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1.
Langenbecks Arch Surg ; 404(7): 831-840, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31748872

RESUMO

PURPOSE: Total pancreatectomy may improve symptoms in patients with severe end-stage chronic pancreatitis. This might be achieved whilst preserving both the duodenum- and spleen-(DPSPTP). Mature clinical outcomes of this approach are presented. METHODS: Single-centre prospective cohort study performed between September 1996 and May 2016. Demographic, clinical details, pain scores and employment status were prospectively recorded during clinic attendance. RESULTS: Fifty-one patients (33 men, 18 women) with a median (interquartile range) age of 40.8 (35.3-49.4) years, a median weight of 69.8 (61.0-81.5) Kg and a median body mass index of 23.8 (21.5-27.8), underwent intended duodenum-and spleen-preserving near-total pancreatectomy for end-stage chronic pancreatitis. Aetiology was excess alcohol in 25, idiopathic (no mutation) in 15, idiopathic (SPINK-1/CFTR mutations) in two, hereditary (PRSS1 mutation) in seven and one each post-necrotising pancreatitis and obstructive pancreatic duct divisum in 1. The main indication for surgery was severe pain. Findings included parenchymal calcification in 79% and ductal calculi in 24%, a dilated main pancreatic duct in 57% and a dilated main bile duct in 17%, major vascular involvement in 27% and pancreato-peritoneal fistula in 2%. Postoperative complications occurred in 20 patients with two deaths. Median pain scores were 8 (7-8) preoperatively and 3 (0.25-5.75) at 5 years (p = 0.013). Opiate analgesic use was significantly reduced postoperatively (p = 0.048). Following surgery, 22 (63%) of 38 patients of working age re-entered employment compared with 12 (33%) working preoperatively (p = 0.016). CONCLUSION: Duodenum-and spleen-preserving near-total pancreatectomy provided long-term relief in adult patients with intractable chronic pancreatitis pain, with improved employment prospects.


Assuntos
Duodeno/cirurgia , Cuidados Paliativos/métodos , Pancreatectomia/métodos , Pancreatite Crônica/cirurgia , Baço/cirurgia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/diagnóstico , Estudos Prospectivos , Resultado do Tratamento
2.
Langenbecks Arch Surg ; 404(4): 439-449, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30972486

RESUMO

INTRODUCTION: There is limited published evidence on duodenal carcinoma due to its rarity. This study aimed to evaluate gastric outlet obstruction and obstructive jaundice along with pathological variables as survival factors in patients with duodenal adenocarcinoma following resection. METHODS: Survival factor analysis was undertaken in patients undergoing duodenal cancer surgery from 1997 to 2015 in a single centre. RESULTS: There were 57 patients of whom 18 had gastric outlet obstruction and 14 had obstructive jaundice. Fifty-three had a partial pancreatoduodenectomy and four had palliative bypass. Perioperative mortality and morbidity were 4% (2/53) and 47% (25/53) respectively in resected patients. With a median (95% confidence interval, CI) follow-up of 72 (57-86) months, median overall and recurrence-free survival was 38 months (95% CI 28-113) and 27 months (95% CI 18-83) respectively. The 1 and 3-year overall survival rates were 84% (95% CI 74-95) and 52% (95% CI 39-69) respectively. Median overall survival was 19 months in patients with gastric outlet obstruction vs 53 months in those without (p = 0.026) and 28 months in patients with obstructive jaundice vs 38 months in those without (p = 0.611). Univariate analysis revealed that tumour stage, resection margin status, pre-operative albumin status, gastric outlet obstruction and age were associated with poorer overall and recurrence-free survival but multivariate analysis confirmed only tumour stage and resection margin status to be significant. CONCLUSION: Whereas gastric outlet obstruction in duodenal cancer appeared to be an important survival factor following partial pancreatoduodenectomy, multivariate analysis showed that only tumour stage and resection margin status were the key independent survival factors. Further multicentre studies are required to elucidate further characteristics of duodenal carcinoma and develop neoadjuvant/adjuvant management strategies.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias Duodenais/patologia , Neoplasias Duodenais/cirurgia , Pancreaticoduodenectomia , Idoso , Feminino , Obstrução da Saída Gástrica/patologia , Obstrução da Saída Gástrica/cirurgia , Humanos , Icterícia Obstrutiva/patologia , Icterícia Obstrutiva/cirurgia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
3.
World J Surg ; 43(6): 1604-1611, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30815742

