Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.305
Filtrar
1.
Nat Commun ; 11(1): 333, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949145

RESUMO

Cutaneous malignant melanoma is an aggressive cancer of melanocytes with a strong propensity to metastasize. We posit that melanoma cells acquire metastatic capability by adopting an embryonic-like phenotype, and that a lineage approach would uncover metastatic melanoma biology. Using a genetically engineered mouse model to generate a rich melanoblast transcriptome dataset, we identify melanoblast-specific genes whose expression contribute to metastatic competence and derive a 43-gene signature that predicts patient survival. We identify a melanoblast gene, KDELR3, whose loss impairs experimental metastasis. In contrast, KDELR1 deficiency enhances metastasis, providing the first example of different disease etiologies within the KDELR-family of retrograde transporters. We show that KDELR3 regulates the metastasis suppressor, KAI1, and report an interaction with the E3 ubiquitin-protein ligase gp78, a regulator of KAI1 degradation. Our work demonstrates that the melanoblast transcriptome can be mined to uncover targetable pathways for melanoma therapy.


Assuntos
Perfilação da Expressão Gênica , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Transcriptoma , Animais , Linhagem Celular Tumoral , Retículo Endoplasmático , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Proteína Kangai-1/genética , Proteína Kangai-1/metabolismo , Pulmão/patologia , Melanócitos/metabolismo , Melanoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica/genética , Segunda Neoplasia Primária/patologia , Fenótipo , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Neoplasias Cutâneas/patologia , Ubiquitina-Proteína Ligases/metabolismo
2.
Ann Hematol ; 99(2): 241-253, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897674

RESUMO

This study aims to investigate the clinicopathological features of in situ follicular neoplasm (ISFN) in Japan. ISFN is a rare condition formerly considered as an early precursor of follicular lymphoma (FL). This is a first original report of ISFN from Asian country. We reviewed 19 biopsy samples of ISFN. ISFNs were categorized into two groups: (1) ISFN, consisting of ISFN with strong positivity for BCL-2 immunohistochemical staining (IHC), and obvious translocation of BCL-2; and (2) ISFN-like FL, featuring cases without obvious translocation but having morphological features and characteristic IHC findings of ISFN. As control, we adopted obvious FL. For some cases showing coexisting ISFN and FL lesions in the same lymph node, we could conduct further clonality analysis for each lesion. Nine of the 19 cases of ISFN coexisted with FL or had a history of overt B- or T-cell lymphoma including FL. Statistical comparison among ISFN-like FL and FL showed no significant differences in pathological features. Molecular analysis suggested that ISFN lesion and FL lesion in the same lymph node each have a different clonality. ISFN coexists or associates with other overt lymphomas frequently.


Assuntos
Linfonodos/metabolismo , Linfoma Folicular , Segunda Neoplasia Primária , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Japão , Linfonodos/patologia , Linfoma Folicular/metabolismo , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia
3.
Int J Cancer ; 146(4): 970-976, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31054153

RESUMO

Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses and family history of cancer may be a risk factor for SPCs. Using the Swedish Family-Cancer Database on non-Hodgkin lymphoma (NHL), we assessed the influence of family history on risk of SPCs and of SPCs on survival. NHL patients were identified from the years 1958 to 2015 and generalized Poisson models were used to calculate relative risks (RRs) for SPCs and familial SPCs. Among 14,393 NHL patients, a total of 1,866 (13.0%) were diagnosed with SPC. Familial risk of nine particular cancers was associated with risks of these cancers as SPCs, with twofold to fivefold increase in RRs. At the end of a 25-year follow-up period, the survival probability for persons with SPC was only 20% of that for patients without SPC; the hazard ratio for SPC was 1.59 (95% CI: 1.46-1.72). Survival could be predicted by the prognostic groups based on first cancers and HRs increase systematically with worse prognosis yielding a trend of p = 4.6 × 10-5 . SPCs had deleterious consequences for survival in NHL patients. Family history was associated with increasing numbers of SPCs. Prevention of SPCs and their early detection is an important target in the overall strategy to improve survival in NHL patients. Counseling for avoidance of risk factors and targeted screening based on family history are feasible steps in risk reduction.


