Nutritional management of chronic pancreatitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Malnutrition is a frequent complication of chronic pancreatitis. Adequate nutritional support is imperative, but there is still uncertainty about the optimal nutritional treatment. This work systematically compiles evidence from randomized controlled trials investigating dietary interventions in chronic pancreatitis and, in a further step, contrasts those findings with existing dietary recommendations. METHODS: The literature search (PubMed and Cochrane Central Register of Controlled Trials) included English and German full-text articles, which had been published in peer-reviewed journals. Two independent reviewers identified and selected studies. For meta-analysis, forest plots with 95% confidence intervals were generated using a random-effects model. RESULTS: Eleven randomized controlled trials fulfilled all selection criteria. In these trials, the following dietary interventions were tested: antioxidant treatment (n = 6), vitamin D supplementation (n = 3), supplementation with oral nutritional supplements (n = 1), and symbiotics supplementation (n = 1). Studies were of good methodological quality (mean Jadad score of 3.6) but heterogeneous in terms of interventions and study populations. Only for vitamin D, there was convincing evidence for efficacy of supplementation. We found no effect for antioxidant treatment on pain relief (standardized mean difference = -0.12; 95% confidence interval -0.73 to 0.48) and limited generalizability for interventions with oral nutritional supplements and symbiotics. CONCLUSIONS: Nutritional management in chronic pancreatitis remains challenging. As well-designed randomized controlled trials are scarce, in large part, recommendations can only be based on low-level evidence studies or expert opinion. For now, consumption of a balanced diet remains the cornerstone recommendation for prevention, whereas more goal-directed interventions are indicated for specific nutrient deficiencies.

Soy-tomato enriched diet reduces inflammation and disease severity in a pre-clinical model of chronic pancreatitis.

Chronic pancreatitis (CP) is a fibro-inflammatory syndrome in individuals who develop persistent pathological responses to parenchymal injury or stress. Novel therapeutic or dietary interventions that could lessen inflammation in this disease could significantly improve quality of life in patients with CP. Complex dietary foods like soy and tomatoes are composed of active metabolites with anti-inflammatory effects. Data from our group reports that bioactive agents in soy and tomatoes can reduce pro-inflammatory cytokines and suppressive immune populations. Additionally, our team has developed a novel soy-tomato juice currently being studied in healthy individuals with no toxicities, and good compliance and bioavailability. Thus, we hypothesize that administration of a soy-tomato enriched diet can reduce inflammation and severity of CP. C57BL/6 mice were injected intraperitoneally with 50 µg/kg caeurlein (7 hourly injections, twice weekly) for 6 weeks to induce CP. After 4 weeks of caerulein injections, mice were administered a control or a soy-tomato enriched diet for 2 weeks. Disease severity was measured via immunohistochemical analysis of pancreata measuring loss of acini, fibrosis, inflammation, and necrosis. Serum lipase and amylase levels were analyzed at the end of the study. Inflammatory factors in the serum and pancreas, and immune populations in the spleen of mice were analyzed by cytokine multiplex detection, qRT-PCR, and flow cytometry respectively. Infra-red (IR) sensing of mice was used to monitor spontaneous activity and distress of mice. Mice fed a soy-tomato enriched diet had a significantly reduced level of inflammation and severity of CP (p = 0.032) compared to mice administered a control diet with restored serum lipase and amylase levels (p < 0.05). Mice with CP fed a soy-tomato diet had a reduction in inflammatory factors (TNF-α, IL-1ß, IL-5) and suppressive immune populations (myeloid-derived suppressor cells; MDSC) compared to control diet fed mice (p < 0.05). Infra-red sensing to monitor spontaneous activity of mice showed that soy-tomato enriched diet improved total activity and overall health of mice with CP (p = 0.055) and CP mice on a control diet were determined to spend more time at rest (p = 0.053). These pre-clinical results indicate that a soy-tomato enriched diet may be a novel treatment approach to reduce inflammation and pain in patients with CP.

Reduction of inflammation in chronic pancreatitis using a soy bread intervention: A feasibility study.

