Expression of hsa-let-7b-5p, hsa-let-7f-5p, and hsa-miR-222-3p and their putative targets HMGA2 and CDKN1B in typical and atypical carcinoid tumors of the lung.

A retrospective study was conducted on 32 patients who had had bronchial carcinoid tumors between 1965 and 1989. The average age of the patients was 48.5 years, with a male to female ratio of 3.6:1. Of the 32 patients, 28 were diagnosed pathologically to have typical bronchial carcinoid tumors and the other four, atypical bronchial carcinoid tumors. Twenty-two of the 28 typical bronchial carcinoid tumors were classified as stage I, but only one of the four atypical bronchial carcinoid tumors was at stage I. Two typical carcinoid tumor patients and two atypical carcinoid tumor patients were found, pathologically, to have lymph node metastasis. The typical carcinoid tumors showed a more significant endobronchial polypoid growth than the atypical carcinoid tumors (P = 0.0138). The five-year-survival rate was 100% in patients with typical carcinoid tumors and 25% in those with atypical carcinoid tumors. The difference between the five-year-survival rate for the typical carcinoid and atypical carcinoid patients was statistically significant (P = 0.001).

Typical and Atypical Pulmonary Carcinoids: Outcome in Patients Presenting With Regional Lymph Node Involvement

Trends in Prognostic Factors for Neuroendocrine Lung Tumors

Surgical treatment was performed in 286 patients with lung cancer. The final morphological study diagnosed typical and atypical carcinoid tumors in 258 (90.2%) and 28 (9.8%) patients, respectively. The central and peripheral tumor sites were established in 245 (85.7%) and 41 (14.3%) patients, respectively. According to disease stage, the patients were distributed as follows: Stage I in 166 patients, Stage II in 84, Stage III in 30, and Stage IV in 6. Five (1.7%) patients were found to have carcinoid syndrome: the tumor had the morphological structure of atypical and typical carcinoid tumors in 3 and 2 patients, respectively. One patient with typical carcinoid was observed to have carcinoid syndrome concurrent with the Itsenko-Cushing syndrome. Two patients with carcinoid syndrome were ascertained to have hepatic metastases; these patients were recognized to be inoperable. The basic type of surgical intervention for typical carcinoid tumors was an organ-saving operation: lobectomy, bilobectomy, reconstructive plastic surgery, precision removal, and segmental resection. Only 7 patients underwent endoscopic removal of typical carcinoid tumors. In atypical carcinoid tumors, the surgical volume depends on the specific features of the extent of a tumor and the presence or absence of metastases. Pneumonectomy with lymphadenectomy and lobectomy in combination with and without bronchial resection were performed in half the cases. The long-term results of radical surgical treatment in patients with bronchopulmonary carcinoid tumors suggest that these operations are warranted.

Lung carcinoid tumors are malignant neuroendocrine neoplasms that account for less than 2% of all lung malignancies and include two histological types: typical and atypical carcinoid tumors. Typical carcinoid tumors do not include areas of necrosis and show less than 2 mitotic figures within 10 high grade fields. On the molecular level, carcinoid tumors present alterations in gene MEN1 as well as a high expression of genes ASCL1 and EIF1AX. We report a systems biology approach using BioNetUCR and Copasi in addition to Cytoscape to identify mi-RNA regulators of the most important altered genes in typical pulmonary carcinoid tumors. The final adjusted and reduced interaction network of our genes of interest included: 3 genes 12 transcription factors and 7 mi-RNAs, leading to a total of 22 nodes and 53 edges. Analysis with Copasi showed that MIR24-2 regulates the expression of MEN1 and MIR129-1 regulates the expression of AIF1AX. Those mi-RNAs could be potential targets for molecular therapy in patients with typical carcinoid tumor of lung.

