Differences in In Vitro Properties of Pancreatin Preparations for Pancreatic Exocrine Insufficiency as Marketed in Russia and CIS.

BACKGROUND: Pancreatic enzyme-replacement therapy (PERT), provided as pancreatin to patients with pancreatic exocrine insufficiency (PEI), is considered an essential substitute for the pivotal physiological function the pancreas fulfills in digestion. PEI involves a reduction in the synthesis and secretion of pancreatic enzymes (lipase, protease, amylase), which leads to an inadequate enzymatic response to a meal and consequently to maldigestion and malabsorption of nutrients. The efficacy of PERT is strongly dependent on enzyme activity, dissolution, and pancreatin particle size. OBJECTIVE: The physiological properties of eight pancreatin preparations (nine batches; five different brands) available in Russia and CIS (Commonwealth of Independent States: Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Uzbekistan) were investigated. METHODS: The lipase activity, dissolution, and particle size distribution of samples from multiple batches of pancreatin of different strengths were measured. RESULTS: Regarding lipase activities, all pancreatin preparations except Micrazim® matched the labeled content. Considerable differences were observed in particle size and dissolution. CONCLUSION: Pancreatin preparations available in Russia and CIS demonstrate product-to-product and batch-to-batch variability regarding the measured properties of lipase activity, dissolution, and particle size. This may impact the efficacy of PERT and therefore clinical outcomes.

Preventive Effect of High-Dose Digestive Enzyme Management on Development of Nonalcoholic Fatty Liver Disease after Pancreaticoduodenectomy: A Randomized Controlled Clinical Trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a complication of pancreaticoduodenectomy (PD). We conducted a randomized clinical trial to determine if high-dose digestive enzymes prevented the development of NAFLD after PD. STUDY DESIGN: This parallel-group, nonblinded, multicenter study enrolled patients undergoing elective PD at Shinshu University School of Medicine, from June 2011 to April 2017. Patients were randomly assigned to receive normal-dose (Excelase: 3.0 g/day [Meiji Seika Pharma Holdings Co, Ltd]) or high-dose digestive enzyme treatment (Excelase: 3.0 g/day; Pancreatin [Tokyo Chemical Industry Co Ltd]: 3.0 g/day; Berizym [Kyowa Pharmaceutical Industry Co Ltd]: 3.0 g/day; and Toughmac-E [Ono Pharmaceutical Co, Ltd]: 3.0 g/day) within 1 week after surgery. Because patients in the control group switched interventions upon receiving a diagnosis of NAFLD, intention-to-treat analysis was used. The primary endpoint was incidence of NAFLD within 1 year, and the secondary endpoints were the incidences of NAFLD at 1, 3, 6, and 12 months and the rate of improvement in NAFLD with high-dose transfer in the control group. The secondary analysis comprised assessment of risk factors for the development of NAFLD. RESULTS: Eighty-four patients were randomly assigned (42 per group), 80 of whom were finally analyzed (39 normal-dose, 41 high-dose). The incidence of NAFLD was significantly lower in the high-dose (8 of 41) compared with the normal-dose (25 of 39) patients (p < 0.001). Multivariate analysis identified normal-dose (odds ratio [OR] 14.65, p < 0.001), total protein ≤ 6.5g/dL (OR 9.01, p = 0.018), pre-albumin ≤ 22.0 mg/dL (OR 7.71, p = 0.018), and pancreatic function diagnostic test ≤ 70% (OR 6.66, p = 0.009) as independent risk factors. There were no adverse effects. The model was accurate (c-index = 0.92) and reliable (Hosmer-Lemeshow test p = 0.32). CONCLUSIONS: High-dose administration of digestive enzymes significantly reduced the onset of NAFLD after PD compared with normal-dose administration. Registration number: UMIN000005595 (http://www.umin.ac.jp/ctr/).

[The effectiveness of pancreatic enzyme replacement therapy using microencapsulated pancreatin preparations in the correction of nutritional status in patients with chronic pancreatitis: a prospective observational study].

