Modern aspects of diagnosis and treatment of chronic pancreatitis in children: experience of the center Center for the treatment of developmental anomalies and diseases of the hepatopancreatobiliary system in children

Chronic pancreatitis is one of the most pressing problems of pediatric gastroenterology and surgery of hepatopancreatobiliary organs. Diagnosis and treatment of this category of patients requires a comprehensive examination using modern highly sensitive research methods and the collegial participation of a surgeon, gastroenterologist and endocrinologist. Due to the fact that the algorithm for managing these patients is not regulated, patients often receive enzyme replacement therapy for a long time, with indications for surgical treatment. In addition, the non-specificity of complaints and clinical manifestations of chronic pancreatitis, the asymptomatic course and the initial detection of exo- and endocrine insufficiency lead to a later choice of the optimal treatment method and increase the risk of complications. The key to effective care for children with chronic pancreatitis is the staging and continuity in research and treatment. At the Center for the Treatment of Developmental Anomalies and Diseases of the Hepatopancreatobiliary System in Children on the basis of the Filatov Hospital, highly effective interventions are carried out for chronic pancreatitis in children, the purpose of which is to ensure an adequate outflow of pancreatic juice using longitudinal pancreaticojejunostomy, which, in addition to draining the pancreas, allows to achieve clinical remission and stop the progression pathological process, including diabetes mellitus. The article reflects the experience of diagnosis and treatment of chronic pancreatitis in children.

Clinical and pharmacological approaches to the management of exocrine pancreatic insufficiency in chronic pancreatitis

Chronic pancreatitis is a multifactorial disease in which repeated episodes of inflammation of the pancreas contribute to the development of fibrous tissue, leading to chronic pain, as well as exocrine and endocrine insufficiency. The incidence and prevalence of chronic pancreatitis in the world are growing, as evidenced by current statistics. In addition, the annual costs associated with the treatment of exocrine and endocrine insufficiency are also increasing. In the United States alone, the annual cost of treating these complications is $ 75.1 million. Exocrine insufficiency is one of the most frequent complications, which is characterized by a deficiency of pancreatic enzymes, leading to the development of malabsorption syndrome (impaired absorption of nutrients, vitamins and minerals). Due to the increased incidence and deterioration of the quality of life associated with this condition, the goal of treatment is to compensate for the deficiency of exocrine enzymes with oral pancreatic enzyme replacement therapy. The core of this therapy is to deliver activated, unbroken enzymes directly to the small intestine during a meal. Many studies have shown that prescribing enzyme replacement therapy improves symptoms associated with exocrine insufficiency, reduces the progression of osteopenia, and improves survival in such patients. The use of pancreatin contributes to the correction of exocrine insufficiency in patients with chronic pancreatitis. The data presented in the article indicate that the drug is a safe and effective agent, meets all modern standards and requirements, and can be used to correct enzymatic pancreatic insufficiency.

Inhibition of Notch activity promotes pancreatic cytokeratin 5-positive cell differentiation to beta cells and improves glucose homeostasis following acute pancreatitis

Some individuals develop prediabetes and/or diabetes following acute pancreatitis (AP). AP-induced beta-cell injury and the limited regenerative capacity of beta cells might account for pancreatic endocrine insufficiency. Previously, we found that only a few pancreatic cytokeratin 5 positive (Krt5+) cells differentiated into beta cells in the murine AP model, which was insufficient to maintain glucose homeostasis. Notch signaling determines pancreatic progenitor differentiation in pancreas development. This study aimed to examine whether Notch signaling inhibition could promote pancreatic Krt5+ cell differentiation into beta cells and improve glucose homeostasis following AP. Pancreatic tissues from patients with acute necrotizing pancreatitis (ANP) were used to evaluate beta-cell injury, Krt5+ cell activation and differentiation, and Notch activity. The murine AP model was induced by cerulein, and the effect of Notch inhibition on Krt5+ cell differentiation was evaluated both in vivo and in vitro. The results demonstrated beta-cell loss in ANP patients and AP mice. Krt5+ cells were activated in ANP pancreases along with persistently elevated Notch activity, which resulted in the formation of massive duct-like structures. AP mice that received Notch inhibitor showed that impaired glucose tolerance was reversed 7 and 15 days following AP, and increased numbers of newborn small islets due to increased differentiation of Krt5+ cells to beta cells to some extent. In addition, Krt5+ cells isolated from AP mice showed increased differentiation to beta cells by Notch inhibition. Collectively, these findings suggest that beta-cell loss contributes to pancreatic endocrine insufficiency following AP, and inhibition of Notch activity promotes pancreatic Krt5+ cell differentiation to beta cells and improves glucose homeostasis. The findings from this study may shed light on the potential treatment of prediabetes/diabetes following AP.

Immunohistochemical features of the fallopian tubes’ structure in case of fetuses with a gestational term of 21-28 weeks from mothers with a chronic infection of the lower genital tracts

In the following article we are disclosing immunohistochemical features of the fallopian tubes’ structure in case of fetuses with a gestational term of 21-28 weeks. We have studied the structure of organs of 15 fetuses from mothers with a chronic infection of the lower genital tracts (HILGT) (the group of comparison) relatively to one in case of 15 fetuses from mothers with a physiological pregnancy (the main group). All fetuses had a gestational term of 21-28 weeks and had died intranatally as a result of an acute disorder of uterine-placental circulation. Methods of reearch: organometric, histological, immunohistochemical and statistical. The complex research allowed to reveal a probable decrease of the organometric data as well as indicators of thickness of the main structural components of the organs’ wall in case of fetuses from mothers of the group of comparison relatively to ones in case of fetuses from the main group. By applying histological method we had reveled a disorder in the strucuture of mucous and muscular membranes in the structure of organs of fetuses from mothers with a pathology of pregnancy, which is manifested by decreasing of number of folds, uneven thickness of the mucous membrane as well as disorder in formation of the muscular membrane’ layers. Immunohistochemical method has revealed an increase of apoptotically changed mucosal cells in the fallopian tubes of fetuses from mothers with HILGT. By applying MCAT to endotheline-1 we have revealed an increased glow of endithelial cells in vessels both of arterial and venous types in the strucuture of the organs’ wall in case of fetuses from the group of comparison. During the study on the endocrine activity of organs of fetuses from mothers with complicated pregnancy we have postulated a probable decrease of the cells’ glow’ intensity towards MCAT of progesterone. At the same time, there is also an inflammatory infiltration in the mucous membrane of the fallopian tubes’ wall. The aforementioned changes in the strucuture as well as in the functional activity of fetuses’ organs from mothers’ with HILGT are formed under the influence of chronic hypoxia and endocrine insufficiency of the feto-placental complex, which is taking place in case of this pathology. Histological and immunohistochemical features of the fallopian tubes’ structure in case of fetuses from mothers with complicated pregnancy are indicating a disorder in formation and maturing of the organ as well as they could lead to development of ectopic pregnancy and tubal infertility in the subsequent ontogenesis.

Association between Pancreatic Burnout and Liver Cirrhosis in Alcoholic Chronic Pancreatitis

<b><i>Background/Objectives:</i></b> In chronic pancreatitis (CP), progressive fibrosis of the pancreas leads to exocrine and endocrine insufficiency and, finally, to pancreatic burnout. Alcohol consumption is associated with fibrosis in the pancreas and the liver, and the activation of stellate cells plays a central role in the induction of fibrosis in both organs. However, the relationship between pancreatic burnout and liver cirrhosis (LC) is still poorly understood in patients with alcoholic CP (ACP). <b><i>Methods:</i></b> We performed a single-center, retrospective, cross-sectional study with 537 CP patients. We analyzed the clinical presence of early and advanced pancreatic burnout and stated LC in cases of typical alterations in histology, liver stiffness measurement, cross-sectional imaging, or ultrasound. We analyzed further clinical parameters. <b><i>Results:</i></b> The frequency of advanced pancreatic burnout was 6.5% for ACP (20/306) and 4% for non-ACP (8/206; <i>p</i> = 0.20; χ² test). Advanced pancreatic burnout was not associated with the amount of alcohol consumption (<i>p</i> = 0.34) but with the disease duration (<i>p</i> = 0.0470) and rate of calcification (<i>p</i> = 0.0056). Furthermore, advanced pancreatic burnout was associated with LC (<i>p</i> &#x3c; 0.0001) but cannot be explained by the amount of alcohol consumption. In ACP with alcohol consumption &#x3e;80 g/day, an isolated LC was significantly more frequently detectable (14%, without pancreatic burnout) than an isolated advanced pancreatic burnout (1%, without LC). These results were confirmed by multivariable analyses. <b><i>Conclusions:</i></b> We identified a close association between LC and pancreatic burnout. The disease duration positively correlates with the development of pancreatic burnout. The liver seems to be more vulnerable to alcohol than the pancreas.

A prospective study of prognostic factors predicting outcome of surgery in chronic pancreatitis at a tertiary care centre in India

Identification of factors predicting the outcome of surgery for chronic pancreatitis and preparation of a scoring system to predict the outcome following surgery. A total number of 76 patients who had undergone surgery for chronic pancreatitis were prospectively followed at Department of General Surgery, S.C.B. Medical College, Cuttack during the period from 2010-2013. Data on demographic details, pain score, opioid addiction, exocrine and endocrine insufficiency, insulin requirement and morphology of pancreas on imaging were recorded. On follow up, improvement in pain score and exocrine and endocrine insufficiency were recorded. Factors affecting surgical outcome were determined and a scoring system was done. The mean age of patients was 39.7±7.9 years (range 18-58 years). Chronic alcohol intake was the predominant cause accounting for 56% (n=34) cases. Mean pain score at admission on Visual Analogue Scale (VAS) was 5.98. Twenty-six patients (43.3%) were found to have endocrine insufficiency and 22 (36.6%) patients had exocrine insufficiency. Forty-two patients underwent Partington-Rochelle procedure, and 18 patients underwent Frey’s procedure. Eighty percent of patients (n=48) had significant pain relief. On logistic regression, preoperative VAS score, number of previous admissions, opioid dependence, main pancreatic duct (MPD) diameter, number and site of calcifications were found to be significant in predicting pain relief. Cohort of patients with chronic pancreatitis likely to get benefit from surgery can be predicted preoperatively.