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1.
Medicine (Baltimore) ; 100(39): e27389, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596162

RESUMO

RATIONALE: Peutz-Jeghers syndrome (PJS), a rare autosomal dominant disorder, is characterized by mucocutaneous pigmentations, hamartomatous polyps in the gastrointestinal tract, and a high risk of developing various malignancies. To the best of our knowledge, only 1 case of appendiceal carcinoid associated with PJS has been previously reported in the pediatric population. PATIENT CONCERNS: We report a 7-year-old girl who was admitted for severe, intermittent abdominal pain and cramps, nausea, and vomiting. Multiple brown melanotic macules on the lips, buccal mucosa, and the tongue were noted. DIAGNOSIS: A plain abdominal X-ray in a standing position revealed dilated intestinal loops with multiple air-fluid levels. A computed tomography scan of the abdomen showing a "coffee bean" appearance of the jejunal loop with a transition point to the duodenal loop. Axial-contrast-enhanced computed tomography scan of the abdomen showing dilated jejunum loops, filled with fluid with the swirled appearance of mesentery typical for volvulus. The diagnosis of PJS was based on clinical findings along with the histopathologic confirmation of the hamartomatous polyps. INTERVENTIONS: An emergency laparotomy was performed, revealing a jejunojejunal intussusception starting 40 cm from the duodenojejunal flexure. Jejunotomy revealed that a lead-point intussusception was a necrotic hamartomatous polyp. After resecting the involved jejunal necrotic segment, including the polyp, end-to-end jejuno-jejunal anastomosis was performed. Further exploration revealed the presence of a jejunal mass 80 cm from the duodenojejunal flexure identified as another hamartomatous pedunculated polyp. The polyp was resected, and the enterotomy was then closed transversely. The grossly normal appendix was also removed. OUTCOMES: Clinical findings along with the histopathologically confirmed hamartomatous polyps were consistent with PJS. An appendiceal carcinoid (well-differentiated neuroendocrine tumor, European Neuroendocrine Tumor Society stage pT2) was incidentally detected during histological examination of the appendix. The patient and parents were counseled accordingly, focusing on active surveillance and control of symptoms. Two additional hamartomatous polyps (gastric and jejunal) were detected endoscopically and resected in the fourth postoperative week. A regular, 1-year follow-up and surveillance revealed no complications or recurrences. LESSONS: Unusual neoplasms can occasionally be encountered in well-defined syndromes such as PJS. Therefore, active follow-up and surveillance are mandatory for all patients with PJS.


Assuntos
Tumor Carcinoide/etiologia , Neoplasias Intestinais/etiologia , Síndrome de Peutz-Jeghers/complicações , Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Criança , Feminino , Humanos , Achados Incidentais , Neoplasias Intestinais/patologia , Neoplasias Intestinais/cirurgia , Obstrução Intestinal/diagnóstico por imagem , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Doenças do Jejuno/diagnóstico por imagem , Doenças do Jejuno/etiologia , Doenças do Jejuno/cirurgia , Síndrome de Peutz-Jeghers/diagnóstico , Tomografia Computadorizada por Raios X
4.
Sci Rep ; 11(1): 10455, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001972

RESUMO

Lung carcinoids are variably aggressive and mechanistically understudied neuroendocrine neoplasms (NENs). Here, we identified and elucidated the function of a miR-375/yes-associated protein (YAP) axis in lung carcinoid (H727) cells. miR-375 and YAP are respectively high and low expressed in wild-type H727 cells. Following lentiviral CRISPR/Cas9-mediated miR-375 depletion, we identified distinct transcriptomic changes including dramatic YAP upregulation. We also observed a significant decrease in neuroendocrine differentiation and substantial reductions in cell proliferation, transformation, and tumor growth in cell culture and xenograft mouse disease models. Similarly, YAP overexpression resulted in distinct and partially overlapping transcriptomic changes, phenocopying the effects of miR-375 depletion in the same models as above. Transient YAP knockdown in miR-375-depleted cells reversed the effects of miR-375 on neuroendocrine differentiation and cell proliferation. Pathways analysis and confirmatory real-time PCR studies of shared dysregulated target genes indicate that this axis controls neuroendocrine related functions such as neural differentiation, exocytosis, and secretion. Taken together, we provide compelling evidence that a miR-375/YAP axis is a critical mediator of neuroendocrine differentiation and tumorigenesis in lung carcinoid cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Tumor Carcinoide/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Células Neuroendócrinas/patologia , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Carcinogênese/genética , Tumor Carcinoide/patologia , Diferenciação Celular/genética , Proliferação de Células/genética , Exocitose/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Knockout , MicroRNAs/genética , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Lung Cancer ; 156: 117-121, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33940544

