Severe Pancreatic Insufficiency Research Articles

Evaluation of the Effectiveness of Using the CFTR Modulator Ivacaftor/Lumacaftor in Children with Cystic Fibrosis in the Sverdlovsk Region (Prospective Cohort Study)

Background. A modern achievement in the treatment of cystic fibrosis has been the discovery of small molecules that restore the processes of synthesis, transport to the membrane, and the work of the defective CFTR protein. Drugs whose action is aimed at restoring the function of the CFTR protein are called CFTR modulators. The aim of the study is the conduction of a comprehensive assessment of the effectiveness of CFTR modulator ivacaftor/lumacaftor therapy in children with cystic fibrosis based on the study of clinical, laboratory, and instrumental data. Methods. CFTR modulator ivacaftor/lumacaftor was received for 12 months by 23 children of the main group aged 2–17 years, who are homozygous carriers of the F508del mutation of the CFTR gene in the absence of the L467F complex allele. A control examination of the main group was conducted at the start of the study and then every 3 months for 12 months of drug administration. Results. The condition of the patients in the observation groups at the start of the study was assessed as moderate to severe, the bronchopulmonary process was in the stage of incomplete clinical remission. In the main group, the level of aspartate aminotransferase significantly decreased, in the control, on the contrary, there was a tendency for this indicator to increase. The level of alkaline phosphatase (alkaline phosphatase) decreased and reached normal in the main group; the relative risk of hyperphosphatasemia during treatment decreased by 5 times (0.187 (0.063–0.557)). The level of gamma-glutamyltranspeptidase (gamma-GTP) and the number of patients with elevated GGTP decreased (24.65 and 19.69 IU/l, respectively; 61 and 13%). In the control group, the level of gamma-GTP increased and the alkaline phosphatase did not normalize. The indicators of forced exhalation volume in the first second and forced vital capacity of the lungs were initially lower in the main group, after 12 months the differences remained. There was a tendency to decrease the frequency of severe pancreatic insufficiency in the main group by 17.3%, and no changes in the control group. Sweat chlorides tended to decrease in the main group in the absence of reaching the standard values. Conclusion. The usage of the CFTR modulator ivacaftor/lumacaftor showed a greater clinical effect in improving the functioning of the digestive organs: a decrease in the risk of hyperphosphatasemia and a significant decrease in the number of patients with high levels of gamma-GTP were established, a stable level of liver enzyme activity was noted, and a tendency to increase the activity of pancreatic elastase was revealed. The tendency to decrease the indicators of sweat chlorides is shown. There were no changes in the indicators of respiratory function.

ОСОБЕННОСТИ НУТРИТИВНОГО СТАТУСА ДЕТЕЙ С МУКОВИСЦИДОЗОМ РАЗЛИЧНЫХ ЭТНИЧЕСКИХ ГРУПП СЕВЕРНОГО КАВКАЗА

Adequate nutritional status in a patient with cystic fibrosis (CF) positively correlates with the normal function of the bronchopulmonary system. Many domestic and foreign studies have been conducted so far to assess the nutritional status of children and adults with CF. However, there is no data as yet on the phenotypic characteristics of children from different ethnic groups of the North Caucasus depending on their genotype. The purpose of this research was to study the peculiarities of nutritional status in children with CF of the following Russia’s North Caucasus ethnic groups: Chechen, Karachay-Circassian, Dagestani, Ingush and Ossetian-Alanian. Materials and methods used: a single-center open prospective study of 117 children with CF aged 2 months to 17 years old (Me 6 y/o) of various North Caucasus ethnic groups was conducted. All patients have undergone molecular diagnosis and assessment of both nutritional status and exocrine pancreatic function. Results: 50.4% of pediatric patients with CF in the Russia’s North Caucasus have had pathological mutations in c.1545_1546delTA, p.(Tyr515*) and c.3846G>A, p.(Trp1282*) in homozygous state. These mutations were most often found in the Ingush (100%) and Chechen (82%) ethnic groups and somewhat less frequently in the Dagestani (57.1%) and Karachay-Circassian (54%) ethnic groups. In the Chechen and Ossetian-Alanian ethnic groups, when these mutations were detected, severe pancreatic insufficiency was established in 40.5% and 100% of cases, respectively. Pseudo-Bartter syndrome was diagnosed in 60% of cases with this genetic variant in a homozygous or compound heterozygous states during the patients’ first years of life. Indicators for the nutritional status of children with CF from different ethnic groups were significantly lower compared to those recorded officially in the 2021 Russian National Register of Patients with CF. Conclusion: it is necessary to study the course of CF and the state of nutritional status separately in each population and its connection with the identified genetic characteristics of the Russia’s North Caucasus ethnic groups. The genotype and phenotype patterns for these patients were the reason for the development of disorders of the exocrine function of the pancreas and pseudo-Bartter syndrome at an early age, which in its turn could lead to further development of nutritional deficiency.

