Cholelithiasis in Children of Early Age (Clinical-Pathogenetic and Epidemiological Aspects)

The dissertation by Natalia Grigoryevna Lupash is devoted to the clinical-pathogenetic and epidemiological aspects of cholelithiasis in children of early age. The research was conducted at the Research Institute of Pediatric Hematology (Moscow) and encompasses a comprehensive study of the prevalence of cholelithiasis in the Krasnodar Region, the clinical manifestations of the disease in children from 1 month to 3 years of age, the role of the genetic component in the genesis of stone formation, and the substantiation of approaches to conservative and surgical treatment. Epidemiological, clinical-genealogical, and morphological research methods were employed in the work, including three-dimensional magnetic resonance imaging for the assessment of the functioning and topography of the biliary system.

Cholelithiasis in children is not only a rare occurrence but is becoming one of the actual problems of pediatric gastroenterology. The prevalence of cholelithiasis in children in terms of age has its own characteristics. The disease is more commonly encountered in children of school age and increases several-fold in the pre- and pubertal age. The detection of gallstones in the early period of childhood is also not a rarity [4, 8, 12, 60, 61, 81, 82].

The rejuvenation of cholelithiasis is conditioned by a complex of factors, among which the following may be highlighted: unbalanced nutrition, food allergy, xenobiotics, deterioration of the ecological situation, and hypodynamia [4, 8, 12, 91, 143].

Cholelithiasis is a multifactorial disease. In childhood, the leading etiological factors are: hereditary predisposition, the presence of developmental anomalies of the biliary tract, and disruption of the regimen and diet. A dependence has been identified between the formation of gallstones upon inheritance of the HLA B12 and B18 haplotypes. Developmental anomalies of the biliary tract that contribute to bile stasis also aggravate pathological processes both in the gallbladder and in the liver. Breastfeeding exerts a lifelong effect with respect to hyperlipidemia, hyperinsulinemia, obesity, and others. Human breast milk contains a large amount of taurine — one of the most important beta-amino acids. Taurine improves the absorption of lipids, and its conjugation with bile acids reduces toxicity and improves their absorbability. Upon entry of taurine into the organism, the rate of secretion of bile acids increases and the production of cholesterol decreases. Early transfer of a child to artificial feeding is considered a risk factor for stone formation [6, 25, 30, 52, 84].

Despite the high interest in the problem of cholelithiasis in recent years, to date the clinical features of cholelithiasis in children of early age have not been described. No correlation between cholelithiasis and environmental factors has been identified, and the role of the genetic component in the genesis of stone formation has not been determined. Morphological characteristics of the gallbladder in children of early age suffering from cholelithiasis are absent. The question of therapeutic approaches upon detection of gallstones in early childhood remains unresolved: is a watchful strategy necessary; litholysis of gallstones or surgical intervention? At the same time, the introduction of new methods of endoscopic diagnosis into pediatric practice opens up possibilities for detecting cholelithiasis at early stages of formation of lithogenic bile [5, 9, 107].

In this regard, the study of age-related features of the clinical course and progression of cholelithiasis in children of early age will contribute to the discovery of new opportunities for the development of prognostic criteria for the course of the pathological process in cholelithiasis in children. Such an approach to solving the above-mentioned problems will allow the treatment of cholelithiasis at early stages of the disease and the forecasting of the development of the pathological process. The development of a diagnostic algorithm and therapeutic approaches for this group of patients will make it possible to reduce the disability of both the pediatric and adult population [3, 4, 143].

Objective of the research:

To study the features of the clinical course of cholelithiasis in children of early age in order to improve diagnostic methods and develop therapeutic and preventive measures.

Research tasks:

1. To determine the prevalence of cholelithiasis in various regions of the Krasnodar Region

2. To describe the features of the clinical manifestations of cholelithiasis in children of early age.

3. To study the correlation between cholelithiasis and the degree of environmental pollution

4. To demonstrate the role of the genetic component in the genesis of gallstone formation

5. To identify risk factors for gallstone formation in early childhood.

6. To substantiate indications and contraindications for conservative and surgical treatment of cholelithiasis in children of early age.

Scientific novelty.

Comprehensive epidemiological investigations have been conducted to study the prevalence of cholelithiasis in the Krasnodar Region. The features of the clinical manifestations of cholelithiasis in children of early age have been described. The role of the genetic component in the genesis of gallstone formation in children of early age has been demonstrated, and the multifactorial nature of cholelithiasis has been statistically substantiated.

Risk factors for stone formation in the observed groups of children have been developed. The morphological picture and the character of development of the pathological process in the mucous membrane of the gallbladder in children with cholelithiasis at the age from 1 month to 3 years have been described. Priority directions of therapeutic strategy in children of early age suffering from cholelithiasis have been determined. Indications and contraindications for surgical and conservative treatment of cholelithiasis in children of early age have been developed. The degree of efficacy of litholytic therapy in children of early age has been demonstrated. An algorithm of therapeutic strategy in cholelithiasis in children of early age has been proposed.

Practical significance.

The conducted research contains new knowledge about the clinical-pathogenetic features of the development of cholelithiasis in children of early age.

New methodological approaches to the study of stone formation processes in childhood make it possible to detect cholelithiasis at early stages of the disease.

The use of three-dimensional magnetic resonance imaging for diagnostic purposes has made it possible to obtain the most accurate information about the functioning and topography of the biliary system in children regardless of the child's age.

Clinical-genealogical analysis of hereditary patterns has made it possible to calculate the risk of stone formation in children with a burdened heredity and to determine the type of inheritance of cholelithiasis.

The factual data obtained in the work on the features of stone formation processes in early childhood will allow practitioners to objectify the therapeutic strategy and conduct preventive measures aimed at preventing the formation of gallstones at this age.

The system of diagnostic coefficients for forecasting the course of the inflammatory process in the gallbladder may serve as an effective method for the early diagnosis of cholelithiasis and the possibility of the formation of recurrences of stone formation.

The newly developed approaches to the treatment of cholelithiasis in early childhood will make it possible to avoid the necessity of surgical treatment.

The substantiated indications and contraindications for the prescription of ursodeoxycholic acid preparations and the proposed schemes of litholytic therapy will contribute to the reduction of errors in the selection of therapeutic strategy in children of early age suffering from cholelithiasis.

Defense of the dissertation and implementation of the results of the work.

The main provisions of the dissertation were discussed at the scientific conference "Actual Problems of Abdominal Pathology in Children" (Moscow, 2004, 2005), the X Congress of Gastroenterologists of Russia (2005), the scientific-practical conference "Actual Questions of Pediatrics" in Krasnodar (2004), and the annual Slavic-Baltic Forum "Gastroenterology - 2004, 2005".

The results of the work have been implemented in the practice of pediatric hospitals and polyclinics of the city of Krasnodar and the city of Moscow. The results of the research are used in the educational process in the training of listeners and physicians at the Department of Pediatrics with Childhood Infectures of the Faculty of Advanced Training of Physicians of the Russian State Medical University, and at the Department of Pediatrics No. 1 of the Kuban State Medical Academy.

Publications.

Based on the materials of the dissertation, 9 scientific works have been published.