V 82 no 1 spring 2013

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The University of Western Ontario Medical Journal Volume 82, Issue 1, Spring 2013

TO URINARY

The University of Western Ontario Medical Journal Volume 82, Issue 1, Spring 2013 www.uwomJ .com EDITORIAL Sailing Ahead Joyce T.W. Cheung

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FEATURE ARTICLES Simultaneous Pancreas-Kidney Transplantation : The Role In The Treatment Of Type 1 Diabetes And End-Stage Renal Disease Alex Jiang Faculty Reviewer: Dr. Patrick Luke, M D, FRCSC

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GENITOURINARY ARTICLES Pathogenic Mechanisms and Direction of Empirical Studies: A Retrospective on Membranoproliferative Glomerulonephritis Alexander Pazionis, Denise Darmawikarta Faculty reviewer: Dr. Faisal Rehma n, M D, FRCPC, M. Ed

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Digital Rectal Examination in Prostate Cancer Screening Angela Zhang, Thomas Fear, Hammood Ahmed Faculty Reviewer: Dr. John Jordan, MD

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A Short Primer on Transplant Tourism Sa ad Ahmed Faculty Reviewer: Dr. Faisal Rehman, MD, FRCPC, M.Ed, Dr. Nelson Chan, MD, LL. B, CCFP

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Matching Theory: Kidney Allocati on Kyle Luong Faculty Reviewer: Dr. Gregory Pavlov, MD

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The Role Of Prostate-Specific Antigen (PSA) Testing In Screening For Prostate Cancer Charlotte Hunter, Paul Zamiara Faculty Reviewer: Dr. D. Scott Ernst, MD, FRCPC

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The living Kidney Donation Process: Role Of The Interdisciplinary Team Yin Hui, Kyle Pangka, Alexander Van Faculty Reviewer: Dr. Faisal Rehman, MD, FRCPC, M.Ed

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The Future Of Surgical Robotics Laura Callan, Nancy Chen Faculty Reviewer: Dr. Stephen Pautler, MD, FRCSC

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Interview with Dr. Faisal Rehman Joyce Zhan g, Sissi Ca o Faculty Reviewer: Dr. Faisal Rehman, MD, FRCPC, M.Ed

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Fever With Incontinence In The Elderly: An Approach For Emergency Medicine Anthony Chow, Elaine Tang Faculty Reviewer: Dr. Derrick Pringle, MD, FRCPC

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Diagnosing In The Dark: Atypical Proteinuria Etiology Stephen Cornish, Eric Rosze ll Facult y Reviewer: Dr. Faisal Rehm an, M D, FRCPC, M. Ed

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The Barriers Surrounding Hemodialysis For Patients With Esrd: Improving Access Since 1945

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Justine Den omme, Wen dy Cui Faculty Reviewer: Dr. Shelley M cKellar, PhD

UWOMJ 182:1 I Spring 2013

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The University of Western Ontario Medical Journal EDITORIAL TEAM EXECUTIVE TEAM EDITOR-IN-CH IEF

JOYCE T.W. CHEUNG (MEDS 2013} PAUL KUDLOW (MEDS 2013}

SENIOR ASSOCIATE EDITOR

MELISSAJ . MACPHERSON (MEDS 2014}

JUNIOR ASSOCIATE EDITOR

JASON L. CHAN (MD/PHD 2017)

SENIOR BLOG EDITOR

LAUREN SHAM (MEDS 2014)

JUNIOR BLOG EDITOR

YIN HUI (MEDS 2015)

FINANCIAL OFFICER

LAURA CALLAN (MEDS 2015 )

LAYOUT EDITOR

JOYCE ZHANG (MEDS 2015)

IT

ALE XANDER VAN (MD/PHD 2018)

DEPARTMENTAL EDITORS CLINICAL PROCEDURES

ALE XANDER PAZIONIS (MEDS 2015}, DENISE DARMAWI KARTA (MEDS 20 16)

DIAGNOSTIC REVIEW

HAMOOD AHMED (MEDS 20 15}, THOMAS FEAR (MEDS 2015}, ANGELA ZHANG (MEDS 2015}

ETHICS AND LAW

SAAD AHMED (MEDS 20 16)

HEALTH POLICY AND ECONOMICS

TOMMY CHOY (MEDS 20 15), JESSICA JACKSON (MEDS 2015), KYLE LUONG (MEDS 2016)

HEALTH PROMOTION

CHARLOTIE HUNTER (MEDS 20 15), PAUL ZAMIARA (MEDS 2016)

INTERDISCIPLINARY

YIN HUI (MEDS 20 15), ALEXANDER VAN (MD/PHD 20 18}, KYLE PANGKA (MEDS 2016)

MEDICINE AND TECHNOLOGY

LAURA CALLAN (MEDS 20 15}, NANCY CHEN (MEDS 2016 )

PROFILES

JOYCE ZHANG (MEDS 2015}, SISSI CAO (MEDS 20 16)

THINKING ON YOUR FEET

ELAINE TANG (MEDS 20 15}, ANTHONY CHOW (MEDS 2016)

ZEBRA FILES

STEPHEN CORNISH (MED S 2015 ), ERIC ROSZELL (MEDS 20 16)

HISTORY OF MEDICINE

JUSTINE DENOMME (MEDS 2015 ), WENDY CUI (MEDS 2016 )

EDITORIAL BOARD DR. LOIS CHAMPION

DR. FAISAL REHMAN

DR . MICHAEL RIEDER

DR . JIM SILCOX

DR . JEFFREY NISKER

DR . DOUGLAS QUAN

COVER ART: Arvand Bargh i FRONT: In my illustration I tried to portray the vibrant and flowing nature of the kidney

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UWOMJ I 82 :1 I Spring 2013

EDITORIAL

Sailing ahead Joyce T.W. Cheung (Meds 2013)

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s the academi c year comes to a close for many of us. we are anticipating a fresh and exc iting chapter of our li ves. I wo uld like to congratulate the 20 13 cl ass and use thi s platform to th ank them fo r thei r contributions to the UWOMJ throughout the years. Personally. it has been a pl easure to be a part of the UWOMJ team and the quality of the contributions has never ceased to amaze me.

All in all , we have prepared an exci ting i ue that covers complex tertiary care topics and also important prim ary care and preventati ve hea lth issues related to genitourinary med icine. Congratul ati ons to our contrib uto rs and rev iewers for a fa ntastic year, and a big th ank yo u to our readers for your continued support'

Our latest issue featu res the incredi ble genitourinary system and development in this fi eld . It is diffic ult to thin k abo ut th e genitourin ary system and not have yo ur curi osity piqued by the fascinating topic of organ transpl antati on. Within the last century. the concept of all ograft transpl antation has evo lved fro m a procedure that was doomed to eventually fail to a comm on reality. due to advances in surgical technique and immunosuppressive med ication. Our feature article by Alex Ji ang outlines the latest in do uble-organ transpl antati on of the pancreas-ki dney, and its therapeutic role fo r th ose suffering from di abetes and end-stage renal disease. Technological advancements have all owed fo r less in vasive methods of performing surgery. and Laura Callan and Na ncy Chen outline the fie ld of surgical robotics and give us the latest on research initi ated here at Western Un ive rsity.

Behind the glamorous fa<;ade, the topi c of organ transpl antation is as complex as they come. Controversial topics range from ethical problems surro unding candidate se lecti on. to the surgical skill requi red in perform ing the transplantation, to medica l care afte rwa rds to reduce the ri sk of organ rejecti on. To start. organs are still an extremely carce resource. so how do we decide on who gets to unde rgo thi s li fe-changing procedure? Kyle Luong writes about the process of kidney all ocation and the complex ities of choosing an appropriate candi date. The un predictabl e nature of having a suitable donor organ has led to the business of transplant touri sm. whi ch is introduced to us in thi s issue by Saad Ahmed. For those that are left on th e waiting list, long-term hemod ialysis is a life-sustaining treatment. Justine Denomme and Wendy Cui outline the barri ers to access ing hemod ialysis, from its introducti on to the current state of the system. Our featured clini cian. Dr. Fa isal Rehman. is no stranger to the world of renal di sease and its treatment. In our interview with Dr. Rehm an. he speaks about hi s vision for the future of renal medicine and recall s a case that reminded him that despite our advances, we still have so much more to learn .

We take a step back from the compl ex world of transpl antati on and march into the front line of medi cine. In the world of primary care medicine, preventati ve health and prostate cancer screening has become a controversial iss ue over the years. Our editors update us on the topics of the role of prostate-specific anti gen and the di gital rectal examination in prostate cancer screening. From the simple urinary tract infection to life-threatening urosepsis, Anthony Chow and Elaine Tang teach us how to approach feve r and incontinence in the emergency department.

UWOMJ 182:1 I Spring 2013

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FEATURE ARTICLE

Simultaneous pancreas-kidney transplantation: the role in the treatment of type 1 diabetes and endstage renal disease Alex Jiang (Meds 2015), BHSc Faculty Reviewer: Dr. Patrick Luke, MD , FRCSC (Division of Urology, Department of Surgery) BACKG RO UN D ype I diabetes mellitu (OM) i one of the most comm on chronic di seases of childhood caused by in s ~! in defic iency secondary to autoi mmune destructiOn of pancreati C beta-ce ll s. The condttt on affects approx imately 1.4 million indi viduals in United States with an annual incidence of 17 cases per 100000 children. 1 Unmanaged. it can lead to severe long-tenn compl icati ons. The se include mi crova cular events. such as retinopath y. neuropath y. and nephropath y. and macrovascular diseases in vo lvi ng cerebrovascu lar. coronary or periph eral vascul ar sy stemsn These complicati ons are large ly attributed to hyperglycemi a resulting from poor insulin secretion . Consequently. th e mortality rate for type I OM is hi gh- 13% after 20 years of di sease'

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One of th e most significati on complicati ons of type I OM is endstage renal di sease (ES RD).' It initi ally manifests as microalbuminuri a w ith subsequent progre ssion to proteinuria. Without intervention. 80% of th ese ca es lead to nephropath y and ultimately. ESRD (glomeru lar filtrati on rate < 15 mL/min/ 1.73 m1) . Eligibl e patients w ith ESRD require dialysis or renal transplantati on for long-term management."

The Di abetes Control and Complicati on T ri al ( DCCT) demonstrated that ti ght glycemic control. achieved through intensive insulin th erapy. slows the progression and red uces th e ri sk of developing mi cro- and macro-vascular complicati ons. 7 Despite use of insulin pumps and intensive insul in th erapy. no exogenous deli very of insulin has been ab le to sustain normogly cemia as effecti ve ly as a fun cti onal pancreas. A s such. all oge neic pancreas transplantati on was developed to ac hi eve norm aglycemi a and insulin independeru;e. The combinati on of pancreas and kidney transplantati on can render a pati ent free of both insulin and dialysis with prevention of furth er diabetic co mp lica ti ons, and occasional reversal of estab li shed di sease.'

PANCREAS TRA SPLA TATIO

HI STORY

SELECT ION PROCESS T he SPK procedure is usual!) reserved for a pati ent with type I OM as confirm ed by IO\\ or absent leve l of C-peptide. 13 Candidates may also have signi fican t neph ropath) or E RD. along with complications such as hypogl ycem ic unawareness. recurrent hospitali zati on from diabetic ketoacidosis. progress ive retin opathy. enteropathy and neuropathy."

SU RG ICALP ROCED RE The techniques used for SPK transplantati on are diverse and instituti ondependent. Most tran spl an t centers use the intraperitoneal approach for graft placement. The pancreas is transplanted to a heterotopi c location. usually the ri ght iliac fossa. \\ hil e the kidn ey is tran splanted to the contralatera l iliac fo sa. T hi s approach results in fewer peripancreati c fluid co llec ti ons and wound compli cat ion s. A n alternati ve approach involves extraperitoneal and ipsilateral placement of both graft s. 15 A rteri al anastomo is ma) be perfonned by conjoining th e donor superior mesenteric artef)' and splenic artery to a Y graft of the recipient ex tern al or comm on ili ac artery. T he donor portal vei n is anastomosed to th e extern al ili ac vei n i f s) stemic drainage is pro vided. An alternative approach is anastomosis of donor porta l ve in to superi or mesenteric vein if portal venou s drainage is ava il able. 16 A lthough thi s was performed to red uce li pid dysrcgu lati on and rej ecti on rates. contemporaty studies have shown vel)' littl e di!Terences in overall long-term outcome between systemic and portal drainages. 17

OUTCOMES

The first pancreas transpl antati on (PT) was perfo rm ed in 1966 by William K elly and Ri chard Lill ehei at th e Uni versity of Minnesota in conjunction w ith a kidn ey tran plant to treat a di abeti c uremic pati ent.'> Earl y procedures were as ociated with significant morbidity and mortality and performed in low numbers in very elect patients. With the advent of cyc losporine and improvements in surgical techniques, one year graft survi val rates exceeded 70% in 1980s. 1"To date. more than 32000 cases ha ve been perform ed world wide w ith ever improv in g outcomes. 11 Currently, th ere are three meth ods of solid organ pancreas transpl antati on. The maj ori ty (83%) of procedures are perform ed in th e context of simultaneous pancreas-kidn ey (SPK) transplantati on where th e pancreas is tran spl anted at th e same tim e as th e k idney. T he second meth od is pancreas aft er kidney (PA K) transpl antati on ( 12%) where a pancreas is transplanted to a pati ent who prev iously received k idney transplanta-

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tion . The third meth od is pancreas transpl ant alone (PTA) (5%). which in vo lves transpl antation of a solitary pancreas to a diabetic patient with norm al renal fun cti on. T hi s is perfonned to counteract life-threatening hypogl ycem ic unawareness or rapidl y progres ive diabeti c complicati on s refractof) to intensive insulin th erapy. 11

Survival It is believed th at th e PK procedure prolongs patient survival beyond th e urvival advantage associated with renal transplantation alone. The 5- and I 0-ycar pati ent surviva l rates for PK transplantation is 87% and 70掳o. respecti ve ly.wfhi s is significantly better than the surv ival rates for type I diabeti cs rece iving maintenance dia lysis and who are on transplant wa iting li st. 19 l-l owever, due to inherent biases in li stin g candidates for transplants. and the differences in donor age between PK and solitary kidn ey (SK) tran spl ant cohorts. the true survival benefit conferred by th e pancrea is unknown .

Graft surviva l rates are excellent. The pancreati c allograft survival rate is 86% at one year and 53 % at I 0 years w hile kid ney urvival rate is >95% at one year and 60% at I 0 years. 1R路211 Th e lower one year graft survi val rates for the pancreas are secondary to early transplant compli-

UWOMJ 182:1 I Spring 2013

FEATURE ARTICLE cati on , including thrombo sis. pancreatic fistula. and infection .l'.l"

Quality of Life

Nep hropathy

Pancreas transp lantati on can improve quality of life (QOL) by eliminatmg dmb_etes associated compli cation s, including hy po/hyperglycemi a, metaboltc derangements. insulin dependence, glucose monitoring and 21 dtetary rest_riction s. . mith et al. co mpared pre- and po st-transplant <?0~ and tound tgntficant improvement foll ow ing PK tran splantaF-36 Mental omponent Sum mar) sco res were signifi cantly ti on. higher 2 years post-tran splant co mpared to pre-tran plant (5 1.8 v .

46.8). Similar results were obtained from the Ph ysica l Component urnmary (PCS) score (48.1 vs. 40.6) n

M ost patients with type I DM and ES RD receive SPK to improve their rena l function. Fioretto et al. reported that I 0 years of sustained normagly ce mia post-tran splant reversed features of diabetic nephropath y. 2 ~ It signifi ca ntl y improved g lomeru lar and tubu lar lesions. and reduced the thickn ess of glomerular basement membrane and mesangia l matrix. A decrea e in urinary albumin excreti on rate was also ob erved (20 mg/ day vs. I 03 mg/day ) high lighting improvem ent in renal fu nct ion. H o~\ 足 ever, improvements in diabetic nephropa th y post-tran splant need to be balanced w ith nephrotox icity incurred by th e use of immuno uppress i ve agents such as tacrolimu s and cy closporin e 3 "

Glycemic Control

Retinopathy

T he vast majori ty of patients ach ieve co mpl ete insulin independence over the hort and long-tem1 following solid-organ pancreas transplant.

In fac t. g lycem ic control is far superi or to th at achi eved by insulin pu~p or islet-ce ll transplantsn Mora et al. demonstrated th at rec ipi en ts acht_ eved long-term norm oglyce mic state foll owing SPK transplantN Dunng the 15 year fo llow -up. HbA I c leve l remained wi thin normal range w ith no significant difference bet\\een th e first and the Ia t year of follo~\-up (4.68% vs. 4.76%. p> 0.05) Y Fasting g luco e level al o remained stab le during the same period (3 .94 vs. 4.38 mmol/ 1, p>0.05)N However, oral glucose to lerance test (OGTT) demon strated decreased pancreatic re pon se. indicating certain deteri orati on in th e functional ca pability of the all ograft over th e long-term H Whether thi s is the effec t of immunosuppressive medications (i .e. tacrolimu s. sirolimus and prednisone) on islet-cell function. insulin res istance. immun e-related chronic changes. or a co mbinati on th ereof, is unknown.

Diabetic retinopathy (DR) is the most common micro vascu lar com pli ca ti on of diabetes. Several studies have reported conflicting result about th e effects ofS PK on retinopathy. However. most recent studie s indicate that SP K , w ith subsequent normali zati o n of blood g lucose leve l. can improve or norm ali ze retinal lesions3 1Fo ll owi ng SPK transplantation.

14% of non-blind eyes howed improvement. 76% rema ined stable and only I 0% progressed further 32 A separate study reported an improvement in post-tran splant vi ual ac ui ty in 32% of th e ey es and frequency/ severity of vitreous hemorrh ages in 46% of eyes31It may take up to 4 years before noti ceab le functional improvement in reti nopa thy and acuity may be observed . Pancreas transpl antati on. however. ca nnot reverse establi shed visual loss.

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1'ascular The pancreas transplant doe not reverse establ ished macrovascular di sease in recipients. Instead. it is believed to slow down th e progression of disease in thi high-risk popu lation. Nevertheless, fi ve years after tran spl antation. th e prevalence of cerebrovasc ular disease (C VD), coronary heart disease (C HD) and peripheral vascular di ease (PVD) is sti ll 33%. 41% and 41 %, respective ly. Ten year after transp lantation s, the ri sk increased only lightly to 4 I %. 50% and 50 % , respecti ve lyY Us ing peripheral th ermography studi e , it is be lieved that microva cu lar perfusion is improved post-pancreas transplan t as a result of better glycemic control 26

Ne uropathy Previou s studi es demonstrated a benefit of SPK transp lant for diabetic polyneuropathy. K enedy et al. analyzed th e effect of pancreas tran plantation on peripheral motor, sensory and autonomi c nerve function based on indexes of nerve conduction ve loc ity and musc le acti on potentiai Y After I 2 months of follow-up. they found a ignificant improvement in motor and sensory indi ces. Thi s i supported by Martinenghi et al. , \\ hich demonstrated th at a sustained norm og lyce mic tate can amel iorate nerve fun cti on even if poly neuropathy is advanced 1 8

CONCLUS ION SPK transplantation is th e most effec ti ve treatm ent for patients " ith type I DM and ES RD . It add resses renal fai l ure and provides phy iologica l means of attai ning stab le insulin secreti on. A lthough it in vo l ves major surgery and is not without ri sks, it nonetheless increases pati en t survival. enhances QOL and prevent progression of diabetic comp li ca ti ons. A s such. they should be co nsidered in all eligible patients.

REFE RENCES 1. van der Boog P. Ringers J, Paul LC, Jukema JW, Baranski A. Lemkes H, de Fijter JW. Simultaneous kidney-pancreas transplantation: the preferred option for patients with type I di abetes mellitu and approachino end- taoe renal disease. Tran spl an t Rev. 2004 : 18, 129. " " 2. Lipshu tz GS. Wi lkinson AH. Pancreas-kidney and pancreas transplantati on for the treatment of diabetes mell itus. Endocrinol Metab Clin North Am. 2007 ;36: 10 15- 1038.

3. Rayhi". SC, D'Aiessandro AM . Odori co JS. Knechtle SJ. Pirsch JD. Heisey DM , K 1rk AD, Van derWerfW. Sollinger HW. Si multaneous pancreas-kidney transpl antation and ilvmg related donor renal transplantation in patients ,, ith d1abete : IS there a difference in survival? Ann Surg. 2000;23: 417-423 .

4. Stadler M, Auinger M, Anderwald C. Kastenbauer T. Kramar R. Feinbock C. lrsigler K, Kronenberg F. Prager R. Long-term mortality and incidence of renal dialys i and transpl antation in type I diabetes mellitus. J Clin Endocrin ol Me tab. 2006;91: 38 14-3820.

5. Gros JL, de Azeve do MJ . Sil veiro SP, Canani LH, Caramori ML, Ze lmanovitz T. Diabetic nephropath y: diagnosis, prevention, and treatment. Diabetes Care. 2005 : 28 : 164-176.

Tab le I : Selection C riteria for SPK Tran splantation 13

6. Nishimura R, Dorman JS. Bosnyak Z. Taj ima . Becker DJ . Orchard TJ . InCidence of ESRD and survival after renal replacement therapy in patients with type I diabetes: a report from the All egheny County Registry. Am J Kidney Dls. 2003 ;42: 117-1 24.

Confirmed diabetic nephropathy on insulin Presence of other secondary diabetic comp l ications A bil ity to endure surgery and immunosuppression Hi story of compliance to medical recommendation s and th erapi es Understanding of potential morbidity and mortality

7. The Diabetes Control and Complicati ons Trial Research Group. The effect of 111tens1ve treatment of diabetes on the development and proore sion of Jon oterm co mplications in insulin-dependent diabetes mellitus~ N Enol J Med 1993 ;329( 14) : 977-986. " .

Crea tinine clearance < 15 ml/min or on dialys is 8. Lerner, SM . Kidney and Pancreas Transplantation in Type 1 Diabetes Mel-

UWOMJ 182:1 I Spring 2013

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FEATURE ARTICLE litus. Mount Sinai Journal of Med icine. 2008 :75 : 372-384.

kidney transpl antation alone. Transplant I nternational. 2005: 18: I 054- 1060.

9. Ke ll y WD. Li ll ehei RC, Merkel FK, ldezuki Y, Goetz FC. A llotransplant ation of the pan creas and duodenum along with the kidney in diabeti c nephropathy.

