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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">LV</journal-id>
<journal-id journal-id-type="nlm-ta">Lijec Vjesn</journal-id>
<journal-title-group>
<journal-title>Lijecnicki Vjesnik</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Lijec. Vjesn.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="ppub">0024-3477</issn>
<issn pub-type="epub">1849-2177</issn>
<publisher><publisher-name>Croatian Medical Association</publisher-name></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">LV-143-1</article-id>
<article-id pub-id-type="doi">10.26800/LV-143-1-2-1</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Original article</subject></subj-group>
</article-categories>
<title-group>
<article-title>Lije&#x010D;enje malih tumora bubrega ablacijskim metodama</article-title>
<trans-title-group xml:lang="en">
<trans-title>Treatment of small renal tumors with ablative techniques</trans-title>
</trans-title-group>
</title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>Alduk</surname><given-names>Ana Marija</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kne&#x017E;evi&#x0107;</surname><given-names>Nikola</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2842-553X</contrib-id><name><surname>Penezi&#x0107;</surname><given-names>Luka</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kuli&#x0161;</surname><given-names>Tomislav</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Golu&#x017E;a</surname><given-names>Eleonora</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Sjekavica</surname><given-names>Ivica</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ka&#x0161;telan</surname><given-names>&#x017D;eljko</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib>
<aff id="aff1"><label>1</label>Klini&#x010D;ki zavod za dijagnosti&#x010D;ku i intervencijsku radiologiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu, Klini&#x010D;ki bolni&#x010D;ki centar Zagreb</aff>
<aff id="aff2"><label>2</label>Klinika za urologiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu, Klini&#x010D;ki bolni&#x010D;ki centar Zagreb</aff>
<aff id="aff3"><label>3</label>Klinika za anesteziologiju, reanimatologiju i intenzivno lije&#x010D;enje, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu, Klini&#x010D;ki bolni&#x010D;ki centar Zagreb</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Adresa za dopisivanje: Luka Penezi&#x0107;, dr. med., <ext-link ext-link-type="uri" xlink:href="https://orcid.org/0000-0003-2842-553X">https://orcid.org/0000-0003-2842-553X</ext-link> Klinika za urologiju, Medicinski fakultet Sveu&#x010D;ili&#x0161;ta u Zagrebu, KBC Zagreb, Ki&#x0161;pati&#x0107;eva 12, 10000 Zagreb, e-po&#x0161;ta: <email xlink:href="penezic.luka@gmail.com">penezic.luka@gmail.com</email></corresp></author-notes>
<pub-date pub-type="epub-ppub"><month>02</month><year>2021</year></pub-date>
<volume>143</volume>
<issue>1-2</issue>
<fpage>1</fpage>
<lpage>5</lpage>
<permissions>
<copyright-year>2021</copyright-year>
<copyright-holder>Croatian Medical Association</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by-nc-nd/4.0/" specific-use="CC BY-NC-ND 4.0"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND) 4.0 License.</license-p></license>
</permissions>
<abstract>
<title>SA&#x017D;ETAK</title>
<p>Mali tumor bubrega je radiolo&#x0161;kim metodama utvr&#x0111;ena tvorba promjera do 4 cm. Kirur&#x0161;ko lije&#x010D;enje je terapija izbora ovakvih tumora, ali se kod starijih bolesnika s komorbiditetima preporu&#x010D;uju i ablacijske metode. Cilj je ovoga rada prikazati na&#x0161;a iskustva lije&#x010D;enja malih tumora bubrega ablacijskim metodama. U&#x010D;inili smo retrospektivnu analizu serije bolesnika lije&#x010D;enih radiofrekventnom i mikrovalnom ablacijom u Klini&#x010D;kom bolni&#x010D;kom centru Zagreb u razdoblju od sije&#x010D;nja 2017. godine do kolovoza 2019. godine. Svim bolesnicima u&#x010D;injena je odgovaraju&#x0107;a radiolo&#x0161;ka i preoperativna obrada, biopsija tumora i ablacija. Pra&#x0107;eni su prema standardnom protokolu radiolo&#x0161;kim metodama 