Optimizing nutrition in chronic pancreatitis.

PURPOSE OF REVIEW: This review aims to discuss recent developments in the nutritional management in chronic pancreatitis. RECENT FINDINGS: Nutritional assessment should be comprehensive and include dietary history, anthropometry, and biochemical nutritional parameters. Micronutrients should be evaluated at least yearly and dual-energy X-ray absorptiometry (DEXA) at every 2-yearly intervals. Studies on pancreatic enzyme replacement therapy (PERT) have primarily evaluated coefficient of fat excretion (CFA), coefficient of nitrogen excretion (CNA), and stool weight. Two RCTs, in which patients were treated with PERT for 7 days in a blinded manner and subsequently extended for 6-12 months in an open-label manner, showed improvement in nutritional parameters. However, two subsequent RCTs failed to show any benefit, and the most recent observational study demonstrated persistence of malnutrition even after PERT. The reason for the latter findings were nonadherence to PERT and poor oral intake of calories. Therefore, it is essential to educate the patients on adherence, counsel on taking high-protein, high-calorie diet, and supplement nutrients in those with inadequate oral intake. Other associated manifestations, such as diabetes and related complications, and anxiety/depression could also contribute to malnutrition directly or indirectly, and should, therefore, be adequately managed. SUMMARY: Nutritional assessment should be performed meticulously. Nutritional therapy should not be restricted to only PERT and nutritional supplementation, but should also include dietary counselling and disease related education.

Efficacy of enteral glutamine supplementation in patients with severe and predicted severe acute pancreatitis- A randomized controlled trial.

BACKGROUND: In severe acute pancreatitis (AP), intravenous glutamine has been shown to reduce the rate of complications, hospital stay, and mortality. In the present randomized trial, we aimed to evaluate the effect of enteral glutamine supplementation on clinical outcomes, gut permeability, systemic inflammation, oxidative stress, and plasma glutamine levels in patients with severe and predicted severe AP. METHODS: Patients with AP admitted within 72 h of onset of symptoms were included. The primary outcome measure was development of infected pancreatic and peri-pancreatic necrosis and in-hospital mortality. High-sensitivity C-reactive protein (HS-CRP) and interleukin-6 (IL-6) were evaluated as markers of inflammation; plasma thiobarbituric acid reactive substances (TBARS) and activities of serum superoxide dismutase and glutathione peroxidase were determined to evaluate oxidative stress; serum polyethylene glycol (PEG) was tested for intestinal permeability; subjective global assessment (SGA) was used for nutritional assessment, and an improvement in organ function was measured by the Modified Marshall score. Intention-to-treat analysis was used. A p-value of < 0.05 was considered statistically significant. RESULTS: After power calculation, we enrolled 18 patients in the glutamine and 22 in the control arm. There was no significant improvement in the development of infected necrosis and in-hospital mortality between the groups. Improvement in Modified Marshall score was observed in a higher proportion of patients receiving glutamine (15 [83.3%] vs. 12 [54.5%]; p = 0.05). Plasma glutamine levels improved more in glutamine-treated group (432.72 ± 307.83 vs. 618.06 ± 543.29 µM/L; p = 0.004), while it was lower in controls (576.90 ± 477.97 vs. 528.20 ± 410.45 µM/L; p = 0.003). PEG level was lower after glutamine supplementation (39.91 ± 11.97 vs. 32.30 ± 7.39 ng/mL; p = 0.02). Statistically significant reduction in IL-6 concentration was observed in the glutamine group at the end of treatment (87.44 ± 7.1 vs. 63.42 ± 33.7 µM/L; p = 0.02). CONCLUSIONS: Despite absence of improvement in infected necrosis and in-hospital mortality, enteral glutamine supplementation showed improvement in gut permeability, oxidative stress, and a trend towards improvement in organ function as depicted by improvement in the Modified Marshall score. TRIAL REGISTRATION: NCT01503320.

