RESUMEN
BACKGROUND: This study aimed to investigate the predictive value of the tumor mitotic rate per mm(2) (TMR) for sentinel lymph node (SLN) status and survival in intermediate and thick cutaneous melanoma. METHODS: Patients treated for stage I and II melanoma with wide local excision and SLN biopsy between May 1995 and May 2013 were analyzed. In case of insufficient data regarding TMR, pathology slides were reanalyzed. Prognostic factors for SLN status and survival were analyzed with the emphasis on TMR, which was analyzed as a continuous variable, dichotomized (median value) and categorized by two methods. RESULTS: The study analyzed 453 patients with complete TMR data. The median Breslow thickness was 2.20 mm, and 31.8 % of patients had tumor-positive sentinel lymph node biopsies (SLNBs). In the univariate analysis, TMR was associated with tumor-positive SLNB. This association was not significant in the multivariate analysis. Breslow thickness, primary tumor location on trunk and legs, and younger age were associated with tumor-positive SNLB. At a median follow-up of 47 months, 119 patients (26.3 %) had recurrent disease, and 92 (20.3 %) had died of melanoma. In the univariate analysis, TMR could be established as a significant prognostic factor for disease-free and disease-specific survival, but not in the multivariate analyses. Breslow thickness, ulcerated melanoma, and tumor-positive SLNB were significant prognostic factors for survival. CONCLUSION: The study was unable to establish TMR as an independent prognostic factor associated with the presence of SLN metastasis. Regarding survival, increasing TMR showed a strong association with decreased survival in the univariate analysis, but this association was rendered nonsignificant by the importance of Breslow thickness and ulceration status in the multivariate model.
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Ganglios Linfáticos/patología , Melanoma/patología , Mitosis , Recurrencia Local de Neoplasia/patología , Biopsia del Ganglio Linfático Centinela/mortalidad , Neoplasias Cutáneas/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Melanoma/mortalidad , Melanoma/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/cirugía , Tasa de Supervivencia , Adulto Joven , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: In order to define patients eligible for only a superficial groin dissection or a combined superficial and deep groin dissection, this study aimed to determine the incidence of deep lymph node metastases (LNM) in patients with melanoma metastasized to the groin, to identify patient and melanoma factors that predict deep nodal involvement, and to analyze the impact of deep nodal involvement on survival and recurrence. METHODS: Patients who underwent a combined superficial (inguinal) and deep (iliac and obturator) complete (CLND) or therapeutic lymph node dissection (TLND) of the groin between 1994 and 2012 were analyzed. RESULTS: QueryDeep LNM were found in 8 of 62 CLND patients (13 %) and in 21 of 67 TLND patients (31 %). More than three superficial LNM was the only independent predictor for deep LNM in both CLND and TLND patients. The 5-year melanoma-specific survival (MSS) for CLND and TLND patients with deep LNM was 14.3 and 16.6 %, respectively, and was significantly worse (hazard ratio [HR] 3.39, 95 % CI 1.34-8.58, p = 0.010; and HR 2.01, 95 % CI 1.04-3.88, p = 0.039) compared with CLND and TLND patients without deep LNM (5-year MSS: 54.1 and 37.2 %, respectively). Distant recurrence was significantly associated with deep LNM in CLND patients (p = 0.032). CONCLUSIONS: The present study showed that LNM in the deep area of the groin are fairly common in both CLND and TLND patients and significantly affect prognosis, especially in CLND patients. The number of superficial LNM is the only factor that was found to predict a finding of deep nodal metastases.