3, 6 i 12 mjeseci postoperativno te nakon toga jednom godi&#x0161;nje. Ablacija 32 mala tumora bubrega u&#x010D;injena je kod 31 pacijenta, od &#x010D;ega 27 radiofrekventnih i 7 mikrovalnih ablacija. Jednogodi&#x0161;nje ukupno i tumor specifi&#x010D;no pre&#x017E;ivljenje bilo je 100%, a kod 12,9% bolesnika utvr&#x0111;en je rezidualni tumor. Troje ih je lije&#x010D;eno ponovnom ablacijom, a jedan radikalnom nefrektomijom. Imali smo &#x010D;etiri komplikacije iz 2. skupine po Clavien-Dindo klasifikaciji. Ablacijske metode su onkolo&#x0161;ki dobra i sigurna terapija kod bolesnika koji nisu pogodni za kirur&#x0161;ki zahvat.</p>
</abstract>
<trans-abstract xml:lang="en">
<title>SUMMARY</title>
<p>Small renal tumor is a radiologically detected renal mass up to four cm in diameter. Surgery is the main therapeutic option in the treatment of these tumors, but in elderly and comorbid patients ablative techniques are the alternative. The aim of this paper is to report our experience in the treatment of small renal tumors with ablative techniques. We retrospectively analyzed patient records of individuals treated with radiofrequency and microwave ablation at the University hospital center Zagreb in the period from January 2017 to August 2019. An appropriate radiological and preoperative work-up was performed for all subjects, and then tumor biopsy and ablation. Patients were followed using the standard follow-up schedule: three, six, and 12 months after the procedure, and then annually, using radiological methods. Ablation of 32 small renal tumors was performed for 31 patients, 27 of which were radiofrequency and seven microwave ablations. One-year overall and cancer specific survival was 100%. In 12.9% of patients a residual mass was diagnosed &#x2013; three were retreated with ablation and one underwent radical nephrectomy. We had four ClavienDindo grade 2 complications. Ablative techniques are an oncologically effective and safe treatment option for patients that are unfit for surgery.</p>
</trans-abstract>
<kwd-group kwd-group-type="author"><kwd>Deskriptori TUMORI BUBREGA &#x2013; dijagnoza, kirurgija, patologija</kwd><kwd>KARCINOM BUBRE&#x017D;NIH STANICA &#x2013; dijagnoza, kirurgija, patologija</kwd><kwd>VELI&#x010C;INA TUMORA</kwd><kwd>ABLACIJSKE TEHNIKE &#x2013; metode</kwd><kwd>RADIOFREKVENTNA ABLACIJA</kwd><kwd>MINIMALNO INVAZIVNI KIRUR&#x0160;KI ZAHVATI &#x2013; metode</kwd><kwd>BIOPSIJA</kwd><kwd>NEFREKTOMIJA</kwd><kwd>ISHOD LIJE&#x010C;ENJA</kwd><kwd>ANALIZA PRE&#x017D;IVLJENJA</kwd><kwd>RETROSPEKTIVNA ISTRA&#x017D;IVANJA</kwd></kwd-group>
<kwd-group kwd-group-type="translator" xml:lang="en"><title>Descriptors </title><kwd>KIDNEY NEOPLASMS &#x2013; diagnosis, pathology, surgery</kwd><kwd>CARCINOM, RENAL CELL - diagnosis, pathology, surgery</kwd><kwd>TUMOR BURDEN</kwd><kwd>ABLATION TECHNIQUES &#x2013; methods</kwd><kwd>RADIOFREQUENCY ABLATION</kwd><kwd>MINIMALLY INVASIVE SURGICAL PROCEDURES &#x2013;methods</kwd><kwd>BOPSY</kwd><kwd>NEPHRECTOMY</kwd><kwd>TREATMENT OUTCOME</kwd><kwd>SURVIVAL ANALYSIS</kwd><kwd>RETROSPECTIVE STUDIES</kwd></kwd-group>
</article-meta>
</front>
<body>
<p>Karcinom bubrega &#x010D;ini 3&#x2013;5% svih karcinoma i tre&#x0107;i je naj&#x010D;e&#x0161;&#x0107;i urolo&#x0161;ki karcinom. U&#x010D;estalost njegova otkrivanja raste, &#x0161;to je prvenstveno uvjetovano pove&#x0107;anim brojem radiolo&#x0161;kih pretraga kao &#x0161;to su ultrazvuk, kompjutorizirana tomografija (CT, prema engl. <italic>computorized tomography</italic>) i magnetna rezonancija (MRI, prema engl. <italic>magnetic resonance imaging</italic>) prilikom dijagnostike ne-urolo&#x0161;kih bolesti (<xref ref-type="bibr" rid="r1"><italic>1</italic></xref>). Posljedi&#x010D;no dolazi do porasta incidencije otkrivanja asimptomatskih bubre&#x017E;nih tumora i fenomena migracija stadija &#x2013; pove&#x0107;ava se udio bubre&#x017E;nih tumora koji su niskog stadija te danas mali tumori bubrega &#x010D;ine oko 50% svih tumora bubrega (<xref ref-type="bibr" rid="r2"><italic>2</italic></xref>). Mali tumor bubrega ili mala bubre&#x017E;na tvorba (SRM, prema engl. <italic>small