Severe Exocrine Pancreatic Insufficiency Research Articles

Comparative analysis of the intestinal microbiota in patients with exocrine pancreatic insufficiency of various severity

Exocrine pancreatic insufficiency (EPI) is a critical host factor in determining the composition of the gut microbiota. Diseases that cause exocrine insufficiency can affect the gut microbiome, which can potentiate disease progression and complications. To date, the relationship of exocrine insufficiency in various pancreatic (PA) pathologies, in chronic pancreatitis (CP), with dysbiotic changes in the intestinal microbiota (IM) has not been reliably studied. The available data are heterogeneous and contradictory, which determines the need for further research. To conduct a comparative analysis of the taxonomic composition of the intestinal microbiota in patients with CP of various etiologies, without or with the presence of EPI of varying severity, as well as patients with severe EPI with a history of surgical intervention (SI) on the pancreas. A total of 85 patients were included in the study. Patients were divided into groups according to the severity of EPI: Group 1 (n=16) - patients with CP without EPI; Group 2 (n=11) - patients with CP and mild EPI; Group 3 (n=17) - patients with severe CP and EPI; Group 4 (n=41) - severe EPI in persons with a history of SI on the pancreas. Verification of CP was carried out according to clinical, anamnestic and instrumental data. The degree of EPI was determined by the level of pancreatic elastase-1 (PE-1) feces. Informed consent for the study was obtained for each patient, an anamnesis was collected, physical and laboratory examinations were performed, and a stool sample was obtained. DNA was extracted from each stool sample, the taxonomic composition of BM was determined by sequencing the bacterial 16S rRNA genes, followed by bioinformatic analysis. We followed the changes in the gut microbiota from a group of patients with CP without EPI to a group with severe EPI, in those who underwent SI. At the level of the phylum, the IM of all groups showed the dominance of Firmicutes, with the lowest representation in the severe EPI group, both with SI and CP, and the growth of the Actinobacteria, Verrucomicrobiota and Fusobacteria types. The differential representation of childbirth varied: in patients with severe EPI and CP, compared with mild, statistically significant genera - Akkermansia, Ruminococcus gauvreauii group and Holdemanella; compared with CP without exocrine insufficiency, Prevotella, Ruminococcus gauvreauii group, Peptostreptococcus and Blautia dominated. The CP group with mild EPI was dominated by the following genera: Lachnospiraceae_ND 2004 group, Faecalitalea, Fusobacterium, Catenibacterium, Roseburia, Atopobium, Cloacibacillus, Clostridium innococum group, Ruminococcus torques group. All groups showed a low diversity of taxa with a predominance of opportunistic flora, including participants in oncogenesis. The results of the study show that patients with CP of various etiologies and patients with severe EPI who underwent specific intervention on the pancreas have intestinal microbiota dysbiosis, the severity of which is significantly influenced by the degree of EPI.

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.

Exocrine Pancreatic Insufficiency is Undiagnosed in Some Patients with Diarrhea-Predominant Irritable Bowel Syndrome Using the Rome IV Criteria.

Irritable bowel syndrome (IBS) is one of the most frequent disorders in clinical practice, with a mean 7.6-10.8% worldwide prevalence. A study showed that 6.1% of patients with diarrhea-predominant IBS (IBS-D) had severe exocrine pancreatic insufficiency (EPI). We aimed to identify the prevalence of EPI based on fecal elastase stool testing (Fel-1) in IBS-D and the clinical characteristics that may predict the diagnosis of EPI. Patients aged > 18years presenting to tertiary hospital outpatient clinics with IBS-D completed validated questionnaires and gave a stool sample where Fel-1 concentration was measured. Patients with Fel-1 < 100µg/g represented EPI and > 100 to < 200µg/g underwent testing for pancreatic pathology with laboratory and endoscopic ultrasound (EUS) evaluation. One hundred forty patients (mean age 60years, females 75.7%) were studied. EPI was found in 5% (95% CI 2.2-10.4), and pancreatic steatosis was the main EUS finding (71%). Dyspepsia was an independent factor associated with EPI (OR 34.7; 95% CI 4.95-366.37, p = 0.0007). After pancreatic enzyme replacement therapy (PERT), patients showed a significant improvement in the Bristol stool scale (p < 0.0001), bowel movements per day (p < 0.005), distension score (0.0009), pain score (0.0277) and IBS severity (0.0034). EPI is present in 5% of patients who fulfill Rome IV criteria for D-IBS, and dyspepsia was an independent symptom strongly associated with EPI. Pancreatic steatosis was the main endoscopic ultrasound finding. After PERT therapy, patients had significantly improved stool frequency, stool consistency, abdominal pain, distension and IBS severity score.

