Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance.

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies (n = 7) included MEN1-related insulinomas (n = 2) or MEN1-associated PHP (n = 2) or analyses of genetic profile (n = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, p < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). MEN1 pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline MEN1 pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: CDC73 gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified (n = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome (n = 1). Normocalcemic and mildly symptomatic hyperparathyroidism (n = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.

Prevalence, treatment efficacy, and risk factors of vascular complications in acute pancreatitis: A case-control study.

OBJECTIVE: We aimed to investigate the prevalence of vascular complications in acute pancreatitis (AP), to compare patient outcomes using various treatments, and to explore the related risk factors. METHODS: Consecutive AP patients admitted from January 2010 to July 2017 were retrospectively included. Demographics, vascular complications, laboratory indices, and imaging findings were collected. Univariate and multivariate analyses were used to explore potential risk factors of vascular complications. RESULTS: Of 3048 AP patients, 808 (26.5%) had vascular complications, including visceral vein thrombosis, sinistral portal hypertension, and arterial complications. And 38 (4.7%) patients received anticoagulant therapy and had a higher rate of recanalization (P < 0.001). Bleeding occurred in 95 (11.8%) patients, who received further treatment. Multivariate analysis identified male gender (odds ratio [OR] 1.650, 95% confidence interval [CI] 1.101-2.472), hyperlipidemia (OR 1.714, 95% CI 1.356-2.165), disease recurrence (OR 3.727, 95% CI 2.713-5.118), smoking (OR 1.519, 95% CI 1.011-2.283), hemoglobin level (OR 0.987, 95% CI 0.981-0.993), white blood cell (WBC) count (OR 1.094, 95% CI 1.068-1.122), non-vascular local complications (OR 3.018, 95% CI 1.992-4.573), computed tomography severity index (CTSI) (OR 1.425, 95% CI 1.273-1.596), and acute physiology and chronic health evaluation (APACHE) II score (OR 1.057, 95% CI 1.025-1.090) were related to vascular complications. CONCLUSIONS: Vascular complications in AP is prevalent and their treatment is challenging. Further investigations are warranted to determine the optimal treatment strategy. Independent risk factors included male gender, hyperlipidemia, disease recurrence, smoking, WBC count, non-vascular local complications, CTSI, and APACHE II score.

Crohn disease but not ulcerative colitis increases the risk of acute pancreatitis: A 2-sample Mendelian randomization study.

Accumulating evidence has indicated an increased risk of acute pancreatitis in individuals with inflammatory bowel disease (IBD); however, the establishment of a clear and direct causal connection between IBD and acute pancreatitis remains uncertain. Utilizing genetic data from publicly accessible genome-wide association studies (GWAS), we conducted a 2-sample MR analysis to identify the associations between IBD, ulcerative colitis (UC), Crohn disease (CD), and acute pancreatitis risk. Rigorous quality control steps ensured the selection of eligible single nucleotide polymorphisms (SNPs) with strong associations to IBD. The primary estimation used the inverse-variance weighted method. We also assessed heterogeneity, potential pleiotropy, and conducted sensitivity analyses. The direction of causality was confirmed using the Steiger test. The MR analysis showed that IBD increased the risk of acute pancreatitis (IVW: OR = 1.032, 95% CI: 1.006-1.06, P = .015). Among the subgroup of IBD, CD (IVW: OR = 1.034, 95% CI: 1.008-1.06, P = .007) indicates a significant increase in the risk of acute pancreatitis compared to UC (IVW: OR = 1.02, 95% CI: 0.99-1.051, P = .189). The MR analysis assessing the association between CD and acute pancreatitis showed no evidence of heterogeneity or horizontal pleiotropy. Likewise, the leave-one-out (LOO) method indicated no significant influence of any individual SNP on the overall findings. In addition, the Steiger direction test revealed that CD was the cause for increased risk of acute pancreatitis, but not vice versa. In summary, this research pioneers in proposing a causal relationship between CD and acute pancreatitis among the European population.

