Objective
To rigorously evaluate the impact of the percentage of parenchymal volume preserved (PPVP) and how well the preserved parenchyma recovers from ischaemia (Recischaemia) on functional ...outcomes after partial nephrectomy (PN) using an accurate and objective software‐based methodology for estimating parenchymal volumes and split renal function (SRF). A secondary objective was to assess potential predictors of the PPVP.
Patients and Methods
A total of 894 PN patients with available studies (2011–2014) were evaluated. The PPVP was measured from cross‐sectional imaging at ≤3 months before and 3–12 months after PN using semi‐automated software. Pearson correlation evaluated relationships between continuous variables. Multivariable linear regression evaluated predictors of ipsilateral glomerular filtration rate (GFR) preserved and the PPVP. Relative‐importance analysis was used to evaluate the impact of the PPVP on ipsilateral GFR preserved. Recischaemia was defined as the percentage of ipsilateral GFR preserved normalised by the PPVP.
Results
The median tumour size and R.E.N.A.L. nephrometry score were 3.4 cm and 7, respectively. In all, 49 patients (5.5%) had a solitary kidney. In all, 538 (60%)/251 (28%)/104 (12%) patients were managed with warm/cold/zero ischaemia, respectively. The median pre/post ipsilateral GFRs were 40/31 mL/min/1.73 m2, and the median (interquartile range IQR) percentage of ipsilateral GFR preserved was 80% (71–88%). The median pre/post ipsilateral parenchymal volumes were 181/149 mL, and the median (IQR) PPVP was 84% (76–92%). In all, 330 patients (37%) had a PPVP of <80%, while only 34 (4%) had a Recischaemia of <80%. The percentage of ipsilateral GFR preserved correlated strongly with the PPVP (r = 0.83, P < 0.01) and loss of parenchymal volume accounted for 80% of the loss of ipsilateral GFR. Multivariable analysis confirmed that the PPVP was the strongest predictor of ipsilateral GFR preserved. Greater tumour size and endophytic and nearness properties of the R.E.N.A.L. nephrometry score were associated with a reduced PPVP (all P ≤ 0.01). Solitary kidney and cold ischaemia were associated with an increased PPVP (all P < 0.05).
Conclusions
A reduced PPVP predominates regarding functional decline after PN, although a low Recischaemia can also contribute. Tumour‐related factors strongly influence the PPVP, while surgical efforts can improve the PPVP as observed for patients with solitary kidneys.
Objectives
To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved ...accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia.
Patients and Methods
Of 1140 patients managed with PN (2012–2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia.
Results
In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range IQR) ischaemia times for cold and warm ischaemia of 30 (25–42) and 22 (18–28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63–92) and 69 (54–81) mL/min/1.73 m2, respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33–47) and 31 (24–38) mL/min/1.73 m2, respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5–12) mL/min/1.73 m2 with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%–102%), 95% (89%–101%), and 97% (91%–102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin‐dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score.
Conclusions
The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia‐related factors that are also independently associated with impaired recovery, although altogether these were much less impactful.
The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although ...microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing or remaining static. The cellular basis of this clinical observation is unknown. Here, we profile the genomic, transcriptomic, and epigenomic landscape of CIS in a unique patient cohort with longitudinally monitored pre-invasive disease. Predictive modeling identifies which lesions will progress with remarkable accuracy. We identify progression-specific methylation changes on a background of widespread heterogeneity, alongside a strong chromosomal instability signature. We observed mutations and copy number changes characteristic of cancer and chart their emergence, offering a window into early carcinogenesis. We anticipate that this new understanding of cancer precursor biology will improve early detection, reduce overtreatment, and foster preventative therapies targeting early clonal events in lung cancer.
To identify factors associated with longitudinal ipsilateral functional decline after partial nephrectomy (PN).
Of 1140 patients managed with PN (2012-2014), 349 (31%) had imaging/serum creatinine ...levels pre-PN, 1-12 months post-PN (new baseline), and >3 years later necessary for inclusion. Parenchymal-volume analysis was used to determine split renal function. Patients were grouped as having significant renal comorbidity (Cohort
: diabetes mellitus with insulin-dependence or end-organ damage, refractory hypertension, or severe pre-existing chronic kidney disease) vs not having significant renal comorbidity (Cohort
) preoperatively. Multivariable regression was used to identify predictors of annual ipsilateral parenchymal atrophy and functional decline relative to new baseline values post-PN, after the kidney had healed.
The median follow-up was 6.3 years with 87/226/36 patients having cold/warm/zero ischaemia. The median cold/warm ischaemia times were 32/22 min. Overall, the median tumour size was 3.0 cm. The preoperative glomerular filtration rate (GFR) and new baseline GFR (NBGFR) were 81 and 71 mL/min/1.73 m
, respectively. After establishment of the NBGFR, the median loss of global and ipsilateral function was 0.7 and 0.4 mL/min/1.73 m
/year, respectively, consistent with the natural ageing process. Overall, the median ipsilateral parenchymal atrophy was 1.2 cm
/year and accounted for a median of 53% of the annual functional decline. Significant renal comorbidity, age, and warm ischaemia were independently associated with ipsilateral parenchymal atrophy (all P < 0.01). Significant renal comorbidity and ipsilateral parenchymal atrophy were independently associated with annual ipsilateral functional decline (both P < 0.01). Annual median ipsilateral parenchymal atrophy and functional decline were both significantly increased for Cohort
compared to Cohort
(2.8 vs 0.9 cm
, P < 0.01 and 0.90 vs 0.30 mL/min/1.73 m
/year, P < 0.01, respectively).
Longitudinal renal function following PN generally follows the normal ageing process. Significant renal comorbidities, age, warm ischaemia, and ipsilateral parenchymal atrophy were the most important predictors of ipsilateral functional decline following establishment of NBGFR.
Supramolecular interactions are fundamental to host-guest binding in many chemical and biological processes. Direct visualization of such supramolecular interactions within host-guest systems is ...extremely challenging, but crucial to understanding their function. We report a comprehensive study that combines neutron scattering, synchrotron X-ray and neutron diffraction, and computational modelling to define the detailed binding at a molecular level of acetylene, ethylene and ethane within the porous host NOTT-300. This study reveals simultaneous and cooperative hydrogen-bonding, π···π stacking interactions and intermolecular dipole interactions in the binding of acetylene and ethylene to give up to 12 individual weak supramolecular interactions aligned within the host to form an optimal geometry for the selective binding of hydrocarbons. We also report the cooperative binding of a mixture of acetylene and ethylene within the porous host, together with the corresponding breakthrough experiments and analysis of adsorption isotherms of gas mixtures.
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