Assuntos
Linfoma não Hodgkin/mortalidade , Segunda Neoplasia Primária/mortalidade , Bases de Dados Factuais , Saúde da Família , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/patologia , Suécia/epidemiologia
4.
Cancer Sci ; 111(2): 739-748, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31799787

RESUMO

There are increased opportunities in oncology clinics to identify multiple pancreatic ductal adenocarcinomas (PDAC) that co-occur simultaneously or arise metachronously in the pancreatic parenchyma, yet their pathogenesis remains elusive. We hypothesized that two potential pathways, multicentric carcinogenesis and intrapancreatic metastasis, might contribute to forming multiple PDAC. Among 241 resected cases, we identified 20 cancer nodules from nine patients with multiple PDAC (six with synchronous PDAC, one with metachronous PDAC, and two with both synchronous and metachronous PDAC). Integrated clinical, pathological, and mutational analyses, using TP53 and SMAD4 immunostaining and targeted next-generation sequencing of 50 cancer-related genes, were conducted to examine the intertumor relationships. Four of the nine patients were assessed as having undergone multicentric carcinogenesis because of heterogeneity of immunohistochemical and/or mutation characteristics. In contrast, tumors in the other five patients showed intertumor molecular relatedness. Two of these five patients, available for matched sequencing data, showed two or more shared mutations. Moreover, all the smaller nodules in these five patients showed identical TP53 and SMAD4 expression patterns to the corresponding main tumors. Consequently, these five patients were considered to have undergone intrapancreatic metastasis. None of the five smaller nodules arising from intrapancreatic metastasis was accompanied by pancreatic intraepithelial neoplasia, and three of them were tiny (≤1mm). Patients whose tumors resulted from intrapancreatic metastasis appeared to have higher disease stages and worse outcome than those with tumors from multicentric carcinogenesis. Our results provide insight into pancreatic carcinogenesis, showing that the development of multiple PDAC involves distinct evolutionary paths that potentially affect patient prognosis.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/cirurgia , Neoplasias Pancreáticas/cirurgia , Proteína Smad4/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Biomarcadores Tumorais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/metabolismo , Neoplasias Primárias Múltiplas/cirurgia , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia , Pancreatectomia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Análise de Sequência de DNA , Proteína Smad4/genética , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética
8.
Urology ; 134: e1-e2, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586569
9.
Dis Colon Rectum ; 62(11): 1283-1293, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567917

