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2</a>C&#41;&#46; The patient tolerated vismodegib very well just reporting a slight muscles spasm&#44; dysgeusia and alopecia of the eyebrows and eyelids&#46; All the side effects were graded as 1 using the Common Terminology Criteria for Adverse Events &#40;CTCAE&#41;&#46; No severe adverse events were observed&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">It is established that neoadjuvant treatment with vismodegib for an average of 4 months before surgery reduces tumor area and surgical defect size&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> In literature&#44; a clinical trial with short-term vismodegib showed a reduction of the surgical defect area by 31&#37; if used for at least 3 months in non-recurrent BCCs of functionally sensitive locations&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Furthermore&#44; previous studies revealed that the clinical appearance of tumors after vismodegib was variable and did not predict histologic cure&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a> This achievement enhances the importance of performing biopsies or diagnostic techniques such as confocal laser scanning microscopy in order to identify residual tumor nests&#46; The margins performed in this case had the intention to excise the clinical residual lesion with 10<span class="elsevierStyleHsp" style=""></span>mm margin and the reconstruction of the inferior eyelid ectropion&#46; Some studies support the idea that vismodegib &#8220;cure&#8221; is temporary&#44; as BCCs recur at the same site within a few months of drug discontinuation&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a> We consider that probably the best surgical option after vismodegib would be micrographic Mohs surgery &#40;MMS&#41; as this surgical technique allows to localize residual nests of BCC that can remain during the reduction of the tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In our clinical case&#44; a modified Tripier flap was performed as eyelid wound repair must be carefully designed so that eyelid function is maintained and the globe is protected&#46; The original Tripier flap is considered a myocutaneous bipedicular flap originating from the upper eyelid and recommended for the reconstruction of lower lateral eyelid defects&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Usually this technique is time-consuming and requires a second surgical stage for sectioning the lateral pedicles&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Its modification consists in planning a single pedicle&#44; lateral&#44; randomized in one-stage surgery which does not rely on the inclusion of orbicularis muscle or innervation&#46; The surgical solution of our case demonstrates an option of the lower eyelid reconstruction&#44; simple and versatile without ectropion or eyelid distortion&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">This case highlights the potential of short-term vismodegib as neoadjuvant to surgery for high-risk locally advanced basal cell carcinomas&#44; especially in functionally sensitive locations as the periocular and orbital areas&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">Dr&#46; C&#233;sar Martins is a member of the Roche Pharmaceutics Advisory board&#46; The other authors declare no conflicts of interest&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Funding sources</span><p id="par0045" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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Case and Research Letters
Aggressive Inferior Eyelid Basal Cell Carcinoma: Advantage of Neoadjuvant Vismodegib
Ana Filipe Monteiroa,
Corresponding author
anafilipemonteiro@gmail.com

Corresponding author.
, Margarida Ratoa, Miguel Trigob, César Martinsa
a Dermatology Department, Hospital de Santarém EPE, Santarém, Portugal, Avenida Bernardo Santareno, 2005-177 Santarém, Portugal
b Plastic Surgery Department, Centro Hospitalar de Lisboa Ocidental EPE, Estrada do Forte do Alto do Duque, 1449-005 Lisboa, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">To the Editor&#58;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Basal cell carcinoma &#40;BCC&#41; is the most common skin cancer and represents 90&#37; of malignant eyelid tumors&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Management options are mainly surgical&#44; including Mohs micrographic surgery and wide surgical excision&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However&#44; some of these lesions can progress to an advanced locally stage and represent a therapeutic challenge&#46; In 2012 the US Food and Drug Administration &#40;FDA&#41; approved Vismodegib&#44; an oral hedgehog pathway inhibitor&#44; for the treatment of locally advanced and metastatic BCCs which are inappropriate for surgery or radiotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> Herein&#44; we report a patient with an infraorbital locally advanced BCC who was offered oral vismodegib before surgery reducing surgery-associated morbidity and allowing the preservation of functional and aesthetic aspect of the affected area&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 81-year-old man presented with a 6-year history of a progressively growing lesion in the left lower eyelid&#46; Examination of the ocular adnexae showed an extensive&#44; infiltrated and centrally erosive lesion&#44; covered by a crust with 6<span class="elsevierStyleHsp" style=""></span>cm of major axis and involving all the left lower eyelid with ectropion and extending onto the left malar cheek &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Biopsy showed