RESUMEN
BACKGROUND: Organoid technology has recently emerged as a powerful tool to assess drug sensitivity of individual patient tumors in vitro. Organoids may therefore represent a new avenue for precision medicine, as this circumvents many of the complexities associated with DNA- or transcriptional-profiling. MATERIALS AND METHODS: The SENSOR trial was a single-arm, single-center, prospective intervention trial to evaluate the feasibility of patient-derived organoids to allocate patients for treatment with off-label or investigational agents. The primary endpoint was an objective response rate of ≥20%. Patients underwent a biopsy for culture before commencing their last round standard of care. Organoids were exposed to a panel of eight drugs and patients were treated after progression on standard-of-care treatment and when a clear signal of antitumor activity was identified in vitro. RESULTS: Sixty-one patients were included and we generated 31 organoids of 54 eligible patients. Twenty-five cultures were subjected to drug screening and 19 organoids exhibited substantial responses to one or more drugs. Three patients underwent treatment with vistusertib and three with capivasertib. Despite drug sensitivity of organoids, patients did not demonstrate objective clinical responses to the recommended treatment. CONCLUSIONS: Organoid technology had limited value as a tool for precision medicine in this patient population because a large fraction of patients could not undergo treatment or because the recommended treatment did not elicit an objective response. We identified several essential parameters, such as the culture success rate, clinical deterioration of patients during standard of care, and rational design of drug panels that need to be accounted for in organoid-guided clinical studies.
Asunto(s)
Neoplasias Colorrectales , Preparaciones Farmacéuticas , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Organoides , Medicina de Precisión , Estudios ProspectivosRESUMEN
OBJECTIVES: To assess the safety and efficacy of percutaneous microwave ablation (MWA) of histologically proven T1 renal cell carcinoma (RCC). METHODS: We analysed patients with a histologically proven RCC (≤ 7 cm) treated by MWA from April 2012-April 2018. Primary and secondary efficacy, local tumour recurrence (LTR), morbidity and mortality were reported. Efficacy was defined as no residual tumour enhancement on follow-up imaging 1 month after the first ablation (primary efficacy) and after re-ablation(s) for residual disease (secondary efficacy). Adverse events (AE) were registered by the Clavien-Dindo classification and the common terminology criteria for AE. Univariable and multivariable logistic regression analyses were performed to investigate a relation among pre-treatment factors incomplete ablation and complications. RESULTS: In 100 patients, a total of 108 RCCs (85 T1a and 23 T1b) were treated by MWA. Median size was 3.2 cm (IQR 2.4-4.0). Primary efficacy was 89% (95%CI 0.81-0.94) for T1a lesions and 52% (95%CI 0.31-0.73) for T1b lesions (p < 0.001). Fifteen lesions (7 T1a) were re-ablated for residual disease by MWA in one (n = 13) and two (n = 2, both T1b) sessions resulting in secondary efficacy rates of 99% (T1a) and 95% (T1b, p = 0.352). LTR occurred in four tumours (2 T1a, 2 T1b) after 10-60 months. Six (4%) AEs grade > 3-5 were observed (2 T1a, 4 T1b, p = 0.045). Multivariable analysis showed that mR.E.N.A.L. nephrometry was independently associated with incomplete ablation (p = 0.012). CONCLUSION: Microwave ablation is safe and effective for T1a and T1b RCC lesions with a significantly lower primary efficacy for T1b lesions.
