Bronchial Carcinoid Research Articles

Prognosis of Patients with Bronchopulmonary Neuroendocrine Neoplasms in a Tertiary Neuroendocrine Tumor Centre of Excellence

Introduction: The European Neuroendocrine Tumor Society (ENETS) reports variables of prognostic significance in bronchopulmonary neuroendocrine neoplasms (BP-NENs). The aim of this study was to investigate prognostic factors, recurrence-free survival (RFS), and overall survival (OS) for patients with typical carcinoid (TC), atypical carcinoid (AC), and large-cell neuroendocrine carcinoma (LCNEC). Current follow-up practices vary as the evidence is sparse, and we aimed to explore the relevance of routine bronchoscopy in follow-up. Methods: This was a cohort study of 208 patients with BP-NENs followed at Aarhus University Hospital in 2008–2019. RFS and OS were determined using the Kaplan-Meier method for the variables such as primary tumor, primary treatment, smoking status, gender, and histological subtypes. Results: The study included 153 patients with TC, 29 with AC, and 26 with LCNEC. Median follow-up was 48 months. The majority of patients (n = 191) received surgical resection, of which 22 (11%) recurred over time. Seventeen patients had nonsurgical treatment, of which 10 (59%) progressed. The 5-year OS rate was 86% for operated and 9% for nonoperated patients (p < 0.05). Patients with TC had a 5-year OS of 90% compared with 63% and 39% for AC and LCNEC, respectively. As for prognostic factors, nonsmokers did not secure a significant difference in OS compared with current/previous smokers (p = 0.51). In the follow-up period, only 2 (9%) of the 22 recurrences were found on a routine bronchoscopy. Both of these recurrences were also found by diagnostic imaging. Conclusions: Surgical treatment, especially, and diagnosis of TC were associated with a good prognosis. Furthermore, our data did not support routine bronchoscopy as part of a follow-up program for bronchial carcinoids.

Multifocal bronchial neuroendocrine tumor (bNET): A new clinical entity.

9135 Background: Bronchial carcinoid (BC) is often categorized into multifocal (MBC) or solitary (SBC). MBC, excluding tumorlet and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, is considered a relatively uncommon subgroup of BC, with much of the MBC literature stemming from case reports/small series. Our study analyzes MBC among a large cohort of 569 patients with BC and argues for change to the current clinical understanding of MBC. We suggest using the term bronchial neuroendocrine tumor (bNET) to more accurately represent its cells of origin and move away from “carcinoid” (historically meaning “carcinoma-like”) and the outdated associated connotation that carcinoids all have a similar, benign clinical and biological behavior. Methods: Using the Mayo Clinic Epidemiology and Genetics of Lung Cancer Database with Institutional Review Board approval, we retrospectively reviewed 569 patients with bNET (204 males, 365 females) presenting to Mayo Clinic Rochester between 1/1997-12/2012. We used univariate and multivariate Cox regression analyses to evaluate factors affecting overall survival. Results: 80 patients (of 569, 14.1%) were diagnosed with multifocal (MbNET) and 489 with solitary (SbNET). Two-sided Fisher’s exact tests found that older age, female gender, never having smoked cigarettes, and tumorlets were associated with MbNET diagnosis. Family lung cancer history, histopathologic grading (pathology: typical vs. atypical), Ki67, and presence of syndromes (carcinoid, Cushing, and MEN1 syndromes) were similar between MbNET and SbNET groups. Most MbNET cases were stage III-IV at the time of diagnosis, while the majority of SbNET cases were stage I. 5-year OS (83%) and 5-year PFS (75%) of MbNET patients were higher than those of their SbNET counterparts (74% and 68%, respectively). Metastasis status was an independent prognostic factor of poor OS in SbNET (P&lt;0.001) but not in MbNET (P=0.71)(Table). Conclusions: Clinical, radiologic, and histopathologic characteristics and prognostic factors differed between SbNET and MbNET. MbNET arose as a new entity often with advanced stage disease, but good prognosis, which does not follow the NSCLC TNM staging system as in the 2009 NCCN guidelines (used during this study) or the updated 2021 NCCN guidelines which continue to stage lung carcinoid similarly to NSCLC. It may be beneficial to consider multifocal lung carcinoid instead as multifocal bNET, a new clinical entity, warranting a novel staging approach that more accurately reflects prognosis.[Table: see text]

