Vol 47, No 6 (2019)

Background: Management of the isolated form of cystic dystrophy of the duodenal wall (CDDW), or pure form of groove pancreatitis, is controversial. Pancreatoduodenectomy is considered to be the most suitable procedure for CDDW. Pancreas-preserving procedures (PPDR) have been described as surgical options for the cases where only the duodenum has been involved. There are no studies comparing pancreas-preserving vs. pancreas-resecting procedures for this disease.

Aim: To analyze the results and outcomes of PPDR and other treatment approaches to CDDW and to review the literature.

Materials and methods: We performed a retrospective analysis of 82 patients with CDDW who received treatment from February 2004 to April 2019. We compared short-term and long-term results of treatment of 15 patients with isolated CDDW after PPDR and 42 patients with CDDW after pancreatoduodenectomy.

Results: The preoperative diagnosis was correct in 81 of the cases (98.8%). The patients experienced abdominal pain (100%), weight loss (76%), vomiting (30%), and jaundice (18%). CT, MRI, and endoUS were the most useful diagnostic modalities. Twelve patients with CDDW took conservative treatment due to rejection of the operation. The other patients underwent cystoenterostomies (8), duodenum-preserving pancreatic head (DPPH) resections (6), pancreatoduodenectomy (42) and PPDR (15) with zero mortality. Full pain control was achieved after PPDR in 93%, after pancreatoduodenectomy in 83%, and after draining procedures in 18% of the cases. Newly onset diabetes mellitus (7) and severe exocrine insufficiency (5) were common after pancreatoduodenectomy and never occurred after DPPH resections and PPDR. Weight gain was significantly higher after pancreatoduodenectomy and PPDR, compared to other treatment modalities.

Conclusion: PPDR is the optimal surgical procedure for the isolated form of CDDW. Early detection of CDDW allows for preservation of the pancreas. The pure form of groove pancreatitis is a disease of the duodenum, and the Whipple procedure should be considered excessive for this disease.

Rationale: Mild and moderate ulcerative colitis (UC) is conventionally treated with oral and rectal 5-aminosalicylic acid (5-ASA) formulations and, if ineffective, with systemic glucocorticosteroids. A huge disadvantage of systemic steroids is that with highly efficacy they have severe side effects and the development of hormone-dependency requiring their withdrawal. The main goal of UC treatment is to achieve clinical and endoscopic remission, and possibility to stop steroids. The introduction of multimatrix (MMX) budesonide (Cortiment®), a new topical steroid for UC treatment, widens the therapeutic armamentarium and allows in some cases to refrain from systemic agents, avoiding their side effects and achieving the necessary treatment goals.

Aim: To evaluate the efficacy of topical steroid budesonide MMX for remission induction of UC in the real clinical practice.

Materials and methods: We have analyzed 122 specially designed case report forms filled in from September 2018 to March 2019 in healthcare centers of Moscow, Voronezh, Lipetsk, Krasnodar, and Krasnoyarsk Regions of Russian Federation. The case report forms included anonymized data on the UC patients treated with budesonide MMX. The results of treatment were analyzed for various severity and extension of UC and depending on budesonide MMX monotherapy or combined therapy with rectal 5-ASA formulations. Treatment was considered effective if clinical and endoscopic remission was achieved.

Results: Total efficacy in terms of improvement of clinical parameters (improvement/remission) after 4 weeks of treatment was 95% (118 patients), with clinical remission induced in 42.6% (52 patients). Positive changes over time in the endoscopic findings (improvement/remission) within the same time period were observed in 93% (60 patients), with endoscopic remission in 24.1% (21 patients).

Conclusion: Budesonide MMX allows for a rapid clinical improvement and/or clinical remission in the majority of the patients with mild and moderate UC of predominantly left-sided location.

Background: Malnutrition is among the predictors of unfavorable outcome of chronic pancreatitis (CP). Our previous study has shown that the malnutrition prevalence in CP patients was 92%; body mass index (BMI) ≤ 19  kg/m2 was found only in 15.5%.

Aim: To identify clinical variants of nutrition status in CP patients. Materials and methods: We have analyzed the data from the first step of an open-label randomized prospective study on 148  patients (80  male) with CP of various etiologies, aged from  22 to  82  years (mean age, 51.8 ± 13.2  years). According to TIGAR-O, the patients were allocated into two groups: the first group with chronic alcoholic pancreatitis (CAP) included 71 patients (57 male and 14  female, mean age 46.3 ± 11.2  years), the second one with chronic obstructive pancreatitis (COP) consisted of 77  patients (29  male and 48  female; mean age 56.81 ± 3  years). Exocrine pancreatic function was assessed by fecal elastase 1  levels. Nutritional status was determined by V.M. Luft classification based on comparison of various anthropometrical parameters, as well as on some laboratory parameters (hemoglobin, total protein, albumin levels, lymphocyte counts, etc.). The anthropometrical and laboratory parameters, as well as smoking and alcohol overconsumption were included into the correlational analysis.

