The neurological core features of the infantile-onset multisystem neurologic, endocrine, and pancreatic disease: A novel nonsense mutation in an Italian family.

AIM: Biallelic mutations in the PTRH2 gene have been associated with infantile multisystem neurological, endocrine, and pancreatic disease (IMNEPD), a rare autosomal recessive disorder of variable expressivity characterized by global developmental delay, intellectual disability or borderline IQ level, sensorineural hearing loss, ataxia, and pancreatic insufficiency. Various additional features may be included, such as peripheral neuropathy, facial dysmorphism, hypothyroidism, hepatic fibrosis, postnatal microcephaly, cerebellar atrophy, and epilepsy. Here, we report the first Italian family presenting only predominant neurological features. METHODS: Extensive neurological and neurophysiological evaluations have been conducted on the two affected brothers and their healthy mother since 1996. The diagnosis of peripheral neuropathy of probable hereditary origin was confirmed through a sural nerve biopsy. Exome sequencing was performed after the analysis of major neuropathy-associated genes yielded negative results. RESULTS: Whole-exome sequencing analysis identified the homozygous substitution c.256C>T (p.Gln86Ter) in the PTRH2 gene in the two siblings. According to American College of Medical Genetics and Genomics (ACMG) guidelines, the variant has been classified as pathogenic. At 48 years old, the proband's reevaluation confirmed a demyelinating sensorimotor polyneuropathy with bilateral sensorineural hearing loss that had been noted since he was 13. Additionally, drug-resistant epileptic seizures occurred when he was 32 years old. No hepatic or endocrinological signs developed. The younger affected brother, 47 years old, has an overlapping clinical presentation without epilepsy. INTERPRETATION: Our findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to PTRH2 variants. We thereby hope to better define IMNEPD and facilitate the identification and diagnosis of this novel disease entity.

Overexpression of Pdx1, reduction of p53, or deletion of CHOP attenuates pancreas hypoplasia in mice with pancreas-specific O-GlcNAc transferase deletion.

Deletion of O-GlcNAc transferase (Ogt) in pancreatic epithelial progenitor cells results in pancreatic hypoplasia at birth, partly due to increased apoptosis during embryonic development. Constitutive loss of Ogt in ß-cells results in increased ER stress and apoptosis, and in the Ogt-deficient pancreas, transcriptomic data previously revealed both tumor suppressor protein p53 and pancreatic duodenal homeobox 1 (Pdx1), key cell survival proteins in the developing pancreas, as upstream regulators of differentially expressed genes. However, the specific roles of these genes in pancreatic hypoplasia are unclear. In this study, we explored the independent roles of p53, ER stress protein CHOP, and Pdx1 in pancreas development and their use in the functional rescue of pancreatic hypoplasia in the context of Ogt loss. Using in vivo genetic manipulation and morphometric analysis, we show that Ogt plays a key regulatory role in pancreas development. Heterozygous, but not homozygous, loss of pancreatic p53 afforded a partial rescue of ß-cell, α-cell, and exocrine cell masses, while whole body loss of CHOP afforded a partial rescue in pancreas weight and a full rescue in exocrine cell mass. However, neither was sufficient to fully mitigate pancreatic hypoplasia at birth in the Ogt-deficient pancreas. Furthermore, overexpression of Pdx1 in the pancreatic epithelium resulted in partial rescues in pancreas weight and ß-cell mass in the Ogt loss background. These findings highlight the requirement of Ogt in pancreas development by targeting multiple proteins such as transcription factor Pdx1 and p53 in the developing pancreas.

Pancreas deficiency modifies bone development in the ovine fetus near term.

Hormones have an important role in the regulation of fetal growth and development, especially in response to nutrient availability in utero. Using micro-CT and an electromagnetic three-point bend test, this study examined the effect of pancreas removal at 0.8 fraction of gestation on the developing bone structure and mechanical strength in fetal sheep. When fetuses were studied at 10 and 25 days after surgery, pancreatectomy caused hypoinsulinaemia, hyperglycaemia and growth retardation which was associated with low plasma concentrations of leptin and a marker of osteoclast activity and collagen degradation. In pancreatectomized fetuses compared to control fetuses, limb lengths were shorter, and trabecular (Tb) bone in the metatarsi showed greater bone volume fraction, Tb thickness, degree of anisotropy and porosity, and lower fractional bone surface area and Tb spacing. Mechanical strength testing showed that pancreas deficiency was associated with increased stiffness and a greater maximal weight load at fracture in a subset of fetuses studied near term. Overall, pancreas deficiency in utero slowed the growth of the fetal skeleton and adapted the developing bone to generate a more compact and connected structure. Maintenance of bone strength in growth-retarded limbs is especially important in a precocial species in preparation for skeletal loading and locomotion at birth.

