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1.
World J Surg ; 42(1): 225-232, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28799103

RESUMO

BACKGROUND: The incidence of spontaneous rupture of hepatocellular carcinoma (HCC) is low in Europe, at less than 3%. HCC rupture remains a life-threatening complication, with mortality reported between 16 and 30%. The risk of bleeding recurrence has never been clearly evaluated in such clinical situation. The objectives of this study were to evaluate the current risk of mortality related to HCC rupture and to focus on the risk of bleeding recurrence following interventional management. METHODS: All patients admitted to 14 French-Italian surgical centers for spontaneous rupture of HCC between May 2000 and May 2012 were retrospectively included. Clinical data, imaging features, relevant laboratory data, treatment strategies, and prognoses were analyzed. RESULTS: Overall, 58 of the 138 included patients (42%) had cirrhosis. Thirty-five patients (25%) presented with hemorrhagic shock, and 19% with organ(s) dysfunction. Bleeding control was obtained by interventional hemostasis, emergency liver resection, and conservative medical management in 86 (62%), 24 (18%), and 21 (15%) patients, respectively. Best supportive care was chosen for 7 (5%) patients. The mortality rate following rupture was 24%. The bleeding recurrence rate was 22% with related mortality of 52%. In multivariate analysis, a bilirubin level >17 micromol/L (HR 3.768; p = 0.006), bleeding recurrence (HR 5.400; p < 0.0001), and ICU admission after initial management (HR 8.199; p < 0.0001) were associated with in-hospital mortality. CONCLUSION: This European, multicenter, large-cohort study confirmed that the prognosis of ruptured HCC is poor with an overall mortality rate of 24%, despite important advances in endovascular techniques. Overall, the rate of bleeding recurrence was more than 20%, with a related high risk of mortality.


Assuntos
Carcinoma Hepatocelular/complicações , Hemorragia/etiologia , Hemorragia/terapia , Técnicas Hemostáticas , Neoplasias Hepáticas/complicações , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Feminino , Hemorragia/mortalidade , Mortalidade Hospitalar , Humanos , Fígado/cirurgia , Cirrose Hepática/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Ruptura Espontânea
2.
Eur J Cancer ; 78: 7-15, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28407529

RESUMO

PURPOSE: Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line. PATIENTS AND METHODS: From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed. RESULTS: After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2. CONCLUSION: CLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo , Neoplasias Hepáticas/cirurgia , Neoplasias Retais , Anticorpos Monoclonais/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Ablação por Cateter/métodos , Ablação por Cateter/mortalidade , Cetuximab/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Irinotecano , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Panitumumabe , Cuidados Pós-Operatórios/mortalidade , Cuidados Pré-Operatórios/mortalidade , Estudos Prospectivos , Sistema de Registros
3.
HPB (Oxford) ; 18(9): 748-55, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27593592

RESUMO

BACKGROUND: Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation. METHODS: A retrospective cross-sectional study, from 27 European high-volume HPB units. RESULTS: 573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients. DISCUSSION: Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered.


Assuntos
Adenoma de Células Hepáticas/cirurgia , Hepatectomia , Laparoscopia , Neoplasias Hepáticas/cirurgia , Adenoma de Células Hepáticas/epidemiologia , Adenoma de Células Hepáticas/patologia , Adulto , Transformação Celular Neoplásica , Estudos Transversais , Europa (Continente)/epidemiologia , Feminino , Hemorragia/epidemiologia , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Incidência , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
5.
Am J Surg ; 210(1): 35-44, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25935229

