An update on the endocrine manifestations of antiphospholipid syndrome.

Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes.

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.

Pancreas units within gastroenterology departments. Organizational and operational standards for a patient-centered service.

The Asociación Española de Pancreatología (AESPANC), Asociación Española de Gastroenterología (AEG), and Sociedad Española de Patología Digestiva (SEPD) have developed a consensus document on the standards and recommendations they consider essential for the organization of pancreas units (PUs) within gastroenterology services (GSs) in order to conduct their activities in an efficient, high-quality manner. The consensus document defines PUs and lays down standards relating to their organization, structure, service portfolio, processes, and teaching and research activities. Standards have been categorized as mandatory (requirements to be met to qualify for certification by the scientific societies responsible for the standards) or recommendations. Standards should be updated at most within five years based on the experience gained in Spanish PUs and the advance of knowledge regarding pancreas disease. Development of health outcome indicators, including patient-reported outcome measures (PROMs), is considered a relevant challenge, as is evidence on the association of PU structure and activity standards with health outcomes.

Public Fear of Pancreatic Diseases: Causes and Clinical Outcomes at a Single Korean Center.

Background/Aims: The public fear of pancreatic diseases including pancreatic cancer (PC) appears to be growing. The aims of this study were to evaluate the causes of fear of pancreatic diseases and assess clinical outcomes of such individuals. Methods: This was a retrospective study of 249 individuals who visited the Pancreatobiliary Diseases Center at Ewha Womans University Seoul Hospital due to the fear of pancreatic diseases between January 2019 and August 2021. Those referred from other departments or external medical facilities were excluded. Collected data included demographic details, comorbidities, causes of fear of pancreatic diseases, and the presence of pancreatic lesions in imaging studies. Results: The median age was 55 years (range, 22 to 82 years). One hundred eleven subjects (44.6%) were male. The causes of fear of pancreatic diseases were abdominal pain (n=144, 57.8%), back pain (n=114, 45.8%), body weight change (n=35, 14.1%), family history of pancreatic diseases (n=32, 12.9%), and others (n=39, 15.7%). Within the group with family history of pancreatic diseases, 25 subjects had a first-degree relative with PC. Of the 200 subjects who underwent imaging, there was no evidence of pancreatic diseases in 182 (91.0%). Pancreatic lesions identified were cystic lesions (n=15, 7.5%), non-specific calcification (n=1, 0.5%), lipoma (n=1, 0.5%), and solid tumor (n=1, 0.5%), later diagnosed as unresectable PC. Conclusions: Abdominal pain and back pain were the major causes of fear of pancreatic diseases. The prevalence of PC among those who underwent imaging was 0.5%. Such characteristics should be considered when consulting individuals with fear of pancreatic diseases.

Aetiological Spectrum of Pancreaticobiliary Diseases in Adult Nigerians on Magnetic Resonance Cholangiopancreatography.

BACKGROUND: Imaging is vital for assessing pancreaticobiliary diseases. AIM: The aim of the study was to investigate the spectrum and pattern of pancreaticobiliary diseases in adult Nigerians using magnetic resonance cholangiopancreatography (MRCP). METHODS: This was a retrospective, descriptive cross-sectional study. The electronic radiological records of 110 adult Nigerians who had undergone MRCP were reviewed. The MRCP images were evaluated for bile duct dilatation, intraluminal filling defects, strictures, calculi, and other abnormalities. RESULTS: There were 45 males (40.9%) and 65 females (59.1%) aged 18-83 years, with a mean age of 51.93 ± 15.22 years. Jaundice (59.1%) and right hypochondrial pain (31.8%) were the most common presenting complaints. Gallstones (32.7%), common bile duct strictures (15.5%), choledocholithiasis (11.8%), pancreatic head carcinoma (10.9%), and gallbladder carcinoma (2.7%) were the most frequent abnormalities. There was biliary obstruction in 56.4% of participants, mostly at the distal and proximal common bile duct. Other findings include hepatomegaly (23.6%), hepatic cysts (6.4%), hepatic steatosis (0.9%), duodenal wall thickening (1.8%), and ascites (5.5%). MRCP was normal in 25 (22.7%) participants. CONCLUSION: Gallstones were the predominant pathology of the various pancreaticobiliary diseases, while Pancreatic head and gallbladder carcinoma were the most common malignant diseases.