RESUMO

BACKGROUND: Autoimmune pancreatitis (AIP) is an uncommon form of chronic pancreatitis. Whilst being corticosteroid responsive, AIP often masquerades radiologically as pancreatic neoplasia. Our aim is to appraise demographic, radiological and histological features in our cohort in order to differentiate AIP from pancreatic malignancy. METHODS: Clinical, biochemical, histological and radiological details of all AIP patients 1997-2016 were analysed. The initial imaging was re-reviewed according to international guidelines by three blinded independent radiologists to evaluate features associated with autoimmune pancreatitis and pancreatic cancer. RESULTS: There were a total of 45 patients: 25 in type 1 (55.5%), 14 type 2 (31.1%) and 6 AIP otherwise not specified (13.3%). The median (IQR) age was 57 (51-70) years. Thirty patients (66.6%) were male. Twenty-six patients (57.8%) had resection for suspected malignancy and one for symptomatic chronic pancreatitis. Three had histologically proven malignancy with concurrent AIP. Two patients died from recurrent pancreatic cancer following resection. Multidisciplinary team review based on radiology and clinical history dictated management. Resected patients (vs. non-resected group) were older (64 vs. 53, p = 0.003) and more frequently had co-existing autoimmune pathologies (22.2 vs. 55.6%, p = 0.022). Resected patients also presented with less classical radiological features of AIP, which are halo sign (0/25 vs. 3/17, p = 0.029) and loss of pancreatic clefts (18/25 vs. 17/17, p = 0.017). There were no differences in demographic features other than age. CONCLUSION: Despite international guidelines for diagnosing AIP, differentiation from pancreatic cancer remains challenging. Resection remains an important treatment option in suspected cancer or where conservative treatment fails.


Assuntos
Doenças Autoimunes/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/diagnóstico , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Doenças Autoimunes/terapia , Biomarcadores/sangue , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Pancreatite Crônica/terapia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
4.
Am J Gastroenterol ; 114(1): 155-164, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30353057

RESUMO

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.


Assuntos
Carcinoma/epidemiologia , Predisposição Genética para Doença , Neoplasias Pancreáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/genética , Carcinoma/patologia , Estudos de Coortes , Detecção Precoce de Câncer , Europa (Continente)/epidemiologia , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Linhagem , Sistema de Registros , Fatores de Risco , Adulto Jovem
5.
Br J Cancer ; 118(7): 947-954, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29515256

RESUMO

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Humanos , Imuno-Histoquímica , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida , Análise Serial de Tecidos , Gencitabina
6.
Br J Cancer ; 118(8): 1084-1088, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29523831

RESUMO

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.


Assuntos
Adenocarcinoma/tratamento farmacológico , Biomarcadores Tumorais/metabolismo , DCMP Desaminase/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia Adjuvante , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Pancreatectomia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ribonucleosídeo Difosfato Redutase , Análise Serial de Tecidos
7.
Br J Surg ; 104(4): 328-336, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28199010

RESUMO

BACKGROUND: Human equilibrative nucleoside transporters (hENTs) are transmembranous proteins that facilitate the uptake of nucleosides and nucleoside analogues, such as gemcitabine, into the cell. The abundance of hENT1 transporters in resected pancreatic ductal adenocarcinoma (PDAC) might make hENT1 a potential biomarker of response to adjuvant chemotherapy. The aim of this study was to see whether hENT1 expression, as determined by immunohistochemistry, was a suitable predictive marker for subsequent treatment with gemcitabine-based adjuvant chemotherapy. METHODS: A systematic review was performed, searching databases from January 1997 to January 2016. Articles pertaining to hENT1 immunohistochemical analysis in resected PDAC specimens from patients who subsequently underwent adjuvant gemcitabine-based chemotherapy were identified. Eligible studies were required to contain survival data, reporting specifically overall survival (OS) and disease-free survival (DFS) with associated hazard ratios (HRs) stratified by hENT1 status. RESULTS: Of 42 articles reviewed, eight were suitable for review, with seven selected for quantitative meta-analysis. The total number of patients included in the meta-analysis was 770 (405 hENT1-negative, 365 hENT1-positive). Immunohistochemically detected hENT1 expression was significantly associated with both prolonged DFS (HR 0·58, 95 per cent c.i. 0·42 to 0·79) and OS (HR 0·52, 0·38 to 0·72) in patients receiving adjuvant gemcitabine but not those having fluoropyrimidine-based adjuvant therapy. CONCLUSION: Expression of hENT1 is a suitable prognostic biomarker in patients undergoing adjuvant gemcitabine-based chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Transportador Equilibrativo 1 de Nucleosídeo/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidade , Quimioterapia Adjuvante , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Gencitabina
8.
Eur J Surg Oncol ; 42(10): 1548-51, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27546012

RESUMO

INTRODUCTION: Indicative numbers for completion of training (CCT) in the UK requires 35 upper Gastrointestinal/Hepatobiliary resections and 110 (50 non HPB trainees) cholecystectomies. We aim to identify whether the training experience in our centre meets the CCT requirements for hepatobiliary surgery and compare training opportunities to those in international fellowships. METHODS: We retrospectively reviewed our hospital's operating theatre database for all patients undergoing a liver or gallbladder resection between January 2008 and July 2015 using corresponding procedural codes and consultant name. The cohort was categorized based on case and primary operating surgeon. The training grade of the surgeon was split into junior registrar (ST3/5), senior registrar (ST6/8) and senior fellow (post-CCT). RESULTS: Over a 7.5 year period we performed 2301 hepatobiliary procedures. The senior fellows and senior registrars performed a median of 42 liver resections (range 15-94) and 77 (range 35-110) cholecystectomies as the primary operator in any given 12 month period. The academic output for the unit was 104 over this period, with a median publication rate of 1.34 papers/trainee in any given 12 months. 15/16 senior fellow/senior registrars went on to secure substantive hepatobiliary consultant posts. CONCLUSIONS: Our centre delivers in excess of the required operative volume and clinical competencies for CCT in Hepatobiliary surgery in a 12 month period and exposure of trainees to operative experience is commensurate to the best performing international fellowships.


Assuntos
Colecistectomia/educação , Hepatectomia/educação , Avaliação Educacional , Bolsas de Estudo , Humanos , Estudos Retrospectivos
9.
J Surg Oncol ; 109(6): 542-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24357463

RESUMO

AIM: To determine the outcome of patients that underwent liver resection for metastases from uveal melanoma. METHODS: Over a 9-year period, patients referred with uveal melanoma metastases were included. Following treatment of primary uveal melanoma, high-risk patients were offered to be enrolled into a 6-monthly non-contrast liver magnetic resonance imaging (MRI) surveillance. Following detection of liver metastases, patients were staged with a contrast-enhanced (Primovist(®)) liver MRI, computer tomography (CT) of the thorax and staging laparoscopy. RESULTS: 155 patients were referred with uveal melanoma liver metastases, of which 17 (11.0%) patients had liver resection and one patient was treated with percutaneous radio-frequency ablation. The majority of patients undergoing liver resection were treated with multiple metastectomies (n = 8) and three patients had major liver resections. The overall median survival for patients treated with surgery/ablation was 27 (14-90) months, and this was significantly better compared to patients treated palliatively [median = 8(1-30) months, P < 0.001]. Following surgery, 11 patients had recurrent disease [median = 13(6-36) months]. Patients who had undergone a major liver resection had a significantly poorer disease-free survival (P = 0.037). CONCLUSIONS: Patients who can undergo surgical resection for metastatic uveal melanoma have a more favorable survival compared to those who do not.


Assuntos
Hepatectomia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Melanoma/mortalidade , Melanoma/cirurgia , Neoplasias Uveais/patologia , Adulto , Idoso , Ablação por Cateter , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Laparoscopia , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética , Masculino , Melanoma/patologia , Melanoma/secundário , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias/métodos , Cuidados Paliativos , Vigilância da População , Radiografia Torácica , Tomografia Computadorizada por Raios X
10.
Int J Surg ; 11(10): 1078-82, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24129124

RESUMO

AIMS: The aims of this study were to assess the outcomes of patients who underwent potentially curative hepatic resection for hepatocellular carcinoma (HCC) in a background of non-cirrhotic/non-fibrotic livers, and to determine prognostic factors that influenced survival. METHODS: Over a 15-year period, all patients undergoing hepatectomy for HCC were identified. Collated data included demographics, laboratory analysis, operative findings and histo-pathological data. Survival differences between these factors following liver resection were determined. RESULTS: 57 patients were included with a median age of 70 years. The majority of patients underwent a hemi-hepatectomy or more radical resection (n = 37). Overall R0 resection rate was 90.4% (n = 51). The overall morbidity and mortality rates were 26.3% and 3.5%, respectively. The median follow-up period was 28 months. The 1-, 3- and 5- year disease-free survival was 65.4%, 41.8% and 39.1%, and the overall survival was 73.5%, 49.6% and 39.5%, respectively. AFP (p = 0.039) was the only predictor of poorer disease-free survival on univariate analysis. On multi-variable analysis, poorly differentiated tumour and large tumour size were independent predictors of overall survival. CONCLUSIONS: Liver resection is a feasible treatment option for HCC in non-cirrhotic/non-fibrotic livers with good survival outcome. Tumour size and differentiation are adverse predictors of outcome in these patients.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Estudos de Casos e Controles , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
11.
Cancer Chemother Pharmacol ; 72(2): 359-68, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23756919

RESUMO

PURPOSE: The response of colorectal liver metastases to the cytotoxic agent irinotecan varies widely. Attempts to correlate tumour metabolism with response have been mixed. This study investigated the hepatic metabolism of irinotecan as a potential predictor of tumour response to irinotecan-eluting beads (DEBIRI). METHODS: Ten patients with colorectal liver metastases were treated with 200 mg irinotecan (as DEBIRI) as part of the PARAGON II study. Hepatic expression of key metabolising enzymes was measured using mass spectrometry-based proteomics. Serum drug concentrations and hepatic irinotecan metabolism were characterised and correlated with tumour response. RESULTS: Serum concentrations of irinotecan metabolites did not correlate with hepatic metabolism or pathological response. There was a strong correlation between hepatic CES-2 expression and activation of irinotecan (r (2) = 0.96, p < 0.001). Patients with a UGT1A1*28 6/7 SNP showed no difference in drug metabolism or pathological response. Hepatic CES-2 mediated activation of irinotecan clearly correlated with tumour replacement by fibrosis (r (2) = 0.54, p = 0.01). CONCLUSION: This study provides the first evidence that hepatic activation of irinotecan predicts tumour response. Delivery of liver-targeted irinotecan to normal liver tissue rather than tumour may be a more rational approach to maximise response.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/patologia , Fígado/metabolismo , Antineoplásicos Fitogênicos/administração & dosagem , Biotransformação , Western Blotting , Camptotecina/administração & dosagem , Camptotecina/metabolismo , Camptotecina/uso terapêutico , Neoplasias Colorretais/cirurgia , DNA de Neoplasias/genética , DNA de Neoplasias/isolamento & purificação , Sistemas de Liberação de Medicamentos , Genótipo , Glucuronosiltransferase/genética , Humanos , Irinotecano , Fígado/enzimologia , Espectrometria de Massas , Microssomos/metabolismo , Proteínas de Neoplasias/metabolismo , Estudos Prospectivos , Reprodutibilidade dos Testes
12.
Br J Surg ; 99(8): 1129-36, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22695869

RESUMO

BACKGROUND: Combined vasculobiliary injury is a serious complication of cholecystectomy. This study examined medium- to long-term outcomes after such injury. METHODS: Patients referred to this institution with Strasberg type E bile duct injuries were identified from a prospectively maintained database (1990-2010). Long-term outcomes were evaluated by chart review. RESULTS: Sixty-three patients were referred with bile duct injury alone (45 patients) or vasculobiliary injury (18). Thirty patients (48 per cent) had septic complications before transfer. Twenty-six patients (41 per cent) had long-term biliary complications over a median follow-up of 96 (range 12-245) months. Nine patients (3 with bile duct injury, 6 with vasculobiliary injury) required further interventions after a median of 22 (8-38) months; five required biliary surgical revision and four percutaneous dilatation of biliary strictures. Vasculobiliary injury and injury-related sepsis were independent risk factors for treatment failure: hazard ratio 7·79 (95 per cent confidence interval 2·80 to 21·70; P < 0·001) and 4·82 (1·69 to 13·68; P = 0·003) respectively. CONCLUSION: Outcome following bile duct injury repair was worse in patients with concomitant vasculobiliary injury and/or sepsis.


Assuntos
Ductos Biliares/lesões , Colecistectomia/efeitos adversos , Lesões do Sistema Vascular/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Artéria Hepática/lesões , Humanos , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/terapia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sepse/diagnóstico , Sepse/etiologia , Sepse/terapia , Lesões do Sistema Vascular/diagnóstico , Lesões do Sistema Vascular/terapia , Adulto Jovem
13.
Br J Surg ; 99(4): 477-86, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22261895

RESUMO

BACKGROUND: The evidence surrounding optimal follow-up after liver resection for colorectal metastases remains unclear. A significant proportion of recurrences occur in the early postoperative period, and some groups advocate more intensive review at this time. METHODS: A systematic review of literature published between January 2003 and May 2010 was performed. Studies that described potentially curative primary resection of colorectal liver metastases that involved a defined follow-up protocol and long-term survival data were included. For meta-analysis, studies were grouped into intensive (more frequent review in the first 5 years after resection) and uniform (same throughout) follow-up. RESULTS: Thirty-five studies were identified that met the inclusion criteria, involving 7330 patients. Only five specifically addressed follow-up. Patients undergoing intensive early follow-up had a median survival of 39·8 (95 per cent confidence interval 34·3 to 45·3) months with a 5-year overall survival rate of 41·9 (34·4 to 49·4) per cent. Patients undergoing routine follow-up had a median survival of 40·2 (33·4 to 47·0) months, with a 5-year overall survival rate of 38·4 (32·6 to 44·3) months. CONCLUSION: Evidence regarding follow-up after liver resection is poor. Meta-analysis failed to identify a survival advantage for intensive early follow-up.


Assuntos
Neoplasias Colorretais , Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Intervalo Livre de Doença , Seguimentos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Recidiva Local de Neoplasia/mortalidade , Cuidados Pós-Operatórios/métodos
14.
Br J Cancer ; 104(9): 1440-51, 2011 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-21448172

RESUMO

BACKGROUND: The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect. METHODS: Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary log(e) hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ(2) test for heterogeneity and its impact on the meta-analysis was assessed by the I(2) statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining. RESULTS: Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18-1.92)) with no evidence of any significant publication bias (Egger's test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38-0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48-0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43-0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96-1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61-1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80-2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups. CONCLUSION: These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.


Assuntos
Adenocarcinoma/química , Adenocarcinoma/patologia , Biomarcadores Tumorais/análise , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patologia , Adenocarcinoma/cirurgia , Biomarcadores Tumorais/imunologia , Inibidor p16 de Quinase Dependente de Ciclina , Receptores ErbB/análise , Humanos , Imuno-Histoquímica , Proteínas de Neoplasias/análise , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/análise , Proteína Smad4/análise , Proteína Supressora de Tumor p53/análise , Fator A de Crescimento do Endotélio Vascular/análise , Proteína X Associada a bcl-2/análise
15.
Clin Oncol (R Coll Radiol) ; 22(9): 755-63, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20805023

RESUMO

Malignant diseases of the upper gastrointestinal tract are common and often diagnosed at a point when the opportunity for curative surgical resection has passed. Symptoms of luminal obstruction include nausea, vomiting, weight loss, pain, pruritus and jaundice. The median survival of patients who cannot be cured surgically is extremely short, with a duration of only a few months. Effective palliative techniques with a low morbidity and associated mortality are required. The length of hospital stay, rapid recovery and reduction in recurrent symptoms are important factors for patients and doctors to consider when planning treatment. Traditionally, surgical techniques were used, but in the last 20 years the availability of both endoscopic and interventional radiological procedures has increased. Furthermore, advances in technology such as the development of self-expanding metal stents and covered stent designs have provided more therapeutic options for the endoscopist and radiologist. Here we discuss the available treatments for the palliation of gastric outlet and biliary tract obstruction and the evidence for the respective approaches.


Assuntos
Colestase/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Drenagem/métodos , Obstrução da Saída Gástrica/cirurgia , Cuidados Paliativos , Colestase/etiologia , Obstrução da Saída Gástrica/etiologia , Neoplasias Gastrointestinais/complicações , Humanos , Stents
16.
Br J Cancer ; 102(3): 577-82, 2010 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-20051949

RESUMO

BACKGROUND: Enzyme-linked immunoassays of full-length (M65) and/or caspase-cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing necrosis and/or apoptosis, respectively, may have prognostic or predictive biomarker utility in a range of solid tumour types. Characterisation of baseline levels of circulating full length and cleaved CK18 specifically in patients with pancreatic cancer. METHODS: Plasma samples from 103 patients with pancreatic cancer stored at -80 degrees C were assayed for M65 and M30 levels. The median (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months. Patients with metastatic disease (n=19) were found to have greater median (IQR) M65 levels (1145 (739-1698) U l(-1)) compared with the locally advanced (n=20; 748 (406-1150) U l(-1)) and resected (n=64; 612 (331-987) U l(-1)) patients (P=0.002). Elevated M65 levels were associated with poorer overall survival on univariate (P<0.001) but not multivariate (P=0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum-bilirubin levels (P<0.001) and the duration of plasma storage (P<0.001). CONCLUSIONS: Baseline plasma CK18 levels in pancreatic cancer are affected by the presence of obstructive jaundice and prolonged plasma storage. Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors.


Assuntos
Biomarcadores Tumorais/sangue , Queratina-18/sangue , Neoplasias Pancreáticas/diagnóstico , Idoso , Apoptose , Antígeno CA-19-9/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade
17.
HPB Surg ; 2009: 425065, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19750237

RESUMO

INTRODUCTION: Increased preoperative platelet and neutrophil counts are risk factors for decreased survival in several different malignancies. Our aim was to investigate the relationship between overall or disease-free survival after resection of CRLM and the preoperative haematological parameters. METHODS: We reviewed a cohort of 140 patients who underwent resection of CRLM with curative intent, utilising prospectively maintained databases. Patient demographics, operative details, FBC, CRP, INR, histopathology results, and survival data were examined. Kaplan-Meier survival and Cox regression analyses were used to determine the impact of all variables on survival. RESULTS: 140 patients (96 males) with a median age of 67 years (range 33-82 years) underwent resection of CRLM. A significant correlation was exhibited between preoperative platelet count and neutrophil count (rho = 0.186, P = .028). When modelled as continuous covariates in a Cox regression hazards, an increased preoperative platelet (P = .02) and neutrophil counts (P

Assuntos
Contagem de Células Sanguíneas , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
18.
Eur J Surg Oncol ; 35(9): 957-62, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19250796

RESUMO

INTRODUCTION: A non-invasive liver function monitoring system, the LiMON, has been developed that measures indocyanine green (ICG) elimination by pulse spectrophotometry. The aim was to assess the relationship between pre and post-operative ICG plasma disappearance rate (ICG PDR %/min) values and the onset of post-hepatectomy liver dysfunction. METHODS: 37 patients scheduled for major liver resections were selected. None had chronic liver disease. IGC PDR was measured preoperatively and on days 1, five and 10 postoperatively. On the same day, serum liver function tests were measured. RESULTS: The median preoperative and post-operative day 1 ICG PDR for the patients who developed liver dysfunction was significantly lower compared to those who did not (p=0.044, p=0.014). Significant correlation was found between ICG PDR measurement taken on postoperative day 1 and bilirubin level on day 1 (p=0.002), 5 (p=<0.001) and 10 (p=0.001). The same was true for ICG PDR on post-operative day 1 and albumin level on day 5 and 10 (p=0.003, p<0.001). DISCUSSION: LiMON ICG PDR measured by pulse spectophotometry is a quick, non-invasive and reliable liver function test in patients undergoing liver resection that aids in the prediction and early detection of post-hepatectomy liver dysfunction.


Assuntos
Hepatectomia/efeitos adversos , Verde de Indocianina , Falência Hepática/diagnóstico , Testes de Função Hepática , Neoplasias Hepáticas/cirurgia , Espectrofotometria , Adulto , Idoso , Diagnóstico Precoce , Feminino , Humanos , Falência Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
19.
Br J Cancer ; 100(2): 246-50, 2009 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-19127260

RESUMO

The ESPAC-1, ESPAC-1 plus, and early ESPAC-3(v1) results (458 randomized patients; 364 deaths) were used to estimate the effectiveness of adjuvant 5FU/FA vs resection alone for pancreatic cancer using meta-analysis. The pooled hazard ratio of 0.70 (95% CI=0.55-0.88) P=0.003, and the median survival of 23.2 (95% CI=20.1-26.5) months with 5FU/FA vs 16.8 (95% CI=14.3-19.2) months with resection alone supports the use of adjuvant 5FU/FA in pancreatic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/radioterapia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
20.
Br J Surg ; 95(12): 1506-11, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18991295

RESUMO

BACKGROUND: Patients with duodenal polyps are at risk of duodenal cancer. Pancreas-preserving total duodenectomy (PPTD) is an alternative to partial pancreatoduodenectomy. METHODS: Twelve patients (seven men and five women) with a median age of 59 (interquartile range (i.q.r.) 50-67) years underwent PPTD for large (over 20 mm) solitary polyps or multiple (more than three) duodenal polyps confined to the muscularis propria on endoscopic ultrasonography. RESULTS: Median hospital stay was 21 (i.q.r. 10-36) days with no deaths and no blood transfusion. Six patients developed postoperative complications, one requiring reoperation. Histology demonstrated gastrointestinal stromal tumour in three patients, low-grade dysplasia in one, moderate-grade dysplasia in eight and duodenal intramucosal adenocarcinoma in one. During a median follow-up of 20 (i.q.r. 8-41) months one patient experienced recurrent acute pancreatitis (due to hypertriglyceridaemia) and one developed a jejunal adenocarcinoma in the neoduodenum. CONCLUSION: The morbidity of PPTD is similar to that of partial pancreatoduodenectomy, but PPTD preserves the whole pancreas and reduces the number of anastomoses.


Assuntos
Duodenopatias/cirurgia , Pólipos Intestinais/cirurgia , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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