renal mass</italic>) definira se kao slu&#x010D;ajno radiolo&#x0161;ki detektirana bubre&#x017E;na tvorba veli&#x010D;ine do 4 cm (<xref ref-type="bibr" rid="r3"><italic>3</italic></xref>), &#x0161;to korelira s T1a tumorom prema TNM klasifikaciji bubre&#x017E;nog karcinoma (RCC, prema engl. <italic>renal cell carcinoma</italic>) (<xref ref-type="bibr" rid="r4"><italic>4</italic></xref>). Mali tumori bubrega imaju razli&#x010D;iti zlo&#x0107;udni potencijal te su u oko 20% slu&#x010D;ajeva dobro&#x0107;udni, dok se u 80% slu&#x010D;ajeva radi o zlo&#x0107;udnom tumoru (<xref ref-type="bibr" rid="r5"><italic>5</italic></xref>), i to u njih 60% o indolentnom, a u 20% slu&#x010D;ajeva agresivnom bubre&#x017E;nom karcinomu. Uz to, va&#x017E;no je napomenuti kako sporo rastu i rijetko metastaziraju (<xref ref-type="bibr" rid="r6"><italic>6</italic></xref>). Strategija lije&#x010D;enja tumora bubrega ovisi o stadiju bolesti, a kod malih tumora bubrega u obzir dolazi parcijalna ili radikalna nefrektomija, aktivno pra&#x0107;enje te ablacijske metode. Prema smjernicama vode&#x0107;ih svjetskih urolo&#x0161;kih dru&#x0161;tava, prvi izbor lije&#x010D;enja T1a tumora bubrega je parcijalna nefrektomija (<xref ref-type="bibr" rid="r7"><italic>7</italic></xref>, <xref ref-type="bibr" rid="r8"><italic>8</italic></xref>). Me&#x0111;utim, s obzirom na starenje populacije i pove&#x0107;ani broj komorbiditeta, sve je ve&#x0107;i broj pacijenata koji nisu u zdravstvenoj formi za operativni zahvat kao &#x0161;to je parcijalna nefrektomija. Kao terapijska opcija u tim slu&#x010D;ajevima nude se perkutane ablacijske metode koje grijanjem ili hla&#x0111;enjem dovode do ireverzibilnog o&#x0161;te&#x0107;enja tkiva. Radiofrekventna ablacija (RFA, prema engl. <italic>radiofrequency ablation</italic>) i krioblacija (CA, prema engl. <italic>cryoablation</italic>) su etablirane metode s dugoro&#x010D;nim rezultatima mnogobrojnih serija te su se u dosada&#x0161;njim istra&#x017E;ivanjima pokazale kao sigurne i onkolo&#x0161;ki prihvatljive opcije lije&#x010D;enja malih tumora bubrega. Mikrovalna ablacija (MWA, prema engl. <italic>microwave ablation</italic>) i ireverzibilna elektroporacija (IRE, prema engl. <italic>irreversible electroporation</italic>) su s druge strane tehnologije koje su se nedavno razvile te se intenzivno istra&#x017E;uju. RFA je ablacijska metoda koja se temelji na me&#x0111;udjelovanju tkiva i visokofrekventne izmjeni&#x010D;ne struje frekvencije 150 &#x2013; 1000 kHz koja se u tumor dovodi elektrodom (<xref ref-type="bibr" rid="r9"><italic>9</italic></xref>). Elektri&#x010D;na struja uzrokuje vibriranje molekula vode u tkivu, &#x0161;to dovodi do porasta temperature i koagulacijske nekroze. Denaturacija proteina, gubitak funkcije enzima, uni&#x0161;tenje stani&#x010D;ne membrane i citoplazme dovodi do uni&#x0161;tenja stanica (<xref ref-type="bibr" rid="r10"><italic>10</italic></xref>). RFA dovodi do potpune ablacije kod tumora manjih od 3 cm, dok su rezultati zna&#x010D;ajno lo&#x0161;iji za tumore ve&#x0107;e od 5 cm (25%). &#x0160;ansa za pre&#x017E;ivljenje bez povrata bolesti (RFS, prema engl. <italic>recurrence free survival</italic>) zna&#x010D;ajno se smanjuje za tumore ve&#x0107;e od 3,6 cm (<xref ref-type="bibr" rid="r11"><italic>11</italic></xref>, <xref ref-type="bibr" rid="r12"><italic>12</italic></xref>). Prednosti RFA su minimalna invazivnost, smanjena bol i kra&#x0107;e vrijeme hospitalizacije, dok su nedostatci karbonizacija tkiva i tzv. <italic>&#x201E;heatsink&#x201D;</italic> efekt koji smanjuju veli&#x010D;inu ablacijske zone (<xref ref-type="bibr" rid="r13"><italic>13</italic></xref>). <italic>&#x201E;Heatsink&#x201D;</italic> efekt je pasivna odvodnja topline od izvora pomo&#x0107;u fluida, a to su u ljudskom tijelu krv i urin, &#x0161;to zna&#x010D;i da se smanjuje u&#x010D;inak ablacije tumora koji su smje&#x0161;teni blizu kanalnog sustava bubrega ili velikih krvnih &#x017E;ila (<xref ref-type="bibr" rid="r14"><italic>14</italic></xref>). MWA se temelji na emisiji elektromagnetskih valova valne duljine od 915 MHz do 2,45 GHz, koji kao