Psychotic symptoms in Cushing’s syndrome secondary to ACTH-secreting lung carcinoid tumor: report of a case

IntroductionCushing’s syndrome is a hormonal disorder caused by chronic exposure to excess glucocorticoids, either exogenous or endogenous. The bronchial carcinoid tumor is an extremely rare origin, described in less than 1% of cases. The most frequent psychiatric symptoms are depression and anxiety, with manic and psychotic symptoms being less frequent. Psychotic symptoms are difficult to manage, as they are usually resistant to antipsychotic treatment, which is why it is considered an indication for medical treatment of Cushing’s syndrome.ObjectivesTo give visibility to this type of psychotic disorders of organic origin to deepen their study as well as raise awareness among professionals dedicated to clinical care with the intention of improving their prevention.MethodsA description of a clinical case is made, accompanied by a bibliographic review on psychosis of endogenous corticosteroid origin.ResultsWe describe the case of a 44-year-old woman who was admitted to the charge of Internal Medicine due to Cushing’s syndrome. During her admission, she presented a debut of positive psychotic symptoms, so the liaison psychiatry team followed her up. She was diagnosed with an ACTH-secreting lung carcinoid tumor.ConclusionsThis entity should be taken into account in cases of atypical psychosis in patients with compatible phenotypic characteristics.DisclosureNo significant relationships.

Avelumab in unresectable/metastatic, progressive, grade 2–3 neuroendocrine neoplasms (NENs): Combined results from NET-001 and NET-002 trials

BackgroundHigher grade neuroendocrine neoplasm (NENs) continues to pose a treatment dilemma, with the optimal treatment undefined. Although immunotherapy has revolutionised the treatment of many cancers, its role in NENs remains unclear. We aimed to investigate the efficacy and safety of avelumab, a PD-L1-directed antibody, in patients with advanced unresectable/metastatic higher grade NENs. MethodsNET001 and NET002 are phase II studies investigating avelumab (NCT03278405 and NCT03278379). Eligible patients had unresectable and/or metastatic WHO G2-3 NENs from a gastroenteropancreatic (GEP) source or a bronchial primary (excluding typical carcinoid) and 0–2 prior lines of systemic therapy (excluding SSAs). Patients were treated with avelumab 10 mg/kg intravenously every two weeks for 26 cycles. NET001 investigated G3 poorly differentiated GEP neuroendocrine carcinomas (NECs) and bronchial small/large cell NEC, whereas NET002 investigated G2-3 well-differentiated GEPNETs and bronchial atypical carcinoids. The primary endpoint in both trials was overall response rate (ORR) by RECIST v1.1; secondary endpoints included progression-free survival, overall survival, disease control rate at six months and toxicity. ResultsTwenty-seven patients were enrolled (21 GEP, 6 lung; 10 in NET-001, 17 in NET-002); median age 64 (range 37–80), 30% ECOG PS 1–2 and 78% received 1+ lines of prior therapy. The median Ki-67 index was 35% (range 10–100). Twelve of the twenty-seven patients had died at the time of data lock. The median time on treatment was 85 days (seven cycles). No objective responses were observed. Stable disease was achieved in 33% of patients, and the disease control rate at 6 mo was 21%. The median PFS was 3.3 months (range 1.2–24.6), and the median OS was 14.2 months. Treatment-related adverse events (all grades) occurred in 58% of patients. Three patients had treatment-related grade 3–4 AEs leading to treatment discontinuation (immune-related hepatitis n = 2 and infusion-related reaction n = 1). ConclusionSingle-agent PD-L1 blockade with avelumab showed limited antitumour activity in patients with G2-3 NENs. Correlative studies are underway. Further studies are needed to explore the role of dual immunotherapy and other combinations in this population with few treatment alternatives.