Pain in chronic pancreatitis: managing beyond the pancreatic duct.

Chronic pancreatitis (CP) continues to be a clinical challenge. Persistent or recurrent abdominal pain is the most compelling symptom that drives patients to seek medical care. Unfortunately, in spite of using several treatment approaches in the clinical setting, there is no single specific treatment modality that can be earmarked as a cure for this disease. Traditionally, ductal hypertension has been associated with causation of pain in CP; and patients are often subjected to endotherapy and surgery with a goal to decompress the pancreatic duct. Recent studies on humans (clinical and laboratory based) and experimental models have put forward several mechanisms, including neuroimmune alterations, which could be responsible for pain. This might explain the partial or no response to single modality treatment in a significant proportion of patients. The current review discusses the recent concepts of pain generation in CP and evidence based therapeutic approaches (other than ductal decompression) to handle persistent or recurrent pain. We focus primarily on parenchymal and neural components; and discuss the role of antioxidants and the existing controversies, drugs that interfere with neural transmission, pancreatic enzyme supplementation, celiac neurolysis, and pancreatic resection procedures. The review concludes with the treatment approach that we follow at our institute.

Pancreatic stellate cells: new target in the treatment of chronic pancreatitis.

Chronic pancreatitis (CP) is characterized by progressive fibrosis, pain and/or loss of exocrine and endocrine functions. Recent in vitro and in vivo experiments have proven objectively the role of activated pancreatic stellate cells (PSC) in fibrogenesis in CP. Molecular mediators shown to regulate the pathogenesis include transforming growth factor beta (TGF-beta), platelet-derived growth factor (PDGF), and pro-inflammatory cytokines such as IL-1, IL-6 and TNF-alpha. Furthermore, molecular pathways involving mitogen-activated protein kinases (MAPK), phosphatidyl inositol 3-kinase (PI3K), Ras superfamily G proteins, serine threonine protein kinase Raf-1 and peroxisome proliferator activated receptor gamma (PPAR-gamma) have been elucidated. Understanding of the pathogenesis has led to identification of novel molecular targets and development of potential newer therapeutic agents. Those found to retard the progression of experimental CP and fibrosis in animal models include interferon (IFN) beta and IFN-gamma; a Japanese herbal medicine called Saiko-keishi-to (TJ-10); curcumin; PPAR-gamma ligand (troglitazone); antioxidants (vitamin A, vitamin E, DA 9601 and epigallocatechin-3-gallate); a protease inhibitor (camostat mesilate) and hydroxymethylglutaryl-CoA inhibitor (lovastatin). This review summarizes the current literature addressing the role of different pharmacological agents aimed at reducing or preventing inflammation and the consequent fibrogenesis in CP.

Chronic pancreatitis: evolving paradigms.

Chronic pancreatitis (CP) is characterized by progressive fibrosis, pain and/or loss of exocrine and endocrine functions. With the identification and characterization of pancreatic stellate cells (PSCs), the pathogenesis of CP and pancreatic fibrosis is now better understood. Molecular mediators shown to regulate the pathogenesis include transforming growth factor-beta, platelet-derived growth factor, and proinflammatory cytokines such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha. Besides these, the roles of cyclooxygenase (COX)-2 and apoptosis-related proteins have also been implicated in the pathogenesis. Furthermore, molecular pathways involving mitogen-activated protein kinases, phosphatidylinositol 3-kinase, Ras superfamily G proteins, serine threonine protein kinase Raf-1 and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) have been elucidated. Newer pathobiologic concepts concerning pain generation have also been put forward. Understanding the pathogenesis has led to the identification of novel molecular targets and the development of newer potential therapeutic agents. Those found to retard the progression of experimental CP and fibrosis in animal models include antioxidants, a Japanese herbal medicine called Saiko-keisi-to (TJ 10), the PPAR-gamma ligand troglitazone, the protease inhibitor Camostat mesilate, and Lovastatin.