Case and Research Letter
Interferon Eyedrops in the Treatment of Basal Cell Carcinoma of the Eyelid
Colirio de interferón y carcinoma basocelular palpebral
V.M. Leis-Dosil
, I. Prats-Caelles, C. Rubio-Flores
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Sección de Dermatología, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain
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Leis-Dosil, I. Prats-Caelles, C. Rubio-Flores" "autores" => array:3 [ 0 => array:4 [ "nombre" => "V.M." "apellidos" => "Leis-Dosil" "email" => array:1 [ 0 => "vmanuel.leis@salud.madrid.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "I." "apellidos" => "Prats-Caelles" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Rubio-Flores" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sección de Dermatología, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Colirio de interferón y carcinoma basocelular palpebral" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 629 "Ancho" => 800 "Tamanyo" => 101036 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Basal cell carcinoma on the lower margin of the left eyelid: appearance before starting treatment.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Interferons (IFN) are a family of pleiotropic cytokines that exert antiviral and antitumor effects through several different mechanisms (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> These cytokines are of interest to dermatologists mainly because of their effectiveness in the treatment of basal cell carcinoma (BCC), squamous cell carcinoma, Kaposi sarcoma, and melanoma.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Intralesional IFN was first demonstrated to effectively treat BCC in 1986,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and it produced complete responses in between 67% and 80% of patients in published series. IFN can be administered as monotherapy or as an adjuvant after surgery. Here, we describe the use of IFN administered topically in ophthalmic eyedrops in the management of a BCC on the free margin of the eyelid. This formulation is used in ophthalmology to treat squamous conjunctival papillomata,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> squamous neoplasms of the ocular surface, Kaposi sarcomas, and conjunctival melanomas.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We report the case of an 88 year-old woman with a histologically-confirmed, solid papular BCC of 5<span class="elsevierStyleHsp" style=""></span>mm in diameter on the margin of the lower left eyelid (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The patient refused surgical treatment. Other treatment options, such as photodynamic therapy and imiquimod cream, were considered, but were ruled out due to the characteristics and location of the lesion. The patient also refused treatment with intralesional IFN due to a fear of injections. It was decided to treat the BCC with IFN alfa-2b in ophthalmic eyedrops at a concentration of 1 million IU/mL, administered 4 times per day.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> This treatment was continued for 4 months, resulting in a decrease in the size of the lesion (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). No adverse effects were observed during treatment, and there was no change in the clinical appearance of the lesion on follow-up at 39 months. The patient still refuses to undergo either surgery or a control biopsy.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The efficacy of IFN alfa-2b eyedrops in various tumors of the conjunctiva, eyelid, and ocular surface is described in the ophthalmic literature.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5,7,8</span></a> The recommended dose is 1 drop of IFN alfa-2b at 1 million IU/mL 4 times per day for 3 to 4 months. Some authors recommend a maintenance regimen of 1 drop every 12<span class="elsevierStyleHsp" style=""></span>hours.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Several studies have compared ophthalmic with intralesional IFN alfa-2b administration<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> in the treatment of both non-invasive and invasive ocular surface squamous neoplasia, reporting better patient compliance and lower rates of local and systemic side effects in patients treated with eyedrops. The only local side effects reported are mild and resolve upon discontinuation of treatment. They include punctate keratitis, follicular conjunctivitis, and conjunctival hyperemia.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,8,9</span></a> Development of the flu syndrome characteristic of systemic or intralesional IFN therapy is rare.