[International multidisciplinary classification of acute pancreatitis severity: the 2013 Spanish edition]. / Clasificación Internacional y Multidisciplinaria de la Pancreatitis Aguda: Edición Española 2013.

OBJECTIVE: To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. BACKGROUNDS: The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of specialist in pancreatic diseases, but are suboptimal because these definitions are based on the empiric description of events not associated with severity. METHODS: A personal invitation to contribute to the development of a new classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists and radiologists currently active in the field of clinical acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global web-based survey was conducted, and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. RESULTS: The new classification of severity is based on the actual local and systemic determinants of severity, rather than on the description of events that are non-causally associated with severity. The local determinant relates to whether there is (peri) pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another, whereby the presence of both infected (peri) pancreatic necrosis and persistent organ failure has a greater impact upon severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: mild, moderate, severe, and critical. CONCLUSIONS: This classification is the result of a consultative process among specialists in pancreatic diseases from 49 countries spanning North America, South America, Europe, Asia, Oceania and Africa. It provides a set of concise up to date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world.

Simultaneous dual scope endotherapy of esophago-airway fistulas and obstructions.

Management of esophago-airway fistulas (EAF) and obstructions often involves therapy with esophageal and/or airway stents. We present a unique approach for the management of EAF and obstructions with simultaneous upper endoscopy and bronchoscopy (two scopes inserted simultaneously through the mouth). The aim is to assess the efficacy and safety of a simultaneous dual scope approach for management of EAF and obstructions. The endoscopy database at the University of Florida was reviewed from October 2007 to April 2012 to identify adult patients who had undergone simultaneous upper endoscopy and bronchoscopy for EAF and obstructions. Medical records were reviewed for demographics, indication, pathology, imaging, simultaneous endoscopic and bronchoscopic findings/maneuvers, outcomes, and adverse events. Outcomes assessed included: (i) technical success, (ii) fistula occlusion, (iii) dysphagia score, and (iv) adverse events. Thirteen patients with EAF and/or obstruction underwent simultaneous dual scope endoscopy. Dual scope procedures were technically successful in 12/13 (92%) patients. Dysphagia score improved from three to one in both patients with dysphagia without EAF. Fistula occlusion was observed in 7/10 patients (70%) with EAF. With this technique, stents were placed accurately without airway compression, migrated esophageal stents extracted from the tracheal lumen without trauma, and tracheal stents not displaced during esophageal manipulations. EAF not otherwise apparent were identified in two patients. Adverse events occurred in 2/13 (15%) patients, and 5/13 (38%) patients died from advanced cancer during follow up (mean 4.1 months, range 1-8 months). Simultaneous dual scope (two scopes inserted through the mouth at the same time) therapy of EAF and obstructions is feasible, effective, and safe, and may develop to be the preferred approach for the management of complex esophago-airway diseases.

[Multidisciplinar international classification of the severity of acute pancreatitis: Italian version 2013]. / Classificazione Internazionale Multidisciplinare della Gravità della Pancreatite Acuta Versione Italiana 2013.

AIM: The aim of this paper was to present the 2013 Italian edition of a new international classification of acute pancreatitis severity. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description of occurrences that are merely associated with severity. METHODS: A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. A global web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. RESULTS: The new international classification is based on the actual local and systemic determinants of severity, rather than description of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity-mild, moderate, severe, and critical. CONCLUSION: This classification provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research.

[Determinant-based classification of acute pancreatitis severity. International multidisciplinary classification of acute pancreatitis severity: the 2013 German edition]. / Einteilung des Schweregrads der akuten Pankreatitis. Internationale, multidisziplinäre klinische Klassifikation auf Basis pathogenetischer Determinanten: Deutsche Version 2013.

