The roles of calcium and ATP in the physiology and pathology of the exocrine pancreas.

This review deals with the roles of calcium ions and ATP in the control of the normal functions of the different cell types in the exocrine pancreas as well as the roles of these molecules in the pathophysiology of acute pancreatitis. Repetitive rises in the local cytosolic calcium ion concentration in the apical part of the acinar cells not only activate exocytosis but also, via an increase in the intramitochondrial calcium ion concentration, stimulate the ATP formation that is needed to fuel the energy-requiring secretion process. However, intracellular calcium overload, resulting in a global sustained elevation of the cytosolic calcium ion concentration, has the opposite effect of decreasing mitochondrial ATP production, and this initiates processes that lead to necrosis. In the last few years it has become possible to image calcium signaling events simultaneously in acinar, stellate, and immune cells in intact lobules of the exocrine pancreas. This has disclosed processes by which these cells interact with each other, particularly in relation to the initiation and development of acute pancreatitis. By unraveling the molecular mechanisms underlying this disease, several promising therapeutic intervention sites have been identified. This provides hope that we may soon be able to effectively treat this often fatal disease.

Endoscopic Pancreatic Drainage Improves Exocrine Pancreatic Function in Patients With Unresectable Pancreatic Cancer: A Double-Blind, Prospective, Randomized, Single-Center, Interventional Study.

OBJECTIVES: Exocrine pancreatic insufficiency is a frequent and clinically relevant complication of pancreatic cancer probably secondary to pancreatic duct obstruction. We aimed at evaluating the impact of endoscopic pancreatic drainage on pancreatic function in patients with unresectable pancreatic cancer. METHODS: A double-blind, prospective, randomized, single-center, interventional study was designed. Patients undergoing endoscopic retrograde cholangiopancreatography for jaundice secondary to unresectable pancreatic cancer were randomized to biliary drainage (group A) or biliopancreatic drainage (group B). Pancreatic function was evaluated by 13C-mixed triglyceride breath test before and 2 weeks after endoscopic retrograde cholangiopancreatography. Breath test result is expressed as 13C-cumulative recovery rate. Abdominal symptoms and nutritional markers were evaluated as secondary outcomes. RESULTS: Twenty patients were included. Sixteen patients had exocrine pancreatic insufficiency, and 13 completed the study (7 in group A and 6 in group B). The median absolute improvement of 13C-cumulative recovery rate was of 23.75% (interquartile range, 9.62-31.74) after biliopancreatic drainage compared with -1.92% (interquartile range, -4.17 to 13.92) after biliary drainage (P = 0.015). Nutritional markers improved after biliopancreatic drainage, but not after biliary drainage. CONCLUSIONS: Biliopancreatic and not biliary endoscopic drainage is associated with a significant improvement of exocrine pancreatic function in patients with unresectable pancreatic cancer.

Shwachman-diamond syndrome: A case report.

RATIONALE: The aim of this study was to analyze the genetic abnormalities and clinical manifestations of Shwachman-Diamond syndrome (SDS). PATIENT CONCERNS: A Chinese infant with elevated transaminase and a novel mutation at of sbdsc.258 +2T>C and c.184a>Tc.292G>A. DIAGNOSES: The female patient was 5 months' old at onset, with elevated transaminase as the first manifestation accompanied by restricted growth and development and oily stool. After sequencing the blood samples from patients and their parents, the heterozygous mutations of sbdsc.258 +2T>C and c.184a>T were detected. INTERVENTIONS: After admission, the patient was provided compound glycyrrhizin, Newtide formula milk supplemented with probiotics, fat-soluble vitamins, oral medication to adjust the spleen and stomach, and other symptomatic treatments. OUTCOMES: The stool traits improved, and the levels of liver function transaminases decreased compared with before. LESSONS: SDS is a rare disease with a variety of clinical manifestations. Pancreatic exocrine dysfunction, blood system manifestations, and bone abnormalities are common clinical manifestations, and genetic testing is helpful for diagnosis.

