Laparoscopic radical 'no-touch' left pancreatosplenectomy for pancreatic ductal adenocarcinoma: technique and results

Background Laparoscopic left pancreatectomy has been well described for benign pancreatic lesions, but its role in pancreatic adenocarcinoma remains open to debate. We report our results adopting a laparoscopic technique that obeys established oncologic principles of open distal pancreatosplenectomy. Methods This is a post hoc analysis of a prospectively kept database of 135 consecutive patients undergoing laparoscopic left pancreatectomy, performed across two sites in the UK and the Netherlands (07/2007–07/2015 Southampton and 10/2013–07/2015 Amsterdam). Primary outcomes were resection margin and lymph node retrieval. Secondary endpoints were other perioperative outcomes, including post-operative pancreatic fistula. Definition of radical resection was distance tumour to resection margin >1 mm. All patients underwent ‘laparoscopic radical left pancreatosplenectomy’ (LRLP) which involves ‘hanging’ the pancreas including Gerota’s fascia, followed by clockwise dissection, including formal lymphadenectomy. Results LRLP for pancreatic adenocarcinoma was performed in 25 patients. Seven of the 25 patients (28 %) had extended resections, including the adrenal gland (n = 3), duodenojejunal flexure (n = 2) or transverse mesocolon (n = 3). Mean age was 68 years (54–81). Conversion rate was 0 %, mean operative time 240 min and mean blood loss 340 ml. Median intensive/high care and hospital stay were 1 and 5 days, respectively. Clavien–Dindo score 3+ complication rate was 12 % and ISGPF grade B/C pancreatic fistula rate 28 %; 90-day (or in-hospital) mortality was 0 %. The pancreatic resection margin was clear in all patients, and the posterior margin was involved (<1 mm) in 6 patients, meaning an overall R0 resection rate of 76 %. No resection margin was microscopically involved. Median nodal sample was 15 nodes (3–26). With an average follow-up of 17.2 months, 1-year survival was 88 %. Conclusions A standardised laparoscopic approach to pancreatic adenocarcinoma in the left pancreas can be adopted safely. Our study shows that these results can be reproduced across multiple sites using the same technique

Statistical modelling of turbidity removal applied to non-toxic natural coagulants in water treatment: a case study

An investigation into two non-toxic natural coagulants abundantly growing in different countries, cactus (Opuntia spp.) and okra was performed on monthly river water samples (one-year period). The studied case was the Euphrates river/Al-Mashroo canal/Iraq. Six statistical models were interpreted and tested describing the residual turbidity after Coagulation-Flocculation for the three studied cases (Optimum-Coagulant-Dose, Optimum-Flocculator-Velocity-Gradient and Optimum-Flocculation-Time). According to the environmental parameters recorded during the study and the statistical analyses, two facts were concluded. The first fact was that controlling the Optimum-Flocculator-Velocity-Gradient of the Coagulation-Flocculation process gave the highest contribution ratio of the models. The second fact was that the most significant environmental parameter (statistically) in the Coagulation-Flocculation process was the initial turbidity. This was proved for the two natural coagulants under study. Also, from the results of the study, it was concluded that the two natural coagulants were of similar coagulation-flocculation properties, and they were competent for turbidity removal

PCR clonality detection in Hodgkin lymphoma

B-cell clonality detection in whole tissue is considered indicative of B-cell non-Hodgkin lymphoma (NHL). We tested frozen tissue of 24 classical Hodgkin lymphomas (cHL) with a varying tumor cell load with the multiplex polymerase chain reaction (PCR) primer sets for IGH and IGK gene rearrangement (BIOMED-2). A clonal population was found in 13 cases with the IGH FR1 and/or FR2/FR3 PCRs. Using the IGK-VJ and IGK-DE PCRs, an additional six cases had a dominant clonal cell population, resulting in a detection rate of 79% in frozen tissue. Of 12 cases, also the formalin-fixed and paraffin-embedded (FFPE) tissue was tested. Surprisingly, in eight of the 12 FFPE cases with acceptable DNA quality (allowing PCR amplification of >200 nt fragments), the IGK multiplex PCRs performed better in detecting clonality (six out of eight clonal IGK rearrangements) than the IGH PCRs (four out of nine clonal rearrangements), despite a rather large amplicon size. There was no evidence of B-cell lymphoma during follow-up of 1 to 6 years and no correlation was found between the presence of a clonal result and Epstein–Barr virus in the tumor cells. Our results indicate that the present routine PCR methods are sensitive enough to detect small numbers of malignant cells in cHL. Therefore, the presence of a clonal B-cell population does not differentiate between cHL and NHL

Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD.

