Predictive Modeling of Long-Term Prognosis After Resection in Typical Pulmonary Carcinoid: A Machine Learning Perspective.

Typical Pulmonary Carcinoid (TPC) is defined by its slow growth, frequently necessitating surgical intervention. Despite this, the long-term outcomes following tumor resection are not well understood. This study examined the factors impacting Overall Survival (OS) in patients with TPC, leveraging data from the Surveillance, Epidemiology, and End Results database spanning from 2000 to 2018. We employed Lasso-Cox analysis to identify prognostic features and developed various models using Random Forest, XGBoost, and Cox regression algorithms. Subsequently, we assessed model performance using metrics such as Area Under the Curve (AUC), calibration plot, Brier score, and Decision Curve Analysis (DCA). Among the 2687 patients, we identified five clinical features significantly affecting OS. Notably, the Random Forest model exhibited strong performance, achieving 5- and 7-year AUC values of 0.744/0.757 in the training set and 0.715/0.740 in the validation set, respectively, outperforming other models. Additionally, we developed a web-based platform aimed at facilitating easy access to the model. This study presents a machine learning model and a web-based support system for healthcare professionals, assisting in personalized treatment decisions for patients with TPC post-tumor resection.

Epidemiology and Prognostic Nomogram for Predicting Long-Term Disease-Specific Survival in Patients With Pancreatic Carcinoid Tumor: A SEER-Based Study.

OBJECTIVES: Pancreatic carcinoid tumor (PCT) is described as a malignant form of carcinoid tumors. However, the epidemiology and prognostic factors for PCT are poorly understood. MATERIALS AND METHODS: The data of 2447 PCT patients were included in this study from the Surveillance, Epidemiology, and End Results database and randomly divided into a training cohort (1959) and a validation cohort (488). The epidemiology of PCT was calculated, and independent prognostic factors were identified to construct a prognostic nomogram for predicting long-term disease-specific survival (DSS) among PCT patients. RESULTS: The incidence of PCT increased remarkably from 2000 to 2018. The 1-, 5-, and 10-year DSS rates were 96.4%, 90.3%, and 86.5%, respectively. Age at diagnosis, stage, surgery, radiotherapy, and chemotherapy were identified as independent prognostic factors to construct a prognostic nomogram. The C -indices; area under the receiver operating characteristic curves for predicting 1-, 5-, and 10-year DSS, and calibration plots of the nomogram in both cohorts indicated a high discriminatory accuracy, preferable survival predictive ability, and optimal concordances, respectively. CONCLUSIONS: The incidence of PCT has increased rapidly since 2000. In addition, we established a practical, effective, and accurate prognostic nomogram for predicting the long-term DSS of PCT patients.

Segmentectomy and wedge resection are equivalent for the treatment of early-stage pulmonary carcinoid tumors: A retrospective cohort study.

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.

Prognosis of unresected versus resected early-stage pulmonary carcinoid tumors ≤3 cm in size: A population-based study.

PURPOSE: 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. CONCLUSION: 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.

Factors Associated With Long-term Survival in Children With Bronchial and Lung Carcinoid Tumors.