Surgery. 1967:6 1: 827-837.

26. Larsen JL, Coll ing CW, Ratanas uwan T, Burkman TW. Lynch TG, Eri ckson JM, Lyden ER, Lane JT, Mack-S hipman LR . Pancreas transplantatiOn improves vascular di sease in patients with type I diabetes. Diabetes Care .

I 0. Stratta RJ. Shokouh-A miri MH. Egidi MF, Grewal HP. Lo A , Kizi li ik AT. Nezakatgoo N. Gaber LW, Gaber AO. Long-tern1 experience w ith simultaneo us kidney-pancreas transpl antation with portal-enteri c drainage and tacrolimus/mycophenolate mofeti l-based immunosuppress ion. Clin Transplant.

2003 : 17(9) : 69-77.

27. Kennedy WR._ Navarro X. Goetz FC, Sutherland DER. Naj ari an JS. Effects of Pancreati c Transpl antation on Diabetic Neuropath y. The New England Journal of Medicine. 1990:332( 15): I 03 1-1 03 7.

2004;27 1706- 17 11.

II . Perosa M. Boggi U. Cantarov ich D. Pa ul R. Pancreas transplantati on outside the USA : an update. Current Opinion in Organ Transplantation. 20 II : 16: 135 -1 41.

28. Martinenghi S, Comi G. Galardi G, Di Car lo V, Pozza G. Secchi A. A mel iorati on o f nerve cond uction veloc ity follow ing simultaneous kidney/pan creas transplantation is due to the glycaemic co ntrol prov ided by the pan creas. Diabeto logia. 1997;40: Ill 0-11 12.

12. Ming CS. Chen Z H. Progress in pancreas transplantation and combined pan creas -kidney transpl antation. Hepatobi li ary Pancreat Di Int. 2007 ;6( I ): 17-23 .

29. Fioreno P, Steffes MW, Sutherl and DER, Goetz FC. Mauer M . Reversal of Lesions of Diabetic Nephropath y after Pancreas Transpl antati on. N Engl J Med . 1998 :339(2) 69-75 .

13. So llin ger HW, Odori co JS. K nechtle SJ , D 'A iessandro AM , Kalayoglu M .

Pirsch JD. Experience "i th 500 simu ltaneo us pancreas-kidney transplant .

A nn Surg. 1998:228: 284-296.

30. Fio retto P. Steffes MW, M ih atsch MJ . Strom EH, Sutherland DER, Mauer M . Cyclo porine associated les ions in nati ve kidn eys of diabeti c pancreas transplant recip ients. K idney Int. 1995:48: 489-495 .

14. Freise CE, arumi S. Stock PG . Melzer JS. Simultaneous Pancreas-K idney Transpl an tation: n Overv iew of Indication . Com pi ications. and Outcomes.

WestJMed . l 999: 170 : 11-1 8.

3 1. Pearce l A, I Iango B. Se ll RA , Wong D. Stabi lizati on of di abeti c retinopathy foll 011 ing simultaneo us pancreas and k idney transplant. Br J Ophth almol.

2000:84: 736-740.

15. Becker BN. Odorico JS. Becker YT. Gros hek M , Werw inski C, Pirsc h JD, Soll inger HW. Simultaneous Pancreas-Kidney and Pancreas Transplantation.

JAm Soc ephrol. 200 1: 12: 25 17-2527.

32 . Cho11 VC, Pai RP, Chapman JR. O'Connell PJ . A ll en RD. Mitchel l P, Nankivell BJ . Diabeti c retinopathy after comb ined kidney-pan creas transpl antation. Cl in Transpl antation. 1999 : 13: 356-362.

16. Gaber AO. Shokouh-A miri MH, Grewe! HP, Britt LG . A techniqu e fo r portal pancreas transpl antati on with enteric drainage. Surg Gyneco l Obstet.

1993 : 177(4): 4 17-419.

17. tratta RJ , Shoko uh -Amiri MH , Egidi MF, Grewal HP, K izilisik AT. Nezakatgoo , Gaber LW, Gaber AO. A prospective comparison of simu ltaneous kidney-pancreas transpl antation with system ic-enteri c versusportal-enteric drain age. A nn Surg. 200 1:233(6): 740-5 1.

Since 1867 l

18. McCull ough KP. Kei th OS, Meyer K H, Stock PG . Brayman KL, Leichtm an AB . K idney and Pancreas Transplantati on in the United States, 1998- 2007: Access for Patients wi th Diabetes and End-Stage Renal Di sease. A meri can Journal of Transplantation. 2009:9: 894-906.

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19. Meier- K riesche HU, Oj o AO, Port FK , A rndor fer JA . Cibrik DM , Kap lan B. Survival Improve ment among Patients wi th End -Stage Re nal Disease: Trends ove r Time for Transplant Recipients and Wa it-L isted Pati ents. J A m Soc Nephro l. 200 1; 12: 1293- 1296.

20. Z iaja J. Chudek J, Kolonko A , Kan1i nska D, Kujawa-Szew ieczek A , Ku ri ataKordek M , K r61 R, K linger M , Wi cek A , Patrzalek D, ierpka L . Does Si multaneo usly Transpl anted Pancreas Improve Long-term Outcome of Kidney Transpl antation in Type I Diabeti c Recipients? Transplantati on Proceedings.

20 11 ;43 : 3097-3 10 1.

2 1. Isla PP. Moncho VJ , Torras RA , Oppenheimer SF, Fern andez CPL. Rican BMJ . Quality of liie in simultaneous pancreas- kid ney transpl ant recipi ents.

Cl in Transplant. 2009:23 : 600- 605.

22. Smith GC, Trauer T, Kerr PG. Chad ban SJ. Prospecti ve Q u a l it y-o i ~L i fe M onitoring of Simultaneous Pancreas and K idney Transpl ant Recipi ents Using the 36-ltem Short Form Health Survey. A meri can Journal of Ki dney Diseases.

20 I 0:55( 4 ): 698-70 7 23 . Gerber PA, Pav lice k V, Demartines N, Zuell ig R, Pfammatter T, Wlithri ch R, Webe r M , Spinas GA, Lehmann R. Simultaneo us i let- kidney vs pancreas- kidney tran plantati on in ty pe I diabetes mel litus: a 5 year single ce ntre foll ow- up. D iabetologia 2008:5 1: 110- 11 9.

24 . Mora M , Rican MJ , Casamitj ana R, A studi llo E, Lopez I, Jimenez A, Fernandez-C ruz L, Esmatjes E. Pancreas and kidney transpl antation: long-term endocrin e function. Cl in Transplant. 20 I 0:24: 236-240.

25. Biesenbach G, Koni gsrainer A , Gross C. Margreiter R. Progress ion of macrovascul ar di sea es is redu ced in ty pe I di abeti c patients after more than 5 years successful co mbined pan creas-kidney transplantation in compar ison to

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UWOMJ 182:1 I Spring 2013

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CANA DIAN MEDICAL ASSOCI ATI ON

CLI NICA L PROC EDURES

Pathogenic mechanisms and direction of empirical studies: a retrospective on membranoproliferative glomerulonephritis Alexander Pazionis (Meds 2015) and Denise Darmawikarta (Meds 2016) Faculty reviewer: Dr. Faisal Rehman , MD , FRCPC, M.Ed (Department of Medicine , Division of Nephrology)

M

embranoproli fe rati ve glomerul onephriti s (MPGN) is an immune-mediated di sease process, underl ying I 0%-20% of nephrotic syndrome cases in children and yo ung adults.' The Ty pe I subtype (C lass ical MPGN) is the most common Hepatiti s C Vi rus (HCV)-as oc iated nephropathy. 2 Still. though all MPGN subtypes (1,11.111 ) can slow ly progress to end-stage renal di sease (E RDS). 3 the condi tion is uncomm on enough to acco unt fo r just 2.8% and 3.3% of all cases in ped iatric dialysis patients and pediatric renal transpl ant recipients. respectively.' This may ex plai n. in part. why studies on the efficacies of va ri ous immunosuppressive agents in thi s conditi on are. on the whole, relatively limited. evertheless, the general fi ndings (w ith excepti ons) appear to indicate these agents are either ineffecti ve or min imally effecti ve in MPGN (depend ing on the subtype). In the current model of evidence-based medici ne (EBM). it is understandabl e that much of clinical practi ce and research be guided by empirical findin gs. Nonetheless. when examining the theoretica l pathogenesis of MPGN along with what is kn own of the mechanisms of action of these age nts. it retros pecti ve ly becomes clear that some of these agents were unlikely to be effecti ve in the fi rst place. Thi s is not to say that theoretical understanding should be trusted without empiri cal veri fica tion. However. in the same way that a clinician should consider what is kn own about an indi vidual pati ent and order tests acco rdingly, it behooves the in vestigator to consider what is kn own about a condition before conducting an empiri cal study.

In this review, we di scuss the underlying pathogeneni c mechani sms of MPGN and rev iew currentl y availabl e treatm ent. We focus on idiopathic MPGN, as most cases of MPGN in adults have secondary causes (e.g. cancer. hepatiti s C) and treatment wo uld accordingly target those underl ying conditi ons.

Ty pe I -Ev idence of act ivati on of th e class ical and alternati ve complement path ways. ex hibiting on imm unohi stoc hemi stry glomerul ar deposits of immunoglobulin (indicating immune complex deposition as a contri buto r to the di sease process). as we ll as components unique to the class ical complement cascade (C Iq. C4) in add it ion to those common to both the classical and altern ati ve path ways (C3 ). 1 Type II - Also known as · Dense Deposit Disease: with conspicuous absence of components unique to th e class ical compliment cascade (C iq. C4) vis-a-vis abse nce of immun og lobulin depositio n. whil e still maintaining ev idence of C3 depositi on in the kidney( s). 1 The impli cation is a ' pure· alternati ve path way component and a theoreti cal absence of an adapti ve immunity contribution.

Ty pe Il l - Less easil y classifi ed and arguably the rarest of the three commonl y acknow ledged subty pes. It is often considered a vari ation of Type I. It di spl ays ev ide nce of poss ibl e immune complex depos ition as a mediator of glomerul ar damage via the observation of immu noglobulin s on immunohi stochemi stry. but, as mentioned previously. is also hi ghl y associated with over acti vati on of the terminal path way of the complement cascade.

While th e pathogenesis of MPGN is now becoming clearer, it is interesting to realize that currentl y employed therapeuti c age nts do not necessaril y target components of the di sease mechani sms. ~9 Binding of complement proteins to microbial cell surface or antibody

The class ical path way is part of the arsenal of the adapti ve immune system's humoral arm .B The alternative path way, on the other hand. is a part of non-specifi c or ' inn ate' immun ity, and does not require antibodies, like the classical path way does. 8 However. after the cleavage of CS to CSa and C5b, classical and alternati ve path ways converge to a common molecul ar sequence.R It is at this stage, the so-called ' terminal' path way that over-acti vati on seems most hi ghly assoc iated with MPGN 111.39. 10 With thi s in mind, we may classify the subtypes of MPGN as follows:

IClassical Pathway I

Formation of C3 convertase Cleavage of C3

Covalent binding of C3bto microbial surface

ILectin Pathway I

~ f3~ ~ t

annose

G antibody

. <:>

~ •

t~

convertase

~~r

•D() to

(J~~ c,

Mannose

{~

C1

'f

PAT HOGEN IC MEC HAN ISMS The complement cascade consists of a seri es of proteo lytic steps catalyzed by the products of prev ious steps in the eri es.R Figure I is a di agrammatic representati on of the complement cascade. which can be acti vated via more than one pathway: the two most relevant to the di scuss ion being the so-called ·c lassical' and ·alternati ve ' path ways.

