<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">JCT</journal-id><journal-title-group><journal-title>Journal of Cancer Therapy</journal-title></journal-title-group><issn pub-type="epub">2151-1934</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/jct.2019.107042</article-id><article-id pub-id-type="publisher-id">JCT-93601</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine&amp;Healthcare</subject></subj-group></article-categories><title-group><article-title>
 
 
  Survival in a Chilean Cohort of Thymic Tumors
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Mauricio</surname><given-names>Salinas</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Mozart</surname><given-names>Liessi</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Patricio</surname><given-names>Vallejo</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Cristian</surname><given-names>Ibarra</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib></contrib-group><aff id="aff1"><addr-line>School of Medicine, Universidad de Chile, Santiago, Chile</addr-line></aff><aff id="aff2"><addr-line>Instituto Nacional del Tórax, Santiago, Chile</addr-line></aff><pub-date pub-type="epub"><day>08</day><month>07</month><year>2019</year></pub-date><volume>10</volume><issue>07</issue><fpage>510</fpage><lpage>517</lpage><history><date date-type="received"><day>22,</day>	<month>January</month>	<year>2019</year></date><date date-type="rev-recd"><day>7,</day>	<month>July</month>	<year>2019</year>	</date><date date-type="accepted"><day>10,</day>	<month>July</month>	<year>2019</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  Introduction
  :
  <b> </b>
  Thymus neoplasm 
  is
   rare tumors and it ha
  s
   low mortality. There are scarce publications in Latin-American about this topic. We present a Chilean casuistic.
   
  <b>Method</b>
  <b>:</b>
   
  Retrospective cohort of every patient
  ’
  s thymic epithelial tumors diagnosed in Instituto Nacional del T&#243;rax, Santiago, Chile, between January 2007 and June 2015. Information was obtained from pathological and clinical registries. Death date was achieved from national registry. We report epidemiological data, clinical manifestations, histology type, Masaoka and WHO classification, therapies and survivor.
  <b> </b>
  <b>Results</b>
  <b>: </b>
  Sixty-five patients were included, with mean age 58 years and 36.9% men. Myasthenia gravis was present in 24 (36.9%) of patients. Ninety four percent of patients had a surgical biopsy. There w
  ere
   60 thymomas and 5 thymic carcinomas. Most of tumors were stage I and II in Masaoka classification and type B in WHO classification. There were no deaths at 30 days. Nosocomial pneumonia was the most common complication.
   
  <b>Conclusions</b>
  <b>:</b>
   
  In this thymic tumor cohort there 
  are
   more wom
  e
  n and they are older than previously reported. Myasthenia gravis prevalence was similar. The survival of patients with thymomas was excellent.
 
</p></abstract><kwd-group><kwd>Thymoma</kwd><kwd> Thymus Neoplasms</kwd><kwd> Thymus Gland</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>The epithelial neoplasms of the thymus correspond to primary tumors of the mediastinum, derivate from the thymic epithelium. They are rare tumors, which present in different series, annual incidence rates from 0.9 to 2.3 per million inhabitants [<xref ref-type="bibr" rid="scirp.93601-ref1">1</xref>] . Thymoma corresponds to the primary mediastinal tumor most commonly presented [<xref ref-type="bibr" rid="scirp.93601-ref2">2</xref>] .</p><p>The natural history of the disease may include asymptomatic patients discovered incidentally or presented as aggressive malignant tumors in terms of growth and dissemination [<xref ref-type="bibr" rid="scirp.93601-ref3">3</xref>] . The prognosis is good in comparison to other types of cancer, with survival rates of 84% at one year and 64% at five years [<xref ref-type="bibr" rid="scirp.93601-ref1">1</xref>] .</p><p>In patients with thymus tumors, the coexistence of other diseases should be considered, especially myasthenia gravis, found in approximately 40% of the thymomas. There has been described other diseases such as: pure aplasia of red blood cells, parathyroid adenoma and hypogammaglobulinemia [<xref ref-type="bibr" rid="scirp.93601-ref4">4</xref>] .</p><p>There are scarce publications in Latin-American, in the last 20 years. In this article we present the different characteristics and survivals of a Chilean cohort of patients with thymic tumors.</p></sec><sec id="s2"><title>2. Methods</title><p>We did a retrospective study, which was developed at the Instituto Nacional del T&#243;rax (INT) in Santiago, Chile. The list of patients was obtained from the pathological registry, with all the biopsies diagnosis of thymoma or thymic carcinoma, from 2007 to 2015.