Hemorrhagic Cysts in the Pancreas: Risk Factors, Treatment, and Outcomes - Insights from a Single-Center Study.

BACKGROUND Hemorrhagic cysts are rarely discussed subtypes of pancreatic pseudocysts that occur in about 10% of these cases. They are caused by erosion of the walls of neighboring vessels by extravasated proteolytic pancreatic enzymes. A retrospective analysis was performed to clinically characterize risk factors, treatment, and outcome in patients with hemorrhagic cysts of the pancreas. MATERIAL AND METHODS The retrospective study included patients from the Department of Digestive Tract Surgery in Katowice, Poland, who were treated surgically for a pancreatic hemorrhagic cyst from January 2016 to November 2022. We gathered and assessed data on cyst etiology, symptoms, imaging examinations, risk factors, time, type, and complications of surgery. RESULTS The main symptom was abdominal pain, noted in 5 (62.5%) patients. The most common etiology of cyst was acute pancreatitis, which occurred in 5 patients (62.5%). The most common localization was the tail of pancreas, found in 3 patients (36.5%). The largest dimension of the cyst was 98±68 (30-200) mm. Every patient needed surgical intervention. Patients underwent distal pancreatectomy (n=3) or marsupialization (n=5). One (12.5%) postoperative complication was observed, while mortality was 0%. CONCLUSIONS Hemorrhagic cyst is a life-threatening complication of pancreatitis requiring immediate treatment. In most cases, open surgery is the treatment of choice. Despite the continuous development of minimally invasive techniques, surgical treatment remains the only effective treatment method. Depending on the cyst localization and technical possibilities, pancreatectomy or marsupialization can be applied, and both of them have low complication and mortality rates.

Predicting gallstone pancreatitis in HIV infected patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection, low cluster of differentiation (CD)4 counts and antiretroviral therapy can cause cholestasis and raised transaminases. In acute pancreatitis, this may render biochemical predictors of a gallstone aetiology inaccurate. METHODS: In a prospective observational study, acute pancreatitis was diagnosed by standard criteria. Cholecystolithiasis and bile duct diameter were diagnosed by ultrasound. Cholestasis was defined as two of the following: bilirubin ≥ 21 umol/l, γ glutamyl transferase ≥ 78 U/l, alkaline phosphatase ≥ 121 U/l. Cholangitis was defined as cholestasis and any two sepsis criteria: (temperature > 38˚C, WCC > 12.6 ×109/L, pulse > 90 beats/min). Cholangitis, cholestasis, and bile duct diameter greater that 1 cm were indications for endoscopic retrograde cholangiopancreatography (ERCP). These parameters' ability to predict gallstone pancreatitis (GSP) and choledocholithiasis were compared in HIV+ve and HIV-ve patients. RESULTS: Sixty-two (26%) of 216 patients had GSP. Twenty four were HIV+ve patients. More HIV+ve patients had cholestasis (p = 0.059) and ERCP (p = 0.004). In HIV+ve patients alanine aminotransferase (ALT) > 100 U/L, gamma glutamyl transferase (GGT) > 2 upper limit of normal and cholestasis had a negative predictive value of 92%, 96.7% and 95.2% respectively. In HIV-ve patients, negative predictive value (NPV) was 84%, 83.8% and 84.6% respectively. Bile duct stones were demonstrated at ERCP in 6 (25%) and 3 (8%) of HIV+ve and HIV-ve patients respectively (p = 0.077). Five of 14 ERCP patients had no bile duct stones. HIV+ve and HIV-ve groups had two deaths each. CONCLUSION: Absence at presentation of the abnormal parameters analysed were good predictors of a non-gallstone aetiology particularly in HIV+ve patients. Prior, magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) would reduce the number of non-therapeutic ERCPs.

