RESUMEN
BACKGROUND: Biomarkers are key tools in cancer management. In neuroendocrine tumors (NETs), Chromogranin A (CgA) was considered acceptable as a biomarker. We compared the clinical efficacy of a multigenomic blood biomarker (NETest) to CgA over a 5-year period. PATIENTS AND METHODS: An observational, prospective, cross-sectional, multicenter, multinational, comparative cohort assessment. Cohort 1: NETest evaluation in NETs (n = 1684) and cancers, benign diseases, controls (n = 731). Cohort 2: (n = 1270): matched analysis of NETest/CgA in a sub-cohort of NETs (n = 922) versus other diseases and controls (n = 348). Disease status was assessed by response evaluation criteria in solid tumors (RECIST). NETest measurement: qPCR [upper limit of normal (ULN: 20)], CgA (EuroDiagnostica, ULN: 108 ng/ml). STATISTICS: Mann-Whitney U-test, AUROC, chi-square and McNemar' test. RESULTS: Cohort 1: NETest diagnostic accuracy was 91% (P < 0.0001) and identified pheochromocytomas (98%), small intestine (94%), pancreas (91%), lung (88%), gastric (80%) and appendix (79%). NETest reflected grading: G1: 40 ± 1, G2 (50 ± 1) and G3 (52 ± 1). Locoregional disease levels were lower (38 ± 1) than metastatic (52 ± 1, P < 0.0001). NETest accurately stratified RECIST-assessed disease extent: no disease (21 ± 1), stable (43 ± 2), progressive (62 ± 2) (P < 0.0001). NETest concordance with imaging (CT/MRI/68Ga-SSA-PET) 91%. Presurgery, all NETs (n = 153) were positive (100%). After palliative R1/R2 surgery (n = 51) all (100%) remained elevated. After curative R0-surgery (n = 102), NETest levels were normal in 81 (70%) with no recurrence at 2 years. In the 31 (30%) with elevated levels, 25 (81%) recurred within 2 years. Cohort #2: NETest diagnostic accuracy was 87% and CgA 54% (P < 0.0001). NETest was more accurate than CgA for grading (chi-square = 7.7, OR = 18.5) and metastatic identification (chi-square = 180, OR = 8.4). NETest identified progressive disease (95%) versus CgA (57%, P < 0.0001). Imaging concordance for NETest was 91% versus CgA (46%) (P < 0.0001). Recurrence prediction after surgery was NETest-positive in >94% versus CgA 11%. CONCLUSION: NETest accurately diagnoses NETs and is an effective surrogate marker for imaging, grade, metastases and disease status compared to CgA. A multigenomic liquid biopsy is an accurate biomarker of NET disease.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Biomarcadores de Tumor/genética , Cromogranina A , Estudios Transversales , Humanos , Biopsia Líquida , Recurrencia Local de Neoplasia , Tumores Neuroendocrinos/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Estudios ProspectivosAsunto(s)
Tumor Carcinoide , Neoplasias Pulmonares , Neoplasias del Timo , Tumor Carcinoide/diagnóstico , Tumor Carcinoide/epidemiología , Tumor Carcinoide/terapia , Estudios de Seguimiento , Humanos , Pulmón , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/terapia , Pronóstico , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/epidemiología , Neoplasias del Timo/terapiaRESUMEN
BACKGROUND: The lack of an accurate blood biomarker in neuroendocrine tumor (NET) disease has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy-liquid biopsy-to facilitate real-time management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD). PATIENTS AND METHODS: A systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was undertaken. The methodological quality was evaluated using the QUADAS-2 tool. We identified ten original scientific papers that met the inclusion criteria. These were assessed by qualitative analysis and thereafter meta-analysis. Data were pooled and a median [95% confidence interval (CI)] diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated. For the meta-analysis, a generic inverse variance method was undertaken using the accuracy and area under the curve (AUC) data. RESULTS: The ten studies exhibited moderate to high methodological quality. They evaluated NETest usage both as a diagnostic and as a monitoring tool. The meta-analysis identified the diagnostic accuracy of the NETest to be 95%-96% with a mean DOR of 5 853, +LR of 195, and -LR of 0.06. The NETest was 84.5%-85.5% accurate in differentiating stable disease from progressive disease. As a marker of natural history, the accuracy was 91.5%-97.8%. As an interventional/response biomarker, the accuracy was 93.7%-97.4%. The pooled AUC for the NETest was 0.954 ± 0.005, with a z-statistic of 175.06 (P < 0.001). CONCLUSIONS: The NETest is an accurate biomarker suitable for clinical use in NET disease management. The meta-analysis supports the utility of the NETest as an IVD to establish a diagnosis and monitor therapeutic efficacy. The use of this as a biomarker provides information relevant to NET management consistent with observations regarding utility of liquid biopsies in other oncological disciplines.
