RESUMO
Abdominal pain is the most common symptom of chronic pancreatitis (CP) and is often debilitating for patients and very difficult to treat. To date, there exists no cure for the disease. Treatment strategies focus on symptom management and on mitigation of disease progression by reducing toxin exposure and avoiding recurrent inflammatory events. Traditional treatment protocols start with medical management followed by consideration of procedural or surgical intervention on selected patients with severe and persistent pain. The incorporation of adjuvant therapies to treat comorbidities including psychiatric disorders, exocrine pancreatic insufficiency, mineral bone disease, frailty, and malnutrition, are in its early stages. Recent clinical studies and animal models have been designed to improve investigation into the pathophysiology of CP pain, as well as to improve pain management. Despite the array of tools available, many therapeutic options for the management of CP pain provide incomplete relief. There still remains much to discover about the neural regulation of pancreas-related pain. In this review, we will discuss research from the last 5 years that has provided new insights into novel methods of pain phenotyping and the pathophysiology of CP pain. These discoveries have led to improvements in patient selection for optimization of outcomes for both medical and procedural management, and identification of potential future therapies.
RESUMO
Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.
RESUMO
Malnutrition in patients with chronic pancreatitis is common, but its evaluation is often missed in clinical practice. Pancreatic exocrine insufficiency is the single most important cause of malnutrition; therefore, it needs to be screened for and treated appropriately. Specific diet regimens in patients suffering from chronic pancreatitis are rarely reported in the literature. Patients suffering from chronic pancreatitis have a higher demand for energy but a lower caloric intake secondary to pancreatic exocrine insufficiency, combined with the malabsorption of liposoluble vitamin and micronutrients, which needs be corrected by appropriate dietary counselling. Diabetes is frequently observed in chronic pancreatitis and classified as type 3c, which is characterized by low levels of both serum insulin and glucagon; therefore, there is a tendency towards hypoglycaemia in patients treated with insulin. Diabetes contributes to malnutrition in chronic pancreatitis. Strategies to treat exocrine and endocrine insufficiency are important to achieve better control of the disease.
Assuntos
Diabetes Mellitus , Insuficiência Pancreática Exócrina , Insulinas , Desnutrição , Pancreatite Crônica , Humanos , Pancreatite Crônica/complicações , Pancreatite Crônica/terapia , Diabetes Mellitus/etiologia , Diabetes Mellitus/terapia , Desnutrição/complicações , Insuficiência Pancreática Exócrina/complicações , Insuficiência Pancreática Exócrina/terapia , Apoio NutricionalRESUMO
Chronic pancreatitis increases the risk of developing pancreatic cancer through the upregulation of pathways favouring proliferation, fibrosis, and sustained inflammation. We established in previous studies that the ligand tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) signals through its cognate receptor fibroblast growth factor-inducible 14 (Fn14) to regulate these underlying cellular processes in the chronic liver injury niche. However, the role of the TWEAK/Fn14 signalling pathway in pancreatic disease is entirely unknown. An analysis of publicly available datasets demonstrated that the TWEAK receptor Fn14 is upregulated in pancreatitis and pancreatic adenocarcinoma, with single cell RNA sequencing revealing pancreatic ductal cells as the main Fn14 producers. We then used choline-deficient, ethionine-supplemented (CDE) diet feeding of wildtype C57BL/6J and Fn14 knockout littermates to (a) confirm CDE treatment as a suitable model of chronic pancreatitis and (b) to investigate the role of the TWEAK/Fn14 signalling pathway in pancreatic ductal proliferation, as well as fibrotic and inflammatory cell dynamics. Our time course data obtained at three days, three months, and six months of CDE treatment reveal that a lack of TWEAK/Fn14 signalling significantly inhibits the establishment and progression of the tissue microenvironment in CDE-induced chronic pancreatitis, thus proposing the TWEAK/Fn14 pathway as a novel therapeutic target.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear. AIM OF THE STUDY: This study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model. MATERIALS AND METHODS: Fifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 µg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin D3 (VD3) and Vitamin D receptor (VDR) in serum and pancreatic tissues, respectively. The expressions of NLRP3 inflammasome related genes and molecules were assayed by WB, IHC and RT-qPCR. RESULTS: The pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VD3 and VDR expression while reduced the pancreatic NLRP3 expression. Correspondingly, XCHT decreased the levels of NLRP3 downstream targets IL-1ß, TNF-α and IL-6. CONCLUSIONS: These results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD3/VDR expression and inhibiting the secretion of NLRP3-assoicated inflammatory factors.
