RESUMEN
BACKGROUND: Most current models for predicting survival after resection of colorectal liver metastasis include largest diameter and number of colorectal liver metastases as dichotomous variables, resulting in underestimation of the extent of risk variation and substantial loss of statistical power. The aim of this study was to develop and validate a new prognostic model for patients undergoing liver resection including largest diameter and number of colorectal liver metastases as continuous variables. METHODS: A prognostic model was developed using data from patients who underwent liver resection for colorectal liver metastases at MD Anderson Cancer Center and had RAS mutational data. A Cox proportional hazards model analysis was used to develop a model based on largest colorectal liver metastasis diameter and number of metastases as continuous variables. The model results were shown using contour plots, and validated externally in an international multi-institutional cohort. RESULTS: A total of 810 patients met the inclusion criteria. Largest colorectal liver metastasis diameter (hazard ratio (HR) 1.11, 95 per cent confidence interval 1.06 to 1.16; P < 0.001), number of colorectal liver metastases (HR 1.06, 1.03 to 1.09; P < 0.001), and RAS mutation status (HR 1.76, 1.42 to 2.18; P < 0.001) were significantly associated with overall survival, together with age, primary lymph node metastasis, and prehepatectomy chemotherapy. The model performed well in the external validation cohort, with predicted overall survival values almost lying within 10 per cent of observed values. Wild-type RAS was associated with better overall survival than RAS mutation even when liver resection was performed for larger and/or multiple colorectal liver metastases. CONCLUSION: The contour prognostic model, based on diameter and number of lesions considered as continuous variables along with RAS mutation, predicts overall survival after resection of colorectal liver metastasis.
Asunto(s)
Neoplasias Colorrectales/patología , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Surgical outcomes may be associated with hospital volume and the influence of volume on minimally invasive liver surgery (MILS) is not known. METHODS: Patients entered into the prospective registry of the Italian Group of MILS from 2014 to 2018 were considered. Only centres with an accrual period of at least 12 months and stable MILS activity during the enrolment period were included. Case volume was defined by the mean number of minimally invasive liver resections performed per month (MILS/month). RESULTS: A total of 2225 MILS operations were undertaken by 46 centres; nine centres performed more than two MILS/month (1376 patients) and 37 centres carried out two or fewer MILS/month (849 patients). The proportion of resections of anterolateral segments decreased with case volume, whereas that of major hepatectomies increased. Left lateral sectionectomies and resections of anterolateral segments had similar outcome in the two groups. Resections of posterosuperior segments and major hepatectomies had higher overall and severe morbidity rates in centres performing two or fewer MILS/month than in those undertaking a larger number (posterosuperior segments resections: overall morbidity 30·4 versus 18·7 per cent respectively, and severe morbidity 9·9 versus 4·0 per cent; left hepatectomy: 46 versus 22 per cent, and 19 versus 5 per cent; right hepatectomy: 42 versus 34 per cent, and 25 versus 15 per cent). CONCLUSION: A volume-outcome association existed for minimally invasive hepatectomy. Complex and major resections may be best managed in high-volume centres.
ANTECEDENTES: Los resultados quirúrgicos pueden estar relacionados con el volumen de casos del hospital, pero no se conoce la influencia en la cirugía mínimamente invasiva del hígado (minimallyinvasive liver surgery, MILS). MÉTODOS: Se incluyeron los pacientes registrados en el registro prospectivo del grupo italiano de MILS desde 2014 a 2018. Solo se consideraron centros con extensión de ≥ 12 meses y actividad estable de MILS durante el periodo de reclutamiento. El volumen de casos se definió como el número de MILS efectuado por mes. RESULTADOS: Se llevaron a cabo un total de 2.225 MILS en 46 centros, 9 de ellos con > 2 MILS/mes (n = 1.376 pacientes) y 37 centros con ≤ 2 MILS/mes (n = 849). La proporción de resecciones de segmentos anterolaterales disminuyó con el volumen de casos, mientras que la proporción de hepatectomías mayores aumentó. Los resultados para ambos grupos fueron similares en las seccionectomías lateral izquierda y en las resecciones del segmento anterolateral. Las resecciones del segmento posterosuperior y las hepatectomías mayores presentaron tasas más altas de morbilidad global y morbilidad grave en centros que realizaban ≤ 2 MILS/mes que en los que realizaban > 2 MILS/mes (resecciones del segmento posterosuperior, morbilidad global 30,4 versus 18,7%, morbilidad grave 9,9 versus 4,0%; hepatectomía izquierda, 46,2 versus 22,0%, 19,2 versus 5,5%; hepatectomía derecha, 41,7 versus 33,8%, 25,0 versus 14.9%). CONCLUSIÓN: Se observó una asociación volumenresultado para la resección hepática mínimamente invasiva. Las resecciones complejas y mayores se pueden manejar mejor en centros de gran volumen.
