James Buxbaum

How good is endoscopic ultrasound-guided fine-needle aspiration in diagnosing the correct etiology for a solid pancreatic mass?: A meta-analysis and systematic review.

Objectives The objective of this study was to evaluate the accuracy of endoscopic ultrasound–guided fine-needle aspiration (EUS-FNA) in diagnosing the correct etiology for a solid pancreatic mass. Method Data extracted from EUS-FNA studies with a criterion standard (either confirmed by surgery or appropriate follow-up) were selected. Articles were searched in MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials & Database of Systematic Reviews. Pooling was conducted by both fixed- and random-effects models. Results Initial search identified 3610 reference articles, of these 360 relevant articles were selected and reviewed. Data were extracted from 41 studies (N = 4766) which met the inclusion criteria. Pooled sensitivity of EUS-FNA in diagnosing the correct etiology for solid pancreatic mass was 86.8% (95% confidence interval [CI], 85.5–87.9). Endoscopic ultrasound–guided FNA had a pooled specificity of 95.8% (95% CI, 94.6–96.7). Positive likelihood ratio of EUS was 15.2 (95% CI, 8.5–27.3), and the negative likelihood ratio was 0.17 (95% CI, 0.13–0.21). Conclusions Endoscopic ultrasound–guided FNA is an excellent diagnostic tool to detect the correct etiology for solid pancreatic masses. When available, EUS-FNA should be strongly considered as the first diagnostic tool for sampling these lesions to optimize patient management.

Aggressive hydration with lactated Ringer's solution reduces pancreatitis after endoscopic retrograde cholangiopancreatography.

BACKGROUND & AIMS Pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP). We performed a pilot study to determine whether aggressive periprocedural hydration with lactated Ringers solution reduces the incidence of pancreatitis after ERCP. METHODS Patients who underwent first-time ERCP were randomly assigned to groups (2:1) that received aggressive hydration with lactated Ringers solution (3 mL/kg/h during the procedure, a 20-mL/kg bolus after the procedure, and 3 mL/kg/h for 8 hours after the procedure, n = 39) or standard hydration with the same solution (1.5 mL/kg/h during and for 8 hours after procedure, n = 23). Serum levels of amylase, visual analogue pain scores (scale of 0-10), and volume overload were assessed at baseline and 2, 8, and 24 hours after ERCP. The primary end point, post-ERCP pancreatitis, was defined as hyperamylasemia (level of amylase >3 times the upper limit of normal) and increased epigastric pain (≥3 points on visual analogue scale) persisting for ≥24 hours after the procedure. Secondary end points included hyperamylasemia, increased pain, and volume overload. RESULTS None of the patients who received aggressive hydration developed post-ERCP pancreatitis, compared with 17% of patients who received standard hydration (P = .016). Hyperamylasemia developed in 23% of patients who received aggressive hydration vs 39% of those who received standard hydration (P = .116, nonsignificant); increased epigastric pain developed in 8% of patients who received aggressive hydration vs 22% of those who received standard hydration (P = .146, nonsignificant). No patients had evidence of volume overload. CONCLUSIONS On the basis of a pilot study, aggressive intravenous hydration with lactated Ringers solution appears to reduce the development of post-ERCP pancreatitis and is not associated with volume overload. ClinicalTrials.gov, Number: NCT 01758549.

Skull base chondrosarcoma originating from the petroclival junction.

Objective: To define the presentation of patients with skull base chondrosarcoma, to elucidate surgical strategies, and to identify the role of postoperative radiotherapy. Study Design: Retrospective review. Setting: Tertiary referral center. Patients: All patients (n = 33) with skull base chondrosarcoma managed at our institution. The average follow-up time was 7.7 years (range, 0-20 years). Main Outcome Measures: Tumor location, presenting symptoms, presence of residual or recurrent tumor, and mortality. Results: The most common tumor location was the petroclival junction (n = 29). Common presenting symptoms were diplopia (48%) and headache (45%). Surgical approaches included retrosigmoid, transtemporal, transfacial, and frontotemporal craniotomies. Biopsy only was performed in four patients, subtotal resection in 19 patients, and total resection in nine patients. Most patients received postoperative radiotherapy (82%). Follow-up revealed residual, stable disease in 28% of patients and recurrent disease in 24% of patients. The mean time to recurrence was 3.0 ± 2.8 years. The lack of postoperative radiation was significantly correlated with an increased risk of recurrence (odds ratio, 28; p = 0.007) but incomplete tumor resection was not (p = 0.6). Life-table analysis revealed that the 5-year survival rate was 85% and the 10-year survival rate was 77%. Five patients died; four of the deaths attributable to recurrent disease. Conclusion: The characteristic growth pattern of skull base chondrosarcoma is tumor eroding the petroclival junction. Current therapeutic strategy is resection through an extradural subtemporal craniotomy with removal of the petrous apex and clivus. Radical resection of uninvolved structures is often not necessary. Nonetheless, gross total removal is often achievable. Postoperative radiotherapy reduces the chance of tumor recurrence.