RESUMO

BACKGROUND: Extramammary Paget's disease is an uncommon intraepidermal adenocarcinoma with poorly defined clinical implications. OBJECTIVE: The purpose of this research was to estimate the risk of second primary neoplasms in patients with extramammary Paget's disease. DESIGN: This was a retrospective analysis of the Surveillance, Epidemiology, and End Results Registry (1973-2014). SETTINGS: The study included population-based cancer registries from the United States. PATIENTS: Patients who were diagnosed with anogenital Paget's disease were included. MAIN OUTCOME MEASURES: Risk of second primary development was measured. RESULTS: We identified 108 patients with anal Paget's disease, 421 patients with male genital (scrotum or penis) Paget's, and 1677 patients with female genital (vagina or vulva) Paget's. Median follow-up time was 5.9 years. The risk of developing colorectal adenocarcinoma was 18.5% for patients with anal Paget's disease. Eighty percent of colorectal adenocarcinoma diagnoses were synchronous (within 2 mo) to anal Paget's diagnoses, whereas metachronous tumors occurred at a median time of 2.4 years. Of patients with anal Paget's disease, 8.3% developed an anal adenocarcinoma or nonsmall cell cancer. In male patients with genital Paget's, the risk of proximal genitourinary malignancy was 9.7%, scrotal or testicular adenocarcinoma was 0.4%, and penile or scrotal squamous carcinoma was 1.7%. In female patients with genital Paget's, the risk of proximal genitourinary malignancy was 3.0%, vaginal or vulvar adenocarcinoma was 1.4%, and vaginal or vulvar squamous neoplasm was 1.0%. Five-year overall survival was 59.7%, 73.5%, and 80.7% in patients with anal, male genital, and female genital Paget's (p < 0.001). LIMITATIONS: The registry did not record surveillance schedule, provider specialty, or nonprocedural therapies for extramammary Paget's disease. CONCLUSIONS: In the largest published cohort of patients with extramammary Paget's disease, patients with anal Paget's had a much higher risk of both proximal and local neoplasms as compared with patients with genital Paget's. Patients with anal Paget's also experienced worse survival as compared with those with purely genital Paget's. See Video Abstract at http://links.lww.com/DCR/B20. ALTO RIESGO DE NEOPLASIAS PROXIMALES Y LOCALES EN 2206 PACIENTES CON ENFERMEDAD DE PAGET EXTRAMAMARIA ANOGENITAL:: La enfermedad de Paget extramamaria es un adenocarcinoma intraepidérmico poco frecuente con implicaciones clínicas poco definidas.Estimar el riesgo de segundas neoplasias primarias en pacientes con enfermedad de Paget extramamaria.Análisis retrospectivo del Registro de Vigilancia, Epidemiología y Resultados Finales (1973-2014).Registros de base poblacional en cáncer de los Estados Unidos.Pacientes que fueron diagnosticados con enfermedad de Paget anogenital.Riesgo de desarrollo un cáncer primario adicional.Se identificaron 108 pacientes con Paget anal, 421 pacientes con Paget genital masculino (escroto o pene) y 1677 pacientes con Paget genital femenino (vagina o vulva). Tiempo mediano de seguimiento fue de 5,9 años. El riesgo de desarrollar adenocarcinoma colorrectal fue del 18,5% para los pacientes con Paget anal. El ochenta por ciento de los diagnósticos de adenocarcinoma colorrectal fueron sincrónicos (dentro de los 2 meses) a los diagnósticos de Paget anal, mientras que los tumores metacrónicos ocurrieron en un tiempo promedio de 2,4 años. De los pacientes con Paget anal, el 8.3% desarrolló un adenocarcinoma anal o cáncer de células no pequeñas. En los pacientes masculinos con Paget genital, el riesgo de malignidad genitourinaria proximal fue del 9,7%, el adenocarcinoma escrotal o testicular fue del 0,4% y el carcinoma escamoso del pene o escroto fue del 1,7%. En pacientes femeninas con Paget genital, el riesgo de malignidad genitourinaria proximal fue de 3.0%, el adenocarcinoma vaginal o vulvar fue de 1.4% y la neoplasia escamosa vaginal o vulvar fue de 1.0%. La supervivencia general a cinco años fue del 59.7%, 73.5% y 80.7% en pacientes con anal, genital masculino y genital femenino, respectivamente (p <0.001).El registro no señalo el cronograma de vigilancia, la especialidad del proveedor o las terapias sin procedimiento para la enfermedad de Paget extramamaria.En la cohorte más grande publicada de pacientes con enfermedad de Paget extramamaria, los pacientes con Paget anal demostraron un riesgo mucho mayor de neoplasias proximales y locales en comparación con los pacientes con Paget genital. Los pacientes con Paget anal además demostraron una peor supervivencia en comparación con aquellos con Paget aislada genital. Vea el Resumen del Video en http://links.lww.com/DCR/B20.


