Currently, there is no consensus regarding the extent of surgery for stage I pulmonary carcinoid (PC) tumors, which encompass typical carcinoid (TC) and atypical carcinoid (AC) tumors. Sublobar resection includes segmental resection and wedge resection; the former is regarded as a type of anatomical resection that is better suited for tumor treatment. Therefore, it needs to be further verified whether differences exist in the effects of the two surgical methods on the survival time of patients. Propensity score matching (PSM) was used. The primary endpoints were cancer-specific survival (CSS) and overall survival (OS) time. Survival differences were analyzed via the Kaplan-Meier method and the log-rank test. There was no significant difference in survival between the sublobar resection and lobectomy groups after PSM in either the TC or AC tumor groups (all p > 0.05). A total of 1680 patients underwent pulmonary wedge resection (TC: n = 1547, AC: n = 133), and 398 patients underwent segmental resection (TC: n = 365, AC: n = 33). After PSM, there were no statistically significant differences in survival, regardless of whether OS or CSS was considered the primary endpoint (OS: p = 0.337; CSS: p = 0.470). Furthermore, segmental resection did not prolong patient survival time compared with wedge resection in different subgroup analyses on the basis of histology, age, and tumor size (all p > 0.05). Finally, the same results were obtained via multivariate Cox analysis (OS: p = 0.153; HR = 1.21; CSS: p = 0.351, HR = 1.32). Sublobar resection could be considered for patients with early-stage typical or atypical pulmonary carcinoid, provided that a rigorous lymph node evaluation is conducted. If the tumor is distant from the pulmonary hilum, either segmentectomy or wedge resection may be performed depending on the specific location of the tumor and the clinical condition of the patient.

Pulmonary carcinoid (PC) tumours typically have a good prognosis, although metastases occur, and the disease may progress after a long period of time. Expression of orthopaedia homeobox protein (OTP) has been recognized as a possible independent prognostic marker in PCs. Immunohistochemical (IHC) OTP expression has been associated with better prognosis, but the staining has yet to be implemented in routine clinical diagnostics. In response to this, two new monoclonal OTP antibodies were recently developed.This retrospective study included 164 PC patients operated on at Helsinki University Hospital between 1990 and 2020. Tissue microarray slides, prepared from formalin-fixed and paraffin-embedded primary tumour samples, were stained with OTP IHC using one polyclonal and two novel monoclonal antibodies.Absence of OTP expression was associated with a shorter disease-specific survival (DSS) and disease progression (p < 0.001). Patients without OTP expression had a 5-year DSS of 73-79%, whereas 5-year DSS was 91-94% with OTP expression, depending on the primary antibody. In a univariable Cox regression model, absence of OTP expression was associated with adverse outcome along with atypical histological subtype, metastatic disease, Ki-67 proliferation index > 1%, and larger tumour size. In a multivariable Cox regression model, only absence of OTP expression and lymph node involvement at the time of diagnosis were associated with risk of worse prognosis. All three antibodies showed good concordance with each other.Our findings support the role of OTP as an independent prognostic marker in PCs and applicability of IHC staining in routine clinical use with novel monoclonal antibodies.

The predictive value of the extent of peri-operative lymph node (LN) sampling in relation to disease relapse in patients with pulmonary carcinoid (PC) is unknown. Furthermore, post-surgery follow-up recommendations rely on institutional retrospective studies with short follow-ups. We aimed to address these shortcomings by examining the relation between LN sampling and relapse in a population-based cohort with long-term follow-up. By combining the Dutch nationwide pathology and cancer registries, all patients with surgically resected PC (2003-2012) were included in this analysis (last update 2020). The extent of surgical LN dissection was scored for the number of LN samples, location (hilar/mediastinal), and completeness of resection according to European Society of Thoracic Surgeons (ESTS) guidelines. Relapse-free interval (RFI) was evaluated using Kaplan Meier and multivariate regression analysis. 662 patients were included. The median follow-up was 87.5 months. Relapse occurred in 10% of patients, mostly liver (51.8%) and locoregional sites (45%). The median RFI was 48.1 months (95% CI 36.8-59.4). Poor prognostic factors were atypical carcinoid, pN1/2, and R1/R2 resection. In 546 patients LN dissection data could be retrieved; at least one N2 LN was examined in 44% and completeness according to ESTS in merely 7%. In 477 cN0 patients, 5.9% had pN1 and 2.5% had pN2 disease. In conclusion, relapse occurred in 10% of PC patients with a median RFI of 48.1 months thereby underscoring the necessity of long-term follow-up. Extended mediastinal LN sampling was rarely performed but systematic nodal evaluation is recommended as it provides prognostic information on distant relapse.

OBJECTIVE: The observation-based prognosis, rather than resection, for small carcinoid tumors is still unclear. This lack of clarity has important implications for counseling elderly patients or patients for whom surgical resection poses a high risk. This study compared the outcomes of observation and surgical resection in patients with pulmonary carcinoid (PC) tumors ≤3 cm in size without metastasis.
METHODS: Data of patients with PC tumors with ≤3 cm in diameter and without lymph node and distant metastases were retrieved from Surveillance, Epidemiology, and End Results (SEER) registry. To reduce the inherent bias of retrospective studies, propensity score matching analysis was performed. Overall survival (OS) and lung carcinoid-specific survival (LCSS) were analyzed using Kaplan-Meier plots. Multivariate analysis was used to determine predictors of LCSS in different size subgroups.
RESULTS: In total, 4552 patients with early-stage PCs ≤3 cm in diameter, including 435 (9.56%) who were observed and 4117 (90.44%) treated by surgery, were recruited. Patients with surgery had significantly better OS and LCSS than those who were observed. However, patients with observation had comparable LCSS to those with surgery for PCs with tumor diameters ≤1 cm. Multivariate analysis indicated that surgical resection was an independent prognostic factor for LCSS in 1 cm < tumors ≤2 cm, and 2 cm < tumors ≤3 cm groups, but not for tumors ≤1 cm in diameter.
CONCLUSIONS: Surgical resection of small PCs is associated with a survival advantage over observation. However, for early PCs ≤1 cm in diameter, observation may be considered in patients with high risk for surgical resection.

Pulmonary neuroendocrine tumors represent a spectrum of disease ranging from typical carcinoid tumors to small cell lung cancers. The incidence of low-grade pulmonary NETs has been increasing, leading to improved awareness and the need for more treatment options for this rare cancer. Somatostatin analogs continue to be the backbone of therapy and may be followed or accompanied by targeted therapy, chemotherapy, and immune therapy. The recent addition of peptide receptor radionuclide therapy (PRRT) to the treatment armamentarium of NETs has led to the development of targeted alpha therapy to overcome PRRT resistance and minimize off-target adverse effects. Herein, we aim to highlight current treatment options for patients with advanced low grade pulmonary NETs along with emerging therapies, sequencing of therapies, upcoming clinical trials, and the importance of a multidisciplinary team to improve patient outcomes.

UNASSIGNED: Orthopedia homeobox protein (OTP), highlighted as a sensitive and specific marker for pulmonary carcinoids, may provide a more objective criterion for subclassification.
UNASSIGNED: A total of 110 patients who underwent surgery for pulmonary carcinoids (2009-2019) were included. Gender, age, application complaint, tumor diameter and location, typical and atypical tumor type, lymph node involvement, stage, recurrence, and survival data were evaluated retrospectively with OTP nuclear staining.
UNASSIGNED: The sensitivity of OTP was 66.4%. OTP in subclassifying pulmonary carcinoids was not significant. There was no significant relationship between OTP and lymph node involvement, recurrence, and survival.
UNASSIGNED: OTP does not provide significant results in the subclassification of typical and atypical carcinoid tumors and the evaluation of recurrence and survival of carcinoid tumor cases.

BACKGROUND: Pulmonary carcinoids are rare, low-grade malignant tumors characterized by neuroendocrine differentiation and relatively indolent clinical behavior. Most cases present as a slow-growing polypoidal mass in the major bronchi leading to hemoptysis and pulmonary infection due to blockage of the distal bronchi. Carcinoid syndrome is a paraneoplastic syndrome caused by the systemic release of vasoactive substances that presents in 5% of patients with neuroendocrine tumors. Due to such nonspecific presentation, most patients are misdiagnosed or diagnosed late and may receive several courses of antibiotics to treat recurrent pneumonia before the tumor is diagnosed.
METHODS: We report the case of a 48-year-old male who presented with cough, dyspnea, a history of recurrent pneumonitis, and therapy-refractory ulcerative colitis that completely subsided after the resection of a pulmonary carcinoid.
CONCLUSIONS: We report and emphasize pulmonary carcinoid as a differential diagnosis in patients with nonresponding inflammatory bowel diseases and recurrent pneumonia.

