Nutrition support in the pediatric total pancreatectomy with islet autotransplantation recipient.

For children with diminished quality of life and chronic pain caused by acute recurrent or chronic pancreatitis who are undergoing total pancreatectomy with islet autotransplantation, postoperative nutrition support has several unique characteristics. Surgical complications may lead to delays in nutrition support initiation or require modifications to the regimen. Early postoperative dysmotility requires the use of temporary enteral nutrition until this improves. The resultant complete exocrine pancreatic insufficiency necessitates lifelong pancreatic enzyme replacement therapy and fat-soluble vitamin supplementation. A low-oxalate diet is recommended to prevent kidney stones. Carbohydrate counting is needed for the provision of short-term insulin dosing and possibly long-term as well, depending on the transplanted islet yield. Children should have careful nutrition assessment and monitoring at several follow-up visits during the first year, then annually, and at any time with concerns.

[The 501st case: elevated blood glucose, chronic pancreatitis, and post- pancreatoduodenectomy malnutrition].

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.

Chronic pancreatitis and nutritional support.

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.

Efficacy and Predictors of Pain Response to Combined Antioxidants in Children with Chronic Pancreatitis.

BACKGROUND: Pain is a major problem in 90% of patients with chronic pancreatitis (CP). Studies evaluating response to antioxidants (AO) are conflicting and no pediatric studies are available. AIMS: To evaluate markers of oxidative stress (OS), and efficacy and predictors of response to AO in improving pain in children with CP. METHODS: Antioxidants were given to CP children for 6 months. Subjects were assessed at baseline and post-therapy for pain and markers of OS [serum thiobarbituric acid reactive substances (TBARS), superoxide dismutase (S-SOD)] and antioxidant levels [vitamin C, selenium, total antioxidant capacity-ferric reducing ability of plasma (FRAP)]. Matched healthy controls were assessed for OS and antioxidant levels. Good response was defined as ≥ 50% reduction in number of painful days/month. RESULTS: 48 CP children (25 boys, age 13 years) and 14 controls were enrolled. 38/48 cases completed 6 months of therapy. CP cases had higher OS [TBARS (7.8 vs 5.2 nmol/mL; p < 0.001)] and lower antioxidant levels [FRAP (231 vs. 381.3 µmol/L; p = 0.003), vitamin C (0.646 vs. 0.780 mg/dL; p < 0.001)] than controls. Significant reduction in TBARS and S-SOD and increase in FRAP, vitamin C, and selenium occurred after 6 months. 10.5% cases had minor side effects. 26(68%) cases had a good response, with 9(24%) becoming pain-free. Subjects with severe ductal changes had lower median BMI (- 0.73 vs 0.10; p = 0.04) and responded less often than those with mild changes (17/29 vs 9/9; p = 0.036). CONCLUSION: CP children have higher OS than healthy controls. Antioxidant therapy is safe. Pain response is seen in 68% cases, less often in patients with severe ductal changes.

The 501st case: elevated blood glucose, chronic pancreatitis, and post- pancreatoduodenectomy malnutrition / 中华内科杂志

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.

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.

Outpatient Pain Management in Children With Chronic Pancreatitis: A Scoping Systematic Review.

OBJECTIVES: Although pain management is central to pediatric chronic pancreatitis (CP) care, no evidence-based guidelines exist. In this scoping systematic review, we sought promising strategies for CP pain treatment in children. METHODS: We systematically reviewed literature on pain management in children and adults with CP, and 2 conditions with similar pain courses: juvenile idiopathic arthritis and sickle cell disease. RESULTS: Of 8997 studies identified, 287 met inclusion criteria. There are no published studies of analgesic medications, antioxidants, dietary modification, integrative medicine, or regional nerve blocks in children with CP. In adults with CP, studies of nonopioid analgesics, pancreatic enzymes, and dietary interventions have mixed results. Retrospective studies suggest that endoscopic retrograde cholangiopancreatography and surgical procedures, most durably total pancreatectomy with islet autotransplant, improve pain for children with CP. Follow-up was short relative to a child's life. Large studies in adults also suggest benefit from endoscopic therapy and surgery, but lack conclusive evidence about optimal procedure or timing. Studies on other painful pediatric chronic illnesses revealed little generalizable to children with CP. CONCLUSIONS: No therapy had sufficient high-quality studies to warrant untempered, evidence-based support for use in children with CP. Multicenter studies are needed to identify pain management "best practices."

Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study.

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.

Long-term effects of clinical interventions on nutritional status in patients with chronic pancreatitis - A systematic review.

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.

The role of extracorporeal shock wave lithotripsy in the treatment of chronic pancreatitis.

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.

Xerophthalmia due to vitamin A deficiency following Frey's procedure for chronic calcific pancreatitis.

We report a rare presentation of xerophthalmia due to partial pancreatic exocrine insufficiency following Frey's surgery (pancreatic resection) in a 12-year-old girl. The child had undergone this surgery for chronic calcific pancreatitis 3 years before and presented with ocular irritation and decreased vision of 3 months duration. Ocular examination showed severe conjunctival and corneal xerosis. Her serum retinol levels and 25-hydroxyvitamin D were tested and were extremely low. The condition rapidly reversed following high-dose replacement therapy with vitamin A and D. This case highlights the importance of continuous enzyme replacement therapy as well as dietary modification and nutritional supplement therapy and monitoring of ocular symptoms in post-pancreatic surgery.

ACG Clinical Guideline: Chronic Pancreatitis.

Chronic pancreatitis (CP) is historically defined as an irreversible inflammatory condition of the pancreas leading to varying degrees of exocrine and endocrine dysfunction. Recently however, the paradigm for the diagnosis has changed in that it breaks with the traditional clinicopathologic-based definition of disease, focusing instead on diagnosing the underlying pathologic process early in the disease course and managing the syndrome more holistically to change the natural course of disease and minimize adverse disease effects. Currently, the most accepted mechanistically derived definition of CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress. The most common symptom of CP is abdominal pain, with other symptoms such as exocrine pancreatic insufficiency and diabetes developing at highly variable rates. CP is most commonly caused by toxins such as alcohol or tobacco use, genetic polymorphisms, and recurrent attacks of acute pancreatitis, although no history of acute pancreatitis is seen in many patients. Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role. Total pancreatectomy represents the only known cure for CP, although difficulty in patient selection and the complications inherent to this intervention make it usually an unattractive option. This guideline will provide an evidence-based practical approach to the diagnosis and management of CP for the general gastroenterologist.

Chronic Pancreatitis and Bone Disease.

Patients with chronic pancreatitis (CP) may have a higher prevalence of osteoporosis than the general population thereby increasing the risk of bone fracture. The pathophysiology of bone disease in CP is multifactorial. Their risk factors for secondary osteoporosis include increasing age, low body mass index from sitophobia, maldigestion due to exocrine pancreatic insufficiency (EPI) with resulting low vitamin D, as well as smoking and alcohol abuse. An obvious association of bone disease with CP is from EPI with maldigestion of fat-soluble vitamins including vitamin-D, which has a significant role in the process of bone formation. Vitamin-D deficiency may be higher in CP patients vs controls, and it is especially so in CP patients with EPI. Screening for CP-associated osteopathy, including osteopenia and osteoporosis, should be initiated early in the course of CP, as the overall prevalence of bone disease is approximately two-thirds of CP patients. Our initial approach in the treatment of osteoporosis should include correction of maldigestion resulting from EPI with use of pancreatic enzyme replacement therapy (PERT). PERT, which is the treatment for EPI is associated with improvement in Dual energy X-ray absorptiometry (DXA) values and vitamin-D levels compared to those who are not treated. This should improve, in addition to body mass index, vitamin-D deficiency and calcium absorption as well as improve overall nutritional status. Osteopathy is common in CP patients, has significant associated morbidity, should be screened for regularly, and corrected with fat soluble vitamin supplementation and PERT to prevent clinical sequelae. In this article, we review the epidemiology, pathophysiology, and treatment of bone disease in patients with CP.

Diabetes and Chronic Pancreatitis: Considerations in the Holistic Management of an Often Neglected Disease.

Diabetes secondary to chronic pancreatitis (CP) or type 3cDM refers to a brittle form of diabetes and is often characterised by hypoglycaemic episodes, erratic glycaemic control, and impaired quality of life. It differs from other forms of diabetes and is typically characterised by concurrent pancreatic endocrine and exocrine insufficiency which can present as malabsorption and nutritional deficiencies. In this review, we discuss the pathogenesis, epidemiology, and the practicalities of diagnosis, screening, and management of this condition.

Study protocol for a randomised double-blinded, sham-controlled, prospective, cross-over clinical trial of vagal neuromodulation for pain treatment in patients with chronic pancreatitis.

INTRODUCTION: The management of chronic pancreatitis (CP) is challenging and requires a personalised approach focused on the individual patient's main symptoms. Abdominal pain is the most prominent symptom in CP, where central pain mechanisms, including sensitisation and impaired pain modulation, often are involved. Recent clinical studies suggest that vagal nerve stimulation (VNS) induces analgesic effects through the modulation of central pain pathways. This study aims to investigate the effect of 2 weeks transcutaneous VNS (t-VNS) on clinical pain in patients with CP, in comparison to the effect of sham treatment. METHODS AND ANALYSIS: Twenty-one patients with CP will be enrolled in this randomised, double-blinded, single-centre, sham-controlled, cross-over study. The study has two treatment periods: A 2-week active t-VNS using GammaCore device and a 2-week treatment with a sham device. During both treatment periods, the patients are instructed to self-administer VNS bilaterally to the cervical vagal area, three times per day. Treatment periods will be separated by 2 weeks. During the study period, patients will record their daily pain experience in a diary (primary clinical endpoint). In addition, all subjects will undergo testing which will include MRI, quantitative sensory testing, cardiac vagal tone assessment and collecting blood samples, before and after the two treatments to investigate mechanisms underlying VNS effects. The data will be analysed using the principle of intention to treat. ETHICS AND DISSEMINATION: The regional ethics committee has approved the study: N-20170023. Results of the trial will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The study is registered at www.clinicaltrials.gov: NCT03357029.

Chronic Pancreatitis and Nutrition Therapy.

Chronic pancreatitis is a complex and irreversible disease of the pancreas and is associated with significant morbidity and mortality. Nutrition deficiencies in chronic pancreatitis are common and can be atypical in nature. As such, the management of these deficiencies can be individualized for patients. The aim of this review is to discuss the components of nutrition deficiencies in chronic pancreatitis, their management, and the current areas of research that are being explored. The clinical guidelines of major national and international societies were analyzed for recommendations on the nutrition management of chronic pancreatitis. The etiology of nutrition deficiencies in chronic pancreatitis is multifactorial and includes aspects of exocrine and/or endocrine dysfunction, significant abdominal pain, often persistent alcohol consumption, and increased metabolic activity. A large number of patients with nutrition deficiencies are underrecognized and undertreated. Although the majority of these patients can be managed by oral and pancreatic enzyme supplementation, some patients may require enteral tube feeding and, in rare cases, parenteral feeding. Current areas of research include the accurate identification of patients at risk for nutrition deficiencies, optimization of feeding regimens, and research into islet cell autotransplantation.

Cingulate glutamate levels associate with pain in chronic pancreatitis patients.

AIMS: Emerging evidence show that patients with chronic pancreatitis (CP) and abdominal pain have structural and functional alterations in the central nervous system. The aim was to investigate cerebral metabolic signatures in CP and the associations to various risk factors/clinical characteristics and patient outcomes. METHODS: Magnetic resonance spectroscopy was used to measure brain metabolites in the anterior cingulate cortex (ACC), insula, prefrontal cortex and the parietal region in patients with CP and healthy controls. Subgroup analyses based on disease characteristics (alcoholic etiology of CP, diabetes and opioid treatment) were performed. Finally, relations to abdominal pain symptoms and quality of life scores were explored. RESULTS: Thirty-one patients with CP (mean age 58.5 ±â€¯9.2 years) and 23 healthy controls (54.6 ±â€¯7.8 years) were included. Compared to healthy controls, patients had increased glutamate/creatine (glu/cre) levels in the ACC (1.24 ±â€¯0.17 vs. 1.13 ±â€¯0.21, p = .045) and reduced parietal N-acetylaspartate/creatine (NAA/cre) levels (1.44 ±â€¯0.18 vs. 1.54 ±â€¯0.12, p = .027). Patients with alcoholic etiology of CP had significant lower levels of parietal NAA/cre as compared to patients without alcoholic etiology and healthy controls (p < .006). Patients with a high level of ACC glu/cre reported more severe abdominal pain than their counterparts with a low level of ACC glu/cre (pain score 4.1 ±â€¯2.7 vs.1.9 ±â€¯2.3, p = .039). CONCLUSIONS: Cerebral spectroscopy revealed novel and complementary information on central pain mechanisms and alcohol mediated toxic effects in patients with CP. Our data suggest that cingulate glutamate levels associate with the patients clinical pain symptoms, while parietal NAA levels more likely associate with an alcoholic etiology of CP.

Duodenum-preserving pancreatic head resection: A retrospective analysis of the Hamburg Modification.

BACKGROUND: Chronic pancreatitis remains a challenging inflammatory disease, causing progressive, irreversible fibrosis of the pancreatic parenchyma. Several surgical options for treatment have been established, but duodenum-preserving pancreatic head resections seem to be the most favorable option other than pancreatoduodenectomy. The aim of this retrospective analysis is to evaluate the outcomes of the Hamburg modification of duodenum-preserving pancreatic head resections. METHODS: We retrospectively evaluated-for long-term outcomes concerning pain control, quality of life, and symptom control-500 consecutive patients suffering from painful chronic pancreatitis who had undergone the Hamburg modification of the duodenum-preserving pancreatic head resection. Additionally, the patients were compared with a database of 104 patients who underwent duodenum-preserving pancreatic head resections according to Beger or Frey. RESULTS: After a mean follow-up of 10 years, overall survival was 90% in those patients having undergone the Hamburg modification. Regarding analgetic medications, the median pain score for frequency of pain attacks, measured by a visual analog scale and inability to work, was 0 (0-100), and the global quality of life revealed a median of 92 (0-100). In addition, we found that a high rate of patients continued consuming alcohol after the operation (37.9%). The rate of redo surgery owing to the recurrence of chronic pancreatitis was 7.6% after this Hamburg modification. CONCLUSION: Duodenum-preserving pancreatic head resections provide adequate outcomes in terms of pain control, quality of life, and symptom control. In this retrospective analysis, the Hamburg modification was found to be a good alternative to other forms of duodenum-preserving pancreatic head resections. The choice of a certain modification of the duodenum-preserving pancreatic head resection may depend on the surgeon's expertise and the individual needs of the patient.

Oral Litholysis in Patients with Chronic Calcific Pancreatitis Unresponsive to or Ineligible for Extracorporeal Shock Wave Lithotripsy and Endoscopic Therapy.

BACKGROUND/AIMS: Our study aimed to evaluate the effect of oral litholysis in patients with chronic calcific pancreatitis (CCP) unresponsive to or ineligible for extracorporeal shock wave lithotripsy (ESWL) and endoscopic therapy. METHODS: Trimethadione, an antiepileptic agent, was administered orally at a dose of 0.6-0.9 g/day to 15 patients with this condition. Treatment outcome was evaluated by assessment of dissolution of the pancreatic stones on plain X-ray films and computed tomography scans of the upper abdomen. Plasma glucose, hemoglobin A1c, and body mass index (BMI) were also monitored throughout the therapy. RESULTS: Litholysis was observed in 13 out of 15 patients (86.7%) and was definite in 10 and partial in 3. Six patients had pancreatitis attacks during the therapy; 5 of whom showed definite litholysis and had only 1 mild attack. Of the 11 patients with normal or impaired glucose tolerance at baseline, none developed diabetes mellitus and all showed litholysis. BMI significantly increased in patients whose pancreatic stones dissolved. There was no vital organ impairment by trimethadione. CONCLUSION: Oral litholysis using trimethadione may represent a noninvasive and effective complementary treatment in patients with CCP unresponsive to or ineligible for ESWL and endoscopic therapy.