Assuntos
Adenocarcinoma , Neoplasias do Ânus , Neoplasias dos Genitais Femininos , Neoplasias dos Genitais Masculinos , Segunda Neoplasia Primária , Doença de Paget Extramamária , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Assistência ao Convalescente/estatística & dados numéricos , Idoso de 80 Anos ou mais , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/patologia , Epiderme/patologia , Feminino , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Masculinos/epidemiologia , Neoplasias dos Genitais Masculinos/patologia , Humanos , Masculino , Massachusetts/epidemiologia , Estadiamento de Neoplasias , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Doença de Paget Extramamária/epidemiologia , Doença de Paget Extramamária/patologia , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
10.
Pediatr Surg Int ; 35(12): 1403-1411, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31555858

RESUMO

PURPOSE: We investigated how local tumor resection affects metastatic lesions in neuroblastoma. METHODS: MYCN Tg tumor-derived cells were injected subcutaneously into 129+Ter/SvJcl wild-type mice. First, the frequency of metastasis-bearing mice was investigated immunohistochemically (metastatic ratio) at endpoint or post-injection day (PID) 90. Second, the threshold volume of local tumor in mice bearing microscopic lymph node metastasis (mLNM) was investigated at PID 30. Finally, local tumors were resected after exceeding the threshold. Mice were divided into local tumor resection (Resection) and observation (Observation) groups, and the metastatic ratio and volume of LNM were compared between the groups at endpoint or PID 74. RESULTS: The metastatic ratio without local resection was 88% at PID 78-90. The threshold local tumor volume in the mice with mLNM was 745 mm3 at PID 30, so local tumors were resected after exceeding 700 mm3. The metastatic ratio and LNM volume were significantly greater in the Resection group (n = 16) than in the Observation group (n = 16) (94% vs. 38%, p < 0.001; 2092 ± 2310 vs. 275 ± 218 mm3, p < 0.01; respectively) at PID 50-74. CONCLUSION: Local tumor resection might augment the growth of synchronous microscopic metastases. Our results provide insights into the appropriate timing of local resection for high-risk neuroblastoma.


Assuntos
Neoplasias da Medula Óssea/secundário , Neoplasias Pulmonares/secundário , Metástase Linfática , Segunda Neoplasia Primária/patologia , Neuroblastoma/patologia , Neuroblastoma/cirurgia , Neoplasias Ovarianas/secundário , Aloenxertos , Animais , Modelos Animais de Doenças , Feminino , Masculino , Camundongos
11.
Int J Pediatr Otorhinolaryngol ; 127: 109648, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31472358

RESUMO

INTRODUCTION: The survival among children with cancer has improved considerably the past decades. Consequently, more children are at risk of second primary cancers (SPC). This study aimed to investigate the incidence of SPC among pediatric head and neck cancer (HNC) patients. METHODS AND MATERIALS: Data on children aged 0-17 years registered with a HNC in the Danish Registry of Childhood Cancer and the Danish National Patient Registry during the period 1980-2014 was obtained. SPC was defined as registration with any second malignancy that was not simultaneous with the first primary cancer (FPC) or a relapse hereof. All information was validated through review of medical charts. Standardized incidence rates (SIR) were calculated using the average incidence of all cancers in the general population of Denmark during the study period as reference. RESULTS: Among 234 pediatric HNC patients, six patients (four females) were registered with a SPC (2.6%), corresponding to an overall SIR of 4.8. No patients were diagnosed with more than one SPC. The median age at FPC and SPC was 15.2 years (range 9-16 years) and 35.0 years (range 19-41 years). The most common tumor histology and location among the patients with SPC was nasopharyngeal lymphoepithelial carcinoma for FPC and basal cell carcinoma of the skin for SPC. CONCLUSION: During 1980-2014 we identified six cases of SPC among 234 pediatric head and neck cancer patients in Denmark, corresponding to an overall SIR of 4.8.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Carcinoma Basocelular/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Dinamarca/epidemiologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Segunda Neoplasia Primária/patologia , Sistema de Registros , Adulto Jovem
12.
Anticancer Res ; 39(9): 5083-5087, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519619

