Classifying the severity of acute pancreatitis: towards a way forward.

BACKGROUND: The recent development of two different severity classifications for acute pancreatitis has appropriately raised questions about which should be used. The aim of this paper is to review the two new severity classifications, outline their differences, review validation studies, and identify gaps in knowledge to suggest a way forward. METHODS: A literature review was performed to identify the purposes and differences between the classifications. Validation studies and those comparing the two different classifications were also reviewed. RESULTS: The Revised Atlanta Classification (RAC) and the Determinants Based Classification (DBC) both rely on assessment of local and systemic factors. The differences between the classifications provides opportunities for further research to improve the accuracy and utility of severity classification. This includes understanding how best to tailor severity classification to setting (e.g. secondary or tertiary hospital) and purpose (e.g. clinical management or research). A key difference is that the RAC does not consider infected pancreatic necrosis an indicator of severe disease. There is also the need to develop methods for the accurate non-invasive diagnosis of infected necrosis and evaluation of the characteristics of organ dysfunction in relation to severity and outcome. CONCLUSION: Further improvement in severity classification is possible and research priorities have been identified. For now, the decision as to which classification to use should be on the basis of setting, validity, accuracy, and ease of use.

Pharmacological therapy for acute pancreatitis: where are we now? where are we going?

Acute pancreatitis is a disease of variable severity that can lead to significant morbidity and mortality. Current management has remained limited to supportive measures and the treatment of complications. A myriad of pharmacologic therapies targeting various aspects of the underlying pathophysiology have been evaluated over the past few decades. These have included antisecretory agents, protease inhibitors, antioxidants, immunomodulators, non-steroidal anti-inflammatory medications, and prophylactic antibiotics. A few of these therapies have demonstrated promise in significantly altering the progression of this disease. Further studies are needed to clearly elucidate these benefits in patients at risk for poor outcomes.

Obesity and the risk of severe acute pancreatitis.

Acute pancreatitis is an acute inflammatory response to pancreatic injury. In humans, the magnitude of the response and complications are highly variable and unpredictable. Recent clinical studies demonstrate that all major complications are more common and more severe in patients who are obese. This raises the question of how adipose tissue interacts with the immune response to worsen the severity of acute pancreatitis. Here we review the results of a series of new studies focusing on various fat-associated cytokines (adipokines) that are produced and released in proportion to the amount of visceral adipose tissue in the body. The primary adipokines that have been studied in acute pancreatitis include adiponectin, leptin, visfatin, resistin, and adipose tissue related MCP-1, TNF-a and IL-6. These new data provide strong evidence that susceptibility and severity in acute pancreatitis are associated with a number of these adipokines. Although no specific therapy exists to block the effects of these factors, recognizing the high risk and anticipating inflammation-associated complications of adipokine release is an important part of optimal patient management. For this review, a PubMed search was performed with the terms "acute pancreatitis", "severe acute pancreatitis", and "obesity". Additional searches were conducted to identify recent reviews on adipokines, Finally, PubMed searches on specific adipokines, including adiponectin, leptin, visfatin and resistin were conducted focusing on acute pancreatitis and systemic inflammation.

Frequency of visualization of presumed celiac ganglia by endoscopic ultrasound.

BACKGROUND AND STUDY AIMS: Celiac ganglia can be visualized by endoscopic ultrasound (EUS). It is unknown how often ganglia are visualized during EUS, and what clinical factors are associated with ganglion visualization. The aim of this study was to prospectively evaluate the frequency of visualization of presumed celiac ganglia by EUS and to identify factors that predict their visualization. PATIENTS AND METHODS: Clinical, demographic, EUS, and cytologic data were collected prospectively from 200 unselected patients who were undergoing EUS in a tertiary referral centre. When presumed celiac ganglia were visualized, their size, number, location, and echo features were noted. When presumed ganglia were aspirated, the results of cytology were recorded. RESULTS: The most common indication for EUS was investigation of a pancreatic mass or cyst (25 %). Presumed celiac ganglia were identified in 81 % of patients overall. Logistic regression analysis determined that female sex and having no prior history of gastrointestinal surgery were independently associated with ganglion visualization. Among patients whose ganglia were visualized, more ganglia were seen per patient with linear echo endoscopes (2, range 0 - 5) than with radial echo endoscopes (1, range 0 - 4) ( P = 0.001). Presumed celiac ganglia were aspirated in 10 patients; and cytologic examination revealed neural ganglia in all of these. CONCLUSIONS: Celiac ganglia can be visualized by EUS in most patients who undergo upper gastrointestinal EUS examinations, and are best seen with linear-array echo endoscopes. Ganglia can usually be differentiated from lymph nodes on the basis of their endosonographic appearance.

Endoscopic transmural entry into pancreatic fluid collections using a dedicated aspiration needle without endoscopic ultrasound guidance: success and complication rates.