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> Comparison of IFN alfa-2b eyedrops with surgical treatment of non-invasive squamous neoplasia has revealed a comparable cure rate (total resolution in 96.4% of patients), with eyedrops producing better cosmetic results and less destruction of limbal stem cells.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">While we found no mention of this treatment in the dermatological literature, several ophthalmologic publications describe the effectiveness of topical IFN alfa-2b in cases of viral warts, intraepidermal carcinomas, and even melanomas on the eyelids and ocular surface, although these results are described in small series or isolated cases and should thus be interpreted with caution. We found no other cases in which IFN alfa-2b eyedrops have been used in the management of BCC of the eyelid. BCC is an accepted indication for IFN alfa-2b, and our findings point to a new potential route of administration. In our case the volume of the tumor decreased considerably, and the patient remains clinically stable after 3 years. However, we have no objective evidence of resolution, which requires close monitoring in a clinical setting. Our isolated experience should in no way change the standard accepted approaches used for the management of nonmelanoma skin cancer. Controlled clinical trials will be necessary to definitively determine the effectiveness of this treatment. However, given its ease of administration and its few, mild side effects, we propose the use of IFN alfa-2b eyedrops as a neoadjuvant therapy in selected cases to reduce tumor size before microscopically controlled surgical excision.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Leis-Dosil VM, Prats-Caelles I, Rubio-Flores C. Colirio de interferón y carcinoma basocelular palpebral. Actas Dermosifiliogr. 2014;105:207–208.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 629 "Ancho" => 800 "Tamanyo" => 101036 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Basal cell carcinoma on the lower margin of the left eyelid: appearance before starting treatment.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 599 "Ancho" => 800 "Tamanyo" => 99233 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Decrease in lesion size after 4 months of treatment.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Interferon subtype: a, alfa-2a; b, alfa-2b; c, alfa-n3.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Indications</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antiviral</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hepatitis B<span class="elsevierStyleSup">a,b</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hepatitis C<span class="elsevierStyleSup">a,b</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Human papilloma virus<span class="elsevierStyleSup">a,c</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antitumor</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hepatocarcinoma<span class="elsevierStyleSup">b</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Chronic myeloid leukemia,<span class="elsevierStyleSup">a,b</span> hairy cell leukemia,<span class="elsevierStyleSup">a,b</span> multiple myeloma<span class="elsevierStyleSup">b</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Kaposi sarcoma<span class="elsevierStyleSup">a,b</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Renal carcinoma<span class="elsevierStyleSup">a</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Basal cell carcinoma<span class="elsevierStyleSup">b</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Squamous cell carcinoma<span class="elsevierStyleSup">b</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Melanoma<span class="elsevierStyleSup">a,b</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Mechanisms of action</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Suppression of cell proliferation</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Increased macrophage-mediated phagocytosis</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Inhibition of viral replication</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Inhibition of angiogenesis</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Increase in cellular immune response of T lymphocytes</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab465421.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Interferons: Indications and Mechanisms of Action.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => 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Huerva" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Arch Soc Esp Oftalmol" "fecha" => "2009" "volumen" => "84" "paginaInicial" => "5" "paginaFinal" => "6" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19173133" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673611601359" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010500000002/v1_201403090058/S1578219014000286/v1_201403090058/en/main.assets" "Apartado" => array:4 [ "identificador" => "6157" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010500000002/v1_201403090058/S1578219014000286/v1_201403090058/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219014000286?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 13 | 13 | 26 |
