Interdisciplinary Management of Cystic Neoplasms of the Pancreas

Cystic neoplasms of the pancreas are increasingly recognized due to the frequent use of abdominal imaging. It is reported that up to 20% of abdominal cross-sectional scans identify incidental asymptomatic pancreatic cysts. Proper characterization of pancreatic cystic neoplasms is important not only to recognize premalignant lesions that will require surgical resection, but also to allow nonoperative management of many cystic lesions that will not require resection with its inherent morbidity. Though reliable biomarkers are lacking, a wide spectrum of diagnostic modalities are available to evaluate pancreatic cystic neoplasms, including radiologic, endoscopic, laboratory, and pathologic analysis. An interdisciplinary approach to management of these lesions which incorporates recent, specialty-specific advances in the medical literature is herein suggested

Mass Spectrometry-Based Proteomics for Translational Research: A Technical Overview

Mass spectrometry-based investigation of clinical samples enables the high-throughput identification of protein biomarkers. We provide an overview of mass spectrometry-based proteomic techniques that are applicable to the investigation of clinical samples. We address sample collection, protein extraction and fractionation, mass spectrometry modalities, and quantitative proteomics. Finally, we examine the limitations and further potential of such technologies. Liquid chromatography fractionation coupled with tandem mass spectrometry is well suited to handle mixtures of hundreds or thousands of proteins. Mass spectrometry-based proteome elucidation can reveal potential biomarkers and aid in the development of hypotheses for downstream investigation of the molecular mechanisms of disease

Subcellular fractionation enhances proteome coverage of pancreatic duct cells

Durante a década de sessenta, numa altura em que o mundo ia assistindo à consolidação triunfante dos independentismos anticoloniais, a ditadura portuguesa persistia em manter o seu domínio ultramarino. Apesar de educados numa certa "mística imperial" e limitados nos seus direitos de expressão e associação, alguns sectores da sociedade, essencialmente enraizados nos territórios estudantis, foram construindo um horizonte de intervenção fortemente crítico do colonialismo do regime. Este texto pretende caracterizar a prática e o discurso de uma destas áreas, no caso a pulverizada corrente maoísta, contextualizando previamente a ideia de violência nas leituras sobre os 'longos anos sessenta' e a especificidade do maoísmo emergente nesse tempo

The Utility of the Systemic Inflammatory Respsonse [Response] Syndrome Score on Admission in Children With Acute Pancreatitis

OBJECTIVES: Pediatric patients with acute pancreatitis (AP) may meet criteria at admission for the systemic inflammatory response syndrome (SIRS). Early SIRS in adults with AP is associated with severe disease. Our aim was to evaluate the importance of SIRS in children presenting with AP on various outcomes. METHODS: This is a retrospective cohort study of children hospitalized with AP at Boston Children\u27s Hospital in 2010. Increased length of stay (LOS) and/or admission to the intensive care unit (ICU) served as the primary outcomes. Statistical analyses of measures studied included the presence of SIRS, demographic, and clinical information present on admission. RESULTS: Fifty encounters, in which AP was the primary admitting diagnosis, were documented. Patients had a median LOS of 4.5 (interquartile range, 2-9) days. Systemic inflammatory response syndrome was present in 22 (44%) of 50 patients at admission. Systemic inflammatory response syndrome at admission was an independent predictor of increased LOS (odds ratio, 7.99; P = 0.045) as well as admission to the ICU (odds ratio, 12.06; P = 0.027). CONCLUSIONS: The presence of SIRS criteria on admission serves as a useful and easy-to-calculate predictor of increased LOS and admission to ICU in children with AP

Incidence and clinical sequelae of portal and hepatic venous thrombosis following percutaneous cryoablation of liver tumors.

PURPOSE: To assess the incidence and sequelae of portal and hepatic venous thrombosis after percutaneous cryoablation of hepatic tumors. METHODS: From November 1998 through December 2010, 223 hepatic tumors were cryoablated during 170 ablation procedures in 135 patients. 24-h post-procedure MR images were reviewed retrospectively by two abdominal radiologists in consensus to identify tumor ablations that developed one or more new portal or hepatic venous thromboses in or outside the ablation zone. On follow-up MRI and CT examinations the outcomes of thromboses were classified as resolved, partially recanalized, persistent, or propagated. RESULTS: Venous thrombosis developed in association with 54 (24%) of 223 tumor ablations treated during 53 (31%) ablation procedures in 39 (28.8%) patients (15 women, 24 men; age range 40-82 years, mean 59 years). Of these 54 thromboses, 49 (91%) were located in portal vein branches, four (7%) in both portal and hepatic vein branches, and one (2%) in a hepatic vein branch. Thrombosed veins were outside but abutted the ablation zone in 36 (66.7%), and within it in 18 (33.3%). On follow-up imaging (n = 49), thrombi resolved in 29 (59%), partially recanalized in two (4%), persisted in 18 (37%) and propagated from sub-segmental or segmental branches to the left or right portal branches in five (10%). No thrombus propagated to the main portal vein or inferior vena cava. CONCLUSION: Portal and hepatic vein branch thromboses are common in small branches following percutaneous cryoablation of hepatic tumors and most resolve spontaneously without sequelae

Differentiating Branch Duct and Mixed IPMN in Endoscopically Collected Pancreatic Cyst Fluid via Cytokine Analysis

Background. Differentiating branch duct from mixed intraductal papillary mucinous neoplasm (BD-IPMN) is problematic, but clinically important as mixed IPMNs are managed surgically, while some BD-IPMN may be followed. Inflammatory mediator proteins (IMPs) have been implicated in acute and chronic inflammatory and malignant pancreatic diseases. Aim. To compare IMP profile of pancreatic cyst fluid collected endoscopically from BD-IPMN and mixed IPMN. Methods. Pancreatic cyst fluid from ten patients (5 BD-IPMN and 5 mixed IPMN) was collected by endoscopic ultrasound-guided fine needle aspiration or endoscopic retrograde cholangiopancreatography. Concentrations of 89 IMPs in these samples were determined using a multiplexed bead-based microarray protein assay and compared between BD-IPMN and mixed IPMN. Results. Eighty-six of 89 IMPs were detected in at least one of the 10 samples. Fourteen IMPs were detected only in mixed IPMN, while none were only in BD-IPMN. Of these, TGF-β1 was most prevalent, present in 3 of 5 mixed IPMNs. Seventy-two IMPs were detected in both BD-IPMN and mixed IPMNs. Of these, only G-CSF (P<0.05) was present in higher concentrations in mixed IPMNs. Conclusion. TGF-β1 and G-CSF detected in endoscopically collected pancreatic cyst fluid are potential diagnostic biomarkers capable of distinguishing mixed IPMN from BD-IPMN

Proteomic Analysis (GeLC–MS/MS) of ePFT-Collected Pancreatic Fluid in Chronic Pancreatitis

Chronic pancreatitis is characterized by inflammation, fibrosis, pain, and loss of exocrine function of the pancreas. We aimed to identify differentially expressed proteins in the ePFT-collected pancreatic fluid from individuals with chronic pancreatitis (CP; <i>n</i> = 9) and controls with chronic abdominal pain not associated with the pancreas (NP; <i>n</i> = 9). Using GeLC–MS/MS techniques, we identified a total of 1391 different proteins in 18 pancreatic fluid samples. Of these proteins, 257 and 413 were identified exclusively in the control and chronic pancreatitis cohorts, respectively, and 721 were identified in both cohorts. Spectral counting and statistical analysis thereof revealed an additional 38 and 77 proteins that were up- or down-regulated, respectively, in the pancreatic fluid from individuals with chronic pancreatitis. As expected, gene ontology analysis illustrated that the largest percentage of differentially regulated proteins was secreted/extracellular in origin. In addition, proteins that were down-regulated with statistical significance in the chronic pancreatitis cohort were determined to have biological function of proteases, corresponding to the canonical pancreatic insufficiency associated with chronic pancreatitis. Proteins enriched in the pancreatic fluid of chronic pancreatitis patients had roles in fibrosis, inflammation, and pain, whereas digestive enzymes were significantly less abundant. Our workflow provided a mass spectrometry-based approach for the further study of the pancreatic fluid proteome, which may lead to the discovery potential biomarkers of chronic pancreatitis

Points to consider : efficacy and safety evaluations in the clinical development of ultra-orphan drugs

Background: The unmet medical needs of individuals with very rare diseases are high. The clinical trial designs and evaluation methods used for 'regular' drugs are not applicable in the clinical development of ultra-orphan drugs (<1000 patients) in many cases. In order to improve the clinical development of ultra-orphan drugs, we examined several points regarding the efficient evaluations of drug efficacy and safety that could be conducted even with very small sample sizes, based on the review reports of orphan drugs approved in Japan. Results: The clinical data packages of 43 ultra-orphan drugs approved in Japan from January 2001 to December 2014 were investigated. Japanese clinical trial data were not included in the clinical data package for eight ultra-orphan drugs, and non-Japanese clinical trial data were included for six of these eight drug. Japanese supportive data that included retrospective studies, published literature, clinical research and Japanese survey results were clinical data package attachments in 22 of the 43 ultra-orphan drugs. Multinational trials were conducted for three ultra-orphan drugs. More than two randomized controlled trials (RCTs) were conducted for only 11 of the 43 ultra-orphan drugs. The smaller the number of patients, the greater the proportion of forced titration and optional titration trials were conducted. Extension trials were carried out for enzyme preparations and monoclonal antibodies with high ratio. Post-marketing surveillance of all patients was required in 36 of the 43 ultra-orphan drugs. For ultra-orphan drugs, clinical endpoints were used as the primary efficacy endpoint of the pivotal trial only for two drugs. The control groups in RCTs were classified as follows: placebo groups different dosage groups, and active controls groups. Sample sizes have been determined on the basis of feasibility for some ultra-orphan drugs. We provide "Draft Guidance on the Clinical Development of Ultra-Orphan Drugs" based on this research. Conclusions: The development of ultra-orphan drugs requires various arrangements regarding evidence collection, data sources and the clinical trial design. We expect that this draft guidance is useful for ultra-orphan drugs developments in future

Patient characteristics, episodes of UTI, treatment and outcome.

<p>M-Male, F-Female, ESRD-End stage renal disease, DM-Diabetes mellitus, HTN-Hypertension, CMV-Cytomegalovirus, UTI-Urinary tract infection, ESBL-Extended spectrum beta lactamase.</p