RESUMEN
Chronic Myeloid Leukemia is a blood cancer for which standard therapy with Tyrosine-Kinase Inhibitors is successful in the majority of patients. After discontinuation of treatment half of the well-responding patients either present undetectable levels of tumor cells for a long time or exhibit sustained fluctuations of tumor load oscillating at very low levels. Motivated by the consequent question of whether the observed kinetics reflect periodic oscillations emerging from tumor-immune interactions, in this work, we analyze a system of ordinary differential equations describing the immune response to CML where both the functional response against leukemia and the immune recruitment exhibit optimal activation windows. Besides investigating the stability of the equilibrium points, we provide rigorous proofs that the model exhibits at least two types of bifurcations: a transcritical bifurcation around the tumor-free equilibrium point and a Hopf bifurcation around a biologically plausible equilibrium point, providing an affirmative answer to our initial question. Focusing our attention on the Hopf bifurcation, we examine the emergence of limit cycles and analyze their stability through the calculation of Lyapunov coefficients. Then we illustrate our theoretical results with numerical simulations based on clinically relevant parameters. Besides the mathematical interest, our results suggest that the fluctuating levels of low tumor load observed in CML patients may be a consequence of periodic orbits arising from predator-prey-like interactions.
Asunto(s)
Simulación por Computador , Leucemia Mielógena Crónica BCR-ABL Positiva , Conceptos Matemáticos , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Humanos , Modelos Inmunológicos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Modelos Biológicos , Carga Tumoral/inmunologíaRESUMEN
OBJECTIVE: Preoperative embolization of paragangliomas decreases tumor volume and reduces intraoperative blood loss. This study aimed to evaluate the effect of the rate of devascularization achieved by preoperative embolization of carotid body tumors on surgical outcomes. METHODS: Patients with carotid body tumors who underwent preoperative transarterial embolization between 2013 and 2024 were included in this retrospective study. The Shamblin classification of all patients was carried out using radiological imaging. Devascularization rates obtained after the embolization of carotid body tumors were determined from angiographic images. Patients were divided into two groups: near-complete embolization (devascularization rate >90%) and incomplete embolization (devascularization rate <90%). Hemoglobin loss was calculated with blood tests before and immediately after surgery. Tumor volume loss was calculated by preoperative radiological tumor volume and postoperative surgical specimen volume. Hemoglobin loss, tumor volume loss, and postoperative complication rates of the two groups were compared. RESULTS: A total of 31 patients with carotid body tumors who underwent surgery were included in the study. Near-complete embolization was achieved in 21 patients (67.74%), while incomplete embolization was achieved in 10 patients (32.25%). Shamblin classification was statistically similar (p>0.05) between the two groups. The vascular complication rate in the near-complete embolization group was significantly lower than in the incomplete embolization group (p=0.027). However, no significant difference was observed in neurological complication rates, hemoglobin loss, and tumor volume loss parameters between the two groups (p>0.05). CONCLUSION: The preoperative devascularization rate should be at least 90% to minimize the risk of vascular complications.
Asunto(s)
Pérdida de Sangre Quirúrgica , Tumor del Cuerpo Carotídeo , Embolización Terapéutica , Cuidados Preoperatorios , Humanos , Embolización Terapéutica/métodos , Tumor del Cuerpo Carotídeo/cirugía , Tumor del Cuerpo Carotídeo/diagnóstico por imagen , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Cuidados Preoperatorios/métodos , Pérdida de Sangre Quirúrgica/prevención & control , Carga Tumoral , Anciano , Complicaciones Posoperatorias/prevención & controlRESUMEN
Objective: Management of suspect adnexal masses involves surgery to define the best treatment. Diagnostic choices include a two-stage procedure for histopathology examination (HPE) or intraoperative histological analysis - intraoperative frozen section (IFS) and formalin-fixed and paraffin-soaked tissues (FFPE). Preoperative assessment with ultrasound may also be useful to predict malignancy. We aimed at determining the accuracy of IFS to evaluate adnexal masses stratified by size and morphology having HPE as the diagnostic gold standard. Methods: A retrospective chart review of 302 patients undergoing IFS of adnexal masses at Hospital de Clínicas de Porto Alegre, between January2005 and September2011 was performed. Data were collected regarding sonographic size (≤10cm or >10cm), characteristics of the lesion, and diagnosis established in IFS and HPE. Eight groups were studied: unilocular lesions; septated/cystic lesions; heterogeneous (solid/cystic) lesions; and solid lesions, divided in two main groups according to the size of lesion, ≤10cm or >10cm. Kappa agreement between IFS and HPE was calculated for each group. Results: Overall agreement between IFS and HPE was 96.1% for benign tumors, 96.1% for malignant tumors, and 73.3% for borderline tumors. Considering the combination of tumor size and morphology, 100% agreement between IFS and HPE was recorded for unilocular and septated tumors ≤10cm and for solid tumors. Conclusion: Stratification of adnexal masses according to size and morphology is a good method for preoperative assessment. We should wait for final HPE for staging decision, regardless of IFS results, in heterogeneous adnexal tumors of any size, solid tumors ≤10cm, and all non-solid tumors >10cm.