Assuntos
Ceruletídeo , Pancreatite Crônica , Actinas/metabolismo , Animais , Ceruletídeo/efeitos adversos , Colágeno/metabolismo , Modelos Animais de Doenças , Fibrose , Inflamassomos/metabolismo , Inflamação , Interleucina-6 , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/metabolismo , Receptores de Calcitriol/uso terapêutico , Transdução de Sinais , Fator de Necrose Tumoral alfa , Vitamina D/efeitos adversosRESUMO
This review summarizes the main pancreatic diseases from a nutritional approach. Nutrition is a cornerstone of pancreatic disease and is sometimes undervalued. An early identification of malnutrition is the first step in maintaining an adequate nutritional status in acute pancreatitis, chronic pancreatitis and pancreatic cancer. Following a proper diet is a pillar in the treatment of pancreatic diseases and, often, nutritional counseling becomes essential. In addition, some patients will require oral nutritional supplements and fat-soluble vitamins to combat certain deficiencies. Other patients will require enteral nutrition by nasoenteric tube or total parenteral nutrition in order to maintain the requirements, depending on the pathology and its consequences. Pancreatic exocrine insufficiency, defined as a significant decrease in pancreatic enzymes or bicarbonate until the digestive function is impaired, is common in pancreatic diseases and is the main cause of malnutrition. Pancreatic enzymes therapy allows for the management of these patients. Nutrition can improve the nutritional status and quality of life of these patients and may even improve life expectancy in patients with pancreatic cancer. For this reason, nutrition must maintain the importance it deserves.
Assuntos
Desnutrição , Neoplasias Pancreáticas , Pancreatite , Humanos , Doença Aguda , Qualidade de Vida , Pancreatite/terapia , Pancreatite/complicações , Apoio Nutricional/efeitos adversos , Nutrição Enteral/efeitos adversos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/terapia , Desnutrição/etiologia , Desnutrição/terapia , Neoplasias PancreáticasRESUMO
Chronic pancreatitis (CP) is a chronic inflammatory and fibrotic disease of the pancreas. The incidence of CP is increasing worldwide but the effective therapies are lacking. Hence, it is necessary to identify economical and effective agents for the treatment of CP patients. Vitamin D (VD) and its analogues have been confirmed as pleiotropic regulators of cell proliferation, apoptosis, differentiation and autophagy. Clinical studies show that VD deficiency is prevalent in CP patients. However, the correlation between VD level and the risk of CP remains controversial. VD and its analogues have been demonstrated to inhibit pancreatic fibrosis by suppressing the activation of pancreatic stellate cells and the production of extracellular matrix. Limited clinical trials have shown that the supplement of VD can improve VD deficiency in patients with CP, suggesting a potential therapeutic value of VD in CP. However, the mechanisms by which VD and its analogues inhibit pancreatic fibrosis have not been fully elucidated. We are reviewing the current literature concerning the risk factors for developing CP, prevalence of VD deficiency in CP, mechanisms of VD action in PSC-mediated fibrogenesis during the development of CP and potential therapeutic applications of VD and its analogues in the treatment of CP.
RESUMO
Emerging research indicates that vitamin D metabolic disorder plays a major role in both acute pancreatitis (AP) and chronic pancreatitis (CP). This has been demonstrated by studies showing that vitamin D deficiency is associated with pancreatitis and its anti-inflammatory and anti-fibrotic effects by binding with the vitamin D receptor (VDR). However, the role of vitamin D assessment and its management in pancreatitis remains poorly understood. In this narrative review, we discuss the recent advances in our understanding of the molecular mechanisms involved in vitamin D/VDR signaling in pancreatic cells; the evidence from observational studies and clinical trials that demonstrate the connection among vitamin D, pancreatitis and pancreatitis-related complications; and the route of administration of vitamin D supplementation in clinical practice. Although further research is still required to establish the protective role of vitamin D and its application in disease, evaluation of vitamin D levels and its supplementation should be important strategies for pancreatitis management according to currently available evidence.
