RESUMEN
Background: Severe aortic stenosis (AS) causes acquired von Willebrand syndrome by the excessive shear stress-dependent cleavage of high molecular weight multimers of von Willebrand factor (VWF). While the current standard diagnostic method is so-called VWF multimer analysis that is western blotting under nonreducing conditions, it remains unclear whether a ratio of VWF Ristocetin co-factor activity (VWF:RCo) to VWF antigen levels (VWF:Ag) of <0.7, which can be measured with an automated coagulation analyzer in clinical laboratories and is used for the diagnosis of hereditary von Willebrand disease. Objectives: To evaluated whether the VWF:RCo/VWF:Ag is useful for the diagnosis of AS-induced acquired von Willebrand syndrome. Methods: VWF:RCo and VWF:Ag were evaluated with the VWF large multimer index as a reference, which represents the percentage of a patient's VWF high molecular weight multimer ratio to that of standard plasma in the VWF multimer analysis. Results: We analyzed 382 patients with AS having transaortic valve maximal pressure gradients of >30 mmHg, 27 patients with peripheral artery disease, and 46 control patients free of cardiovascular disease with osteoarthritis, diabetes, and so on. We assumed a large multimer index of <80% as loss of VWF large multimers since 59.0% of patients with severe AS had the indices of <80%, while no control patients or patients with peripheral artery disease, except for 2 patients, exhibited the indices of <80%. The VWF:RCo/VWF:Ag ratios, measured using an automated blood coagulation analyzer, were correlated with the indices (rs = 0.470, P < .001). When the ratio of <0.7 was used as a cut-off point, the sensitivity and specificity to VWF large multimer indices of <80% were 0.437 and 0.826, respectively. Conclusion: VWF:RCo/VWF:Ag ratios of <0.7 may indicate loss of VWF large multimers with high specificity, but low sensitivity. VWF:RCo/VWF:Ag ratios in patients with AS having a ratio of <0.7 may be useful for monitoring the loss of VWF large multimers during their clinical courses.
RESUMEN
BACKGROUND: Interactions between adipocyte and breast cancer (BC) cells have yet to be fully elucidated. Here we investigated the prognostic impact of marginal adipose tissue invasion in both luminal breast cancer (HR+/HER2-) and triple-negative breast cancer (TNBC) (HR-/HER2-). METHODS: A total of 735 patients with early-stage invasive BC (1999-2014) were retrospectively registered. Median length of patient follow-up was 8.9 years. Survival curves were calculated using a Kaplan-Meier cumulative survival plot. The prognostic difference between two groups were assessed by the univariate Cox-proportional hazard regression model. RESULTS: Patients with adipose tissue invasion (n = 614) had a significantly poorer prognosis than those without adipose tissue invasion (n = 121) in overall survival (OS) (hazard ratio, 2.1; 95% Confidence interval [CI], 1.1 to 4.0; P = 0.025). While a poorer prognosis was observed in TNBC (n = 137) than in luminal BC patients (n = 496) (hazard ratio, 0.45; 95% CI, 0.30 to 0.68, P < 0.001), this aggressive nature of TNBC was noted in node-positive disease (hazard ratio, 0.3; 95% CI, 0.18 to 0.5, P < 0.001) but not in node-negative disease (hazard ratio, 0.78; 95% CI, 0.39 to 1.55, P = 0.472), and also noted in adipose tissue invasion-positive patients (hazard ratio, 0.4; 95% CI, 0.26 to 0.6, P < 0.001) but not in adipose tissue invasion-negative patients (hazard ratio, 0.73; 95% CI, 0.16 to 3.24, P = 0.675). In addition, although patients suffering from TNBC with adipose tissue invasion had a poorer outcome than those without adipose tissue invasion (hazard ratio, 3.63; 95% CI, 1.11 to 11.84; P = 0.033), the difference was not observed in luminal BC (hazard ratio, 1.75; 95% CI, 0.64 to 4.82; P = 0.277). CONCLUSIONS: Adipose tissue invasion was correlated with poor survival in TNBC. Cancer cell invasion into local fat may be a first step on cancer progression and systemic disease in TNBC.