The Pivotal Role of Macrophages in the Pathogenesis of Pancreatic Diseases.

The pancreas is an organ with both exocrine and endocrine functions, comprising a highly organized and complex tissue microenvironment composed of diverse cellular and non-cellular components. The impairment of microenvironmental homeostasis, mediated by the dysregulation of cell-to-cell crosstalk, can lead to pancreatic diseases such as pancreatitis, diabetes, and pancreatic cancer. Macrophages, key immune effector cells, can dynamically modulate their polarization status between pro-inflammatory (M1) and anti-inflammatory (M2) modes, critically influencing the homeostasis of the pancreatic microenvironment and thus playing a pivotal role in the pathogenesis of the pancreatic disease. This review aims to summarize current findings and provide detailed mechanistic insights into how alterations mediated by macrophage polarization contribute to the pathogenesis of pancreatic disorders. By analyzing current research comprehensively, this article endeavors to deepen our mechanistic understanding of regulatory molecules that affect macrophage polarity and the intricate crosstalk that regulates pancreatic function within the microenvironment, thereby facilitating the development of innovative therapeutic strategies that target perturbations in the pancreatic microenvironment.

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries.

BACKGROUND: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. METHODS: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. RESULTS: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 per cent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 per cent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 per cent; however, it was 41 per cent in low-to-middle- compared with 19 per cent in very high-HDI countries. CONCLUSION: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761).

Pancreatic surgery can sometimes lead to health problems afterwards. Although some top hospitals report good results, it is not clear how patients are doing all over the world. The aim was to find out how people are recovering after pancreatic surgery in different countries, and to see whether where they live affects their health outcomes after pancreatic surgery. The health records of 4223 patients from 67 countries who had pancreatic surgery in a 3-month interval in 2021 were studied, especially looking at how many people faced serious complications or passed away within 90 days of the surgery. Almost 7 in 10 patients faced some health problems after operation. The chance of having a major health issue or dying after the surgery was higher in countries with fewer resources and less developed healthcare. For example, 10 of 100 patients died after the surgery in these countries, but only 5 of 100 patients did in richer countries. What stands out is that countries with fewer resources have a tougher time getting patients back to health when things go wrong after surgery. It is hoped that doctors and medical groups worldwide can work together to improve these outcomes and give everyone the best chance of recovering well after pancreatic surgery.

Application of artificial intelligence in pancreas endoscopic ultrasound imaging- A systematic review.

The pancreas is a vital organ in digestive system which has significant health implications. It is imperative to evaluate and identify malignant pancreatic lesions promptly in light of the high mortality rate linked to such malignancies. Endoscopic Ultrasound (EUS) is a non-invasive precise technique to detect pancreas disorders, but it is highly operator dependent. Artificial intelligence (AI), including traditional machine learning (ML) and deep learning (DL) techniques can play a pivotal role to enhancing the performance of EUS regardless of operator. AI performs a critical function in the detection, classification, and segmentation of medical images. The utilization of AI-assisted systems has improved the accuracy and productivity of pancreatic analysis, including the detection of diverse pancreatic disorders (e.g., pancreatitis, masses, and cysts) as well as landmarks and parenchyma. This systematic review examines the rapidly developing domain of AI-assisted system in EUS of the pancreas. Its objective is to present a thorough study of the present research status and developments in this area. This paper explores the significant challenges of AI-assisted system in pancreas EUS imaging, highlights the potential of AI techniques in addressing these challenges, and suggests the scope for future research in domain of AI-assisted EUS systems.

Micelle-based fluorogenic sensing of trypsin: a sensitive method in pancreatic disease diagnosis.

Protamine-mediated micellar aggregates, featuring an AIE-based fluorescent sensor, facilitate efficient detection of trypsin activity. This method enables the detection of trypsin at exceptionally low concentrations (0.01-0.1 µg mL-1) in urine, demonstrating its potential for early clinical diagnosis of trypsin-related pancreatic diseases.