Asunto(s)
Hepatectomía/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Anciano , Femenino , Hepatectomía/efectos adversos , Hepatectomía/métodos , Hepatectomía/mortalidad , Humanos , Italia/epidemiología , Neoplasias Hepáticas/cirugía , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/mortalidad , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to assess the best achievable outcomes in laparoscopic liver resection (LLR) after risk adjustment based on surgical technical difficulty using a national registry. METHODS: LLRs registered in the Italian Group of Minimally Invasive Liver Surgery registry from November 2014 to March 2018 were considered. Benchmarks were calculated according to the Achievable Benchmark of Care (ABC™). LLRs at each centre were divided into three clusters (groups I, II and III) based on the Kawaguchi classification. ABCs for overall and major morbidity were calculated in each cluster. Multivariable analysis was used to identify independent risk factors for overall and major morbidity. Significant variables were used in further risk adjustment. RESULTS: A total of 1752 of 2263 patients fulfilled the inclusion criteria: 1096 (62·6 per cent) in group I, 435 (24·8 per cent) in group II and 221 (12·6 per cent) in group III. The ABCs for overall morbidity (7·8, 14·2 and 26·4 per cent for grades I, II and II respectively) and major morbidity (1·4, 2·2 and 5·7 per cent) increased with the difficulty of LLR. Multivariable analysis showed an increased risk of overall morbidity associated with multiple LLRs (odds ratio (OR) 1·35), simultaneous intestinal resection (OR 3·76) and cirrhosis (OR 1·83), and an increased risk of major morbidity with intestinal resection (OR 4·61). ABCs for overall and major morbidity were 14·4 and 3·2 per cent respectively for multiple LLRs, 30 and 11·1 per cent for intestinal resection, and 14·9 and 4·8 per cent for cirrhosis. CONCLUSION: Overall morbidity benchmarks for LLR ranged from 7·8 to 26·4 per cent, and those for major morbidity from 1·4 to 5·7 per cent, depending on complexity. Benchmark values should be adjusted according to multiple LLRs or simultaneous intestinal resection and cirrhosis.
ANTECEDENTES: Este estudio tuvo como objetivo evaluar los mejores resultados que se pueden conseguir en la resección hepática laparoscópica (laparoscopic liver resection, LLR) después del ajuste por riesgos basado en la dificultad de la técnica quirúrgica utilizando un registro nacional. MÉTODOS: Se consideraron las LLRs incluidas en el Registro del Grupo Italiano de Cirugía Hepática Mínimamente Invasiva desde 11/2014 a 03/2018. Los resultados de referencia (benchmarks) se calcularon de acuerdo con el Achievable Benchmark of Care (ABC™). Las LLRs de cada uno de los centros se dividieron en 3 grupos (Grupo I, II y III) en base a la clasificación de Kawaguchi. Se calculó el ABC de la morbilidad global y de la morbilidad mayor para cada grupo. Se realizó un análisis multivariable para identificar los factores independientes de riesgos para la morbilidad global y morbilidad mayor. Se utilizaron variables significativas para realizar ajustes de riesgo adicionales. RESULTADOS: Un total de 1.752 pacientes de los 2.263 cumplían los criterios de inclusión, de los cuales 1.096 (62,6%) se incluyeron en el Grupo I, 435 (24,8%) en el Grupo II y 221 (12,6%) en el Grupo III. El ABC de la morbilidad global (7,8%, 14,2%, 26,4%) y de la morbilidad mayor (1,4%, 2,2%, 5,7%) aumentó del Grupo I al Grupo III. El análisis multivariable mostró un incremento del riesgo para la morbilidad global asociada con múltiples LLRs (razón de oportunidades, odds ratio, OR 1,349), resección intestinal simultánea (OR 3,760) y cirrosis (OR 1,825), y para la morbilidad mayor con la resección intestinal (OR 4,606). Los ABC de la morbilidad global y morbilidad mayor fueron 14,4% y 3,2% para las LLR múltiples, 30% y 11% para la resección intestinal, y 14,9% y 4,8% para la cirrosis, respectivamente. CONCLUSIÓN: Los resultados de referencia (benchmark) para la morbilidad global y morbilidad mayor en la LLR variaron entre un 8% y un 26% y entre un 1,4% y un 5,7%, dependiendo de la complejidad. Los valores de referencia deberían ajustarse de acuerdo con la práctica de LLRs múltiples o resección intestinal simultánea y cirrosis.