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Biomarcadores de Tumor , Tumores Neuroendocrinos , Biomarcadores de Tumor/genética , Genómica , Humanos , Biopsia Líquida , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/genética , ARN MensajeroRESUMEN
PURPOSE: Peptide receptor radionuclide therapy (PRRT) and radioembolization are increasingly used in neuroendocrine neoplasms patients. However, concerns have been raised on cumulative hepatotoxicity. The aim of this sub-analysis was to investigate hepatotoxicity of yttrium-90 resin microspheres radioembolization in patients who were previously treated with PRRT. METHODS: Patients treated with radioembolization after systemic radionuclide treatment were retrospectively analysed. Imaging response according to response evaluation criteria in solid tumours (RECIST) v1.1 and clinical response after 3 months were collected. Clinical, biochemical and haematological toxicities according to common terminology criteria for adverse events (CTCAE) v4.03 were also collected. Specifics on prior PRRT, subsequent radioembolization treatments, treatments after radioembolization and overall survival (OS) were collected. RESULTS: Forty-four patients were included, who underwent a total of 58 radioembolization procedures, of which 55% whole liver treatments, at a median of 353 days after prior PRRT. According to RECIST 1.1, an objective response rate of 16% and disease control rate of 91% were found after 3 months. Clinical response was seen in 65% (15/23) of symptomatic patients after 3 months. Within 3 months, clinical toxicities occurred in 26%. Biochemical and haematological toxicities CTCAE grade 3-4 occurred in ≤ 10%, apart from lymphocytopenia (42%). Radioembolization-related complications occurred in 5% and fatal radioembolization-induced liver disease in 2% (one patient). A median OS of 3.5 years [95% confidence interval 1.8-5.1 years] after radioembolization for the entire study population was found. CONCLUSION: Radioembolization after systemic radionuclide treatments is safe, and the occurrence of radioembolization-induced liver disease is rare. LEVEL OF EVIDENCE: 4, case series.
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Braquiterapia/métodos , Neoplasias Hepáticas/radioterapia , Tumores Neuroendocrinos/radioterapia , Radioisótopos de Itrio/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Tumores Neuroendocrinos/secundario , Receptores de Péptidos/uso terapéutico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Radioembolization of liver metastases of neuroendocrine neoplasms (NEN) has shown promising results; however, the current literature is of limited quality. A large international, multicentre retrospective study was designed to address several shortcomings of the current literature. MATERIALS: 244 NEN patients with different NEN grades were included. METHODS: Primary outcome parameters were radiologic response 3 and 6 months after treatment according to RECIST 1.1 and mRECIST. Secondary outcome parameters included clinical response, clinical and biochemical toxicities. RESULTS: Radioembolization resulted in CR in 2%, PR in 14%, SD in 75% and PD 9% according to RECIST 1.1 and in CR in 8%, PR in 35%, SD in 48% and PD in 9% according to mRECIST. Objective response rates improved over time in 20% and 26% according to RECIST 1.1. and mRECIST, respectively. Most common new grade 3-4 biochemical toxicity was lymphocytopenia (6.7%). No unexpected clinical toxicities occurred. Radioembolization-specific complications occurred in < 4%. In symptomatic patients, improvement and resolution of symptoms occurred in 44% and 34%, respectively. Median overall survival from first radioembolization was 3.7, 2.7 and 0.7 years for G1, G2 and G3, respectively. Objective response is independent of NEN grade or primary tumour origin. Significant prognostic factors for survival were NEN grade/Ki67 index, ≥ 75% intrahepatic tumour load, the presence of extrahepatic disease and disease control rate according to RECIST 1.1. CONCLUSION: Safety and efficacy of radioembolization in NEN patients was confirmed with a high disease control rate of 91% in progressive patients and alleviation of NEN-related symptoms in 79% of symptomatic patients. LEVEL OF EVIDENCE: 4.
