Impact of risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy of space-occupying lesions.

INTRODUCTION: Ultrasound-guided percutaneous liver biopsy is considered the technique of choice for the histological diagnosis of space-occupying lesions, given its high level of safety and diagnostic performance. However, since it is an invasive diagnostic procedure, complications can occur. Various clinical and radiological parameters have been analysed as factors related with the efficacy of the technique or with its complications; however, the results have been contradictory. Thus, we aimed to evaluate the impact of various risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy in the diagnosis of space-occupying lesions in ordinary clinical practice. MATERIAL AND METHODS: This retrospective observational study included all patients who underwent real-time ultrasound-guided percutaneous biopsies of space-occupying liver lesions with the free-hand technique between December 2012 and February 2018 in the diagnostic imaging department at the Hospital Clínico Universitario de Santiago de Compostela. We analysed the following risk factors: location of the lesion in upper liver segments (II, IVa, VII, or VIII); proximity to the liver capsule, distance from the skin >100mm, interposition of osseus or vascular structures, inability to go through healthy parenchyma, and lack of patient cooperation during the procedure. Efficacy was analysed in terms of the number of cylinders obtained and the percentage of adequate biopsies; safety was analysed in terms of the percentage of complications, which were classified as major or minor. RESULTS: We included 295 biopsies in 278 patients (median age, 69 years; 64.1% male; 44.7% had prior neoplasms). In 61.4%, the biopsy was indicated for the initial diagnosis; 82.4% of biopsies were done in hospitalised patients, and 65% of the lesions were located in the right liver lobe. The median number of cylinders obtained was 3 (range 1-6); 91.2% of the biopsies were adequate and 92.2% were considered clinically useful. These percentages did not differ significantly according to the presence of risk factors. Complications occurred in 10 (3.4%) patients. Complications were considered major in 3 (0.9%) patients (2 (0.6%) bleeding complications and 1 (0.3%) infectious complication) and minor in 7 (2.4%). The percentage of complications was significantly higher in patients who did not cooperate during the procedure (P=.04). CONCLUSIONS: Ultrasound-guided percutaneous liver biopsy is an efficacious and safe technique for the histological diagnosis of space-occupying liver lesions. Our results confirm the increased rate of complications when patients fail to cooperate during the procedure.

Impacto de los factores de riesgo en la eficacia y complicaciones de la biopsia hepática percutánea ecoguiada de lesiones ocupantes de espacio / Impact of risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy of space-occupying lesions

Introducción: La biopsia hepática percutánea ecoguiada se considera la técnica de elección para el diagnóstico histológico de las lesiones ocupantes de espacio (LOE), dada su elevada seguridad y rentabilidad diagnóstica. Sin embargo, al tratarse de una técnica de diagnóstico invasiva, no se encuentra exenta de complicaciones. Diversos parámetros clínico-radiológicos han sido analizados como factores relacionados con la eficacia o complicaciones, con resultados contradictorios. Por todo ello, el objetivo de nuestro estudio es evaluar el impacto de diversos factores de riesgo en la eficacia y complicaciones de la biopsia hepática percutánea ecoguiada en el diagnóstico de LOE, en el ámbito de la práctica clínica habitual. Material y métodos: Llevamos a cabo un estudio observacional, retrospectivo, unicéntrico de pacientes sometidos a biopsia hepática percutánea ecoguiada en tiempo real con técnica de manos libres para el diagnóstico de LOE, realizadas en el Servicio de Radiodiagnóstico del Hospital Clínico Universitario de Santiago de Compostela entre diciembre 2012 y febrero 2018. Seleccionamos como factores de riesgo: la localización de la LOE en los segmentos hepáticos superiores (II, IVa, VII y VIII), la proximidad a la cápsula hepática, la distancia entre piel y LOE mayor de 100mm, la interposición de estructuras óseas o vasculares, la incapacidad para atravesar parénquima sano o la falta de colaboración del paciente durante el procedimiento. La eficacia fue analizada en términos de número de cilindros extraídos y porcentaje de biopsias satisfactorias; y la seguridad, en términos de porcentaje de complicaciones presentadas, clasificándolas, a su vez, en complicaciones mayores y menores. Resultados: Se incluyeron 295 biopsias de 278 pacientes. La mediana de edad fue de 69 años, el 64,1% eran varones y el 44,7% tenía una neoplasia previa.(AU)

Introduction: Ultrasound-guided percutaneous liver biopsy is considered the technique of choice for the histological diagnosis of space-occupying lesions, given its high level of safety and diagnostic performance. However, since it is an invasive diagnostic procedure, complications can occur. Various clinical and radiological parameters have been analyzed as factors related with the efficacy of the technique or with its complications; however, the results have been contradictory. Thus, we aimed to evaluate the impact of various risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy in the diagnosis of space-occupying lesions in ordinary clinical practice. Material and methods: This retrospective observational study included all patients who underwent real-time ultrasound-guided percutaneous biopsies of space-occupying liver lesions with the free-hand technique between December 2012 and February 2018 in the diagnostic imaging department at the Hospital Clínico Universitario de Santiago de Compostela. We analyzed the following risk factors: location of the lesion in upper liver segments (II, IVa, VII, or VIII); proximity to the liver capsule, distance from the skin > 100mm, interposition of osseus or vascular structures, inability to go through healthy parenchyma, and lack of patient cooperation during the procedure. Efficacy was analyzed in terms of the number of cylinders obtained and the percentage of adequate biopsies; safety was analyzed in terms of the percentage of complications, which were classified as major or minor. Results: We included 295 biopsies in 278 patients (median age, 69 years; 64.1% male; 44.7% had prior neoplasms). In 61.4%, the biopsy was indicated for the initial diagnosis; 82.4% of biopsies were done in hospitalized patients, and 65% of the lesions were located in the right liver lobe.(AU)

Phase I, first-in-human study of MSC-1 (AZD0171), a humanized anti-leukemia inhibitory factor monoclonal antibody, for advanced solid tumors.

BACKGROUND: Activation of leukemia inhibitory factor (LIF) is linked to an immunosuppressive tumor microenvironment (TME), with a strong association between LIF expression and tumor-associated macrophages (TAMs). MSC-1 (AZD0171) is a humanized monoclonal antibody that binds with high affinity to LIF, promoting antitumor inflammation through TAM modulation and cancer stem cell inhibition, slowing tumor growth. In this phase I, first-in-human, open-label, dose-escalation study, MSC-1 monotherapy was assessed in patients with advanced, unresectable solid tumors. MATERIALS AND METHODS: Using accelerated-titration dose escalation followed by a 3 + 3 design, MSC-1 doses of 75-1500 mg were administered intravenously every 3 weeks (Q3W) until progression or unmanageable toxicity. Additional patients were enrolled in selected cohorts to further evaluate safety, pharmacokinetics (PK), and pharmacodynamics after escalation to the next dose had been approved. The primary objective was characterizing safety and determining the recommended phase II dose (RP2D). Evaluating antitumor activity and progression-free survival (PFS) by RECIST v1.1, PK and immunogenicity were secondary objectives. Exploratory objectives included pharmacodynamic effects on circulating LIF and TME immune markers. RESULTS: Forty-one patients received treatment. MSC-1 monotherapy was safe and well tolerated at all doses, with no dose-limiting toxicities. The maximum tolerated dose was not reached and the RP2D was determined to be 1500 mg Q3W. Almost half of the patients had treatment-related adverse events (TRAEs), with no apparent trends across doses; no patients withdrew due to TRAEs. There were no objective responses; 23.7% had stable disease for ≥2 consecutive tumor assessments. Median PFS was 5.9 weeks; 23.7% had PFS >16 weeks. On-treatment changes in circulating LIF and TME signal transducers and activators of transcription 3 signaling, M1:M2 macrophage populations, and CD8+ T-cell infiltration were consistent with the hypothesized mechanism of action. CONCLUSIONS: MSC-1 was very well tolerated across doses, with prolonged PFS in some patients. Biomarker and preclinical data suggest potential synergy with checkpoint inhibitors.

Impact of risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy of space-occupying lesions. / Impacto de los factores de riesgo en la eficacia y complicaciones de la biopsia hepática percutánea ecoguiada de lesiones ocupantes de espacio.

INTRODUCTION: Ultrasound-guided percutaneous liver biopsy is considered the technique of choice for the histological diagnosis of space-occupying lesions, given its high level of safety and diagnostic performance. However, since it is an invasive diagnostic procedure, complications can occur. Various clinical and radiological parameters have been analyzed as factors related with the efficacy of the technique or with its complications; however, the results have been contradictory. Thus, we aimed to evaluate the impact of various risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy in the diagnosis of space-occupying lesions in ordinary clinical practice. MATERIAL AND METHODS: This retrospective observational study included all patients who underwent real-time ultrasound-guided percutaneous biopsies of space-occupying liver lesions with the free-hand technique between December 2012 and February 2018 in the diagnostic imaging department at the Hospital Clínico Universitario de Santiago de Compostela. We analyzed the following risk factors: location of the lesion in upper liver segments (II, IVa, VII, or VIII); proximity to the liver capsule, distance from the skin > 100mm, interposition of osseus or vascular structures, inability to go through healthy parenchyma, and lack of patient cooperation during the procedure. Efficacy was analyzed in terms of the number of cylinders obtained and the percentage of adequate biopsies; safety was analyzed in terms of the percentage of complications, which were classified as major or minor. RESULTS: We included 295 biopsies in 278 patients (median age, 69 years; 64.1% male; 44.7% had prior neoplasms). In 61.4%, the biopsy was indicated for the initial diagnosis; 82.4% of biopsies were done in hospitalized patients, and 65% of the lesions were located in the right liver lobe. The median number of cylinders obtained was 3 (range 1-6); 91.2% of the biopsies were adequate and 92.2% were considered clinically useful. These percentages did not differ significantly according to the presence of risk factors. Complications occurred in 10 (3.4%) patients. Complications were considered major in 3 (0.9%) patients (2 (0.6%) bleeding complications and 1 (0.3%) infectious complication) and minor in 7 (2.4%). The percentage of complications was significantly higher in patients who did not cooperate during the procedure (p=0.04). CONCLUSIONS: Ultrasound-guided percutaneous liver biopsy is an efficacious and safe technique for the histological diagnosis of space-occupying liver lesions. Our results confirm the increased rate of complications when patients fail to cooperate during the procedure.

Adjuvant treatment with infusional 5-fluorouracil in high risk adenocarcinoma of the stomach or gastroesophageal junction

Purpose. In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5-fluorouracil continuous infusion scheme. Methods. We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m2 iv with leucovorin 200 mg/m2 iv and 1200 mg/m2 in 46-hour infusion of 5-fluorouracil (D’Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5-fluorouracil continuously infusion 225 mg/m2/day and four additional infusions of chemotherapy one month after complete radiochemotherapy. Results. Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3–102.1 months), and the 3-year survival rates were 52.7 %. Conclusions. This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results (AU)

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Adjuvant treatment with infusional 5-fluorouracil in high risk adenocarcinoma of the stomach or gastroesophageal junction.

PURPOSE: In high risk gastric and gastroesophageal adenocarcinoma, adjuvant radiochemotherapy with 5-fluorouracil bolus became a standard adjuvant treatment, showing significant improvement in overall survival after surgery, although with substantial toxicity. We explored the efficacy and toxicity of a modified 5-fluorouracil continuous infusion scheme. METHODS: We conducted an observational retrospective study in our centre. Gastric/gastroesophageal junction adenocarcinoma patients were treated with a schedule consisting in four infusions of bolus 5-fluorouracil 400 mg/m(2) iv with leucovorin 200 mg/m(2) iv and 1200 mg/m(2) in 46-hour infusion of 5-fluorouracil (D'Gramont scheme), followed by concomitant radiochemotherapy (45 Gy in 25 fractions of 1.8 Gy) with 5-fluorouracil continuously infusion 225 mg/m(2)/day and four additional infusions of chemotherapy one month after complete radiochemotherapy. RESULTS: Between January 2007 and December 2013, 55 patients received a mean of 3.16 bi-weekly adjuvant infusions followed by 4.6 weeks of continuous treatment concurrent with radiotherapy and 3.72 bi-weekly infusions after radiotherapy treatment. During adjuvant treatment, grade III toxicity was mostly haematologic, while gastrointestinal and cutaneous toxicity was predominant during concurrent treatment. There were no grade IV- or treatment-related deaths during this study. Disease-free survival (DFS) was 79.2 months (56.3-102.1 months), and the 3-year survival rates were 52.7 %. CONCLUSIONS: This 5-fluorouracil infusional scheme has an excellent tolerability profile and favourable efficacy results.