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Review article
Adenocarcinoma of the Anal Canal. Narrative Review
Adenocarcinoma del canal anal. Revisión de conjunto
Manuel Ferrer Márqueza,
Corresponding author
Manuferrer78@hotmail.com

Corresponding author.
, Francisco Javier Velasco Albendeab, Ricardo Belda Lozanoa, María del Mar Berenguel Ibáñezb, Ángel Reina Duartea
a Servicio de Cirugía General y del Aparato Digestivo, Hospital Torrecárdenas, Almería, Spain
b Servicio de Anatomía Patológica, Hospital Torrecárdenas, Almería, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The anal canal is the terminal part of the large intestine&#59; it is a tubular structure measuring 3&#8211;4<span class="elsevierStyleHsp" style=""></span>cm that extends from the perianal skin up to the end of the rectum&#46; The superior portion is covered with rectal mucosa&#44; the middle part &#40;coinciding with the pectineal line&#41; with transitional mucosa and the inferior portion with mucosa with stratified squamous epithelium&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Carcinomas in this region are classified as anal canal cancer and the patterns of differentiation are&#44; mainly&#44; basaloid &#40;basically squamous in nature&#44; similar to its homonym in the upper respiratory&#47;digestive tract&#41;&#44; epidermoid&#44; analogous to skin tumors&#44; and those with a line of differentiation toward adenocarcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The objective of this article is to review the literature on the histopathology&#44; symptoms&#44; diagnosis and treatment of adenocarcinoma of the anal canal&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Methodology</span><p id="par0020" class="elsevierStylePara elsevierViewall">We reviewed the literature published in the MEDLINE&#47;Pubmed and Ovid databases from 1997 to 2012&#44; using the following keywords &#8220;anal adenocarcinoma&#8221;&#44; &#8220;anal neoplasm&#8221;&#44; &#8220;anal gland carcinoma&#8221;&#44; &#8220;anal duct carcinoma&#8221;&#44; &#8220;anal canal&#8221;&#44; &#8220;immunohistochemistry&#8221;&#44; &#8220;chemoradiotherapy&#8221; and &#8220;radical surgery&#8221;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Histopathology</span><p id="par0025" class="elsevierStylePara elsevierViewall">Although the anal canal is short in length&#44; it can present a great variety of tumors&#44; which reflects the anatomic&#44; embryologic and histologic complexities of this structure&#46; Tumor localization and the interpretation of morphologic findings are both controversial and&#44; occasionally&#44; very difficult&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Adenocarcinoma &#40;ADC&#41; of the anal canal is a rare entity&#46; Most cases of ADC have a colorectal phenotype and represent tumors derived from the upper part of the anal canal or cells with glandular characteristics from the transitional zone&#46; Distinguishing between true anal canal ADC and lower rectal ADC with extension to the anal canal can be extremely difficult&#46; According to the World Health Organization &#40;WHO&#41;&#44; three types of ADC can be distinguished&#44; mainly determined by their origin&#58; those that originate in the superior part of the anal canal&#44; those that are derived from anal ducts or glands and those associated with chronic anorectal fistulae<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a>&#58;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Tumors that originate in the mucosa of the superior portion of the anal canal are the most common &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; and present with a colorectal phenotype&#46; In evolved stages&#44; it is extremely difficult to differentiate them from distal rectal ADC&#46; Their main clinical implication is based on their capacity for local extension&#44; owing to the double lymphatic drainage toward the inguinal and femoral chains&#46; The usual immunohistochemical phenotype coincides with the immunohistochemical profile of ADC of the lower rectal segment&#44; consisting in CK20&#43;&#44; CK7&#8722; and CDX2&#43;&#46; CK7 is occasionally positive&#44; as can also occur exceptionally in rectal ADC&#44; but it would similarly and characteristically co-express CK20&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;5</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">ADC that develops in the duct or glands of the anal canal &#40;anal ductal ADC or anal gland ADC&#41; is extremely rare&#46; It corresponds with a specific intramural subtype of anal canal ADC &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A and B&#41;&#46; Its diagnosis is sometimes done by exclusion&#44; since histologically detecting normal gland elements and associated ducts&#44; or extension of ADC&#44; generally occurs in very early stages&#46; The recent definition of anal gland ADC by Hobbs et al&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> does not require demonstrating this continuity with the anal canal glands&#46; In addition to the morphological