Natural history of acute upper GI bleeding due to tumours: Short-term success and long-term recurrence with or without endoscopic therapy

Scant information is available regarding patients with upper gastrointestinal bleeding (UGIB) from tumours.

Gastrointestinal Manifestations of Cystic Fibrosis.

Gastrointestinal symptoms of cystic fibrosis are the most important non-pulmonary manifestations of this genetic illness. Pancreatic manifestations include acute and chronic pancreatitis as well as pancreas insufficiency resulting in malnutrition. Complications in the gastrointestinal lumen are diverse and include distal intestinal obstruction syndrome (DIOS), meconium ileus, intussusception, and constipation; biliary tract complications include focal biliary cirrhosis and cholangiectasis. The common pathophysiology is the inspissation of secretions in the hollow structures of the gastrointestinal tract. Improved survival of CF patients mandates that the adult gastroenterologist be aware of the presentation and treatment of pancreatic, luminal, and hepatobiliary CF complications.

Predictors of endoscopic treatment outcomes in the management of biliary problems after liver transplantation at a high-volume academic center

BACKGROUND Biliary tract problems are the most common complications after liver transplantation. ERCP is increasingly being used to address posttransplantation biliary problems. OBJECTIVE To identify predictors of endoscopic treatment outcomes in the management of post-liver transplantation complications. SETTING AND PATIENTS All adult patients who underwent liver transplantation at the University of California, San Francisco between January 1999 and December 2008 were reviewed. DESIGN A multivariate regression analysis. MAIN OUTCOME MEASUREMENTS Identification of donor and recipient factors as well as technical considerations that predicted success or failure in the endoscopic management of posttransplantation biliary complications. RESULTS In 1062 patients who underwent liver transplantation, there were 224 biliary complications. ERCP was the primary treatment modality and was successful in the majority of patients treated. Patients with biliary complications who had take-back surgery for a nonbiliary indication during the first month after liver transplantation (odds ratio [OR], 0.32; P = .03), particularly for bleeding (OR, 0.18; P = .02), were less likely to respond to endoscopic therapy. Those who received a graft from a donor after cardiac death (OR, 0.15; P = .02) or a living donor (OR, 0.11; P < .01) were also less likely to respond to endoscopic therapy. Take-back surgery for a nonbiliary indication in the first month after liver transplantation was also identified as a novel risk factor for the development of biliary complications (OR, 1.80; P = .02). LIMITATIONS Retrospective design. CONCLUSIONS ERCP can be used to treat the majority of posttransplantation biliary problems. However, endoscopic therapy is less efficacious in the treatment of complications associated with ischemia.

Hepatitis resulting from liver-specific expression and recognition of self-antigen.

Liver-specific immune reactivity in response to aberrant expression of antigen on the surface of hepatocytes is thought to be a major factor in development of autoimmune hepatitis (AIH). Persistent inflammation develops when these antigens are not eliminated and/or responses are not appropriately regulated. We have developed transgenic mice (OVA-HEP), which express chicken ovalbumin on the surface of hepatocytes. These mice are tolerant to ovalbumin, develop normally and have shown no evidence of liver or other disease up to 2 years of age. Adoptive transfer of naïve ovalbumin-specific T cells into OVA-HEP transgenic mice led to liver-specific inflammation in a dose dependent manner. This hepatic necroinflammation was dependent upon CD8(+) Valpha2 OVA-specific T cells, was limited to the liver, and was augmented by OVA-specific CD4(+) T cell help; but did not result from adoptive transfer of ovalbumin-specific CD4 T cells alone. The response was self-limited but persistent inflammation developed after repeated transfer of antigen-specific T cells. This model of T cell recognition of antigen on hepatocytes may be used to understand many liver-specific aspects of the immune response in autoimmune hepatitis.