IAhem aUve Pathway I

,.rtase

al~D<:>~ t

binding protein

~

convertase ·.·

!)-~~~DC~ \•

~~~ I

cs

convertase

I

cs

convertase

I cs

convertase

Figure I. The complement cascade"

UWOMJ 182:1 I Spring 2013

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CLINICAL PROCEDURES CORTICOSTEROIDS

An important tudy to consider in detai l is a report of th e Internati onal Study of Kidney Di ease in Children. '' This study showed a stati sti call y significant decrease in treatment fai lure for children with MPGN I and Ill. meeting th eir inclusion criteria when treated with predni sone rather than placebo (p = 0.028). However. results were not stati sticall y significant for chi ldren with MPGN II included in th e study, though it was underpowered in thi s regard. Th is was corroborated by Donadi o and Offord, 12 whose study also failed to show benefi t in adult MPG N II pati ents comparing predni sone to place bo. Finall y, thou gh not quite reaching stati stical signifi cance (p = 0.07). there was a trend toward stab le, improved renal fun cti on considering all participants with MPG I. II and Ill at 130 months of foll ow-up.' ' A 11 eak.n ess of this study is th at it did not diA'erentiate betwee n MPG I and MPG Ill und er th e assumption th at MPGN Ill was a subcategory ofM PGN I. Potential differences between these two groups 11ere eva luated in a retrospective study by Braun et. al '3 th at showed statisticall y significant differences between a number of characteri stics between MPG I and MPGN Ill pati ents treated with pred ni sone at 3 years of follow up. Patie nts with MPGN I, compared with th ose hav ing MPGN Ill. ~ere found to have more stabl e GF R's, lower rates of persistent hypocom plimentemia (C3). and lower rate of persistent hematuria and proteinuria. to name a few.

Thus. with what evidence th ere is. a possibl e theoreti ca l simplification is as follows wi th respect to th e effect iveness of stero ids in MPG MPGN I - Effecti ve MPG

Ill - Less Effecti ve

MPGN ll -

ot Effecti ve

The effects of steroids are so categori cally broad th at any ex plan ati on on a mechani stic bas is of these categories would amount to spec ul at ion.

More simply put, it is diffi cult to identify differences in similar di sease entities based on responses to a drug with broad effects. Oth er agents with greater specifi city allow us to better di stinguish such differences on th e bas is of theoreti cal know ledge. Thi s is illustrated nex t, by th e admittedl y limited number of stud ies perform ed on calcineurin inhibitors.

CALCI EURIN INHIBITORS

Calcineurin med iates the acti vati on of nuclear factor of ac ti va ted t-cells (NFAT). a transcripti on factor encodin g a number of ge nes including I L-2 .~ IL-2 is necessary forT-ce ll proliferati on." Other ge ne , such as C D40L and oth ers req uired forT-ce ll s to be able to acti vate B-ce ll s are also produced. Bl ocking calcineurin, th erefore, is expected to ha ve a number of effects on th e adapti ve immune system including decreased antibody production and dec reased T-ce ll inA amm atory mediator release.

The possibility of using ca lcineurin inhibitors is best illu trated in two studies. The first, by Bagheri et. al. studied 18 patients with idiopathic MPGN (lMPG ) 15 . They showed th at partial or complete remission of proteinuri a was achieved in 94% (p<O.O I) of patients, and th at at an ave rage follow-up of I08 weeks. just one of th ose showed remission once treatm ent was di scont inued 11 .A noth er study. by Singh et. al. similarly sho wed tatisticall y signifi cant reductions in proteinuria in 8 patient with MPGN treated with cyclosporine 16.However, both of th ese studies fa il ed to di stin gui sh betwee n different subtypes of MPG N. Bagheri et al. made no mention at all of different subtypes, and though Singh et al. disclosed that 5 of the MPGN pati ents were Type I and 3 were Type II , th e data for all these patients were ultimatel y combined .

The pathoge ne is of MPGN l is directl y linked to th e classical pathway of compliment ac ti vation. wh ich constitutes part of adaptive immunity and th erefore is, in th eory. potentially susceptibl e to inhibition by ca l-

8

UWOMJ I 82:1

cineurin inhibitors. Thi s cannot be stated with certainty based on the studies di scussed as they did not di ssociate the effects of calcineunn inhibitors on ty pe I vs . type II. MPGN II. on th e other hand. IS lmked to innate immunity, and though there have been incidental case reports of MPGN II patients respondin g to cyclosporine", long-teml foll_owup studies of small numbers of patients show that calcineurin Inhibitors have no impact on renal survival in MPGN II patients 17â&#x20AC;˘ Long-tenn renal survi val in MPGN I patients treated with cyc lospo rin e should be further in vesti gated.

CONCLUSION/FUTURE DIRECTION

Whil e some ev idence exists th at suggests a role for other treatments, such as acety l ali cy li c ac id. dipyridamole, cyclophosphamide and Coum adin (warfarin). in MPG . it is unfortunately of poor quality 1R. Randomi zed controlled trials should be conducted to study these variou treatment option for MPGN. Given th e ge neral ineffectiveness of current MPGN treatm ent. it is imperative that future in vestigations on potenti al th erapeutic agents be conducted on the bas is of known pathoge nic mechani sms.

A promi sing treatment opti on fo r MPG that has been elucidated by case reports 5-7 is Eculi zu mab . Eculizumab is a monoclonal antibody for C5, a member of the complement cascade that form s part of th e MAC. Given the path ogenesis of MPGN . th e use of Ecu lizumab makes intuiti ve sense and thus it is unfortunate that littl e is yet known about th eir effecti ve ness in the treatment of MPG . Insofar as C5 is in vo lved in both th e classical and altemative pathways of complement acti vation. all three subtypes of MPG (w hich. somewhat simplified. may be characterized by di ffe rential ratios of classical:alternative pathway acti vati on). could theo reticall) be treated with thi s medicati on. Future studies should th erefore investigate the potential for Eculi zumab in treatin g MPGN. insofar as potentially. all three subtypes of MPGN could be treated with thi s age nt.

REFERENCES

I. Kumar V. Abbas AK . Fausto N. Aster JC. editors. Pathologic Basis of Disease. 8th ed. Phil adelphia: Elsevier: 20 I0.

2. Fabrizi F. Hepatitis C virus. cryoglobulinemia. and kidney: Novel evidence.

Scientifica. 20 12:20 12 3. Alchi B. Jayne D. Membranopro li ferative glomerul onephritis. Pediatr Neph rol. 20 10 Aug:25(8) : 1409-18 4. Warady BA . Hebert D. Sulli van EK, Alexande r SR, Tejani A. Renal transplantation, chronic di alys is, and chronic renal insuffi ciency in children and adolescents. the 1995 annual report of the north american pediatric renal transplant cooperative study. Ped iatr Nephrol. 1997 Feb: II ( 1):49-64.

5. Daina E, Noris M, Remuzzi G. Eculizumab in a patient with dense-deposit disease. N Eng I J Med. 20 12 Mar 22 ;366( 12) : 11 61-3.

6. Vivarelli M, Pasini A, Emma F. Eculizum ab for the treatment of dense-deposit disease. N Engl J Med. 20 12 Mar 22 :366( 12) : 11 63-5 .

7. Radhakrishnan S, Lu nn A, Kirschfink M, Thorner P. Hebert D, Langlois V, Pluthero F, Licht C. Eculi zumab and refractory membranoproliferative glomerulonephntJs. N Engl J Med. 20 12 Mar 22;366( 12) : 11 65-6.

8. Abbas AK , Lichtman Al-l, ed itors. Basic Immunology: Functions and Disorders of the Immune System. 3rd ed. Philadelphia: Elsevier; 2011 .

9. Clardy W, Forristal J, Strife CF, West CD. Serum terminal complement component levels 111 hypocomplementemic glomerul onep hritides. Clin Jmmunollmmunopathol. 1989 Mar;50(3):307-20.

I0. Varade WS, Forri tal J, West CD. Pattems of co mplement acti vati on in idiopathic membranoproliferative glomerulonephritis, types I, 11 . and 111. Am J Kidn ey Dis. 1990 Sep;l6(3) :196-20.

II . Tarshish P, Bernstei n J. Tobin JN, Edelmann CM.Jr. Treatment of mesan-

I Spring

2013

CLINICAL PROCEDURES giocapill ary glomerul onephritis with alternate-day predni sone--a report of the international study of kidney disease in children. Pediatr Nephro l. 1992 Mar;6(2): 123-30.

16. Singh A, Tejani C. Tejani A. One-center ex perience with cyclo porine in refraciOry nephrotic synd rome in children. Pediatr ephro l. 1999 Jan; 13( I ):2632 .

12. Donadio JV)r. Offord KP. Reassessment of treatment res ults in membranoproli ferati ve glomerul onephritis. with emphas is on life-tabl e analys is. Am J Kidney Dis. 1989 Dec;l4(6):445-5 1.

17. Appel GB. Cook HT. Hageman G, Jennette JC, Kas hgarian M. Kirschfink M. Lambris JD, Lanning L. Lutz H . Meri S. Rose NR. Salant DJ. Sethi S. Smith RJ . Smoyer W. Tull y HF, Tu ll y SP, Walker P. We lsh M. Wurzner R. Zipfe l PF. Membranoprolife rative glomerul onephritis ty pe II (dense depos it di sease) : An upd ate. J Am Soc Ne phrol. 2005 May: 16(5): 1392-403 .

13. Braun MC, We t CD, Strife CF. Difference between membran oproliferati ve glomerul onephritis types I and Ill in long-tem1 res ponse to an alternate-day predni sone regi men. Am J Kidney Dis. 1999 Dec;34(6): I022-3 .

14. Ho S. li pstone N. Timmermann L. orth rop J. Grae ff. Fiorentino D. Nourse J, Crabtree GR. The mech anism o r acti on or cyclosporin A and FK506. Cl in lmmunol lmmunopathol. 1996 Sep;80(3 Pt 2):S-1 0-5.

18. Longo DL. Kaspe r DL. Jarne on J L, Fauci AS, Hau er SL. Loscalzo J, editors. Harri son 路s Principles or Interna l Medi cine. 18th ed. United States of Ameri ca : McGraw-Hi ll Professional; 20 12.

IS. Bagheri , Ne mati E. Rahbar K. obakht A, Einoll ahi B. Taheri S. Cyclos porine in the treatment of membranoprolirerative glomeru lonephritis. Arch Iran Med . 2008 Jan ; II ( I ):26-9.

UWOMJ 182 :1 I Spring 2013

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DIAGNOSTIC REVIEW

Digital rectal examination in prostate cancer screening Angela Zhang (Meds 2015), Thomas Fear (Meds 2015) , and Hammood Ahmed (Meds 2015) Faculty Reviewer: Dr. John Jordan, MD (Department of Family Medicine)

I TROD UCTION Digital rec tal examination (O RE) ma) be performed in order to identi fy rectal di sease, prostate cancer. exami ne anal ph incter tone. or to examine female gyneco logica l stru ctu re . Rectal examinati on has been descri bed by conflicting opini ons as both a cause of .. more harm than good .. and conversely as a .. crucial part of the examinati on [of a pati entr .u Despi te its man) diagnostic appli cati ons. the test is also uncomfortab le for some pati en ts. doctors. and medica l students. T hi s arti cle w ill foc us on th e characteristics of the test in pro tate ca ncer screening. and how th e chall enges of pati ent resistance and medical student educati on can be addressed.

ROLE OF DRE I N PROSTATE CANCE R SCREEN ING What lies at th e center of the ORE debate is its utility for iden ti fy ing and diagnosing differen t diseases. One applicati on for ORE is for th e detection of prostate cancer which is the most comm on cancer in men oth er non-melanoma skin cancers. It was diagnosed in 26.500 Canadians in 20 12, and resulted in 4000 death s3 However the disease is often indolent. and while one in seven men are diagnosed. only one in 27 men die from th e disease.' T he va lue of ORE can come into questi on because studies confl ict as to wheth er screening fo r pro tate cancer can lower morbidity' oneth eless. because of th e frequency of th e di sease and th e poss ibili ty detect ing th e disease when it is curabl e many pati ents and physicians choose to screen.

T he ORE is an inexpensive test th at in vo lves asse sment of pro tate size. consistency, mob ility. and irregu larit ies in shape. However th e size alone is not a use ful pred ictor of prostate cancer ri sk and th ere is low correlati on be tween transrectal ul trasonograph y (TRUS) measured prostate vo lum e and OR E estim ated vo lum e.H A dditi onall y, whi le carcinomas are fe lts as hard irregu lar nod ul es similar indurati ons may also be cau ed by benign prostati c hypertrophy ( 13PI I) or ca lculi . Thi s means an examiner mu st ord er further tests when any indurati on is felt, and repea t th e test regul arl y to detect for any changes or progression 5 路 ' Th e exam also req uires techni ca l skill. Not all examiners can palpate the entire posteri or surface of th e prostate. T he abi I ity of an exa miner to reach and examine th e ape x of th e prostate. hal f of th e prostate. three quart er of it, and th e entire prostate in a recent study was 93.7%. 66.3%. 23 .2% and 3. 2% for th ese respec ti ve components of the prostate gland. 7 Ev idence for th e importance of techni cal skil l in OR Eal o comes from studi es of inter-examiner vari ation. One study compared consultant and res ident urologists who perform ed OREs to determin e if prostates were suspicious for cancer. Th e overall agreement was ex pressed with a kappa tati sti c of 0.22, whi ch suggests only fa ir agreement between examiners.

However, whil e th e kappa stati sti c among residents was 0.25; among consultants it was 0.63 whi ch suggests a substanti al level of agreement. ' Further research has shown th at more ex peri enced urol ogists tend to as-

10

sess th e size of a prostate more accurately. 9 Th ese findings upport th e idea th at techni ca l skill i important to success full y performing OREs. One means to address thi s i th rough improved educati on of medical train ees. a topic addressed later in th is arti cle.

Wh en ORE is used to screen for prostate cancer in men over 50 years of age. the cancer detecti on rate is 3.2% w ith a pos iti ve predi cti ve value of2 1%. T he sensiti vity and spec ifi city of DR E are 21 % and 86% respectively. 1" It is also recomm ended that ORE is perform ed in conjunction 1~ ith prostate specific anti gen (PSA) in prostate cancer screening because thi s improves th e overall sensiti vity. Whereas th e prostate cancer detec tion rate was 3.2% fo r digital rec tal examinati on, it was 4. 6% for PSA and 5.8% for the 2 meth ods combined. 11 Of note is th at the detec ti on rates of the two tests onl y partially overl ap. and together the two te ts detect more cases of prostate cancer.

In conclusion. because the disease is relative ly indolent, it is recomm ended th at an in fo rmed dec ision is made by pati ents wheth er or not to screen fo r prostate cancer. Because the test is technically diffi cult to per fo rm . steps shoul d be taken to improve th e education of medi cal tra in ees. I f screen ing is to be perform ed. then regul ar ORE is recommended to be used conjuncti on w ith PSA testing to increases th e rate of cancer detecti on.

PAT I ENT BA RRI ERS Some pati ent barr iers to th e acceptance o f OR Es include di scomfort. embarrassment and men assoc iatin g th e exam w ith homosexuality. Furth erm ore some men arc 1-1orri ed about fee lin g stimul ated and having an un wanted and uncontrolled ph ysica l response during a ORE. M en may not seek medica l attenti on th at includes ORE until they' re no longer able to cope w ith sy mptoms: thi s could be due to both fear of th e procedure or fear of disco verin g i ll ness. One ~~ ay to improve pati ent acceptance of OR E i to im prove pati ent educa ti on. A mpl e in fo rm ati on on th e process and reason for perfo rmin g the procedure should be provided for pati ents.

To be included in th e conver ation coul d be di cussion about past experi ence with ORE. whether positi ve or negati ve. Positi oning can also be chosen to reduce pati ent embarrassment during th e procedure. The left lateral position has been show to be th e least embarrass ing w ithout compromi sing th e re ults of th e test. 11 Furthem1ore. many patients view co lonoscopy drasti call y differently th an OR E. Th e reason is that co lonoscopy is often perce ived as more technol og ical and hence perceived as more scientifi c. Therefore extra care should be taken by physicians to maintain a professional environment during ORE. Language used should be chosen carefu l ly. For example, phrases li ke ' examine' th e prostate rath er than ' fee l ' the prostate make the proce s ound more cl in ica l and scientifi c, hence more accepted by pati ents w ho are wary of th e procedure. 13

TEACHING OF THE DRE

UWOMJ 182:1 I Spring 2013

DIAGNOSTIC REVIEW One factor limiting the usefulness of ORE is in ter-examiner vari abi lity, w hi ch results in inconsistent exam findings. Thi s has promoted studi es th at examin e how th e digital rec tal exam is taught to med ical stud ents and res idents. Teaching during medical schoo l has a huge bearin g on a physician's future kill in performin g ORE, yet se veral aspects limit what students learn . ORE is often learned through tex tbook reading and facilitator demonstrati ons. T he three dimensional nature of th e prostate is di ffic ult to convey in tex tbooks. In demonstrati ons. it is challenging to teach th e subtl eti es of palpati on because OR E is a very intern al procedure.1 4 One attempt to solve thi s problem uses rectal simul ators whi ch are currently being deve loped to teach th e OR E. A manneq uin mode ling th e rectum and prostate i attached to electroni c sensors, so th at when an examiner palpates the rectu m sensors analyze th e pressure and locati on of palpation for instructors to assess and give feedback . Beyond use as a teaching tool. thi s simulator can also detect differences in performance between examiners and so attempts to quanti fy inter-examiner vari ability in ORE. Un ive rsity of Ca lifornia Medical Schoo l deve loped a ORE teaching mode l that include didacti c lectures. practical learning by performing the procedure on a standardi zed pati ent, and small group sessions led by fac ulty members. In a study conducted by K apl an et. al. stud ents路 comfort level in term s of performin g ORE were comparin g bel\veen group of students that recei ved ORE trai ning from the new teaching mode l and students th at didn ' t receive forma l training in performing ORE. Students who had received the teaching model were more comfortable performing OREs. Examiner comfort and confidence level is crucial to pati ent comfort and confidence; hence thi s mode l of learnin g through three modalities shou ld be given consideration for more widespread use in th e teaching of medical students. 15

CONCLUS ION De pite differences in prostate cancer screening guidelines bel\-veen vari ous co untri es, the majority of co untri es recomm end a com binati on approach of serum PSA w ith DRE. 1r' T herefore OR E is still an important part of undergrad uate and postgrad uate medical curricul a.

Things to keep in mind : Reassure your pati ent: explain to th em why you' re doing thi s exam and what to ex pect during the exam.

Use medical term s to describe procedure: examine. palpate, drape, examination tabl e etc.

Ask th e patient if they have ever had a bad ex peri ence during a ORE. Position choice: left lateral po iti on is perceived by pati ents to be least embarrassing, while ach ievi ng simil ar results as oth er positions. 16 There are limitations to use of ORE in pro tate cancer sc reening. However as a procedure that is low ri sk. fast and office setting proced ure when used in combin ation with PSA increase cancer detection comparing to PSA alone, th ere is still a place for ORE in medicine and prostate cancer screening today. There is inter-examiner vari ab ili ty meaning th at experi ence leve l has an impact on efficacy of thi s test. Therefore ORE should to be more ri gorou sly taught to new generation s of phys icians and care should be taking regardin g how OR E is taught. M odifications should be made to th e teaching of thi s procedure in medical school s.

Traditional learning from texts and demonstrations should be enh anced by the incorporati on of modem technology like ORE simul ators and more comprehen sive teaching models to educate future phys icians.

REFE RENCES I. Spence D. Bad Medicine : Digital Rectal Examin ati on. Brit Med J. 20 II Jun ; I ;342:d342 1.

2. Snape .I, Ell iott B. Good Med ical Practice. Brit Med J. 200 1 Jun ;28:342 :d3949.

3. Pros tate cance r stati sti cs at a glance [Internet]. Toronto (ON): 20 12 Canad ian Cance r Society ; 2005 Jan I [updated 20 12 May I; ci ted 20 12 May 4) . Avail able from: http://www.cance r.ca/Ontario/ Abo ut%20cancer/Cance r%20stati st ics/Stats%20at%20a%20glance/Prostate%2 Ocance r. aspx?sc_ Iang=en& r= I 4. lzawa, Jl , Klotz J. Siemens RD, Kassouf W, So A. Jordan J, Chetner M. lansavichene A. Prostate ca nce r scree ning: Canadi an guidelines 20 II. CUAJ-Can Urol Assoc. 20 11 August;5(4):235-240.

5. Longo DL, Fauci AS , Kasper DL, Hause r SL, Jameson JL, Loscalzo J. Harrison's principles of internal medi cine. 18th ed. New Yo rk: McG raw-H ill Medical Pub Iishing Division: c20 12. Chapter 95. Benign and Mali gnant Diseases of the Pro tate; p. 796-805 .

6. Roe hrborn CG , Gin11an C.l, Rhodes T. Hanso n KA , Collins GN. Sech SM, et al. Correlati on between prostate size estim ated by di gital rectal examinati on and meas ured by transrectal ultraso und . Urology. 1997 Apr:49(4):548-57.

7. Koulikov D, Mamber A, Fridmans A, Abu Ara feh W, Shenfe ld OZ. Why I cannot find the prostate? Behind the subj ectivity of rectal exam. ISRN Uro logy. 20 12 Feb:20 12. Epub 20 12 Feb 15. Mar 19:[4 p.).

8. Smith DS, Catalona WJ . lnterexaminer vari abili ty of digital rectal examin ati on in detecting prostate cance r. Urology. 1995 Jan:45( 1):70-4.

9. Cheng WC Ng FC Chan KC, Cheung YH. Chan WL. Wong SW. lnterobse rver variation of prostati c volume estim ati on with di gital rectal examinati on by urological staffs with di ffe rent ex peri ences . Intern ational Braz J Uro l.

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I0. Richi e JP, atalona WJ , Ahm ann FR, Hudson MA. Scardino PT, et al. Effect of pati ent age on early detecti on of prostate cancer with erum prostate-specifi c anti gen and di gital rectal examinati on. Uro logy. 1993 Oct: 42(4 ):365-74.

II . Catalona WJ, Richi e JP, Ahmann FR, Hudson MA, Scard ino PT, Flani gan RC, et al. Comparison of di gital rectal examin ati on and serum prostate specifi c antigen in the earl y detection of prostate cancer: results of a multi center clinical trial of 6,630 men. J Uro logy. 1994 May; 15 1(5) : 1283-90.

12. Romero FR, Romero AW, Tambara Filho R, Brenny Filho T, de Olive ira Junior FC. Pati ent pos itioning during di gital rectal examinati on of the prostate: preferences, tolerab ility, and results. Intern ati onal Braz J Uro l. 20 11 MayJun :3 7(3) :37 1-7.

13. Winterich JA, Quandt SA, Grzywacz JG, Clark PE, Miller DP. Acun a J, et al. Mascul inity and the body: how Afri can American and White men ex peri ence cance r screening exams in vo lvin g the rectum . Am J Mens Health . 2009 Dec;3(4):300-9.

14. Balkissoo n R, Blossfield K, Salud L, Ford D, Pugh C. Lost in tran slati on: unfoldin g medi cal students' mi sconcepti ons of how to perform a clinical di gital rectal examination. Am J Surg. 2009 Apr; 197( 4):525-32.

15. KaplanAG , Abdelshehid CS, Alipanah N, Zamansani T, Lee J. Ko ll a SB, et al.

Genitourinary exam ski ll s trai ning curri culum fo r medical students : a foll owup study of comfo rt and skill utili zati on. J Endourol. 20 12 Oct:26( I 0) : 1350-5.

16. Gomell a LG , Li u XS, Trabul si EJ, Ke ll y WK, Myers R, Showalter T, et al.

Scree ning for prostate cance r: the current ev idence and guidelines controversy. Can J Urol. 20 I I Oct;1 8(5):5875 -83.

UWOMJ 182:1 I Spring 2013

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ETH ICS AND LAW

A short primer on transplant tourism Saad Ahmed (Meds 20 16) Facu lty Reviewer: Dr. Fa isal Rehman , MD, FRCPC , M.Ed (Department of Medicine, Division of Nephrology) , Dr. Nelson Chan , MD, LL .B, CCFP (Department of Fam ily Medicine)

ale. 45 )ears old. presenting wi th severe sepsis- ru shed in straight from th e airport. On fu rth er in vest igati on th e pati ent also has an inA amed incision lateral to th eir upper ri ght abdominal quadrant th at seems infected. T he famil) seems ti ght-lipped abo ut th e detai ls of th e trip. but on pressing they menti oned a ki dne) transpl ant done abroad as the rea on.