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.

Clinical and Analytical Characterization of the DiaSorin and ScheBo Fecal Pancreatic Elastase 1 Assays

Fecal pancreatic elastase (PE) assays are screening tests for exocrine pancreatic insufficiency (EPI). We analytically evaluated a new PE assay and retrospectively analyzed data from an academic hospital and reference laboratory to understand the clinical utility. Forty stool samples with different PE concentrations were tested on the ScheBo enzyme-linked immunosorbent assay (ELISA) versus DiaSorin LIAISON immunoassay; a simple-to-use extraction device was assessed. The cross-reactivity of porcine enzymes was investigated in the immunoassay. Charts of 207 patients with PE results less than 250 μg/g at an academic hospital were reviewed, and data were analyzed for 5136 patients with repeat PE results from a reference laboratory. The LIAISON immunoassay gave comparable results to the ScheBo ELISA, with 87.5% agreement of PE results in classifying as sufficient, mild/moderate insufficiency, or severe insufficiency. The extraction device worked well compared with manual weighing, and no cross reactivity with porcine enzymes was observed. In agreement with prior studies, our clinical data suggested that PE assays were most useful in detecting severe EPI. The new DiaSorin LIAISON immunoassay preforms similarly to the well-known ScheBo ELISA. Pancreatic elastase assays can help identify patients with severe EPI but are not as useful in classifying mild/moderate EPI.

Risk factors deteriorating severe exocrine pancreatic insufficiency measured by stool elastase after pancreatoduodenectomy and the risk factors for weight loss.

PurposeThe measurement of stool elastase (SE) level is useful for evaluating pancreatic exocrine function. This study aimed to determine the risk factors for severe exocrine pancreatic insufficiency (EPI) after pancreatoduodenectomy (PD), and analyze serial changes in nutritional markers and weight based on the SE level.MethodsAmong patients who underwent PD for periampullary disease, patients whose preoperative and postoperative SE levels were measured were included in the study. The deteriorated (exocrine function) group comprised patients whose SE levels decreased from ≥100 µg/g preoperatively to <100 µg/g postoperatively. Patients whose weight 12 months postoperatively was greater than that 3 months postoperatively were classified into the weight-recovery group.ResultsOf the 202 included patients, the deteriorated group had a higher incidence of preoperative SE level above 200 µg/g, benign pathology, and the presence of a clinically relevant postoperative pancreatic fistula than the maintained group. Patients who did not undergo weight recovery had a higher rate of history of adjuvant radiotherapy compared to the no-recovery group.ConclusionThe evaluation of EPI by measuring SE alone is not sufficient because it does not reflect the nutritional status of patients, and a comprehensive approach that considers other parameters is required for EPI management.