Asunto(s)
Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Ablación por Catéter/métodos , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Microondas/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Ablación por Radiofrecuencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. METHODS: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 µg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. DISCUSSION: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. TRIAL REGISTRATION: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/patología , Floxuridina/administración & dosificación , Hepatectomía , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/prevención & control , Adulto , Quimioterapia Adyuvante/instrumentación , Quimioterapia Adyuvante/métodos , Ensayos Clínicos Fase III como Asunto , Neoplasias Colorrectales/mortalidad , Humanos , Bombas de Infusión Implantables , Infusiones Intraarteriales/instrumentación , Infusiones Intraarteriales/métodos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Estudios Multicéntricos como Asunto , Países Bajos , Supervivencia sin Progresión , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Recurrent disease following thermal ablation therapy is a frequently reported problem. Preoperative identification of patients with high risk of recurrent disease might enable individualized treatment based on patients' risk profile. The aim of the present work was to investigate the role of metabolic parameters derived from the pre-ablation 18F-FDG PET/CT as imaging biomarkers for recurrent disease in patients with colorectal liver metastases (CLM). METHODS: Included in this retrospective study were all consecutive patients with CLM treated with percutaneous or open thermal ablation therapy who had a pre-treatment baseline 18F-FDG PET/CT available. Multivariable cox regression for survival analysis was performed using different models for the metabolic parameters (SULpeak, SULmean, SULmax, partial volume corrected SULmean (cSULmean), and total lesion glycolysis (TLG)) corrected for tumour and procedure characteristics. The study endpoints were defined as local tumour progression free survival (LTP-FS), new intrahepatic recurrence free survival (NHR-FS) and extrahepatic recurrence free survival (EHR-FS). Clinical and imaging follow-up data was used as the reference standard. RESULTS: Fifty-four patients with 90 lesions were selected. Univariable cox regression analysis resulted in eight models. Multivariable analysis revealed that after adjusting for lesion size and the approach of the procedure, none of the metabolic parameters were associated with LTP-FS or EHR-FS. Percutaneous approach was significantly associated with a shorter LTP-FS. It was demonstrated that lower values of SULpeak, SULmax, SULmean , and cSULmean are associated with a significant better NHR-FS, independent of the lesion size and number and prior chemotherapy. CONCLUSION: We found no association between the metabolic parameters on pre-ablation 18F-FDG PET/CT and the LTP-FS. However, low values of the metabolic parameters were significantly associated with improved NHR-FS. The clinical implication of these findings might be the identification of high-risk patients who might benefit most from adjuvant or combined treatment strategies.
Asunto(s)
Técnicas de Ablación , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Fluorodesoxiglucosa F18 , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: The success of radiofrequency (RF) ablation is limited by the inability to assess thermal tissue damage achieved during or immediately after the procedure. The goal of this proof-of-principle study was to investigate whether diffuse reflectance (DR) spectroscopy during and after RF ablation of liver tumours could aid in detecting complete tissue ablation. MATERIAL AND METHODS: DR spectra were acquired in vivo in eight patients undergoing RF ablation for unresectable colorectal liver metastases, using a disposable spectroscopy needle. Intraoperative ultrasound imaging was used for accurate positioning of the RF electrode and the spectroscopy needle. Spectral changes were quantified and correlated to tissue histopathology and follow-up CT imaging. RESULTS: For the lesions in which ablation was monitored by DR spectroscopy (N = 8), median tumour size was 1.6 cm (range 0.8-3.3 cm). We found an excellent correlation (97-99%) between thermal damage suggested by spectral changes and histology. DR spectroscopy allowed discrimination between non-ablated and ablated tissue, regardless whether the needle was placed in tumour tissue or in surrounding liver tissue. Additional measurements performed continuously during ablation confirmed that the magnitude of spectral change correlates with the histochemical degree of thermal damage. CONCLUSIONS: Diffuse reflectance spectroscopy allows accurate quantification of thermal tissue damage during and after RF ablation. Real-time feedback by DR spectroscopy could improve the accuracy and quality of the RF procedures by lowering incomplete ablation rates.
