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  • Introduction Pulmonary carcinoid tumors are family of


    Introduction Pulmonary carcinoid tumors are family of the neuro-endocrine tumors (NET), originating from the neuro-endocrine Kulchitsky cells, and comprise around 2% of all pulmonary cancers [1]. By morphological analysis, carcinoid tumors can be classified as typical carcinoid (TC) and atypical carcinoid (AC), depending on mitotic cell count (TC 0–2 and AC 2–10 per 2-mm²) and on the presence of necrosis (AC) [2]. AC’s exhibit a slightly more aggressive behaviour with a higher rate of recurrences and tendency to metastasize when compared to TC [1]. Carcinoids are often centrally located, predominantly intraluminal tumors without invasion of adjacent tissues [3]. These characteristics make them particularly suitable for Amiloride HCL sparing surgical treatment options such as sleeve lobectomy or bronchoplastic procedures. Although surgery still is the standard treatment to date, endobronchial treatment modalities (e.g. laser treatment, cryotherapy) are gaining popularity. For selected patients with TC and AC, good results have been reported after endobronchial treatment (EBT) [[4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]] and the low-grade nature of carcinoids, makes that incomplete endobronchial resection can still be completed by radical surgical resection, with good results 6,12. To justify its use, the outcomes of (initial) endobronchial treatment should not be inferior to surgical resection. Against this background this review of available literature was performed to identify the optimal curative treatment strategy for patients with pulmonary carcinoid, with a particular focus on the feasibility and outcome of endobronchial treatment and surgical techniques.
    Materials and methods
    Results The study selection flow-chart is presented in Fig. 1. Combining the two main searches for endobronchial therapy and surgical therapy yielded 3111 records. Subsequently, 693 duplicates were removed. After abstract and title screening, 2981 records were excluded, leaving 130 studies for full text screening. Finally, 9 studies for endobronchial treatment (Appendix A), and 43 studies for surgical treatment (Appendix B) meeting the inclusion criteria, were included and analyzed.
    Discussion This is the first systematic review evaluating both surgical -and endobronchial treatment for patients with pulmonary carcinoid tumors. Studies describing new techniques such as EBT and parenchyma sparing resection, are limited. However for selected patients, at least comparable survival, recurrence rate and complication rate can be achieved. Because of the low-grade nature of carcinoids, even incomplete endobronchial resection followed by radical surgical resection can result in good outcome 6,12. In patients with non-small cell lung carcinoma (NSCLC), parenchyma sparing resections are associated with better QOL compared to pneumonectomy [56]. Although pulmonary carcinoid tumors have a different morphology compared to other NSCLC, it is likely that parenchyma sparing resection or EBT for patients with pulmonary carcinoid also result in better QOL when compared with anatomical resections, although we could not conclude this from the included studies. Not all patients with carcinoid located in the central airways are candidates for endobronchial treatment. Pulmonary carcinoids with extraluminal growth, larger tumor diameter, or with suspected loco-regional or distant metastasis, are generally considered not suitable for EBT [12]. If curation cannot be achieved, other advantages of EBT arise, including desobstruction of the involved bronchus with ensuing resolution of post-obstructive pneumonia and limiting the extension of the subsequent surgical resection [13]. Survival is negatively affected by several prognostic factors such as tumor diameter, atypical carcinoid histology, and lymph node involvement. These prognostic factors have to be taken into account when selecting the appropriate treatment. Regarding tumor diameter, Aydin et al. described a median tumor diameter of 22.5 mm to be associated with N0 and a median tumor diameter of 33.5 mm and of 38 mm with N1 and N2, respectively [31]. Yang et al. showed that a tumor size of ≥3 cm outcome was significantly worse than for patients with a tumor size <3 cm [39]. So, when EBT is selected, it is likely that patients with small tumors will benefit the most. A recent study, assessing prognostic factors for EBT in pulmonary carcinoid, showed that small intraluminal tumors of ≤2 cm are suitable for endobronchial resection. All other tumors should be referred for surgery [12]. Histological classification and tumor localization have shown prognostic significance in many studies. AC is associated with other poor prognostic factors such as larger diameter, peripheral location and increased incidence of lymph node involvement. Tumor localization is also important for selecting treatment, as only central carcinoids will be suitable for EBT. Although AC behaves more aggressively than TC, patients with small intraluminal AC and TC tumors and no signs of lymph node involvement might be appropriate candidates for lung parenchyma sparing procedures [6,8,12,13,27,42]. Lymph node status is also an important prognostic factor. Presence of lymph node involvement does not exclude surgical treatment because long-term survival is still possible for TC and AC treated with resection. About 90% of lymph node negative pulmonary carcinoid patients are still alive after 10 years, compared to around 50% in patients with lymph node involvement. Amiloride HCL Although lymph node involvement is rare in pulmonary carcinoid, compared to NSCLC, lymph node dissection is recommended. De Leyn et al. published the revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer [57]. Whether these guidelines for pulmonary carcinoid should be applied in the diagnostic work-up for carcinoid tumors is unclear. Hilar (N1) or mediastinal (N2) lymph node involvement in pulmonary carcinoid will in most patients not change treatment, because neo-adjuvant treatment in pulmonary carcinoid has never been shown effective in increasing resectability or survival [58,59]. In addition, lymph node metastasis is rare, like it is in patients with T1 NSCLC. A growing number of T1N0 NSCLC patients are nowadays treated with stereotactic body radiation (SBRT) [60,61]. In these patients surgical lymph node staging, like in EBT for carcinoid, is lacking. The results of SBRT however, seem comparable. Therefore, small intraluminal typical and atypical tumors, without signs of extraluminal growth are good candidates for EBT, which is a less invasive treatment.