characteristics of the neoplasia&#44; what has acquired greater protagonism in the diagnosis is that no intraluminal growth is observed &#40;the normal glands of the anal canal are distributed in the submucosal layer&#44; penetrating the sphincter musculature and even reaching the perianal fat&#41;&#46; Furthermore&#44; this tumor subtype is not associated with dysplasia of the mucosal surface &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; and is not generally related to pre-existing fistulae&#46; These tumors may produce small quantities of mucin and their immunochemical profile is CK20&#8722;&#44; CK7&#43; and CDX2&#8722; &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; comparable to the immunohistochemical profile of normal glands of the anal canal and similar to the profile of the transitional epithelium of the anal canal&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#8211;8</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Finally&#44; ADC associated with chronic colorectal fistulae &#40;congenital or acquired&#44; with a long-term evolution of 10&#8211;20 years&#41; is usually secondary to chronic inflammatory processes such as Crohn&#39;s disease or other evolved benign perianal diseases&#46; Sometimes&#44; fistulae are secondary to dilatations of the anal canal glands or ducts&#44; and the morphology and immunohistochemistry of the tumor would be identical to that of anal gland&#47;duct ADC&#46; Jones and Morson<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> have suggested that some of these carcinomas associated with fistulae originate in congenital duplications in the distal end of the hindgut&#46; Generally&#44; they adopt a well-differentiated mucinous ADC pattern&#44; but the exact histogenetic origin is often impossible to demonstrate and may belong to any of the anterior subtypes&#46; In addition&#44; they must be differentiated from mucin-producing adenocarcinoma of the lower rectum&#46; In this context&#44; the immunohistochemical study &#40;CK20&#44; CK7 and CDX2&#41; can be variable&#44; and only by combining morphological&#44; immunophenotypic and clinical-evolutive characteristics are we able to propose one origin or another&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;5&#44;7&#8211;9</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Epidemiology</span><p id="par0050" class="elsevierStylePara elsevierViewall">Anal tumors are rare neoplasms of the digestive tube that represent 5&#37; of all anorectal neoplasms and 1&#46;5&#37; of gastrointestinal tumors&#46; The key microscopic aspects in anal canal tumors have progressively changed over the years&#46; The increased experience and support of immunohistochemical techniques and molecular studies have brought about numerous changes in the nomenclature&#46; The most frequent lesion &#40;70&#37;&#8211;80&#37; of tumors&#41; in both the anal canal as well as the perianal skin is squamous carcinoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;13</span></a> Around 10&#37; of all malignant anal lesions are anal ADC &#40;5&#37;&#8211;19&#37;&#41;&#44; which present a more aggressive natural history than squamous carcinoma&#44; with shorter survival times and higher rates of local as well as distant relapse&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;6&#44;10&#44;13&#8211;15</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Although good results have been reported in patients with neoplasms detected in early evolutive phases&#44; the clinical similarity with other benign diseases and the lower expression of the tumor component in the mucosa are usually reasons that delay diagnosis and&#44; therefore&#44; make for a poorer prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> A greater percentage of patients with anal canal ADC present with advanced disease&#44; distant metastasis and&#44; consequently&#44; shorter overall survival compared with squamous carcinoma&#46; Data from the National Cancer Data Base &#40;NCDB&#41; reveal that&#44; at the time of presentation&#44; 9&#46;8&#37; of patients with anal ADC are stage <span class="elsevierStyleSmallCaps">iv&#44;</span> compared with 5&#37; of squamous carcinomas&#46; Likewise&#44; distant lesions occur in 28&#46;1&#37; of patients with ADC compared with 11&#46;8&#37; of squamous cancers&#46; The 5-year survival rate in patients with ADC is poorer in all the stages than in patients with epidermoid carcinoma&#44; with the greatest difference observed in stage <span class="elsevierStyleSmallCaps">iv</span> &#40;13&#37; for patients with ADC and 29&#37; for those with epidermoid cancer&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The age of presentation is around the sixth decade of life&#44; with equal distribution between the sexes&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;14</span></a> Multiple risk factors have been proposed&#44; such as HPV and HIV&#44; smoking and immunosuppression&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;17</span></a> The presence of chronic perianal fistulae&#44; either with