e-Case Research
Treatment of Bowen Disease With Photodynamic Therapy and the Advantages of Sequential Topical Imiquimod
Tratamiento de la enfermedad de Bowen con terapia fotodinámica y ventajas de la aplicación secuencial de imiquimod tópico
A.M. Victoria-Martínez
, L. Martínez-Leborans, J.M. Ortiz-Salvador, A. Pérez-Ferriols
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Servicio de Dermatología, Hospital General Universitario de Valencia, Valencia, Spain
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Recibió 3 sesiones de TFD con MAL con respuesta completa a los 3 meses del tratamiento (A). A los 6 meses presentaba una lesión costrosa en la zona (B). Tras descostrado y biopsia se confirmó recidiva. Se inició tratamiento con imiquimod tópico al 5% (C). Respuesta completa sin recidiva en el seguimiento (D).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.M. Victoria-Martínez, L. Martínez-Leborans, J.M. Ortiz-Salvador, A. Pérez-Ferriols" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A.M." "apellidos" => "Victoria-Martínez" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Martínez-Leborans" ] 2 => array:2 [ "nombre" => "J.M." "apellidos" => "Ortiz-Salvador" ] 3 => array:2 [ "nombre" => "A." 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A, Multiple formations with a glomeruloid appearance in the dermis, hematoxylin-eosin, original magnification × 10. B, Image with greater detail, hematoxylin-eosin, original magnification × 20. C, Stain showing CD34-positive cells exclusively in the capillary vessels, hematoxylin-eosin, original magnification × 20. D, Stain showing CD31-positive cells in sinusoidal vessels and capillary vessels of the glomeruloid hemangioma, hematoxylin-eosin, original magnification × 20. E, Stain showing cells positive for vascular endothelial growth factor in both types of vessels, hematoxylin-eosin, original magnification × 20. gr2.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. Hernández Aragüés, A. Pulido Pérez, C. Ciudad Blanco, V. Parra Blanco, R. Suárez Fernández" "autores" => array:5 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Hernández Aragüés" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Pulido Pérez" ] 2 => array:2 [ "nombre" => "C." 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Victoria-Martínez, L. Martínez-Leborans, J.M. Ortiz-Salvador, A. Pérez-Ferriols" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A.M." "apellidos" => "Victoria-Martínez" "email" => array:1 [ 0 => "anamercevictoria@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Martínez-Leborans" ] 2 => array:2 [ "nombre" => "J.M." "apellidos" => "Ortiz-Salvador" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Pérez-Ferriols" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital General Universitario de Valencia, Valencia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento de la enfermedad de Bowen con terapia fotodinámica y ventajas de la aplicación secuencial de imiquimod tópico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1125 "Ancho" => 1500 "Tamanyo" => 236500 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>, Bowen disease lesion that would have been difficult to treat surgically on the posterior surface of the left leg in an 80-year-old woman. <span class="elsevierStyleBold">B</span>, Complete clearance of the lesion after 3 cycles of photodynamic therapy with methyl aminolevulinate. No evidence of sequelae or recurrence was detected during follow-up.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bowen disease (BD) is a squamous cell carcinoma (SCC) in situ. It typically affects elderly patients and usually manifests as a slow-growing solitary erythematous, scaling plaque that can reach a considerable size. Lesions are mainly located on the head, the neck, or the extremities.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Several treatment options exist, including surgery, electrocoagulation, cryotherapy, 5-fluorouacil, 5% imiquimod, laser therapy, radiation therapy, and photodynamic therapy (PDT).<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">PDT is approved for the treatment of actinic keratosis, superficial and nodular basal cell carcinoma (BCC), and BD. It is a simple technique, suitable for outpatient use, and has proven to be both useful and effective in BD.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Topical 5% imiquimod has also been used in the treatment of BD. It has been combined with PDT to treat diverse forms of non-melanoma skin cancer, including BD, and the combination appears to have a synergic effect.</p><p id="par0025" class="elsevierStylePara elsevierViewall">We present a series of 13 BD lesions treated with PDT or with PDT and topical imiquimod at our department.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Descriptions</span><p id="par0030" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the characteristics of the 13 lesions treated with PDT at our department. The lesions corresponded to 10 patients (7 women and 3 men) and they were all biopsied to confirm diagnosis and in some cases to investigate suspected cases of partial clearance or recurrence.