Carcinoid tumors of the lung: A report of 11 cases

This study examines the experience of the Spanish Multi-centric Study of Neuroendocrine Tumours of the Lung with patients treated surgically for typical and atypical carcinoid tumours. From 1980 to 2002, 661 patients were treated surgically for 569 typical carcinoid tumours and 92 atypical carcinoid tumours. Three hundred and four cases were studied retrospectively from 1980 to 1997 (261 typical carcinoid and 43 atypical carcinoid tumours); the other 357 new cases (308 typical carcinoid and 49 atypical carcinoid tumours) were collected prospectively from 1998 to 2002. Tumours were classified according the 1999 classification from the WHO and the International Association for the Study of Lung Cancer (IASLC). Several variables were reviewed in all patients. Univariate and multivariate statistical analyses were performed in order to determine whether clinical characteristics were associated with significant differences in survival. In the total of the patients, 5-year survival for different tumours was as follows: typical carcinoid: overall survival 97%; with nodal involvement 100%; atypical carcinoid: overall 78%; with nodal involvement 60%. A significant difference in survival was found between patients in the retrospective and prospective groups with atypical carcinoid and nodal involvement. The comparative analysis of several factors in typical and atypical carcinoid tumours showed a significant difference for mean age, tumour size, nodal involvement and distant metastases. Nodal involvement and histological sub-type appear as the most important factors influencing the prognosis. Adequate lung resection and systematic radical mediastinal lymphadenectomy should always be performed. Sleeve resection could be performed in central typical and atypical carcinoid tumours, avoiding pneumonectomy.

Tumeurs carcinoïdes bronchopulmonaires : une série tunisienne de 115 cas opérés

The spectrum of primary neuroendocrine tumors of the lungs ranges from typical carcinoid tumors, which are relatively benign, to highly aggressive small-cell carcinoma. In this review, we summarize the treatment of bronchopulmonary carcinoid, a disease with an incidence of 0.5 per 100,000 persons per year in Western countries. We selectively searched the PubMed database for scientific evidence on the treatment of bronchopulmonary carcinoid, considering only articles published up to February 2015. We also performed a survival analysis of 84 patients with this disease who underwent interdisciplinary treatment at the University of Freiburg Medical Center. Carcinoid tumors account for less than 1% of all lung tumors. They manifest themselves clinically with cough (35%), hemoptysis (25%), and/or bronchial obstruction (40%), depending on their location, size, and pattern of growth. 30% of patients are asymptomatic, and less than 1% have hormone-associated symptoms. Typical and atypical carcinoid tumors are distinguished on a histological basis; the histologic differential diagnosis also includes large-cell neuroendocrine tumors and small-cell carcinoma of the lung. 80% of patients who undergo resection of typical carcinoid tumors survive at least 10 years. Atypical carcinoid tumors recur more commonly than typical ones. If the mediastinal lymph nodes are involved, adjuvant treatment should be considered. Because of their rarity, the treatment of bronchopulmonary carcinoid tumors presents an interdisciplinary challenge. Surgical resection, the treatment of choice for local carcinoid tumors, generally leads to long-term survival. The existing registers should be made more comprehensive so that the treatment of this disease can be better in the future.

Anatomic Pulmonary Resection is Associated With Improved Survival in Typical Carcinoid Lung Tumor Patients.

1993). The initial management of NET comprises surgical excision of the primary tumour (aimed at reducing as much as possible of the tumour mass); additionally, in patients who are not cured by surgery alone, medical therapy is used for the control of symptoms and humoral syndromes with agents such as somatostatin analogues and/or a-interferon. Specific therapy with radiopharmaceuticals using radio-labelled substances such as meta-iodobenzylguanidine (MIBG) or somatostatin analogues appears promising for some tumours which show diagnostic uptake, and is the first-line systemic management for sensitive cases. Hepatic artery ligation and/or chemoembolization is also used in patients with excessive hepatic tumour load and uncontrollable symptoms. The control of tumour growth with chemotherapeutic agents is currently mainly reserved for patients with recurrent and/or progressive disease and where other therapeutic modalities have failed. Chemotherapy may be particularly helpful for selected cases of advanced NET, especially pancreatic or poorly differentiated NET. This review deals with the general role of chemotherapy in the management of malignant NET, its integration with other modes of therapy, and the specific protocols which have been used. Histological classification and differentiation of NET