RESUMO

INTRODUCTION: Diffuse Idiopathic Pulmonary NeuroEndocrine Cell Hyperplasia (DIPNECH) is a rare disease often associated with carcinoid tumors. We aimed at evaluating the impact of DIPNECH on characteristics and prognosis of patients who underwent radical treatment of pulmonary carcinoid tumors. MATERIAL AND METHODS: We reviewed all patients operated on for curative-intent resection of carcinoid tumor in our department from 2001 to 2020. Cases exhibiting both pathological and radiological features of DIPNECH, as assessed by respective thoracic expert physicians, were analyzed separately. RESULTS: 172 cases of resected carcinoid tumors were identified, including 25 (14.5 %) harboring pathological criteria of DIPNECH and radiologic features like mosaic attenuation (92.0 %), multiple nodules < 5 mm (76.0 %), and mucoid impactions (32 %). In DIPNECH patients, major pulmonary resections were usually performed (92.0 %) and resected tumors were mostly classified as pT1 (92 %). Mean Ki67 staining was 3.7 ± 5.2 %. The early postoperative period was mostly uneventful (96.0 %) and 5-year survival was 92.9 ± 6.9 %. Compared to non-DIPNECH cases, we found that patients were older (mean 65.6 ± 9.3 versus 54.1 ± 17.9, p = 0.002), more frequently female (84.0 % versus 56.5 %, p = 0.009), and exhibiting diabetes mellitus (45.8 % versus 18.5 %, p < 0.001) or hypertension (45.8 % versus 24.1 %, p = 0.039). The rate of atypical carcinoid tumors was significantly higher in DIPNECH patients (40.0 % versus 19.9 %, p = 0.027), as well as rate of mediastinal lymph-nodes involvement (pN2+) (36.0 % versus 4.1 %, p < 0.001). At multivariate analysis, only DIPNECH pattern and atypical histology were independent factors of pN2 invasion which was the only predictor of poorer prognosis on Log-Rank test. CONCLUSION: Carcinoid tumors with proven DIPNECH are associated with negative pathological features and may deserve a dedicated perioperative management.


Assuntos
Tumor Carcinoide , Neoplasias Pulmonares , Células Neuroendócrinas , Tumores Neuroendócrinos , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patologia , Feminino , Humanos , Hiperplasia/patologia , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Células Neuroendócrinas/patologia , Tumores Neuroendócrinos/patologia
6.
Curr Opin Pulm Med ; 27(4): 255-261, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33927131

RESUMO

PURPOSE OF REVIEW: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare premalignant condition. Over the past decade, there has been increased recognition and reporting of DIPNECH in the literature. Currently, our understanding is that DIPNECH has a predilection to nonsmoking females around their sixth decade of life. The patients usually present with chronic cough, dyspnea, and computed tomography (CT) showing multifocal pulmonary nodules with associated mosaic attenuation. The clinic history is largely driven by constrictive obliterative bronchiolitis, which typically has an indolent course with progressive respiratory decline and difficult to treat symptoms. RECENT FINDINGS: DIPNECH has been found to be associated with carcinoid tumors. Recent data has found that symptomatic DIPNECH patients respond to somatostatin analog (SSA). SSAs provide improvement in symptoms and pulmonary function tests. According to small studies and case series SSAs can be used in conjunction with steroids and bronchodilators for the treatment of respiratory symptoms. SUMMARY: DINPNECH is a premalignant condition that can transform into carcinoid tumors. Although the recent data suggest the potential efficacy of SSA, further studies are needed to validate such results in prospective fashion in addition to investigating other therapeutic agents.


