Wetenschappelijke publicaties van het Deventer Ziekenhuis, RISO en Dimence

Wetenschappelijke publicaties van het Deventer Ziekenhuis, RISO en Dimence Het Deventer Ziekenhuis is lid van de Samenwerkende Topklinische opleidings Ziekenhuizen (STZ). Dit is een vereniging van 27 ziekenhuizen die niet academisch zijn, maar door hun voorzieningenniveau, opleidings- en onderzoeksinspanningen tot de top van de algemene ziekenhuizen behoren. Dit lidmaatschap koesteren we als een erkenning voor onze onderwijs- en (wetenschappelijk) onderzoeksinspannnigen.

Deventer, oktober 2010

Inhoud

Voorwoord

Voorwoord

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Deventer Ziekenhuis Anesthesiologie Cardiologie Dermatologie Geriatrie Gynaecologie, Verloskunde en Voorplantingsgeneeskunde Heelkunde Interne Geneeskunde Keel-, Neus- en Oorheelkunde Kindergeneeskunde Klinische Chemie Klinische Farmacie Klinische Fysica Maag-, Darm en Levergeneeskunde Medische Microbiologie Neurologie Oogheelkunde Orthopedie Pathologie Radiologie Urologie Opleidingsinstituut Deventer Ziekenhuis

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Radiotherapeutisch Instituut Stedendriehoek en Omstreken (RISO)

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Dimence

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Impact Factors

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State of the Art Lectures 2009

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Van de Griekse filosoof Heraclites (540 – 480 vC) is de uitspraak ‘Alles vloeit, niets blijft’. Hij heeft dit ongetwijfeld bedoeld om aan te geven dat je als mens moet blijven (mee) veranderen. Voor wetenschappelijk onderzoek geldt het omgekeerde. We veranderen niet mee, we initiëren de verandering zelf. We zijn op zoek naar veranderingen, verbeteringen wel te verstaan. We wíllen dingen laten vloeien, ze actief veranderen. Voor u ligt het tweede boekje met een weergave van het onderzoek dat in 2009 heeft plaatsgevonden in het Deventer Ziekenhuis, het Radiotherapeutisch Instituut Stedendriehoek en Omstreken en Dimence. Van promoties en wetenschappelijke artikelen tot voordrachten en posters. Maar altijd met een relatie met de directe patiëntenzorg waar deze organisaties voor staan én waar hun focus en hun kracht ligt. Het (mee) doen aan onderzoek is voor onze instellingen van belang. Belangrijk in het kader van de opleiding tot medisch specialisten voor andere opleidingen. Maar ook belangrijk voor het ‘state-of –the-art’ blijven. Het dwingt ons om de ontwikkelingen in de medische zorg en in opleidingen te blijven volgen en mee te helpen de zorg nog beter te maken. Ik ben er trots op dat wij ook in 2009 weer in staat zijn geweest om - naast het verlenen van patiëntenzorg en naast alle projecten rondom veiligheid, logistiek en kwaliteit - ook een mooie bijdrage te leveren aan wetenschap en daarmee aan innovatie. Tineke Hirschler, Voorzitter Raad van Bestuur, Deventer Ziekenhuis

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Deventer Ziekenhuis

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Vakgroep Anesthesiologie

Vakgroep Cardiologie

Artikelen

Artikelen

Iedere chirurg kan een kind opereren SMHJ Nooijen, RHGP van Erve Medisch Contact 2009; 64(31/32): 1356

Optimal level of oral anticoagulant therapy for the prevention of arterial thrombosis in patients with mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction: a prospective study of 4202 patients. Torn M, Cannegieter SC, Bollen WL, van der Meer FJ, van der Wal EE, Rosendaal FR Arch Intern Med. 2009; 169(13): 1203-9 Abstract Background: Oral anticoagulant therapy is effective for the prevention of arterial thromboembolism in various patient groups. The increased risk of hemorrhage remains the major drawback to this therapy and is associated with the intensity of anticoagulation. Finding the optimal intensity at which the overall incidence rate of both bleeding and thromboembolic events is minimized represents a way to improve the safety of oral anticoagulant treatment. Methods: We evaluated all patients visiting the Leiden Anticoagulation Clinic with mechanical heart valve prostheses, atrial fibrillation, or myocardial infarction from 1994 to 1998. Untoward events were major thromboembolism and major hemorrhage. We calculated intensityspecific incidence rates of untoward events to assess the optimal intensity per indication of treatment. We enrolled 4202 patients for a total of 7788 patient-years. RESULTS: A total of 3226 hospital admissions were reported, 306 owing to an untoward event. Incidence rates of untoward events were around 4% per year for all indications: 4.3 (95% confidence interval [CI], 3.1-5.6) for patients with mechanical heart valve prostheses, 4.3 (95% CI, 3.7-5.1) for patients with atrial fibrillation, and 3.6 per year (95% CI, 3.0-4.4) for patients treated after a myocardial infarction. The optimal intensity of anticoagulation for patients with mechanical heart valve prostheses was an international normalized ratio (INR) of 2.5 to 2.9; for patients with atrial fibrillation, an INR of 3.0 to 3.4; and for patients after myocardial infarction, an INR of 3.5 to 3.9. Conclusion: Our study suggests target INRs of 3.0 for patients with mechanical heart valve prostheses and atrial fibrillation and 3.5 after myocardial infarction as a starting point in future clinical trials.

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One-year mortality after a first visit to a cardiology outpatient clinic: a useful performance indicator? Oerlemans MI, Lok DJ, Cornel JH, Mosterd A Neth Heart J. 2009; 17(2): 52-5 Abstract Purpose: in 2003 the dutch health care inspectorate introduced performance indicators to monitor and compare quality of care in dutch hospitals. In 2007, the new performance indicator ‘one-year mortality after a first visit to a cardiology outpatient clinic’ was introduced. We set out to evaluate this new indicator in three dutch teaching hospitals. Methods: using electronic medical records, information was collected retrospectively of patients aged >/=70 years who visited the cardiology outpatient clinic of medical centre alkmaar, meander medical centre amersfoort and deventer hospital between 1 january 2006 and 31 january 2006. Diagnoses were based on the diagnosis treatment combination (dbc) coding system. Results: 547 patients (mean age 78.0 Years, 53% men) were included, 35 (6.4%) Of whom had died after one year. Cardiovascular disease was the most frequent cause of death (22/35, 62.9%). The oneyear mortality among the three hospitals varied from 5.0 To 7.3% (Ns). Conclusion: one-year mortality after the first visit to a cardiology outpatient clinic amounted to 6.4% In patients aged >/=70 years and did not differ significantly between the three dutch teaching hospitals. The administrative load to obtain the necessary information was considerable. One-year mortality should be regarded as an ‘outcome’ parameter rather than a ‘performance’ indicator. (Neth heart j 2009;17:52-5.). RESPONSE study: Randomised Evaluation of Secondary Prevention by Outpatients Nurse SpEcialists: Study design, objectives and expected results. Jørstad HT, Alings AM, Liem AH, von Birgelen C, Tijssen JG, de Vries CJ, Lok DJ, Kragten JA, Peters RJ. Neth Heart J. 2009; 17(9): 322-8 Abstract Background. Patients with coronary artery disease are at high risk of coronary events and death, but effective secondary prevention can reduce this risk. There is a gap between guidelines on secondary prevention and the implementation of these measures, which could potentially be reduced by nurse led prevention clinics (NLPC).

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Objectives. The aim of the current study is to quantify the impact of NLPC on the risk of cardiovascular events in patients with established coronary artery disease. Methods. A randomised, multicentre clinical trial of NLPC in addition to usual care or usual care alone in post-acute coronary syndrome patients. (Neth Heart J 2009;17:322-8.). Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Schwartz GG, Olsson AG, Ballantyne CM, Barter PJ, Holme IM, Kallend D, Leiter LA, Leitersdorf E, McMurray JJ, Shah PK, Tardif JC, Chaitman BR, DuttlingerMaddux R, Mathieson J, dal-OUTCOMES Committees and Investigators, [Lok DJ] Am Heart J. 2009; 158(6): 896-901.e3. Dabigatran versus warfarin in patients with atrial fibrillation. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Poque J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators, [Lok DJ] N Engl J Med. 2009; 361(12): 1139-51 Effect of clopidogrel added to aspirin in patients with atrial fibrillation. ACTIVE Investigators, Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, Yusuf S, [Lok DJ] N Engl J Med. 2009; 360(20): 2066-78

Voordrachten Van DEAL-HF naar ketenzorg voor hartfalen Pieta W.F. Bruggink-André de la Porte Congres Ketenzorg en Geïntegreerde Zorg Recente nationale en internationale ontwikkelingen in onderzoek projecten, bekostiging en beleid van ketenzorg en geïntegreerde zorg Utrecht, 3 juli 2009 New antithrombotic therapies D.J. Lok National Institute of Health Washington, June 20, 2009

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Ketenzorg hartfalen D.J. Lok Nederlandse Vereniging voor Cardiologie Utrecht, 20 oktober 2009 Ketenzorg binnen de cardiologie D.J. Lok Limburgse Cardiologen Vereniging Roermond, 4 november 2009

Allereerst onderzochten wij de effecten van dit hartfalen management programma op de adherentie van voorschrijvers (volgens nationale en internationale richtlijnen) en patiënten aan de medicatie. Vervolgens bestudeerden wij de correlatie tussen de verandering in de biochemische parameter, NT-proBNP, en de verandering in kwaliteit van leven en functionele status gedurende de follow-up van de hoofdstudie. Tenslotte analyseerden wij de kosten van het hartfalen management programma in relatie tot de waargenomen effecten. Van de substudies zal in deze samenvatting alleen de kosten-effectiviteit besproken worden.

Promoties Effects of heart failure management programmes P.W.F. Bruggink-André de la Porte Utrecht, Universitair Medisch Centrum, 16 januari 2009 Samenvatting: Het belangrijkste doel van de studies, beschreven in dit proefschrift, was om een antwoord te krijgen op de vraag, of een intensieve begeleiding door een hartfalenpolikliniek voor patiënten met hartfalen in de NYHA classificatie III of IV, het aantal ziekenhuisopnames als gevolg van verslechterend hartfalen en/ of overlijden zou kunnen verminderen, of anderszins de kwaliteit van functioneren en leven zou kunnen verbeteren tegen acceptabele kosten, en of de waargenomen effecten mogelijk (gedeeltelijk) toegeschreven zouden kunnen worden aan gunstige veranderingen in de therapietrouw van patiënten aan hun medicatie. Er waren enkele belangrijke verschillen met vele eerder uitgevoerde studies: onze hartfalenpolikliniek werd geleid door een combinatie van een clinicus en een hartfalenverpleegkundige en bovendien werd de studie uitgevoerd in een land met een betrekkelijk sterk eerstelijnszorg systeem. In een systematisch overzicht in het begin van dit proefschrift worden de uitkomsten van eerder uitgevoerde studies over hartfalenmanagement programma’s kritisch beschouwd en hun toepasbaarheid op landen met goed functionerende eerstelijnszorg faciliteiten, zoals Nederland, bestudeerd. In het belangrijkste hoofdstuk van het proefschrift worden de resultaten van het Deventer-Alkmaar Hartfalen Project (DEAL-HF studie) gepresenteerd en vervolgens verscheidene substudies binnen de DEAL-HF populatie.

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Resultaten van de DEAL-HF studie Om te kunnen beoordelen of een hartfalen management programma met de interventie van een combinatie van een verpleegkundige en een arts additionele voordelen zou opleveren, ook in een land met een zorgsysteem, gebaseerd op eerstelijnszorg hebben wij het Deventer-Alkmaar Hartfalen Project, een gerandomiseerde studie in 2 regionale opleidingsziekenhuizen in Nederland, uitgevoerd (Hoofdstuk 3). In de DEAL-HF studie bestudeerden wij het effect van een intensieve interventie onder begeleiding van een verpleegkundige en een arts, gedurende een periode van 1 jaar, op het aantal ziekenhuisopnames als gevolg van verslechterend hartfalen en/of overlijden bij patiënten met matig tot ernstig hartfalen. van 2000 tot 2004. Additionele eindpunten waren het effect op functionele status ( inclusief de Linker Ventrikel Ejectie Fractie en NYHA klasse), kwaliteit van leven, NT-proBNP, tijd van overlijden, gebruik van hartfalenmedicatie en kosten van zorg. De interventie bestond uit 9 bezoeken aan de hartfalenpolikliniek gedurende een jaar. Patiënten ontvingen uitgebreide instructie en informatie van de verpleegkundige omtrent hartfalen en vele aspecten van het lijden aan en omgaan met hartfalen. De verpleegkundige voerde ook een kort lichamelijk onderzoek uit. Daarnaast optimaliseerde de arts de hartfalen medicatie, overeenkomstig de beschikbare klinische richtlijnen voor de behandeling van hartfalen. Bij 6 van de negen bezoeken voerden arts en verpleegkundige samen een algemene beoordeling uit. Voor de begeleiding van de patiënten in de controlegroep bestond geen speciaal protocol. Deze patiënten ontvingen “gebruikelijke zorg”. De resultaten van onze studie lieten zien dat het aantal opnames als gevolg van verslechterend hartfalen en/of overlijden in de interventiegroep lager was dan in de controlegroep (23 vs 47; relatief risico (RR) 0.49; 95% betrouwbaarheidsinterval 0.30 tot 0.81; p=0.001).

