RESUMO
BACKGROUND: Immune checkpoint inhibitor (ICI) combination therapy offers a new option for treatment of unresectable intrahepatic cholangiocarcinoma (uICC). AIM: To compare the effect of different anti-PD-1 combination therapies as the first-line treatments for uICC. METHODS: This study included 318 patients who received chemotherapy alone (Chemo), anti-PD-1 plus chemotherapy (ICI-chemo), anti-PD-1 plus targeted therapy (ICI-target) or anti-PD-1 plus targeted therapy and chemotherapy (ICI-target-chemo) as first line for uICC from 22 centres in China. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and safety. RESULTS: Patients with ICI-chemo (median PFS [mPFS], 6.3 months; HR: 0.61, 95% CI: 0.42-0.88; p = 0.008; median OS [mOS], 10.7 months; HR: 0.61, 95% CI: 0.39-0.94; p = 0.026), ICI-target (7.2 months; HR: 0.54, 95% CI: 0.36-0.80; p = 0.002; 15.8 months; HR: 0.54, 95% CI: 0.35-0.84; p = 0.006) or ICI-target-chemo (6.9 months; HR: 0.65, 95% CI: 0.47-0.90; p = 0.009; 14.4 months; HR: 0.47, 95% CI: 0.31-0.70; p < 0.001) achieved better clinical outcomes than those with Chemo (3.8 months; 9.3 months). ICI-target was not inferior to ICI-chemo in survival outcomes (HR for PFS: 0.88, 95% CI: 0.55-1.42; p = 0.614; HR for OS: 0.89, 95% CI: 0.51-1.55; p = 0.680). ICI-target-chemo yielded similar prognoses as ICI-chemo (HR for PFS: 1.07, 95% CI: 0.70-1.62; p = 0.764; HR for OS: 0.77, 95% CI: 0.45-1.31; p = 0.328) and ICI-target (HR for PFS: 1.20, 95% CI: 0.77-1.88; p = 0.413; HR for OS: 0.86, 95% CI: 0.51-1.47; p = 0.583) but resulted in more adverse events (p < 0.001; p = 0.010). Multivariable and propensity score analyses supported these findings. CONCLUSIONS: Among patients with uICC, ICI-chemo or ICI-target provided more survival benefits than Chemo while achieving comparable prognoses and fewer adverse events than ICI-target-chemo.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia Combinada , Colangiocarcinoma/tratamento farmacológico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-HepáticosRESUMO
BACKGROUND: Microvascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI. METHODS: A multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed. RESULTS: Of 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities. CONCLUSION: Post-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatectomia/efeitos adversos , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: The aim of the study is to assess the efficacy and safety of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in patients with hepatitis B virus-related hepatocellular carcinoma (HCC). BACKGROUND: ALPSS allows curative resection of conventionally-unresectable liver tumors. However, its role in HCC is largely unknown. METHODS: Consecutive HCC patients who underwent ALPPS at our center between April 2013 and September 2017 were retrospectively studied. The oncological results were compared with patients receiving transcatheter arterial chemoembolization (TACE), and patients undergoing one-stage resection by using propensity score matching (PSM) analysis. RESULTS: The median tumor diameter was 13âcm (range: 6-22âcm) in patients with a single tumor (n = 28), whereas the median total tumor diameter was 12âcm (range: 9-31âcm) in patients with multiple tumors (n = 17). After stage-1 ALPPS, the median future liver remnant (FLR) increased by 56.8%. The stage-2 ALPPS was completed in 41 patients (91.1%) after a median of 12 days. The 90-day mortality rate was 11.1% (5/45). The overall survival (OS) rates at 1- and 3-year were 64.2% and 60.2%, whereas the disease-free survival (DFS) rates at 1 and 3 years were 47.6% and 43.9%, respectively. On PSM analysis, the long-term survival of patients undergoing ALPPS was significantly better than those receiving TACE (OS, P = 0.004; DFS, P < 0.0001) and similar to those subjected to one-stage liver resection (OS, P = 0.514; DFS, P = 0.849). CONCLUSIONS: The long-term survival after ALPPS was significantly better than TACE, and similar to those after one-stage liver resection. ALPPS is a viable treatment option for patients with unresectable HCC in selected patients.