Successful surgical management of pancreatic torsion in a 3-month-old Bernese Mountain dog without evidence of long-term pancreatic dysfunction.

To describe the clinical presentation, diagnosis, perioperative management and the short- and long-term outcomes of a dog diagnosed with pancreatic torsion. A 3-month-old female intact Bernese Mountain dog presented for an acute onset of vomiting, anorexia and abdominal pain. Abdominal ultrasonography showed a hypoechoic mass effect cranial to the stomach. A pancreatic torsion was diagnosed during exploratory laparotomy and treated with partial pancreatectomy. Histopathology confirmed pancreatic torsion. The patient recovered uneventfully and pancreatic function and inflammation testing that was performed 14 months postoperatively showed no evidence of ongoing dysfunction. This is the first report that demonstrates long-term follow-up with pancreatic function testing in a patient who had a partial pancreatectomy due to pancreatic torsion. There was no evidence of long-term pancreatic dysfunction due to partial pancreatectomy secondary to pancreatic torsion. Additionally, this is the youngest patient with pancreatic torsion to be described in the veterinary literature.

Relationship of TNFα-238 G/A (rs 361525) genotypes with TNFα gene expression in liver and pancreas disorders in sample of beta thalassemia major adult Iraqi patients.

BACKGROUND: Tumor necrosis factor-α (TNFα) is a crucial physiologic regulator of immune responses, and several disorders have been associated with its dysregulation. OBJECTIVE: This study aimed to understand TNFα gene expression in adult patients with liver and pancreas disorders and examine the impact of TNFα-238 genotypes on this population. METHODS: At the Ibn Al-Baladi Hospital in Baghdad, blood samples were collected from forty patients who were diagnosed with beta thalassemia together with pancreatic disease, forty patients who were diagnosed with thalassemia together with liver disorder, and forty patients who were diagnosed with thalassemia without pancreas or liver disorder. For the purpose of establishing a control group, forty samples were collected from persons who were of the same age and gender and seemed to be in good health. All of these individuals were deemed to be older than 18 years old. Through the utilization of real-time polymerase chain reaction (PCR), the level of TNF-α gene expression was investigated and assessed. The T-ARMS-PCR method was performed for detection and genotyping of TNFα-238 in thalassemia patients and healthy control samples. RESULTS: The result showed that TNF α gene expression assessment showed that group B (thalassemia patients with liver disorder) had higher folding than other groups while the lowest gene expression was in group D (as control group). Furthermore, the relationship between TNFα gene expressions folding with TNFα-238 genotypes in beta thalassemia major patients, discovered a considerable increase at GA genotype patients in TNFα gene expression level, followed by AA genotype compared to the GG genotype. Furthermore, the results of the current study showed an association between the presence of the mutant (A) allele whether heterozygous (GA) and homozygous (AA) with the TNF-α gene expression in thalassemia patients with liver and pancreatic disorders. CONCLUSION: Based on the results, it can be concluded that there is a relationship between the presence of the mutant (A) allele, whether heterozygous (GA) or homozygous (AA) of TNF-α 238, and TNF-α gene expression in liver and pancreatic diseases as well as in patients with thalassemia.

Study of non-alcoholic fatty pancreatic disease among the Egyptian population and the value of serum fatty acid binding protein-1 (FABP-1) as a non-invasive biomarker.