i kod RFA dovode do vibracija molekula vode u tkivu, &#x0161;to uzrokuje porast temperature i koagulacijsku nekrozu (<xref ref-type="bibr" rid="r15"><italic>15</italic></xref>). MWA posjeduje sve dobrobiti ablacijskih metoda kao i RFA, ali pru&#x017E;a i nekoliko prednosti: posti&#x017E;e se vi&#x0161;a temperatura, mogu&#x0107;e je u&#x010D;initi ablaciju ve&#x0107;eg volumena tumora, ablacija se provodi br&#x017E;e, mo&#x017E;e se primijeniti vi&#x0161;e aplikatora istovremeno, manji je u&#x010D;inak <italic>&#x201E;heatsink&#x201D;</italic> efekta te je manja periproceduralna bol (<xref ref-type="bibr" rid="r15"><italic>15</italic></xref>), &#x0161;to omogu&#x0107;uje provo&#x0111;enje zahvata u lokalnoj anesteziji uz analgosedaciju.</p>
<sec sec-type="other1">
<title>Materijali i metode</title>
<p>U ovo retrospektivno istra&#x017E;ivanje uklju&#x010D;eni su uzastopni bolesnici s malim tumorima bubrega lije&#x010D;eni s RFA ili MWA u Klini&#x010D;kom bolni&#x010D;kom centru Zagreb od sije&#x010D;nja 2017. godine do kolovoza 2019. godine. Radiolo&#x0161;ka obrada je klju&#x010D;na za planiranje zahvata, CT ili MRI uz primjenu kontrastnog sredstva neophodni su za procjenu odnosa tumora prema susjednim organima i planiranje sigurnog puta elektrode ili antene. Kod svih bolesnika u&#x010D;injeno je R.E.N.A.L. nefrometrijsko stupnjevanje tumora bubrega (<xref ref-type="bibr" rid="r16"><italic>16</italic></xref>) te adekvatna preoperativna anesteziolo&#x0161;ka obrada. Bolesnici su hospitalizirani u Klinici za urologiju jedan dan prije ili na dan zahvata, a sam zahvat ablacije u&#x010D;injen je u Klini&#x010D;kom zavodu za dijagnosti&#x010D;ku i intervencijsku radiologiju u op&#x0107;oj ili lokalnoj anesteziji uz analgosedaciju pod kontrolom CT-a (Somatom Definition AS+ 128, Siemens, Erlangen, Njema&#x010D;ka). Biopsija tumora je u&#x010D;injena prije ablacije: kao zaseban zahvat ili u istom aktu, neposredno prije ablacije. Radiofrekventna energija se u tumorsko tkivo dovodi jednom elektrodom Starburst<sup>&#x00AE;</sup>SemiFlex (Angiodynamics, New York, SAD) koja izgleda kao igla koja se rastvori poput obrnutog ki&#x0161;obrana (<xref ref-type="fig" rid="f1">slika 1</xref>.). Kod svih bolesnika lije&#x010D;enih s RFA kori&#x0161;ten je prepogramirani protokol ablacije u trajanju 9 minuta s ciljnom temperaturom 105&#x00BA;C generatora Sunbrust XL 1500<sup>&#x00AE;</sup> (Angiodynamics, New York, SAD) i Intelli Flow pumpom za perfuziju. Ablaciju je mogu&#x0107;e ponoviti nakon repozicioniranja elektrode u slu&#x010D;aju ve&#x0107;ih tumora ili ovisno o obliku tumora. Za MWA je kori&#x0161;ten Emprint<sup>TM</sup> ablacijski sustav s Thermosphere<sup>TM</sup> tehnologijom, s jednom antenom i maksimalnom izlaznom snagom od 100 W, a duljina ablacije je odre&#x0111;ena &#x017E;eljenom veli&#x010D;inom ablacijske zone, odnosno veli&#x010D;inom tumora. Kod slu&#x010D;ajeva kada postoji blizak odnos tumora i okolnih osjetljivih struktura (poput crijeva ili neuralnih struktura) koristi se hidrodisekcija (instilacija otopine 5-postotne glukoze u svrhu odmicanja struktura) kako bi se osjetljive strukture udaljile od zone ablacije. Pacijent se nakon zahvata vra&#x0107;a u Kliniku za urologiju na postoperativni oporavak. Otpust je naj&#x010D;e&#x0161;&#x0107;e prvoga ili drugoga postoperativnog dana. Prva radiolo&#x0161;ka kontrola provodi se za tri mjeseca CT-om prema vi&#x0161;efaznom protokolu, kada se provjerava u&#x010D;inak ablacije. Potom slijede kontrole 6 i 12 mjeseci postoperativno te nakon toga jednom godi&#x0161;nje, CT-om ili ultrazvukom. U&#x010D;injena je analiza osnovnih demografskih podataka, parametara tumora bubrega i komorbiditeta. Bolesnici su redovito pra&#x0107;eni prema protokolu te je utvr&#x0111;eno ukupno pre&#x017E;ivljenje (OS, prema engl. <italic>overall-survival</italic>), tumor specifi&#x010D;no pre&#x017E;ivljenje (CSS, prema engl. <italic>cancer specific survival</italic>) i u&#x010D;inak terapije. Podatci su statisti&#x010D;ki obra&#x0111;eni pomo&#x0107;u programa MS Excel (<xref ref-type="bibr" rid="r17"><italic>17</italic></xref>).</p>
