Background. A definition of chronic pancreatitis (CP) is needed for diagnosis and distinguishing CP from other disorders. Previous definitions focused on morphology. Advances in epidemiology, genetics, molecular biology, modeling and other disciplines provide new insights into pathogenesis of CP, and allow CP to be better defined. Methods. Expert physician-scientists from the United States, India, Europe and Japan reviewed medical and scientific literature and clinical experiences. Competing views and approaches were debated until a new consensus definition was reached. Results: CP has been defined as ‘a continuing inflammatory disease of the pancreas, characterized by irreversible morphological change, and typically causing pain and/or permanent loss of function’. Focusing on abnormal morphology makes early diagnosis challenging and excludes inflammation without fibrosis, atrophy, endocrine and exocrine dysfunction, pain syndromes and metaplasia. A new mechanistic definition is proposed— ‘Chronic pancreatitis is a pathologic fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress.’ In addition, “Common features of established and advanced CP include pancreatic atrophy, fibrosis, pain syndromes, duct distortion and strictures, calcifications, pancreatic exocrine dysfunction, pancreatic endocrine dysfunction and dysplasia.” This definition recognizes the complex nature of CP, separates risk factors from disease activity markers and disease endpoints, and allows for a rational approach to early diagnosis, classification and prognosis. Conclusions: Initial agreement on a mechanistic definition of CP has been reached. This definition should be debated in rebuttals and endorsements, among experts and pancreatic societies until international consensus is reached.

Abdominal pain is the foremost complication of chronic pancreatitis (CP). Pain can be related to recurrent or chronic inflammation, local complications or neurogenic mechanisms with corresponding changes in the nervous systems. Both pain intensity and the frequency of pain attacks have been shown to reduce quality of life in patients with CP. Assessment of pain follows the guidelines for other types of chronic pain, where the multidimensional nature of symptom presentation is taken into consideration. Quantitative sensory testing may be used to characterize pain, but is currently used in a research setting in advanced laboratories. For pain relief, current guidelines recommend a simple stepwise escalation of analgesic drugs with increasing potency until pain relief is obtained. Abstinence from alcohol and smoking should be strongly advised. Pancreatic enzyme therapy and antioxidants may be helpful as initial treatment. Endoscopic treatment can be used in patients with evidence of ductal obstruction and may be combined with extracorporeal shock wave lithothripsy. The best candidates are those with distal obstruction of the main pancreatic duct and in early stage of disease. Behavioral interventions should be part of the multidisciplinary approach to chronic pain management particularly when psychological impact is experienced. Surgery should be considered early and after a maximum of five endoscopic interventions. The type of surgery depends on morphological changes of the pancreas. Long-term effects are variable, but high success rates have been reported in open studies and when compared with endoscopic treatment. Finally, neurolytical interventions and neuromodulation can be considered in difficult patients.

Acute pancreatitis may be associated with both local and systemic complications. Systemic injury manifests in the form of organ failure which is seen in approximately 20% of all cases of acute pancreatitis and defines 'severe acute pancreatitis'. Organ failure typically develops early in the course of acute pancreatitis, but may also develop later due to infected pancreatic necrosis induced sepsis. Organ failure is the most important determinant of outcome in acute pancreatitis. We review here the current understanding of the risk factors, pathophysiology, timing, impact on outcome and therapy of organ failure in acute pancreatitis. As we discuss the pathophysiology of severe systemic injury, the distinctions between markers and mediators of severity are highlighted based on evidence supporting their causality in organ failure. Emphasis is placed on clinically relevant end points of organ failure and the mechanisms underlying the pathophysiological perturbations, which offer insight into potential therapeutic targets to treat.

hronic pancreatitis (CP) is a chronic progressive disease with an annual incidence of 5 to 8 and prevalence of 42 to 73 cases per 100 000 adults in the United States. 1-3 Prevalence rates varying from 36 to 125 per 100 000 population have been reported from Japan, China, and India, of which India has the highest prevalence. 4,5 Chronic pancreatitis is characterized by fibrosis and inflammation of the pancreas in individuals with genetic, environmental, and other risk factors such as hypertriglyceridemia. Chronic pancreatitis is characterized by pancreatic atrophy, fibrosis, ductal strictures and distortion, calcifications, dysplasia, exocrine insufficiency and diabetes, and chronic pain. 6 This review summarizes current evidence regarding risk factors, pathophysiology, clinical features, diagnostic evaluation, treatment, and prognosis of CP. MethodsWe searched PubMed for relevant English-language articles published from January 1, 2000, to July 1, 2019. Search terms included chronic pancreatitis and each of the following:

Background & Aims The role of trypsinogen activation in pathogenesis of acute pancreatitis (AP) has not been clearly established. Methods We generated and characterized mice with disruption in the gene that encodes trypsinogen7 (T7; T−/− mice), the mouse correlate of human cationic trypsinogen. The effects of pathologic activation of trypsinogen were studied in these mice, during induction of AP with caerulein. Acinar cell death, tissue damage, early intra-acinar activation of the transcription factor NF-κB, and local and systemic inflammation were compared between T−/− and wild-type mice with AP. Results Deletion of T7 reduced the total trypsinogen content by 60%, and resulted in total loss of cationic trypsinogen, but did not affect physiologic function. T−/− mice lacked pathologic activation of trypsinogen, which occurs within acinar cells early during AP progression. Absence of trypsinogen activation in T−/− mice led to near complete inhibition of acinar cell death in vitro and a 50% reduction in acinar necrosis during AP progression. However, T−/− mice had similar degrees of local and systemic inflammation during AP progression, as well as comparable intra-acinar levels of NF-κB activation—which was previously shown to occur concurrently with trypsinogen activation during early stages of pancreatitis. Conclusions T7 is activated during pathogenesis of AP in mice. Intra-acinar trypsinogen activation leads to acinar death during early stages of pancreatitis, which is responsible for 50% of the pancreatic damage in AP. However, progression of local and systemic inflammation in AP does not require trypsinogen activation. NF-κB is activated early in acinar cells, independently of trypsinogen activation, and might be responsible for progression of AP.

This randomized controlled trial confirmed the efficacy of chemotherapy (mGEMOX) compared with BSC and FUFA in improving OS and PFS in unresectable GBC.

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Single- and two-stage management for uncomplicated concomitant gallbladder and CBD stones had similar success and complication rates, but the single-stage strategy was better in terms of shorter hospital stay, need for fewer procedures, and cost effectiveness.