Can we screen high-risk individuals to detect early pancreatic carcinoma?

Goggins, Michael; Canto, M. I.; Hruban, Ralph H.

doi:10.1002/1096-9098(200008)74:4<243::aid-jso1>3.0.co;2-c

Cited by 61 publications

(26 citation statements)

References 39 publications

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“…In addition, there is a need to develop screening and diagnostic methods that identify pancreatic neoplasia at the advanced PanIN stage or immediately after invasion but before metastasis and the onset of symptoms. 92 Effective therapy for the metastatic stage will require a substantial expansion in the exploration of novel clinical trials for this disease 93 and attention to newly recognized genetic and histologic subgroups.…”

Section: Resultsmentioning

confidence: 99%

An Introduction to Pancreatic Adenocarcinoma Genetics, Pathology and Therapy

Kern

Hruban²,

Hidalgo³

et al. 2002

Cancer Biology & Therapy

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Cancer is bad, but pancreatic cancer is especially so. Underlying the aggressive behavior of pancreatic cancer is a highly patterned set of biologic rules for its development. The accumulating discoveries regarding the genetic basis of pancreatic cancer and developments in the clinical management of the disease provide hope for meaningful improvements in the understanding and control of this disease. WHAT IS A TYPICAL PRESENTATION FOR THIS DISEASE?Pancreatic cancer is usually diagnosed at a biologically late stage. A patient, usually in their 60s or 70s, may notice unexplained weight loss, back pain, altered bowel habits, or the sudden onset of jaundice. During the clinical evaluation, a mass is found in the pancreas, usually in the head, the right-sided region of pancreas adjacent to the duodenum. Unfortunately, in 80% of these patients it is clinically evident that the cancer has already spread to other organs, most commonly in the liver. The only options for these patients include palliation (procedures such as placement of a stent within an occluded biliary duct) or noncurative courses of chemotherapy. A subset of patients, about 20%, will, however, have no detectable metastatic disease. These patients are candidates for a surgical resection.Pancreatic adenocarcinoma affects close to 30,000 persons a year in the United States and is the fourth most common form of cancer death in both sexes. WHAT ARE THE SURGICAL OPTIONS?For patients with tumors in the head of the gland, options for resection include a pancreaticoduodenectomy (or Whipple operation). A minority of patients will have tumors originating in the left side, or tail, of the gland, and are candidates for distal pancreatectomy, usually with splenectomy. The five-year survival for the groups of patients who do not undergo resectional procedures is clearly less than five percent. In the group of patients who undergo surgical resection, five-year survival rates are largely between 15 and 20%. 1 Within this latter group, patients with small cancers, cancer-free margins of resection, and without metastases to local lymph nodes will be expected to have an even better prognosis approaching 40% five-year survival overall. Nearly all patients who undergo surgical resection, unfortunately, eventually succumb to metastatic disease, including even the cases resected when the primary lesion is extremely small. 2,3 The implication is that pancreatic cancer must metastasize distantly, prior to clinical presentation, in virtually all cases. WHERE SHOULD PANCREATIC CANCER SURGERY BE DONE?Considerable data would support the centralization of pancreatic cancer surgery to specific "centers of excellence". The first such analyses came from the state of Maryland and compared cost and outcome between one high-volume regional provider and 38 other Maryland hospitals during a five-year period. 4 Hospital mortality was six times higher for patients treated at low-volume providers; mortality rates specifically increased with decreasing volume, from 2.2% at the regional ...

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Section: Resultsmentioning

confidence: 99%

An Introduction to Pancreatic Adenocarcinoma Genetics, Pathology and Therapy

Kern

Hruban²,

Hidalgo³

et al. 2002

Cancer Biology & Therapy

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“…However, no biomarker suitable for screening of pancreatic cancer is currently available (12). CA19-9 is an established biomarker useful for the follow-up of pancreatic cancer patients receiving treatment, but has not been recommended for cancer screening because of its insufficient sensitivity and specificity (7,13). Therefore, the discovery of a new biomarker that would be able to supplement CA19-9 has been anticipated.…”

Section: Introductionmentioning

confidence: 99%

Reduced Plasma Level of CXC Chemokine Ligand 7 in Patients with Pancreatic Cancer

Matsubara¹,

Honda

Ono

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Early detection is essential to improve the outcome of patients with pancreatic cancer. A noninvasive and cost-effective diagnostic test using plasma/serum biomarkers would facilitate the detection of pancreatic cancer at the early stage.Methods: Using a novel combination of hollow fiber membrane-based low-molecular-weight protein enrichment and LC-MS-based quantitative shotgun proteomics, we compared the plasma proteome between 24 patients with pancreatic cancer and 21 healthy controls (training cohort). An identified biomarker candidate was then subjected to a large blinded independent validation (n ¼ 237, validation cohort) using a high-density reverse-phase protein microarray.Results: Among a total of 53,009 MS peaks, we identified a peptide derived from CXC chemokine ligand 7 (CXCL7) that was significantly reduced in pancreatic cancer patients, showing an area under curve (AUC) value of 0.84 and a P value of 0.00005 (Mann-Whitney U test). Reduction of the CXCL7 protein was consistently observed in pancreatic cancer patients including those with stage I and II disease in the validation cohort (P < 0.0001). The plasma level of CXCL7 was independent from that of CA19-9 (Pearson's r ¼ 0.289), and combination with CXCL7 significantly improved the AUC value of CA19-9 to 0.961 (P ¼ 0.002).Conclusions: We identified a significant decrease of the plasma CXCL7 level in patients with pancreatic cancer, and combination of CA19-9 with CXCL7 improved the discriminatory power of the former for pancreatic cancer.Impact: The present findings may provide a new diagnostic option for pancreatic cancer and facilitate early detection of the disease. Cancer Epidemiol Biomarkers Prev; 20(1); 160-71. Ó2011 AACR.

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“…Currently, rare genetic syndromes with a high incidence of pancreatic cancer are being targeted for screening using endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography. [1][2][3] To make headway in screening for sporadic pancreatic cancer, efforts to define populations at high risk for having or developing sporadic pancreatic cancer will have to develop pari passu with advances in imaging studies and identification of novel biomarkers. In this study, we highlight the potential for utilizing hyperglycemia and diabetes to define a population at high risk for having pancreatic cancer.…”

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confidence: 99%