Fecal microbiota transplantation in patients with spinal cord injury with recurrent Clostridioides difficile infection: a case report

Objective: Fecal microbiota transplantation (FMT) is an emerging treatment for Clostridioides difficile infection (CDI) through reconstruction of the gut microbiota, but its impact in people with spinal cord injury (PWSCI) is limited. The aim of this paper is to report the use of FMT in a PWSCI with CDI. Methods: The FMT was conducted on October 30, 2019. Results: A 72-year-old man with T8 complete paraplegia from compression of the spinal cord due to an epidural hematoma was referred. He has known severe pancreatic enzyme insufficiency, malabsorption, and a history of recurrent CDI. Despite intensive dietetic treatment (probiotics, enteral nutrition, and parenteral nutrition), and multiple courses of antibiotics (vancomycin and fidaxomicin at various doses and durations) for CDI, he continued to be CDI-positive. His CDI was successfully treated after 2 colonoscopically delivered FMTs. At the 24-month follow-up, he remains CDI-negative and reports improved independence. Although there has been considerable variability in the criteria for the FMT and its mode of delivery, FMT can be an option to treat recurrent CDI. Conclusion: This case report reports a PWSCI with recurrent CDI who has been successfully treated with FMT and remains in long-term remission. It supports the consideration of FMT in PWSCI with CDI when antibiotic treatment has been unsuccessful.

The effect of steroid therapy on pancreatic exocrine function in autoimmune pancreatitis

Background/objectivesAutoimmune pancreatitis (AIP) is a steroid-responsive inflammatory disease of the pancreas. Few studies investigated pancreatic exocrine function (PEF) in patients suffering from AIP and no definitive data are available on the effect of steroids in PEF recovery. Aim of the study is the evaluation of severe pancreatic insufficiency (sPEI) prevalence in AIP at clinical onset and after steroid treatment. Methods312 Patients with diagnosis of AIP between January 1st, 2010 and December 31st, 2020 were identified in our prospectively maintained register. Patients with a pre-steroid treatment dosage of fecal elastase-1 (FE-1) were included. Changes in PEF were evaluated in patients with available pre- and post-treatment FE (between 3 and 12 months after steroid). ResultsOne-hundred-twenty-four patients were included, with a median FE-1 of 122 (Q1-Q3: 15–379) μg/g at baseline. Fifty-nine (47.6 %) had sPEI (FE-1<100 μg/g). Univariable analysis identified type 1 AIP, radiological involvement of the head of the pancreas (diffuse involvement of the pancreas or focal involvement of the head), weight loss, age and diabetes as associated with a greater risk of sPEI. However, at multivariable analysis, only the involvement of the head of the pancreas was identified as independent risk factor for sPEI. After steroids, mean FE-1 changed from 64 (15–340) to 202 (40–387) μg/g (P = 0.058) and head involvement was the only predictor of improvement of sPEI. ConclusionThe inflammatory involvement of the head of the pancreas is associated with PEF severity, as well as PEF improvement after treatment with steroids in patients with AIP.

Investigation of lipid digestion by fungal and porcine lipase supplements for severe pancreatic insufficiency using the in vitro dynamic TIM model