or without associated Crohn&#39;s disease&#44; represents an important risk factor&#44; especially with a history of 10 or more years of disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a><span class="elsevierStyleItalic">Lymphogranuloma venereum</span> &#40;LGV&#41;&#44; as a cause of proctitis&#44; can cause stenosis and perianal fistulae and is also associated with increased risk for rectal ADC&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Symptoms and diagnosis</span><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical manifestations are usually nonspecific&#46; Patients may present pain&#44; indurations&#44; abscesses&#44; fistulae or palpable masses&#46; Other symptoms include bleeding&#44; pruritus&#44; spotting&#44; prolapse and weight loss&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;13</span></a> In the series by Kline et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> 15&#37; of the patients were asymptomatic&#46; Typical symptoms include the presence of perianal fistula for more than 10 years or the existence of recurring fistulae&#44; even after surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Early diagnostic suspicion is crucial in order to avoid any delays in diagnosis or treatment&#46; Although the clinical characteristics can lead us to suspect this type of tumor&#44; the definitive diagnosis can only be established with biopsy and histological studies&#46; In cases of advanced fistulous disease&#44; it is not clear whether the biopsy should be taken from the anal canal close to the internal orifice or by curettage of the external orifice&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Furthermore&#44; inguinal lymphadenopathies should be explored because&#44; as it has been explained previously&#44; these are aggressive lesions with a high capacity for both local and distant invasion&#46; Local dissemination tends to be greater in those tumors that originate in the glands of the anal canal or fistulous tracts since&#44; as they are located outside the intestinal wall&#44; the dissemination is initiated from a more advanced position&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Other diagnostic methods used to study local and distant extension include endoanal ultrasound&#44; pelvic magnetic resonance and computed tomography&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Treatment</span><p id="par0085" class="elsevierStylePara elsevierViewall">The limited number of cases published of anal canal ADC does not allow a thoroughly proven therapeutic approach&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Until the 1990s&#44; most authors recommended radical surgery &#40;abdomino-perineal amputation &#91;APA&#93;&#41; as the treatment of choice for anal canal ADC&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#8211;23</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">In a retrospective analysis of 192 patients with anal canal cancer treated at the University of Minnesota&#44; Klas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> reported their experience with 36 patients diagnosed with ADC&#46; Twenty-two &#40;61&#37;&#41; were treated with surgery alone &#40;6 APA and 16 local resections&#41; and 14 &#40;39&#37;&#41; with surgery followed by chemoradiotherapy &#40;CRT&#41;&#46; 5-year survival and local recurrence were 63&#37; and 21&#37;&#44; respectively&#46; The authors did not compare the two therapeutic methods due to the insufficient number of patients&#46; They attributed the good results to the fact that the majority of the lesions &#40;78&#37;&#41; were smaller than 5<span class="elsevierStyleHsp" style=""></span>cm&#44; and they propose treatment with pre- or postoperative CRT for larger lesions &#40;&#62;5<span class="elsevierStyleHsp" style=""></span>cm&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">A multicenter retrospective study that included 82 patients diagnosed with anal ADC treated in different European centers<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> recommended combined CRT as the best treatment&#44; while reserving radical surgery &#40;APA&#41; only for rescue therapy&#46; In this study&#44; the patients were managed with combined CRT&#44; radiotherapy &#40;RT&#41; plus surgery or surgery alone&#46; Overall survival and disease-free interval were higher in those patients with CRT&#44; compared with those with RT plus surgery or surgery alone&#46; The multivariate analysis showed that the T and N stages&#44; histologic grade and therapeutic method were independent prognostic factors for survival&#46; Nevertheless&#44; this study has several shortcomings&#58; neoadjuvant therapy was not used in any of the groups&#44; adjuvant chemotherapy was not used after surgery&#44; the patients who were included in the RT plus surgery group were significantly older than the patients in the combined CRT group&#44; and in 75&#37; of the surgical patients local resection was performed&#46; These factors could be responsible for the high level of local and distant recurrence of the group