<fig id="f1" position="float" fig-type="figure"><label>Figure 1</label><caption><p>Native CT examination during RFA procedure showing electrode positioned inside the right renal tumor.</p></caption><graphic xlink:href="LV-143-1-f1"></graphic></fig>
</sec>
<sec sec-type="other2">
<title>Rezultati</title>
<p>Ablacija malih tumora bubrega u&#x010D;injena je kod 31 pacijenta. Osnovni demografski podatci pacijenata i komorbiditeti prikazani su u <xref ref-type="table" rid="t1">Table 1</xref>., a karakteristike tumora u <xref ref-type="table" rid="t2">Table 2</xref>. U&#x010D;injeno je 34 zahvata od &#x010D;ega je 27 bilo RFA, a 7 MWA. Prosje&#x010D;no vrijeme trajanja RFA procedure bilo je 9,6 minuta (raspon od 9 do 18 minuta) te su svi zahvati napravljeni dok je bolesnik bio u op&#x0107;oj anesteziji. S druge strane, prosje&#x010D;no vrijeme trajanja MWA procedure bilo je 4,9 minuta (raspon od 2,5 do 9 minuta), s time da su 3 zahvata napravljena dok je bolesnik bio u op&#x0107;oj anesteziji, a 4 zahvata u lokalnoj anesteziji uz analgosedaciju. Jedan ispitanik lije&#x010D;en je zbog dva sinkrona tumora na istom bubregu za koje je patohistolo&#x0161;ki utvr&#x0111;eno kako se radi o onkocitomima. Kod dvaju bolesnika u&#x010D;injena je ablacija recidiva u lo&#x017E;i ranije nefrektomije, a kod 11 bolesnika u&#x010D;injena je ablacija tumora na solitarnom bubregu. Prosje&#x010D;no vrijeme hospitalizacije bilo je 1,9 dana (raspon od 1 do 7 dana). Nije bilo nikakvih zna&#x010D;ajnijih komplikacija osim &#x010D;etiri Clavien-Dindo gradus 2 komplikacije: urtikarija, retencija urina i dva perirenalna hematoma koji su konzervativno lije&#x010D;eni. Prosje&#x010D;no vrijeme pra&#x0107;enja bolesnika je 14,5 mjeseci (raspon od 3 do 33 mjeseca), a kod jednoga je bolesnika pra&#x0107;enje prekinuto. Ukupno jednogodi&#x0161;nje OS je bilo 100%, isto kao i jednogodi&#x0161;nje CSS koje je tako&#x0111;er bilo 100%. Jedan je od ispitanika u razdoblju promatranja umro od komplikacija komorbiditeta (leukemija) 17 mjeseci nakon zahvata. Kod &#x010D;etvoro ispitanika (12,9%) utvr&#x0111;en je rezidualni tumor, kod troje nakon RFA i jednog nakon MWA. Troje bolesnika je lije&#x010D;eno ponovnom ablacijom, jedan pomo&#x0107;u RFA i dva MWA te je u daljnjem pra&#x0107;enju utvr&#x0111;en uspjeh ponovnog zahvata. Kod jednog bolesnika u&#x010D;injena je radikalna nefrektomija.</p>
<table-wrap id="t1" position="float">
<label>Table 1</label><caption><title>Basic demographic data</title>
</caption>
<table frame="hsides" rules="groups">
<col width="34.14%"/>
<col width="65.86%"/>
<thead>
<tr>
<th valign="top" align="left" scope="col" style="border-left: solid 0.75pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Broj bolesnika/Number of patients</th>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">N=31</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Prosje&#x010D;na dob/Average age</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">70,2 godina/years (raspon/range: 54 &#x2013; 85)</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Spol/Sex</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Mu&#x0161;ko/Male &#x2013; N=21<break/>&#x017D;ensko/Female &#x2013; N=10</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Solitarni bubreg/Solitary kidney</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">N=11</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt" scope="row">Komorbiditeti/Comorbidities</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.75pt">Sr&#x010D;ano&#x017E;ilne bolesti/Cardiovascular diseases N=26 (Zna&#x010D;ajne kardiovaskularne bolesti/Significant cardiovascular diseases N=13)<break/>Kroni&#x010D;na bubre&#x017E;na bolest/Chronic kidney disease N=12<break/>&#x0160;e&#x0107;erna bolest/Diabetes mellitus N=8<break/>Druge maligne bolesti/Other malignancies N=7</td>
</tr>
</tbody></table></table-wrap>
<table-wrap id="t2" position="float">
<label>Table 2</label><caption><title>Basic tumor characteristics</title>
</caption>
<table frame="hsides" rules="groups">
<col width="41.48%"/>
<col width="58.52%"/>
<thead>
<tr>