Asunto(s)
Tejido Adiposo/patología , Neoplasias de la Mama Triple Negativas/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Comunicación Celular , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/etiología , Neoplasias de la Mama Triple Negativas/mortalidad , Neoplasias de la Mama Triple Negativas/terapia , Microambiente TumoralRESUMEN
BACKGROUND: Microvascular invasion (MVI) is recognized as a risk factor for early recurrence of hepatocellular carcinoma (HCC) within the Milan criteria after curative treatment. METHODS: One hundred eleven consecutive patients with HCC within the Milan criteria who underwent hepatic resection were retrospectively reviewed. Independent preoperative predictors of MVI were identified, and a scoring system was developed using significant predictors. RESULTS: MVI was identified in 51 of 111 patients (46%). Multivariate analysis identified the following independent predictors of MVI: alpha-fetoprotein (AFP) of > 95 ng/mL (odds ratio [OR], 9.87; 95% confidence interval [95% CI], 2.24-56.8; P = 0.002), des-γ-carboxy prothrombin (DCP) of > 55 mAU/mL (OR, 5.50; 95% CI, 2.09-15.4; P < 0.001), tumor size of > 2.8 cm (OR, 6.10; 95% CI, 2.07-20.0; P < 0.001), and non-smooth tumor margin in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) (OR, 5.34; 95% CI, 1.84-16.9; P = 0.002). A clinical scoring system was developed using these four variables. Within a total possible score of 0 to 4, the prevalence of MVI with a score of 0, 1, 2, 3, and 4 was 4.5%, 24.0%, 45.5%, 91.7%, and 100%, respectively (P < 0.001). The area under the curve of the scoring system was 0.865 based on the receiver operating characteristic curve analysis of the prediction score. CONCLUSIONS: Our clinical scoring system, consisting of AFP, DCP, tumor size, and tumor margin in Gd-EOB-DTPA-enhanced MRI, can be valuable for predicting MVI in HCC within the Milan criteria before curative treatment.
Asunto(s)
Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Microvasos/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirugía , Medios de Contraste , Femenino , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , Curva ROC , Estudios Retrospectivos , Carga Tumoral , alfa-Fetoproteínas/metabolismoRESUMEN
BACKGROUND: Indications and efficacy of surgical treatment for liver metastases from gastric cancer (LMGCs) remain controversial. This retrospective study was designed to clarify the benefits of surgical treatment and identify prognostic factors. METHODS: Between December 1997 and December 2015, 34 consecutive patients underwent hepatic resection and surgical microwave ablation for synchronous or metachronous LMGCs at our institution. We analyzed their cumulative overall survival (OS) and recurrence-free survival (RFS) rates and clinical parameters to identify predictors of prognosis. RESULTS: Of the 34 patients, 14 underwent hepatic resection, 13 underwent surgical microwave ablation, and 7 underwent hepatic resection combined with surgical microwave ablation. Their OS rates were 1-year: 84.4%, 3-year: 38.6%, and 5-year: 34.7%; and their RFS rates were 1-year: 38.5%, 3-year: 28.0%, and 5-year: 28.0%. OS did not significantly vary among the surgical procedures. In multivariable analysis, positive of both CEA and CA19-9 were independent predictors of poor survival (hazard ratio [HR] 4.51; P = 0.049) and early recurrence (HR 5.70; P = 0.047). CONCLUSIONS: Both hepatic resection and surgical microwave ablation for LMGCs are effective and can improve survival in selected patients.