</p><sec id="s2_1"><title>2.1. Histopathology</title><p>The histological samples were analyzed by certified pathologists from the Instituto Nacional del T&#243;rax. The neoplasms of the thymus were classified as a thymoma or thymocarcinoma. Other types of thymus neoplasms were excluded from this analysis.</p><p>The selected thymomas were classified according to recommendation of the World Health Organization (WHO), as A, AB or B [<xref ref-type="bibr" rid="scirp.93601-ref5">5</xref>] . In the surgically removed tumors, it was stated if there was capsule penetration, lymph nodes compromise or if there was an invasion to the adjacent organs. Immunohistochemically studies were performed according to the pathologist’s criteria.</p></sec><sec id="s2_2"><title>2.2. Clinical Information</title><p>The register of the patients was obtained from physical and electronic. Demographic and clinical information was registered, with emphasis in: the presence and treatment of myasthenia gravis, the surgical technique performed, the post-surgery complications and the result from the surgery in relation to the tumor resection. The classification of the thymus neoplasms was done according to the modified Masaoka classification [<xref ref-type="bibr" rid="scirp.93601-ref6">6</xref>] .</p></sec><sec id="s2_3"><title>2.3. Adjuvant Therapy</title><p>In our center, all patients were presented to the oncological committee to decide chemotherapy or radiotherapy indication.</p><p>In the time frame analyzed, patients received chemotherapy with platinum plus etoposide chemotherapy and/or conventional radiotherapy. All this information was recorded and registered as well as the intention of the adjuvant therapy, which could’ve been curative or palliative.</p></sec><sec id="s2_4"><title>2.4. Statistical Analysis</title><p>The description of the numerical variables was made using averages and standard deviation with continuous variables. Absolute and relative frequencies were used with categorical variables.</p><p>The date of death was obtained from the national Chilean registry. The cohort was followed until January 1, 2017.</p><p>The survival rate is presented using the Kaplan Meier graphs. To comparison between the groups Log-rank test was performed. For multiple comparisons, bonferroni correction was utilized. A level of signification of 0.05 with to 2 tails was considered.</p><p>All analysis was done in Stata 14.0.</p></sec></sec><sec id="s3"><title>3. Results</title><p>Information was obtained from the results of 65 patients, between the years 2007 and 2015. More than 90 percent of the patients had a surgical biopsy.</p><p>The patients had age average of 58 years old; 37% male subjects. About the presentation symptoms, 36.9% of patients showed myasthenia gravis. There were no cases of Sjogren, red blood cells aplasia or hypogammaglobulinemia.</p><p>Sixty patients had thymoma-tumors and only five patients corresponded to thymic carcinomas. Characteristics of the patients were summarized in <xref ref-type="table" rid="table1">Table 1</xref>.</p><p>About the Masaoka classification, more than half of the tumors corresponded to stages I and II. According to WHO classification, most of cases were type B. One patient had all thymoma types areas in the biopsy, therefore, it was classified as mixed type (<xref ref-type="table" rid="table2">Table 2</xref>).</p><p>The most common complication seen was nosocomial pneumonia in 9.8% of the patients. There was no death related to the surgery.</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Baseline characteristics</title></caption><table><tbody><thead><tr><th align="center" valign="middle" ></th><th align="center" valign="middle" >Value*</th></tr></thead><tr><td align="center" valign="middle" >Age</td><td align="center" valign="middle" >57.9 &#177; 12.9 years</td></tr><tr><td align="center" valign="middle" >Men</td><td align="center" valign="middle" >24 (36.9%)</td></tr><tr><td align="center" valign="middle" >Symptoms</td><td align="center" valign="middle" ></td></tr><tr><td align="center" valign="middle" >Cough</td><td align="center" valign="middle" >7 (10.8%)</td></tr><tr><td align="center" valign="middle" >Dyspnea</td><td align="center" valign="middle" >14 (21.5%)</td></tr><tr><td align="center" valign="middle" >Pain</td><td align="center" valign="middle" >10 (15.4%)</td></tr><tr><td align="center" valign="middle" >Cava superior syndrome</td><td align="center" valign="middle" >1 (4.3%)</td></tr><tr><td align="center" valign="middle" >Myasthenia gravis</td><td align="center" valign="middle" >24 (36.9%)</td></tr><tr><td align="center" valign="middle" >Asymptomatic</td><td align="center" valign="middle" >19 (29.2%)</td></tr><tr><td align="center" valign="middle" >Surgical biopsy</td><td align="center" valign="middle" >61 (93.8%)</td></tr><tr><td align="center" valign="middle" >Thymoma</td><td align="center" valign="middle" >60 (92.3%)</td></tr></tbody></table></table-wrap><p>*Mean (SD) for continuous variables; n (%) for categorical variables.