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Er was ook een verbetering van de linker ventrikel ejectie fractie (LVEF) in de interventiegroep (plus 2.6%), vergeleken met een afname in de controlegroep (minus 3.1%; p=0.004). Patiënten in de interventiegroep werden opgenomen gedurende een periode van in totaal 359 dagen, vergeleken met een aantal van 644 dagen voor de patiënten in de controlegroep. Er werden ook gunstige effecten waargenomen met betrekking tot de NYHA classificatie, kwaliteit van leven, ”selfcare” en zorgkosten. De DEAL-HF studie toonde aan dat een hartfalen management programma met een intensieve interventie volgens protocol, door een combinatie van een cardiovasculaire verpleegkundige en een arts in een land met een adequate eerste lijns gezondheidszorg, waarin huisartsen optreden als de “gatekeepers” voor de tweedelijns zorg, toegevoegde klinische waarde kan opleveren. Kosten-effectiviteit In Hoofdstuk 6 geven wij een gedetailleerde vergelijking van de effecten van dit hartfalen management programma alsmede de kosten. Overleving, ernst van de ziekte, aan ziekte en gezondheid gerelateerde kwaliteit van leven, economisch nut, “Quality adjusted life years” (QALYs) en kosten worden behandeld met een tijdshorizon van1 jaar. Het hartfalen management programma verbeterde de verwachte tijd van overleven gedurende het eerste follow-up jaar met 0.025 jaar (95% CI: (-0.020; 0.071)). Veranderingen in de ernst van de ziekte (NYHA classificatie) waren significant beter bij de interventiegroep. Als we de effecten op overleven buiten beschouwing laten, was de gemiddelde toename in SF-36 (schaal 0-100) 5.6 punten groter (p-waarde 0.062) in de interventiegroep en het verschil in de verandering in de MLWHF (schaal 105-0) was 5.2 punten (p -waarde 0.108). De winst in QALYs werd geschat op 0.032 (95% CI: (-0.018,+0.078)). De kostenbesparingen per patiënt werden geschat op E 2.484 (95% CI: -E5328; -E145). De waarschijnlijkheid dat de interventie kostenbesparend is wordt op 98% geschat en de waarschijnlijkheid dat er een winst aan QALYs is op 87%. Deze meer gedetailleerde analyse van de kosten en effecten van het hartfalen management programma, in de DEAL HF studie, bevestigt dat zo’n programma van toegevoegde klinische waarde is en kostenbesparend.

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Algemene discussie In de algemene discussie (Hoofdstuk 7) werden de schijnbaar tegenstrijdige resultaten van twee recent uitgevoerde gerandomiseerde hartfalen management onderzoeken in Nederland, nl het DEAL-HF onderzoek en de COACH studie (Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) in beschouwing genomen. Meer nadruk op optimalisatie van HF medicatie, een HF management programma geleid door een arts en een verpleegkundige en een groter contrast tussen interventiegroep en gebruikelijke zorggroep in de DEAL-HF studie hebben waarschijnlijk bijgedragen aan de verschillen, die gezien worden met de resultaten van het COACH onderzoek. Toekomstig onderzoek zal moeten uitwijzen welke hartfalen management programma’s meest effectief zijn in welke patiënten. En vooral of meer individuele zorg door verschillende zorgverleners het hartfalen management en de uitkomsten verbetert tegen acceptabele kosten. Zulke studies zullen complex van ontwerp zijn en nogal moeilijk om uit te voeren. Echter, de snel groeiende populatie van patiënten met hartfalen heeft deze onderzoeken nodig.

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Vakgroep Dermatologie Artikelen The effect of combined treatment with oral clindamycin and oral rifampicin in patients with hidradenitis suppurativa. van der Zee H, Boer J, Prens EP, Jemec GB Dermatology 2009; 219(2): 143-7 Abstract Background: a previous limited study showed promising results of combined oral treatment with rifampicin 600 mg and clindamycin 600 mg for 10 weeks. Objective: to expand and to validate the basis for this therapy, we reviewed the response to different treatment durations. Method: a retrospective study in 34 patients. Results: twenty-eight of 34 patients (82%) experienced at least partial improvement, and 16 (47%) showed a total remission. The maximum effect of treatment appeared within 10 weeks. Following total remission, 8 of 13 (61.5%) Patients treated as mentioned above experienced a relapse after a mean period of 5.0 Months. Nonresponders were predominantly patients with severe disease. Conclusion: combination treatment with oral rifampicin and clindamycin is a promising treatment option for hidradenitis suppurativa, despite the frequent occurrence of diarrhea as a side effect. The length and the dosage of treatment are not yet firmly established. Copyright 2009 s. Karger ag, basel. The DESIRE study – psoriasis patients’ satisfaction with topical treatment using a fixed combination of calcipotriol and betamethasone dipropionate in daily clinical practice. Claréus BW, Houwing RH, Sindrup JH, Wigchert S Eur J Dermatol. 2009; 19(6): 581-5 Abstract Daivobet (Dovobet) is a fixed combination ointment of calcipotriol and betamethasone dipropionate. The real-life clinical use of calcipotriol/ betamethasone dipropionate treatment was assessed in this multi-centre, single-group, non-interventional study. Patients with psoriasis vulgaris who had a recent calcipotriol/betamethasone dipropionate prescription prior to the study start evaluated their satisfaction with the treatment after a 4-week course and after repeated courses for up to 6 months. Of the 1224 patients enrolled, 81.5% completed the 6-month study period. Approximately 75% of the patients were satisfied/very satisfied after one calcipotriol/betamethasone dipropionate treatment course and the satisfaction was high regardless of initial disease severity. 16

Repeated calcipotriol/betamethasone dipropionate courses were prescribed for 22.9% of the patients and treatment satisfaction remained high (about 80%). The majority (60%) of the patients were willing to provide co-payments for calcipotriol/betamethasone dipropionate within their national health insurance system. Geheugenverlies na fotodynamische therapie. Onderdijk AJ, Ossenkoppele PM, Houwing RH Ned Tijdschr Dermatol Venereol. 2009; 19(6): 308-9 Allergisch contacteczeem door beroepsmatig contact met hortensia (Hydrangea). De Graaf M, Van Ginkel CJW, Bruijnzeel-Koomen CAFM, Rooeckmann H. Ned Tijdschr Dermatol Venereol. 2009; 19: 279-81 Behandeling van actinische keratose in de huisartsenpraktijk. Van Ginkel CJW Derma Actueel 2009; 8(1) Wat is de rol van de huisarts in de diagnostiek en behandeling van ­ non-melanoma huidkanker? Van Ginkel CJW Vademecum permanente nascholing huisartsen 2009 (nr 47) Samenvatting Het belang voor de gezondheidszorg van het tijdig onderkennen van het maligne karakter van een huidlesie overstijgt het belang van al dan niet zelf nemen van biopsie of zelf behandelen; immers zonder correcte diagnose van maligniteit, nimmer adequate behandeling. De grote handicap bij het zelf behandelen van huidtumoren door de huisarts is het beperkte aantal patiënten waarmee hij/zij ervaring kan opdoen. Deels zou dit probleem ondervangen kunnen worden door alle patiënten met huidkanker binnen een groepspraktijk te bundelen bij een specifiek in dit onderwerp geïnteresseerde collega.

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Vakgroep Geriatrie Voordrachten

Artikelen

Hidradenitis suppurativa: Resorcinol peels and deroofing. J. Boer Education course Dermatologists. Dessau, Germany, February 9, 2009

De diabetespatiënt wordt steeds ouder, maar blijft de behandeling gelijk? M. Zeeman EADV Magazine 2009; 24(4): 14-5

Webcasting over actinische keratose en huidkanker CJW van Ginkel Nascholing voor huisartsen Hilversum, 18 juni en 17 sept

Ingezonden brieven Successful treatment of dissecting cellulitis with ciprofloxacin. Onderdijk AJ, Boer J Clin Exp Dermatol. 2009; 34(7): e507

Boekbijdrages Richtlijn decubitus. Hoofdstuk 3 Decubitus pag. 30 -41 R.H. Houwing Samenvatting Richtlijnen Dermatologie NVDV DCHG. Red. J.J.J.E. van Everdingen, R.J. Borgonjen ISBN 9789081164665

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Vakgroep Gynaecologie, Verloskunde en Voortplantingsgeneeskunde Artikelen Do patient characteristics influence the accuracy of hysterosalpingography in the diagnosis of tubal pathology: an individual patient data metaanalysis? Broeze KA, Opmeer BC, Coppus S, Den Hartog J, Van der Linden PJ, Marianowski P, Ng E, Van der Steeg JW, Strandell A, Idahl A, Mol BW Hum Reprod. 2009; 24 suppl 1: i201 Estimation of the accuracy of the Chlamydia Antibody Test based on individual data of subfertile women. Broeze KA, Opmeer BC, Coppus S, Anestad G, Bhattacharya S, Debattista J, Guerra-infante MF, Land J, Idahl A, Van der Linden PJ, Mouton J, Ng E, Van der Steeg JW, Svenstrup HF, Tiitinen A, Toye B, Mol BW Hum Reprod. 2009; 24 suppl 1: i202 Perforation of an intrauterine device in a cesarean scar. Van der Voet L, Graziosi G, Veersema S, Bij de Vaate M, Huirne J, Brölmann H Gynecol Surg. 2009; 6 suppl 1: S106

Voordrachten Perforation of an intrauterine device in a cesarean scar. L. van der Voet, G. Graziosi, S. Versema, M. Bij de Vaate, J. Huirne, H. Brölmann 18th congress ESGE, Florence Italy, October 31, 2009

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Vakgroep Heelkunde Artikelen Een vrouw met een woekering aan de teennagel. Wagenaar FC, de Vries H Ned Tijdschr Geneeskd. 2009; 153: B355 Abstract A 34-year-old woman presented with a progressive subungual swelling of the hallux caused by subungual exostosis. Buikpijn en rectaal bloedverlies. Luxwolda MF, de Wit LT, Karthaus AJM Ned Tijdschr Tandheelkd. 2009; 116(9): 467-470 Samenvatting De medische voorgeschiedenis van een 46-jarige man vermeldde op 28-jarige leeftijd osteomen in het os maxilla, hermorroïden en nierstenen. Hij kwam op de afdeling Spoedeisende hulp van een medisch centrum in verband met pijn rechts in de onderbuik en rectaal bloedverlies. De symptomen werden gediagnosticeerd als familiaire adenomateuze polyposis, waarbij een sigmoïdcarcinoom was ontstaan. In verband met de uitgebreidheid van de poliepen en de daarbij aanwezige verhoogde kans op een recidiefcarcinoom was een chirurgische behandeling geïncideerd. Symptomen van een variant van familiaire adenomateuze polyposis, het syndroom van Gardner, zijn osteomen in het os maxillaris. Tandartsen en kaakchirurgen zouden bij een patiënt met orofaciale osteomen alert moeten zijn op dit zeldzame syndroom, vooral als de patiënt familiair is belast met het risico op adenomateuze polyposis. The dynamic locking blade plate, a new implant for intracapsular hip fractures biomechanical comparison with the sliding hip screw and twin hook. Roerdink WH, Aalsma AMM, Nijenbanning G, van Walsum ADP Injury 2009; 40(3): 283-7

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Abstract Internal fixation of intracapsular hip fractures results in a high failure rate with non-union and avascular necrosis being the two most important complications. In order to prevent these possible complications treatment should consist of an anatomical reduction and stable fixation by insertion of a low volume, dynamic implant, providing angular and rotational stability to the femoral head. According to these principles a new implant, the dynamic locking blade plate (DLBP) was designed for the fixation of intracapsular hip fractures. We performed a biomechanical analysis in synthetic bone to compare the rotational stability and cut out resistance of the DLBP with a conventional sliding hip screw (SHS) and the more recently developed Twin Hook. The rotational stability of the DLBP proved to be three times higher than the rotational stability of a SHS and two times higher than the Twin Hook. There was no major difference in cut out resistance between the different implants. The design of the DLBP and possible advantages with regard to the healing of an intracapsular hip fracture are discussed.

Laparoscopic recto-sigmoid resection for diverticular disease is suitable as a training operation. R.J.I. Bosker European Association of Endoscopic Surgery Praag, mei 2009

Voordrachten

MDL/NVGIC unit, wat is de winst? Eddes EH Nederlandse Vereniging voor Gastrointestinale Chirurgie Oegstgeest, 24 maart 2009

Geen aanvullende chirurgie bij maligne colonpoliepen de rol van biopten uit het poliepectomie litteken. L. van Nunspeet, E.J. Kuipers, J.W. Arends, M. Eeftinck Schattenkerk, F. ter Borg Najaarsvergadering NvvH Ede, 27 november 2009 Themabijeenkomst ‘De toekomst van de Gastro-intestinale Chirurgie in Nederland’ De 2-2-2 opzet: de noodzaak tot verdere differentiatie. M. Eeftinck Schattenkerk Corpus Experience Leiden, 24 maart 2009 Laparoscopic resection for diverticular disease is suitable as a training operation. R.J.I. Bosker European Association of Endoscopic Surgery Praag, 19 juni 2009

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Endoscopically removed malignant colorectal polyps with uncertain histological radicality: surgery or endoscopic follow-up? L. van Nunspeet, F. ter Borg, J.W. Arends, M. Eeftinck Schattenkerk, E.J. Kuipers Voorjaarscongres NVGE Veldhoven, 19 maart 2009 Nieuwe registraties, eenvoudige realisaties met hulp van een gedetailleerd draaiboek. Eddes EH Symposium Dutch Surgical Colorectal Audit Utrecht, 12 februari 2009

Dutch surgical colorectal audit. Eddes EH Dutch Colorectal Cancer Group Leiden, 2 oktober 2009 Results of patients with haemorrhoids treated with Doppler-guided haemorrhoidal artery ligation. Pol RA, van der Zwet WC, Hoornenborg D, Lodewijk L, Makkinga B, Wallis de Vries BM, Kaijser M, Eeftinck Schattenkerk M, Eddes EH Nederlandse Vereniging voor Gastroenterologie Veldhoven, 8 oktober 2009 Dutch surgical colorectal audit, goed voorbeeld doet goed volgen. Eddes EH Nederlandse Vaatdagen Emmen, 16 oktober 2009

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Vakgroep Interne Geneeskunde Colorectale tumoren. Eddes EH Invitational Conference, Kwaliteit van Kankerzorg Koningin Wilhelmina Fonds Utrecht, 12 november 2009 Dutch surgical colorectal audit, update en toekomstperspectief. Eddes EH Nederlandse Vereniging voor Heelkunde Ede, 27 november 2009 Abdominoperineale resectie (APR) na korte pre-operatieve radiotherapie in verband met rectumcarcinoom. Minder pre-sacrale abcessen bij toepassen van een omentum plastiek. Kaijser MA, Eeftinck Schattenkerk M, Eddes EH Nederlandse Vereniging voor Heelkunde Ede, 27 november 2009 Colonic stenting is good as bridge to surgery in acute obstruction. Eddes EH Nederlandse Vereniging voor Gastrointestinale Chirurgie Rotterdam, 11 december 2009 Factors associated with success and complication rate of colonic stenting. J.J. Driest, M. Ledeboer, M. Eeftinck Schattenkerk, E.J. Kuipers, F. ter Borg Voorjaarscongres NVGE, maart 2009 Factors associated with success and complication rate of colonic stenting. J.J. Driest, M. Ledeboer, M. Eeftinck Schattenkerk, E.J. Kuipers, F. ter Borg Digestive Diseases Week Chicago, mei 2009

