Surgical approaches to adenocarcinoma of the gastroesophageal junction: the Siewert II conundrum.

BACKGROUND: The Siewert classification system for gastroesophageal junction adenocarcinoma has provided morphological and topographical information to help guide surgical decision-making. Evidence has shown that Siewert I and III tumors are distinct entities with differing epidemiologic and histologic characteristics and distinct patterns of disease progression, requiring different treatment. Siewert II tumors share some of the characteristics of type I and III lesions, and the surgical approach is not universally agreed upon. Appropriate surgical options include transthoracic esophagogastrectomy, transhiatal esophagectomy, and transabdominal extended total gastrectomy. PURPOSE: A review of the available evidence of the surgical management of Siewert II tumors is presented. CONCLUSIONS: Careful review of the data appear to support the fact that a satisfactory oncologic resection can be achieved via a transabdominal extended total gastrectomy with a slight advantage in terms of perioperative complications, and overall postoperative quality of life. Overall and disease-free survival compares favorably to the transthoracic approach. These results can be achieved with careful selection of patients balancing more than just the Siewert type in the decision-making but considering also preoperative T and N stages, histological type (diffuse type requiring longer margins that are not always achievable via gastrectomy), and the presence of Barrett\u27s esophagus

A standardized comparison of peri-operative complications after minimally invasive esophagectomy: Ivor Lewis versus McKeown.

BACKGROUND: While our institutional approach to esophageal resection for cancer has traditionally favored a minimally invasive (MI) 3-hole, McKeown esophagectomy (MIE 3-hole) during the last five years several factors has determined a shift in our practice with an increasing number of minimally invasive Ivor Lewis (MIE IL) resections being performed. We compared peri-operative outcomes of the two procedures, hypothesizing that MIE IL would be less morbid in the peri-operative setting compared to MIE 3-hole. METHODS: Our institution\u27s IRB-approved esophageal database was queried to identify all patients who underwent totally MI esophagectomy (MIE IL vs. MIE 3-hole) from June 2011 to May 2016. Patient demographics, preoperative and peri-operative data, as well as post-operative complications were compared between the two groups. Post-operative complications were analyzed using the Clavien-Dindo classification system. RESULTS: There were 110 patients who underwent totally MI esophagectomy (MIE IL n = 49 [45%], MIE 3-hole n = 61 [55%]). The majority of patients were men (n = 91, 83%) with a median age of 62.5 (range 31-83). Preoperative risk stratifiers such as ECOG score, ASA, and Charlson Comorbidity Index were not significantly different between groups. Anastomotic leak rate was 2.0% in the MIE IL group compared to 6.6% in the MIE 3-hole group (p = 0.379). The rate of serious (Clavien-Dindo 3, 4, or 5) post-operative complications was significantly less in the MIE IL group (34.7 vs. 59.0%, p = 0.013). Serious pulmonary complications were not significantly different (16.3 vs. 26.2%, p = 0.251) between the two groups. CONCLUSIONS: In this cohort, totally MIE IL showed significantly less severe peri-operative morbidity than MIE 3-hole, but similar rates of serious pulmonary complications and anastomotic leaks. These findings confirm the safety of minimally invasive Ivor Lewis esophagectomies for esophageal cancer when oncologically and clinically appropriate. Minimally invasive McKeown esophagectomy remains a satisfactory and appropriate option when clinically indicated

Quiet in the Operating Room! Team STEPPS and OR Distractions

Background and Objective: From the moment that a patient enters the operating room to the time that they are brought to the post anesthesia care unit, a distraction has the potential to lead to an adverse outcome for the patient. During the critical portions of the surgery, it is even more important for all members of the operating staff to be focused and engaging in safe practices. Distractions in the operating room can hinder safe communication and potentially endanger patient safety. Team training has been shown to both improve team communication and reduce distractions. The objective of this project was using Team STEPPS training to reduce distractions during the critical portions of surgery, defined as the time of anesthesia induction, the time out, and the time of emergence from anesthesiahttps://jdc.jefferson.edu/patientsafetyposters/1060/thumbnail.jp

Silencing the GUCA2A-GUCY2C tumor suppressor axis in CIN, serrated, and MSI colorectal neoplasia.