Assuntos
Tumor Carcinoide , Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Células Neuroendócrinas , Lesões Pré-Cancerosas , Tumor Carcinoide/patologia , Feminino , Humanos , Hiperplasia/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/tratamento farmacológico , Células Neuroendócrinas/patologia , Lesões Pré-Cancerosas/patologia
7.
Indian J Pathol Microbiol ; 64(2): 376-378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851639

RESUMO

The carcinoids are the most frequent tumors arising from the appendix, in majority of the cases, these are asymptomatic and are discovered after appendectomy. The lipid-rich carcinoid, also known as clear cell carcinoid; is histologically characterized by the presence of clear vacuoles in the cytoplasm of tumor cells. Only 24 cases of lipid-rich carcinoid of the appendix are described in the English literature, and there is no report of this entity in the Indian literature. In this report we describe a first case of lipid-rich carcinoid of the appendix in India and also present a review of the literature.


Assuntos
Apendicite/cirurgia , Apêndice/patologia , Tumor Carcinoide/patologia , Síndrome do Carcinoide Maligno/patologia , Adulto , Apendicectomia , Biomarcadores Tumorais/análise , Feminino , Humanos , Lipídeos/análise , Prognóstico
8.
Indian J Pathol Microbiol ; 64(2): 385-389, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33851642

RESUMO

Mature cystic teratoma of the ovary (MCT) is rare in pre and postmenopausal age patients. Among various types of malignant transformation in MCT, adenocarcinoma is a rare subtype. Dual type tumors arising from ovarian MCT have been described in the literature very rarely. A 47-year-old postmenopausal female patient presented with abdominal mass for ten years. The radiological opinion was a dermoid cyst. Grossly, a 22 × 20 × 10 cm, unilocular cystic left ovarian mass with intact capsular surface and focal thickened wall measured 3.0 cm. Microscopically, it showed components of all three germ cell layers. In addition, features of colonic type adenocarcinoma and well-differentiated neuroendocrine tumor (carcinoid) were noted and confirmed by immunohistochemistry (IHC). We report this rare case of synchronous malignancy arising from an ovarian MCT with a clinicopathological review.


Assuntos
Adenocarcinoma/patologia , Tumor Carcinoide/patologia , Neoplasias do Colo/patologia , Neoplasias Ovarianas/patologia , Teratoma/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Adulto , Idoso , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/cirurgia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Ovário/patologia , Pós-Menopausa , Teratoma/diagnóstico , Teratoma/cirurgia
9.
Ann Diagn Pathol ; 52: 151724, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33667971

RESUMO

BACKGROUND: Appendectomy is the most common emergent surgical procedure. Primary appendiceal neoplasms are rare entities that are usually detected incidentally in less than 2% of all appendectomies. The increase in the incidence rates of appendiceal neoplasms over time raises the question whether there is an actual change in the disease occurrence or is it a matter of increased recognition and reporting of what would have been previously missed and undiagnosed. OBJECTIVES: In our study, we aimed to review the archived tissue specimens of patients who were diagnosed with appendiceal neoplasms during the past decade at our institution and compare our clinical experience with published data to identify possible reasons that contribute to the increase in incidence rates of such neoplasms over the past few years. METHODS: Using a pathological database of surgical specimens from patients who underwent appendectomies between January 01, 2010 and September 30, 2020 at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 1568 patients included, 102 (6.5%) had appendiceal neoplasms divided between primary (79.4%) and secondary/metastatic (20.6%) neoplasms. Annual incidence of appendiceal neoplasms over the past 10 years in our institution demonstrated an increasing trend from 5.6% in 2010 to 12.7% in 2020, which we hypothesize might be attributed to submitting more representative sections of the appendix for pathological examination than we had previously. Our results also showed that 2.8% of patients initially presenting with a typical clinical picture of acute appendicitis had appendiceal neoplasms as a truly incidental finding, while 20.3% of patients who underwent elective appendectomies for a suspicious appendiceal mass were found to be neoplastic. Interestingly, among the 80 cases of epithelial neoplasms, more non-carcinoid neoplasms were detected than carcinoid tumors. CONCLUSION: Based on our results and what has been published recently, we confirm an additional increase in incidental appendiceal neoplasms found in appendectomies performed for a clinical picture of acute appendicitis, which may be related to more thorough specimen assessment. Whether this is clinically impactful remains to be determined. However, these data support a modification in the way appendectomy specimens are handled in pathology labs post-operatively.