Asunto(s)
Ablación por Catéter , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Análisis Espectral/métodos , Anciano , Área Bajo la Curva , Femenino , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Curva ROC , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
AIM: Twelve to 13% of patients with colorectal cancer (CRC) develop peritoneal carcinomatosis (PC), the majority of whom present with unresectable disease. This study aimed to document the actual response rate to and response characteristics of preoperative modern systemic chemotherapy in this patient group. METHOD: Patients underwent a positron emission tomography (PET)/CT scan, laparoscopy and peritoneal biopsy to document unresectable PC. After four courses of preoperative chemotherapy (capecitabine/oxaliplatin ± bevacizumab), the extent of PC was re-evaluated by PET/CT(or CT), laparoscopy and peritoneal biopsy (if considered safe). RESULTS: Ten patients (seven men, three women) with good performance status of median age 60.3 (45.6-72.8) years were studied. The first laparoscopy documented unresectable PC. One patient was excluded because of systemic metastases on PET/CT. Nine proceeded to follow the trial protocol. Of these, one developed early progressive disease, two had macroscopically stable disease and five had progressive disease at second laparoscopy. One patient developed a small bowel perforation at first laparoscopy and received palliative chemotherapy outside the protocol, after which progressive disease was found at an explorative laparotomy. Thus, 7 (78%) patients with unresectable PC from CRC developed progressive disease under neoadjuvant chemotherapy and 2 (22%) patients remained stable. No clear macroscopic response to chemotherapy could be demonstrated. CONCLUSION: Unresectable PC from CRC does not respond well to systemic chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma/tratamiento farmacológico , Neoplasias Colorrectales/patología , Terapia Neoadyuvante/métodos , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Capecitabina , Antígeno Carcinoembrionario/sangre , Carcinoma/sangre , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Laparoscopía , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/sangre , Proyectos Piloto , Pronóstico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
At diagnosis 10-25% of patients with colorectal liver metastases (CRLM) present as resectable disease. Liver resection is the gold standard treatment, resulting in a 5-year overall survival (OS) of 22-58%, local recurrence rates of 1.2-10.4% and a perioperative mortality of less than 5%. Multiple attempts have been made to assess the possible contribution of radiofrequency ablation (RFA) to improve OS and progression-free survival (PFS) in patients with unresectable colorectal liver metastases. The aim of this paper is to review the RFA literature in the setting of colorectal liver metastases: RFA with and without chemotherapy, RFA with and without resection, RFA for solitary unresectable CRLM, surgical and percutaneous imaging-guided RFA, RFA compared with chemotherapy. The reported OS, PFS, local recurrence rates, morbidity and mortality in these different settings are analyzed. This paper reflects on a possible role of RFA in resectable CRLM.
Asunto(s)
Ablación por Catéter , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Hígado/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Ablación por Catéter/mortalidad , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
PURPOSE: To apply single-photon emission computed tomography (SPECT) in combination with computed tomography (CT) for preoperative identification of sentinel lymph nodes (SNs) and to investigate surgical feasibility and safety of intraoperative sampling. METHODS: A retrospective combined interim analysis of 20 patients from two prospective trials who underwent injection of 99mTc-nanocolloid into the renal tumour for preoperative identification of SN with SPECT/CT and subsequent removal of the tumour and intraoperative sampling using a gamma probe and portable camera. Lymphadenectomy was completed locoregionally. Surgical approach, time, blood loss, intraoperative yield, Clavien complications and anatomical location of SN in correlation with preoperative imaging were evaluated. RESULTS: SPECT/CT detected SN in 14/20 patients (70%), including 4 patients with non-visualisation on planar lymphoscintigraphy. Twenty-six SNs were seen: 17 para-aortic (including interaorto-caval), 4 retrocaval, 1 hilar, 1 celiac trunc, 1 internal mammary and 2 mediastinal and pleural. These latter 4 nodes were not harvested according to protocol. All other SNs, except for 2 weakly radioactive interaorto-caval nodes, were identified and excised with a mean additional time of 20 min. None of the removed SN and locoregional nodes was tumour-bearing. CONCLUSIONS: Intraoperative SN identification and sampling in RCC with preoperative detection on SPECT/CT is surgically safe and feasible. SN from the kidney are mainly localised in the para-aortic region, but aberrant nodes receive direct drainage. Non-visualisation of SN appears in almost a third of the patients. Further studies are required to demonstrate whether accurate mapping of lymphatic drainage and extent of lymphatic spread may have diagnostic and therapeutic implications.
