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<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD v1.2d1 20130915//EN" "http://jats.nlm.nih.gov/archiving/1.2d1/JATS-archivearticle1.dtd">
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  <front>
    <journal-meta id="journal-meta-1">
      <journal-title-group>
        <journal-title>Biomedical Research and Therapy</journal-title>
      </journal-title-group>
      <publisher>
        <publisher-name>Biomedpress</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta id="article-meta-1">
      <title-group>
        <article-title id="at-ca919aaac9de">
          <bold id="strong-1">A non-</bold>
          <bold id="strong-2">secretory</bold>
          <bold id="strong-3"> malignant</bold>
          <bold id="strong-4"> </bold>
          <bold id="strong-5">insulinoma</bold>
          <bold id="strong-6">: a </bold>
          <bold id="strong-7">case report</bold>
          <bold id="strong-8"> </bold>
        </article-title>
      </title-group>
      <contrib-group>
        <contrib id="c-213ba3697626">
          <name id="n-6b1c4c60b7b0">
            <surname>Zarei</surname>
            <given-names>Mohammad</given-names>
          </name>
          <contrib-id contrib-id-type="orcid">0000-0001-7294-2556</contrib-id>
          <xref id="x-128485e3be58" rid="a-992ee0d9913a" ref-type="aff">1</xref>
        </contrib>
        <contrib id="c-589dd263f12b" corresp="true">
          <name id="n-66c6dbb68f6a">
            <surname>Dastras</surname>
            <given-names>Majid</given-names>
          </name>
          <email>dastrasm1@gmail.com</email>
          <contrib-id contrib-id-type="orcid"/>
          <xref id="x-18631c544c67" rid="a-528c77ab7d45" ref-type="aff">2</xref>
        </contrib>
        <contrib id="c-4b9fa63d4c95">
          <name id="n-5b7233210f17">
            <surname>Roshanravan</surname>
            <given-names>Mostafa</given-names>
          </name>
          <contrib-id contrib-id-type="orcid"/>
          <xref id="x-422d72b3ee99" rid="a-afeec1b324a3" ref-type="aff">3</xref>
        </contrib>
        <aff id="a-992ee0d9913a">
          <institution>Nursing Department, Shirvan Center of Higher Health Education, North Khorasan University of Medical Sciences, Bojnurd, Iran</institution>
        </aff>
        <aff id="a-528c77ab7d45">
          <institution>Nursing Department, Zahedan University of Medical Sciences, Zahedan, Iran </institution>
        </aff>
        <aff id="a-afeec1b324a3">
          <institution>Nursing Department, Faculty of Nursing and Midwifery, North Khorasan University of Medical Sciences, Bojnurd, Iran</institution>
        </aff>
      </contrib-group>
      <abstract id="abstract-64325a892c4c">
        <title id="abstract-title-3eae154b500c">Abstract</title>
        <p id="paragraph-095c25f5d80e"><bold id="s-f6dea31876bc">Introduction:</bold> We report a rare case of non-insulin secreting malignant insulinoma of the pancreas and discuss its medical and surgical management. <bold id="s-ec6a7d03674f">Case Presentation:</bold> Our patient was a 62-year-old Persian female. Over the previous year, she had developed increased abdominal mass, dizziness, weakness, and fatigue. After surgical operation, chemotherapy was given to the patient. Treatment with cisplatin and etoposide was commenced in a 4-month course. <bold id="s-e9e8f1e94e67">Conclusion: </bold>As a result, chemotherapy showed an important role in the management of insulinoma.</p>
        <p id="p-1790e888cfea"/>
        <p id="p-f672674eb6e5"/>
      </abstract>
      <kwd-group id="kwd-group-1">
        <title>Keywords</title>
        <kwd>Insulinoma</kwd>
        <kwd>Malignant</kwd>