Posters The effect of proctoring on the implementation of laproscopic surgery. R.J.I. Bosker European Association of Endoscopic Surgery Prague, June 19 2009

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Artikelen Stent placement in patients with artherosclerotic renal artery stenosis and impaired renal function a randomized trial. Bax L, Woittiez AJ, Kouwenberg HJ, Mali WP, Buskens E, Beek FJ, Braam B, Huysmans FT, Schultze Kool LJ, Rutten MJ, Doorenbos CJ, Aarts JC, Rabelink TJ, Plouin PF, Raynaud A, van Montfrans GA, Reekers JA, van den Meiracker AH, Pattynama PM, van de Ven PS, Vroegindeweij D, Kroon AA, de Haan MW, Postma CT, Beutler JJ Ann Intern Med. 2009; 150(12): 840-8, W150-1 Abstract Background: little is known about the efficacy and safety of renal artery stenting in patients with atherosclerotic renal artery stenosis (aras) and impaired renal function. Objective: to determine the efficacy and safety of stent placement in patients with aras and impaired renal function. Design: randomized clinical trial. Randomization was centralized and computer generated, and allocation was assigned by e-mail. Patients, providers, and persons who assessed outcomes were not blinded to treatment assignment. Setting: 10 european medical centers. Participants: 140 patients with creatinine clearance less than 80 ml/min per 1.73 M(2) and aras of 50% or greater. Intervention: stent placement and medical treatment (64 patients) or medical treatment only (76 patients). Medical treatment consisted of antihypertensive treatment, a statin, and aspirin. Measurements: the primary end point was a 20% or greater decrease in creatinine clearance. Secondary end points included safety and cardiovascular morbidity and mortality. Results: forty-six of 64 patients assigned to stent placement had the procedure. Ten of the 64 patients (16%) in the stent placement group and 16 patients (22%) in the medication group reached the primary end point (hazard ratio, 0.73 [95% Ci, 0.33 To 1.61]). Serious complications occurred in the stent group, including 2 procedure-related deaths (3%), 1 late death secondary to an infected hematoma, and 1 patient who required dialysis secondary to cholesterol embolism. The groups did not differ for other secondary end points. Limitation: many patients were falsely identified as having renal artery stenosis greater than 50% by noninvasive imaging and did not ultimately require stenting. Conclusion: stent placement with medical treatment had no clear effect on progression of impaired renal function but led to a small number of significant procedure-related complications. The study findings favor a conservative approach to patients with aras, focused on cardiovascular risk factor management and avoiding stenting.

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A familial disorder with low bone density and renal phosphate wasting. Grondel IM, van der Deure J, Zanen AL, Dogger M, van den Heuvel LP Eur J Intern Med. 2009; 20(5): 503-8 Abstract: Zie kindergeneeskunde

Randomized double-blind phase II trial comparing gemcitabine plus LY293111 versus gemcitabine plus placebo in advanced adenocarcinoma of the pancreas Saif MW, Oettle H, Vervenne WL, Thomas JP, Spitzer G, Visseren-Grul C, Enas N, Richards DA Cancer J. 2009; 15(4): 339-43 Abstract Background: ly293111 (ly) is a novel oral anticancer agent with leukotriene b4 receptor antagonist and peroxisome proliferator-activated receptor gamma agonist properties, producing promising results alone and in combination with gemcitabine in pancreatic cancer xenograft models. A phase i study proved that the combination (gemcitabine plus ly) is safe and well tolerated. Patients and methods: chemotherapy-naive patients with histologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas were randomly assigned to gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and continuously administered ly 600 mg twice daily or gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and daily oral placebo. Arms were balanced for eastern cooperative oncology group performance status and disease stage. The primary end point was 6-month survival; secondary objectives include response rate (rr), progression-free survival, and overall survival. Results: six-month survival was not different between groups (p>0.2, 1-Sided); progression-free survival and rr were not different (p>0.05, 2-Sided). Rr was also not impacted. Ly did not increase grades 3-4 hematologic toxicities, but was associated with a trend toward more, grades 3-4 diarrhea. Conclusions: these results do not demonstrate any benefit to adding ly to gemcitabine in unpretreated patients with advanced pancreatic carcinoma.

Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. Van Cutsem E, Vervenne WL, Bennouna J, Humblet Y, Gill S, Van Laethem JL, Verslype C, Scheithauer W, Shang A, Cosaert J, Moore MJ. J Clin Oncol. 2009; 27(13): 2231-7 Abstract Purpose: treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (os) versus gemcitabine alone. Phase ii results for bevacizumab plus gemcitabine provided the rationale for a phase iii trial of gemcitabine-erlotinib plus bevacizumab or placebo. Patients and methods: patients with metastatic pancreatic adenocarcinoma were randomly assigned to receive gemcitabine (1,000 mg/m(2)/week), erlotinib (100 mg/day), and bevacizumab (5 mg/kg every 2 weeks) or gemcitabine, erlotinib, and placebo in this double-blind, phase iii trial. Primary end point was os; secondary end points included progression-free survival (pfs), disease control rate, and safety. Results: a total of 301 patients were randomly assigned to the placebo group and 306 to the bevacizumab group. Median os was 7.1 And 6.0 Months in the bevacizumab and placebo arms, respectively (hazard ratio [hr], 0.89; 95% Ci, 0.74 To 1.07; P = .2087); This difference was not statistically significant. Adding bevacizumab to gemcitabine-erlotinib significantly improved pfs (hr, 0.73; 95% Ci, 0.61 To 0.86; P = .0002). Treatment with bevacizumab plus gemcitabine-erlotinib was well tolerated: safety data did not differ from previously described safety profiles for individual drugs. Conclusion: the primary objective was not met. The addition of bevacizumab to gemcitabine-erlotinib did not lead to a statistically significant improvement in os in patients with metastatic pancreatic cancer. Pfs, however, was significantly longer in the bevacizumab group compared with placebo. No unexpected safety events were observed from adding bevacizumab to gemcitabine-erlotinib. Escherichia coli, een zeldzame verwekker van cellulitis. Sprenger RA, Sebens FW, Diekman T Nederlands Tijdschrift voor Infectieziekten 2009; 6: 235-9 Cerebrospinal fluid leak. Diekman T, Mees B N Engl J Med. 2009; 361(14): e26 [Images in clinical medicine]

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Bijwerkingen van valacyclovir bij gestoorde nierfunctie. Klinische les. I.R.F. van Berlo-van de Laar, E.R. Goet, A. Helldén, H.E. Sluiter Ned Tijdschr Geneesk. 2009; 153(15): B198 Patients’ representations of their end-stage renal disease: relation with mortality. van Dijk S, Scharloo M, Kaptein AA, Thong MS, Boeschoten EW, Grootendorst DC, Krediet RT, Dekker FW; NECOSAD Study Group, [Doorenbos CJ] Nephrol Dial Transplant. 2009 Oct;24(10):3183-5 Association of body mass index with decline in residual kidney function after initiation of dialysis. Drechsler C, de Mutsert R, Grootendorst DC, Boeschoten EW, Krediet RT, le Cessie S, Wanner C, Dekker FW ; NECOSAD Study Group, [Doorenbos CJ] Am J Kidney Dis. 2009 Jun;53(6):1014-23 Disordered mineral metabolism is not a risk factor for loss of residual renal function in dialysis patients. Noordzij M, Voormolen NM, Boeschoten EW, Dekker FW, Bos WJ, Krediet RT, Korevaar JC; NECOSAD study group, [Doorenbos CJ] Nephrol Dial Transplant. 2009 May;24(5):1580-7 Subjective global assessment of nutritional status is strongly associated with mortality in chronic dialysis patients. de Mutsert R, Grootendorst DC, Boeschoten EW, Brandts H, van Manen JG, Krediet RT, Dekker FW; Netherlands Cooperative Study on the Adequacy of Dialysis-2 Study Group, [Doorenbos CJ] Am J Clin Nutr. 2009 Mar;89(3):787-93

Gynaecomastia and gallstone disease due to estrogen therapy for metastatic prostate carcinoma with acanthosis nigricans of the areola mammae as a paraneoplastic phenomenon T. Diekman Society for Endocrinology Manchester, UK, 2009 Transient gestational diabetes insipidus in a patient with pre-eclampsia. R.A. Sprenger, T. Diekman Nederlandse Internisten dagen Maastricht, 2009 Nieuwe opleidingseisen voor internisten. H.E. Sluiter Voordracht internistensymposium INNOVA Ameland, 14-16 mei 2009

Posters Incidence of metformin associated lactic acidosis estimated from metformin serum concentration measurements. I.R.F. van Berlo-van de Laar, C.G. Vermeij, C.J. Doorenbos 11th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology Montreal, October 3-8, 2009 Abstract gepucliceerd in Ther Drug Monit. 2009; 31(5): 636

Voordrachten

Valproate-related hyperammonemic encephalopathy in a haemodialysis patient E.R. Goet, C.G. Vermeij, F.J.J. Prick, A.L. Zanen Abstractboek 21e Internistendagen 2009

Improving lives through more physiological alternate day hemodialysis. C.J. Doorenbos, A.M.V. Reijlink American Society of Nephrology San Diego, 2009

Actual incidence of metformin associated lactic acidosis in type 2 diabetes mellitus is underestimated in the literature Vermeij CG, van Berlo-van de Laar IRF, Doorenbos CJ, Abstractboek 21e Internistendagen, 2009 Rash as a marker for the efficacy of gemcitabine plus erlotinib-based therapy in pancreatic cancer: Results from the AViTA study. E. Van Cutsem, W.L..Vervenne, J. Bennouna, Y. Humblet, J. Cosaert Proceedings ASCO GI, San Francisco, USA, January 2009

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Vakgroep Keel Neus Oorheelkunde Artikelen Surgical or medical management of subperiosteal abscess in children: a critical appraisal of the literature. Coenraad S, Buwalda J Rhinology 2009; 47(1): 18-23 Abstract Objective: subperiosteal orbital abscesses (spoa) are a complication of sinusitis. Traditional treatment of spoa is surgical. Recently, a number of studies report successful medical treatment. To our knowledge, it is unclear which patients can benefit from medical management alone. Therefore, we questioned (1) what is the outcome of medical versus surgical treatment? (2) Which patients can be cured with antibiotics alone? (3) What are the absolute criteria for surgical treatment? Methods: a structured search was conducted in pubmed, embase and the cochrane library for relevant papers which were critically appraised. Results: five studies addressing our clinical questions were included, one prospective case series and four retrospective studies. Evidence levels varied from 2b to 3. Overall, a high cure rate was achieved with combined modality treatment (95.3-100%). The cure rate of medical treatment alone varied between 26% and 93%. The outcome of medical treatment improved after prior selection of surgical cases. In general, responders to medical treatment had a medial abscess associated with ethmoid sinusitis. Criteria for initial surgical or medical management differed among authors. Most authors agreed upon initial surgical treatment for patients with non-medial abscesses, decreased visual acuity and signs of systemic involvement. Surgery was also indicated when lack of improvement or worsening of symptoms and signs after 48-72 hours of medical treatment were observed. Conclusions: the outcome of surgical versus medical management of spoa within and between studies could not be compared. Higher cure rates were observed when both modalities were combined. There is some evidence that medical treatment can cure medially located spoa. Loss of visual acuity, non-medial abscess, clinical detoriation and failure to improve within 48 hours of antibiotic treatment can be considered as criteria for surgical treatment. In the absence of these criteria a trial of antibiotic treatment can be considered with close monitoring of the patient.

The AMORE protocol for advanced-stage and recurrent nonorbital rhabdomyosarcoma in the head-and-neck region of children: a radiation oncology view. Blank LE, Koedooder K, Pieters BR, van der Grient HN, van de Kar M, Buwalda J, Balm AJ, Merks JH, Strackee SD, Freling NJ, Koning CC Int J Radiat Oncol Biol Phys. 2009; 74(5): 1555-62 Abstract Purpose: a multidisciplinary approach, consisting of consecutive ablative surgery, mold technique with afterloading brachytherapy and immediate surgical reconstruction (amore) applied after chemotherapy, was designed for children with rhabdomyosarcoma in the head-and-neck region. Analysis of the first 42 patients was performed. Methods and materials: after macroscopically radical tumor resection, molds were constructed for each individual to fit into the surgical defect. The molds, made of 5-mm-thick layers of thermoplastic rubber, consisted of different parts. Flexible catheters were positioned between layers. After brachytherapy, the molds were removed. Surgical reconstruction was performed during the same procedure. Results: dose to the clinical target volume varied from 40 to 50 gy for the primary treatment (31 patients) and salvage treatment groups (11 patients). There were 18 females and 24 males treated from 1993 until 2007. Twenty-nine tumors were located in the parameningeal region, and 13 were located in the nonparameningeal region. Patient age at the time of amore was 1.2-16.9 Years (average, 6.5 Years). Follow-up was 0.2-14.5 Years (average, >5.5 Years). Eleven patients died, 3 with local recurrence only, 6 with local and distant disease, 1 died of distant metastases only, and 1 patient died of a second primary tumor. Overall 5-year survival rates were 70% for the primary treatment group and 82% for the salvage group. Treatment was well tolerated, and acute and late toxicity were mild. Conclusions: the amore protocol yields good local control and overall survival rates, and side effects are acceptable. Anosmia after endovascular and open surgical treatment of intracranial aneurysms. Moman MR, Verweij BH, Buwalda J, Rinkel GJ J. Neurosurg. 2009; 110(3): 482-6 Abstract OBJECT: Patients treated for aneurysmal subarachnoid hemorrhage (SAH) often report a loss of smell. To discriminate between the effects of aneurysmal rupture and treatment, the authors assessed the occurrence of anosmia after clipping and coiling of unruptured aneurysms as well as after the coiling of

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ruptured aneurysms. Methods: the authors interviewed patients in whom an unruptured aneurysm was treated by clipping (32 cases) or endovascular coiling (26 cases) as well as patients with sah who underwent coil therapy (32 cases). A geographically defined subset of 20 patients per group was invited to undergo olfactory testing. Results: nine clip-treated patients (28% [95% ci 14-47%]) in the unruptured group reported having anosmia, and no coil-treated patient in the unruptured group (95% [ci 0-13%]) reported having anosmia; in the sah group, 7 patients (22% [95% ci 9-40%]) reported having anosmia. Anosmia had improved over time in 3 of the clip-treated patients and in all but 1 of the patients with sah. Examination revealed olfactory disturbance in 13 (65% [95% ci 41-85%]) of the clip-treated and 8 (42% [95% ci 20-67%]) of the coil-treated patients with unruptured aneurysms, and also in 7 (35% [95% ci 15-59%]) coil-treated patients with sah. In 20 patients who underwent clip therapy for unruptured aneurysms, 19 (95% [95% ci 75-100%]) had olfactory dysfunction on the side ipsilateral to surgery (anosmia reported by 8 of them). Conclusions: both clip treatment and sah contribute to the occurrence of anosmia, with different chances of improvement. Olfactory dysfunction occurs in almost all patients on the side of surgery and can occur subclinically after coil deployment. Botulinum toxin A injection into corrugator muscle for frontally localised chronic daily headache of chronic tension-type headache. de Ru JA, Buwalda J J Laryngol Otol. 2009; 123(4): 412-7 Abstract Objective: to describe our results with botulinum toxin type a injection for headache in carefully selected patients, and to present the rationale behind this therapy. Setting: tertiary referral centre. Patients and methods: this article describes a case series of 10 consecutive patients with frontally localised headache, whose pain worsened when pressure was applied at the orbital rim near the supratrochlear nerve. The patients received a local anaesthetic nerve block with xylocaine 2 per cent at this site. If this reduced the pain, they were then offered treatment with botulinum toxin. Intervention: injection with 12.5 Iu of botulinum toxin a into the corrugator supercilii muscle on both sides (a total of 25 iu). Main outcome measure: pain severity scoring by the patients, ranging from zero (no pain) to 10 (severe pain) on a verbal scale. Results: following injection, all patients had less pain for approximately two months. This treatment did not appear to have lasting side effects. Conclusion: xylocaine injection is a good predictor of the effectiveness of botulinum toxin injection into the corrugator muscle as treatment of frontally localised headache.