M

What do) ou do in this situation?

I NTE RNAT IO ALLY: In 2008 delegates from all around the \\ orl d drafted th e Istanbul Declaration. It expl ici tl y stated th at organ trafficking and comm ercialism expl oits the poor and should be completely bann ed.' Wh ereas orga n trafficking is done with coercion and usually violence. even organ commerciali sm in volve a certain amount of monetary coe rcion, espec ially sin ce th ere are power asy mmetri es between someone in a deve loped country and a desperately poor person in a developing country.' Th ose wh o are fo rced to sell th eir kidne)S as a result of fi nancial hardships frequently report th at they are left frai l and sick. w ith th e money di sappearing in no time. 2 Secondly. multipl e studi es from Canada. th e US, and A ustrali a have hown that the health outcome of transpl ants tourists are signi fi cantly worse than pati ents who rece ived th eir transpl ants domesti cally and legitim ately.

T he policy makers at the Istanbul Dec larati on recognized th at organ traffi ckin g and commerciali sm is ultimately dri ven by demand from peopl e in deve loped co untries who are sufferin g on organ rec ipi ent waitli sts. To thi s end. th ey reinforced th e importance of policies th at increase dome ti c organ donati on rates.' some of whi ch have been adopted in Canada. A n exampl e of th ese poli cies being put into prac ti ce is th e L iv ing Donor Paired Exchange (LOP E) Reg istry, a nati onal registry for pati ents suffe rin g from chroni c k idn ey di ca e. and th e Li ving Organ Donor Reimbursement Program ( LO DRP), which has been adopted in at least 5 prov inces. Th e LO DRP reim burses organ donors for va ri ous ex penses and tim e lost throughout th e process of donati on and recovery.

Th e LOPE matches transpl ant pati ent who have incompatibl e living donors w ith each oth er - th e idea being th at one pati ent 's incompatibl e donor may be compatib le w ith anoth er pati ent, who e li ving donor may be compatibl e w ith th e fo rm er pati ent. It ha been shown to incn.:asc organ donati on by up to I 0%.3 Th e Dec larati on has had signifi cant inAuence globall y - especially in countries form erl y considered to be hotbeds of organ traffi cking and commercialism, such as Chin a. Paki stan and th e Philippines. Legislati on is now in pl ace to prohibit th e practi ce.'' Countries are also workin g togeth er to apprehend and charge those w ho continue to participate in organ traffi cking. For instance. European and Canadian authoriti es in K osovo recently di smantled an infamous organ traffi cking rin g spread out across three continents: and a crimin al tri al has begun to sentence

12

th e traffi ckers2 DOMEST I CALLY: In Canada. the Canadi an Society of Transplantation and the Canadian Society of eph ro logy j ointly released a policy statement on organ traffic king and transpl ant tourism. In th eir preambl e, th e) affirm ed the principl es of th e I tanbul Dec larati on 5 and a physician ¡s duty to never deny care to a pa ti ent. T he main crux of the policy statement is focused on preventing peopl e fro m undergoi ng transplant touri sm in th e first pl ace.~ T he myri ad pro blems and complications of transplant touri sm should be coherent!) communi cated to patients- such as th e diffi culty in receiving in surance coverage for long-term anti-rejecti on medi cati ons due to th e lack of documentati on and unethical nature of th e transplantâ&#x20AC;˘ To thi s end . the Kidney Foundati on of Canada released a set of pamphlets that warn people about the possible consequences of transplant touri sm (see http : //www.kidney.ca /docu ment.doc?id- 1239).

T he data from a ingle centre study whi ch looked at 93 transplant touri sts fro m British Co lumbia. affi rm s the need to r th orough and proper pre-tran plant counseling. 6 T he tud) fo und that 30% of th e re pondents had never been referred for a transplant consult, and had thus preempti vely undergone a kidn ey transpl ant. noth er 33% of th e transpl ant touri ts in th e study had compl eted a transpl ant consult. and after being waitli sted lo r a transplant sought a commercial transpl ant. T hi s speaks to a need for a multi-faceted policy. I f 30% of transpl ant touri sts are pre-empti ve ly rece iving transpl ants without an actual referral after the development of end-stage renal disease, it speaks to a need for public campaigns di sco uraging transpl ant touri sm. as well as a need to educate pati ents before the deve lopment of end-stage renal di sease. Secondly. oth er pati ents recei ved a referral. but fail ed to foll ow up and were lost to th e system - hence th e tud y mentions that pati ents must be track ed better. Furtherm ore. considerin g th at th e vast maj ority of tran spl ant tourists were ethni c minorities.j th e stud y argued th at outreach effot1s must be made to members of the e communiti es to discourage transplant tour' ~n . A nd for th e 33% of _pati ents wh o had gone abroad to r a transplant alter bctng put on a wa1tlt sl , th e study advocated for poli cie such as the Paired Li ving Donor Exchange Registry. Studi es held in centres across the US and Australia had simi lar findin gs and recomm endation s_7.a.9 N umerous pub lic hea lth problems have been rai sed by a anadi an ~tudy o f transplant touri sts. 10 Th ere have been cases of pati ents presenttn g wtlh mu lttpl e drug-res tslant Escherichia coli, acti ve tuberculosi a ~ve il as oth er viru es ~ nd funga l in fecti ons not typically seen in an a,da. fh e pre~ence ofmu lttpl e drug resistant bacteri a certainl y poses a domeslt c publtc hea lth conce rn .

LEGALLY & SOME DEFI NITIONS: Under Section 279.04 or th e Crimin al Code of

UWOMJ 182:1 I Spring 2013

anada, it is a crimin al

ETHICS AND LAW offe nce to ex pl o it a noth e r pe rson a nd by th e use of fo rce, decepti o n, o r coe rc ion re move th e ir organs o r ti ssues - be it do m esti ca ll y o r inte m a tiona ll y.11 · 12 The re is however c urre ntl y no overa rc hin g fed e ra l law pro hibitin g C an adi a ns from o bta ining co mm e rc ia l o rgan tra nsp la nts overseas. whi c h we re so ld by a con se ns ua l do no r. 13 · 14 In 2009, th e Ho use of Co mm o ns ne arl y passed Bill C -381 into law. 15 It so ug ht to ex pli c itl y pro hibit Canadi a ns fro m go ing a broad to purc hase a n o rgan a nd wo uld have crimin a li zed a ny so rt o f pa rti c ipa ti o n, eve n indirect, in o rgan traffi c king o r tra nspl a nt comm e rc ia li sm .

Bill C -3 8 1 wo uld have a lso required hea lth care pro fess io na ls to repo rt a n y pa ti e nts of the irs w ho had und e rgo ne tra ns pl a nt to uri s m , muc h a kin to m andatory re po rting m echa ni sm s a lready in pl ace . 16 So m e acade mi cs a rg ue th at si mpl y ba nning thi s practi ce w ill no t wo rk .4 To co ntro l a n indu stry tha t has bee n roug hl y estim a ted to gene ra te $600 milli o n to $ 1. 2 billi o n a year-3 in profits w ill be diffi c ult, espec ia ll y w he n a m a rke t of despe ra te ly ill a nd despe rate ly poo r peo pl e co ntinues to ex ist. T hey co nte nd th a t o rga n scarc ity, w hi c h dri ves de m a nd .. need s to be dealt w ith by in c reas ing o rgan d o na ti o n via po li c ies suc h as offe rin g in ce nti ve fo r do na ti o n. Howeve r. it is ha rd to extrapo late th ese acade mi cs' a rg um e nts furthe r, as it wo uld o th e rw ise lead to th e unjustifi a bl e posi ti o n o f a ll ow in g tra nspl a nt to uri sm in som e s ha pe o r fo m1 .

CONCLUS ION: Fundam e nta ll y. th e iss ue o f o rga n trans pl a nta ti o n a nd comm e rc ia l ism is o ne o f despe ra ti o n-dri ve n de m a nd . Phys ic ia ns sho uld e ns ure th a t th e ir pa ti e nts unde rsta nd th e severe a nd f req uent s ide e ffects of tra nsp lant to uri sm . Th ey sho uld ex pl a in the he in o us facts - the va ri o us c rimina l o rgani zati o ns th a t th e tra ns pl a nt trad e fund s. a nd the in c redibl y une thical na ture of the trade, w hi c h is no thing sho rt o f th e ex pl o ita tio n of th e poo r. T hese pe ril s mu st be communi cate d ea rl y. be fo re o rgan fa ilure, so that pa ti e nts d o no t act o ut of despe ra ti o n . A nd if a pati e nt w ith a comm e rc ia l tra nspl a nt com es into th e ir care. they must s impl y re m e mbe r th e ir duty to minimi ze th e pati e nt's s uffe ring a nd prov ide the best poss ibl e care for the m .

Pusse ll BA. O ut come of overseas comme rcial kidney transpl antat ion: an Austral ian perspecti ve . Med J A us. 2005 Mar 7;1 82(5):224-7.

8. Canales MT. Kasiske BL. Rosenberg ME. Transpl ant touri sm: o utcomes of United States re ide rlts who undergo kidney transpl antati on overseas. Transpl antatio n. 2006 Dec 27 : 82( 12) : 1658-6 1.

9. G ill J, Madhira BR. Gjertson D, Li pshutz G. Cec ka JM . Pham PT, Wilk inson A. Bunnapradi st S, Danov itch G M. Trans pl ant tour is m in the United States: a sin gle-center ex perie nce. Clin J Am Soc Nephro l. 2008 Nov : 3(6): 1820-8.

10. Prasad GY. Shukl a A. Hu ang M, D'A Ho ney RJ, Za ltzman JS . O utcomes of Commercial Re nal Transpl antatio n: A Canadi an Ex peri ence. Trans pl antati on.

2006; 82(9~ 11 30- 11 35 .

11. Criminal Code of 1985, R.S. c. C-46 [In te rn e t] . Ava il able fro m: b..trp_Jj laws. justi ce gc ca/e n /C-46 / ind ex btml 12. An Act to amend the Crimin al Code (traffi ck in g in persons), S.C. 20 12, c. 15 [Inte rn e t] . Avail a bl e from: http ://laws-lojs. ju stice gc ca/e ng/A onu aiSta tutes/2 01 2 15/ page- l.html 13. Christi an L. Hum an Tratlicki ng and Se llin g yo ur Own Organs in Canada (Inte rne t]. Onawa (ON): Law o tli ce of Lisa Chri sti an; 20 12, Nov 09 [cited 20 13, Fe b 18). Avail abl e from: http -1/chri s tj a ncrimin all awo ttawa .co m / b log I 2 3 0-hu rna o-traffickin g -a nd -se llin g-yo u r-ow o -o r ga ns. h tml 14. Ca nadia n laws lax o n sa le o f o rga ns, says tra nspl a nt expe rt [Inte rn et].

CBC News: 2008 Jan 3 1 [Cited 20 13, Feb 18]. Avail abl e from: http ://www. cbc.ca / news/ health /s to ry/2 00 8/0 1 /3 1 / be-canada -lax-o n-o rga n-trade. html 15. Sher J. Transplant to urism a fo rm of cannibali sm [Inte rne t] . Toronto Star; 20 12, Jan 22 [Cited 20 13, Fe b 18]. Avail abl e from: http ://www tb esta r com / news/canad a /a rti cle I 111 93 38-- tran s pl a nt-to u r is rn -a- fo rm-ofcannjbali sm 16. Chan C. Canadi an MP Re-introduces Bill to C urb ' horrifi c' Organ Trade [In te rnet] . Epoch Ti mes. 2009, May 13 [Updated 2009. May 14 : cited 20 13 Feb I Avail abl e fro m:

T he sta k es a re no thin g m o re tha n th e li ves o f th e most v uln e ra bl e and di stressed indi v idua ls in o ur communi ties a nd a ro und th e world.

REFERENCES: I. Intern ational Summit on Transplant Touri sm and Organ Traffi ckin g. The Declaration of Istanbul on O rgan Trafficking and Transpl ant Tourism. Clio J Am Soc Ne phrol. 2008 SepJ(5): 1227 -3 1.

2. Sher J. To ronto ma n w ho bought kidn ey a broad is key w itness in tra ns plant sale trial in Kosovo [In te rne t] . Toronto Star: 20 12 Jan 22 [C ited 20 13, Feb 18]. Avail abl e from: http ://www th es tar com / ne ws/ canada /articl e I 1119 33 7 --toronto- mao-who -bought-kidn ey-abro ad- is· key-witness -in- trans pi a at-sale-trial- in- kosovo 3. Ferrari P, de Kierk, M. Paired kidney donatio ns to expa nd th e living do no r pool. J Nephrol. 200 9 Nov-Dec; 22 (6 ):699-7 07.

4. Ambagts hee r F, We imar W. A C riminological Perspecti ve: Why Prohibiti on of Organ Trade Is Not Effectiv e and How th e Dec larati on o f Istanbul Can Move Forward . Am J Transplant 20 12 Mar; 12(3) :571-5.

5. G ill JS, Goldberg A, Prasad G Y. Fo rtin MC, Han sen TB, Lev in A, G ill J, Tonelli M, Tibbl es LA, Knoll G, Co le EH, Caulfi eld T. Policy State ment of Canadian Soc iety of Transplantatio n and Canadi an Soc iety of Ne phro logy on Organ Traffi cking and Transplant Tourism. Transpl antation. 20 10 Oct 27 ; 90(8):8 17-20.

6. G ill J, Di ec 0 . Landsberg DN, Rose C, Johnston 0 , Keown PA, G ill JS. Opportunities to deter transplant to urism exist before referral for transpl antati on and during the workup and manageme nt o f transplant candidates. Kidney lnt 20 II May; 79(9) : I 026-3 1.

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UWOMJ 182:1 I Spring 2013

13

HEALTH POLICY AND ECONOMICS

Matching theory: kidney allocation Kyle Luong (Meds 2016) Faculty Reviewer: Dr. Gregory Pavlov, PhD (Department of Economics)

ABSTRACT Lloyd Shapl ey and A lvin E. Roth have recently been awarded th e obe l Prize in Econom ics for their work in match ing theory. A lthough branching from the field of economics. matching th eory has had many implications in the world of medicine. For exampl e. the Na ti onal Residency Matching Program in the United States is an app licati on of matching th eory. The focus of thi s artic le is th e applicati on of matching th eory to kidney tran splant all ocation. Kidn ey tran splantation is th e best treatment fo r end stage renal fai lure. Unfortunately. th e demand for k idn ey exceeds supply. Kidn ey paired exchange programs. which have begun to gamer great success in increasing the number of kidney transpl ants worl dwide. base thei r fo undations on matching th eory. Overviewed in thi s paper wi l l be how these programs were created and work. their successes. and some of the unique challenges and logistical obstac les they face.

I NTRODUCTION Trad iti onally, markets functi on wi th monetary exchange faci litatin g th e movement of goods to buyers from sellers. However in some instances monetary exchange is unfeasibl e due to th e nature of th e market and as a result. prototypical market structure is inapp licable. Matching theory is a branch of game th eory that deals with thi s non-price allocation. Pi oneered by Ll oyd Shapley in the 1950s and 1960s, it has been appli ed to real markets w ith great ucces . Two med ica l markets where matching theory has garnered thi success are re idency matching and kidney tran splant all ocati on whose designs owe greatl y to A lvin E. Roth . an A meri can economi st who made great foray s into th e app licati on of Shapl ey 's th eori es and their furt her development. Recent ly. both men were award ed the Nobe l Pri ze in Economics fo r th eir work . In li ght of its contem porary step back into the pub lic eye. thi arti cle wil l briefl y outline matching th eory w ith some example from rea l markets. Finally, th e application of matchin g th eory to kidney transplant all ocati on wil l be ex pl ored, w ith a di scuss ion of its succe s and future direction s.

MATCH I NG THEORY: BA SICS Shapl ey·s th eory is based on stable matching. In their 1962 paper. Gale and Shapley demonstrated thi s idea w ith th e stab le marri age problem. 1 T he stab le marri age prob lem asked how a number of women could be match ed to a number of men, con iderin g their respecti ve preferences to r each member of th e opposite sex . They showed th at no matter th e preferences. th ere would alway s exist a stabl e all ocati on. A stable all ocati on is one whereby no parties can be better off by further exchange. tabi I ity is desirable in thi s exampl e and its rea l world ex trapo lati ons as stability is seen as an indicati on of efficiency because furth er improvement of happiness from exchange is impossib le. Addi ti onally, stability imparts robustn ess to all ocation systems since it eliminates incenti ves for parti es to disobey or manipul ate th e rul es of th e system. In the stable marri age

14

prob lem. the soluti on was th e Gale-Shap ley .. deferred acceptance"' algorithm . Suppose the men are aii O\\ ed to propose to th e women. Each man would propose to hi s favo urite woman. A woman w ith more th an one proposa l would keep her favo urite proposal ·on hold ' without accepting. and rejectin g all oth er . (Women wi th only one proposal would keep that propo a! on hold as well. ) With th e second round of proposals. men who were rej ected in th e preceding round would propose to their second ranked woman. The women beha ve similarly as before. keeping their best proposal on hold and rejecting the rest. including any proposals from prev ious round s. Eventually. all women w ill have been proposed to at which point they are all requ ired to accept their on hold proposals. It was shovm that all matches made in thi s manner were stable. A n im pli ca ti on of the Gale-Shaple) algorithm was that th e propos ing party wou ld secure more favourable matches.

MATCHING THEORY: APPLICATION At the crux of thi s deferred acceptance algorithm is free trading. In th e stable marri age problem. th e women were able to trad e tentati ve proposals fo r anything better th at came along. A lthough th e marri age problem may seem con tri ved. it indeed has real world counterparts. One such market is residency matching in the US. Roth demonstrated that the matching algorithm used by the Nati onal Resident M atching Program (N RMP) \\as able to make stab le matche becau se it was essentially an ada ~ta ll o n o f th e Ga le-Shapl ey algorithm . 1 The allocati on of residency positions was anoth er stab le marri age problem . w ith th e hospitals proposing to th e appli cants. Harkening back to th e stable marri age probl em.

Roth noted th at the algorithm produced outcomes favouring hospital s.

Moreover. With more physician coupl es w i hing to match to th e same areas. th e algorithm was proving insuffi cient in meeting th ese new needs.

In 1995 , Roth and Elli ot Peranson were enli sted to redesign th e NRMP to accommodate coupl e matching. T heir algorithm was adopted in 1997 and used ever ince. 3

KIDNEY TRANSPLANT T he best treatm ent lo r end stage renal failure is kidn ey transplant. Pati ents rece iving transplants li ve I 0 years longer than th ose 0 d. 1 · • U r I h . n 1a ysis. n ortun ate y. t e demand for kidn eys outpaces the supply of deceased donors With over 70% of Canad ians w ho are on organ waiting lists, 5 need mg a k i dney~ Livmg donors are another resource. prov iding > 16 yeats of dialysis-free survival compared to th e 8.6 years fronl a d d d ' u · ecease onor. ntortun atel y, th e challenge with utilizing thi s pool of li ving do~ors wa that many pairs of wi lling donors and recipients were deemed mcompallbl e after. screenmg. In formation from th ese donor was usufor follow up and th e pair would be sen t home. 1 Wtth · ally not recorded . such congestiOn .on donor waiting li st• th ere was an uroent . th e. deceased . need to better uttltze lt vmg donors. "' A so lution to th e problem wou ld be another applicati on of Gale

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HEALTH POLICY AND ECONOMICS and Shapley 's matching th eory. Wh ereas th e marri age prob lem and th e NRMP represented a two-sided mark et (two parti es matching with one anoth er), th e kidn ey exchange problem is one-sided as every indi vidual and their initial donor candidate is regarded as a sin gle item. Gale路s toptrading cyc le algorithm. whi ch also produces stabl e matches. wa the answer to thi s mod ifi ed allocati on problem. Objects are initi all y di stributed to each entity and like the deferred acceptance algorithm . subsequent trading occurs.' In kidn ey transpl antati on. th e initial all ocati on o f objects is analogous to th e pairs of incompatibl e donors and their intended rec tpt ents. ow, imagine two incompatibl e pairs of a donor and rec ipi ent. I f each donor happened to be a match for the rec ipient in th e other pair. a mutually beneficial exchange wo uld be poss ible w hereby both patients receive a compatibl e donor. T hi s system of exchanges has been dubbed Kidney Paired Exchange (K PE). Exchanges could and have become more com pi icated. with further pairs participating in a daisy chain of trad es. KPE has also been adapted to make use of th e grow in g number of altrui sti c or non-directed donors. 9 In domino-paired donati on, the altrui stic donor donates th e kidney to a recipient or an incompatibl e pair.

The donor of said pair wou ld th en donate th eir kidney to a compatibl e rec ipient on the waitli st. Longer domino chain s have been accompli shed, with the longest to date spanning 30 kidn eys and 60 indi viduals. 'u SUCCESS 11

Si nce it was first suggested by Rapaport in 1986. several inform al exchanges have been reported . 12 Not until 2005 was the first nati onal KPE program establi shed in the Netherl ands. 13 In the US. Roth helped design th e New England Program for Kidney Exchange, 14 and along w ith th e Ohio program was one of the early preludes to the national program propo ed by UNOS in 20 10. In Canada. a three prov ince pilot program initiated in 2009 and has become nationwide as of October 20 I 0. ,; Th e Ameri can programs have seen increased numbers of kidn ey exchanges in each subsequent year with > 1000 cumul ati ve transpl ants since 1998.

11 Researchers suggest that optim al utilizati on of th e program co uld see as many as I 000-2000 additional tran splants per year in th e US; 16 aving th e country $750 milli on USD in dialys i costs annually. 17 With the Canad ian program still in its infancy. th ere is insuffi cient data to evaluate its success. To date. the Canadian L iving Paired Donor Exchange Registry has facilitated 144 tran splan ts w ith 14 more scheduled before th e end of th e year. Increased tran spl ants mean more pati ents are experiencing a lessened burden of dialysis. better mortality. and a higher quality of li fe. 'R

CHALLENGES AND FUTURE DIRECT IONS KPE program impl ementati on elicits vari ous chall enges. One impli cation that arose was that all transplants wou ld have to be done simultaneousl y to prevent donor reneg ing. Only recentl y have non- imultaneous donations been performed w ith altrui sti c donors bein g incorporated into non-simultaneous extended altrui sti c donor (NEAD) chai ns. NEAD resembles domino-paired exchange except th e last donor in th e chain does not donate to a waiting li st recipient. but rath er becomes a bridge donor. awaiting more pairs. Optimi sti cally, th e potenti al for ex tending th e wave of exchanges outweighs the ri sk of donor ren eging. Some argue however, to not be overconfident because of th e honeymoon phase where a single donor is abl e to initiate a large chain of donations. Many chain s wi ll not propagate indefinitely and bridge donors accumulate as matches become rarer. M any drop out after some peri od of tim e. 19 A national KP E exchange also presents the need for co-ordination between the variou s transplant centers and a centrali ze d registry. It is no surpri se th at additional viable exchanges are easier to find with a larger pool of pairs. However, there needs to be incentives for hospitals to enroll donor-recipient pairs instead of performing short chain exchanges internally. As well , the tran sport of donors across th e country presents an-

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oth er chall enge both log isti ca ll y and fin ancially. T hese are all issues th at need to be addressed i f KPE is to be used to its full potenti al.

CONCLUS ION Thi s arti cle has prov ided an introd ucti on to matching th eory and th e ways it has been applied in rea l markets. w ith special regard to kidn ey transplant alloca ti on. The di scussion of KP E's permutat ions. successes and shortcomings here are definitely not ex hausti ve. For in stance. th e ethical issues associated with KPE have not been add ressed here.

Further reading is encouraged for those interested. U ltim ately. matching th eory proves to be applicab le in many contex ts. and has especially found some utility in th e fi eld of kidn ey transplantati on.

REFERENCES I. Gale D. Shapley LS . Coll ege admi ss ions and the stability of marri age. Am Math Mo n. 1962 Jan;69( I ):9- 15.

2. Roth AE. The Evolution of the Labor Market fo r Med icallntems andRe idents: A Case Study in Game Theory. JP E. 1984;92(6) :99 1- 10 16.