INTRODUCTION: Chronic pancreatitis is a chronic inflammatory disease, which progresses to fibrosis. Currently there are no interventions to delay or stop the progression to irreversible organ damage. In this study, we assessed the tolerability and feasibility of administering soy bread to reduce circulating inflammatory mediators. METHODS: Subjects with chronic pancreatitis diagnosed using the American Pancreatic Association diagnostic guidelines were enrolled. During the dose escalation (DE) phase, subjects received one week of soy bread based using a 3 + 3 dose-escalation design, which was then followed by a maximally tolerated dose (MTD) phase with four weeks of intervention. Dose-limiting toxicities (DLTs) were monitored. Plasma cytokine levels were measured using a Meso Scale Discovery multiplex assay kit. Isoflavonoid excretion in 24-h urine collection was used to measure soy bread compliance. RESULTS: Nine subjects completed the DE phase, and one subject completed the MTD phase without any DLTs at a maximum dosage of three slices (99 mg of isoflavones) per day. Reported compliance to soy bread intervention was 98%, and this was confirmed with urinary isoflavones and their metabolites detected in all subjects. There was a significant decline in the TNF-α level during the DE phase (2.667 vs 2.382 pg/mL, p = 0.039); other levels were similar. CONCLUSIONS: In this feasibility study, there was excellent compliance with a short-term intervention using soy bread in chronic pancreatitis. Reduction was seen in at least one pro-inflammatory cytokine with short-term intervention. Larger cohorts and longer interventions with soy are warranted to assess the efficacy of reducing pro-inflammatory mediators of disease.

Does the Healthy Eating Index and Mediterranean Diet Score Identify the Nutritional Adequacy of Dietary Patterns in Chronic Pancreatitis?

BACKGROUND: Chronic pancreatitis (CP) is a progressive, irreversible disease characterized by maldigestion and frequently accompanied by epigastric pain, exocrine insufficiency, and/or endocrine insufficiency. There is limited information about the dietary patterns in CP from which to guide medical nutrition therapy recommendations. METHODS: Study design was a cross-sectional, case-control study comparing subjects with CP (n = 52) to healthy controls (n = 48). Vioscreen™ food frequency questionnaire was used to assess the dietary pattern and nutrient intake in both groups. Dietary quality scores (the Healthy Eating Index, Mediterranean Diet score), and daily energy, macronutrient, and micronutrient intake levels were compared between groups. ANALYSIS: Two sample t tests and Wilcoxon rank sum tests were used to evaluate differences in continuous variables, and Chi-squared tests were used for categorical variables. RESULTS: CP was associated with a lower body mass index (BMI) (24 vs. 31 mg/kg2; p < 0.001), lower HEI (57 vs. 65; p = 0.002), and aMED scores (29 vs. 32; p = 0.043) compared to healthy controls. Subjects with CP in the highest BMI quartile had the highest median aMED score compared to those in the lowest BMI quartile. There were no differences in kilocalories, macronutrients, or fat-soluble vitamin intake between groups, with the exception that vitamin K intake was lower in the CP group. CONCLUSIONS: The overall quality of dietary intake is lower in subjects with CP compared to controls when assessed by two independent nutritional measurement tools. Further research is needed to examine contributing factors, such as food insecurity and coexisting endocrine or exocrine insufficiency, to dietary patterns in patients with CP from which to guide evidence-based recommendations for medical nutritional therapy.

[THERAPEUTIC FEEDING FEATURES OF PATIENTS WITH CHRONIC PANCREATITIS].

The article presents the principles of diet therapy in chronic pancreatitis taking into account the pathophysiological aspects of the development of malnutrition.

Islet autotransplantation and total pancreatectomy.

The goal of IAT is the preservation of beta-cell mass at the time of pancreatectomy. The majority of recipients have significant endogenous beta-cell function with positive blood C-peptide after surgery, even if only approximately one third achieve insulin independence. In appropriately selected patients, total pancreatectomy combined with IAT achieves relief of pain and improves quality of life with relatively easier-to-manage glycemic control and avoidance of hyper- and hypoglycemic episodes. Current research is focused on improving techniques of islet isolation and engraftment as well as long-term survival of autografted islets.

The role of high fat diet in the development of complications of chronic pancreatitis.

BACKGROUND: Little is known about risk factors for complications in chronic pancreatitis (CP). High fat diet (HFD) has been demonstrated to aggravate pancreatic injury in animal models. The aim of this study was to investigate the role of HFD in age at diagnosis of CP and probability of CP related complications. METHODS: A cross-sectional case-case study was performed within a prospectively collected cohort of patients with CP. Diagnosis and morphological severity of CP was established by endoscopic ultrasound. Pancreatic exocrine insufficiency (PEI) was diagnosed by ¹³C mixed triglyceride breath test. Fat intake was assessed by a specific nutritional questionnaire. Odds ratios (OR) for CP related complications were estimated by multivariate logistic regression analysis. RESULTS: 168 patients were included (128 (76.2%) men, mean age 44 years (SD 13.5)). Etiology of CP was alcohol abuse in 89 patients (53.0%), other causes in 30 (17.9%) and idiopathic in the remaining 49 subjects (29.2%). 24 patients (14.3%) had a HFD. 68 patients (40.5%) had continuous abdominal pain, 39 (23.2%) PEI and 43 (25.7%) morphologically severe CP. HFD was associated with an increased probability for continuous abdominal pain (OR = 2.84 (95% CI, 1.06-7.61)), and a younger age at diagnosis (37.0 ± 13.9 versus 45.8 ± 13.0 years, p = 0.03) but not with CP related complications after adjusting for sex, years of follow-up, alcohol and tobacco consumption, etiology and body mass index. CONCLUSIONS: Compared with a normal fat diet, HFD is associated with a younger age at diagnosis of CP and continuous abdominal pain, but not with severity and complications of the disease.