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Eleven lesions were treated with methyl aminolevulinate (MAL) 160<span class="elsevierStyleHsp" style=""></span>mg/g cream and 2 were treated with a 5-aminolevulinic acid (ALA) 78<span class="elsevierStyleHsp" style=""></span>mg/g nanoemulsion-based gel. The same PDT protocol was used in all cases. Following curettage of the area, the photosensitizing agent was applied to the lesion, which was covered with an occlusive dressing for 3<span class="elsevierStyleHsp" style=""></span>hours before illumination. The lesions were irradiated with red light (PDT 1200<span class="elsevierStyleHsp" style=""></span>L, Waldmann) at a wavelength of between 580 and 760<span class="elsevierStyleHsp" style=""></span>nm (dose, 75<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span>; fluence, 69-75<span class="elsevierStyleHsp" style=""></span>mw/cm<span class="elsevierStyleSup">2</span>). All the patients were treated with 3 sessions, each separated by a week. The lesions were photographed before and after treatment. Patients with recurrent lesions or lesions that only partially cleared were treated with 5% imiquimod applied 5 times a week for 6 weeks.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The mean age of the patients was 85.4 years. The most common locations were the lower limbs (38%), the head (31%), the trunk (24%), and the upper limbs (7%).</p><p id="par0045" class="elsevierStylePara elsevierViewall">Most patients had a history of prolonged sun exposure and 1 patient, a radiologist, had been chronically exposed to ionizing radiation at work. Seven (70%) of the 10 patients had a history of nonmelanoma skin cancer. One patient also had a systemic lymphoma being treated with chemotherapy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Most of the lesions were large (mean diameter, ><span class="elsevierStyleHsp" style=""></span>3.5<span class="elsevierStyleHsp" style=""></span>cm).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment response was evaluated at 3 and 18 months. At the 3-month evaluation, 11 of the 13 lesions (84.6%) had cleared completely, while the other 2 (15.4%) showed partial clearance. At the 18-month follow-up, 2 recurrences (18.1%) were detected among the 11 lesions that had initially cleared. The 2 recurrent lesions and the 2 that had responded only partially to PDT were treated with imiquimod. They all cleared completely (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) and had not recurred at the time of writing. The 4 lesions were all large (5<span class="elsevierStyleHsp" style=""></span>cm, 4.5<span class="elsevierStyleHsp" style=""></span>cm, 4<span class="elsevierStyleHsp" style=""></span>cm, and 3<span class="elsevierStyleHsp" style=""></span>cm); 2 were located on the face, 1 on the leg, and another on the chest.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The most common adverse effect during PDT was pain, which was rated with a mean score of 5.2 on a visual analog scale of 1 to 10. None of the treatments had to be interrupted due to pain. Some patients were administered local anesthesia. Transient swelling and redness were also observed after illumination.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Sequelae consisted of hyperpigmentation or hypopigmentation of the treated area. The cosmetic results were very good (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) and the patients were all very satisfied with the outcome.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Mean follow-up was 3 years (range, 18 months-7.5 years).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">We have reported on a series of patients with BD treated with PDT or with PDT and 5% imiquimod in the case of partial response or recurrence.</p><p id="par0075" class="elsevierStylePara elsevierViewall">BD is an intradermal SCC. The risk of progression to invasive SCC has been estimated at between 3% and 8%, but it may be higher in the case of genital involvement (erythroplasia of Queyrat).<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">2,3</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">PDT was approved for the treatment of BD in 2006. According to European guidelines, its use is supported by a level of evidence I and a strength-of-recommendation grade A. It is classified as a good or very good option for the treatment of large lesions, multiple lesions (which may need to be treated simultaneously), lesions in areas where surgical reconstruction is complicated, lesions in elderly patients with a high surgical risk, and lesions in immunosuppressed patients with altered wound healing.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Several studies have shown that PDT is more effective and has fewer adverse effects than other nonsurgical alternatives.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> Complete clearance rates of 86% to 93% were reported at 3 months following 1 or 2 cycles (separated by a week) of PDT with MAL, and sustained clearance rates at 24 months ranged from 68% to 71%. One study reported a clearance rate of 76% at 16 months following 2 sessions of PDT with MAL.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> Our findings support previous reports of lower complete clearance rates in larger lesions.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">7,8</span></a> A recent study of 31 BD lesions and 44 superficial BCC lesions treated with PDT reported a recurrence rate of 53.8% for BD and 33.3% for BCC after a mean follow-up of 43.5 months.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> The risk of recurrence was higher in BD than in BCC and also in younger patients. Long-term follow-up is therefore advisable, as late recurrence, which typically affects small areas and is easy to treat, is a possibility (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">There are no standardized PDT protocols for BD.