Pancreatic intraductal sampling during ERCP in patients with chronic pancreatitis and pancreatic cancer: cytologic studies and k-ras-2 codon 12 molecular analysis in 47 cases

Pugliese, V.; Pujic, N; Saccomanno, S.; Gatteschi, Beatrice; Pera, C; Aste, H.; Ferrara, Giovanni Battista; Nicoló, Guido

doi:10.1067/mge.2001.119220

Cited by 73 publications

(49 citation statements)

References 30 publications

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“…6). Based on these observations, several attempts have been made to improve the accuracy of preoperative diagnostics by analyzing molecular markers in pancreatic juice (7,8), brush cytologies (7,9), or FNAB's (10 -(10 -12) by means of RNA, DNA, or protein analysis. Most of these studies were aimed at detecting mutant K-ras in the biopsy samples because this is the gene most frequently affected by mutations (>85% of cases) in pancreatic ductal adenocarcinoma.…”

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confidence: 99%

Specialized DNA Arrays for the Differentiation of Pancreatic Tumors

Buchholz¹,

Kestler

Bauer

et al. 2005

Clinical Cancer Research

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Purpose: Malignant tumors of the pancreas are frequently indistinguishable from inflammatory tumors arising in the context of a chronic pancreatitis with the use of conventional imaging techniques. Thus, cytologic analysis of cells obtained by abdominal ultrasound, computed tomography, or endoscopic ultrasound^guided fine needle aspiration biopsy is required for diagnosis. However, the reliability of cytologic analyses of pancreatic fine needle aspirates remains unsatisfactory, with a diagnostic accuracy of V80%. The purpose of the current study was therefore to develop a novel diagnostic approach based on expression profiling of biopsy material using a specialized diagnostic cDNA array. Experimental Design: Previous gene expression profiling studies were reevaluated to design a 558-feature diagnostic array. Minimal amounts of residual material from pancreatic cytology samples as well as surgically resected tumor and control tissue specimens were analyzed using the diagnostic array and a newly developed statistical classification system. Results and Conclusions: Our diagnostic approach resulted in 95% accurate differentiation between ductal adenocarcinomas and nonmalignant tumors of the pancreas.The diagnostic array, in conjunction with conventional diagnostic procedures, is thus suitable to significantly improve the reliability of pancreatic cancer diagnostics and can be expected to become a valuable new tool in the routine workup of suspect masses in the pancreas.Pancreatic cancer is the fifth leading cause of cancer-related deaths in industrialized countries. With a 5-year survival rate of <5% and a median survival of <6 months, pancreatic cancer carries the most dismal prognosis of all solid tumors.

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confidence: 99%

Specialized DNA Arrays for the Differentiation of Pancreatic Tumors

Buchholz¹,

Kestler

Bauer

et al. 2005

Clinical Cancer Research

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“…Detection of KRAS2 mutations were first reported in surgically removed pancreatic tumoural tissue or at autopsy (Almoguera et al, 1988;Tada et al, 1991). Thereafter mutations were discovered in 63 to 83% of samples of pure pancreatic juice or main pancreatic duct brushing obtained during endoscopic retrograde pancreatography (Iguchi et al, 1996;Kondo et al, 1997;Tada et al, 1998;Van Laethem et al, 1998;Okai et al, 1999;Watanabe et al, 1999;Ha et al, 2001;Pugliese et al, 2001;Seki et al, 2001) or at fine-needle tumour aspiration (Pabst et al, 1999;Puig et al, 2000), and in 20 to 54% of stools (Caldas et al, 1994;Wenger et al, 1999) from patients with pancreatic cancer. Circulating deoxyribo nucleic acid (DNA) was first detected in serum or plasma of normal subjects in 1975 (Steinman, 1975).…”

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confidence: 99%

Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA

et al. 2002

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KRAS2 mutations in codon 12 have been detected in about 80% of pancreatic cancers. The aim of this study was to evaluate the value of KRAS2 mutations detection in circulating deoxyribo nucleic acid to differentiate pancreatic cancer from chronic pancreatitis. Circulating deoxyribo nucleic acid was isolated from serum in 47 patients with histologically proven pancreatic adenocarcinomas (26 males, median age 65 years) and 31 controls with chronic pancreatitis (26 males, median age 48 years). Mutations at codon 12 of KRAS2 gene were searched for using polymerase chain reaction and allele specific amplification. Serum carbohydrate antigen 19.9 levels were also determined. KRAS2 mutations were found in 22 patients (47%) with pancreatic cancer and in four controls with chronic pancreatitis (13%) (P50.002). None of the latter developed a pancreatic cancer within the 36 months of median follow-up. The sensitivity, specificity, positive and negative predictive values of serum serum KRAS2 mutations for the diagnosis of pancreatic cancer were 47, 87, 85 and 52%, respectively. KRAS2 mutations were not related to age, gender, smoking habit, tumour stage, or survival. Among the 26 patients with normal or non-contributive (due to cholestasis) serum carbohydrate antigen 19.9 levels, 14 (54%) had KRAS2 mutations. The combination of KRAS2 and carbohydrate antigen 19.9 gave a sensitivity, specificity, positive and negative predictive values for the diagnosis of pancreatic cancer of 98, 77, 87 and 96%, respectively. Detection of KRAS2 mutations in circulating deoxyribo nucleic acid has a low sensitivity but a specificity about 90% for the diagnosis of pancreatic cancer. It seems particularly useful when serum carbohydrate antigen 19.9 levels are normal or inconclusive. A combined normal serum carbohydrate antigen 19.9 and absence of circulating KRAS2 mutations makes the diagnosis of pancreatic cancer extremely unlikely.

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“…For instance, Wilentz et al (26) reported that 75-100% of pancreatic cancer patients had a mutation in K-ras codon 12, suggesting that K-ras detection may be used as an early detection marker for pancreatic cancer. In addition, K-ras mutation increased the risk of pancreatic cancer in patients with chronic pancreatitis (27), while K-ras mutations were also observed in certain benign pancreatic diseases (28). In the patient cohort of the present study, a certain percentage of cases with pancreatic benign diseases had fecal K-ras mutations.…”

Section: Discussionmentioning

confidence: 44%

Detection of K‑ras gene mutations in feces by magnetic nanoprobe in patients with pancreatic cancer: A preliminary study

Wang

Chen

et al. 2017

Exp Ther Med

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Abstract. The present study aimed to investigate the feasibility and effectiveness of detecting K-ras mutation by using magnetic nanoparticles in fecal samples of patients with pancreatic cancer at different stages. The novel methodology of K-ras mutation detection was compared to the existing methodology of cancer antigen (CA)19-9 examination. Patients with pancreatic cancer (n=88), pancreatic benign diseases who displayed chronic pancreatitis (n=35), pancreatic mucinous cyst neoplasms (n=10) and pancreatic serous cyst (n=9) admitted to the Department of Surgery, Jiaxing Second Hospital were enrolled in the present study. Fecal samples were collected from all patients, DNA was extracted and magnetic nanoprobe was then used to detect K-ras mutation. The results obtained using the novel magnetic nanoprobe detection technique showed a K-ras mutation rate of 81.8% (72/88) in the patients with pancreatic cancer and 18.5% (10/54) in patients with pancreatic benign diseases. In patients with pancreatic cancer, the K-ras mutation rate was comparable in stages I + IIA and IIB + III + IV (78.9 vs. 84.0%; P>0.05). The sensitivity and specificity of K-ras mutation for detection of pancreatic cancer was 81.8 and 81.5%, respectively. Sixty-eight pancreatic cancer patients had >37 U/ml CA99 with a sensitivity and specificity for pancreatic cancer detection of 77.3 and 77.8%, which was not significantly lower than detection by the fecal K-ras mutations (P>0.05). Combinational detection of fecal K-ras mutations and serum CA19-9 significantly increased the sensitivity regarding pancreatic cancer detection to 97.7% (P<0.05), while the specificity was not enhanced (80.9%; P>0.05) compared with fecal K-ras mutations or CA19-9 alone. The findings showed that the magnetic nanoprobe is able to detect fecal K-ras mutations in different stages of pancreatic cancer, with comparable sensitivity and specificity to CA19-9 examination for differentiating pancreatic cancer. Furthermore, combined detection of CA19-9 and K-ras mutations has enhanced sensitivity compared with CA19-9 alone.

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Pancreatic intraductal sampling during ERCP in patients with chronic pancreatitis and pancreatic cancer: cytologic studies and k-ras-2 codon 12 molecular analysis in 47 cases

Cited by 73 publications

References 30 publications

Specialized DNA Arrays for the Differentiation of Pancreatic Tumors

Specialized DNA Arrays for the Differentiation of Pancreatic Tumors

Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA

Detection of K‑ras gene mutations in feces by magnetic nanoprobe in patients with pancreatic cancer: A preliminary study

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