Assuntos
Apendicectomia/métodos , Neoplasias do Apêndice/patologia , Apendicite/patologia , Manejo de Espécimes/métodos , Centros Médicos Acadêmicos , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Apendicectomia/estatística & dados numéricos , Neoplasias do Apêndice/epidemiologia , Neoplasias do Apêndice/cirurgia , Apendicite/diagnóstico , Apendicite/epidemiologia , Apendicite/cirurgia , Tumor Carcinoide/epidemiologia , Tumor Carcinoide/patologia , Feminino , Humanos , Incidência , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Estadiamento de Neoplasias/métodos , Estudos Retrospectivos , Manejo de Espécimes/tendências
10.
Medicine (Baltimore) ; 100(8): e24714, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663082

RESUMO

RATIONALE: Primary renal carcinoid tumors are very rare and only about 100 cases have been reported in the medical literature. There are even fewer articles on the imaging manifestations of primary renal carcinoid tumors. PATIENT CONCERNS: We present 3 cases of patients with lumbago and hematuria. These were cases of primary renal carcinoid tumors with initial suspicion of suprarenal epithelioma. DIAGNOSES: Renal lesions were detected on abdomen computed tomography (CT) imaging. The 3 cases presented as solid/cystic solid renal mass with uniform or non-uniform density, calcification in the mass, and enhanced heterogeneity. INTERVENTIONS: The laparoscopic partial/radical nephrectomy were performed. OUTCOMES: The postoperative histological diagnosis were primary renal carcinoid tumors. Case 2 been lost to follow-up in 3 patients, and the other 2 patients (Case 1 and 3) are still alive. Case 1 had intrahepatic metastases. LESSONS: Primary renal carcinoid tumors mostly present as solid mass/cystic solid mass with calcification and delayed enhancement of heterogeneity on CT imaging, but the diagnosis depends on pathological diagnosis. Hence, raising awareness of the CT features of the rare tumor in the kidney may broaden the knowledge base of radiologists.


Assuntos
Tumor Carcinoide/patologia , Neoplasias Renais/patologia , Idoso , Tumor Carcinoide/cirurgia , Feminino , Humanos , Rim/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Tomografia Computadorizada por Raios X
11.
J Cancer Res Ther ; 17(1): 258-261, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33723165

RESUMO

Multiple primary malignancies are defined as two or more primary malignant tumors diagnosed in one individual; they are further classified to synchronous or metachronous based on the period between each cancer diagnosis and the other. The diagnosis of four synchronous cancers is exceedingly rare. We report a case of a 72-year-old man, diagnosed with synchronous quadruple cancers, Hurthle cell carcinoma and papillary carcinoma of the thyroid, as well as squamous cell carcinoma and carcinoid tumor of the lung.