Asunto(s)
Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Imagen Multimodal , Tomografía de Emisión de Positrones , Biopsia del Ganglio Linfático Centinela/métodos , Tomografía Computarizada por Rayos X , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Femenino , Humanos , Periodo Intraoperatorio , Riñón/diagnóstico por imagen , Riñón/cirugía , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Metástasis Linfática/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Imagen Multimodal/efectos adversos , Estudios Retrospectivos , Tecnecio , Factores de TiempoAsunto(s)
Carcinoma de Células Renales/cirugía , Ablación por Catéter/métodos , Neoplasias Renales/cirugía , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico por imagen , Ablación por Catéter/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Riñón/anomalías , Neoplasias Renales/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Nefrectomía , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
INTRODUCTION: Local therapies for liver tumors are considered to be safe. However, cryoablation (CA) has been associated with an exaggerated systemic inflammatory response (SIR). Aim of this study was to assess the degree of SIR after radiofrequency ablation (RFA) in comparison with major (MR) or minor (mR) liver resection. MATERIAL AND METHODS: Thirty-nine patients were treated with RFA (n = 11), MR (n = 10) or mR (n = 18). SIR parameters [white blood count (WBC) and C-reactive protein (CRP)], proinflammatory mediators [IL-6, TNF-alpha and sPLA2], liver damage parameters [AST/ALT] and platelet counts were determined at different time points. The volume of ablated liver was calculated on the first CT after RFA in order to correlate ablated liver volume with liver enzyme release and SIR. All data are expressed as median values with quartiles [25%, 75%]. RESULTS: RFA induced a moderate SIR, as demonstrated by a significant elevation of CRP (77 mg/L vs 3 mg/L), IL-6 (96 pg/ml vs 4 pg/ml) and sPLA2 (41 ng/ml vs 7 ng/ml, p < 0.05). Peak point values of SIR (WBC and CRP at 24 vs 48 h and 48 vs 72 h) and proinflammatory response parameters (24 vs 48 h) occurred earlier after RFA than after mR or MR. Time-to-time comparison revealed even increased levels of CRP (77 mg/L [59, 160]) 24h after RFA when compared to patients undergoing major or minor resection (50 mg/L [28, 66] and 59 mg/L [24, 91], respectively) and increased levels of IL-6 (67 pg/ml [42, 131]) 4 h after RFA when compared to patients undergoing minor resection (29 pg/ml [20, 55]). Postoperative levels of AST and LDH correlated significantly with the ablated liver volume 1h after RFA (RC = 0.860 and RC = 0.868, respectively, p < 0.05). CONCLUSION: RFA induced a moderate SIR of the same magnitude as in patients undergoing partial liver resection. None of the patients showed signs of an exaggerated SIR, as has been reported after cryoablation.
Asunto(s)
Ablación por Catéter/efectos adversos , Neoplasias Hepáticas/terapia , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Ablación por Catéter/métodos , Citocinas/sangre , Femenino , Hepatectomía/efectos adversos , Humanos , Pruebas de Función Hepática , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Fosfolipasas A2 Secretoras/sangre , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Radiofrequency ablation (RFA) is a new treatment for liver tumours. Complications encountered after RFA in the Netherlands were evaluated in the present study. METHODS: Between June 1999 and November 2003 patients undergoing RFA of irresectable liver tumours in eight medical centres were registered prospectively. RESULTS: One hundred and forty-three RFA procedures were performed in 122 patients. RFA was combined with partial hepatectomy in 37 instances. Death occurred after two procedures (1.4 per cent), and was mainly due to concomitant partial hepatectomy. A total of 19 major complications occurred after ten procedures, including biliary tract damage (seven patients), liver failure (four), hepatic abscess (three), peritoneal infection (two), intrahepatic haematoma (one), hepatic artery aneurysm (one) and pulmonary embolism (one). Twenty-four minor complications were related to concomitant partial hepatectomy or laparotomy. The overall complication rate was 20.3 per cent and the rate of complications related directly to RFA was 9.8 per cent. CONCLUSION: The procedure-specific complication rate was almost 10 per cent and it is recommended that RFA should be performed only by an experienced team comprising a hepatobiliary surgeon, gastroenterologist, hepatologist and interventional radiologist. Biliary stricture, hepatic vascular damage and hepatic abscesses were the most common major complications.
Asunto(s)
Ablación por Catéter/efectos adversos , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pruebas de Función Hepática , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Países Bajos , Estudios ProspectivosRESUMEN
Breast cancers in gene mutation carriers may escape mammographic detection because of rapid growth and tumor expansion. Therefore, they may mimic benign lesions on the mammogram. Twenty-nine BRCA 1/2 mutation carriers under surveillance developed 31 breast cancers between 1994 and 2001 at a mean age of 44.2 years. Controls were 63 women with 67 breast cancers in the same period at a mean age of 53.8 years, also under surveillance because of a life time risk of at least 15%. In 26% of the carriers vs. 48% of the controls, mammography was the method that first suspected a malignancy. Seven radiologists performed a retrospective review of the original mammograms to establish technical assessment, with special attention for circumscribed lesions and estimated probability of malignancy. In the mutation carriers seven (23%) circumscribed non-calcified mammographic masses were found and three in the controls (4.5%) P=0.01. These masses were proven to be malignant. In both groups around 70% of these fast-growing circumscribed lesions were detected by the patients. The masses were situated in breasts with a good interpretable breast pattern. BRCA 1/2 mutation carriers had a significantly higher percentage of circumscribed non-calcified mammographic masses that proved to be malignant. These mammographic lesions in women at high risk should be described as at least Birads 0 and worked-up with ultrasound and needle biopsy.
