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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">yLQjFrvKYyNqzpMSJkg3QhB</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2023001000501</article-id>
      <article-id pub-id-type="other">00501</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20220912</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Carta Cient&#237;fica</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Instila&#231;&#227;o Intraperic&#225;rdica de Cisplatina para Derrame Peric&#225;rdico Maligno: Uma Experi&#234;ncia em um &#218;nico Centro</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6429-9780</contrib-id>
          <name>
            <surname>Medeiros</surname>
            <given-names>Paulo</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados e An&#225;lise estat&#237;stica</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2981-4978</contrib-id>
          <name>
            <surname>Rodrigues</surname>
            <given-names>Jorge</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados e An&#225;lise estat&#237;stica</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gaspar</surname>
            <given-names>Ant&#243;nio</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label> 1 </label>
        <institution content-type="orgname">Hospital de Braga</institution>
        <addr-line>
          <named-content content-type="city">Braga</named-content>
        </addr-line>
        <country country="PT">Portugal</country>
        <institution content-type="original"> Hospital de Braga , Braga &#8211; Portugal </institution>
      </aff>
      <author-notes>
        <corresp id="c01">Correspond&#234;ncia: Paulo Medeiros &#8226; Sete Fontes - S&#227;o Victor, 4710-243, Braga - Portugal E-mail: <email>paulo.duarte.medeiros@gmail.com</email> </corresp>
        <fn fn-type="conflict">
          <p>Potencial conflito de interesse</p>
          <p>N&#227;o h&#225; conflito com o presente artigo</p>
        </fn>
        <fn fn-type="edited-by">
          <p>Editor respons&#225;vel pela revis&#227;o: Gl&#225;ucia Maria Moraes de Oliveira</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>30</day>
        <month>10</month>
        <year>2023</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>10</month>
        <year>2023</year>
      </pub-date>
      <volume>120</volume>
      <issue>10</issue>
      <elocation-id>e20220912</elocation-id>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>12</month>
          <year>2022</year>
        </date>
        <date date-type="rev-recd">
          <day>03</day>
          <month>06</month>
          <year>2023</year>
        </date>
        <date date-type="accepted">
          <day>17</day>
          <month>07</month>
          <year>2023</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <kwd>Derrame Peric&#225;rdio</kwd>
        <kwd>Instila&#231;&#227;o de Medicamentos</kwd>
        <kwd>Pericardiocentese</kwd>
        <kwd>Antineopl&#225;sicos Alquilantes</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="4"/>
        <equation-count count="0"/>
        <ref-count count="13"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>O envolvimento do cora&#231;&#227;o e do peric&#225;rdio ocorre em cerca de 10% de todos os pacientes com c&#226;ncer e tem impacto significativo na sobrevida. <sup><xref ref-type="bibr" rid="B1">1</xref></sup> Carcinomas de pulm&#227;o e mama, melanoma e linfoma s&#227;o os tumores malignos mais comuns que afetam o cora&#231;&#227;o e o peric&#225;rdio. <sup><xref ref-type="bibr" rid="B2">2</xref></sup> O envolvimento do cora&#231;&#227;o &#233; um marcador de progn&#243;stico muito ruim, representando doen&#231;a neopl&#225;sica em est&#225;gio terminal.</p>
      <p>A descompress&#227;o peric&#225;rdica via pericardiocentese resulta no al&#237;vio imediato da dispneia e desempenha um papel importante no tratamento sintom&#225;tico. <sup><xref ref-type="bibr" rid="B3">3</xref></sup> Contudo, n&#227;o &#233; incomum a necessidade de m&#250;ltiplos procedimentos no mesmo paciente. Nas &#250;ltimas d&#233;cadas surgiram relatos sobre a utiliza&#231;&#227;o de agentes citot&#243;xicos para pericardiodese qu&#237;mica, mas a literatura &#233; escassa e nenhum documento de sistematiza&#231;&#227;o foi publicado. Os autores tiveram como objetivo avaliar a recorr&#234;ncia de derrame peric&#225;rdico maligno clinicamente significativo em pacientes submetidos &#224; pericardiocentese e instila&#231;&#227;o de cisplatina.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <p>Este foi um estudo observacional transversal retrospectivo. Este estudo est&#225; em conformidade com a Declara&#231;&#227;o de Helsinque e foi conduzido seguindo os requisitos do comit&#234; de &#233;tica local.</p>
      <p><underline>Sele&#231;&#227;o de pacientes</underline>: Os autores coletaram dados de pacientes com idade &#8805;18 anos, internados em seu hospital por derrame peric&#225;rdico maligno entre janeiro de 2019 e janeiro de 2022, que foram submetidos &#224; pericardiodese qu&#237;mica com cisplatina. O &#250;nico crit&#233;rio de exclus&#227;o foi a depend&#234;ncia total do paciente (status 4 de desempenho do Eastern Cooperative Oncology Group).</p>