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> This makes it difficult to compare results, as the protocols described to date have numerous differences, including type of photosensitizing agent used, interval between application of agent and irradiation, type of illumination, and number of sessions. Protocols typically consist of 2 PDT sessions separated by a week and the use of red light with a continuous spectrum of 570 to 670<span class="elsevierStyleHsp" style=""></span>nm and a total dose of 75 to 200<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span> or a narrower spectrum, around 630<span class="elsevierStyleHsp" style=""></span>nm, and a dose of approximately 37<span class="elsevierStyleHsp" style=""></span>J/cm2. Although 4 sessions have been used in some series, we opted for 3 sessions separated by a week. If we compare our results with those described for 2 sessions, however, the 3-session protocol did not result in higher complete clearance rates.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Complete clearance rates of 73% to 93% have been reported for 5% imiquimod cream in the treatment of BD. Sequential PDT and imiquimod has been used successfully to treat actinic keratosis,<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> basal cell carcinoma,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> vulvar intraepithelial neoplasia,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> and more recently some cases of BD.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">11,14</span></a> The mechanism of action underlying the combined treatment is unclear, although it is thought that the residual inflammation associated with PDT may help to activate innate immunity induced by imiquimod, improving the recruitment of effector cells activated in the tumor tissue,<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> as occurs in cryoimmunotherapy.</p><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion, PDT is an excellent treatment option for BD, particularly in patients with larger or multiple lesions or elderly patients with a high surgical risk. In our experience, the sequential use of PDT and imiquimod induces improved clinical and histologic response. Both treatments are well tolerated, cause minimum adverse effects, and produce satisfactory cosmetic outcomes.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Ethical Disclosures</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Protection of humans and animals</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that no tests were carried out in humans or animals for the purpose of this study.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Confidentiality of data</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Right to privacy and informed consent</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data appear in this article.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of Interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres806203" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec804271" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres806204" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec804272" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Descriptions" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of humans and animals" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of Interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec804271" "palabras" => array:4 [ 0 => "Bowen disease" 1 => "Photodynamic therapy" 2 => "Topical imiquimod" 3 => "Treatment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec804272" "palabras" => array:4 [ 0 => "Enfermedad de Bowen" 1 => "Terapia fotodinámica" 2 => "Imiquimod tópico" 3 => "Tratamiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Photodynamic therapy (PDT) has been shown to be useful and effective in the treatment of actinic keratosis, Bowen disease, and basal cell carcinoma. We present a series of 13 Bowen disease lesions treated using PDT. Complete responses were achieved in 11 (84%) of the lesions after 3 months of treatment; at 18 months, complete responses were seen in 9 (70%) of the lesions. Patients who presented a partial response or recurrence were treated with topical 5% imiquimod and achieved complete responses. The lesions that presented partial response or recurrence were the largest lesions, between 3 and 5<span class="elsevierStyleHsp" style=""></span>cm in diameter. PDT in monotherapy or combined sequentially with imiquimod is an excellent and well-tolerated therapeutic option for Bowen disease. The treatment has few adverse effects and shows satisfactory results, particularly in multiple large lesions in areas of difficult surgical reconstruction or in elderly patients with a high surgical risk.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La terapia fotodinámica (TFD) ha demostrado ser un tratamiento útil y eficaz en queratosis actínicas, enfermedad de Bowen (EB) y carcinoma basocelular. Presentamos una serie de 13 lesiones de EB tratados con TFD. A los 3 meses del tratamiento 11/13 (84%) lesiones presentaron respuesta completa. A los 18 meses la respuesta completa fue de 9/13 (70%) lesiones. Los pacientes que presentaron respuesta parcial o recidiva fueron tratados con imiquimod tópico al 5%, con la consiguiente respuesta completa. Las lesiones con respuesta parcial o recidiva fueron las de mayor tamaño: entre 3 y 5<span class="elsevierStyleHsp" style=""></span>cm de diámetro. La TFD en monoterapia o combinada secuencialmente con imiquimod es una excelente opción terapéutica para la EB, bien tolerada, con mínimos efectos secundarios y unos resultados satisfactorios, y sobre todo indicada en lesiones de gran tamaño, múltiples, en áreas de difícil reconstrucción quirúrgica o en pacientes ancianos con riesgo quirúrgico elevado.