Asunto(s)
Benchmarking/métodos , Hepatectomía , Laparoscopía , Femenino , Hepatectomía/efectos adversos , Hepatectomía/normas , Humanos , Italia/epidemiología , Laparoscopía/efectos adversos , Laparoscopía/normas , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Calidad de la Atención de Salud/normas , Sistema de Registros , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Although the number of colorectal liver metastases (CLM) is decreasingly considered as a contraindication to surgery, patients with 10 CLM or more are often denied liver surgery. This study aimed to evaluate the outcome after liver surgery and to identify prognostic factors of survival in such patients. METHODS: The study population consisted of a multicentre cohort of patients with CLM (N=12 406) operated on, with intention to resect, from January 2005-June 2013 and whose data were prospectively collected in the LiverMetSurvey registry. RESULTS: Overall, the group ⩾10 CLM (N=529, 4.3%) experienced a 5-year overall survival (OS) of 30%. A macroscopically complete (R0/R1) resection (72.8% of patients) was associated with a 3- and 5-year OS of 61% and 39% vs 29% and 5% for R2/no resection patients (P<0.0001). At multivariate analysis, R0/R1 resection emerged as the strongest favourable factor of OS (HR 0.35 (0.26-0.48)). Other independent favourable factors were as follows: maximal tumour size <40 mm (HR 0.67 (0.49-0.92)); age <60 years (HR 0.66 (0.50-0.88)); preoperative MRI (HR 0.65 (0.47-0.89)); and adjuvant chemotherapy (HR 0.73 (0.55-0.98)). The model showed that 5-year OS rates of 30% was possible provided R0/R1 resection associated with at least an additional favourable factor. CONCLUSIONS: Liver resection might provide long-term survival in patients with ⩾10 CLM staged with preoperative MRI, provided R0/R1 resection followed by adjuvant therapy. A validation of these results in another cohort is needed.
Asunto(s)
Neoplasias Colorrectales/patología , Hepatectomía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Carga Tumoral , Factores de Edad , Anciano , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasia Residual , Recurrencia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: Despite advances in perioperative care, hepatectomy remains associated with morbidity rates of up to 40%. Currently, available nomograms for predicting severe post-hepatectomy complications do not include early postoperative data. This retrospective observational study aimed to determine whether the parameters routinely measured in patients admitted to the Intensive Care Unit (ICU) after hepatectomy could represent risk factors for severe morbidity and to propose a nomogram scoring system to predict severe postoperative complications. PATIENTS AND METHODS: 411 adult patients who underwent elective hepatectomy at a high-volume tertiary care center for hepatic surgery from December 2016 to June 2022 were enrolled. The primary outcome was the assessment of predictors of 30-day severe postoperative complications following hepatectomy, defined as Clavien-Dindo grade 3a or higher. As a secondary outcome, we aimed to develop an easy-to-use scoring system to estimate the risk of severe postoperative complications. RESULTS: Severe complications occurred in 78 patients (19%). The final model included body mass index, preoperative bilirubin level, and ICU data (i.e., pH, lactate clearance, arterial lactate concentration 12 hours after ICU admission, need for packed red blood cell transfusions, and length of stay). Notably, the latter three variables were proven to be independent predictors of the outcomes. The model showed an overall good fit (C-index=0.754, corrected Dxy=0.692). A calibration plot using bootstrap internal validity resampling confirmed the stability of the model (mean absolute error=0.017, root mean square error of approximation=0.00051). CONCLUSIONS: We developed an accurate and practical scoring system based on preoperative and early postoperative data to predict poor outcomes after hepatectomy. Further external validation on larger series could lead to the integration of such a tool in the routine clinical practice to support patients' management and early warning during ICU stay. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical-Abstract-NEW-2.pdf.