      <p><underline>Dados cl&#237;nicos e defini&#231;&#245;es</underline>: Derrame peric&#225;rdico significativo foi definido por crit&#233;rios ecocardiogr&#225;ficos: espessura do espa&#231;o peric&#225;rdico de pelo menos 20mm, altera&#231;&#245;es respirat&#243;rias exageradas nas velocidades E mitral e tric&#250;spide, veia cava inferior &gt;20 mm e varia&#231;&#227;o &lt;50% com a respira&#231;&#227;o e sinais de comprometimento do enchimento do ventr&#237;culo direito. A combina&#231;&#227;o de hipotens&#227;o e crit&#233;rios ecocardiogr&#225;ficos definiu tamponamento card&#237;aco. A recidiva foi definida como interna&#231;&#227;o por derrame peric&#225;rdico significativo, com ou sem tamponamento.</p>
      <p><underline>T&#233;cnica de instila&#231;&#227;o</underline>: A pericardiocentese foi realizada por via subxifoide ou apical. O espa&#231;o peric&#225;rdico foi deixado em drenagem livre at&#233; que menos de 50 mL/24h de l&#237;quido fossem coletados. Duas ou tr&#234;s instila&#231;&#245;es da prepara&#231;&#227;o citot&#243;xica (10 mg de cisplatina dilu&#237;da em 20 mL de soro fisiol&#243;gico) foram administradas por paciente em intervalos de 24 horas, com reavalia&#231;&#227;o ecocardiogr&#225;fica antes de cada instila&#231;&#227;o. Ap&#243;s todas as instila&#231;&#245;es, o cateter peric&#225;rdico foi retirado.</p>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Onze pacientes foram tratados com cisplatina intraperic&#225;rdica. As caracter&#237;sticas basais est&#227;o descritas na <xref ref-type="table" rid="t1">Tabela 1</xref> . A m&#233;dia de idade foi de 57 &#177; 14 anos (m&#237;nimo 36 anos, m&#225;ximo 82 anos) e o sexo feminino foi predominante (64%; n=7).</p>
      <p>
        <table-wrap id="t1">
          <label>Tabela 1</label>
          <caption>
            <title>&#8211; Caracter&#237;sticas basais e diagn&#243;stico de c&#226;ncer</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Paciente n&#186;.</th>
                <th>Sexo</th>
                <th>Anos de idade)</th>
                <th>Diagn&#243;stico de c&#226;ncer</th>
                <th>Diagn&#243;stico conhecido antes da admiss&#227;o</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>1</td>
                <td align="center">F</td>
                <td align="center">36</td>
                <td align="center">Adenocarcinoma de mama</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>2</td>
                <td align="center">M</td>
                <td align="center">40</td>
                <td align="center">Adenocarcinoma pulmonar</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>3</td>
                <td align="center">F</td>
                <td align="center">52</td>
                <td align="center">Adenocarcinoma pulmonar</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>4</td>
                <td align="center">F</td>
                <td align="center">52</td>
                <td align="center">Adenocarcinoma pulmonar</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>5</td>
                <td align="center">M</td>
                <td align="center">54</td>
                <td align="center">Adenocarcinoma de c&#233;lulas renais</td>
                <td align="center">N&#227;o</td>
              </tr>
              <tr>
                <td>6</td>
                <td align="center">M</td>
                <td align="center">57</td>
                <td align="center">Adenocarcinoma pulmonar</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>7</td>
                <td align="center">F</td>
                <td align="center">61</td>
                <td align="center">Adenocarcinoma pulmonar</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>8</td>
                <td align="center">F</td>
                <td align="center">63</td>
                <td align="center">Adenocarcinoma pulmonar</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>9</td>
                <td align="center">F</td>
                <td align="center">68</td>
                <td align="center">Adenocarcinoma pulmonar</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>10</td>
                <td align="center">F</td>
                <td align="center">73</td>
                <td align="center">Adenocarcinoma g&#225;strico</td>
                <td align="center">Sim</td>
              </tr>
              <tr>
                <td>11</td>
                <td align="center">M</td>
                <td align="center">82</td>
                <td align="center">Adenocarcinoma de pr&#243;stata</td>
                <td align="center">N&#227;o</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </p>
      <sec>
        <title>Derrame peric&#225;rdico e instila&#231;&#227;o de cisplatina</title>