AIM: The goal is to evaluate the effectiveness of pancreatic enzyme replacement therapy (PERT) using microencapsulated pancreatin preparations for the correction of nutritional status in patients with chronic pancreatitis (CP) and associated exocrine pancreatic insufficiency (EPI). MATERIALS AND METHODS: The study included 58 patients with CP who were divided into two groups depending on the results of a laboratory assessment of indicators of nutritional status: group I (n=30) consisted of patients with CP and signs of EPI (according to low elastase test values) without deviations in nutritional status; Group II (n=28) consisted of patients with CP with a EPI and an abnormal nutritional status. In both groups, patients during the entire observation period (8-12 months) received PERT using microencapsulated pancreatin preparations at a dose adjusted for the severity of permanent residence permit. Before and after the PERT course, the dynamics of anthropometric [body weight, body mass index (BMI)] and laboratory indicators of nutritional status (total protein, albumin, vitamins D and B12, transferrin, iron and magnesium) were evaluated. RESULTS: After the completion of PERT, a significant tendency towards an increase in BMI in patients was noted in both groups. In group I, this indicator increased from 21.45 [95% confidence interval (CI) 19.80-23.92] kg/m2 to 22.15 (95% CI 20.31-23.86) kg/m2, and in II group - from 19.22 (95% CI 18.33-21.99) kg/m2 to 22.0 (95% CI 19.97-24.08) kg/m2. At the same time, the duration of PERT (months) significantly correlated with the dynamics of the patient's body weight (r=0.4679; 95% CI 0.2384-0.6479, p=0.0002). When assessing laboratory markers of nutritional status after PERT, a general tendency was found to increase the levels of total protein, albumin, vitamin D, magnesium, transferrin, and iron in both groups, however, statistically significant differences in the dynamics were observed mainly in group II patients. So, the level of total protein in group II increased from 69.05 (95% CI 65.6717-70.9000) g/l to 72.8 (95% CI 71.1358-74.9000) g/l, vitamin D - from 10.6 (95% CI 32.8397-38.9603) ng/ml to 17.1 (95% CI 12.0166-23.6232) ng/ml, magnesium - from 0.72 ( 95% CI 0.6892-0.7825) mmol/L to 0.795 (95% CI 0.7692-0.8800) mmol/L, and transferrin from 2.91 (95% CI 2.1800-3.3656 ) g/l to 2.92 (95% CI 2.4000-3.5200) g/l. CONCLUSION: A prospective observational study demonstrated the effectiveness of PERT using microencapsulated pancreatin preparations in the correction of nutritional status in patients with CP.

Two cases of agenesis of the dorsal pancreas and a review of the literature.

BACKGROUND: Agenesis of the dorsal pancreas (ADP) is a very rare disease with no specific symptoms, and the pathogenesis is not clear. Some patients will be accompanied by other diseases, such as pancreatic tumor or pancreatitis. But most cases are very atypical and difficult to distinguish. Some syndromes of pancreatic exocrine insufficiency are common in patients with ADP. Here, we report two cases of ADP and summarize the clinical features, diagnosis, and treatment of ADP. CASE PRESENTATION: Case A is a 65-year-old Chinese woman who presented with abdominal pain accompanied by nausea, bloating and acid reflux. The enhanced abdominal CT scan found nothing meaningful except the absence of the body and tail of the pancreas. The diagnosis was considered as gastrointestinal dysfunction cause by exocrine pancreatic insufficiency and recovered after symptomatic treatment. Case B is a 61-year-old Chinese woman who presented with abdominal pain accompanied by fever, vomiting and bloating. The abdominal CT showed multiple stones in the gallbladder, and the body and tail of the patient's pancreas were absent. She was diagnosed with cholelithiasis and recovered after laparoscopic cholecystectomy. CONCLUSION: Agenesis of the dorsal pancreas (ADP) is a rare congenital disease with an unclear pathogenesis that presents multiple symptoms. It should be considered when the patients have non-specific, persistent and unexplained symptoms such as bloating or uncontrolled blood sugar. Imaging examination is helpful for diagnosis. And it does not require surgical intervention unless it accompanies other diseases, EPI need to be considered when the non-specific gastrointestinal symptoms appear.