BACKGROUND AND AIMS: Bronchial carcinoids are rare in children and the treatment is based on tumor behavior in adults. The purpose of this study was to determine factors and management strategies associated with long-term survival in the pediatric population using a national cohort. METHODS: Patients aged ≤20 years with bronchial carcinoid tumors were identified in the 2004-2020 National Cancer Database using ICD-O-3 codes. Tumor characteristics and management were compared among typical (TC) and atypical (AC) histological subtypes using Chi-square and Fisher's exact tests. Kaplan-Meier and univariate Cox proportional hazards analyses were used to assess survival. RESULTS: Of 273 patients, 251 (92%) had TCs, and 22(8%) had ACs. The median (IQR) age was 18 (16,19) years. Most patients underwent lobectomy or bilobectomy (67%), followed by sublobar resection (17%), no resection or bronchoscopic excision or ablation (8%), and pneumonectomy (7.7%). Margins were negative in 96%. Lymph node (LN) assessment was performed in 216 patients (84%) with a median (IQR) of 7(3,13) LNs, and 50 (23%) had ≥1 positive LN. There was no difference in age, resection, margin status, LN assessment, or positivity between TC and AC (all p > 00.05). Detection of nodal metastasis did not increase beyond the resection of 1-3 LNs (p = 0.72). Ten-year survival was worse for AC than TC (79% (41, 100) vs 98% (95, 100), HR = 6.9 (95% CI: 1.2-38.3, p = 0.03). Ten-year survival among those with and without LN assessment was 97% (94, 100) vs 91% (81, 100), HR = 4.0, 95% CI: 0.8-19.9, p = 0.09). There were no deaths in those with negative LN while 10-year survival was 89% (72, 100) in those with ≥1 positive LN. CONCLUSION: Among children with bronchial carcinoids, survival is excellent with TC or negative LN. Atypical histology and positive LN have poor survival and should prompt close monitoring. These risk factors may be missed in the absence of surgical resection and lymph node sampling. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Retrospective Study.

Prognostic Immunohistochemistry for Ki-67 and OTP on Small Biopsies of Pulmonary Carcinoid Tumors: Ki-67 Index Predicts Progression-free Survival and Atypical Histology.

Prognostic stratification of pulmonary carcinoids into "typical" and "atypical" categories requires examination of large tissue volume. However, there is a need for tools that provide similar prognostic information on small biopsy samples. Ki-67 and OTP immunohistochemistry have shown promising prognostic value in studies of resected pulmonary carcinoids, but prognostic value when using biopsy/cytology specimens is unclear. Ki-67 immunohistochemistry was performed on small biopsy/cytology specimens from pulmonary carcinoid tumors (n=139), and labeling index was scored via automated image analysis of at least 500 cells. OTP immunohistochemistry was performed on 70 cases with sufficient tissue and scored as positive or negative (<20% tumor nuclei staining). Higher Ki-67 index was associated with worse disease-specific progression-free survival (ds-PFS), with 3% and 4% thresholds having similarly strong associations with ds-PFS ( P <0.001, hazard ratio ≥11). Three-year ds-PFS was 98% for patients with Ki-67 <3% and 89% for patients with Ki-67≥3% ( P =0.0006). The optimal Ki-67 threshold for prediction of typical versus atypical carcinoid histology on subsequent resection was 3.21 (AUC 0.68). Negative OTP staining approached significance with atypical carcinoid histology ( P =0.06) but not with ds-PFS ( P =0.24, hazard ratio=3.45), although sample size was limited. We propose that Ki-67 immunohistochemistry may contribute to risk stratification for carcinoid tumor patients based on small biopsy samples. Identification of a 3% hot-spot Ki-67 threshold as optimal for prediction of ds-PFS is notable as a 3% Ki-67 threshold is currently used for gastrointestinal neuroendocrine tumor stratification, allowing consideration of a unified classification system across organ systems.

Prognostic nomogram and epidemiological analysis for lung atypical carcinoid: A SEER database and external validation study.

PURPOSE: Our study aims to delineate the epidemiological distribution of pulmonary carcinoids, including atypical carcinoid (AC) and typical carcinoid (TC), identify independent prognostic factors, develop an integrative nomogram and examine the effects of various surgical modalities on atypical carcinoid-specific survival (ACSS). METHODS: Joinpoint regression model and age-group distribution diagram were applied to determine the epidemiological trend of the pulmonary carcinoids. Univariate and least absolute shrinkage and selection operator (LASSO)-based Cox regression models were used to identify independent factors, and a nomogram and web-based predictor were developed to evaluate prognosis of AC patients individually. We performed Kaplan-Meier survival analyses to compare the scope of various surgical interventions, with and without G-computation adjustment, utilising restricted mean survival time (RMST) to assess survival disparities. RESULTS: A total of 1132 patients were recruited from the Surveillance, Epidemiology, and End Results database (SEER) and a separate medical centre in China. The mean age of AC patients was 63.4 years and a smoking history was identified in 79.8% of AC patients. Joinpoint analysis shows rising annual rates of new AC and carcinoid cases among lung cancers. Both the proportion of pulmonary TC and AC within the total lung cancer population exhibits an L-shaped trend across successive age groups. The nomogram predicted 1, 3 and 5 years of AC with excellent accuracy and discrimination. Kaplan-Meier survival analyses, conducted both pre- and post-adjustment, demonstrated that sublobar resection's survival outcomes were not inferior to those of lobectomy in patients with stage I-II and stage III disease. CONCLUSION: This study is the first to reveal epidemiological trends in pulmonary carcinoids over the past decade and across various age cohorts. For patients with early-stage AC, sublobar resection may be a viable surgical recommendation. The established nomogram and web-based calculator demonstrated decent accuracy and practicality.

Most small bowel cancers are revealed by a complication / A maioria dos cânceres de intestino delgado são revelados por uma complicação

ABSTRACT Objective To characterize the pattern of primary small bowel cancers in a tertiary East-European hospital. Methods A retrospective study of patients with small bowel cancers admitted to a tertiary emergency center, over the past 15 years. Results There were 57 patients with small bowel cancer, representing 0.039% of admissions and 0.059% of laparotomies. There were 37 (64.9%) men, mean age of 58 years; and 72 years for females. Out of 57 patients, 48 (84.2%) were admitted due to an emergency situation: obstruction in 21 (38.9%), perforation in 17 (31.5%), upper gastrointestinal bleeding in 8 (14.8%), and lower gastrointestinal bleeding in 2 (3.7%). There were 10 (17.5%) duodenal tumors, 21 (36.8%) jejunal tumors and 26 (45.6%) ileal tumors. The most frequent neoplasms were gastrointestinal stromal tumor in 24 patients (42.1%), adenocarcinoma in 19 (33.3%), lymphoma in 8 (14%), and carcinoids in 2 (3.5%). The prevalence of duodenal adenocarcinoma was 14.55 times greater than that of the small bowel, and the prevalence of duodenal stromal tumors was 1.818 time greater than that of the small bowel. Obstruction was the complication in adenocarcinoma in 57.9% of cases, and perforation was the major local complication (47.8%) in stromal tumors. Conclusion Primary small bowel cancers are usually diagnosed at advanced stages, and revealed by a local complication of the tumor. Their surgical management in emergency setting is associated to significant morbidity and mortality rates.

RESUMO Objetivo Caracterizar o padrão de neoplasias malignas primárias do intestino delgado em um hospital terciário de Leste Europeu. Métodos Estudo retrospectivo de pacientes com câncer de intestino delgado, internados em um hospital terciário e de emergência, ao longo dos últimos 15 anos. Resultados Foram avaliados 57 pacientes com neoplasias malignas gastrintestinais, o que representou 0,039% das admissões e 0,059% das laparotomias realizadas. Total de 37 (64,9%) pacientes masculinos, média de idade de 58 anos, e de 72 anos para mulheres. Dentre os 57 pacientes, 48 (84,2%) foram internados em situação de emergência: obstrução intestinal em 21 (38,9%), perfuração em 17 (31,5%), hemorragia digestiva alta em 8 (14,8%), e hemorragia digestiva baixa em 2 (3,7%). Houve 10 (17,5%) tumores duodenais, 21 (36,8%) jejunais e 26 (45,6%) ileais. As neoplasias mais frequentes foram tumor estromal gastrintestinal, em 24 (42,1%) pacientes, adenocarcinoma em 19 (33,3%), linfoma em 8 (14%) e carcinoides em 2 (3,5%). A prevalência de adenocarcinoma duodenal foi 14,55 vezes maior do que a do intestino delgado, e a prevalência de tumores estromais duodenais foi 1,818 vez maior do que a do intestino delgado. A obstrução intestinal foi complicação do adenocarcinoma em 57,9% dos casos, e a perfuração foi a principal complicação local (47,8%) dos tumores estromais. Conclusão As neoplasias malignas primárias do intestino delgado foram geralmente diagnosticadas em estado avançado e reveladas por uma complicação local do tumor. O tratamento cirúrgico em situação de emergência está associado à significativa morbimortalidade.

Carcinoide gastrointestinal: experiencia de siete años en el Instituto Nacional del Cáncer (2000-2006) / Carcinoid tumors: retrospective review of 25 patients

Background: The incidence of carcinoid tumors (CT) has increased in the last five decades. These supposedly benign tumors may not always behave as such. The largest series of CT show that the most common primary tumor site (appendiceal) changed over the years. Aim: To evaluate the management of gastrointestinal CT at the National Cancer Institute from 2000 to 2006, describe their anatomic location and estimate disease specific survival. Material and Methods: Review of the database of the Cancer Committee, during a period of 7 years, looking for patients with a pathological diagnosis of CT, whose clinical records were analyzed. Results: The records of 25 patients with gastrointestinal CT, aged 18 to 79 years (19 females) were analyzed. Five years disease specific survival was 91.1 percent. The most common location was appendiceal in 56 percent of cases, with a 5 years disease specific survival of 100 percent. Right hemicolectomy was performed in seven patients with appendiceal carcinoid. Other seven patients only underwent appendectomy. Five years disease specific survival was 100 percent in both groups. Conclusions: The appendix is still the most common location of CT in this series and long term survival is acceptable.

Los tumores carcinoides (TC) gastrointestinales han aumentando su incidencia en las últimas 5 décadas. Inicialmente estos tumores eran considerados de comportamiento benigno, sin embargo, con el tiempo han mostrado ser capaces de diseminarse y tener una evolución más agresiva. En general se considera al apéndice cecal como la ubicación más frecuente de TC pero esto ha cambiado en el último tiempo según publicaciones internacionales. El objetivo de este trabajo es presentar nuestra experiencia en el manejo de los TC gastrointestinales en el período 2000-2006 en el Instituto Nacional del Cáncer (INC) reportando una serie de casos, describir su ubicación anatómica y estimar la sobrevida específica de enfermedad. Método: Estudio descriptivo. Se revisó la base de datos del Comité Oncológico del INC, durante un período de 7 años, incluyendo pacientes con diagnóstico anatomopatológico de TC. Se revisaron las fichas clínicas y se recolectaron registros de defunción. Resultados: 25 pacientes con diagnóstico de TC confirmado por patología, presentando una sobrevida específica de enfermedad a 5 años de 91,1 por ciento. La ubicación más frecuente de TC fue apéndice cecal (56 por ciento) y este grupo de pacientes presenta sobrevida específica de enfermedad de 100 por ciento a 5 años. De los TC apendiculares, en 7 pacientes se realizó una hemicolectomía derecha en un segundo tiempo, y en 7 pacientes sólo se realizó apendicectomía, con sobrevida específica de enfermedad de 100 por ciento en ambos grupos a 5 años (p = 0,475). Conclusiones: El apéndice cecal continúa siendo el lugar más frecuente de presentación del TC y la sobrevida alejada es adecuada en esta serie de pacientes.

Tumores apendiculares en 6.093 apendicectomías de urgencias: sobrevida a 5 años / Appendiceal malignant tumors among patients with acute appendicitis

Background: Acute appendicitis can be the first manifestation of an appendiceal tumor. Aim: To evaluate the incidence of appendiceal tumors among patients operated for acute appendicitis. Material and Methods: All patients operated for acute appendicitis between 1998 and 2008 and whose appendix had a pathological study were included. Survival was calculated using national death register databases. Results: Data from 6.093 patients was analyzed. A malignant tumor was found in 17 patients (0.3 percent). Eleven patients aged 23 +/- 14 years had a carcinoid tumor, that was more commonly located distally, five patients aged 66 +/-18 years had an adenocarcinoma, that was more commonly located proximally, and one patient had a non Hodgkin lymphoma. Curative surgery was carried out in all carcinoid tumors and 40 percent of adenocarcinomas. No patient had regional lymph node involvement. Five years survival of patients with carcinoid tumors was 100 percent. Conclusions: The finding of malignant tumor among patients with acute appendicitis is uncommon.

Introducción: Al enfrentarnos a un paciente con apendicitis aguda, pocas veces pensamos que puede ser la primera manifestación de un cáncer apendicular. Objetivo: Describir el número de casos nuevos de cáncer apendicular en las apendicectomías de urgencia en el Hospital Base Osorno (HBO) durante los años 1998-2008. Material y Métodos: Serie de casos. Se incluyeron pacientes operados por abdomen agudo en el servicio de urgencia del HBO, que en cuyo informe anatomopatológico de la biopsia diferida se informara cáncer apendicular, entre los años 1998 y 2008. Se excluyeron pacientes en los que el apéndice estaba comprometido por contigüidad. Algunas variables incluidas: edad, sexo, diagnóstico preoperatorio, tipo de cirugía, resección completa tumoral, reintervención, características histoanatomopatológicas, terapia adyuvante. Descripción de variables en porcentajes, medias o medianas. Curvas de sobrevida: Kaplan Meier. Programa estadístico Stata 10.0. Resultados: Se analizaron 6.093 pacientes. Se encontró un cáncer en el 0,28 por ciento (17 pacientes) de los casos. 11 (64 por ciento) fueron carcinoides, 5 (29 por ciento) adenocarcinomas y 1 (6 por ciento) linfoma no Hodgkin. Edad promedio 23,45 (DS +/- 14,45) años en los carcinoidesy 65,75 (DS +/- 18,46) en los adenocarcmomas. En los carcinoides predominó el sexo femenino, contrario a lo sucedido en los adenocarcmomas. Se practicó cirugía curativa al 100 por ciento de los carcinoides y al 40 por ciento de los adenocarcinomas. Ubicación más frecuente: Carcinoides en tercio distal y adenocarcinoma en tercio proximal. Ningún tumor tuvo linfonodos comprometidos. 100 por ciento de sobrevida a 5 años en carcinoides. Conclusiones: El número de casos nuevos de cáncer en una apendicitis aguda es bajo. En los carcinoides, la sobrevida a 5 años es alta.

Colonic carcinoid tumors: a clinicopathologic study of 23 patients from a single institution / Tumores carcinóides do cólon: estudo clinicopatológico de 23 doentes de uma única instituição

Context: Colonic carcinoids, excluding those arising in the appendix, have proved to be extremely rare. Due to their rarity, the characteristics and behavior of this unusual malignancy remain unclear. Objective: To review the clinicopathologic features of patients operated on carcinoid tumors of the colon. Methods: Twenty-three patients (12 males and 11 females) were operated on colonic carcinoids. The mean age of the patients was 63.0 ± 12.9 years (42 to 85 years). The clinical and histopathological data of patients who were pathologically diagnosed as having carcinoid tumors and submitted to surgical treatment over a 30-year period (1977-2007) were gathered. Actuarial patient survival was estimated using the Kaplan-Meier method, with carcinoid-specific death as the outcome. Results: The mean time elapsed between onset of symptoms and surgical treatment was 8.3 months (1.5 to 20 months). The most frequent symptoms or signs encountered were abdominal pain followed by anorexia or weight loss, diarrhea, abdominal tenderness, palpable abdominal mass, and rectal bleeding. No carcinoid syndrome was noted. The lesion was located in the cecum in 16 (69.6 percent) patients, in the sigmoid in 3 patients (13.0 percent), in the ascending colon in 3 patients (13.0 percent), and in the transverse colon in one patient (4.3 percent). Twenty-one (91.3 percent) patients were operated on curative intent. Spreading of the disease to the liver and peritoneum was found in two (8.7 percent) patients who submitted to intestinal bypass. The mean size of the largest mass was 3.7 ± 1.2 cm (1.5 to 6.2 cm). There were multiple (two or more) lesions in three cases (13.0 percent). In the resected cases, the lymph nodes were compromised in 10 patients (47.6 percent) and disease-free in 11 (52.4 percent). Venous invasion and neural infiltration were both present in five (23.8 percent) patients. The tumors had penetrated the muscularis propria in all resected cases...