Asunto(s)
Enfermedades de los Anexos , Secciones por Congelación , Ultrasonografía , Humanos , Femenino , Estudios Retrospectivos , Adulto , Enfermedades de los Anexos/diagnóstico por imagen , Enfermedades de los Anexos/patología , Persona de Mediana Edad , Anciano , Adulto Joven , Adolescente , Carga Tumoral , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: To retrospectively investigate the impact of pre-treatment Extracellular Volume Fraction (ECV) measured by Computed Tomography (CT) on the response of primary lesions to preoperative chemotherapy in abdominal neuroblastoma. METHODS: A total of seventy-five patients with abdominal neuroblastoma were retrospectively included in the study. The regions of interest for the primary lesion and aorta were determined on unenhanced and equilibrium phase CT images before treatment, and their average CT values were measured. Based on patient hematocrit and average CT values, the ECV was calculated. The correlation between ECV and the reduction in primary lesion volume was examined. A receiver operating characteristic curve was generated to assess the predictive performance of ECV for a very good partial response of the primary lesion. RESULTS: There was a negative correlation between primary lesion volume reduction and ECV (r = -0.351, p = 0.002), and primary lesions with very good partial response had lower ECV (p < 0.001). The area under the curve for ECV in predicting the very good partial response of primary lesion was 0.742 (p < 0.001), with a 95 % Confidence Interval of 0.628 to 0.836. The optimal cut-off value was 0.28, and the sensitivity and specificity were 62.07 % and 84.78 %, respectively. CONCLUSIONS: The measurement of pre-treatment ECV on CT images demonstrates a significant correlation with the response of the primary lesion to preoperative chemotherapy in abdominal neuroblastoma.
Asunto(s)
Neoplasias Abdominales , Neuroblastoma , Tomografía Computarizada por Rayos X , Humanos , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/cirugía , Neuroblastoma/patología , Masculino , Femenino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Preescolar , Niño , Lactante , Neoplasias Abdominales/diagnóstico por imagen , Neoplasias Abdominales/tratamiento farmacológico , Neoplasias Abdominales/patología , Neoplasias Abdominales/cirugía , Resultado del Tratamiento , Curva ROC , Valor Predictivo de las Pruebas , Adolescente , Carga Tumoral/efectos de los fármacos , Sensibilidad y Especificidad , Valores de Referencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION AND OBJECTIVES: The absence of melanoma 2 (AIM2) protein triggers the activation of the inflammasome cascade. It is unclear whether AIM2 plays a role in hepatocellular carcinoma (HCC) and radiofrequency ablation (RFA), which uses radiofrequency waves to treat tumors. In this study, we investigated if RFA could induce pyroptosis, also called cell inflammatory necrosis, in HCC through AIM2-inflammasome signaling in vivo and in vitro. MATERIALS AND METHODS: BALB/c nude mice were used to generate HepG2 or SMMC-7721 cell-derived tumor xenografts. HCC cells with knockdown or overexpression of AIM2 were created using short hairpin RNA (shRNA) and expression vector transfection, respectively, for functional and mechanistic studies. Downstream effects were examined using flow cytometry, qRT-PCR, ELISAs, and other molecular assays. RESULTS: RFA significantly suppressed tumor growth in HCC cell xenografts. Flow cytometry analysis revealed that RFA could induce pyroptosis. Furthermore, AIM2, NLRP3, caspase-1, γ-H2AX, and DNA-PKc had significantly greater expression levels in liver tissues from mice treated with RFA compared with those of the controls. Additionally, interleukin (IL)-1ß and IL-18 expression levels were significantly higher in the HCC cell-derived xenograft mice treated with RFA compared with those without RFA. Notably, a significantly greater effect was achieved in the RFA complete ablation group versus the partial ablation group. Knockdown or overexpression of AIM2 in HCC cells demonstrated that AIM2 exerted a role in RFA-induced pyroptosis. CONCLUSIONS: RFA can suppress HCC tumor growth by inducing pyroptosis via AIM2. Therefore, therapeutically intervening with AIM2-mediated inflammasome signaling may help improve RFA treatment outcomes for HCC patients.