Paraneoplastisch syndroom van Cushing

Paraneoplastic Cushing’s syndrome Introduction. Paraneoplastic Cushing’s syndrome (ECS) is a rare condition which is related to an ectopic adrenocorticotropic hormone (ACTH) or, rarely, corticotropin-releasing hormone (CRH) production. Diverse tumours can cause ECS; small-cell lung cancer (SCLC) and bronchial carcinoids account for the majority of the cases. In this report, the medical history of a patient with ECS due to SCLC is presented. The main purpose of this case-report is to outline the difficult clinical presentation. Case description. A 72-year-old cachectic man was diagnosed with SCLC. The coexistence of hypokalemia and hyperglycemia raised the suspicion of ECS, which was confirmed by high levels of plasma cortisol, plasma ACTH and urinary cortisol. Discussion. The diagnostic process of Cushing’s syndrome is outlined. Conclusion. The diagnosis of ECS can be challenging since typical clinical symptoms may be absent. Hypokalemia or hyperglycemia in a context of SCLC or a neuro-endocrine tumour (NET) should prompt further evaluation with determination of the plasma cortisol and ACTH.

Haemorrhage post biopsy of a bronchial carcinoid

Background: Bronchial carcinoid tumours are rare, indolent, malignant neuroendocrine tumours derived from Kulchitsky cells and are not related to smoking. As these tumours can be asymptomatic or present with nonspecific symptoms, a high index of suspicion is essential to make an early diagnosis which determines the prognosis. Surgery is curative and remains the mainstay of treatment.&#x0D; Case presentation: A 41-year-old female with no background medical illness first presented with a spontaneous left sided pneumothorax requiring a chest tube insertion. High-resolution CT (HRCT) thorax detected an incidental solitary pulmonary nodule. Bronchoscopy revealed a smooth round tumour sitting at the ostium of the basal right lower lobe bronchus. Endobronchial biopsy was complicated with massive bleeding requiring emergency exploration via rigid bronchoscopy. Multiple attempts to secure haemostasis using Watanabe spigot and argon plasma coagulation failed. She was intubated with a double lumen tube to isolate the healthy left lung. An urgent CT pulmonary angiogram (CTA) was performed to look for collaterals and feasibility of embolization, but no collaterals were seen. She was then referred to the cardiothoracic surgeon for an emergency right lobectomy. Histopathological examination revealed typical carcinoid tumour. She was discharged from the hospital in a stable condition.&#x0D; Discussion: Bronchial carcinoids embryologically originate from the foregut and patients rarely present with features suggestive of carcinoid syndrome and crisis. Mostly are asymptomatic resulting in late presentation and diagnosis. Majority of the typical carcinoids are centrally located and may present with obstructive symptoms and recurrent pneumonia. Bronchoscopists may face massive bleeding following endobronchial biopsy in bronchial carcinoids.&#x0D; Conclusion: Massive bleeding after endobronchial biopsy can occur and therefore the bronchoscopist should have anaesthesia, interventional radiology, and cardiothoracic support to handle this complication. Using tumour markers may obviate the need for biopsy in typical bronchial carcinoids to prevent massive bleeding after endobronchial biopsy.&#x0D;

Combined use of 177 Lu-DOTATATE peptide receptor radionuclide therapy and fluzoparib for treatment of well-differentiated neuroendocrine tumors: A preclinical study.

