Pancreatic and non-pancreatic causes of hyperamylasemia

Surgical Management of Acute Pancreatitis

Genetically Defined Models of Chronic Pancreatitis

Macroamylasemia is a rare disorder characterized by the formation of an amylase-globulin complex that is too large to be easily cleared by the kidneys, resulting in elevated serum amylase levels. It is a benign condition with no serious signs or symptoms and requires no treatment. This article presents a case of long-term asymptomatic hyperamylasemia in a 10-year-old child. The child was admitted to the gastroenterology department with complaints of abdominal pain. Since the age of 8, there have been unexplained increases in serum amylase to 235 U/L and pancreatic amylase to 63.5 U/L, without clinical manifestations of pancreatitis, with normal levels of urine amylase and coprological elastase. An examination was performed, during which pancreatic pathology was excluded. The ratio of amylase and creatinine clearances was 0.754%. This ratio turned out to be less than 1%, which is more likely to indicate macroamysalemia. After further examination, type 1 macroamylasemia was diagnosed, which was the cause of hyperamylasemia — a non-life-threatening biochemical anomaly that requires a detailed examination, broad differential diagnostics, but does not require treatment. However, macroamylasemia is a diagnostic challenge because it must be differentiated from other causes of hyperamylasemia to avoid unnecessary testing and treatment. Hyperamylasemia is one of the main diagnostic criteria for pancreatitis, requiring extensive additional testing and treatment, often in a hospital setting. Therefore, it is important that physicians can recognize and diagnose macroamylasemia at an early stage to avoid unnecessary diagnostic and therapeutic measures. In this regard, we hope that the clinical example we have provided will be interesting and useful for physicians of various specialties.

Alcoholic pancreatitis: is it a priori chronic disease?

Controversies in clinical pancreatology: autoimmune pancreatitis: does it exist?

Gastric cystic duplication communicating with a bifid pancreas: a rare cause of recurrent pancreatis.

Blood tests possessing higher diagnostic accuracy are needed for all the major pancreatic diseases. Glycoprotein 2 (GP2) is a protein that is specifically expressed by the pancreatic acinar cell and that has previously shown promise as a diagnostic marker in animal models of acute pancreatitis. This study describes the development of an assay for GP2, followed by the determination of plasma GP2 levels in patients with acute pancreatitis, chronic pancreatitis, and pancreatic cancer. Rabbit polyclonal antisera and mouse monoclonal antibodies were generated against human GP2 and used to develop an enzyme-linked immunosorbent assay. The assay was tested in patients with an admitting diagnosis of pancreatic disease at 2 tertiary care facilities. The diagnosis of acute or chronic pancreatitis and pancreatic cancer was determined using previously established criteria that incorporated symptoms, radiology, pathology, and serology. Plasma GP2 levels were determined in 31 patients with acute pancreatitis, 16 patients with chronic pancreatitis, 36 patients with pancreatic cancer, and 143 control subjects without pancreatic disease. Amylase and lipase levels were also determined in patients with acute pancreatitis. The GP2 assay's sensitivity values were 0.94 for acute pancreatitis, 0.81 for chronic pancreatitis, and 0.58 for pancreatic cancer, which were greater than the 0.71 for acute pancreatitis and 0.43 for chronic pancreatitis (P =.02) observed for amylase. The lipase assay sensitivity for acute pancreatitis was 0.66. The accuracy of the GP2 assay was greater than that of the amylase or lipase assays for acute pancreatitis (GP2 vs lipase, P =.004; GP2 vs amylase, P =.003) when analyzed using receiver operator characteristic curves. When daily serial blood samples were obtained for 13 patients with acute pancreatitis, GP2 levels remained abnormally elevated for at least 1 day longer than the amylase or lipase levels. The GP2 assay is a useful new marker for acute and chronic pancreatitis.

Response

Secretin-Stimulated MRCP to Optimally Select Patients for Pancreatic Endotherapy?