Asunto(s)
Carcinoma Hepatocelular , Proteínas de Unión al ADN , Inflamasomas , Interleucina-1beta , Neoplasias Hepáticas , Piroptosis , Ablación por Radiofrecuencia , Animales , Humanos , Ratones , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirugía , Caspasa 1/metabolismo , Caspasa 1/genética , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Células Hep G2 , Histonas/metabolismo , Inflamasomas/metabolismo , Interleucina-18/metabolismo , Interleucina-18/genética , Interleucina-1beta/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Ratones Endogámicos BALB C , Ratones Desnudos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Transducción de Señal , Carga TumoralRESUMEN
BACKGROUND: The incidence of thyroid cancer in the United States has risen dramatically since the 1970s, driven by an increase in the diagnosis of small tumors. There is a paucity of published New Mexico (NM) specific data regarding thyroid cancer. We hypothesized that due to New Mexico's unique geographic and cultural makeup, the incidence of thyroid cancer and tumor size at diagnosis in this state would differ from that demonstrated on a national level. METHODS: The New Mexico Tumor Registry (NMTR) was queried to include all NM residents diagnosed with thyroid cancer between 1992 and 2019. For 2010 to 2019, age-adjusted incidence rates were calculated via direct method using the 2000 United States population as the adjustment standard. Differences in incidence rate and tumor size by race/ethnicity and residence (metropolitan vs non-metropolitan) were assessed with rate ratios between groups. For 1992 to 2019, temporal trends in age-adjusted incidence rates for major race/ethnic groups in NM [Non-Hispanic White (NHW), Hispanic, and American Indian (AI)] were assessed by joinpoint regression using National Cancer Institute software. RESULTS: Our study included 3,161 patients for the time period 2010 to 2019, including NHW (1518), Hispanic (1425), and AI (218) cases. The overall incidence rates for NM AIs were lower than those for Hispanics and NHWs because of a decreased incidence of very small tumors (<1.1 cm). The incidence rates for large tumors (>5.1 cm) was equivalent among groups. In the early 2000s, Hispanics also had lower rates of small tumors when compared to NHWs but this trend disappeared over time. CONCLUSION: AIs in New Mexico have been left out of the nationwide increase in incidental diagnosis of small thyroid tumors. This same pattern was noted for Hispanics in the early 2000s but changed over time to mirror incidence rates for NHWs. These data are illustrative of the health care disparities that exist among New Mexico's population and how these disparities have changed over time.
Asunto(s)
Hispánicos o Latinos , Neoplasias de la Tiroides , Población Blanca , Humanos , Neoplasias de la Tiroides/epidemiología , Neoplasias de la Tiroides/etnología , Neoplasias de la Tiroides/patología , Incidencia , New Mexico/epidemiología , Masculino , Hispánicos o Latinos/estadística & datos numéricos , Femenino , Persona de Mediana Edad , Adulto , Población Blanca/estadística & datos numéricos , Anciano , Sistema de Registros , Indígenas Norteamericanos/estadística & datos numéricos , Carga TumoralRESUMEN
OBJECTIVES: This study aimed to compare the intestinal and pancreatobiliary subtypes of ampullary adenocarcinoma in a large patient group due to limited data on survival and risk factors. METHODS: A retrospective analysis of the clinical and pathological findings and the survival of 184 patients with ampullary adenocarcinoma who underwent curative operation between 2007 and 2018 was performed. RESULTS: Pancreatobiliary subtype had a higher prevalence of jaundice before operation than the intestinal subtype (p < 0.05). Pancreatobiliary subtype had a larger tumor size (> 2 mm) (p < 0.01) and poorer differentiation (p < 0.05) than the intestinal subtype. Perineural invasion more frequently occurred in pancreatobiliary subtype than the intestinal subtype (p < 0.01) and pancreatobiliary subtype had a higher prevalence of positive dissected lymph nodes (p < 0.05) with an advanced disease stage (p < 0.01) than the intestinal subtype. Patients of the pancreatobiliary subtype had poorer disease-free and overall survival than patients of the intestinal subtype. No survival benefit of adjuvant chemotherapy was found in either patients of the intestinal subtype or pancreatobiliary subtype. No significant difference was found in any subtypes regarding the recurrent regions. CONCLUSIONS: Pancreatobiliary subtype exhibited a higher recurrence rate and a poorer overall survival rate with more unfavorable pathological characteristics than the intestinal subtype.