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We hypothesise that this pain is caused by entrapment of the supratrochlearis nerve in the corrugator muscle. Furthermore, we found botulinum toxin injection to be a safe and effective means of achieving pain relief in this patient group. No detectable hypoxia in malignant salivary gland tumors preliminary results. Wijffels Ki, Hoogsteen Ij, Lok J, Rijken Pf, Marres Ha, De Wilde Pc, Van Der Kogel Aj, Kaanders Jh Int j radiat oncol biol phys. 2009; 73(5): 1319-25 Abstract Purpose: hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type. Methods and materials: twelve patients scheduled for surgical resection of a salivary gland tumor were preoperatively injected with the hypoxia marker pimonidazole and the proliferation marker iododeoxyuridine. Tissue samples of the dissected tumor were immunohistochemically stained for blood vessels, pimonidazole, carbonic anhydrase-ix, glucose transporters-1 and -3 (glut-1, glut-3), hypoxiainducible factor-1alpha, iododeoxyuridine, and epidermal growth factor receptor. The tissue sections were quantitatively assessed by computerized image analysis. Results: the tissue material from 8 patients was of sufficient quality for quantitative analysis. All tumors were negative for pimonidazole binding, as well as for carbonic anhydrase-ix, glut-1, glut-3, and hypoxiainducible factor-1alpha. The vascular density was high, with a median value of 285 mm(-2) (range, 209-546). The iododeoxyuridine-labeling index varied from <0.1% To 12.2% (Median, 2.2%). Epidermal growth factor receptor expression levels were mostly moderate to high. In one-half of the cases, nuclear expression of epidermal growth factor receptor was observed. Conclusion: the absence of detectable pimonidazole binding, as well as the lack of expression of hypoxia-associated proteins in all tumors, indicates that malignant salivary gland tumors are generally well oxygenated. It is unlikely that hypoxia is a relevant factor for their clinical behavior and treatment responsiveness. Cerebrospinal fluid leak. Diekman T, Mees B N engl j med. 2009; 361(14): E26 [images in clinical medicine] 33

Promoties Microenvironmental parameters in head and neck tumours. K.I.E.M. Wijffels Nijmegen, Radboud Universiteit, 25 mei 2009 Samenvatting De behandelingsuitkomst van de individuele patiënt met een hoofd-hals tumor staat steeds meer in de belangstelling. Belangrijke factoren die het resultaat van een bestraling beïnvloeden, zijn hypoxie en proliferatie. Hypoxie is onder te verdelen in diffusie-gelimiteerd ofwel chronische hypoxie en perfusie-gelimiteerd ofwel acute hypoxie. Arcon is een bestralingsbehandeling die hierop is gebaseerd. In het umc st radboud te nijmegen vindt een onderzoek plaats waarbij patiënten naast een versnelde bestraling (accelerated radiotherapy) tevens tijdens de behandeling carbogeen en nicotinamide krijgen toegediend. De versnelde bestraling voorkomt tussentijdse celdeling. Carbogeen is een zuurstofrijk mengsel (95-98%) en heeft een positief effect op de chronische hypoxie. Nicotinamide voorkomt vaatspasme en heeft daarbij een goed effect op de acute hypoxie. Het doel van dit promotieonderzoek was om hypoxie en mate van proliferatie bij patiënten aan te tonen en vervolgens te relateren aan de behandelresultaten. We hopen hiermee in de toekomst tot een betere patiëntenselectie voor arcon of andere behandelingen te komen. Patiënten met een hoofd-halstumor kregen intraveneus pimonidazol (hypoxische marker) en idurd (proliferatie marker) toegediend. Vervolgens werden routinematig biopten afgenomen. De biopten werden immunohistochemisch gekleurd voor hypoxie, vaten en proliferatie. De biopten werden gescand waarop de beelden werden omgezet naar een binair beeld. Met behulp van een aanpalende he-coupe werd niet vitaal tumorweefsel uitgetekend. Het bleek goed mogelijk om met pimonidazol hypoxie aan te kleuren. De hoeveelheid hypoxie was heel divers. Zo konden we in speekselkliertumoren helemaal geen hypoxie aantonen, ook niet met andere immunohistochemische markers. In plaveiselcelcarcinomen daarentegen varieerde de hypoxische fractie van ongeveer 2% tot 29%. Niet alleen de hoeveelheid hypoxie toonde een grote variatie, ook de verdeling van de hypoxie toonde een grote intertumorvariabiliteit. Zo vonden we tumoren met vitale hypoxische velden op grote afstand van de vaten (>200µm), terwijl bij andere tumoren de hypoxie in nauwe relatie met de vaten verliep. Deze verschillen konden we ook kwantitatief vastleggen.

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De locoregionale tumorvrije controle na twee jaar bedroeg 48 versus 87% voor tumoren met een hoge en lage pimonidazolaan­kleuring (p=0.01) En 48 en 88% voor tumoren met een lage en hoge vaatdichtheid (p=0.01). Deze verschillen verdwenen bij de groep patiënten die was behandeld met arcon. Tevens is een retrospectief onderzoek verricht bij met arcon behandelde patiënten, met verschillende endogene hypoxiegerelateerde markers (ca-ix, glut-1 en glut-3). Met idurd werd eveneens een betrouwbare en reproduceerbare kleuring verkregen. Wij vonden ook met de proliferatie verschillende patronen in relatie met de vaten. Na xenotransplantatie in een naakte muis behield de helft van de tumoren hetzelfde patroon. De kans op groei na implantatie in de muis was significant hoger voor tumoren met een labelingindex en vaatdichtheid boven de mediaan in vergelijking met tumoren waarbij deze waarden onder de mediaan lagen (82-35%). Aangezien hypoxische klonogene cellen van belang zijn bij de tumorrespons na radiotherapie werd tevens een dubbelkleuring uitgevoerd op hypoxie en idurd. Het aantal idurd-positieve cellen in hypoxisch gebied bedroeg slechts 0.09% Van het totaal aantal vitale tumorcellen. Er was geen verband tussen deze subpopulatie en lokale tumorcontrole of overleving. Concluderend is het mogelijk om met routinematig verkregen biopten een indruk te krijgen van de hypoxie en proliferatie, en hiermee kan de behandeling in de toekomst beter op de patiënt worden toegespitst.

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Vakgroep Kindergeneeskunde Artikelen

Voordrachten

A familial disorder with low bone density and renal phosphate wasting. Grondel IM, van der Deure J, Zanen AL, Dogger M, van den Heuvel LP Eur J Intern Med. 2009; 20(5): 503-8

Incontinentie bij kinderen trainingsresultaten in een perifeer ziekenhuis. J. van de Deure Wetenschappelijke bijscholing kinderurotherapie WKZ Utrecht, 13 maart 2009

Abstract Hereditary forms of renal phosphate wasting have been studied thoroughly in the past years. X-linked Hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets/osteomalacia (ADHR) and autosomal recessive hypophosphatemic rickets (ARHR) are known genetic disorders in which a disturbance of phosphatonins is a causative factor in the pathogenesis. We describe a comparable but yet undescribed disorder in a family in which a 53 year old man presented with a spontaneous fracture after suffering for years with severe fatigue and musculoskeletal pains. A low serum phosphate was discovered. The two subsequent generations of this family developed the same symptoms but at an earlier age. Almost all family members have been investigated and the majority appears to have low bone density and/or renal phosphate wasting and/or low serum phosphate. Remarkably no rickets was found. No elevation of FGF23 or mutations in the gene encoding FGF23 were found. We believe this is a new familial disorder of bone metabolism and phosphate homeostasis in which a disturbance of bone modulators may play a central role. 2009 European Federation of Internal Medicine.

24-uurs bloeddrukmeting bij kinderen een evaluatie in de algemene praktijk. J. Alink, J. van der Deure Voordracht Congres Nederlandse Vereniging Kindergeneeskunde, Veldhoven, 5 nov 2009

Posters Incidence of CAKUT and concomitant anomalies in children with a congenital solitary functioning kidney – The KIMONO-STUDY R. Westland, M.F. Schreuder, J. van der Deure, W.W. Hack, H.J.R. van der Horst, J.A.E. van Wijk Congres of the European Society of Pediatric Nephrology, Birmingham, UK, 2-5 September

Even een beta-lactam-allergie uitsluiten bij een kind. Gorissen DMW Ned Tijdschr Allergie 2009; 9(6): 199-204 Samenvatting In dit artikel wordt een 5-jarige jongen beschreven met een tweetal reacties op verschillende antibiotica. Er worden internationale diagnostische protocollen geschetst met betrekking tot beta-lactam-antibiotica-allergie. Hierbij worden de beperkingen bij kinderen geschetst, met het accent op de geneesmiddelenprovocatie als gouden standaard.

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Vakgroep Klinische Chemie

Vakgroep Klinische Farmacie

Artikelen

Artikelen

Minder bloedtransfusies na invoering van autotransfusiesysteem bij heup- en knievervanging. Hendriks HGE, van Erve RHGP, Salden H, van der Zwet WC, Barnaart LFW Ned Tijdschr Geneeskd. 2009; 153: B187

Bijwerkingen van valacyclovir bij gestoorde nierfunctie. Klinische les. I.R.F. van Berlo-van de Laar, E.R. Goet, A. Helldén, H.E. Sluiter Ned Tijdschr Geneesk. 2009; 153(15): B198 Reply: long-term retention rate of pramipexole in the treatment of Parkinson’s disease. Arbouw MEL, Movig KLL, van Vugt JPP, Egberts TCG Eur J Clin Pharmacol. 2009; 65(9): 957

Abstract Zie vakgroep orthopedie

Promotie The optimization of coumarin anticoagulant therapy pharmacogenetics and computer assisted dose finding Beinema, M.J. Groningen, Rijksuniversiteit Groningen, 2009

Posters Total lab automation and coagulation testing M. Deckers, G. Bülüt, T. Hofman, J. de Kok The International Society on Thrombosis and Haemostasis Boston, July 11, 2009

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Clinical and pharmacogenetic determinants for the discontinuation of non-ergoline dopamine agonists in Parkinson’s disease. Arbouw MEL, Movig KLL, Egberts TCG, Poels PJE, van Vugt JPP, Wessels JAM, van der Straaten RJHM, Neef C, Guchelaar HJ Eur J Pharmacol. 2009; 65(12): 1245-51 Abstract Objective: to identify determinants for the discontinuation of non-ergoline dopamine agonist (da) treatment in patients with parkinson’s disease (pd) and to identify genetic determinants in genes encoding dopamine receptor (dr)d2 and drd3 in a exploratory analysis. Methods: patients included were first-time users of the non-ergoline da ropinirole or pramipexole who had been diagnosed with pd before 2005. Treatment discontinuation was defined as a gap of 180 days or more between two refills of the da. Non-genetic determinants for discontinuation were studied in the overall population, and genetic determinants [drd2 141c ins/del, drd2 (ca)(n) str, drd2 taqia, drd3 msci single nucleotide polymorphism (snp) and drd3 mspi snp] were studied in a subgroup. Cox proportional hazard analysis was used to estimate the hazard ratios (hr) for the discontinuation of non-ergoline da treatment. Results: the study population comprised 90 patients. Apomorphine use was associated with non-ergoline da discontinuation, although the apomorphine group consisted only of three patients [hr 6.26; 95% Confidence interval (ci) 1.8521.2]. Daily levodopa dosages between 500 and 1000 mg were positively associated with discontinuation (hr 2.31; 95% Ci 1.08-4.93). Included in the exploratory pharmacogenetic analysis were 38 patients. The absence of a 15x drd2 ca repeat allele was significantly related with a decreased discontinuation of non-ergoline treatment (hr 0.23; 95% Ci 0.07-0.81). The drd3 mspi polymorphism showed a non-significant allele dose effect, suggestive of a causal relationship.

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Conclusion: this study identified apomorphine use and levodopa dosages between 500 and 1000 mg as non-genetic and the 15x drd2 ca repeat allele as genetic determinants for the discontinuation of non-ergoline da treatment in patients with pd. More research is needed to replicate these findings.

