Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature review

Neuroendocrine tumors (NET) previously called carcinoid tumors are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid syndrome. The annual incidence of patients with NET is 8.4 per 100000; yet many NET remain asymptomatic and clinically undetected. A majority of NET follows a benign course; however, some will display malignant characteristics. NET most commonly occur in the gastrointestinal tract (67%) and bronchopulmonary system (25%). Gastrointestinal NET occur within the stomach, small intestine, liver, and rectum. We report a retrospective study of 11 subjects: Eight with benign carcinoid tumors: duodenal bulb (n = 2), terminal ileum (n = 1), sigmoid colon (n = 2), and rectum (n = 3); three with malignant carcinoid: liver (n = 1) and intra-abdominal site (n = 2). The diagnosis, endoscopic images, outcome, treatment and review of the literature are presented.     

Challenges in the Diagnosis and Management of Well‐Differentiated Neuroendocrine Tumors of the Lung (Typical and Atypical Carcinoid): Current Status and Future Considerations

Neuroendocrine tumors (NET) of the lung represent approximately 25% of all primary lung tumors and can be classified as low grade (typical carcinoids), intermediate grade (atypical carcinoids), or high grade (large cell neuroendocrine carcinoma or small cell lung carcinoma). Low- and intermediate-grade lung NET are increasingly recognized as biologically distinct from high-grade lung NET based on clinical behavior and underlying molecular abnormalities. This review summarizes current knowledge and challenges in the diagnosis and management of low- and intermediate-grade lung NET. Accurate histopathologic classification of lung NET is critical to determining appropriate treatment options but can be challenging even for experts. For low- and intermediate-grade lung NET, surgery remains the mainstay of treatment for localized disease. Although no standard systemic therapy has been established for the treatment of advanced, unresectable disease, a number of promising treatment options are emerging, including somatostatin analogs, temozolomide-based chemotherapy, targeted therapy with mammalian target of rapamycin or vascular endothelial growth factor inhibitors, and peptide receptor radionuclide therapy. Given the difficulty in accurately diagnosing these tumors, and the paucity of data supporting establishment of standard systemic therapy options, management of patients within the setting of a multidisciplinary team, including specialists with expertise in NET, is recommended. Ongoing and future clinical trials hopefully will provide stronger evidence to support treatment recommendations for low- and intermediate-grade lung NET.

Implications for Practice:

Treatment of neuroendocrine tumors (NET), particularly those of lung origin, continues to evolve. This review seeks to educate oncologists on the most up-to-date options and supporting data regarding management of two rare lung neoplasms, typical and atypical carcinoid tumors. Although surgical resection has been the mainstay of treatment, several systemic options have been studied in the treatment of NET of various origins that may potentially play a role in treating typical carcinoid tumors and atypical carcinoid tumors.     

Neuroendocrine tumor metastasis to the thyroid gland

It has been reported that the thyroid is relatively immune to malignant metastasis. Therefore, in a practical setting, it is difficult to diagnose whether synchronous nodules in both lung and thyroid are independent or have metastasized from one to the other. In the present study, we report a treatment approach in a patient with such nodules, using a molecular technique. A 68-year-old woman presented with synchronous solitary thyroid mass and a nodular lesion in the right lung. Both tumors, which were surgically resected, morphologically showed neuroendocrine differentiation, which was confirmed by immunohistochemical analysis. These features required differential diagnosis from possible (1) medullary thyroid carcinoma (MTC) with metastasis to the lung, (2) pulmonary neuroendocrine carcinoma with metastasis to the thyroid, and (3) independent MTC and pulmonary neuroendocrine carcinoma. Identical mutations of the p53 gene were detected in both the thyroid and lung tumors, indicating the same origin for both tumors. In addition, these mutations and a lack of calcitonin expression suggested a pulmonary origin of the tumors. Metastatic thyroid cancers are well known to cause miliary lesions in the lung, while lung cancers can metastasize to various tissues. Furthermore, pulmonary neuroendocrine carcinoma has been reported as having a tendency of metastasizing to the thyroid. Head and neck surgeons should be aware that a particular subset of lung cancers may develop a metastatic solitary nodule in the thyroid, as presented. An effective therapeutic strategy is largely dependent on the differential diagnosis.     

Peritoneal carcinomatosis secondary to carcinoid tumour

Carcinoid tumours are neuroendocrine neoplasms that can appear in every location of the digestive tract. They are low aggressive tumours, although they often produce local invasion and hepatic metastases, whose resection allows long-term survival. We report a case of a 64-year-old man with ileal carcinoid tumour, that underwent ileal resection and metastasectomy of one lesion in liver segment II. Surgical findings indicated peritoneal carcinomatosis. Carcinoid dissemination as peritoneal carcinomatosis has been rarely described in the literature. Cytoreductive surgery, always when complete resection is aimed, achieves asymptomatic long-term survivals.     

唑来膦酸联合放疗治疗骨转移癌的临床疗效观察

目的 探讨唑来膦酸联合局部放疗治疗恶性肿瘤局限件骨转移的临床疗效.方法 45例局限性骨转移患者随机分为2组,联合治疗组23例,采用唑来膦酸静脉滴注加局部放疗;单纯放疗组22例,只采用局部放疗.结果 联合治疗组和单纯放疗组的疼痛缓解率分别为91.3%和86.4%.差异无统计学意义(P>0.05);联合治疗组和单纯放疗组的溶骨病灶再钙化的有效率分别为52.2%和22.7%,差异有统计学意义(P<0.01);联合治疗组和单纯放疗组出现新的骨转移病灶的患者比例分别为13.0%和40.9%,联合治疗组显著低于单纯化疗组(P<0.05).联合治疗组的不良反应主要为短暂低热和恶心.结论 唑来膦酸联合放疗治疗恶性肿瘤局限性骨转移疗效确切,其控制骨痛作用强,可高效修复溶骨病灶,并能降低新的骨转移灶发生率.     

A phase II study of docetaxel in patients with metastatic carcinoid tumors

Twenty-one patients with metastatic carcinoid tumors were treated with docetaxel. Although the treatment was well tolerated, no objective radiologic responses were observed. Novel, more effective agents are needed for this disease. Background. Traditional combination chemotherapy regimens containing streptozocin, doxorubicin, and 5-fluorouracil have yielded disappointing results in patients with metastatic carcinoid tumors. The lack of efficacy of these combinations, together with their toxicity, has led to efforts to investigate therapeutic agents that are potentially more active and tolerable. We, therefore, assessed the efficacy of docetaxel in the treatment of patients with metastatic carcinoid tumors. Methods. Twenty-one patients with metastatic carcinoid tumors were treated with docetaxel, administered at a dose of 75 mg/m² every three weeks. Patients were followed for evidence of toxicity, response, and survival. Results. Docetaxel was well tolerated in this patient population. However, no objective radiologic responses were noted in any of the 21 patients. Of the 13 patients who were evaluable for biochemical responses to therapy, four (31%) experienced decreases in 24-hour urinary 5-hydroxyindole acetic acid (5HIAA) excretion of greater than 50%. The clinical course of the patients enrolled in this study was marked by a high incidence of radiologically stable disease (81%), a median progression-free survival time of 10 months, and a median overall survival time of 24 months. Conclusion. Although treatment with docetaxel results in biochemical responses in patients with metastatic carcinoid tumors, the lack of more significant antitumor activity demonstrates the need for novel, more effective agents in this disease.     

放疗联合内生场热疗对骨转移癌疗效的临床研究

目的观察热疗联合放疗治疗骨转移癌的疗效。方法经X线、CT、MRI或ECT证实的骨转移癌患者56例,随机分为治疗组和对照组,各28例;对照组行单纯放疗,治疗组在放疗后采用迈达NRL-002型内生场肿瘤热疗机加热60min,每周2次;观察疼痛缓解、体力状况、骨病灶好转情况及不良反应。结果治疗组疼痛缓解总有效率（显效＋有效）82.14%,明显优于对照组（57.14%）;治疗后1周内起效者20例（71.42%）,体力改善总有效率78.57%,骨病灶疗效总有效率75%,无严重不良反应发生。结论放疗配合内生场热疗治疗骨转移癌较单纯放疗更为有效,能明显地缓解疼痛,提高患者的生活质量。     

调强适形放射治疗结合热疗治疗颈部转移肿瘤的疗效分析

目的观察调强适形放射治疗（IMRT）结合热疗治疗颈部转移性肿瘤的治疗效果。方法将选取的111例颈部转移肿瘤患者随机分为观察组（56例）和对照组（55例）。对照组患者采用IMRT,观察组患者采用IMRT＋热疗,比较两组患者的临床疗效。结果观察组患者鼻咽癌、食管癌、肺癌、口腔癌和喉癌的颈部转移癌的有效率分别为91．7％、87．5％、83．3％、100．0％和80．0％,对照组患者分别为45．5％、28．6％、28．6％、33．3％和33．3％,差异有统计学意义（P〈0．05）。结论调强适形放射治疗结合热疗治疗颈部转移肿瘤疗效好,对无法切除的颈部转移肿瘤是一种较好的治疗手段。     

Whole abdominal radiation in the management of metastatic gastrointestinal carcinoid tumor

Twenty-eight patients with metastatic gastrointestinal carcinoid tumor were treated with whole abdominal radiation. Twenty-one of these patients had the carcinoid syndrome. The prescribed mid-line tumor dose was 2000 to 2500 rad. in 20 to 25 fractions in 4 to 5 weeks. The overall 5 year survival was 35% (median survival 2.5 years). A marked survival difference was noted in those patients with carcinoid syndrome compared to the non-functioning group. None of the syndrome patients survived five years (median survival 1.7 years) whereas six of the seven non-syndrome patients are five year survivors.     

Neuroendocrine Carcinoma of the Breast: Current Evidence and Future Perspectives

Neuroendocrine carcinoma of the breast is considered a rare entity, and for this reason there are no data from prospective clinical trials on its optimal management. Early stage tumors are usually treated with the same strategy used for the other types of invasive breast cancer. Anthracycline- and taxane-based regimens represent the most frequently administered chemotherapy in neoadjuvant and adjuvant setting, as well as for metastatic disease, although combinations of platinum compounds and etoposide have been widely used, in particular for small-cell histology and tumors with a high proliferation index. For metastatic disease, a multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination of the above. In the near future, a better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment. In this review, we discuss the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast.

Implications for Practice:

Neuroendocrine carcinoma of the breast (NECB) is a distinct entity of breast cancer. Clinical features and morphology are not helpful to distinguish NECB from other subtypes of breast cancer; therefore, immunohistochemistry markers for neuroendocrine differentiation, mainly chromogranin and synaptophysin, should be routinely used to confirm the diagnosis, especially in cases of mucinous or solid papillary carcinoma in which the suspicion of NECB may be relevant. Adjuvant treatment should be offered according to the same recommendations given for the other types of invasive breast cancer. An accurate diagnosis of NECB is also important in the metastatic setting, in which a multimodality approach including specific therapies such as peptide receptor radionuclide therapy can be considered.     

放射治疗转移性肝癌的临床预后因素研究

目的:分析转移性肝癌应用放疗的疗效及预后因子。方法:转移性肝癌患者38例,21例经肝动脉栓塞化疗药物灌注(TACE)2~3次后行外放疗,17例进行单纯放射治疗,38例患者总照射剂量TD2000Gy~6600CGy,分割剂量150Gy~200CGy/次,每周5次。结果:所有患者均完成治疗过程,总有效率(PR CR)为86.8%,1年及2年生存率为55.3%,36.8%。应用SAS6.0软件单因素分析显示肝内转移数量、经动脉栓塞化疗(TACE)、适形放疗、Child-Pugh分级是对预后的影响有统计学意义的因素(P<0.001),COX回归分析上述因素也是独立的预后因子(P<0.05)。结论:经动脉栓塞化疗(TACE)、适形放疗、肝内转移数量和Child-Pugh分级对转移性肝癌放疗的生存率有显著影响,同时也是独立的预后因子。