Peptide receptor radionuclide therapy (177 Lu-DOTATATE) causes DNA strand breaks and has been validated for well-differentiated neuroendocrine tumor treatment. Poly-(ADP-ribose)-polymerase inhibitors have also been used for malignant tumors with deficient DNA repair. We aimed to determine whether the poly-(ADP-ribose)-polymerase inhibitor fluzoparib could enhance the anti-tumor effects of 177 Lu-DOTATATE in neuroendocrine tumor cells and xenografts. The neuroendocrine characteristics of NCI-H727 bronchial carcinoid cells were evaluated by immunofluorescence staining. The synergistic effects of fluzoparib and 177 Lu-DOTATATE were evaluated by cell proliferation and flow cytometry assays. Tumor response and the side effects of combination therapy were also assessed in xenograft mice treated with 77 Lu-DOTATATE and fluzoparib alone or in combination. Somatostatin receptors were specifically expressed in NCI-H727 cells and tumor xenografts. 177 Lu-DOTATATE (22.20MBqmL-1 ) and fluzoparib (50µm) inhibited cell proliferation by 16.6% and 35.6%, respectively, compared to 73.2% in cells treated with their combination. Tumor cell proliferation was significantly suppressed by 177 Lu-DOTATATE (22.20MBqmL-1 , 4.4-fold) and fluzoparib (50µm, 2.1-fold). 177 Lu-DOTATATE caused cell cycle arrest mainly at G1 phase, whereas fluzoparib caused arrest at G2/M phase, and combined treatment with both agents caused cell cycle arrest at G1 phase, similar to 177 Lu-DOTATATE alone. The volume of tumor xenografts was reduced by 18.6% in mice receiving combined treatment, compared to 4.9% and 11.4% in mice treated with 177 Lu-DOTATATE or fluzoparib alone. Fluzoparib can potentiate the anti-tumor effect of 177 Lu-DOTATATE in NCI-H727 cells in a synergistic manner by arresting the cell cycle at G1 phase. Further preclinical and clinical studies are warranted to validate these findings.

Bronchial Carcinoids: From Molecular Background to Treatment Approach.

Simple SummaryBronchial carcinoids (BCs) are uncommon and usually slow growing neuroendocrine epithelial malignancies that represent less than 2% of all lung cancers. Differences in the extent of molecular alterations between neuroendocrine carcinomas and BCs may underline the differences in the aggressiveness of these lesions. Moreover, although atypical BCs and typical BCs have similar set of mutations, some differential molecular and genetic alterations have been described between these two entities. A better understanding of the genetic and molecular background of BCs would allow a better selection of medical treatments in these patients. Regarding treatment, most BCs can be cured by surgery; however, inoperable tumors are mostly insensitive to chemotherapy and radiotherapy. In advanced BCs, the only drug that has a positive phase III clinical trial in BCs is everolimus. Somatostatin analogues constitute the gold standard for symptomatic relief. Peptide receptor radionuclide therapy has been associated with longer progression free. The efficacy of other treatments such as antiangiogenic agents and immunotherapy is still not established.A better understanding of the genetic and molecular background of bronchial carcinoids (BCs) would allow a better estimation of the risk of disease progression and the personalization of treatment in cases of advanced disease. Molecular studies confirmed that lungs neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) are different entities; thus, no progression of NET to NEC is expected. In BCs, MEN1 gene mutations and deletions and decreased gene expression have been associated with a poor prognosis. ATRX mutation has also been linked to a shorter disease-specific survival. In terms of therapeutic targets, PI3K/AKT/mTOR pathway mutations have been described in 13% of typical carcinoids (TCs) and 39% of atypical carcinoids (ACs), representing a targetable mutation with kinase inhibitors. Regarding treatment, surgical resection is usually curative in localized BCs and adjuvant treatment is not routinely recommended. Multiple options for systemic therapy exist for patients with advanced BCs, although limited by a heterogeneity in the scientific evidence behind their use recommendation. These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor.

SURGICAL APPROACH OF LUNG CARCINOID TUMORS.

Bronchial carcinoid tumours (typical and atypical carcinoid) are endobronchial tumours that can benefit from both local endobronchial treatment and surgical treatment. Given their relatively good prognosis compared to the other two forms of pulmonary neuroendocrine tumours, there is a current concern about the implications of lymph node involvement as well as the identification of new prognostic factors to shape the treatment of these patients in the future.

Correction: Next-generation multimodality of nutrigenomic cancer therapy: sulforaphane in combination with acetazolamide actively target bronchial carcinoid cancer in disabling the PI3K/Akt/mTOR survival pathway and inducing apoptosis

[This corrects the article DOI: 10.18632/oncotarget.28011.].

Endobronchial resection as a bridge to curative resection in patient with poor preoperative lung function secondary to an airway blocking endobronchial carcinoid tumour

We present a 70-year-old gentleman with chronic cough with haemoptysis found to have left lower zone collapse on imaging. The bronchoscopy showed an endobronchial mass histologically of a non-secreting atypical carcinoid. Poor baseline lung function excluded surgical resection, and instead, he successfully underwent a bronchoscopic debulking procedure which improved his FEV1 to 84% and DLCO 83% predicted. Unfortunately, the tumour regrew, but the calculated percentage predicted postoperative for FEV1 (64%), and DLCO (65%) enabled definitive surgical resection to take place. Surgical resection remains the definite curative option for localised endobronchial atypical carcinoid tumours. Achieving this in proximal endobronchial carcinoid tumour is a challenge. We described an endoscopic tumour debulking procedure as a bridge for curative surgical resection in a patient with an inoperable proximal atypical carcinoid tumour due to poor predicted postoperative lung function. We highlighted the need to assess predicted postoperative lung function with functional and quantitative perfusion methods to aid surgical planning. Debulking the tumour by endoscopy can be used as a conduit to curative surgical resection in bronchial carcinoid tumour. The choice of calculating the percentage predicted values by either or both methods must be individualised based on tumour location and the probability of converting a lobectomy to a pneumonectomy. This precautionary approach could evaluate the postoperative lung function and morbidity and mortality risk if considering a pneumonectomy. Endoscopic debulking can be a successful bridge to a curative surgical resection aided by comprehensive preoperative lung function tests to predict postoperative lung values

Ектопічний АКТГ-синдром Кушинга, обумовлений бронхіальним карциноїдом

У статті висвітлено поняття ектопічних АКТГ-пухлин нейроендокринної системи. Описано рідкісний випадок ектопічного АКТГ-синдрому Кушинга, зумовленого бронхіальним карциноїдом, у клініці якого, поряд з типовою симптоматикою, домінував тромбоемболічний синдром. Хірургічне видалення бронхіального карциноїда призвело до регресу кушингоїдної та іншої симптоматики.

M131 DIAGNOSIS OF A BRONCHIAL CARCINOID TUMOR IN A PATIENT WITH RECENT DYSPNEA AND WHEEZING

Bronchial carcinoid tumors are the second most common tumors of the tracheobronchial tree, accounting for 2%-5% of pulmonary neoplasms. Patients can present with acute or chronic respiratory symptoms or can be asymptomatic with the tumor being found incidentally.

P8‐135: Typical bronchial carcinoid tumor: A case report

P8‐135: Typical bronchial carcinoid tumor: A case report

P66.04 A Multimodal Biomarker Predicts Dissemination of Bronchial Carcinoid

Endobronchial treatment (EBT) for selected patients with bronchial carcinoids is gaining popularity. Currently, therapeutic decision making is mainly based on tumor morphology and patient characteristics. However, differentiation between prognostic favorable and unfavorable bronchial carcinoid tumors is essential for therapeutic decision making between EBT or surgery. Alternatives for subdivision of TC and AC into prognostic relevant categories are therefore desired. This study defined prognostic factors for patients with bronchial carcinoid tumors.