</p><table-wrap id="table2" ><label><xref ref-type="table" rid="table2">Table 2</xref></label><caption><title> Thymic tumors stages</title></caption><table><tbody><thead><tr><th align="center" valign="middle" ></th><th align="center" valign="middle" >n (%)</th></tr></thead><tr><td align="center" valign="middle" >Masaoka</td><td align="center" valign="middle" ></td></tr><tr><td align="center" valign="middle" >Stage I</td><td align="center" valign="middle" >23 (35.4%)</td></tr><tr><td align="center" valign="middle" >Stage II</td><td align="center" valign="middle" >18 (27.7%)</td></tr><tr><td align="center" valign="middle" >Stage III</td><td align="center" valign="middle" >11 (16.9%)</td></tr><tr><td align="center" valign="middle" >Stage IV</td><td align="center" valign="middle" >13 (20.0%)</td></tr><tr><td align="center" valign="middle" >WHO (n = 60)</td><td align="center" valign="middle" ></td></tr><tr><td align="center" valign="middle" >A</td><td align="center" valign="middle" >4 (6.7%)</td></tr><tr><td align="center" valign="middle" >AB</td><td align="center" valign="middle" >9 (15.0%)</td></tr><tr><td align="center" valign="middle" >B</td><td align="center" valign="middle" >46 (76.7%)</td></tr><tr><td align="center" valign="middle" >Mixed</td><td align="center" valign="middle" >1 (1.6%)</td></tr></tbody></table></table-wrap><p>Three (12.5%) of the twenty-four patients with myasthenia, presented myasthenic crisis during the post-operatory period; myasthenic crisis were treated using steroids and plasmapheresis with complete recovery in all patients.</p><p>In 49 (80.3%) patients a total resection of the tumor was accomplished according to the anatomopathological review of the biopsy.</p><p>Nineteen patients were treated via complementary radiotherapy. In 12 (63.1%) patients the radiotherapy was done with curative intention. Twelve patients (17.2%) received chemotherapy, only one of them with curative intention (<xref ref-type="table" rid="table3">Table 3</xref>).</p><table-wrap id="table3" ><label><xref ref-type="table" rid="table3">Table 3</xref></label><caption><title> Treatment and complications</title></caption><table><tbody><thead><tr><th align="center" valign="middle" ></th><th align="center" valign="middle" >n (%)</th></tr></thead><tr><td align="center" valign="middle" >Surgery outcome (n = 60)</td><td align="center" valign="middle" ></td></tr><tr><td align="center" valign="middle" >Complete resection (R0)</td><td align="center" valign="middle" >49 (80.3%)</td></tr><tr><td align="center" valign="middle" >Microscopic positive margin (R1)</td><td align="center" valign="middle" >1 (1.6%)</td></tr><tr><td align="center" valign="middle" >Macroscopic positive margin (R2)</td><td align="center" valign="middle" >11 (18.1%)</td></tr><tr><td align="center" valign="middle" >Post-operative myasthenic crisis*</td><td align="center" valign="middle" >3 (12.5%)</td></tr><tr><td align="center" valign="middle" >Mortality (30 days)</td><td align="center" valign="middle" >0 (0%)</td></tr><tr><td align="center" valign="middle" >Perioperative complications</td><td align="center" valign="middle" ></td></tr><tr><td align="center" valign="middle" >Nosocomial pneumonia</td><td align="center" valign="middle" >6 (9.8%)</td></tr><tr><td align="center" valign="middle" >Mediastinitis</td><td align="center" valign="middle" >1 (1.6%)</td></tr><tr><td align="center" valign="middle" >Wound infection</td><td align="center" valign="middle" >2 (3.3%)</td></tr><tr><td align="center" valign="middle" >Chylothorax</td><td align="center" valign="middle" >1 (1.6%)</td></tr><tr><td align="center" valign="middle" >Hemothorax</td><td align="center" valign="middle" >1 (1.6%)</td></tr><tr><td align="center" valign="middle" >Chemotherapy</td><td align="center" valign="middle" >12 (18.4%)</td></tr><tr><td align="center" valign="middle" >Curative intention</td><td align="center" valign="middle" >1 (8.3%)</td></tr><tr><td align="center" valign="middle" >Palliative intention</td><td align="center" valign="middle" >11 (91.7%)</td></tr><tr><td align="center" valign="middle" >Radiotherapy</td><td align="center" valign="middle" >19 (29.2%)</td></tr><tr><td align="center" valign="middle" >Curative intention</td><td align="center" valign="middle" >12 (63.1%)</td></tr><tr><td align="center" valign="middle" >Palliative intention</td><td align="center" valign="middle" >7 (36.8%)</td></tr></tbody></table></table-wrap><p>*over 24 patients with myasthenia.