Pulmonary carcinoids are rare neoplasms, accounting for approximately 1%-2% of all lung malignancies. A retrospective analysis was undertaken of all patients who underwent surgical resection of pulmonary carcinoid tumours across multiple institutions in Melbourne, Australia. From May 2000 through April 2020, 241 patients who underwent surgical resection of pulmonary carcinoid tumours were retrospectively reviewed. Patient demographics, pathologic data, and long-term outcomes were recorded. Median age was 57.7 years and the majority of patients were female (58.9% vs. 41.1%). Typical carcinoid was present in 77.1%. Histological subtype was associated with several factors. Atypical carcinoid was more likely to have larger tumour size and nodal involvement. Overall survival for typical carcinoid at 5, 10, and 15 years was 98%, 95%, and 84%, and for atypical carcinoid was 88%, 82%, and 62%, respectively. Histological subtype and age were found to be independent predictors of overall survival, with worse outcomes for atypical and those above 60 years of age. Disease-free survival was related to sublobar resection (p < 0.001, sub-hazard ratio (SHR): 6.89), lymph node involvement (p = 0.022, SHR: 3.18), and atypical histology (p < 0.001, SHR: 9.89). Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoids. Atypical histology and lymph node involvement are significant prognostic factors, and sublobar resection should not be considered in patients with either of the above features. Typical carcinoid tumour without nodal involvement may be appropriate for sublobar resection. Typical and atypical carcinoid tumours should be considered distinct disease entities, and as such treated accordingly.

According to the 1999 World Health Organisation classification of lung tumors, the classification of neuroendocrine (NE) tumors is solely based on light-microscopic features. Typical and atypical carcinoid tumors are distinguished from large cell (LCNEC) and small cell neuroendocrine carcinomas (SCLC). We used comparative genomic hybridization (CGH) on 50 samples to investigate the cytogenetic relationships between NE tumors. On average, carcinoid tumors showed markedly fewer chromosomal imbalances (1.8/case, 23 cases) than LCNEC (13.3/case, 17 cases) or SCLC (17/case, 10 cases). The frequency of amplicons increased accordingly. Typical carcinoid tumors exhibited significant defects on chromosomes 11 and 13 only. Interestingly, only the frequency of losses on chromosome arm 11q was very similar for all three tumor entities (about 30%). In conclusion, the CGH results support the classification of typical carcinoid tumors as a separate entity in clear distinction from the NE carcinomas.

We sought to determine the long-term survival of patients treated for bronchial carcinoid tumors and whether lesser resections have had an effect on outcomes. We conducted a retrospective, multi-institutional review of patients treated surgically for primary bronchial carcinoid tumors since 1980. Operative approach, pathologic stage, histology, surgical complications, tumor recurrence, and long-term survival were assessed. There were 50 men and 89 women with a mean age of 52.2+/-17.4 and 58.9+/-13.3 years, respectively (P=0.021). Men were more likely to be current or former smokers than were women. Operations included lobectomy or bilobectomy in 110, pneumonectomy in four, wedge resection in 22, and bronchial sleeve resection only in three patients; resection was performed thoracoscopically in six patients. One patient died postoperatively. Stages were I, 121; II, nine; III, six; and IV, three. Typical carcinoid tumors were stage I in 100 and more advanced (stages II-IV) in nine, whereas atypical carcinoid tumors were stage I in 18 and more advanced in eight (P=0. 002). Median follow-up was 43 months (range 1-149) during which 21 (15%) patients died (four from recurrent cancer) and 19 patients (14%) were lost to follow-up. Recurrent cancer developed in 2/98 patients with typical and 5/25 patients with atypical subtypes (P<0. 001; log-rank test). The likelihood of recurrence was related to histological subtype (relative risk 7.9 for atypical carcinoid; 95% confidence interval 1.4-43.5). Five-year survival was 88% for stage I patients and was 70% for patients with more advanced stages. When stratified by stage, survival was related to age (relative risk=1.9 for a 10 year increase in age; 95% confidence interval 1.2-2.9) and possibly to the histological subtype, but not to patient gender, year of operation, or type of operation performed. Either major lung resection or wedge resection is appropriate treatment for patients with early stage typical bronchial carcinoid tumors. Survival is favorable for early stage tumors regardless of histological subtype. Local recurrence is more common among patients with atypical subtypes, suggesting that a formal resection may improve long-term outcome.

Wedge Resection Offers Similar Survival to Segmentectomy for Typical Carcinoid Tumors