Assuntos
Adenoma Oxífilo/patologia , Tumor Carcinoide/patologia , Carcinoma Papilar/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias da Glândula Tireoide/patologia , Adenoma Oxífilo/complicações , Idoso , Tumor Carcinoide/complicações , Carcinoma Papilar/complicações , Carcinoma de Células Escamosas/complicações , Humanos , Neoplasias Pulmonares/complicações , Masculino , Neoplasias Primárias Múltiplas/complicações , Neoplasias da Glândula Tireoide/complicações
12.
BMC Cancer ; 21(1): 141, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557782

RESUMO

BACKGROUND: Lung carcinoid is a rare malignant tumor with poor survival. The current study established a nomogram model for predicting cancer-specific survival (CSS) in patients with lung carcinoid tumors. METHODS: A total of 1956 patients diagnosed with primary lung carcinoid tumors were extracted from the Surveillance, Epidemiology, and End Results database. The specific predictors of CSS for lung carcinoid tumors were identified and integrated to build a nomogram. Validation of the nomogram was conducted using parameters concordance index (C-index), calibration plots, decision curve analyses (DCAs), and the receiver operating characteristic (ROC) curve. RESULTS: Age at diagnosis, grade, histological type, N stage, M stage, surgery of the primary site, radiation of the primary site, and tumor size were independent prognostic factors of CSS. High discriminative accuracy of the nomogram model was shown in the training cohort (C-index = 0.873), which was also testified in the internal validation cohort (C-index = 0.861). In both cohorts, the calibration plots showed good concordance between the predicted and observed CSS at 3, 5, and 10 years. The DCA showed great potential for clinical application. The ROC curve showed superior survival predictive ability of the nomogram model (area under the curve = 0.868). CONCLUSIONS: We developed a practical nomogram that provided independent predictions of CSS for patients with lung carcinoid tumors. This nomogram may have the potential to assist clinicians in prognostic evaluations or developing individualized therapies for patients with this neoplasm.


Assuntos
Tumor Carcinoide/mortalidade , Neoplasias Pulmonares/mortalidade , Nomogramas , Medição de Risco/métodos , Programa de SEER/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Tumor Carcinoide/patologia , Tumor Carcinoide/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
13.
Lung Cancer ; 154: 186-194, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33551175

RESUMO

BACKGROUND: Well-differentiated lung neuroendocrine tumors (NETs), also known as typical and atypical carcinoids, have a decreased incidence of lymph node (LN) and distant metastases compared to poorly differentiated lung NETs. We aimed to (i) examine the clinicopathologic features associated with LN involvement in lung carcinoids and (ii) describe the postoperative management of patients with LN metastases. METHODS: We identified 98 patients who underwent surgical resection and lymph node sampling at Stanford University. We assessed the following and used AJCC staging version 7: clinical features (age, sex, race, prior malignancy, smoking history), tumor features (functional syndrome, histology, size, location, laterality), pre-operative workup performed (imaging and suspicion of LN metastases), surgery (nodes and stations sampled, margin status, surgical approach, and type of surgery), and recurrence outcome. These features were examined between patients with and without LN metastases using the Wilcoxon test (continuous variables) and Fisher's exact test (categorical variables). RESULTS: 87 patients (89%) had typical carcinoid and 11 patients (11%) had atypical carcinoid. 17 patients were found to have at least one positive lymph node, with 11 having N1 disease and 6 having N2 disease. In the univariable analysis, patients with lymph node disease were more likely to have recurrence of lung carcinoid (29% vs. 6%, p=0.01). In the multivariable logistic regression, there was a trend towards performance of preoperative SSTR imaging and lymph node involvement (OR = 3.06, p=0.07). No patients received adjuvant therapy. CONCLUSION: We found a trend for the performance of SSTR imaging and association of lymph node metastases in both univariable and multivariable analysis. A large proportion (41%) of patients with lymph node positive disease had < 2 cm tumors. This suggests the potential importance of incorporating SSTR imaging into routine practice and not restricting the use of this staging modality in patients with small tumors.


