Pathophysiology of acute experimental pancreatitis: Lessons from genetically engineered animal models and new molecular approaches

The incidence of acute pancreatitis is growing and worldwide population-based studies report a doubling or tripling since the 1970s. 25% of acute pancreatitis are severe and associated with histological changes of necrotizing pancreatitis. There is still no specific medical treatment for acute pancreatitis. The average mortality resides around 10%. In order to develop new specific medical treatment strategies for acute pancreatitis, a better understanding of the pathophysiology during the onset of acute pancreatitis is necessary. Since it is difficult to study the early acinar events in human pancreatitis, several animal models of acute pancreatitis have been developed. By this, it is hoped that clues into human pathophysiology become possible. In the last decade, while employing molecular biology techniques, a major progress has been made. The genome of the mouse was recently sequenced. Various strategies are possible to prove a causal effect of a single gene or protein, using either gain-of-function (i.e., overexpression of the protein of interest) or loss-of-function studies (i.e., genetic deletion of the gene of interest). The availability of transgenic mouse models and gene deletion studies has clearly increased our knowledge about the pathophysiology of acute pancreatitis and enables us to study and confirm in vitro findings in animal models. In addition, transgenic models with specific genetic deletion or overexpression of genes help in understanding the role of one specific protein in a cascade of inflammatory processes such as pancreatitis where different proteins interact and co-react. This review summarizes the recent progress in this field. Copyright (c) 2005 S. Karger AG, Basel

Primary hyperparathyroidism can generate recurrent pancreatitis and secondary diabetes mellitus – A case report

Introduction. Acute or recurrent pancreatitis may be a complication of primary hyperparathyroidism and patients with previous episodes of pancreatitis may develop secondary diabetes mellitus. Case report. We describe the clinical case of a 52-year old Caucasian man diagnosed with chronic recurrent pancreatitis in 2007. The first episode of acute pancreatitis occurred in 2002, followed by another 4 episodes in 2004 and 2007. In 2004, papilosfincterectomy was implemented with a stent mount that was removed one month later. In 2005, the patient underwent a surgical intervention for the diagnosis of chronic lithiasis, and cholecystectomy was performed. Additional investigations on the etiology of recurrent chronic pancreatitis, initially diagnosed as idiopathic, revealed elevated values of total serum calcium, serum parathormone, and the presence of a parathyroid adenoma in the right lower pole of the thyroid. In September 2007, parathyroidectomy was performed with a favorable evolution and the remission of the acute pancreatitis episodes. The patient had not had any family history of diabetes; in 2017 he was diagnosed with diabetes. Conclusion. In cases of recurrent pancreatitis, screening for hyperparathyroidism is recommended. Metabolic evaluation is required, because the risk of developing diabetes in patients with recurrent pancreatitis is high

Pancreatitis following Olanzapine Therapy: A Report of Three Cases

CONTEXT: Atypical antipsychotic agents (clozapine, olanzapine) have been linked to metabolic effects and acute pancreatitis. CASE REPORT: We reviewed the inpatient and outpatient records of three patients who developed acute pancreatitis while being treated with olanzapine. The mean age of the patients was 37.7 years (range 18–54 years, 2 female, 1 male). No alternative cause of acute pancreatitis was found in two of the three patients. In the remaining patient, olanzapine may have contributed to acute pancreatitis in the setting of hypertriglyceridemia. Olanzapine was discontinued in all instances. Over a mean follow-up of 14 months, one patient has had a relapsing course, but the remaining two patients have been symptom free without recurrence of acute pancreatitis. CONCLUSIONS: Our case series adds further support to the potential link between olanzapine use and acute pancreatitis. Close monitoring of metabolic parameters is suggested in patients treated with olanzapine. Alternative antipsychotic agents should be considered in patients at high risk for pancreatitis

