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

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Presentation on theme: "Simon Davies University Hospital of North Staffordshire, Stoke-on-Trent Institute for Science and Technology in Medicine Keele University, UK Controversies."— Presentation transcript:

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

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 Are EPS and SS/fibrosis the same? 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

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 = Lambie et al, KI in press

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

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

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

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

19 HDPDEPS 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 CA125mesothelial cell health IL-6local production   transport VEGFlocal production   transport TGF-βdriver of EMT MCP-1, CCL18local production ?fibrosis Hyaluronan? Membrane health/healing Fibrinolytic system CRPsystemic 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 Study Nomoto et al 1996 Rigby et al 1998 Lee et al 2003 Kawanishi et al 2001 Kawanishi et al 2004 Summers et al 2005 Brown et al (current study) Number of EPS Cases (those meeting ISPD 2000 criteria in brackets) 6254 (46) (23)46 Dates of Study – – Study Design Retrospective Multi-centre Retrospective Multi-centre Retrospective Multi-centre Prospective Multi-centre Prospective Multi-centre Retrospective Single-centre Retrospective Multi-centre Denominator Population (prevalent + incident PD Patients) Overall Rate 0.9%0.7%0.8% 2.5%3.3%2.8% Mean PD Exposure (yrs) Mortality (over study period) 43.5 %56 %25.8 %35 %37.5 %29.6 %56.5%

24 Incidence and outcome of EPS in relation to time on PD. PD duration (yrs) No of ptsEPS incidence MortalityRecovery <33370% 3 to < %0%100% 5 to < %8.3%83.3% 8 to < %28.6%42.9% 10 to %61.5%15.3% > %100%0% Total %37.5%45.8% Kawanishi H et al Am J Kid Dis :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 % 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 % 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 Experience Referrals 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 LENGTH OF DIALYSIS 1-4 YRS4-8YRS8-12YRS SYMPTOMSMild fullness,discomfort Distension,fullness,early satiety,vomiting,subacute obstruction Gross distension, Recurrent subacute obstruction, obstruction*, Peritonitis*, Major Hemoperitoneum* ALBUMINNormalModerateLow ANEMIAHb>10gm%Hb 8-10gm%, EPO,Transfusions Hb<8gm%, Transfusions,EPO WEIGHTNORMALSUB-OPTIMALSIGNIFICANT WEIGHT LOSS CRP< >100 LENGTH OF SYMPTOMS/ADMISSION 0-4 WEEKS4-8 WEEKS>8 WEEKS CT FINDINGSEssentially normalThickened peritoneum, some fluid, Mild dilatation of small bowel Thickened calcified peritoneum, retracted mesentry, encapsulation,ascites TREATMENT OPTIONSMEDICALMEDICAL/SURGICALSURGICAL ABSOLUTE SURGICAL INDICATIONS* OBSTRUCTION*PERITONITIS*MAJOR HEMOPERITONEUM*

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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