Asunto(s)
Técnicas de Ablación/métodos , Hepatectomía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Microondas/uso terapéutico , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: Some patients experience very late recurrence of HCC more than 5 years after initial therapy. We aimed to clarify the predictive factors for very late recurrence of HCC in such cases. METHODS: Among 807 HCC patients undergoing surgical resection or ablative therapy with curative intent, the patients who survived for 5 years without any recurrence were reviewed. The prognosis and possible predictive factors for late recurrence were analyzed retrospectively. RESULTS: A total of 184 patients survived for more than 5 years without recurrence. Among them, 61 patients experienced recurrence, at a median of 6 years after initial therapy. In univariate analysis, the pre-treatment aspartate aminotransferase, alanine aminotransferase, Child-Pugh class, and ALBI grade were not related to recurrence, but those at 5 years after treatment were significantly related to recurrence. By multivariate analysis, an ALBI grade of 2-3 at 5 years was an independent risk factor for recurrence (P < 0.0001). Moreover, variation of the ALBI grade over the 5 years after the initial treatment was significantly related to recurrence-free survival. CONCLUSIONS: The ALBI grade is an effective index of the variation in liver function after curative therapy and may be a useful prognostic factor for the long-term recurrence-free survival of HCC patients.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Estadificación de Neoplasias/métodos , Anciano , Carcinoma Hepatocelular/diagnóstico , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico , Imagen por Resonancia Magnética , Masculino , Recurrencia Local de Neoplasia , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND AIM: The effects of achieving sustained virological response (SVR) on recurrence and survival after curative treatment in patients with hepatitis virus C (HCV)-related hepatocellular carcinoma (HCC) is unclear. This study examined the influence of SVR achievement by interferon therapy before HCC occurrence on recurrence and survival. METHODS: This retrospective study included 518 patients who underwent surgical microwave ablation for initial HCV-related HCC between January 2001 and December 2015. Thirty-four patients had achieved SVR (SVR group) and 484 patients had not (control group). Clinical characteristics and long-term outcomes were compared between the two groups. RESULTS: Overall survival rates at 5 and 10 years after curative ablation were 95.8 and 80.4% in the SVR group, and 50.7 and 23.4% in the control, respectively (p < 0.0001). Recurrence-free survival rates at 5 and 10 years were 68.7 and 26.4% in the SVR group, and 24.5 and 7.8% in the control group, respectively (p < 0.0001). Multivariate analyses revealed that achieving SVR as an independent prognostic factor for both overall and recurrence-free survival. In the SVR group, the 5-year recurrence-free survival rates for patients with an interval of 5 years or fewer (n = 24) vs. more than 5 years (n = 10) between achieving SVR and curative ablation were 58.7 and 88.9%, respectively (p = 0.03). CONCLUSIONS: Achieving SVR before HCC occurrence allowed a favorable clinical outcome after curative ablation in HCV-related HCC patients. Patients with HCC that occurred more than 5 years after achieving SVR had longer recurrence-free survival.
Asunto(s)
Antivirales/uso terapéutico , Carcinoma Hepatocelular/cirugía , Ablación por Catéter/métodos , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Femenino , Hepatitis C Crónica/mortalidad , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Masculino , Microondas/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Recurrencia , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
