Pancreatic Carcinoma

Warshaw, Andrew L.; Castillo, Carlos Fernández‐del

doi:10.1056/nejm199202133260706

Cited by 1,310 publications

(835 citation statements)

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“…However, many patients with pancreatic cancer present with advanced disease due to early lymphatic and hematogenous spread and the tendency toward infiltrative growth; therefore, only 10 -30% of pancreatic cancers are considered to be resectable at the time of diagnosis (4,6 -9). Pancreaticoduodenectomy, even with an expert surgeon's hands, carries a 5% mortality and postoperative morbidity approaching 50% (2,5,7,9). Therefore, early diagnosis and an accurate assessment of tumor resectability are an essential step in the treatment planning so that unnecessary surgical procedures can be avoided (8,10 -15).…”

mentioning

confidence: 99%

Preoperative evaluation of pancreatic cancer: Comparison of gadolinium‐enhanced dynamic MRI with MR cholangiopancreatography versus MDCT

Park

Lee

Choi

et al. 2009

Magnetic Resonance Imaging

138

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Purpose:To determine the accuracy of magnetic resonance imaging (MRI) including dynamic imaging using three-dimensional gradient-echo (3D-GRE) sequences and MR cholangiopancreatograpy (MRCP) compared with that of multidetector row CT (MDCT) with regard to resectability in pancreas cancer. Materials and Methods:From February 2004 to July 2008, 54 patients (32 men, 22 women: age range, 28 -83 years; mean age, 63.1 years old) with surgically proven pancreatic carcinoma, who had undergone preoperative gadolinium-enhanced 3D-GRE MRI with MRCP and triplephase MDCT, were included in this retrospective study. Two, clinically experienced attending radiologists independently reviewed the two image sets. These readers evaluated the tumor conspicuity, presence of vascular invasion, choledochal and duodenal invasion, lymph node metastases, distant metastasis, and tumor resectability. The results were compared with the surgical and histopathologic findings using receiver operating characteristic analysis (Az) and kappa statistics. Results:Curative resections were performed on 42 patients. Regarding the tumor conspicuity, MRI had a significantly higher Az value compared with MDCT according to both reviewers (P Ͻ 0.05). The accuracy of resectability was Az ϭ 0.753 and 0.768 on MRI and Az ϭ 0.829 and 0.762 on MDCT for each reviewer, and the difference in the accuracy of resectability was not significant between MRI and MDCT for either reviewer (P Ͼ 0.05). Two imaging sets showed a similar diagnostic performance in the evaluation of vascular involvement, lymph node metastasis, and distant metastasis.Conclusion: Dynamic 3D-GRE MRI with MRCP shows superior tumor conspicuity and similar diagnostic performance compared with MDCT in evaluating the resectability of pancreatic cancer.

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confidence: 99%

Preoperative evaluation of pancreatic cancer: Comparison of gadolinium‐enhanced dynamic MRI with MR cholangiopancreatography versus MDCT

Park

Lee

Choi

et al. 2009

Magnetic Resonance Imaging

138

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“…Pancreatic cancer is one of the major causes of cancer-related deaths in industrialized countries (Poston et al, 1991;Warshaw and Castillo, 1992;Bramhall et al, 1995). Most pancreatic cancer patients were first diagnosed at an advanced stage of the disease and only 3% of all these patients survived for 5 years (Niederhuber et al, 1995).…”

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confidence: 99%

NK4, a four-kringle antagonist of HGF, inhibits spreading and invasion of human pancreatic cancer cells

et al. 2001

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Summary Because of the highly aggressive behaviour, i.e. invasive, disseminative and metastatic properties, the outcome for patients with pancreatic cancer is morbid. A better understanding and interference with the malignant behaviour of pancreatic cancer may provide new directions for treatment. We report here the induction of highly motile and invasive properties in human pancreatic cancer cells by hepatocyte growth factor (HGF) and blockage of these properties by NK4, a newly identified antagonist for HGF. In all of eight human pancreatic cancer cell lines we used (AsPC-1, BxPC-3, H-48N, KP-1N, KP-2, KP-3, MIA PaCa-2 and SUIT-2 cells), the c-Met/HGF receptor was expressed at varying levels. Although weak mitogenic activity of HGF was seen only in SUIT-2 and KP-3 cells, HGF strongly stimulated migration and invasion of these pancreatic cancer cells, except for BxPC-3 and MIA PaCa-2 cells. In contrast, migration and invasion potently induced by HGF in KP-1N, KP-3 and SUIT-2 cells were inhibited by NK4. The invasion of SUIT-2 cells was also potently stimulated with the influence of cocultured pancreatic fibroblasts and by ascitic fluid obtained after pancreatic cancer resection, however, invasiveness of the cancer cells in such conditions was practically abolished by NK4. Consistently, the ascitic fluid in patients who had undergone pancreatic cancer surgery contained high levels of HGF. These findings mean that HGF is probably involved in invasion, dissemination, and metastasis of pancreatic cancer, particularly through tumour-stromal interaction and after resection of the pancreatic cancer. While competitive inhibitory effects of NK4 on HGF and cMet/receptor interaction have been demonstrated in some distinct types of human cancer cells (Date et al, 1998;Hiscox et al, 2000;Kuba et al, 2000;Parr et al, 2000), inhibitory and promising therapeutic effects of NK4 have to be evaluated in cases of highly aggressive pancreatic cancer. In the current study, cancer-stromal interaction through HGF and c-Met coupling and inhibitory effects of NK4 were investigated in human pancreatic cancer cells. The invasion of pancreatic cancer cells was potently stimulated by HGF, cocultivation with fibroblasts, and by ascitic fluid from patients who had undergone pancreatic cancer resection, but this invasion was almost completely inhibited by NK4. The potential inhibition of pancreatic cancer invasion and dissemination by NK4 was thus deemed worthy of investigation. MATERIALS AND METHODS MaterialsHuman recombinant HGF was purified from the conditioned medium of Chinese hamster ovary cells transfected with human HGF cDNA (Nakamura et al, 1989;Seki et al, 1990). Polyclonal antibody against human HGF was prepared from the serum of a rabbit immunized with human recombinant HGF and IgG was purified using protein A-Sepharose (Pharmacia Biotech, Uppsala). Anti-human HGF IgG (1 µg ml -1 ) completely neutralized the biological activities of 1 ng ml -1 human HGF. NK4 was prepared by proteolytic digestion with elastase, as described elsewher...

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“…Of ~30,000 new reported cases in the USA each year, less than 1% of patients will survive 5 years [10]. The insidious nature of pancreatic cancer stems largely from the inability to clinically detect its earliest forms.…”

Section: Pancreatic Cancermentioning

confidence: 99%

Chronic pancreatitis, pancreatic adenocarcinoma and the black box in-between

2005

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Pancreatic cancer is a challenging disease for patients, doctors and researchers who for decades have searched for a cure for this deadly malignancy. Although existing mouse models of pancreatic cancer have shed light on the mechanistic basis of the neoplastic conversion of the pancreas, their impact in terms of offering new diagnostics and therapeutic modalities remains limited. Chronic pancreatitis is an inflammatory disease of the pancreas that is associated with a gradual damage of the organ and an increased risk of developing neoplastic lesions. In this review, we propose that detailed studies of chronic inflammatory processes in the pancreas will provide insights into the evolution of pancreatic cancer. This information may prove useful in the design of effective therapeutic strategies to battle the disease.

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Pancreatic Carcinoma

Cited by 1,310 publications

References 140 publications

Preoperative evaluation of pancreatic cancer: Comparison of gadolinium‐enhanced dynamic MRI with MR cholangiopancreatography versus MDCT

Preoperative evaluation of pancreatic cancer: Comparison of gadolinium‐enhanced dynamic MRI with MR cholangiopancreatography versus MDCT

NK4, a four-kringle antagonist of HGF, inhibits spreading and invasion of human pancreatic cancer cells

Chronic pancreatitis, pancreatic adenocarcinoma and the black box in-between

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