OBJECTIVE: The aim of this study was to develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. BACKGROUND: The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric descriptions of occurrences that are merely associated with severity. METHODS: A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensive medicine specialists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organised to bring contributors from different disciplines together and discuss the concept and definitions. RESULT: The new international classification is based on the actual local and systemic determinants of severity, rather than descriptions of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity - mild, moderate, severe, and critical. CONCLUSIONS: This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America, Europe, Asia, Oceania, and Africa. It provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world.

Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States.

BACKGROUND: Effectiveness of medical therapies in chronic pancreatitis has been described in small studies of selected patients. AIM: To describe frequency and perceived effectiveness of non-analgesic medical therapies in chronic pancreatitis patients evaluated at US referral centres. METHODS: Using data on 516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we evaluated how often medical therapies [pancreatic enzyme replacement therapy (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB)] were utilized and considered useful by physicians. RESULTS: Oral PERT was commonly used (70%), more frequently in the presence of exocrine insufficiency (EI) (88% vs. 61%, P < 0.001) and pain (74% vs. 59%, P < 0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87-9.18), constant (OR 3.42, 95% CI 1.93-6.04) or intermittent pain (OR 1.98, 95% CI 1.14-3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36-3.42). AO were tried less often (14%) and were more effective in idiopathic and obstructive vs. alcoholic chronic pancreatitis (25% vs. 4%, P = 0.03). Other therapies were infrequently used (CPB - 5%, octreotide - 7%) with efficacy generally <50%. CONCLUSIONS: Pancreatic enzyme replacement therapy is commonly utilized, but is considered useful in only subsets of chronic pancreatitis patients. Other medical therapies are used infrequently and have limited efficacy.

Prospective evaluation of gastroenterologist-guided, nurse-administered standard sedation for spiral deep small bowel enteroscopy.

BACKGROUND: Sedation of patients for deep small bowel enteroscopy presents unique challenges and is traditionally provided by anesthesiologists. No study has directly evaluated gastroenterologist-guided, nurse-administered sedation for deep enteroscopy. Further, no comparison exists between gastroenterologist-guided versus anesthesiologist-guided sedation during deep enteroscopy. AIMS: To evaluate safety and efficacy of performing deep (spiral) enteroscopy using gastroenterologist-guided sedation and compare outcomes between patients receiving gastroenterologist-guided and anesthesiologist-guided sedation. METHODS: This prospective case series contains 91 consecutive patients who underwent deep enteroscopy with spiral Endo-Ease Discovery SB overtube. Of the patients, 64 received gastroenterologist-guided and 27 received anesthesiologist-guided sedation. RESULTS: In the 64 patients receiving gastroenterologist-guided sedation, successful completion occurred in 59 of 64 enteroscopies (92.2%). Mean insertion depth was 231.0+/-85.8 cm beyond the ligament of Treitz. Total procedure time was 39.9+/-15.7 min (diagnostic time 34.7+/-12.3 min; therapy time 5.2+/-8.9 min). Positive findings were noted in 32 cases (50.0%), with therapy performed in 27 cases (42.2%). Six minor complications occurred. Compared to the anesthesiologist-guided sedation group, there was no difference in patient characteristics except mean American Society of Anesthesiologists score (2.5+/-0.5 in gastroenterologist-guided group versus 2.7+/-0.6 in anesthesiologist-guided group; p=0.046) and presence of adhesions (ten in gastroenterologist-guided group and zero in anesthesiologist-guided group; p=0.030). Outcomes for both groups were not significantly different except for shorter times in the gastroenterologist-guided group (39.9+/-15.7 min versus 46.0+/-12.1 min; p=0.047) and more frequent findings in the anesthesiologist-guided group (50.0% vs. 74.1%; p=0.034). CONCLUSIONS: Deep enteroscopy using the spiral overtube can be successfully and safely accomplished with gastroenterologist-guided, nurse-administered standard sedation.

Review article: pain and chronic pancreatitis.