Influence of pre-diabetic and pancreatic exocrine states on pulmonary and nutritional status in adults with Cystic Fibrosis.

BACKGROUND: In 1992, a landmark study demonstrated clinical deterioration in respiratory function and nutritional status prior to the onset of cystic fibrosis-related diabetes (CFRD). We re-evaluated this outcome. METHODS: The Montreal Cystic Fibrosis Cohort is a prospective CFRD screening study. We performed a 6-year retrospective analysis of nutritional parameters and FEV1 (%) in subjects who developed incident CFRD and in controls who maintained normoglycemia (NG). In the former group, data was collected over 6 years prior to diabetes onset. RESULTS: Subjects (n = 86) had a mean age of 31.7 ± 8.1 years, BMI of 23.0 ± 4.0 kg/m2, and FEV1% of 70.1 ± 24.2%. Eighty-one percent had pancreatic insufficiency (PI). Patients were grouped as follows: NG+PS (pancreatic sufficient) (n = 16), NG+PI (pancreatic insufficient) (n = 21), CFRD+PS (n = 3) and CFRD+PI (n = 46). At their most recent screen NG+PS subjects had significantly greater BMI, as compared to NG+PI and CFRD+PI groups (26.2 ± 3.6 kg/m2 vs 22.6 ± 4.2 kg/m2 vs 22.1 ± 3.5 kg/m2, p = 0.0016). FEV1 was significantly greater in the NG+PS group (91.5 ± 16.8% vs 67.8 ± 25.3% vs 63.5 ± 22.2%, p = 0.0002). The rates of change in weight, BMI, fat mass (%), and FEV1 prior to the most recent visit (NG+PS, NG+PI groups) or to the diagnosis of de novo CFRD were similar between groups. CONCLUSION: In a contemporary context, CFRD onset is not preceded by deterioration in BMI, fat mass, or pulmonary function. Low BMI and FEV1 are more closely associated with PI than a pre-diabetic state.

Organisation of the human pancreas in health and in diabetes.

For much of the last century, our knowledge regarding the pancreas in type 1 and type 2 diabetes was largely derived from autopsy studies of individuals with these disorders or investigations utilising rodent models of either disease. While many important insights emanated from these efforts, the mode for investigation has increasingly seen change due to the availability of transplant-quality organ-donor tissues, improvements in pancreatic imaging, advances in metabolic assessments of living patients, genetic analyses, technological advances for laboratory investigation and more. As a result, many long-standing notions regarding the role for and the changes that occur in the pancreas in individuals with these disorders have come under question, while, at the same time, new issues (e.g., beta cell persistence, disease heterogeneity, exocrine contributions) have arisen. In this article, we will consider the vital role of the pancreas in human health and physiology, including discussion of its anatomical features and dual (exocrine and endocrine) functions. Specifically, we convey changes that occur in the pancreas of those with either type 1 or type 2 diabetes, with careful attention to the facets that may contribute to the pathogenesis of either disorder. Finally, we discuss the emerging unknowns with the belief that understanding the role of the pancreas in type 1 and type 2 diabetes will lead to improvements in disease diagnosis, understanding of disease heterogeneity and optimisation of treatments at a personalised level. Graphical abstract.

A tale of two pancreases: exocrine pathology and endocrine dysfunction.

The islets of Langerhans are well embedded within the exocrine pancreas (the latter comprised of ducts and acini), but the nature of interactions between these pancreatic compartments and their role in determining normal islet function and survival are poorly understood. However, these interactions appear to be critical, as when pancreatic exocrine disease occurs, islet function and insulin secretion frequently decline to the point that diabetes ensues, termed pancreatogenic diabetes. The most common forms of pancreatogenic diabetes involve sustained exocrine disease leading to ductal obstruction, acinar inflammation, and fibro-fatty replacement of the exocrine pancreas that predates the development of dysfunction of the endocrine pancreas, as seen in chronic pancreatitis-associated diabetes and cystic fibrosis-related diabetes and, more rarely, MODY type 8. Intriguingly, a form of tumour-induced diabetes has been described that is associated with pancreatic ductal adenocarcinoma. Here, we review the similarities and differences among these forms of pancreatogenic diabetes, with the goal of highlighting the importance of exocrine/ductal homeostasis for the maintenance of pancreatic islet function and survival and to highlight the need for a better understanding of the mechanisms underlying these diverse conditions. Graphical abstract.

