Aim. To evaluate the possibilities of post-processing of multidetector computed tomography (CT) results in the non-invasive diagnosis of pancreatic fibrosis (PF). Materials and methods. The study included 165 patients aged 57.91±13.5 years who underwent preoperative CT during surgical treatment for chronic pancreatitis and pancreatic cancer from April 2022 to February 2024. The normalized contrast ratios of pancreatic tissue in the pancreatic (NCPP) and venous (NCVP) phases, as well as the contrast ratio (CR) were measured. Pathomorphological assessment of PF performed in tissues outside neoplasm or desmoplastic reaction by the Kloppel and Maillet scale. Results. The values of post-processing CT results were compared in groups with different degrees of PF. Mean CR values were significantly higher (p=0.001) in patients with severe PF (CR 1.16±0.65 HU) than in patients with mild PF (CR 0.78±0.31 HU). CR value significant increase (p=0.03) was found in patients with signs of inflammatory changes in the pancreas tissue (CR 1.14±0.6 HU) than in those without them (CR 0.81±0.3 HU). There were no significant differences between the values of NCPP and NCVP, and the degree of PF. Conclusion. The CR value increased in patients with severe degree of PF. There was a relationship between CR value increase and the radiological density of pancreatic tissue in non-contrast phase and presence of early signs of pancreatic inflammatory changes. Thus, there was a relationship between CT postprocessing results and morphological signs of PF, which can be used for pancreatic fibrosis non-invasive diagnosis and identification of additional signs of early chronic pancreatitis.

Background: Chronic pancreatitis is a long-term fibro-inflammatory disease of the pancreas that worsens the quality of life of patients and is associated with life-threatening complications. Chronic pancreatitis is based on fibro-inflammatory changes in the tissue of the pancreas. The necessity of a more accurate identification of early fibrosis is related to discrepancies in assessments done with conventional visual scales. Aim: To evaluate the diagnostic accuracy of existing scales for visual assessment of the degree of pancreatic fibrosis compared to the techniques of whole-slide images (WSI) digital analysis. Methods: The morphometric analysis of the assessment of pancreatic fibrosis grade was carried out in the postoperative material from 118 patients with the use of two assessment semi-quantitative visual scales (those proposed by G. Klöppel B. Maillet in 1991 and by O. V. Paklina et al. in 2011), as well as with the use of the digital image marking in the ASAP software and an artificial intelligence algorithm in the QuPath software. Both intralobular and perilobular fibrosis grades were assessed, as well as their integrative index (II). Results: The assessment of pancreatic fibrosis with a 12-point rating system (II) according to Klöppel Maillett showed the following distribution: low grade fibrosis (LF), 55.9% of the cases, moderate fibrosis (MF), 25.4%, severe fibrosis (SF), 16.1%, no fibrosis (NF), 2.5% of the cases. According to the Paklina et al. scale, the results were as follows: LF, 66.1%, MF, 15.2%, SF, 12.7%, and NF, 5.9% of the cases. The comparison of the classical systems revealed a mismatch in the fibrosis grade in 27.9% of the cases; this resulted in the use of more objective methods for the WSI digital analysis. When comparing the average percentage of fibrosis area detected with ASAP with the fibrosis level according to Klöppel Maillett, the data were distributed as follows: with LF, the mean fibrosis area by ASAP was 6.9%, with MF, the fibrosis area was 30%, and with SF, 65%. Similarly, when counting cells in QuPath the following values were obtained: LF, 8.2%, MF, 27.9%, SF, 69.3%. The use of the WSI digital image analysis showed a higher concordance between them (R = 0.937) relative to the comparison between the classical rating scales (R = 0.811). When comparing the methods for assessment of fibrosis for the accurate diagnosis of chronic pancreatitis with ROC analysis, the best result was shown by the cell counting method with QuPath (AUC = 0.943). The method of area calculation with ASAP showed the AUC of 0.910, the classical Klöppel Maillett method demonstrated the AUC of 0.879 and the assessment according to Paklina et al. showed the AUC of 0.808. Conclusion: the WSI digital analysis has higher and significant concordance and diagnostic accuracy; therefore it can be used in clinical practice.

