Chris E. Forsmark

Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation.

Objective: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 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. 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. Result: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. 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.

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.

Management of Chronic Pancreatitis

Advances in our understanding of chronic pancreatitis have improved our care of patients with this disease. Although our therapies are imperfect and many patients remain symptomatic, appropriate medical care improves the quality of life in these patients. Proper management requires an accurate diagnosis, recognition of the modifiable causes of disease, assessment of symptoms and complications, treatment of these symptoms and complications utilizing a multidisciplinary team, and ongoing monitoring for the effect of therapy and the occurrence of complications.

American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines.

Abstract The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Diagnostic accuracy of conventional and cholangioscopy-guided sampling of indeterminate biliary lesions at the time of ERCP: a prospective, long-term follow-up study

BACKGROUND The diagnostic accuracy of cholangioscopy-guided sampling has not been rigorously evaluated. OBJECTIVE To prospectively evaluate the accuracy of cholangioscopy-guided mini-forceps sampling and compare it with standard cytology brushings and forceps biopsies for the tissue diagnosis of indeterminate biliary lesions. DESIGN Prospective, long-term follow-up, paired design cohort study. SETTING Tertiary center. PATIENTS Patients undergoing cholangioscopy for the evaluation of indeterminate biliary lesions. INTERVENTIONS Each patient underwent triple sampling with cholangioscopy-guided mini-forceps, cytology brushing, and standard forceps. MAIN OUTCOME MEASUREMENTS Diagnostic accuracy of each sampling method compared with the patient final status (cancer vs no cancer). RESULTS A total of 26 patients (17 cancer positive/9 cancer negative) were enrolled. The mean follow-up in the patients with no cancer was 21.78 (SD ±6.78) months. The procedure was technically successful in all cases (100%). Sample quality was adequate in 25 of 26 (96.2%) of the cytology brushings, in 26 of 26 (100%) of the standard forceps biopsies, and in 25 of 26 (96.2%) of the mini-forceps biopsies. The sensitivity, accuracy, and negative predictive values were 5.9%, 38.5%, and 36% for standard cytology brushings; 29.4%, 53.8%, and 42.8% for standard forceps biopsies; and 76.5%, 84.6%, and 69.2% for mini-forceps biopsies, respectively. When comparing the 3 methods of sampling, mini-forceps biopsy provided significantly better sensitivity and overall accuracy compared with standard cytology brushing (P < .0001) and standard forceps biopsy (P = .0215). LIMITATIONS Potential for selection bias. CONCLUSIONS Cholangioscopy-guided biopsies of indeterminate biliary lesions have significantly higher accuracy compared with ERCP-guided cytology brushings and standard forceps biopsies, but negative findings on mini-forceps biopsy cannot rule out malignancy with a high degree of certainty. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01227382.).

Prospective evaluation of the use of fully covered self-expanding metal stents for EUS-guided transmural drainage of pancreatic pseudocysts

2. Rumalla A, Baron TH. Results of direct percutaneous endoscopic jejunostomy, an alternative method for providing jejunal feeding. Mayo Clin Proc 2000;75:807-10. 3. Panagiotakis PH, DiSario JA, Hilden K, et al. DPEJ tube placement prevents aspiration pneumonia in high-risk patients. Nutr Clin Pract 2008;23:172-5. 4. Kwon RS, Banerjee S, Desilets D, et al. Enteral nutrition access devices. Gastrointest Endosc 2010;72:236-48. 5. Maple JT, Petersen BT, Baron TH, et al. Direct percutaneous endoscopic jejunostomy: outcomes in 307 consecutive attempts. Am J Gastroenterol 2005;100:2681-8. 6. Foutch PG, Talbert GA, Waring JP, et al. Percutaneous endoscopic gastrostomy in patients with prior abdominal surgery: virtues of the safe tract. Am J Gastroenterol 1988;83:147-50. 7. Varadarajulu S, Delegge MH. Use of a 19-gauge injection needle as a guide for direct percutaneous endoscopic jejunostomy tube placement. Gastrointest Endosc 2003;57:942-5. 8. Cotton PB, Eisen GM, Aabakken L, et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010;71:446-54.

Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zollinger-Ellison syndrome.

BACKGROUND & AIMS Parenteral control of gastric acid hypersecretion in conditions such as Zollinger-Ellison syndrome (ZES) or idiopathic gastric acid hypersecretion is necessary perioperatively or when oral medications cannot be taken for other reasons (e.g., during chemotherapy, acute upper gastrointestinal bleeding, or in intensive care unit settings). METHODS We evaluated the efficacy and safety of 15-minute infusions of the proton pump inhibitor pantoprazole (80-120 mg every 8-12 hours) in controlling acid output for up to 7 days. Effective control was defined as acid output >10 milliequivalents per hour (mEq/h) (<5 mEq/h in patients with prior acid-reducing surgery) for 24 hours. RESULTS The 21 patients enrolled had a mean age of 51.9 years (range, 29-75) and a mean disease duration of 8.1 years (range, <0.5-21); 13 were male, 7 had multiple endocrine neoplasia syndrome type I, 4 had undergone acid-reducing surgery, 2 had received chemotherapy, and 13 had undergone gastrinoma resections without cure. Basal acid output (mean +/- SD) was 40.2 +/- 27.9 mEq/h (range, 11.2-117.9). In all patients, acid output was controlled within the first hour (mean onset of effective control, 41 minutes) after an initial 80-mg intravenous pantoprazole dose. Pantoprazole, 80 mg every 12 hours, was effective in 17 of 21 patients (81%) for up to 7 days. Four patients required upward dose titration, 2 required 120 mg pantoprazole every 12 hours, and 2 required 80 mg every 8 hours. At study end, acid output remained controlled for 6 hours beyond the next expected dose in 71% of patients (n = 15); mean acid output increased to 4.0 mEq/h (range, 0-9.7). No serious or unexpected adverse events were observed. CONCLUSIONS Intravenous pantoprazole, 160-240 mg/day administered in divided doses by 15-minute infusion, rapidly and effectively controlled acid output within 1 hour and maintained control for up to 7 days in all ZES patients.