Protective Effects of PACAP in Peripheral Organs.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide widely distributed in the nervous system, where it exerts strong neuroprotective effects. PACAP is also expressed in peripheral organs but its peripheral protective effects have not been summarized so far. Therefore, the aim of the present paper is to review the existing literature regarding the cytoprotective effects of PACAP in non-neuronal cell types, peripheral tissues, and organs. Among others, PACAP has widespread expression in the digestive system, where it shows protective effects in various intestinal pathologies, such as duodenal ulcer, small bowel ischemia, and intestinal inflammation. PACAP is present in both the exocrine and endocrine pancreas as well as liver where it reduces inflammation and steatosis by interfering with hepatic pathology related to obesity. It is found in several exocrine glands and also in urinary organs, where, with its protective effects being mainly published regarding renal pathologies, PACAP is protective in numerous conditions. PACAP displays anti-inflammatory effects in upper and lower airways of the respiratory system. In the skin, it is involved in the development of inflammatory pathology such as psoriasis and also has anti-allergic effects in a model of contact dermatitis. In the non-neuronal part of the visual system, PACAP showed protective effects in pathological conditions of the cornea and retinal pigment epithelial cells. The positive role of PACAP has been demonstrated on the formation and healing processes of cartilage and bone where it also prevents osteoarthritis and rheumatoid arthritis development. The protective role of PACAP was also demonstrated in the cardiovascular system in different pathological processes including hyperglycaemia-induced endothelial dysfunction and age-related vascular changes. In the heart, PACAP protects against ischemia, oxidative stress, and cardiomyopathies. PACAP is also involved in the protection against the development of pre-senile systemic amyloidosis, which is presented in various peripheral organs in PACAP-deficient mice. The studies summarized here provide strong evidence for the cytoprotective effects of the peptide. The survival-promoting effects of PACAP depend on a number of factors which are also shortly discussed in the present review.

Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic cancer are poorly investigated with heterogeneous results. We sought to determine the prevalence and clinical consequences of pancreatic exocrine insufficiency and the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer by systematic review and meta-analysis. METHODS: Scopus, Medline, and Embase were searched for cohort studies or randomised clinical trials reporting pancreatic exocrine insufficiency and/or the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer. We considered pancreatic exocrine insufficiency as an abnormal result on direct and/or indirect pancreatic exocrine function tests. Pancreatic enzyme replacement therapy was evaluated by its effect on survival and quality of life in patients with advanced pancreatic cancer. RESULTS: A total of 11 studies were included; seven studies reported the prevalence of pancreatic exocrine insufficiency and seven the effect of pancreatic enzyme replacement therapy in advanced pancreatic cancer. The pooled prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer was 72% (95% confidence interval: 55-86%), being significantly higher when tumours were located in the pancreatic head (relative risk = 3.36, 1.07-10.54; p = 0.04) six studies investigated the impact of pancreatic enzyme replacement therapy on survival/quality of life. Pancreatic enzyme replacement therapy was associated with 3.8 months (95% confidence interval: 1.37-6.19) survival benefit. Patients receiving pancreatic enzyme replacement therapy had a trend towards a better quality of life.Conclusions The prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer is substantial and its treatment can improve the outcomes of these patients.

Islet Amyloid in Patients With Diabetes Due to Exocrine Pancreatic Disorders, Type 2 Diabetes, and Nondiabetic Patients.

