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Treatment of carcinoid tumors. Proposed algorithm based on the type and stage of the tumor.
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Elise Noel-Savina,1 Renaud Descourt2 1Pulmonary Service, 2Thoracic Oncology Service, Hospital de la Cavale Blanche, CHU – Brest, Brest, France Abstract: Bronchial typical carcinoid tumors are neuroendocrine bronchopulmonary tumors with a low-grade malignancy, and an atypical carcinoid is an intermediate form of these tumors. There is a lack of know...
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Context 1
... therapy could be used in this indication, but there is a lack of studies to recommend these therapies. The treatment depends on the type of carcinoid tumor (typical or atypical), the presence of hepatic metas- tasis (local treatment) or extrahepatic metastasis, and the operability of the patient (Figure 1). ...
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Citations
... However, this task becomes a difficult task when considering abnormal CT images such as the CT scans of NSCLC patients. Therefore, lung segmentation could be a challenge in many studies about lung diseases [8,35,26]. ...
Lung segmentation is an initial step to provide accurate lung parenchyma in many studies on lung diseases based on analyzing the Computed Tomography (CT) scan, especially in Non-Small Cell Lung Cancer (NSCLC) detection. In this work, Coordinate-UNet 3D, a model inspired by UNet, is proposed to improve the accuracy of lung segmentation in the CT scan. Like UNet, the proposed model consists of a contracting/encoder path to extract the high-level information and an expansive/decoder path to recover the features to provide the segmentation. However, we have considered modifying the structure inside each level of the model and using the Coordinate Convolutional layer as the final layer to provide the segmentation. This network was trained end-to-end from a small set of CT scans of NSCLC patients. The experimental results show the proposed network can provide a highly accurate segmentation for the validation set with a Dice Coefficient index of 0.991, an F1 score of 0.976, and a Jaccard index (IOU) of 0.9535.
... 1,2 Less than 1% of all pulmonary tumors are carcinoid tumors. 3 Only 1%-5% of bronchopulmonary carcinoids produce ACTH. 4 Another study specifically reporting on resected pulmonary carcinoids, 24.8% of tumors produced ACTH, and 17.4% of those tumors were associated with Cushing's syndrome. 5 Carcinoid tumors are highly sensitive to detection by somatostatin receptor scintigraphy (SRS) because of the high expression of somatostatin receptors, but some cases may go undetected. ...
Background:
Carcinoid tumors can on rare occasions ectopically produce adrenocorticotropic hormone (ACTH), causing Cushing's syndrome, and patients could become immunocompromised. Care must therefore be taken regarding infectious complications. In particular, ACTH-producing pulmonary carcinoid is not easy to diagnose by itself, and when combined with pulmonary nodules as infectious foci, each is very difficult to diagnose.
Case:
The patient was a 71-year-old woman with refractory diabetes. She showed clinical symptoms of Cushing's syndrome during treatment for diabetes and ectopic ACTH production was suspected based on biochemical and imaging tests. Nodules were identified in the left lung apex and lingual segment. Examination of resected nodules revealed that the nodule in the apex was pulmonary cryptococcosis, while the nodule in the lingual segment represented typical carcinoid. After surgery, clinical symptoms, laboratory findings, and diabetes all improved.
Conclusion:
We present this very instructive case in terms of the difficulty of diagnosing ACTH-producing tumors, the possibility of infection complicating the immunodeficiency caused by ACTH-producing tumors, and the surgical strategy.
... The use of cytotoxic agents as adjuvant therapy is mixed and highly debated among clinicians. While guidelines state the use of adjuvant therapy may be appropriate in certain cases, there are a lack of high-quality data due to the rarity of the disease [6]. While there is some evidence for treatment of aggressive metastatic pulmonary carcinoid, the evidence for use after surgical resection is lacking [7]. ...
Pulmonary carcinoid tumors are a rare subtype of neuroendocrine cell tumor found in approximately 1–2% of lung cancers. Management is primarily through surgical resection, with limited benefit of adjuvant therapy in the clinical setting. Genomic profiling is in the nascent stages to molecularly classify these tumors, but there are promising insights for future targeted therapy. A total of 80 abstracts were analyzed for further review with 11 included in our final analysis. Only 4 of the 11 reviewed in depth provided statistical analysis. We evaluated PFS, OS, 1- and 5-year survival as mentioned in the studies. Nodal and KI67 status were also analyzed. Based on the current literature, there is no definitive evidence that adjuvant chemotherapy after resection confers a survival benefit in typical or atypical carcinoids.
... Functioning NENs cause clinical symptoms of secreted hormones, and both functioning and nonfunctioning tend to present late with nonspecific symptoms that are attributed to differential diagnosis. The symptoms of lung NENs are chronic cough, chest pain, dyspnea, hemoptysis, fever, unilateral wheezing, and recurrent infections [13]. Lung NENs may be a source of ectopic adrenocorticotropic hormone (ACTH) production and may be diagnosed as unexplained Cushing syndrome [14]. ...