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.

Proximal subtotal pancreatectomy as an alternative to total pancreatectomy for malnourished patients.

PURPOSE: To investigate whether proximal subtotal pancreatectomy (PSTP) is superior to total pancreatectomy (TP) for preserving postoperative endocrine function, and to identify the pre-operative risk factors influencing prognosis after TP and PSTP. METHODS: The subjects of this retrospective study were patients who underwent TP (n = 15) or PSTP (n = 16) between 2008 and 2018 in our hospital. First, we compared the incidence of hypoglycemia within 30 days after surgery and the total daily amount of insulin needed in the 30 days after TP vs. PSTP. Then, we compared the prognoses between the groups. RESULTS: The incidence of hypoglycemia in the 30 days after surgery was significantly lower in the PSTP group than in the TP group (n = 0 vs. n = 5; p < 0.001). The total amount of daily insulin given was also significantly lower after PSTP than after TP: (0 units vs. 18 units, p = 0.001). Lower lymphocyte counts (p = 0.014), lower cholinesterase (p = 0.021), and lower prognostic nutrition index (p = 0.021) were identified as significant risk factors for hypoglycemia in the TP group. Low cholinesterase (p = 0.015) and a low prognostic nutrition index (p = 0.048) were significantly associated with an unfavorable prognosis in the TP group, but not in the PSTP group. CONCLUSIONS: PSTP may be a feasible alternative to TP to preserve endocrine function, especially for malnourished patients.

Prolactin Is Associated With Insulin Resistance and Beta-Cell Dysfunction in Infertile Women With Polycystic Ovary Syndrome.

Background: Our study aimed to investigate if serum prolactin (PRL) levels associated with insulin resistance and beta-cell dysfunction in infertile patients with polycystic ovary syndrome (PCOS). Methods: This was a retrospective cross-sectional study performed in the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University. From January 2007 to August 2018, a total of 792 PCOS and 700 non-PCOS infertile women were included. All patients' prolactin levels were in the normal range. PCOS was diagnosed according to the Rotterdam Criteria. Anthropometric parameters, blood pressure, serum prolactin levels, sex hormones, fasting lipids, fasting plasma glucose (FPG), fasting insulin (FINS) and hepatic biological parameters were measured in all subjects. Results: Serum prolactin levels in PCOS women were significantly decreased compared with levels in non-PCOS women after adjusting for age and BMI (P < 0.05). Moreover, we found that prolactin levels were positively associated with high-density lipoprotein cholesterol (HDL-C) and negatively associated with age, BMI, waist circumference (WC), hip circumference (HC), luteinizing hormone/follicle stimulating hormone (LH/FSH), estradiol (E2), FINS, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of ß (HOMA-ß), triglyceride (TG) and alanine aminotransferase (ALT) (P < 0.05). After adjusting for age and BMI, multiple linear regression analysis revealed that LH, LH/FSH, E2, FINS, HOMA-IR, and HOMA-ß were negatively associated with serum PRL (P < 0.05). Conclusions: Low serum PRL levels within the normal range associates with a higher incidence of insulin resistance and beta-cell dysfunction in infertile women with PCOS.

Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India.

OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India. METHODS: A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects. RESULTS: In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one-half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported. CONCLUSION: This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.

Risk Factors Associated With Progression Toward Endocrine Insufficiency in Chronic Pancreatitis.

OBJECTIVE: Little data exist describing the change over time in islet function and glycemic control in patients with chronic pancreatitis (CP). METHODS: In 325 CP patients who underwent 2 mixed meal tolerance tests and/or glycated hemoglobin (HbA1c) levels, we estimated the rate of change in metabolic measures per 6 months and assessed the association between potential risk factors for diabetes and rate of change using multivariate regression models. RESULTS: Per 6-month time, HbA1c increased by 0.062% with a standard error of 0.029% (P = 0.037) and the ratio (area under the curve (AUC) C-peptide to AUC glucose from mixed meal tolerance testing) decreased by 0.0028 with a standard error of 0.0011 (P = 0.014). We observed more rapid decline in smokers (AUC C-peptide, P = 0.043) and patients with surgical drainage (AUC glucose, P = 0.001; ratio, P = 0.03) or with calcific pancreatitis (HbA1c, P = 0.003). In multivariate models, AUC C-peptide and ratio declined at a greater rate in smokers and HbA1c in those with pancreatic calcifications (both P < 0.05). CONCLUSIONS: We observed a measurable decline in ß-cell function and glycemic control in patients with CP. Patients with a history of tobacco smoking, surgical drainage, or pancreatic calcification may be at highest risk.