        <kwd>Pancreas</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec>
      <title id="t-4c989365be5d">Introduction</title>
      <p id="t-62936effb18f">Pancreatic endocrine tumors (PETs), with mild to moderate malignancies, originate from pancreatic islets. The first case was detected in 1869 by Langerhans. These tumors are rare and the prevalence is 1-4 per million people <xref rid="462486:10304549" ref-type="bibr">1</xref>,<xref rid="462486:10304550" ref-type="bibr">2</xref>. Among all, insulinoma is the most common type and can be seen mostly in people between the ages of 30- to 60-year-old <xref rid="462486:10304551" ref-type="bibr">3</xref>,<xref rid="462486:10304552" ref-type="bibr">4</xref>.</p>
      <p id="p-260e58aeca4b">Insulinoma accounts for only 1 percent of malignant pancreatic tumors and can occur with or without secretory function; and if it is combined with a hormonal syndrome, we considered it a secretory form <xref id="x-14df6d4b7fa5" rid="462486:10304553" ref-type="bibr">5</xref>. In non-secretory insulinoma, patients are asymptomatic until they develop gastric outlet obstruction or bile duct, or unless the tumor causes pain or are specified in imaging <xref id="x-9fccd9724b0f" rid="462486:10304554" ref-type="bibr">6</xref>.  </p>
    </sec>
    <sec>
      <title id="t-1a4d2a71d76f">
        <bold id="s-11f27ba11012">Case Presentation</bold>
      </title>
      <p id="p-dfb174eac9c3">A 62-year-old Persian female, who showed symptoms of headache, dizziness, fatigue and muscle jump about two years ago, had admitted in a hospital with a diagnosis of meningiomas and was operated to remove the mass.<bold id="s-2966986467c7"> </bold></p>
      <p id="p-aeb9ecac81c2">Over the previous year, she had developed increased abdominal mass, dizziness, weakness, and fatigue. This time, since the early studies on suspicion of insulinoma secretary, a fasting test was performed according to protocol. At first, the blood samples were collected to check for glucose, insulin and C-peptide levels of patient, and then fasting was given to patient under close supervision. It was recommended to measure the patient's blood sugar in a serial form according to protocol if the symptoms of hypoglycemia persisted. Due to the normality of the test results, an abdominal Computed Tomography (CT) scan was requested to complete the studies. The CT scan showed a pancreatic tumor sized 13 x 8 mm along with extensive metastases to the surrounding area (<bold id="s-9e1a631ee180"><xref id="x-af9439eab4c7" rid="f-a6a430baa989" ref-type="fig">Figure 1</xref></bold>). For a definitive diagnosis, a needle biopsy and a pathologic examination were performed, and the malignant insulinoma diagnosis was confirmed. The dimension of the tumor was 6 × 5.8 × 13 mm.</p>
      <p id="p-a634e99942c0"/>
      <p id="p-7f885f6e6559"/>
      <fig id="f-a6a430baa989" orientation="potrait" width="twocolumn" fig-type="graphic" position="anchor">
        <graphic id="g-079e084b54f5" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/a7c9d421-03a1-4552-8eb6-9e830ab57740/image/f1a8030a-9b1a-4ace-beae-f8872de3c845-u131-1541658937-1.jpg"/>
        <label>Figure 1 </label>
        <caption id="c-d4e5489d9a31">
          <title id="t-b22df7ba7440">
            <bold id="s-a96f2265810a">Pancreatic tumor sized 13 × 8 mm along with extensive metastases to the surrounding area. </bold>
          </title>
        </caption>
      </fig>
      <p id="p-e730989c5e38"/>
      <p id="p-9a973b8edbc2">After surgical operation, chemotherapy was given to the patient. Treatment with cisplatin (I.V 170 mg/week) and etoposide (I.V 85 mg/daily) was commenced in a 4-month course. The current state of patient is acceptable and stable. Currently, the patient is under constant monitoring and care. </p>
      <p id="p-a6163c865fe3"/>
    </sec>
    <sec>
      <title id="t-7a7b4f778c31">
        <bold id="s-493b32bd8e1e">Discussion and Conclusions</bold>
      </title>
      <p id="p-66318be4b5e7">Endocrine tumors comprise a small percentage (1-2%) of all pancreatic neoplasms. They are mostly seen in adults, but few cases have been reported in children and infants <xref id="x-8bd033de65df" rid="462486:10304555" ref-type="bibr">7</xref>. Overall it is a rare tumor (with a prevalence of 1 in 250 million) and the annual incidence is 1 to 5 per million <xref id="x-e405b97c22f3" rid="462486:10304556" ref-type="bibr">8</xref>. 80% of cases were benign tumors and 40% of their size is below 1 cm <xref rid="462486:10304557" ref-type="bibr">9</xref>,<xref rid="462486:10304558" ref-type="bibr">10</xref>.<bold id="s-5b772cabc44e"> </bold></p>
      <p id="p-1ef766663d69">In a previous study, mean duration of symptoms before diagnosis was less than 1.5 years <xref id="x-5bcacca7802c" rid="462486:10304559" ref-type="bibr">11</xref>. However, some patients may be asymptomatic for decades. Approximately 20% of patients are misdiagnosed with neurological or mental disorder before the diagnosis of insulinoma <xref rid="462486:10304560" ref-type="bibr">12</xref>,<xref rid="462486:10304561" ref-type="bibr">13</xref>.</p>
      <p id="p-0cbc0a246aa1">The results of non-invasive centralization techniques including ultrasonography, CT and magnetic resonance imaging (MRI) have been desponding, and sensitivities ranging from 0 to 33% have been reported <xref id="x-2d27a4427687" rid="462486:10304562" ref-type="bibr">14</xref>. In the present case, detection with CT Scan and final approval with needle biopsy was performed. </p>
      <p id="p-0885512dab2e">PET treatments include two-part problem solving: problems related to secreted hormones, and problems related to tumor growth and metastasis. Chemotherapy is one of the treatment methods that shows good result in patients <xref id="x-2a007b9b1f8d" rid="462486:10304563" ref-type="bibr">15</xref>. In our case, according to the symptoms of abdominal pain and swelling, and no proof of secretory insulinoma, treatment with chemotherapy in the same regimen to small cell lung cancer based on CT Scan showed positive outcome. As a result, chemotherapy showed an important role in the management of insulinoma.</p>
      <p id="p-f980b36f1dda"/>
    </sec>
    <sec>
      <title id="t-02253f5a2251">
        <bold id="s-419dbadcc263">Abbreviations</bold>
      </title>
      <p id="t-3c732e001c64"><bold id="s-536723347b49">CT</bold>: Computed tomography </p>
      <p id="p-e424658a1e59"><bold id="s-7d9b982f6c5c">PET:</bold> Pancreatic endocrine tumor</p>
      <p id="p-612550a38ad6"><bold id="s-fdf1399c94ca">MRI:</bold> Magnetic resonance imaging</p>
      <p id="p-182b6f6d29ab"/>
    </sec>
    <sec>
      <title id="t-bdb87369992f">Competing Interests</title>
      <p id="p-40efb5fd77cc">The authors report no conflicts of interest in this work.</p>
      <p id="p-c230771de988"/>
    </sec>
    <sec>
      <title id="t-353bd7ffda68">Authors' Contributions</title>
      <p id="t-062412ccaed9">MZ and MD followed this case and drafted the manuscript; MZ and MR helped for the follow up of this case; MZ, MD, and MR revised this paper. All authors read and approved the final manuscript.</p>
      <p id="p-8f3f54678457"/>
    </sec>
  </body>
  <back>
    <ack id="ack-b0c67277c6ba">
      <title id="ack-title-6b9d1cdeed9e">Acknowledgments</title>
      <p id="paragraph-1e1873bd463c"> The authors wish to acknowledge the following individuals for their contributions to this case report.</p>
    </ack>
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