Voordrachten Oncologie F.G.A. Jansman PAO Cyclus van farmacotherapiecolleges deel II Utrecht, 4 en 11 februari 2009

Glycopyrroniumbromide for the treatment of sialorrhea in Parkinson’s disease Maurits Arbouw, Kris Movig, Miriam Koopmann, Petra Poels, Henk-Jan Guchelaar, Toine Egberts, Cees Neef, Jeroen van Vugt Mededelingendag Nederlandse Vereniging voor Klinische Farmacologie en Biofarmacie Utrecht, 27 maart 2009 Abstract gepubliceerd in Br J Clin Pharmacol. 2009; 68(5): 782

Posters Incidence of metformin associated lactic acidosis estimated from metformin serum concentration I.R.F. van Berlo-van de Laar, C.G. Vermeij, C.J. Doorenbos International Congress of Therapeutic Drug Monitoring and Clinical Toxicology Montreal, October 7, 2009 Abstract gepucliceerd in Ther Drug Monit. 2009; 31(5): 636

Interacties van oncolytica F.G.A. Jansman 9e PCM Seminar Utrecht, 22 april 2009

F.G.A. Jansman, voorzitter Post American-Gastroenterological-Association (AGA) 2009 Utrecht, 17 juni 2009 Interacties met oncolytica F.G.A. Jansman KNMP-Congres 2009 Oncologie en medicijnen Amsterdam, 6 oktober 2009 Interacties tussen veel gebruikte geneesmiddelen en oncolytica F.G.A. Jansman Oncologiedagen 2009 voor Nederland en Vlaanderen Arnhem, 19 november 2009 Use of dopaminergic drugs and risk of hip of femur fracture: a populationbased case-control study Maurits Arbouw, Kris Movig, Tjeerd van Staa, Toine Egberts, Patrick Souverein, Frank de Vries 25th Anniversary International Conference for Pharmacoepidemiology and Therapeutic Risk Management. Providence, Rhode Island, USA, August 19, 2009 Abstract gepubliceerd in Pharmacoepidemiol Drug Saf. 2009; 18: S201-2

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Pharmacogenetic determinants for discontinuation of non-ergoline dopamine agonists in Parkinson’s disease Maurits Arbouw, Kris Movig, Toine Egberts, Petra Poels, Jeroen van Vugt, Judith Wessels, Tahar van der Straaten, Cees Neef, Henk-Jan Guchelaar 25th Anniversary International Conference for Pharmacoepidemiology and Therapeutic Risk Management. Providence, Rhode Island, USA, August 15, 2009 Abstract gepubliceerd in Pharmacoepidmiol Drug Saf. 2009; 18: S163 Pharmacogenetic determinants for discontinuation of non-ergoline dopamine agonists in Parkinson’s disease Maurits E.L. Arbouw, Kris L.L. Movig, Toine C.G. Egberts, Petera J.E. Poels, Jeroen P.P. van Vugt, Judith A.M. Wessels, Tahar van der Straaten, Cees Neef, Henk-Jan Guchelaar The Movement Disorder Society’s 13th International Congress of Parkinson’s Disease and Movement Disorders Parijs, Frankrijk, 7 juni 2009 Abstract gepubliceerd in Mov Disord. 2009; 24: S124

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Vakgroep Klinische Fysica Glycopyrroniumbromide for the treatment of sialorrhea in Parkinson’s disease Maurits Arbouw, Kris Movig, Miriam Koopmann, Petra Poels, Henk-Jan Guchelaar, Toine Egberts, Cees Neef, Jeroen van Vugt The Movement Disorder Society’s 13th International Congress of Parkinson’s Disease and Movement Disorders Parijs, Frankrijk, 9 juni 2009 Abstract gepubliceerd in Mov Disord. 2009; 24: S255 Actual incidence of metformin associated lactic acidosis in type 2 diabetes mellitus is underestimated in the literature Vermeij CG, van Berlo-van de Laar IRF, Doorenbos CJ Abstractboek 21e Internistendagen, 2009

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Voordrachten Bismuth breast shielding in CT pulmonary embolism protocols C.J. Veeken, R.E. Westerbeek, A. van ’t Riet, K. Koster Radiologendagen 18 september 2009, Amsterdam

Posters Bismuth breast shielding in CT pulmonary embolism protocols C.J. Veeken, R.E. Westerbeek, A. van ’t Riet, K. Koster Annual Meeting of the North American Society for Cardiovascular Imaging NASCI Orlandao, Florida, USA, October 3, 2009

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Vakgroep Maag Darm en Leverziekten Artikelen Serum levels of leptin as marker for patients at high risk of gastric cancer. Capelle LG, de Vries AC, Haringsma J. Steyerberg EW, Looman CW, Nagtzaam NM, van Dekken H, ter Borg F, de Vries RA, Kuipers EJ Helicobacter 2009; 14(6) 596-604

The use of clinical, histologic, and serologic parameters to predict the intragastric extent of intestinal metaplasia: a recommendation for routine practice. de Vries AC, Haringsma J, de Vries RA, ter Borg F, Nagtzaam NM, Steyerberg EW, van Dekken H, Kuipers EJ Gastrointest Endosc. 2009; 70(1): 18-25

Abstract Background: serological screening for gastric cancer (gc) may reduce mortality. However, optimal serum markers for advanced gastric precursor lesions are lacking. Aim: to evaluate in a case-control study whether serum leptin levels correlate with intestinal metaplasia (im) and can serve as a tool to identify patients at high risk for gc. Materials and methods: cases were patients with a previous diagnosis of im or dysplasia, controls were patients without such a diagnosis. All patients underwent endoscopy. Fasting serum was collected for the measurement of leptin, pepsinogens i/ii, gastrin, and helicobacter pylori. Receiver operating characteristic (roc) curves and their area under the curve (auc) were provided to compare serum leptin levels with other serological markers. Results: one hundred nineteen cases and 98 controls were included. In cases, the median leptin levels were 116.6 Pg/ml versus 81.9 Pg/ml in controls (p = .01). After adjustment for age, sex and bmi, leptin levels remained higher in cases than in controls (p < .005). In multivariate analysis, male sex (p = .002), Age (<0.001), Low pepsinogen levels (p = .004) And high leptin levels (p = .04) Were independent markers for the presence of im. In addition, a roc curve including age, sex and pepsinogen i levels had an auc of 0.79 (95% Ci (0.73-0.85)). Adding serum leptin levels increased the auc to 0.81 (95% Ci (0.75-0.86)). Conclusions: high leptin levels are associated with an increased risk of im. Moreover, serum leptin levels are a significant independent marker for the presence of im. However, in combination with the serological test for pepsinogen I the additional value of serum leptin levels is rather limited.

Abstract Background: surveillance of intestinal metaplasia (im) of the gastric mucosa should be limited to patients at high risk of gastric cancer. Patients with extensive im are at increased cancer risk; however, the intragastric extent of im is usually unknown at the time of the initial diagnosis. Objective: to assess the predictive value of clinical, histologic, and serologic parameters for the intragastric extent of im. Design and setting: prospective, multicenter study. Patients: eighty-eight patients with a previous diagnosis of im of the gastric mucosa. Intervention: surveillance gastroscopy with extensive random biopsy sampling. Main outcome measurements: biopsy specimens were evaluated according to the sydney classification system. In addition, serologic testing of helicobacter pylori and caga status, pepsinogens i and ii, gastrin, and intrinsic factor antibodies was performed. The association between the available parameters and extensive im was evaluated with logistic regression analysis. Results: in 51 patients (58%), im was present in the biopsy specimens from at least 2 intragastric locations. The most important predictors of extensive im were a family history of gastric cancer, alcohol use > or = 1 unit/d (1 glass, approximately 10 ml or 8 g ethanol), moderate or marked im of the index biopsy specimen, and a pepsinogen i to ii ratio < 3.0. A simple risk score based on these factors could identify extensive im in 24 of 25 patients (sensitivity 96%). Limitation: a prospective cohort study should confirm the proposed risk stratification. Conclusions: a risk score of clinical, histologic, and serologic parameters can predict extensive intragastric im and may serve as a practical tool to select patients for surveillance endoscopy in routine clinical practice. Eosinophilic oesophagitis an enigmatic, emerging disease. Sprenger RA, Arends JW, Poley JW, Kuipers EJ, ter Borg F Neth J Med. 2009; 67(1): 8-12 Abstract Eosinophilic oesophagitis is a disease that has emerged in recent years. It is often associated with dysphagia and oesophageal food impaction in adults. The disease is characterised by infiltration of eosinophilic granulocytes into the oesophageal mucosa.

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This infiltrate may be responsible for the subtle peristaltic abnormalities that can be found in these patients. Endoscopic findings are usually absent or nonspecific, although a discrete circular ring pattern of the mucosa may be noticed. Occasionally, overt endoscopic abnormalities (such as exudative changes and shearing of the mucosa) can be found. The presence of at least 15 intraepithelial eosinophilic granulocytes per high-power field in random biopsies from the whole length of the oesophagus is considered to be diagnostic. Gastro-oesophageal reflux needs to be excluded as it may lead to eosinophilic infiltration as well. Adequate diagnosis is relevant for treatment and the prevention of unnecessary further investigations. The disease responds well to the ingestion of fluticasone propionate and its long-term prognosis is generally good. But when fluticasone is discontinued recurrent symptoms are common, and some cases are severe, needing treatment with systeic corticosteroids.

Conclusions: alpha-galcer (0.1-10 Microg/kg) used as monotherapy for chronic hepatitis b infection resulted in a strong decrease of nkts, but did not clearly affect hbv dna and alanine aminotransferase levels. Alpha-galcer was poorly tolerated and is unlikely to be suitable as an alternative monotherapy to the current treatment regimen. Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 subunit gene (GNB3). de Vries DR, ter Linde JJ, van Herwaarden MA, Smout AJ, Samsom M. Am J Gastroenterol. 2009; 104(2): 281-5

Abstract Background: The glycosphingolipid alpha-galactosylceramide (alpha-GalCer) is known to stimulate invariant natural killer T-cells (iNKTs) and is able to induce powerful antiviral immune responses. The present dose-escalating randomized placebo-controlled Phase I/II trial aimed to investigate antiviral activity and safety of alpha-GalCer as a novel class of treatment for chronic hepatitis B patients. METHODS: Patients were randomly assigned to 0.1 microg/kg (n=8), 1 microg/kg (n=6) or 10 microg/kg (n=6) alpha-GalCer or placebo (n=7) treatment. RESULTS: Almost all alpha-GalCer-treated patients showed a rapid and strong decrease in natural killer T-cell (NKT) numbers. Patients with high baseline NKT numbers showed immune activation, including natural killer cell activation, increased serum tumour necrosis factor-alpha and interleukin-6 levels, and development of fever. Three patients demonstrated a transient decrease in hepatitis B virus (HBV) DNA. Only one alpha-GalCer-treated patient had a sustained decrease in HBV DNA at the end of follow-up. Four patients discontinued therapy because of fever shortly after drug administration. No significant side effects were observed.

Abstract Objectives: visceral hypersensitivity is involved in the etiology of reflux symptoms. Familial clustering and twin studies demonstrated a genetic predisposition to gastroesophageal reflux disease (gerd). G-protein-coupled receptors (gpcrs) mediate the response to acid, neurotransmitters and humoral factors modulating esophageal sensory function. Thus, polymorphisms in g-proteins are putative genetic factors contributing to gerd manifestation. A functional polymorphism in the g-protein beta3 subunit gene (gnb3) is associated with functional dyspepsia (fd), in which visceral hypersensitivity is implicated in symptom generation. We evaluated the association of the gnb3 c825t polymorphism with gerd and gerd subgroups classified according to esophageal acid exposure time, symptom-reflux correlation, or coexistence of fd and/or irritable bowel syndrome (ibs) symptoms. Methods: in total, 363 gerd patients, defined as having esophageal ph < 4 > or = 6% of time and/or symptom index (si) > or = 50% or symptom association probability (sap) > or = 95%, participated. In addition, 373 healthy controls free of gastrointestinal symptoms were studied. Genotyping was performed by molecular beacon assay. Results: the ct genotype was more prevalent in gerd patients relative to healthy controls (adjusted odds ratio (or)=1.43, 95% Ci 1.04-1.98). Gerd patients sensitive to physiological amounts of reflux displayed a higher or (1.59), As did gerd patients with a positive symptom association score (1.50). The strongest association was detected in patients without concomitant fd and/or ibs symptoms (or=1.66). Conclusions: gerd is associated with gnb3 c825t. The results for gerd subgroups support the hypothesis that enhanced perception of reflux events, as a consequence of the increased signal transduction upon gpcr activation associated with the 825t allele, underlies this association.

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Alpha-Galactosylceramide in chronic hepatitis B infection: results from a randomized placebo-controlled Phase I/II trial. Woltman AM, ter Borg MJ, Binda RS, Sprengers D, von Blomberg BM, Scheper RJ, Hayashi K, Nishi N, Boonstra A, van der Molen R, Janssen HL Antivir Ther. 2009; 14(6): 809-18

Increased intragastric pressure gradients are involved in the occurrence of acid reflux in gastroesophageal reflux disease. Frankhuisen R, van Herwaarden MA, Scheffer RCh, Hebbard GS, Gooszen HG, Samsom M. Scand J Gastroenterol. 2009; 44(5): 545-50 Abstract Objective: increased pressure gradients across the esophagogastric junction (deltaegjp) play a role in gastroesophageal flow during tlesr. The aim of this study was to further explore deltaegjp in patients with gastroesophageal reflux disease (gerd) and controls. Material and methods: twenty gerd patients were studied along with 20 control subjects. High resolution manometry and ph recording were performed 1 h before and 2 h after a liquid meal (500 ml/300 kcal). Deltaegjp was calculated at the start of a tlesr and at 180, 60, and 10 s before tlesr. Results: deltaegjp at the start of a tlesr and at 180, 60, and 10 s before tlesr was markedly increased in gerd patients compared with that in control subjects (9.9 Mmhg and 7.5 Mmhg, respectively; p<0.05). Whilst intragastric pressure gradients in gerd patients were increased compared with those in controls (4.6 Mmhg and 2.5 Mmhg, respectively; p<0.01), Intraesophageal pressure gradients were similar in both groups. Furthermore, in controls, first- and second-hour postprandial intragastric pressures were decreased compared with in fasting periods (1.9 +/- 0.4 Mmhg and 2.1 +/- 0.4 Mmhg versus 3.5 +/- 0.4 Mmhg; p<0.05), While this was not observed in gerd patients. Conclusions: in gerd patients, deltaegjp is greater than that in controls both before and during tlesr. This phenomenon is caused by increased intragastric pressure and might contribute to increased rates of acid reflux during tlesr in gerd patients.