[Treatment of postprandial discomfort syndrome in the elderly: a multi-centered prospective randomized controlled clinical study].

Objective: To evaluate the efficacy and safety of Oryz-Aspergillus enzyme and pancreatin tablets (Combizym(®)) in the treatment of postprandial distress syndrome (PDS) in the elderly, compared with gastrointestinal motility drugs. Methods: A prospective randomized controlled trial was designed and registered in the China Clinical Trials Registry (ChiCTR-IPR-16008185). The elderly patients with PDS were randomly divided into three groups, including Mosapride group with Mosapride citrate tablets 5 mg 3 times per day for 2 weeks; Combizym(®) group with Combizym tablets 244 mg 3 times per day for 2 weeks; combined treatment group with both drugs and same doses for 2 weeks. The modified Nepean dyspepsia index (NDSI) score, discomfort intensity score and PDS score were calculated on patients before treatment, at the end of first and second week of treatment, as well as 4 weeks after treatment finished, respectively. Adverse effects were evaluated. Results: A total of 323 patients from 16 tertiary hospitals in China were enrolled in this study. Among them, 105 patients were in Mosapride group, 109 in Combizym(®) group and 109 in combined treatment group. There were 148 males (45.8%) and 175 females (54.2%) with median age 71.4±9.0 years (60-100 years). Baseline characteristics of three groups were comparable. After treatment, the NDSI scores in three groups all decreased significantly (P<0.001), while they were similar between groups (P>0.05). The discomfort intensity score and PDS score in three groups showed a significant reduction after treatment (P<0.001), especially in the combined treatment group. Compared with Mosapride group, the scores in Combizym(®) group decreased significantly after one or two weeks [discomfort intensity score: after one week, 4.0(2.5, 8.0) vs. 6.0(3.0, 10.0); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 6.0); all P<0.05. PDS score: after one week, 6.0(3.0, 9.0) vs. 7.0(3.5, 10.5); after two weeks, 3.0(0.0, 5.0) vs. 4.0(2.0, 7.0); all P<0.05]. The efficacy rate in all patients after first week of treatment was over 15.0%. The efficacy rates after two weeks were 55.2%, 68.8% and 73.4% in Mosapride group, Combizym(®) group and combined treatment group, respectively. After two week treatment, the efficacy rates in Combizym(®) group (P=0.041) and combined group (P=0.006) were higher than that of Mosapride group. The recurrence rate of Mosapride group was 9.5%, which was significantly higher than that of Combizym(®) group (1.8%, P<0.05) and combined treatment group (1.8%, P<0.05). There were no serious adverse effects in the three groups. Conclusions: The efficacy of Oryz-Aspergillus enzyme and pancreatin tablets is comparable with that of Mosapride in elderly PDS patients, with fewer adverse effects and low recurrence rate. Combination regimen indicates better efficacy than that of Oryz-Aspergillus enzyme and pancreatin tablets or Mosapride alone.

Treatment of Severe Protein Malnutrition After Bariatric Surgery.

BACKGROUND: Severe protein malnutrition, with a serum albumin < 25 g/L, is one of the complications that may develop after bariatric surgery. It is associated with increased morbidity and mortality and requires timely diagnosis and appropriate treatment to prevent rapid clinical deterioration. However, evidence-based recommendations for a specific treatment approach are currently not available. The present study describes the efficacy of a newly developed treatment regimen for post-bariatric patients presenting with severe hypoalbuminemia. METHODS: A single-centre, retrospective analysis of eleven post-bariatric patients presenting with severe hypoalbuminemia, treated with continuous 24 h nasal-jejunal tube feeding of a medium chain triglyceride (MCT) formulation in combination with pancreatic enzyme supplementation every 3 h. RESULTS: Duration of tube feeding ranged from 25 to 156 days (median 64 days) and pancreatic enzyme was supplemented for 22-195 days (median 75 days). An increase in serum albumin levels of 5 g/L and 10 g/L was achieved after a median period of 20 (range 6-26 days) and 36 days (range 21-57 days), respectively. Albumin levels were > 35 g/L after a median period of 58 days (range 44-171 days). CONCLUSION: In this case series, a continuous 24-h nasal-jejunal MCT tube feed combined with frequent pancreatic enzyme supplementation was effective in all patients presenting with severe post-bariatric hypoalbuminemia and was not associated with adverse effects.

Total pancreatic necrosis after organophosphate intoxication.

Cases of acute pancreatitis induced by organophosphate intoxication are encountered occasionally in clinics, but very few of them develop into severe pancreas necrosis and irreversible pancreatic function impairment. Here, we report a 47-year-old female organophosphate poisoning case after ingestion of massive insecticides; she was considered to have total necrosis and function failure of the pancreas via serum amylase test, glucose level test, and CT imaging. The patient exhibited no relief under the regular medicine treatment, which included sandostatin, antibiotics, intravenous atropine, and pralidoxime methiodide. She received percutaneous catheterization and drainage of pancreatic zone to expel hazardous necrotic waste, also by which the pathogenic evidence was obtained and the antibiotics were adjusted subsequently. The patient recovered gradually, was discharged after 2 weeks, and was prescribed with oral pancreatin capsules before meals and hypodermic insulin at meals and bedtime to compensate the impaired pancreatic function.

Cellulase, Coca-Cola®, pancreatin and ursodeoxycholic acid in the dissolution of gastric bezoars: why not all together?

Two cases of a chemical dissolution of gastric phytobezoars are presented. The novel approach of that management is the pharmacological mixture than completely made disappear the bezoars in patients fated to surgery removal.

Pancreatic Exocrine Insufficiency in Type 1 and 2 Diabetes: Therapeutic Implications.

The objective of the present review is to focus on pancreatic exocrine insufficiency that is associated with Type 1 and 2 diabetes, its clinical and therapeutic implications, including the utility and efficacy of pancreatin supplementation. A literature search was conducted on Pubmed / Medline to identify relevant articles using terms pancreatic exocrine insufficiency in diabetes mellitus patients, pathophysiology, prevalence, treatment and management published between 2006-2016 in English language. Meta-analysis has revealed the prevalence of PEI in patients with type-1 and type-2 diabetes mellitus to be 37.7% (CI 27.2-49.5) and 26.2% (CI 19.4-34.3) respectively. Very scanty data are available that evaluates the efficacy of pancreatin in patients with diabetes. In the available studies, pancreatin was found to reduce hypoglycemia in insulin treated patients. Pancreatic exocrine insufficiency in type 1 and 2 diabetes mellitus is not uncommon and correct use of pancreatin may have a positive effect on the glycemic status of the diabetic patients.

Efficacy of pancreatic exocrine replacement therapy for patients with unresectable pancreatic cancer in a randomized trial.

BACKGROUND: Weight loss in pancreatic cancer is associated with maldigestion due to pancreatic duct obstruction. Pancreatic exocrine replacement therapy (PERT) may significantly improve fat and protein absorption. OBJECTIVES: This prospective, double-blind, randomized, placebo-controlled phase II trial assessed whether PERT could reduce or prevent weight loss in patients with unresectable pancreatic cancer. METHODS: Sixty seven patients with unresectable pancreatic cancer were randomized to receive enteric coated PERT, consisting of 6-9 capsules of pancreatin (457.7 mg/capsule), or placebo. Patients took two capsules each three times daily during main meals and one capsule each up to three times daily when having between-meal snacks. The primary endpoint was the percentage change in body weight at eight weeks. RESULTS: The mean percentage change in body weight (1.49% [1.12 kg] vs. 2.99% [1.63 kg], P = 0.381) and the mean percent change in Patient-Generated Subjective Global Assessment (PG-SGA) score (8.85% vs. 15.69%, p = 0.18) did not differ significantly between the PERT and placebo groups. There was no improvement in quality of life and overall survival did not differ significantly between the PERT and placebo groups (5.84 months vs 8.13 months, p = 0.744). CONCLUSIONS: PERT did not reduce weight loss in patients with unresectable pancreatic cancer. Larger randomized trials are needed to identify those patients who may benefit from PERT. TRIAL REGISTRATION: ClinicalTrials.gov Number NCT01587534.