Pancreatic steatosis: an update.

PURPOSE OF REVIEW: Pancreatic steatosis is a clinical entity with emerging significance and impacts patient health in a multitude of ways. It has a high prevalence in the global population with predilections for different demographics by age, sex and ethnicity. Understanding the pathophysiology, clinical features and complications of this entity may be important to understanding the consequences of the ongoing obesity global epidemic. RECENT FINDINGS: Obesity and metabolic syndrome contribute to metabolic derangements that result in lipid mishandling by adipocytes. Adipocytokine imbalances in circulation and in the pancreatic microenvironment cause chronic, low-grade inflammation. The resulting beta cell and acinar cell apoptosis leads to pancreatic endocrine and exocrine dysfunction. Furthermore, these adipocytokines regulate cell growth, differentiation, as well as angiogenesis and lymphatic spread. These consequences of adipocyte infiltration are thought to initiate carcinogenesis, leading to pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma. SUMMARY: Obesity will lead to millions of deaths each year and pancreatic steatosis may be the key intermediate entity that leads to obesity-related complications. Enhancing our understanding may reveal strategies for preventing mortality and morbidity related to the global epidemic of obesity. Further research is needed to determine the pathophysiology, long-term complications and effective treatment strategies for this condition.

Pancreatic Steatosis: An Emerging Clinical Entity.

Pancreatic steatosis is an emerging clinical entity whose pathophysiology, natural history, and long-term complications are poorly characterized in the current literature. Epidemiological and prospective studies have described prevalence rates between 16% and 35%. Although the natural history is not well known, there are strong associations with obesity, metabolic syndrome, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Ectopic fat accumulation of the pancreas can cause chronic, low-grade inflammation from adipocytokine imbalances that involve beta cells and acinar cells. This mechanism can lead to pancreatic endocrine and exocrine dysfunction and initiate carcinogenesis. Although it is associated with morbid conditions, pancreatic steatosis may be amendable to treatment with a healthy diet, less meat consumption, exercise, and smoking cessation. Pancreatic steatosis should factor into clinical decision-making and prognostication of patients with pancreatic and systemic disease. This review seeks to describe the pathophysiology, natural history, diagnosis, and complications of this emerging clinically relevant entity.

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.

Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans.

The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5- to 10-fold higher basal and stimulated blood flow, which is separately regulated. This is reflected in the vascular anatomy of the pancreas where islets have separate arterioles. There is also an insulo-acinar portal system, where numerous venules connect each islet to the acinar capillaries. Both islets and acini possess strong metabolic regulation of their blood perfusion. Of particular importance, especially in the islets, is adenosine and ATP/ADP. Basal and stimulated blood flow is modified by local endothelial mediators, the nervous system as well as gastrointestinal hormones. Normally the responses to the nervous system, especially the parasympathetic and sympathetic nerves, are fairly similar in endocrine and exocrine parts. The islets seem to be more sensitive to the effects of endothelial mediators, especially nitric oxide, which is a permissive factor to maintain the high basal islet blood flow. The gastrointestinal hormones with pancreatic effects mainly influence the exocrine pancreatic blood flow, whereas islets are less affected. A notable exception is incretin hormones and adipokines, which preferentially affect islet vasculature. Islet hormones can influence both exocrine and endocrine blood vessels, and these complex effects are discussed. Secondary changes in pancreatic and islet blood flow occur during several conditions. To what extent changes in blood perfusion may affect the pathogenesis of pancreatic diseases is discussed. Both type 2 diabetes mellitus and acute pancreatitis are conditions where we think there is evidence that blood flow may contribute to disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:799-837, 2019.

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.

Association between pancreatic fat and incidence of metabolic syndrome: a 5-year Japanese cohort study.