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Victoria-Martínez AM, Martínez-Leborans L, Ortiz-Salvador JM, Pérez-Ferriols A. Tratamiento de la enfermedad de Bowen con terapia fotodinámica y ventajas de la aplicación secuencial de imiquimod tópico. Actas Dermosifiliogr. 2017;108:e9–e14.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1050 "Ancho" => 1400 "Tamanyo" => 200676 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>, Bowen disease lesion on the anterior surface of the right leg of a 90-year-old woman with systemic lymphoma being treated with chemotherapy. <span class="elsevierStyleBold">B</span>, Complete clearance of lesion after 3 cycles of photodynamic therapy with methyl aminolevulinate. No recurrences were detected during follow-up.</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" => 1125 "Ancho" => 1500 "Tamanyo" => 255760 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>, Large Bowen disease lesion on the right temple of a 95-year-old woman. The lesion was treated with 3 sessions of photodynamic therapy with methyl aminolevulinate and cleared completely within 3 months. <span class="elsevierStyleBold">B</span>, The patient developed a crusted lesion in the same area 6 months after treatment. Recurrence was confirmed by biopsy following removal of the crust. <span class="elsevierStyleBold">C</span>, Treatment with topical 5% imiquimod was started. <span class="elsevierStyleBold">D</span>, The treatment resulted in complete clearance and no recurrences were detected during follow-up.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1125 "Ancho" => 1500 "Tamanyo" => 236500 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">A</span>, Bowen disease lesion that would have been difficult to treat surgically on the posterior surface of the left leg in an 80-year-old woman. <span class="elsevierStyleBold">B</span>, Complete clearance of the lesion after 3 cycles of photodynamic therapy with methyl aminolevulinate. No evidence of sequelae or recurrence was detected during follow-up.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ALA, aminolevulinic acid; M, man; MAL, methyl aminolevulinate; PDT, photodynamic therapy; W, woman.</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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Lesion \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sex/Age, y \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Location \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Size \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Anesthesia \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Photosensitizer \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Response (3 PDT Cycles) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Follow-up \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W/95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Forearm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5<span class="elsevierStyleHsp" style=""></span>y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W/95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right temple \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrence at 6 mo Complete clearance after 5% imiquimod \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5<span class="elsevierStyleHsp" style=""></span>y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W/90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right leg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W/84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Left thigh \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ALA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W/80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Left leg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M/74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right hemithorax \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Persistence of lesions Complete clearance after 5% imiquimod \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M/74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Left hemithorax \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ALA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W/93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right leg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M/83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right temple \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrence at 18 mo Complete clearance after 5% imiquimod \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W/81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Forehead \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Persistence of lesions Complete clearance after 5% imiquimod \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.5 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W/81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right leg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M/93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Left side \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.5 y \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M/93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right retroaurical region \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>cm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MAL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.5 y \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1352993.