Results: In the CAP group, the number of smoking patients was 2.5-fold higher than that in the COP group (р < 0.001). The smokers had a  lower BMI (р = 0.002) and lower pre-albumin levels (р = 0.04), compared to the non-smokers. There were associations between: the number of cigarettes per day and the daily amount of alcohol (r = 0.55), the smoking index and thickness of the skin/fat fold over the triceps muscle of the arm (r = -0.4), severity of chronic alcohol abuse and malnutrition grade (r = -0.5), duration of excess alcohol consumption and thickness of the skin/fat fold over the triceps (r = -0.4), hemoglobin levels and malnutrition grade (r = 0.5), hemoglobin level and shoulder circumference (r = 0.47), blood cholesterol level and shoulder circumference (r = 0.37), low density lipoprotein level and shoulder circumference (r = 0.41). Four basic clinical types of nutrition status could be identified: malnutrition of various grades (66%), overweight/obesity without malnutrition (3%), sarcopenic obesity with some malnutrition (26%), euthrophic type (5%). In the patients with malnutrition without sarcopenia, the etiology of CP had no effect on the prevalence of malnutrition. Low albumin levels were found in 54%  (80/98) of the patients with pancreatic exocrine insufficiency and malnutrition, indicating a  risk of sarcopenia. Sarcopenic obesity with malnutrition was most prevalent in COP (24  vs. 14  patients with CAP) and at higher age (56.8  vs. 46.3  years, respectively, р < 0.001).

Conclusion: Smoking, chronic alcohol abuse, low hemoglobin levels are associated (negative correlation) with the development of malnutrition in CP patients. The most prevalent clinical types of nutrition status in CP patients are characterized by various degrees of malnutrition, as well as by malnutrition with sarcopenic obesity. 

Aim: To raise the awareness of general practitioners with special characteristics of the clinical manifestations of the drug-induced liver injury (DILI), which can manifest with various signs, symptoms and types of morphological injury, from asymptomatic increase in transaminases and liver steatosis to chronic hepatitis with advanced fibrosis.
Key points: NSAID is one of the most commonly prescribed groups of agents worldwide. Most of them have low risk of liver toxicity. However, prolonged uncontrolled intake of NSAID by patients without proper medical follow-up and monitoring may lead to serious liver injury, illustrated by the clinical case presented. The case manifested as an extremely rare liver injury in the form of chronic hepatitis with advanced fibrosis that developed after prolonged NSAID use.
Conclusion: DILI usually occur as idiosyncratic (non-predictable) reactions. This is an exclusion diagnosis requiring comprehensive medical knowledge and awareness on potential drug-induced liver toxicity, including that associated with drug interactions. To minimize potential risk of liver toxicity induced by NSAID, it is recommended to take them in the lowest effective dose and for a minimally required period. A thorough assessment of a patient's past history, monitoring of clinical chemistry parameters, and clinical judgment of the physician remain to be decisive for prevention, timely diagnosis, and treatment of DILI.

Background: For a long time there has been a discussion about how chronic pancreatitis (CP) and diabetes mellitus (DM) are related to each other. If a patient has both conditions, should they be viewed as two separate disorders, or one of them is a plausible consequence of the other? If the latter is true, what are pathophysiological mechanisms of DM in CP? Current consensus documents by specialists in pancreatic diseases pay little attention to this issue, and their main statements have low level of evidence. The Russian consensus on the diagnosis and treatment of CP (2016) contains no statements on DM. In the Russian guidelines and consensus documents to be developed, it is necessary to include provisions on the pancreatogenic DM as an independent “other type DM’, with consideration of its pathophysiological mechanisms and clinical particulars.

Aim: To characterize the state-of-the-art in pancreatogenic DM, to demonstrate its differences from DM types 1 and 2 from pathogenetic and clinical perspectives.

Methods: The review is based on the results of meta-analyses, systematic reviews and main provisions of the existing clinical guidelines and consensus documents available from PubMed and E-library.