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Braquiterapia/métodos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundario , Microesferas , Tumores Neuroendocrinos/patología , Radioisótopos de Itrio/uso terapéutico , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
An array of treatment modalities is currently available in the management of patients with neuroendocrine tumors (NETs). Complete resection of the primary tumor and all metastatic lesions represents the only approach possessing intent to cure. However, due to patients' disease frequently being at an advanced stage on initial diagnosis only a minority of individuals are candidates for radical procedures. Cytoreductive surgery (debulking) may potentially confer improvements in quality of life and prolong overall survival. In light of the recent introduction of effective nonsurgical treatment options, the indication for cytoreductive surgery needs to be carefully assessed. The presence of nonresectable liver metastases is not a contraindication for resection of the primary tumor including locoregional disease in small bowel NETs. Resection of primary pancreatic NETs in the setting of unresectable metastatic liver disease may have a beneficial effect on the prognosis of selected patients with a tumor requiring less aggressive local surgery. Liver transplantation presents a generally accepted approach in meticulously selected patients with unresectable liver metastases. Stringent and validated selection criteria are not available. While overall survival is satisfactory, high recurrence rates hinder outcomes and call for the development and implementation of neoadjuvant and adjuvant concepts. Advances in intestinal transplantation over time may justify consideration of an individual with advanced neuroendocrine tumor disease unresponsive to standard medical or surgical treatment.
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Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias del Sistema Digestivo/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Trasplante de Hígado/métodos , Tumores Neuroendocrinos/cirugía , HumanosRESUMEN
PURPOSE: To determine MR-imaging features for the differentiation between hepatocellular carcinoma (HCC) and benign hepatocellular tumors in the non-cirrhotic liver. MATERIAL AND METHODS: 107 consecutive patients without liver cirrhosis (46 male; 45 ± 14 years) who underwent liver resection due to suspicion of HCC were included in this multi-center study. The following imaging features were assessed: lesion diameter and demarcation, satellite-lesions, central-scar, capsule, fat-content, hemorrhage, vein-infiltration and signal-intensity (SI) on native T1-, T2- and dynamic-enhanced T1-weighted images (center versus periphery). In addition, contrast-media (CM) uptake in the liver specific phase was analyzed in a sub-group of 42 patients. RESULTS: Significant differences between HCC (n=55) and benign lesions (n=52) were shown for native T1-, T2- and dynamic-enhanced T1-SI, fat-content, and satellite-lesions (all, P<.05). Independent predictors for HCC were T1-hypointensity (odds-ratio, 4.81), T2-hypo-/hyperintensity (5.07), lack of central tumor-enhancement (3.36), and satellite-lesions (5.78; all P<0.05). Sensitivity and specificity of HCC was 91% and 75% respectively for two out-of four independent predictors, whereas specificity reached 98% for all four predictors. Sub-analysis, showed significant differences in liver specific CM uptake between HCC (n=18) and benign lesions (n=24; P<0.001) and revealed lack of liver specific CM uptake (odds-ratio, 2.7) as additional independent feature for diagnosis of HCC. CONCLUSION: Independent MRI features indicating HCC are T1-hypointensity, T2-hypo- or hyperintensity, lack of central tumor-enhancement, presence of satellite-lesions and lack of liver specific CM-uptake. These features may have the potential to improve the diagnosis of HCC in the non-cirrhotic liver.
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Carcinoma Hepatocelular/diagnóstico , Aumento de la Imagen/métodos , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética/métodos , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/patología , Adulto , Anciano , Carcinoma Hepatocelular/patología , Medios de Contraste/administración & dosificación , Diagnóstico Diferencial , Femenino , Hiperplasia Nodular Focal/diagnóstico , Hiperplasia Nodular Focal/patología , Estudios de Seguimiento , Gadolinio DTPA/administración & dosificación , Hepatectomía/métodos , Hepatitis C/complicaciones , Humanos , Hígado/patología , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Neuroendocrine tumors originating from the small bowel frequently metastasize to the lymph nodes and/or liver. Although surgical extirpation of the primary tumor and locoregional metastases epitomizes the management of patients with such tumors, this is not always possible with conventional surgical techniques. Nonresectable, slow-growing tumors involving the mesenteric root represent a generally accepted indication for deceased donor intestinal and multivisceral transplantation. Furthermore, vascularized sentinel forearm flaps offer opportunities for monitoring graft rejection and tailoring immunosuppression regimens. Here, we report the first documented case of modified liver-free multivisceral transplantation preceded by neoadjuvant 177-lutetium peptide receptor radionuclide therapy in a patient with a small bowel neuroendocrine tumor and extensive lymph node metastases in the mesenterium. At a follow-up of 21 months the patient is biochemically and radiologically disease-free.