| 2024 Octubre | 104 | 57 | 161 |
| 2024 Septiembre | 97 | 32 | 129 |
| 2024 Agosto | 115 | 69 | 184 |
| 2024 Julio | 102 | 41 | 143 |
| 2024 Junio | 117 | 46 | 163 |
| 2024 Mayo | 110 | 64 | 174 |
| 2024 Abril | 85 | 27 | 112 |
| 2024 Marzo | 90 | 28 | 118 |
| 2024 Febrero | 83 | 29 | 112 |
| 2024 Enero | 78 | 33 | 111 |
| 2023 Diciembre | 106 | 22 | 128 |
| 2023 Noviembre | 97 | 32 | 129 |
| 2023 Octubre | 98 | 20 | 118 |
| 2023 Septiembre | 112 | 35 | 147 |
| 2023 Agosto | 64 | 13 | 77 |
| 2023 Julio | 85 | 35 | 120 |
| 2023 Junio | 92 | 26 | 118 |
| 2023 Mayo | 110 | 30 | 140 |
| 2023 Abril | 74 | 27 | 101 |
| 2023 Marzo | 73 | 30 | 103 |
| 2023 Febrero | 76 | 31 | 107 |
| 2023 Enero | 72 | 39 | 111 |
| 2022 Diciembre | 84 | 55 | 139 |
| 2022 Noviembre | 54 | 28 | 82 |
| 2022 Octubre | 48 | 23 | 71 |
| 2022 Septiembre | 53 | 41 | 94 |
| 2022 Agosto | 28 | 30 | 58 |
| 2022 Julio | 36 | 31 | 67 |
| 2022 Junio | 53 | 44 | 97 |
| 2022 Mayo | 133 | 34 | 167 |
| 2022 Abril | 191 | 51 | 242 |
| 2022 Marzo | 140 | 49 | 189 |
| 2022 Febrero | 149 | 31 | 180 |
| 2022 Enero | 193 | 37 | 230 |
| 2021 Diciembre | 145 | 49 | 194 |
| 2021 Noviembre | 153 | 69 | 222 |
| 2021 Octubre | 112 | 52 | 164 |
| 2021 Septiembre | 85 | 44 | 129 |
| 2021 Agosto | 67 | 30 | 97 |
| 2021 Julio | 73 | 25 | 98 |
| 2021 Junio | 137 | 40 | 177 |
| 2021 Mayo | 86 | 44 | 130 |
| 2021 Abril | 240 | 71 | 311 |
| 2021 Marzo | 142 | 38 | 180 |
| 2021 Febrero | 78 | 29 | 107 |
| 2021 Enero | 49 | 35 | 84 |
| 2020 Diciembre | 44 | 14 | 58 |
| 2020 Noviembre | 35 | 23 | 58 |
| 2020 Octubre | 36 | 21 | 57 |
| 2020 Septiembre | 39 | 19 | 58 |
| 2020 Agosto | 31 | 22 | 53 |
| 2020 Julio | 40 | 16 | 56 |
| 2020 Junio | 38 | 37 | 75 |
| 2020 Mayo | 34 | 21 | 55 |
| 2020 Abril | 34 | 19 | 53 |
| 2020 Marzo | 33 | 30 | 63 |
| 2020 Febrero | 5 | 11 | 16 |
| 2020 Enero | 4 | 6 | 10 |
| 2019 Diciembre | 6 | 6 | 12 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Octubre | 0 | 8 | 8 |
| 2019 Septiembre | 10 | 28 | 38 |
| 2019 Agosto | 4 | 7 | 11 |
| 2019 Julio | 4 | 13 | 17 |
| 2019 Junio | 4 | 14 | 18 |
| 2019 Mayo | 6 | 12 | 18 |
| 2019 Abril | 2 | 23 | 25 |
| 2019 Marzo | 0 | 12 | 12 |
| 2019 Febrero | 5 | 15 | 20 |
| 2019 Enero | 1 | 3 | 4 |
| 2018 Diciembre | 4 | 5 | 9 |
| 2018 Noviembre | 2 | 7 | 9 |
| 2018 Octubre | 1 | 0 | 1 |
| 2018 Septiembre | 4 | 3 | 7 |
| 2018 Agosto | 0 | 5 | 5 |
| 2018 Julio | 0 | 2 | 2 |
| 2018 Junio | 0 | 3 | 3 |
| 2018 Mayo | 0 | 5 | 5 |
| 2018 Abril | 0 | 3 | 3 |
| 2018 Marzo | 5 | 2 | 7 |
| 2018 Febrero | 83 | 3 | 86 |
| 2018 Enero | 102 | 6 | 108 |
| 2017 Diciembre | 98 | 10 | 108 |
| 2017 Noviembre | 66 | 9 | 75 |
| 2017 Octubre | 69 | 3 | 72 |
| 2017 Septiembre | 71 | 11 | 82 |
| 2017 Agosto | 87 | 18 | 105 |
| 2017 Julio | 69 | 16 | 85 |
| 2017 Junio | 94 | 16 | 110 |
| 2017 Mayo | 79 | 15 | 94 |
| 2017 Abril | 68 | 17 | 85 |
| 2017 Marzo | 84 | 21 | 105 |
| 2017 Febrero | 60 | 7 | 67 |
| 2017 Enero | 55 | 15 | 70 |
| 2016 Diciembre | 86 | 13 | 99 |
| 2016 Noviembre | 138 | 10 | 148 |
| 2016 Octubre | 117 | 11 | 128 |
| 2016 Septiembre | 229 | 16 | 245 |
| 2016 Agosto | 197 | 9 | 206 |
| 2016 Julio | 90 | 4 | 94 |
| 2016 Junio | 18 | 5 | 23 |
| 2016 Mayo | 15 | 5 | 20 |
| 2016 Abril | 3 | 18 | 21 |
| 2016 Marzo | 3 | 3 | 6 |
| 2016 Febrero | 8 | 2 | 10 |
| 2016 Enero | 13 | 12 | 25 |
| 2015 Diciembre | 10 | 8 | 18 |
| 2015 Noviembre | 15 | 10 | 25 |
| 2015 Octubre | 13 | 4 | 17 |
| 2015 Septiembre | 9 | 2 | 11 |
| 2015 Agosto | 9 | 1 | 10 |
| 2015 Julio | 165 | 11 | 176 |
| 2015 Junio | 94 | 7 | 101 |
| 2015 Mayo | 82 | 13 | 95 |
| 2015 Abril | 93 | 9 | 102 |
| 2015 Marzo | 70 | 3 | 73 |
| 2015 Febrero | 68 | 6 | 74 |
| 2015 Enero | 49 | 7 | 56 |
| 2014 Diciembre | 59 | 7 | 66 |
| 2014 Noviembre | 51 | 5 | 56 |
| 2014 Octubre | 67 | 10 | 77 |
| 2014 Septiembre | 49 | 3 | 52 |
| 2014 Agosto | 60 | 4 | 64 |
| 2014 Julio | 38 | 5 | 43 |
| 2014 Junio | 52 | 9 | 61 |
| 2014 Mayo | 45 | 11 | 56 |
| 2014 Abril | 25 | 6 | 31 |
| 2014 Marzo | 16 | 2 | 18 |
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