Molecular and Clinical Markers of Pancreas Cancer

Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those with hereditary pancreatitis and genetic syndromes which predispose to cancer. Ongoing work to identify early markers of pancreas cancer consists of high throughput discovery methods including gene arrays and proteomics as well as hypothesis driven methods. While several promising candidates have been identified none has yet been convincingly proven to be better than CA 19-9. New methods including endoscopic ultrasound are improving detection of pancreas cancer and are being used to acquire tissue for biomarker discovery.

Active cathepsins B, L, and S in murine and human pancreatitis.

Cathepsins regulate premature trypsinogen activation within acinar cells, a key initial step in pancreatitis. The identity, origin, and causative roles of activated cathepsins in pancreatic inflammation and pain are not defined. By using a near infrared-labeled activity-based probe (GB123) that covalently modifies active cathepsins, we localized and identified activated cathepsins in mice with cerulein-induced pancreatitis and in pancreatic juice from patients with chronic pancreatitis. We used inhibitors of activated cathepsins to define their causative role in pancreatic inflammation and pain. After GB123 administration to mice with pancreatitis, reflectance and confocal imaging showed significant accumulation of the probe in inflamed pancreas compared with controls, particularly in acinar cells and macrophages, and in spinal cord microglia and neurons. Biochemical analysis of pancreatic extracts identified them as cathepsins B, L, and S (Cat-B, Cat-L, and Cat-S, respectively). These active cathepsins were also identified in pancreatic juice from patients with chronic pancreatitis undergoing an endoscopic procedure for the treatment of pain, indicating cathepsin secretion. The cathepsin inhibitor K11777 suppressed cerulein-induced activation of Cat-B, Cat-L, and Cat-S in the pancreas and ameliorated pancreatic inflammation, nocifensive behavior, and activation of spinal nociceptive neurons. Thus pancreatitis is associated with an increase in the active forms of the proteases Cat-B, Cat-L, and Cat-S in pancreatic acinar cells and macrophages, and in spinal neurons and microglial cells. Inhibition of cathepsin activation ameliorated pancreatic inflammation and pain. Activity-based probes permit identification of proteases that are predictive biomarkers of disease progression and response to therapy and may be useful noninvasive tools for the detection of pancreatic inflammation.

Causes of bleeding and outcomes in patients hospitalized with upper gastrointestinal bleeding.

Goals: To evaluate sources of upper gastrointestinal bleeding (UGIB) at an urban US hospital and compare them to sources at the same center 20 years ago, and to assess clinical outcomes related to source of UGIB. Background: Recent studies suggest changes in causes and outcomes of UGIB. Study: Consecutive patients with hematemesis, melena, and/or hematochezia undergoing upper endoscopy with an identified source at LA County+USC Medical Center from January 2005 to June 2011 were identified retrospectively. Results: Mean age of the 1929 patients was 52 years; 75% were male. A total of 1073 (55%) presented with hematemesis, 809 (42%) with melena alone, and 47 (2%) with hematochezia alone. The most common causes were ulcers in 654 patients (34%), varices in 633 (33%), and erosive esophagitis in 156 (8%), compared with 43%, 33%, and 2% in 1991. During hospitalization, 207 (10.7%) patients required repeat endoscopy for UGIB (10.6% for both ulcers and varices) and 129 (6.7%) died (5.2% for ulcers; 9.2% for varices). On multivariate analysis, hematemesis (OR=1.38; 95% CI, 1.04-1.88) and having insurance (OR=1.44; 95% CI, 1.07-1.94) were associated with repeat endoscopy for UGIB. Varices (OR=1.53; 95% CI, 1.05-2.22) and having insurance (OR=4.53; 95% CI, 2.84-7.24) were associated with mortality. Conclusion: Peptic ulcers decreased modestly over 2 decades, whereas varices continue as a common cause of UGIB at an urban hospital serving lower socioeconomic patients. Inpatient mortality, but not rebleeding requiring endoscopy, was higher with variceal than nonvariceal UGIB, indicating patients with variceal UGIB remain at risk of death from decompensation of underlying illness even after successful control of bleeding.