic retrograde cholangiopancreatography(ERCP)was unsuccessfully performed by experts in a tertiary center. METHODS:From January 2000 to June 2003,22 patients fulfilled the inclusion criteria.The indications for ERCP were obstructive jaundice(n=9),abnormal liver enzymes(n=8), suspected chronic pancreatitis(n=2),recurrent acute pancreatitis(n=2),or suspected pancreatic cancer(n=1). The reasons for the ERCP failure were the postsurgical anatomy(n=7),duodenal stenosis(n=3),duodenal diverticulum(n=2),and technical failure(n=10).MRCP images were evaluated before and 5 and 10 rain after i.v. administration of 0.5 IU/kg secretin. RESULTS:The MRCP images were diagnosed in all 21 patients.Five patients gave normal MR findings and required no further intervention.MRCP revealed abnormalities(primary sclerosing cholangitis,chronic pancreatitis,cholangitis,cholecystolithiasis or common bile duct dilation)in 20 patients,who were followed up clinically.Four patients subsequently underwent laparotomy(hepaticojejunostomy in consequence of common bile duct stenosis caused by unresectable pancreatic cancer;hepaticotomy+Kehr drainage because of insufficient biliary-enteric anastomosis;choledochoj- ejunostomy,gastrojejunostomy and cysto-Wirsungo gastrostomy because of chronic pancreatitis,or choledochojejunostomy because of common bile duct stenosis caused by chronic pancreatitis).Three patients participated in therapeutic percutaneous transhepatic drainage.The indications were choledocholithiasis with choledochojejunostomy,insufficient biliary-enteric anastomosis,or cholangiocarcinoma. CONCLUSION:MRCP can assist the diagnosis and management of patients in whom ERCP is not possible.

Role of ultrasound in colorectal diseases

Ultrasound is an undervalued non-invasive examination in the diagnosis of colonic diseases. It has been replaced by the considerably more expensive magnetic resonance imaging and computed tomography, despite the fact that, as first examination, it can usefully supplement the diagnostic process. Transabdominal ultrasound can provide quick information about bowel status and help in the choice of adequate further examinations and treatment. Ultrasonography,as a screening imaging modality in asymptomatic patients can identify several colonic diseases such as diverticulosis, inflammatory bowel disease or cancer. In addition, it is widely available, cheap, non-invasive technique without the use of ionizing radiation, therefore it is safe to use in childhood or during pregnancy, and can be repeated at any time. New ultrasound techniques such as elastography, contrast enhanced and Doppler ultrasound, miniprobes rectal and transperineal ultrasonography have broadened the indication. It gives an overview of the methodology of various ultrasound examinations, presents the morphology of normal bowel wall and the typical changes in different colonic diseases. We will pay particular attention to rectal and transperineal ultrasound because of their outstanding significance in the diagnosis of rectal and perineal disorders. This article seeks to overview the diagnostic impact and correct indications of bowel ultrasound.

Efficacy of 6-mercaptopurine treatment after azathioprine hypersensitivity in inflammatory bowel disease

AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indicies (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA- intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients.

Network meta-analysis of randomized controlled trials on esophagectomies in esophageal cancer:The superiority of minimally invasive surgery

BACKGROUND Previous meta-analyses,with many limitations,have described the beneficial nature of minimal invasive procedures.AIM To compare all modalities of esophagectomies to each other from the results of randomized controlled trials(RCTs)in a network meta-analysis(NMA).METHODS We conducted a systematic search of the MEDLINE,EMBASE,Reference Citation Analysis(https://www.referencecitationanalysis.com/)and CENTRAL databases to identify RCTs according to the following population,intervention,control,outcome(commonly known as PICO):P:Patients with resectable esophageal cancer;I/C:Transthoracic,transhiatal,minimally invasive(thoracolaparoscopic),hybrid,and robot-assisted esophagectomy;O:Survival,total adverse events,adverse events in subgroups,length of hospital stay,and blood loss.We used the Bayesian approach and the random effects model.We presented the geometry of the network,results with probabilistic statements,estimated intervention effects and their 95% confidence interval(CI),and the surface under the cumulative ranking curve to rank the interventions.RESULTS We included 11 studies in our analysis.We found a significant difference in postoperative pulmonary infection,which favored the minimally invasive intervention compared to transthoracic surgery(risk ratio 0.49;95%CI:0.23 to 0.99).The operation time was significantly shorter for the transhiatal approach compared to transthoracic surgery(mean difference-85 min;95%CI:-150 to-29),hybrid intervention(mean difference-98 min;95%CI:-190 to-9.4),minimally invasive technique(mean difference-130 min;95%CI:-210 to-50),and robot-assisted esophagectomy(mean difference-150 min;95%CI:-240 to-53).Other comparisons did not yield significant differences.CONCLUSION Based on our results,the implication of minimally invasive esophagectomy should be favored.

Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy

AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC).

Utility of serum TNF-a,infliximab trough level,and antibody titers in inflammatory bowel disease

AIM:To assess tumor necrosis factor-a(TNF-a),infliximab(IFX)concentrations,and antibodies against IFX molecules in patients with inflammatory bowel disease(IBD)who develop loss of response,side effects,or allergic reaction during anti TNF-a therapy.METHODS:Blood samples of 36 patients with response loss,side effects,or hypersensitivity to IFX therapy(Group?Ⅰ)and 31 patients in complete clinical remission(GroupⅡ)selected as a control group were collected to measure trough serum TNF-a level,IFX,and anti-IFX antibody(ATI)concentration.We examined the correlation between loss of response,the development of side effects or hypersensitivity,and serum TNF-a,IFX trough levels,and ATI concentrations.RESULTS:The serum TNF-a level was shown to be correlated with the presence of ATI;ATI positivity was significantly correlated with low trough levels of IFX.ATIs were detected in 25%of IBD patients with loss of response,side effects,or hypersensitivity,however no association was revealed between these patients and antibody positivity or lower serum IFX levels.Previous use of IFX correlated with the development of ATI,although concomitant immunosuppression did not have any impact on them.CONCLUSION:On the basis of the present study,we suggest that the simultaneous measurement of serum TNF-a level,serum anti TNF-a concentration,and antibodies against anti TNF-a may further help to optimize the therapy in critical situations.

A case of interstitial pneumonitis in a patient with ulcerative colitis treated with azathioprine

The early hypersensitivity reaction and late bone marrow depression are well-known side-effects of azathioprine, whereas interstitial pneumonia is a rare complication. A 40-year old male patient had been treated with azathioprine in consequence of extensive ulcerative colitis for 10 years. He then complained of 7 d of fever, cough and catarrhal signs, without symptoms of active colitis. Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy demonstrated the presence of interstitial inflammation. Azathioprine therapy was discontinued as a potential source of the pulmonary infiltrate. In response to steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased within 4 wk. Three months later, his ulcerative colitis relapsed, and ileo-anal pouch surgery was performed. In cases of atypical pneumonia, without a proven infection, azathioprine-associated interstitial pneumonitis may be present, which heals after withdrawal of the drug.

What Is the Personal Experience of IBD Patients about Their Anti-TNF-Alpha Therapy?

AIM: To evaluate and compare the patients opinion on the two types of anti- TNF-α therapies in a Hungarian cohort of IBD patients. METHODS: This was a prospective, multicentre, questionnaire-based observational study carried out in three Hungarian tertiary centres. From April to September 2014, an anonymous questionnaire was distributed to patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD), who have received infliximab (IFX) and/or adalimumab (ADA). The survey focused on the preferences of the two anti-TNF-α therapies on the basis of the efficacy, the administration routes and the side effects. RESULTS: 292 IBD patients, 216 CD, 75 UC and 1 indeterminate colitis patient completed the questionnaire. The mean duration of biological therapy was 1.7 (1 - 7) years. IFX treated patients noticed improvement of symptoms at 4 - 5 weeks while ADA treated patients noticed at 5 - 6 weeks. There was no difference between the patients’ satisfaction regarding the types of anti-TNF-α therapy if they received both. However, subcutaneous administration was preferred by ADA-treated patients previously receiving IFX (p = 0.007) compared to intravenous route and they did not intend to change the mode of therapy (p = 0.040). 90% of the patients, receiving only IFX or ADA were satisfied with their present therapy. The majority of patients (186/292, 63.7%) would not switch therapy. 63 of 291, 22% of the patients reported to have some concern with biological therapy—the majority (32/63, 50.8%) due to fear from side effects. CONCLUSION: Generally, patients preferred and would not change the present anti-TNF-α therapy, however, subcutaneous administration was preferred among those patients who had have experience with both.

Autoimmune pancreatitis: Functional and morphological recovery after steroid therapy

Autoimmune pancreatitis, a recently recognized type of chronic pancreatitis, is not rare in Japan, but reports of it elsewhere are relatively uncommon. We report the first preoperatively diagnosed case of autoimmune pancreatitis in Hungary, which responded well to steroid treatment and provided radiographic and functional evidence of this improvement. A 62-year-old female presented with a 4-month history of recurrent epigastric pain and a 5-kg weight loss. The oral glucose tolerance test （OGTT） indicated diabetes mellitus and the result of the fecal elastase test was abnormal. Ultrasonography （US） and the CT scan demonstrated a diffusely enlarged pancreas, and endoscopic retrograde cholangiopancreatography （ERCP） an irregular main pancreatic duct with long strictures in the head and tail. Autoimmune pancreatitis was diagnosed. The patient was started on 32 mg prednisolone daily, After 4 wk, the OGTT and faecal elastase test results had normalized. The repeated US and CT scan revealed a marked improvement of the diffuse pancreatic swelling, while on repeated ERCP, the main pancreatic duct narrowing was seen to be ameliorated. It is important to be aware of this disease and its diagnosis, because AIP can clinically resemble pancreatobiliary malignancies, or chronic or acute pancreatitis, However, in contrast with chronic pancreatitis, its symptoms and morphologic and laboratory alterations are completely reversed by oral steroid therapy.

Therapeutic proteasome inhibition in experimental acute pancreatitis

AIM： To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 （Z-Leu-Leu-Leu-aldehyde） in an experimental model of acute pancreatitis. METHODS： Pancreatitis was induced in rats by two hourly intraperitoneal （ip） injections of cholecystokinin octapeptide （CCK; 2×100μg/kg） and the proteasome inhibitor MG132 （10 mg/kg ip） was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK. RESULTS： Administering the proteasome inhibitor MG132 （at a dose of 10 mg/kg, ip） 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein （HSP72） and decreased DNA-binding of nuclear factor-κB （NF-κB）. Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress. CONCLUSION： Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis.

Association between autoimmune pancreatitis and systemic autoimmune diseases

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sj gren's syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto's thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.

Biological Therapy in IBD—Is There Any Optimal End Point?

Biological therapy has been used in the treatment of inflammatory bowel disease (IBD-Crohn’s disease [CD], ulcerative colitis [UC]) for more than a decade. Although guidelines exist on how to start and adjust biological therapy, information on when and how it should be stopped is still scarce. In this review, our aim is to summarize the results of the recently published papers on the outcome of the discontinuation of biological therapy in patients with CD and UC.