        <p>A maioria dos pacientes apresentou tamponamento card&#237;aco; o volume m&#233;dio de drenagem foi de 800&#177;500 mL. Esses pacientes foram submetidos a duas instila&#231;&#245;es de cisplatina, exceto nos casos com hist&#243;ria pr&#233;via de derrame peric&#225;rdico, nos quais foram realizadas tr&#234;s instila&#231;&#245;es. Em rela&#231;&#227;o aos efeitos colaterais, tr&#234;s pacientes apresentaram fibrila&#231;&#227;o atrial de novo e dois tiveram febre autolimitada. Nenhum paciente apresentou complica&#231;&#245;es graves relacionadas &#224; t&#233;cnica de pericardiocentese ou &#224; presen&#231;a do cateter peric&#225;rdico. Os detalhes individuais s&#227;o relatados na <xref ref-type="table" rid="t2">Tabela 2</xref> .</p>
        <p>
          <table-wrap id="t2">
            <label>Tabela 2</label>
            <caption>
              <title>&#8211; Caracter&#237;sticas do derrame peric&#225;rdico e da instila&#231;&#227;o de cisplatina</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Paciente n&#186;.</th>
                  <th>Tamponamento na admiss&#227;o</th>
                  <th>Volume drenado (mL)</th>
                  <th>Apar&#234;ncia macrosc&#243;pica</th>
                  <th>N&#186; de instila&#231;&#245;es de cisplatina</th>
                  <th>Efeitos colaterais</th>
                  <th>Recorr&#234;ncia de derrame durante o acompanhamento</th>
                  <th>Tempo desde a instila&#231;&#227;o at&#233; a morte (dias)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>1</td>
                  <td align="center">Sim</td>
                  <td align="center">500</td>
                  <td align="center">Serohem&#225;tico</td>
                  <td align="center">2</td>
                  <td align="center">FA</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">7</td>
                </tr>
                <tr>
                  <td>2</td>
                  <td align="center">Sim</td>
                  <td align="center">1700</td>
                  <td align="center">Serohem&#225;tico</td>
                  <td align="center">2</td>
                  <td align="center">-</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">87</td>
                </tr>
                <tr>
                  <td>3</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">800</td>
                  <td align="center">Citrino</td>
                  <td align="center">3</td>
                  <td align="center">-</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">233</td>
                </tr>
                <tr>
                  <td>4</td>
                  <td align="center">Sim</td>
                  <td align="center">1120</td>
                  <td align="center">Hemorr&#225;gico</td>
                  <td align="center">2</td>
                  <td align="center">-</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">528</td>
                </tr>
                <tr>
                  <td>5</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">850</td>
                  <td align="center">Hemorr&#225;gico</td>
                  <td align="center">2</td>
                  <td align="center">-</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">148</td>
                </tr>
                <tr>
                  <td>6</td>
                  <td align="center">Sim</td>
                  <td align="center">1900</td>
                  <td align="center">Hemorr&#225;gico</td>
                  <td align="center">2</td>
                  <td align="center">Febre</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">438</td>
                </tr>
                <tr>
                  <td>7</td>
                  <td align="center">Sim</td>
                  <td align="center">850</td>
                  <td align="center">Hemorr&#225;gico</td>
                  <td align="center">2</td>
                  <td align="center">FA</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">-*</td>
                </tr>
                <tr>
                  <td>8</td>
                  <td align="center">Sim</td>
                  <td align="center">800</td>
                  <td align="center">Hemorr&#225;gico</td>
                  <td align="center">2</td>
                  <td align="center">FA</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">386</td>
                </tr>
                <tr>
                  <td>9</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">1000</td>
                  <td align="center">Hemorr&#225;gico</td>
                  <td align="center">3</td>
                  <td align="center">Febre</td>
                  <td align="center">Sim</td>
                  <td align="center">284</td>
                </tr>
                <tr>
                  <td>10</td>
                  <td align="center">Sim</td>
                  <td align="center">1700</td>
                  <td align="center">Hemorr&#225;gico</td>
                  <td align="center">2</td>
                  <td align="center">-</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">235</td>
                </tr>
                <tr>