Introduction. Neuroendocrine neoplasms are rare heterogeneous malignancies that may occur in almost any organ in the body. These neoplasms are associated with a wide range of clinical and pathophysiological manifestations. Case Report. A 67-year-old female patient, non-smoker with a history of rheumatoid arthritis and osteoporosis, visited her general practitioner complaining of back pain, heart palpitations, and change in stool consistency. Physical examination revealed multiple subcutaneous nodules in the neck and chest area that were painful to touch. Due to suspected hyperthyroidism, she was referred to an endocrinologist. The ultrasound of the thyroid gland showed multiple cysts in the right lobe and a nodule in the left lobe of the thyroid gland. Laboratory tests showed elevated calcitonin and carbohydrate antigen levels. Based on the assumption that medullary thyroid carcinoma was the most likely diagnosis, she was referred to the Nuclear Medicine Department of the Oncology Institute of Vojvodina. A fine-needle aspiration biopsy of the left thyroid nodule was done and thyroid malignancy was excluded. By histopathological analysis of the enlarged right chest lymph node and a skin lump on the left loin, a lung cancer with neuroendocrine morphology with positive neuroendocrine markers was diagnosed. Computed tomography revealed a tumor infiltrating the left hilum with metastases. Conclusion. Skin metastases of neuroendocrine neoplasms are rare and may occur in any part of the human body. They may develop before the primary tumor is recognized and are associated with disseminated malignancy. Diagnosis and treatment are important to control the disease and improve the quality of life of patients.
... Karsinoid tanımı ilk olarak gastrointestinal trakt için kullanılmış olup, daha sonra akciğerler için de tanımlanmıştır. Gastrointestinal traktan sonra lokalizasyon açısından nöroendokrin tümörler ikinci sıra olarak akciğerlerde olup, akciğer tümörlerinin %1 ini kapsamaktadır (33). Nöroendokrin tümörler rölatif benign karsinoid olarak görülebildiği gibi aşırı agresif küçük hücreli akciğer kanserleri olarak da görülebilir. ...
Paraneoplastiksendrom; primer tümöre veya metastazlarına ait bir etki sebebi ile oluşmayan ancak tümörün varlığına bağımlı olarak gelişen belirti ve bulgulardan oluşan klinik tablo olarak adlandırılır. Paraneoplaziler varlığı bilinen bir tümörün seyri sırasında görülebildiği gibi, klinik olarak ortaya çıkmamış gizli bir tümörün ilk ve tek belirtisi olabilir ve bu sayede primer kanserin erken evrede tanınmasına yardımcı olabilmektedir. Akut febrilnötrofilik dermatoz olarak da bilinen Sweet Sendromu; ani başlangıçlı, ağrılı, inflamatuvar papül veya nodüllerden oluşmuş eritemli plaklar, ateş, eklem ağrısı, periferiklökositoz ve cildin dermis tabakasında yoğun nötrofil infiltrasyonu ile karakterize nadir görülen tekrarlayan inflamatuvar bir cilt hastalığıdır. Hastalık; inflamatuar bağırsak hastalığı, enfeksiyonlar, ilaçlara sekonder, malignite yesekonder (paraneoplastik) olarak gözlemlenebilmektedir.Bu yazımızda akut gelişen döküntü ve ateş şikayetleri ile başvurduğu hastanede Sweet Sendromu ön tanısı ile interne edilen yapılan etyolojik araştırmasında metastatik akciğer karsinoid tümör tanısı konulan 69 yaşında erkek hasta ile ilgili bir olgu sunmayı amaçladık.
... (Ann Thorac Surg 2019;108:859-65) Ó 2019 by The Society of Thoracic Surgeons T ypical carcinoids (TC) of the lung are low-grade tumors characterized by a neuroendocrine morphology and differentiation. 1 They are rare and indolent, with a low rate of lymph node and distant metastases at presentation (5% to 15% and 3%, respectively), limited rate of recurrence after surgical resection (2% to 9%), and excellent long-term survival (5-year survival rate more than 90% after surgery). [2][3][4] According to the National Comprehensive Cancer Network guidelines, the standard of care for pulmonary TC is anatomic resection, but their optimal operative management is still debated. 5 For TC that are predominantly endoluminal and confined to the airway there is a general consensus that treatment with a bronchial sleeve resection with negative margins, with the aim of sparing lung tissue, is an acceptable oncologic operation. ...
Background:
The role of sublobar resection in the treatment of pulmonary typical carcinoids is controversial. This study aims to compare long-term outcomes between sublobar and lobar resections in patients with peripheral typical carcinoid.
Methods:
We retrospectively compared consecutive patients who underwent curative sublobar resection with patients who underwent lobectomy for cT1-3 N0 M0 peripheral pulmonary typical carcinoid in eight centers between 2000 and 2015. Primary outcomes were rates and patterns of recurrence and overall survival. Cox regression modeling was performed to identify factors influencing overall survival and recurrence. Propensity score analysis was done, and overall survival was compared between the two groups.
