EDITORIAL
ORIGINAL ARTICLES
Aim of investigation. To detect molecular-genetic features of Helicobacter pylori and polymorphism of main immunoregulatory interleukins genes at Khakases, to estimate their effect on outcomes of infection pathogen.
Material and methods. Investigation was carried out at native population of Khakasia with H. pyloriassociated diseases: peptic ulcer and chronic gastritis. Prevalence of interleukins IL1β, IL1Ra, IL8 and CYP2C19 gene polymorphism was studied by restriction analysis, VacA +– and CagA +– subtypes of H. pylori – by polymerase chain reaction.
Results. Peptic ulcer was associated to S1S2 Vac A subtypes at Caucasians, while at Khakases – to Cag А strains of H. pylori. Interrelation between CagA, АА251 ILs – 8 and the risk of peptic ulcer development was revealed at Khakases (OR=3,1, 95% CI 1,1–8,8). Most common variants among Khakases were – СС +3953 IL1 β (84%) and R4/R4 IL1Ra (76%), with not high expression level. Frequent genotype wt/wt +681 CYP2C19 (89,3%) was associated to the risk of peptic ulcer development (OR=4,17, 95% CI 1,04–19,39).
Conclusions. Population-based genetic determinants (СС +3954 IL1β, R4/R4 IL1Ra), that establish higher protection level from H. pylori-associated diseases at Khakases, than at Caucasians were revealed. Risk factors for peptic ulcer at Khakases include carriage of CagA H. pylori strain, АА-251 of IL8 gene, GG +681 of CYP2C19 gene.
Aim of investigation. Studying of efficacy of genetic therapy of liver fibrosis at mice by human hepatocyte growth factor (HGF) and evaluation of potentials of hydroporation method for delivery of genetic complexes to the liver.
Material and methods. During experiment male mice of Balbc line received intraperitoneal injections of 30% perchloromethane (CCl4) diluted in oil in a dose of 1 ml/kg once per week. Animals (n=4–6) dropped from the experiment at the 1, 2, 4 and 6-th week from its onset. After obtaining liver tissue samples, histological study was carried out, and by real time polymerase chain reaction (RT-PCR) contents of mPNA of liver fibrosis-associated genes were analyzed: transforming growth factor β1 (TGF-β1), collagen 1α1 (Coll1α1), matrix metalloproteinase-13 (ММР-13), tissue inhibitor of matrix metalloproteinase (TIMP-1) and smooth-muscle actin α (α-SMA). A blood was extracted for assessment of liver enzymes activity (AST and ALT). Human HGF was injected into liver tissue by hydroporation method. Contents of human HGF in mice liver tissue was detected by PCR. For evaluation of stage of liver fibrosis Knodell index and morphometrical analysis was used.
Results. According to Knodell index development of CCl4-induced liver fibrosis at the 4-th week of experiment was found. Liver cirrhosis developed at the 6-th week of experiment. These data correlated well to the RT-PCR results and evaluation of liver enzymes activity. Morphometrical analysis demonstrated, that after HGF therapy in the main group of animals the degree of fibrosis (%) was lower in comparison to that in the control group. Efficacy of transfection of complementary HGF DNA at application of hydroporation method was higher, than at direct method of injection into parenchyma of the organ.
Conclusions. Obtained results allow to consider gene therapy by hepatocyte growth factor in composition of non-viral vectors as one of perspective methods of treatment of chronic liver diseases.
Aim of investigation. To study efficacy of albumin dialysis (MARS) at complications of end-stage liver diseases having various etiology.
Material and methods. Overall 65 patients with chronic terminal liver diseases of Child–Pugh B and C classes have been included in original study. The first (main group) included 25 patients, that received albumin dialysis in addition to traditional drug therapy. The second group (comparison group) included 40 patients who received only traditional pharmaceutical therapy. In relation to etiology of disease all patients were divided into three groups: 1) cirrhoses of the nontoxic etiology as an outcome of viral hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis; 2) cirrhosis of toxic (alcohol-induced) etiology and 3) focal liver lesions – hepatocellular carcinoma (HCC).