Assuntos
Pancreatite , Deficiência de Vitamina D , Doença Aguda , Humanos , Pancreatite/complicações , Pancreatite/etiologia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêuticoRESUMO
INTRODUCTION: Despite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. METHODS: An online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. RESULTS: Overall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. CONCLUSION: This survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.
Assuntos
Insuficiência Pancreática Exócrina , Pancreatite Crônica , Esteatorreia , Tomada de Decisão Clínica , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/etiologia , Insuficiência Pancreática Exócrina/terapia , Humanos , Pâncreas , Pancreatite Crônica/complicações , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/terapia , Esteatorreia/diagnóstico , Esteatorreia/etiologia , Esteatorreia/terapiaRESUMO
BACKGROUND AND AIMS: Malnutrition in chronic pancreatitis is complex and multifactorial, with malabsorption, pain, toxic dependencies and co-morbidities, such as diabetes, each playing a role. The aims of this systematic review were to assess the impact of nutritional intervention on markers of nutritional status in this complex patient group. MATERIALS AND METHODS: A systematic review of EMBASE and PubMed was carried out in February 2020, identifying 2620 articles. After screening to exclude those reporting short term changes (less than 3 months), with only one data point, or in the wrong population, eight papers were selected for analysis. RESULTS: Seven studies documented the impact of a nutritional intervention, one was an observational study only. Overall, studies were limited by predominantly retrospective designs, heterogenous populations and poor control of potentially confounding variables. Data could not be combined due to variability in reporting methods. All studies exploring nutritional intervention, whether that consisted of advice by a specialist dietitian, dose escalation of pancreatic enzymes, oral nutritional supplements or enteral feeding, demonstrated improved body weight and pain control, whereas patients who did not receive an intervention deteriorated nutritionally. CONCLUSION: Patients with chronic pancreatitis benefit from nutritional intervention. Further work is required to explore the impact of nutritional intervention on body composition and functional outcomes.
Assuntos
Desnutrição , Pancreatite Crônica , Suplementos Nutricionais , Humanos , Estado Nutricional , Estudos Observacionais como Assunto , Pancreatite Crônica/complicações , Estudos RetrospectivosRESUMO
Most cases of pancreatic cancer develop in patients with chronic pancreatitis (CP). Berberine is natural product that exhibits anti-tumor effects in various types of cancer and is used in traditional Chinese medicine. In this study, we demonstrated that berberine inhibited the development of pancreatic intraepithelial neoplasia (PanIN) in an in vivo CP model and an in vitro acinar-to-ductal metaplasia model. As berberine may inhibit glycolysis during the development of PanIN, we measured indicators of glycolysis. Quantitative reverse transcription polymerase chain reaction and western blotting assays revealed that berberine activated the adenosine monophosphate-activated protein kinase (AMPK) pathway. This demonstrated that berberine suppressed glycolysis by targeting AMPK, a key metabolic sensor. Furthermore, berberine acted via the AMPK-hypoxia-inducible factor 1 alpha pathway to achieve suppression of PanIN. These findings show that berberine is a potential therapeutic candidate for preventing the progression of CP to PanIN.