RESUMO

BACKGROUND/AIM: Keratinocyte carcinoma (KC) is a marker of increased risk of other cancer types. To assess if this association exhibits a dose-response relationship, a case-control study was carried out. PATIENTS AND METHODS: This was a clinic-based study of cases with KC plus another type of cancer matched by age, race (all Caucasian), sex and histologic type to controls with KC only (n=48 matched pairs). RESULTS: Compared with the KC only group, those with KC plus another cancer had a mean number of lesions that were 43%, 35%, and 41% greater for basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and total KC, respectively. The odds ratio (OR) of developing another type of cancer increased from 1.0 to 1.09 (95% confidence interval (CI)=0.23-5.13) to 2.12 (95%CI=0.50-9.08) according to whether the patient had zero, one, or ≥two BCC lesions; for SCC, the corresponding ORs were 1.0, 1.24 (95%CI=0.48-3.24), and 1.39 (95%CI=0.29-6.61). CONCLUSION: A dose-response relationship seems to exist between the number of skin lesions and the risk of another type of cancer, but the lack of statistical significance weakens this evidence.


Assuntos
Queratinócitos/patologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/patologia , Razão de Chances , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/patologia , South Carolina/epidemiologia
13.
J Clin Exp Hematop ; 59(3): 140-144, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31391407

RESUMO

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal large B-cell lymphoma, and initial or predominant presentation in the lungs is uncommon. The synchronous occurrence of IVLBCL and malignant tumors is less frequent, and no such reports have described pulmonary presentations. We report a rare case of pulmonary IVLBCL accompanying lung cancer and interstitial lesions. A 73-year-old man with a history of pneumonia underwent a follow-up examination. Computed tomography revealed diffuse, bilateral ground-glass opacities (GGO) with a partial solid mass. Histologically, the mass consisted of adenocarcinoma. However, two other types of interstitial lesions were scattered throughout the resected lung: 1) peribronchovascular thickening with the aggregation of macrophages and anthracosis, and 2) alveolar septal thickening in the centrilobular area with atypical CD20-positive large cells in the capillaries. These two types of lesions were not mixed. Computed tomography and positron emission tomography demonstrated no other organ involvement. The patient was considered to have the synchronous occurrence of pulmonary IVLBCL and lung cancer (adenocarcinoma). After R-CHOP therapy, GGO on CT disappeared. Lung cancer often accompanies benign background lesions, and the combination of these lesions with lung cancer may make it difficult to detect the presence of pulmonary IVLBCL. However, the histological distribution pattern of IVLBCL may be a clue to the correct diagnosis.


Assuntos
Adenocarcinoma de Pulmão , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Intestinais , Neoplasias Pulmonares , Linfoma Difuso de Grandes Células B , Segunda Neoplasia Primária , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Idoso , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Humanos , Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/tratamento farmacológico , Neoplasias Intestinais/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Segunda Neoplasia Primária/diagnóstico por imagem , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Prednisona/administração & dosagem , Rituximab/administração & dosagem , Vincristina/administração & dosagem
14.
Gastroenterology ; 157(5): 1222-1232.e4, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31419435