Results:
In all, 177 patients were analyzed, consisting of 74 sublobar resections and 103 lobectomies, with a total of 857 person-years of follow-up. The R1 resection rates were 7% and 1% after sublobar resection and lobectomy, respectively (P = .08). One of 5 patients with sublobar R1 resection had recurrence. Recurrence rate was 0.02 (95% confidence interval [CI]: 0.009 to 0.044) per person-year of follow-up after sublobar resection and 0.008 (95% CI: 0.003 to 0.02) after lobectomy (P = .15). Five-year survival rates were 91.7% (95% CI: 78.5% to 96.9%) and 97.4% (95% CI: 90.1% to 99.4%) after sublobar and lobar resection, respectively (P = .08). Extent of resection was not a predictor of recurrence or survival. Propensity score analysis confirmed a similar survival and freedom from recurrence between the two groups.
Conclusions:
Sublobar resection of peripheral cT1-3 N0 M0 pulmonary typical carcinoid was not associated with worse short- or long-term outcomes compared with lobectomy. In select patients, sublobar resection may be considered for treatment of peripheral typical carcinoids if an R0 resection is obtained.
... While these cancers are grossly defined, they lack a molecular phenotype. Treatment for lung cancers also depends on the type and severity of the disease and generally include surgery, chemotherapy, and radiation therapy [89][90][91]. However, several have suggested that lung cancer treatment would benefit from clearly defining molecular phenotypes [92][93][94]. ...
Standard methods for detecting cancer-associated genes rely on comparison of sample means between cancer patients and healthy controls. While such methods have successfully identified several oncogenes and tumor suppressor genes, they neglect to account for heterogeneity within the cancer population. Genetic mutations, translocations, and amplifications are often inconsistent across tumors, and instead they often affect smaller subsets of patients. This concept gives rise to the idea of bimodally expressed genes, or genes that display two modes of expression within one population. Analysis of bimodal gene expression has been explored via a variety of techniques including test statistics and clustering. In this review, we summarize the methodologies used to quantify bimodal gene expression and address the utility of these genes in patient stratification and specialized therapeutics in breast and lung cancer. Finally we discuss the limitations and future directions for bimodal genes in the era of high-throughput sequencing and personalized medicine.
... Carcinoid tumors are rare endocrine tumors that represent less than 1% of all pulmonary tumors [1]. ...
A partial or complete resolution of the neoplastic lesion, either spontaneously or in the presence of therapy that is considered inadequate to exert significant influence on the growth of the neoplastic lesion, is considered a spontaneous regression. This phenomenon is extremely rare in lung neoplasms. A close follow up with imaging along with bronchoscopy and a biopsy of the lesion is essential, as they may have potential for distant spread even during radiological regression. Here, we report a case of a partial resolution of a bronchial carcinoid tumor that had a high mitotic activity and was resected.
... Carcinoid tumors are rare endocrine tumors that represent less than 1% of all pulmonary tumors [1]. They can develop in various organs in the body, most commonly in gastrointestinal tract followed by the bronchopulmonary region. ...
... The presence of pneumoconiotic nodules on the chest CT scans makes it difficult to localize the tumor (3,4). Because of a false-positive results that may occur with the use of [ 18 providing a unique and specific molecular target for imaging (6,7). SSTRs are a G-protein coupled transmembrane receptors that gets internalized after binding to specific ligand. ...
... Total resection should be the primary goal of any form of surgical therapy. Lymph node dissection should accompany resection (9,18,19). ...
Objective: Sites with a high prevalence of pneumoconiosis are especially challenging to physicians. The presence of pneumoconiotic nodules on chest computed tomography (CT) scans makes it difficult to localize the source of ectopic adrenocorticotropic hormone (ACTH). Because of false-positive results that may occur with the use of fluorine 18-fluorodeoxyglucose positron emission tomography CT (PET/CT) scans, alternative imaging modalities are needed.
Methods: Gallium 68-dodecanetetraacetic acid tyrosine-3-octreotate (68Ga-DOTATATE) is a positron emitter-labeled somatostatin analog used with PET/CT. 68Ga-DOTATATE may improve the diagnostic accuracy of localizing ectopic ACTH-secreting carcinoid tumors in patients with pneumoconiosis by reducing false-positive results.
Results: We describe a patient with pneumoconiosis and Cushing syndrome due to ectopic ACTH from a pulmonary carcinoid tumor, highlighting challenges in diagnosis and management.
Conclusion: Prospective studies comparing fluorine 18-fluorodeoxyglucose PET/CT with 68Ga-DOTATATE PET/CT for diagnosis of bronchial carcinoid tumors in patients with ectopic ACTH and pneumoconiosis are highly needed. We also review the scarce available literature and provide recommendations based on our experience.
Abbreviations: 18F-FDG = fluorine 18-fluorodeoxyglucose; 68Ga-DOTATATE = gallium 68-dodecanetetraacetic acid tyrosine-3-octreotate; CTH = adrenocorticotropic hormone; CT = computed tomography; MRI = magnetic resonance imaging; NET = neuroendocrine tumor; PET = positron emission tomography; SSTR = somatostatin receptor; SUV = standardized uptake value; SUVmax = maximum tandardized uptake value