BACKGROUND: Pain in chronic pancreatitis chronic pancreatitis is a frustrating and challenging symptom for both the patient and clinician. It is the most frequent and most significant symptom. Many patients fail the currently available conservative options and require opiates or endoscopic/surgical therapy. Aim To highlight the pathophysiology and management of chronic pancreatitis pain, with an emphasis on recent developments and future directions. METHODS: Expert review, utilizing in addition a comprehensive search of PubMed utilizing the search terms chronic pancreatitis and pain, treatment or management and a manual search of recent conference abstracts for articles describing pain and chronic pancreatitis. RESULTS: Pancreatic pain is heterogenous in its manifestations and pathophysiology. First-line medical options include abstinence from alcohol and tobacco, pancreatic enzymes, adjunctive agents, antioxidants, and non-opiate or low potency opiate analgesics. Failure of these options is not unusual. More potent opiates, neurolysis and endoscopic and surgical options can be considered in selected patients, but this requires appropriate expertise. New and better options are needed. Future options could include new types of pancreatic enzymes, novel antinociceptive agents nerve growth factors, mast cell-directed therapy, treatments to limit fibrinogenesis and therapies directed at the central component of pain. CONCLUSIONS: Chronic pancreatitis pain remains difficult to treat. An approach utilizing conservative medical therapies is appropriate, with more invasive therapies reserved for failure of this conservative approach. Treatment options will continue to improve with new and novel therapies on the horizon.

Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions.

BACKGROUND: Zollinger-Ellison syndrome and idiopathic hypersecretion are gastrointestinal hypersecretory conditions requiring long-term maintenance. AIMS: The safety and efficacy data for short-term (6-month) treatment of Zollinger-Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were previously published. This study extends the initial observations to 3 years. METHODS: The primary efficacy end point for this report was the control of gastric acid secretion in the last hour before the next dose of oral pantoprazole (acid output of <10 mmol/h; <5 mmol/h in subjects with prior acid-reducing surgery). Dose titration was permitted to a maximum of 240 mg per 24 h. RESULTS: Twenty-four subjects completed the study. The acid output of 28 of 34 subjects was controlled at initial enrolment. The mean acid output rates were <10 mmol/h throughout the 36 months of treatment for 90-100% of the patients. The majority of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36 months (acid output was controlled in 24 of 24 subjects). Pantoprazole was generally well tolerated with minimal adverse events reported. CONCLUSIONS: Maintenance oral pantoprazole therapy up to 3 years at dosages of 40-120 mg b.d. was effective and well tolerated in patients with Zollinger-Ellison syndrome and other hypersecretory conditions.

Review article: Pancreatic function testing.

Pancreatic function tests are most commonly used to diagnose chronic pancreatitis. These tests include tests which document exocrine or endocrine gland insufficiency and tests which instead measure gradations of decreased secretory capacity. The tests in the former category generally become abnormal when advanced, longstanding chronic pancreatitis is present. Tests in the latter category, however, have the potential to detect chronic pancreatitis at an earlier stage than other available diagnostic tests, including commonly used imaging tests such as computed tomography and endoscopic retrograde cholangiopancreatography. This potential advantage of diagnostic sensitivity is, however, counterweighed by the fact that these tests which measure stimulated secretory capacity are only available at a very few referral centres. This article will review the variety of pancreatic function tests and describe their rationale, accuracy, cost, and clinical usefulness.

Pancreatic and biliary disorders in the elderly.

Structural and functional changes in the biliary tract and pancreas associated with advanced age are well documented in the literature and must be taken into account in evaluating patients with possible biliary and pancreatic disorders. The relationship between normal, age-related physiologic changes and various pancreatico-biliary diseases is not well defined. Elderly patients may present with severe biliary and pancreatic disease that may pose difficult management problems because of coexisting medical illnesses. Despite these challenges, all but the most frail elderly patients can benefit from appropriate medical, endoscopic, and surgical therapy.