BACKGROUND: Amyloid deposits are a typical finding in pancreatic islets from patients with type 2 diabetes. Whether this is linked to the pathogenesis of type 2 diabetes is currently unknown. Therefore, we compared the occurrence of islet amyloid in patients with type 2 diabetes, diabetes secondary to pancreatic disorders, and nondiabetic individuals. PATIENTS AND METHODS: Pancreatic tissue from 15 nondiabetic patients, 22 patients with type 2 diabetes, and 11 patients with diabetes due to exocrine pancreatic disorders (chronic pancreatitis, pancreatic carcinoma) were stained for insulin, amyloid, and apoptosis. ß-cell area, amyloid deposits, and ß-cell apoptosis were quantified by morphometric analysis. RESULTS: The proportion of islets containing amyloid deposits was significantly higher in both type 2 diabetes and diabetes due to exocrine pancreatic disorders than in healthy subjects. Islets with both amyloid and apoptosis were observed more frequently in type 2 diabetes and significantly more so in diabetes due to exocrine pancreatic disorders. In both diabetic groups, apoptotic ß-cells were found significantly more frequently in islets with more prominent amyloid deposits. CONCLUSIONS: The occurrence of amyloid deposits in both type 2 diabetes and diabetes secondary to exocrine pancreatic disorders suggests that islet amyloid formation is a common feature of diabetes mellitus of different etiologies and may be associated with a loss of pancreatic ß-cells.

Diabetes of the Exocrine Pancreas Related to Hereditary Pancreatitis, an Update.

PURPOSE OF REVIEW: The aim was to review evidence about diabetes secondary to hereditary pancreatitis, seeking novel diagnostic and treatment features. RECENT FINDINGS: Hereditary pancreatitis (HP) is an autosomal dominant condition, characterized by recurrent episodes of acute pancreatitis, progression to fibrosis, and chronic pancreatitis. Clinical presentation includes diabetes of the exocrine pancreas (DEP). HP prevalence ranges from 0.3 to 0.57 per 100,000 people, with up to 80% of these develop DEP. This condition often requires specific interventions: with regard to metabolic control, metformin is the first choice for those with mild DEP, and for those in advanced disease, insulin is considered the first-line therapy. Insulin analogues and insulin pump therapy are preferred due to the brittle glycemic pattern and risk of hypoglycemia. In case of exocrine insufficiency, pancreatic enzyme replacement therapy is recommended. Pancreatic polypeptide administration is a promising novel treatment feature. DEP due to HP appears to be a misdiagnosed condition. The requirement of specific management demonstrates the importance of this matter; therefore, appropriate recognition and classification are important.

Long-Term Functional Outcome After Pancreatoduodenectomy for Periampullary Carcinoma With Morphological Correlation.

OBJECTIVE: The aim of the study was to evaluate the long-term functional outcome (exocrine and endocrine) and morphological changes in remnant pancreas after pancreatoduodenectomy and its clinical impact. METHODS: Periampullary carcinoma patients with minimum follow-up of 2 years and without recurrence were included (N = 102). Exocrine insufficiency includes clinical steatorrhea and fecal elastase-1 (FE-1) levels; endocrine insufficiency, glucose levels and glycated hemoglobin; and morphological changes, main pancreatic duct (MPD) diameter and thickness of remnant pancreas. RESULTS: The mean (standard deviation) follow-up period was 59 (26) months. Of the 102 patients, 81 (80%) had severely deficient FE-1 (0-100 µg/g). The preoperative MPD was significantly more and thickness of remnant pancreas was significantly less in patients with severely deficient FE-1. Overall, 15.6% (16/102) developed steatorrhea and improved on enzyme replacement therapy. The presence of MPD stricture (P = 0.008) and weight loss (P = 0.001) were significantly associated with steatorrhea. New-onset diabetes was seen in 17% (15/90) patients, of whom 3 of 5 developed it after 4 years (range, 4-7 years). The blood glucose was controlled on oral hypoglycemics in 2 (10/15) of 3 patients. CONCLUSIONS: The assessment by FE-1 indicates loss of exocrine function in more than 90%, whereas only 1 of 6 developed steatorrhea and new-onset diabetes. Morphological changes especially MPD stricture affect the functional status of remnant pancreas.

Assessment of Exocrine Pancreatic Function During Endoscopy in Children.

This article will review briefly the physiology of pancreatic enzyme secretion and the role of stimulated endoscopic testing for assessing exocrine pancreatic function. Published studies in both the pediatric and adult literature are reviewed. The technique and utility of endoscopic pancreatic function testing as the method of choice in the differential diagnosis of pancreatic disorders in childhood is described. Finally, emerging, clinically useful markers that can be measured in the pancreatic fluid will be described.

In utero and postnatal VX-770 administration rescues multiorgan disease in a ferret model of cystic fibrosis.

Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). In patients with CF, abnormalities initiate in several organs before birth. However, the long-term impact of these in utero pathologies on disease pathophysiology is unclear. To address this issue, we generated ferrets harboring a VX-770 (ivacaftor)-responsive CFTR G551D mutation. In utero VX-770 administration provided partial protection from developmental pathologies in the pancreas, intestine, and male reproductive tract. Homozygous CFTR G551D/G551D animals showed the greatest VX-770-mediated protection from these pathologies. Sustained postnatal VX-770 administration led to improved pancreatic exocrine function, glucose tolerance, growth and survival, and to reduced mucus accumulation and bacterial infections in the lung. VX-770 withdrawal at any age reestablished disease, with the most rapid onset of morbidity occurring when withdrawal was initiated during the first 2 weeks after birth. The results suggest that CFTR is important for establishing organ function early in life. Moreover, this ferret model provides proof of concept for in utero pharmacologic correction of genetic disease and offers opportunities for understanding CF pathogenesis and improving treatment.

Type-3c Diabetes Mellitus, Diabetes of Exocrine Pancreas - An Update.

BACKGROUND: The incidence of diabetes is increasing steeply; the number of diabetics has doubled over the past three decades. Surprisingly, the knowledge of type 3c diabetes mellitus (T3cDM) is still unclear to the researchers, scientist and medical practitioners, leading towards erroneous diagnosis, which is sometimes misdiagnosed as type 1 diabetes mellitus (T1DM), or more frequently type 2 diabetes mellitus (T2DM). This review is aimed to outline recent information on the etiology, pathophysiology, diagnostic procedures, and therapeutic management of T3cDM patients. METHODS: The literature related to T3cDM was thoroughly searched from the public domains and reviewed extensively to construct this article. Further, existing literature related to the other forms of diabetes is reviewed for projecting the differences among the different forms of diabetes. Detailed and updated information related to epidemiological evidence, risk factors, symptoms, diagnosis, pathogenesis and management is structured in this review. RESULTS: T3cDM is often misdiagnosed as T2DM due to the insufficient knowledge differentiating between T2DM and T3cDM. The pathogenesis of T3cDM is explained which is often linked to the history of chronic pancreatitis, pancreatic cancer. Inflammation, and fibrosis in pancreatic tissue lead to damage both endocrine and exocrine functions, thus leading to insulin/glucagon insufficiency and pancreatic enzyme deficiency. CONCLUSION: Future advancements should be accompanied by the establishment of a quick diagnostic tool through the understanding of potential biomarkers of the disease and newer treatments for better control of the diseased condition.

Association of fatty pancreas with pancreatic endocrine and exocrine function.

AIM: The purpose of this study was to clarify whether fatty pancreas might lead to impaired pancreatic endocrine or exocrine function. MATERIAL AND METHODS: The study involved 109 participants who had undergone the glucagon stimulation test and N-benzoyl-L-tyros-p-amino benzoic acid (BT-PABA) test to assess pancreatic function as well as unenhanced abdominal computed tomography (CT). Pancreatic endocrine impairment was defined as ΔC peptide immunoreactivity less than 2 [mmol/L] in the glucagon stimulation test, and pancreatic exocrine impairment was defined as a urinary PABA excretion rate less than 70% on the BT-PABA test. We defined as the mean CT value of pancreas / CT value of spleen (P/S ratio) as a marker to assess fatty pancreas. We analyzed the association between fatty pancreas and pancreatic impairment using the logistic regression model. The odds ratio (OR) is shown per 0.1 unit. RESULTS: Pancreatic endocrine function was impaired in 33.0% of the participants, and 56.9% of those were regarded as having pancreatic exocrine impairment. The P/S ratio was significantly correlated with pancreatic endocrine impairment in univariate analysis (OR = 0.61, 95% confidence interval (CI) = 0.43-0.83, P = 0.0013) and multivariate analysis (OR = 0.38, 95% CI = 0.22-0.61, P < .0001) for all participants. Similar significant relationships were observed in both univariate (OR = 0.70, 95% CI = 0.49-0.99, P = 0.04) and multivariate (OR = 0.39, 95% CI = 0.21-0.66, P = 0.0002) analyses for the participants without diabetes (n = 93). The amount of pancreatic fat was not associated with exocrine impairment in univariate analysis (OR = 0.80, 95% CI = 0.59-1.06, P = 0.12). CONCLUSION: Fatty pancreas was associated with pancreatic endocrine impairment but did not have a clear relationship with pancreatic exocrine impairment.

Sonographic pancreas echogenicity in cystic fibrosis compared to exocrine pancreatic function and pancreas fat content at Dixon-MRI.

OBJECTIVE: Fatty infiltration of the pancreas is a dominating feature in cystic fibrosis (CF). We evaluate the association between pancreatic fat content assessed by Dixon magnetic resonance imaging (MRI), pancreatic echogenicity at ultrasonography (US) and exocrine function in CF patients and healthy controls (HC). MATERIAL AND METHODS: Transabdominal US, pancreatic Dixon-MRI and diffusion-weighted imaging (DWI) were performed in 21 CF patients and 15 HCs. Exocrine function was assessed by endoscopic secretin test and fecal elastase. RESULTS: CF patients were grouped according to exocrine pancreatic function as subjects with normal (CFS: n = 11) or reduced (CFI: n = 10) function. Among CFI 90% (9/10) had visual hyperechogenicity. CFI also had increased echo-level values (p<0.05 vs others). All CFI (10/10) had markedly increased pancreatic fat content estimated by MRI compared to sufficient groups, p<0.001). Among CFS patients and HC, 27% (3/11) and 33% (5/15), respectively, had hyperechoic pancreas. However, all these had low pancreatic fat-content at MRI compared to CFI. In CFI, pancreatic fat content was correlated to ADC (r = -0.93, p<0.001). CONCLUSION: Pancreas insufficient CF patients exhibit severe pancreatic fatty-infiltration at MRI and hyperechoic pancreas at US. Pancreas hyperechogenicity in pancreatic sufficient subjects does not co-exist with fatty infiltration at MRI. MRI evaluates pancreatic fatty infiltration more accurately than US and fat infiltration estimated by MRI outperforms sonographic hyper-echogenicity as a marker for exocrine pancreatic failure in CF.

Age- and sex-specific prevalence of diabetes associated with diseases of the exocrine pancreas: A population-based study.

BACKGROUND AND AIMS: Diabetes associated with diseases of the exocrine pancreas (DP) is a recognized clinical condition but data on its prevalence are limited to a few single centre studies. Relative contribution of the three major diseases of the exocrine pancreas (acute pancreatitis, chronic pancreatitis, pancreatic cancer) to prevalence of DP as well as the effect of age and sex is largely unknown. The study aimed to determine age- and sex-specific prevalence of DP overall and after acute pancreatitis, chronic pancreatitis, and pancreatic cancer alone at the population level. METHODS: Nationwide population database covering nearly 3 million residents in New Zealand over a 10-year study period was used. DP was identified based on International Classification of Diseases-10 codes. Data were reported as prevalence per 1000 population and corresponding 95% confidence intervals. RESULTS: The crude prevalence of DP was 1.13 [1.12, 1.14] per 1000, with 70-79 years age group having the highest prevalence at 3.94 [3.92, 3.97] per 1000. Men had an overall prevalence of 1.32 [1.31, 1.33] per 1000 and women-0.93 [0.92, 0.94] (p<0.05). Acute pancreatitis contributed 61% to overall prevalence of DP. CONCLUSIONS: Prevalence of DP in the general population is close to that of type 1 diabetes. Three out of five DP cases develop after acute pancreatitis. There is a variation in age of onset of DP, with the working and ageing population most affected. Men have a 40% higher risk of developing DP than women.