OBJETIVOS: Los datos sobre la supervivencia y los factores de riesgo del adenocarcinoma ampular son limitados debido a su rareza. Este estudio buscó comparar el subtipo intestinal y el subtipo pancreático-biliar en pacientes con adenocarcinoma ampular. MÉTODOS: Análisis retrospectivo de hallazgos clínicos y patológicos y la supervivencia de 184 pacientes con adenocarcinoma ampular tratados entre 2007 y 2018. RESULTADOS: El subtipo pancreático-biliar tuvo una mayor prevalencia de ictericia antes de la operación y un tamaño de tumor mayor, y una peor diferenciación, que el subtipo intestinal. La invasión perineural fue más frecuente en el subtipo pancreático-biliar, con una mayor prevalencia de linfonodos disecados positivos y un estadio avanzado de la enfermedad. Los pacientes del subtipo pancreático-biliar tuvieron una supervivencia libre de enfermedad y una supervivencia general peores que los pacientes del subtipo intestinal. No se encontró ningún beneficio de la quimioterapia adyuvante en pacientes del subtipo intestinal o pancreático-biliar. No hubo diferencia significativa en las regiones recurrentes. CONCLUSIÓN: El subtipo pancreático-biliar mostró una tasa de recurrencia y una tasa de supervivencia general peores, con características patológicas más desfavorables que el subtipo intestinal.
Asunto(s)
Adenocarcinoma , Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Humanos , Estudios Retrospectivos , Ampolla Hepatopancreática/patología , Masculino , Femenino , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/clasificación , Neoplasias del Conducto Colédoco/patología , Neoplasias del Conducto Colédoco/cirugía , Neoplasias del Conducto Colédoco/mortalidad , Neoplasias del Conducto Colédoco/clasificación , Persona de Mediana Edad , Anciano , Quimioterapia Adyuvante , Adulto , Invasividad Neoplásica , Anciano de 80 o más Años , Recurrencia Local de Neoplasia , Metástasis Linfática , Carga Tumoral , Supervivencia sin EnfermedadRESUMEN
INTRODUCTION AND AIMS: Hepatocellular carcinoma (HCC) is a primary malignant tumor of liver epithelial cells and is the most frequent primary liver cancer. The broadening of transplantation and resectability criteria has made therapeutic decisions more complex. Our aim was to describe the clinical and survival characteristics of patients with HCC treated through resection or liver transplantation at our hospital and identify the presence of factors that enable outcome prediction and facilitate therapeutic decision-making. MATERIALS AND METHODS: Patients with HCC that underwent surgery with curative intent at the Hospital Universitario Marqués de Valdecilla, within the time frame of 2007 and 2017, were retrospectively identified. Survival, mortality, disease-free interval, and different outcome-related variables were analyzed. RESULTS: Ninety-six patients with a mean follow-up after surgery of 44 months were included. Overall mortality and recurrence were higher in the resection group. Mean survival was 51.4 months in the liver transplantation group and 37.5 months in the resection group, and the disease-free interval was 49.4⯱â¯37.2 and 27.4⯱â¯28.7 months, respectively (pâ¯=â¯0.002). The tumor burden score was statistically significant regarding risk for recurrence and specific mortality. CONCLUSIONS: There appears to be no patient subgroup in whom the results of surgical resection were superior or comparable to those of transplantation. Tumor burden determination could be a useful tool for patient subclassification and help guide therapeutic decision-making.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Trasplante de Hígado , Centros de Atención Terciaria , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Trasplante de Hígado/mortalidad , Anciano , Análisis de Supervivencia , Adulto , Recurrencia Local de Neoplasia/cirugía , Resultado del Tratamiento , Estudios de Seguimiento , Carga Tumoral , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: Bilateral carotid body tumors (CBTs) clinical manifestation is infrequent. We conducted this work to describe our experience in the surgical treatment of bilateral CBT and to analyze our results. METHODS: A retrospective, observational study. We analyzed the totality of bilateral CBT resections that had been performed in our institution from January 2008 to September 2023. Data was obtained from medical records and anonymized, ethics approval was obtained from our institution committee. As the number of observations was less than those required by the central limit theorem our sample was considered nonparametric. Statistical analysis was performed on Stata 17. RESULTS: We evaluated 16 patients with a total of 32 CBT; surgical resection was performed in 28 cases (87.50%). Median age of the patients was 60 years (interquartile range [IQR] 46-64). Regarding the Shamblin classification, 9 CBTs (32.14%) were classified as Shamblin I, 11 (39.29%) as Shamblin II, and 8 (28.57%) as Shamblin III. The median Distance to the Base of the Skull (DTBOS) was 3.5 cm (IQR 2.7-5.1), and the median tumor volume was 11.25 cc (IQR 3.4-18.7). The median bleeding volume was 300 ml (IQR 200-500), and the median surgical time was 190 min (IQR 145-240). All surgeries were performed using the Retrocarotid Dissection technique. We documented 9 (32.14%) cases of nerve injuries, all of which were transitory. In the median regression a statistically significant association was found between DTBOS, Shamblin classification and tumor volume with intraoperative bleeding and length of stay. CONCLUSIONS: Surgical treatment remains safe and should be considered the gold standard for accurate histologic diagnosis. DTBOS and tumor volume, in addition to Shamblin classification, must be considered in preoperative planning to predict bleeding and hospital stay.