Cystic Fibrosis in two Ghanaian Children

Cystic fibrosis (CF) is a severe life-limiting genetic disorder resulting from mutations in the cystic fibrosis transmembrane regulator gene and is reported to be more prevalent among Caucasians than people of African descent. The past three decades have seen a gradual increase in the reporting of CF in non-European populations with CF in all regions including Africa. We report on the first two known Ghanaian children diagnosed with CF presenting early in infancy. The first patient presented with severe acute malnutrition and persistent diarrhea resulting from severe exocrine pancreatic insufficiency. In the second patient, there were recurrent wheeze and recurrent pneumonia, severe dehydration with metabolic alkalosis. Diagnosis of CF in Ghana is challenging due to the absence of diagnostic tools such as sweat testing equipment. In the first patient, sweat testing and genetic testing were done in South Africa. In the second patient, sweat testing was not done but diagnosis was confirmed by genetic testing. Both patients presented with classical CF symptoms including Pseudomonas aeruginosa airway infection before age 6 months. Both children are currently alive and healthy on appropriate treatment. These case reports highlight the growing evidence of CF occurring in people of African descent and the diagnostic challenges faced in Africa.

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.

Analysis between vitamin D receptor Bsml polymorphism and exocrine pancreatic insufficiency in patients with comorbidity: chronic pancreatitis and chronic obstructive pulmonary disease

The objective of the research is to analyze the association of Bsml polymorphism of the vitamin D receptor gene in patients with comorbidity - chronic pancreatitis (CP) and chronic obstructive pulmonary disease (COPD), as well as to correct the serum vitamin D level.Material and methods. The study included 57 patients with CP with concomitant COPD, who were hospitalized in the gastroenterology department of the Chernivtsi Regional Clinical Hospital. COPD was in a state of stable or unstable remission. The average age of the examined patients was 52.36 ± 1.83 years. The inclusion criterion was vitamin D deficiency diagnosed in patients with chronic pancreatitis and chronic obstructive pulmonary disease. The exclusion criterion was another nosology that could cause disorders of vitamin D metabolism. Results. 57 patients had vitamin D deficiency. No patients with normal vitamin levels were recorded. Thus, the average level of vitamin D in respondents with vitamin D deficiency was 36.13 ± 7.61. After genotyping and distribution according to a specific genotype, a vitamin deficiency correction scheme was selected. Cholecalciferol at a dose of 6000 IU for 2 months was prescribed for the G/G genotype patients. Patients with G/A and A/A genotypes received the same drug at a dose of 8000 IU for 2 months, followed by determination of serum vitamin D levels.Conclusions. For patients with A allele (genotypes AA and AG), the genetic risk of developing vitamin D deficiency is higher than the average population level. For patients with moderate and severe exocrine pancreatic insufficiency and signs of malabsorption syndrome, it is recommended to check not only the level of 25 (OH) D in the serum, but also to determine the polymorphic variant of the VDR gene to approve further treatment tactics - determine the optimal dose and check its effectiveness.

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.

Los criterios de Rosemont en ultrasonografía endoscópica: ¿son predictores de insuficiencia pancreática exocrina?

Endoscopic ultrasonography is the method of choice for detection of morphologic changes related to chronic pancreatitis. There are criteria, in the literature, that evaluate morphologic changes by endoscopic ultrasonography suggestive of chronic pancreatitis. The most widely used are the Rosemont criteria. Currently, the most effective diagnostic methods for exocrine pancreatic insufficiency are fat quantification (disused) and the 13C-mixed triglyceride breath test, not available in our country. However, the probability of diagnosis of pancreatic insufficiency can be estimated over the base of symptoms, malnutrition parameters, faecal elastase and signs of chronic pancreatitis in images. The aim of this study was to determine the correlation, probability and severity of exocrine pancreatic insufficiency, according to Rosemont criteria, in patients with chronic pancreatitis. A retrospective descriptive study was performed. Data were collected from patients between April of 2017 and April of 2018. The data gathered was based on pancreatic morphologic characteristics according to Rosemont criteria and related to the diagnosis of exocrine pancreatic insufficiency diagnosis based on the levels of stool elastase. Twenty one patients with chronic pancreatitis were included. The presence of hyperechogenic foci &gt; 2 mm with posterior acoustic shadowing was associated with the presence of severe exocrine pancreatic insufficiency (p &lt; 0.001). In our study, the association between parenchymal morphologic findings of chronic pancreatitis was significant in predicting exocrine pancreatic insufficiency. The role of endoscopic ultrasonography in predicting functional compromise in patients with chronic pancreatitis is promising.

Effect of Pancrelipase Therapy on Exocrine Pancreatic Insufficiency Symptoms and Coefficient of Fat Absorption Associated With Chronic Pancreatitis.

The aim of this study was to evaluate whether improvement in coefficient of fat absorption (CFA) with pancreatic enzyme replacement therapy correlates with clinical symptoms in patients with chronic pancreatitis with moderate to severe exocrine pancreatic insufficiency. Data were pooled from 2 randomized double-blind trials of the effects of 1 week of pancrelipase (n = 59) versus placebo (n = 57) on CFA and stool frequency, stool consistency, abdominal pain, and flatulence; 1 trial included a 51-week open-label pancrelipase treatment period (n = 34). Compared with placebo, significantly more patients receiving pancrelipase reported decreased stool frequency at week 1 (72% vs 38%; P < 0.001). Although 30% of patients receiving pancrelipase and 20% receiving placebo reported improved stool consistency, changes in stool consistency, abdominal pain, and flatulence were not different between groups. Mean CFA absolute change from baseline was significantly greater with pancrelipase versus placebo (24.7% vs 6.4%; P < 0.001). Improvements in stool consistency and frequency correlated with CFA improvement. Symptom improvements persisted or further improved through 52 weeks of treatment. Pancrelipase significantly improved exocrine pancreatic insufficiency maldigestive symptoms. Improvements in objective stool symptoms with pancreatic enzyme replacement therapy correlated with CFA improvement at 1 week.

Assessment of bioelectrical impedance analysis in patients with chronic pancreatitis and chronic obstructive pulmonary disease considering exocrine pancreatic insufficiency

The article describes and analyzes the results of bioelectrical impedance analysis in patients with chronic pancreatitis and chronic obstructive pulmonary disease considering the level of fecal elastase-1.The aim of our study was to investigate the features of Bioelectrical impedance analysis in patients with chronic pancreatitis (CP) and chronic obstructive pulmonary disease (COPD) considering the level of fecal elastase-1.Materials and methods. We examined 84 patients: 30 patients with CP and 54 patients with comorbid pathology - CP and COPD aged 30-65 years (52.36 ± 1.83 years). Patients were hospitalized in the gastroenterology department of theRegionalClinicalHospital,Chernivtsy,Ukraine with exacerbation of CP. COPD was in stable or unstable remission. Fecal elastase-1 level was determined by using the Pancreatic Elastase ELISA (BIOSERV Diagnostics). Biometric measurements were performed with a body composition analyzer BC-601 (TANITA,Japan). All examined patients were divided into groups depending on the exocrine pancreatic insufficiency (EPI): severe (n=9), moderate (n=34), mild (n=23) and normal (n=18).Results. The group of patients with severe EPI was characterized by weight loss. It can be explained by the appearance of absorption disorders of nutrients (malabsorption and maldigestion syndromes). In the groups of moderate and mild EPI fat and cell mass were significantly lower than normal rate in control group. There is a positive correlation between fecal elastase-1 and the level of patients’ metabolism (p&lt;0,05).Conclusions. Bioelectrical impedance analysis (percentage of fat mass, visceral fat level and muscle mass) correlates with the level of fecal elastase-1, which can be used as an additional criteria for the severity of CP and for the control of the effectiveness of substitution therapy.

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.

Pancreatic steatosis: a giant step forward or recognition of ignorance

This review analyzes the terminology of pancreatic steatosis, the data about the prevalence of non-alcoholic fatty pancreas disease (NAFPD) were given.&#x0D; The etiological factors of NAFPD are usually subdivided into hereditary, metabolic, and toxic ones. The main etiopathogenetic factor of pancreatic fatty infiltration is obesity: it causes pancreatic infiltration by adipocytes, leading to the development of NAFPD. The pathogenesis of the disease is associated with adipocytic tissue dysfunction, which induces local and systemic inflammatory response with corresponding clinical consequences. Insulin resistance and oxidative stress play major role in the pathogenesis of NAFPD. From a histological point of view, NAFPD is a heterogeneous process, characterized by excessive intracellular accumulation of lipids and fatty infiltration followed by fatty replacement of the pancreas.&#x0D; NAFPD clinical picture is asymptomatic and nonspecific. Diagnosis of NAFPD is based primarily on the results of imaging methods (ultrasound, CT, MRI). A consequence of NAFPD is exocrine pancreatic insufficiency requiring enzyme replacement therapy. One of the NAFPD complications is the development of pancreatic adenocarcinoma.&#x0D; Currently, standards for the diagnosis, treatment and management of patients with NAFPD have not been developed yet, but on used the guidelines for the treatment of non-alcoholic fatty liver disease (rational diet, exercises, weight loss). The “gold standard” of enzyme replacement therapy, such as Creon®, is used for correction of exocrine pancreatic insufficiency. The detailed analysis of the clinical case of total pancreatic steatosis with severe exocrine pancreatic insufficiency was done in this article.

Painless chronic pancreatitis

BackgroundPainless chronic pancreatitis (CP) is a rare form of the disease. AimTo evaluate the prevalence and the characteristics of this overlooked form of pancreatitis. MethodsPatients with a diagnosis of CP and absence of pain were selected, excluding patients suffering from autoimmune pancreatitis. Clinical data, imaging features, and exocrine and endocrine function were therefore analyzed. ResultsAmong 781 patients observed between 2010 and 2016, 74 patients with painless CP (9.5%) were selected. Mean age at diagnosis was 60.8 (SD 10.8) years. 38(51%) individuals did not report any symptom, 36(49%) were affected by symptoms other than pain. Pancreatic calcifications were diagnosed in 70 patients (95%), main pancreatic duct dilation in 55(74%), and pancreatic atrophy in 39(53%).Thirty-six patients (55%) had severe exocrine pancreatic insufficiency(EPI). Diabetes was observed in 34 out of 72 patients (47%). During a mean follow-up of 2.9 (SD 2.8) years, only a mild pancreatitis was diagnosed in a 71-year old female. No patient underwent endoscopic treatment or surgery, developed pancreatic cancer or died. ConclusionsIn a tertiary center painless CP is observed in 10% of cases, and it is frequently associated with EPI. The probability of onset of pain is very low in a short-term follow-up.

Study of the gastrointestinal bioavailability of a pancreatic extract product (Zenpep) in chronic pancreatitis patients with exocrine pancreatic insufficiency

IntroductionThe Food and Drug Administration in 2006 required that all pancreatic enzyme products demonstrate bioavailability of lipase, amylase, and protease in the proximal small intestine. MethodsIn this phase I open-label, randomized, crossover trial, 17 adult chronic pancreatitis (CP) patients with severe exocrine pancreatic insufficiency (EPI) underwent two separate gastroduodenal perfusion procedures (Dreiling tube suctioning and [14C]-PEG instillation by an attached Dobhoff tube in the duodenal bulb). Patients received Ensure Plus® alone and Ensure Plus with Zenpep (75,000 USP lipase units) in random order. The bioavailability of Zenpep was estimated by comparing the recovery of lipase, amylase, chymotrypsin activity in two treatment conditions. 14C-PEG was used to correct duodenal aspirates volume. The primary efficacy endpoint was lipase delivery in the duodenum after Zenpep administration under fed conditions. Secondary efficacy endpoints included chymotrypsin and amylase delivery, serum CCK levels, and measuring duodenal and gastric pH. ResultsZenpep administration with a test meal was associated with significant increase in duodenal aspiration of lipase (p = 0.046), chymotrypsin (p = 0.008), and amylase (p = 0.001), compared to the test meal alone, indicating release of enzymes to the duodenum. Lipase delivery was higher in the pH subpopulation (the efficacy population with acid hypersecretors excluded) (p = 0.01). Recovery of [14C]-PEG was 61%. Zenpep was generally well tolerated. All adverse events were mild and transient. ConclusionsIn CP patients with severe EPI, lipase, chymotrypsin and amylase were released rapidly into the duodenum after ingestion of Zenpep plus meal compared to meals alone. Results also reflected the known pH threshold for enzyme release from enteric coated products.

Occurrence of exocrine pancreatic insufficiency in patients with advanced neuroendocrine tumors treated with somatostatin analogs

BackgroundAlthough exocrine pancreatic insufficiency (EPI) has been described in patients with neuroendocrine neoplasia (NEN) treated with somatostatin analogs (SSAs), its role in the therapeutic management of these patients is not well established. AimTo determine the frequency of EPI in patients with NEN long-term treated with SSAs. MethodsThis is a prospective single-center study evaluating 35 patients treated with SSAs for >12 months due to unresectable/advanced nonpancreatic well-differentiated NEN. Clinical evaluation, biochemical parameters, and fecal elastases 1 (FE-1) were assessed to diagnose EPI. ResultsA total of 7 patients (20%) had EPI, given the presence of abdominal symptoms and a median FE-1 value of 180 mcg/g stool (150–198). No patient had severe EPI, defined as FE-1 < 100 mcg/g stool. Elevated glycated Hb levels were a significant predictor for developing EPI (OR 4.81, p = 0.01). No significant difference in terms of duration of SSA treatment was observed between patients with or without EPI diagnosed (84 months and 72 months, respectively; p = 0.950). ConclusionsMild-moderate EPI is a relatively common condition in patients receiving long-term treatment with SSAs. Specific clinical and biochemical evaluations, including FE-1, should be planned in these patients to diagnose this relevant condition early, which may deteriorate quality of life and cause malnutrition.

Effectivity of Pancreatic Enzyme Replacement Therapy in Malnourished Children.

Malnutrition is commonly seen in children with exocrine pancreatic insufficiency (EPI). Pancreatic enzyme replacement therapy (PERT) is the mainstay treatment of acute malnutrition in children detected with a disease closely associated with EPI (eg, cystic fibrosis). The effectiveness of PERT in children with malnutrition without any chronic disease, however, remains unclear. The aim of this study was to investigate the effectiveness of PERT on weight gain and EPI in children classified as moderately and severely malnourished according to the World Health Organization (WHO) classification. The study included a total of 40 children aged 2-16 years who were classified as moderately and severely malnourished according to the WHO classification. The patients were randomly divided into 2 groups: PERT group (n = 20) received 2000 U lipase/kg/day (in 4 doses) in addition to hypercaloric enteral supplements and control group received hypercaloric enteral supplements only. In both groups, anthropometric measurements and the assessment of fecal elastase-1 (FE-1) levels were performed both at first admission and at the end of the 8-week treatment period. On the basis of WHO classification, 10 (25%) children were classified as severely malnourished and 30 (75%) children as moderately malnourished. EPI was detected in all the patients, among whom 24 (60%) patients had severe EPI. At the end of the treatment, body weight, height, and body mass index (BMI) increased significantly in both groups compared to their pre-treatment values, whereas no significant difference was found with regard to waist circumference (WC) and FE-1 levels. Similarly, no significant difference was found between pre- and posttreatment measurements of PERT and control groups (P > 0.05) and between pre- and posttreatment measurements of patients with moderate and severe malnutrition (P > 0.05). Malnutrition remains a serious public health problem, and thus, the development of novel treatment methods is highly essential. PERT is one of the most commonly considered alternatives, although there is little documentation of PERT in the literature. In the present study, although PERT resulted in higher weight gain, it established no significant difference between the 2 groups.