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Ingle/patología , Ganglios Linfáticos/patología , Melanoma/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Secundarias/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Ingle/cirugía , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Melanoma/mortalidad , Melanoma/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/mortalidad , Neoplasias Primarias Secundarias/cirugía , Pronóstico , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/cirugía , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Angiosarcomas may develop as primary tumours of unknown cause or as secondary tumours, most commonly following radiotherapy to the involved field. The different causative agents may be linked to alternate tumorigenesis, which led us to investigate the genetic profiles of morphologically indistinguishable primary and secondary angiosarcomas. METHODS: Whole-genome (18k) c-DNA-mediated annealing, selection, extension and ligation analysis was used to genetically profile 26 primary and 29 secondary angiosarcomas. Key findings were thereafter validated using RT-qPCR, immunohistochemistry and validation of the gene signature to an external data set. RESULTS: In total, 103 genes were significantly deregulated between primary and secondary angiosarcomas. Secondary angiosarcomas showed upregulation of MYC, KIT and RET and downregulation of CDKN2C. Functional annotation analysis identified multiple target genes in the receptor protein tyrosine kinase pathway. The results were validated using RT-qPCR and immunohistochemistry. Further, the gene signature was applied to an external data set and, herein, distinguished primary from secondary angiosarcomas. CONCLUSIONS: Upregulation of MYC, KIT and RET and downregulation of CDKN2C characterise secondary angiosarcoma, which implies possibilities for diagnostic application and a mechanistic basis for therapeutic evaluation of RET-kinase-inhibitors in these highly aggressive tumours.
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Genes myc , Hemangiosarcoma/genética , Neoplasias Primarias Secundarias/genética , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-ret/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Amplificación de Genes , Genoma Humano , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas Proto-Oncogénicas c-ret/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Synovial sarcoma (SS) is an aggressive soft-tissue tumor. Despite being considered as a chemosensitive disease, the real impact of perioperative chemotherapy on metastasis-free survival (MFS) is controversial. We have shown that metastatic relapse of SS is strongly associated with genomic complexity. There are no data regarding the potential correlation between genomic complexity and response to chemotherapy. PATIENTS AND METHODS: The study population included 65 SS patients diagnosed between 1991 and 2013 and with available tissue material. Genomic profiling was carried out by using array-CGH. Forty-five SS out of the 65 patients were treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy. Radiological response was assessed according to RECIST criteria. Histological response was defined by the percentage of recognizable tumor cells on the surgical specimen. RESULTS: Genomic complexity was significantly associated with MFS. However, there was no statistically significant association between radiological or histological response and genomic complexity. CONCLUSION: The absence of significant association between response to chemotherapy and genomic complexity suggests that the prognostic value of chromosome instability in SS is independent of response to chemotherapy; mechanisms leading to metastatic relapse of SS are intrinsic to the biology of the tumor and current cytotoxic drugs are only poorly efficient to prevent it.
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Inestabilidad Cromosómica/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pronóstico , Sarcoma Sinovial/tratamiento farmacológico , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Genoma Humano , Humanos , Ifosfamida/administración & dosificación , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologíaRESUMEN
AIM: To investigate the feasibility of using bevacizumab to improve the survival of American Joint Committee on Cancer (AJCC) stage III melanoma patients, we investigated how a single bevacizumab treatment affected nodal disease and a panel of biomarkers in clinically fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT)-staged, stage III melanoma patients, prior to therapeutic lymph node dissection (TLND). METHODS: Four weeks before TLND, nine patients (median age 50, range 28.8-62.1 years; two male, seven female) with palpable lymph node metastases received 7.5 mg/kg bevacizumab. Before and after this treatment, all patients were assessed by measurements of the maximum standardized uptake value (SUVmax) by FDG-PET scan, and serum S-100B and lactate dehydrogenase (LDH). After TLND, the dissection specimen was analyzed for number of removed lymph nodes, number of metastatic lymph nodes, and tumor necrosis. RESULTS: Median follow-up was 15.5 (2.2-32.9) months. Histopathological analysis revealed tumor necrosis in six patients, of whom five had an S-100B decline and one had an unchanged S-100B level after bevacizumab. The other three patients showed an S-100B increase and no necrosis. Tumor necrosis was correlated with S-100B decrease (P = 0.048). No association was found between necrosis and the markers SUVmax and LDH. No wound healing disturbances were encountered. CONCLUSION: Tumor necrosis in dissection specimens was associated with declining S-100B levels, while elevated S-100B was only found in cases with no necrosis. Bevacizumab might be useful in treating AJCC stage III melanoma patients prior to TLND, and S100-B appears to be a useful marker for assessment of treatment effects.