Asunto(s)
Tumor del Cuerpo Carotídeo , Humanos , Tumor del Cuerpo Carotídeo/cirugía , Tumor del Cuerpo Carotídeo/diagnóstico por imagen , Tumor del Cuerpo Carotídeo/patología , Estudios Retrospectivos , Persona de Mediana Edad , Masculino , Femenino , Resultado del Tratamiento , Factores de Tiempo , Carga Tumoral , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Procedimientos Quirúrgicos Vasculares/efectos adversosRESUMEN
BACKGROUND: Dermoscopy is a non-invasive, cost-effective tool useful in the assessment of pigmented lesions. The aim of this study was to analyze the dermoscopic features in excised melanomas in a tertiary hospital in Brazil and the influence of Breslow thickness on the dermoscopic features observed. METHODS: An observational, cross-sectional study in which dermoscopic images of 43 melanomas were evaluated. The patients were divided into three groups: in situ, thin invasive melanoma (Breslow thickness <1 mm), and thick invasive melanoma (Breslow thickness ≥1 mm). RESULTS: We studied 33 patients with 43 melanomas. Twenty-one (48.8%) were melanoma in situ, 16 (37.2%) were thin melanomas, and 6 (14%) were thick melanomas. The most frequent dermoscopic criteria observed in all cases were atypical pigment network, multiple colors (3 or more), asymmetrical blotches, and peripheral asymmetric dots and globules. There was a statistically significant difference in the three groups regarding the frequency of atypical vessels, white scar areas, blue-white veil, shiny white structures, and radial streaming. The group of invasive melanomas presented with a higher frequency and statistical significance (P < 0.05) of atypical vessels, white scar areas, blue-white veil, and shiny white structures when compared to in situ melanomas. The presence of radial streaming and blue-white veil was more frequent in thick invasive melanomas than in thin invasive melanomas. The presence of a higher number of structures was seen in invasive melanomas, with a median of 5 and 7.5 structures for thin and thick invasive tumors, respectively. CONCLUSIONS: In line with prior data, we identified an association between invasive melanomas and structures linked to fibrosis and tumor vascularity. Specifically, we noted the presence of atypical vessels, scar-like white areas, a blue-white veil, and shiny white structures. Also, a higher number of dermoscopic structures was seen in invasive melanomas. In thicker melanomas, we observed additional findings, including a higher frequency of radial streaming and a blue-white veil.
Asunto(s)
Dermoscopía , Melanoma , Invasividad Neoplásica , Neoplasias Cutáneas , Centros de Atención Terciaria , Humanos , Melanoma/patología , Melanoma/diagnóstico por imagen , Melanoma/cirugía , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/cirugía , Estudios Transversales , Brasil , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Carga Tumoral , Anciano de 80 o más AñosRESUMEN
Cutaneous squamous cell carcinoma (cSCC) is the most common skin malignancy in kidney transplant recipients (KTRs) as a result of immunosuppression. A worldwide increase in kidney transplantation justifies the determination of prognostic biomarkers by collecting detailed patient data on metastasis development. This study aims to characterize the clinical, epidemiological, and histopathological profiles of KTRs who developed metastasis of cSCC. We conducted a retrospective single-center study on 18 KTRs and 21 immunocompetent patients (ICs) with metastatic cSCC, using data from 2004 to 2021. ICs were older (median age 70.5 years) than KTRs (median age: 59.5 years). Both groups were predominantly male with Fitzpatrick skin phototype I/II. The primary tumor appeared around 83.5 months post-transplant, usually in sun-exposed areas (61.1%), though some non-exposed areas in ICs (23.8%) contradicted literature findings. KTRs took longer to develop metastasis (median: 11.0 months) compared to ICs (median: 5.5 months). The mean size of the primary tumor was smaller in KTRs (2.50 cm2) compared to ICs (4.55 cm2). The main lymph node chain affected by metastasis was parotid lymph nodes in KTRs (27.8%) and cervical/axillar lymph nodes in ICs (both 19.0%). Both groups exhibited similar primary tumor grades and metastasis evolution, but KTRs had a higher prevalence of lymphovascular invasion. Metastasis of cSCC was more common in males with low skin phototype, in KTRs, particularly on the head and neck. The study suggests a possible link between lymphovascular invasion and metastasis development in KTRs.
Asunto(s)
Carcinoma de Células Escamosas , Trasplante de Riñón , Metástasis Linfática , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/epidemiología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Anciano , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/secundario , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Inmunocompetencia , Carga Tumoral , Ganglios Linfáticos/patología , Huésped Inmunocomprometido , Luz Solar/efectos adversosRESUMEN
BACKGROUND: Cutaneous melanoma is characterized by a high risk of metastasis to distant organs and a substantial mortality rate. For planning treatment and assessing outcomes, the Breslow micrometric measurement is critical. The tumor macroscopic dimension is not considered a prognostic parameter in cutaneous melanoma, although there are studies showing that tumor size is an independent prognostic factor for melanoma-specific survival. Therefore, this study aimed to evaluate the macroscopic dimension of melanoma and other known prognostic factors (i.e., Breslow index, mitoses, regression, and ulceration) as predictors of sentinel lymph node outcome and survival outcome. METHODS: We performed a retrospective cross-sectional study of 227 melanoma lesions subjected to sentinel lymph node biopsy at two Brazilian referral centers. RESULTS: On univariate analysis, there was a statistically significant correlation between the largest macroscopic tumor dimension and the sentinel lymph node result (P = 0.001); however, on multivariate analysis considering all evaluated parameters, there was no significant difference between the sentinel lymph node result and the tumor macroscopic dimension (P = 0.2689). Regarding melanoma-specific survival, the macroscopic dimension showed no significant correlation (P = 0.4632) in contrast to Breslow's dimension (P < 0.0001). CONCLUSION: The Breslow thickness was the only significant factor related to both the sentinel lymph node outcome and melanoma specific survival among the evaluated variables.
Asunto(s)
Melanoma , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas , Carga Tumoral , Humanos , Melanoma/mortalidad , Melanoma/patología , Melanoma/cirugía , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/cirugía , Masculino , Femenino , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Estudios Transversales , Adulto , Pronóstico , Metástasis Linfática/patología , Anciano de 80 o más Años , Ganglio Linfático Centinela/patología , Índice Mitótico , Tasa de Supervivencia , Adulto Joven , Análisis de Supervivencia , Brasil/epidemiología , Úlcera Cutánea/patología , Úlcera Cutánea/etiología , Úlcera Cutánea/mortalidad , Estadificación de NeoplasiasRESUMEN
Melanoma, an aggressive and potentially fatal skin cancer, is constrained by immunosuppression, resistance, and high toxicity in its treatment. Consequently, there is an urgent need for innovative antineoplastic agents. Therefore, this study investigated the antimelanoma potential of guttiferone E (GE). In an allogeneic murine B16 melanoma model, GE was administered subcutaneously and intraperitoneally. Antitumor evaluation included tumor volume/weight measurements and histopathological and immunohistochemical analysis. Furthermore, the toxicity of the treatments was evaluated through body/organ weights, biochemical parameters, and genotoxicity. Subcutaneous administration of 20 mg/kg of GE resulted in a significant reduction in both tumor volume and weight, effectively suppressing melanoma cell proliferation as evidenced by a decrease in mitotic figures. The tumor growth inhibition rate was equivalent to 54%. This treatment upregulated cleaved caspase-3, indicating apoptosis induction. On the other hand, intraperitoneal administration of GE showed no antimelanoma effect. Remarkably, GE treatments exhibited no toxicity, evidenced by non-significant differences in body weight gain, as well as organ weight, biochemical parameters of nephrotoxicity and hepatotoxicity, and genotoxic damage. This study revealed, for the first time, the efficacy of subcutaneous administration of GE in reducing melanoma, in the absence of toxicity. Furthermore, it was observed that the apoptotic signaling pathway is involved in the antimelanoma property of GE. These findings offer valuable insights for further exploring GE's therapeutic applications in melanoma treatment.