a positive si and/or sap. Manometry and endoscopy reports were reviewed. Subjects completed questionnaires about demographics and medical history, functional dyspepsia and irritable bowel syndrome, the nepean dyspepsia index symptom score and the rand-36 quality of life scale. Ph- patients were younger (45 vs 50 years, p = 0.003), More often female (60%vs 39%, p = 0.001), Smoked more (31%vs 19%, p = 0.021) And reported proton pump inhibition failure more often (47%vs 32%, p = 0.027). A hypotensive lower oesophageal sphincter was less common in ph- patients (18%vs 34%, p = 0.008) And distal oesophageal contraction amplitude was higher (11 vs 9.5 Kpa, p = 0.045). Ph- patients had hiatal hernia and oesophagitis less often (48%vs 73%, p < 0.0005; 36%Vs 54%, p = 0.012 Respectively). Ph- patients less often reported no other symptoms besides gord (20%vs 34%, p = 0.015). Ph- patients scored worse at the nepean (reflux 19 vs 12 out of 39, p < 0.0005; Dyspepsia 54 vs 38 out of 156, p < 0.0005). In the subgroup of patients who have physiological oesophageal acid exposure the enhancement of the perceived symptom burden appears to be the most important mechanism in gord pathogenesis. Functional dyspepsia and irritable bowel syndrome in patients with achalasia and its association with non-cardiac chest pain and a decreased health-related quality of life. Frankhuisen r, van herwaarden ma, heijkoop r, baron a, vermeijden r, smout aj, gooszen hg, samsom m Scand j gastroenterol. 2009; 44(6): 687-91

Abstract Studies comparing ph-metrically well-characterized gastro-oesophageal reflux disease (gord) patients with physiological reflux to gord patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 gord patients with pathological 24-h ph-monitoring (ph+), defined as ph<4 > or = 6% of time. A symptom index (si) > or = 50% was considered positive, as well as a symptom association probability (sap) > or = 95%. We included 84 gord patients with physiological acid exposure (ph-) and

Abstract Objective: in patients with achalasia, little is known about symptoms of the gastrointestinal tract other than the esophagus. The purpose of this study was to determine the prevalence of two functional disorders, functional dyspepsia (fd) and irritable bowel syndrome (ibs), in a group of treated achalasia patients and to assess the additional impact of these disorders on health-related quality of life (hrqol). Material and methods: questionnaires assessing the rome ii criteria for fd and ibs together with the eckardt clinical symptom score and rand-36 were sent to 171 treated achalasia patients. Results: of these patients, 76.6% Returned their questionnaires. In the group of achalasia patients, 23% fulfilled the criteria for fd (dutch general population 13-14%), and 21% fulfilled the criteria for ibs (dutch general population 1-6%). The prevalence of frequent chest pain (at least weekly) was higher in patients with fd and/or ibs than in those without these symptoms (54.2% Versus 28.2%; P=0.004). Female patients with achalasia and with frequent chest pain showed a higher probability of fulfilling the fd and/or ibs criteria (adjusted or 2.90 (1.18-7.14) And 3.35 (1.4-8.1), Respectively; both with p <0.05).

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Patients with physiological acid exposure and positive symptom association scores: a distinct group within the gord spectrum. De vries dr, van herwaarden ma, smout aj, samsom m. Neurogastroenterol motil. 2009; 21(8): 820-E53

Patients fulfilling the fd and/or ibs criteria scored a lower hrqol on the rand-36 subscales--pain, social functioning, and vitality--as compared with patients not fulfilling these criteria (p <0.006). Conclusions; symptoms of fd and ibs in patients with treated achalasia are common and have a negative impact on hrqol. Therefore, this has to be included in the standard evaluation of achalasia patients. The association with chest pain suggests a mutual underlying mechanism.

Voordrachten

In gerd patients, mucosal repair associated genes are upregulated in non-inflamed oesophageal epithelium. De vries dr, ter linde jj, van herwaarden ma, schwartz mp, shephard p, geng mm, smout aj, samsom m. J cell mol med. 2009; 13(5): 936-47

Factors associated with success and complication rate of colonic stenting. J.J. Driest, M. Ledeboer, M. Eeftinck Schattenkerk, E.J. Kuipers, F. ter Borg Voorjaarscongres NVGE, maart 2009

Abstract Previous studies addressing the effects of acid reflux and ppi therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non-inflamed oesophageal epithelium of gerd patients. Therefore, we included 20 gerd patients with pathological total 24-hr acid exposure of 6-12% and sap > or = 95%. Ten patients discontinued ppi treatment (ppi-), 10 took pantoprazole 40 mg bid (ppi+). Ten age/sex-matched healthy controls were recruited. Biopsies were taken from non-inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (scj). Gene expression profiling of biopsies from 6 cm was performed on human genome u133 plus 2.0 Arrays (affymetrix). Genes exhibiting a fold change >1.4 (T-test p-value < 1(e)- 4) were considered differentially expressed. Results were confirmed by real-time rt-pcr. In ppipatients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell-cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti-apoptotic or anti-proliferative functions or stress-protective functions were also deregulated. No probesets were deregulated in ppi+ patients. Qpcr analysis of 20 selected genes confirmed most of the deregulations in ppi- patients, and showed several deregulated genes in ppi+ patients as well. In the biopsies taken at 16 cm qpcr revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up-regulation of anti-apoptotic, anti-oxidant and migration associated genes. Possibly this process helps maintaining barrier function.

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Endoscopically removed malignant colorectal polyps with uncertain histological radicality: surgery or endoscopic follow-up? L. van Nunspeet, F. ter Borg, J.W. Arends, M. Eeftinck Schattenkerk, E.J. Kuipers Voorjaarscongres NVGE Veldhoven, 19 maart 2009

Factors associated with success and complication rate of colonic stenting. J.J. Driest, M. Ledeboer, M. Eeftinck Schattenkerk, E.J. Kuipers, F. ter Borg Digestive Diseases Week Chicago, mei 2009 Mutations in the precore and basal core promoter regions do not influence responsiveness to pegylated interferon alfa-2A treatment for Hbeagnegative chronic hepatitis B. V. Rijckborst, B.E. Hansen, M.J. ter Borg, Y. Cakaloglu, P. Ferenci, F. Tabak, M. Akdogan, Krzysztof Simon, U.S. Akarca, R. Flisiak, E. Verhey, S.D. Pas, M. Schutten, H.L. Janssen American Association for the Study of Liver Diseases Boston, 2009 On-treatment prediction of sustained response in HbeAg-negative chronic hepatitis B patients treated with pegylated interferon alfa-2a. V. Rijckborst, B.E. Hansen, F. Tabak, M. Raptopoulou-Gigi, N. Örmeci, K. Simon, U.S. Akarca, R. Flisiak, I. Vafiadis-Zouboulis, S. Tripi, E Verhey, M.J. ter Borg, A.J. van Vuuren, H.L.A. Janssen, for the PARC Study Group NVGE najaarscongres Veldhoven, 8 oktober 2009 On-treatment prediction of sustained response in HbeAg-negative chronic hepatitis B patients treated with pegylated interferon alfa-2a. V. Rijckborst, B.E. Hansen, F. Tabak, M. Raptopoulou-Gigi, N. Örmeci, K. Simon, U.S. Akarca, R. Flisiak, I. Vafiadis-Zouboulis, S. Tripi, E Verhey, M.J. ter Borg, A.J. van Vuuren, H.L.A. Janssen, for the PARC Study Group American Association for the Study of Liver Diseases Boston, 2009 51

Geen aanvullende chirurgie bij maligne colonpoliepen: de rol van biopten uit het poliepectomie litteken. L. van Nunspeet, E.J. Kuipers, J.W. Arends, M. Eeftinck Schattenkerk, F. ter Borg Najaarsvergadering NvvH Ede, 27 november 2009

Posters Polyp location is an independent risk factor for delayed type postpolypectomy haemorrhage a multi-centre case control study. Thomas Herngreen, K. Tim Buddingh, Jelle Haringsma, Frank P. Vleggaar, Ronald Breumelhof, Frank ter Borg UEGW / World Congres of Gastroenterology Londen, October 2009

Wetenschappelijke stage M3 co-assistent Surveillance after polypectomy Endoscopically removed malignant colorectal polyps with uncertain histological radicality: surgery or endoscopic follow-up? Author: Student number: Project teacher: Project counsellor: Department: Research period:

L. van Nunspeet 1417347 Dr. F. ter Borg Dr. J.W. Arends Gastroenterology, Deventer Hospital 29 September 2008 - 13 February 2009

Methode De ontwikkeling van recidieven in deze patiënten werd retrospectief vastgelegd in de periode 1999 tot en met 2008. Patiënten met gemetastaseerde ziekte, of die chirurgische colonresectie ondergingen werden geëxcludeerd. Resultaten Achtendertig patiënten voldeden aan de selectie criteria (13 intramucosale en 25 submucosale carcinomen). Twee patiënten prefereerden chirurgie; endoscopische follow-up met biopten uit het litteken vond plaats in 36 patiënten. Eén patiënt ontwikkelde een recidief adenocarcinoom na 11 maanden: de tumor kon chirurgisch radicaal verwijderd worden (2.6%, 95% eenzijdig betrouwbaarheidsinterval <12%). Drie patiënten ontwikkelden laesies die wederom endoscopisch verwijderd konden worden. Eén patiënt viel uit de follow-up. Geen van de patiënten met een litteken vrij van maligniteit die aanvullende chirurgische resectie prefereerden, had achtergebleven tumor in het resectiepreparaat. Van de 33 patiënten die zich nog in ons follow-up programma bevinden heeft niemand tekenen van recidief. Follow-up was meer dan 2 jaar in 20 patiënten; 14 van hen hebben na meer dan 2 jaar (mediaan 4,8 jaar) een colonoscopie ondergaan. Conclusie Onze data suggereren dat endoscopische follow-up van endoscopisch verwijderde intramucosale en submucosale adenocarcinomen veilig is wanneer biopten uit het litteken geen maligniteit laten zien. Prospectief onderzoek naar deze strategie is wenselijk.

Achtergrond en studiedoel Aanvullende chirurgische resectie van endoscopisch verwijderde maligne colorectale poliepen wordt aanbevolen wanneer de pathologische beoordeling tumorcellen in de resectiemarge van 2mm toont. Echter toont het resectiepreparaat geregeld geen achtergebleven tumor. Wij onderzochten de veiligheid van endoscopische follow-up met littekenbiopten in patiënten die endoscopische resectie van submucosale en intramucosale coloncarcinomen ondergingen en waarbij de radicaliteit histologisch niet gegarandeerd kon worden, maar biopten uit het litteken geen maligniteit lieten zien.

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Vakgroep Medische Microbiologie

Vakgroep Neurologie

Artikelen

Posters

Escherichia coli, een zeldzame verwekker van cellulitis. Sprenger RA, Sebens FW, Diekman T Nederlands Tijdschrift voor Infectieziekten 2009; 6: 235-9

Valproate-related hyperammonemic encephalopathy in a haemodialysis patient E.R. Goet, C.G. Vermeij, F.J.J. Prick, A.L. Zanen Abstractboek 21e Internistendagen 2009

Voordrachten De waarde van de logistiek van monster tot uitslag. F.W. Sebens Roche symposium Utrecht, 16 juni 2009

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Vakgroep Oogheelkunde

Vakgroep Orthopedie

Artikelen

Artikelen

Introduction of epithelial cells in the flapgraft interface during descemet stripping automated endothelial keratoplasty Saelens IE, Bartels MC, Van Rij G, Dinjens WN, Mooy CM Arch Ophthalmol. 2009; 127(7): 936-7

Conversion of patellofemoral arthroplasty to total knee arthroplasty: a matched case control study van Jonbergen HPW, Werkman DM, van Kampen A Acta Orthopaedica 2009; 80(1): 62-6

Voordrachten The phakic Artisan lens M.C. Bartels Access to Ophthalmologic Advances, ATOA Congres Paramaribo Suriname, 20 november 2009

Abstract Background and purpose: the long-term outcome of patellofemoral arthroplasty is related to progression of femorotibial osteoarthritis with need for conversion to total knee arthroplasty. We investigated whether prior patellofemoral arthroplasty compromises the results of total knee arthroplasty. Methods: 13 patients who had had 14 richards type ii patellofemoral arthroplasties converted to total knee arthroplasty because of femorotibial osteoarthritis, were individually matched to a control group of 13 patients with 14 primary total knee arthroplasties. The mean follow-up times for the patients and the control group were 5.7 (2-13) Years and 5.2 (2-13) Years, respectively. Clinical outcome was assessed using knee society score (kss), womac score, range of motion, and complications. Results: kss and womac scores were similar in the two groups (kss in patient and control groups: 82 and 86 (p = 0.6); Kss function: 76 and 88 (p = 0.5); Womac score: 33 and 21 (p = 0.1)). Within 6 months after conversion, 3 knees had to be manipulated under anesthesia for limited motion. No patients in the control group required manipulation under anesthesia. Interpretation: patellofemoral arthroplasty appears not to have a negative effect on the outcome of later total knee arthroplasty. Dissociation of mobile-bearing patellar component in low contact stress patellofemoral arthroplasty, its mechanisms and management: two case reports van Jonbergen HPW, Werkman DM, Barnaart AFW Cases J. 2009; 2: 7502 Abstract Introduction: isolated patellofemoral osteoarthritis can be treated with patellofemoral arthroplasty. Case presentation: we present two cases of isolated patellofemoral osteoarthritis treated with low contact stress patellofemoral arthroplasty; in both cases the polyethylene mobile-bearing of the patellar component dissociated from the metal backing. One patient had a revision to a richards patellofemoral prosthesis, and in the second patient the arthroplasty was converted to a total knee prosthesis because of clinically

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important femorotibial osteoarthritis. Conclusion: the possible failure mechanisms are described. We suggest avoiding the use of a metal-backed mobile-bearing patellar component due to the risk of dissociation. Traumatische atlanto-axiale rotatoire subluxatie ; case report en behandelvoorstel Bisschop R, van Jonbergen HPW Ned Tijdschr Traum. 2009; 17: 100-4 Geschiedenis van patellofemorale gewrichtsvervanging Huizinga M, Hentenaar B, van Jonbergen HPW Ned Tijdschr Orthop. 2009; 16: 152-5

Composition of the groups and the number of transfusion units of homologous blood (packed cells) required were compared using student’s t test and the chi2 test. In addition multivariate logistic regression analysis was used with the following variables as risk factors for requirement of homologous blood transfusion: gender, age, type of surgery and the use of an auto-transfusion system. Results: after introduction of the auto-transfusion system there was a reduction in the number of transfusion units given in both the hip- and the knee-replacement group (83% and 98% respectively). The use of the auto-transfusion system was the only variable for prediction of the requirement for homologous blood transfusion in the logistic regression model. Conclusion: after the introduction of an auto-transfusion system there was a reduction in the number of homologous blood transfusions required as part of total hip and knee surgery.