<th valign="top" align="left" scope="col" style="border-left: solid 0.75pt; border-top: solid 0.75pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt">Ukupni broj tumora/Total number of tumors</th>
<th valign="middle" align="left" scope="col" style="border-left: solid 0.50pt; border-top: solid 0.75pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">N=32</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Prosje&#x010D;ni promjer tumora/Average tumor diameter</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">2,4 cm (raspon/range: 1,1 &#x2013; 3,6 cm)</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Lateralizacija/Side</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Lijevo/left N=19<break/>Desno/right N=13</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Morfologija/Morphology</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Egzofiti&#x010D;an/exophytic N=20<break/>Endofiti&#x010D;an/endophytic N=10<break/>Lokalni recidiv nakon radikalne nefrektomije/Local tumor recurrence after radical nephrectomy N=2</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">R.E.N.A.L. ocjena tumora/R.E.N.A.L. score</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Medijan/Median 6 (raspon/range: 4 &#x2013; 10)<break/>Niska kompleksnost/Low complexity (R.E.N.A.L. 4&#x2013;6) N=19 (63,4%)<break/>Srednja kompleksnost/Intermediate complexity (R.E.N.A.L. 7&#x2013;9) N=10 (33,3%)<break/>Visoka kompleksnost/High complexity (R.E.N.A.L. 10&#x2013;12) N=1 (3,3%)</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.50pt" scope="row">Biopsija tumora/Tumor biopsy</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.50pt">Zasebno prije ablacije/Prior to ablation N=4<break/>Intraoperativno<break/>/During ablation N=28</td>
</tr>
<tr>
<td valign="top" align="left" style="border-left: solid 0.75pt; border-top: solid 0.50pt; border-right: solid 0.50pt; border-bottom: solid 0.75pt" scope="row">Rezultat patohistolo&#x0161;ke analize/Pathology report</td>
<td valign="middle" align="left" style="border-left: solid 0.50pt; border-top: solid 0.50pt; border-right: solid 0.75pt; border-bottom: solid 0.75pt">Svijetlostani&#x010D;ni karcinom bubre&#x017E;nih stanica/Clear cell renal carcinoma N=22 (68,8%)<break/>Onkocitom/Oncocytoma N=7 (21,9%)<break/>Liposarkom/Liposarcoma N=1 (3,1%)<break/>Angiomiolipom/Angiomyolipoma N=1 (3,1%)<break/>Bez malignog tumora/No malignant tumor N=1 (3,1%)</td>
</tr>
</tbody></table></table-wrap>
</sec>
<sec sec-type="other3">
<title>Rasprava</title>
<p>Prikazali smo seriju bolesnika s malim tumorima bubrega lije&#x010D;enih ablacijskim metodama koji imaju odli&#x010D;no jednogodi&#x0161;nje OS i CSS uz minimalne komplikacije. Indikacija za ablaciju postavlja se na temelju radiolo&#x0161;ke dijagnoze malog tumora bubrega kod bolesnika koji zbog komorbiditeta ili dobi nisu pogodni za operativno lije&#x010D;enje. RFA je naj&#x010D;e&#x0161;&#x0107;e kori&#x0161;tena ablacijska metoda koja je i najvi&#x0161;e istra&#x017E;ivana (<xref ref-type="bibr" rid="r9"><italic>9</italic></xref>). Dugoro&#x010D;ni su rezultati po pitanju onkolo&#x0161;kih ishoda vrlo dobri te objavljene serije izvje&#x0161;tavaju o petogodi&#x0161;njem CSS od 97 do 99%, petogodi&#x0161;njem RFS od 88 do 98% i petogodi&#x0161;njem OS od 66 do 97% (<xref ref-type="bibr" rid="r18"><italic>18</italic></xref>&#x2013;<xref ref-type="bibr" rid="r21"><italic>21</italic></xref>). Za MWA u ovome trenutku jo&#x0161; nema dugoro&#x010D;nih rezultata kao za RFA, ali su kratkoro&#x010D;ni rezultati retrospektivnih serija tijekom medijana pra&#x0107;enja od oko dvije godine obe&#x0107;avaju&#x0107;i &#x2013; RFS od 87,9 do 97%, CSS od 97 do 100% te OS od 80,6 do 97% (<xref ref-type="bibr" rid="r22"><italic>22</italic></xref>). Kod ve&#x0107;ine pacijenata u ovoj seriji u&#x010D;injena je RFA tumora, budu&#x0107;i da je na po&#x010D;etku serije to bila jedina dostupna ablacijska tehnologija u Klini&#x010D;kom bolni&#x010D;kom centru Zagreb, dok je MWA postala dostupna po&#x010D;etkom 2019. godine, kada je zbog brzine postupka, manje proceduralne boli te manje osjetljivosti na <italic>&#x201E;heatsink&#x201D;</italic> efekt postala glavni izbor za ablaciju tumora bubrega. Rezultati patohistolo&#x0161;ke analize iz na&#x0161;e serije (<xref ref-type="table" rid="t2">tablica 2</xref>.) utvrdili su zlo&#x0107;udnu promjenu u 71,9% slu&#x010D;ajeva, &#x0161;to je u skladu s patologijom malih tumora bubrega (<xref ref-type="bibr" rid="r5"><italic>5</italic></xref>). Osim onkolo&#x0161;kih rezultata, potrebno je razmotriti i funkcionalne ishode lije&#x010D;enja. Prednosti ablacijskih metoda su minimalno invazivan pristup i o&#x010D;uvanje bubre&#x017E;ne funkcije. Poznato je kako 22% bolesnika s tumorom bubrega unato&#x010D; urednim vrijednostima kreatinina ima lo&#x0161;u bubre&#x017E;nu funkciju te se taj udio pove&#x0107;ava na 40% kod bolesnika koji su stariji od 70 godina (<xref ref-type="bibr" rid="r23"><italic>23</italic></xref>). Za ablacijske metode se pokazalo kako dugoro&#x010D;no u manjoj mjeri utje&#x010D;u na smanjenje bubre&#x017E;ne funkcije u usporedbi s kirur&#x0161;kim metodama &#x2013; radikalnom i parcijalnom nefrektomijom (<xref ref-type="bibr" rid="r24"><italic>24</italic></xref>). Iako su ablacijske metode izrazito popularne u svijetu, do sada nije provedeno niti jedno visoko kvalitetno randomizirano kontrolirano istra&#x017E;ivanje koje bi usporedilo onkolo&#x0161;ku u&#x010D;inkovitost ovih metoda s parcijalnom nefrektomijom &#x2013; zlatnim standardom lije&#x010D;enja T1a tumora bubrega. Upravo zbog toga postoji odre&#x0111;ena doza opreza kod kori&#x0161;tenja ovih metoda. Unato&#x010D; tomu, ima autora koji smatraju kako je ablacija dovoljno dobra alternativa parcijalnoj nefrektomiji, kao &#x0161;to su Ma Y i suradnici, koji su u svojoj seriji ablacija kod bolesnika koji nisu stari i nemaju zna&#x010D;ajnih komorbiditeta postigli dugoro&#x010D;ni rezultat bez recidiva od 94% (<xref ref-type="bibr" rid="r25"><italic>25</italic></xref>). Tako&#x0111;er, ASCO smjernice smatraju ablaciju opcijom za sve bolesnike s malim tumorima bubrega ako se pouzdano mo&#x017E;e posti&#x0107;i kompletna ablacija (<xref ref-type="bibr" rid="r26"><italic>26</italic></xref>). Kada se uspore&#x0111;uju ablacijske metode s parcijalnom nefrektomijom, utvr&#x0111;en je vi&#x0161;i postotak recidiva kod ablacijskih metoda, me&#x0111;utim i ti se recidivi mogu uspje&#x0161;no tretirati ponovnom ablacijom (<xref ref-type="bibr" rid="r27"><italic>27</italic></xref>). Potrebno je istaknuti kako se ipak najbolji rezultati ablacije posti&#x017E;u kod tumora do 3 cm u promjeru, dok se iznad te vrijednosti pove&#x0107;ava postotak recidiva (<xref ref-type="bibr" rid="r28"><italic>28</italic></xref>). S obzirom na slo&#x017E;enost tehnologije ablacijskih sustava, u rijetkim slu&#x010D;ajevima mo&#x017E;e do&#x0107;i do tehni&#x010D;kog neuspjeha zahvata, &#x0161;to rezultira rezidualnim tumorom. Tehni&#x010D;ki neuspjeh u ve&#x0107;oj seriji Atwell i suradnika opisuje se u 1,1% slu&#x010D;ajeva (<xref ref-type="bibr" rid="r18"><italic>18</italic></xref>). U na&#x0161;oj seriji utvrdili smo rezidualni tumor kod 12,9% ispitanika, od &#x010D;ega se jedan slu&#x010D;aj mo&#x017E;e pripisati tehni&#x010D;kom neuspjehu procedure, a ostala tri kombinaciji veli&#x010D;ine tumora (tumori ve&#x0107;i od 3 cm) te blizini velikim krvnim &#x017E;ilama i kanalnom sustavu (vi&#x0161;e R.E.N.A.L. stupnjevanje) &#x010D;ime dolazi do <italic>&#x201E;heatsink&#x201D;</italic> efekta, &#x0161;to je istaknuti faktor smanjenja u&#x010D;inka ablacije (<xref ref-type="bibr" rid="r14"><italic>14</italic></xref>). Ne postoji jedinstveni stav kojom metodom tretirati rezidualni tumor te u obzir dolaze tri opcije: aktivni nadzor, ponovna ablacija i kirur&#x0161;ko lije&#x010D;enje (<xref ref-type="bibr" rid="r29"><italic>29</italic></xref>, <xref ref-type="bibr" rid="r30"><italic>30</italic></xref>), pa se terapija prilago&#x0111;ava osobinama bolesnika, tumora i tehni&#x010D;kim mogu&#x0107;nostima. Tri od &#x010D;etiri rezidualna tumora u na&#x0161;oj seriji uspje&#x0161;no su ponovno lije&#x010D;ena ablacijskom metodom, a samo je kod jednog u&#x010D;injena nefrektomija. Taj pacijent je inicijalno bio