3. Roth AE. Pe ranson E. The Redesign of the Matching Market for American Ph ys icians: Some Engin eering As pects of Economi c Design. Am Econ Rev. 1999 Sep:89(4):748- 780.

4. Wolfe RA , Ashby VB. Milford EL et al. Comparison of monality in all pati ents on dia lys is. pati ents on di alys is awaiting transpl antati on, and recipients of a first cadaveri c transpl ant. N Engl J Med. Dec 1999:341 (23): 1725- 1730.

5. CIHI. ca [Internet). Canadi an Institut e fo r Health lnfom1 ati on. c l996-20 13 [cited 20 12 Dec 16]. Avail able from: www.ci hi .ca.

6. SRTR. 2008 Annual Report of th e U.S. Organ Proc urement and Transplantati on Network and the Scientifi c Registry o fTran splant Recip ients: Transplant Data 1998-2007 . Rockville, MD: Health Reso urces and Services Administrati on. Healthcare Systems Bureau, Division of Transplantation.

7. Roth AE. What have we learned from market des i g n ~ Eco nomi c Journ al (Royal Economic Society). 2008 Mar; 11 8(52 7):285- 3 I0.

8. The Prize in Economi c Sciences 20 12 - Popular In formation [Internet] . The Royal Swedi sh Academy of Sciences; 20 12 [cited 20 12 Dec 16). Available from: hnp://ww\\ .nobelprize.orgjnobel pri zes/economics/laureates/10 IIf pop ul ar.html.

9. Matas AJ, Garvey CA. Jacobs CL, Kahn JP. Nondirected donati on of kidneys from living donors. N Engl J Med. 2000 Aug:343(6):433- 36.

I0. Sack K. 60 Lives. 30 Kid neys, All Linked. NYT. 20 12 Feb 19;Secl. A: I. II . Rapaport FT. The case for a li ving emoti onall y related international kidney donor exchange re gistry. Transpl an t Proc. 1986 Jun : 18(3 Supp 2) :5-9.

12. Wallis CB, San1 y KP, Roth AE, Rees MA. Kidney paired donation. Nephrol Dial Transpl ant. 20 II Ju 1:26(7) :209 1-2099.

13. de Klerk M. Keizer KM , Claas FH, et al. The Dutch nati onal li ving donor kidney exchange program. Am J Transpl ant. 2005 Sep:5(9):2302- 2305 .

14. Roth AE, Sonmez T, Unve r MU. Kidney Exchange. Q J Econ.

2004: 11 9(2):457-488.

15. Fortin MC, Williams-Jones B. Who sho uld travel in kidney exchange programs: the donor, or the organ? Open Med. 20 II :5( I ):e23-e25 .

16. Segev DL Kucirka LM , Gentry SE, Montgomery RA . Utili zati on and outcomes of kidney paired donati on in th e United States. Transpl antation. 2008 Aug;86(4) :502- 5 10.

17. Gold farb DA. Kidney paired donati on and optimizing the use of li ve donor organs. J Urol. 2005 Nov;l 74(5) :19 11 - 19 12.

18. Tonelli M, Wi ebe , Knoll G, Bell o A, Browne S, Jadh av D. et al. Systemati c Rev iew: Kidney Transplantati on Compared With Dial ys is in Clinicall y Relevant Outcomes. Am J Transpl ant. 20 11 Jun ; II :2093-2109.

19. Gentry SE, Segev DL. The Honeymoon Phase and Studi es of onsimultaneo us Chain s in Kidney-Paired Donati on. Am J Transplant. 20 II

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HEALTH POLICY AND ECONOMICS Dec: ll ( l 2):2778-2779.

Sun Country HEALTH REGION

Rewa rding Physic ian Job Opportunities in South East Saskatchewan.

Sun Country Health Region is currently recruiting for General Practice Physicians, General Practice/Surgeon, and a Regional Locum. Each opportunity has strong and established earnings potential and each opportunity partners with other physicians . If you are eligible for registration with the College of Physicians and Surgeons of Saskatchewan we are interested in you!

Sun Country Health Region (SCHR) covers the southeast portion of Saskatchewan Canada, from the Manitoba border to the U.S. border, encompassing serene prairie and parkland . SCHR provides health care services to the population of 54 ,000 residing in the region .

See www.suncountry.sk.ca for a complete listing of physician job opportunities.

Contact the Recruitment Team: Phone: 306-842-8320 Toll Free: 1-866-578-7247 jobs@schr.sk.ca

-

.suncountry.sk.ca

Bluewater Health Sarnia & Petrolia, Ontario Bluewater Health is recruiting for the following positions to provide services to the residents of Sarnia-Lambton both in the community and at the hospital.

• • • •

Dermatologist Paediatrician Rheumatologist Hospitalists

• • • •

Neurologist Psychiatrist Emergency Physicians Family Physicians (Petrolia)- including low acuity Emergency

Bluewater Health is a 320 bed hospital operating on 2 sites which includes a recently completed $319 million redevelopment. The hospital offers excellent medical and diagnostic supports : • A broad range of diagnostic services, including CT and MRI. • Full spectrum of specialists available 24/7 (neurosurgery not available) Sarnia was rated the Most Livable City in Ontario by the Pembina Institute (August 2007). Situated on the shores of Lake Huron at the border to Michigan, Sarnia offers excellent quality of life, sports, arts and culture, education , state of the art health care, and beautiful natural environment To inquire about these positions , please contact: Dr. Mark Taylor, Chief of Professional Staff Bluewater Health Medica I_affairs@bluewaterhea lth .ca 519-464-4400 ext 4534 .

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UWOMJ I 82 :1 I Spring 2013

BLUEWATER HEALTH Life, health and renewal.

HEALTH PROMOTION

The role of prostate-specific antigen (PSA) testing in screening for prostate cancer Charlotte Hunter (Meds 2015) and Paul Zamiara (Meds 2016) Faculty Reviewer: Dr. D. Scott Ernst, MD, FRCPC (Department of Oncology, Division of Medical Oncology)

rostate spec ifi c ant igen (PSA) is a serin e protease ex pressed mainly by th e prostate gland and detectab le in norm al, beni gn hy pertrophic. and neoplasti c prostate ti ue. Whi le th e majority of the PSA produced by the prostate gland is released into emen, a small amount (approximately one million-fold lower) norm ally leaks into th e circul ati on and is detectable by immunoa a) . In the hyper- and neopl astic prostate, though. its secreti on into prostate ducts is lost and consequently more PSA is released into ex trace llul ar fluid and th e circul ati on.1 Serum PSA levels can therefore be used to track th e growth or shrinkage of prostate tumors: indeed. th e FDA approved it u e to monitor cancer progres ion (i.e. tumor grow th. response to treatm ent. recurrence) in already diagnosed men in 1986.1

P

PSA became th e first biomarker (indi ca tor of biological state) approved for screening asymptomati c men for cancer in 1994, when the FDA approved its use in conjunction with the digital rectal exam (ORE) to screen for prostate cancer. A PSA level of 4.0 ~ g/ L was traditionall y con idered th e upper limit of norm al. and a prostate biopsy was recommended to patients exceed ing thi s level. However. prostate cancer screening based on PSA level has limited specificity (33%. versus 86% sensiti vity 3 ). as inflammation (prostatiti s) and benign growth (benign prostati c hyperplasia) of th e prostate will also elevate PSA leve ls.2 Therefore, despite the PSA test 路s utility in monitoring tumor progre sion and response to treatm ent, its u e as a creen ing test for prostate cancer in asymptomati c men remains controversial. Because of the con siderabl e publi c health burden imposed by prostate cancer - it was the most diagnosed cancer in males in 2008 (about 899 000 cases and 258 000 deaths world w ide). w ith 72% of cases occurring in developed countries' - proper screening too ls and guidelines are ex tremely important.

The Canadian Cancer Society has suggested th at th e benefits of having a PSA test for screening purposes in clude the peace of mind granted by a norm al result: identifi cation of those in need of further testing ( if the result is higher than expected for th e pati ent" age): and the ability to detect prostate cancer before it is symptomati c and/or before it has spread beyond th e prostate.' However, th ey also point out th e potential for harm as ociated with prostate cance r screening. such as the unnecessary anxiety cau ed by a fal se positi ve: the potenti al for a fal se negative and th e propensity to then ignore worri some symptoms that may emerge later: and th e ri sks associated with treatm ent of slow grow ing prostate cancer that could have been left alone.

Th e current guidelines for prostate cancer screen ing in Ontario state that PSA te tin g should not be used as a population-wide screen ing too l for early detection of prostate cancer in asymptom ati c men.6 Instead, physician should di scuss the benefits and potenti al harm s of testin g w ith men who are between th e ages of 50 and 75 and have a life expectancy of at least I 0 years. Thi s di scu ss ion should also include men over

UWOMJ I 82:1

40 w ith a first degree relati ve who has had prostate cancer. and men of Afri can ancestry. With thi s inform ati on. men can th en decide for th em sel ve wheth er th ey would like to undergo testin g. A PSA va lue >4.0 ~t g/ L or an abnorm al OR E \varrants furth er in vesti gati on.

Dr. George Kim (personal communi cati on. December 4. 20 12). a famil y ph ys ician workin g in outh western Ontari o. restri cts hi s orderin g of PSA tests to sy mptomati c men. In th e event of a 11 0rri some change in prostate-related symptoms (i.e. increased urinal") urgency or freq uency. or poor urinary stream 11 ith urinal")' trac t infection unlike!). e peciall y when th e pati ent is of African descent or has a first degree relative diagnosed with prostate cancer prior to age 65 ). he prefers to send patients for prostate ultrasound and possibl e biopsy. However. Dr. Kim find s the PSA test to be a conveni ent test in th e interim i f th e ultrasound cannot take pl ace within 10 days. In term s of screening. Dr. Kim be l ieves pati ents wo uld like to undergo a simp le test, like th e PSA test th at could defi nitively detect cancer: because of thi s desire for certainty. patients may have unreali sti c expectati ons regarding th e validity of test results.

He th erefore recommends di cu sing with pati ents th e advantages and limitati ons of PSA testin g (including its low pecificity). and exp laining why it cannot replace oth er surveill ance meth ods (i.e. th e ORE).

Tak ing a more ex treme stance th an th e Ontario gu idelines. the .S. Preventi ve ervices Task Force recent!) recomm ended agai nst any PSA-based screening for prostate cancer. regardl ess of age. based on th eir conclusion th at many men are harm ed by thi s screening test and few benefit from it 7 The Task Force路 conclu ions were largely based upon two ongo ing studi es: the U.S. Prostate. Lung. Co lorectal & Ovarian Cancer (PLCO) Screening Tria l and th e European Randomi zed tudy of Screening for Prostate Cancer (ERSPC).

The PLCO tri al in vo lved 76 693 men bet11 een the ages of 55 and 74 who were randomi zed to annual P A screening for 6 year . co mbin ed wi th a ORE for 4 yea rs. or care as usual.x A PSA va lue >4.0 ~g/ L was used as th e cutoA路 for a positi ve screen resu lt. The incidence of prostate cancer was signifi cantly hi gher in th e screening group after 7 years of fo ll ow-up (RR. 1.22 [95% C L 1. 16-1.29]). but th ere was no signifi cant di lference in prostate cancer mortality (RR. 1.1 3 [95% C L 0. 75 -1. 70)) .

Th e I 0 yea r follow-up data. wh il e onl y 67% complete. was also con si tent w ith th ese findin gs.

The ERSPC trial rand omized 182.000 men bet11een the age of 50 and 74 to either th e screening group. w hich received a PSA te st ever)' 2-7 years (depend ing on the centre). or the control group, which received care as usual.'1 Most centres in th e tri al used a PSA cutoff value of 3 ~g/ L, with a positi ve screen result 1路\ arranting a biopsy. After a median follow-up of 9 years. th ere was no stati sti ca lly significant difference in pros tate cancer mortality bet11 een the men ass igned to th e screening group and the controls ( RR. 0.85 [95% C L 0. 73~1.00]) . However. in ;

I Spring 2013

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HEALTH PROMOTION prespecifi ed subgroup of 162 243 men aged 55 to 69 there was a signifi cant abso lute ri sk redu ction in prostate cancer mortality for the men ass igned to screening (RR. 0.80 [95% Cl, 0.65-0.98]).

REFE RENCES

Beyond the fact that th e resul ts of these t11 0 tri als do not prov ide u with a consi tent answer to the questi on of whether PSA-based screening redu ces prostate cancer mortali ty, the U.S. Preventi ve Services Task Force was som ewh at critical of the methods used in these trials. Both trials failed to exclude men who had had previou P A testin g, the PLCO tri al had substantial contamin ation of the control group (up to 52% of controls received a PSA test duri ng the trial). and the ERSPC trial used a range of PSA cut-off points (>2.5 to 4 11g/ L) and screening intervals depending on the centre."'

2. National Cancer Institute. Prostate-Specifi c Antigen (PSA) Test. Reviewed Jul y 24, 201 2. http://'"' 11 ll .ca ncer.gov/cancenooics/fact sheet/detecti on/PSA (Accessed on December I, 20 12).

The Task Force 路s dec ision-makin g was also influenced by harms associated with PSA -based creening. For exampl e. 75.9% of men who underwe nt a bi opS) because of an elevated PSA va lue in the ERPSC tri al had received fa l e-pos iti ve re ult .9 Complicati on of di agnosti c eva luations occurred in 68 o f I0 000 procedures in the PLCO trial. and in cluded bl eedin g. in fec tions. and urinary diffi cul ty' Given the un certainty surrounding the interim res ults of these two maj or tri als. it will be important to see whether longer-term foll owup of the study part icipants conveys a clearer message about whether PSA-based screenin g red uce morta lity. Eve n with the current evidence, the Task Force's strict recomm endation aga inst any PSA testin g for creening purposes has been criticized for preventing patients from being in vo lved in decision-making." In a ew England Journal of Medicine commentary written in response to the Task Force's report, Drs. McNaughton-Co llins and Barry (two prostate cancer speciali sts affi liated with Harvard Medi cal School and Massachusetts General Hospital) argued for a strategy simil ar to Ontari o's guidelines in which patients are made aware of the benefit s and harms assoc iated with PSA-based screening and are able to dec ide for themselves whether the potenti all y small benefit is worth it to th em. " However. they al so suggested that if physicians continue to order PSA tests for screening purposes they must do a better job of emphas izing the potenti al harm assoc iated with PSA testing. rather than touting onl y the benefits of screening. Phys icians must also make sure that th ey are not overtreatin g pati ents who might benefit more from a "watchful wa iting" approach.

Thus fa r. measurement of abso lute PSA level for the purposes of prostate cancer monitorin g and screening have been disc ussed. There are other measurements to increase screening specifi city that are currentl y being ex pl ored. A recent retrospecti ve cohort stud y eva luated the utility or a measure ca lled the PSA ve loc ity (P AV) ri sk count in 18 214 men enrolled in a prostate cancer screening study. 12 PSAV refers to the yea rly change in PSA units, and th e ri sk count is a mea ure of the number of times PSAV exceeds 0.4 11 g/L. A PSAV ri sk count :::: 2 (i. e. two consecuti ve yearl y increases in PSA leve ls exceedin g 0.4 11g/L) showed 96% specificity (compared to the reported 33% specifi city for the absolute PSA leveJ3) and was associated with a signifi cantl y in creased ri sk of prostate cancer (O R 8.2 [95% Cl. 7.0-9.6]). In thi s stud y. the odds ratio for prostate cancer determined by PSA level. in contrast. was onl y 1.25 (95% Cl. 1.22-1 .28). These results suggest that furth er in vesti gation or PSAV utility in prostate cancer screening is wa rranted.12 The US Nati onal Cancer Institute al so li sts PSA density of the transition zone (PSA le ve l di vided by the vo lume or the prostate 's transiti on zo ne) and age-specifi c PSA reference ranges as parameters under in vesti ga ti on for improve ment of PSA screening spec ificity.2 While these altern ati ve screening opti on are being in vesti ga ted, Ontari o's recomm end ation that patients hould be properl y informed about PSA testin g and encouraged to participate in deci sion-makin g seems appropri ate.

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I. Stenman U-H. Lei nonen J, Zhang W-M , Finne P. Prostate-specifi c anti gen.

Sernin. Cancer Bioi. 1999;9:83-93.

3. Holfm an RM . Gilliland FD. Adam s-Cameron M. Hunt WC. Ke y CR. Prostate- pec ifi c antigen testing accuracy in community practi ce. BMC Fam .

Pract. 2002 :3: 19.

4. Center MM, Jemal A, Lortet-Ti eul ent J. Ward E. Ferlay J, Brawley 0. et al.

Intern ational vari ati on in prostate cancer inciden ce and monali ty rates. Eur. Urol. 20 12:6 1(6) : I079-92.

5. Canadi an Cancer Society. Wh at you should know about PSA testing. March 4, 20 I0. http://www.cance r. ca/Canada-wide/Prevention/Getting%20checked/ What%20yo u%20s houl d%20 kn ow%20about%20 PSA %20testi ng.aspx?sc_ lang=en (Accessed on Nove mber 27. 20 12 ).

6. Ministry of Hea lth and Long-Term Care. Ontario Prostate Specifi c Antigen {PSA) Clini cal Guidelines - Summ ary. June 27. 20 12. http://www.health.gov. on.ca/englishlprov iders/pu b/cancer/psa/psa_summ ary/summary.htm I. (Accessed on Nove mber 27. 20 12).

7. U.S. Preventi ve Se rvi ces Task Force. Sc reening for prostate cancer. Jul y 20 12. http://www.uspreventi vese rvi cestas kforce.org/prostatecancerscreening.htm. (Accessed on November 27. 20 12).

8. Andri ole GL. Crawford ED. Grubb RL 3rd. Buys SS. Chia D, Church TR. et al. Monali ty res ults from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360( 13): 13 10-9.

9. SchrOder FH, Hugosson J. Roobol MJ, Tammela TL, Ciano S. Nelen V, et al. cree ning and prostate-cancer monali ty in a randomi zed European study. N Engl J Med. 2009;360( 13 ): 1320-8.

I0. Lin K, Croswell JM. Koe ni g H. Lam C. Maltz A. Prostate-Spec ifi c Anti genBased Screening for Prostate ancer: An Ev idence Update fo r the U.S. Preventi ve Services Task Force. Ev idence ynthes is No. 90. AHRQ Publication No. 12-05 160-EF-1. Rockvill e, MD: Agency for Healthcare Research and Quali ty; October 20 II .

II . McNaughton-Collins MF. Barry MJ. One man at a time - resolvin g the PSA controversy. N Engl J Med. 20 11:365(2 1): 195 1-1 953 .

12. Loeb S, Mener EJ. Kan D. Roehl KA. Catalona WJ . Prostate-specifi c antigen ve locity (PSAV) risk co unt improves the pecifi city of screening for clini cally signifi cant pro tate cancer. BJU Int. 20 12: 109 :508-14 .

UWOMJ 182 :1 I Spring 2013

INTERDISCIPLINARY

The living kidney donation process: role of the interdisciplinary team Yin Hui (Meds 2015) , Kyle Pangka (Meds 2016), and Alexander Yan (Meds 2015) Faculty Reviewer: Dr. Faisal Rehman , MD, FRCPC , M.Ed (Department of Medicine, Division of Nephrology)

I NT ROD UCTION End stage renal disease (ES RD ) is becoming an in creasingly preva lent illness in Canada. 1 Th e Canadi an Organ Replacement Register A nnual Report released by the Canadi an In stitut e for Hea lth In fo rm ati on (CIHI ) stated th at the number of Canadians I iving with ES RD has tripl ed from 1990 to 2009. 1 Unfortunately. the number of kidn eys donated has not kept pace w ith thi s increase in demand . In 2009. appro ximately 38.000 Canadi ans are li ving with ES RD. with 59% on di aly is. and 3.000 pati ents on th e transplant wait li st. 1 Th e increase in di alysis trea tm ent also comes w ith a ub tanti al cost to th e hea lth care system - th e estim ated cost for hemodi alysis is $60.000 per pati ent. per year. 1 Th e C I HI estimates th at a renal transpl ant saves th e health care sy stem $250,000 per pati ent over a fi ve-year peri od. 1 Due to th e shortage of cadaveri c kidn ey s. th ere has been an increase in using donati ons fro m li ving donors. often from an offspring. parent, or other geneti cally related family members. Donati ons from unrelated donors also make up 30% of th e donati on poo l. with a porti on being strangers to th e recipient. Several studi es have shown th at pati ents receivi ng li ving kidney donati ons from either geneti cally re lated and unrelated donors achieve better outcomes th an pati ents rece iving a kidn ey transplant from cadaveri c donors.u; Livi ng-donor transplantati ons have been shown to be assoc iated w ith a shorter time to transpl antati on, and results in a better long-term graft and pati ent surv iva l 6 A s a result of the in creasing importance o f li ving donati on, protocols have been deve loped to accommodate li ving donati ons: Li ve-Donor Paired Exchange, L ive-Donor/Deceased-Donor Exchange. and A ltruisti c Li v ing ondirected Exchange.2 In th e Li ve-Donor Paired Exchange. a donor-reci pi ent pair (th e pati ent req uiring a transpl ant, and a w illing donor who cannot prov ide a matching kidney) is matched w ith anoth er donor-rec ipi ent pair such th at a compatibl e donor-rec ipient exchange is made. Thi s matching proce ss, or chain , is continued until all rec ip ients receive a kidn ey.

In the Li ve-donor/ Deceased-donor exchange, a donor-rec ipi ent pair is reassigned such that th e live-donor is matched w ith a rec ipient already waiting on the deceased donor li st. In exchange, th e fi rst recipi ent is moved nearer to th e top of th e cadaver li st. Finally. th e A ltrui sti c L iving Nondirected Exchange is true to its name- th e kidn ey donati on comes from a generous person who is a stranger to th e rec ipi ent.

To prov ide suffi cient care for both th e donor and recipient. a large multidi sciplin ary team is required to address different facets of care, including processe of donati on. matching, and maintenance of care. Thi s articl e will di scuss th e li ving kidney donati on process, as well as th e role and importance of th e multidi sciplin ary team.

THE MATCHING PROCESS Th e Li ving Donor Paired Exchan ge is a program run through the Canadi an Bl ood Services that identifi es matches betwee n potential li ving

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ki dney donors and transpl ant recipients in Canada.7 M atching refers to th e tests carri ed out by clini cal scienti sts prior to transpl anta ti on to minimi ze th e ri sks of acute or delayed graft rejecti on. Thi s in vol ves ensuring the blood ty pe of th e donor and recipi ent are compatib le. testin g th e hi stocompati bil ity of th e donor kidn ey. and screening th e pl asma of th e rec ip ient fo r anti bodi es against donor ki dney cell s.8 To test fo r hi stocompati bili ty th e surface molecules pre ent on th e donor and recip ient cell s. specifically hum an leukocyte antigen ( l-I LA) complexes. are compared and assessed f or simil arity." Hi gher simil arity bet\veen donor and recipient l-ILA complexes are associated with increased long term surviva l rates. and a decreased chance that th e immune system of th e recipient w ill identi fy th e donor cel ls as foreign." In dividuals may have antibodi es against l-I LA complexes circul atin g in their blood due to past transpl ants. pregnancies. or bl ood transfusions where th eir immune system was exposed to foreign human cell s. 111 T hi s is w hy the pl asma of recipi ents must be screened for antibodi es targeting donor ce ll s pri or to transplantati on in a process kn own as cross matchin g. 1"

THE LI V ING KIDNEY DONATION PROCESS In thi s secti on we wi ll focus on several components of th e organ donation process in cluding assessment of th e li ving donor. in fo rm ed consent. and fo llow-up. T hese steps typically in vo lve th e presence of a transplant coordinator. physician. social worker. psychologist or psychi atri st. and surgeon. Furthermore. throughout th e entire process th ere i usually a designated li ving-donor advocate who is ex peri enced in th e fie ld o f transpl antati on. T he advocate can be a soc ial worker. coordinator. psycholog ist. psychi atri st. or physician. Thi s advoca te shoul d advi se th e donor independent fro m rec ipi ent interests.2

Assessment of the living donor T he proces fo r determinin g donor accep tabi l ity may vary between transplant programs. According to gui delines outlined by the Mu ltiOrgan Transpl ant Program of th e Uni versity Hea lth Network ( UI-IN) in Toronto, separate hea lth care teams assess potential li vi ng donors and rec ipi ents. Idea lly, thi s would include eac h donor and recipi ent w ith hi s/ her own physician. coordin ator. soc ial workers. and psychi atry staff.

