Do Uro-Oncology Day Care Procedures Need to Be Differed during COVID-19 Pandemic?-An Experience from Tertiary Cancer Care Center.

Mahendra PalBackground The SARS-CoV-2 virus pandemic has affected millions all over the world in very short span and changed the way how health care system work across the globe. It is essential to continue cancer treatment in spite of such pandemics. Various recommendations were proposed for cancer management based on risk stratification, however, in urological malignancies, day care procedures (DCPs) are a part of complete spectrum of cancer care and standard operating procedures (SOPs) for day care procedures (DCPs)in oncology is lacking at present. Materials and Methods This is an institutional review board approved retrospective observational analytical study performed in tertiary cancer care center, with aim to assess the impact of COVID-19 on Uro-oncology day care procedures (U-DCPs)in terms of changes in appointments and actual U-DCPs performed, demographic changes such as sex ratio and age wise attendance in pre and post lockdown period and to provide a SOPs to accomplishU-DCPsefficiently in pandemics. Results There was 67.89% and 68.16% reduction in total numbers of appointment and performed U-DCPs. A statistically significant difference was found in cystoscopy, intravesicalinstallation and miscellaneous UDCPs. Overall, 4.45% reduction and 4.52% increase in male and female patients underwent UDCPs respectively, M:F ratio reduced from 3.58:1 to 2.79:1 and 30% to 50% reduction in overall patient statistics in post lockdown compare to pre lockdown procedures. For various age groups there was a statistically significant change in the number for males underwent cystoscopy in (p<0.001), Intravesical therapies (p<0.001) and miscellaneous procedures(p< 0.004). Conclusion We are now coming up to the fact that effective management of healthcare system during pandemics require establishment and effective implementation of standard protocols. Routine major urological surgical care is continued using a tiered standard of protocols (SOPs) and adequate precautions. This study may provide an insight into impact of COVID-19 on UDCPs and what precautions and strategies can be institutionalized so that the patients and the health care workers remain protected from contracting infection while in performing DCPs during pandemic or similar circumstances.

Prognostic Nutritional Index Prior to Rectal Cancer Resection Predicts Overall Survival.

Prognostic nutritional index (PNI) correlates with postoperative complications and survival in colorectal cancers. Separate studies for rectal cancers are not available where the majority have preoperative radiation, operated by minimally invasive approaches and have diverting ostomies.Consecutive rectal resections between October 2014 and December 2017 from a single center were included. PNI was calculated as 10 x (serum Albumin) + 0.005 x TLC (per mm3) before operation. Multivariate cox regression was used with overall survival (OS) as the dependent variable. Interaction terms of PNI with neoadjuvant therapy, surgical approach and postoperative complications were used to assess specific subgroups.Three-hundred forty elective rectal resections were included with a mean PNI of 46.711 (SD - 6.692), and a median follow up of 44 mo. In multivariable regression, PNI predicted OS (HR - 0.943; p-0.001). Interaction of PNI with preoperative radiation or surgical approach (open, laparoscopic, or robotic) did not change its influence on survival. PNI predicted survival with similar hazard even in patients without major postoperative complicationsDespite routine diversion after rectal resections, PNI predicted OS with an absolute survival benefit of 1.2% at 3-year for every unit increase in PNI irrespective of preoperative therapy or surgical approach.

Genetic instability from a single S phase after whole-genome duplication.

Diploid and stable karyotypes are associated with health and fitness in animals. By contrast, whole-genome duplications-doublings of the entire complement of chromosomes-are linked to genetic instability and frequently found in human cancers1-3. It has been established that whole-genome duplications fuel chromosome instability through abnormal mitosis4-8; however, the immediate consequences of tetraploidy in the first interphase are not known. This is a key question because single whole-genome duplication events such as cytokinesis failure can promote tumorigenesis9. Here we find that human cells undergo high rates of DNA damage during DNA replication in the first S phase following induction of tetraploidy. Using DNA combing and single-cell sequencing, we show that DNA replication dynamics is perturbed, generating under- and over-replicated regions. Mechanistically, we find that these defects result from a shortage of proteins during the G1/S transition, which impairs the fidelity of DNA replication. This work shows that within a single interphase, unscheduled tetraploid cells can acquire highly abnormal karyotypes. These findings provide an explanation for the genetic instability landscape that favours tumorigenesis after tetraploidization.

mTOR and S6K1 drive polycystic kidney by the control of Afadin-dependent oriented cell division.

mTOR activation is essential and sufficient to cause polycystic kidneys in Tuberous Sclerosis Complex (TSC) and other genetic disorders. In disease models, a sharp increase of proliferation and cyst formation correlates with a dramatic loss of oriented cell division (OCD). We find that OCD distortion is intrinsically due to S6 kinase 1 (S6K1) activation. The concomitant loss of S6K1 in Tsc1-mutant mice restores OCD but does not decrease hyperproliferation, leading to non-cystic harmonious hyper growth of kidneys. Mass spectrometry-based phosphoproteomics for S6K1 substrates revealed Afadin, a known component of cell-cell junctions required to couple intercellular adhesions and cortical cues to spindle orientation. Afadin is directly phosphorylated by S6K1 and abnormally decorates the apical surface of Tsc1-mutant cells with E-cadherin and α-catenin. Our data reveal that S6K1 hyperactivity alters centrosome positioning in mitotic cells, affecting oriented cell division and promoting kidney cysts in conditions of mTOR hyperactivity.