Objective Sorafenib is a standard therapy for advanced hepatocellular carcinoma (HCC), whereas radiotherapy is effective for local control of extrahepatic spread (EHS) or macrovascular invasion (MVI). This study investigated the safety and efficacy of this combined therapy to treat advanced HCC. Methods This retrospective study reviewed 62 patients with advanced-stage HCC with EHS or MVI who received sorafenib therapy, excluding the patients with only lung metastases. Results Of the 62 patients, 15 were treated using the combined therapy of sorafenib and radiotherapy (group RS), and 47 were treated with sorafenib monotherapy (group S). In group RS, patients were treated using three-dimensional conformal radiotherapy with a total irradiation dose of 30-60 Gy (median, 50 Gy). Irradiation was targeted at the bone, lymph nodes, adrenal gland, and MVI in 6, 5, 1, and 4 patients, respectively. The overall incidence of adverse events was 93.3% in group RS and 91.5% in group S (p=N.S.). Incidences of thrombocytopenia, leukopenia, and skin reaction were significantly higher in group RS (73.3%, 40.0%, and 66.7%, respectively) than in group S (36.2%, 10.6%, and 27.7%, respectively, p=0.02, 0.02, and <0.01, respectively). The incidence of severe adverse events, however, was comparable in the 2 groups: 20% in group RS and 19.2% in group S. The median progression-free survival (PFS) of EHS or MVI, PFS of whole lesions, and overall survival were longer in group RS (13.5, 10.6, and 31.2 months, respectively) than in group S (3.3, 3.5, and 12.1 months, respectively) (p<0.01 for all). Conclusion Sorafenib in combination with radiotherapy is a feasible and tolerable treatment option for advanced HCC.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Radioterapia Conformacional , Anciano , Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Dosis de Radiación , Radioterapia Conformacional/efectos adversos , Estudios Retrospectivos , Sorafenib , Análisis de SupervivenciaRESUMEN
The prognostic implications of the expression patterns of three tumor markers, alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxy prothrombin (DCP), have been evaluated in patients with hepatocellular carcinoma (HCC). From January 1994 to December 2014, 1182 consecutive patients underwent hepatic resection and surgical microwave ablation for HCC at our institution. This study analyzed 475 patients within the Milan criteria and Child-Pugh class A. Cumulative overall survival (OS) and disease-free survival (DFS) rates were analyzed relative to the number of positive tumor markers. OS and DFS at 5 years postoperatively were 85.3 and 44.2% in triple-negative patients, 79.4 and 48.0% in single-positive patients, 56.2 and 32.9% in double-positive patients, and 61.7 and 35.7% in triple-positive patients with statistical significance. OS in triple-negative or single-positive patients was 85.3%, and that in all double- or triple-positive patients was 58.0% (P < 0.0001); DFS at 5 years postoperatively in these two groups was 45.9 and 34.0%, respectively (P < 0.0013). Both double- and triple-positive tumor markers are associated with early recurrence and poor survival in HCC patients within the Milan criteria and Child-Pugh class A.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Hepatectomía , Neoplasias Hepáticas/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/mortalidad , Lectinas de Plantas/metabolismo , Pronóstico , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , Estudios Retrospectivos , Análisis de Supervivencia , alfa-Fetoproteínas/metabolismoRESUMEN
PURPOSE: To establish the efficacy and safety of simultaneous microwave coagulo-necrotic therapy (MCN) and laparoscopic splenectomy (Lap-Sp) for the treatment of hepatocellular carcinoma (HCC) with cirrhotic hypersplenism. METHODS: Seventeen patients with HCC and cirrhotic hypersplenism underwent simultaneous MCN and Lap-Sp at our institution between January, 2010 and July, 2015. Eight and nine patients had Child-Pugh class A and B liver cirrhosis, respectively. The median number of tumors ablated was 1 (range 1-7) and the median largest dimension of the resected lesions was 1.7 cm (range 1.1-3.6 cm). We analyzed postoperative complications and long-term outcomes retrospectively. RESULTS: The median operating time was 283 min (range 197-418 min) and the median blood loss was 125 mL (range 5-1312 mL). Postoperative morbidity and mortality rates were 29 and 0 %, respectively. The median follow-up time after surgery was 22.5 months (range 4.3-70.9 months). The 1-, 3-, and 5-year disease-free survival rates were 68.8, 10.7, and 10.7 %, respectively, and the 1-, 3-, and 5-year overall survival rates were 88.2, 75.6, and 63.0 %, respectively. CONCLUSIONS: The findings of this study suggest that simultaneous MCN and Lap-Sp is safe and effective for treating HCC with cirrhotic hypersplenism.