RARE PRESENTATION OF DISSEMINATED TB: MULTIPLE RING ENHANCING LESIONS IN BRAIN

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Cerebral tuberculomas is a rare form of extrapulmonary tuberculosis (TB). Due to lack of tests available for confirmatory diagnosis, the diagnosis is difficult. However, missing the diagnosis could lead to catastrophic consequences. Here, we report a case of disseminated tuberculosis presented with multiple ring enhancing lesions in the brain. CASE PRESENTATION: A 75-year-old male presented with progressive generalized weakness associated with fever and chills for 3 weeks. He has a history of bronchial carcinoid tumor status post radiation therapy, Waldenstrom's macroglobulinemia, heart failure with reduced ejection fraction, implantable cardiac defibrillator placement, coronary artery disease, stroke, and type 1 diabetes. He appeared tired with mild symmetrical lower limb weakness, but there were no meningeal signs. CT of head revealed innumerable ring-enhancing lesions in both cerebrum, cerebellum and brainstem. Analysis of cerebrospinal fluid (CSF) showed lymphocyte predominant pleocytosis (WBC of 253/cumm), elevated protein (155 mg/dl) with low glucose ratio (CSF/serum glucose ratio of 0.4). Empirical treatment for meningitis were started, but intermittent spiking fever persisted. Unfortunately, the patient had a cardiac arrest while he was undergoing brain MRI. Postmortem autopsy revealed multiple necrotizing granulomatous nodules with AFB positive bacteria in multiple organs, including brain, lung, liver, spleen, thyroid, pulmonary and extrapulmonary lymph nodes. Mycobacterium tuberculosis complex was isolated from CSF subsequently. A diagnosis of disseminated TB was made. Upon further investigation, the patient did not have exposure history, except for travelling around the globe when he was young. DISCUSSION: The differential of multiple ring-enhancing lesions in the brain is broad, which include neurocysticercosis, toxoplasmosis, cryptococcosis, bacterial abscess, CNS lymphoma and cerebral metastases. Given the complicated medical history of our patient and lack of risk factor for TB, empirical treatment for TB was not given. In such a clinical scenario, a more sensitive test, e.g. nucleic acid amplification (NAA), would be the deciding factor for initiation of therapy. Unfortunately, there is a lack of data to support the use of NAA in patients at risk for cerebral tuberculoma. Future studies would be warranted to explore the use of NAA in the setting of extra-pulmonary tuberculosis. CONCLUSIONS: Disseminated tuberculosis is a lethal disease if missed. However, diagnosis of disseminated tuberculosis remains a huge challenge, especially when pulmonary symptoms are absent. A high index of suspicion is required to diagnose and treat disseminated tuberculosis. More researches are warranted to expedite the diagnosis of TB. REFERENCE #1: Suárez I, Fünger SM, Jung N, et al. Severe disseminated tuberculosis in HIV-negative refugees. Lancet Infect Dis 2019; 19: e352–e359. REFERENCE #2: Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis 2017; 64:e1–33. DISCLOSURES: No relevant relationships by Gin Yi Lee, source=Web Response No relevant relationships by Kaiqing Lin, source=Web Response No relevant relationships by Guangchen Zou, source=Web Response

Case Report: Rare Cause of Hemoptysis in A Young Person

Introduction: Hemoptysis is an emergency, its diagnosis is often made on questioning, it must lead to rigorous etiological research. The thoracic CT angiography makes it possible to specify the exact mechanism and therefore to adapt the management. Observation: We report the case of a 20-year-old patient, with no particular pathological history, admitted for low-abundance hemoptysis that has progressed for 6 months. A thoracic CT angiography was performed showing a mediastino-pulmonary lesion process centered on the left lower lobe bronchus. Bronchoscopy with biopsy and pathological examination was indicated and demonstrated the presence of a bronchial carcinoid tumor. The patient underwent a lower left lobectomy, the operative consequences were simple, the patient was discharged after 10 days of hospitalization. Conclusion: Patients with recurrent respiratory symptoms should be carefully examined with chest CT and bronchoscopy followed by tissue biopsy for an accurate and early diagnosis.