RESUMO

BACKGROUND: The role of liver resection (LR) of hepatocellular carcinoma with macroscopic vascular thrombosis (MVT) remains controversial. The aim of this study is to evaluate whether the presence of MVT should still be considered a contraindication for LR. METHODS: Retrospective study was carried out on 62 patients who underwent LR and thrombectomy for hepatocellular carcinoma complicated by MVT. Of the 62 patients, 15 (36.5%) had tumor thrombus (TT) in the peripheral portal vein (Vp1), 5 (12.2%) in second branch (Vp2), and 21 (51.3%) in the first branch/portal vein trunk (Vp3), while on the hepatic/cava vein side, 8 (12.9%) had TT in the main trunk of the hepatic veins (Vv2) and 3 (4.8%) had TT reaching the vena cava/right atrium (Vv3). RESULTS: Perioperative major morbidity was 14.5%, while in-hospital mortality was 4.8%. Overall, 1, 3, and 5-year survival rates were 53.3%, 30.1%, and 20%, and disease-free survival rates were 31.7%, 20.8%, and 15.6%, respectively. There were no differences in survival about the MVT localized in Vp1, Vp2, or Vp3 (P = .77), while we found a statistical trend between patients with Vv2 and Vv3 (P = .06). CONCLUSION: Surgical resection seems to be justified in these patients, and the presence of MVT should no longer be considered an absolute contraindication for LR.


Assuntos
Carcinoma Hepatocelular/secundário , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Células Neoplásicas Circulantes , Trombectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
6.
J Surg Oncol ; 111(6): 716-24, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25864987

RESUMO

BACKGROUND AND OBJECTIVES: The use of neo-adjuvant chemotherapy in resectable synchronous liver metastasis is ill defined. The aim of this study was to evaluate neo-adjuvant chemotherapy on outcomes following liver resection for synchronous CLM. METHODS: An analysis of a multi-centric cohort from the LiverMetSurvey International Registry, who had undergone curative resections for synchronous CLM was undertaken. Patients who received neo-adjuvant chemotherapy prior to liver surgery (group NAS; n = 693) were compared with those treated by surgery alone (group SG; n = 608). Baseline clinicopathological variables were compared. Predictors of overall (OS) and disease free survival (DFS) were subsequently identified. RESULTS: Clinicopathological comparison of the groups revealed a greater proportion of solitary metastasis in the SG compared to the NAS group (58.8% versus 38.4%; P < 0.001) therefore a separate analysis of solitary versus multi-centric analysis was performed. N-stage (> N1), number of metastasis (> 3), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer OS, while N-stage (> N1), serum CEA (> 5 ng/ml) and no adjuvant chemotherapy independently predicted poorer DFS. Neo-adjuvant chemotherapy did not independently affect outcome. CONCLUSION: We present an analysis of a large multi-center series of the role of neo-adjuvant chemotherapy in resectable CLM and demonstrate no survival advantage in this setting.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Terapia Neoadjuvante , Antígeno Carcinoembrionário/sangue , Quimioterapia Adjuvante , Estudos de Coortes , Intervalo Livre de Doença , Europa (Continente)/epidemiologia , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Sistema de Registros , Estudos Retrospectivos
7.
Ann Surg Oncol ; 22(13): 4149-57, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25845431