Asunto(s)
Técnicas de Ablación/métodos , Carcinoma Hepatocelular/cirugía , Electrocoagulación/métodos , Hiperesplenismo/cirugía , Laparoscopía/métodos , Neoplasias Hepáticas/cirugía , Esplenectomía/métodos , Anciano , Carcinoma Hepatocelular/complicaciones , Femenino , Hepatectomía , Humanos , Hiperesplenismo/complicaciones , Neoplasias Hepáticas/complicaciones , Masculino , Microondas , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Five or more colorectal liver metastases (CRLM) are considered marginally resectable and cannot be treated solely by hepatic resection (Hr). This study investigated the long-term effectiveness of surgical treatment using microwave coagulo-necrotic therapy (MCN) and/or Hr for marginally resectable or unresectable multiple CRLM. METHODS: This study retrospectively analyzed 82 consecutive CRLM patients with ≥5 CRLM who underwent MCN, Hr, or both, at our institution from 1994 to 2012. Presuming all CRLM were resected curatively, virtual remnant liver volume was calculated using preoperative computed tomography or magnetic resonance imaging. Virtual remnant liver volume <30% was defined as unresectable. Patients were divided into marginally resectable (Group Y; n=29) and unresectable (Group N; n=53). Overall and recurrence-free survival were assessed. RESULTS: Mean maximum tumor diameter and tumor number were 3.1 and 6.0 cm in Group Y and 3.3 and 11.3 cm in Group N. Surgical methods included MCN (n=16), MCN+Hr (n=9), and Hr (n=4) in Group Y, and MCN (n=28) and MCN+Hr (n=25) in Group N. One- and 2-year recurrence-free survival rates were 38.0% and 22.8% in Group Y, and 18.9% and 3.8% in Group N (P=0.01). However, 1-, 3-, and 5-year overall survival rates of Group N (86.8%, 44.6%, and 33.7%, respectively) were similar to those of Group Y (82.8%, 51.4%, and 33.3%, respectively; P= not significant each). CONCLUSION: MCN may improve survival for patients with unresectable multiple CRLM, similar to that in patients with marginally resectable multiple CRLM.
RESUMEN
BACKGROUND: Because the recurrence rate of hepatocellular carcinoma (HCC) is high, even after curative treatments such as hepatic resection and microwave ablation, chemopreventive agents that can effectively suppress HCC recurrence are required. Cyclooxygenase-2 (Cox-2) was recently found to be overexpressed in HCC. Therefore, Cox-2 inhibitors may offer a chemopreventive therapy for HCC. This randomised controlled trial (RCT) investigated the potential for meloxicam, a clinically used Cox-2 inhibitor, to prevent HCC recurrence after initial curative treatment. METHODS: A total of 232 consecutive patients underwent hepatic resection and/or microwave ablation as initial therapy for HCC at our institute between July 2008 and April 2011. Eight patients were excluded because of poor renal function, history of non-steroidal anti-inflammatory drug-related ulceration, or multiple cancers. The remaining 224 patients were randomised to a control group (n = 113) or a meloxicam group (n = 111). To patients in the meloxicam group, meloxicam was administered at 15 mg daily (5 mg three times a day) as long as possible. The overall survival (OS) and disease-free survival (DFS) rates were determined. RESULTS: The 1-, 3-, and 5-year OS rates of the meloxicam group were 95.4, 82.4, and 70.1 %, respectively. Those of the control group were 98.2, 85.1, and 71.5 %, respectively (p = 0.9549). The corresponding DFS rates of the meloxicam group were 89.2, 53.9, and 44.0 % and those of control group were 86.5, 57.0, and 43.4 %, respectively (p = 0.6722). In the OS and DFS of subsets including patients with hepatitis B or C virus infection, we could not find significant differences between the meloxicam and control groups. However, in the subgroup of analysis of patients without viral hepatitis (NBNC-HCC), significant differences were observed in the DFS between the meloxicam group (1-year DFS, 92.3 %; 3-year DFS, 75.8 %; 5-year DFS, 70.4 %) and control group (1-year DFS, 83.3 %; 3-year DFS, 48.1 %; 5-year DFS, not obtained) (p = 0.0211). CONCLUSION: Administration of the Cox-2 inhibitor meloxicam may have a possibility to suppress HCC recurrence after initial curative treatments in patients with NBNC-HCC.
Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Tiazinas/administración & dosificación , Tiazoles/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/enzimología , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Neoplasias Hepáticas/enzimología , Masculino , Meloxicam , Persona de Mediana Edad , Recurrencia Local de Neoplasia/enzimología , Resultado del TratamientoRESUMEN
BACKGROUND: Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC. METHODS: We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled. RESULTS: Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107-0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047-0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355-5.691), and post-PD sorafenib administration (0.279, 0.150-0.510). CONCLUSION: Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Anciano , Antineoplásicos/farmacología , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Niacinamida/farmacología , Niacinamida/uso terapéutico , Compuestos de Fenilurea/farmacología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Radiografía , Sorafenib , Resultado del TratamientoRESUMEN
BACKGROUND: Sorafenib therapy improves survival in unresectable hepatocellular carcinoma (HCC) patients without an objective response. The present study investigated whether the initial imaging response might be a prognostic indicator after administration of sorafenib therapy in HCC patients. PATIENTS AND METHODS: This retrospective study reviewed unresectable HCC patients undergoing sorafenib therapy. Patients evaluated without complete response, partial response (PR), or progressive disease (PD) at the initial imaging response evaluation by modified Response Evaluation Criteria in Solid Tumors were divided into three groups according to more detailed categorization of the shrinkage/progression ratio in initial imaging response. A comparison of progression-free and overall survival among these groups was performed. RESULTS: Of the 43 non-PR non-PD patients with target lesions, ten (23.3%) exhibited mild response (MR; -30% to -5%), 14 (32.6%) exhibited no change (NC; -5% to +5%), and 19 (44.2%) exhibited mild-PD (MPD; +5% to +20%). There was no statistical difference in progression-free or overall survival between MR and NC patients. The median progression-free survivals in NC+MR and mild-PD patients were 15.0 and 5.3 months, respectively (P<0.01), and the median survival times were 31.9 and 17.1 months, respectively (P<0.001). In multivariate analysis, etiology (hepatitis C virus) and initial imaging response (MR+NC) was identified as an independently good prognostic factor. CONCLUSION: More detailed categorization of shrinkage or progression at the initial imaging response evaluation may be a useful marker for predicting sorafenib treatment outcomes in HCC patients. If the initial imaging response is not progression but stability, sorafenib may have a survival benefit.
RESUMEN
Sorafenib is an effective treatment for unresectable hepatocellular carcinoma (HCC) characterized by disease stabilization. However, the response rates are very low (<9%percnt;), and a complete response is rarely achieved. We report an extremely rare case of a HCC patient with multiple lung metastases treated with sorafenib who achieved a complete response for a long period. A 77-year-old woman was diagnosed with chronic hepatitis C in 1990. In 2007, a HCC detected in the liver was treated with percutaneous ethanol injection therapy. Subsequently, recurrence of HCC in the liver was treated with microwave coagulonecrotic therapy in 2010. In April 2011, a computed tomography (CT) scan revealed innumerable multiple metastases spread diffusely in both lungs. Tumor marker levels were extremely high [α-fetoprotein (AFP) 76,170 ng/ml, lens culinaris agglutinin-reactive fraction of AFP 7.5%percnt;, des-γ-carboxyprothrombin (DCP) 63,400 mAU/ml]. Sorafenib was administered at a reduced dose of 400 mg/day because of old age. Four months after sorafenib treatment, AFP and DCP had decreased to within normal levels, and the multiple lung metastases had disappeared. Currently, sorafenib is administered at a reduced dose of 400 mg/day, and the complete response has been maintained for 48 months.
RESUMEN
Carcinosarcoma is a rare neoplasm with epithelial and mesenchymal components. We herein report the case of a 68-year-old male with a carcinosarcoma of the gallbladder. Preoperative examinations revealed the gallbladder cancer infiltrating the liver with a multinodular mass with a portal vein tumor thrombus through the right anterior branch of the portal vein. Extended right hepatectomy with portal thrombectomy was performed. Histologically, the tumor comprised a distinct adenocarcinoma and pleomorphic mononuclear cell components. The adenocarcinoma mainly lined the gallbladder lumen, forming irregular papillary glands. The pleomorphic mononuclear cells formed the majority of the tumor. Immunohistochemical analysis revealed that the pleomorphic mononuclear component was strongly positive for vimentin and slightly positive for cytokeratin. These findings suggested that the mononuclear cells formed a degenerated neoplasm of adenocarcinoma cells. The pathological diagnosis was carcinosarcoma of the gallbladder. After curative surgery, adjuvant chemotherapy with gemcitabine chloride was conducted for 3 years. The patient was alive for 5 years without recurrence after resection. The present case showed the longest reported survival among patients with advanced stage carcinosarcoma.