Asunto(s)
Hepatectomía , Hígado , Adulto , Humanos , Hepatectomía/efectos adversos , Hígado/cirugía , Factores de Riesgo , Estudios Retrospectivos , Ácido Láctico , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND: Advances in surgical techniques and systemic treatments have increased the likelihood of achieving radical surgery and long-term survival in metastatic colorectal cancer (mCRC) patients with initially unresectable colorectal liver metastases (CRLMs). Nonetheless, roughly half of the patients resected after an upfront systemic therapy experience disease relapse within 6 months from surgery, thus leading to the question whether surgery is actually beneficial for these patients. MATERIALS AND METHODS: A real-world dataset of mCRC patients with initially unresectable liver-limited disease treated with conversion chemotherapy followed by radical resection of CRLMs at three high-volume Italian institutions was retrospectively assessed with the aim of investigating the association of baseline and pre-surgical clinical, radiological and molecular factors with the risk of relapse within 6 or 12 months from surgery. RESULTS: Overall, 268 patients were included in the analysis and 207 (77%) experienced recurrence. Ninety-six (46%) of them had disease relapse within 6 months after CRLM resection and in spite of several variables associated with early recurrence at univariate analyses, only primary tumour resection at diagnosis [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.32-0.89, P = 0.02] remained significant in the multivariable model. Among patients with resected primary tumours, pN+ stage was associated with higher risk of disease relapse within 6 months (OR 3.02, 95% CI 1.23-7.41, P = 0.02). One hundred and forty-nine patients (72%) had disease relapse within 12 months after CRLMs resection but none of the analysed variables was independently associated with outcome. CONCLUSIONS: Clinical, radiological and molecular factors assessed before and after conversion chemotherapy do not reliably predict early recurrence after secondary resection of initially unresectable CRLMs. While novel markers are needed to optimize the cost/efficacy balance of surgical procedures, CRLM resection should be offered as soon as metastases become resectable during first-line chemotherapy to all patients eligible for surgery.
Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Hepatectomía/métodosRESUMEN
PURPOSE: We evaluated whether the addition of delayed phase imaging (DPI) gadobenate dimeglumine-enhanced MRI to dynamic postcontrast imaging improves the characterization of small hepatocellular carcinoma (HCC) and the differentiation between HCC, high grade dysplastic nodules (HGDN), and low grade dysplastic nodules (LGDN). METHODS: Twenty-five cirrhotic patients with 30 nodules (16 HCC, 8 HGDNs, and 6 LGDNs; maximum size of 3 cm) were included in this retrospective study. The diagnostic reference standard was histology. All the patients underwent MRI both prior to and following intravenous administration of gadobenate dimeglumine. The lesions were classified as hypointense, isointense, hyperintense on DPI for qualitative assessment. In the quantitative analysis the relative tumor-liver contrast to noise ratio (CNR) of the lesions on DPI was calculated. RESULTS: All HCCs were hypointense on DPI while only 8 (57.1%) of 14 DNs were hypointense and only 1 of 6 (16.6%) LGDNs was hypointense. There was a statistically significant difference in the hypointensity on DPI between HCCs and DNs (p = 0.003) in the qualitative analysis but not in the CNR values while there was a strong statistically significant difference in the hypointensity on DPI in the qualitative (p = 0.00001) and quantitative analysis (p < 0.05) between LGDNs and the group obtained by unifying HGDNs and HCCs. CONCLUSION: DPI is helpful in differentiating HCCs and HGDNs from LGDNs. Demonstration of hypointensity on DPI should raise the suspicion of HGDN or hypovascular HCC in the case of nodules with atypical dynamic pattern.
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Carcinoma Hepatocelular/diagnóstico , Cirrosis Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética/métodos , Anciano , Biopsia con Aguja Gruesa , Carcinoma Hepatocelular/patología , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Aumento de la Imagen , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Masculino , Meglumina/análogos & derivados , Persona de Mediana Edad , Compuestos OrganometálicosRESUMEN
We report a case of symptomatic massive liver echinococcosis due to Echinococcus granulosus, unexpectedly found in a 34 year old woman living in Apulia, Italy. Based on size (max diameter 18 cm), clinical presentation, geographical area, and natural history of echinococcosis, we estimate that the initial infection should have occurred 9-20 yrs before. Presenting symptoms were those of typical mass effect with RUQ pain, pruritus, malaise, and recent weight loss. Abdominal ultrasound diagnosis of probable echinococcal cyst was subsequentely confirmed by positive serology and further detailed by radiological imaging. The cyst was massively occupying subdiaphragmatic liver segments and extending to the omentum and the stomach. The characteristics of the lesion were compatible with the WHO 2003 classification type CE2l, indicating a large active fertile cyst with daughter cysts. The cyst was successfully treated with medical therapy followed by surgery. The prevalence, diagnostic workup, management, and costs of echinococcosis are discussed in this case presentation.