Asunto(s)
Melanoma Experimental , Ratones Endogámicos C57BL , Animales , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Melanoma Experimental/metabolismo , Apoptosis/efectos de los fármacos , Ratones , Masculino , Antineoplásicos/toxicidad , Antineoplásicos/administración & dosificación , Benzofenonas/farmacología , Benzofenonas/administración & dosificación , Benzofenonas/toxicidad , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Proliferación Celular/efectos de los fármacos , Carga Tumoral/efectos de los fármacos , Línea Celular Tumoral , Inyecciones Subcutáneas , FemeninoRESUMEN
The poor response, adverse effects and drug resistance to treatment of acute myeloid leukemia (AML) have led to searching for safer and more effective therapeutic alternatives. We previously demonstrated that the alcoholic extract of Petiveria alliacea (Esperanza) has a significant in vitro antitumor effect on other tumor cells and also the ability to regulate energy metabolism. We evaluated the effect of the Esperanza extract in vitro and in vivo in a murine model of AML with DA-3/ER-GM cells. First, a chemical characterization of the extract was conducted through liquid and gas chromatography coupled with mass spectrometry. In vitro findings showed that the extract modulates tumor metabolism by decreasing glucose uptake and increasing reactive oxygen species, which leads to a reduction in cell proliferation. Then, to evaluate the effect of the extract in vivo, we standardized the mouse model by injecting DA-3/ER-GM cells intravenously. The animals treated with the extract showed a lower percentage of circulating blasts, higher values of hemoglobin, hematocrit, and platelets, less infiltration of blasts in the spleen, and greater production of cytokines compared to the control group. These results suggest that the antitumor activity of this extract on DA-3/ER-GM cells can be attributed to the decrease in glycolytic metabolism, its activity as a mitocan, and the possible immunomodulatory effect by reducing tumor proliferation and metastasis.
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Leucemia Mieloide , Phytolaccaceae , Animales , Ratones , Carga Tumoral , Cromatografía de Gases y Espectrometría de Masas , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
INTRODUCTION: cutaneous melanoma (MC) is a malignant neoplasm derived from melanocytic cells with an aggressive behavior. It is usually associated with the multifactorial interaction of genetic susceptibility and environmental exposure, usually ultraviolet radiation. Despite advances in treatment, the disease remains relentless with poor prognosis. Sentinel lymph node (SLN) biopsy is a technique used to screen patients in need of lymph node dissection. OBJECTIVES: to correlate the tumor burden in the SLN with the mortality of patients undergoing SLN biopsy. METHODOLOGY: the medical records and histological slides of patients with MC who underwent SLN biopsy treated at HC-Unicamp from 2001 to 2021 were retrospectively analyzed. The positive SLN were measured according to the size of the tumor infiltration area, for analysis of the depth of invasion (DI), closest proximity to the capsule (CPC) and tumor burden (TB). For statistical analysis, associations between variables were analyzed using Fishers exact test, with post Bonferroni test and Wilcoxon test. RESULTS: 105 records of patients who underwent SLN biopsy of MC were identified. Of these, nine (8.6%) had positive SLN and 81 (77.1%) had negative SLN. The performed lymphadenectomies resulted in 55.6% (n=5) affected, 22.2% (n=2) without disease and 22.2% (n=2) were not performed. Mean CPC, TB, and DI were 0.14mm, 32.10mm and 2.33mm, respectively. Patients with T2 and T3 tumors were more likely to show the SLN affected (p=0.022). No patient with positive SLN died during follow-up. CONCLUSION: patients who presented T3 staging are the ones who most presented positive SLN.