RESUMO

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a severe form of chemotherapy-related liver injury (CALI) that may worsen the short-term outcome of liver resection (LR) for colorectal metastases (CRLM). The present study aimed to clarify the incidence, risk factors, preoperative assessment, and clinical impact of NRH. METHODS: Overall, 406 patients undergoing 478 LRs for CRLM after chemotherapy between 2000 and 2012 were studied. All resection specimens were reviewed. After Gomori staining, NRH was graded according to the Wanless score. RESULTS: NRH was diagnosed in 87 (18.2 %) patients, grades 2-3 in 14 (2.9 %) patients. At multivariate analysis, the prevalence of NRH was increased after oxaliplatin administration (21.4 vs. 8.4 %; p = 0.003), and reduced by the addition of bevacizumab (11.7 vs. 19.8 %; p = 0.020). Two parameters predicted the presence of NRH: the APRI score (AST to platelet ratio index: 25.5 % if >0.36 vs. 9.8 % if ≤0.36; p = 0.004), and the platelet count (63.6 % if <100 × 10(3)/mm(3) vs. 25.3 % if 100-200 × 10(3)/mm(3) vs. 11.9 % if >200 × 10(3)/mm(3); p = 0.032). Ninety-day mortality and liver failure rates were 0.6 and 3.6 %. NRH was an independent predictor of postoperative liver failure (9.2 % if present vs. 2.3 % if not present; p = 0.021). In patients with grades 2-3 NRH, the rate of liver failure was 14.3 %, 25.0 % after major hepatectomy. No other forms of CALI impacted short-term outcomes. CONCLUSIONS: NRH was the most relevant form of CALI, increasing the risk of postoperative liver failure. Oxaliplatin increased the incidence of NRH, while bevacizumab decreased it. The APRI score and platelet count were useful tools for predicting NRH.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/cirurgia , Hiperplasia Nodular Focal do Fígado/etiologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Regeneração Hepática , Idoso , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Terapia Combinada , Feminino , Hiperplasia Nodular Focal do Fígado/diagnóstico , Seguimentos , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Cuidados Pré-Operatórios , Prognóstico , Fatores de Risco
8.
J Hepatol ; 63(1): 93-101, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25646890

RESUMO

BACKGROUND & AIMS: The incidence of metabolic syndrome-related hepatocellular carcinoma (MS-HCC) is increasing worldwide. High resection risks are anticipated because of underlying steatohepatitis, but long-term results are unknown. To clarify the outcomes following liver resection in patients with MS-HCC and to compare the outcomes of MS-HCC to HCV-related HCC (HCV-HCC). METHODS: All the consecutive patients undergoing liver resection for HCC in six high-volume HPB units between 2000 and 2012 were retrospectively considered. The patients with MS-HCC were identified and matched one-to-one with HCV-HCC patients without metabolic syndrome. Matching was based on age, cirrhosis, Child-Pugh class, portal hypertension, HCC number and diameter and liver resection extension. RESULTS: Among 1563 patients undergoing liver resection for HCC in the study period, 96 (6.1%) had MS-HCC. They were matched with 96 HCV-HCC patients. All patients were Child-Pugh class A, 22.9% had cirrhosis. Forty-one patients per group (42.7%) required major hepatectomy. The MS-HCC group had a higher prevalence of steatohepatitis (25.0% vs. 9.4%, p=0.004). Operative mortality was 2.1% (1 MS-HCC, 3 HCV-HCC, p=0.621). Morbidity and liver failure rates were similar between the two groups. In the multivariate analysis, cirrhosis, major hepatectomy, and MELD >8, but not steatohepatitis, impacted severe morbidity and liver failure rates. The MS-HCC group had better 5-year overall survival (65.6% vs. 61.4%, p=0.031) and recurrence-free survival (37.0% vs. 27.5%, p=0.077). Independent negative prognostic factors were HCV-HCC, multiple HCC, microvascular invasion, and satellite nodules. CONCLUSIONS: Liver resection is safe for MS-HCC, as for HCV-HCC. Cirrhosis, but not steatohepatitis, affects short-term outcomes. MS-HCC is associated with excellent long-term outcomes, better than HCV-HCC.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Hepatite C Crônica/complicações , Neoplasias Hepáticas/cirurgia , Síndrome Metabólica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/virologia , Feminino , Seguimentos , Hepatite C Crônica/virologia , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/virologia , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
9.
Ann Surg Oncol ; 22(3): 1000-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25190116