Assuntos
BerberinaRESUMO
Chronic pancreatitis (CP) is a multifactorial, inflammatory syndrome characterized by acinar atrophy and fibrosis. Activation of NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome is a central mediator of multiple chronic inflammatory responses and chronic fibrosis including pancreatic fibrosis in CP. The Psidium guajavaleaf is widely used in traditional medicine for the treatment of chronic inflammation, but the anti-inflammatory effect of Psidium guajavaleaf on CP has not yet been revealed. In this study, we investigated whether the extract of total flavonoids from Psidium guajava leaves (TFPGL) plays a therapeutic mechanism on CP through NLRP3 inflammasome signaling pathway in a mouse CP model. The H&E and acid-Sirius red staining indicted that TFPGL attenuated the inflammatory cell infiltration and fibrosis significantly. The results of immunohistological staining, western blot and RT-qPCR showed that the expressions of NLRP3 and caspase-1 were significantly increased in the CP model group, while TFPGL significantly decreased the NLRP3 and caspase-1 expression at both the gene and protein levels. Moreover, ELISA assay was used to examine the levels of NLRP3 inflammasome target genes, such as caspase-1, IL-1[Formula: see text] and IL-18. We found that TFPGL treatment decreased the expression of caspase-1, IL-1[Formula: see text] and IL-18, which is critical for the NLRP3 inflammasome signaling pathway and inflammation response significantly. These results demonstrated that TFPGL attenuated pancreatic inflammation and fibrosis via preventing NLRP3 inflammasome activation and TFPGL can be used as a potential therapeutic agent for CP.
Assuntos
Pancreatite Crônica , Psidium , Animais , Fibrose , Flavonoides/farmacologia , Inflamassomos , Interleucina-1beta , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Pancreatite Crônica/tratamento farmacológico , Pancreatite Crônica/genéticaRESUMO
Pain is the most frequent symptom in chronic pancreatitis (CP) and has an important impact on quality of life. One of its major pathophysiological mechanisms is ductal hypertension, caused by main pancreatic duct stones and/or strictures. In this article, we focus on extracorporeal shock wave lithotripsy (ESWL) as a treatment for main pancreatic duct stones, which have been reported in >50% of CP patients. ESWL uses acoustic pulses to generate compressive stress on the stones, resulting in their gradual fragmentation. In patients with radiopaque obstructive main pancreatic duct (MPD) stones larger than 5 mm, located in the pancreas head or body, ESWL improves ductal clearance, thereby relieving pain and improving quality of life. In case of insufficient ductal clearance or the presence of an MPD stricture, ESWL can be followed by endoscopic retrograde cholangiopancreatography (ERCP) to increase success rate. Alternatively, direct pancreaticoscopy with intracorporeal lithotripsy or surgery can be performed.
Assuntos
Cálculos , Litotripsia , Pancreatite Crônica , Cálculos/terapia , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Pancreatite Crônica/complicações , Pancreatite Crônica/terapia , Qualidade de Vida , Resultado do TratamentoRESUMO
Chronic pancreatitis (CP) is a progressive fibro-inflammatory syndrome. The damage of acinar cells is the main cause of inflammation and the activation of pancreatic stellate cells (PSCs), which can thereby possibly further aggravate the apoptosis of more acinar cells. Saikosaponind (SSd), a major active ingredient derived from Chinese medicinal herb bupleurum falcatum, which exerted multiple pharmacological effects. However, it is not clear whether SSd protects pancreatic injury of CP via regulating the apoptosis of pancreatic acinar cells. This study systematically investigated the effect of SSd on pancreatic injury of CP in vivo and in vitro. The results revealed that SSd attenuate pancreatic damage, decrease the apoptosis and suppress the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2, and p38 MAPK) significantly in the pancreas of CP rats. In addition, SSd markedly reduced the apoptosis and inflammation of pancreatic acinar AR42J cells induced by cerulein, a drug induced CP, or Conditioned Medium from PSCs (PSCs-CM) or the combination of PSCs-CM and cerulein. Moreover, SSd significantly inhibited the activated phosphorylation of JNK1/2, ERK1/2, and p38 MAPK induced by cerulein or the combination of PSCs-CM and cerulein in AR42J cells. Furthermore, SSd treatment markedly decreased the protein levels of p-JNK and p-p38 MAPK caused by PSCs-CM alone. In conclusion, SSd ameliorated pancreatic injury, suppressed AR42J inflammation and apoptosis induced by cerulein, interrupted the effect of PSCs-CM on AR42J cells inflammation and apoptosis, possibly through MAPK pathway.
