Randomised non-inferiority trial: 1600 mg versus 400 mg tablets of mesalazine for the treatment of mild-to-moderate ulcerative colitis.

BACKGROUND: High concentration mesalazine formulations are more convenient than conventional low concentration formulations for the treatment of ulcerative colitis (UC). AIM: To compare the efficacy and safety of 1600 mg and 400 mg tablet mesalazine formulations. METHODS: Patients with mild-to-moderate active UC (Mayo Clinic Score >5; N=817) were randomised to 3.2 g of oral mesalazine, administered as two 1600 mg tablets once, or four 400 mg tablets twice daily. We hypothesised that treatment with the 1600 mg tablet was non-inferior (within a 10% margin) to the 400 mg tablet for induction of clinical and endoscopic remission at week 8. Open-label treatment with the 1600 mg tablet continued for 26-30 weeks based on induction response. Predictors of treatment response were also explored. RESULTS: At week 8, remission occurred in 22.4% and 24.6% of patients receiving the 1600 mg and 400 mg tablets, respectively (absolute difference -2.2%, 95% CI: -8.1% to 3.8%, non-inferiority P=.005). Endoscopic and histopathologic disease activity, leucocyte concentration and age were significantly associated with clinical remission (P=.022, .042, .014 and .023, respectively). At week 38, 43.9% (296/675) of patients who continued treatment with the 1600 mg formulation were in remission, including 70.3% (142/202) of patients who received a reduced dose of mesalazine (1.6 g/d). The overall incidence of serious adverse events was low. CONCLUSIONS: Induction therapy with 3.2 mg mesalazine using two 1600 mg tablets once-daily was statistically and clinically non-inferior to a twice-daily regimen using four 400 mg tablets (NCT01903252).

[Adherence with proton pump inhibitor therapy, by continuously taking nonsteroidal anti-inflammatory drugs].

AIM: To estimate the impact of adherence with proton pump inhibitor (PPI) therapy on the incidence of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy (NSAID gastropathy) in patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: PPI pharmacotherapy adherence was estimated using the Medication Adherence Questionnaire (MAQ) in 92 patients with RA, including 32 patients did not take a PPI and 60 used a PPI. The groups were matched for age, disease duration, and used NSAIDs. All those asked underwent video esophagogastroduodenoscopy. RESULTS: According to the data of MAQ survey, low, moderate, and high adherence subgroups could be identified among the patients treated with a PPI. NSAID gastropathy was detected in 43.8% of the patients taking no PPI, in 50% of those with low PPI treatment adherence, in 12.5% with moderate adherence, and in 4.5% with high adherence. In the patients with low adherence to PPI therapy, NSAID gastropathy was recorded 11 times more frequently than in those with high adherence (c2 = 7.77; p = 0.005). This condition occurred in 28.6% of the patients taking NSAID without preventively using a PPI in the absence of risk factors for NSAID gastropathy. CONCLUSION: Only 36.7% patients who had been recommended to use a PPI for the prevention of NSAID gastropathy strictly observed their doctor's directions. Low PPI pharmacotherapy adherence may serve as an additional risk factor for NSAID gastropathy in patients in whom preventive antisecretory therapy used in combination with NSAID is indicated.

[Time course of gastric mucosal changes in the assessment of long-term results of Helicobacter pylori eradication].

The impact of Helicobacter pylori (H. pylori) eradication on the gastric mucosa (GM) was studied in patients with gastroduodenal ulcers. Clinical and morphological changes in the GM were assessed in 122 patients 3-7 years (mean 4.4 +/- 1.3 years) after eradication therapy and in 12 patients who had undergone H. pylori eradication. Successful H. pylori eradication in the gastric antral and body mucosa reduced inflammation, the degree of chronic inflammation, the number of lymphoid follicles, and the magnitude of gland atrophy. There were no statistically significant changes in intestinal metaplasia. The patients who had not received eradication therapy showed no significant GM changes as compared to the baseline values. In the unsuccessful eradication group, inflammation statistically significantly diminished in the gastric antrum and body with a reduction in the density of H. pylori contamination.

[Fecal oncomarkers in the diagnostics of colorectal cancer].