Cyclic ectopic Cushing'ssyndromedue to bronchial carcinoid tumor: diagnostic challenge

Cyclic ectopic Cushing'ssyndromedue to bronchial carcinoid tumor: diagnostic challenge

Next-generation multimodality of nutrigenomic cancer therapy: sulforaphane in combination with acetazolamide actively target bronchial carcinoid cancer in disabling the PI3K/Akt/mTOR survival pathway and inducing apoptosis.

Objective: Aberrations in the PI3K/AKT/mTOR survival pathway in many cancers are the most common genomic abnormalities. The phytochemical and bioactive agent sulforaphane (SFN) has nutrigenomic potential in activating the expression of several cellular protective genes via the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 is primarily related to mechanisms of endogenous cellular defense and survival. The efficacy of SFN in combination with acetazolamide (AZ) was investigated in reducing typical H727 and atypical H720 BC survival, migration potential, and apoptosis in vitro and in vivo preclinical xenograft tissues.Materials and Methods: Microscopic imaging, immunocytochemistry, wound healing assay, caspase-cleaved cytokeratin 18 (M30, CCK18) CytoDeath ELISA assay, immunofluorescence labeling assays for apoptosis, hypoxia, Western Blotting, Tunnel assay, measurement of 5-HT secretion by carbon fiber amperometry assay, quantitative methylation-specific PCR (qMSP), morphologic changes, cell viability, apoptosis activity and the expression levels of phospho-Akt1, Akt1, HIF-1α, PI3K, p21, CAIX, 5-HT, phospho-mTOR, and mTOR in xenografts derived from typical H727 and atypical H720 BC cell lines.Results: Combining AZ+SFN reduced tumor cell survival compared to each agent alone, both in vitro and in vivo xenograft tissues. AZ+SFN targeted multiple pathways involved in cell cycle, serotonin secretion, survival, and growth pathways, highlighting its therapeutic approach. Both H727 and H720 cells were associated with induction of apoptosis, upregulation of the p21 cell cycle inhibitor, and downregulation of the PI3K/Akt/mTOR pathway, suggesting that the PI3K/Akt/mTOR pathway is a primary target of the AZ+SFN combination therapy.Conclusions: Combining SFN+AZ significantly inhibits the PI3K/Akt/mTOR pathway and significantly reducing 5-HT secretion in carcinoid syndrome.

Treatment of Pulmonary Carcinoid Tumors With Bronchoscopic Cryotherapy: A 28-Year Single-center Experience.

Pulmonary carcinoids are rare tumors originating from neuroendocrine cells in the lungs. Because of their potentially infiltrative nature, surgical resection remains the treatment of choice. However, not all patients with technically resectable disease will be able to undergo surgery, primarily because of poor lung function or medical co-morbidities. Centrally located, intraluminal tumors have been reported to be amenable to bronchoscopic treatment. We specifically examined the role of cryotherapy in the treatment of bronchial carcinoid tumors. Sixty-three patients (52.38% female) who underwent a combined total of 243 cryotherapy procedures for treatment of bronchial carcinoid between 1992 and 2020 in our institution were included in the study. Following discussion in multidisciplinary meetings, patients were considered for first-line cryotherapy when lung resection was deemed not possible or when they had rejected surgery. Cryotherapy resulted in complete remission in 21 (33.33%) patients with maximum tumor diameter less than 20 mm (mean: 11.08 mm, 95% confidence interval: 8.76-13.40), and allowed 22 (34.92%) patients with larger lesions (mean: 24.04 mm, 95% confidence interval: 18.78-29.30) to proceed with parenchymal sparing resections. Marked symptomatic relief (P<0.001) was reported by 58 (92.06%) patients. The median follow-up was 33 months (range: 0 to 243 mo). One (1.59%) patient was diagnosed with recurrence in a contralateral lobe 3 years after surgery and was treated with radiofrequency ablation. In the absence of a definitive randomized controlled trial comparing bronchoscopic treatment with surgical resection, we provide evidence on the safety and efficacy of cryotherapy and encourage wider adoption of this inexpensive and minimally invasive technique for treatment of bronchial carcinoids.