BACKGROUND: Endoscopic drainage of pancreatic fluid collections (PFC) is performed with increasing frequency. A variety of techniques for performing transmural entry have been described. However, data are lacking on the technical success and safety of transmural entry using a single technique. The authors describe the largest experience in transmural entry of PFCs without endoscopic ultrasound (EUS) guidance using a dedicated aspiration needle. METHODS: All patients who underwent endoscopic transmural drainage of PFC from October 1998 to May 2006 were identified from the endoscopy database. Data were abstracted from the endoscopic procedure report and the patient records then placed in a JMP drive. All drainages were performed without EUS guidance after visualization of an obvious intraluminal bulge using a dedicated large-bore aspiration needle. The transmural tract into the PFC was dilated using a balloon with a diameter of 6 to 20 mm followed by subsequent placement of one or two 10-Fr double pigtail stents with or without nasocystic irrigation tubes. Successful entry was defined as entry allowing for the placement of stents. RESULTS: No significant difference in the complication rates was observed when they were analyzed for the following variables: age, gender, balloon diameter, presence of endoscopic impression, drainage approach, and size and type of fluid collection. CONCLUSION: Endoscopic transmural drainage of pancreatic fluid collections can be performed safely and effectively via the Seldinger technique without endoscopic ultrasound guidance. The study data will allow sample size calculations to be made if direct comparisons with this technique and others are undertaken.

Endoscopic retrograde cholangiopancreatography catheter and accessory exchange using a short hydrophilic guide wire: a prospective study.

BACKGROUND AND STUDY AIMS: Although hydrophilic guide wires can be used to facilitate stricture cannulation during endoscopic retrograde cholangiopancreatography (ERCP), some endoscopists avoid using them because of concerns about wire loss during exchange. There are no data available on the outcomes of using a short hydrophilic guide wire during ERCP. The aim of this study was to assess the outcomes of therapeutic ERCP procedures in which a short, completely hydrophilic guide wire was used exclusively. PATIENTS AND METHODS: A total of 100 patients undergoing ERCP were studied prospectively. A 0.035-inch, 260-cm long, angled-tip hydrophilic wire (Terumo Glidewire) was used initially. Hydraulic catheter exchange was performed as follows: during catheter withdrawal the assistant advanced all the available wire into the catheter; a 12-ml syringe was then attached to the catheter and water was flushed under pressure to "float the wire" and maintain its position during catheter removal. Variables evaluated included exchange times and wire loss rates. RESULTS: A total of 223 catheter exchanges were performed, 132 (59%) using the Olympus V-Scope (which held the wire in 62% of cases): 15% of exchanges were with catheters/accessories designed for short-wire use (Boston Scientific Rapid Exchange Biliary System or Rx System), and 85% were with a variety of standard-length accessories. Overall, the mean exchange time was 26 seconds (range 6 - 90 seconds, standard deviation 12 seconds). The mean exchange time was faster with the V-Scope and with non-Rx-System accessories. Wire loss occurred in 5 % of all exchanges. Desired ductal/stricture access was achieved in all the patients. CONCLUSIONS: Exchange of short hydrophilic wires is quick and reliable. The Olympus V-Scope is able to hold the wire in some cases. Monorail-type devices and accessories slow catheter exchange down slightly because hydraulic exchange cannot be performed using these systems.

The MAPK-AP-1/-Runx2 signalling axes are implicated in chondrosarcoma pathobiology either independently or via up-regulation of VEGF.

AIMS: To investigate whether and how the JNK/ERK-AP-1/-Runx2 signalling pathways and vascular endothelial growth factor (VEGF) are engaged in the pathogenesis of cartilaginous tumours. Chondrosarcoma is the third most common primary skeletal malignancy. Nevertheless, the molecular events underlying its pathogenesis remain elusive. JNK/ERK MAPKs and their downstream effectors, c-Jun and c-Fos (AP-1), are involved in chondroblastic differention/proliferation. These proteins interact with the Runx2 transcription factor, which is also implicated in chondroblast biology. VEGF, a key angiogenic factor, is up-regulated in human chondrosarcomas. METHODS AND RESULTS: Normal cartilage and neoplastic cells from 45 chondrosarcomas and 21 enchondromas were investigated immunohistochemically. We evaluated the cellular levels of JNK2, p-JNK2 (phosphorylated/activated JNK2), its main substrate, c-Jun, pc-Jun (phosphorylated/activated c-Jun) and c-Fos. Moreover, the levels of p-ERK (phosphorylated/activated ERK), Runx2 and VEGF were assessed. Positive immunostaining for all proteins was observed in the majority of the examined chondrosarcomas and in a small fraction of enchondromas. The expression levels of all proteins were positively and significantly correlated with each other. These levels were substantially augmented in high-grade compared with low-grade chondrosarcomas and in low-grade tumours compared with benign enchondromas, implying a potential use as molecular markers for prediction of high-grade neoplasms. CONCLUSIONS: The JNK/ERK-AP-1/-Runx2 signal transduction 'network' is associated with chondroblastic malignant transformation and chondrosarcoma development, either separately or through coordinated induction of VEGF.