Colorectal cancer (CRC) presents one of the central problems in modern medicine. In approximately every third patient, colon cancer is revealed at stage IV, which determines the patient's outcome. Early diagnosis is possible only at the pre-clinical stage. To find a cheap and non-invasive diagnostic method which would determine indications to endoscopy is an important task of modern medicine. The authors studied what benefits in CRC diagnostics were provided by fecal calprotectin test and different methods for detection of occult blood in feces as well as combinations of these. The study found that calprotectin test and immunochemical test were more sensitive than hemocult-test for CRC diagnostics (p < 0.05). Immunochemical occult blood test proved to be more sensitive for the detection of polyps or any kind of colon dysplasia (p < 0.05). Hence, despite its relatively high cost, immunochemical occult blood test may be recommended as a non-invasive colorectal cancer marker in individuals with moderate risk, while fetal calprotectin test, being cheap and easily repeatable, may be used for screening only in patients with a high risk of CRC development. Combined application of tests for occult blood and calprotectin in feces makes it possible to increase the sensitivity of the method up to 97.2%, its specificity up to 93.3%, and its effectiveness up to 95.6% in the detection of CRC.

[Impact of Helicobacter pylori eradication on morphological changes in gastric mucosa].

The purpose of the study was to examine gastric mucosal morphological changes in patients with gastroduodenal pathology after eradication therapy for Helicobacter pylori (H. pylori). A hundred and thirty-eight patients (40 females and 98 males) were examined. Of them, there were 122 patients with duodenal peptic ulcer, 8 with gastric peptic ulcer, 5 with erosive gastritis, 2 with chronic atrophic antral gastritis, and 1 with non-atrophic gastritis. Two months and a year after therapy, manifestations of gastric mucosal atrophy, the degree of inflammation, and its activity significantly diminished in patients with complete H. pylori eradication. Positive changes were observed mainly in the antral portion of the stomach. In patients with partial eradication, chronic inflammation and its activity became less. Two months and a year following therapy, positive changes in the gastric mucosa were absent in patients without H. pylori eradication.

[Time course changes in morphological and functional characteristics of gastric mucosa after eradication of Helicobacter pylori in duodenal ulcers].

AIM: To study trends in morphological changes of gastric mucosa (GM) and its functional characteristics (serum gastrin-17, pepsinogens I and II) in eradication of Helicobacter pylori (HP) in patients with duodenal ulcer (DU). MATERIAL AND METHODS: HP infection was detected with a rapid urease test, morphological study of gastrobiopsies and polymerase chain reaction in 59 patients with DU. The results of HP eradication were assessed two months after the treatment. Morphological study of gastrobiopsies, assays for gastrin-17, pepsinogens I and II in blood serum were made before the treatment and one year after HP eradication. RESULTS: By the results of eradication two groups were formed: with effective eradication and uneffective eradication of H. pylori. Examination of GM one year after successful H. pylori eradication in DU patients GM inflammation relieved: reduction in polymorphonuclear (by 42.6%), mononuclear (by 29.3%) infiltration and number of lymphocytic follicules (16.8-fold). GM atrophy decreased by 47.8%. In patients with uneffective eradication the above positive changes were not registered. After H. pylori eradication, serum gastrin-17 lowered by 46. 7%, pepsinogen I--by 30.5%, pepsinogen II--by 36.9%. In uneffective eradication this decrease did not occur. CONCLUSION: H. pylori eradication leads to positive changes in morphological and functional indices reflecting GM condition.

[Chronic gastritis: last decade's achievements and problems]. / Khronicheskii gastrit dostizheniia i problemy poslednego desiatiletiia.

Classifications of chronic gastritis and neoplastic gastric diseases, developed in recent years (1996 Houston update of 1990 Sidney classification system, 2002 New Orlean classification of atrophic gastritis according to recommendations of International Group for Atrophy Studies; 1998 Padova classification of gastric displasia, and 1998 Vienna classification of gastrointestinal neoplasia) allow to statandardize international research and perform more objective diagnostics of pathological changes in the gastric mucosa. Studies carried out in recent years have established that morphological manifestations of chronic gastritis caused by Helicobacter pylori infection can be reduced after its eradication. Longterm treatment with proton pump inhibitors have been demonstrated not to cause atrophic changes in the gastric mucosa when undertaken after successful eradicational therapy. It has been established that corporal gastritis intensifies in patients treated with proton pump inhibitors. The studies show that measurement of serum levels of Helicobacter pylori antibodies, gastrine, pepsinogen I and II can be used in non-invasive serologic diagnostics of atrophic gastritis. Achievements in diagnostics and treatment of chronic gastritis create the necessary prerequisites for the development of gastric cancer preventing measures.

[The type of pain in duodenal peptic ulcer]. / Varianty simptoma boli pri iazvennoi bolezni dvenadtsatiperstnoi kishki.

The paper presents the results of an examination of 269 patients (including 205 males and 64 females) aged 18-62 years who had gastroduodenal ulcers; amongst them, 137 and 132 patients were treated in the in- and out-patient settings, respectively. It was ascertained that the pathomorphism of the clinical picture of peptic ulcer had occurred. About a third of all the exacerbations became asymptomatic or displayed few symptoms. In patients with duodenal ulcer, the epigastrium rather than the right hypochondrium is the most common site of pain on an exacerbation.

[Ultrasonic diagnosis of pyloroduodenal stenosis]. / Ul'trazvukovaia diagnostika piloroduodenal'nogo stenoza.

The method and semeiotics of noninvasive ultrasonic diagnosis of pyloroduodenal stenosis are described. Seventy-six patients with duodenal ulcer and 13 patients with gastric ulcer were examined, and also 18 patients with gastric carcinoma and 24 healthy individuals. The echographic picture of an empty stomach in compensated pyloroduodenal stenosis did not differ from that in healthy persons, though study of the motor-evacuation activity of the stomach revealed intensified peristalsis and increased gastric half-evacuation period. In subcompensated pyloroduodenal stenosis the stomach contained fluid and the period of half-evacuation of its contents was sharply increased. All patients with decompensated pyloroduodenal stenosis had an increased volume of the stomach which contained much fluid and food remnants. Pyloric spasm was differentiated by means of the spasmolytics test. Patients with a marked periulcerous inflammatory infiltration must be kept under dynamic follow-up to evaluate the degree of the stenosis. Taking into consideration the peculiarity of the echographic picture of the pyloric part, the neoplastic character of the pyloroduodenal stenosis may be presumed with high precision.

[Ultrasonic diagnosis of duodenogastric reflux]. / Ul'trazvukovaia diagnostika duodenogastral'nogo refluksa.

A method of ultrasound diagnosis of duodenogastric reflux was developed. It enables the reflux identification with a high accuracy. It is suggested that 3 grades of the intensity of echographically recordable duodenogastric reflux may be distinguished. The method enables an individual estimation of the action efficacy and the choice of an adequate dose of pharmacological agents, particularly metoclopramide, for the treatment of duodenogastric reflux.

[Ultrasonic diagnosis of gastric motor-emptying disorders]. / Ul'trazvukovaia diagnostika motorno-évakuatornykh narushenii zheludka.

A method for ultrasonic examination of gastric motor evacuatory function, available for clinical practice, has been developed. Results of parallel estimation of the gastric contents half-life period by the ultrasonic and scintigraphic techniques evidence a high accuracy of the suggested method of echographic estimation of gastric function. Accelerated evacuation of the gastric contents was revealed in patients with duodenal ulcer without ++pyloric stenosis++.

[Improvement of ultrasonographic diagnosis of stomach cancer]. / Sovershenstvovanie ul'trazvukovoi diagnostiki raka zheludka.

A method for abdominal ultrasonographic diagnosis of gastric cancer is suggested which includes evaluation of the gastric wall and regional lymph nodes, and search for distant metastases. Gastric tumors were visualized in 92.9% of cases. The procedure should be performed both in cancer suspects and cases with reliably established gastric neoplasm to assess local extent of tumor and detect regional and distant metastases.

[Clinical interpretation of the results of the studies of gallbladder contractility]. / Klinicheskaia interpretatsiia rezul'tatov issledovaniia sokratimosti zhelchnogo puzyria.

Gallbladder contractility was assessed using ultrasound in 111 patients with biliary pathology and 34 normal controls. The original and literature data show that food stimulus-induced contractility of the gallbladder is related to the pattern of gastric evacuation, duodenal mucosa status, nervous regulation, morphological inflammatory and sclerotic lesions in the gallbladder wall. Echographic evaluation of motor-evacuatory function of the stomach contributes to more accurate interpretation of the contractility. Hypotonic biliary dyskinesia is thought nonidentical to hypomotor dyskinesia. These disorders reflect different aspects of gallbladder dysfunction.

[The ultrasonic diagnosis of chronic cholecystitis using the choleretic test]. / Ul'trazvukovaia diagnostika khronicheskogo kholetsistita s ispol'zovaniem kholereticheskoi proby.

To raise the accuracy of ultrasonic diagnosis of chronic cholecystitis, it is suggested that the choleretic test designed by the author may be used, making it possible to study gallbladder extensibility. As many as 124 patients with chronic cholecystitis and 50 healthy persons were examined. In 63 patients, the diagnosis was verified morphologically after cholecystectomies. Chronic cholecystitis patients demonstrated the lowering of gallbladder extensibility, especially after atropine administration preceded by the use of dehydrocholic acid. Echography with the use of the choleretic test considerably raises the accuracy, efficacy, specificity and sensitivity of ultrasonic diagnosis of chronic cholecystitis.