RESUMO

BACKGROUND AND AIMS: In patients who have undergone surgery for colorectal cancer (CRC), 3% have recurrence of (metachronous) CRC. We investigated whether tumor seeding during colonoscopy (iatrogenic implantation of tumor cells in damaged mucosa) increases risk for metachronous CRC. METHODS: In a proof of principle study, we collected data from the Dutch National Pathology Registry for patients with a diagnosis of CRC from 2013 through 2015, with a second diagnosis of CRC within 6 months to 3.5 years after surgery. We reviewed pathology reports to identify likely metachronous CRC (histologically proven adenocarcinoma located elsewhere in the colon or rectum from the surgical anastomosis). For 22 patients fulfilling the inclusion criteria, we ascribed the most likely etiology to tumor seeding when endoscopic manipulations, such as biopsies or polypectomy, occurred at the location where the metachronous tumor was subsequently detected, after endoscopic manipulation of the primary tumor. We collected clinical data from patients and compared molecular profiles of the primary and metachronous colorectal tumors using next-generation sequencing. We then examined the source of seeded tumor. We tested whether tumor cells stay behind in the working channel of the endoscope after biopsies of colorectal tumors, and whether these cells maintain viability in organoid cultures. RESULTS: In total, tumor seeding was suspected as the most likely etiology of metachronous CRC in 5 patients. Tumor tissues were available from 3 patients. An identical molecular signature was observed in the primary and metachronous colorectal tumors from all 3 patients. In 5 control cases with a different etiology of metachronous CRC, the molecular signature of the primary and metachronous tumor were completely different. Based on review of 2147 patient records, we estimated the risk of tumor seeding during colonoscopy to be 0.3%-0.6%. We demonstrated that the working channel of the colonoscope becomes contaminated with viable tumor cells during biopsy collection. Subsequent instruments introduced through this working channel also became contaminated. These cells were shown to maintain their proliferative potential. CONCLUSIONS: In an analysis of primary and secondary tumors from patients with metachronous CRC, we found that primary tumor cells might be seeded in a new location after biopsy of the primary tumor. Although our study does not eliminate other possibilities of transmission, our findings and experiments support the hypothesis that tumor seeding can occur during colonoscopy via the working channel of the endoscope. The possibility of iatrogenic seeding seems low. However, our findings compel awareness on this potentially preventable cause of metachronous CRC.


Assuntos
Pólipos Adenomatosos/cirurgia , Pólipos do Colo/cirurgia , Colonoscopia/efeitos adversos , Neoplasias Colorretais/cirurgia , Inoculação de Neoplasia , Segunda Neoplasia Primária/patologia , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/patologia , Idoso , Biomarcadores Tumorais/genética , Pólipos do Colo/genética , Pólipos do Colo/patologia , Colonoscópios , Colonoscopia/instrumentação , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Contaminação de Equipamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/genética , Estudo de Prova de Conceito , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Células Tumorais Cultivadas
15.
Anticancer Res ; 39(8): 4333-4335, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366526

RESUMO

Secondary malignancies are relatively common and clinically important phenomena following both chemotherapy and radiotherapy. The majority of these cases are acute leukemias, the occurrence of which have been thoroughly documented and studied. More rarely, chronic myeloid leukemias (CML) may arise subsequent to treatment of a primary malignancy. Literature review on such developments following treatment of Hodgkin's Lymphoma (HL) is scant. Herein, the authors present three cases of CML diagnosed within five years of treatment initiation for Hodgkin's Lymphoma (HL); one of the three patients had CML with atypical variant carrying a rare mutation with BCR-JAK2 fusion.


Assuntos
Doença de Hodgkin/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Segunda Neoplasia Primária/genética , Proteínas de Fusão bcr-abl/genética , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Janus Quinase 2/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Segunda Neoplasia Primária/sangue , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/patologia , Proteínas Proto-Oncogênicas c-bcr/genética
16.
World J Gastroenterol ; 25(30): 4261-4277, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31435178

RESUMO

BACKGROUND: In recent years, increasing evidence of second neoplasms associated with gastrointestinal stromal tumors (GIST) has been found. Numerous case reports, mostly retrospective studies and a few reviews, have been published. To our knowledge, however, no systematic review or meta-analysis of the existing data has been performed so far. AIM: To prepare a compilation, as complete as possible, of all reported second tumor entities that have been described in association with GIST and to systematically analyze the published studies with regard to frequency, localization, and types of GIST-associated neoplasms. METHODS: The MEDLINE and EBSCO databases were searched for a combination of the keywords GIST/secondary, synchronous, coincident/tumor, neoplasm, and relevant publications were selected by two independent authors. RESULTS: Initially, 3042 publications were found. After deletion of duplicates, 1631 remained, and 130 papers were selected; 22 of these were original studies with a minimum of 20 patients, and 108 were case reports. In the 22 selected studies, comprising a total number of 12050 patients, an overall rate of GIST-associated neoplasias of 20% could be calculated. Most second neoplasias were found in the gastrointestinal tract (32%) and in the male and female urogenital tract (30%). The specific risk scores of GISTs associated with other tumors were significantly lower than those without associated neoplasias. CONCLUSION: In this first systematic review, we could confirm previously reported findings of a more than coincidental association between GIST and other neoplasias. The question whether there is an underlying causal association will need further investigation. Our data suggest that even GIST with a very low risk of disease progression should prompt screening for second neoplasia and subsequent frequent controls or extended staging.


Assuntos
Neoplasias Gastrointestinais/epidemiologia , Tumores do Estroma Gastrointestinal/epidemiologia , Neoplasias Primárias Múltiplas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Progressão da Doença , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/patologia , Humanos , Incidência , Programas de Rastreamento , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/prevenção & controle , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/prevenção & controle , Fatores de Risco
17.
BMC Cancer ; 19(1): 838, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455293

RESUMO

BACKGROUND: Adrenal tumors in patients with previous/synchronous extra-adrenal malignancy are diverse and are a dilemma in clinical practice. This study investigated the differentiation of adrenal malignant and benign tumors in these patients. METHODS: Data from patients with a pathological diagnosis of adrenal tumors were retrospectively retrieved from April 1991 to November 2015. Patients without extra-adrenal malignancy were excluded. Clinical and imaging characteristics, including sex, age, tumor size, tumor location, isolated lesion, time interval between the diagnosis of the two tumors and retrieved imaging diagnosis, were collected and analyzed. The selected patients were divided into 2 groups: those with primary or secondary malignancies (PSM) and those with primary benign tumors (PB). Chi-squared tests were used to evaluate differences between the two groups. Logistic regression was performed to explore potential risk factors related to the differentiation of PSM and PB, and a receiver operating characteristic (ROC) curve was used to evaluate their diagnostic values. RESULTS: Ninety-one patients were selected; 54 were male, and the median age was 56 years old. Between the groups of PSM and PB, sex (p = 0.004), age (p = 0.029), tumor size (p < 0.001), isolated lesion (p < 0.001) and imaging diagnosis (p < 0.001) were significantly different, while tumor size (p = 0.001), sex (p = 0.047) and imaging diagnosis (p = 0.002) were independent predictors of PSM. With ROC curve analysis, risk factors ≥2 was the optimal cutoff to differentiate these adrenal tumors, and their sensitivity and specificity were 73 and 77%, respectively. With a median follow-up of 32 months, only 4 of 32 patients with PB died from cancer, and 24 of 47 patients with PSM died from cancer, although aggressive treatment was performed. CONCLUSIONS: Tumor size, sex and imaging diagnosis were independent predictors of adrenal primary or secondary malignancies. These predictors might be helpful for differentiation of adrenal tumors in patients with previous/synchronous extra-adrenal cancers.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/etiologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias/epidemiologia , Adolescente , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Segunda Neoplasia Primária/patologia , Prognóstico , Curva ROC , Carga Tumoral , Adulto Jovem
18.
Ann Hematol ; 98(10): 2367-2377, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31455988