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Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Biomarcadores de Tumor/sangre , Melanoma/sangre , Melanoma/tratamiento farmacológico , Factores de Crecimiento Nervioso/sangre , Proteínas S100/sangre , Adulto , Bevacizumab , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Melanoma/patología , Persona de Mediana Edad , Imagen Multimodal , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Subunidad beta de la Proteína de Unión al Calcio S100 , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: FDG PET/CT is an excellent tool to detect melanoma metastases and also allows quantification of FDG uptake using standardized uptake value (SUV). The aim of this study was to prospectively investigate the potential prognostic value of SUV for disease-free survival (DFS) and disease-specific survival (DSS) for patients with stage IIIB melanoma. METHODS: From November 2003 to March 2008, all consecutive patients were included in the present study. Inclusion criteria were: palpable, histology- or cytology-proven lymph node metastases of melanoma, and referred to the University Medical Centre Groningen for FDG PET and CT examination. Patients without distant metastases were evaluated. Multivariable survival analysis was performed to determine whether SUV was associated with DFS and DSS (Cox proportional hazard analysis). RESULTS: In 80 patients (without distant metastases, 65 %) SUV could be measured. Overall 5-year DFS was 41 % (95% CI 26-56 %) and 24 % (95% CI 12-38 %) in patients with a low and high SUVmean (p = 0.02), respectively. Overall 5-year DSS was 48 % (95% CI 31-62 %) and 30 % (95% CI 17-45 %) in patients with a low and high SUVmean (p = 0.04), respectively. In the multivariable analysis, SUVmean was associated with DFS (hazard ratio 1.7; p = 0.048), but was not associated with DSS (hazard ratio 1.6; p = 0.1). The number of positive nodes, extranodal growth and gender were also associated with survival. CONCLUSION: FDG uptake in clinically overt nodal melanoma metastases is inversely associated with DFS. Univariate analysis showed an association with DSS. However, after adjustment for potential confounders this association was no longer significant. If these findings are confirmed in larger studies, SUVmean could potentially be used (in addition to the number of positive nodes, tumour size and extranodal growth) as a factor in deciding on adjuvant systemic treatment.
Asunto(s)
Fluorodesoxiglucosa F18 , Melanoma/diagnóstico por imagen , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Glucosa/metabolismo , Humanos , Metástasis Linfática , Masculino , Melanoma/mortalidad , Melanoma/patología , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
BACKGROUND: Melanoma lymph nodes metastases may be detected by patients or by physicians. Understanding the outcomes of self-detection or physician detection is essential for the design of follow-up studies. We evaluated the role of the method of detection in nodal disease in the prognosis of melanoma patients who underwent therapeutic lymph node dissection (TLND). MATERIALS AND METHODS: All melanoma patients with palpable lymph nodes were included in a prospective database (n = 98), and the method of detection was recorded. Detection of lymph node metastases compared with pathological findings in the TLND was assessed by multivariate logistic regression. Disease-free survival (DFS) and disease-specific survival (DSS) were assessed by univariate and multivariate Cox proportional hazard analysis. RESULTS: Nodal metastases were detected by physicians in 45% and by patients in 55% (P < 0.001). Age was significantly associated with method of detection. Patients ≤60 years detected 69% their lymph node metastases as opposed to 32% of patients >60 years (odds ratio [OR] 0.3; P = 0.007). However, this was not associated with prognostic findings in TLND, number of positive nodes, tumor size, or extranodal spread. Method of detection or age at the time of nodal metastases was not significantly associated with 2-year DFS or DSS. CONCLUSIONS: 45% of all lymph node metastases in stage I-II melanoma patients are physician detected. Younger patients detect their own lymph node metastases significantly more often than elderly patients. However, neither the method of detection nor age correlates with DSS. More frequent follow-up would not alter DFS and DSS significantly.
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Melanoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Melanoma/secundario , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias Cutáneas/patología , Análisis de SupervivenciaRESUMEN
OBJECTIVE: Patients with a gastrointestinal stromal tumour (GIST) suffering from non-islet cell tumour-induced hypoglycaemia (NICTH), being associated with increased plasma levels of pro-insulin-like growth factor (IGF)-IIE[68-88], have been reported occasionally. We studied the clinical relevance of pro-IGF-IIE[68-88] and other IGF-related proteins in GIST patients. PATIENTS AND METHODS: Twenty-four patients were included. Plasma samples were collected before 1 week and median 5 months after start of treatment with imatinib, and levels of IGF-I, total IGF-II, pro-IGF-IIE[68-88], insulin-like growth factor-binding protein (IGFBP)-2, -3 and -6 were determined. GIST specimens from 17 patients and tumour cyst fluid from two patients were analysed for IGF-II and IGFBP-2. RESULTS: Before treatment and/or during follow-up, 3 of 24 (13%) patients showed increased plasma levels of pro-IGF-IIE[68-88]. All three developed NICTH. Overall, patients with metastatic disease, elevated serum lactate dehydrogenase activity or total tumour size >12 cm had the highest pro-IGF-IIE[68-88] levels. Most patients had increased plasma IGFBP-2 levels and these levels were significantly higher in patients with progressive disease. (Pro-)IGF-II was expressed in 82% of GISTs and IGFBP-2 only in one case. CONCLUSION: We identified pro-IGF-IIE[68-88] as a marker that may be used in the surveillance of GIST.
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Tumores del Estroma Gastrointestinal/complicaciones , Hipoglucemia/etiología , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Somatomedinas/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Líquido Quístico/química , Líquido Quístico/metabolismo , Femenino , Tumores del Estroma Gastrointestinal/sangre , Tumores del Estroma Gastrointestinal/patología , Humanos , Hipoglucemia/sangre , Hipoglucemia/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Elevation of the tumor marker S-100B in melanoma patients is a highly specific indicator of recurrence. MATERIALS AND METHODS: The role of S-100B in disease-free survival (DFS) was evaluated in stage III melanoma patients (staged with fluorodeoxyglucose positron emission tomography [FDG-PET] and computed tomography [CT]) with palpable lymph node metastases who underwent therapeutic lymph node dissection. S-100B and LDH were measured on the day before surgery (d = -1) and on days 1, 2, and 7 postoperatively. Multivariate logistic regression was used to study factors associated with preoperative elevation of S-100B. Univariate (log-rank test) and multivariate (Cox regression) survival analyses were performed to identify factors associated with DFS. RESULTS: Between 2004 and 2008, 56 patients (median age 57, range 24-93) years, 27 males (48%) and 29 females (52%) entered the study. Preoperative S-100B elevation was found in 27 patients (48%) and elevated LDH in 20 patients (36%). No association was found between these two markers at any time. Multivariate analysis showed that elevated S-100B preoperatively (hazard ratio [HR] 2.7, P = .03) was associated with DFS. S-100B elevation was associated with increased tumor size (odds ratio [OR] 3.40; P = .03). CONCLUSION: Elevated S-100B preoperatively in patients with optimally staged clinical stage III melanoma is associated with decreased disease-free survival. S100-B could be used as a prognostic marker in the stratification of new adjuvant trials to select stage III melanoma patients for adjuvant systematic treatment.
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Melanoma/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Proteínas S100/metabolismo , Neoplasias Cutáneas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Supervivencia sin Enfermedad , Femenino , Fluorodesoxiglucosa F18 , Humanos , Técnicas para Inmunoenzimas , L-Lactato Deshidrogenasa/metabolismo , Metástasis Linfática , Masculino , Melanoma/diagnóstico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Estadificación de Neoplasias , Atención Perioperativa , Tomografía de Emisión de Positrones , Pronóstico , Radiofármacos , Subunidad beta de la Proteína de Unión al Calcio S100 , Neoplasias Cutáneas/diagnóstico , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Although the tyrosine kinase inhibitor imatinib has been shown to be an active agent in patients with gastrointestinal stromal tumours (GIST), complete remissions are almost never seen and most patients finally experience disease progression during their course of treatment. An alternative therapeutic option is to target death receptors such as Fas. We showed that a panel of imatinib-sensitive (GIST882) and imatinib-resistant (GIST48, GIST430 and GIST430K-) cell lines expressed Fas. MegaFasL, a recently developed hexameric form of soluble Fas ligand (FasL), appeared to be an active apoptosis-inducing agent in these cell lines. Moreover, MegaFasL potentiated the apoptotic effects of imatinib. Immunohistochemical evaluations, in 45 primary GISTs, underscored the relevance of the Fas pathway: Fas was expressed in all GISTs and was expressed strongly in 93%, whereas FasL was expressed at moderate and strong levels in 35 and 53% of GISTs, respectively. Fas and FasL expression were positively correlated in these primary GISTs, but there was no association between Fas or FasL expression and primary site, histological subtype, tumour size, mitotic index, risk classification, and KIT mutation status. The abundant immunohistochemical Fas and FasL expression were corroborated by western blot analysis. In conclusion, our data implicate Fas as a potential therapeutic target in GIST.
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Proteína Ligando Fas/uso terapéutico , Tumores del Estroma Gastrointestinal/metabolismo , Receptor fas/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Benzamidas , Línea Celular Tumoral , Femenino , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Piperazinas/farmacología , Piperazinas/uso terapéutico , Pirimidinas/farmacología , Pirimidinas/uso terapéuticoRESUMEN
BACKGROUND: The diagnosis of tumors of soft tissue and bone (STB) heavily relies on histological biopsies, whereas cytology is not widely used. CellientTM cell blocks often contain small tissue fragments. In addition to Hematoxylin and Eosin (H&E) interpretation of histological features, immunohistochemistry (IHC) can be applied after optimization of protocols. The objective of this retrospective study was to see whether this cytological technique allowed us to make a precise diagnosis of STB tumors. METHODS: Our study cohort consisted of 20 consecutive STB tumors, 9 fine-needle aspiration (FNAC) samples, and 11 endoscopic ultrasonography (EUS) FNACs and included 8 primary tumors and 12 recurrences or metastases of known STB tumors. RESULTS: In all 20 cases, H&E stained sections revealed that diagnostically relevant histological and cytological features could be examined properly. In the group of 8 primary tumors, IHC performed on CellientTM material provided clinically important information in all cases. For instance, gastrointestinal stromal tumor (GIST) was positive for CD117 and DOG-1 and a PEComa showed positive IHC for actin, desmin, and HMB-45. In the group of 12 secondary tumors, SATB2 was visualized in metastatic osteosarcoma, whereas expression of S-100 was present in 2 secondary chondrosarcomas. Metastatic chordoma could be confirmed by brachyury expression. Two metastatic alveolar rhabdomyosarcomas were myf4 positive, a metastasis of a gynecologic leiomyosarcoma was positive for actin and estrogen receptor (ER) and a recurrent dermatofibrosarcoma protuberans expressed CD34. CONCLUSION: In the proper clinical context, including clinical presentation with imaging studies, the CellientTM cell block technique has great potential for the diagnosis of STB tumors.
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Neoplasias Óseas/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Neoplasias de los Tejidos Blandos/patología , Coloración y Etiquetado/métodos , Adhesión del Tejido/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/normas , Humanos , Coloración y Etiquetado/instrumentación , Coloración y Etiquetado/normas , Adhesión del Tejido/instrumentación , Adhesión del Tejido/normasRESUMEN
BACKGROUND: This pilot study investigated the feasibility of (18)F-3'-deoxy-3'-fluoro-l-thymidine ((18)F-FLT) as a positron emission tomography (PET) tracer for the visualisation of breast cancer. METHODS: Patients with breast cancer underwent (18)F-FLT-PET prior to surgery. The uptake of (18)F-FLT was determined in the primary tumour and in the axilla. RESULTS: Eight tumours were visualized by (18)F-FLT-PET with a mean uptake value (SUV(mean)) of 1.7 and mean tumour-non-tumour ratio (TNT) of 5.0. In seven patients, axillary lymph-node metastases were found at pathological examinations, however, (18)F-FLT-PET showed uptake in only two large (and clinically evident) lymph-node metastases. CONCLUSIONS: (18)F-FLT shows uptake in most primary breast tumours and in large axillary lymph-node metastases.
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Neoplasias de la Mama/diagnóstico por imagen , Carcinoma/diagnóstico por imagen , Didesoxinucleósidos , Radioisótopos de Flúor , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Axila , Neoplasias de la Mama/cirugía , Carcinoma/cirugía , Estudios de Factibilidad , Femenino , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática , Mastectomía , Persona de Mediana Edad , Proyectos Piloto , Cuidados Preoperatorios , Estudios Prospectivos , Reproducibilidad de los Resultados , Biopsia del Ganglio Linfático CentinelaRESUMEN
A 42-year-old heterosexual man presented with bluish-purple spots on his skin and in his mouth cavity that had been present for a few months; a 48-year-old homosexual man had painful lymphadenopathy in the groins and left axilla. Both men appeared to have a Kaposi's sarcoma and to be HIV-positive. During highly active antiretroviral therapy (HAART) and radiotherapy or chemotherapy, both the AIDS parameters and the skin lesions improved. Kaposi's sarcoma is AIDS-defining in HIV-seropositive patients. Human herpesvirus-8 infection seems to play a role in the development of Kaposi's sarcoma. The incidence of Kaposi's sarcoma has declined since the introduction of HAART. Nowadays, Kaposi's sarcoma is frequently the presenting symptom of HIV-seropositivity. Patients present with purple cutaneous lesions and/or generalised lymphadenopathy. Visceral lesions are associated with a shorter median survival. The treatment of Kaposi's sarcoma is palliative, whereas immune restitution can lead to regression of the sarcoma.
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Terapia Antirretroviral Altamente Activa , Infecciones por VIH/complicaciones , Herpesvirus Humano 8/inmunología , Sarcoma de Kaposi/virología , Adulto , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/patología , Homosexualidad Masculina , Humanos , Masculino , Persona de Mediana Edad , Sarcoma de Kaposi/tratamiento farmacológico , Sarcoma de Kaposi/patologíaRESUMEN
A 50-year-old man awaiting liver transplantation for primary sclerosing cholangitis developed iron-deficiency anaemia. Repeated occult gastrointestinal bleeding led to an increasing need for blood transfusions. After multiple oesophagogastroduodenoscopies and colonoscopies, videocapsule endoscopy finally demonstrated a polyp-like lesion in the terminal ileum. The lesion had not been detected despite two attempts (oral and anal) at double-balloon enteroscopy and even a peroperative enteroscopy. Only during a second laparotomy, again involving peroperative enteroscopy, a small red lesion was detected and resected 80 cm proximal to the ileocecal valve (Bauhin's valve). Histology revealed a Dieulafoy lesion. Four months later, after normalisation and stabilisation of his haemoglobin level, the patient received a successful liver transplant. If the cause of occult gastrointestinal bleeding in a patient remains unclear despite regular endoscopic procedures, new techniques like videocapsule endoscopy and double-balloon enteroscopy may contribute to identifying the cause. This may lead to an exceptional finding such as a Dieulafoy lesion in the distal ileum.
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Endoscopios Gastrointestinales , Endoscopía Gastrointestinal/métodos , Hemorragia Gastrointestinal/diagnóstico , Íleon/patología , Anemia Ferropénica/etiología , Diagnóstico Diferencial , Hemorragia Gastrointestinal/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Grabación en VideoRESUMEN
BACKGROUND: Soft tissue sarcomas (STS) are uncommon malignancies and elderly STS patients have been reported to receive less definitive treatment compared to young STS patients. The present study was performed to investigate whether withholding treatment was based on disease specific aspects, patients' general health condition, comorbidity or a combination of these. METHODS: Patients with primary STS, registered by the Comprehensive Cancer Center North-Netherlands (CCCN) from 1989 to 1999, were analyzed retrospectively with regard to the inclusion-criteria: no primary anti-tumor treatment. RESULTS: From 1989 to 1999, 620 patients (including 56 Kaposi sarcoma) were registered with primary STS. Seventy-six patients (13%) were registered as untreated. Nineteen patients were excluded. Records of 57 patients, median age 71 years (range 23-92, 40 patients > or =65 years, 17 patients < 65 years) were examined. The reasons for no treatment were irresectability of the sarcoma (65%), metastatic disease (11%), comorbidity (4%), poor general health (5%), death prior to therapy (7%) and refusal of therapy (3%) (motivation not documented in 5%). CONCLUSIONS: Thirteen percent of all STS patients within the CCCN region were not treated, 70% of these patients were elderly. Withholding treatment was mostly disease-related (76%), e.g. irresectable retroperitoneal STS or metastatic disease; for 19% of the patients, it was related to their poor general health. The decision to refrain from cancer treatment was justifiable in all these STS patients.
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Sarcoma/terapia , Neoplasias de los Tejidos Blandos/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Motivación , Estadificación de Neoplasias , Países Bajos , Pronóstico , Estudios Retrospectivos , Sarcoma/patología , Neoplasias de los Tejidos Blandos/patología , Privación de TratamientoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the advantages and disadvantages of sentinel lymph node biopsy (SLNB) in patients with cutaneous melanoma. DESIGN: Descriptive follow-up study. METHOD: In the period 1995-2004, 300 patients with cutaneous melanoma (Breslow thickness: > or = 1.0 mm) underwent SLNB and, in case of a tumour-positive result, regional lymph node dissection. Results of the SLNB procedure, postoperative complications, follow-up, recurrences, disease-free survival and disease-specific survival were evaluated. RESULTS: The SLNB detection rate was 99%. 85 patients had a tumour-positive SLNB (28%) and underwent completion regional lymph node dissection; 215 patients underwent SLNB alone. The rate of postoperative complications after SLNB was 7%. With a median follow up of 51 months, the false-negative rate was 11%. The recurrence rate was 23% (SLNB negative: 19%; SLNB positive 34%; p = 0.005). In-transit metastases were found in 4% of the SLNB-negative group and in 20% of the SLNB-positive group (p < 0.001). The 5-year disease-free survival and disease-specific survival rates were 79% and 86%, respectively, in SLNB-negative patients and 57% and 71%, respectively, in SLNB-positive patients. Multivariate analysis showed that the independent prognostic factors for disease-free survival were presence of ulceration (p < 0.001) and SLNB positivity (p < 0.01). Prognostic factors for overall survival were presence of ulceration (p < 0.001) and male sex (p < 0.05), but not the SLNB results. Multivariate analysis also showed that SLNB positivity (p < 0.001) and presence of ulceration (p < 0.01) were independent prognostic factors for developing in-transit metastases. CONCLUSION: SLNB in patients with cutaneous melanoma is still only of prognostic value since survival benefit is not proven. Disadvantages of SLNB were the false-negative rate, the possibility of an increased risk of in-transit metastases in SLNB-positive patients, and postoperative complications. These must be kept in mind when offering patients SLNB.
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Metástasis Linfática/diagnóstico , Melanoma/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/mortalidad , Melanoma/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/cirugía , Análisis de SupervivenciaRESUMEN
To determine whether superhydrophobic modification of small diameter expanded polytetrafluoroethylene (ePTFE) vascular grafts improves the performance of these grafts, we assessed neointima formation and platelet deposition in standard and superhydrophobic modified ePTFE grafts. Standard and superhydrophobic vascular grafts were implanted in the carotid arteries of two rabbits and two pigs. Furthermore, standard and superhydrophobic vascular patches were implanted in the carotid arteries of seven pigs. After 4 weeks of implantation all patches were removed and histomorphometric data were analyzed. The early thrombotic effect of superhydrophobic modification was examined by quantifying platelet glycoprotein receptor IIIa deposition onto each type of vascular graft after 15 min of in vitro circulation with human blood. All superhydrophobic and standard ePTFE vascular grafts occluded 15 min to 1 h after implantation in both rabbit and pig carotid arteries. All implanted patches remained patent and were completely covered by endothelium. Superhydrophobic modification of ePTFE vascular grafts did not lead to less neointima formation and resulted in significantly more platelet deposition than did standard ePTFE vascular grafts. Thus, superhydrophobic modification does not improve the performance of small diameter ePTFE vascular grafts.