Acute recurrent pancreatitis is a common clinical problem. The etiology and clinical management vary widely. Pancreas divisum is the most common congenital anomaly of the pancreas. However, only a small percentage of individuals with pancreas divisum develop acute or recurrent pancreatitis. Clinical manifestations range from isolated episodes of acute recurrent pancreatitis to chronic pancreatitis, and in some cases unexplained pain without any recognizable inflammation. The variations in clinical presentation, clinical progression of the disease, and responses to endoscopic or nonendoscopic treatments are not entirely predictable. 1 These facts have led to substantial controversy about the association of pancreas divisum with pancreatic disease. They lead us to believe that mere presence of an anatomic anomaly is not in itself sufficient and there have to be other disease modifiers or cofactors that are responsible for pancreatic injury. Environmental insults such as oxidative stresses could play a role, however, these do not seem to be universally reproducible. A key may lie in the genetic make up of the individual. In this issue of the journal, Garg and colleagues 2 have investigated the association of genetic mutations and acute recurrent pancreatitis in individuals with pancreas divisum. They have tested for genetic mutations known to be associated with pancreatitis: cystic fibrosis transmembrane conductance regulator gene (CFTR), cationic trypsinogen (PRSS1), and serine protease inhibitor Kazal type 1 (SPINK1) gene. This study was conducted in a tertiary referral center in Northern India. They studied 12 subjects with pancreas divisum and acute recurrent pancreatitis. Their control group included patients with acute recurrent pancreatitis but no pancreas divisum, patients with chronic pancreatitis due to other causes, and healthy volunteers. Mutations in individuals with asymptomatic pancreas divisum were not evaluated. Detailed work-up was carried out including analysis for the presence of microcrystals in the bile before considering etiology of pancreatitis to be idiopathic. All subjects with pancreas divisum and acute recurrent pancreatitis underwent endoscopic retrograde cholangiopancreatography with minor papillotomy and temporary stenting of the dorsal duct. Response to endoscopic therapy was defined as reduction in >50% of acute pancreatitis episodes/year. Prevalence of SPINK1 gene mutations was found to be similar in patients with recurrent acute pancreatitis with or without pancreas divisum and those with chronic pancreatitis. However, only 1 in 50 of the control group had SPINK1 gene mutation. Polymorphism in the CFTR gene was seen at a higher frequency in those with pancreas divisum. One could argue that the ideal control should be those with pancreas divisum but without symptoms. From clinical practice, we know that these controls would be hard to identify without the use of secretin-stimulated magnetic resonance cholangiopancreatography or other expensive noninvasive imaging. SPINK1 gene mutations along with mutations in CFTR have been previously shown to occur at a higher frequency in patients with idiopathic chronic and acute recurrent pancreatitis. 3,4 Some animal studies have demonstrated that genetic mutations in CFTR might be responsible for an increased inflammatory response in mice. 5 SPINK1 gene mutations were previously found in a Finnish study to occur at a higher rate in those with acute pancreatitis, suggesting that the SPINK1 gene mutation probably enhances the susceptibility to acute pancreatitis. 6 This study of Garg and colleagues raises a very thought-provoking question: is pancreatitis in patients with pancreas divisum related to the outflow obstruction at the minor papilla? From previous studies we know that only a minority of those with pancreas divisum are symptomatic and the responses to therapy are not uniformly the same despite minor papillotomy, which should relieve any obstruction. The findings of this and other studies suggest an etiology other than a simple mechanical obstruction alone. In this study, responses to endoscopic therapy were similar to those already reported, with significant improvement in approximately 70% of patients. 7 This study involved numbers that were too small to examine whether the response to therapy is predictable based on the genetic mutations. Despite the

Pre-Existing Pancreatitis and Elevated Risks of COVID-19 Severity and Mortality

Ulcerated, tender nodules of the lower extremities

A Proinflammatory, Antiapoptotic Phenotype Underlies the Susceptibility to Acute Pancreatitis in Cystic Fibrosis Transmembrane Regulator (−/−) Mice