Colorectal cancers (CRCs) initiate through distinct mutations, including in APC pathway components leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI). Transformation through the APC pathway involves loss of the hormone GUCA2A that silences the tumor-suppressing receptor GUCY2C. Indeed, oral hormone replacement is an emerging strategy to reactivate GUCY2C and prevent CRC initiation and progression. Moreover, retained expression by tumors arising from TAs has established GUCY2C as a diagnostic and therapeutic target to prevent and treat metastatic CRC. Here, we defined the potential role of the GUCA2A-GUCY2C axis and its suitability as a target in tumors arising through the SA and MSI pathways. GUCA2A hormone expression was eliminated in TAs, SAs, and MSI tumors compared to their corresponding normal adjacent tissues. In contrast to the hormone, the tumor-suppressing receptor GUCY2C was retained in TA and MSI tumors. Surprisingly, GUCY2C expression was nearly eliminated in SAs, reflecting loss of the transcription factor CDX2. Changes in the GUCA2A-GUCY2C axis in human SAs and MSI tumors were precisely recapitulated in genetic mouse models. These data reveal the possibility of GUCA2A loss silencing GUCY2C in the pathophysiology of, and oral hormone replacement to restore GUCY2C signaling to prevent, MSI tumors. Also, they highlight the potential for targeting GUCY2C to prevent and treat metastases arising from TA and MSI tumors. In contrast, loss of GUCY2C excludes patients with SAs as candidates for GUCY2C-based prevention and therapy

Surgical Apgar Score (SAS) Predicts Perioperative Morbidity and Length of Stay in Patients Undergoing Esophagectomy at a High-Volume Center

Background: Esophagectomy is a procedure that carries considerable morbidity. Many studies have evaluated factors to predict patients at risk and improve clinical outcomes. The aim of this study was to determine whether the SAS predicts complications, length of stay, and anastomotic leak for patients undergoing esophagectomy at a high-volume institution.https://jdc.jefferson.edu/surgeryposters/1002/thumbnail.jp

The Salmonella effector SseJ disrupts microtubule dynamics when ectopically expressed in Normal Rat Kidney cells

Salmonella effector protein SseJ is secreted by Salmonella into the host cell cytoplasm where it can then modify host cell processes. Whilst host cell small GTPase RhoA has previously been shown to activate the acyl-transferase activity of SseJ we show here an un-described effect of SseJ protein production upon microtubule dynamism. SseJ prevents microtubule collapse and this is independent of SseJ's acyl-transferase activity. We speculate that the effects of SseJ on microtubules would be mediated via its known interactions with the small GTPases of the Rho family

Measuring temporal, spectral and spatial changes in electrophysiological brain network connectivity

The topic of functional connectivity in neuroimaging is expanding rapidly and many studies now focus on coupling between spatially separate brain regions. These studies show that a relatively small number of large scale networks exist within the brain, and that healthy function of these networks is disrupted in many clinical populations. To date, the vast majority of studies probing connectivity employ techniques that compute time averaged correlation over several minutes, and between specific pre-defined brain locations. However, increasing evidence suggests that functional connectivity is non-stationary in time. Further, electrophysiological measurements show that connectivity is dependent on the frequency band of neural oscillations. It is also conceivable that networks exhibit a degree of spatial inhomogeneity, i.e. the large scale networks that we observe may result from the time average of multiple transiently synchronised sub-networks, each with their own spatial signature. This means that the next generation of neuroimaging tools to compute functional connectivity must account for spatial inhomogeneity, spectral non-uniformity and temporal non-stationarity. Here, we present a means to achieve this via application of windowed canonical correlation analysis (CCA) to source space projected MEG data. We describe the generation of time–frequency connectivity plots, showing the temporal and spectral distribution of coupling between brain regions. Moreover, CCA over voxels provides a means to assess spatial non-uniformity within short time–frequency windows. The feasibility of this technique is demonstrated in simulation and in a resting state MEG experiment where we elucidate multiple distinct spatio-temporal-spectral modes of covariation between the left and right sensorimotor areas

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente