Neuroendocrine neoplasms of gastrointestinal tract and secondary primary synchronous tumors: A systematic review of case reports. Casualty or causality?

BackgroundNeuroendocrine neoplasms (NENs) can arise in most of the epithelial organs of the body and are not a rare condition in the gastrointestinal tract (GIT). The presence of NENs in GIT associated with other secondary primary malignancies (SPM) has been considered an exotic event. This study aims to describe the case reports of NENs accompanied by synchronous primary tumors.Methods and findingsWe performed a systematic literature search of the databases Scopus, PubMed, Scielo and LILACS to identify case reports that described the presence of NENs in GIT with SPM. 78 case reports were included. The mean of age of the cases was 60.2 years. 60% were male. 95.4% were NENs G1. 17 cases of NENs had metastasis. 80% of SPM were recognized in the GIT (36% in stomach, 27% in large intestine, 11.2% in small intestine, and 5.6% in esophagus). The most common type of SPM was adenocarcinoma (49.4%), followed by GIST (13.5%), other NENs in different GIT segment (7.9%), lymphoma (6.8%), and squamous cell carcinoma (4.5%). The most common tumor in GIT was adenocarcinoma (97.6%) and the presence of adenocarcinoma in the same segment of GIT was found in 68.4% of the cases. Association between adenocarcinomas and NENs in GIT (p:ConclusionThese results demonstrate that NENs with SPM are not a rare condition. Several theories have been proposed to explain this association; one of these is the ability of NENs to generate synchronous tumors by autocrine and paracrine effect. We observed an association between adenocarcinomas and NENs in the same segment of GIT.

背景 神经内分泌肿瘤（Neuroendocrine neoplasms, NENs）可发生于人体绝大多数上皮器官，在胃肠道（gastrointestinal tract, GIT）中并非罕见疾病。既往认为，胃肠道神经内分泌肿瘤合并其他继发性原发恶性肿瘤（secondary primary malignancies, SPM）属于罕见事件。本研究旨在阐述合并同步原发肿瘤的胃肠道神经内分泌肿瘤的病例报告。
方法与结果 我们对Scopus、PubMed、Scielo及LILACS数据库开展系统性文献检索，以筛选报道胃肠道神经内分泌肿瘤合并继发性原发恶性肿瘤的病例报告。最终纳入78篇病例报告。纳入病例的平均年龄为60.2岁，其中60%为男性。95.4%的病例为G1级神经内分泌肿瘤，17例神经内分泌肿瘤发生远处转移。80%的继发性原发恶性肿瘤发生于胃肠道（其中36%位于胃，27%位于大肠，11.2%位于小肠，5.6%位于食管）。继发性原发恶性肿瘤最常见的类型为腺癌（49.4%），其次为胃肠道间质瘤（Gastrointestinal Stromal Tumor, GIST，13.5%）、发生于胃肠道不同节段的其他神经内分泌肿瘤（7.9%）、淋巴瘤（6.8%）及鳞状细胞癌（4.5%）。胃肠道最常见的继发肿瘤类型为腺癌（97.6%），且68.4%的病例中，腺癌与神经内分泌肿瘤位于胃肠道同一节段。我们观察到胃肠道内腺癌与神经内分泌肿瘤存在关联。结论 本研究结果表明，合并继发性原发恶性肿瘤的神经内分泌肿瘤并非罕见病症。目前已提出多种理论以解释二者的关联，其中之一为神经内分泌肿瘤可通过自分泌与旁分泌作用诱导同步肿瘤的形成。