a ulcerated BCC and computed tomography &#40;CT&#41; scan of the head did not identify alterations in the facial bones &#40;left maxilla&#44; inferior orbital rim&#44; and base of the nasal bone&#41;&#46; Due to the advanced nature of the lesion and involvement of more than two-thirds of the tarsal conjunctiva with a complex location for surgery and radiotherapy&#44; the patient was offered oral vismodegib 150<span class="elsevierStyleHsp" style=""></span>mg PO daily in order to shrink the tumor before surgery and reduce surgery-associated morbidity&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The reassessment was performed at 4&#44; 8 and 16 weeks after initiation of oral therapy &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; At 16 weeks the lesion showed a significant clinical improvement with substantial regression and a biopsy of the tarsal conjunctiva was performed&#46; The histopathologic examination of the tarsal conjunctiva was compatible with &#8220;absence of neoplasia&#8221;&#46; Vismodegib treatment was discontinued at 23 weeks and wide excision of the residual lesion with reconstruction was performed&#46; The pre-surgical clinically visible lesion size was 2&#44;5<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>0&#44;8<span class="elsevierStyleHsp" style=""></span>cm and the final surgical defect measured 3&#44;2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#44;5<span class="elsevierStyleHsp" style=""></span>cm&#46; For the reconstruction of the defect&#44; it was suggested to perform a modified Tripier flap &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; A single pedicle&#44; randomized and lateral&#44; was drawn with a relatively wide base &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; The surgical solution was consistent with a good functional result&#46; Histological evaluation of the surgical specimen revealed &#8220;absence of neoplasia&#8221;&#46; The follow-up 6 months after surgery revealed no recurrences and an excellent functional and aesthetic result &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C&#41;&#46; The patient tolerated vismodegib very well just reporting a slight muscles spasm&#44; dysgeusia and alopecia of the eyebrows and eyelids&#46; All the side effects were graded as 1 using the Common Terminology Criteria for Adverse Events &#40;CTCAE&#41;&#46; No severe adverse events were observed&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">It is established that neoadjuvant treatment with vismodegib for an average of 4 months before surgery reduces tumor area and surgical defect size&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a> In literature&#44; a clinical trial with short-term vismodegib showed a reduction of the surgical defect area by 31&#37; if used for at least 3 months in non-recurrent BCCs of functionally sensitive locations&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Furthermore&#44; previous studies revealed that the clinical appearance of tumors after vismodegib was variable and did not predict histologic cure&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a> This achievement enhances the importance of performing biopsies or diagnostic techniques such as confocal laser scanning microscopy in order to identify residual tumor nests&#46; The margins performed in this case had the intention to excise the clinical residual lesion with 10<span class="elsevierStyleHsp" style=""></span>mm margin and the reconstruction of the inferior eyelid ectropion&#46; Some studies support the idea that vismodegib &#8220;cure&#8221; is temporary&#44; as BCCs recur at the same site within a few months of drug discontinuation&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a> We consider that probably the best surgical option after vismodegib would be micrographic Mohs surgery &#40;MMS&#41; as this surgical technique allows to localize residual nests of BCC that can remain during the reduction of the tumor&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In our clinical case&#44; a modified Tripier flap was performed as eyelid wound repair must be carefully designed so that eyelid function is maintained and the globe is protected&#46; The original Tripier flap is considered a myocutaneous bipedicular flap originating from the upper eyelid and recommended for the reconstruction of lower lateral eyelid defects&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Usually this technique is time-consuming and requires a second surgical stage for sectioning the lateral pedicles&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Its modification consists in planning a single pedicle&#44; lateral&#44; randomized in one-stage surgery which does not rely on the inclusion of orbicularis muscle or innervation&#46; The surgical solution of our case demonstrates an option of the lower eyelid reconstruction&#44; simple and versatile without ectropion or eyelid distortion&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">This case highlights the potential of short-term vismodegib as neoadjuvant to surgery for high-risk locally advanced basal cell carcinomas&#44; especially in functionally sensitive locations as the periocular and orbital areas&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">Dr&#46; C&#233;sar Martins is a member of the Roche Pharmaceutics Advisory board&#46; The other authors declare no conflicts of interest&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Funding sources</span><p id="par0045" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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ISSN: 15782190
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