Effect of Octreotide on Refractory AIDS-associated Diarrhea: A Prospective, Multicenter Clinical Trial

OBJECTIVE To determine the efficacy and safety of octreotide for treatment of refractory, profuse diarrhea in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN A prospective, open-label study. SETTING Inpatient metabolic units of four university medical centers. PATIENTS Fifty-one patients infected with human immunodeficiency virus (HIV) who had uncontrolled diarrhea (greater than or equal to 500-mL liquid stool per day) despite treatment with maximally tolerable doses of antidiarrheal medications. INTERVENTION After initial baseline studies, patients received octreotide, 50 micrograms every 8 hours for 48 hours. If stool volume was not reduced to less than 250 mL/d, the dose of octreotide was increased stepwise to 100, 250, and 500 micrograms. MAIN RESULTS Fifty men and one woman (mean age, 36.3 +/- 1.1 years) entered and completed the 28-day protocol (14 days of inpatient therapy and 14 days of outpatient therapy). Stool frequency and volume decreased significantly (6.5 +/- 0.5 stools per day on day 0 compared with 3.8 +/- 0.3 stools per day on day 21 [P less than 0.001] and 1604 +/- 180 mL/d on day 0 compared with 1084 +/- 162 mL/d on day 14 [P less than 0.001], respectively). Twenty-one patients (41.2%) were considered to be partial or complete responders (reduction in daily stool volume by greater than or equal to 50% of initial collections or reduction to less than or equal to 250 mL/d). Of the 21 responders, 14 (67%) had no identifiable pathogens at initial screening compared with 9 of 30 (30%) nonresponders (P less than 0.01). CONCLUSION Patients with AIDS-associated refractory watery diarrhea, especially those without identifiable pathogens, may respond favorably to subcutaneously administered octreotide. This drug deserves further study in a randomized, placebo-controlled trial.

Rapid-sequence endoscopic management of posttransplant anastomotic biliary strictures

BACKGROUND Post-liver-transplant anastomotic biliary strictures generally have been managed through ERCP with gradual balloon dilation and placement of multiple stents over an extended period of time. OBJECTIVE Our purpose was to evaluate the long-term outcome of rapid sequence dilation and to shorten the duration of stenting as a therapy for anastomotic biliary strictures. DESIGN Prospective case series. SETTING Academic tertiary referral center. INTERVENTIONS ERCP with rapid-sequence balloon dilation of post-liver-transplant anastomotic biliary strictures followed by stenting with multiple stents over a short time period. MAIN OUTCOME MEASUREMENT Long-term anastomotic stricture resolution. RESULTS Thirty-eight patients were prospectively enrolled into a standardized ERCP treatment protocol. The mean number of ERCPs per patient was 3.4 (range 2-6), the mean number of maximum stents inserted was 2.5 (range 1-6), and the mean total stenting period was 107 days (range 20-198 days); the mean follow-up time from completion of the endoscopic therapy was 360 days (range 140-1347 days). Long-term stricture resolution was achieved in 33 of the 38 (87%) patients. LIMITATIONS Lack of control group, relatively small patient population. CONCLUSIONS Accelerated dilation and shorter total length of stenting leads to long-term success in the majority of patients with post-liver-transplant anastomotic biliary strictures.

Diagnosis of pancreatic cancer and prediction of unresectability using the tumor-associated antigen CA19-9

Marked elevations of the tumor-associated antigen CA19-9 are relatively specific for pancreatic carcinoma and are associated with more advanced malignancies. We retrospectively reviewed 53 patients with CA19-9 values >90 U/ml in whom the test had been done because of clinical suspicion of pancreatic malignancy. Pancreatic cancer was found in 45 patients (85%). If a cutoff value of CA19-9 >200 U/ml is used, 36 of 37 (97%) patients had pancreatic cancer. Thirty patients with pancreatic cancer and no radiographic criteria of unresectability underwent attempted resection; five of these patients were judged to be potentially resectable and four of them underwent attempted resection. In only one patient with a CA19-9 value >300 U/ml was resection possible; this patient had advanced carcinoma. Our results suggest that, in patients in whom the clinician suspects pancreatic carcinoma, CA19-9 >90 U/ml is highly suggestive of pancreatic malignancy, while CA19-9 >200 U/ml is virtually diagnostic of pancreatic malignancy. In similar patients with CA19-9 >300 U/ml, resection is rarely possible and tumors are advanced.