Exocrine pancreaticinsufficiency (EPI) is caused by insufficient secretion or limited activity ofpancreatic enzymes, especially lipase. Chronic pancreatitis (CP) is the mostcommon EPI disease. CP patients suffer from gastrointestinal symptoms such asdiarrhea, abdominal pain, and decreased uptake of nutrients as a consequence ofinadequate food digestion. To improve their nutritional status, pancreaticenzyme supplements can be orally administered, known as pancreatic enzymereplacement therapy (PERT). PERT is commonly based on oral porcinepreparations, despite their pH sensitivity which results in a limited timeframefor optimal activity. Instead, fungal enzymes could be used to prolong enzymeactivity duration, since they are active over a wide pH range. The performanceof fungal enzymes was compared to porcine enzymes by measuring total fattyacids under severe pancreatic insufficiency conditions in the tiny-TIMsgdynamic in vitro gastrointestinal model. Administration of 14.000 fungallipase units (Nortase) led to similar lipid digestion compared to 20.000porcine lipase units (Kreon and Pangrol). Additionally, opening the Nortasecapsules had no negative effect on fungal lipase activity. This workdemonstrates that fungal lipases, administered as capsules or powder, can beused as an alternative treatment for EPI patients.

Genotype-phenotype correlation in siblings with cystic fibrosis

Introduction. Despite the genetic counseling, families with cystic fibrosis (CF) patients and modern possibilities of prenatal molecular genetic screening, the occurrence of CF in more than one child in a family is not rare. The same genotype is expected to determine the specific phenotype in CF patients, especially in siblings. However, broad clinical heterogeneity could indicate the influence of secondary genetic factors on the course of the disease.&#x0D; The aim of the study is to examine the genotype-phenotype correlation and disease course features in CF siblings, including twins.&#x0D; Materials and methods. A clinical retrospective cohort observational study included fifty three sibs (23 boys, 30 girls) aged from 6 months to 17 years 9 months (median age of 8.3 (4.8–12.9) years, age difference 5 ± 2 years) with a diagnosis of CF confirmed by molecular genetic methods. Group 1 consisted of 9 twin pairs (3 — monozygotic, 6 — dizygotic), group 2 — 35 complete sibs.&#x0D; Results. The mean age of diagnosis for older sibs is 2.5 years (8 months — 9,8 years; min — 1 months, max — 17 years) and for younger sibs — 8.5 months (1.3 months–3 years). Chronologically, the onset of CF was registered earlier in younger sibs than in older sibs in 3 (16.7%). In 6 (22.2%) of families, the pancreatic status of sibs varied from normal function to severe pancreatic insufficiency, with the occurrence of pancreatitis observed in only 4 (7.6%) patients. In 21 (77.8%) families with sibs infected by P.aeruginosa, 5 (23.8%) had a simultaneous primary culture of the pathogen, 8 (38,1%) had culture in both children but with an interval from 1 month to 9.5 years (Ме: 3.2 (5 months–4.9 years), and in 8 (38.1%) had culture in only 1 sibling. All younger sibs had the primary contamination at an earlier age with a 5.3 year (2–6.6 years;) difference. In 10 (37.0%) of the families, the pulmonary function of the sibs was variable. The number of bronchopulmonary exacerbations per year ranged in 8 (29.6%) of sib pairs and averaged 1.3 ± 0.5 in older sibs, 1.1 ± 0.3 in younger sibs, and 1.7 ± 1.3 in twins. The severity of hepatic involvement varied in 9 (33.3%) of sib pairs: no morbidity in 6 (33.3%), cystic fibrosis-associated fibrosis in 7 (38.9%), and cirrhosis with portal hypertension in 5 (27.8%).&#x0D; Conclusion. CF siblings, despite the same genotype, similar environmental conditions, and high risk of cross-infection, are characterized by wide phenotypic heterogeneity. Aside from the pathogenic CFTR variants, there are other genetic (modifier genes) and epigenetic (microRNA, DNA methylation) factors that could contribute to the clinical features of cystic fibrosis.