Hyperparathyroidism Presenting as Acute Pancreatitis: Case Report of Mortality

Background: Acute pancreatitis may be caused by a myriad of factors, hypercalcemia secondary to hyperparathyroidism, albeit is a rare cause of acute pancreatitis but not unheard of. If the underlying cause of acute pancreatitis is diagnosed, goal-directed management becomes possible, reducing morbidity and mortality. Though acute pancreatitis on its own presents significant mortality, hypercalcemia, especially detected late, augments this. Case Report: We report a case of acute pancreatitis secondary to hyperparathyroidism. The patient was undiagnosed at the time of admission and presented with non-specific gastrointestinal symptoms. After admission, he developed multi-organ dysfunction and was managed by intensive care. The patient died within hours of admission despite our best efforts. Diagnosis of acute pancreatitis secondary to hyperparathyroidism was suspected on the basis of hypercalcemia, confirmed by a posthumous result of a raised parathyroid hormone assay. Conclusion: When a patient is admitted in the emergency department with a suspicion of acute pancreatitis, serum calcium levels and its reporting should be expedited to as early as possible. Hypercalcemia in the setting of acute pancreatitis merits a multidisciplinary approach and expedited parathyroid hormone levels sent with a high suspicion of long standing untreated hyperparathyroidism. Hyperparathyroidism is a cause of silent hypercalcemia and can be lethal if not diagnosed in time

The great pretender : Autoimmune Pancreatitis

Autoimmune pancreatitis is a benign disorder which frequently presents with symptoms and imaging suggestive of pancreatic malignancy. Up to 21% of pancreatoduodenectomies performed for suspected pancreatic cancer are found to have benign disease. Autoimmune pancreatitis responds rapidly to corticosteroids and may be associated with extra- pancreatic manifestations. Type 1 forms part of the IgG4-related disease while type 2 autoimmune pancreatitis is less likely to have elevated levels of IgG4. This review discusses the characteristics of the two types of autoimmune pancreatitis and highlights the management and prognosis of this condition.peer-reviewe

Acute pancreatitis after liver transplantation: incidence and contributing factors

In order to assess the incidence and possible predisposing and contributing factors in the development of acute pancreatitis after liver transplantation, we reviewed the medical records of all 1832 adult patients who underwent 2161 orthotopic liver transplantation (OLTx) procedures in our center between January 1987 and September 1992. Of these patients, 55 (3 % incidence) developed clinical pancreatitis and 247 (13.4 % incidence) developed hyperamylasemia (biochemical pancreatitis). Overall mortality in cases of clinical pancreatitis was 63.6 %. The mortality in cases of hyperamylasemia was similar to that found in the general liver transplant population (i. e., 23 %). A strong correlation was found between pancreatitis after liver transplantation and end-stage liver disease due to hepatitis B (30 % of the cases, P = 0.00001). Extensive surgical dissection around the pancreas (P < 0.05), the type of biliary reconstruction following liver transplantation (P < 0.05), and the number of liver grafts received by the same patient (P = 0.00001) appeared to be possible contributing factors as did the duration of venovenous bypass and the quantity of IV calcium chloride administered intraoperatively

Pancreatic complications following orthotopic liver transplantation

During fiscal year 1986, 40 out of 196 patients (21%) developed hyperamylasemia following orthotopic liver transplantation. The placement of a retropancreatic aortohepatic arterial interposition graft was associated with hyperamylasemia (p < 0.025). Eight patients (20%) developed clinically significant acute pancreatitis and its sequelae; abscesses and pseudocysts each in 2. Pancreatitis was attributable to the retropancreatic arterial graft in 4, viral infection in 2 and obstruction of the pancreatic duct in 1 patient. All 4 patients with arterial graft-related pancreatitis exhibited poor graft function immediately postoperatively, of whom 2 required retransplantation - both of which failed to function. Five patients died (63%); 2 from primary graft non-function, 2 due to sepsis and 1 from systemic cytomegalovirus infection. We conclude that acute pancreatitis after liver transplantation is a life-threatening complication which is often associated with graft non-function