Patellofemoral arthroplasty for symptomatic nonunion after trochlear osteotomy for patellar instability: a case report van Jonbergen HPW, van Egmond C Cases J. 2009; 2: 9086

Intertrochantere fracturen, altijd kopsparend? Reuver jm, barnaart afw, van jonbergen hpw Ned tijdschr traum. 2009; 17(6): 43-6

Abstract Introduction: patients with patellofemoral instability with trochlear dysplasia may be treated with trochlear osteotomy. Case presentation: we present a patient with patellofemoral instability treated with trochlear osteotomy. The procedure resulted in nonunion with painful bony impingement and isolated patellofemoral osteoarthritis. Patellofemoral arthroplasty was performed. Conclusion: patellofemoral arthroplasty may be considered a salvage procedure for failed surgical treatment for trochlear dysplasia.

Samenvatting De incidentie van intertrochantere femurfracturen neemt door de vergrijzing snel toe. De gangbare behandeling is een extra- of intramedullaire osteosynthese, waarbij de keuze voornamelijk afhankelijk is van het fractuurtype. Bij patiënten met pre-existente symptomatische coxartrose of bij patiënten met osteoporose en een instabiel fractuurpatroon zou het plaatsen van een endoprothese een goed alternatief kunnen zijn. Dit wordt geïllustreerd aan de hand van twee casus.

Minder bloedtransfusies na invoering van autotransfusiesysteem bij heup- en knievervanging Hendriks HGE, van Erve RHGP, Salden H, van der Zwet WC, Barnaart LFW Ned Tijdschr Geneeskd. 2009; 153: B187 Abstract Objective: to establish the effect of the introduction of an auto-transfusion system on the number of homologous blood transfusions required as part of total hip- and knee-replacement surgery. Design: prospective observational study. Methods: the number of homologous blood transfusions required after total hip or knee replacement was compared between a group of 195 patients before and a group of 176 patients after introduction of an auto-transfusion system. The ‘4-5-6 flexinorm’ was strictly implemented when deciding to use homologous blood transfusion. 58

Voordrachten History of patellofemoral arthroplasty Jpw van jonbergen International meeting for unicompartimetnal knee arthritis, imuka Maastricht, 4-6 februari 2009

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Vakgroep Pathologie Ingezonden brieven

Artikelen

Iedere chirurg kan een kind opereren SMHJ Nooijen, RHGP van Erve Medisch Contact 2009; 64(31/32): 1356

Eosinophilic oesophagitis: an enigmatic, emerging disease. Sprenger RA, Arends JW, Poley JW, Kuipers EJ, ter Borg F Neth J Med. 2009; 67(1): 8-12 Abstract Eosinophilic oesophagitis is a disease that has emerged in recent years. It is often associated with dysphagia and oesophageal food impaction in adults. The disease is characterised by infiltration of eosinophilic granulocytes into the oesophageal mucosa. This infiltrate may be responsible for the subtle peristaltic abnormalities that can be found in these patients. Endoscopic findings are usually absent or nonspecific, although a discrete circular ring pattern of the mucosa may be noticed. Occasionally, overt endoscopic abnormalities (such as exudative changes and shearing of the mucosa) can be found. The presence of at least 15 intraepithelial eosinophilic granulocytes per high-power field in random biopsies from the whole length of the oesophagus is considered to be diagnostic. Gastro-oesophageal reflux needs to be excluded as it may lead to eosinophilic infiltration as well. Adequate diagnosis is relevant for treatment and the prevention of unnecessary further investigations. The disease responds well to the ingestion of fluticasone propionate and its long-term prognosis is generally good. But when fluticasone is discontinued recurrent symptoms are common, and some cases are severe, needing treatment with systemic corticosteroids.

Voordrachten Endoscopically removed malignant colorectal polyps with uncertain histological radicality: surgery or endoscopic follow-up? L. van Nunspeet, F. ter Borg, J.W. Arends, M. Eeftinck Schattenkerk, E.J. Kuipers Voorjaarscongres NVGE Veldhoven, 19 maart 2009

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Vakgroep Radiologie Geen aanvullende chirurgie bij maligne colonpoliepen: de rol van biopten uit het poliepectomie litteken. L. van Nunspeet, E.J. Kuipers, J.W. Arends, M. Eeftinck Schattenkerk, F. ter Borg Najaarsvergadering NvvH Ede, 27 november 2009

Artikelen Diagnostic management of clinically suspected acute deep vein thrombosis Tan M, van Rooden CJ, Westerbeek RE, Huisman MV Br J Haematol. 2009; 146(4): 347-60 Abstract Deep vein thrombosis (DVT) is a common disease that may lead to potentially fatal complications, such as pulmonary embolism. In the past decades several diagnostic tools and algorithms for DVT have been studied. Currently the combination of a clinical decision rule, D-dimer testing and compression ultrasonography has proved to be safe and effective for the diagnosis of DVT in the lower extremities. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) can be useful as additional or secondary imaging modalities. This review will discuss the elements currently used in making the clinical diagnosis of DVT. These elements include clinical decision rules and D-dimer testing, different imaging investigations and the appropriate use of these within diagnostic algorithms in patients with clinically suspected DVT. Although current knowledge of the options available to diagnose DVT of the lower extremities is well established, there are still unresolved issues, including the optimal diagnosis of recurrent DVT and distal DVT. Furthermore, the diagnosis of DVT of the upper extremities will be discussed, including the different imaging modalities and the limitations of these techniques.

Stent placement in patients with artherosclerotic renal artery stenosis and impaired renal function: a randomized trial. Bax L, Woittiez AJ, Kouwenberg HJ, Mali WP, Buskens E, Beek FJ, Braam B, Huysmans FT, Schultze Kool LJ, Rutten MJ, Doorenbos CJ, Aarts JC, Rabelink TJ, Plouin PF, Raynaud A, van Montfrans GA, Reekers JA, van den Meiracker AH, Pattynama PM, van de Ven PS, Vroegindeweij D, Kroon AA, de Haan MW, Postma CT, Beutler JJ Ann Intern Med. 2009; 150(12): 840-8, W150-1 Abstract Background: little is known about the efficacy and safety of renal artery stenting in patients with atherosclerotic renal artery stenosis (aras) and impaired renal function. Objective: to determine the efficacy and safety of stent placement in patients with aras and impaired renal function. Design: randomized clinical trial. Randomization was centralized and computer generated, and allocation was assigned by e-mail. 62

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Patients, providers, and persons who assessed outcomes were not blinded to treatment assignment. Setting: 10 european medical centers. Participants: 140 patients with creatinine clearance less than 80 ml/min per 1.73 M(2) and aras of 50% or greater. Intervention: stent placement and medical treatment (64 patients) or medical treatment only (76 patients). Medical treatment consisted of antihypertensive treatment, a statin, and aspirin. Measurements: the primary end point was a 20% or greater decrease in creatinine clearance. Secondary end points included safety and cardiovascular morbidity and mortality. Results: forty-six of 64 patients assigned to stent placement had the procedure. Ten of the 64 patients (16%) in the stent placement group and 16 patients (22%) in the medication group reached the primary end point (hazard ratio, 0.73 [95% Ci, 0.33 To 1.61]). Serious complications occurred in the stent group, including 2 procedure-related deaths (3%), 1 late death secondary to an infected hematoma, and 1 patient who required dialysis secondary to cholesterol embolism. The groups did not differ for other secondary end points. Limitation: many patients were falsely identified as having renal artery stenosis greater than 50% by noninvasive imaging and did not ultimately require stenting. Conclusion: stent placement with medical treatment had no clear effect on progression of impaired renal function but led to a small number of significant procedure-related complications. The study findings favor a conservative approach to patients with aras, focused on cardiovascular risk factor management and avoiding stenting.

Radiation reduction in noninvasive coronary multidetector computed tomography using prospective ECG-triggering compared to retrospective ECG-gating J.B. Houwers, H.W. Wiersma, M.M.J.J.R. Jaspers, K. Koster Radiologendagen 2009 Amsterdam, 18 september 2009

Voordrachten

Posters

Is a 3.0 Tesla MRI cost effective for brain imaging in a general hospital? L.A. de Leeuw, B.G. Ziedses des Plantes, B.J.G.L. Zonneveld, J.C.N.M. Aarts, J.J. Nahuis Highfield MR in clinical applications Bonn, July 30, 2009

Bismuth breast shielding in CT pulmonary embolism protocols C.J. Vreeken, R.E. Westerbeek, A. van ’t Riet, K. Koster Annual meeting of the North American Society for Cardiovascular Imaging Orlando, Florida (USA), October 3, 2009

Dosisreductie bij noninvasieve diagnostiek coronairen met 64-MDCT J.B. Houwers, H.W. Wiersma, M.M.J.J.R. Jaspers, K. Koster Radiologendagen 2009 Amsterdam, 18 september 2009 Cost-effectiveness of 3T MRI versus 1,5T in imaging the knee in general radiology practice R.E. Westerbeek, H.W. Wiersma, L.A. de Leeuw, B.G. Ziedses des Plantes 8th International Meeting on Highfield MR in Clinical Applications Bonn, August 29, 2009 Bismuth breast shielding in CT pulmonary embolism protocols C.J. Vreeken, R.E. Westerbeek, A. van ’t Riet, K. Koster Radiologendagen 2009 Amsterdam, 18 september 2009

Mac-based open-source DICOM viewer OsiriX in a hospital setting L.A. de Leeuw, K. Koster Radiologendagen 17 september 2009

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Vakgroep Urologie Is a 3.0 Tesla MRI cost effective compared to 1.5 Tesla in a general hospital? L.A. de Leeuw, B.G. Ziedses des Plantes, B.J.G.L. Zonneveld, J.C.N.M. Aarts, J.J. Nahuis European Society for Magnetic Resonance in Medicine and Biology, ESMRMB 2009 Antalya, October 3, 2009 High percentage of non-diagnostic compression ultrasonography results in the diagnosis of ipsilateral recurrent deep vein thrombosis M. Tan, S.I. Velthuis, C.J. van Rooden, R.E. Westerbeek, M.V. Huisman XXII Congress of The International Society on Thrombosis and Haemostasis, ISTH 2009 Boston (USA), July 15, 2009

Artikelen Urologie op het dak van de wereld (Nepal) A.F.G.V.M. Ypma Urograaf; okt 2009 Pro’s en contra’s van androgeensuppletie A.F.G.V.M. Ypma Mednet Magazine; nov 2009

Voordrachten Blaasdistensie volgens Helmstein: een effectieve behandeling bij onbehandelbare klachten? P. Oude Elferink, A.F.G.V.M. Ypma, E.B. Joustra Voorjaarsvergadering NVU Nieuwegein, 3 april 2009 Workshop erectiele dysfunctie voor praktijkondersteuners A.F.G.V.M. Ypma Utrecht, 16 december 2009 Seksuologie in de huisartsenpraktijk A.F.G.V.M. Ypma Landelijke huisartsen Den Bosch, 28 november 2009

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Opleidingsinstituut Deventer Ziekenhuis Artikelen Minder bloedtransfusies na invoering van autotransfusiesysteem bij heup- en knievervanging Hendriks HGE, van Erve RHGP, Salden H, van der Zwet WC, Barnaart LFW Ned Tijdschr Geneeskd. 2009; 153: B187 Abstract Zie vakgroep orthopedie AO Speciality Course on MIO. A.J.M. Karthaus Faculty Member Amsterdam, 22 en 23 januari 2009

Voordrachten Visitatie als kwaliteitsinstrument in STZ ziekenhuizen. H.E. Sluiter, D. Weltevreden, H. Hendrikx O&O&O bijeenkomst leerhuizen Amersfoort, 11 februari 2009 Teach the teacher. H.E. Sluiter, K. Prince Cursus deel I Wenckebach Instituut UMCG\PAOG Amsterdam, 12-13 februari 2009 Idem met J.Otto 28-29 mei 2009. Idem met P. Teunissen in Alkmaar, 14-16 mei 2009 Invoering van het nieuwe opleidingsplan. H.E. Sluiter Buitengewone vergadering Concillium Medicinae Internae Utrecht, 3 juni 2009

Clinical Governance. A.J.M. Karthaus, Bornleff Wenckebach Instituut Groningen, 30 januari 2009 Teach the Teacher module M2: Onderwijs in de dagelijkse praktijk. A.J.M. Karthaus, P. Boendermaker Wenckebach Instituut Groningen, 2 en 3 april 2009 Teach the Teacher module M3: Toetsen en beoordelen. A.J.M. Karthaus, r. Venekamp Wenckebach Instituut Groningen, 29 en 30 september 2009

Workshop “Implementatie Medische Vervolgopleidingen: landelijk of in de OOR?” A.K. Meininger, H.E. Sluiter Congres Nederlandse Vereniging voor Medisch Onderwijs (NVMO) Egmond aan Zee, 12-13 november 2009 Workshop “Opleidingsfonds en productonafhankelijke opleidingen” A.K. Meininger, H.E. Sluiter Inleiding door H.E. Sluiter Congres Nederlandse Vereniging voor Medisch Onderwijs Egmond aan Zee, 12-13 november 2009 Het nieuwe opleidingsplan interne geneeskunde: de algemene competenties. H.E. Sluiter Opleidersdag NIV Amerfoort, 19 november 2009

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Results of patients with haemorrhoids treated with Doppler-guided haemorrhoidal artery ligation. Pol RA, van der Zwet WC, Hoornenborg D, Lodewijk L, Makkinga B, Wallis de Vries BM, Kaijser M, Eeftinck Schattenkerk M, Eddes EH Nederlandse Vereniging voor Gastroenterologie Veldhoven, 8 oktober 2009

Radiotherapeutisch Instituut Stedendriehoek en Omstreken

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Artikelen Lacrimal gland radiosensitivity in uveal melanoma patients. Muller K, Nowak PJ, Naus N, de Pan C, van Santen CA, Levendag P, Luyten GP. Int J Radiat Oncol Biol Phys. 2009 Jun 1;74(2):497-502 Abstract Purpose: to find a dose-volume effect for inhomogeneous irradiated lacrimal glands. Methods and materials: between 1999 and 2006, 72 patients (42 men and 30 women) were treated with fractionated stereotactic radiotherapy in a prospective, nonrandomized clinical trial (median follow-up, 32 months). A total dose of 50 gy was given on 5 consecutive days. The mean of all schirmer test results obtained > or =6 months after treatment was correlated with the radiation dose delivered to the lacrimal gland. Also, the appearance of dry eye syndrome (des) was related to the lacrimal gland dose distribution. Results: of the 72 patients, 17 developed a late schirmer value <10 mm; 9 patients developed des. A statistically significant relationship was found between the received median dose in the lacrimal gland vs. Reduced tear production (p = 0.000) And vs. The appearance of des (p = 0.003), Respectively. A median dose of 7 gy/fraction to the lacrimal gland caused a 50% risk of low schirmer results. A median dose of 10 gy resulted in a 50% probability of des. Conclusion: we found a clear dose-volume relationship for irradiated lacrimal glands with regard to reduced tear production and the appearance of des. Pathological analysis after neoadjuvant chemoradiotherapy for esophageal carcinoma: the rotterdam experience. Van meerten e, van der gaast a, tilanus hw, poley jw, muller k, van dekken h. J surg oncol. 2009 Jul 1;100(1):32-7 Abstract Multimodality treatment is increasingly used in the treatment for esophageal cancer. We determined the tumor regression grade after preoperative chemoradiation and correlated the effect of specific pathologic and clinical findings to overall survival. For this purpose esophageal biopsies and surgical specimens of 67 patients treated with neoadjuvant paclitaxel and carboplatin concurrent with radiotherapy were reviewed. Neoadjuvant chemoradiotherapy led to a significant downstaging. Complete tumor regression was found in 24% of the patients resulting in a trend towards better survival. It was found more frequently in poorly differentiated tumors.

