Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.

BACKGROUND: Chromosomal instability (CIN) has repeatedly been identified as a prognostic marker. Here we evaluated the percentage of aberrant genome per cell (PAG) as a measure of CIN in single disseminated tumour cells (DTC) isolated from patients with operable oesophageal adenocarcinoma (EAC), to assess the impact of CINhigh DTCs on prognosis. METHODS: We isolated CK18positive DTCs from bone marrow (BM) or lymph node (LN) preparations of operable EAC patients. After whole-genome amplification, single DTCs were analysed for chromosomal gains and losses using metaphase-based comparative genomic hybridisation (mCGH). We calculated the PAG for each DTC and determined the critical threshold value that identifies high-risk patients by STEPP (Subpopulation Treatment Effect Pattern Plot) analysis in two independent EAC patient cohorts (cohort #1, n=44; cohort #2; n=29). RESULTS: The most common chromosomal alterations observed among the DTCs were typical for EAC, but the DTCs showed a varying PAG between individual patients. Generally, LNDTCs displayed a significantly higher PAG than BMDTCs. STEPP analysis revealed an increasing PAG of DTCs to be correlated with an increased risk for short survival in two independent EAC cohorts as well as in the corresponding pooled analysis. In all three data sets (cohort #1, cohort #2 and pooled cohort), PAGhigh DTCs conferred an independent risk for a significantly decreased survival. CONCLUSIONS: The analysis of PAG/CIN in solitary marker-positive DTCs identifies operable EAC patients with poor prognosis, indicating a more aggressive minimal residual disease.

Combined Baerveldt glaucoma implant and scleral buckling surgery for patients with retinal detachment and coexisting glaucoma.

PURPOSE: To report on the usefulness of combined Baerveldt glaucoma implantation (BGI) and scleral buckling surgery for patients with glaucoma requiring a scleral buckle for retinal detachment repair. METHODS: Retrospective, consecutive, noncomparative, and interventional case series of 30 eyes (30 patients) that underwent simultaneous scleral buckle and BGI surgery, using a staged (group 1, n=21 patients) or nonstaged (group 2, n=9 patients) approach to BGI implantation. Successful intraocular pressure (IOP) control was defined as 6 mm Hg≤IOP≤18 mm Hg. RESULTS: Although not statistically significant, mean best corrected visual acuity (LogMAR) improved from 2.0 before surgery to 1.7 after surgery (P=0.13) with a mean follow-up of 27.7 months. Of the 21 patients in group 1, only 13 (62%) required second-stage tube insertion at a mean of 7.0±8.0 months (range, 1 to 24 mo) postoperatively. For these eyes combined with group 2 eyes, mean IOP was reduced from 31.1±10.8 to 12.7±6.0 mm Hg (P<0.0001), and the mean number of glaucoma medications was reduced from 2.9±1.4 to 1.2±1.3 (P<0.001). Life table rates of successful IOP control were 90% and 80% at 12 and 24 months, respectively. CONCLUSIONS: Combined scleral buckle and BGI is an effective technique for managing coexisting glaucoma and retinal detachment and provides the clinician with a useful surgical option while minimizing surgical risk.

Intermedin stabilized endothelial barrier function and attenuated ventilator-induced lung injury in mice.

BACKGROUND: Even protective ventilation may aggravate or induce lung failure, particularly in preinjured lungs. Thus, new adjuvant pharmacologic strategies are needed to minimize ventilator-induced lung injury (VILI). Intermedin/Adrenomedullin-2 (IMD) stabilized pulmonary endothelial barrier function in vitro. We hypothesized that IMD may attenuate VILI-associated lung permeability in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Human pulmonary microvascular endothelial cell (HPMVEC) monolayers were incubated with IMD, and transcellular electrical resistance was measured to quantify endothelial barrier function. Expression and localization of endogenous pulmonary IMD, and its receptor complexes composed of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) 1-3 were analyzed by qRT-PCR and immunofluorescence in non ventilated mouse lungs and in lungs ventilated for 6 h. In untreated and IMD treated mice, lung permeability, pulmonary leukocyte recruitment and cytokine levels were assessed after mechanical ventilation. Further, the impact of IMD on pulmonary vasoconstriction was investigated in precision cut lung slices (PCLS) and in isolated perfused and ventilated mouse lungs. IMD stabilized endothelial barrier function in HPMVECs. Mechanical ventilation reduced the expression of RAMP3, but not of IMD, CRLR, and RAMP1 and 2. Mechanical ventilation induced lung hyperpermeability, which was ameliorated by IMD treatment. Oxygenation was not improved by IMD, which may be attributed to impaired hypoxic vasoconstriction due to IMD treatment. IMD had minor impact on pulmonary leukocyte recruitment and did not reduce cytokine levels in VILI. CONCLUSIONS/SIGNIFICANCE: IMD may possibly provide a new approach to attenuate VILI.

Combined multiplanar optical coherence tomography and confocal scanning ophthalmoscopy.

We demonstrate the clinical application of a multiplanar imaging system that simultaneously acquires en face (C-scan) optical coherence tomography (OCT) and the corresponding confocal ophthalmoscopic images, along with cross-sectional (B-scan) OCT at specifiable locations on the confocal image. The advantages of the simultaneous OCT and confocal acquisition as well as the challenges of interpreting the C-scan OCT images are discussed. Variations in tissue inclination with respect to the coherence wave surface alter the sampling of structures within the depth of the retina, producing novel slice orientations that are often challenging to interpret. We have evaluated for the first time the utility of C-scan OCT for a variety of pathologies, including melanocytoma, diabetic retinopathy, choroidal neovascular membrane, and macular pucker. Several remarkable new aspects of clinical anatomy were revealed using this new technique. The versatility of selective capture of C-scan OCT images and B-scan OCT images at precise points on the confocal image affords the clinician a more complete and interactive tool for 3-D imaging of retinal pathology.