Results. Among patients, receiving treatment with albumin dialysis the stage of hepatic encephalopathy at patients in the subgroup with cirrhosis of toxic (alcohol-induced) etiology significantly decreased (р<0,01). In general the level of biochemical scores of blood at patients after MARS was lower, than at patients who did not receive MARS, however no improvement in AST, ALT activity was found. Study results (triple decrease of bilirubin level and significant decrease of creatinine> <0,01). In general the level of biochemical scores of blood at patients after MARS was lower, than at patients who did not receive MARS, however no improvement in AST, ALT activity was found. Study results (triple decrease of bilirubin level and significant decrease of creatinine contents) testify the greater efficacy of albumin dialysis in subgroup of patients with liver cirrhosis of toxic (alcohol-induced) etiology. At patients with nontoxic cirrhosis (mainly cholestatic), who received MARS-therapy, the majority of whom were in the waiting list of liver transplantation (9 patients), decrease of total bilirubin level was accompanied by decrease of pruritis. In group of patients with HCC no significant decrease of bilirubin level was observed. It is necessary to point, that in none patients MARS was complicated by bleeding or progression of other manifestations of hemorrhagic syndrome.
Conclusions. Albumin dialysis in the patients with cirrhosis enrolled to the waiting list of liver transplantation, allows to prolong scheduled interim to liver transplantation that is the extremely important factor, allowing to survive to operation and to decrease mortality in patients with terminal liver failure.
Aim of investigation. To study efficacy and safety of sodium phosphate solution (Fleet® phospho-soda) as an agent for preparation of intestine to endoscopic investigation.
Material and methods. Overall 28 teenagers aged 13–17 years were enrolled to original study (mean age 14,96±1,05 year). Study inclusion criterion was the necessity of preparation of intestine before endoscopy. Exclusion criteria were: incomplete/complete ileus, megacolon (congenital/acquired), acute inflammatory diseases and disorder of large intestine integrity, renal/ heart failure. Estimated parameters included: general state of the patient, dynamics of clinical manifestations, quality of preparation of intestine (visualization capability, presence of fecal masses), time of bowel movement (development of stool), changes of hemodynamic scores.
Results. In 89,3% of children good visualization of intestine has been achieved. Tolerability of agent was regarded as good in 46,4%, in 53,6% of patients – as satisfactory. Side effects (nausea, dizziness, flatulence etc.) were short-term and transient. Hemodynamic parameters did not undergo statistically significant changes.
Conclusion. Solution of sodium phosphate (FLEET® phospho-soda) is an efficient agent for preparation of intestine for endoscopic investigations as it provides good visualization of mucosa and has few side effects. Its application in pediatric practice provides the best compliance, as compared to other modes, because it does not require intake of high volume of fluid.
NATIONAL COLLEGE OF GASTROENTEROLOGISTS, HEPATOLOGISTS
The aim of review. To discuss possible relation of gastroesophageal reflux disease (GERD) and other functional diseases of gastro-intestinal tract (GIT) and demonstrate, which forms of GERD can be taken into account from the standpoints of functional diseases.
Received data. It is shown, that the GERD is frequently combined with functional dyspepsia and irritable bowel syndrome. It can be caused by common pathophysiological mechanisms of these diseases. Within the framework of non-erosive form of GERD it is possible to define 2 subgroups of patients, at which: 1)correlation of clinical symptoms to episodes of physiological gastroesophageal reflux (GER) is present – patients with hypersensitive esophagus or 2) clinical symptoms are not related to GER at all – patients with functional heartburn, which can be considered within the framework of functional pathology. Further studies are necessary to improve diagnostics and treatment of these forms of GERD.
Conclusion. Within the framework of GERD there are forms of disease which can be assessed from positions of functional disorders of GIT.
The aim of review. To present up-to-date data on diagnostics of gastrointestinal stromal tumors (GIST) and experience N.N. Burdenko Chief military clinical hospital in treatment of such patients.
Original positions. Gastrointestinal stromal tumors, that were described in 1983 by M.T.Mazur and H.B.Clark, fall into to group of rare tumors of gastro-intestinal tract of mesenchymal origin with characteristic morphological and immunohistochemical pattern. Issues of treatment of these patients were extremely actual. Surgical resection was the first line treatment, however the mean survival rate after successful operative treatment was only 5 years, even at complete resection. In the case if relapse or metastases occurs surgical methods were ineffective, and chemo- or radiation therapy allowed to receive rather limited response (in particular, survival rate at late stages of GIST did not exceed 1 year). Diagnostics, treatment and outcome at patients with GIST underwent significant changes for last 10 years due to discovering of molecular mechanisms, resulting in development of tumor: activated mutations of KITand PDGFR α-tyrosine kinase. These findings promoted development of tyrosine kinase inhibitor – imatinib which demonstrated essential advantage in terms of survival rate of patients. Experience of treatment GIST within N.N. Burdenko Chief military clinical hospital corresponds the level of leading clinics.