Asunto(s)
Equinococosis Hepática/diagnóstico , Hígado , Adulto , Equinococosis Hepática/parasitología , Equinococosis Hepática/patología , Equinococosis Hepática/terapia , Femenino , Interacciones Huésped-Parásitos , Humanos , Hígado/parasitología , Hígado/patología , Hígado/cirugía , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: This study was undertaken to evaluate the feasibility, safety and efficacy of a new combined single-step therapy in patients with unresectable multinodular unilobar hepatocellular carcinoma (HCC), with at least one lesion >3 cm, with balloon-occluded radiofrequency ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE) of the main lesion and TACE of the other lesions. The second purpose of our study was to compare the initial effects in terms of tumour necrosis of this new combined therapy with those obtained in a matched population treated with TACE alone in a singlestep treatment in our centre in the previous year. METHODS AND MATERIALS: This pilot study was approved by the institutional review board, and informed consent was obtained from all patients. Ten consecutive patients with multinodular (two to six nodules) unilobar unresectable HCC and with a main target lesion >3 cm (range, 3.5-6 cm) not suitable for curative therapy were enrolled in our single-centre multidisciplinary pilot study. The schedule consisted of percutaneous RFA (single 3-cm monopolar needle insertion) of the target lesion during occlusion of the hepatic artery supplying the tumour, followed by selective TACE, plus lobar TACE for other lesions (450-mg carboplatin and lipiodol plus temporary embolisation with SPONGOSTAN). Adverse events and intra- and periprocedural complications were clinically assessed. Early local efficacy was evaluated on 1-month follow-up multiphasic computed tomography (CT) on the basis of the Modified Response Evaluation Criteria in Solid Tumors (m-RECIST). A separate evaluation of target lesions in terms of enhancement, necrotic diameter and presence and distribution of lipiodol uptake was also performed. RESULTS: No major complications occurred. Overall technical success, defined as complete devascularisation of all nodules during the arterial phase, was achieved in seven of 10 patients, with three cases of partial response (persistence of small hypervascular nodules). When considering only target lesions, technical success was obtained in all patients, with a nonenhancing area corresponding in shape to the previously identified HCC (necrotic diameter, 3.5-5 cm) and with circumferential peripheral lipiodol uptake (safety margin) of at least 0.5 cm (0.5-1.3cm). CONCLUSIONS: TACE and BO-RFA, plus TACE in a singlestep approach seems to be a safe and effective combined therapy for treating advanced, unresectable HCC lesions, allowing a high rate of complete local response to be achieved in large lesions also.
Asunto(s)
Oclusión con Balón/métodos , Carcinoma Hepatocelular/terapia , Ablación por Catéter/métodos , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Anciano , Algoritmos , Profilaxis Antibiótica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Terapia Combinada , Aceite Etiodizado/administración & dosificación , Femenino , Esponja de Gelatina Absorbible/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Proyectos Piloto , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of this study is to find a contrast-enhanced CT-radiomic signature to predict clinical incomplete response in patients affected by hepatocellular carcinoma who underwent locoregional treatments. PATIENTS AND METHODS: 190 patients affected by hepatocellular carcinoma treated using focal therapies (radiofrequency or microwave ablation) from September 2018 to October 2020 were retrospectively enrolled. Treatment response was evaluated on a per-target-nodule basis on the 6-months follow-up contrast-enhanced CT or MR imaging using the mRECIST criteria. Radiomics analysis was performed using an in-house developed open-source R library. Wilcoxon-Mann-Whitney test was applied for univariate analysis; features with a p-value lower than 0.05 were selected. Pearson correlation was applied to discard highly correlated features (cut-off=0.9). The remaining features were included in a logistic regression model and receiver operating characteristic curves; sensitivity, specificity, positive and negative predictive value were also computed. The model was validated performing 2000 bootstrap resampling. RESULTS: 56 treated lesions from 42 patients were selected. Treatment responses were: complete response for 26 lesions (46.4%), 18 partial responses (32.1%), 10 stable diseases (17.9%), 2 progression diseases (3.6%). Area-Under-Curve value was 0.667 (95% CI: 0.527-0.806); accuracy, sensitivity, specificity, positive and negative predictive values were respectively 0.66, 0.85, 0.50, 0.59 and 0.79. CONCLUSIONS: This contrast-enhanced CT-based model can be helpful to early identify poor responder's hepatocellular carcinoma patients and personalize treatments.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).