Thi s is done to avo id potenti al conflict of interests. T he criteri a for assessment include low medica l/surgica l ri sk, ability to give inform ed consent. realisti c ex pectati ons of donati on. vo luntary moti vati on. and suffi ciency of economi c. practi ca l. and emoti onal re ources to cope w ith th e donati on process. 17 The assessment process includes a ful l physical eva luati on to ensure th at th e donor is hea lthy and th at th ere are no maj or ri sk factors th at would lead to renal di sease in the future. Th e donor is also evaluated for psychological and soc ial barri ers to donati on 2 T his process requi res in vo lvement from all members of th e multidi sciplinary team. Similar processes ex ist aero s Canada wi thin other multi -organ transpl ant centres.

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INTERDISCIPLINARY In th e case of a di spute wi th in th e transplantati on team about th e suitabi l ity of a potenti al donor. th e team may rev iew the criteri a used to measure suitability. A dditional sources of input may inc lude advi ce from other pro fessional members of th e staff, ho pita! ethics serv ices. legal coun el. hospital admini strati ve resources. or outside hospital consultati on.1 7

Informed consent Inform ed con sent in vo l ves confirming th e pati ent's capacity to understand and consent. di sc losing inform ati on about th e proposed procedure. and ensuring vo luntarin ess. In th e contex t of organ donati on thi s in vol ves a detailed discuss ion of th e ri sks and benefits to th e li v ing donor and rec ipient. T he potenti al donor sho uld be inform ed about altern ati ve treatm ent opti ons for th e recipient as we ll as th e poss ible impact o f donati on on the donor 's lifesty le. famil y relati onships. fin ances. future empl oyment. and abil ity to rece i ve li fe insurance. Donor and rec ipi ent are ty pi call y prov ided w ith general info rm ati on and detail s on programspec i fi e outcomes. 17 Wh en a donor appears undecided. co un selling can be offered by a social wo rker or psychiatri st to assist th e po tenti al donor to so lve problems and address psychosoc ial aspects of thi s dec ision such as emoti onal issues and how to in fo rm others. Potenti al donors should be in form ed that th ey can wi thdraw from th e process of donati on at any tim e w ith th e full support of th e ITanspl antati on team. A cru c ial part o f th e assessment proces is to ensure th at th e donor is makin g his or her dec ision free from coerci ve or manipul ative intluences n

Follo111-up It is important to evaluate donor and recipient exper iences in cluding medica l. psychosocial and economi c outcom es. Accordin g to U HN guidelines, early and late morbidi ty, graft functi on. mortali ty rates and m easures o f recipient and donor sati sfac ti on are docum ented in an annual rev iew. In th e event th at a donor requires furth er ca re, appro pri ate care is arranged. 17 T H E IMPORTANCE OF THE I NTERDI SC IPLI NA RY TEAM As outl ined by th e prev ious sec ti on, th e interd isciplinary team plays a cruc ial role in every step of the donation process. In additi on, th ere has been a growing body of ev idence show ing th e benefit o f interdi sciplinary in vo l ve ment on quali ty of pati ent care (bo th donor and recipi ent). pati ent sati facti on and surv iva l. In parti cular, a paper by Win sett and Hath away identifi ed three areas of interventi on th at w ill increase the pati ent 's quality o f life post-transpl ant: post-tran plant adverse events. employm ent. and social support. 11 Literature has shown intcrdi ciplinary team s have been benefi cial for prov iding support fo r th e pati ent and th eir family pre- and po !-transplant. A t th e Q ueen Eli zabeth II Hea lth ciences Centre in Hali fax. it was shown th at a mu ltidisc ip linary k idn ey di sease clinic co nsi ting of nephrologists, nur e educator and dietiti ans was able to improve metabo lic and blood pressure co ntro l, and fac ilitate th e use o f peritonea l d ialys is in late referrals for pati ents w ith chronic kidn ey disease. 12 In a study by Fonouni , Go lriz, M ehrabi . et al. , an interdi sciplinary team con sistin g o f a transp lant surgeon, a nephro logi t, a pediatri cian, a radi ologist, a psycho logist. a tran plant coo rdin ator. and a transp lant nur e was shown to have improved staff communicati on. pati ent outco mes and satisfac tion w ith th e hospital stay. 13 Several studies also showed an increase in favo urable mental and phy sica l outcomes post-transpl ant w ith the in vo l ve ment of an in terdi sc ip linary team. 14路15-1"

C ONC L US ION Th e increasing prevalence o f end stage renal di sease and th e shortage of cadaveri c kidn eys underline th e growing importance o f li v ing kidn ey donati on. However, li ving kidn ey donati on is a complex proce s th at

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merits carefu l ethi cal considerati on . T hi s process in vol ves co llaboration between multiple health care professions on the side o f the don?r and the recipi ent. Health care workers should ha ve an understa nding ot drfferent aspects of support th at are in vo l ved in kidn ey donation in order to Illform others and alleviate anx i ety surround ing kidn ey donation . Several studi es have already dem onstrated th at the current shift to w ard s a more integrated and multidi sciplinary approach in kidney transp lantation improves pati ent care. sa ti sfacti on. and surv i val. Th erefore it should be made clear th at the preparati on and ultim ate outcome of kidney tran splantati on does not depend solel y on the efforts of a nephrologi st or transplant surgeon. but rath er a team effort.

REFERENCES I . Canadian Institute for Health Inform ation. Canadian Organ Replacement Register A nnual Report. 20 11 Jan [cited 20 12 Dec 7] :(14 0 p.]. Avail abl e from: hnps://secure.cihi .ca/free_products/20 II _CORR_A nnual_ Report_ final_e.pd f 2. Dav is CL, Delmonico FL. Living-donor kidney transpl antation: a review of current practi ces for the I ive donor. Nephrol Dial Transpl ant. 1998 Jul : 13(7): 1799-803.

3. Terasaki PI , Cecka JM. Gj ertson DW, Takemoto S. High survi val rates of kidney transplants from spou al and li ving unrelated donor . Engl J Med. 1995 A ug I 0:333(6):333 -6.

4. Asderak is A. A ugustine T, Dyer P, Short C. Campbell B. Parrott N R, John son RW. Pre-emptive kidney transpl antation: the attracti ve altern ati ve. ephrol Di al Transpl ant. 1998 Jul : 13(7): 1799-803.

5. Roozbeh J. Mehdi zadeh AR, lzadfar MA . Razmkon A. Salahi H. M alek-H osseini SA . Comparison of spousal with other donor groups: Study of a single center. Transplant Proc. 2006 Mar:38(2):562 -3.

6. Meier-Kriesche HU. Kapl an B. Wa iting time on dialys is as the strongest modi fiabl e risk factor for renal transpl ant outcomes: a paired donor kidney analys is. Transpl antation 2002 : 74: 1377- 138 1.

7. Jimenez M, L iving donors help strangers get a second chance. The Globe and Mail 20 12 Sept 6: 8. Gelllry SE. Montgomery RA. Segev DL. Kidney paired donati on: fundanlentals.

9. limitations. and expansions. Am J Ki dney Dis. 20 11 Jan:57( 1): 144-51.

I 0. Cccka JM. Signi ficance of hi tocompatib ility in organ transpl antation. Current Opin ion in Organ Transpl antation 2007 : 12(4):402-408.

II . M ulley WR. Kane!lis J. Understanding crossmatch testing in organ tran spl antati on: case-based guide for the general nephrologist. Nephro logy (Carlton). 20 II Feb: 16(2) : 125 -33 .

12. Winsett RP, Hath away DK. Predictors of QoL in renal transpl ant recipients: bridging the gap between research and clinical practi ce. Pos ttransplant Quality of Life Intervention Study Group. ANNA .1 . 1999 Apr:26(2):235 -40.

I 3. Thanamayooran S. Rose C, 1-1 irsch DJ . Effectiveness of a rnultidi scipl inary kidney disease clin ic in achieving tTeatment guideline targets. Nephrol Di al Transplant. 2005 Nov:20( II ):23 85-93 .

14. Fonouni H, Golriz M, Mehrabi A , Oweira H. Schmied BM, Mu ller SA, Jarahian P. Tahmasbi Rad M, Esrnaeil zadeh M, Tonshotr B, Weitz J, Boehler MW, Zeier M, Schmidt J. The role of an interdi sciplinary transplant team on I iving donation kidney transplantation program. Transplant Proc. 20 10 JanFeb:42( 1): 137 -40.

15. Ehlers SL, Rodrigue JR. Patton PR, Lloyd-Tumer J. Kaplan B. Howard RJ . Treating tobacco use and dependence in kidney transplant recipients: development and impl ementation of a program. Prog Transplant. 2006 Mar: 16( I ):33- 7.

16. Porter GA . Renal rehabilitation: effecting improvement through the team approach. Nephrology 1997 :3(3):22 1-9.

17. M artin JE, Zavala EY. The expanding role of the transplant ph armacist in the

UWOMJ 182:1 I Spring 2013

INTERDISCI PLINARY mu ltidisc iplinary practi ce oftran pl antation. Clin Tran pl ant. 2004 : 18 Suppl 12:50-4.

18. Wright, L. , Faith. K ., Ri chardson, R., Grant, D., & Joint entre for Bioethi cs, University of Toronto, Toronto, Onl. (2004). Ethica l guidel in es lo r the evaluation o f li v ing organ donors. Canadian Journ al of Surgery.Jou rnal Canad ien De Chirurgie, 47(6), 408-4 13.

MEDICAL

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MEDICINE AND TECHNOLOGY

The future of surgical robotics Lau ra Callan , MASc (Meds 2015) and Nancy Chen , BSc (Meds 20 16) Faculty Reviewer: Dr. Stephen Pautler, MD, FRCSC (Department of Surgery, Division of Urology)

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obotic surgery is a growing technology w ith th e potential to revolutioni ze surgical procedures. especia lly in th e field of urology. Urology is at th e forefront of advances in thi s field. and has integrated robotics into many procedures includin g rad ical cystectom ies. surgical nerve grafti ng and pyelop lasty. 1 Robo ti c surgery has almost enti rely taken over rad ica l prostatectomy and th e role of robotics is conti nuous ly expanding. Robotic surgery helps improve patient outcome b) minimizin g th e surgeon's movement tremors. increasin g range of motion. decreasing blood loss. decreasing length of hospital stay. and decreasing post-operati ve pain u Since the field of Urology deal s wi th very difficu lt and delicate procedures. robotics offe rs an advantage by allowing for greater accuracy. flexibi lity, smoother action s, and greate r range of motion.

An important area of advancement for surgical roboti c is in the field of imaging and vi sual feedback . Robotic surgery can be performed either with a surgeon con trolling the robot such as is done w ith the da Vinci system to perform robotic-ass isted radical prostatectomies (R'ARPs). or autonomou ly based on a predetermin ed algorithm such as in th e case of rad iosurgery for pituitary adenomas.â&#x20AC;˘ While autonomous robotic systems offer higher prec ision, and ti ssue-damage avoidance. surgeon-controlled systems are much better at decision makin g in unstructured or chaoti c situations. For th e surgeon contro lling th e robot. vi sual feedback can be attained using endoscop ic ca meras; however. for au tonomous procedures. the con trol program req uires much more detail about the patient 's anatomy.

General ly speaking. there are tw9 type s of imaging performed for roboti c surgerie : pre-operati ve and intra-operati ve. Pre-operative imaging is acqu ired before a procedure and u ed for surgica l planning to locate pathologies. a feed-forward system . In computer-guided systems thi s can be prob lemat ic since th e images which are used fo r instrum ent nav igation are based on ti ssue locati on at the tim e of imaging. However. in strument deflection caused by instrum ent-ti ssue interac ti on as wel l as ti ss ue movement can mean that the instrum ent positi on is not as preci se as is desirab le. Thi s is especially problemati c when dealin g w ith small er anatomi ca l targets. such as vascul ar surgery and in paediatrics.' Intraoperat ive imaging is used to provide close to rea l-tim e feed back. thereby closing the feedback loop and all ow ing for adjustm ents throughout th e proced ure. While tor surgeon control led roboti c , surgeons have th e fl ex ibility of compensating via visual feed -back, for autonomous computer-controlled systems thi s cannot be as easily imp lemented due to th e need for code to interpret th e vi ual feedback into a con trol for th e robot.

Resea rch into methods of providing a closed- loop feedback system wh ich takes into account instrument deflection and ti ssue move ment has been carri ed out u ing vari ou approaches. M eth ods of measuring in strument position include computer vision techniques, 6 and electromagnetic sensor sy tems. 7 Thi s inform ation th en needs to be integrated

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into the computer control ystem to al lo w for changes in position as the surgery progres es. Thi s has been achieved using Direct Image Guided Interventi on (D IGI) robots. These robots use pre-operative images to locate targets and create an initial nav igation protocol. They are also connected to an im agi ng modality which all ows for real-time adjustments to thi s protocol. providing greater accuracy and prec ision than a feed -fo rward system. Some challenges to DIGI include compatibility bet\\ een robot and imaging modality such as MRI which has a dense magnetic field. and most components of the robotic system cannot be safe ly used in proximi ty to the magnet. Oth er problems include spatial re so lution, and exposure to radiati on if fluoro copy or CT is used 8 The Robarts Research Institute at Western Universi ty is investi gating the use of two-dimen siona l transrec tal ultrasound (TRUS) to create three-dimensional real-time im ages by sweeping the probe about its axis. This technology has been combined with surgeon operated roboti c surgery for urologic procedures such as prostate brachytherapy or biopsy. 9 Another area of research wi th the potential to improve computer ass isted surger) is haptics. Hapti cs is the general term used for touch feedback. Thi s includes both tactil e feedback (i.e. temperature, vibrati on. tex ture. etc) and kinaesthetic feedback (i .e. force and position ).

The majority of th e work done regardi ng haptics in surgical roboti cs is surrounding kin aesth etic feedback. rather th an tactile feedback. 10 A known dra\\ back of robot ass isted minimally invasive surgery using such surgica l robots is th e lack of haptic feedback . 11 â&#x20AC;˘ 13 This drawback has been fou nd to be most limiting during compl ex tasks and can lead to difficulty identifyi ng ti ssue ba ed on consi tency (i.e. between normal and tum our ti ssue) and su ture breakage during knot ty ing. 14¡ " The reason for th e lack or hapti c feedback in such system s is simple: th e technology required is incredibly comp lex. The problem of providing hap ti c feedback can be broken down into two di stinct tasks: measuring the interact ion to rces and di splaying these to rces to the surgeon.

Measuring of interacti on forces during roboti c surgery has been attempted in a few different manners. Retrofi ttin g ex istin g surgical manipulators with commercially avail ab le force senso rs has been attempted; 19 however. constraints regarding size. geometry, biocompatibi li ty, steri lizab ility and cost have limited thi s approach. 11 ' Another method is to use th e distance betwee n desired posit ion and actual position of the manipulator to determine force interactions between th e manipul ator and the environment. Th is meth od has been imp lemented with some success; however. it is limited by the non-ideal nature of the robot and the environment. meaning th at fri cti on and other dynami c forces are di fficult to account lo r and can be large in comparison to the interaction fo rces between th e manipu lator and th e pati ent. IO.lo Methods of prov iding feedback to th e surgeon include direct force feedback where motors in th e robot contro ls are programmed to recreate th e forces sensed by the manipu lator, and the use of other sensOJy

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MEDICINE AND TECHNOLOGY feedback such as audio or visual feedback to represent th e forces ex peri ence d by the surg ica l in strum ent. Th e first meth od i th e mo t co mmonl y impl em ented meth od : 11 ' however. enabling a system to prov ide force feedback in all directi ons actu ated by the system ( i.e. six degrees o f freedo m plu s g ripping ) i not possible\\ ithout impl em enting a second feedback system n U e o f motors to prov ide feedbac k also introdu ces th e poss ibility o f feedback instability w hich ca n lead to uncontro lled osc illati on . an o bv io usly undes irabl e event during surgery' " To get around th ese pro bl em . va ri o u gro ups have attempted to impl ement feedback system s using visual or aud io di spl a) s o f fo rce. 1 ~ - 13 - 1 ' T hese system s have experi enced som e uccess and have potential fo r further impl em entati o n as long as th ey do no t interfere with th e surgeon路 v iew of th e ti ssue thro ug h the v ideo displ ay o f th e endoscopi c cam era. 1" Robotic surgery allo w s prec ise and repeated m oti ons w ith decreased fa ti gue, m ooth er acti ons and increased accuracy. fl ex i bilit). and range of moti on. especi ally in sm all confined anatomica l locati o ns such as th e male pel v is during pro tate surgery. H owever, there are still limitati ons in v isual and hapti c feedback . Th ese limitations. as we ll as training o f surgeons. have stunted th e g ro wth o f thi s fi eld in om e ways: however. as described. intensi ve re earch i s underway. It is c lear th at in certain situati ons. it is be t to rely on image g uidance, allow ing th e surgeon to be guided by more th an w hat is vi sible through th e vi sual fi eld . For thi s to happen. imaging m odaliti es whi c h allow for greater compatibili ty w ith th e surg ical robot w hile m aintaining as lo w radiati on dose to the pati ent and surgeon as possibl e will need to be deve loped beyond th e current techno logy. Similarl y. to ben er enabl e thi s ph ys ic ian to identify spec ific ti ss ues. hapti c techno logy and its implementati on into surgery w ill also need to be furthered . As th ese techno logies becom e increa ing ly incorporated in th e fi eld of surg ica l robotics. we can ex pect rapid growth in th e number of surgeri es to m ak e th e transition from traditional to roboti ca ll y -assisted or even full y autom ated.

REFE RENCES I. K umar R, Hemal AK . Emerging role of roboti cs in urology. J Minim Access Surg. 2005 Oct: 1(4): 202 -2 10.

2. Ahlering TE, Woo D. Eichel L. Lee Dl, Edwards R. Skarecky DW. Robotas isted versus open radical prostatectomy: a comparison of one surgeon 路s outcomes. J Urol. 2004 May; 63(5): 8 19-822.

3. Patel VR. Chamm as MF, hah S. Roboti c assisted laparoscopi c radical prostatectomy: a review of the current state of affairs. lnt J Clin Pract. 2007 Feb: 6 1(2): 309-3 14.

4. Moustri s GP, Hirid is SC. Deliparaschos K M , Konstantinidis K M . Evolution of autonomous and se mi-autonomous roboti c surgical sy tems: a rev iew of the literature. lnt J Med Robot Comp. 20 II Dec; 7(4): 375 -392.

5. Kimura T, Sakuramachi S. Yos hida M , Kobayashi T, Takeuchi Y. Laparoscopi c cholecystectomy using fine-caliber instruments. Surg Endosc. 1998 Mar: 12(3): 283 -286.

Curr Opin Urol. 2009: 19( I ): I 02-1 07.

II . Vi ve kananda U, Henderson A . Murphy DG . A lthocfer L. Seneviratne L. Dasgupta P. The science behind haptics in robotic urological surgery. BJ Int. 2009 A ug: I 04( 4): 433 -434.

12. Bark 1\., M cM ahan W. Remington A. Ge1-1irtz J. Wedmid A. Lee Dl. K uchenbecker K.l . In vivo vali dation of a system for haptic feedback of tool vibrati ons in ro boti c surgery. Surg Endosc. 20 12 Jul. 13. Freschi C. Ferrari V. Melfi F. Ferrari M . Mo ca F. Cuschieri . Technica l rev ie11 of th e da Vinci surgicaltelemanipulator. lnt J Med Ro bot. 20 12.

14. K itagawa M . Dokko D. Okamura AM. Yuh DD. Effect of sensory sub titution on suture-m anipul ati on forces for roboti c surgica l systems. .I T horac Cardi avase Surg. 2005 .Jan : 129( I ): 151-1 58.

15. Th oley G. Desai JP. Castellanos AE. Force feedback pl ays a signi ficant ro le in minimall y in vasive surgery : results and analys is. A nn Surg. 2005 Jan: 2-t I ( I ): 102- 109.

16. .Judkins TN . Oleynikov D. Stergiou N. Real-time augmented feedback benefits roboti c laparoscopi c training. Stud Health Technol Inform . 2006: 11 9: 243-248 .

17. Diks J. Nio D. Linse n MA . Rauwe rda JA . Wissel ink W. Suture damage during robot-assisted vascul ar surgery: is it an is ue? Surg Laparosc Endosc Percutan Tec h. 2007 Dec: 17(6): 524 -527.

18. Ricchiuti D. Cerone J. ShieS. Jetl ey A, Noe D. Kovacik M . Diminished suture strength after roboti c needl e dri ver manipul ation. J Endourol. 20 I 0 Sep; 24(9) : 1509-1 5 13.

19. Dargahi J. Sedaghati R. Singh H. aj arian S. Modeling and testing of an endoscopi c piezoelectri c-based tactil e sensor. J Mechatron. 2007: 17(8) : 462-467.

20. Mavash M , Okamura AM . Fri cti on co mpensation for enhancing transparency of a teleoperator with co mpli ant transmission. IEEE T Roboti c A utom. 2007 23(6): 1240- 1246.

2 1. Semere W, Ki taga11 a M . OkamuraAM . Te leoperati on 11 ith Sensor/Actuator Asymmetry: Task Perform ance with Parti al Force Feedback . 12th Symposium on Haptic Interfaces for Virtual Environments and Te leoperator Systems. 2004: 12 1-1 27 .

22. Verner LN. Okamura A M . Effect of tran slati onal and gripping force feedback are decoupled in a 4-degree -of-freedom telemanipulator. Second Joint Eurohapti cs Conference and Symposium on Haptic Interface for Vi rtual Environment and Te leoperator Systems (World Hapti cs). 2007 : 286-29 1.

23 . Okamura, A M . Methods for hapti c fee dback in teleoperated ro bot-as isted surgery. lnd Rob. 2004 Dec; 3 1(6): 499-5 08.

24. Schoonmaker RE. Caroline GL. Vibrotac til e force feedback system for minimall y invas ive surgical procedures. IEEE Sys Man Cybern . 2006: 2464-2469.

25 . Tavakoli M , Aziminej ad A . Patel RV. Moall em M . Methods and mechanisms for contact feedback in a robot-a sisted minimall y in vas ive environment.

Surg Endosc. 2006 Oct; 20( I 0): 1570- 1579.

6. Lee C. Wang YF. Uecker DR, Wang Y. Image analys is for automated tracking in robot-assi ted endoscopic surgery. omput Vis Image Proc. 1994: 88-92 .

7. Ri ener R, Rasmus W, Feuss ner. Acquisition of arm and instrument movements during laparo copi c interventions. Minim Invasive Ther Alli ed Techno!. 2003 Sep; 12(5) : 235 -24 0.

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8. Wei Wan G. Gardi L. Mills G. Downey D. Fenster A. Robot-ass isted 3DTR us' guided prostate brachytherapy: system integration and validation. Med Phys. 2004 Mar: 3 1(3 ): 539-548 9. Dimaio S, Kapur T, Cleary K, Aylward S, Kazanzides P, Vosburgh K, Elli s R. Duncan J. Farahani K, Lemke H, Peters T, Lorense n WB, Gobbt D, Hailer J. Clarke LL, Pize r S, Taylor R, Gall oway R Jr. Fichtinger G, Hata N, Lawson K, Tempany C. Kikinis R, Jolesz F. Challenges in image -guided therapy system design. Neuroimage. 2007 A pr: 37.

10. Okamura AM . Haptic feedback in robot-ass isted minimall y invas ive surgery.

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PROFILES

Interview with Dr. Faisal Rehman Joyce Zhang (Meds 20 15) and Sissi Cao (Meds 2016) Faculty Reviewer: Dr. Faisal Rehman MD, FRCPC , M.Ed (Department of Medicine, Division of Nephrology)

!epping into Dr. Faisal Rehman·s office. \\e could not help but notice the count ies degree s. teaching award s. photographs and thank-y ou notes th at decorated hi s wa ll s. On a Friday aftern oon. we were luc!..··y to sit down and speak with the di stingui shed clini cian. teacher and boxer at the Schu li ch School of Medicine & Dentistry.

