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    Krishna Epari

    Surgeons are noticing increasing numbers of cholecystectomy waiting list patients presenting with complications of their gallstones. In this study, we analysed the outcome of these to ascertain natural history and outcome. Data for 5298... more
    Surgeons are noticing increasing numbers of cholecystectomy waiting list patients presenting with complications of their gallstones. In this study, we analysed the outcome of these to ascertain natural history and outcome. Data for 5298 waiting list patients in Western Australia, from 1999 to 2006, were analysed. Negative binomial regression was used to analyse waiting times data with Waitlist Year, Urgency Category and Aboriginality, after adjusting for Gender, Location and Age at Cholecystectomy. The overall median waiting time for surgery was 40 days (interquartile range (IQR) = 15-103). The median waiting times for Urgent, Semi-Urgent, and Routine categories were 21 (IQR = 8-63), 44 (IQR = 20-97) and 50 (IQR = 17-131) days, respectively. While waiting for surgery, 240 (5%) patients had gallstone-related admissions. Eighty (33.3%) patients had previous gallstone-related admissions prior to their enrolment on the waiting list. Analysis of the crude odds ratio showed that the probability of readmission during wait for surgery was three times more, when the surgery was not performed within the recommended time. Aboriginal and Torres Strait Islanders wait 1.77 times longer than non aboriginals (P < 0.001) and waiting time decreased with more recent calendar years. (P= 0.001) Patients in the metropolitan hospitals waited twice as long compared with the regional hospitals (P < 0.001). Approximately 5% of patients on the waiting list for an elective cholecystectomy were readmitted to the hospital for gallstone-related problems. Proper categorization of patients and definitive surgical treatment of acute gallbladder disease at index presentation might decrease this readmission rate. More effort needs to be made to ensure equity of access for gallstone patients.
    Acute care surgical teams are a new concept in the provision of emergency general surgery. Juggling emergency patients around the... more
    Acute care surgical teams are a new concept in the provision of emergency general surgery. Juggling emergency patients around the surgeons' and staffs' elective commitments resulted in semi-emergency procedures routinely being delayed. In an era of increasing financial pressure and the recent introduction of 'safe work hours' practices, the need for a new system which optimized available resources became apparent. At Fremantle Hospital we developed a new system in a concerted effort to minimize the waiting time for general surgical referrals in the Emergency Department, as well as to move semi-urgent operating from the afterhours to the daytime. To analyse the impact of the ASU, data were collected during February, March, and April 2009 and compared with data from the same period in 2008. Although most referrals were received afterhours, over 85% of operations were performed during working hours compared with 72% in the 2008 period. The time from referral to review decreased from an average of 3.2 h in 2008 to 2.1 h. The mean duration of stay in 2009 was 3 days, which was a reduction from 4.2 days in 2008. An increase in weekend discharge rates was seen after the introduction of the ASU. Despite an increased workload, more referrals were seen and more operations performed during working hours and the time from referral to review was reduced. Higher discharge rates and reduced length of stays increased the availability of beds. We have demonstrated a successful new model which continues to evolve.
    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification,... more
    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Im...
    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal... more
    Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of D...