Serum amylase levels can be elevated in various pathological conditions. However, acute gastroenteritis has not been widely recognized as a cause for hyperamylasemia. We conducted a retrospective study of amylase results for all patients hospitalized or discharged from the emergency department with a diagnosis of gastroenteritis from April through November 1999. Patients with other possible medical causes for elevated amylase levels were excluded. We also compared the clinical and laboratory parameters of hyperamylasemic vs. normoamylasemic hospitalized patients with gastroenteritis. A total of 1041 patients with acute gastroenteritis were identified. Serum amylase levels were determined in 701 patients and were abnormally elevated in 66 of them. In 15 patients, other possible causes of hyperamylasemia were present, and these patients were excluded. The mean serum amylase level among the remaining 51 patients (7.4% of the remaining 686 patients with gastroenteritis) was 1.32 of the upper normal level, with a range of up to 2.2 times the upper normal range. Clinicians tended to admit more hyperamylasemic patients than normoamylasemic patients (10 of 51 vs. 65 of 635; P =.03, 1 sided). However, the course of gastroenteritis in the hospitalized hyperamylasemic patients did not differ significantly from that in the hospitalized normoamylasemic patients, as judged by the clinical signs and symptoms, laboratory results, length of hospital stay, and need for antibiotics. Gastroenteritis is associated with a mild to moderate elevation of serum amylase levels in a significant portion of patients and should be included in the differential diagnosis of hyperamylasemia. Such elevation, however, does not seem to bear clinical significance in terms of the severity of disease.

Acute pancreatitis is an uncommon but clinically important complication in people living with HIV (PLWH) and has been linked to HIV itself, older nucleoside reverse transcriptase inhibitors, protease inhibitors via hypertriglyceridemia, and multiple opportunistic or metabolic comorbidities. Atraumatic splenic rupture (ASR) is rare and has been described in association with acute or chronic pancreatitis and, more rarely, with HIV infection. However, the coexistence of chronic HIV infection, pancreatitis with pancreatic tail pseudocyst, and ASR has seldom been reported. We present a complex case highlighting the interaction between long-standing HIV infection, chronic pancreatitis, and splenic injury. To our knowledge, no previous report has described chronic HIV infection complicated simultaneously by acute-on-chronic pancreatitis, a pancreatic tail pseudocyst, and atraumatic splenic rupture. A 35-year-old man with a 9-year history of HIV infection on antiretroviral therapy (ART) presented with acute worsening of upper abdominal pain and dizziness on the background of intermittent epigastric pain over one year. He had no history of abdominal trauma, alcohol abuse, gallstones, or hypertriglyceridemia, and had never received didanosine or stavudine. Initial assessment revealed pallor, hypotension, generalized abdominal tenderness with peritoneal signs, severe anemia, leukocytosis, and markedly elevated serum amylase and lipase levels. Contrast-enhanced abdominal CT showed hemoperitoneum, irregular laceration and heterogeneous enhancement of the spleen, chronic pancreatitis with atrophic, calcified pancreas and dilated main pancreatic duct, and a pseudocyst in the pancreatic tail abutting the splenic hilum. Emergency laparotomy revealed approximately 1500 mL of hemoperitoneum, a ruptured upper pole splenic laceration extending towards the hilum, and a pancreatic tail pseudocyst adherent to the splenic hilum. Splenectomy plus distal pancreatectomy with drainage were performed. Pathology confirmed chronic pancreatitis with pseudocyst formation and splenic rupture without malignancy. Postoperative recovery was uneventful apart from reactive thrombocytosis, which was managed with antiplatelet therapy. The patient remained well with no recurrence of pancreatitis or splenic complications at 15-month follow-up. This case illustrates a plausible "pancreas-spleen axis" in which chronic pancreatitis with a pancreatic tail pseudocyst leads to local vascular and parenchymal fragility, predisposing to ASR in a patient with chronic HIV infection and incomplete immune reconstitution. It emphasizes the need to consider ASR in PLWH presenting with acute abdomen, particularly when imaging shows pancreatic tail pathology. Early CT, prompt surgical decision-making, and multidisciplinary management between infectious disease specialists and surgeons are critical for favorable outcomes.