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A s the Nephrology Site Chief and the Director of Intern al Medicine clerkship program at ni versity Hospital and chair of th e ge nitourinary block in the first-year curri cu lum . Dr. Rehman has a longstanding history \~ith Western Uni versity. After completing a Bachelors degree in pharm acology at the Univer ity of A lberta and a Medical degree at Queen·s Uni versity. Dr. Rehman began his training in internal medicine at Schuli ch . He comp leted his nephrology fellowship in 200 1 and wen t on to pursue a Masters of med ica l educati on at th e University of Toronto. Dr. Rehman returned to Western Uni versity where he has since establi shed a rewarding and successful academic medical career.

Dr. Rehman developed a fascinati on with medicine at a young age under the influence of fa mil y and friend s in the profession . He set hi s mind on internal medicine after expl oring clinical observerships but admitted that choosing a specialty was a more difficu lt challenge th an being accepted to medical schoo l. Dr. Rehman recognized near graduati on that intell ectually stimu lation through problem solving was what he enjoyed most in med ici ne, leadi ng him to choo e a residency in internal medicine. Intern al med icine·s range combined with Dr. Rehm an·s interest in longitud in al care ultim ate ly drew him to th e fi eld of nephrology. He loves nephro logy. he tell s us. because it involves comp licated physiology, offers diversity - from transpl ants to glomerul ar nephritis to diabetes- and all ows him to help patients in va riou s stage life: from disease in the outpat ient clini c to dialysis, to transplan t, to tran splant failure and return to dialysis.

When asked about th e future direction of research in hi s fi eld. Dr. Rehm an says he see s portab le art ifi cial kidneys helping restore independence and improve quality of life fo r th e chronic hemodi alysis pat ients he works closely with . l-Ie is hopefu l new kidney technology cou ld be translated into clini cal practice since dialysis is an inconveni ence and unpl easan t experience for patients. In addition. Dr. Rehman believes th at th e delivery of care need s to be altered to accommodate th e in creasing prevalence of chronic kidney di sea e. .. Unless we can have novel in venti ons like th e artifi cial kidney, I see our dia ly si populati on exp loding. I see ou r CKD (chronic kidney di sease) cl inics being overw helmed. Unfortunately di sease prevention has not gotten a lot of hype."

A s for what he enjoys most abou t hi s career. Dr. Rehman 's respon se was trongly echoed by the awards on his wa ll s: ·' t love to teach:· he says. and especially being around students to teach them in the early stages of th eir careers. In add ition to trad iti onal teaching in th e clas sroom. he has served as hon orary president of the Hippocrati c student

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co unci l and oth er class co uncil s. Even his research interests complemen t med ica l educati on. The projects he has overseen have included artificial kidney modeling. training renal fellows and developing nephrology related research filters. In hi s words... the best reward is to see a student mature and develop to the point they know more than you. And t·ve seen th at in my students who are now consultants who have really excelled in research or medical ed ucati on. It makes you proud that you have con tributed to that person developing.·· We could not leave Dr. Rehman's office without sati sfying our cu rio ity about hi s chari ty boxing career that lent him th e name King Faisal.

Outside of medicine. the physician indulges in boxing, which he enjoyed watching as a child and training in as a youth. When the department needed to raise money fo r kidney research 5 years ago, Dr. Rehman volunteered to rai se money fo r the Kidn ey Clini ca l Research Unit, thinkin g at the tim e. .. I f t·m goi ng to do thi s. I w ill do my kind of event.'' With th e help of a friend who was an internati onal boxing champion. the first Knock Ou t Kidney Di sease annual gala was put together in a little over a year in 2008. Not only did Dr. Rehman mastermind the organization of the even t. he also trained to fight in the ring in order to rai se more money. His initi ati ve and training paid off in a huge way : the event has rai sed over $600 000 over th e past 4 years for th e Kidn ey Clinical Research nit and the Mathew Mailing Cen tre for Transitional Transplant Studi es at Un iversity Hospital.

Dr. Rehman also shared with us one of hi s most memorab le pati ents, w hi ch was an incredible case of hum an resilience. Thi s pati ent was Ms. AL. a single moth er of five you ng children.\\ ho suffe red from sy stemic lupus er) th ematous ( LE) and presented wi th severe skin rash. hematouri a. and proteinuria. Even though her kidney disease of membranou s lupus nephritis was initial!) managed accordin gly w ith immunosuppressant • she started to develop severe hemoptysis secondary to lupus vascu liti s of th e lungs. She experienced further worsening of kidney functi on (acute kidney inju ry) and required multip le transfu sions of 20 to 30 units of blood. A ny further management of immunosuppression and plasmophoresisju t seemed to make matters worse. She had a pro longed hospital stay of 2 months, deve loped myocarditi s and lost a sionificant amount of weight that severely lim ited her mobility. But just \~hen the story could not get any worse. the pati ent sudden ly got better. She started to recover after Dr. Rehman stopped one o f her immunosuppressive med rcatr ons. Now. she leads an active and fu ll li fe, does charity work for a lupus society and is healthy enough to trave l all over th e world. Dr. Rehman can only speculate that perh aps the powerfu l immunosuppressron meant to contro l her lupus had essentially functiona lly ablated her bone marrow as a side effect. It was a memorabl e case for him because she had been so close to death but then spontaneously got better with no more signs of lupu . l-Ie says, ·'this case helped to reinforce that 1 need to constantl y re-evaluate w hat I ' m doing, and to not stick to a recipe. It

UWOMJ 182:1 I Spring 2013

PROF ILES

made me realize th at medicine is an art for some pati ents."'

For any medical stu dents considering the fie ld of intern al medi cine and perh aps nephrology. Dr. Rehm an has some words of w isdom to offer. .. In my opin ion nephro logists are the classic interni sts. T hey have to k n o\~ everyth ing about the body."' he says. A nephro logist is someone who enjoys compl icated physio logy and longitudi na l care of pati ents. eph ro logist work in a unique fie ld where pati ents can never be signed off. T hey may need to be fo llowed from age I 0 to 12 years old until death and everything in between: from dialysis. a transpl ant. back to dialys i . and th ro ugh fami ly catastrophe. Lastl y. he tell s us th at. " th e fi rst few year of medical school are not conducive to learning about what you want to do when you grow up. What I found help ful is to really max imize th e opportun ity to do observerships to get a fl avour of what's invo lved to make a better decision. Tryi ng to narrow it down between surgery and med icine up front may be help ful."

A lthough many clin icians lead rewardin g academi c medical careers. few can claim th eir stud ents know th em as King Faisal. Dr. Rehm an exemplifi es how extensive a phys ician's in vo lvement in medicine can be. Hi s in vo lvement in pati ent care. medi ca l educati on. stud ent initi ati ves. research and fundraising all refl ect his di verse passions and speak to hi s abili ty to maintain balance in his life and career. It is cl ear that Dr. Rehman loves what he does and his pati ents and tudents clearl y appreciate all th e tim e he gives.

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THINKING ON YOUR FEET

Fever with incontinence in the elderly: an approach for emergency medicine Anthony Chow (Meds 2016) and Elaine Tang (Meds 2015) Faculty Reviewer: Dr. Derrick Pringle, MD , FRCPC (Division of Emergency Medicine)

72-year-old man develops a high fever and is taken to the ER by hi s conce rn ed w i fe and daughter. During th e intake interview. he w i fe report th at th e man is experi encing worsening incontinence and occasionally complain s of dysuri a. Past medical record s indi cate th at th e man is alread) being treated and fo ll owed f or hypertension and early A lzheimer 路 di sease. but th e wife notes th at it has become increasingly di ffic ult to manage her husband 's confusion over the past week.

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duce a list of medi cati ons th e pati ent is takin g currently (ch lorthalidone and rami pril for hypertension. galantamine for dementia, cyclazine for nau ea. loratadine for seasonal al lergies) and confirm th at thi s degree of confusion is hi ghly aty pical. Unexpected change in cognitive status is a hall mark of pain in dementi a so I 000 mg acetaminophen is ordered.; aft er establ ishi ng th at th e pati ent would have no kn own allergy or drug interac ti ons. Vital signs are assessed and no abnorm al ities beyond high blood pressure ( 145/90) and high oral temperature (40.5 掳C) are found.

A n emergency physician receives th e above inform ati on from the tri age nurse. Th e nurse adds th at th e man and hi s family have been 1\ ailing for two hours and all three appear qu ite distressed. How could such a situation be managed?

SIGNS OF I NFECTION I N THE ELDERLY

GERIATRICS AN D DEMENT IA: CONSIDERATIONS FOR THE BEDSIDE The age of a patient carri es important implica ti ons for pati ent assessment and treatm ent. Th e phy siology of a hea lthy. older adult adapts to functi oning w ith tissues th at have deteri orated with age. achi eving a state of compromi sed balance term ed homeostenosis. ' Pati ents in thi subpopulati on thu s have a reduced capacity to respond and adapt to th e stresses brought on by ac ute illness and are more vulnerable to such insults.

Thi s affects patient assessment. as it may be diffi cult to di stingui sh symptoms of underl y ing disease from th ose of acute ill ness. Determining th e pati ent"s medical hi tory. current medi cati on regim e and soc ial circum stances is also chall enging in an emergency scttin g 2 Prospecti ve treatm ents are limited in th at th ey must not exacerbate or interact w ith existin g conditi ons and treatm ents. Polypharm acy, in parti cul ar, di proporti onately affects th e elderl y and contributes to increased adverse drug events. ph ysician visits, emergency admi ssions and hospital isati ons3 All th e above can be further comp li cated by dementi a in th e pati ent.

Th e pati ent's history may need to be obtained from fami ly members or caregivers present in th e ER or staff at a care faci lity, potenti ally leading to mi stakes in interpreting symptom severity or mi sing incipi ent problems entirely. Furtherm ore, th e pati ent may be unwilling or unable to participate in diagnosti c or intervent ional measures th at become indicated through the co urse of care.'

Pain management is especially diffi cult and no less important for pati ents w ith dementia. Th ough not ideal. prim ary care physicians must take care to detect surrogate mark ers of pain , uch as confusion. gesturing or posturing. through th e ph ysical examinati on.'

Returni ng to th e case, it is determ ined upon examin ati on that the pati ent does not have the capac ity to make hi s own medical dec isions when he is unable to g ive hi s own name. Fortun ately, his wife and daughter are attenti ve and meticulous prin cipal caregi vers. On request, they pro-

26

Fever as a sign of in fecti on can operate quite differently in older adults.

Agei ng-m ediated impairment of th erm oregulati on means that fever can fai I to occur in up to hal f of elderl y persons. despite the ex istence of I ifethreatening infecti on. Even norm al body temperature can be lower than expected in th e elderly and even lower in th ose with dementi a due to the same age-related changes.'路 G iven th e above. the fi nding of feve r in th e pati ent is a definite ca use for conce rn . A n expl anati on for thi s sign is sought in th e next prominent set of symptom : worsening incontinence and dysuria.

U RI NA RY I NCO TINENCE: DIFFERE NTIAL DIAGNOSIS Age is the greatest determin ant of urinary incontinence ri sk . Many factors th at negati vely affect norm al micturi tion are more likely to occur v. ith increasing age. With respect to transient incontinence. these include urinary trac t infec ti ons (UTl s). genitourinary muscle path ology, acute i llncsses th at mandate immobi I isation or cath eteri sati on, fecal impac ti on, medicati ons with autonomi c etTects or psychological expression o f dependency or rebelli on7 Th ough female are much more likely to experi ence incon tinence th an males. several urologica l causes of in continence are exclusive to male . For y ounger males. in parti cular, urethral and prostatic infecti on seco ndary to a sex uall y-transmitled disease is a frequent cause of incontinence.' In older men, incontinence is more often related to prostate disease. Prostate surgery is th e most common cause of stress urinary incontinen ce in men and prostate hypertrophy may cause overflow incontin ence by compressing the bladder.'' M ore importantly, UT! s are much more comm on in older th an yo unger men, w ith an incidence approaching th at seen in women.'

In th e emergency departm ent, life-threatening causes such a cauda equina sy ndrome, spinal cord compress ion and paraspinal abscess must additionally be rul ed out i f suspected. A bacteri al abscess cou ld be consistent wi th typical infection-related observati on , li ke fever. and can lead to both th e oth er conditi ons by direct or vascular compression.

A n MR I i necessary for rulin g out thi s po s ibility. ~<' I f additional lower body motor or sensory symptoms are present, it is important to more defini ti vely determin e wheth er th e cauda equ ina or spinal cord is af-

UWOMJ 182:1 I Spring 2013

THINKING ON YOUR FEET fected.''

In th e present ca e. th e physica l examinati on is continued wi th an awareness o f poss ibl e urologica l di sease. Palpati on of th e abdomen does not reveal a di stended or swo ll en bladder. whi ch would have suggested overfl ow incontinence.7 A s fever. dysuria and incontinence togeth er point convincingly toward a urologic prob lem. an abdomin al CT sca n is not indi cated at thi s point. Instead. blood is drawn for routine chemi stry. A urethral cath eterisati on is perform ed to obtain a steril e urine sampl e for urinalys is and urine culture. The pati ent is mildly uncooperative but accepting of oral med icati on. so oral sedatives are adm inistered. ' 2 A bedside ultrasound bladder scan is ordered to rul e out urinary retention and th e need to leave the catheter in silu u A n hour later. several r~po rt s are fonvarded fro m th e laboratory.

Blood urea nitrogen (BUN) and creatinin e are both normaL indicatin g good kidney function. especia ll y for the patient's age.'â&#x20AC;˘ The routin e urinalysis report, on th e oth er hand. shows bacteria and l ~ uk ocy t e s in high numbers in the urine (bacteriuria and pyuria) and th e nitrate test is positive. Thi s and urine turbi dity shift suspicion to urinary tract infection (UTI) as opposed to th e more common urethriti s.' A nn ed with all of th e above, the doctor return s to the bedside.

URINARY TRACT INFECTIONS: DIAGNOSIS In th e elderly. investi gat ion for T i s needs to be justifi ed by a hi gh degree of suspicion because urinary incon tin ence and dysuri a alone are very common and non-speci fi c. as di scus ed. In fact. conditions like pol laki uri a (frequent urinati on) and nocturi a (night urinati on) are estim ated to be present in over 50% of individua ls over 60 years of age. 15 In thi s population, even indi viduals w ith ou t infect ion often present 1vith th e classic tri ad of UTI di agnosis: freq uency. urgency and dysuri a. 16 Diagnosis of UTI in an older adu lt. then. otien depends on nonurological indications. Th ese comm onl y in clude a general decrease in day-to-day function. loss of v1eight or appetite. decreased alertn ess or flank or abdominal tenderness. For patients w ith dementia. behavioural deterioration and confusion can be extreme ly important symptoms. I(' For th e current patient. fever. confusion. dysuria and inco ntinence create a strong suspicion of UTI, strengthened by th e subsequent findings of bacteriuria and pyuria. Upon further questioning. th e daughter additionall y confinns th at lately the pati ent's appetite has decreased noticeably.

URINARY TRACT I NFECTIO S: MANAGEMENT IN THEELDERLY Diagnosis and treatm ent ofUT i s in th e emergency department frequently occurs without formal bacteria culturin g.' 7 Though it is possible for asymptomati c urologic bacteremi a to reso lve spontaneou sly in th e elderl y, seri ous complications like renal damage. pyelonephriti s and sepsis may occur, so it is prudent to treat all UT i s in th e elderly as complicated ."' 17 For most cases. a I 0- or 14-day course of the broad-spectrum antibiotic levo floxacin is indicated. Parti cul arl y for elderl y men. a fluoroquinolone like levo floxacin has the additional benefi t of high prostate gland penetration. Recurrence and relapse are comm only seen in the elderly, 16 so proper follow-up must be arranged.

Returnin g to the case, th e pati ent is prescribed oral levo floxac in. 250 mg per day for 14 days and allowed to take acetaminophen as needed.

Given th e fever and neuro logical symptom s. however, the pati ent is con sidered at ri sk of developing sepsis. so it is decided w ith the wife and daughter 's consent that it wou ld be most prudent to admit th e patient to the medicine service.

T he next clay. th e patient's serum lactate remain s unremarkable and repeat measurement of hi s vitals - particu larl y heart rate and 0 2 saturati on - return norm al findin gs. He is coo perative and much more aware or hi s situati on. correctly provid ing hi s name. th e approximate date and the fact th at he was in a hospital. " Sati sfied wi th the above improvem~nts . the phys ician di scharges the patient and asks th e wife and daughter to help fill and admini ster th e r~mainde r of th e prescripti on. T he) are also instru cted to bring th e patient to ee hi s fami ly doctor in one week to ensure clearance of the mi croorgani sm. confirm reli ef of neu rolog ica l symptoms and con sider management of incontin ence. i f it becomes chronic. Refe rral to a urologi st is deemed unnecessary unl ess further compli cat ion occ ur.

REFERENCES I. Matti son M. Marcantoni o. ER . Hospital manageme nt of older adu lts [Internet]. UpToDate: 20 12 .Jan 26 [updated 20 12 Jan 26: cited 20 12 Nov 24].

Ava il ab le from: http://www.uptodate .com/contents/hos pital-management-ofold er-ad ults .

2. Wilber ST. Ge rson LW. Terrell KM . Carpenter CR. Shah M . Heard K. Hwang U. Geri atri c emerge ncy med icine and the 2006 Institute of Medicine reports from the ommittee on the Future of Emergency Care in the U.S. Health System. Acad Emerg Med . 2006 Dec: 13( 12). 1345-5 1.

3. Huebe rge r R. Polypharmacy and food-dru g interacti ons among older persons: A review. J Nutr Gerontol Geri atr. 20 12:3 1(4 ).325-403 .

4. Va leri ani L. Management of demented patients in emerge ncy department. lnt J Alzheimers Dis. 20 11:20 ll .arti cle ID 8403 12.

5. Miner JR. Analgesia and anesthesia in the emerge ncy departm ent. Emergency Medi cine & Criti cal Care. 2008:4.6 1-4.

6. Garlin gton W. Hi gh K. Eva luation of infection in the older adu lt [Internet].

UpToDate: 20 12 Oct 16 [updated 20 12 Oct 16: cited 20 12 Nov 25]. Available from http ://\\ ww. uptodate.com/contents/evaluati on-of-in fection-in-theold er-ad ult .

7. Ouslander JG . Urinary incontinence in the elderl y. West J Med. 198 1: 135( 6).482-9 1.

8. Bru sch JL. Urin ary tract infections in males [Internet) . Medscape: 20 12 Feb 21 [updated 20 12 Fe b 2 1: cited 20 12 Nov 24]. Ava il able from emedi ci ne. medscape.com/article/23 15 74-overv iew .

9. Clemens JQ. Urin ary incontinence in men [Internet]. UpToDate: 20 12 Feb 7 [updated 20 12 Feb 7: cited 20 12 Nov 24). Avai lable from: http://www.uptodate.com/contents/urin ary-i ncontinence-in-men .

I0. Hutf JS . Spinal Ep idural Abscess [Internet] . Medscape: 20 12 May 7 [updated 20 12 May 7: cited 20 12 Nov 2-ll- Ava il ab le fro m: emedicine.medscape.com/ arti cle/ 11 65840-overview .

II . Dawodu ST. Cauda equina and conus med ull ari s syndromes [Internet] . Medscape : 20 II Aug 2 ~ [updated 20 II Aug 24: cited 20 12 Nov 24]. Avai lable from: emed icine.med cape .com/arti cle/1 148960-overvie\1 .

12. Nass isi D. Okuda Y. ED Management of Delirium and Ag itati on. Emergency Medi cine Practice. 2007 :9( I).

13. Schaeffer A.l. Placement and management of urin ary bladder cat heters [Internet] . UpToDate: 20 I 0 Oct 7 [updated 20 I0 Oct 7: ci ted 20 12 Dec 20]. Avai lable from : http ://www.uptodate .co m/contents/pi ace ment-and -managementof-urinary-bl ad der-catheters .

14. Vasavada SP. Urin ary incontinence [Internet]. Medscape: 20 12 Apr 5 [updated 20 12 Ap r 5: cited 20 12 Nov 25). Avail able from: emedi ci ne.medscape. com/article/452289-overview .

15. Goepel M. Kirschner-Hermanns R. Welz-Barth A. Stei nwachs KC. RUbben H. Urinary in continence in th e elderly : Part 3 of a seri es on in continence.

Dtsch Arztebl Int. 20 I 0: I07(30).53 1-6.

16. Murphy DP. Urinary tract infections in elderl y patients: How best to diagnose and treat. Consultant. 2005;45( 12).

UWOMJ 182:1 I Spring 2013

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THINKING ON YOUR FEET 17. Foxman B. Epidemiology of urinary tract in fec ti ons: Incidence. morbidity. and economic costs. m J Med. 2002 : 11 3 Suppl IA:5S-13S .

18. Bakker J. Jansen TC. Don路t take vital . take a lactate. Intensive Care Med. 2007 :33( I I ). 1863 -5.

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28

UWOMJ 182:1 I Spring 2013

ZEBRA FILES

Diagnosing in the dark: atypical proteinuria etiology Stephen Corn ish (Meds 20 15) and Eri c Roszell (Meds 2016) Faculty Reviewer: Dr. Faisal Rehman , MD , FRCPC , M.Ed (Department of Medicine, Division of Nephrology)

zebra is a member of th e species of Afri can eq uids. of th e horse family, whose appearance i defin ed by strikin g bl ack and 1vhite tripes. These animals are rarely seen outside of th eir nati ve continent. except for th eir requi site presence in zoos. menageri es. and circuses. Wh en we think of someth ing th at is comm on. a zebra may defi ne the direct antithes is to our noti on of commonality. L ikewise, a zebra pati ent is, fo r a physician. a peculiar blend of an exciting presentati on and a fru strating di agnosis. T he helpful adage "comm on thin gs are common" can be summarily thrown out of th e nearest w indow when dealing w ith th e contents of th e Zebra Files.

Our case begin s wi th an 80 year old gentl eman presenting to hi s primary care physician w ith an ac ute hi story of leg swelling and urinary frequency ove r the past three weeks. A n eva luati on of the present compl aint determin ed th at he wa al o ex peri encing a reduced appetite. nausea and vomiting. On examinati on. th e man 路s blood pressure was 138/78. and the lower ex tremi ties demonstrated th e fea tures of pitting edema. ln ve Li gati ons were ordered. and return ed as foll ows: blood urea nitrogen (BUN) of 7.3 mm oi/ L (norm al range 2.9 - 8.6 mm oi/ L). serum creatinin e (Cr) of 45 7.6 umoi/L (norm al range 53 - 115 umoi/L). and a serum album in leve l of 25 giL (norm al range 35 - 50 g/L ). Urinalysis was perform ed. whi ch detected th e presence of protein (graded as a 3+ ) as well as gluco e in the urine. ~~ ith no remarkab le microscopi c findin g .1 With these results and the clini ca l pi cture revea led. we can begin to hypoth esize.