American College of Gastroenterology Guidelines: Management of Acute Pancreatitis.

Acute pancreatitis (AP), defined as acute inflammation of the pancreas, is one of the most common diseases of the gastrointestinal tract leading to hospital admission in the United States. It is important for clinicians to appreciate that AP is heterogenous, progressing differently among patients and is often unpredictable. While most patients experience symptoms lasting a few days, almost one-fifth of patients will go on to experience complications, including pancreatic necrosis and/or organ failure, at times requiring prolonged hospitalization, intensive care, and radiologic, surgical, and/or endoscopic intervention. Early management is essential to identify and treat patients with AP to prevent complications. Patients with biliary pancreatitis typically will require surgery to prevent recurrent disease and may need early endoscopic retrograde cholangiopancreatography if the disease is complicated by cholangitis. Nutrition plays an important role in treating patients with AP. The safety of early refeeding and importance in preventing complications from AP are addressed. This guideline will provide an evidence-based practical approach to the management of patients with AP.

GGT1 is a SNP eQTL gene involved in STAT3 activation and associated with the development of Post-ERCP pancreatitis.

Post-ERCP pancreatitis (PEP) is an acute pancreatitis caused by endoscopic-retrograde-cholangiopancreatography (ERCP). About 10% of patients develop PEP after ERCP. Here we show that gamma-glutamyltransferase 1 (GGT1)-SNP rs5751901 is an eQTL in pancreatic cells associated with PEP and a positive regulator of the IL-6 amplifier. More PEP patients had the GGT1 SNP rs5751901 risk allele (C) than that of non-PEP patients at Hokkaido University Hospital. Additionally, GGT1 expression and IL-6 amplifier activation were increased in PEP pancreas samples with the risk allele. A mechanistic analysis showed that IL-6-mediated STAT3 nuclear translocation and STAT3 phosphorylation were suppressed in GGT1-deficient cells. Furthermore, GGT1 directly associated with gp130, the signal-transducer of IL-6. Importantly, GGT1-deficiency suppressed inflammation development in a STAT3/NF-κB-dependent disease model. Thus, the risk allele of GGT1-SNP rs5751901 is involved in the pathogenesis of PEP via IL-6 amplifier activation. Therefore, the GGT1-STAT3 axis in pancreas may be a prognosis marker and therapeutic target for PEP.

Management of ERCP complications.

Managing complications of ERCP poses a significant clinical challenge to endoscopists. ERCP complications can occur even after all preventive measures, which can lead to significant morbidity and even mortality. Major complications include pancreatitis, bleeding, perforation, cholangitis, and sedation-related adverse events. Early recognition of post-ERCP pancreatitis (PEP) is feasible by monitoring clinical parameters and specific cutoffs of serum amylase and lipase at 2-6 h post-ERCP. Pancreatic stenting for PEP is not recommended and can increase the incidence of infected necrosis in addition to being technically challenging. Post-sphincterotomy bleeds can be treated by diluted epinephrine with or without thermal therapy, or mechanical therapy (clips or fully covered metallic stents) failing which angiographic embolization and rarely open surgical vessel ligation may be warranted. Post-ERCP perforations can lead to significant morbidity and are usually treated with endoscopic closure of the defect, diverting bile flow, draining collections, and reducing fluid load at the site of perforation failing which surgery may be warranted. Broad-spectrum antibiotics with endoscopic or radiologic drainage of undrained segments help treat post-ERCP cholangitis. Hypoxia and hypertension are the most common sedation-related adverse events without long-term consequences except aspiration pneumonia (<0.5%). Awareness with a high index of suspicion is crucial for timely diagnosis and management of uncommon post-ERCP complications.

Gastrointestinal Conditions: Pancreatitis.