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Neoplasias Intestinales/patología , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/cirugía , Trasplante de Órganos/métodos , Vísceras/trasplante , Adulto , Femenino , Rechazo de Injerto/cirugía , Humanos , Metástasis Linfática , Masculino , Mesenterio/patología , Persona de Mediana Edad , Terapia Neoadyuvante , Receptores de Péptidos , Receptores de Somatostatina , Colgajos QuirúrgicosRESUMEN
CONTEXT: Prognosis in patients with neuroendocrine tumors (NETs) is often poor, frequently reflecting delayed diagnosis. Hence, accurate and practical NET markers are needed. Cocaine- and amphetamine-regulated transcript (CART) peptide is a potential novel NET marker. DESIGN AND PARTICIPANTS: Circulating levels of CART peptide and the established NET markers chromogranin A (CgA) and chromogranin B (CgB) were measured using RIA in 353 patients with NET (normal renal function) and in controls. Clinical data were collected retrospectively. MAIN OUTCOME MEASURE(S): The comparative and combined utility of CART, CgA, and CgB for diagnosis and assessment of disease progression was measured in different NET subtypes. RESULTS: CgA and CgB in combination improved diagnostic accuracy in patients with gut NETs, nongastroenteropancreatic NETs, and NETs with an unknown primary origin compared with each biomarker alone. Measuring CART did not further improve diagnosis in these NET subtypes. For pancreatic NETs, CgB was superior to CgA and CART in detecting stable disease (P < .007), whereas CgA and CART in combination were most effective in identifying progressive disease. In phaeochromocytomas/paragangliomas (PCC/PGL), CART was the most useful biomarker for identifying stable (P < .001) and progressive (P = .001) disease. Consistent with this, plasma CART decreased following PCC/PGL tumor resection, remaining low in all patients in remission, but increasing in those with progressive disease. CONCLUSIONS: CART is a useful marker for identifying progressive pancreatic NETs. CART is superior to CgA and CgB in detecting stable and progressive PCC/PGLs, and may have a role as a surveillance marker for PCC/PGL patients.
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Neoplasias de las Glándulas Suprarrenales/diagnóstico , Biomarcadores de Tumor/sangre , Cromogranina A/sangre , Cromogranina B/sangre , Proteínas del Tejido Nervioso/sangre , Tumores Neuroendocrinos/diagnóstico , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Neoplasias de las Glándulas Suprarrenales/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Técnicas de Diagnóstico Endocrino , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/sangre , Paraganglioma/sangre , Feocromocitoma/sangre , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Neuroendocrine neoplasias (NEN) of the gastroenteropancreatic (GEP) system frequently present with metastatic deposits. The proliferation marker Ki-67 is used for diagnosis and to assess the prognosis of disease. The aim of our study was to evaluate the usefulness of Ki-67 % in the assessment of NEN patients with regard to their disease stage in clinical practice. Additionally, a comparative analysis of Ki-67 levels among different sites of disease was performed. METHODS: This retrospective study included patients with GEP NEN referred to our center from 2010 to 2012. The NEN diagnosis was confirmed by standard histopathology. Ki-67 immunohistochemistry was done on paraffin-embedded sections using an automated Leica immunohistochemistry machine. NEN grading was carried out according to European Neuroendocrine Tumor Society recommendations (low grade [G1] to intermediate grade [G2], well to moderately differentiated neuroendocrine neoplasms; high-grade [G3], moderately to poorly differentiated neuroendocrine neoplasms). Results of tumor staging and grading were correlated. In a subgroup of cases, comparative analysis of Ki-67 levels in different sites of disease was carried out. RESULTS: One hundred sixty-one GEP NEN patients were included in the study. Metastatic disease was seen in 46.1 % (53/115) of G1 tumors, 77.8 % (28/36) of G2 tumors, and 100 % of (10/10) G3 tumors (p = 0.0002). When stratified according to primary tumor site, metastatic disease was documented in 42.9 % (36/84) of patients with pancreatic NEN and in 91.9 % (34/37) of those with small intestinal primary. Stage IV metastatic disease was present in 27.8 % (32/115) and 72.2 % (26/36) of the G1 and G2 tumors, respectively, and in 90 % (9/10) of the G3 tumors. Assessment of the Ki-67 index for a subset of cases at metastatic sites as well as the primary tumor site showed discrepancies in 35.3 % cases. In 7/9 (77.8 %) patients with liver metastases, Ki-67 % was higher in the liver lesions than in the primary tumor. CONCLUSIONS: Patients with GEP NEN exhibiting a high Ki-67 proliferation index present with metastatic disease in the vast majority of cases. Depending upon the primary tumor site, metastases are to be expected also in tumors with low Ki-67 %, although they are considered less aggressive. Different disease sites may express heterogeneous Ki-67 levels.
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Biomarcadores de Tumor/metabolismo , Neoplasias del Sistema Digestivo/patología , Antígeno Ki-67/metabolismo , Ganglios Linfáticos/patología , Tumores Neuroendocrinos/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Estudios de Cohortes , Neoplasias del Sistema Digestivo/mortalidad , Neoplasias del Sistema Digestivo/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Índice Mitótico , Clasificación del Tumor , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/cirugía , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Rol , Sensibilidad y Especificidad , Tasa de Supervivencia , Adulto JovenRESUMEN
INTRODUCTION: Complex bile duct injury (BDI) is a serious condition requiring hepatectomy in some instances. The present study was to analyse the factors that led to hepatectomy for patients with BDI after laparoscopic cholecystectomy (LC). METHODS: The medical records of patients referred to our department from April 1998 to September 2007 for management of BDI following LC were reviewed, and patients who underwent hepatectomy were identified. The type of BDI, indication for liver resection, interval between LC and liver surgery, histology of the liver specimen, postoperative morbidity and long-term results were analysed. RESULTS: Hepatectomy was performed in 10 of 76 patients (13.2%), with BDI either as isolated damage or in combination with vascular injury (VI). Proximal BDI (defined as disruption of the biliary confluence) and injury to the right hepatic artery were found to be independent risk factors of hepatectomy, with odds ratios of 16 and 45, respectively. Five patients required early liver resection (within 5 weeks post-LC) to control sepsis caused by confluent liver necrosis or bile duct necrosis. In five patients, hepatectomy was indicated during long-term follow-up (over 4 months post-LC) to effectively manage recurrent cholangitis and liver atrophy. Despite of high postoperative morbidity (60%) and even mortality (10%), the long-term results (median follow-up of 34 months) were satisfactory, with either no or only transitory symptoms in 67% of the patients. CONCLUSION: Hepatectomy may inevitably be necessary to manage early or late complications after LC. Proximal BDI and VI were the two independent risk factors of hepatectomy in this series.
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Conductos Biliares/lesiones , Conductos Biliares/patología , Colecistectomía Laparoscópica/efectos adversos , Hepatectomía , Arteria Hepática/lesiones , Hígado/patología , Atrofia/etiología , Colangitis/etiología , Intervalos de Confianza , Humanos , Hígado/cirugía , Necrosis/etiología , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Sepsis/etiología , Sepsis/cirugía , Factores de TiempoRESUMEN
A 63-year-old woman underwent living donor liver transplantation for hepatic metastases of an extragastrointestinal stromal tumor (EGIST) originating from the rectovaginal space. Due to a multifocal extrahepatic tumor recurrence, treatment with imatinib mesylate was started after extensive pharmacokinetic studies to rule out possible interactions with immunosuppressives. We performed several re- resections for EGIST recurrence thereafter. At the last follow-up, 17 years after primary tumor resection and 10 years after living donor liver transplantation, the patient is symptom-free under immunosuppressive and imatinib mesylate treatments with a 2-cm stable recurrent pararectal EGIST. To our knowledge, this is the only report published on a patient who underwent transplantation for hepatic EGIST metastases with a posttransplantation follow-up of 10 years and the first report on living donor liver transplantation for metastasized EGIST. This is the first description of pharmacokinetics of imatinib and its main active metabolite CGP74588 in a liver transplant recipient.
