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Simon Davies University Hospital of North Staffordshire, Stoke-on-Trent Institute for Science and

Controversies in EPS Bari, March 2010. Simon Davies University Hospital of North Staffordshire, Stoke-on-Trent Institute for Science and Technology in Medicine Keele University, UK. What are the controversies surrounding EPS?. Diagnostic criteria Are EPS and membrane fibrosis the same?

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Simon Davies University Hospital of North Staffordshire, Stoke-on-Trent Institute for Science and

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  1. Controversies in EPS Bari, March 2010 Simon Davies University Hospital of North Staffordshire, Stoke-on-Trent Institute for Science and Technology in Medicine Keele University, UK

  2. What are the controversies surrounding EPS? • Diagnostic criteria • Are EPS and membrane fibrosis the same? • Is EPS after transplantation the same? • Should we screen? How? • Should all patients stop PD at 5 years? • Is surgery the only treatment?

  3. Abdominal Cocoon

  4. Defining EPS – learning form the Japanese experience • clinical symptoms/signs of obstructive ileus, with or without a systemic inflammatory reaction, (e.g.  CRP) • Presence of peritoneal thickening and encapsulation, intestinal obstruction, cocooning, ± peritoneal calcification, confirmed by radiological investigations or at laparotomy,± typical biopsy

  5. What are the controversies surrounding EPS? • Diagnostic criteria • Are EPS and membrane fibrosis the same? • Is EPS after transplantation the same? • Should we screen? How? • Should all patients stop PD at 5 years? • Is surgery the only treatment?

  6. Davies, SJ, KI, 2004

  7. EPS Inflammatory Visceral Rare No intermediate Rapid onset Triggers Longevity Fibrinous exudate Simple Sclerosis Non-inflammatory Parietal Common Continuum Gradual change No triggers Longevity Fibrosis Are EPS and SS/fibrosis the same?

  8. Stoke PD Study Longitudinal changes in membrane function for 9 patients developing EPS and controls matched (x4) for duration of completed time (mean 78.5 months) on PD * P < 0.02 † P = 0.007 * * * † Lambie et al, KI in press

  9. Lambie et al, KI in press

  10. Lambie et al, KI in press

  11. Longitudinal membrane change in EPS v. patients with normal UF or UF Failure Solute transport Net Total UF Sampimon, DE, Krediet R et al, awaiting publication

  12. Longitudinal membrane change in EPS v. patients with normal UF or UF Failure Small pore fluid transport Aquaporin fluid transport Sampimon, DE, Krediet R et al, awaiting publication

  13. Variability in membrane function • Effective contact area • Osmotic conductance Start PD Increasing solute transport IL-1/IL-6 VEGF Increasing vascularity Increase in blood flow Dissociation of solute transport and osmotic conductance ? TGF EMT Progressive fibrosis Loss RRF Glucose/GDP Peritonitis Ultrafiltration failure ? Impaired fibrinolysis Additional trigger/2nd hit Stop PD Peritonitis Visceral involvement EPS

  14. What are the controversies surrounding EPS? • Diagnostic criteria • Are EPS and membrane fibrosis the same? • Is EPS after transplantation the same? • Should we screen? How? • Should all patients stop PD at 5 years? • Is surgery the only treatment?

  15. EPS after transplantation • Not described in Japan – but low transplantation rates • Recently described in Europe • Why? Time on treatment/Tx waiting list? Immunosupression? • Manchester (Summers et al); long time on PD, immuosupression changes CyA only to include MMF • Netherlands (Korte et al); long time on PD

  16. What are the controversies surrounding EPS? • Diagnostic criteria • Are EPS and membrane fibrosis the same? • Is EPS after transplantation the same? • Should we screen? How? • Should all patients stop PD at 5 years? • Is surgery the only treatment?

  17. Radiological features of EPS (CT scanning) • peritoneal calcification • bowel distribution • bowel wall thickening and dilatation • loculation of ascites • peritoneal thickening

  18. Calcification Bowel Distribution Bowel wall thickening Loculation Peritoneal Thickening Bowel wall dilatation HD PD EPS HD PD EPS HD PD EPS Tarzi et al, CJASN, 2008

  19. HD PD EPS HD PD EPS Tarzi et al, CJASN, 2008

  20. CT can diagnose EPS, but... • Early signs of EPS are not easily identified or agreed by radiologists • In CT studies several patients had normal CT scans a short time before diagnosis was confirmed – so not useful for screening

  21. What are the mediators/potential biomarkers? • Protein leak  = fibrosis, = inflammation/EPS • CA125 mesothelial cell health • IL-6 local production   transport • VEGF local production   transport • TGF-β driver of EMT • MCP-1, CCL18 local production ?fibrosis • Hyaluronan ? Membrane health/healing • Fibrinolytic system • CRP systemic inflammation  EPS

  22. What are the controversies surrounding EPS? • Diagnostic criteria • Are EPS and membrane fibrosis the same? • Is EPS after transplantation the same? • Should we screen? How? • Should all patients stop PD at 5 years? • Is surgery the only treatment?

  23. Comparison of estimated EPS risk in 7 studies worldwide conducted by the Scottish Renal registry

  24. Incidence and outcome of EPS in relation to time on PD. Kawanishi H et al Am J Kid Dis 2004 44:729-37

  25. Stoke PD Study: Risk of developing EPS Lambie et al, KI in press

  26. Patients are not the same... Imagine two different patients on PD for 5 years: • 45 yrs, anuric for 2 years, requires 2 2.27% glucose exchanges per day, no live donor – an exit strategy from PD needs to be planned • 71 yrs, 300 ml urine, 2 comorbidities, enjoys good QOL on PD, also needs 2 2.27% exchanges per day – discussion required but staying on PD is reasonable

  27. What are the controversies surrounding EPS? • Diagnostic criteria • Are EPS and membrane fibrosis the same? • Is EPS after transplantation the same? • Should we screen? How? • Should all patients stop PD at 5 years? • Is surgery the only treatment?

  28. Cocoon Opened

  29. Thickened Visceral Membrane Dissected

  30. Released gut

  31. Manchester ExperienceReferrals Jan 2000 – Dec 2008 n = 83 • Local -61 • MRI (42) Hope (7) Preston (9) Wythenshawe (3) • National - 18 • Exeter(3) Dorset (2) London (2) Epsom St.Helier(1) North Staffs (2) Derby (1) Cumberland (1) Sheffield (1) Bristol (1) Sunderland (1) Birmingham (1) Cardiff (1) Inverness(1) • International - 4 • Dublin (3) Slovenia (1)

  32. Post Surgery Outcomes 49 ALIVE None on TPN All home 3 patients have symptoms of colic and early satiety but on oral diet

  33. Suggested Risk Stratification For Surgical Intervention

  34. UK approach to EPS management • Funded supra-regional service • 2 centres of excellence with dedicated expert teams and funding that follows the patient • National Guidelines (Renal Association Website) • suspected or diagnosed patients should be referred for assessment • UK PD Research network – EPS registry and gene/biomarker bank • Parenteral feeding to optimise nutrition • CT scanning – diagnosis not screening

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