Aberrant allele-specific replication, independent of parental origin, in blood cells of cancer patients

Abstract Background Allelic counterparts of biallelically expressed genes display an epigenetic symmetry normally manifested by synchronous replication, different from genes subjected to monoallelic expression, which normally are characterized by an asynchronous mode of replication (well exemplified by the SNRPN imprinted locus). Malignancy was documented to be associated with gross modifications in the inherent replication-timing coordination between allelic counterparts of imprinted genes as well as of biallelically expressed loci. The cancer-related allelic replication timing aberrations are non-disease specific and appear in peripheral blood cells of cancer patients, including those with solid tumors. As such they offer potential blood markers for non-invasive cancer test. The present study was aimed to gain some insight into the mechanism leading to the replication timing alterations of genes in blood lymphocytes of cancer patients. Methods Peripheral blood samples derived from patients with prostate cancer were chosen to represent the cancerous status, and samples taken from patients with no cancer but with benign prostate hyperplasia were used to portray the normal status. Fluorescence In Situ Hybridization (FISH) replication assay, applied to phytohemagglutinin (PHA)-stimulated blood lymphocytes, was used to evaluate the temporal order (either synchronous or asynchronous) of genes in the patients' cells. Results We demonstrated that: (i) the aberrant epigenetic profile, as delineated by the cancer status, is a reversible modification, evidenced by our ability to restore the normal patterns of replication in three unrelated loci (CEN15, SNRPN and RB1) by introducing an archetypical demethylating agent, 5-azacytidine; (ii) following the rehabilitating effect of demethylation, an imprinted gene (SNRPN) retains its original parental imprint; and (iii) the choice of an allele between early or late replication in the aberrant asynchronous replication, delineated by the cancer status, is not random but is independent of the parental origin. Conclusion The non-disease specific aberrant epigenetic profile displayed in peripheral blood cells of patients with a solid tumour (unlike genetic aberrations) can be reversed, by an epigenetic drug applied in vitro, to the normal. It appears that the cancerous status differentiates between two allelic counterparts in a non-random manner, but independent of the parental origin</p

Laparoscopic Versus Robot-Assisted Pyeloplasty in Adults&mdash;A Single-Center Experience

Background: Laparoscopic (LP) and robot-assisted pyeloplasty (RAP) are minimally invasive techniques for correcting uretero-pelvic junction obstruction (UPJO). We retrospectively compared the clinical outcomes of all adults who underwent RAP (n = 41) to those who underwent LP (n = 24) for UPJO at our institution between 2003&ndash;2022. Methods: Age, sex, body mass index, surgical side, past abdominal/endoscopic surgeries, pre- and postoperative renal scans, pre- and postoperative serum creatinine levels, operative time (OT), presence of crossing vessels, estimated blood loss, postoperative complications, length of hospital stay, time to JJ stent removal, follow-up length, and postoperative hydronephrosis were analyzed. Results: The groups were demographically comparable. The mean total and skin-to-skin OTs (minutes) were significantly longer in the RAP group than in the LP group (242.4 &plusmn; 55 vs. 161.4 &plusmn; 40 p &lt; 0.001; 163.7 &plusmn; 41.8 vs. 124.3 &plusmn; 30.3 p = 0.006, respectively). Hospital stay (days) was shorter in the RAP group (3.3 &plusmn; 2.1 vs. 7.3 &plusmn; 2.5 p &lt; 0.001). Postoperative complication rates were identical for both groups. The LP group had a significantly longer follow-up period (85.2 &plusmn; 73 vs. 19 &plusmn; 14 months p &lt; 0.001). The success rates for the LP and RAP groups were 87.5% and 90.6% (p = 0.708). Conclusions: RAP achieves equivalent results to LP, in adult patients. A longer OT may be expected with the robotic system since it can handle more complicated cases

The Added Value of Systematic Sampling in In-Bore Magnetic Resonance Imaging-Guided Prostate Biopsy

We sought to quantify the additive value of systematic biopsy (SB) using in-bore magnetic resonance (MR)-guided prostate biopsy (IBMRGpB) by retrospectively reviewing the records of 189 patients who underwent IBMRGpB for suspected prostate cancer or as part of the surveillance protocol for previously diagnosed prostate cancer. The endpoints included clinically significant and non-clinically significant cancer diagnosis. SB detected clinically significant disease in 67 (35.5%) patients. Five (2.65%) patients whose targeted biopsies indicated benign or non-clinically significant disease had clinically significant disease based on SB. SB from the lobe contralateral to the lesion detected clinically significant disease in 15 (12%) patients. The size of the prostate was larger and the percentage of lesions located in the peripheral zone of the prostate was higher in patients with SB-detected clinically significant disease. The location of the main lesion in the peripheral zone of the prostate was a predictor for clinically significant disease in the multivariate analysis (OR = 8.26, p = 0.04), a finding supported by a subgroup analysis of biopsy-naïve patients (OR = 10.52, p = 0.034). The addition of SB during IBMRGpB increased the diagnosis of clinically significant as well as non-clinically significant prostate cancer. The location of the main lesion in the peripheral zone emerged as a positive predictive factor for clinically significant disease based on SB. These findings may enhance patient-tailored management

Association between COVID-19 Burden, Population Vaccination Status, and Urologic Oncology Surgery Volume: A National Multicenter Cross-Sectional Study

Initial deleterious effects of the COVID-19 pandemic on urologic oncology surgeries are well described, but the possible influence of vaccination efforts and those of pandemic conditions on surgical volumes is unclear. Our aim was to examine the association between changing vaccination status and COVID-19 burden throughout the pandemic and the volume of urologic oncology surgeries in Israel. This multi-center cross-sectional study included data collected from five tertiary centers between January 2019 and December 2021. All 7327 urologic oncology surgeries were included. Epidemiological data were obtained from the Israeli Ministry of Health database. A rising trend in total urologic oncology surgery volumes was observed with ensuing COVID-19 wave peaks over time (X2 = 13.184, df = 3, p = 0.004). Total monthly surgical volumes correlated with total monthly hospitalizations due to COVID-19 (R = −0.36, p = 0.015), as well as with the monthly average Oxford Stringency Index (R = −0.31, p = 0.035). The cumulative percent of vaccinations and of new COVID-19 cases per month did not correlate with total monthly urologic surgery volumes. Our study demonstrates the gradual acclimation of the Israeli healthcare system to the COVID-19 pandemic. However, hospitalizations due to COVID-19, as well as restriction stringency, correlate with lower volumes of urologic oncological surgeries, regardless of the population’s vaccination status