                  <td>11</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">400</td>
                  <td align="center">Hemorr&#225;gico</td>
                  <td align="center">2</td>
                  <td align="center">-</td>
                  <td align="center">N&#227;o</td>
                  <td align="center">134</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1">
                <p>FA: fibrila&#231;&#227;o atrial. *Paciente vivo durante o acompanhamento.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
      </sec>
      <sec>
        <title>Acompanhamento</title>
        <p>O seguimento m&#233;dio foi de 290 dias. Durante o acompanhamento, dez pacientes morreram em m&#233;dia de 248 dias por pericardiodese qu&#237;mica. Nenhum dos pacientes morreu de causas cardiovasculares. A recorr&#234;ncia de derrame peric&#225;rdico ocorreu em um caso de adenocarcinoma pulmonar ap&#243;s aproximadamente 12 meses da instila&#231;&#227;o de cisplatina.</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Os autores descrevem uma experi&#234;ncia unic&#234;ntrica de pericardiodese qu&#237;mica com cisplatina ap&#243;s pericardiocentese percut&#226;nea, em pacientes com derrame peric&#225;rdico maligno.</p>
      <p>Um dos primeiros relatos humanos de tentativa de controle de derrame peric&#225;rdico recorrente com instila&#231;&#227;o intraperic&#225;rdica de uma subst&#226;ncia foi publicado em 1953 por Bachman KP et al., utilizando ouro radioativo. <sup><xref ref-type="bibr" rid="B4">4</xref></sup> Desde ent&#227;o, outros compostos foram testados, como a tetraciclina, <sup><xref ref-type="bibr" rid="B5">5</xref></sup> bleomicina, <sup><xref ref-type="bibr" rid="B6">6</xref></sup> colchicina, <sup><xref ref-type="bibr" rid="B7">7</xref></sup> entre outros. Agentes intraperic&#225;rdicos tamb&#233;m foram testados em outros contextos, como na s&#237;ndrome de Dressler <sup><xref ref-type="bibr" rid="B8">8</xref></sup> e pericardite aguda ap&#243;s estudos eletrofisiol&#243;gicos. <sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
      <p>A maior s&#233;rie de pacientes tratados com cisplatina intraperic&#225;rdica foi publicada por Maisch et al., <sup><xref ref-type="bibr" rid="B10">10</xref></sup> e Tomkowski et al., <sup><xref ref-type="bibr" rid="B11">11</xref></sup> incluindo 42 e 46 pacientes, respectivamente. Assim como no presente estudo, a maioria dos pacientes apresentava c&#226;ncer de pulm&#227;o. Em Maish et al., <sup><xref ref-type="bibr" rid="B10">10</xref></sup> uma &#250;nica instila&#231;&#227;o intraperic&#225;rdica de cisplatina evitou a recorr&#234;ncia de derrame peric&#225;rdico hemodinamicamente relevante durante os primeiros tr&#234;s meses de acompanhamento em 92,8% dos pacientes. Embora o progn&#243;stico geral tenha sido ruim, nenhum dos pacientes morreu devido a tamponamento card&#237;aco. Em Tomkowski et al., <sup><xref ref-type="bibr" rid="B11">11</xref></sup> nenhum ac&#250;mulo de grandes quantidades de l&#237;quido peric&#225;rdico foi alcan&#231;ado em 93,5% dos pacientes ap&#243;s a instila&#231;&#227;o de cisplatina. Todos os pacientes inscritos morreram devido a malignidade avan&#231;ada. A fibrila&#231;&#227;o atrial transit&#243;ria foi o efeito colateral mais comum. Outros efeitos colaterais relatados incluem dor, febre, n&#225;usea e taquicardia ventricular n&#227;o sustentada. <sup><xref ref-type="bibr" rid="B12">12</xref> , <xref ref-type="bibr" rid="B13">13</xref></sup></p>
      <p>Esta s&#233;rie relata achados semelhantes, incluindo um controle bem-sucedido do ac&#250;mulo de l&#237;quido peric&#225;rdico. Esses resultados apoiam a ideia de uma op&#231;&#227;o segura e eficaz para pacientes com derrame peric&#225;rdico maligno, que provavelmente apresentar&#227;o recorr&#234;ncias ap&#243;s uma pericardiocentese bem-sucedida. A sobrevida global &#233; baixa. A pericardiodese qu&#237;mica visa aliviar os sintomas e pode at&#233; prevenir algumas mortes por tamponamento card&#237;aco; n&#227;o obstante, n&#227;o h&#225; evid&#234;ncia de benef&#237;cio de sobreviv&#234;ncia, uma vez que os pacientes ainda apresentam progress&#227;o da doen&#231;a neopl&#225;sica. Tanto quanto &#233; do conhecimento dos autores, esta &#233; a primeira s&#233;rie publicada de instila&#231;&#227;o intraperic&#225;rdica de um agente esclerosante/quimioter&#225;pico desenvolvido em Portugal.</p>
      <p>Este estudo tem algumas limita&#231;&#245;es importantes. Primeiro, este &#233; um estudo retrospectivo e observacional realizado em uma pequena amostra de pacientes. Segundo, por raz&#245;es &#233;ticas, n&#227;o houve grupo de controle; como tal, n&#227;o pudemos avaliar o efeito exclusivo da cisplatina independentemente do tratamento padr&#227;o da neoplasia prim&#225;ria. Al&#233;m disso, n&#227;o foi poss&#237;vel realizar ecocardiogramas de acompanhamento programados para avaliar a reacumula&#231;&#227;o subcl&#237;nica de l&#237;quido peric&#225;rdico. Estes resultados merecem uma investiga&#231;&#227;o mais aprofundada, nomeadamente em estudos prospectivos e maiores.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#245;es</title>
