Digital pathology for reporting histopathology samples, including cancer screening samples - definitive evidence from a multisite study.

AIMS: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples. METHODS: A total of 2024 cases (608 breast, 607 GI, 609 skin, 200 renal) were studied, including 207 breast and 250 bowel cancer screening samples. Cases were examined by four pathologists (16 study pathologists across the four speciality groups), using both LM and DP, with the order randomly assigned and 6 weeks between viewings. Reports were compared for clinical management concordance (CMC), meaning identical diagnoses plus differences which do not affect patient management. Percentage CMCs were computed using logistic regression models with crossed random-effects terms for case and pathologist. The obtained percentage CMCs were referenced to 98.3% calculated from previous studies. RESULTS: For all cases LM versus DP comparisons showed the CMC rates were 99.95% [95% confidence interval (CI) = 99.90-99.97] and 98.96 (95% CI = 98.42-99.32) for cancer screening samples. In speciality groups CMC for LM versus DP showed: breast 99.40% (99.06-99.62) overall and 96.27% (94.63-97.43) for cancer screening samples; [gastrointestinal (GI) = 99.96% (99.89-99.99)] overall and 99.93% (99.68-99.98) for bowel cancer screening samples; skin 99.99% (99.92-100.0); renal 99.99% (99.57-100.0). Analysis of clinically significant differences revealed discrepancies in areas where interobserver variability is known to be high, in reads performed with both modalities and without apparent trends to either. CONCLUSIONS: Comparing LM and DP CMC, overall rates exceed the reference 98.3%, providing compelling evidence that pathologists provide equivalent results for both routine and cancer screening samples irrespective of the modality used.

Outcome of acute kidney injury in Sudanese children - an experience from a sub-Saharan African unit.

UNLABELLED: ♦ BACKGROUND: Acute Kidney Injury (AKI) is an important cause of morbidity and mortality in developing countries. Although continuous renal replacement therapy is gaining more popularity worldwide, peritoneal dialysis (PD) in children remains an appropriate therapy for AKI in children for all age groups including neonates. ♦ METHODOLOGY: We retrospectively reviewed all children who have been admitted with AKI at the pediatric nephrology unit, Soba University Hospital, Khartoum, during the period from January 2005 to December 2011. ♦ RESULTS: Over 7 years we recorded 659 children of whom 362 (54.9%) were male. The spectrum of age was variable with the majority being neonates, 178 (27.1%). The average patient admission rate was 94 patients per year, with an estimated incidence of 9.8 patients/million population/year. Common causes of AKI were sepsis 202 (30.8%), acute glomerulonephritis 75 (11.5%) and obstructive uropathy due to stones 56 (8.5%). The most common dialysis modality used was PD, 343 (52.4%), and peritonitis was reported in 53 (15.4%) patients. Recovery from AKI was achieved in 450 (68.9%) children, 37 (5.7%) went into chronic kidney disease (CKD), 33 (5.1%) referred to the pediatric surgery and 194 (29.7%) died. ♦ CONCLUSION: In the setting of developing countries where AKI is a common cause of morbidity and mortality, reasonably equipped renal units with adequately trained medical staff may save many lives. International funding programs for communicable diseases and charity organizations should include AKI management in their programs. Acute PD remains the treatment modality of choice for AKI in developing countries.

The renin-angiotensin system and hypertension in autosomal recessive polycystic kidney disease.

Hypertension is a well-recognized complication of autosomal recessive polycystic kidney disease (ARPKD). The renin-angiotensin system (RAS) is a key regulator of blood pressure; however, data on the RAS in ARPKD are limited and conflicting, showing both up- and down-regulation. In the current study, we characterized intrarenal and systemic RAS activation in relationship to hypertension and progressive cystic kidney disease in the ARPKD orthologous polycystic kidney (PCK) rat. Clinical and histological measures of kidney disease, kidney RAS gene expression by quantitative real-time PCR, angiotensin II (Ang II) immunohistochemistry, and systemic Ang I and II levels were assessed in 2-, 4-, and 6-month-old cystic PCK and age-matched normal rats. PCK rats developed hypertension and progressive cystic kidney disease without significant worsening of renal function or relative kidney size. Intrarenal renin, ACE and Ang II expression was increased significantly in cystic kidneys; angiotensinogen and Ang II Type I receptor were unchanged. Systemic Ang I and II levels did not differ. This study demonstrates that intrarenal, but not systemic, RAS activation is a prominent feature of ARPKD. These findings help reconcile previous conflicting reports and suggest that intrarenal renin and ACE gene upregulation may represent a novel mechanism for hypertension development or exacerbation in ARPKD.

Renin-angiotensin system activation in congenital hepatic fibrosis in the PCK rat model of autosomal recessive polycystic kidney disease.

OBJECTIVES: Congenital hepatic fibrosis (CHF) is an important cause of morbidity and mortality in patients with autosomal recessive polycystic kidney disease (ARPKD). The pathogenesis of CHF remains undefined. Several recent studies suggest that the renin-angiotensin system (RAS) is an important mediator of progressive hepatic fibrosis through activation of profibrotic mediators, such as transforming growth factor-beta (TGF-beta). RAS activation has not previously been studied in patients with CHF or in animal models. The aim of the present study was to characterize RAS expression during the course of CHF in the PCK rat. MATERIALS AND METHODS: Studies were conducted in the PCK rat, an orthologous ARPKD/CHF model, and age-matched normal control Sprague-Dawley rats. Expression of the RAS components, renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R), as well as the profibrotic mediator TGF-beta, was examined in cystic PCK and control rat livers at 2, 4, and 6 months of age by quantitative real-time polymerase chain reaction (qRT-PCR). Angiotensin II (ANG II) was examined by immunohistochemistry (IHC). Fibrosis was assessed by IHC using reticulin staining and Masson trichrome. Collagen content was determined by hydroxyproline analysis. RESULTS: Progressive fibrosis and increased hepatic collagen content occurred in PCK rats with age. In 4- and 6-month-old PCK rat livers, ACE gene expression was markedly increased, 8- and 17-fold, respectively, compared with age-matched control livers. Expression of the other RAS components, renin, angiotensinogen, and AT1R were not significantly different. IHC demonstrated prominent ANG II protein expression in periportal regions in PCK rats. In contrast, no expression was noted in control livers. TGF-beta expression was also increased in PCK rat livers with progressive disease. CONCLUSIONS: The present study demonstrates, for the first time, RAS upregulation in an orthologous rat ARPKD/CHF model. Increases in ACE and ANG II, as well as the downstream target, the profibrotic mediator TGF-beta, suggest that RAS activation may be an important mediator of CHF disease progression. The findings also suggest that treatment with RAS inhibitors, specifically ACE inhibitors or AT1R blockers, could be therapeutic in slowing disease progression in CHF.