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Clinical Characteristics of Bowen Disease Lesions Treated With PDT at Our Department.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. of Lesions \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Protocol/Photosensitizer/Light Source \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Complete Clearance Rate/Follow-up \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Truchuelo et al. (2011) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 sessions separated by 1 wk/MAL 160<span class="elsevierStyleHsp" style=""></span>mg/g cream/red light (Aktilite; Photocure ASA), 630<span class="elsevierStyleHsp" style=""></span>nm, 38<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76.09%/16 mo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">López et al. (2012) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 sessions separated by 1 wk/MAL 160<span class="elsevierStyleHsp" style=""></span>mg/g cream/red light (Aktilite; CL128), 630<span class="elsevierStyleHsp" style=""></span>nm, 37<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">86.2%/12 mo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cabete et al. (2015) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 sessions separated by 1 wk/MAL 160<span class="elsevierStyleHsp" style=""></span>mg/g cream/red light (Aktilite; Photocure ASA), 630<span class="elsevierStyleHsp" style=""></span>nm, 37-40<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72.1%/12 mo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Victoria et al. (2016) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 sessions separated by 1 wk/MAL MAL 160<span class="elsevierStyleHsp" style=""></span>mg/g cream and ALA 78<span class="elsevierStyleHsp" style=""></span>mg/g gel/luz roja (PDT 1.200<span class="elsevierStyleHsp" style=""></span>L; Waldmann, 580-760<span class="elsevierStyleHsp" style=""></span>nm, 75<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69.2%/18 mo \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1352994.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Summary of Other Series in the Literature Describing the Treatment of Bowen Disease With Photodynamic Therapy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interventions for cutaneous Bowen's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.1 Bath-Hextall" 1 => "R.N. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 20 | 9 | 29 |
| 2024 Octubre | 145 | 38 | 183 |
| 2024 Septiembre | 163 | 28 | 191 |
| 2024 Agosto | 142 | 60 | 202 |
| 2024 Julio | 149 | 39 | 188 |
| 2024 Junio | 139 | 45 | 184 |
| 2024 Mayo | 134 | 61 | 195 |
| 2024 Abril | 123 | 24 | 147 |
| 2024 Marzo | 145 | 42 | 187 |
| 2024 Febrero | 148 | 34 | 182 |
| 2024 Enero | 112 | 34 | 146 |
| 2023 Diciembre | 111 | 36 | 147 |
| 2023 Noviembre | 137 | 58 | 195 |
| 2023 Octubre | 126 | 54 | 180 |
| 2023 Septiembre | 126 | 38 | 164 |
| 2023 Agosto | 117 | 19 | 136 |
| 2023 Julio | 96 | 32 | 128 |
| 2023 Junio | 105 | 31 | 136 |
| 2023 Mayo | 95 | 26 | 121 |
| 2023 Abril | 78 | 27 | 105 |
| 2023 Marzo | 110 | 40 | 150 |
| 2023 Febrero | 65 | 22 | 87 |
| 2023 Enero | 57 | 41 | 98 |
| 2022 Diciembre | 74 | 43 | 117 |
| 2022 Noviembre | 45 | 27 | 72 |
| 2022 Octubre | 61 | 26 | 87 |
| 2022 Septiembre | 39 | 41 | 80 |
| 2022 Agosto | 28 | 30 | 58 |
| 2022 Julio | 34 | 33 | 67 |
| 2022 Junio | 39 | 25 | 64 |
| 2022 Mayo | 107 | 52 | 159 |
| 2022 Abril | 110 | 28 | 138 |
| 2022 Marzo | 107 | 57 | 164 |
| 2022 Febrero | 135 | 29 | 164 |
| 2022 Enero | 137 | 41 | 178 |
| 2021 Diciembre | 105 | 42 | 147 |
| 2021 Noviembre | 79 | 47 | 126 |
| 2021 Octubre | 101 | 54 | 155 |
| 2021 Septiembre | 94 | 39 | 133 |
| 2021 Agosto | 105 | 63 | 168 |
| 2021 Julio | 81 | 43 | 124 |
| 2021 Junio | 119 | 36 | 155 |
| 2021 Mayo | 132 | 64 | 196 |
| 2021 Abril | 292 | 106 | 398 |
| 2021 Marzo | 127 | 53 | 180 |
| 2021 Febrero | 115 | 43 | 158 |
| 2021 Enero | 79 | 32 | 111 |
| 2020 Diciembre | 72 | 25 | 97 |
| 2020 Noviembre | 69 | 24 | 93 |
| 2020 Octubre | 56 | 22 | 78 |
| 2020 Septiembre | 72 | 25 | 97 |
| 2020 Agosto | 65 | 28 | 93 |
| 2020 Julio | 61 | 26 | 87 |
| 2020 Junio | 61 | 41 | 102 |
| 2020 Mayo | 48 | 18 | 66 |
| 2020 Abril | 49 | 16 | 65 |
| 2020 Marzo | 60 | 27 | 87 |
| 2020 Febrero | 6 | 0 | 6 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Septiembre | 4 | 0 | 4 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Junio | 3 | 0 | 3 |
| 2019 Mayo | 6 | 0 | 6 |
| 2019 Abril | 3 | 3 | 6 |
| 2019 Marzo | 1 | 0 | 1 |
| 2019 Febrero | 2 | 0 | 2 |
| 2018 Diciembre | 6 | 0 | 6 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 7 | 0 | 7 |
| 2018 Septiembre | 5 | 0 | 5 |
| 2018 Febrero | 54 | 4 | 58 |
| 2018 Enero | 80 | 8 | 88 |
| 2017 Diciembre | 76 | 6 | 82 |
| 2017 Noviembre | 59 | 8 | 67 |
| 2017 Octubre | 39 | 3 | 42 |
| 2017 Septiembre | 33 | 14 | 47 |
| 2017 Agosto | 45 | 15 | 60 |
| 2017 Julio | 29 | 10 | 39 |
| 2017 Junio | 48 | 7 | 55 |
| 2017 Mayo | 46 | 15 | 61 |
| 2017 Abril | 35 | 21 | 56 |
| 2017 Marzo | 65 | 38 | 103 |
| 2017 Febrero | 16 | 13 | 29 |
| 2017 Enero | 2 | 8 | 10 |
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