DON'T SWEAT IT: A CASE OF PID-LUNG DISEASE MISDIAGNOSED AS CYSTIC FIBROSIS

<h3>Introduction</h3> Chronic lung disease in primary immunodeficiency is common and contributes to significant morbidity and mortality. Bronchiectasis has a broad differential which includes Cystic Fibrosis and several other disease processes. In patients with primary immunodeficiency, this inflammatory destruction of airway walls is a complication of recurrent pneumonia and immune dysregulation. <h3>Case Description</h3> A 16-year-old boy from Bangladesh with history of Cystic Fibrosis (CF) was referred by pulmonology for management of known hypogammaglobulinemia. Patient came to the United States for treatment of CF-associated severe lung disease. His course in Bangladesh had been complicated by multiple episodes of sinopulmonary infections and failure to thrive secondary to severe diarrhea and pancreatic insufficiency. He had been initially diagnosed with CF in 2019 in Thailand with positive sweat chloride test with additional finding of hypogammaglobulinemia. Chest CT at our institution showed severe bronchiectasis with multifocal consolidations and ground glass opacities consistent with CF. Our immunological evaluation revealed agammaglobulinemia with IgG <109, IgA <2, IgM <5, as well as B-cell and T-cell lymphopenia. Pulmonology then performed repeat sweat chloride testing and genetics which were both negative for CF. GI evaluation revealed evidence of colitis with no pancreatic insufficiency. Patient's history could all be explained by primary immunodeficiency (PID). PID gene panel was unrevealing and whole exome sequencing is pending. Following his diagnosis, patient was managed with IVIG, prophylactic antibiotics, and enteral feeds with great improvement. <h3>Discussion</h3> This case illustrates the importance of early recognition of primary immunodeficiency, especially in resource-poor areas. Hypogammaglobulinemia should be on the differential for childhood-onset bronchiectasis.

Prevalence, trends and outcomes of long-term inhaled antibiotic treatment in people with cystic fibrosis without chronic Pseudomonas aeruginosa infection – A European cystic fibrosis patient registry data analysis

BackgroundLong-term treatment with inhaled antibiotics is recommended for people with cystic fibrosis (pwCF) chronically infected with Pseudomonas aeruginosa (PA). However, pwCF without chronic PA infection are also commonly treated with inhaled antibiotics. Using data from the European Cystic Fibrosis Patient Registry (ECFSPR) we aimed to determine the prevalence and factors associated with inhaled antibiotic treatment in pwCF without chronic PA infection, and long-term outcomes with inhaled antibiotics use. MethodsThe ECFSPR was searched for pwCF 6 years of age and older who were not chronically infected with PA at baseline. Factors associated with inhaled antibiotic use were first assessed through a logistic regression. From this model a propensity score was computed for each individual, providing the likelihood of being treated with inhaled antibiotics. Long-term outcomes with and without inhaled antibiotics were assessed separately for propensity scores tertiles. Results7210 pwCF without chronic PA infection at baseline were included, with 2722 (37.75%) receiving long-term treatment with inhaled antibiotics. Treatment with inhaled antibiotics was more prevalent with severe genotype, diabetes, pancreatic insufficiency, and past infection with chronic PA (OR 3.8, 95% CI, 2.88–5.04). Treatment with inhaled antibiotics was not associated with a reduced risk for acquisition of PA or other resistant pathogens, or with improved lung function decline, mortality, or transplantation. ConclusionsMany pwCF without chronic PA infection are receiving long-term treatment with inhaled antibiotics despite lack of support from clinical trials or practice guidelines. We did not observe improve outcomes with inhaled antibiotics. Our findings suggest controlled studies evaluating specific inhaled antibiotic regimens targeting specific pathogens or indications be performed to determine their effect.

Abbreviated 13C-mixed triglyceride breath test for detection of pancreatic exocrine insufficiency performs equally as standard 5-hour test in patients after gastrectomy performed for gastric cancer.

Background13C-mixed triglyceride breath test (13C-MTGT) is a non-invasive test for the detection of moderate and severe pancreatic exocrine insufficiency (PEI), but it requires prolonged breath sampling. The aim of this study was to determine the diagnostic power of abbreviated 13C-MTGT in detecting PEI in patients after subtotal and total gastrectomy performed due to gastric cancer.Subjects and methodsThis cross-sectional observational study included 3 groups of subjects; healthy controls, patients with subtotal and patients with total gastrectomy. Demographic and clinical data of patients were collected. Stool samples to determine faecal elastase (Fe-1) and chymotrypsin were collected and measured by ELISA. All subjects performed 5-hour 13C-MTGT breath test. The concentration and relative content of 13C in exhaled air was measured by isotope ratio mass spectrometer (IRMS). PEI was confirmed as values of 13C-exhalation < 26.8% after 5 hours.ResultsOverall, 65 participants were included into analysis, 22 having PEI (n = 11 after subtotal and n = 11 after total gastrectomy, both performed for gastric cancer). 13C-MTGT breath test showed difference in percent of exhaled 13C between PEI and non-PEI patients already after 60 minutes (p = 0.034). Receiver operating characteristic (ROC) curve analysis showed that cut-off value of 13.74% after 150 minutes is showing equivalent diagnostic power to the longer test with sensitivity and specificity both above 90% for the exclusion of PEI in patients after subtotal and/or total gastrectomy.ConclusionsIn this study abbreviated 13C-MTGT test could be shortened from 5 to 2.5 hours without decrease in its diagnostic accuracy for detection of PEI in patients with subtotal or total gastrectomy performed for gastric cancer. This allows significant time savings in the diagnostics of PEI in this subgroup of patients.