with RT plus surgery&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Papagikos et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> studied 16 patients with anal ADC who were treated with RT either with or without chemotherapy with curative intent&#46; The results of this treatment were compared with a group of patients with epidermoid carcinoma who were treated with CRT&#46; Mean follow-up was 45 months for patients with ADC and 44 for those with epidermoid cancer&#46; Although the patients with epidermoid carcinoma presented more advanced primary tumors&#44; the local and distant recurrences were significantly higher in patients with ADC&#46; Moreover&#44; 5-year disease-free survival after CRT was 19&#37; in patients with ADC compared with 77&#37; of those with epidermoid carcinoma&#46; This study concluded that treatment with definitive CRT&#44; which has been demonstrated to be useful in epidermoid tumors&#44; presents poor local control and a high level of distant recurrences in patients with ADC&#46; They recommend preoperative CRT followed by APA to maximize the pelvic control of the disease&#46; Adjuvant chemotherapy should be considered for micrometastatic disease&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">A retrospective study by Li et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> that included 49 patients with anal canal ADC concluded that APA together with CRT is the recommended treatment&#46; Five-year survival in patients with APA alone&#44; CRT&#44; APA plus CRT&#44; and with no treatment was 34&#46;4&#37;&#44; 0&#37;&#44; 37&#46;5&#37; and 0&#37;&#44; respectively&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Chang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> published a series with more than 20 years of experience including 34 patients&#46; The patients&#44; who were considered potentially curable&#44; were treated with local surgery followed by RT or CRT&#44; or radical surgical treatment &#40;APA&#41; plus pre- or postoperative CRT&#46; The disease-free survival was 13 months after local resection and 32 months after radical surgery&#44; and overall 5-year survival was 43&#37; for local treatment and 63&#37; for patients treated with radical surgery &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Patients with inguinal lymphadenopathies at disease presentation have poorer prognoses due to the higher percentage of distant disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;18</span></a> According to some authors&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6&#44;26</span></a> the inguinal dose of RT should vary in correlation with the existence of inguinal affectation and the therapeutic modality&#46; Therefore&#44; it is recommended to use doses above 54&#8211;55<span class="elsevierStyleHsp" style=""></span>Gy when initial CRT is used&#44; while&#44; in cases where only RT was used&#44; the corresponding dose should be increased to 60&#8211;66<span class="elsevierStyleHsp" style=""></span>Gy&#46; In patients with no known inguinal node invasion who receive treatment with CRT either with or without associated surgery&#44; the recommended prophylactic dose is 45<span class="elsevierStyleHsp" style=""></span>Gy&#46; Due to the poor prognosis of patients who present with inguinal lymphadenopathies&#44; Papagikos et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> prioritize the use of initial CRT &#40;with doses above 55<span class="elsevierStyleHsp" style=""></span>Gy&#41; and additional systemic chemotherapy&#44; with surgical resection used selectively or for isolated local relapse&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Currently&#44; most authors advocate maximizing the local control of the disease&#44; avoiding transanal resection &#40;which has had a negative impact on survival in some series&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;27</span></a> and diminishing the risk of metastasis with the use of intensive chemotherapy&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Given the fact that the anal glands are histologically and embryologically different from the anal squamous epithelium&#44; the recommended chemotherapy regime does not usually include mitomycin&#46; What is generally used are classic rectal AC regimes based on 5-fluorouracil&#44; either with or without associated oxaliplatin&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7&#44;15</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="par0130" class="elsevierStylePara elsevierViewall">Anal canal adenocarcinoma is a rare entity that is occasionally difficult to distinguish from adenocarcinoma of the lower rectum with extension to the anal canal&#46; Due to its aggressive behavior&#44; early suspicion is crucial to avoid delayed diagnosis and treatment&#46; Although there is no standardized protocol for the treatment of anal canal ADC&#44; the current recommended approach is preoperative CRT followed by radical surgery &#40;APA&#41;&#44; with subsequent adjuvant therapy for the prevention of micrometastasis&#46; CRT used alone should be reserved for those patients who would not tolerate radical surgery and&#44; according to some authors&#44; when there are proven inguinal lymph node metastases&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflict of interests</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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          "identificador" => "xres293526"
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          "titulo" => "Palabras clave"
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          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Methodology"
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        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Histopathology"
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          "identificador" => "sec0020"
          "titulo" => "Epidemiology"
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          "identificador" => "sec0025"
          "titulo" => "Symptoms and diagnosis"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Treatment"
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        10 => array:2 [
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          "titulo" => "Conclusions"
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        11 => array:2 [
          "identificador" => "sec0040"
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        12 => array:1 [
          "titulo" => "References"
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    "fechaRecibido" => "2012-11-23"
    "fechaAceptado" => "2013-01-27"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec277466"
          "palabras" => array:4 [
            0 => "Anal adenocarcinoma"
            1 => "Anal neoplasm"
            2 => "Chemoradiotherapy"
            3 => "Radical surgery"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec277467"
          "palabras" => array:4 [
            0 => "Adenocarcinoma anal"
            1 => "Neoplasia anal"
            2 => "Quimiorradioterapia"
            3 => "Cirug&#237;a radical"
          ]
        ]
      ]
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    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Adenocarcinoma &#40;ADC&#41; of the anal canal is a rare disease comprising only 5&#37; of all anorectal neoplasias and 1&#46;5&#37; of all gastrointestinal tumors&#46; The World Health Organization classifies anal ADC into 3 types&#58; the first may arise from the mucosa of the transitional zone in the upper canal&#44; the second from the anal glands &#40;ducts&#41; and the last can develop in the environment of a chronic anorectal fistula&#46; Patients with ADC of the anal canal have high rates of pelvic failure&#44; distant metastasis&#44; and lower overall survival than patients with epidermoid carcinoma&#46; Because of limited case reports about this neoplasia&#44; management strategies have not been well established&#46; Most authors of related studies recommend preoperative chemoradiotherapy &#40;CRT&#41; followed by radical surgery&#46; The aim of the present study is to review clinicopathology features and management of anal canal ADC&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El adenocarcinoma &#40;ADC&#41; del canal anal es una entidad rara que representa el 5&#37; de todas las neoplasias anorrectales y un 1&#44;5&#37; de los tumores gastrointestinales&#46; De acuerdo con la Organizaci&#243;n Mundial de la Salud se pueden distinguir 3 tipos&#58; el primero tiene su origen en la mucosa de transici&#243;n del canal superior&#44; el segundo deriva de las gl&#225;ndulas &#40;ductos&#41; anales&#44; y el &#250;ltimo deriva de una f&#237;stula perianal cr&#243;nica&#46; Los pacientes con ADC del canal anal presentan mayor porcentaje de enfermedad avanzada&#44; de met&#225;stasis a distancia y menor supervivencia global que aquellos con carcinoma escamoso&#46; La escasa casu&#237;stica publicada sobre esta neoplasia implica que no existe un esquema terap&#233;utico plenamente comprobado&#46; La mayor&#237;a de los autores abogan por un tratamiento con quimiorradioterapia &#40;QRT&#41; neoadyuvante seguido de cirug&#237;a radical&#46; El objetivo de este art&#237;culo es realizar una revisi&#243;n de la literatura existente sobre las caracter&#237;sticas clinicopatol&#243;gicas y el manejo del ADC del canal anal&#46;</p>"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ferrer M&#225;rquez M&#44; Velasco Albendea FJ&#44; Belda Lozano R&#44; Berenguel Ib&#225;&#241;ez MM&#44; Reina Duarte &#193;&#46; Adenocarcinoma del canal anal&#46; Revisi&#243;n de conjunto&#46; Cir Esp&#46; 2013&#59;91&#58;281&#8211;286&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional surface of an adenocarcinoma &#40;ADC&#41; originated in the mucosa of the superior portion of the anal canal with circumferential and endoluminal growth&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Sequential cross-sections of intramural ADC evolved from the anal glands&#58; &#40;A&#41; from the middle third of the anal canal&#44; close to the radial margin&#59; and &#40;B&#41; from the distal part of the anal canal with infiltration of the perianal musculature&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Disorganized and infiltrative tubular gland proliferation underlying non-neoplastic squamous anal mucosa on the endoscopic biopsy of an ADC of the anal glands &#40;hematoxylin and eosin &#215;10&#41;&#46;</p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Submucosal neoplastic gland component in ADC of the anal glands &#40;hematoxylin and eosin &#215;20&#41;&#59; &#40;B&#41; ADC of the anal glands with positive immunoexpression in the glands for CK7 &#40;cytokeratin 7&#215;10&#41;&#59; &#40;C&#41; ADC of the anal glands negative for CK20 &#40;cytokeratin 20&#215;10&#41;&#59; &#40;D&#41; ADC of the anal glands negative for CDX2 &#40;CDX 2&#215;10&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">CRT&#44; chemoradiotherapy&#59; DFS&#44; disease-free survival&#59; RT&#44; radiotherapy&#59; SV&#44; survival&#59; Tx&#44; treatment&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Author&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Study year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">No&#46; of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><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">Belkac&#233;mi et al&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2003 &#40;retrospective comparative&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">- CRT- Radiotherapy<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>surgery- Surgery alone&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">5-year DFS&#58;- 54&#37; &#40;CRT&#41;- 25&#37; &#40;RT&#43; surgery&#41;- 22&#37; &#40;surgery alone&#41;&nbsp;\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">Klas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">1999 &#40;retrospective descriptive&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">- Surgery alone- Surgery<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span> CRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">5-year SV and local recurrence were 63&#37; and 21&#37;&#44; respectively&nbsp;\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">Papagikos et al&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2003 &#40;retrospective comparative between ADC and epidermoid&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">RT<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>CT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">5-year DFS after CRT&#58;- 19&#37; in anal ADC- 77&#37; in epidermoid&nbsp;\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">Li et al&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2006 &#40;retrospective comparative&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">- Only surgery- CRT- Surgery<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CRT- No Tx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">5-year SV&#58;- 34&#46;4&#37; &#40;only surgery&#41;- 0&#37; &#40;CRT&#41;- 37&#46;5&#37; &#40;surgery<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CRT&#41;- 0&#37; &#40;no Tx&#41;&nbsp;\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">Chang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2009 &#40;retrospective comparative&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">- Local surgery<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CRT- Radical surgery<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>CRT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">5-year SV&#58;- 42&#37; &#40;local surgery&#41;- 63&#37; &#40;radical surgery&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Studies About the Treatment of Anal ADC&#46;</p>"
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      "titulo" => "References"
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ISSN: 21735077
Original language: English
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2018 February 25 0 25
2018 January 48 0 48
2017 December 25 0 25
2017 November 23 0 23
2017 October 38 9 47
2017 September 53 4 57
2017 August 52 1 53
2017 July 63 4 67
2017 June 63 2 65
2017 May 121 9 130
2017 April 51 3 54
2017 March 50 34 84
2017 February 130 2 132
2017 January 56 5 61
2016 December 55 4 59
2016 November 63 4 67
2016 October 101 10 111
2016 September 207 14 221
2016 August 88 6 94
2016 July 58 3 61
2016 June 53 4 57
2016 May 44 4 48
2016 April 36 18 54
2016 March 42 13 55
2016 February 32 9 41
2016 January 24 10 34
2015 December 41 7 48
2015 November 28 5 33
2015 October 48 6 54
2015 September 39 8 47
2015 August 53 7 60
2015 July 45 6 51
2015 June 25 2 27
2015 May 48 6 54
2015 April 54 12 66
2015 March 30 7 37
2015 February 18 6 24
2015 January 54 9 63
2014 December 80 13 93
2014 November 54 7 61
2014 October 24 6 30
2014 September 17 5 22
2014 August 23 7 30
2014 July 24 10 34
2014 June 22 5 27
2014 May 38 5 43
2014 April 13 6 19
2014 March 18 6 24
2014 February 15 7 22
2014 January 19 8 27
2013 December 17 3 20
2013 November 4 8 12
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos