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1.
J Surg Oncol ; 121(3): 503-510, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31907941

RESUMO

BACKGROUND: The survival benefit of lymphadenectomy among patients with gallbladder cancer (GBC) remains poorly understood. METHODS: Patients who underwent resection for GBC between 2000 and 2015 were identified from a US multi-institutional database. The therapeutic index (LNM rate multiplied by 3-year overall survival [OS]) was determined to assess the survival benefit of lymphadenectomy. RESULTS: Among 449 patients, less than half had LNM (N = 183, 40.8%). The median number of evaluated and metastatic lymph nodes (LNs) was 3 (interquartile range [IQR]: 1-6) and 1 (IQR: 0-1), respectively. 3-year OS among patients with LNM in the entire cohort was 26.8%. The therapeutic index was lower among patients with T4 (5.9) or T1 (6.0) tumors as well as carbohydrate antigen (CA19-9) ≥200 UI/mL (6.0). Of note, a therapeutic index difference ≥10 was noted relative to CA19-9 (<200: 18.7 vs ≥200: 6.0), American Joint Committee on Cancer T Stage (T1: 6.0 vs T2: 17.8 vs T4: 5.9) and number of LNs examined (1-2: 6.9 vs ≥6: 16.9). Concomitant common bile duct resection was not associated with a higher therapeutic index among patients with either T2 or T3 disease. CONCLUSION: Certain clinicopathological factors including T1 or T4 tumor and CA19-9 ≥200 UI/mL were associated with a low therapeutic index. Resection of six or more LNs was associated with a meaningful therapeutic index benefit among patients with LNM.


Assuntos
Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Linfonodos/cirurgia , Idoso , Estudos de Coortes , Ducto Colédoco/cirurgia , Bases de Dados Factuais , Feminino , Neoplasias da Vesícula Biliar/patologia , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Excisão de Linfonodo/mortalidade , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Índice Terapêutico , Estados Unidos/epidemiologia
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(11): 1461-1469, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31838822

RESUMO

Objective: The aim of the present study was to investigate the survival rate and its prognostic factors for patients with biliary tract cancer, and then a prognostic risk prediction model was constructed to predict the survival probability of patients. Methods: A total of 14 005 patients with biliary tract cancer (including gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer), who were diagnosed between 2010 and 2015 in the US National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) were included in the development cohort. The prognostic risk factors of biliary tract cancer were investigated using multivariate Cox regression models. The predictive nomograms were then constructed to predict the overall survival probability of 1, 3, and 5 years, and the predictive discrimination and calibration ability of the nomograms were further evaluated. Meanwhile, 11 953 patients who were diagnosed during 2004 to 2009 from SEER Program were then selected to validate the external predictive accuracy of the prediction models. Results: The 1, 3 and 5-year cumulative survival rates of patients with biliary tract cancer were 41.9%, 20.4% and 15.3%, respectively, in the development cohort. Age greater than 50 years, African Americans and Native Americans and Alaska Natives, higher T, N and M stage and poor histological differentiation grade were risk factors for death, while married status, Asia-Pacific Islanders, insured status and surgery on primary site were protective factors. Gender was not significantly associated with the overall survival. The C statistic of the prediction model was 0.73 (95%CI: 0.72-0.74), and the calibration curve showed that the interaction curves of predictive and actual survival rates of 1, 3 and 5 years were close to the 45 degree diagonal. Results in the validation cohort were similar with those in the construction cohort, with a C statistic of 0.70 (95%CI: 0.69-0.72), indicating high external applicability of the prediction model. Findings from gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer are in consistent with the overall biliary tract cancer. Conclusions: The survival rate of patients with biliary tract cancer is relatively poor, and the survival prediction model based on prognostic factors has high prediction accuracy. In the future, this prognostic prediction model could be applied to clinical practice to guide individualized treatment for patients with biliary tract cancer.


Assuntos
Neoplasias do Sistema Biliar/diagnóstico , Neoplasias da Vesícula Biliar/diagnóstico , Nomogramas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/mortalidade , Neoplasias do Sistema Biliar/terapia , Grupos de Populações Continentais/estatística & dados numéricos , Técnicas de Apoio para a Decisão , Grupos Étnicos/estatística & dados numéricos , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Programa de SEER , Taxa de Sobrevida , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
3.
Zhonghua Wai Ke Za Zhi ; 57(11): 834-839, 2019 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-31694132

RESUMO

Objective: To discuss the rationality of stage pT3 in the AJCC 8(th) TNM criteria of gallbladder carcinoma. Methods: A retrospective study was performed to analyze the clinical and pathological data of 88 patients with pT3 gallbladder carcinoma admitted to Department of Second Biliary Surgery of Eastern Hepatobiliary Surgery Hospital, affiliated to Naval Medical University from May 2013 to September 2018.pT3 stage tumors were divided into two groups: (1) pT3a stage: tumors had penetrated serosa but not directly invaded liver and/or an adjacent organ or structure; (2) pT3b stage: tumor penetrating serosa and directly invaded liver and/or an adjacent organ or structure. There were 45 patients with pT3a stage, including 15 males and 30 females, aged 36 to 80 years, with a median age of 59 years; 43 patients with pT3b, including 24 males and 19 females, aged 41 to 78 years old, median aged 63 years old.Patients with pT3a and pT3b were further divided into two groups respectively: radical resection group and extended radical resection group according to surgical radicalization. Independent sample t-test was used for comparison between two groups with normal distribution measurement data. Wilcoxon rank sum test was used between groups of non-normally distributed measurement data.The comparison of the count data was performed by χ(2) test or Fisher exact probability method. Survival analysis was performed using Kaplan-Meier method, and survival rate was compared using Log-rank test. Results: (1)Serum total bilirubin(15.6(90.3)mmol/L), albumin(40.2(4.8)mmol/L), and CA19-9(132.90(455.78)U/ml) levels in pT3b patients were higher than that in pT3a patients(10.2(6.8)mmol/L, 41.8(4.9)mmol/L, 14.35(36.27)U/ml), respectively(Z=-3.816, -1.966, -3.739, all P<0.05),postoperative complication rate in pT3b patients(24.4%) was higher than that in pT3a patients(8.9%)(P<0.05),postoperative hospital stay(12(7)days) and overall hospital stay((26±17)days) of pT3b patients were longer than that of pT3a patients((10±5) days and (19±7)days) (P<0.05). (2) The 1-, 3-, 5-year survival rates of pT3b and pT3a patients were 53%,22%,22% and 69%, 46%,38%,and the median survival time was 13 months and 26 months, respectively. The difference in survival rates between the two groups was statistically significant(χ(2)=5.117, P=0.024). (3)The 1-, 3-year survival rates of extended radical resection group(n=19) and radical resection group(n=24) in the pT3b stage were 73%, 36% and 28%, 7%, respectively.The survival time was 20 months and 9 months,respectively,and the difference in survival rates between the two groups was statistically significant(χ(2)=4.976, P=0.026). Conclusions: pT3 gallbladder carcinoma could be further subdivided into pT3a stage and pT3b stage based on the TNM criteria of AJCC 8(th) gallbladder carcinoma. Extended radical resection for pT3b gallbladder carcinoma should be further considered after comprehensive assessment of the patient's basic condition and surgical tolerance.


Assuntos
Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Estadiamento de Neoplasias/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
4.
Chin Clin Oncol ; 8(4): 38, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31431034

RESUMO

BACKGROUND: The extent of liver resection for gallbladder cancer (GBC) is still debated. We evaluated the post-operative and oncological outcomes of patients with GBC who underwent liver wedge excision. METHODS: Patients who underwent an upfront radical cholecystectomy (with a liver wedge excision of 2.5- 3 centimetres) from June 2010 to December 2015 were retrospectively analysed. RESULTS: In total, 558 patients underwent surgery for GBC of which 97 cases of primary GBC who underwent upfront radical cholecystectomy were selected. At a median follow up of 47 months, 57.7% of patients were disease free where as 16.5% were alive with disease. Two (2.1%) patients died in postoperative period, 17 (17.5%) patients died of disease, and 6 (6.2%) died of unrelated causes. Eleven patients had loco-regional recurrence and 22 failed at distant sites. Only one patient recurred in the gall bladder bed. Three-year overall survival (OS) of stage II was 86.1% and of stage III was 59.6%. CONCLUSIONS: In our series surgical outcomes of radical cholecystectomy with wedge resection of the liver emphasizes its oncological equivalence compared to formal segment IVb/V excision. Our experience with wedge resection gains significance in the absence of any level I evidence and can prompt a multicentre randomised controlled trial (RCT) in future which may help in standardizing surgery for GBC.


Assuntos
Neoplasias da Vesícula Biliar/cirurgia , Fígado/cirurgia , Adulto , Idoso , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Fígado/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Taxa de Sobrevida
5.
BMC Public Health ; 19(1): 1025, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366338

RESUMO

BACKGROUND: The mortality-to-incidence ratio (MIR) is a marker that reflects the clinical outcome of cancer treatment. MIR as a prognostic marker is more accessible when compared with long-term follow-up survival surveys. Theoretically, countries with good health care systems would have favorable outcomes for cancer; however, no report has yet demonstrated an association between gallbladder cancer MIR and the World's Health System ranking. METHODS: We used linear regression to analyze the correlation of MIRs with the World Health Organization (WHO) rankings and total expenditures on health/gross domestic product (e/GDP) in 57 countries selected according to the data quality. RESULTS: The results showed high crude rates of incidence/mortality but low MIR in more developed regions. Among continents, Europe had the highest crude rates of incidence/mortality, whereas the highest age-standardized rates (ASR) of incidence/mortality were in Asia. The MIR was lowest in North America and highest in Africa (0.40 and 1.00, respectively). Furthermore, favorable MIRs were correlated with good WHO rankings and high e/GDP (p = 0.01 and p = 0.030, respectively). CONCLUSIONS: The MIR variation for gallbladder cancer is therefore associated with the ranking of the health system and the expenditure on health.


Assuntos
Assistência à Saúde/normas , Neoplasias da Vesícula Biliar/epidemiologia , Saúde Global/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Neoplasias da Vesícula Biliar/mortalidade , Produto Interno Bruto/estatística & dados numéricos , Humanos , Incidência , Organização Mundial da Saúde
6.
J Surg Oncol ; 120(4): 603-610, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31292970

RESUMO

BACKGROUND: Gallbladder adenocarcinoma is often incidentally identified following cholecystectomy. We hypothesized that intraoperative bile spillage would be a negative prognostic factor. METHODS: A retrospective review of patients treated at a cancer center with histologically confirmed gallbladder adenocarcinoma, 2009-2017, was performed. Patient, disease, and treatment factors were analyzed in terms of progression-free survival (PFS) and overall survival (OS). RESULTS: Sixty-six patients were identified. Tumor stage was T1 (n = 8, 12%), T2 (n = 23, 35%), T3 (n = 35, 53%). Node stage was N0 (n = 22, 33%), N1+ (n = 26, 39%), Nx (n = 18, 27%). Operations included cholecystectomy alone (n = 27, 36%), cholecystectomy and partial hepatectomy (n = 30, 45%), or hepaticojejunostomy (n = 9, 14%). Median PFS was 7 months (interquartile range [IQR], 2-19); median OS was 16 months (IQR, 10-31). Subset multivariate proportional hazards regression of 41 patients who underwent initial cholecystectomy showed decreased PFS was associated with intraoperative spillage (n = 12, 29%; hazard ratio [HR], 5.5; P = .0014); decreased OS was associated with drain placement (n = 21, 51%; HR, 8.1; P = .006). CONCLUSIONS: Intraoperative bile spillage and surgical drain placement at initial cholecystectomy are negatively associated with PFS and OS in gallbladder adenocarcinoma. Explicit documentation of spillage and drain placement rationale is critical, possibly indicating locally advanced disease and prompting stronger consideration of systemic therapy before definitive resection.


Assuntos
Adenocarcinoma/mortalidade , Bile , Colecistectomia/mortalidade , Neoplasias da Vesícula Biliar/mortalidade , Vesícula Biliar/lesões , Complicações Intraoperatórias/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
7.
Am Surg ; 85(6): 671-675, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31267910

RESUMO

This study aims to provide some experience in diagnosis and treatment of unexpected gallbladder cancer (UGBC) and find the major risk factors. Retrospective data were collected and analyzed on 22 patients who were diagnosed with UGBC during or after laparoscopic cholecystectomy from January 2013 to January 2018 at our hospital. Average age of the patients was (60.2 ± 12.8) years (range, 42-83 years). Among them, there were 6 men and 16 women. Gallbladder stones, atrophic gallbladder, uneven thickened wall of the gallbladder, and choledocholithiasis were found to be the major risk factors. Eight patients (36.4%) were diagnosed intraoperatively. Seven cases (31.8%) were at the T1 stage; of these, three were treated with laparoscopic cholecystectomy; two were converted to cholecystectomy; and two underwent cholecystectomy, lymph node dissection, and liver resection. Eight (36.4%) T2 patients, five (22.7%) T3 patients, and one T4 patient had radical cholecystectomy. Partial cholecystectomy and cholecystotomy were carried out in another T4 patient. T1 patients did not receive chemotherapy or radiotherapy. Eleven had chemotherapy and four received chemoradiotherapy. The follow-up period ranged from six months to five years. The one-year survival rate for T1 to T4 patients was 100 per cent, 75 per cent, 40 per cent, and 0 per cent, respectively. A high index of clinical suspicion of UGBC is needed if one patient suffered from both gallbladder stones and choledocholithiasis with atrophic gallbladder or uneven thickened wall of the gallbladder preoperatively. To avoid more UGBC and reoperation, imaging examinations combined with tumor marker tests and intraoperative histopathologic examination are highly recommended.


Assuntos
Causas de Morte , Colecistectomia Laparoscópica/métodos , Colelitíase/cirurgia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Achados Incidentais , Adulto , Fatores Etários , Idoso , Colecistectomia Laparoscópica/efeitos adversos , Colelitíase/diagnóstico por imagem , Bases de Dados Factuais , Feminino , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Incidência , Complicações Intraoperatórias/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Prognóstico , Reoperação/métodos , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Análise de Sobrevida
8.
Br J Surg ; 106(9): 1216-1227, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31259388

RESUMO

BACKGROUND: Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade. METHODS: Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007-2011 and 2012-2016) to evaluate changes over time. RESULTS: In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36·9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12·4 versus 44·1 months for pT2, and 9·7 versus 23·0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32·2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0·030). CONCLUSION: Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival.


Assuntos
Neoplasias da Vesícula Biliar/diagnóstico , Achados Incidentais , Idoso , Colecistectomia/estatística & dados numéricos , Feminino , Vesícula Biliar/patologia , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Sistema de Registros , Análise de Sobrevida , Suécia/epidemiologia
9.
J Exp Clin Cancer Res ; 38(1): 247, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182136

RESUMO

BACKGROUND: Gallbladder cancer (GBC) is an extremely malignant tumor with a high mortality rate. Little is known about its invasion and metastasis mechanism so far. METHODS: To identify the driver genes in GBC metastasis, we performed a mRNA microarray of metastatic GBC and paired non-tumor samples, and found PLEK2 was markedly upregulated in GBC tissues. Next, the expression of PLEK2 in GBC were examined in a larger cohort of patients by qRT-PCR, western blot and IHC staining. The clinicopathologic correlation of PLEK2 was determined by statistical analyses. The biological involvement of PLEK2 in GBC metastasis and the underlying mechanisms were investigated. RESULTS: In this study, we found that PLEK2 had higher expression in GBC tumor tissues compared to non-cancerous adjacent tissues and cholecystolithiasis tissues. The clinicopathologic analyses showed PLEK2 expression was positively correlated with tumor TNM stage, distant metastasis and PLEK2 was an independent predictor of overall survival (OS) in GBC patients. The cellular function assays showed PLEK2 promoted GBC cells migration, invasion and liver metastasis in mouse model via the regulation of epithelial-mesenchymal transition (EMT) process. Our mass spectrum and co-immunoprecipitation (co-IP) assays demonstrated that PLEK2 could interact with the kinase domain of EGFR and suppress EGFR ubiquitination mediated by c-CBL, leading to constitutive activation of EGFR signaling. Furthermore, RNA-sequencing and qRT-PCR results demonstrated chemokine (C-C motif) ligand 2 (CCL2), a target gene downstream of PLEK2/EGFR signaling, mediated the motility-promoting function of PLEK2. CONCLUSIONS: On the basis of these collective data, we propose that PLEK2 promotes the invasion and metastasis of GBC by EGFR/CCL2 pathway and PLEK2 can serve as a potential therapeutic target for GBC treatment.


Assuntos
Quimiocina CCL2/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/patologia , Proteínas de Membrana/metabolismo , Transdução de Sinais , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Receptores ErbB/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Ligação Proteica
10.
Anticancer Res ; 39(6): 3095-3100, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177154

RESUMO

BACKGROUND/AIM: To retrospectively evaluate the outcome of patients with unresectable biliary cholangiocarcinoma (CC) treated with radiotherapy (RT) plus/minus chemotherapy (CHT). MATERIALS AND METHODS: Data of patients with intrahepatic CC (ICC), Klatskin's tumor (KT), distal extrahepatic CC (ECC), and gallbladder cancer (GBC) diagnosed from 1991 to 2017 were retrospectively analyzed. The treatment was mainly based on RT plus concurrent CHT +/- brachytherapy (BRT) boost. The Kaplan-Meier method was used to calculate survival curves that were compared using the log-rank test. RESULTS: Seventy-six patients were included in this analysis (males: 59%; females: 41%; median age: 66.5 years). A minority of patients (7.9%) were treated for disease recurrence after surgery. According to TNM, 78.5% of patients had T stage >3 and 77.6% of patients were treated with concurrent CHT-RT while 22.3% received RT followed by sequential CHT. Median RT dose was 50 Gy (range: 16-75 Gy) delivered with conventional fractionation. CHT was based on Gemcitabine or 5-fluorouracil. BRT was prescribed to 51.3% of patient with a median dose of 14 Gy. Reported Grade ≥3 acute GI and hematological toxicity were 13.2% and 8.1%, respectively. No other severe acute toxicities were reported. One- and 2-year overall survival (OS) were 58.1% and 25.8%, respectively (median: 13.5 months), while 1- and 2-year progression-free survival (PFS) were 43.4% and 9.4%, respectively. None of the following variables had a significant impact on OS and PFS: BRT boost, tumor site, concurrent CHT, and the drugs used in concurrent CHT. In contrast, patients receiving RT with 2D technique showed a PFS significantly higher compared to patients treated with the 3D technique (median: 15.5 vs. 8.5 months; p=0.02). CONCLUSION: Combined modality treatment (RT+CHT±BRT) in unresectable biliary cancer was associated with acceptable toxicity and OS comparable to the actual standard treatment (CHT). The significantly improved PFS in patients undergoing 2D-RT raises doubts regarding the adequacy of target delineation in these neoplasms.


Assuntos
Neoplasias dos Ductos Biliares/terapia , Braquiterapia , Quimiorradioterapia , Colangiocarcinoma/terapia , Neoplasias da Vesícula Biliar/terapia , Tumor de Klatskin/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Braquiterapia/efeitos adversos , Braquiterapia/mortalidade , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/mortalidade , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fracionamento da Dose de Radiação , Feminino , Fluoruracila/administração & dosagem , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Tumor de Klatskin/mortalidade , Tumor de Klatskin/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
11.
Virchows Arch ; 475(1): 59-66, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31177317

RESUMO

Sarcomatoid carcinomas recently came into the spotlight through genetic profiling studies and also as a distinct model of epithelial-mesenchymal transition. The literature on sarcomatoid carcinomas of gallbladder is limited. In this study, 656 gallbladder carcinomas (GBC) were reviewed. Eleven (1.7%) with a sarcomatoid component were identified and analyzed in comparison with ordinary GBC (O-GBC). Patients included 9 females and 2 males (F/M = 4.5 vs. 3.9) with a mean age-at-diagnosis of 71 (vs. 64). The median tumor size was 4.6 cm (vs. 2.5; P = 0.01). Nine patients (84%) presented with advanced stage (pT3/4) tumor (vs. 48%). An adenocarcinoma component constituting 1-75% of the tumor was present in nine, and eight had surface dysplasia/CIS; either in situ or invasive carcinoma was present in all cases. An intracholecystic papillary-tubular neoplasm was identified in one. Seven showed pleomorphic-sarcomatoid pattern, and four showed subtle/bland elongated spindle cells. Three had an angiosarcomatoid pattern. Two had heterologous elements. One showed few osteoclast-like giant cells, only adjacent to osteoid. Immunohistochemically, vimentin, was positive in six of six; P53 expression was > 60% in six of six, keratins in six of seven, and p63 in two of six. Actin, desmin, and S100 were negative. The median Ki67 index was 40%. In the follow-up, one died peri-operatively, eight died of disease within 3 to 8 months (vs. 26 months median survival for O-GBC), and two were alive at 9 and 15 months. The behavior overall was worse than ordinary adenocarcinomas in general but was not different when grade and stage were matched. In summary, sarcomatoid component is identified in < 2% of GBC. Unlike sarcomatoid carcinomas in the remainder of pancreatobiliary tract, these are seldom of the "osteoclastic" type and patients present with large/advanced stage tumors. Limited data suggests that these tumors are aggressive with rapid mortality unlike pancreatic osteoclastic ones which often have indolent behavior.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Carcinoma in Situ/patologia , Neoplasias da Vesícula Biliar/patologia , Neoplasias Complexas Mistas/patologia , Sarcoma/patologia , Adenocarcinoma/química , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Idoso , Carcinoma in Situ/química , Carcinoma in Situ/mortalidade , Carcinoma in Situ/cirurgia , Feminino , Neoplasias da Vesícula Biliar/química , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Complexas Mistas/química , Neoplasias Complexas Mistas/mortalidade , Neoplasias Complexas Mistas/cirurgia , Sarcoma/química , Sarcoma/mortalidade , Sarcoma/cirurgia , Fatores de Tempo , Resultado do Tratamento
12.
Acta Med Okayama ; 73(3): 241-246, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31235972

RESUMO

Gallbladder carcinoma (GBC) is a common malignancy with a poor prognosis. With the average life expectancy increasing globally, the incidence of GBC is predicted to increase as well. We investigated the safety and feasibility of surgical treatment for elderly patients with GBC. We retrospectively compared clinical pathological data and treatment outcomes in 45 consecutive GBC patients (23 patients ≥ 75 years [elderly group] and 22 patients < 75 years [younger group]) who underwent curative resection at the Iwakuni Center from January 2008 to December 2017. The proportion of preoperative comorbidities and anticoagulant use was significantly higher in the elderly group. The American Society of Anesthesiologists score was higher in the elderly versus the younger group, and the elderly group had significantly shorter operation times. Reduced activities of daily living was more common in the elderly versus younger group. The percentage of radical resection and overall 3-year survival (66.6% younger vs. 64.4% elderly) were similar between the groups. Controlling Nutritional Status (CONUT) score ≥ 3 and R0 resection were identified as prognostic factors for overall survival rate among all patients. After careful patient selection.


Assuntos
Neoplasias da Vesícula Biliar/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prognóstico , Taxa de Sobrevida
13.
Cir Cir ; 87(3): 313-320, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31135772

RESUMO

Objective: To describe the results of the extension of surgical treatment and adjuvant chemotherapy (ACT) in incidental gallbladder cancer (CVB), in terms of postoperative morbidity (POM) and 5-year overall survival rate. Method: Case series of patients operated on for incidental GBC in Clínica Mayor, Temuco, Chile (2001-2016). All cases were treated by partial hepatectomy (segments IVb and V), and regional lymphadenectomy. The minimum follow-up time was 12 months. Outcome variables were MPO and 5-year overall survival rate. Other variables of interest were: infiltration depth in vesicular wall, lymph nodes and resected liver; surgical time, need for reoperation, hospital stay, follow-up and mortality. Descriptive statistics were applied as well as bivariate analysis applying Fisher's exact and t-test and non-parametrical tests for continuous variables and Kaplan Meier curves. Results: The series was composed of 50 patients, whose average age was 58.6 ± 9.6 years; 68.0% of which were women. The mean surgical time and hospital stay were 224 ± 93 min (90 to 480) and 6.9 ± 2.9 days (4 to 20), respectively. POM was 28.0%. 5-year overall survival rate was 47%. There were no reoperations or mortality. Conclusions: The results verified in terms of POM and 5-year overall survival rate are similar to previously reported series.


Assuntos
Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/cirurgia , Idoso , Quimioterapia Adjuvante , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Taxa de Sobrevida , Resultado do Tratamento
14.
Medicine (Baltimore) ; 98(8): e14550, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813165

RESUMO

The neutrophil-lymphocyte ratio (NLR) is an immune response-related indicator and it is associated with poor prognosis of various cancers. The carbohydrate antigen19-9 (CA19-9) is a tumor-associated antigen and it has prognostic relevance in gallbladder carcinoma (GBC). We aimed to analyze whether preoperative NLR and serum CA19-9 were associated with outcomes of GBC patients after surgery with curative intent.Between January 2010 and May 2015, 90 resectable GBC patients who underwent curative surgery in our institution were included. All final diagnoses were confirmed by pathologic examination. The demographics, clinical, and histopathology data were analyzed. The Cox regression proportional hazard model and Kaplan-Meier method were used to assess prognostic factors.The cutoff values of 4.33 and 250.90 U/mL were defined as high NLR and high CA19-9, respectively. The univariate analyses showed that TNM stage, lymph node metastasis, the degree of tumor differentiation, margin status, combined hepatectomy, CA19-9, NLR, and PNI were all associated with overall survival (P < .05). According to the multivariable analysis, NLR (hazard ratio (HR) 3.840, 95% confidence interval (95% CI): 2.122-6.947, P < .001), CA19-9 (HR 2.230, 95% CI: 1.297-3.835, P = .004), TNM stage (HR 3.864, 95% CI: 1.819-8.207, P < .001), lymph node metastasis (HR 1.679, 95% CI: 1.005-2.805, P = .048), and margin status (HR 1.873, 95% CI: 1.063-3.300, P = .030) were independent prognostic factors. The median survival time in low NLR and CA19-9 group was better than high NLR and CA19-9 group (P < .05).The preoperative NLR and serum CA19-9 are associated with prognosis of patients with GBC. High NLR and high CA19-9 were predictors of poor long-term outcome among patients with GBC undergoing curative surgery.


Assuntos
Antígeno CA-19-9/sangue , Neoplasias da Vesícula Biliar/sangue , Contagem de Linfócitos/métodos , Neutrófilos/patologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
15.
Surg Technol Int ; 34: 101-106, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30888678

RESUMO

Neuroendocrine carcinoma (NEC) of the gallbladder is highly aggressive and has a poor prognosis even after curative resection. The purpose of this study was to collate and analyze published data to clarify the surgical outcome of NEC of the gallbladder and the relationships between potential prognostic factors and survival after surgery. We surveyed worldwide literature from 1981 to 2018 and obtained clinicopathological data for 65 patients who had undergone surgical resection for NEC of the gallbladder. The relationships between potential prognostic factors and survival rates were examined by the Kaplan-Meier method and the log-rank test. The 1-, 3-, and 5-year disease-specific survival rates after surgery were 70.2%, 39.3%, and 29.5%, respectively. A multivariate analysis revealed that the factors that were independently associated with poor outcomes after surgery in patients with NEC of the gallbladder were older age, higher pathologic T stage, and positive lymph node metastasis. The major sites of recurrence were the liver, lung, lymph node, and local recurrence. The median time to the event for recurrence was 4.0 months. Even when curative resection was achieved, 36.9% of patients exhibited recurrence within 12 months after curative resection of gallbladder NEC. Although NEC of the gallbladder remains a rare disease worldwide, its poor prognosis, even after curative resection, demands further epidemiological and pathological studies that could lead to the development of new management strategies.


Assuntos
Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Recidiva Local de Neoplasia/mortalidade , Carcinoma Neuroendócrino/mortalidade , Neoplasias da Vesícula Biliar/mortalidade , Humanos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
16.
Mol Cancer ; 18(1): 33, 2019 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-30825877

RESUMO

BACKGROUND: The long non-coding RNA PVT1 (lncRNA PVT1) has been reported to act as an oncogenic regulator of several cancers. However, its expression and function in gallbladder cancer (GBC) remain largely unknown. METHODS: In situ hybridization (ISH) and quantitative real-time PCR (qPCR) were performed to detect the expression of PVT1 and miR-143 in GBC tissues and cell lines. Immunohistochemistry (IHC) assays were performed to assess the expression of the hexokinase 2 (HK2) protein. The relationships among PVT1, miR-143 and HK2 were evaluated using dual-luciferase reporter, RNA immunoprecipitation (RIP) and biotin pull-down assays. The biological functions of PVT1, miR-143 and HK2 in GBC cells were explored with cell counting kit 8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation, transwell, wound healing and glucose metabolism assays in vitro. For in vivo experiments, a xenograft model was used to investigate the effects of PVT1 and HK2 on GBC. RESULTS: PVT1 was upregulated in GBC tissues and cells and was positively associated with malignancies and worse overall survival. PVT1 knockdown inhibited cell proliferation, migration, and invasion in vitro and restrained tumor growth in vivo. Further studies demonstrated that PVT1 positively regulated HK2 expression via its competing endogenous RNA (ceRNA) activity on miR-143. Additionally, HK2 expression and function were positively correlated with PVT1. Furthermore, we observed that the PVT1/miR-143/HK2 axis promoted cell proliferation and metastasis by regulating aerobic glucose metabolism in GBC cells. CONCLUSIONS: The results of our study reveal a potential ceRNA regulatory pathway in which PVT1 modulates HK2 expression by competitively binding to endogenous miR-143 in GBC cells, which may provide new insights into novel molecular therapeutic targets for GBC.


Assuntos
Carcinoma/genética , Neoplasias da Vesícula Biliar/genética , Regulação Neoplásica da Expressão Gênica , Hexoquinase/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Adolescente , Adulto , Animais , Carcinoma/metabolismo , Carcinoma/mortalidade , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Neoplasias da Vesícula Biliar/metabolismo , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Glucose/metabolismo , Glicólise/genética , Hexoquinase/metabolismo , Humanos , Metástase Linfática , Masculino , Camundongos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Redox Biol ; 22: 101149, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30822690

RESUMO

Gallbladder cancer (GBC) is a highly malignant bile duct cancer with poor prognosis characterized by its insensitivity to chemotherapy. Emerging evidence indicates that cytoprotective antioxidation is involved in drug resistance of various cancers; however, the underlying molecular mechanisms remain obscure. Here, we demonstrated that atypical protein kinase Cι (aPKCι) mediated reactive oxygen species (ROS) inhibition in a kinase-independent manner, which played a crucial role in tumorigenesis and chemoresistance. Mechanistically, we found that aPKCι facilitated nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation, nuclear translocation and activated its target genes by competing with Nrf2 for binding to Kelch-like ECH-associated protein 1 (Keap1) through a highly conserved DLL motif. In addition, the aPKCι-Keap1 interaction was required for antioxidant effect, cell growth and gemcitabine resistance in GBC. Importantly, we further confirmed that aPKCι was frequently upregulated and correlated with poor prognosis in patients with GBC. Collectively, our findings suggested that aPKCι positively modulated the Keap1-Nrf2 pathway to enhance GBC growth and gemcitabine resistance, implying that the aPKCι-Keap1-Nrf2 axis may be a potential approach to overcome the drug resistance for the treatment of GBC.


Assuntos
Transformação Celular Neoplásica/metabolismo , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Vesícula Biliar/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína Quinase C/metabolismo , Animais , Antioxidantes/metabolismo , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Modelos Animais de Doenças , Feminino , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/etiologia , Neoplasias da Vesícula Biliar/mortalidade , Técnicas de Silenciamento de Genes , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/química , Camundongos , Modelos Biológicos , Fator 2 Relacionado a NF-E2/química , Prognóstico , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
18.
J Surg Oncol ; 119(8): 1099-1107, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30864246

RESUMO

BACKGROUND: The aim of the current study was to identify the minimum number and the optimal range of lymph nodes (LNs) to be examined among patients with gallbladder cancer (GBC). METHODS: Between January 1, 2004, and December 31, 2015, patients with a diagnosis of GBC were identified in the National Cancer Database. A machine-based learning approach was used to identify the minimum number and range of LNs to evaluate relative to long-term outcomes. RESULTS: Among 6531 patients with GBC, median number of LNs evaluated was 2 (IQR:1-5); only 21.1% (n = 1376) of patients had 6 or more LNs evaluated. The median number of metastatic LNs was 0 (IQR: 0-1). On multivariable analysis, evaluation of < 4 LNs was associated with a higher hazard of death (referent 4-7 LNs: < 4 LNs, HR = 1.27, 95% CI, 1.16-1.40; P < 0.001), whereas, patients who had 4 to 7 LNs and > 7 LNs evaluated had comparable long-term mortality risk (HR = 1.10, 95%CI, 0.98-1.24; P = 0.11). There was no difference in the proportion of patients who had at least one metastatic LN identified per T category based on total number of nodes resected (all P > 0.05). CONCLUSION: The overwhelming majority of patients did not have the American Joint Committee on Cancer (AJCC) recommended 6 total LN count . A machine-based learning approach identified evaluation of 4 to 7 LNs as the LN number associated with optimal staging and survival. While obtaining 6 LNs may be challenging, evaluation of at least 4 LNs may be a more appropriate threshold as this cut-off value was associated with optimal patient outcomes and staging.


Assuntos
Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Idoso , Bases de Dados Factuais , Feminino , Neoplasias da Vesícula Biliar/patologia , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Excisão de Linfonodo/normas , Metástase Linfática , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estados Unidos/epidemiologia
19.
Br J Surg ; 106(5): 626-635, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30762874

RESUMO

BACKGROUND: The indications for major hepatectomy for gallbladder cancer either with or without pancreatoduodenectomy remain controversial. The clinical value of these extended procedures was evaluated in this study. METHODS: Patients who underwent major hepatectomy for gallbladder cancer between 1996 and 2016 were identified from a prospectively compiled database. Postoperative outcomes and overall survival were compared between patients undergoing major hepatectomy alone or combined with pancreatoduodenectomy (HPD). RESULTS: Seventy-nine patients underwent major hepatectomy alone and 38 patients had HPD. The patients who underwent HPD were more likely to have T4 disease (P < 0·001), nodal metastasis (P = 0·015) and periaortic nodal metastasis (P = 0·006), but were less likely to receive adjuvant therapy (P = 0·006). HPD was associated with a high incidence of grade III or higher complications (P = 0·002) and death (P = 0·037). Overall survival was longer in patients who underwent major hepatectomy alone than in patients who underwent HPD (median survival time 32 versus 10 months; P < 0·001). In multivariable analysis, surgery in the early period (1996-2006) (P = 0·002), pathological T4 disease (P = 0·005) and distant metastasis (P < 0·001) were associated with shorter overall survival, and cystic duct tumour (P = 0·002) with longer overall survival. CONCLUSION: Major hepatectomy alone for gallbladder cancer contributes to favourable overall survival with low morbidity and mortality, whereas HPD is associated with poor overall survival and high morbidity and mortality rates. HPD may eradicate locally spreading gallbladder cancer; however, the indication for the procedure is questioned from an oncological viewpoint.


Assuntos
Neoplasias da Vesícula Biliar/cirurgia , Hepatectomia , Pancreaticoduodenectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Hepatectomia/efeitos adversos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias , Estudos Retrospectivos , Análise de Sobrevida
20.
J Surg Res ; 234: 269-276, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30527484

RESUMO

BACKGROUND: Preliminary study on the feasibility and efficacy of laparoscopic cholecystectomy and radical cholecystectomy in stage Tis-T3 gallbladder cancer (GBC). METHODS: Retrospective analysis of the clinical data of 102 patients with GBC from August 2008 to August 2017 in the Department of Hepatopancreatobiliary Surgery at the Third Affiliated Hospital of Soochow University. The clinical and pathological data of laparoscopic surgery and open surgery were compared. RESULTS: Of 102 patients with GBC, 41 underwent laparoscopic treatment, 12 of whom underwent laparoscopic cholecystectomy, and the others underwent laparoscopic radical cholecystectomy/extended radical cholecystectomy. Sixty-one patients underwent radical cholecystectomy/extended radical cholecystectomy. Based on the individual patient's condition, excision of the extrahepatic biliary tract and cholangioenterostomy were performed. There were no perioperative deaths. There was no significant difference in the operative blood loss (P = 0.732), operative time (P = 0.058), postoperative complications (P = 0.933), R0 margins (P = 0.679), and tumor-related death (P = 0.396) between the laparoscopic group and the laparotomy group. The postoperative activity time (P < 0.001), postoperative eating time (P < 0.001), drainage tube removal time (P < 0.001), and postoperative hospital discharge time (P < 0.001) in the laparoscopic group were all earlier than those in the laparotomy group, and the difference was statistically significant. The number of lymph nodes resected in the laparoscopic group and the laparotomy group was 1-17, average (5 ± 3) and 1-13 average (5 ± 3), respectively, with no statistically significant difference (P = 0.973). The 1-, 3-, and 5-y survival rates in the laparoscopic group were 97.1%, 69.4%, and 51.9%, respectively, and those in the laparotomy group were 94.7%, 64.9%, and 55.7%, respectively; there were no significant difference between the two groups (P = 0.453). In terms of different pathologic T stages, the 5-y survival rates of patients with stage Tis (9 cases), T1a (2 cases), T1b (8 cases), T2 (14 cases), and T3 (8 cases) disease in the laparoscopic group were 100%, 100%, 75%, 48.1%, and 12.5%, respectively, and the 5-y survival rates in patients with stage Tis (4 cases), T1b (9 cases), T2 (32 cases), and T3 (16 cases) disease in the laparotomy group were 100%, 87.5%, 64.7%, and 16%, respectively; there were no significant differences between the two groups. CONCLUSIONS: Laparoscopic treatment of stage Tis-T3 GBC is feasible. Laparoscopic treatment of GBC does not increase the incision metastasis rate on the basis of the intact gallbladder wall. The same survival rates can be achieved with laparoscopic treatment as with open treatment of GBC. In terms of postoperative rehabilitation, laparoscopic treatment has more advantages.


Assuntos
Adenocarcinoma/cirurgia , Adenoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Colecistectomia/métodos , Neoplasias da Vesícula Biliar/cirurgia , Laparoscopia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenoma/mortalidade , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Estudos de Viabilidade , Feminino , Seguimentos , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
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