upu&#x0107;en na ablaciju zbog kroni&#x010D;ne bubre&#x017E;ne bolesti i komorbiditeta, tumor je bio promjera 3,6 cm i prema R.E.N.A.L. stupnjevanju ocjene 10a, a biopsija je pokazala da se radi o svijetlostani&#x010D;nom karcinomu bubrega. Temeljem tih razloga nakon utvr&#x0111;ivanja rezidue tumora postavljena je sumnja u uspjeh ponovnog postupka ablacije te je u&#x010D;injena radikalna nefrektomija. Sve bitne svjetske smjernice za lije&#x010D;enje tumora bubrega ablacijom preporu&#x010D;uju biopsiju tumora (<xref ref-type="bibr" rid="r7"><italic>7</italic></xref>, <xref ref-type="bibr" rid="r8"><italic>8</italic></xref>, <xref ref-type="bibr" rid="r26"><italic>26</italic></xref>). Postoji teoretska &#x0161;ansa &#x201E;sijanja&#x201D; tumorskih stanica du&#x017E; biopsijskog kanala kod manje od 1 na 10.000 zahvata kada se ne koristi koaksijalna igla prilikom biopsije (<xref ref-type="bibr" rid="r31"><italic>31</italic></xref>). Budu&#x0107;i da mi uvijek koristimo koaksijalnu iglu, taj rizik je zanemariv. U na&#x0161;oj seriji (<xref ref-type="table" rid="t2">tablica 2</xref>.) biopsija tumora je kod 27 bolesnika u&#x010D;injena u sklopu zahvata, a samo je kod 4 bolesnika prvo u&#x010D;injena biopsija, a ablacija nakon dospije&#x0107;a patohistolo&#x0161;ke analize, jer se radilo o svijetlostani&#x010D;nom karcinomu bubrega. Iako se smjernice ne izja&#x0161;njavaju o optimalnom vremenu izvo&#x0111;enja biopsije, Tsang Mui Chung i suradnici utvrdili su kako prethodno u&#x010D;injena biopsija u samo 2,2% slu&#x010D;ajeva odla&#x017E;e indikaciju za ablaciju kod radiolo&#x0161;ki jasnih tumora bubrega i zaklju&#x010D;ili su kako nema jasne koristi od prethodne biopsije (<xref ref-type="bibr" rid="r32"><italic>32</italic></xref>). Na&#x0161;a serija relativno malog broja bolesnika nije imala niti jednu zna&#x010D;ajnu komplikaciju, a svi bolesnici hospitalizirani su vrlo kratko, &#x010D;ime se financijski opravdava relativno skupi zahvat koji uklju&#x010D;uje potro&#x0161;ni materijal elektrode. Na temelju na&#x0161;ih iskustava mo&#x017E;emo istaknuti koje su prednosti pojedinih metoda. RFA je ve&#x0107; dulje vrijeme prisutna, etablirana je, ima dugoro&#x010D;ne rezultate, ali s&#x00E2;m zahvat traje dulje i manje je uspje&#x0161;an za tumore ve&#x0107;e od 3 cm. MWA je, s druge strane, novija tehnologija koja je skuplja, ali su glavne prednosti &#x0161;to kratko traje, mo&#x017E;e se izvesti u lokalnoj anesteziji uz analgosedaciju te uspje&#x0161;no ablira i tumore ve&#x0107;e od 3 cm. Koju god tehniku izabrali, obvezno treba napraviti biopsiju tvorbe, a temeljem smjernica Europskoga urolo&#x0161;kog dru&#x0161;tva ablaciju se preporu&#x010D;uje koristiti kod starijih bolesnika i bolesnika s komorbiditetima (<xref ref-type="bibr" rid="r8"><italic>8</italic></xref>). Moderno lije&#x010D;enje karcinoma bubrega zahtijeva multidisciplinarni pristup zbog brzog razvoja i kirur&#x0161;ke tehnike i novih tehnologija, a i naprednih metoda onkolo&#x0161;kog lije&#x010D;enja. Bitna je kvalitetna suradnja urologa, intervencijskog radiologa i onkologa jer samo tako mo&#x017E;emo dobiti najbolje rezultate lije&#x010D;enja.</p>
</sec>
<sec sec-type="other4">
<title>Zaklju&#x010D;ak</title>
<p>Zbog niskog mortaliteta i odli&#x010D;nih rezultata, kirur&#x0161;ki zahvat &#x2013; parcijalna nefrektomija i dalje predstavlja terapiju izbora u lije&#x010D;enju malih tumora bubrega. Me&#x0111;utim, s obzirom na razli&#x010D;iti maligni potencijal malih tumora bubrega te komorbiditete bolesnika, primjenjuju se i ablacijske metode. One imaju nisku stopu komplikacija, mogu se izvesti bez op&#x0107;e anestezije, manje utje&#x010D;u na bubre&#x017E;nu funkciju i u velikog postotka bolesnika dovode do izlje&#x010D;enja malih tumora bubrega. Upravo zbog toga predstavljaju terapiju izbora kod bolesnika koji nisu podobni za kirur&#x0161;ki zahvat. U lije&#x010D;enju bolesnika s malim tumorima bubrega klju&#x010D;an je multidisciplinarni pristup i timski rad kako bi im se mogla ponuditi indvidualizirana terapija.</p>
</sec>
</body>
<back>
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