RESUMO
Pancreatic fibrosis is a pathological characteristic of chronic pancreatitis (CP) and pancreatic cancer. Chaihu Guizhi Ganjiang Decoction (CGGD) is a traditional Chinese medicine, which is widely used in the clinical treatment of digestive diseases. However, the potential anti-fibrosis mechanism of CGGD in treating CP remains unclear. Here, we conducted a series of experiments to examine the effect of CGGD on the CP rat model and primary isolated pancreatic stellate cells (PSCs). The results revealed that CGGD attenuated pancreatic damage, decreased collagen deposition, and inhibited PSC activation in the pancreas of CP rats. However, compared with the CP group, CGGD had no effect on body weight and serum amylase and lipase. In addition, CGGD suppressed autophagy by downregulating Atg5, Beclin-1, and LC3B and facilitated phosphorylation of mTOR and JNK in pancreatic tissues and PSCs. Moreover, the CGGD-containing serum also decreased LC3B or collagen I expression after rapamycin (mTOR inhibitor) or SP600125 (JNK inhibitor) treatment in PSCs. In conclusion, CGGD attenuated pancreatic fibrosis and PSC activation, possibly by suppressing autophagy of PSCs through the JNK/mTOR signaling pathway.
RESUMO
AIM: To identify and compare the frequency of alcohol consumption, tobacco smoking, levels of main macronutrients, vitamins and mineral elements consumption in patients with acute (AP) and chronic pancreatitis (CP) and pancreatic cancer (PC). MATERIALS AND METHODS: At the observational clinical cross-sectional uncontrolled case-study 65 patients with AP or CP (group 1) and 45 patients with PC (group 2) were examined. A survey of patients was carried out: questionnaire on tobacco smoking, a frequency questionnaire on alcohol consumption, a questionnaire for assessing the frequency of food consumption. RESULTS: The frequency of smoking (33.8, 20.0%; p0.05), alcohol consumption 1 times/week during the last year (21.5, 15.6%; p0.05) did not differ significantly between the two groups. The highest consumption rates of total, vegetable, animal protein, total carbohydrates, refined sugar, animal fat, cholesterol, MUFA, dietary fiber, vitamins (-carotene, vitamin B1, B2, C, PP), mineral elements (iron, potassium, calcium, magnesium, sodium, phosphorus) and the daily energy content of the diet were determined in PC than in the AP and CP group. Among patients of group 1, deficient intake of fat-soluble vitamin A (93.3, 54.8%; p=0.009) and vitamin E (80.0, 48.4%; p=0.041) was more common in the subgroup of patients with excretory pancreatic insufficiency than without it, and the chance of having hypercholesterolemia was associated with a deficient intake of vitamin E [Ex(B)=3.3, 95% CI 1.59.3; p=0.027]. CONCLUSION: There were no differences in the frequency of smoking and alcohol consumption between patients with AP and CP and PC. The highest indices of the main macronutrients, daily energy content of the diet, micronutrients (except for vitamins A, E) were found in PC than in the group of patients with AP and CP. Among patients with AP and CP with excretory pancreatic insufficiency, a lower intake of fat-soluble vitamins was noted and associations of hypercholesterolemia with deficient intake of vitamin E were obtained.
Assuntos
Insuficiência Pancreática Exócrina , Hipercolesterolemia , Neoplasias Pancreáticas , Pancreatite Crônica , Animais , Vitamina A , Estudos Transversais , Magnésio , Cálcio , Vitaminas , Vitamina E , Micronutrientes , Fatores de Risco , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/etiologia , Fibras na Dieta , Insuficiência Pancreática Exócrina/epidemiologia , Insuficiência Pancreática Exócrina/etiologia , Minerais , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/etiologia , Tiamina , Sódio , Ferro , Potássio , Fósforo , AçúcaresRESUMO
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.