Acute pancreatitis is among the most common gastrointestinal disorders requiring hospitalization. The main causes are gallstones and alcohol use. Patients typically present with upper abdominal pain radiating to the back, worse with eating, plus nausea and vomiting. Diagnosis requires meeting two of three criteria: upper abdominal pain, an elevated serum lipase or amylase level greater than 3 times the normal limit, and imaging findings consistent with pancreatitis. After pancreatitis is diagnosed, the Atlanta classification and identification of the systemic inflammatory response syndrome can identify patients at high risk of complications. Management includes fluid resuscitation and hydration maintenance, pain control that may require opioids, and early feeding. Feeding recommendations have changed and "nothing by mouth" is no longer recommended. Rather, oral feeding should be initiated, as tolerated, within the first 24 hours. If it is not tolerated, enteral feeding via nasogastric or nasojejunal tubes should be initiated. Antibiotics are indicated only with radiologically confirmed infection or systemic infection symptoms. Surgical or endoscopic interventions are needed for biliary pancreatitis or obstructive pancreatitis with cholangitis. One in five patients will have recurrent episodes of pancreatitis; alcohol and smoking are major risk factors. Some develop chronic pancreatitis, associated with chronic pain plus pancreatic dysfunction, including endocrine failure (insulin insufficiency) and/or exocrine failure that requires long-term vitamin supplementation.

Case report: GLP1RA for the treatment of diabetes in liver transplanted people. Do they increase the risk of pancreatitis?

The incidence of acute pancreatitis (AP) in liver transplanted people is reported to be 1.5-8%. On the other hand, the evidence for a causal relationship between glucagon-like peptide 1 receptor agonists (GLP1RAs) and pancreatitis in people with type 2 diabetes is still weak. In addition, there are currently no data on a possible increased risk of AP in liver-transplanted individuals with diabetes treated with GLP1RAs. In a population of liver-transplanted individuals with diabetes receiving GLP1RA-based therapy, we reported an incidence of AP of 3.0% (two subjects). No cases were reported in liver-transplanted individuals with diabetes receiving SGLT2 inhibitors, insulin or metformin, neither in kidney or lung-transplanted patients treated with GLP1RAs. In both patients with AP, the only additional risk factor for its development was a history of re-transplantation (liver or combined kidney/liver). For this reason, we suggest particular caution when considering GLP1RAs-based therapies in liver transplanted patients with multiple risk factors for AP, such as a history of repeated and complex abdominal surgery.

Acute pancreatitis: A narrative review.

Acute pancreatitis is a common cause of acute abdominal pain and can range from mild oedema to severe necrosis of the pancreas. It has a significant impact on morbidity, mortality and financial burden. The global prevalence of pancreatitis is substantial, with the highest rates observed in central and eastern Europe. Diagnosing acute pancreatitis involves considering clinical symptoms, elevated serum amylase and/or lipase levels, and characteristic imaging findings. The causes of acute pancreatitis include obstructive disorders, such as gallstones and biliary sludge, alcohol consumption, smoking, drug-induced pancreatitis, metabolic disorders, trauma, medical procedures, infections, vascular diseases and autoimmune pancreatitis. Appropriate management of acute pancreatitis involves determining the severity of the condition, providing supportive care, addressing the underlying cause, and preventing complications. Advances in classifying the severity of acute pancreatitis and implementing goal-directed therapy have contributed to a decrease in mortality rates. Understanding its prevalence, aetiology and management principles is crucial for clinicians to appropriately diagnose and manage patients with acute pancreatitis.

Endoscopic Retrograde Cholangiopancreatography for the Management of Pancreatic Duct Leaks and Fistulas.

Pancreatic duct (PD) leaks are a common complication of acute and chronic pancreatitis, trauma to the pancreas, and pancreatic surgery. Diagnosis of PD leaks and fistulas is often made with contrast-enhanced pancreatic protocol computed tomography or magnetic resonance imaging with MRCP. Endoscopic retrograde pancreatography with pancreatic duct stenting in appropriately selected patients is often an effective treatment, helps to avoid surgery, and is considered first-line therapy in cases that fail conservative management.

Endoscopic Drainage of Pancreatic Fluid Collections.

Pancreatic fluid collections (PFCs) are commonly encountered complications of acute and chronic pancreatitis. With the advancement of endoscopic ultrasound (EUS) techniques and devices, EUS-directed transmural drainage of symptomatic or infected PFCs has become the standard of care. Traditionally, plastic stents have been used for drainage, although lumen-apposing metal stents (LAMSs) are now favored by most endoscopists due to ease of use and reduced procedure time. While safety has been repeatedly demonstrated, follow-up care for these patients is critical as delayed adverse events of indwelling drains are known to occur.

Role of leucine-rich repeat kinase 2 in severe acute pancreatitis.

Introduction: Intrapancreatic activation of trypsinogen caused by alcohol or high-fat intake and the subsequent autodigestion of the pancreas tissues by trypsin are indispensable events in the development of acute pancreatitis. In addition to this trypsin-centered paradigm, recent studies provide evidence that innate immune responses triggered by translocation of intestinal bacteria to the pancreas due to intestinal barrier dysfunction underlie the immunopathogenesis of acute pancreatitis. Although severe acute pancreatitis is often associated with pancreatic colonization by fungi, the molecular mechanisms linking fungus-induced immune responses to the development of severe acute pancreatitis are poorly understood. Leucine-rich repeat kinase 2 (LRRK2) is a multifunctional protein that mediates innate immune responses to fungi and bacteria. Mutations in Lrrk2 is a risk factor for Parkinson's disease and Crohn's disease, both of which are driven by innate immune responses to gut organisms. Discussion: In this Minireview article, we discuss how activation of LRRK2 by the recognition of fungi induces severe acute pancreatitis.

Trauma to the solid abdominal organs: The missed dark box of colonoscopy.

Colonoscopy is an integral part of the lower bowel care and is generally considered a potentially safe diagnostic and therapeutic procedure performed as a daycare outpatient procedure. Colonoscopy is associated with different complications that are not limited to adverse events related to the bowel preparation solutions used, the sedatives used, but to the procedure related as well including bleeding and perforation. Injuries to the extra-luminal abdominal organs during colonoscopy are uncommon, however, serious complications related to the procedure have been reported infrequently in the literature. Life threatening injuries to the spleen, liver, pancreas, mesentery, and urinary bladder have been reported as early as in mid-1970s. These injuries should not be overlooked by clinicians and endoscopists. Steadily increasing abdominal pain, abdominal distension, and hemodynamic instability in absence of rectal bleeding should raise the possibility of severe organ injury. Splenic and hepatic injury following colonoscopy are usually serious and may be life threatening. Although conservative management may help, yet they usually need interventional radiology or surgical intervention. Acute pancreatitis following colonoscopy is usually mild and is mostly managed conservatively. The mechanism of abdominal organ injuries during colonoscopy is not fully understood, however many risk factors have been identified, which can be classified as- organ related, procedure related, and local abdominal factors. Difficult colonoscopy and prior intra-abdominal adhesions are probably the most relevant risk factors for these injuries. Left lateral position, avoidance of looping and excessive force during the procedure would probably reduce the risk of such injuries.

Nonsteroidal anti-inflammatory drugs before endoscopic ultrasound guided tissue acquisition to reduce the incidence of post procedural pancreatitis.

Endoscopic ultrasound (EUS) with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and autoimmune pancreatitis or to analyze cyst fluid. The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis, which is likely induced by the same pathophysiological mechanisms as after endoscopic retrograde cholangiopancreatography (ERCP). According to the current European Society of Gastrointestinal Endoscopy guideline, nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate. A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition (TA) is harmless in healthy adults. Since it is associated with low costs and, most important, may prevent a dreadsome complication, we strongly recommend the administration of 100 mg diclofenac rectally prior to EUS-TA. We will explain this recommendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.