Contexto: Carcinóides cólicos, excluindo aqueles que se originam no apêndice cecal, são extremamente raros. Devido a esta raridade, as características e comportamento desta neoplasia permanecem indefinidas. Objetivo: Rever as características clinicopatológicas de doentes operados por carcinoma cólico. Método: Vinte e três doentes (12 homens e 11 mulheres) foram operados. A média de idade dos doentes foi de 63,0 ± 12,9 anos (42 a 85 anos). Os dados clínicos e histopatológicos dos doentes com diagnóstico patológico de tumor carcinóide e submetidos ao tratamento cirúrgico no período de 30 anos (1977-2007) foram obtidos a partir dos prontuários. A sobrevivência atuarial dos doentes foi estimada pelo método de Kaplan-Meier, considerando-se como óbito específico aquele devido ao tumor carcinóide. Resultados - A média de tempo decorrida entre o início dos sintomas e o tratamento cirúrgico foi de 8,3 meses (1,5 a 20 meses). O sintoma mais frequente encontrado foi dor abdominal seguida por anorexia ou perda de peso, diarréia, massa abdominal palpável e sangramento pelo reto. Não foram observados doentes com síndrome carcinóide. A lesão estava localizada no ceco em 16 (69,6 por cento) doentes, no cólon sigmóide em 3 (13,0 por cento), no colo ascendente em 3 (13,0 por cento) e no cólon transverso em 1 (4,3 por cento). Vinte e um (91,3 por cento) doentes foram operados com intenção curativa. Disseminação da doença para o fígado e peritônio foi encontrada em dois (8,7 por cento) doentes que foram submetidos ao desvio intestinal. A média do tamanho das lesões intestinais foi 3,7 ± 1,2 cm (1,5 a 6,2 cm). Lesões múltiplas (duas ou mais) ocorreram em três (13,0 por cento) casos. Nas lesões ressecadas, os linfonodos estavam comprometidos em 10 (47,6 por cento) e livres em 11 (52,4 por cento). Invasão venosa e infiltração neural estavam ambas presentes em cinco (23,8 por cento) doentes. A neoplasia penetrava a muscularis propria em todos as lesões ressecadas...

Diagnóstico e prognóstico dos tumores pulmonares neuroendócrinos mediante microscopia eletrônica e análise multivariavel de agrupamento / Using electron microscopy and multivariate cluster analysis to determine diagnosis and prognosis in cases of neuroendocrine lung carcinoma

OBJECTIVE: To establish reproducible electron microscopic criteria for identifying the four major types of neuroendocrine tumors of the lung: carcinoid; atypical carcinoid; large cell neuroendocrine carcinoma; and small cell carcinoma. METHODS: Measurements were made on electron micrographs using a digital image analyzer. Sixteen morphometric variables related to tumor cell differentiation were assessed in 27 tumors. The examination under electron microscopy revealed that all of the tumors could be classified as belonging to one of the four categories listed above. Cluster analysis of the morphometry variables was used to group the tumors into three clusters, and Kaplan-Meier survival function curves were employed in order to draw correlations between each cluster and survival. RESULTS: All three clusters of neuroendocrine carcinomas were found to be associated with survival curves, demonstrating the prognostic significance of electron microscopic features. The tumors fell into three well-defined clusters, which represent the spectrum of neuroendocrine differentiation: typical carcinoid (cluster 1); atypical carcinoid and large cell neuroendocrine carcinoma (cluster 2); and small cell carcinoma (cluster 3). Cluster 2 represents an intermediate step in neuroendocrine carcinogenesis, between typical carcinoid tumors and small cell carcinomas. CONCLUSIONS: Our findings confirm that electron microscopy is useful in making the diagnosis and prognosis in cases of lung tumor.

