Role for targeted resection in the multidisciplinary treatment of metastatic gastrointestinal stromal tumor

The management of advanced gastrointestinal stromal tumors (GISTs) has evolved in the modern era due to the discovery of c-kit mutations and the development of tyrosine kinase inhibitors (TKIs). Until the advent of TKIs such as imatinib, the median survival reported for patients with advanced GIST was 19 months. Although surgery is the treatment of choice for resectable primary GIST, its role in cases of recurrence and metastasis remains to be unclear. This review outlines the potential beneficial role of repeat surgical resection in the multidisciplinary treatment of advanced GIST in the era of TKIs

Nonlinear Optical Corneal Crosslinking, Mechanical Stiffening, and Corneal Flattening Using Amplified Femtosecond Pulses.

Purpose:We have shown that nonlinear optical corneal crosslinking (NLO CXL) and stiffening can be achieved in ex vivo rabbit corneas using an 80-MHz, 760-nm femtosecond (FS) laser, however the required power was beyond the American National Standard Institute limit. The purpose of this study was to test the efficacy of amplified FS pulses to perform CXL to reduce power by increasing pulse energy. Methods:A variable numerical aperture laser scanning delivery system was coupled to a 1030-nm laser with a noncollinear optical parametric amplifier to generate 760 nm, 50 to 150 kHz amplified FS pulses with 79.5-μm axial and 2.9-μm lateral two-photon focal volume. Ex vivo rabbit corneas received NLO CXL, and effectiveness was assessed by measuring collagen autofluorescence (CAF) and mechanical stiffening. NLO CXL was also performed in 14 live rabbits, and changes in corneal topography were measured using an Orbscan. Results:Amplified pulses (0.3 μJ) generated significant CAF that increased logarithmically with decreasing scan speed; achieving equivalent CAF to UVA CXL at 15.5 mm/s. Indentation testing detected a 62% increase in stiffness compared to control, and corneal topography measurements revealed a significant decrease of 1.0 ± 0.8 diopter by 1 month (P < 0.05). Conclusions:These results show that NLO CXL using amplified pulses can produce corneal collagen CXL comparable to UVA CXL. Translational Relevance:NLO CXL using amplified pulses can produce corneal CXL comparable to UVA CXL, suggesting a potential clinical application in which NLO CXL can be used to perform personalized crosslinking for treatment of refractive errors and keratoconus

Ambiguities of neutrino(antineutrino) scattering on the nucleon due to the uncertainties of relevant strangeness form factors

Strange quark contributions to neutrino(antineutrino) scattering are investigated on the nucleon level in the quasi-elastic region. The incident energy range between 500 MeV and 1.0 GeV is used for the scattering. All of the physical observable by the scattering are investigated within available experimental and theoretical results for the strangeness form factors of the nucleon. In specific, a newly combined data of parity violating electron scattering and neutrino scattering is exploited. Feasible quantities to be explored for the strangeness contents are discussed for the application to neutrino-nucleus scattering.Comment: 17 pages, 7 figures, submit to J. Phys.

What Is the Best Pain Control After Major Hepatopancreatobiliary Surgery?

In the modern era, hepato-pancreato-biliary (HPB) surgery has become safe with significant reductions in morbidity and mortality at high volume centers for both liver and pancreas surgery. While laparoscopic surgery has provided a safe approach with superior pain control laparotomy is still needed for the majority of HPB operations. Inadequate pain control is not only associated with poor patient experience but contributes to inferior outcomes. Specifically, inadequate pain control affects the neuroendocrine stress response, increases complication rates, and prolongs length of stay. Furthermore, there is an ongoing opioid epidemic and all fields of medicine should strive to reduce narcotic use to limit transformation into chronic opiate dependence. As such, successful pain control after HPB surgery continues to be a challenge and rigorous studies evaluating postoperative results are needed. The following article reviews the modalities debated to be the best strategies for pain control after major HPB surgery, as well as a discussion of other important considerations when executing these plans

Approach to wild-type gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) arise from the intestinal pacemaker cells of Cajal. Wild-type gastrointestinal stromal tumors (WT-GIST) are a unique and uncommon subtype of GISTs that lack activating mutations in the tyrosine kinase c-KIT or platelet derived growth factor receptor alpha (PDGFRA) receptors. The lack of these growth-stimulating mutations renders tyrosine kinase receptor inhibitors, such as imatinib mesylate, relatively ineffective against these tumors. WT-GIST arises most commonly due to underlying alternate proliferative signals associated with germ-line, genetic mutations. WT-GIST frequently arises in patients with BRAF mutations, Carney’s Triad or neurofibromatosis type-1 (NF-1). All patients with WT-GIST require a careful examination for germ-line mutations and very close observation for recurrent tumors. Surgery remains a mainstay therapy for these patients. This review aims to discuss the most recent data available on the diagnosis and treatment of WT-GIST

National Cancer Institute Centers and Society of Surgical Oncology Cancer Research Synergy