The Prevalence and Characteristics of Exocrine Pancreatic Insufficiency in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Background Exocrine pancreatic insufficiency (EPI) is common in patients with type 2 diabetes. However, the prevalence of EPI varies significantly in different studies. Untreated EPI in these patients can adversely affect their nutrition and metabolism. The aim of this study is to estimate the pooled prevalence of EPI in patients with type 2 diabetes and to explore the potential risk factors. Methods A systematic search was performed in PubMed, Web of Science, and Embase, which included studies meeting inclusion criteria from 1960 to 1 April 2022. Relevant articles were searched using the combination of Medical Subject Heading (MeSH) terms of “Type 2 diabetes” and “pancreatic exocrine insufficiency.” The Stata 16.0 software was used for data analyses. The random-effects model was used to estimate the pooled prevalence rates and 95% CI using “metaprop program.” Results The pooled prevalence of EPI was 22% (95% CI: 15%–31%) in patients with type 2 diabetes and 8% (95% CI: 4%–14%) of them developed severe pancreatic insufficiency. In the subgroup analyses, the prevalence of EPI in type 2 diabetes was correlated with geographic location. The prevalence in Asian countries (35%, 95% CI: 22%–49%) is higher than in Europe (18%, 95% CI: 10%–29%) and Australia (9%, 95% CI: 4%–16%). Furthermore, patients with higher insulin requirements, who are more likely to be insulin-deficient, have a higher prevalence of EPI. The pooled prevalence was 27% (95% CI: 17%–37%) in type 2 diabetes with higher insulin requirement (1 group) and 15% (95% CI: 1%–40%) in patients with lower insulin requirement (2 group). In addition, the morbidity of severe EPI in the higher insulin requirement group (12%, 95% CI: 7%–19%) was sextuple as much as the lower insulin requirement group (2%, 95% CI: 0%–13%). EPI was more common in subjects younger than 60 compared with elderlies (25% vs. 19%). Conclusion The prevalence of EPI in type 2 diabetes may be overestimated. Furthermore, the higher prevalence may be closely related to β-cell function. Endocrine disease therapy would potentially represent a novel therapeutic approach for patients with type 2 diabetes and EPI.

Risk factor analysis and nomogram development for steatorrhea in idiopathic chronic pancreatitis.

Steatorrhea, a sign of severe pancreatic exocrine insufficiency (PEI), is related to consequences caused by pancreatitis. This study aimed to identify predictors and to construct a nomogram for steatorrhea in idiopathic chronic pancreatitis (ICP). ICP patients admitted to our hospital from January 2000 to December 2013 were enrolled in this retrospective-prospective cohort study and randomly assigned to the training and validation cohorts. The cumulative rate of steatorrhea was calculated. A Cox proportional hazard regression model was used to identify predictors for steatorrhea and construct the nomogram. Internal and external validation of the nomogram was then performed. There were 1633 ICP patients enrolled, with a median follow-up duration of 9.8 years and 20.8% (339/1633) of patients developed steatorrhea following onset of ICP. Steatorrhea was observed in 93, 115, and 133 patients at 1, 3, and 5 years following diagnosis of CP, with a cumulative rate of 6.5% (95% confidence interval [CI] 5.1%-7.9%), 8.0% (95% CI 6.2%-9.8%), and 9.3% (95% CI 6.6%-12.0%), respectively. Male sex (hazard ratio [HR] 2.479, P < 0.001), diabetes mellitus at/before diagnosis of ICP (HR 2.274, P=0.003), and aged less than 18 years at onset of ICP (HR 0.095, P < 0.001) were identified risk factors for steatorrhea. Initial manifestations were associated with development of steatorrhea. The nomogram was proven to have good concordance indexes. We identified predictors and developed a nomogram for predicting steatorrhea in ICP. It was recommended that high-risk populations be followed up closely, which might contribute to the early diagnosis and treatment of PEI.

Exocrine pancreas functions in children with type 1 diabetes mellitus

Background and study aimWe evaluated exocrine pancreas functions using a noninvasive indicator in a case–control study conducted on children and adolescents diagnosed with type 1 diabetes mellitus. Patients and methodsSixty-seven patients who participated in a summer camp were enrolled in this study. Nineteen healthy children in the same age group were assigned to the control group. Fecal pancreatic elastase was assayed using the enzyme-linked immunosorbent assay technique. Values higher than 200 µg/g were considered an indication of sufficient exocrine pancreatic functioning, values between 100 µg/g and 200 µg/g were considered mild exocrine pancreatic insufficiency, and values below 100 µg/g were considered severe exocrine pancreatic insufficiency. ResultsThe mean concentration of fecal elastase was 158.38 ± 59.67 µg/g. The patients were assigned to three groups according to these values. Thirteen patients (22%) had sufficient fecal elastase levels, whereas 36 patients (62%) had mildly insufficient levels, and nine patients (16%) had severely insufficient fecal elastase concentrations. The levels of fecal elastase, amylase, lipase, and zinc were significantly different between the patients and controls (p < 0.001). Only the duration of diabetes was significantly different between patients with different severities of exocrine pancreatic insufficiency (p = 0.037). Additionally, the group with severe pancreatic insufficiency had more frequent hypoglycemic attacks. ConclusionExocrine pancreatic insufficiency may develop in children with diabetes, and hypoglycemia attacks are observed more frequently depending on the severity of pancreatic insufficiency.

The risk factors influencing severe pancreatic exocrine insufficiency measured by stool elastase after pancreatoduodenectomy

Pancreatic exocrine insufficiency after pancreatectomy affects clinical outcomes of patients in postoperative course. This study aimed to analyze risk factors influencing severe pancreatic exocrine insufficiency (PEI) after pancreaticoduodenectomy measured by patient's stool elastase (SE) level. Among patients who received pancreaticoduodenectomy in Seoul National University Hospital from October 2007 through February 2013, patients who measured both preoperative and postoperative SE level were included. Deteriorated (exocrine function) group was defined as patients who decreased from 100 µg/g or more preoperatively to less than 100 µg/g postoperatively. Of 202 included patients, 135 patients were deteriorated group and 67 patients were maintained group. Patients in deteriorated group had higher preoperative stool elastase level (309.6 vs. 143.0, p < 0.001), benign diseases (26.7% vs. 13.4, p = 0.033), presence of clinically relevant postoperative pancreatic fistula (19.3% vs. 7.5%, p = 0.029) compared to maintained group. Postoperative weight showed the lowest at postop 3 months and recovery at 12 months. Weight change in postop 3 months was significantly different between two groups (-4.6 vs. -3.5, p = 0.045). Patients who did not recover their weight of postop 3 months at postop 12 months had higher portion of adjuvant radiotherapy, presence of postoperative pancreatic fistula and high grade of complication compared to recovery group. Those with benign diseases and clinically relevant postoperative pancreatic fistula have a tendency of marked deterioration of pancreatic exocrine function after pancreatoduodenectomy. Therefore physicians should pay attention to support PEI in those with risk factors such as monitoring of exocrine function and optimal enzyme supplements.

Severe Genotype, Pancreatic Insufficiency and Low Dose of Pancreatic Enzymes Associate with Abnormal Serum Sterol Profile in Cystic Fibrosis.

Background: Several factors could lead to lipid disturbances observed in cystic fibrosis (CF). This study aimed to assess sterol homeostasis in CF and define potential exogenous and endogenous determinants of lipid dysregulation. Methods: The study involved 55 CF patients and 45 healthy subjects (HS). Sterol concentrations (μg/dL) were measured by gas chromatography/mass spectrometry. CF was characterised by lung function, pancreatic status, liver disease and diabetes coexistence, Pseudomonas aeruginosa colonisation and BMI. CFTR genotypes were classified as severe or other. Results: Campesterol and β-sitosterol concentrations were lower (p = 0.0028 and p < 0.0001, respectively) and lathosterol levels (reflecting endogenous cholesterol biosynthesis) were higher (p = 0.0016) in CF patients than in HS. Campesterol and β-sitosterol concentrations were lower in patients with a severe CFTR genotype, pancreatic insufficiency and lower pancreatic enzyme dose (lipase units/gram of fat). In multiple regression analyses, β-sitosterol and campesterol concentrations were predicted by genotype and pancreatic insufficiency, whereas cholesterol and its fractions were predicted by phytosterol concentrations, age, dose of pancreatic enzymes, nutritional status and genotype. Conclusions: Independent determinants of lipid status suggest that malabsorption and pancreatic enzyme supplementation play a significant role in sterol abnormalities. The measurement of campesterol and β-sitosterol concentrations in CF patients may serve for the assessment of the effectiveness of pancreatic enzyme replacement therapy and/or compliance, but further research is required.

Comparison of longterm exocrine and endocrine function following duct to mucosa versus dunking pancreaticojejunostomy in pancreaticoduodenectomy

Aim: Though survival following Pancreaticoduodenectomy (PD) has improved, long term impairment of exocrine and endocrine function remains problematic. This study aims at evaluating any difference in long term pancreatic function between those who underwent Duct to Mucosa Vs. Dunking PJ (pancreaticojejunostomy) following PD. Methodology: Patients who underwent PD between the year 2010-18 and were disease free on follow up were evaluated. Patients with chronic pancreatitis were excluded. All survivors beyond 18 months were evaluated for their pancreatic exocrine (Fecal Elastase-1) and endocrine (FBS/PPBS; HbA1c) function as per the Departmental protocol. The risk of developing nutritional impairment was assessed using the Mini Nutritional Assessment (MNA®) tool and by Serum albumin and Hemoglobin. Results: 136 patients satisfied the inclusion criteria. 30 day mortality was 5, 26 had expired and 53 were lost to follow up. Of the remaining 52 who were evaluated, 32 had dunking PJ, 20 had duct to mucosa PJ. Exocrine insufficiency was present in 29/32(90.6%) of dunking PJ and 17/20(85%) of duct to mucosa PJ (P = 0.24). 11(34.4%) & 4 (20%) had endocrine insufficiency in dunking and duct to mucosa groups respectively (P=0.21). Endocrine insufficiency was significantly higher in adjuvant chemoradiotherapy group (P=0.04). The relative risk of developing nutritional impairment in presence of severe pancreatic exocrine insufficiency was 2.68. Conclusion: Exocrine and Endocrine dysfunction post PD can occur irrespective of the type of pancreatic anastomosis and is comparable between the two groups. There appears to be a significant risk of nutritional impairment post PD.

Коррекция метаболических расстройств у больных раком поджелудочной железы

Presented the case of complex examination of a patient with pancreatic cancer using a bioimpedance method for assessing the nutritional status before and after surgical treatment. Provided the literature data related to this problem. The presented clinical case demonstrates the features of correction of the nutritional status of a patient with conditionally resectable pancreatic cancer in conditions of cholestasis, severe external pancreatic insufficiency and pancreatogenic diabetes mellitus on the background of constitutional obesity

Secretin-Enhanced Magnetic Resonance Cholangiopancreatography - A Reliable Approach to Assess Exocrine Pancreatic Function?

Objectives: To investigate the relation between exocrine pancreatic function and secretin-stimulated magnetic resonance cholangiopancreatography (sMRCP) fluid volumes and its concordance to pancreatic elastase using a case-control approach. Methods: Navigator-triggered T2-weighted 3D-turbo-spin-echo sMRCP was performed on a 1·5-T-system in 977 subjects including volunteers without a history of pancreatitis (group: A n=917) and chronic pancreatic disorder patients without (group: B, n=32) and with diagnosis of exocrine pancreatic insufficiency (EPI) (group: C, n=28). After intravenous administration of 1 unit/kg secretin duodenal filling was graded (0-3) and quantified as sMRCP fluid volume. According to pancreatic elastase ELISA subjects were grouped as severe (<100 μg/g) and moderate (100-200 μg/g) pancreatic elastase insufficiency (PEI). Statistic evaluation comprised Kruskal-Wallis Test, multinomial logistic, linear regression and area-under-the-curve (AUC) analysis. Findings: sMRCP fluid volume was lower in patients with pancreatic disorders compared to controls (P=0·001), but independent of the presence of PEI. The odds ratio of a reduced grading of duodenal filling was higher in patients with EPI (group: C compared to controls) (P=0·001) but not significantly different between controls and patients without EPI (group: B P=0·911) or between both patient groups (group: B versus group: C P=0·059). There was only a small association of sMRCP fluid volume with pancreatic elastase (R2=0·04,P=0·001). AUCs of sMRCP fluid volume were 0·967 (95%CI 0·950-0·985) to detect EPI and 0·581 (95% CI 0·471-0·691) to detect severe PEI. Interpretation: Static sMRCP allows assessment of exocrine pancreatic function and can differentiate patients with diagnosis of EPI from volunteers, but is not suitable for screening of patients with PEI because of its discordance to pancreatic elastase. Funding Statement: The work is part of the Community Medicine Research net, which was funded by following institutions: Federal Ministry of Education and Research (grants 01ZZ9603, 01ZZ0103, 01ZZ0403, 01ZZ0701, 03ZIK012), Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, Federal Ministry of Nutrition, Agriculture and Consumer’s Safety (07HS003), German Research Foundation (projects Gr 1912/5-1, Ko 799/5-1, Vo 955/5-1, Vo 955/6-1, Vo 955/10-1), Competence Network Heart Failure (01GI0205), Competence Network Diabetes (01GI0855), German Asthma and COPD Network (COSYCONET; BMBF 01GI0883), Genopathomik (BMBF FZK 03138010), Alfried Krupp von Bohlen und Halbach Foundation, Alexander v. Humboldt Foundation, Leibniz Society, Siemens AG, Health Care Sector (Erlangen, Germany), Pfizer Pharma GmbH (SBU Endocrinology and Ophthalmology; Berlin Germany), Novo Nordisk (Mainz, Germany), Data Input GmbH (Darmstadt, Germany), GABA International AG (Therwil, Switzerland), Imedos Systems (Jena, Germany) and Heinen and Lowenstein (Bad Ems, Germany). Declaration of Interests: There are no conflicts of financial interest. Ethics Approval Statement: The local ethics committee approved the SHIP study, and written informed consent was obtained from all participating subjects before study inclusion.

Inherited Cholestatic Diseases in the Era of Personalized Medicine.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-mack a video presentation of this article.

Cystic fibrosis related diabetes in Europe: Prevalence, risk factors and outcome; Olesen et al

BackgroundCystic fibrosis related diabetes (CFRD) has implications for morbidity and mortality with several risk factors identified. We studied the epidemiology of CFRD in the large dataset of the European Cystic Fibrosis Society Patient registry. MethodsData on CF patients were investigated for the prevalence of CFRD as well as for any association with suggested risk factors and effects. ResultsCFRD increased by approximately ten percentage points every decade from ten years of age. Prevalence was higher in females in the younger age groups. CFRD was associated with severe CF genotypes (OR = 3.11, 95%CI: 2.77–3.48), pancreatic insufficiency (OR = 1.46, 95%CI: 1.39–1.53) and female gender (OR = 1.28, 95%CI: 1.21–1.34). Patients with CFRD had higher odds of being chronically infected with Pseudomonas aeruginosa, Burkholderia cepacia complex and Stenotrophomonas maltophilia than patients without CFRD, higher odds of having FEV1% of predicted <40% (OR = 1.82, 95%CI: 1.70–1.94) and higher odds of having BMI SDS ≤−2 than patients without CFRD (OR = 1.24, 95%CI: 1.15–1.34). ConclusionsSevere genotype, pancreatic insufficiency and female gender remain considerable intrinsic risk factors for early acquisition of CFRD. CFRD is associated with infections, lower lung function and poor nutritional status. Early diagnosis and aggressive treatment of CFRD are more important than ever with increasing life span.

Multicystic adenomatoid hamartoma of the pancreas

Abstract Multicystic adenomatoid hamartoma is an extremely rare tumor of the pancreas, with only 4 other cases reported in the literature. We report a case of a 4-year old boy who presented with an 8 month history of abdominal pain, steatorrhea, and failure to thrive. Work-up showed severe pancreatic insufficiency and a large, multiseptated, cystic mass originating from the head of the pancreas and compressing the duodenum. The child underwent a classic pancreaticoduodenectomy with portal vein reconstruction. He tolerated the procedure well and has been seen in follow-up.