Effect of bile and pancreatic juice on adenoviral-mediated gene delivery: implications on the feasibility of gene delivery through ERCP.

Current research in gene delivery to the liver is focused on the intravenous, intraarterial, intraportal, or intratumoral route. Another possible route for gene delivery is via the common bile duct through endoscopic retrograde cholangiopancreatography (ERCP). Whether bile and pancreatic juice have any effect on gene delivery is not established. To evaluate the effect of bile and pancreatic juice on adenoviral-mediated gene delivery, liver and pancreatic cell lines were infected with a recombinant adenovirus expressing an E. coli beta-galactosidase gene under the control of a cytomegalovirus promoter (rAdCMVpLacZ) in the absence or presence of various concentrations of bile and pancreatic juice. The proportion of cells infected was evaluated through X-gal staining. The toxicity of bile and pancreatic juice was also evaluated through cell morphology and detachment. Bile appeared to induce significant cytotoxicity in HepG2 and Huh7 cells (50% viability with 15 min of incubation). Neither bile nor pancreatic juice affected transgene expression. In the absence of bile/pancreatic juice, HepG2 (15-25%) and PANC-1 cells (10-18%) were less susceptible to rAdCMVpLacZ compared to Huh7 cells (75-84%, vs HepG2, P < 0.001) and BxPc-3 (82-95%, vs PANC-1, P < 0.001) at a multiplicity of infection (MOI) of 5. Bile reduced the transduction efficiency, but 5-10% HepG2 and 5-42% of Huh7 cells were still transduced in the presence of 80% bile for up to 10 min. Adenoviral-mediated gene delivery was reduced in the presence of pancreatic juice with a low multiplicity of infection (MOI of 5), but this effect was negated with an MOI of 50. These data provide encouragement to develop adenoviral-mediated gene delivery through ERCP.

Monolobar Caroli's Disease and cholangiocarcinoma.

Caroli's Disease (CD) is a rare congenital disorder characterized by cystic dilatation of the intrahepatic bile ducts. This report describes a patient with cholangiocarcinoma arising in the setting of monolobar CD. In spite of detailed investigations including biliary enteric bypass and endoscopic retrograde cholangiography, the diagnosis of mucinous cholangiocarcinoma (CCA) was not made for almost one year. The presentation, diagnosis and treatment of monolobar CD and the association between monolobar CD and biliary tract cancer are discussed. Hepatic resection is the treatment of choice for monolobar CD.

Mirizzi syndrome: A rare cause of obstructive jaundice.

Mirizzi syndrome is a rare cause of bile duct obstruction secondary to extrinsic compression of the hepatic duct by stones impacted in the cystic duct or infundibulum of the gallbladder. The suspicion of Mirizzi syndrome primarily relies on radiographic means such as ultrasound, computed tomography and cholangiography. The recognition of this rare syndrome is crucial in developing the proper treatment approach. We present 3 cases of Mirizzi syndrome and a review of the literature pertaining to the diagnosis and treatment of this rare cause of obstructive jaundice.

Pancreatic duct stenting in benign pancreatic disease.

The ability to place endoscopic stents into the pancreatic duct has led to a dramatic increase in stent therapy for benign pancreatic diseases, particularly chronic pancreatitis and pancreas divisum. The overall effectiveness of this therapy remains unknown. This article critically reviews the available literature with a focus on patient selection, efficacy, and risk. The risk of pancreatic duct stenting is only now beginning to be appreciated, and clinicians must understand not only the potential effectiveness of pancreatic duct stenting but also the magnitude of the potential risk when considering this therapy.

Differential diagnosis of pancreatic tumors.

Endosonography is the most sensitive method to detect even small pancreatic tumors. A number of endosonographic criteria have been evaluated, but there are not specific features that allow malignant tumors to be differentiated from benign tumors. The role and timing of endoscopic ultrasound as part of a more diagnostic evaluation in patients with pancreatic tumors is not yet defined.