The finding of pitting edema on phy ical exam suggests an accumulati on of fluid in the interstitial space of body ti ssues. Fluid typica ll y poo ls in dependent areas of the body like th e legs and feet. 2 T hi s is refl ected in our pati ent, who had noticed an abnorm al swelling of hi s lower limbs. Pitting edema i a ign of vo lume overl oad in pati ents. which results in excess fluid eeping out of th e vascul ature into th e interstiti al space of body ti s ues. There are everal mechani sms by whi ch thi s vo lum e overl oad phenomenon can occur. For th e ake of brev ity. heart fai lure. li ver di seases such as cirrhosis. renal sodium retenti on. neph ro ti c syndrome, drug-induced. and idiopathi c edema are all potential culprits. espec ially in an indi vidual of advanced age.3 Differenti ating between th ese etiol ogies is critical in ord er to proceed.

Building on our understanding of thi s pati ent 's volume statu s. we can examine th e results of the initial in vesti gati ons. Both urea and creatinine were found to be elevated, which indicate impairment of renal fun cti on.

The key to the pi cture here is th e urinalysis test. The significant presence of protein in the urine, classifi ed in this case as proteinuria of 3 out of a poss ible 4 degree of severity, should not be seen in a healthy person and is an indi cator of di sease.

A differenti al di agnosis for heavy proteinuri a would include glomerular causes such as glomerulon ephriti s, , diabetic glomeruloscle-

rosis. systemi c lupu erythematosus. amyloidosi s. and va culi tis. Other causes may include. monoclonal proteinuria. multipl e myeloma. I) mphoma. or oth er neopl asia. 4 Renal fun cti on is dependent upon fi ltrati on in th e glomerul ar un it. resulting in th e remova l of 11as tes and th e retention of bl ood ce ll s and protei ns. Fai lure to retain proteins sugge Is damage to th e glomerulu. th e fi ltrati on unit of th e kidne) . The absence of blood in the urine. or hematuri a. is also help fu l. Heavy proteinuri a w ithout hematuri a fa ll into one category of renal di sease (nephrotic). whil e th e combinati on is indica ti ve of a di fte rent type of path ology (nephritic) 5 T he measurement of a low albumin in th e in vesti gati on of thi pati ent is refl ecti ve of th e heavy proteinuri a.

T he pati ent was referred by his primary care phys ician to a nephrology clinic for further evaluati on. Repeat urinalysis was perform ed . A 24 hour urine co ll ecti on for protein was perfonned. whi ch is more helpful for evaluatin g th e amount of proteinuria th an a di psti ck urinalys i T he patient was losing 20 .7 g of protei n over a 24 hour period in hi urine. Thi s more focused analysis returned anoth er curio us resul t: in addition to th e prev iously detected proteinuria. trace bl ood also appea red in th e urine. Mi croscopic analys is identifi ed I 0-20 red blood cell s per magnifi ca ti on fie ld, w ith some granu lar casts. 1 T he pati ent has now demonstrated some degree of hematuri a observed in th e sett ing of heav) proteinuri a.

T he findin g of hematuri a shifts the diagnosti c foc us away from a nephroti c sy ndrome, which is categori cally limited to protein wastin g in th e urine. and usually not blood. Glomerulonephriti s is an inflammatory process defi ned by th e presence of red blood ce ll casts or d) smorphi c red blood ce ll s in urine. moderate prote inuria hypertension. and renal fa ilure.'' Ca uses of the nephriti c sy ndrome all relate to vari ous defecti ve autoimmune proce ses: damage from th ese circ ulating factors occurs progress ive ly as th ese factors accumul ate during glomeru lar fi ltrati on.

The underl y ing ca use of th e glomeru lonephriti s can be determin ed by serologica l tests for th ese autoimmune facto rs. aturall y. in our "Zebra" pati ent. th e usua l suspects in th e nephriti c syndrome (anti-nuclear anti bod ies. A CA and anti-GBM antibodi es. cryoglobulins. Hep C antibody. ASO titres) turned up negati ve. However. two protein s (C3 and C4) were fo und to be abnorm ally low.1 These are norm ally in vo lved in th e compl ement cascade vital to the body's immune respon e.

A renal biopsy was perform ed to determin e th e glomerul ar path ology. Light mi croscopi c eva luation showed classic charac teri stics of a membranoproliferati ve glorn eru lonephriti . w ith form ati on of path ologica l crescents in 50% of glomeruli . A Congo red stai n was perform ed on th e bi opsy ample: it return ed w ith a negati ve result. ruling out renal amy loido is. 1 A fter a circuitous di agnosti c route. th e elec tron microscop) and immun oflu orescence on th e kidn ey bi opsy specimen did prov ide an

UWOMJ 182:1 I Spring 2013

29

ZEBRA FILES ans" er. The architec ture of the glomeru lar basement membrane was being di srupted by randomly arranged fibri llary deposits. Final d iagnosis was determined: fibril lary g lomerulon ephriti s with crescent form ati on. in th e presence of hypocompl emen temia.

Fibrill ary g lomerul onephriti s is an uncomm on di ease of th e g lomeru lus leading to ren al dysfu nction .7 T his dys functi on is caused by a buildup of randoml y arranged fibrillar deposit in th e glomerular base m embrane and mesangium .8 The di ease was first distingu ished in 1977 from amy lo idosis on the basis th at co ngo red stains. which stain amy lo id fibers. were negati ve in several patient" kidne) biopsies.' Fibri ll ary g lomerul onephriti s has been associated with different malignancies, m onoclonal gamm opathie s. and autoimmune di sorders.7 Despite th e th oro ugh characteri zati on of fibri ll ary g lomerul onephriti s, the path o logy of th e disorder is not fully understood although it is kno11 n that th e fibrillary depo its are derived from immunoglobulin .''

Cresce nts formation. as seen in our ··zebra·· pati ent. is seen in approx imate ly 20% of cases of fibrillary g lomeru lonephriti s. Crescent result from a nonspecific respon se to severe injury of the glomerular capill ary wa ll. These crescents can invo lve anyw here from 10% to 80% of th e g lomeru lus. ' Since ere cents result from a nonspec ifi c re pon se. th ey can be seen in any type of severe glomerul ar di sease.

PA : Saunders Elsevier. 324 p.

7. Ray S, Rouse K, Appis A. Novak R_ Haller NA. Fibrill ary glomerulonephriti s wi th hepatitis C viral infection and hypocomplementemia. Ren Fatl.

2008:30(7):759-762 .

8. Javaid MM. Denl ey H. Tagboto S. Fibri ll ary glomerulonephritis with small fibril s in a patient with the antiphospholipid antibody syndrome success full y treated with immunosuppressive therapy. BMC Nephrol. 2007 May:8( I ):7.

9. Schwartz MM . Korbel SM. Lew is EJ. lmmunotactoid glomerul opathy. JAm Soc Nephrol. 2002 May: 13( 5): 1390- 1397.

I 0.

asr SH, Valeri AM , ornell LD, Fidler ME. Sethi S. Leung N. Fervenza FC. Fibrillary glomerul onephriti s: a report of 66 cases from a single institution.

Clin JAm Soc Nephrology. 20 11 Apr;6(4):775- 784.

II . Collins M. Navaneeth an SD. Chung M, Sloand J, Goldman B. A ppel G. Rovin BH . Rituximab treatment of fibrillary glomerulonephritis. Am J Kid Dis. 2008 Dec:52(6) : 11 58- 11 62 .

12. Rosenstock JL. Markowitz OS. Valeri AM . Sacchi G. A ppel GB, D' Agati VD. Fibri llary and immunotactoi d glomerul onephritis: distinct entitie wit h different clinical and pathologic features . Kidney Int. 2003 Apr:63(4 ): 1450- 1461.

A lthough fibri ll ary glomerul onephriti s is not generall y considered a rare disease. as it is present in approx imately I % of kidney biopsies. th e added com plicati on of hypoco mplementemia has onl y been reported on one oth er occasion in the literature.7 H) pocomplentemia can refer to low levels of the mo lecular mediators of compl ement: in our ··zebra·· pati ent it refers to th e decreased amount of 3 and C4.

The treatment of fibri ll ary glomerulonephriti s w ith cresce nt form ation and hy pocompl ementemi a has not been we ll e tabli shed due to th e rarity of th e condition . nfortunately. many of th e treatment option for oth er ty pes of g lomerul onephriti s. such as teroid s or cytotox ic agents. are ineffecti ve on fibrillary glomerul onephriti s7 Con er va tive use of angiotensin inhibiti on is often used to contro l blood pressure and slow th e progress of th e disease.' " Some o f th e th erapi es that have been attempted to ome uccess in vo lve th e use o f g lucoco rti co ids. predni sone, cyto toxic agents such as cyc loph osphamide. and rituxi mab. 11 The prognosis for patients with fibri llary glomerul onephriti s is o ften grave due to th e dearth of treatment opti on . The ex pected tim e co ur e can be estim ated at th e tim e of a renal biopsy by different hi tologica l features see n under li ght microsco py.12 Approximate ly 50% o f pati ent w ill progress to end-stage renal di sease w ithin t'A o to six years. A mong th e remaining patient . onl y 10% achieve co mplete or parti al remi ssion w hile 40% have progressi ve renal di ease.'" With thi outl ook, our pati ent may have become one of th e grow ing numbers of pati ents w ho are dependent on renal d ialys is th erapy. a d i fficult rea lity th at defines th e medica l care of so many elder! ) pati ent .

REFE RENCES: I . Adey DB, MacPherson BR, Groggel G . Glomerul onephritis with associated hypocomplementemia and ere ce nts: an unusual case or fibrillary glomeru lonephritis. J Am Soc Nephrol. 1995 Aug:6(2): 171 - 176.

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2. Humphreys MH . Mechanisms and management of nephrotic edema. Kidney Int. 1994 Jan;45 ( 1):266-28 1.

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3. Cho S. Atwood JE. Peripheral edema. JAMA. 2002 Nov: 11 3(7) :580-586.

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4. Fine LG, Salchmoghaddam S. Clinical methods: the history. phys ical, and laboratory examinations. Boston. MA : Butterworths; 1990. 872-873 p.

5. Orth SR, Ritz E. The nephroti c syndrome. NEJM . 1998 Apr:338( 17): 120212 11.

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30

Western~

UWOMJ 182:1 I Spring 2013

HISTORY OF MEDICINE

The barriers surrounding hemodialysis for patients with ESRD: improving access since 1945 Justine Denomme (Meds 2015) and Wendy Cui (Meds 2016) Faculty Reviewer: Dr. Shelley McKellar, PhD (Jason A. Hannah Chair in the History of Medicine)

emodi alys is is one option for renal rep lacement th erapy in people wi th End Stage Renal Di sease ( ES RD ). It is required when a person· kidn eys are unabl e to comp lete th eir normal fu nction. th at of maintaining th e norm al intracell ular and ex tracell ul ar fluid env ironment with in the body. 1 It en tail s remov ing excess fluid . as we ll as waste such as urea. whil e rep lacing necessary substances such as bicarbonate. 1 In thi s article. we present some of th e barriers surrounding the implementation of di alysi for patients and ex plore how some of th ese barriers were overcome.

H

EARLY DEVELO PME NT A D IMPLEMENTAT ION OF HEMODI ALYS IS The first successful use o f hemodi alysis occurred in th e Netherlands in 1945 by Dr Will em J. Kolffwith a machine dubbed th e ·'artifi cial kidney.'"2 A 67-year-old woman suffer ing from acute kidney injury was nearl y anuric. but wi th 11 .5 hour of dialysis. her blood urea nitrogen and serum potassium levels dropped and she eventually made a full recovery. Di alysis. still experimental th en. wa re erved. as in thi s case. for failures of conven ti onal treatm ent. 2 Interestingly. a Canadian surgeon, Dr. Gordon Murray, also invented a hemod ialysis machine around the same time as Dr. Kolff3 In 1946, he successfull y di alyzed a woman in a uremi c coma at Toronto General Hospital. Despite these succes es. hemodialysis wa initially met with concern from physicians regarding afety and efficacy. especi ally since treatment course was detennined largely by tri al-and-error and few peop le were trained to operate th e machineH However, throu ghout th e 1950 's. hemod ialysis gained populari ty and improvements and modificati ons were made to faci litate treatment and improve outcomes 5 It wa s indicated primaril y for pati ents with acute kidney injury who on ly needed to be di alyzed temporari ly rather than for ES RD as it wa difficult to maintain vascular access for repeated di alysis to take place. 5 Thi s problem was reso lved in 1960 when Dr. Beld ing H. Scribner and co ll eagues introduced an arteriovenous shunt. which kept the rad ial artery and forearm vein in the arm of the patient connected using Teflon tubing. 6 Thi hunt remained on th e patient to maintain vascu lar access, faci litating connecti on with the hemodialyzer w henever dialy is was needed .6

O NCE HEMODIALYSIS BECAME AVAILABLE TO THOSE WITH ESRD, WHO RECEIVED CA RE? The Scribner shunt made hemodialysis a viable option for ESRD. In 1962. Dr. Scribner opened the world 's first outpatient dialys is centre in Seattl e. 7 The Seattle Artific ial Kidn ey Centre consisted of on ly three sets of dialys is eq uipment w ith limited staff. Thu , th e centre form ed two committees to detennine wh ich patients were be t suited for hemodialysis. The first cons isted of nephrologi sts who ensured patients met stringent medical criteri a. The second, the Admi ssion s and Policy Committee. consi sted of two phys icians, a Chri stian mini ster. lawyer, house-

w ife. businessman. and labour leader. It was also nicknamed ··the God committee'" as its rol e was to asses the ·· relati ve worth .. of a candidate to th eir fami ly and to soc iety at large and chose whi ch pati ents wo uld survive and which would di e from th eir di seaseY Choices were al101\ ed to be gu ided by each member ·s conscience and pati ents cou ld be eva luated on marital tatu s. occupati on. income. ed ucati on. emoti onal stability. future potential. gender. and ageY Successful candidates were usually th ose who were hard-working. had many chi ldren. were ac ti vely in vo lved in church and communi ty affairs. but had few monetary sa vings such that i f th ey died. th e state would ha ve to support th e family.

As a result. th e decisions of th e Committee were large ly biased tO\\ ard White. Protestant. middle-class m e n. ~ Committee members agonized over th ese diffi cult decisions and criti cs fe lt that determining ··social worth .. was unethical and sugge ted th at dec ision-making be based on a method that does not penn it the compari son of socia l worth among indi vidual s. such as choosing by lottery.7· 111 Fortun ately. such committees became unnecessary a hemodialysis became more wid ely avai labl e. In 1972. U.S. Congress agreed to prov ide dialysis in end-stage renal disease for th ose who could not afford it. 9 The initial situati on in Canada is not unlike that in the United States.

Prior to th e implementati on o f th e 1966 Medical Care Act. regular dialysis trea tm ents were onl y offered in a fe\\ hospital due to prohibiti ve costs.11 Again. th e question of who wou ld receive treatm ent and how such al locat ions would be detennined posed a dilemma for physician s and policy-m akers. Selec ti on com mittees regul ated who rece ived dialysis. based on criteria uch a age. th e stage of renal di sease. absence of oth er comorbiditi es. and suitabili ty for kidney tran pl antation . It was the death of a young man from kidn ey di sease in Montreal th at precipitated th e creati on of th e charitabl e Kidn ey Foundation of anada in 1964. dedica ted to advocacy. research. and support fo r Canadi ans w ith renal disease. Eventua lly. under M edicare. th e cost of dia lys is was fully covered. all owi ng pati ents with renal di sease access to pre viously unattainable I i le-sav ing care. 11 Advocacy for hemodial ys is has saved many I ives.

In 2009. 22,3 I 0 Canadi ans \\ ith E RD were being treated w ith di aly sis.1 2A lthough it is known th at renal transp lantation is th e best treatment for ES RD. the number of kidneys ava il able for transpl ant i not increasing as sharp ly as diagnoses of ES RD and demand for hemodialysis is expected to increase in the future. 12

DEVE LOPME NT OF HOM E DI A LY S IS Even with improved access, hemodia lysi , alth ough li fe- av ing. is very tim e-consuming, invasive. and may negatively im pact qua lity of li fe. 13 One aspect of initial treatment wa that most patients needed to trave l to a hospita l and dedicate everal hours a week to being di alyzed. A method that circum vents thi s necessity. promoted in Canada by Dr. Robert U ldall and Dr. A ndreas Pierratos at the Uni versity of Toronto in 1993. is home hemodialysis. Thi s method allow pati ents to perform dia lysis at

UWOMJ 182:1 I Spring 2013

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HISTORY OF MEDICINE home during sleep fo r most. i f not all. ni ghts o f the 11 eek." A lthough pati ents mu st be trained. hom e dialys is has been associated w ith im proved quality of life and a higher cost uti l ity compared to traditional in -ce nter hemodi alys is.' 5 Whil e home di alys is peaked in 1993 at 37.4% of all d ial) sis in Canada. in 20 I I th at fi gure w as only 23 -2-1% in O ntari o.1 1 H om e dialy i can be di f fi cult to implement and unsuitab le for some pati ents, but it o ffers an alternati ve fo r pati ents w ho wo uld prefer to be trea ted at home.

I . Himmelfab J, Jkizler TA. Hemodialys is. N Eng! J M ed 201 0:363 : 1833 -4 5.

2. Gottschalk CW, Fellner SK. History of the science ofdi alys i . A m J Nephrol.

199 7 May-Aug; 17:289-298.

3. McKellar S. Gordon Murray and the artifi cial kidney in Canada. Nephrol Di al Transpl ant. 1999: 14:2766-70.

4. BMJ Publishing Group. The artifi cial kidney. Br Med J. 1949 Oct 22 ;2( 4633 ):920-92 1.

5. A Iwall N. Hi tori ca l perspecti ve on the devel opment of the artifi cial kidney.

A rti fOrgans. 1986 Apr: l 0(2):86-99.

EXPANS ION OF DIALYS I S TO RURAL SITES Canada is a vast co untry and many communities are isolated from large hospital centres containing di al) sis units. Many pati ents are faced w ith a shortage of dialys i stati ons i n th eir area and have a limited abilit) to se lect th eir pref erred locati on or chedul e for di aly sis. Pati ents li v ing in rural areas may need to make hours-l ong dri ves to th e nearest hospit al. a heavy burde n in vu lnerabl e popul ati on uch as th e elderl y and d isabl ed.'6 A del ivery model proven to be safe and effecti ve in Ontari o is the satell i te mode l. in w hi ch rural satellite sites are paired w ith a larger centre or 路路hub.. to ensure th at w hil e pati ents may recei ve hem odi alys is in a rural sett ing. the) are still granted access to an experienced nephro logy team. 17 A n example of a sa tellite di alys is unit ca n be fo und in Goderi ch. O ntari o. a town of 8, 000 residents abo ut an hour north of L ondon, O ntari o. Opening in 200 I as a atellite of th e L ondon Hea lth Science Centre Renal Program. th e fac ility can accomm odate 12 pati ent per day w ho wo uld oth erw ise need to travel to L ondon for hemodi alys is."

A nephrologi t from L ondon v i its approx im ately once a month for pati ent assessment and adj ustm ent of medi cati ons and co nference ca lls are made to discu s pati ent ca re on a 1\ eekl y basis. A lthough such fac ilit ie are prim aril y for the m ost stabl e pati ents requiring d ialys is. th ey have empowered small er co mmuniti es and helped alleviate some of th e added di ffic ulties of havi ng ES RD in a rural settin g."

6. Quinton W. Dillard D. Scribner BH. Cannul ati on of bl ood vesse ls for prolonged hemodialys is. Trans Am Soc A rtif Intern Organs. 1960 A pr 1011 ;6: 104- 13.

7. Blagg CR. Development of ethi cal conce pts in dialys is: Seattl e in the 1960s.

Neprhology 1998 A ug:4 :235 -38.

8. Jonsen AR . The god squad and the origins of transpl antation ethi cs and policy. J Law Med Ethi cs. 2007;35(2):238-40.

9. McGough LJ , Reynolds SJ, Quinn TC, Ze nilman JM . Whi ch patients first?

Setting pri oriti es for antiretroviraltherapy where resources are limited. A m J Public Health. 2005 Jul ;95(7): 11 73 -80.

I 0. Sanders D. Dukeminier J Jr. Medical advan ce and legal lag: hemodialys is and kidne} transplantation. UCLA Law Rev iew. 1968 Feb: 15(2):357-41 3.

II. K idney Foundation of Canada. (20 12). Vision and M iss ion. Retrieved from http://www.kidney.calpage.aspx? pid=305 12. Canadian Institute for Health Jnforn1 ation (C IHI ), Canadian Organ Replacement Register Annual Report : Treatment of End-S tage Organ Failure in Canada. 2000 to 2009 (Ottawa. Ont. : Cl HI. 20 II ).

13. K immel PL. Just whose quali ty of life is it anyway? Controversies and consistencies in measurements of quali ty of li fe . Ki dney Int. 2000;57 :S 11 3-S 120.

14. Pierratos A . Noctumal home haemodialysis: an update on a 5-year experience. ephrol Dial Tran splant. 1999 Dec: 14( 12):2835 -40.

CONCL SIONS Access to hemod ialys is has improved ove r th e yea rs and pati ents are now empowered w ith more opti ons for treatm ent. inc luding home dialys is and access to atellite si tes. However. accessi bility to trea tm ent remain s an iss ue fo r chronic ki dney di ease and ES RD pati ents. A s th e prevalence o f k idney disease ha increased. so has demand for dialys is. from more th an 5 900 Canadi ans on di alys is in 1990 to 22 300 in 2009. an increa e from 53% to 59% of all ES RD pati ents. 11 Furtherm ore, for m any pati ents, transpl antati on remains th e ultimate goa l o f treatm ent. It is known th at renal transpl antation is &enerall y more effecti ve at treatin g pati ents w ith ES RD and th ose transpl anted report a g reater qualit) o f li fe.' " In addition. th ee tim ated cost for hem odialys is is approx imately $60 000 per year of treatm ent, per pati ent, w hil e th e cost for a one-tim e kidney transpl ant. inc luding annual maintenance medicati on. is $29 000.

T he sav ings are $2 50 000 over a fi ve year peri od, especiall y relevant in I ight of many recent cuts to hea lthca re in O ntari o.' 1 Du e to limited acce s to donor organ . guidelines have been deve loped to determin e w hi ch pati ents are eli gi bl e for kidn ey transpl antati on, hearkening back to th e earl y days of hemodialys is. A s bi oethi cs has evol ved from dark er days in Sea ttl e, th ese criteri a are much more transparent and ev idence-ba ed. ontroversies in organ donati on remain. such as w hether pati ents o f ad va nced age or cogniti ve impairment are treated fa irl y w ith i n th e sy tem.211 By advoca tin g for pati ents to sign donor cards and ex press th eir w ishes to famil y and fri ends, ensuring th at all pati ents w ho may benefi t from transpl antati on are as e se d and added to wa iting lists. we ca n pl ay a ro le in ensuring th at acce s to hemodi aly sis rem ain w ide pread, and open to newly di agnosed pati ents and th o e in elig ible for transpl ant.

15. McFarl ane. P. A ., Bayoumi, A . M .. Pi erratos. A .. and Redelmeier, D. A. The quali ty of l ife and cost util ity of home noctumal and conve ntional in-ce nter hemodialys is. Kidney lntemational (2003) 64, I 004- 10 II : doi: I 0. 1046/ j . l 523 -1 755.2003 .00 157 .x 16. Manns BJ . Mendelssohn DC, Taub KJ. The economi cs of end-stage renal disease care in Canada: ince nti ves and impact on deli very of are. lnt J Health Care Finance Econ 7(2 -3): 149-1 69. 2007 .

17. L indsay RM , Hu x J. Holland D, Ri chardson R. et al. : A n in ves ti gation of satellite hemodial} sis fa llbacks in the prov in ce of Ontario. Clin JAm Soc Nephrol. 2009 Mar:4(3):603 -8.

18. A lexandra Marine and General Hos pital. Di alys is [Internet] . Goderi ch, Ontario: !cited 20 12 Dec 5]. Availabl e from: http://www.amgh.ca/Defaull. aspx?cid=75& 1ang= I .

19. Laupac is A, Keol\ n P. Pus N. Krueger H. Ferguson B, Wong C. Muirhead N. A stud y of the quality or life and co t路util ity of renal transpl antation. Kidney Int. 1996 .Ju1 ;50( 1):235 -42.

20. Knoll G, Cockfi eld S, Bl ydt-Han en T, Baran D, Kiberd B. Landsberg D. Rush D. Cole E. Canadian Society of Transpl antation consensus guidelines on eligibility for kidney transplantati on. CMAJ . 2005 Nov 8; 173( I 0): 118 1-4 .

REFERE CES

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NOTES

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UWOMJ 182:1 I Spring 2013