RESUMO

BACKGROUND: The role of extended resections in the management of advanced pancreatic neuroendocrine tumors (PNETs) is not well defined. METHODS: Between 1995 and 2012, 134 patients with PNET underwent isolated (isoPNET group: 91 patients) or extended pancreatic resection (synchronous liver metastases and/or adjacent organs) (advPNET group: 43 patients). RESULTS: The associated resections included 27 hepatectomies, 9 vascular resections, 12 colectomies, 10 gastrectomies, 4 nephrectomies, 4 adrenalectomies, and 3 duodenojejunal resections. R0 was achieved in 41 patients (95%) in the advPNET. The rates of T3-T4 (73 vs 16%; p < .0001) and N+ (35 vs 13%; p = .007) were higher in the advPNET group. Mortality (5 vs 2%) and major morbidity (21 vs 19%) rates were similar between the 2 groups. The 5-year overall survival (OS) of the series was 87% in the isoPNET group and 66% in the advPNET group (p = .006). Only patients with both locally advanced disease and liver metastases showed worse survival (p = .0003). The advPNET group developed recurrence earlier [disease-free survival (DFS) at 5 years: 26 vs 81%; p < .001]. In univariate analysis, negative prognostic factors of survival were: poor degree of differentiation (p < .001), liver metastasis (p = .011), NE carcinoma (p < .001), and resection of adjacent organs (p = .013). The multivariate analysis did not highlight any factor that influenced OS. In multivariate analysis independent DFS factors were a poor degree of differentiation (p = .03) and the European Neuroendocrine Tumor Society stage (p = .01). CONCLUSIONS: An aggressive surgical approach for locally advanced or metastatic tumors is safe and offers long-term survival.


Assuntos
Hepatectomia/mortalidade , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Tumores Neuroendócrinos/cirurgia , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Agências Internacionais , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
10.
Surg Endosc ; 29(4): 1002-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25135446

RESUMO

BACKGROUND: Intraoperative liver ultrasound has an established role in liver surgery to complete staging and to guide resection. The same performances should be expected by laparoscopic ultrasound (LUS). METHODS: LUS is first performed to identify relationships between tumor and vasculo-biliary pedicles. The planes where the main vascular structures run are marked on the liver surface. Parenchymal transection is performed and each vessel recognized during LUS exploration is divided. RESULTS: From 01/2009 to 10/2013, in 61 out of 742 liver resections (8.2 %), a laparoscopic approach was attempted. The conversion rate was 9.8 % (six patients). No conversion was related to bleeding or intraoperative complications. The remnant 55 patients were affected by benign lesions in 11 cases and malignant tumors in 44. The resections included 3 left hepatectomies, 14 bisegmentectomies Sg2-3, 5 segmentectomies, and 38 wedge resections. Associated procedures were performed in eight patients (14.5 %), including four colorectal resections. Median duration of surgery was 150 min (60-345 min). Median operative blood loss was 100 mL (0-500 mL). Median size of resected tumor was 2.5 cm (0.9-8 cm). Median surgical margin in oncological resections was 7 mm (0-50 mm). Postoperative complications occurred in four patients (7.2 %), all grade 2 according to Dindo classification. No liver-related morbidity occurred. Median length of hospital stay was 5 days (3-9 days). CONCLUSIONS: Ultrasound-guided liver resections can be performed by laparoscopic approach with the same accuracy than open surgery.


Assuntos
Hepatectomia/métodos , Laparoscopia/métodos , Neoplasias Hepáticas/cirurgia , Cirurgia Assistida por Computador/métodos , Seguimentos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
11.
Ann Surg Oncol ; 22(3): 811-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25201500