OBJETIVO: Estabelecer, com ajuda do microscópio eletrônico, critérios que possibilitem uma diferenciação mais exata entre os quatro tipos maiores de tumores neuroendócrinos pulmonares: tumor carcinóide típico e atípico, carcinoma de grandes células neuroendócrino e carcinoma de pequenas células. MÉTODOS: Todos os tumores foram avaliados morfometricamente e 16 variáveis foram relacionadas com diferenciação das células tumorais; estas variáveis foram analisadas sob microscopia eletrônica com ajuda de um analisador de imagem digital em 27 tumores. A avaliação através da microscopia eletrônica revelou que todos os tumors investigados podiam ser classificados a um dos quarto tipos listados acima. A análise das variáveis morfométricas foi usada para agrupar os tumores em três grandes grupos, os quais foram relacionados à sobrevivência pelas curvas de Kaplan Meier. RESULTADOS: Os três grupos de carcinoma neuroendócrino associaram-se às curvas da sobrevivência, as quais mostraram características ultrastruturais na microscopia eletrônica de significância prognóstica distinta. Os tumores foram contidos em três grupos bem definidos, que representam o espectro da diferenciação neuroendócrina: tumor carcinóide (grupo 1); tumor carcinóide atípico e carcinoma de grandes células neuroendócrino (grupo 2); e carcinoma de pequenas células (grupo 3). O grupo 2 representa um espectro intermediário na carcinogênese neuroendócrina, entre o carcinóide típico e o carcinoma de pequenas células. CONCLUSÕES: Nossos achados confirmam que a microscopia eletrônica é uma ferramenta útil no diagnóstico e prognóstico dos casos de tumores pulmonares.

Tumores carconoides de pulmón: diagnóstico, tratamiento y factores pronósticos / Carconoides tumors of lung: diagnosis, treatment and factors prognoses

Antecedentes: Los tumores carcinoides pertenecen al grupo de neoplasias neuroendocrinas de pulmón. Objetivos: Determinar su forma más frecuente de presentación clínica, método diagnóstico más seguro y el éxito del tratamiento quirúrgico ofrecido a estos pacientes, evaluando factores pronósticos en relación a hallazgos anatomopatológicos. Métodos: Se realizó un análisis retrospectivo de todos los tumores carciniodes pulmonares operados desde enero de 1975 hasta agosto del 2005, incluyendo ambos tipos histológicos: típicos y atípicos. Resultados: De los 47 pacientes operados, 27 fueron mujeres y 18 hombres, con un promedio de edad de 39 + 15 años. La sintomatología de comienzo de la enfermedad fue tos, hemoptisis e infección respiratoria. El método diagnóstico más frecuentemente utilizado fue la fibrobroncoscopia (FBC) con toma de biopsia. Se realizaron 6 neumonectomías, 22 lobectomías y 19 plásticas bronquiales seguidas o no de resecciones pulmonares. La histología demostró 43 carcinoides típicos y 4 carcinoides atípicos. Entre los primeros, en 12 pacientes el tamaño del tumor fue mayor de 3 cm, se halló metástasis ganglionar en el nivel N2 en 3 y permeación linfática, afectación de la grasa periganglionar e invasión vascular en 9 casos, habiéndose observado supervivencia del 100% a 5 y 10 años. Conclusiones: Los tumores carcinoides típicos son lesiones de buen pronóstico. Para los carcinoides atípicos la evolución es marcadamente diferente y la supervivencia de estos enfermos pareciera estar relacionada con la extensión local de la enfermedad.