BACKGROUND AND AIM: Previous cross-sectional studies showed that pancreatic fat was associated with metabolic syndrome. However, no longitudinal study has evaluated whether people with high pancreatic fat are likely to develop future metabolic syndrome. This study investigated the association between baseline pancreatic fat and metabolic syndrome incidence. METHODS: In 2008-2009, 320 participants without metabolic syndrome underwent health checks, which included unenhanced computed tomography, and were followed up annually for 4-5 years. Baseline pancreatic fat amounts were evaluated using a histologically validated method that measured differences between pancreas and spleen attenuations on computed tomography. The participants were divided into low (reference), intermediate, and high pancreatic fat groups based on pancreas and spleen attenuation tertiles. Metabolic syndrome incidence was evaluated annually over a median follow-up period of 4.99 (interquartile range, 4.88-5.05) years, in accordance with the 2009 harmonized criteria. Risk ratios (RRs) for the association between baseline pancreatic fat amounts and metabolic syndrome incidence were estimated using Poisson regression models adjusted for age, sex, body mass index, liver fat, pre-metabolic syndrome, cigarette use, alcohol use, and physical activity. RESULTS: Metabolic syndrome incidence was 30.6% (98/320). Pancreatic fat was associated with an increased incidence of metabolic syndrome, based on a univariate analysis (RRs [95% confidence interval], 3.14 [1.74-5.67] and 3.96 [2.23-7.03] in the intermediate and high pancreatic fat groups, respectively). The association remained statistically significant in the multivariate analysis (RR [95% confidence interval], 2.04 [1.14-3.64] and 2.30 [1.28-4.14] for the same groups, respectively). CONCLUSIONS: Pancreatic fat predicts the future risk of metabolic syndrome.

Alveolar echinococcosis in the head of pancreas: A case report.

RATIONALE: Pancreatic alveolar echinococcosis (AE) is an exceptionally rare disease; no more than 10 cases have been published to date. It is characterized as extensive local tissue infringement and destruction; thus, extended surgical resection, such as duodenopancreatectomy, is often needed to obtain a negative resection margin so as to improve the long-term outcome and prognosis. PATIENT CONCERNS: A middle-aged Tibetan man was admitted due to a 16-year history of recurrent pain in the right upper abdomen. Magnetic resonance imaging scan showed a cystic lesion in the VI segment of his liver and several cystic lesions in the head of pancreas. DIAGNOSES: Pancreatic AE. INTERVENTIONS: The patient adopted a preserved surgery of partial cystectomy and completely removing the content of the cyst and then soaking by hypertonic saline combined with adjuvant medical therapy of albendazole. OUTCOMES: The patient was monitored on a regular basis at the outpatient department; the patient is still alive and has already survived 8 years till now. LESSONS: A preserved surgery combined with adjuvant medical therapy of albendazole can also contribute to a good survival outcome for AE located at the head of pancreas.

Non-Alcoholic Fatty Pancreas Disease (NAFPD): A Silent Spectator or the Fifth Component of Metabolic Syndrome? A Literature Review.

BACKGROUND AND OBJECTIVE: Fat accumulation in the pancreas has remained a relatively unknown disease since it was initially described in 1926. However, it has gained increasing attention in the past two decades with the emergence of the obesity epidemic. Pancreatic steatosis is a general term used for fat accumulation in the pancreas. It is further classified into fatty replacement, fatty infiltration, lipomatous pseudo-hypertrophy, non-alcoholic fatty pancreas disease (NAFPD) and non-alcoholic fatty steatopancreatitis (NASP). NAFPD is defined as obesity-associated accumulation of fat in the pancreas without significant alcohol consumption. Data on the prevalence of NAFPD are limited due to a lack of standardized screening tests. METHODS: MEDLINE/PubMed was searched to find relevant studies and abstracts on pancreatic steatosis. RESULTS: Pancreatic fat can be quantified by various imaging techniques including ultrasonography, computed tomography, magnetic resonance imaging and magnetic resonance spectroscopy. The pathophysiology of NAFPD has not been completely understood. Chronic exposure of ß-cells to hyperglycemia and higher levels of free fatty acids results in increased intracellular triglyceride accumulation, which ultimately causes reduced insulin secretion, insulin resistance, cell apoptosis and subsequent fatty replacement. This vicious cycle likely is a determining factor in the development of diabetes mellitus and metabolic syndrome. There is no approved pharmacologic therapy for NAFPD. Caloric restriction might have a role in normalization of ß-cell function by reducing pancreatic fat content. Troglitazone (blend of telmisartan and sitagliptin) has demonstrated effectiveness in animal models but is still in experimental stages. CONCLUSION: The cause and effect relationship between the metabolic syndrome and NAFPD has not yet been established. Further studies are required to study the effect of NAFPD on glucose hemostasis.

Páncreas divisum y pancreatitis: su importancia en la práctica cotidiana / Pancreas divisum and pancreatitis: its importance in everyday practice

Pancreas divisum (PD) is the most common congenital anatomical variant of the pancreas. Its etiological implication in recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) has been recurrently questioned. Normal anatomy and variants: 80-90% of the population has normal anatomy, with excretion of exocrine pancreatic secretion to the duodenum by the major papilla. Three anatomical variants of PD have been described: classic PD with visible ventral duct, but total absence of fusion; PD with absence of ventral duct; and incomplete PD, with a rudimentary connection between the ventral and dorsal ducts. Clinical implication: This anatomical variant is symptomatic in less than 5% of the carriers, being associated to higher prevalence in patients with RAP However, the relationship between PD and RAP is considered probable, only in cases of association with mutation of the CFTR gene. Obstructive CP can develop in the segment drained by the dorsal duct. Diagnosis: Magnetic resonance cholangiopancreatography (MRCP) is the most sensitive diagnostic method. Other non-invasive diagnostic methods are endosonography and computed tomography (CT), the latter with lower performance. Treatment: The current trend in acute pancreatitis (AP) where PD is assumed as an etiological factor, is endoscopic resolution, with papillotomy with or without a pancreatic stent.

El páncreas divisum (PD) es la variante anatómica congénita más frecuente del páncreas. Su implicancia etiológica en pancreatitis aguda recurrente (PAR) y pancreatitis crónica (PC) ha sido frecuentemente cuestionada. Anatomía normal y variantes: 80-90% de la población presenta anatomía normal, con salida de secreción pancreática exocrina al duodeno por la papila mayor. Se han descrito 3 variantes anatómicas: PD clásico con conducto ventral visible, pero ausencia total de fusión; PD con ausencia de conducto ventral; y PD incompleto, con conexión rudimentaria entre los conductos ventral y dorsal. Implicancia clínica: Esta variante anatómica da síntomas en menos de 5% de los portadores, asociándose a mayor prevalencia en pacientes con PAR. Sin embargo, se considera probable la relación entre PD y PAR, solo en casos de asociación con mutación del gen CFTR. Pancreatitis crónica (PC) obstructiva se puede desarrollar en el segmento drenado por el conducto dorsal. Diagnóstico: La colangiopancreatografía por resonancia magnética (CPRM) es el método diagnóstico más sensible. Otros métodos diagnósticos no invasivos son la endosonografía y tomografía computada (TC), este último de menor rendimiento. Tratamiento: La tendencia actual en PA donde se asume PD como factor etiológico, es la resolución endoscópica, con papilotomía con o sin stent.

A spontaneous hematoma arising within an intrapancreatic accessory spleen: A case report and literature review.

RATIONAL: Hematoma arising within an intrapancreatic accessory spleen (IPAS) is an extremely rare pathological entity. PATIENT CONCERN: We present the case of a 39-year-old man with acute abdominal pain. DIAGNOSES: The patient was initially diagnosed as pancreatic cystic neoplasm according to CT and MRI imaging. INTERVENTIONS: Distal pancreatectomy was conducted because of the possibility of malignancy. OUTCOMES: Surgical resection showed that the lesion was a hematoma in an IPAS. LESSONS: Our case indicated that the differential diagnosis of hematoma in IPAS should be born in mind for cases with cystic neoplasm in tail of pancreas and an epidermoid cyst arising within an intrapancreatic accessory spleen (ECIAS).

Severe infantile isolated exocrine pancreatic insufficiency caused by the complete functional loss of the SPINK1 gene.

Exocrine pancreatic insufficiency (EPI) is rare in children, with most if not all cases occurring as part of syndromic conditions such as cystic fibrosis and Shwachman-Diamond syndrome. Here we report two cases, both presenting with severe EPI around 5 months of age. Characterized by diffuse pancreatic lipomatosis, they otherwise exhibited no remarkable deficiencies in other organs. Novel non-identical homozygous variants (a deletion removing the entire SPINK1 gene and an insertion of a full-length inverted Alu element into the 3'-untranslated region of the SPINK1 gene) resulting in the complete functional loss of the SPINK1 gene (encoding pancreatic secretory trypsin inhibitor) were identified in each patient. Having correlated our findings with current knowledge of SPINK1's role in exocrine pancreas pathophysiology, we propose that complete and partial functional losses of the SPINK1 gene are associated with quite distinct phenotypes, the former causing a new pediatric disease entity of severe infantile isolated EPI.