Results: According to various sources, Type 3c DM, or latent impaired glucose tolerance in CP, can eventually develop in 25 to 80% patients with CP. Impaired glucose tolerance is found in 40 to 60% of patients with acute pancreatitis, with persistent hyperglycemia after acute episode seen in 15 to 18% of the patients. Exocrine pancreatic insufficiency is commonly seen in Type 1 and Type 2 diabetic patients, although the data on its prevalence are highly contradictory indicating a lack of knowledge in the field. Type 3c DM is characterized by its manifestation at later stages of CP, concomitant excretory deficiency of the pancreas, brittle course with proneness to hypoglycemia and no ketoacidosis. The highest risk group includes patients with longstanding CP, previous partial pancreatic resection and patients with early calcifying pancreatitis, mainly of the alcoholic origin. Optimal and rational medical treatment of pancreatogenic DM still remains disputable, while the evidence base of the efficacy and safety of various anti-diabetic agents in this disease is lacking, and no consensus on the issue has been yet reached. General treatment guidelines given in a number of international consensus documents are limited to cautious insulin administration.

Conclusion: Pancreatogenic DM differs from Type 1 and Type 2 DM in a number of aspects, namely, mechanisms of hyperglycemia, hormonal profiles, clinical particulars and treatment approaches. Endocrine pancreatic insufficiency in CP is caused by secondary inflammatory injury of the pancreatic islets. The key to specifics of Type 3c DM lies in anatomical and physiological interplay of the exocrine and endocrine compartments of the pancreas. At presents, most provisions on pancreatogenic DM are empirical and seem to be rather declarative, because intrinsic mechanisms of this type of diabetes and moreover its pathogenetically based treatment have been poorly studied. Nevertheless, all patients with CP or other pancreatic diseases should be assessed for pancreatogenic DM.

This literature review deals with specifics of the natural course of inflammatory bowel disease (IBD) in patients from various ethnic groups and -308G/A and -238G/A promoter polymorphisms in tumor necrosis factor-alpha (TNF-α) gene. The search in PubMed, Medline, Еlibrary.ru databases has led to identify in total 20 studies, including 2 meta-analyses, on the role of TNF-α-308G/A and -238G/A gene polymorphism in the etiology and pathophysiology of IBD. The TNF-α-308G/A polymorphism is associated with increased secretion of this proinflammatory cytokine, whereas the TNF-α-238G/A genotype is characterized by reduced TNF-α secretion. A  number of studies have shown an association between TNF-α-308G/A gene polymorphism and severe course of IBD, requiring more active treatment of patients (cytostatics, corticosteroids, biological agents). Some investigators have found that the patients carriers of TNF-α-308G/A had a  higher probability of surgical interventions. The association between TNF-α-308G/A and the phenotypic characteristics of IBD has been identified in studies performed in Europe, Asia, and Russia. The association of this polymorphism with the prevalence of ulcerative colitis has been proven in some studies, in particular, in the Asian population. Similar associations have been noted in few publications originating from Europe and North America, while some studies have found no links between TNF-α-308G/A, -238G/A, and the course of IBD. TNF-α-238G/A gene polymorphism has not shown any significance for the prevalence and course of ulcerative colitis and Crohn's disease. One can assume that the differences in the study results arising from one and the same geographical area are related to genetic heterogeneity of the study groups, phenotypic variances between the study subjects, as well as relatively small sample sizes. Currently, the search for genetic, biochemical and other prognostic criteria for IBD course is in progress. There are studies in progress to investigate the mechanisms of transformation of the genetic information into the particulars of ulcerative colitis and Crohn's disease manifestations, with consideration of ethnicity.

Psoriasis and inflammatory bowel disease (IBD) are multifactorial chronic immuno-inflammatory potentially disabling disorders with similar genetic factors and immunological pathways, in particular, genetic polymorphisms of IL-23R, which determines the signal IL-12/23-mediated pathway of immunopathogenesis. The emergence of genetically engineered biological agents has changed the prognosis for both psoriasis and IBD. The intersection of the therapeutic spectrum in psoriasis and IBD is a very important point when choosing the management strategy for these patients. Infliximab and adalimumab are effective in the treatment of psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis (evidence level 1A). Ustekinumab demonstrates effectiveness in the treatment of psoriasis, psoriatic arthritis (evidence level 1A) and Crohn's disease (evidence level 1B). Etanercept and secukinumab have been shown to be effective against psoriasis, psoriatic arthritis (evidence level 1A) and ineffective and even associated with exacerbation risk in Crohn's disease and ulcerative colitis. Inhibition of regulatory cytokines IL-12/23 also has a number of advantages compared to the blockade of effector cytokines (TNF-α, IL-17) due to potentially long-term and stable treatment results and less frequent administration.