</p><p>Averages survival were 12 months for the thymic carcinoma group and 164 months in the thymoma group (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p><p>Averages survival for Masaoka stages 1, 2, 3 and 4 were 144, 72, 53 and 23 months respectively (<xref ref-type="fig" rid="fig2">Figure 2</xref>), with statistical significance between stages 1 and 3 (p &lt; 0.01) and stages 1 and 4 (p &lt; 0.01). There were no survival differences by WHO classification.</p></sec><sec id="s4"><title>4. Discussion</title><p>In this article we presented a cohort of a relatively big number of patients diagnosed with thymic neoplasms, which represent a group of unusual malignant neoplasms [<xref ref-type="bibr" rid="scirp.93601-ref7">7</xref>] . The true incidence rate of the thymomas is yet unknown but represents approximately 47% of the tumors from the anterior mediastinum [<xref ref-type="bibr" rid="scirp.93601-ref8">8</xref>] .</p><p>Thymomas may be asymptomatic and discovered by accident. Depending on the series of patients, up to 40% of the patients had local symptoms, which may include chest pains, cough and dyspnea by compression of the airway or by neuromuscular effect from the myasthenia gravis [<xref ref-type="bibr" rid="scirp.93601-ref9">9</xref>] . The paraneoplastic myasthenia gravis has been described in 30% - 40% of the cases of thymoma [<xref ref-type="bibr" rid="scirp.93601-ref10">10</xref>] . In this series, almost one third of the total were asymptomatic, and another third were studied within the context of the myasthenia. There were no cases with paraneoplastic syndrome.</p><p>Thymomas might be classified by histological subtypes such as A, B and AB, but in the last group, 30% present histological heterogeneity [<xref ref-type="bibr" rid="scirp.93601-ref11">11</xref>] . This constitutes a problem for the pathologist’s classification. In the series presented, the majority was classified as part of the B group, but one case had different areas in the tumor which presented the three subtypes and could not be classified according to the WHO recommendation.</p><p>Epithelial tumors of the thymus are distinguished by the invasive local growth and pleural dissemination, while the lymphatic and distant metastasis is very rare in the presence of a thymoma (&lt;5%). For thymic carcinoma, metastasis may reach more than 10% of patients and can explain a much worse prognosis [<xref ref-type="bibr" rid="scirp.93601-ref12">12</xref>] [<xref ref-type="bibr" rid="scirp.93601-ref13">13</xref>] [<xref ref-type="bibr" rid="scirp.93601-ref14">14</xref>] .</p><p>In the series showed, survival rate of the stage IV thymomas and thymic carcinomas was poor compared to the thymomas in early stages. The histopathology of thymomas has also been described as a prognosis factor [<xref ref-type="bibr" rid="scirp.93601-ref5">5</xref>] .</p><p>In an advanced thymoma or thymic carcinoma, patients may require multimodal therapies, which should include either induction or adjuvant chemotherapy, extended resections and post-operatory radiotherapy [<xref ref-type="bibr" rid="scirp.93601-ref15">15</xref>] [<xref ref-type="bibr" rid="scirp.93601-ref16">16</xref>] [<xref ref-type="bibr" rid="scirp.93601-ref17">17</xref>] . In the period recorded, the recommended drugs for this kind of neoplasms were not available at our center. Despite this, the survivals reported are concordant with what has been shown in the international literature.</p><p>The study has multiple limitations, including retrospective analysis, lack of standardized follow up of patients and chemotherapy used. The study was done in only one center, which receives most of the patients in the country with this kind of tumor, although the total number of thymic tumors is not known.</p></sec><sec id="s5"><title>Conflicts of Interest</title><p>The authors do not declare conflicts of interest.</p></sec><sec id="s6"><title>Cite this paper</title><p>Salinas, M., Liessi, M., Vallejo, P. and Ibarra, C. (2019) Survival in a Chilean Cohort of Thymic Tumors. Journal of Cancer Therapy, 10, 510-517. https://doi.org/10.4236/jct.2019.107042</p></sec></body><back><ref-list><title>References</title><ref id="scirp.93601-ref1"><label>1</label><mixed-citation publication-type="other" xlink:type="simple">Siesling, S., van der Zwan, J.M., Izarzugaza, I., Jaal, J., Treasure, T., Foschi, R., et al. (2012) Rare Thoracic Cancers: Including Peritoneum Mesothelioma. 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