Autoimmune Pancreatitis - A Riddle Wrapped in an Enigma.

Autoimmune pancreatitis (AIP) was recognized as a clinical entity, at least in the West little more than 10 years ago. Since then, studies globally, and international collaboration, have led to important advances in our understanding of its clinical features, disease course, and management, although the aetiopathogenesis of this curious disease remains to be fully elucidated. Types 1 and 2 AIP have been described, of which type 1 is the commonest form, and best defined. International consensus now recognizes it as one of the many clinical manifestations of IgG4-related disease, and is now termed IgG4-related pancreatitis (IgG4-RP). The disease is not confined to a particular race, gender, or age, but often presents after the fifth decade in men. A common presentation is with jaundice due to low bile duct obstruction related to diffuse pancreatic enlargement (historically often leading to a misdiagnosis of cancer). Acute pancreatitis is unusual. Other organ involvement is a particular feature, including biliary disease, retroperitoneal fibrosis, generalized lymphadenopathy, renal, and lung involvement. No single test makes the diagnosis, and diagnostic criteria for type 1 AIP/IgG4-RP, which incorporate clinical, laboratory, radiological, pathological, and therapeutic parameters should be applied. A particular attempt should be made to make a histological diagnosis, which is characterized by an IgG4-positive lymphoplasmacytic infiltrate. Management is not based on randomized studies, but corticosteroids are the mainstay of treatment, providing rapid clinical and radiological benefit. However, clinical relapse is common (particularly in type 1 AIP, and in those with associated other organ involvement). Additional immunosuppression may be required, including azathioprine, and rituximab may play an emerging role. The disease course is variable, but loss of organ function (especially pancreatic exocrine failure and pancreatic atrophy) may occur.

Thirty-day outcomes underestimate endocrine and exocrine insufficiency after pancreatic resection.

BACKGROUND: Long-term incidence of endocrine and exocrine insufficiency after pancreatectomy is poorly described. We analyze the long-term risks of pancreatic insufficiency after pancreatectomy. METHODS: Subjects who underwent pancreatectomy from 2002 to 2012 were identified from a prospective database (n = 227). Subjects who underwent total pancreatectomy or pancreatitis surgery were excluded. New post-operative endocrine and exocrine insufficiency was defined as the need for new pharmacologic intervention within 1000 days from resection. RESULTS: 28 (16%) of 178 subjects without pre-existing endocrine insufficiency developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days, 8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214 subjects without pre-operative exocrine insufficiency developed exocrine insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days, and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine insufficiency. On multivariate regression, pancreaticoduodenectomy and chemotherapy were associated with a greater risk of exocrine insufficiency. CONCLUSION: Reporting 30-day functional outcomes for pancreatic resection is insufficient, as nearly 45% of subjects who develop disease do so after 90 days. Reporting of at least 90-day outcomes may more reliably assess risk for post-operative endocrine and exocrine insufficiency.

[Pancreatic infringement exocrine and endocrine in cystic fibrosis]. / Atteinte pancréatique exocrine et endocrine dans la mucoviscidose.

The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent phase of diabetes, screening it is recommended by the realization of an annual OGTT from 10 years of age, or before in severe forms of CF. New treatments of CF able to target CFTR showed their efficacy in slowing the decline of lung function, and could also contribute to slow or prevent the onset of diabetes.