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Melanoma , Ganglio Linfático Centinela , Neoplasias Cutáneas , Humanos , Melanoma/patología , Neoplasias Cutáneas/patología , Carga Tumoral , Ganglio Linfático Centinela/patología , Estudios Retrospectivos , Rayos Ultravioleta , Metástasis Linfática , Biopsia del Ganglio Linfático Centinela/métodos , Escisión del Ganglio Linfático , Pronóstico , Estadificación de Neoplasias , Melanoma Cutáneo MalignoRESUMEN
OBJECTIVE: The role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. METHODS: Between January 20 and November 2011, 498 consecutive NPC patients with stage I-IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. RESULTS: The 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTVâ¯≤â¯38â¯mL vs. PTVâ¯>â¯38â¯mL were 94.1% vs. 90.4% (pâ¯=â¯0.063), 87.9% vs. 76.3% (pâ¯<â¯0.001), 78.5% vs. 58.5% (pâ¯<â¯0.001) and 86.3% vs. 66.7% (pâ¯<â¯0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (pâ¯=â¯0.034), DFS (pâ¯=â¯0.002) and OS (pâ¯=â¯0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, pâ¯=â¯0.025. CONCLUSIONS: PTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTVâ¯>â¯38â¯mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. LEVEL OF EVIDENCE: III.
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Carcinoma , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/patología , Estudios de Cohortes , Carcinoma/radioterapia , Estudios Retrospectivos , Radioterapia de Intensidad Modulada/efectos adversos , Puntaje de Propensión , Carga Tumoral , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patología , Pronóstico , Estadificación de NeoplasiasRESUMEN
PURPOSE: The ellipsoid equation came in an attempt to facilitate the estimation of tumor volume, by measuring the height, width, and anteroposterior length of the lesion. The estimated tumor volume can sometimes be different between methods, thus, it is of extreme interest to evaluate if the methods are significantly different, as well as to discuss the main limitations of each one. METHODS: This is an observational, analytical, cross-sectional study. A systematic review of the literature was also performed in order to discuss the results observed in the present study. RESULTS: A total of 82 patients (43 males and 39 females) ranging in age from 15 to 78 years (mean 47.95 ± 14.76) were included in the study. Seven patients were classified as Knosp grade 0 (8.5%), 36 Knosp grade 1 (44%), 14 Knosp grade 2 (17%), 20 Knosp grade 3 (24.4%), 5 Knosp grade 4 (6.1%). The tumor volume estimated by 3D planimetric assessment, non-simplified ellipsoid equation, and simplified ellipsoid formula averaged 10.68 cm³, 10.36 cm³, and 9.9 cm³ respectively. CONCLUSION: A simplified form of the ellipsoid equation increases the divergence between the measurement obtained in planimetry, and should be discouraged, in view of the new automated methods of performing quick calculations using periodic digits. The non-simplified form underestimated the tumor volume by 2.9% on average but did so regularly. In clinical practice, measurement should be accompanied by an evaluation of tumor morphology.
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Neoplasias Hipofisarias , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Neoplasias Hipofisarias/patología , Carga Tumoral , Estudios Transversales , Tamaño de los Órganos , Estudios Observacionales como AsuntoRESUMEN
PURPOSE: To compare the accuracy of three volumetric methods in the radiological assessment of meningiomas: linear (ABC/2), planimetric, and multiparametric machine learning-based semiautomated voxel-based morphometry (VBM), and to investigate the relevance of tumor shape in volumetric error. METHODS: Retrospective imaging database analysis at the authors' institutions. We included patients with a confirmed diagnosis of meningioma and preoperative cranial magnetic resonance imaging eligible for volumetric analyses. After tumor segmentation, images underwent automated computation of shape properties such as sphericity, roundness, flatness, and elongation. RESULTS: Sixty-nine patients (85 tumors) were included. Tumor volumes were significantly different using linear (13.82 cm3 [range 0.13-163.74 cm3]), planimetric (11.66 cm3 [range 0.17-196.2 cm3]) and VBM methods (10.24 cm3 [range 0.17-190.32 cm3]) (p < 0.001). Median volume and percentage errors between the planimetric and linear methods and the VBM method were 1.08 cm3 and 11.61%, and 0.23 cm3 and 5.5%, respectively. Planimetry and linear methods overestimated the actual volume in 79% and 63% of the patients, respectively. Correlation studies showed excellent reliability and volumetric agreement between manual- and computer-based methods. Larger and flatter tumors had greater accuracy on planimetry, whereas less rounded tumors contributed negatively to the accuracy of the linear method. CONCLUSION: Semiautomated VBM volumetry for meningiomas is not influenced by tumor shape properties, whereas planimetry and linear methods tend to overestimate tumor volume. Furthermore, it is necessary to consider tumor roundness prior to linear measurement so as to choose the most appropriate method for each patient on an individual basis.
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Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Estudios Retrospectivos , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética/métodos , Carga Tumoral , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Aprendizaje AutomáticoRESUMEN
Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.