Effect of antioxidant supplementation on surrogate markers of fibrosis in chronic pancreatitis: a randomized, placebo-controlled trial.

OBJECTIVES: This study aimed to determine the effect of antioxidant (AO) supplementation on surrogate markers of fibrosis in patients with chronic pancreatitis (CP). METHODS: In a randomized, placebo (PL)-controlled trial, patients with CP were randomized to groups that were given PL or AO for 3 months. Outcome measures were change in serum levels of transforming growth factor ß1 and platelet-derived growth factor AA (PDGF-AA) (primary outcome) as well as blood markers of oxidative stress (thiobarbituric acid-reactive substances) and AO status (ferric-reducing ability of plasma) (secondary outcome). Pain relief and analgesic requirement was also recorded. RESULTS: Patients (n = 61; mean [SD] age, 35.2 [10.0]; male patients, 43) were assigned to AO (n = 31) and PL (n = 30) groups. The median (range) percent reduction from baseline to 3 months in levels of PDGF-AA (17.1% [-25.3% to 88.7%] vs 2.8% [-243.1% to 30.2%]; P = 0.001), transforming growth factor ß1 (P = 0.573), and thiobarbituric acid-reactive substances (P = 0.207) as well as percent increment from baseline to 3 months in ferric-reducing ability of plasma (P = 0.003) were higher in the AO group compared with the PL group. Proportion of patients who had both reduced PDGF-AA and reduced pain was greater in AO as compared with PL group (17/31 vs 9/30, P = 0.05) CONCLUSIONS: Reduction in markers of fibrosis (PDGF-AA) translated into clinical outcome (reduction in pain and analgesic requirements) in those supplemented with AOs in CP (trial registration, CTRI/2011/05/001747).

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Diet, nutrient deficiency and chronic pancreatitis.

The aetiopathogenesis of chronic pancreatitis (CP) appears to be multifactorial with interplay of genetic and environmental factors such as alcohol, smoking and diet. Dietary factors in the form of a fat- and protein-rich diet are important cofactors in the aetiopathogenesis of alcoholic pancreatitis. Malnutrition used to be a hallmark in tropical pancreatitis. Presently, it appears that malnutrition is an effect rather than a causative factor for tropical pancreatitis; however, micronutrient deficiency could possibly be implicated in the aetiopathogenesis. The role of dietary toxins such as cassava is no longer considered an important risk factor; however, these patients are at a higher risk for defective detoxification of cyanogens. Decrease in levels of sulphur amino acids (SAAs), folate and zinc have been reported. Oxidative stress and antioxidant depletion are key pathogenetic mechanisms. The role of antioxidants in pain relief is an area of interest. Supplementation of fat-soluble vitamins and micronutrients is a cornerstone in medical management. Folate and zinc supplementation may be beneficial and is a focus of ongoing research. In the future, prophylaxis for CP by a daily micronutrient tablet among high-risk groups in endemic areas could prove to be a potentially important public health measure. However, further studies are required.

Changes in 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D are associated with maturation of regulatory T lymphocytes in patients with chronic pancreatitis: a randomized controlled trial.

OBJECTIVES: We studied the impact of changes in 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) on regulatory T lymphocytes (Tregs) in patients with chronic pancreatitis (CP) and fat malabsorption in a prospective clinical trial. METHODS: The patients were randomized to 1 of 3 treatments during 10 weeks: weekly UV-B in a tanning bed (group A), 1520-IU/d vitamin D supplement (group B), or placebo (group C). A placebo tanning bed was used in groups B and C. We determined the levels of CD4 Tregs (CD3(+)CD4(+)CD25(+)CD127(low)FoxP3(+)) and CD8(+) Tregs (CD3(+)CD8(+)CD25(+)CD127(low)FoxP3(+)), together with 25OHD and 1,25(OH)2D. For baseline comparisons, we included 8 healthy individuals. Of the 30 included patients, 27 (group A, 7 patients; group B, 9 patients; and group C, 11 patients) completed the protocol. RESULTS: The baseline levels of CD4(+) Tregs relative to total CD4(+) count were higher in 22 patients with CP compared with healthy controls (2.8% vs 1.9%, P < 0.05) and were comparable for CD8+ Tregs (0.13% vs 0.05%, P = 0.3). Increases in levels of CD4(+) Tregs correlated to changes in 1,25(OH)(2)D (2% per 100 pmol/L, P = 0.002) and 25OHD (3% per 100 nmol/L, P = 0.01). CONCLUSIONS: Patients with CP have elevated relative levels of CD4(+) Tregs. Increases in 25OHD and 1,25(OH)(2)D were both related with increases in levels of Tregs.