[Duodenal dystrophy: An interdisciplinary problem].

Duodenal dystrophy (DD) is the pathological change in the wall of the duodenum, which is caused by chronic inflammation in its ectopic pancreatic tissue. The most common complications of DD are acute or chronic pancreatitis and impaired duodenal patency, which along with severe pain are an indication for surgical treatment. Pancreaticoduodenal resection is recognized as the operation of choice. The paper describes a clinical case demonstrating the efficiency and safety of minimally invasive (laparoscopic) surgical technologies in this category of patients. Resectional interventions of this volume are also shown to be accompanied by the development of pancreatic insufficiency that necessitates continuous enzyme replacement therapy.

Efficacy and Safety of Pancrelipase/Pancreatin in Patients With Exocrine Pancreatic Insufficiency and a Medical History of Diabetes Mellitus.

OBJECTIVES: The aim of this study was to perform exploratory analyses of the efficacy and safety of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency (EPI) with (n = 36) and without (n = 18) concurrent diabetes mellitus (DM). METHODS: This was a retrospective, post hoc, subgroup (±DM) analysis of a double-blind, randomized, placebo-controlled trial of pancrelipase in patients with EPI due to chronic pancreatitis or pancreatectomy (total or partial). After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units/meal, 36,000/snack) or placebo for 7 days. Outcomes included changes in coefficients of fat absorption (CFA) and nitrogen absorption (CNA) from baseline to the end of the double-blind period. RESULTS: Mean changes in nutrient absorption were greater with pancrelipase versus placebo in patients with DM (CFA, 36.0% vs 7.5%, P < 0.0001; CNA, 33.4% vs 3.7%, P = 0.0002) and without DM (CFA, 25.2% vs 12.3%, P = 0.0326; CNA, 39.1% vs 17.6%, P = 0.1187). Diabetes mellitus was not significantly associated with outcomes for CFA (P = 0.0802) and CNA (P = 0.2934). Incidences of adverse events, including hypoglycemia and hyperglycemia, were similar in the pancrelipase and placebo arms. CONCLUSIONS: Pancrelipase improved fat and protein absorption in patients with EPI due to chronic pancreatitis or pancreatectomy, with or without DM, and matched the safety profile previously reported.

Nutrition Management of Cystic Fibrosis in the 21st Century.

Despite significant advancements made in life expectancy over the past century, cystic fibrosis remains a life-threatening genetic disease that affects the gastrointestinal tract, and it has significant impact on the nutrition status of those with the disease. Nutrition management includes a high-calorie/high-fat diet, pancreatic enzyme replacement therapy, vitamin and mineral replacement, and enteral support as needed. As patients are living longer, clinicians may encounter patients with cystic fibrosis in obstetrician offices, endocrine clinics, or hospital settings, owing to lung transplantation or for treatment for distal intestinal obstruction syndrome.

[PANCREATIC EXOCRINE INSUFFICIENCY AND ITS CORRECTION IN CHILDREN WITH TYPE I DIABETES IN COMBINATION WITH CELIAC DISEASE].

The results of the examination of patients with type I children,which was diagnosed with celiac disease and pancreatic exocrine insufficiency. To correct the PEN used pancreatin preparations and studied its effectiveness.

[Pathogenetic grounds of trophological impact of chronic pancreatitis complex therapy].

In chronic pancreatitis patients was found persistent state of oxidative stress on the level of malonic aldehyde, which ran against the lowered levels of antioxidant enzymatic and non-enzymatic composition, and it has been found in the state of hypoproteinemia proteinogram indices (P < 0.05). The use of complex treatment of patients with chronic pancreatitis multivitamin-aminoacid drug Moriamin forte contributes to a significant regression effects oxidative stress and reduces the effects of hypoproteinemia (P < 0.05).

Pancreatic enzyme replacement therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis: a 1-year disease management study on symptom control and quality of life.

OBJECTIVE: Exocrine pancreatic insufficiency (EPI) is frequent in patients with chronic pancreatitis (CP). This 1-year, prospective, multicenter, observational, disease management study aimed to assess symptom improvement and quality of life in patients with CP with EPI who were receiving pancreatic enzyme replacement. METHODS: Patients with CP and chronic EPI were either assigned to cohort 1 that consisted of patients already taking pancreatin (Kreon; Abbott Arzneimittel GmbH, Hannover, Germany) or cohort 2 that consisted of patients with newly diagnosed EPI without prior pancreatic enzyme treatment. Symptoms were documented, and quality of life was assessed using the gastrointestinal quality of life index (GIQLI) at baseline, 6 months, and 1 year. RESULTS: A total of 294 patients were evaluated (cohort 1, n = 206; cohort 2, n = 88). The proportion of patients experiencing gastrointestinal symptoms and recurrent pain after 1 year was significantly reduced in both cohorts (P < 0.001). The alleviation of symptoms was reflected in GIQLI score improvements at 1 year in both cohorts (P < 0.001), independent of CP severity and etiology. Improvements in GIQLI score were more pronounced in cohort 2 (P < 0.001). CONCLUSIONS: Pancreatin demonstrated symptom relief and improvement in quality of life in patients with CP-related EPI in this disease management study.

A 51-week, open-label clinical trial in India to assess the efficacy and safety of pancreatin 40000 enteric-coated minimicrospheres in patients with pancreatic exocrine insufficiency due to chronic pancreatitis.

BACKGROUND/OBJECTIVES: To assess the efficacy and safety of pancreatin (pancrelipase) enteric-coated minimicrospheres (MMS) over a one-year period in patients with pancreatic exocrine insufficiency (PEI) due to chronic pancreatitis (CP). METHODS: This was a 51-week, open-label extension (OLE) of a one-week, multicenter, double-blind, randomized, placebo-controlled trial in India that enrolled patients ≥18 years of age with confirmed PEI due to CP. Patients received pancreatin (Creon(®) 40000 MMS™) at a dose of 80,000 Ph. Eur. lipase units with each of three main meals/day and 40,000 with each of up to three snacks/day. RESULTS: Of 61 patients entering the OLE, 48 completed treatment (nine were lost to follow up, two withdrew consent, one discontinued due to adverse event [acute exacerbation of CP], one protocol violation). There were significant improvements from baseline to end of OLE in mean ± SD coefficient of fat absorption (CFA: 22.7 ± 12.2%), coefficient of nitrogen absorption (CNA: 6.5 ± 7.9%), body weight (4.9 ± 4.9 kg), BMI (1.9 ± 1.9 kg/m(2)), and most nutritional laboratory parameters tested (p ≤ 0.001). Mean daily stool frequency was reduced from 2.8 to 1.6 (p < 0.001). Improvements in clinical symptoms, clinical global impression of disease symptoms, and quality of life were also observed. Treatment-emergent adverse events (TEAEs) were observed in 64% of patients overall. Only 13% of patients experienced TEAEs judged treatment related. CONCLUSIONS: In patients with PEI due to CP, treatment with pancreatin for one year was associated with significant improvements in fat absorption, nitrogen absorption, and nutritional parameters, improvements in clinical symptoms, and a favorable safety and tolerability profile.