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Embolización Terapéutica , Neoplasias Hepáticas , Acreditación , Embolización Terapéutica/métodos , Hepatectomía/métodos , Venas Hepáticas/patología , Hepatomegalia , Humanos , Hipertrofia/etiología , Hipertrofia/patología , Hipertrofia/cirugía , Hígado/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Estudios Multicéntricos como Asunto , Vena Porta/patología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
AIM: The properties of plasma cholinesterase (CHE) are partly undiscovered. Equally unknown are the correlations between changes in CHE and other blood variables during the acute phase response related to acute surgical and critical illness. METHODS: Data from 432 measurements of CHE and other variables performed in 92 patients were systematically evaluated and processed by regression analysis. RESULTS: There was a strong direct correlation between CHE and albumin (r=0.77, P<0.0001). CHE was also directly correlated to cholesterol, iron binding capacity, hematocrit, prothrombin activity, and inversely correlated to bilirubin and to presence of sepsis or liver dysfunction (P<0.0001 for all). Postoperatively CHE decreased to about 60% of the preoperative value, remaining directly related to it (r=0.69, P<0.0001), and decreasing further in the presence of sepsis or liver dysfunction, with slow reversal of the decrease during recovery from illness. In parenterally fed septic patients the decrease in CHE was moderated by increasing the amino acid dose (P<0.0001). CONCLUSION: In acute surgical and critical illness CHE mostly behaves as a negative acute phase reactant, independently of the modifications related to other already known factors. This should be taken into account when interpreting the implications of decreased CHE in the clinical setting.
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Reacción de Fase Aguda/sangre , Colinesterasas/sangre , Enfermedad Crítica , Insuficiencia Hepática/sangre , Adulto , Anciano , Bacteriemia/sangre , Infecciones Bacterianas/sangre , Biomarcadores/sangre , Colestasis/sangre , Colesterol/sangre , Femenino , Hematócrito , Hepatectomía , Humanos , Hierro/sangre , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Cuidados Preoperatorios , Estudios Prospectivos , Protrombina/metabolismo , Análisis de Regresión , Albúmina Sérica/metabolismoRESUMEN
OBJECTIVE: During pancreatic surgery for malignancies, hepatic revascularization is needed in case of en bloc resection with hepatic artery involvement. In these cases, the use of the splenic artery is described in the literature, including transposition and interposition techniques. PATIENTS AND METHODS: We report the case of pancreatic cancer resection with involvement of the right hepatic artery, anomalous arising from the superior mesenteric artery, and hepatic revascularization with splenic artery reconstruction. A literature review to analyze the use of splenic artery in hepatic revascularization during pancreatic cancer surgery was performed. RESULTS: A 61-year-old man with a 55-mm hypovascular tumor in the pancreatic head, in wide contact with the right hepatic artery, underwent total pancreatectomy and splenectomy. Right hepatic artery was resected, and the distal part of the splenic artery was transposed to the right hepatic artery with a termino-terminal anastomosis. Histopathological examination revealed R0 resection. CONCLUSIONS: Hepatic revascularization with splenic artery should be considered in patients suitable to extend resectability in pancreatic cancer surgery. A multidisciplinary approach and careful pre-operative planning are essential.
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Arteria Hepática/cirugía , Hígado/irrigación sanguínea , Hígado/cirugía , Neoplasias Pancreáticas/irrigación sanguínea , Neoplasias Pancreáticas/cirugía , Arteria Esplénica/cirugía , Humanos , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica , Procedimientos Quirúrgicos VascularesRESUMEN
Hilar cholangiocarcinoma (HC) is a rare tumor which has to be distinguished by intrahepatic cholagiocarcinoma invading hepatic hilum because the former has better prognosis then the latter. Patients with HC are difficult to manage because many challenging issues remain in the treatment of this tumour regarding correct diagnosis and therapeutic strategy. HC is resectable in about 30% of cases, but operative risk is highly influenced by septic complications of preoperative biliary drainage and by the need of major liver resection associated with biliary resection. We report the results of 43 resected patients (28 M/15 F; mean age 60 years, range 33-78), accounting for 29% of 149 patients with HC. Symptomless jaundice was the most common clinical presentation (87%; 130 patients). Biliary stricture was classified according to the Bismuth-Corlette classification as type 1 in 3 patients (7%); type 2 in 12 patients (28%); type 3 in 28 patients (65%). Ten patients underwent preoperative right portal vein embolization. Main biliary confluence excision associated with major hepatectomy was performed in 40 patients (93%), with R0 resection rate by 77%. Postoperative mortality rate was 6.9% (3 patients). Morbidity rate was 52.5% (21 patients), being biliary fistula (38%) and liver failure (19%) the most frequent complications. Five-year overall and disease-free survival rate were 36.1% and 28.2, respectively. Surgical resection remains the only chance of cure for patients with HC. However, due to the complexity of surgery immediate results remain unsatisfactory with morbidity and mortality rates higher than those reported after liver resection for other malignancies. This is mainly related to septic complications, strictly linked to complications of preoperative biliary drainage. Selective biliary drainage, careful management of biliary drains, drainage of excluded ducts in case of cholangitis, bile culture guided antibiotic use and preoperative portal vein embolization are important factors to reduce the risk of cholangitis and of postoperative complications. Because of the significant perioperative risk, the demanding operative management and the rarity of this tumor, patients with HC should be referred to tertiary surgical centers.
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Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/cirugía , Neoplasias Hepáticas/cirugía , Hígado/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/mortalidad , Colangiocarcinoma/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Hígado/patología , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Liver failure is the principal cause of death after hepatectomy. Its progression towards death and its relationship with sepsis are unclear. This study analysed predictors of mortality in patients with liver dysfunction and the role of sepsis in the death of these patients. METHODS: The study focused on patients with liver dysfunction, excluding those with vascular thrombosis, after liver resection at one of two centres between 1998 and 2006. RESULTS: Liver dysfunction occurred after 57 (4.5 per cent) of 1271 hepatectomies. Fifty-three patients without vascular thrombosis were included in the analysis, with a mortality rate of 23 per cent. Independent predictors of death were age (odds ratio (OR) 1.18 per year increase; P = 0.017), cirrhosis (OR 54.09; P = 0.004) and postoperative sepsis (OR 37.58; P = 0.005). Sepsis occurred in 15 patients (28 per cent), seven of whom died. Intestinal pathogens were isolated in 12 patients with sepsis. The risk of sepsis was significantly increased in those with surgical complications (11 of 16 versus four of 37; P < 0.001). CONCLUSION: Sepsis plays a key role in the death of patients with liver dysfunction after hepatectomy. Early recognition and aggressive treatment of sepsis may reduce mortality.
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Hepatectomía/mortalidad , Fallo Hepático/mortalidad , Complicaciones Posoperatorias/mortalidad , Sepsis/mortalidad , Adulto , Anciano , Diagnóstico Precoz , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/mortalidad , Fallo Hepático/diagnóstico , Fallo Hepático/etiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Estudios Retrospectivos , Sepsis/diagnóstico , Sepsis/etiología , Adulto JovenRESUMEN
BACKGROUND: "Cancer stem cells" (CSC) have been identified as a minority of cancer cells responsible for tumor initiation, maintenance and spreading. Although a universal marker for CSC has not yet been identified, CD133 has been proposed as the hallmark of CSC in colon cancer. The aim of our study was to assess the presence of a CD133+ cell fraction in samples of colon cancer and liver metastasis from colon cancer and evaluate their potential as tumor-initiating cells. METHODS: Tissue samples from 17 colon cancers and 8 liver metastasis were fragmented and digested using collagenase. Cell suspensions were characterized by flow cytometry using anti-CD133, CD45 and CD31 antibodies. CD133+ cells were also isolated by magnetic cell sorting and their tumor-initiating potential was assessed versus the remaining CD133- fraction by soft-agar assay. RESULTS: Our results confirmed the existence of a subset of CD133+ tumor cells within human colon cancers. Interestingly, CD133+ cells were detectable in liver metastasis at a higher percentage when compared to primary tumors. Soft-agar assay showed that CD133+ cell fraction was able to induce larger and more numerous colonies than CD133-cells. CONCLUSION: Our findings data that the CD133+ colon cancer cells might play an important role in both primary tumors as well as in metastatic lesions thus warranting further studies on the role(s) of this subset of cells in the metastatic process.
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Antígenos CD/metabolismo , Biomarcadores de Tumor/análisis , Neoplasias del Colon/patología , Glicoproteínas/metabolismo , Neoplasias Hepáticas/patología , Células Madre Neoplásicas/metabolismo , Péptidos/metabolismo , Antígeno AC133 , Anciano , Femenino , Citometría de Flujo , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Ensayo de Tumor de Célula MadreRESUMEN
OBJECTIVE: Interventional oncology (IO) is an emergent field in interventional radiology that can be considered the fourth pillar of oncology. Interventional oncology has the unique capability to treat malignancy in a loco-regional fashion enabling curative (percutaneous ablation), disease stabilization (intra-arterial chemo/radioembolization), and palliative treatment (such as biliary drainage or nephrostomy). The whole arsenal of IO acts by inducing necrosis and apoptosis, with interactions with the tumour's microenvironment potentially crucial for oncological outcomes. Considering that tumour's microenvironment is a pivotal target for both immuno-oncology and interventional-oncology, the interactions between these two anti-tumour weapons must be investigated to understand their synergy. Interestingly, substantial efforts have been directed to understand which technique combinations are best for specific tumours. This review article summarizes the latest scientific evidence highlighting the future prospective of this winning combination, integrating evidence-reported literature and experience-based perceptions.
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Técnicas de Ablación/métodos , Antineoplásicos Inmunológicos/administración & dosificación , Oncología Médica/métodos , Neoplasias/terapia , Radiología Intervencionista/métodos , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Ensayos Clínicos como Asunto , Humanos , Oncología Médica/tendencias , Neoplasias/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología , Supervivencia sin Progresión , Radiología Intervencionista/tendencias , Resultado del Tratamiento , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de la radiaciónRESUMEN
OBJECTIVE: To evaluate the performance of major features, ancillary features, and categories of Liver Imaging Reporting and Data System (LI-RADS) version 2018 at magnetic resonance (MR) imaging in the differentiation of small hepatocellular carcinoma (HCC) from dysplastic nodules (DNs). PATIENTS AND METHODS: This retrospective study included cirrhotic patients with pathologically proven untreated HCCs and DNs (≤ 2 cm) and liver MR imaging performed with gadobenate dimeglumine contrast agent within 3 months before pathological analysis, between 2015 and 2018. 37 patients with 43 observations (17 HCCs and 26 DNs) met the inclusion criteria. Two radiologists assessed major and ancillary imaging features for each liver observation and assigned a LI-RADS v2018 category in consensus. Estimates of diagnostic performance of major features, ancillary features, and LI-RADS categories were assessed based on their sensitivity, specificity, positive (PPV), and negative predictive values (NPV). RESULTS: Major features (nonrim arterial phase hyperenhancement, nonperipheral "washout", and enhancing "capsule") had a sensitivity of 94.1%, 88.2%, and 41.2%, and a specificity of 57.7%, 42.3%, and 88.5% for HCC, respectively. Ancillary features (hepatobiliary phase hypointensity, mild-moderate T2 hyperintensity, restricted diffusion, and fat in the lesion more than adjacent liver) had a sensitivity of 94.1%, 64.7%, 58.8%, and 11.8%, and a specificity of 26.9%, 61.5%, 65.4%, and 76.9% for HCC, respectively. The LR-5 category (determined by using major features only vs. the combination of major and ancillary features) had a sensitivity of 88.2% at both evaluations and a specificity of 76.9% and 80.8% for HCC, respectively. The combination of LR-4, LR-5 categories (determined by using major features only vs. the combination of major and ancillary features) had a sensitivity of 94.1% at both interpretations and a specificity of 65.4% and 26.9% for HCC, respectively. The use of ancillary features modified LI-RADS category in 25.6% of observations (11/43), predominantly upgraded from LR-3 to LR4 (10/11), increasing the proportion of low-grade DNs and high-grade DNs categorized as LR-4 (from 15.4% to 61.5% and from 7.7% to 46.1%, respectively). CONCLUSIONS: The added value of ancillary features in combination with major features is limited for the non-invasive diagnosis of small HCC; however, their use modifies the final category in a substantial proportion of observations from LR-3 to LR-4, thus allowing possible changes in the management of patients at risk for HCC.
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Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Meglumina/análogos & derivados , Compuestos Organometálicos/metabolismo , Anciano , Diferenciación Celular , Consenso , Femenino , Humanos , Masculino , Meglumina/administración & dosificación , Meglumina/metabolismo , Persona de Mediana Edad , Compuestos Organometálicos/administración & dosificación , Valor Predictivo de las Pruebas , Radiólogos/estadística & datos numéricos , Cintigrafía/métodos , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0-2.5 µM) of OCA were added to culture media and, after 3-10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 µM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients.
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Neoplasias de los Conductos Biliares/prevención & control , Ácido Quenodesoxicólico/análogos & derivados , Colangiocarcinoma/prevención & control , Receptores Citoplasmáticos y Nucleares/agonistas , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Ácido Quenodesoxicólico/farmacología , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Receptores Citoplasmáticos y Nucleares/genética , Células Tumorales CultivadasRESUMEN
Percutaneous liver ablation has become a cornerstone of the recently developed subspecialty of radiology - that is, interventional oncology. Thermal ablation technology has evolved rapidly during the past decades, with substantial technical and procedural improvements that can help obtain better clinical outcomes and safety profiles. Due to the widespread use of percutaneous ablation, a comprehensive review of the methodologic and technical considerations seems to be mandatory. This article summarizes the expert discussion and report from Mediterranean Interventional Oncology Live Congress (MIOLive 2017) that was held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions, to assist not only residents and fellows who are training in interventional radiology but also practicing colleagues who are approaching to this locoregional treatment.