Assuntos
Tumor Carcinoide , Neoplasias Pulmonares , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/patologia , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
14.
BMC Cardiovasc Disord ; 21(1): 54, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509095

RESUMO

BACKGROUND: Thymic carcinoid is one of an extremely rare type of malignant neuroendocrine tumor with a poor prognosis. Invasion of thymic carcinoid to other organs could lead to devastating consequences. It has been reported that thymic carcinoid mainly invaded to the pleura, lungs, liver, pancreas and bone, while rarely to the cardiac, especially to the ventricle. CASE PRESENTATION: A 53-year-old man presented with gastrointestinal symptoms and persistent pericardial effusion. Multiple imaging tools, including chest computed tomography (CT), magnetic resonance imaging (MRI), 18F-Fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) showed a malignant neoplasm arising from the thymus invading into the biventricular myocardium, pericardium, and left superior pulmonary veins. The tumor was finally diagnosed as a thymic carcinoid through pathological examination. CONCLUSION: This is a rare case of thymic carcinoid invading the ventricular myocardium, which presented as subacute heart failure. The observations in this case would be useful for differential diagnosis of primary heart disease and invasion of heart due to thymic carcinoid.


Assuntos
Tumor Carcinoide/complicações , Gastroenteropatias/etiologia , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/patologia , Derrame Pericárdico/etiologia , Neoplasias do Timo/complicações , Biópsia , Tumor Carcinoide/diagnóstico por imagem , Tumor Carcinoide/patologia , Diagnóstico Diferencial , Gastroenteropatias/diagnóstico , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/patologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Invasividade Neoplásica , Derrame Pericárdico/diagnóstico por imagem , Valor Preditivo dos Testes , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia
15.
Cell Physiol Biochem ; 55(S2): 1-12, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33398982

RESUMO

BACKGROUND/AIMS: Lung carcinoids are uncommon neuroendocrine tumours. Molecular features of lung carcinoids have been poorly defined. microRNAs (miRNAs) are potent gene expression regulators with important roles in cancer development and progression. However, little is known on the role of miRNAs in the pathogenesis of lung carcinoids. Our goals were to identify commonly deregulated miRNAs in a rare case of lung carcinoid of typical histology with metastasis, as well as map miRNA target genes in pathways potentially associated with disease development and progression. METHODS: miRNA expression profiles were assessed using the TaqMan Low Density Arrays, which is a platform including 384 miRNAs. miRNA profiles were generated in the tumor and its corresponding lymph node metastasis, compared to reference normal lung tissues. Furthermore, miRNA expression was validated in a separate, publicly available external dataset (n=19 typical lung carcinoids; 2/19 were metastatic tumors, compared to six normal lung tissues, GSE77380). Following this analysis, computational tools were applied for data interpretation. miRTarBase was used to determine miRNA-target genes, followed by ToppGene Suite analysis to identify pathways and biological functions. In addition, the expression of genes targeted by miRNAs was validated in a second, separate external dataset (n=13 tumour samples, GSE35679). GEO2R data analysis tool was used in both validation analyses (miRNAs and genes). RESULTS: We identified 15 commonly significantly downregulated miRNAs (fold change, FC≥2 and p<0.05) in the tumour and its paired metastasis, with further decreasing levels in the metastatic lesion. Downregulation of miR-126-3p and miR-146b-5p was validated in the external dataset GSE77380. In addition, SOX2 and TCF4 genes, targeted by miR-126-3p, were consistently overexpressed in a subset of six typical lung carcinoids from the external dataset GSE35679. Pathways analysis showed that miRNAs miR-126-3p and miR-146b-5p target genes with a role in the regulation of adaptive immune response. CONCLUSION: Our results contribute to the identification of miRNA expression changes in a typical lung carcinoid and its corresponding lymph node metastasis. Down-regulated levels of miR-126-3p and miR-146b-5p and target gene over-expression could play a role in the progression of this case of primary typical lung carcinoid to regional metastasis. Identified miRNAs and target genes are potential candidates for validation in a larger number of cases.


Assuntos
Tumor Carcinoide/genética , Tumor Carcinoide/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , MicroRNAs/imunologia , Imunidade Adaptativa/genética , Adulto , Biomarcadores Tumorais/genética , Tumor Carcinoide/patologia , Biologia Computacional/métodos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , MicroRNAs/genética , Estadiamento de Neoplasias
17.
Eur J Surg Oncol ; 47(5): 1132-1139, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33280949

RESUMO

BACKGROUND: Appendiceal non-mucinous neoplasms (AnMN) are rare and poorly understood malignancies with no standard treatment. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is largely used to treat peritoneal disseminations from appendiceal mucinous neoplasms (AMN), but its role with AnMN is unclear. METHODS: A prospective database of 315 patients with advanced appendiceal primaries undergoing CRS/HIPEC during 1996-2020 was reviewed. Baseline characteristics, operative and long-term outcomes of AnMN were compared with those of AMN. AMN were categorized according to PSOGI classification into high-grade, low-grade, and acellular mucin (AC), based on peritoneal disease histology. RESULTS: Twenty-three patients (7.3%) with goblet cell carcinoma (GCC; n = 9), intestinal-type adenocarcinoma (ITAC; n = 12), and mixed adeno-neuroendocrine carcinoma (MANEC; n = 2) were identified. AnMN patients were more likely to be males (P = 0.006), have preoperative systemic chemotherapy (P = 0.001), grossly incomplete CRS (P = 0.001), and nodal metastases (P = 0.001), but not systemic relapse after CRS/HIPEC (P = 0.133). Median follow-up was 25.1 months (range 0.8-77.3) for AnMN, and 80.9 months (range 0.1-279.2) for AMN. Median overall survival was 24.0 months for AnMN, 66.2 months for high-grade AMN (P = 0.015), 160.0 months for low-grade ANM (P = 0.001), and not reached for AC (P = 0.001). Among AnMN patients, median survival was 23.4 months for GCC, 38.7 months for ITAC, 20.3 months for MANEC (P = 0.855). In the overall series, histological subtype (P = 0.001), incomplete cytoreduction (P = 0.001), and positive lymph-nodes (P = 0.003) correlated with poorer survival at multivariate analysis. CONCLUSIONS: AnMN share with AMN a predominant local-regional dissemination pattern, but prognosis after CRS/HIPEC is worse. This strategy needs to be carefully considered for AnMN.


Assuntos
Adenocarcinoma Mucinoso/terapia , Neoplasias do Apêndice/terapia , Tumor Carcinoide/terapia , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Tumores Neuroendócrinos/terapia , Adenocarcinoma Mucinoso/patologia , Idoso , Neoplasias do Apêndice/patologia , Tumor Carcinoide/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/patologia , Prognóstico , Estudos Prospectivos
19.
Surg Oncol ; 36: 120-129, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33360118

RESUMO

BACKGROUND: Goblet cell carcinoma (GCC), formerly known as goblet cell carcinoid, of the appendix constitutes less than 14% of all primary appendiceal neoplasms. Surgical resection is the main treatment and the role of adjuvant chemotherapy (AC) is not established. This study aims to evaluate the impact of AC in stage II-III appendiceal GCC. METHODS: Patients with pathological stage II and III GCC who underwent surgical resection between 2006 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8243/3 (goblet cell carcinoid) and C18.1. Patients treated with neoadjuvant systemic and/or radiation therapy and adjuvant radiation were excluded. Univariate and multivariable analyses were conducted, and Kaplan-Meier Curves were used to compare overall survival (OS) based on treatment received with Log-rank test. RESULTS: A total of 619 patients were identified. 54.4% males and 89.0% Caucasian; median age 56 (range, 23-90) years. Distribution across pathological stages II-III was 82.7% (N = 512) and 17.3% (N = 107) respectively. AC was administered in 9.4% (N = 48) of stage II and 47.7% (N = 51) of stage III patients. For stage II patients, AC was not associated with better OS in univariate (HR 0.32; 95% CI 0.04-2.34; p = 0.261) or multivariable analyses (HR 0.29; 95% CI 0.04-2.12; p = 0.221). By contrast, in stage III patients, AC was associated with better OS in univariate (HR 0.35; 95% CI 0.17-0.71; p = 0.004) and multivariable analyses (HR 0.25; 95% CI 0.07-0.88; p = 0.031). In the entire cohort 5-year OS for patients that received AC was 85.5% (74.0%, 92.1%) versus 82.7% (77.5%, 86.8%) (p = 0.801) with no AC. For stage II patients, 5-year OS was 96.9% with AC vs. 89.1% with no AC (p = 0.236). For stage III patients, 5-year OS was 77.1% with AC vs. 42.8% with no AC (p = 0.003). CONCLUSION: AC was associated with improved OS in patients with pathological stage III GCC of the appendix, but not with pathological stage II.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/tratamento farmacológico , Tumor Carcinoide/tratamento farmacológico , Quimioterapia Adjuvante/mortalidade , Terapia Neoadjuvante/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Apêndice/patologia , Tumor Carcinoide/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
20.
Ann Intern Med ; 174(2): 157-166, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33315473

RESUMO

BACKGROUND: Early-onset colorectal cancer (EOCRC) incidence rates (IRs) are rising, according to previous cancer registry analyses. However, analysis of histologic subtypes, including adenocarcinoma (the focus of CRC screening and diagnostic testing) and carcinoid tumors (which are classified as "colorectal cancer" in SEER [Surveillance, Epidemiology, and End Results] databases but have a distinct pathogenesis and are managed differently from adenocarcinoma), has not been reported. OBJECTIVE: To assess EOCRC IRs and changes in IRs over time, stratified by histology. DESIGN: Retrospective analysis. SETTING: Yearly IRs according to SEER 18 data from 2000 to 2016 on age-specific colon-only, rectal-only, and combined-site CRC cases, stratified by histology ("overall" CRC [all histologic subtypes], adenocarcinoma, and carcinoid tumors) and age. PATIENTS: 119 624 patients with CRC. MEASUREMENTS: IRs per 100 000 population, changes in 3-year average annual IRs (pooled IRs from 2000 to 2002 vs. those from 2014 to 2016), and annual percentage change (APC) in persons aged 20 to 29, 30 to 39, 40 to 49, and 50 to 54 years. RESULTS: The steepest changes in adenocarcinoma 3-year average annual IRs were for rectal-only cases in persons aged 20 to 29 years (+39% [0.33 to 0.46 per 100 000]; P < 0.050) and 30 to 39 years (+39% [1.92 to 2.66 per 100 000]; P < 0.050) and colon-only cases in those aged 30 to 39 years (+20% [3.30 to 3.97 per 100 000]; P < 0.050). Corresponding APCs were 1.6% (P < 0.050), 2.2% (P < 0.050), and 1.2% (P < 0.050), respectively. In persons aged 40 to 49 years, 3-year average annual IRs increased in both colon-only (+13% [12.21 to 13.85 per 100 000]; P < 0.050) and rectal-only (+16% [7.50 to 8.72 per 100 000]; P < 0.050) subsites. Carcinoid tumors were common, representing approximately 4% to 20% of all colorectal and 8% to 34% of all rectal cancer cases, depending on age group and calendar year. Colon-only carcinoid tumors were rare. Colorectal carcinoid tumor IRs increased more steeply than adenocarcinoma in all age groups, thus affecting the contribution of carcinoid tumors to overall cancer cases over time. These changes were driven by rectal subsites and were most pronounced in persons aged 50 to 54 years, in whom rectal carcinoid tumors increased by 159% (2.36 to 6.10 per 100 000) between 2000 to 2002 and 2014 to 2016, compared with 10% for adenocarcinoma (18.07 to 19.84 per 100 000), ultimately accounting for 22.6% of all rectal cancer cases. LIMITATION: Population-based data. CONCLUSION: These findings underscore the importance of assessing histologic CRC subtypes independently. Doing so may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of outcomes from efforts to reduce adenocarcinoma risk, and can guide future research. PRIMARY FUNDING SOURCE: None.


Assuntos
Adenocarcinoma/epidemiologia , Tumor Carcinoide/epidemiologia , Neoplasias Colorretais/epidemiologia , Adenocarcinoma/patologia , Adulto , Fatores Etários , Idade de Início , Tumor Carcinoide/patologia , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/epidemiologia , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Estados Unidos/epidemiologia , Adulto Jovem
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