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Tumores del Estroma Gastrointestinal/patología , Neoplasias Hepáticas/cirugía , Trasplante de Hígado , Neoplasias del Recto/patología , Neoplasias Vaginales/patología , Antineoplásicos/farmacocinética , Benzamidas , Femenino , Humanos , Mesilato de Imatinib , Inmunosupresores/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Donadores Vivos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Piperazinas/farmacocinética , Pirimidinas/farmacocinética , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: This study evaluated the outcome of liver surgery for colorectal metastases (CLM) in patients over 70 years old in a large international multicentre cohort. METHODS: Among 7764 patients who had resection of CLM, 999 (12.9 per cent) were aged 70-75 years, 468 (6.0 per cent) were aged 75-80 years and 157 (2.0 per cent) were at least 80 years old. Elderly patients were compared with the younger population. RESULTS: Multinodular and bilateral metastases were less common in elderly than in younger patients (P < 0.001). Preoperative chemotherapy was used less frequently and more limited surgery was performed (P < 0.001). Sixty-day postoperative mortality and morbidity rates were 3.8 and 32.3 per cent respectively, compared with 1.6 and 28.7 per cent in younger patients (both P < 0.001). Three-year overall survival was 57.1 per cent in elderly and 60.2 per cent in younger patients (P < 0.001), and was similar among patients aged 70-75, 75-80 or at least 80 years (57.8, 55.3 and 54.1 per cent respectively; P = 0.160). Independent predictors of survival were more than three metastases, bilateral metastases, concomitant extrahepatic disease and no postoperative chemotherapy. CONCLUSION: Liver resection for CLM in elderly patients can achieve a reasonable 3-year survival rate, with an acceptable morbidity rate. There should be no upper age limit but risk factors may help predict potential benefit.
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Neoplasias Colorrectales , Hepatectomía/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Cuidados Intraoperatorios , Neoplasias Hepáticas/mortalidad , Masculino , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Hepatic surgery is presumed to improve survival of patients with liver metastases (LM) from neuroendocrine tumours (NET). This study identified LM-specific variables that could be used as additional selection criteria for aggressive treatment. METHODS: A novel classification of LM from NET was established based on their localization and presentation. RESULTS: From 1992 to 2006, 119 patients underwent staging and treatment of LM. Three growth types of LM were identified radiologically: single metastasis (type I), isolated metastatic bulk accompanied by smaller deposits (type II) and disseminated metastatic spread (type III). The three groups differed significantly in terms of chronological presentation of LM, hormonal symptoms, Ki-67 index, 5-hydroxyindoleacetic acid and chromogranin A levels, lymph node involvement, presence of bone metastases and treatment options. The 3-, 5- and 10-year disease-specific survival rates for the entire cohort were 76.4, 63.9 and 46.5 per cent respectively. There were significant differences in survival between the three groups: 5- and 10-year rates were both 100 per cent for type I, 84 and 75 per cent respectively for type II, and 51 and 29 per cent for type III. CONCLUSION: The localization and biological features of LM from NET defines therapeutic management and is predictive of outcome.
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Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Tumores Neuroendocrinos/secundario , Tumores Neuroendocrinos/terapia , Adulto , Anciano , Ablación por Catéter/métodos , Supervivencia sin Enfermedad , Embolización Terapéutica/métodos , Femenino , Compuestos Heterocíclicos/uso terapéutico , Humanos , Neoplasias Hepáticas/patología , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Péptidos Cíclicos/uso terapéutico , Estudios Prospectivos , Radiofármacos/uso terapéuticoRESUMEN
Sixteen years after its first successful application, living donor liver transplantation now has a small but well-established role in treatment for liver failure in Germany. It remains problematic in both child and adult patients concerning effort, expected results, and assessment of risks to the donor. Therefore the method shall remain limited to more research-oriented institutions for the time being before it can be established more broadly as an alternative to postmortal donation. In Germany it presents generally the same limitations as living donor kidney transplantation.
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Hepatectomía/métodos , Trasplante de Hígado/métodos , Donadores Vivos , Recolección de Tejidos y Órganos/métodos , Adulto , Niño , Alemania , Humanos , Hígado/patología , Pruebas de Función Hepática , Regeneración Hepática/fisiología , Tamaño de los Órganos , Pronóstico , Donantes de Tejidos/provisión & distribución , Listas de EsperaRESUMEN
PURPOSE: This study sought to compare iodine-124 positron emission tomography/computed tomography (124I-PET/CT) and 2-[18F]fluoro-2-deoxy-D: -glucose- (FDG-) PET in the detection of recurrent differentiated thyroid carcinoma (DTC) lesions in patients with increasing serum thyroglobulin (Tg), Tg-antibodies, or both, but without pathological cervical ultrasonography. We assessed the lesion detection accuracy of 124I-PET alone, CT alone, (124)I-PET/CT, FDG-PET, and all these modalities combined. MATERIAL AND METHODS: The study included 21 patients (9 follicular, 12 papillary DTC) who had been rendered disease-free by thyroidectomy and radioiodine treatment (RIT) and followed up for 21-275 months after the last RIT. In all patients, FDG-PET was performed first. Within 1 week, 124I-PET/CT was performed 24 h after oral administration of 43 +/- 11 MBq 124I. Imaging results were correlated with further clinical follow-up with (n = 12) or without (n = 9) post-study histology as the reference standard. RESULTS: The sensitivities for DTC lesion detection were: 124I-PET, 49%; CT, 67%; 124I-PET/CT, 80%; FDG-PET, 70%; and all modalities combined, 91%. For local recurrences (distant metastases), the sensitivities were: 124I-PET, 60% (45%); CT, 20% (84%); and FDG-PET, 65% (71%). One-third of lesions demonstrated pathological tracer uptake with both 124I- and FDG-PET, while two-thirds were positive with only one of these modalities. CONCLUSION: Used together, 124I-PET and CT allow localization of foci of highly specific 124I uptake as well as non-iodine-avid lesions. The combination of 124I-PET/CT and FDG-PET improves restaging in recurrent DTC by enabling detection on whole-body scans of local recurrence or metastases that are often not found if only one of the methods or other imaging modalities are applied.
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Fluorodesoxiglucosa F18 , Radioisótopos de Yodo , Tomografía de Emisión de Positrones/métodos , Tiroglobulina/sangre , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Reacciones Falso Negativas , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Liver transplantation is currently recognized as the optimal treatment for both early hepatocellular carcinoma in the setting of cirrhosis (HCC) as well as for alcoholic liver disease (ALD). The purpose of this study was to evaluate the outcome of patients with HCC and ALD in the absence of viral hepatitic infections. METHODS: Twelve recipients were transplanted with a diagnosis of HCC and ALD in the absence of viral hepatitis during a 6-year period. Nine received deceased donor livers, and 3 live donor grafts. Our results were compared to those obtained by a search of the world literature. RESULTS: The postoperative course was uneventful in all but one patient. All recipients experienced a good quality of life postoperatively. Three-year overall and recurrence-free survival rates were 82 and 73%, respectively. Nine patients are currently alive, after a median follow-up of 29 months. CONCLUSION: This is the first study to evaluate liver transplantation for HCC in ALD. Although outcomes are excellent, the evaluation of patients with ALD and HCC constitutes a challenging topic in transplantation surgery, especially when live liver donation is considered. An interdisciplinary structured approach is recommended, with special emphasis on ethical considerations.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Cirrosis Hepática Alcohólica/cirugía , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/ética , Anciano , Carcinoma Hepatocelular/complicaciones , Supervivencia sin Enfermedad , Femenino , Humanos , Cirrosis Hepática Alcohólica/complicaciones , Neoplasias Hepáticas/complicaciones , Donadores Vivos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , RecurrenciaRESUMEN
BACKGROUND: Concomitant hepatic artery injury is a rare but severe complication associated with bile duct injury during laparoscopic cholecystectomy (LC). METHODS: Sixty patients referred with biliary injury after LC between April 1998 and December 2005 were divided into two groups according to the time elapsed between injury and definitive surgical revision; patients in group 1 were referred early (within 4 days) after operation and those in group 2 were referred later. Hepatic rearterialization was performed in addition to biliary reconstruction when technically possible. RESULTS: Damage to the hepatic artery was detected in ten patients. Hepatic rearterialization was carried out in five patients by end-to-end anastomosis (one), or by using an autologous graft (three) or allogeneic vascular graft (one). Three patients in group 2 underwent right hemihepatectomy without arterial reconstruction owing to liver necrosis or lobar atrophy. Three of ten patients died from postoperative complications. CONCLUSION: Combined bile duct and hepatic artery injury during LC led to a complicated clinical course, with a high mortality rate. Reconstruction of the right hepatic artery might be helpful in reducing hepatic ischaemia, but is usually feasible only if the injury is identified early.