RESUMO

BACKGROUND: Lymph node (LN) status is one of the strongest prognostic factors after gallbladder cancer (GBC) resection. The adequate extension of LN dissection and the stratification of the prognosis in N+ patients have been debated. The present study aims to clarify these issues. METHODS: A total of 112 consecutive patients who underwent operations for GBC with LN dissection were analyzed. Twenty-five patients (22.3%) had D1 dissection (hepatic pedicle), and 87 (77.7%) had D2 dissection (hepatic pedicle, celiac and retro-pancreatic area). The LN ratio (LNR) was computed as follows: number of metastatic LNs/number of retrieved LNs. RESULTS: The median number of retrieved LNs was 7 (1-35). Fifty-nine patients (52.7%) had LN metastases (22 N2). D2 dissection allowed the retrieval of more LNs (8 vs. 3, p = 0.0007), with similar short-term outcomes. Common bile duct (CBD) resection (n = 41) did not increase the number of retrieved LNs. In five patients, D2 dissection identified skip LN metastases that otherwise would have been missed. LN metastases negatively impacted survival (5-years survival 57.2% if N0 vs. 12.4% if N+, p < 0.0001), but N1 and N2 patients had similar survival rates. The number of LN+ (1-3 vs. ≥4) did not impact prognosis. An LNR = 0.15 stratified the prognosis of N+ patients: 5-years survival 32.7% if LNR ≤ 0.15 vs. 10.3% if LNR > 0.15 (multivariate analysis p = 0.007). CONCLUSIONS: A D2 LN dissection is recommended in all patients, because it allows for better staging. CBD resection does not improve LN dissection. An LNR = 0.15, not the site of metastatic LNs, stratified the prognoses of N+ patients.


Assuntos
Adenocarcinoma/secundário , Neoplasias da Vesícula Biliar/patologia , Hepatectomia/mortalidade , Neoplasias Hepáticas/secundário , Excisão de Linfonodo/mortalidade , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
14.
Ann Surg ; 261(4): 733-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24854451

RESUMO

OBJECTIVE: To determine the prognostic impact of tumor location in gallbladder cancer. BACKGROUND: Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. METHODS: For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as "hepatic side" or "peritoneal side," and the prognostic significance of tumor location was evaluated. RESULTS: Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection. CONCLUSIONS: After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival.


Assuntos
Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Internacionalidade , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento
15.
BMC Cancer ; 14: 918, 2014 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-25479910

RESUMO

BACKGROUND: Standard chemotherapy in unresectable biliary tract carcinoma (BTC) patients is based on gemcitabine combined with platinum derivatives. However, primary or acquired resistance is inevitable and no second-line chemotherapy is demonstrated to be effective. Thus, there is an urgent need to identify new alternative (chemo)therapy approaches. METHODS: We evaluated the mechanism of action of ET-743 in preclinical models of BTC. Six BTC cell lines (TFK-1, EGI-1, TGBC1, WITT, KMCH, HuH28), two primary cell cultures derived from BTC patients, the EGI-1 and a new established BTC patient-derived xenografts, were used as preclinical models to investigate the anti-tumor activity of ET-743 in vitro and in vivo. Gene expression profiling was also analyzed upon ET-743 treatment in in vivo models. RESULTS: We found that ET-743 inhibited cell growth of BTC cell lines and primary cultures (IC50 ranging from 0.37 to 3.08 nM) preferentially inducing apoptosis and activation of the complex DNA damage-repair proteins (p-ATM, p-p53 and p-Histone H2A.x) in vitro. In EGI-1 and patient-derived xenografts, ET-743 induced tumor growth delay and reduction of vasculogenesis. In vivo ET-743 induced a deregulation of genes involved in cell adhesion, stress-related response, and in pathways involved in cholangiocarcinogenesis, such as the IL-6, Sonic Hedgehog and Wnt signaling pathways. CONCLUSIONS: These results suggest that ET-743 could represent an alternative chemotherapy for BTC treatment and encourage the development of clinical trials in BTC patients resistant to standard chemotherapy.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Neoplasias do Sistema Biliar/tratamento farmacológico , Dioxóis/farmacologia , Tetra-Hidroisoquinolinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Neoplasias do Sistema Biliar/irrigação sanguínea , Neoplasias do Sistema Biliar/genética , Adesão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Reparo do DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Histonas/metabolismo , Humanos , Interleucina-6/genética , Camundongos , Camundongos Endogâmicos NOD , Neovascularização Patológica/tratamento farmacológico , Fosforilação , Trabectedina , Proteína Supressora de Tumor p53/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
16.
Ann Surg ; 260(5): 878-84; discussion 884-5, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25379857

RESUMO

OBJECTIVES: To compare outcomes following liver resection of colorectal metastases (CRLM) from mucinous adenocarcinoma (Muc-CRLM) versus nonmucinous adenocarcinoma (non-Muc-CRLM). BACKGROUND: Among colorectal adenocarcinomas, 10%-15% are mucinous and have worse prognoses than nonmucinous ones. Outcomes of liver resection for Muc-CRLM remain unknown. METHODS: Among 701 patients undergoing liver resection for CRLM between 1998 and 2012, 102 (14.6%) had Muc-CRLM. Each was matched with a non-Muc-CRLM patient, based on tumor N status, disease-free interval (DFI) between primary tumor and metastases, CRLM number and diameter, extrahepatic disease, and preoperative chemotherapy. RESULTS: Within the 2 groups, 69.6% of patients had N+ primary tumor, 72.5% had DFI of less than 12 months, 28.4% had 4 or more CRLM, and 22.5% had associated extrahepatic disease. 59.8% of patients received preoperative chemotherapy. Muc-CRLM patients had higher prevalences of right/transverse colon cancer (55.9% vs 29.4%; P<0.0001) and K-ras mutation (67 patients tested, 61.8% vs 36.4%; P=0.037), as well as lower response to preoperative chemotherapy (63.9% vs 85.2%; P=0.006). Multivariate analysis showed Muc-CRLM to have lower rates of 5-year overall (33.2% vs 55.2%; P=0.010) and disease-free survival (32.5% vs 49.3%; P=0.037). Muc-CRLM recurrence was more often peritoneal (20.3% vs 6.5%; P=0.024) and at multiple sites (47.5% vs 21.0%; P=0.002), and had lower rates of re-resection (16.9% vs 43.5%; P=0.002) and 3-year post-recurrence survival (11.7% vs 43.4%; P=0.0003). CONCLUSIONS: Muc-CRLM patients strongly differed from non-Muc-CRLM patients, showing a lower chemotherapy response and higher K-ras mutation prevalence. Muc-CRLM appears to be a separate disease, which is associated with worse survival and aggressive rarely re-resectable recurrences.


Assuntos
Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Quimioterapia Adjuvante , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
17.
J Gastrointest Surg ; 18(11): 1974-86, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25159501

RESUMO

BACKGROUND: The role of hepatectomy for patients with liver metastases from gastric and esophageal cancer (GELM) is not well defined. The present study examined the morbidity, mortality, and long-term survivals after liver resection for GELM. METHODS: Clinicopathological data of patients who underwent hepatectomy for GELM between 1995 and 2012 at two European high-volume hepatobiliary centers were assessed, and predictors of overall survival (OS) were identified. In addition, the impact of preoperative chemotherapy for GELM on OS was evaluated. RESULTS: Forty-seven patients underwent hepatectomy for GELM. The primary tumor was located in the stomach, cardia, and distal esophagus in 27, 16, and 4 cases, respectively. Twenty patients received preoperative chemotherapy before hepatectomy. After a median follow-up time of 76 months, 1-, 3-, and 5-year OS rates were 70, 37, and 24%, respectively. Postoperative morbidity and mortality rates were 32 and 4%, respectively. Outcomes were comparable between the two centers. Preoperative chemotherapy for GELM (5-year OS: 45 vs 9%, P = .005) and the lack of posthepatectomy complications (5-year OS: 34 vs 0%, P < .0001) were significantly associated with improved OS in univariate and multivariate analyses. When stratifying OS by radiologic response of GELM to preoperative chemotherapy, patients with progressive disease despite preoperative treatment had significantly worse OS (5-year OS: 0 vs 70%, P = .045). CONCLUSION: For selected patients with GELM, liver resection is safe and should be regarded as a potentially curative approach. A multimodal treatment strategy including systemic therapy may provide better patient selection resulting in prolonged survival in patients with GELM undergoing hepatectomy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Hepatectomia/métodos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Terapia Neoadjuvante/métodos , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Seguimentos , Hepatectomia/mortalidade , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
18.
Crit Rev Oncol Hematol ; 92(3): 218-26, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24985058