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Hepatite B/complicações , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Quimioembolização Terapêutica , Humanos , Ligadura , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The aim of this study was to evaluate the effect of portal vein tumor thrombus (PVTT) on the prognosis of patients undergoing liver resection (LR) for primary liver malignancies (PLC). METHODS: The recurrence-free survival (RFS) and overall survival (OS) for patients undergoing LR with and without PVTT for three primary liver malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepato-cholangio carcinoma (CHC) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: In total, 3775 patients with PLC who underwent LR were included in this study. The incidence of PVTT in patients undergoing LR with HCC, IHC and CHC were 46%, 20%, and 17%, respectively. The median RFS and OS were significantly better for patients with HCC as compared to ICC or CHC (16 vs 11 vs 13 months; 21 vs 16 vs 18 months, respectively; P < 0.001). However, the presence of PVTT resulted in similarly poor RFS and OS in these 3 subgroups of patients (9 vs 8 vs 8 months, P = 0.062; 14 vs 13 vs 12 months, respectively, P = 0.052). CONCLUSION: Although the prognosis of patients with PLC varied by histological subtype, once PVTT occurred, survival outcomes after LR were similarly poor across all three subgroups.
Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombose , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Carcinoma Hepatocelular/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Estudos Retrospectivos , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/cirurgiaRESUMO
BACKGROUND: Several studies have noted that the discriminatory ability and stratification performance of the AJCC 8th edition staging system is not entirely satisfactory. We aimed to improve the American Joint Committee on Cancer (AJCC) 8th edition staging system for intrahepatic cholangiocarcinoma (ICC). METHODS: A multicentric database from three Chinese mainland centers (n = 1601 patients) was used to modify the 8th edition staging system. This modified TNM (mTNM) staging system was then validated using the SEER database (n = 761 patients). A new TNM staging system, by incorporating serum tumor markers (TNMIS) into the mTNM staging system was then proposed. RESULTS: The 8th edition staging system did not provide an adequate stratification of prognosis in the Chinese multicentric cohort. The mTNM staging system offered a better discriminatory capacity in the multicentric cohort than the original 8th edition. External validation in the SEER cohort showed that the mTNM staging system also had a good stratification performance. After further incorporating a serum marker stage into the mTNM staging, the TNMIS staging system was able to stratify prognosis even better. CONCLUSION: The proposed mTNM staging system resulted in better stratification performance and the TNMIS staging system provided even more accurate prognostic classification than the conventional TNM system.
Assuntos
Antígenos Glicosídicos Associados a Tumores/sangue , Neoplasias dos Ductos Biliares/patologia , Antígeno Carcinoembrionário/sangue , Colangiocarcinoma/patologia , Estadiamento de Neoplasias/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Biomarcadores Tumorais/sangue , China , Colangiocarcinoma/mortalidade , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Fatores de Risco , Programa de SEER , Adulto JovemRESUMO
BACKGROUND: Microvascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR). METHODS: The data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed. RESULTS: 728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease. CONCLUSIONS: PA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Sorafenibe/uso terapêutico , Adulto , Quimioterapia Adjuvante , Feminino , Hepatectomia , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Invasividade Neoplásica , Pontuação de Propensão , Estudos RetrospectivosRESUMO
BACKGROUND: Lymph node metastasis (LNM)has widely been recognized as a poor prognostic indicator for hepatocellular carcinoma (HCC) patients. Preoperative prediction of LNM is important for clinicians to decide on treatment. This study was designed to develop a simple and convenient system to predict LNM. METHODS: Consecutive HCC patients who were suspected to have LNM were divided into a training, an internal validation and an external validation cohort. The receiver operating characteristic (ROC) analysis was used to determine the threshold value of the preoperative serological variables. A nomogram visualization system model was then established. RESULT: Of the 287 patients, there were 31 patients who had LNM (10.8%), and 21 of 203 patients (10.3%) were in the training cohort and 10 of 84 patients (11.9%) in the internal validation cohort. Sixteen of 176 patients (9.1%) in the external validation cohort had LNM. The serological indices including neutrophil/lymphocyte rate, age, platelet, prothrombin time, and total protein, were included in the nomogram. The areas of the ROC curve were 0.846, 0.679 and 0.738 in predicting LNM in the training cohort, the internal validation cohort and the external validation cohort, respectively. CONCLUSION: The scoring system constructed using the preoperative serological variables predicted LNM in HCC patients.
Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/secundário , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Adulto , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Medição de RiscoRESUMO
BACKGROUND: Serum prealbumin is a sensitive and stable marker for nutritional status and liver function. Whether preoperative prealbumin level is associated with long-term prognosis in patients undergoing liver resection for hepatocellular carcinoma (HCC) is unclear. METHODS: Patients who underwent liver resection for HCC between 2001 and 2014 at six institutions were enrolled. These patients were divided into the low and normal prealbumin groups using a cut-off value of 170 mg/L for preoperative prealbumin level. The overall survival (OS) and recurrence-free survival (RFS) were compared between them. RESULTS: In 1483 patients, 437 (29%) had a low prealbumin level. The 3- and 5-year OS and RFS rates of patients in the low-prealbumin group were 57 and 31%, and 40 and 20%, respectively, which were significantly poorer than those in the normal-prealbumin group (76 and 43%, and 56 and 28%, respectively, both p < 0.001). Multivariable Cox-regression analyses revealed that preoperative prealbumin level was an independent predictor of OS (HR, 1.45, 95% CI: 1.24-1.70, p <0.001) and RFS (HR, 1.28, 95% CI: 1.10-1.48, p <0.001). CONCLUSIONS: Preoperative prealbumin level could be used in predicting long-term prognosis for patients undergoing liver resection for HCC.
Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Albumina Sérica Humana/análise , Adulto , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , China , Bases de Dados Factuais , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Pancreatic head adenocarcinoma is commonly diagnosed at an advanced stage when adjacent vascular invasion is present. This study aimed to establish a preoperative prognostic nomogram for patients who underwent attempted curative resectional surgery for pancreatic head cancer with suspected peripancreatic venous invasion. METHODS: Data on all consecutive patients were retrospectively collected from 2012 to 2016 at four academic institutions. The demographic and radiological parameters were analyzed using univariate and multivariate Cox regression analyses. The final nomogram was established using the concordance Harrell's C-indices and calibration curves from data obtained in three institutions and validated in the cohort of patients coming from the fourth institution. RESULTS: The nomogram was constructed using data from 178 patients while the validation cohort consisted of 61 patients. Age, length of tumor contact, peripancreatic venous abnormalities and lymph node staging were independent factors of overall survival. The nomogram showed good probabilities of survival on calibration curves. The C-index of the model in predicting overall survival (OS) was 0.824 for the validation cohort. CONCLUSIONS: The nomogram accurately predicted OS in patients with pancreatic head cancer with suspected peripancreatic venous invasion after attempted curative pancreatic resectional surgery.
Assuntos
Adenocarcinoma/cirurgia , Técnicas de Apoio para a Decisão , Nomogramas , Neoplasias Pancreáticas/cirurgia , Veias/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Veias/diagnóstico por imagem , Veias/patologiaRESUMO
BACKGROUND: Reports show that selective internal radiation therapy (SIRT) may downsize inoperable liver tumors to resection or transplantation, or enable a bridge-to-transplant. A small-cohort study found that long-term survival in patients undergoing resection following SIRT appears possible but no robust studies on postsurgical safety outcomes exist. The Post-SIR-Spheres Surgery Study was an international, multicenter, retrospective study to assess safety outcomes of liver resection or transplantation following SIRT with yttrium-90 (Y-90) resin microspheres (SIR-Spheres®; Sirtex). METHODS: Data were captured retrospectively at participating SIRT centers, with Y-90 resin microspheres, surgery (resection or transplantation), and follow-up for all eligible patients. Primary endpoints were perioperative and 90-day postoperative morbidity and mortality. Standard statistical methods were used. RESULTS: The study included 100 patients [hepatocellular carcinoma: 49; metastatic colorectal cancer (mCRC): 30; cholangiocarcinoma, metastatic neuroendocrine tumor, other: 7 each]; 36% of patients had one or more lines of chemotherapy pre-SIRT. Sixty-three percent of patients had comorbidities, including hypertension (44%), diabetes (26%), and cardiopathy (16%). Post-SIRT, 71 patients were resected and 29 received a liver transplant. Grade 3+ peri/postoperative complications and any grade of liver failure were experienced by 24 and 7% of patients, respectively. Four patients died <90 days postsurgery; all were trisectionectomies (mCRC: 3; cholangiocarcinoma: 1) and typically had one or more previous chemotherapy lines and presurgical comorbidities. CONCLUSIONS: In 100 patients undergoing liver surgery after receiving SIRT, mortality and complication rates appeared acceptable given the risk profile of the recruited patients.
Assuntos
Hepatectomia/efeitos adversos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Braquiterapia/métodos , Feminino , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Falência Hepática/etiologia , Transplante de Fígado/mortalidade , Masculino , Microesferas , Pessoa de Meia-Idade , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Radioisótopos de Ítrio/uso terapêuticoRESUMO
OBJECTIVES: The role of serum α-fetoprotein (AFP) measurements in the diagnosis of hepatocellular carcinoma (HCC) remains controversial. Some guidelines have advised against the use of AFP in the diagnosis of HCC. This study was conducted to evaluate the performance of AFP in the diagnosis of HCC, and to identify the optimal cut-off value of serum AFP in the diagnosis of HCC in patients with a hepatic mass. METHODS: Patients who presented during the period from May 1997 to March 2003 with hepatic lesions, for whom paired data on serum AFP values at baseline and lesion histology were available, were reviewed. The performance of AFP in the diagnosis of HCC was determined using receiver operating characteristic curve analysis. RESULTS: Data for a total of 805 patients were evaluated. The mean AFP value was 26,900 ng/ml (range: 0-1,965,461 ng/ml). The histological diagnosis was HCC in 557 patients. The optimal AFP cut-off value was 10 ng/ml (for sensitivity of 82.6% and specificity of 70.4%). At a cut-off level of 200 ng/ml, sensitivity, specificity, and positive and negative predictive values were 47.7%, 97.1%, 97.5% and 44.4%, respectively. The diagnostic performance of AFP remains similar in patients with chronic hepatitis B virus infection, despite a lower negative predictive value. Common aetiologies of liver lesions associated with elevated AFP include cholangiocarcinoma and neuroendocrine tumours. CONCLUSIONS: In Asian patients with suspicious liver lesions, the cut-off AFP level of 200 ng/ml is useful to achieve a diagnosis of HCC with high specificity and reasonable sensitivity. The measurement of serum AFP should not be excluded from guidelines for the diagnosis of HCC.
Assuntos
Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , alfa-Fetoproteínas/análise , Adulto , Idoso , Área Sob a Curva , Povo Asiático , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , China/epidemiologia , Hepatite B Crônica/sangue , Hepatite B Crônica/etnologia , Humanos , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is recommended as standard care for intermediate hepatocellular carcinoma (HCC). We analyse the rationality and effectiveness of TACE with BCLC B stage HBV-related HCC in a large cohort. METHODS: A total of 1516 patients with BCLC B stage from 7724 HBV-related HCCs who received TACE as initial treatment were retrospectively studied. The treatment response was assessed by the mRECIST criteria. The overall survival was calculated with life-table method and compared with the Mantel-Cox test. The prognostic factors were assessed using Cox proportional hazards. RESULTS: The 1-, 3- and 5-year overall survival rates were 84%, 29% and 19% respectively for all patients. Alpha-foetoprotein, Child-Pugh classification, tumour size and number were independent prognostic factors. The 5-year survival for patients with CR, PR, SD and PD were 39%, 19%, 2% and 0%, respectively (P < 0.0001). Child-Pugh A liver function (P = 0.002) and smaller tumour (P < 0.0001) were associated with CR/PR response. After TACE, the 5-year survival rates for patients who received surgical resection, local ablation, repeated TACE and other therapies were 52%, 29%, 12%, 10% respectively (P < 0.0001). In 328 CR patients, the prognosis of 151 patients received surgical resection is better than 177 patients not undergo liver resection (5-year survival: 52% & 27%, P < 0.0001). CONCLUSIONS: Transarterial chemoembolization is a safe and efficacious treatment for BCLC B stage HBV-related HCC. A low AFP level, small tumour, low tumour number and good liver function predicted good survival. Tumour response after initial TACE, an independent prognostic factor of overall survival, was associated with tumour extent and influenced subsequent treatment.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Hepatite B/complicações , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , China , Estudos de Coortes , Feminino , Humanos , Tábuas de Vida , Testes de Função Hepática , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The long-term survival outcomes of hepatic resection (HR) compared with transcatheter arterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) are unclear. MATERIALS AND METHODS: Between December 2002 and December 2007, 201 consecutive patients diagnosed with resectable HCC with PVTT received HR as an initial treatment in our center. These patients were compared with 402 case-matched controls selected from a pool of 1798 patients (with a 1:2 ratio) who received TACE as an initial treatment during the study period. PVTT was classified to 4 types: PVTT involving the segmental branches of the portal vein or above (type I), PVTT extending to involve the right/left portal vein (type II), the main portal vein (type III), or the superior mesenteric vein (type IV). RESULTS: The 1-, 3-, and 5-year overall survivals for the HR and TACE groups were 42.0%, 14.1%, and 11.1% and 37.8%, 7.3%, and 0.5%, respectively (P < .001). On subgroup analyses, the overall survivals for the HR group were better than the TACE group for type I PVTT, type II PVTT, single tumor, and tumor size >5 cm (P < .001, P = .002, P < .001, P < .001, respectively), but not for type III PVTT, type IV PVTT, multiple tumors, and tumor size <5 cm (P = .541, P = .371, P = .264, P = .338, P = .125, respectively). Multivariate analysis showed the type of PVTT and initial treatment allocation were significant prognostic factors for overall survival. CONCLUSIONS: Compared with TACE, HR provided survival benefits for patients with resectable HCC with PVTT, especially for those with a type I PVTT or a type II PVTT.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/terapia , Células Neoplásicas Circulantes , Veia Porta , Trombose/terapia , Adulto , Idoso , Análise de Variância , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Trombose/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: To retrospectively evaluate the effectiveness and safety of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with a multi-pin bipolar system. METHODS: Between August 2005 and December 2006, 18 patients with 30 HCCs (3.40 ± 1.24 cm, range 1.30-6.0 cm; median number of treated lesions is two per patient, range, 1-3) underwent percutaneous RFA with a multi-pin bipolar system under ultrasound guidance. The primary end-point were treatment efficacy, major and minor complications, and the secondary end-point were overall survival and tumor-free survival. RESULTS: Complete ablation with conformed shape to the index tumor was achieved in 16 of 18 patients, and 28 of the 30 tumors were completely ablated. On follow-up, local and distant intrahepatic tumor progression rates were 12.5% (2 of 16 patients) and 62.5% (10 of 16 patients). There was no patient who developed extrahepatic metastasis. There were no major complications. The 1-, 2-year overall survival rates for all patients were 83.3%, 55.6%, respectively, and the corresponding tumor-free survivals were 50.0%, 22.2%, respectively. CONCLUSION: RFA with a multi-pin bipolar system was effective and safe for HCC. A large ablation volume could be achieved which conformed to the shape of the index tumor.
Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/instrumentação , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Ablação por Cateter/métodos , Eletrodos , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
AIM: To investigate whether microproteinuria could be used as an early and sensitive indicator to detect calcineurin inhibitor (CNI)-related nephrotoxicity after liver transplantation. METHODS: All liver transplant recipients with normal serum creatinine (SCr) and detectable microproteinuria at baseline were included in this study. The renal function was monitored by the blood clearance of (99m)Tc-diethylenetriaminepentaacetic acid every 6 mo. Microproteinuria, SCr and blood urea nitrogen (BUN) were measured at entry and at subsequent follow-up visits. The patients were divided into different groups according to the mean values of glomerular filtration rate (GFR) at the follow-up time points: Group 1, GFR decreased from baseline by 0%-10%; Group 2, GFR decreased from baseline by 11%-20%; Group 3, GFR decreased from baseline by 21%-40%; Group 4, GFR decreased from baseline by > 40% and/or SCr was increasing. RESULTS: A total of 143 patients were enrolled into this study (23 females and 120 males). The mean follow-up was 32 mo (range 16-36 mo). Downward trends in renal function over time were observed in the study groups. SCr and BUN increased significantly only in Group 4 patients (P < 0.001). beta2-microglobulin (beta2m) and alpha1-microglobulin (alpha1m) significantly increased with the subtle change of renal function in recipients who were exposed to CNI-based immunosuppression regimens. The reductions in GFR were closely correlated with elevated alpha1m (r(2) = -0.728, P < 0.001) and beta2m (r(2) = -0.787, P < 0.001). CONCLUSION: beta2m and alpha1m could be useful as early and sensitive indicators of CNI-induced nephrotoxicity.
Assuntos
Inibidores de Calcineurina , Imunossupressores/toxicidade , Falência Renal Crônica , Transplante de Fígado/efeitos adversos , Proteinúria/induzido quimicamente , Adulto , Idoso , Feminino , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/etiologia , Testes de Função Renal , Transplante de Fígado/imunologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To study the effect of total body irradiation of the donor in a spontaneous tolerance rat liver transplantation model and the role of CD4(+)CD25(+) regulatory T cells on induction of immunotolerance in the recipient. METHODS: Liver transplantation was performed using male Lewis rats as donors and male DA rats as recipients. These rats were randomly allocated into the following groups:Control group, Homogeneity Liver Transplantation group, Idio-immunotolerance group and Acute Rejection group. After transplantation, survival time rate of each group were observed. Serum ALT, TB level, Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of GITR on T cell subgroup, histopathology of the hepatic graft on day 14, spleen CTL lytic activity on day 14 were measured. RESULTS: In the Idio-immunotolerance group, the recipients suffered from transient rejection after surgery but acquired immunotolerance and survived long. In the Acute Rejection group, the donors were preconditioned with total body irradiation before liver transplantation. All recipients died between day 17 to 21. Serum ALT and TB increased significantly and the ratio of Foxp3(+)CD4(+)CD25(+) regulatory T cells decreased significantly compared with the Idio-immunotolerance group, the Homogeneity Liver Transplantation group and the Control group. The expression of GITR on CD3(+)CD4(+)T cells in the peripheral blood decreased, the expression of GITR on CD3(+)CD8(+) T cells and CTL lytic activity of the recipients increased by preconditioning of the donors with total body irradiation. CONCLUSIONS: Preconditioning of the donors with total body irradiation eliminated the passenger lymphocytes of the liver graft, decreased the expression of Foxp3(+)CD4(+)CD25(+) regulatory T cells in peripheral blood, and increased the expression of GITR on CD3(+)CD8(+) T cells, thus affected the course of tolerance and induced acute rejection after liver transplantation.
Assuntos
Transplante de Fígado/imunologia , Linfócitos T Reguladores/imunologia , Doadores de Tecidos , Condicionamento Pré-Transplante , Irradiação Corporal Total , Animais , Masculino , Ratos , Ratos Endogâmicos Lew , Transplante Homólogo/imunologiaRESUMO
AIMS: This study aimed to determine the risk factors of survival in patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (PRFA). PATIENTS AND METHODS: Between August 1999 and May 2005, 281 patients (250 males and 31 females) who were 33-80 years old (mean 65.3 years) received PRFA only or PRFA in combination with percutaneous ethanol injection (PEI) in our center. Patients were treated with PRFA or PEI by a percutaneous approach with ultrasound (US) guidance and were evaluated at regular intervals to determine disease recurrence and survival. The survival curves were constructed by the Kaplan-Meier method and compared by the log-rank test. The relative significance of the variables in the risk factors of overall survival was assessed by multivariate Cox proportional hazards regression analysis. RESULTS: At the end of the study, 189 patients were alive, and 92 were dead. Median survival was 48.7 months. The overall 1-, 3-, and 5-year survival rates were 89%, 54%, and 43%, respectively. The overall 1-, 3-, and 5-year survival rates for small tumor (size < or = 3cm) were 97.8%, 65.7%, 58.6%, respectively, for medium tumor (size 3.1-5cm) 94.1%, 57.1%, 37.1%, respectively, and for large tumor (size >5cm) 62.8%, 40.3%, 0%, respectively. Survival of patients treated with PRFA was dependent on tumor size (p<0.001; risk ratio [RR] 9.6, 95% CI 5.2-17.8), number of tumors (p=0.003; RR 1.6, 95% CI 1.2-2.0), combination with PEI (p=0.01; RR 0.6, 95% CI 0.4-0.9), Child-Pugh class (p=0.002; RR 2.0, 95% CI 1.3-3.0) and safety margin (p=0.0026; RR 0.6, 95% CI 0.4-0.9). CONCLUSIONS: PRFA is an effective treatment for HCC. This study showed after PRFA, tumor size, number of tumors, combination with PEI, safety margin, and Child-Pugh class were independent risk factors of survival.
Assuntos
Carcinoma Hepatocelular/mortalidade , Ablação por Cateter/métodos , Neoplasias Hepáticas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos Locais/administração & dosagem , Carcinoma Hepatocelular/cirurgia , China/epidemiologia , Etanol/administração & dosagem , Feminino , Seguimentos , Humanos , Injeções Intralesionais , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendênciasRESUMO
PURPOSE: To prospectively evaluate whether use of combined radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) results in better survival compared with use of RFA alone in patients with hepatocellular carcinoma. MATERIALS AND METHODS: This study was local ethical committee approved; all patients gave written informed consent. One hundred thirty-three patients were randomly assigned to undergo RFA-PEI (n = 66; 57 men, nine women; mean age, 53.3 years; age range, 32-73 years) or RFA alone (n = 67; 58 men, nine women; mean age, 52.2 years; age range, 33-74 years). Patients with viable tumors at computed tomography (CT) 4 weeks after treatment received additional treatment. Overall survival rates were calculated and 3-year survival rates were compared with life-table and Mantel-Haenszel analyses, respectively. Survival curves were constructed and compared by using Kaplan-Meier and log-rank tests, respectively. The relative prognostic significance of variables in predicting overall survival and the time to tumor recurrence or metastasis were assessed with multivariate Cox proportional hazards regression and logistic regression analyses, respectively. RESULTS: One-, 2-, 3-, 4-, and 5-year overall survival rates were 95.4%, 89.2%, 75.8%, 63.3%, and 49.3%, respectively, with RFA-PEI and 89.6%, 68.7%, 58.4%, 50.3%, and 35.9%, respectively, with RFA alone. The survival curve for the RFA-PEI group was significantly better than that for the RFA-only group (P = .04). The survival curve for the RFA-PEI group was better than that for the RFA-only group with 3.1-5.0-cm tumors (P = .03) but not for those with 3.0 cm or smaller (P = .44) or 5.1-7.0-cm (P = .70) tumors. Overall tumor recurrence was lower with RFA-PEI (23 patients) than with RFA alone (33 patients, nonsignificant difference). Local recurrence was significantly lower with RFA-PEI (four patients) than with RFA alone (14 patients, P = .012). Tumor diameter proved to be the only significant prognostic factor for overall recurrence and intrahepatic recurrence. Treatment type and tumor size were significant prognostic factors for local recurrence. CONCLUSION: RFA-PEI facilitated better local tumor control and long-term survival compared with RFA alone.
Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Etanol/administração & dosagem , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Terapia Combinada , Feminino , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/tratamento farmacológico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Taxa de Sobrevida , Tomografia Computadorizada Espiral , Resultado do TratamentoRESUMO
BACKGROUND: The administration of concanavalin A (ConA) induces severe hepatic fibrosis in mice. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) were the key cytokines involved in the process. The aim of this research was to explore the effects and the mechanisms of IL-18 and anti-IL-18 on hepatic fibrosis in a ConA induced hepatic fibrosis model in BABL-C mice. MATERIALS AND METHODS: One hundred eighty BABL-C mice were randomly divided into five groups (Group a, b, c, d, e). The mice were administered saline, immunoglobulin G, ConA, IL-18 + ConA, Anti-IL-18 + ConA, respectively. At 1, 7, 14, 21 wk, the levels of serum alanine aminotransferase, TNF-alpha, IFN-gamma, IL-4, matrix metalloproteinase (MMP)-2-RNA, and tissue inhibitor of metalloproteinase-1-mRNA were measured. RESULTS: The levels of serum TNF-alpha and IFN-gamma detected in the IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). Similarly, the levels of MMP-2-RNA and tissue inhibitor of metalloproteinase-1-mRNA expressed in IL-18 + ConA group was higher than in the anti-IL-18 + ConA group (P < 0.05). A majority of these cytokines was secreted by CD4(+)T cells. CONCLUSIONS: The immunological response to hepatic fibrosis by repeated injection of ConA in the mouse model was aggravated by IL-18 and blocked by anti-IL-18.
Assuntos
Anticorpos/farmacologia , Interleucina-18/imunologia , Interleucina-18/farmacologia , Cirrose Hepática/prevenção & controle , Animais , Anticorpos/imunologia , Apoptose/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Proliferação de Células/efeitos dos fármacos , Concanavalina A , Modelos Animais de Doenças , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Mitógenos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To compare the results of percutaneous local ablative therapy (PLAT) with surgical resection in the treatment of solitary and small hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: PLAT is effective in small HCC. Whether it is as effective as surgical resection in the long-term survivals remains unknown. METHODS: We conducted a prospective randomized trial on 180 patients with a solitary HCC Assuntos
Carcinoma Hepatocelular/cirurgia
, Ablação por Cateter/métodos
, Hepatectomia/métodos
, Neoplasias Hepáticas/cirurgia
, Adolescente
, Adulto
, Idoso
, Carcinoma Hepatocelular/mortalidade
, Carcinoma Hepatocelular/patologia
, Feminino
, Seguimentos
, Humanos
, Neoplasias Hepáticas/mortalidade
, Neoplasias Hepáticas/patologia
, Masculino
, Pessoa de Meia-Idade
, Estudos Prospectivos
, Taxa de Sobrevida
, Resultado do Tratamento