Background: The objective of this study was to examine the influence of Surgical Society Oncology (SSO) membership and National Cancer Institute (NCI) status on the academic output of surgical faculty. Methods: NCI cancer program status for each department of surgery was identified with publically available data, whereas SSO membership was determined for every faculty member. Academic output measures such as NIH funding, publications, and citations were analyzed in subsets by the type of cancer center (NCI comprehensive cancer center [CCC]; NCI cancer center [NCICC]; and non-NCI center) and SSO membership status. Results: Of the surgical faculty, 2537 surgeons (61.9%) were from CCC, whereas 854 (20.8%) were from NCICC. At the CCC, 22.7% of surgeons had a history of or current NIH funding, compared with 15.8% at the NCICC and 11.8% at the non-NCI centers. The academic output of SSO members was higher at NCICC (52 ± 113 publications/1266 ± 3830 citations) and CCC (53 ± 92/1295 ± 4001) compared with nonmembers (NCICC: 26 ± 78/437 ± 2109; CCC: 37 ± 91/670 ± 3260), respectively, P < 0.05. Multivariate logistic regression revealed that SSO membership imparts an additional 22 publications and 270 citations, whereas NCI-designated CCC added 10 additional publications, but not citations. Conclusions: CCCs have significantly higher academic output and NIH funding. Recruitment of SSO members, a focus on higher performing divisions, and NIH funding are factors that non-NCI cancer centers may be able to focus on to improve academic productivity to aid in obtaining NCI designation

Failure Mode Analysis of the Endologix Endograft

Objective Type III (T-III) endoleaks following endovascular aneurysm repair (EVAR) remain a major concern. Our center experienced a recent concentration of T-III endoleaks requiring elective and emergency treatment and prompted our review of all EVAR implants over a 40-month period from April 2011 until August 2014. This report represents a single center experience with T-III endoleak management with analysis of factors leading to the T-III-related failure of EVAR. Methods A retrospective review of all the operative reports, medical records, and computed tomography scans were reviewed from practice surveillance. Using Society for Vascular Surgery aneurysm reporting standards, we analyzed the morphology of the aneurysms before and after EVAR implant using computed tomography. Index procedure and frequency of reinterventions required to maintain aneurysm freedom from rupture were compared across all devices using SAS v 9.4 (SAS Institute, Inc, Cary, NC). Major adverse events (MAEs) requiring secondary interventions for aneurysm treatment beyond primary implant were analyzed for methods of failure. Aneurysm morphology of patients requiring EVAR was compared across all endograft devices used for repair. For purposes of MAE analysis, patients receiving Endologix (ELX) endograft were combined into group 1; Gore, Cook, and Medtronic endograft patients were placed into group 2. Results Overall, technical success and discharge survival were achieved in 97.3% and 98% of patients regardless of device usage. There was no significant device related difference identified between patient survival or freedom from intervention. MAEs involving aneurysm treatment were over seven-fold more frequent with ELX (group 1) vs non-ELX (group 2) endografts (P < .01). Group 1 patients with aneurysm diameters larger than 65 mm were associated with a highly significant value for development of a T-III endoleak (odds ratio, 11.16; 95% confidence interval, 2.17, 57.27; P = .0038). Conclusions While EVAR technical success and survival were similar across all devices, ELX devices exhibited an unusually high incidence of T-III endoleaks when implanted in abdominal aortic aneurysms with a diameter of more than 65 mm. Frequent reinterventions were required for Endologix devices for prevention of aneurysm rupture due to T-III endoleaks

ConPlex: a server for the evolutionary conservation analysis of protein complex structures

Evolutionary conservation analyses are important for the identification of protein–protein interactions. For protein complex structures, sequence conservation has been applied to determine protein oligomerization states, to characterize native interfaces from non-specific crystal contacts, and to discriminate near-native structures from docking artifacts. However, a user-friendly web-based service for evolutionary conservation analysis of protein complexes has not been available. Therefore, we developed ConPlex (http://sbi.postech.ac.kr/ConPlex/) a web application that enables evolutionary conservation analyses of protein interactions within protein quaternary structures. Users provide protein complex structures; ConPlex automatically identifies protein interfaces and carries out evolutionary conservation analyses for the interface regions. Moreover, ConPlex allows the results of the residue-specific conservation analysis to be displayed on the protein complex structure and provides several options to customize the display output to fit each user’s needs. We believe that ConPlex offers a convenient platform to analyze protein complex structures based on evolutionary conservation of protein–protein interface residues

Research with real photons at the MAMI 1.6 GeV electron accelerator

The A2-CB Collaboration at Mainz is studying the structure of hadrons by meson photoproduction using unpolarised, linearly polarised and circularly polarised photons with energies up to 1.6 GeV. Photons are energy-tagged using the Glasgow-Mainz tagged photon spectrometer and a new high-energy end-point tagger which allows η’ reactions to be studied. Reaction products are detected in a ~4π detector consisting of the Crystal Ball detector and TAPS forward wall. Transverse or longitudinally polarised proton targets are available and new techniques have been developed to measure the polarisation of recoiling protons. These facilities have allowed an extensive programme of double-polarisation meson-photoproduction experiments to be carried out to search for so-called “missing baryon resonances” on proton and deuteron targets. Searches have also been carried out to investigate narrow resonances in the η-photoproduction channel at invariant masses around 1680 MeV. Coherent π0 production measurements have been used to estimate the neutron skin thickness in 208Pb. This paper presents selected highlights from the A2-CB collaboration research programme at MAMI