Conclusion. Discoveries in the area of GIST biology allowed to introduce the new scientific and practical developments in treatment of patients.
EXCHANG OF EXPERIENCE
The aim of review. To demonstrate features of diagnostics and treatment of constipation at patients of elderly age.
Original positions. Constipation is present at 40% of persons at the age of 60 years and older. Risk factors of constipation at people of elderly age include: change of pattern of nutrition (decrease of alimentary fibers content in ration); still lifestyle (compelled bed rest); presence of concomitant diseases (endocrine, neurologic, mental disorders – depression, dementia); drug-induced constipations; age-related changes of the large intestine. Diagnostic concept is based on the position, that constipation is not a disease, but is just a symptom. Diagnostic actions should be aimed to recognition of etiology and type of constipation. Treatment should be provided according to the basic disease, and the age of patient. Main components of treatment are: diet, broadening of physical activity regimen, purging. Review presents characteristics of basic types of laxatives that are used at patients of elderly age at constipations of various origin.
Conclusion. Constipation at patients of elderly age is quite frequent and can aggravate general state of the patient. Complex treatment of constipation essentially improves quality of life of patients.
NEWS OF COLOPROCTOLOGY
Aim of investigation. To estimate efficacy of the Register of patients with familial adenomatosis coli.
Material and methods. Overall 1036 patients with familial adenomatosis coli were observed. Of them 117 proposituses with detailed hereditary history taken to the present time, and 118 their natural relatives actively involved in investigation, were included in the Register of family adenomatosis.
Results. Presence of the Register of patients with familial adenomatosis coli with subsequent summons and investigation of relatives of proposituses allowed to decrease age of patients at the moment of diagnosis from 30 to 18 years, to reduce number of patients with developed colorectal cancer from 43,6 to 4,9%, to reduce cases of total involvement of the large intestine by polyps from 72 to 5%. Genetic testing detected disease at preclinical stage in 18 (56%) of 32 actively investigated relatives of proposituses, allowed to form the risk group of patients from АРС-negative families and to remove patients who have not inherited АРС (Adenomatous Polyposis Coli) mutation from further observation.
Conclusion. Presence of the Register of patients with familial adenomatosis coli promotes early diagnostics, improves of results of treatment and optimize monitoring of this category of patients.
Aim of investigation. To estimate efficacy of extrafascial surgical interventions in patients with locally advanced cancer of rectum.
Material and methods. From a prospective database of the patients treated in department of coloproctology and surgery of pelvic floor of B.V.Petrovsky Russian scientific center of surgery of Russian Academy of Medical Science from June, 2006 to December, 2009, serially admitted patients, who underwent surgical resection for cancer of rectum T1-4N0-2M0 were chosen for investigation. The first group included patients, with standard volume of operation (nervepreserving mesorectumectomy), the second group included patients with extended resections for locally advanced tumors adherent to neighbouring structures and organs, that was revealed in preoperative and/or intraoperative periods.
Results. Original investigation evaluated results of treatment of 159 patients (87 men, mean age – 62 years), of them combined rectal surgery have been executed in 68 cases (43%). Locally advanced tumors were localized in low- and mid-ampullary regions of the rectum most often. The true tumor progression to resected structures and organs was revealed in 22% of the cases. Both in males and females resection of organs of genitourinary system, as well as the structures of a lateral pelvic wall was carried out most often. The overall mortality in studied cohort of patients was 1,9%. The two-year-old overall survival rate was nonsignificantly higher in patients after standard surgery (93,9%), than in the patients after extrafascial interventions (85,9%, р=0,18). The two-year cumulative relapse-free survival rate in group of standard operations (97,6%) appeared significantly higher, than in group of extrafascial resections: 92,4 and 88,2% respectively (р=0,02). Two-year cumulative cancer-specific survival rate did not differ significantly between groups of comparison - after standard resections this rate was 96,0%, after extrafascial surgery – 93,4% (р=0,37).
Conclusions. Extrafascial resections for locally advanced rectal cancer doesn’t lead to decrease of overall and cancer-specific and cancer-specific survival rates in comparison to standard operations.
INFORMATION
O.I. Malomuzh – Chronic liver diseases: indications and optimal terms for transplantation.
Ye.V. Stepanova – Clinical and genetic aspects of a Crohn’s disease.
ISSN 2658-6673 (Online)