OBJECTIVE: Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD). DESIGN: We constructed a novel hepatocyte-specific PPARα knockout (Pparα(hep-/-)) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we investigated which physiological challenges impact on PPARα. Moreover, we measured the contribution of hepatocytic PPARα activity to whole-body metabolism and fibroblast growth factor 21 production during fasting. Finally, we determined the influence of hepatocyte-specific PPARα deficiency in different models of steatosis and during ageing. RESULTS: Hepatocyte PPARα deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis. Fasting mice showed acute PPARα-dependent hepatocyte activity during early night, with correspondingly increased circulating free fatty acids, which could be further stimulated by adipocyte lipolysis. Fasting led to mild hypoglycaemia and hypothermia in Pparα(hep-/-) mice when compared with Pparα(-/-) mice implying a role of PPARα activity in non-hepatic tissues. In agreement with this observation, Pparα(-/-) mice became overweight during ageing while Pparα(hep-/-) remained lean. However, like Pparα(-/-) mice, Pparα(hep-/-) fed a standard diet developed hepatic steatosis in ageing. CONCLUSIONS: Altogether, these findings underscore the potential of hepatocyte PPARα as a drug target for NAFLD

Towards Business-to-IT Alignment in the Cloud

Cloud computing offers a great opportunity for business process (BP) flexibility, adaptability and reduced costs. This leads to realising the notion of business process as a service (BPaaS), i.e., BPs offered on-demand in the cloud. This paper introduces a novel architecture focusing on BPaaS design that includes the integration of existing state-of-the-art components as well as new ones which take the form of a business and a syntactic matchmaker. The end result is an environment enabling to transform domain-specific BPs into executable workflows which can then be made deployable in the cloud so as to become real BPaaSes

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis : Fundamentals Of Care for UveitiS (FOCUS) Initiative

Supplemental material available at www.aaojournal.org. Supported by AbbVie, Inc., and the Fundamentals of Care for Uveitis Initiative National Faculty. This manuscript was developed subsequent to an AbbVie-sponsored literature review of noninfectious, nonanterior uveitis. The meeting was conducted to understand the available literature regarding the management of patients with noninfectious, nonanterior uveitis. The program involved a total of 139 experts from 28 countries, who were selected for participation by AbbVie. However, AbbVie was not involved in the development of the manuscript. The authors maintained complete control over the content and this manuscript reflects the opinions of the authors. AbbVie selected the discussion participants and reviewed the final manuscript draft for scientific accuracy, but the authors determined the final content. All authors made substantial contributions to the article or critically revised it for important intellectual content and approved the final manuscript. AbbVie provided funding to invited participants, including honoraria for their attendance at the meetings. Travel to and from the meetings was reimbursed. No payments were made to the authors for the development of this manuscript. Dhinakaran Sambandan, PhD, and Shula Sarner, PhD, of Lucid Partners, Burleighfield House, Buckinghamshire, United Kingdom, provided medical writing and editorial support to the authors in the development of this manuscript; financial support for these services was provided by AbbVie. AbbVie reviewed the manuscript, but was not involved in the methodology, data collection and analysis, or completion of this manuscript.Peer reviewedPublisher PD

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism

Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate haematopoetic cell movement are implicated in the metastatic process of malignant tumours, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited the implantation and the growth of human and mouse CRC cells within lung without affecting that in the liver. In addition, we measured increased levels of CXCR3 and ligands expression within lung nodules compared with liver tumours. Altogether, our findings indicate that activation of CXCR3 receptors by its cognate ligands facilitates the implantation and the progression of CRC cells within lung tissues and that inhibition of this axis decreases pulmonary metastasis of CRC in two murine tumour models