To investigate the clinical efficacy of thermal ablation in the treatment of pulmonary carcinoid (PC) tumor.
Data of patients with inoperable PC diagnosed from 2000 to 2019 were obtained from the SEER database and analyzed according to different therapeutic modality: thermal ablation vs non-ablation. Propensity score matching (PSM) was used to reduce intergroup differences. Kaplan-Meier curves and the log-rank test were used to compare intergroup differences of overall survival (OS) and lung cancer-specific survival (LCSS). Cox proportional risk models were used to reveal prognostic factors.
After PSM, the thermal ablation group had better OS (p < .001) and LCSS (p < .001) than the non-ablation group. Subgroup analysis stratified by age, sex, histologic type and lymph node status subgroups showed similar survival profile. In the subgroup analysis stratified by tumor size, the thermal ablation group showed better OS and LCSS than those of the non-ablation group for tumors ≤3.0 cm, not statistically significant for tumors >3.0 cm. Subgroup analysis by M stage showed that thermal ablation was superior to non-ablation in OS and LCSS for patients with M0 stage, but no significant difference was found in subgroups with distant metastatic disease. Multivariate analysis showed that thermal ablation was an independent prognostic factor for OS (HR: 0.34, 95% CI: 0.25-0.46, p < .001) and LCSS (HR: 0.23, 95%CI: 0.12-0.43, p < .001).
For patients with inoperable PC, thermal ablation might be a potential treatment option, especially in M0-stage with tumor size ≤3 cm.

Pulmonary carcinoids (PCs) are part of a spectrum of well-differentiated neuroendocrine neoplasms (NENs) and are classified as typical carcinoid (TC) and atypical carcinoid (AC). TC differ from AC not only for its histopathological features but also for its \"functional imaging pattern\" and prognosis. ACs are more undifferentiated and characterized by higher aggressiveness. Positron emission tomography/computed tomography (PET/CT) with somatostatin analogs (SSA) labeled with Gallium-68 (68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE) has widely replaced conventional imaging with gamma camera using 111In- or 99mTc-labelled compounds and represents now the gold standard for diagnosis and management of NENs. In this setting, as already described for gastro-entero-pancreatic NENs, 18F-Fluorodeoxiglucose ([18F]FDG) in addition to 68Ga-SSA can play an important role in clinical practice, particularly for ACs that show a more aggressive behavior compared to TCs. The aim of this systematic review is to analyze all original studies collected from the PubMed and Scopus databases regarding PCs in which both 68Ga-SSA PET/CT and [18F]FDG PET/CT were performed in order to evaluate the clinical impact of each imaging modality. The following keywords were used for the research: \"18F, 68Ga and (bronchial carcinoid or carcinoid lung)\". A total of 57 papers were found, of which 17 were duplicates, 8 were reviews, 10 were case reports, and 1 was an editorial. Of the remaining 21 papers, 12 were ineligible because they did not focus on PC or did not compare 68Ga-SSA and [18F]FDG. We finally retrieved and analyzed nine papers (245 patients with TCs and 110 patients with ACs), and the results highlight the importance of the combined use of 68Ga-SSA and [18F]FDG PET/CT for the correct management of these neoplasms.

Typical (TC) and atypical carcinoids (AC) are the most common neuroendocrine tumors (NETs) of the lung. Because these tumors are rare, their management varies widely among Swiss centers. Our aim was to compare the management of Swiss patients before and after the publication of the expert consensus of the European Neuroendocrine Tumor Society (ENETS) in 2015. We used data from the Swiss NET registry from 2009 to 2021 with patients with TC and AC. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Overall, 238 patients were included, 76% (180) thereof with TC and 24% (58) with AC, including 155 patients before and 83 patients after 2016. An increase in the use of functional imaging was observed, 16% (25) before and 35% (29) after 2016, p < 0.001. The presence of SST2A-receptors was determined more often: 32% (49 times) before 2016 and 47% (39 times) after, p = 0.019. Concerning therapy, higher removal of lymph nodes after 2016 was observed, 54% (83) before versus 78% (65) after, p < 0.001. Median overall survival for patients with AC was significantly shorter, with 89 months compared to 157 months for patients with TC, p < 0.001. While the implementation of a more standardized approach was observed over the years, there is still room for amelioration in the management of TC and AC in Switzerland.