Asunto(s)
Neoplasias de la Mama/genética , Genes BRCA1 , Genes BRCA2 , Mamografía , Adulto , Anciano , Biopsia , Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Tamización de Portadores Genéticos , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Variaciones Dependientes del Observador , Vigilancia de la Población , Probabilidad , Estudios Retrospectivos , Sensibilidad y Especificidad , Tecnología Radiológica , Ultrasonografía MamariaRESUMEN
BACKGROUND: A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine-lowering treatment with folic acid plus vitamin B(6) on markers of cerebrovascular atherosclerosis and cerebral microangiopathy. MATERIALS AND METHODS: Using 158 healthy siblings (mean age 46.0 +/- 7.6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo-controlled trial using 5 mg of folic acid plus 250 mg of vitamin B(6) daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy). RESULTS: Seventeen (10.8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61.8%) and 48 (65.8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty-four participants (15.2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13-fold vs. placebo; P < 0.001) and vitamin B(6) (8.8-fold; P < 0.001). Fasting and postmethionine total homocysteine concentrations decreased 38.7% (95% CI, 27.4-50.0) and 29.1% (95% CI, 19.2-39.0) vs. placebo (all P < 0.001). During follow up six individuals in the vitamin-treated and 11 in the placebo-treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0.48; 95% CI 0.17-1.41; P = 0.18 and 0.48; CI 0.14-1.60; P = 0.23, respectively). CONCLUSIONS: These results could indicate a possible favourable effect of homocysteine-lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.
Asunto(s)
Arteriosclerosis/prevención & control , Ácido Fólico/uso terapéutico , Hematínicos/uso terapéutico , Homocisteína/sangre , Vitamina B 6/uso terapéutico , Adulto , Biomarcadores/sangre , Circulación Cerebrovascular/fisiología , Estudios Cruzados , Quimioterapia Combinada , Femenino , Ácido Fólico/sangre , Hematínicos/sangre , Humanos , Angiografía por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del Tratamiento , Vitamina B 6/sangreRESUMEN
AIMS: The aim of this study is to report initial experience with radiofrequency thermoablation (RFA) of malignant hepatic tumours. METHODS: From June 1999 to November 2001, a seven centre study of 50 patients who had undergone RFA, included 102 primary or metastatic tumours. Multimodality therapy, complications, disease free survival and location of recurrence were recorded. Histopathologic examination was performed in a number of tumours treated with RFA and subsequently resected to determine the effect of RFA on the tissue level. RESULTS: 11 tumours (seven patients) were resected after prior treatment with RFA; NADH-diaphorase staining in all these tumours demonstrated non-viable tumour. Postoperative morbidity and mortality occurred in 14 patients and one patient, respectively, in three cases related to the RFA procedure. Median follow-up of 41 patients with non-resected RF ablated tumours was 11 months (range 1-24 months). 26 patients developed a recurrence of which three at the RFA site after 6-12 months. CONCLUSIONS: RFA provides a simple method for local treatment of liver tumours. The introduction of this technique nevertheless involves morbidity and mortality.
Asunto(s)
Ablación por Catéter , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Países Bajos , Evaluación de Resultado en la Atención de Salud , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: Laparoscopic solid organ surgery has gained growing acceptance, but this does not hold for laparoscopic surgery of the liver. Laparoscopic liver surgery mainly comprizes diagnostic procedures and treatment of liver cysts. However, we believe there is room for a laparoscopic approach to the liver in selected cases, with the benefits that may be expected from laparoscopic solid organ surgery. METHODS: Between 1993 and 2000, 10 patients with various lesions of the liver underwent laparoscopic surgery. Indications consisted of cystic disease (n = 2), hemangioma (n = 2), focal nodular hyperplasia (n = 2), liver abcess (n = 1), and liver metastasis (n = 3). Laparoscopic treatment varied from fenestration (n = 3) to wedge resections (n = 5), and formal left lateral hepatectomy (n = 2). RESULTS: The mean patient age was 54 years (range, 34-71 years). The mean operative time, including laparoscopic ultrasonography, measured 180 min (range, 80-240 min). Peroperative blood loss ranged from 200 to 450 ml. There was no mortality. In two patients, conversion to laparotomy was necessary. There were no postoperative complications. The mean hospital stay was 6 days (range, 4-11 days). CONCLUSION: Laparoscopic treatment should be considered in selected patients with benign and malignant lesions in the left lobe or frontal segments of the liver.
