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.

[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.

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.

[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).

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.

Exocrine pancreatic insufficiency following esophagectomy.

Weight loss following esophagectomy is a management challenge for all patients. It is multifactorial with contributing factors including loss of gastric reservoir, rapid small bowel transit, malabsorption, and adjuvant chemotherapy. The development of a postoperative malabsorption syndrome, as a result of exocrine pancreatic insufficiency (EPI), is recognized in a subgroup of patients following gastrectomy. This has not previously been documented following esophageal resection. EPI can result in symptoms of flatulence, diarrhea, steatorrhea, vitamin deficiencies, and weight loss. It therefore has the potential to pose a significant level of morbidity in postoperative patients. There is some evidence that patients with proven EPI (fecal elastase-1 < 200 µg/g) may benefit from a trial of pancreatic enzyme replacement therapy (PERT). We observed symptoms compatible with EPI in a subgroup of patients following esophagectomy. We hypothesized that this was contributing to malabsorption and malnutrition in these patients. To investigate this, fecal elastase-1 was measured in postoperative patients, and in those with proven EPI, a trial of PERT was commenced in combination with specialist dietary education. At routine postoperative follow-up, which included assessment by a specialist dietitian, those patients with symptoms suggestive of malabsorption were given the opportunity to have their fecal elastase-1 measured. PERT was then offered to patients with fecal elastase-1 less than 200 µg/g (EPI) as well as those in the 200-500 µg/g range (mild EPI) with more severe symptoms. Fecal elastase-1 was measured in 63 patients between June 2009 and January 2011 at a median of 4 months (range 1-42) following surgery. Ten patients had fecal elastase-1 less than 200 µg/g, and all had failed to maintain preoperative weight. All accepted a trial of PERT. Nine (90%) had symptomatic improvement, and seven (70%) increased their weight. Thirty-nine patients had a fecal elastase-1 in the 200-500 µg/g range. Twelve were given a trial of PERT based on level of symptoms, five (42%) reported an improvement in symptoms, but only two (17%) gained weight. Our early results support the observation that EPI is a factor contributing to postoperative morbidity in patients recovering from esophagectomy and that these patients can benefit from a trial of PERT. Our study has limitations, and a formal trial is required to evaluate the impact of EPI and PERT following esophagectomy. Currently, our practice is to measure fecal elastase-1 in any patient with unexplained weight loss or symptoms of malabsorption. In patients with proven EPI or those who are symptomatic with mild EPI, a trial of PERT should be offered and symptoms reassessed.

A blinded randomised controlled trial to determine the effect of enteric coating on enzyme treatment for canine exocrine pancreatic efficiency.

BACKGROUND: Enzyme treatment is the mainstay for management of exocrine pancreatic insufficiency (EPI) in dogs. 'Enteric-coated' preparations have been developed to protect the enzyme from degradation in the stomach, but their efficacy has not been critically evaluated. The hypothesis of the current study was that enteric coating would have no effect on the efficacy of pancreatic enzyme treatment for dogs with EPI.Thirty-eight client-owned dogs with naturally occurring EPI were included in this multicentre, blinded, randomised controlled trial. Dogs received either an enteric-coated enzyme preparation (test treatment) or an identical preparation without the enteric coating (control treatment) over a period of 56 days. RESULTS: There were no significant differences in either signalment or cobalamin status (where cobalamin deficient or not) between the dogs on the test and control treatments. Body weight and body condition score increased in both groups during the trial (P<0.001) but the magnitude of increase was greater for the test treatment compared with the control treatment (P<0.001). By day 56, mean body weight increase was 17% (95% confidence interval 11-23%) in the test treatment group and 9% (95% confidence interval 4-15%) in the control treatment group. The dose of enzyme required increased over time (P<0.001) but there was no significant difference between treatments at any time point (P=0.225). Clinical disease severity score decreased over time for both groups (P=0.011) and no difference was noted between groups (P=0.869). No significant adverse effects were reported, for either treatment, for the duration of the trial. CONCLUSIONS: Enteric coating a pancreatic enzyme treatment improves response in canine EPI.

Adherence to pancreatic enzyme supplementation in adolescents with cystic fibrosis.

PURPOSE: Levels of adherence to pancreatic enzyme supplementation were investigated in Atlantic Canada adolescents with cystic fibrosis (CF). METHODS: Participants were recruited from CF clinics at the Izaak Walton Killam Health Centre in Halifax, Nova Scotia, and the Janeway Children's Health & Rehabilitation Centre in St. John's, Newfoundland and Labrador. Self-report questionnaires were mailed to potential participants (n=51) by clinic staff and completed surveys (n=9) were mailed to the principal investigator. RESULTS: Nine adolescents (mean age 15.2 ± 1.9 years) participated in the study. The adherence survey indicated that the majority perceived themselves to be adherent to taking enzymes with meals (67%), but only 44% perceived themselves to be adherent to taking enzymes with snacks. Recorded amounts of enzymes, taken over three days, indicated that 67% of participants were actually adherent to taking enzymes with meals and 56% with snacks. Including those who correctly predicted non-adherence, 56% and 44% of participants accurately predicted their adherence to taking enzymes with meals and snacks, respectively. CONCLUSIONS: Adherence rates in the literature vary because of differences in definition and measurement. In the CF population, adherence has been shown to have a positive effect on quality of life. Results for this small group of patients suggest that Atlantic Canada adolescents with CF are able to estimate correctly their adherence to taking pancreatic enzymes, but definite conclusions cannot be made because of the small number of respondents.

[Peculiarities of diabetes mellitus course in chronic pancreatitis].

In order to identify features of the course pancreatic diabetes and discussion of the principles of conservative therapy were examined 66 patients with CP in age of 30 to 65 years (55 men, 11 women). Among them in 22 cases disease was followed with formation of calcification of pancreas, 13 - pancreatic cysts, and 5 revealed pseudo tumor form of CP, 10 patients had clinical and laboratory evidence of diabetes. Concerning CP complicated course were performed 14 resection and 11 draining operations on the pancreas. Based on clinical, instrumental and laboratory data was made the diagnosis of CP. Exocrine pancreatic function was assessed on the results of the breath test, using 13C-trioktanaine, which is applied for exocrine pancreatic function in vivo test. The content of C-peptide was investigated by enzyme-linked immunosorbent assay (ELISA). The data indicate pancreatic exocrine function decrease in patients with CP with complications and without complications in compare with the norm of 44% (24,3 +/- 1,7, 26,6 +/- 1,3%, respectively) according to the breath test. Significant decrease of the cumulative output tags based on the test data of patients with CP and pancreatic calcification, diabetes mellitus, after resection surgery with CP complications, and there were significant differences in compare with a group of patients with CP without complications (p = 0.5). The level of C-peptide in these groups of patients decreased significantly in compare with a group of patients with CP without complications, and patients with CP and Diabetes was reduced to 0,11 +/- 0,02 ng/ml, at a rate range of 0.7-1.9 ng/ml, ie below the minimum values of norm. Obtained a direct correlation between the level of C-peptide and indicators breath test in patients after resection HP (r = 0,84, p = 0,03). Antibodies to insulin in the whole group of studied patients CPs were negative, which proves the specific type of Diabetes at HP. Antibodies to insulin can be detected only at diabetes type 1. In 7 patients with CP and CD detected calcification, 5 patients performed resection surgery, 3 patients had calcification and conducted the pancreas resection. Thus, we can conclude that in patients with CP and formation of pancreas calcification, pancreas resections may predict the development of diabetes.

[Chronic pancreatitis: microbe-intestinal tissue complex and systemic inflammatory response].

Today in Russian Federation, we observe significant growth of the chronic pancreatitis incidence with the depression of its therapy efficiency (more than 20% of the patients) and complications rate growth. In many respects given tendency is associated with the inefficiency of traditional medications combination in the context of inflammation process reduction, gut dysbiosis correction and chronic inflammation reaction depression. Present-day studies indicates, that the grade and character of inflammation in the pancreas depends on the pro- and anti-inflammatory cytokines balance, which is associated with the elevation of the pathogenic microbiota concentration and permeability of the gut. We estimate clinical efficacy of complex treatment regimen (PPI, spasmolytic, multienzyme and prebiotic therapy) in the patients with chronic pancreatitis and its effect on chronic system inflammation. We established that efficacy of modern complex treatment regimen depends on its influence on chronic system inflammation and that prebiotics addition potentiates correction of dysbiotic changes in the gut microbial-tissular complex and reduces grade of system inflammation.

[Effect of enzyme supportive therapy of the Ermital' on a quality of life of patients with chronic pancreatitis].

The purpose of the study was to evaluate the quality of life in patients with chronic pancreatitis with the presence of complications treated conservatively and surgical treatment. With the help of a questionnaire MOS SF-36 were asked 80 patients with CP, of whom 15 patients were after the operation, the PDR, 10 patients underwent draining operations, 15 patients had a history of pancreatic necrosis, in 20 patients with CP were characterized by complications (cyst calcification, kalkulez, pseudotumoral form of HP, diabetes) and surgical interventions were not performed in 20 CPs proceeded without complications. Were obtained significant differences on all scales of the questionnaire with the control group all CP patients. Assessment of coping with pain in long-terms after various operations was revealed significantly better results and got rid of persistent pain in patients with a complicated course, who underwent surgery. 23 CP patients with a complicated course, as enzyme replacement therapy received in ermital dose of 20,000 IU lipase 3-4 times a day for 3 weeks. The assessment of quality of life before and after therapy with ermital. The intensity of pain significant changes in the groups received. On the other hand the improvement in general health, physical and social functioning.

[Discriminant function analysis in the assessment of laboratory test data in the correction of traditional therapy for mild icteric form of viral hepatitis B in children with food allergy].

The purpose of this investigation was to define the efficiency of inclusion of antihistamines (suprastin or tavegil), enzyme drugs (pancreatin or mesim forte) and their combinations into therapy for a mild icteric form of acute viral hepatitis B (VHB) in children with food allergy (FA). Among the examinees, there were 61 children with FA who had experienced a mild icteric form of VHB and who received traditional therapy at the age of 3-14 years. Of them, 36 children were additionally given antihistamines (n = 7), enzyme drugs (n = 20), and their combination (n = 9). About half the children (47.54%) were boys. Blood samples were biochemically tested in children for bilirubin and enzymes 1, 3, 6, 9, and 12 months after their hospital discharge. The similar laboratory tests were carried out in 20 healthy children--a comparison (control) group. Analysis of discriminant functions stated the high efficiency of inclusion of enzyme drugs, or antihistamines in particular, or their combinations with enzyme drugs, that considerably reduce the time it takes to normalize the complexes of the indices of a blood biochemical test for bilirubin and enzymes.

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/).

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.

Preparation and in vivo efficacy study of pancreatin microparticles as an enzyme replacement therapy for pancreatitis.

Deficiency manifestations because of pancreatic insufficiency are treated by oral administration of pancreatic enzymes. As pancreatic enzymes get denatured in hostile acidic conditions of stomach, this investigation was aimed at formulating multiparticulates of pancreatic enzymes coated with enteric polymers such as eudragit L100, cellulose acetate phthalate, and hydroxyl propyl methyl cellulose phthalate, which will circumvent gastric inactivation in addition to providing optimal mixing with chyme. Pancreatin microspheres were prepared by emulsification phase separation by nonsolvent addition and solvent evaporation techniques. This process was optimized for core : coat ratio (1:0.5), stirrer speed (350-400 rpm), dispersant concentration, and amount of nonsolvent added to precipitate microspheres. Optimized formulations were assessed for % enzyme content, acid resistance, flow properties, particle size, particle morphology (by standard electron microscopy), compatibility of drug and polymer in formulation (by differential scanning calorimetry), in vitro release kinetics, and in vivo efficacy study in pancreatitis-induced animal model. Capsules containing enteric-coated pancreatin microspheres offered adequate protection to enzymes and prevented their denaturation in acidic environment. Developed multiparticulate dosage forms promoted effective mixing, instant and complete in vitro release compared with marketed tablets.