RESUMO

The coexistence of dual hematological neoplasms is very rare. Sequential or synchronous neoplasms in hematology are an uncommon and complex clinical situation. The aim of the Hemo2 study was to describe the clinical characteristics and analyze the outcome of these patients. We performed a retrospective review of all patients diagnosed with sequential or synchronous hematological malignancies in the university hospital of Tours, between 2007 and 2018. We identified 49 patients in our study, with a prevalence of 0.89%. Sequential and synchronous combinations were found in 36 (73%) and 13 (27%) patients, respectively. One patient presented three sequential neoplasms. The median cumulative incidence was 6 years (95% CI 3-7). Among all neoplasms diagnosed (n = 99), we found 79 lymphoid neoplasms (LNs) (80%) and 20 myeloid neoplasms (MNs) (20%). Sex ratio was 1.88 with 65% of males and 35% of females. The most common LNs were Hodgkin lymphoma (n = 16; 16%) and multiple myeloma (n = 11; 11%). The most frequent MN was essential thrombocythemia (n = 5; 5%). The most common combination was Hodgkin lymphoma and follicular lymphoma in five (10%) patients. The overall survival from the first diagnosis (OS1) at 5 years was 82.4% (95% CI 72.1-94.3). The median overall survival from the second diagnosis (OS2) was 98 months (95% CI 44-NR) and 5-year OS2 was 58.7% (95% CI 45.5-75.7). Median progression-free survival from the second diagnosis (PFS) was 47 months (95% CI 27-NR) with 5-year PFS of 49% (95% CI 35.9-67). OS and PFS did not statistically differ between synchronous and sequential dual neoplasms. In this cohort, that the death relative risk (RR) was significantly lower if the second neoplasm appeared after more than 4 years following the first diagnosis (OR 0.37 (95% CI 0.16-0.90)). The Hemo2study confirmed the rarity of dual hematological neoplasms. In this cohort, HL and FL were the most frequent combinations. Our results may support that synchronous and sequential dual neoplasms bear the same prognosis. Further studies are needed to better characterize these uncommon clinical situations.


Assuntos
Neoplasias Hematológicas , Segunda Neoplasia Primária , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Prevalência , Estudos Retrospectivos , Taxa de Sobrevida
19.
Adv Exp Med Biol ; 1152: 75-104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456181

RESUMO

Breast cancer encompasses a heterogeneous collection of neoplasms with diverse morphologies, molecular phenotypes, responses to therapy, probabilities of relapse and overall survival. Traditional histopathological classification aims to categorise tumours into subgroups to inform clinical management decisions, but the diversity within these subgroups remains considerable. Application of massively parallel sequencing technologies in breast cancer research has revealed the true depth of variability in terms of the genetic, phenotypic, cellular and microenvironmental constitution of individual tumours, with the realisation that each tumour is exquisitely unique. This poses great challenges in predicting the development of drug resistance, and treating metastatic disease. Central to achieving fully personalised clinical management is translating new insights on breast cancer heterogeneity into the clinical setting, to evolve the taxonomy of breast cancer and improve risk stratification.


Assuntos
Neoplasias da Mama/patologia , Segunda Neoplasia Primária/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Recidiva Local de Neoplasia
20.
Hematol Oncol ; 37(4): 456-463, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31348835

RESUMO

To illustrate the clinical and genetic features of elderly and secondary acute myeloid leukemia (AML) patients, we compared 145 elderly AML (e-AML) and 55 secondary AML (s-AML) patients with 451 young de novo AML patients. Both e-AML and s-AML patients showed lower white blood cell (WBC) and bone marrow (BM) blasts at diagnosis. NPM1, DNMT3A, and IDH2 mutations were more common while biallelic CEBPA and IDH1 mutations were less seen in e-AML patients. s-AML patients carried a higher frequency of KMT2A-AF9. In treatment response and survival, e/s-AML conferred a lower complete remission (CR) rate and shorter duration of event-free survival (EFS) and overall survival (OS) compared with young patients. In multivariate analysis, s-AML was an independent risk factor for OS but not EFS in the whole cohort. Importantly, intensive therapy tended to improve the survival of e/s-AML patients without increasing the risk of early death, and hematopoietic stem cell transplantation (HSCT) could rescue the prognosis of s-AML, which should be recommended for the treatment of fit patients.


Assuntos
Leucemia Mieloide Aguda/genética , Segunda Neoplasia Primária/genética , Adolescente , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Aberrações Cromossômicas , Feminino , Genes Neoplásicos , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasia Residual , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Células-Tronco Neoplásicas/patologia , Prognóstico , Intervalo Livre de Progressão , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA