Current standards of surgery for pancreatic cancer

Alexakis, N.; Halloran, Christopher; Raraty, Michael; Ghaneh, Paula; Sutton, Robert; Neoptolemos, John P.

doi:10.1002/bjs.4794

Cited by 281 publications

(198 citation statements)

References 180 publications

(238 reference statements)

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“…It is well known that pancreatic adenocarcinoma does not respond to chemotherapy well despite the recent Meta-analysis of expression profiling on pancreatic cancer R Grützmann et al advance of adjuvant chemotherapy (Alexakis et al, 2004). The origin of the refractory behavior of PDAC is still unknown.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of microarray data on pancreatic cancer defines a set of commonly dysregulated genes

Boriss²,

et al. 2005

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Pancreatic ductal adenocarcinoma is the eighth most common cancer with the lowest overall 5-year relative survival rate of any tumor type today. Expression profiling using microarrays has been widely used to identify genes associated with pancreatic cancer development. To extract maximum value from the available gene expression data, we applied a meta-analysis to search for commonly differentially expressed genes in pancreatic ductal adenocarcinoma. We obtained data sets from four different gene expression studies on pancreatic cancer. We selected a consensus set of 2984 genes measured in all four studies and applied a meta-analysis approach to evaluate the combined data. Of the genes identified as differentially expressed, several were validated using RT-PCR and immunohistochemistry. Additionally, we used a class discovery algorithm to identify a gene expression signature. Our meta-analysis revealed that the pancreatic cancer gene expression data sets shared a significant number of up-and downregulated genes, independent of the technology used. This interstudy crossvalidation approach generated a set of 568 genes that were consistently and significantly dysregulated in pancreatic cancer. Of these, 364 (64.1%) were upregulated and 204 (35.9%) were downregulated in pancreatic cancer. Only 127 (22%) were described in the published individual analyses. Functional annotation of the genes revealed that genes presumably associated with the cell adhesionmediated drug resistance pathway are frequently overexpressed in pancreatic cancer. Meta-analysis is an important tool for the identification and validation of differentially expressed genes. These could represent good candidates for novel diagnostic and therapeutic approaches to pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of microarray data on pancreatic cancer defines a set of commonly dysregulated genes

Boriss²,

et al. 2005

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“…Clinical biomarker studies utilising serial CK18 levels are warranted in pancreatic cancer, provided consideration is given to these potentially confounding factors. Pancreatic ductal adenocarcinoma is a leading cause of cancer deaths (http://www-dep.iarc.fr/) wherein, because of its characteristically late presentation, only 10 -15% of patients present with resectable tumours (Alexakis et al, 2004). For the remaining 85 -90% of patients presenting with inoperable disease, administration of systemic chemotherapy represents the most widely utilised palliative treatment modality (Yip et al, 2006).…”

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confidence: 99%

Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

et al. 2010

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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 À80 1C 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 ¼ 19) were found to have greater median (IQR) M65 levels (1145 (739 -1698) U l À1 ) compared with the locally advanced (n ¼ 20; 748 (406 -1150) U l À1 ) and resected (n ¼ 64; 612 (331 -987) U l À1 ) patients (P ¼ 0.002). Elevated M65 levels were associated with poorer overall survival on univariate (Po0.001) but not multivariate (P ¼ 0.202) analysis. M65 concentrations also exhibited significant associations with concurrent serum -bilirubin levels (Po0.001) and the duration of plasma storage (Po0.001). 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. Pancreatic ductal adenocarcinoma is a leading cause of cancer deaths (http://www-dep.iarc.fr/) wherein, because of its characteristically late presentation, only 10 -15% of patients present with resectable tumours (Alexakis et al, 2004). For the remaining 85 -90% of patients presenting with inoperable disease, administration of systemic chemotherapy represents the most widely utilised palliative treatment modality (Yip et al, 2006). Conventional chemotherapy regimens incorporating either 5-FU or gemcitabine typically result in only modest improvement in overall survival (Sultana et al, 2007). One of the key challenges in accelerating improved cancer therapeutics is the identification of biomarkers to enable early objective assessment of tumour responses to chemotherapy (Kummar et al, 2007).Necrosis of malignant and normal epithelial cells cause release of cytokeratin 18 (CK18) (Kramer et al, 2004), a type I intermediate filament protein and a component of the intracellular cytoskeleton (Fuchs and Weber, 1994). Caspase-mediated cleavage of the CK18 contributes to the degradation of the intracellular cytoskeleton if epithelial cells undergo apoptosis (Leers et al, 1999). Enzymelinked immunosorbent assays (ELISAs) have been developed to measure circulating concentrations of both full-length CK18 (M65) and caspase-cleaved CK18 fragments (M30) (Kramer et al, 2004). Thus, the M65 ELISA reports necrotic and apoptotic epithelial cell death, whereas the M30 ELISA reports levels of epithelial apoptosis specifically (Kramer et al, 2004). Early studies suggest that these assays ...

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“…De acordo com várias publicações, a tomografia de abdome com múltiplos detectores é na atualidade o exame preferido para o diagnóstico e estadiamento do AP 2,6,30,34,35 . Ela permite exame rápido em um único evento de apnéia, com fases arterial, portal e parenquimatosa, com cortes finos e reconstrução em vários planos.…”

Section: Estadiamento Exames Pré-operatóriosunclassified

Diagnóstico, estadiamento e tratamento cirúrgico do adenocarcinoma de pâncreas

Amico¹,

Barreto²,

Dantas-Filho³

et al. 2008

ABCD, arq. bras. cir. dig.

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Isso pode ser facilmente demonstrado pela estreita correlação entre o número de novos casos diagnosticados e a incidência de morte pela doença por ano nas várias regiões do mundo 1 . Felizmente no Brasil essa doença não figura entre as mais prevalentes causas de câncer, sendo responsável apenas por 4% das mortes por neoplasia maligna em nosso país 15 . A despeito disso os esforços se concentram para que a cura, possível em minoria dos pacientes, e a melhoria da qualidade de vida, naqueles com doença avançada localmente ou metastática, seja oferecida aos pacientes nos quais o diagnóstico de AP é feito.Admite-se que a única alternativa para a sua cura seja o tratamento cirúrgico. Ainda assim, apenas poucos pacientes submetidos à pancreatectomia sobrevivem mais que cinco anos. Mesmo naqueles pacientes com tumores pequenos, submetidos à ressecção com margens negativas e com gânglios livres de tumor a taxa de sobrevida em cinco anos alcança apenas 41% 5 . Para a maioria dos pacientes, no entanto, a cura não pode ser oferecida. Quando analisado a totalidade dos pacientes, apenas em 15-20% dos casos a ressecção é possível em virtude de doença avançada localmente ou pela presença de metástase à distância. Nesses casos é esperada sobrevida média de aproximadamente seis meses 33 .Em virtude dessa realidade, o cirurgião tem papel central na abordagem do AP sendo seus objetivos: 1) promover a ressecção cirúrgica com margens livres e 2) proporcionar um mínimo possível de morbidade e mortalidade com o tratamento. Acrescenta-se a isso a participação no processo decisório quanto à melhor paliação possível a ser aplicada aos pacientes que pode ser realizada de forma cirúrgica ou endoscópica.Frente à possibilidade do diagnóstico e tratamento alguns aspectos persistem controversos enquanto outros estão mais bem definidos. Esta revisão aborda o estado cialmente curativo. Na grande maioria dos pacientes o tumor é diagnosticado em fase avançada, comumente na presença de doença metastática. A introdução de modernos métodos diagnósticos associados ao aperfeiçoamento dos já existentes tem gerado controvérsia quanto à melhor maneira de se estabelecer o diagnóstico e estadiamento do tumor. Da mesma forma, o papel da cirurgia na paliação e aspectos técnicos da ressecção de lesões localizadas estão longe de alcançarem consenso na prática. Método -Revisão da literatura sobre os aspectos controversos relacionados ao tema e um algoritmo para a abordagem dos pacientes com suspeita de tumor de pâncreas são apresentados. Foram utilizados os descritores: "adenocarcinoma" e "pâncreas" para pesquisa no PubMed (www.pubmed.com) e na Bireme (www.bireme.br) e a seguir selecionadas as publicações pertinentes a cada tópico escolhido com atenção especial para metanálises, estudos clínicos controlados, revisões sitemáticas e ainda publicações de grandes centros especializados em doenças pancreáticas. Conclusões -Na suspeita de adenocarcinoma de pâncreas é possível realizar estadiamento muito próximo do real sem a necessidade da exploração cirúrgica sistemát...

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Current standards of surgery for pancreatic cancer

Abstract: The surgical management of pancreatic cancer has undergone a significant change in the past decade. It has moved away from no active treatment. The standard of care can now be defined as potentially curative resection in a specialist centre followed by adjuvant systemic chemotherapy.

Cited by 281 publications

References 180 publications

Meta-analysis of microarray data on pancreatic cancer defines a set of commonly dysregulated genes

Meta-analysis of microarray data on pancreatic cancer defines a set of commonly dysregulated genes

Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic cancer

Diagnóstico, estadiamento e tratamento cirúrgico do adenocarcinoma de pâncreas

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