Assuntos
Suplementos Nutricionais , Terapia Nutricional/métodos , Pancreatite Crônica/dietoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Antioxidantes/administração & dosagem , Humanos , Vitamina D/administração & dosagemRESUMO
BACKGROUND: Pancreatic diseases involve complex nutritional challenges. Despite this, conflicting evidence exists regarding the clinical relevance of detecting the risk of malnutrition and implementing systematic nutrition support for these patients. Thus, our aims were to investigate whether screening for malnutrition risk and initiating nutrition support are predictive of mortality for hospitalized patients with pancreatic diseases. DESIGN: From 2008 to 2018, 34 prevalence surveys of nutrition were conducted at Haukeland University Hospital (HUH), Norway. Risk of malnutrition was defined by a score of ≥3 in Nutritional Risk Screening 2002 (NRS 2002). Primary outcomes included overall, one-year, and one-month mortality, and were compared according to malnutrition risk and nutrition support for adult patients with ICD-10 codes of K85: acute pancreatitis, K86: other diseases of pancreas, and C25: malignant neoplasm of pancreas. Length of hospital stay (LOS) was included as a secondary outcome. RESULTS: Of the 283 patients investigated, risk of malnutrition was present in 61.5%. Risk of malnutrition was associated with higher overall mortality (Hazard Ratio (HR) = 1.67, 95% confidence interval (CI): 1.2-2.4, P = 0.003) and one-year mortality (HR = 1.89, 95% CI: 1.2-2.9, P = 0.004) compared to patients not at risk. Not receiving nutrition support for at-risk patients was associated with higher overall mortality (HR = 1.60, 95% CI: 1.1-2.4, P = 0.019) and one-year mortality (HR = 1.64, 95% CI: 1.04-2.6, P = 0.034) compared to patients at risk who received nutrition support. Patients at risk of malnutrition had increased LOS (20.5 nights vs 15.2 nights, P = 0.044) compared to patients not at risk of malnutrition. CONCLUSION: This study of hospitalized patients with pancreatic disease suggests that risk of malnutrition may be associated with higher mortality rates, whereas nutrition support may decrease mortality rates. CLINICAL TRIAL REGISTRY: Not registered.
Assuntos
Desnutrição/epidemiologia , Apoio Nutricional/estatística & dados numéricos , Pancreatopatias/mortalidade , Pancreatopatias/terapia , Adulto , Idoso , Feminino , Humanos , Tempo de Internação , Masculino , Desnutrição/diagnóstico , Programas de Rastreamento , Pessoa de Meia-Idade , Noruega/epidemiologia , Avaliação Nutricional , Apoio Nutricional/métodos , Neoplasias Pancreáticas , Pancreatite/mortalidade , Pancreatite/terapia , Modelos de Riscos Proporcionais , Fatores de Risco , Taxa de SobrevidaRESUMO
Most of the pigs on a farm in Aichi Prefecture, Japan had chronic diarrhea and severe wasting. The pigs had consumed 8,000 ppm zinc oxide (ZnO) as a feed additive. The pancreas of each of 4 autopsied pigs was less than half the normal size. Acinar cells were considerably decreased. Epithelial duct-like cells were increased and tested positive for cytokeratin AE1/AE3, Ki67, PGP9.5, and Sox9. Pancreatic islet cells were decreased and shrunken. The α and δ cells were relatively decreased, and their distribution was abnormal. Islet cells were positive for PGP9.5. The livers and kidneys had high accumulations of zinc (Zn; 788 µg/g and 613 µg/g, respectively). Copper was deficient in the liver, likely as a result of Zn poisoning. Our immunohistologic examination suggested that the high dose of ZnO could influence the function of islet cells in addition to that of acinar cells. Given that colistin sulfate has been banned as a feed additive in order to reduce antimicrobial use in Japan, the use of ZnO in the livestock industry is expected to increase. Zn supplementation of pig feed must be monitored to prevent Zn poisoning and contamination of soil and water.
Assuntos
Pancreatite Crônica/veterinária , Doenças dos Suínos/patologia , Óxido de Zinco/toxicidade , Criação de Animais Domésticos , Animais , Cobre/deficiência , Feminino , Japão , Rim/química , Fígado/química , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , Sus scrofa , Suínos , Doenças dos Suínos/induzido quimicamente , Doenças dos Suínos/metabolismo , Zinco/intoxicação , Zinco/toxicidade , Óxido de Zinco/intoxicaçãoRESUMO
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.