      <p>A instila&#231;&#227;o intraperic&#225;rdica de cisplatina parece ser uma op&#231;&#227;o de tratamento eficaz e segura para pacientes com derrame peric&#225;rdico maligno. Embora n&#227;o haja evid&#234;ncia de aumento da sobrevida, estes dados sugerem que o al&#237;vio dos sintomas e a preven&#231;&#227;o da recorr&#234;ncia s&#227;o provavelmente alcan&#231;&#225;veis. Portanto, a pericardiodese deve ser inclu&#237;da no arsenal dos profissionais de cuidados paliativos.</p>
    </sec>
  </body>
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    <fn-group>
      <fn fn-type="other">
        <p>Vincula&#231;&#227;o acad&#234;mica</p>
        <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        <p>Aprova&#231;&#227;o &#233;tica e consentimento informado</p>
        <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica do Hospital de Braga sob o n&#250;mero de protocolo 19_2022. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#237;dos no estudo.</p>
      </fn>
      <fn fn-type="supported-by">
        <p>Fontes de financiamento: O presente estudo n&#227;o teve fontes de financiamento externas.</p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Research Letter</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Intrapericardial Cisplatin Instillation for Malignant Pericardial Effusion: A Single-center Experience</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6429-9780</contrib-id>
          <name>
            <surname>Medeiros</surname>
            <given-names>Paulo</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data and Statistical analysis</role>
          <role>Analysis and interpretation of the data</role>
          <role>Writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2981-4978</contrib-id>
          <name>
            <surname>Rodrigues</surname>
            <given-names>Jorge</given-names>
          </name>
          <role>Acquisition of data and Statistical analysis</role>
          <role>Analysis and interpretation of the data</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Gaspar</surname>
            <given-names>Ant&#243;nio</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Analysis and interpretation of the data</role>
          <role>Critical revision of the manuscript for important intellectual content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label> 1 </label>
        <country country="PT">Portugal</country>
        <institution content-type="original"> Hospital de Braga, Braga &#8211; Portugal </institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Paulo Medeiros &#8226; Sete Fontes - S&#227;o Victor, 4710-243, Braga - Portugal E-mail: paulo.duarte.medeiros@gmail.com</corresp>
        <fn fn-type="conflict">
          <p>Potential conflict of interest</p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="edited-by">
          <p>Editor responsible for the review: Gl&#225;ucia Maria Moraes de Oliveira</p>
        </fn>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Pericardial Effusion</kwd>
        <kwd>Instillation, Drugs</kwd>
        <kwd>Pericardiocentesis</kwd>
        <kwd>Antineoplastic, Agents, Alkylating</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Heart and pericardium involvement occurs in about 10% of cancer patients, significantly impacting survival. <sup><xref ref-type="bibr" rid="B1">1</xref></sup> Lung and breast carcinomas, melanoma, and lymphoma are the most common malignant tumors affecting the heart and pericardium. <sup><xref ref-type="bibr" rid="B2">2</xref></sup> Involvement of the heart is a marker of very poor prognosis, representing end-stage neoplastic disease.</p>
        <p>Pericardial decompression via pericardiocentesis results in immediate dyspnea relief and plays an important role in symptomatic treatment. <sup><xref ref-type="bibr" rid="B3">3</xref></sup> Notwithstanding, the need for multiple procedures in the same patient is not uncommon. During the last decades, reports emerged regarding the utilization of cytotoxic agents for chemical pericardiodesis, but literature is scarce overall, and no systematization document has been published. The authors aimed to assess the recurrence of clinically significant malignant pericardial effusion in patients submitted to pericardiocentesis and cisplatin instillation.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <p>This was a retrospective cross-sectional observational study. This study complies with the Declaration of Helsinki and was conducted following the local ethics committee requirements.</p>
        <p><underline>Patient selection</underline>: The authors collected data from patients aged &#8805;18 years, admitted to their hospital due to malignant pericardial effusion between January 2019 and January 2022, who were submitted to chemical pericardiodesis with cisplatin. The only exclusion criterion was total patient dependency (Eastern Cooperative Oncology Group Performance Status of 4).</p>
        <p><underline>Clinical data and definitions</underline>: Significant pericardial effusion was defined by echocardiographic criteria: pericardial space thickness of at least 20mm, exaggerated respiratory changes in the mitral and tricuspid E velocities, inferior vena cava &gt;20 mm and &lt;50% variation with respiration and signs of right ventricle filling impairment. The combination of hypotension and echocardiographic criteria defined cardiac tamponade. Recurrence was defined as a hospitalization due to significant pericardial effusion, with or without tamponade.</p>
        <p><underline>Instillation technique</underline>: Pericardiocentesis was performed using a subxiphoid or apical approach. Pericardial space was left on free drainage until less than 50 mL/24h of fluid was collected. Two or three instillations of the cytotoxic preparation (10 mg of cisplatin diluted in 20 mL of normal saline) were administered per patient in 24h intervals, with echocardiography reassessment before each instillation. After all the instillations, the pericardial catheter was removed.</p>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>Eleven patients were treated with intrapericardial cisplatin. Baseline characteristics are described in <xref ref-type="table" rid="t1001">Table 1</xref> . The mean age was 57 &#177; 14 years (minimum 36 years, maximum 82 years), and female sex was predominant (64%; n=7).</p>
        <p>
          <table-wrap id="t1001">
            <label>Table 1</label>
            <caption>
              <title>&#8211; Baseline characteristics and cancer diagnosis</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Patient No.</th>
                  <th>Sex</th>
                  <th>Age (years)</th>
                  <th>Cancer diagnosis</th>
                  <th>Diagnosis known before admission</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>1</td>
                  <td align="center">F</td>
                  <td align="center">36</td>
                  <td align="center">Breast adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>2</td>
                  <td align="center">M</td>
                  <td align="center">40</td>
                  <td align="center">Lung adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>3</td>
                  <td align="center">F</td>
                  <td align="center">52</td>
                  <td align="center">Lung adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>4</td>
                  <td align="center">F</td>
                  <td align="center">52</td>
                  <td align="center">Lung adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>5</td>
                  <td align="center">M</td>
                  <td align="center">54</td>
                  <td align="center">Renal cell adenocarcinoma</td>
                  <td align="center">No</td>
                </tr>
                <tr>
                  <td>6</td>
                  <td align="center">M</td>
                  <td align="center">57</td>
                  <td align="center">Lung adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>7</td>
                  <td align="center">F</td>
                  <td align="center">61</td>
                  <td align="center">Lung adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>8</td>
                  <td align="center">F</td>
                  <td align="center">63</td>
                  <td align="center">Lung adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>9</td>
                  <td align="center">F</td>
                  <td align="center">68</td>
                  <td align="center">Lung adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>10</td>
                  <td align="center">F</td>
                  <td align="center">73</td>
                  <td align="center">Gastric adenocarcinoma</td>
                  <td align="center">Yes</td>
                </tr>
                <tr>
                  <td>11</td>
                  <td align="center">M</td>
                  <td align="center">82</td>
                  <td align="center">Prostate adenocarcinoma</td>
                  <td align="center">No</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </p>
        <sec>
          <title>Pericardial effusion and cisplatin instillation</title>
          <p>Most patients presented with cardiac tamponade; the mean drainage volume was 800&#177;500 mL. These patients were submitted to two cisplatin instillations, except in cases with previous history of pericardial effusion, in which three instillations were performed instead. Regarding side effects, three patients experienced <italic>de novo</italic> atrial fibrillation, and two had self-limited fever. No patients experienced serious complications related to the pericardiocentesis technique or the presence of the pericardial catheter. Individual details are reported in <xref ref-type="table" rid="t2001">Table 2</xref> .</p>
          <p>
            <table-wrap id="t2001">
              <label>Table 2</label>
              <caption>
                <title>&#8211; Pericardial effusion and cisplatin instillation features</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Patient No.</th>
                    <th>Tamponade at admission</th>
                    <th>Drained volume (mL)</th>
                    <th>Macroscopic appearance</th>
                    <th>No. of cisplatin instillations</th>
                    <th>Side effects</th>
                    <th>Effusion recurrence during follow-up</th>
                    <th>Time from instillation to death (days)</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>1</td>
                    <td align="center">Yes</td>
                    <td align="center">500</td>
                    <td align="center">Serohematic</td>
                    <td align="center">2</td>
                    <td align="center">AF</td>
                    <td align="center">No</td>
                    <td align="center">7</td>
                  </tr>
                  <tr>
                    <td>2</td>
                    <td align="center">Yes</td>
                    <td align="center">1700</td>
                    <td align="center">Serohematic</td>
                    <td align="center">2</td>
                    <td align="center">-</td>
                    <td align="center">No</td>
                    <td align="center">87</td>
                  </tr>
                  <tr>
                    <td>3</td>
                    <td align="center">No</td>
                    <td align="center">800</td>
                    <td align="center">Citrine</td>
                    <td align="center">3</td>
                    <td align="center">-</td>
                    <td align="center">No</td>
                    <td align="center">233</td>
                  </tr>
                  <tr>
                    <td>4</td>
                    <td align="center">Yes</td>
                    <td align="center">1120</td>
                    <td align="center">Hemorrhagic</td>
                    <td align="center">2</td>
                    <td align="center">-</td>
                    <td align="center">No</td>
                    <td align="center">528</td>
                  </tr>
                  <tr>
                    <td>5</td>
                    <td align="center">No</td>
                    <td align="center">850</td>
                    <td align="center">Hemorrhagic</td>
                    <td align="center">2</td>
                    <td align="center">-</td>
                    <td align="center">No</td>
                    <td align="center">148</td>
                  </tr>
                  <tr>
                    <td>6</td>
                    <td align="center">Yes</td>
                    <td align="center">1900</td>
                    <td align="center">Hemorrhagic</td>
                    <td align="center">2</td>
                    <td align="center">Fever</td>
                    <td align="center">No</td>
                    <td align="center">438</td>
                  </tr>
                  <tr>
                    <td>7</td>
                    <td align="center">Yes</td>
                    <td align="center">850</td>
                    <td align="center">Hemorrhagic</td>
                    <td align="center">2</td>
                    <td align="center">AF</td>
                    <td align="center">No</td>
                    <td align="center">-*</td>
                  </tr>
                  <tr>
                    <td>8</td>
                    <td align="center">Yes</td>
                    <td align="center">800</td>
                    <td align="center">Hemorrhagic</td>
                    <td align="center">2</td>
                    <td align="center">AF</td>
                    <td align="center">No</td>
                    <td align="center">386</td>
                  </tr>
                  <tr>
                    <td>9</td>
                    <td align="center">No</td>
                    <td align="center">1000</td>
                    <td align="center">Hemorrhagic</td>
                    <td align="center">3</td>
                    <td align="center">Fever</td>
                    <td align="center">Yes</td>
                    <td align="center">284</td>
                  </tr>
                  <tr>
                    <td>10</td>
                    <td align="center">Yes</td>
                    <td align="center">1700</td>
                    <td align="center">Hemorrhagic</td>
                    <td align="center">2</td>
                    <td align="center">-</td>
                    <td align="center">No</td>
                    <td align="center">235</td>
                  </tr>
                  <tr>
                    <td>11</td>
                    <td align="center">No</td>
                    <td align="center">400</td>
                    <td align="center">Hemorrhagic</td>
                    <td align="center">2</td>
                    <td align="center">-</td>
                    <td align="center">No</td>
                    <td align="center">134</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN1001">
                  <p>AF: atrial fibrillation. * Patient alive during follow-up.</p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
        </sec>
        <sec>
          <title>Follow-up</title>
          <p>The mean follow-up was 290 days. During follow-up, ten patients died within a mean of 248 days from chemical pericardiodesis. None of the patients died from cardiovascular causes. Recurrence of pericardial effusion occurred in one case of lung adenocarcinoma after approximately 12 months from cisplatin instillation.</p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>The authors describe a single-center experience on chemical pericardiodesis with cisplatin following percutaneous pericardiocentesis, in patients with malignant pericardial effusion.</p>
        <p>One of the first human reports of an attempt to control recurrent pericardial effusion with intrapericardial instillation of a substance was published in 1953 by Bachman K.P. et al., using radioactive gold. <sup><xref ref-type="bibr" rid="B4">4</xref></sup> Since then, other compounds have been tested, such as tetracycline, <sup><xref ref-type="bibr" rid="B5">5</xref></sup> bleomycin, <sup><xref ref-type="bibr" rid="B6">6</xref></sup> colchicine, <sup><xref ref-type="bibr" rid="B7">7</xref></sup> among others. Intrapericardial agents have also been tested in other settings, such as in Dressler&#8217;s syndrome <sup><xref ref-type="bibr" rid="B8">8</xref></sup> and acute pericarditis following electrophysiology studies. <sup><xref ref-type="bibr" rid="B9">9</xref></sup></p>
        <p>The largest series of patients treated with intrapericardial cisplatin were published by Maisch et al. <sup><xref ref-type="bibr" rid="B10">10</xref></sup> and Tomkowski et al., <sup><xref ref-type="bibr" rid="B11">11</xref></sup> including 42 and 46 patients, respectively. As in the present study, most patients had lung cancer. In Maish et al., a single intrapericardial cisplatin instillation prevented the recurrence of a hemodynamically relevant pericardial effusion during the first three months of follow-up in 92.8% of the patients. Although the overall prognosis was poor, none of the patients died due to cardiac tamponade. In Tomkowski et al., no accumulation of large amounts of pericardial fluid was achieved in 93.5% of patients after cisplatin instillation. All enrolled patients died because of advanced malignancy. Transient atrial fibrillation was the most common side effect. Other reported side effects include pain, fever, nausea, and non-sustained ventricular tachycardia. <sup><xref ref-type="bibr" rid="B12">12</xref> , <xref ref-type="bibr" rid="B13">13</xref></sup></p>
        <p>This series reports similar findings, including a successful control of pericardial fluid accumulation. These results support the idea of a safe and effective option for patients with malignant pericardial effusion, who are likely to experience recurrences after successful pericardiocentesis. The overall survival is poor. Chemical pericardiodesis aims to alleviate symptoms and may even prevent some deaths due to cardiac tamponade; notwithstanding, there is no evidence of survival benefit, as patients still experience neoplastic disease progression. To the authors&#8217; knowledge, this is the first published series of intrapericardial instillation of a sclerosing/chemotherapeutic agent developed in Portugal.</p>
        <p>This study has some important limitations. First, this is a retrospective and observational study performed on a small sample of patients. Second, for ethical reasons, there was no control group; as such, we could not evaluate the sole effect of cisplatin independently of the standard treatment of the primary neoplasm. Also, scheduled follow-up echocardiograms to assess subclinical reaccumulation of pericardial fluid could not be performed. These results warrant further investigation, namely in prospective and larger studies.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusions</title>
        <p>Intrapericardial instillation of cisplatin seems to be an effective and safe treatment option for patients with malignant pericardial effusion. Although there is no evidence of increased survival, this data suggests that symptom relief and recurrence prevention are likely achievable. Therefore, pericardiodesis should be included in the armamentarium of palliative care practitioners.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>Study association</p>
          <p>This study is not associated with any thesis or dissertation work.</p>
          <p>Ethics approval and consent to participate</p>
          <p>This study was approved by the Ethics Committee of the Hospital de Braga under the protocol number 19_2022. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
        </fn>
        <fn fn-type="supported-by">
          <p>Sources of funding: There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