Pancreatitis crónica: nuevas terapias / Chronic pancreatitis: new therapies

Chronic pancreatitis occurs by the prolonged inflammation of pancreatic tissue that induces the irreversible destruction of the organ, leading to a global pancreatic insufficiency. The most common manifestations are abdominal pain, diarrhea, malabsorption, and possibly diabetes mellitus. Chronic pancreatitis treatment includes dietary restrictions, enzymatic supplementation, vitamins, and endoscopic or surgical methods depending on the degree of ductal involvement. In addition to the known therapies, new therapies are under development and research.

La pancreatitis crónica se desarrolla por la inflamación prolongada del tejido pancreático que induce la destrucción irreversible del órgano, llevando a una insuficiencia pancreática global. Las manifestaciones más frecuentes son dolor abdominal, diarrea, malabsorción y eventualmente diabetes mellitus. El tratamiento en pancreatitis crónica incluye restricciones dietarias, suplementación enzimática, vitamínica, y métodos endoscópicos o quirúrgicos, dependiendo del grado de compromiso ductal. Además de lo descrito, están en desarrollo y experimentación nuevas terapias.

Micronutrient therapy for chronic pancreatitis: rationale and impact.

Micronutrient therapy, designed to buttress tissue methyl and thiol groups, curbs attacks and controls background pain in patients with chronic pancreatitis, irrespective of aetiology. This outcome and the premises upon which it is based facilitate an understanding of links with mutations in genes for hereditary pancreatitis and cystic fibrosis, demography, and predisposition to pancreatic cancer. Above all, there is an opportunity for prophylaxis in individuals at high risk of developing the disease.

'Not knowing something is normally a milestone on the way to knowledge'. An interview with Joan M. Braganza, DSc, FRCP, FRCPath, Reader Emeritus, University of Manchester, UK.

Dr. Joan Braganza, a world expert in the field of chronic pancreatitis, proposed a new template for its pathogenesis based on the role of free radical pathology, in particular the heightened but unmitigated oxidative detoxification reactions via cytochromes P450. Dr. Braganza has gone on to show how pancreatic damage in cystic fibrosis, acute pancreatitis and pancreatic cancer fit into the scheme, paving the way for new treatment modalities. In this interview, Dr. Braganza shares her life experience as an investigator and provides a perspective for young researchers entering the field of pancreatology.

A safe, effective, and cheap method of achieving pancreatic rest in patients with chronic pancreatitis with refractory symptoms and malnutrition.

OBJECTIVES: Chronic pancreatitis (CP) is common. It is associated with a substantial morbidity, including malnutrition, malabsorption, pseudocysts, metabolic disturbances, and intractable abdominal pain. Approximately 5% of patients with CP are refractory to nutritional support and opiate analgesia, making management challenging.Pancreatic rest can provide symptomatic relief. However, achieving simultaneous pancreatic rest and adequate nutritional support in these patients is difficult. We describe a technique for providing nutritional support and pancreatic rest in patients with intractable symptomatic CP. METHODS: Three patients with symptomatic CP refractory to standard treatment were included in the study. All 3 patients had masses associated with the pancreas. Symptom relief and adequate nutritional support were achieved by inserting a long-term nasojejunal (NJ) tube (Flocare Bengmark, Nutricia Clinical Care, United Kingdom) under ambulatory endoscopic guidance. Data were recorded prospectively. RESULTS: Long-term NJ tube feeding achieved pancreatic rest and significant symptomatic relief while delivering adequate nutritional support. Pseudocyst size decreased substantially in 2 patients. The third patient was found to have pancreatic carcinoma after pancreaticoduodenectomy. CONCLUSIONS: In patients with symptomatic CP refractory to standard nutritional support and opiate analgesia, long-term NJ tube feeding can be a cheap, well-tolerated, safe, and effective method of providing adequate nutritional support and substantially relieving intractable symptoms.

[Study of intestinal time in patients with chronic pancreatitis with the help of hydrogen breath test].

With the help of hydrogen breath test (HRT) the state of small intestina micro flora was studied and the time of transiting chyme in it was defined in 72 patients with chronic biliary-dependent pancreatitis. It was determined that in small intestine of 40% of patients there took place an excessive bacterial growth and chime transiting time increased. After dietary (a standard high-protein diet) and enzyme (Mezim, Creon) therapies, the bacterial semination and HRT were in norm. The use of HRT in gastroetherology permits to evalu ate the efficacy of performed therapy, m particular in patients with body weight deficiency, the character of diarrhea, its possible link with exoennous function of pancreas and excessive bacterial growth in intestine.