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Patients with pre-treatment nodal involvement, assessed by endoscopic ultrasound, had a significantly worse survival compared to patients without. Contrastingly, this was not found for post-treatment nodal involvement, as determined by pathological examination, speculating that survival is more determined by (submicroscopic) distant disease, than by locoregional tumor cells. (C) 2009 wiley-liss, inc. Prediction of dvh parameter changes due to setup errors for breast cancer treatment based on 2d portal dosimetry. Nijsten sm, van elmpt wj, mijnheer bj, minken aw, persoon lc, lambin p, dekker al. Med phys. 2009 Jan;36(1):83-94 Abstract Electronic portal imaging devices (epids) are increasingly used for portal dosimetry applications. In our department, epids are clinically used for two-dimensional (2d) transit dosimetry. Predicted and measured portal dose images are compared to detect dose delivery errors caused for instance by setup errors or organ motion. The aim of this work is to develop a model to predict dose-volume histogram (dvh) changes due to setup errors during breast cancer treatment using 2d transit dosimetry. First, correlations between dvh parameter changes and 2d gamma parameters are investigated for different simulated setup errors, which are described by a binomial logistic regression model. The model calculates the probability that a dvh parameter changes more than a specific tolerance level and uses several gamma evaluation parameters for the planning target volume (ptv) projection in the epid plane as input. Second, the predictive model is applied to clinically measured portal images. Predicted dvh parameter changes are compared to calculated dvh parameter changes using the measured setup error resulting from a dosimetric registration procedure. Statistical accuracy is investigated by using receiver operating characteristic (roc) curves and values for the area under the curve (auc), sensitivity, specificity, positive and negative predictive values. Changes in the mean ptv dose larger than 5%, and changes in v90 and v95 larger than 10% are accurately predicted based on a set of 2d gamma parameters. Most pronounced changes in the three dvh parameters are found for setup errors in the lateral-medial direction. Auc, sensitivity, specificity, and negative predictive values were between 85% and 100% while the positive predictive values were lower but still higher than 54%. Clinical predictive value is decreased due to the occurrence of patient rotations or breast deformations during treatment, but the overall reliability of the predictive model remains high. Based on our predictive model, 2d transit dosimetry 73

measurements can now directly be translated in clinically more relevant dvh parameter changes for the ptv during conventional breast treatment. In this way, the possibility to design decision protocols based on extracted dvh changes is created instead of undertaking elaborate actions such as repeated treatment planning or 3d dose reconstruction for a large group of patients. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized portec-2 trial. Nout ra, putter h, jürgenliemk-schulz im, jobsen jj, lutgens lc, van der steenbanasik em, mens jw, slot a, stenfert kroese mc, van bunningen bn, smit vt, nijman hw, van den tol pp, creutzberg cl J clin oncol. 2009 Jul 20;27(21):3547-56 Abstract Purpose studies on quality of life (qol) among women with endometrial cancer have shown that patients who undergo pelvic radiotherapy report lower role functioning and more diarrhea and fatigue. In the post operative radiation therapy in endometrial cancer (portec) trial, patients with endometrial carcinoma were randomly assigned to receive external-beam radiotherapy (ebrt) or vaginal brachytherapy (vbt). Qol was evaluated by using the european organisation for research and treatment of cancer quality of life questionnaire c30 and subscales from the prostate cancer module, pr-25, and the ovarian cancer module, ov-28. Patients and methods portec-2 accrued 427 patients between 2002 and 2006, of whom 214 were randomly assigned to ebrt, and 213 were randomly assigned to vbt. Three-hundred forty-eight patients (81%) were evaluable for qol. Qol outcomes were analyzed at a median follow-up of 2 years. Results at baseline after surgery, patient functioning was at the lowest level, and it increased during and after radiotherapy to reach a plateau after 12 months. Patients in the vbt group reported better social functioning (p < .002) And lower symptom scores for diarrhea, fecal leakage, the need to stay close to the toilet, and limitation in daily activities because of bowel symptoms (p < .001). At baseline, 15% of patients were sexually active; this increased significantly to 39% during the first year (p < .001). Sexual functioning and symptoms did not differ between the treatment groups. Conclusion patients who received ebrt reported significantly higher levels of diarrhea and bowel symptoms. This resulted in a higher need to remain close to a toilet and, as a consequence, more limitation of daily activities because of bowel symptoms and decreased social functioning. Vaginal brachytherapy provides a better qol, and should be the preferred treatment from a qol perspective.

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Nieuwe behandelmogelijkheden door Tomotherapie. Vonk EJA, Bouma P, Althof VGM Ned Tijdsch Oncol. 2009; 6(7): 307-13 Samenvatting Bij bestraling van maligne tumoren wordt gestreefd naar het geven van een zo hoog mogelijke dosis bij het zoveel mogelijk sparen van het gezonde weefsel teneinde een goede lokale controle te verkrijgen met zo weinig mogelijk acute en late toxiciteit. De grote technische vooruitgang in de radiotherapie de afgelopen jaren heeft dit doel een stap dichterbij gebracht. Met name de toepassing van intensiteitsgemoduleerde radiotherapie heeft hierbij een belangrijke rol gespeeld. De Hi-Art® Tomotherapy-unit is speciaal ontwikkeld om intensiteits­ gemoduleerde radiotherapie op een gebruikersvriendelijke, maar ook zeer geavanceerde manier mogelijk te maken. Dit artikel beschrijft de basisprincipes van het Hi-Art® Tomotherapysysteem, de technische mogelijkheden en de toepassingsgebieden. Er worden enkele voorbeelden gegeven van situaties die in het verleden met conventionele technieken niet op een adequate manier konden worden behandeld.

Voordrachten Frameless head-fix system effectively limits intra fraction motion during brain radiosurgery. Steenberg R, Westendorp R, Althof V, Kattevilder R ESTRO European Society for Therapeutic Radiology & Oncology Maastricht, 30 aug – 3 sept Computer aided objective rime trends of implanted prostate volumes after I-125 brachytherapy. Westendorp R, Kattevilder R, Minken A, Hoekstra A, Immerzeel J ESTRO European Society for Therapeutic Radiology & Oncology Maastricht, 30 aug – 3 sept Filmless quality assurance for helical tomotherapy with a cylindrical stair like aluminium phantom. Althof V, Kramer D, Westendorp R, Wispelweij M, Minken A ESTRO European Society for Therapeutic Radiology & Oncology Maastricht, 30 aug – 3 sept

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Intraoperative adaptive brachytherapy is necessary for high quality I-125 implants on day 30. Kattevilder R, Hoekstra C, Immerzeel J, Minken A, Westendorp R GEC/ESTRO, Porto, Portugal, May 13-16 2009 Development of a cylindrical stepwedge for QA in helical mode. Althof V, Kramer D, Westendorp R, Wispelweij M, Minken A Tomo EMEA user meeting Praag, May 7-9 2009 Monitoring machine behaviour and predicting machine failure. Kramer D, Althof D, Westendorp R, Wispelweij M, Minken A Tomo EMEA user meeting Praag, May 7-9 2009

Posters The prognostic significance of the number of extensions of metastisi for stage IIIA endometrial carcinoma. Jobsen J, Naudin ten Cate L, Lybeert M, van der Steen-Banasik E, Scholten A, van der Palen J, Slot A, Stenfert Kroese M, van der Sijde R, Siesling S ESGO, Belgrado, 11-14 october 2009 Tomotherapy reduces the dose to organs at risk for gynaecological malignancies. ten Brinke M, van de Pol SMG, Althof V, Immerzeel J, Minken A ESTRO European Society for Therapeutic Radiology & Oncology Maastricht, 30 aug – 3 sept

Dimence

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Boeken

Impact Factors

Secondary gain: Illness gain in psychiatric practice / Jaques van Egmond – Saarbrücken Lambert Academic Publishing, 2009. – 116 p Bewerking van de oorspr. uitg.: Secondary gain in psychiatry / Jacob Jan van Egmond; [red.: Mirca Groenen]. – Deventer Stichting Adhesie, cop. 2005. – 130 p ill. Proefschrift Vrije Universiteit Amsterdam. ISBN 978-3838318127

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Acta Orthopaedica Am J Clin Nutr. Am J Gastroenterol. Am J Kidney Dis. Ann Intern Med. Antivir Ther. Arch Intern Med. Arch Ophthalmol. Br J Haematol. Cancer J. Cases J. Clin Auton Res. Derma Actueel Dermatology EADV Magazin Eur J Clin Pharmacol. Eur J Dermatol. Eur J Intern Med. Gastrointest Endosc. Gynecol Surg. Helicobacter Hum Reprod. Injury Int J Radiat Oncol Biol Phys. J Cell Mol Med. J Clin Oncol. J Laryngol Otol. J Neurosurg. J Plast Reconstr Aesthet Surg.

J Surg Oncol. 2.478 Medisch Contact Mednet Magazine Med Phys. 3.871 Ned Tijdschr Allergie Ned Tijdschr Dermatol Venereol. Ned Tijdschr Geneeskd. Ned Tijdschr Infectieziekten Ned Tijdschr Oncol. -

1.762 6.740 6.444 4.822 17.457 4.105 9.110 3.242 4.478 2.769 1.517 2.227 2.497 1.968 1.045 7.367 2.470 3.773 1.946 4.639 5.114 17.157 0.796 2.124 1.235

Ned Tijdschr Orthop. Ned Tijdschr Tandheelkd. Ned Tijdschr Traum. Neth Heart J. Neth J Med. Nephrol Dial Transplant. Neurogastroenterol Motil. New Engl J Med. Rhinology Scand J Gastroenterol. Urograaf Vadem Perm Nascholing Huisartsen

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1.541 3.568 3.480 50.017 1.845 1.980 -

State of the art lectures 2009 Datum 8 januari

Spreker(s) Mariska Koster, longarts

Wetenschapsavond 2009 Titel Longkanker

5 februari Paul Bergervoet, Bijzonder Resistente ziekenhuishygiënist Micro-Organismen; Nico van Riessen, einde van het antibiotisch ziekenhuishygiënist tijdperk? Wil van der Zwet, arts-microbioloog 5 maart Jan Willem Arends, Deconstructie van patholoog mammapathologie; over meten, micro-arrays en metabletica. 2 april Mariska Koster, longarts Contouren van de dood; palliatieve zorg, palliatieve sedatie, euthanasie 7 mei Fred de Jong, revalidatiearts Functionele electrostimulatie van de hand na CVA 3 september Frank Jansman, Farmacogenetica; hype of ziekenhuisapotheker / vooruitgang? klinisch farmacoloog  29 oktober Michiel Tebbes, spoedeisende Signalering hulp arts kindermishandeling 3 december Jan-Hein Cobben, Electrische epidurale anaesthesioloog neurostimulatie voor therapieresistente neuropathische pijn in de extremiteit(en) als gevolg van benigne lumbosacrale aandoeningen

1 oktober 2009 Auditorium Deventer Ziekenhuis

Presentaties Laura van Nunspeet (co-assistent MDL) Geen aanvullende chirurgie bij maligne colon-poliepen: de rol van biopten uit het polypectomielitteken. Peder Nygaard (apotheker i.o.) Onderzoek naar het effect van kortdurend gecombineerd gebruik van NSAID’s naast diuretica en/of RAAS-remmers op de nierfunctie. Hessel van der Zee (co-assistent dermatologie) De behandeling van hidradenitis suppurativa met de combinatie therapie bestaande uit clindamycine en rifampicine. Alex Wiekenkamp (co-assistent orthopedie) Veiligheid van intra-operatieve ongewassen autologe bloedreïnfusie met een nieuw prototype reïnfusie-systeem, bij totale heup arthroplastiek patiënten. Sibylla van Nooijen (anaesthesioloog) ‘Slikken of stikken?’: incidentie en duur van saturatiedalingen tijdens nietgeïntubeerde adeno-tonsillectomie volgens Sluder. Eva Stekkinger (AIOS gynaecologie) Urineresidu na voorwandplastiek: gerandomiseerde vergelijking tussen suprapubische en transurethrale katheterisatie. Gerda van den Berg (diëtist) Is voeding tijdens de medicijnronde effectief? Wat vindt de patiënt en hulpverlener er van? Jaap Driest (AIOS MDL) Self Expandable Metal Stents (SEMS) bij acute maligne colonobstructie als “bridge to surgery”: is het een veilige procedure? Martine Deckers (klinisch chemicus i.o.) Gebruik van de Sysmex UF 1000i® urineflow-cytometer in de diagnostische work-up van urineweginfecties.

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