RESUMO

Colorectal cancer is one of the most common cancers worldwide. In recent years, the survival of patients with metastatic disease has improved due to the developments in both medical and surgical care. Patients with technically unresectable metastatic disease could benefit from a multidisciplinary approach for their possible shift toward a technically resectable condition; the choice of the most effective systemic treatment is then crucial to allow conversion to resectability. Systemic conversion therapy may include chemotherapy agents' combinations (fluoropyrimidine, irinotecan and oxaliplatin), with or without targeted agents (cetuximab, panitumumab, bevacizumab). The choice of the best treatment option has to be evaluated by taking into account each patient's baseline characteristics, biological and pathological information and surgical strategy. In particular, the role of some biologic characteristics of the disease, namely the mutational status of EGFR-pathway oncogenes, is emerging as an important predictive factor of response to anti-EGFR targeted agents. Patients presenting with colorectal cancer metastases should be evaluated for multimodal management with curative intent as the appropriate chemotherapy regimen may induce tumor shrinkage, conversion to resectability and improved survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Terapia Combinada , Humanos , Terapia de Alvo Molecular , Metástase Neoplásica , Medicina de Precisão , Resultado do Tratamento
19.
J Am Coll Surg ; 219(2): 285-94, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24933714

RESUMO

BACKGROUND: We aimed to evaluate the feasibility and long-term results of 2-stage hepatectomy (TSH) in patients with bilobar colorectal liver metastases (CRLM). STUDY DESIGN: We performed a retrospective multicenter study including 4 Italian hepatobiliary surgery units. One hundred thirty patients were selected for TSH between 2002 and 2011. The primary endpoint was feasibility of TSH and analysis of factors associated with failure to complete the procedure. The secondary endpoint was the long-term survival analysis. RESULTS: Patients presented with synchronous CRLM in 80.8% of cases, with a mean number of 8.3 CRLM and with concomitant extrahepatic disease in 20.0% of cases. The rate of failure to complete TSH was 21.5% and tumor progression was the most frequent reason for failure (18.5% of cases). Primary tumor characteristics, type, number, and distribution of CRLM were not associated with significantly different risks of disease progression. Multivariable logistic regression analysis showed that tumor progression during prehepatectomy chemotherapy was the only independent risk factor for failure to complete TSH. The 5- and 10-year overall survival rates for patients who completed TSH were 32.1% and 24.1%, respectively, with a median survival of 43 months. Duration of prehepatectomy chemotherapy ≥6 cycles was found to be the only independent predictor of overall and disease-free survival. CONCLUSIONS: This study showed that selection of patients by response to prehepatectomy chemotherapy may be extremely important before planning TSH because tumor progression while receiving prehepatectomy chemotherapy was associated with significantly higher risk of failure to complete the second stage. For patients who completed the TSH strategy, long-term outcomes can be achieved with results similar to those observed after single-stage hepatectomy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Progressão da Doença , Embolização Terapêutica , Estudos de Viabilidade , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Falha de Tratamento
20.
Updates Surg ; 66(1): 1-6, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24523031

RESUMO

The topic chosen by the Board of the Italian Society of Surgery for the 2013 annual Consensus Conference was gastric cancer. With this purpose, under the direction of 2 chairmen, 36 experts nominated by the Regional Societies of Surgery and by the Italian Research Group for Gastric Cancer (GIRCG) participated in an experts consensus exercise, preceded by a questionnaire and mainly held by telematic vote, in accordance with the rules of the Delphi method. The results of this Consensus Conference, presented to the 115th National Congress of the Italian Society of Surgery, and approved in plenary session, are reported in the present paper.


Assuntos
Neoplasias Gástricas/terapia , Técnica Delphi , Endossonografia , Feminino , Humanos , Itália , Excisão de Linfonodo , Masculino , Estadiamento de Neoplasias , Sociedades Médicas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
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