Asunto(s)
Laparoscopía/métodos , Hepatopatías/cirugía , Adulto , Anciano , Carcinoma/secundario , Supervivencia sin Enfermedad , Estudios de Factibilidad , Femenino , Humanos , Tiempo de Internación , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana EdadRESUMEN
Macrophages play a role in the host defence against cancer. Little is known about changes in macrophage populations during early metastatic growth. To evaluate the distribution, number and phenotype of macrophages in the development of hepatic metastases in a rat model (Wag/Rij rats and syngeneic CC531 colon carcinoma cell line), an immunohistochemical study was performed with the monoclonal antibodies ED1 (monocytes, and all macrophages), ED2 (resident tissue macrophages, like Kupffer cells) and ED3 (a subpopulation of macrophages which may play a role in the recruitment of lymphocytes). OX19 and His14 were used to identify lymphocytes. In this study a new monoclonal antibody CC52 is described, which recognizes the CC531 tumour cell line. Liver metastases were induced by injection of CC531 colon carcinoma cells into a mesenteric vein. Rats were killed at various intervals. Results show three major macrophage populations during hepatic tumour growth: (1) on day 3, infiltrates are observed around the micrometastases, which contain mainly newly recruited macrophages (ED1+ and ED2-); (2) after 7 days, ED3-positive (ED3+) macrophages together with T lymphocytes are found in the infiltrates; (3) an increase in the number of ED2-positive (ED2+) Kupffer cells is observed in the liver parenchyma after 14 days. In conclusion, the present results suggest that various populations of macrophages, newly recruited (ED1+) as well as resident Kupffer cells (ED2+), are involved in the immune response against tumour cell deposits in the liver.
Asunto(s)
Adenocarcinoma/inmunología , Biomarcadores de Tumor/análisis , Neoplasias del Colon/inmunología , Macrófagos/inmunología , Adenocarcinoma/patología , Animales , Anticuerpos Monoclonales , Neoplasias del Colon/patología , Inmunohistoquímica , Inmunofenotipificación , Masculino , Metástasis de la Neoplasia/inmunología , Ratas , Ratas Endogámicas , Células Tumorales Cultivadas/inmunología , Células Tumorales Cultivadas/trasplanteRESUMEN
Intraoperative ultrasonography (IOUS) of the liver is a very useful tool during surgery for gastrointestinal tumors or hepatic tumors. In a prospective study of 82 elective operations for 57 gastrointestinal tumors and 25 hepatic tumors or metastases, we compared IOUS with preoperative ultrasonography, CT-scanning and MRI. IOUS supplied additional information in 38% of the operations. In 22% of the cases, this had a major impact on the intraoperative strategy with an alteration of the procedure. IOUS has a higher detection rate of intrahepatic lesions, discriminates better between solid or cystic nature of the tumor and offers the possibility of performing a safe and radical hepatic resection by its ability to localize lesions in relation to vascular structures. IOUS is a safe and simple technique which will be more cost-effective than extensive preoperative evaluation of the liver. It provides a more complete clinical staging of patients for whom adjuvant therapy is considered after resection of a colorectal carcinoma.
Asunto(s)
Neoplasias del Sistema Digestivo/patología , Neoplasias Hepáticas/cirugía , Hígado/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Periodo Intraoperatorio , Hígado/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
The results and consequences of intra-operative ultrasonography of the liver were studied in 50 patients who had laparotomy for colorectal cancer. Compared with preoperative imaging techniques like US, CT and MRI, intra-operative US had a higher sensitivity for intrahepatic lesions. Especially in case that adjuvant therapy could have been considered, intra-operative US gave relevant information in 10 patients (20%) by altering the stage of the primary tumour. Four of the 50 patients showed more liver metastases at intra-operative US than detected by preoperative imaging techniques. Resectional therapy of liver metastases could be prevented in these four patients. We advise intra-operative US as routine for all patients undergoing laparotomy for colorectal cancer especially if adjuvant chemotherapy is considered. When surgery is scheduled extensive preoperative liver examination can be avoided if intra-operative US is available.