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Prótesis Vascular/normas , Politetrafluoroetileno , Animales , Arterias Carótidas , Microscopía Electrónica de Rastreo , Conejos , Porcinos , Túnica ÍntimaRESUMEN
Two men aged 47 and 56 and one woman aged 21 presented at our cardiology department with presyncope, heart failure and exercise induced palpitations, respectively. Using the criteria of McKenna et al., a diagnosis of arrhythmogenic right-ventricular cardiomyopathy (ARVC) was made. Following implantation of a defibrillator, one of the men experienced seven appropriate interventions within six months and also developed psychological problems. The other man was problem-free and the woman recovered reasonably well, having only one appropriate intervention from the defibrillator one year after implantation. Indications of ARVC were also found in her mother but not in any other family members. Because ARVC manifests itself in various different ways it is difficult to diagnose. It is important to consider ARVC in patients with exercise-induced palpitations, presyncope, and unexplained cardiomyopathies or arrhythmias, especially if there is a family history of unexpected deaths. ARVC is a potentially life-threatening disease, that may require implantation of a cardioverter defibrillator. Furthermore, since genetics play an important role and ARVC can be asymptomatic, evaluation of close relatives for preclinical symptoms is important.
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Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/terapia , Muerte Súbita Cardíaca/prevención & control , Desfibriladores Implantables , Adulto , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/genética , Diagnóstico Diferencial , Electrocardiografía , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Atypical cartilaginous tumours are usually treated by curettage. The purpose of this study was to show that radiofrequency ablation was an effective alternative treatment. We enrolled 20 patients (two male, 18 female, mean age 56 years (36 to 72) in a proof-of-principle study. After inclusion, biopsy and radiofrequency ablation were performed, followed three months later by curettage and adjuvant phenolisation. The primary endpoint was the proportional necrosis in the retrieved material. Secondary endpoints were correlation with the findings on gadolinium enhanced MRI, functional outcome and complications. Our results show that 95% to 100% necrosis was obtained in 14 of the 20 patients. MRI had a 91% sensitivity and 67% specificity for detecting residual tumour after curettage. The mean functional outcome (MSTS) score six weeks after radiofrequency ablation was 27.1 (23 to 30) compared with 18.1 (12 to 25) after curettage (p < 0.001). No complications occurred after ablation, while two patients developed a pathological fracture after curettage. We have shown that radiofrequency ablation is capable of completely eradicating cartilaginous tumour cells in selective cases. MRI has a 91% sensitivity for detecting any residual tumour. Radiofrequency ablation can be performed on an outpatient basis allowing a rapid return to normal activities. If it can be made more effective, it has the potential to provide better local control, while improving functional outcome.
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Neoplasias Óseas/cirugía , Cartílago/cirugía , Ablación por Catéter/métodos , Adulto , Anciano , Biopsia , Neoplasias Óseas/diagnóstico , Cartílago/diagnóstico por imagen , Cartílago/patología , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: To assess the long-term outcome after sentinel lymph node biopsy (SLNB) in melanoma patients. METHODS: Between 1995-2009 450 melanoma patients underwent SLNB in a single center. Survival and prognostic factors were analyzed for 429 patients. RESULTS: Median age was 53 (range 11-84) years. Median Breslow thickness was 2.4 (range 1-20) mm and 36% were ulcerated melanomas. Median follow-up time was 64.8 (range 2-174) months. A tumor-positive SLN was present in 140 patients (31%). Completion lymph node dissection (CLND) was performed in 119 patients and these patients were analyzed for recurrence and survival. 124 Patients (29%) relapsed during follow-up; 55 in the node-positive group who underwent CLND (55/119; 46%) and 69 in the node-negative group (69/310; 22%; p < 0.001). In the node-negative group 17 patients developed recurrence in the regional node field; false-negative rate 11%. On multivariate analysis strongest prognostic factors for disease free survival (DFS) were primary melanoma ulceration and SLN positivity (Hazard Ratio (HR) of 2.2 and 2.3; p < 0.001). For disease specific survival (DSS) the same was found to be true with an HR of 2.1 for ulceration and 2.0 for SLN positivity (p = 0.001 and p = 0.002 respectively). 10-Year DFS was 71% for node-negative patients compared with 48% for node-positive patients (p < 0.001). 10-Year DSS was 77% for node-negative patients compared to 60% for node-positive patients (p < 0.001). CONCLUSIONS: This study shows a remarkably high percentage of tumor-positive SLN. The long-term follow-up data confirm that tumor-positive SLN patients have a worse DFS and DSS than tumor-negative SLN patients. Ulceration and SLN status proved to be the strongest prognostic factors for long-term DFS and DSS.