Schwachman – Diamond syndrome is a rare genetic disease manifested mainly by extrinsic pancreatic insufficiency and neutropenia, as well as changes in the bone skeleton. The disease is characterized by phenotypic variability. The presented observations consider similar and different manifestations of the Schwachman – Diamond syndrome.

Background. Exocrine pancreatic insufficiency (EPI) occurs in most patients with advanced pancreatic cancer (PC) and even more often when a tumor is localized in the head of the pancreas. However, insufficient attention is paid to the diagnosis of EPI and assessment of nutritional status, which negatively affects the results of treatment. Materials and methods. One hundred fifty eight patients with primary diagnosed locally advanced and metastatic PC were included in the retrospective study. We used the calculation of the odds ratio with 95% CI with an assessment of the p value using the Pearson ÷2 test to compare the incidence of clinical and laboratory parameters of nutritional status with values below the lower limit of normal (LLN) depending on the location of the tumor in the pancreas. Results. Fecal elastase test was performed in only 19 (12%) patients. In this group, the incidence of EPI was 73.6%. Pancreatic enzyme replacement therapy in the minimal sufficient dose was prescribed in 17.1% of the general cohort. The level of hemoglobin, erythrocytes and albumin below the LLN was found in patients with the tumor in the pancreatic head, respectively, 2.742 (95% CI 1.27–5.92), 3.788 (95% CI 1.554–9.232) and 9.767 (95% CI 1.255–76.027) times more often than in patients with cancer in the body-tail of the pancreas. In patients with the tumor in the pancreatic head, the lower levels of hemoglobin (median 125 g/l vs 132 g/l, respectively), erythrocytes (4.19 mil/μl vs 4.51 mil/μl), total protein (69.6 g/l vs 71.5 g/l), and albumin (40.1 g/l vs 42 g/l), as well as the values of nutritional indices: prognostic nutritional index, nutritional risk index, hemoglobin, albumin, lymphocyte and platelet ratio index, and prognostic immune nutritional index were observed. Conclusion. Diagnosis and treatment of EPI remains inadequately attended. The values of nutritional status parameters in patients with PC in the head are lower than in patients with a tumor in the body-tail of the pancreas, which reflects the contribution of EPI.

Diagnostics of pancreatic diseases represents a difficult task for doctors in multiple fields. Autoimmune pancreatitis is one of the hardest to diagnose among other pancreatic diseases, as it is a rare disease and can mimic groove pancreatitis or pancreatic cancer. Similar manifestation, laboratory changes pattern, and data of imaging methods become peculiarities of differential diagnosis. The article presents a clinical case of difficulties in diagnosing autoimmune pancreatitis at its early stages.

Pancreatic cancer (PC) is a serious public health problem. The mortality rate of patients with PC remains one of the highest among cancers. Early diagnosis of PC is challenging, so it is often diagnosed in the later stages. Current treatment approaches, including surgery, neoadjuvant and adjuvant chemotherapy, chemoradiotherapy, and supportive care, have demonstrated improved outcomes. A significant problem remains exocrine pancreatic insufficiency (EPI) in patients with PC, which requires enzyme replacement therapy. However, this is not given due attention in the Russian literature. This review addresses the survival trends of patients with PC, current therapies, and enzyme replacement therapy as an integral part of supportive care and improvement of nutritional status; also, the issues of routing patients with PC are addressed. It is emphasized that the diagnosis and treatment of EPI are mandatory to improve and maintain the nutritional status and quality of life; failure to treat EPI renders antitumor treatment ineffective.

The immune inflammatory reaction is involved in the formation of structural damage in organs with low immune resistance, but the causal stages of the formation of this reaction are poorly understood. Clinicians are faced with the fact that in patients with acute and chronic pancreatitis of alcoholic etiology, a reactive inflammatory reaction is observed in the mucous membrane (MM) of the stomach and / or duodenum. This effect was the reason that experimental studies were carried out on 45 white Wistar rats weighing 180-220 g. and duodenum (DOD). For this, a classical immunization scheme was used. Rats were taken out of the experiment on days 5, 10, and 17; after autopsy, morphological studies of the pancreas, gastric mucosa, and SOD were performed. Undoubtedly, the emerging immune response of the macroorganism to damage contributes to the development of an autoimmune reaction, in response to destruction and an inflammatory reaction, as a result, structural and functional damage to its own tissues occurs. The involvement of several organs in the inflammatory reaction depends on the local immune tolerance of the organ to endoantigens. A decrease in tolerance leads to a combined pathology, the impetus for which is damage to the “primary” organ, which is not always possible to identify. At the same time, antibodies to endoantigens are formed from damaged cellular structures.

The aim of the study was to define the spectrum of genetic risk factors of chronic pancreatitis (CP) development in patients living in the European part of the Russian Federation.Materials and Methods. The study group included 105 patients with CP, with the age of the disease onset under 40 years old (the averageThe aim of the study was to define the spectrum of genetic risk factors of chronic pancreatitis (CP) development in patients living in the European part of the Russian Federation.Materials and Methods. The study group included 105 patients with CP, with the age of the disease onset under 40 years old (the average age of onset was 26.9 years). The control group consisted of 76 persons without clinical signs of pancreatitis. The diagnosis of chronic pancreatitis in patients was made on the basis of clinical manifestations and the results of laboratory and instrumental investigations. Genetic examination of patients was conducted using the next-generation sequencing (NGS) technology and included targeted sequencing of all exons and exon-intron boundaries of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes. The genotyping of the rs61734659 locus of the PRSS2 gene was also conducted. age of onset was 26.9 years). The control group consisted of 76 persons without clinical signs of pancreatitis. The diagnosis of chronic pancreatitis in patients was made on the basis of clinical manifestations and the results of laboratory and instrumental investigations. Genetic examination of patients was conducted using the next-generation sequencing (NGS) technology and included targeted sequencing of all exons and exon-intron boundaries of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes. The genotyping of the rs61734659 locus of the PRSS2 gene was also conducted. Results. Genetic risk factors of the CP development were found in 61% of patients. Pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the following genes: CTRC (37.1% of patients), CFTR (18.1%), SPINK1 (8.6%), PRSS1 (8.6%), and CPA1 (6.7%). The frequent gene variants in Russian patients with CP were as follows: CTRC gene - c.180C>T (rs497078), c.760C>T (rs121909293), c.738_761del24 (rs746224507); cumulative odds ratio (OR) for all risk alleles was 1.848 (95% CI: 1.054-3.243); CFTR gene - c.3485G>T (rs1800120), c.1521_1523delCTT (p.Phe508del, rs113993960), and c.650A>G (rs121909046); OR=2.432 (95% CI: 1.066-5.553). In the SPINK1, PRSS1, and CPA1 genes, pathogenic variants were found only in the group of patients with CP. The frequent variants of the SPINK1 gene include c.101A>G (p.Asn34Ser, rs17107315) and c.194+2T>C (rs148954387); of the PRSS1 gene - c.86A>T (p.Asn29Ile, rs111033566); of the CPA1 gene - c.586-30C>T (rs782335525) and c.696+23_696+24delGG. The OR for the CP development for the c.180TT genotype (rs497078) CTRC according to the recessive model (TT vs. CT+CC) was 7.05 (95% CI: 0.86-263, p=0.011). In the CTRC gene, the variant c.493+49G>C (rs6679763) appeared to be benign, the c.493+51C>A (rs10803384) variant was frequently detected among both the diseased and healthy persons and did not demonstrate a protective effect. The protective factor c.571G>A (p.Gly191Arg, rs61734659) of the PRSS2 gene was detected only in the group of healthy individuals and confirmed its protective role. 12.4% of the patients with CP had risk factors in 2 or 3 genes. Conclusion. Sequencing of the coding regions of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes allowed to identify genetic risk factors of the CP development in 61% of cases. Determining the genetic cause of CP helps to predict the disease course, perform preventive measures in the proband's relatives, and facilitate a personalized treatment of the patient in future.

Pancreatic fibrosis (PF) is a part of the pathogenesis in most pancreatic disorders and plays a crucial role in chronic pancreatitis development. The aim of our study was to investigate a relationship between PF grade and signs in resected pancreatic specimens, and the results of both multidetector computed tomography (MDCT) post-processing parameters and fibronectin (FN), hyaluronic acid (HA), matrix metalloproteinase (MMP)-1, and MMP-9 serum levels. The examination results of 74 patients were analyzed. The unenhanced pancreas density (UPD) value and contrast enhancement ratio (CER) showed statistically significant differences in groups with peri- and intralobular fibrosis grades, an integrative index of fibrosis, inflammation in pancreatic tissue, and pancreatic duct epithelium metaplasia, while the normalized contrast enhancement ratio in the venous phase (NCER VP) significantly differed with the perilobular fibrosis grade, integrative fibrosis index, and inflammation (p < 0.05). The blood FN level showed a weak positive correlation with the intralobular fibrosis grade (rho = 0.32, p = 0.008). The blood level of HA positively correlated with the presence of prominent and enlarged peripheral nerves (rho = 0.28, p = 0.02) and negatively correlated with the unenhanced pancreas density value (rho = −0.42, p = 0.0001). MMP-1 and MMP-9 values’ intergroup analysis and correlation did not show any statistical significance. The UPD value, NCER VP, and CER, as well as blood levels of FN and HA, could be used in non-invasive PF diagnosis.

Chronic pancreatitis is one of the most challenging disorders from the perspective of its early diagnosis and effective treatment. Within the last decade, the diagnosis of early chronic pancreatitis has been firmly introduced into the practice of gastroenterology. The delineation of this form as an initial stage of chronic pancreatitis is based on the need in early and effective treatment that could cease the progression of the disease and reduce the possibility of its complications. The diagnostic criteria of chronic pancreatitis have been described in details in the literature; however, specifics of the diagnosis in its early stage have been scarcely highlighted. Chronic pancreatitis is commonly diagnosed with a number of imaging techniques (they can show abnormalities in morphology of the pancreas), as well as laboratory tests (showing functional organ deficit). However, morphological and imaging techniques are insufficient for the diagnosis of the early chronic pancreatitis. A new integral strategy towards early diagnosis seems necessary, that would consider not only the morphology, but also potential etiology, risk factors of the disease and its complications in patients with suspected chronic pancreatitis. The review of the literature presents the definition of the early pancreatitis and discusses the potential of imaging techniques and functional tests in its diagnosis. An adequate strategy for the diagnosis of the early pancreatitis is formulated, based on an individual patient characteristic with suspected early chronic pancreatitis, namely, risk factors, clinical manifestations, imaging results and serological biomarkers.

AIM:The assessment of pancreatic resection volume influence on exo- and endocrine pancreatic functions.MATERIALS AND METHODS:The resected pancreatic volume influence was assessed in 47 patients: 31 (66%) patients after resections of pancreatic body and tail, and 16 (34%) patients after distal resections. The exocrine pancreatic function was assessed by pancreatic fecal elastase 1 as well as endocrine pancreatic function was assessed by C-peptide level measurement. Computed tomography with intravenous contrast enhancement and postprocessing was used for pre- and postoperative pancreatic volume assessment. All tests were performed before and 1, 3, and 6 months after surgery.RESULTS:Type of surgery had no influence on C-peptide and pancreatic fecal elastase 1 levels (p>0.05). Exo- and endocrine pancreatic functions markers tended to decrease in 1st month after surgery with consequent functions restoration towards 6 months after surgery. There were 15 (35.7%) patients from 42 patients with normal exocrine pancreatic function with a fecal elastase 1 level decrease to 114.7±61.8 μg/g; exocrine insuficiency remained only in 2 (4.8%) patients after 6 months after surgery. C-peptide concentration decrease before surgery to less than 1.1 ng/ml was noticed only in 8 (17%) patients. C-peptide concentration decreased in 30 (63.8%) patients in 1st month after surgery, but after 6 months after surgery, C-peptide level decrease was only in 7 (14.9%) patients.CONCLUSION:The exo- and endocrine function of the pancreas is restored in more than 80% of patients after DR. Probably it could be associated with the activation of the pancreatic compensatory abilities.

Despite of achieved progress in advanced pancreatic cancer treatment, the disease outcomes remain far from satisfying. The peculiarity of malnutrition treatment in these patients is the result of its causes complexity and progressively growing manifestations extent. The review represents mechanisms of malnutrition and approaches to their treatment.

Changes in the exocrine function of the pancreas often develops after proximal and distal resections. Exocrine pancreatic insufficiency (EPI) is characterized by a reduced secretion of pancreatic enzymes, because of which the digestion and absorption of nutrients is impaired. Clinical manifestations of EPI and, as a consequence, changes in nutritional status significantly affect the quality of life of patients.

The aim was to evaluate the metabolic activity of the colonic microbiota in patients with chronic pancreatitis (CP) as a marker of changes in the functional state of the pancreas. Material and methods. 40 patients (20 men and 20 women) aged 35 to 74 years (50.6 ± 9.4 years) were examined, 26 patients of which had external secretory pancreatic insufficiency (ESPI), which was confirmed by the data of the elastase test, and 14 patients had no ESPI. The diagnosis of CP was established on the basis of instrumental data. Patients with proven ESPI received enzyme replacement therapy (ERT) in accordance with international and Russian recommendations. The concentration and spectrum of short-chain fatty acids were evaluated by gas-liquid chromatography. The control group consisted of 22 healthy volunteers (13 women and nine men aged 43.4± 6.2 years). Results. As a result of the analysis of the profiles of short-chain fatty acids (SCFAs), a significant change in the content of propionic acid was revealed in patients with CP without GNP when compared with a group of healthy volunteers, no differences were found between the groups of patients with CP. These studies indicate a decrease in the activity of certain types of colon microbiota that produce C3 (propionic acid) in patients with CP without ESPI and, accordingly, who did not receive ERT. This, apparently, is due to the violation of the fermentation of individual substrates entering the lumen of the colon. Conclusion. Indicators of the concentration and spectrum of SCFAs can serve as additional tools for detecting changes in the metabolic activity of the colonic microbiota as a marker of the functional state of the pancreas in CP.

Chronic pancreatitis (CP) is an end-stage disease with no specific therapy; therefore, an early diagnosis is of crucial importance. In this study, data from 1315 and 318 patients were analysed from acute pancreatitis (AP) and CP registries, respectively. The population from the AP registry was divided into AP (n = 983), recurrent AP (RAP, n = 270) and CP (n = 62) groups. The prevalence of CP in combination with AP, RAP2, RAP3, RAP4 and RAP5 + was 0%, 1%, 16%, 50% and 47%, respectively, suggesting that three or more episodes of AP is a strong risk factor for CP. Laboratory, imaging and clinical biomarkers highlighted that patients with RAP3 + do not show a significant difference between RAPs and CP. Data from CP registries showed 98% of patients had at least one AP and the average number of episodes was four. We mimicked the human RAPs in a mouse model and found that three or more episodes of AP cause early chronic-like morphological changes in the pancreas. We concluded that three or more attacks of AP with no morphological changes to the pancreas could be considered as early CP (ECP).The new diagnostic criteria for ECP allow the majority of CP patients to be diagnosed earlier. They can be used in hospitals with no additional costs in healthcare.