BACKGROUND: Non-alcoholic fatty pancreas disease (NAFPD) can be detected using various imaging techniques, but accurately measuring the amount of fat in the pancreas remains difficult. Fatty acid binding protein-1 (FABP-1) is a marker specific to certain tissues and can aid in diagnosing NAFPD. However, this study aimed to investigate the prevalence of NAFPD among obese and non-obese people with and without diabetes mellitus (DM). Additionally, it aimed to evaluate the associated risk factors for NAFPD and the utility of the FABP-1 level as a simple, non-invasive biomarker for diagnosing NAFPD. METHODS: This study is a prospective cross-sectional study. RESULTS: Ninety-five patients were enrolled in the study, comprising 35 males and 60 females, with a mean age of 44 years and a standard deviation (SD) of 11 years. However, 26.3 % were morbidly obese, 22.1 % were severely obese, 31.6 % were obese, 12.6 % were overweight, and 7.4 % were normal. Additionally, 35.8 % had diabetes mellitus, while 26.3 % of patients had hypertension. Regarding the ultrasonographic findings, 94.7 % of the patients had fatty liver, with the majority (41.1 %) classified as grade II, followed by 38.9 % classified as grade I, and 14.7 % classified as grade III fatty liver. Among these patients, 78.9 % had fatty pancreas, with 38.9 % classified as grade II, 31.6 % classified as grade I, and 8.4 % classified as grade III fatty pancreas. The median FABP-1 level among patients with fatty pancreas was 3.3 ng/ml, which exhibited a significant fair negative correlation with total bilirubin and a fair, positive correlation with alkaline phosphatase and portal vein diameter. A statistically substantial distinction was observed between the levels of AFABP-1 and the presence or grading of the fatty pancreas (p-value = 0.048 and < 0.001, respectively). Using multivariate analysis, FABP-1 was the only significant predictor of a fatty pancreas. The receiver operating characteristic (ROC) curve analysis indicated that at a cut-off point of FABP-1 of ≤ 3.7, it had a sensitivity of 58 %, specificity of 80 %, positive predictive value (PPV) of 96.6 %, negative predictive value (NPV) of 17 %, and an area under the curve (AUC) of 0.77. CONCLUSION: NAFPD is becoming an increasingly significant challenge. FABP-1 can potentially be a straightforward and non-invasive predictor of the fatty pancreas.

Pancreatic stellate cells: Key players in pancreatic health and diseases (Review).

As a pluripotent cell, activated pancreatic stellate cells (PSCs) can differentiate into various pancreatic parenchymal cells and participate in the secretion of extracellular matrix and the repair of pancreatic damage. Additionally, PSCs characteristics allow them to contribute to pancreatic inflammation and carcinogenesis. Moreover, a detailed study of the pathogenesis of activated PSCs in pancreatic disease can offer promise for the development of innovative therapeutic strategies and improved patient prognoses. Therefore, the present study review aimed to examine the involvement of activated PSCs in pancreatic diseases and elucidate the underlying mechanisms to provide a viable therapeutic strategy for the management of pancreas­related diseases.

Pancreatoscopy-Guided Endotherapies for Pancreatic Diseases.

Per-oral pancreatoscopy (POP) is a pancreas-preserving modality that allows for targeted pancreatic duct interventions, particularly in cases where standard techniques fail. POP specifically has an emerging role in the diagnosis, risk stratification, and disease extent determination of main duct intraductal papillary mucinous neoplasms (IPMNs). It has also been successfully used for laser ablation of IPMNs in poor surgical candidates, lithotripsy for complex stone disease, and laser stricturoplasty. As experience with POP increases beyond select referral center practices, further studies validating POP efficacy with long-term follow-up will help clarify when POP-guided intervention is most beneficial in relation to surgical intervention.

History of the Interventional Pancreaticobiliary Endoscopy.

With the introduction of endoscopic retrograde cholangiopancreatography and linear endoscopic ultrasound, interventional pancreaticobiliary (PB) endoscopy has had an enormous impact in the management of pancreatic and biliary diseases. Continuous efforts to improve various devices and techniques have revolutionized these treatment modalities as viable alternatives to surgery. In recent years, trends toward combining endoscopic techniques with other modalities, such as laparoscopic and radiological interventions, for complex PB diseases have emerged using a multidisciplinary approach. Ongoing research and clinical experience will lead to refinements in interventional PB endoscopic techniques and subsequently improve outcomes and reduce complication rates.

Contrast-enhanced guided endoscopic ultrasound procedures.

Contrast-enhanced endoscopic ultrasound (CH-EUS) can overcome the limitations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours. Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions, further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS. This review details the knowledge based on the available data on contrast-guided procedures. The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions, which occur in select cases. Additionally, the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage, and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented. Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours, in which case CH-EUS can be used to reveal the incomplete tumour destruction.