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Norio Sawabu

Publications and source records attributed to Norio Sawabu.

At least 19 recordsLinked to original sources
PubMed2006

Diagnostic utility of aberrant methylation of tissue factor pathway inhibitor 2 in pure pancreatic juice for pancreatic carcinoma.

The tissue factor pathway inhibitor 2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor. Recently, the aberrant methylation of TFPI-2 was detected frequently in pancreatic carcinoma (PCa) tissues but not in normal pancreatic tissues. We analyzed the aberrant methylation of TFPI-2 in the pure pancreatic juice (PPJ) aspirated endoscopically from patients with various pancreatic diseases. Using the highly sensitive methylation-specific polymerase chain reaction (MSP) and quantitative MSP (Q-MSP) assay, we investigated the aberrant methylation of TFPI-2 in nine human PCa cell lines and in the PPJ from patients with PCa, intraductal papillary mucinous neoplasms (IPMN) and chronic pancreatitis (CP). The incidence of aberrant TFPI-2 methylation was seven (77.8%) of nine PCa cell lines by Q-MSP. In cell lines, the expression of TFPI-2 mRNA by quantitative reverse transcription-polymerase chain reaction showed an inverse correlation to the aberrant methylation of TFPI-2. The incidence of aberrant TFPI-2 methylation in the PPJ was 21 (58.3%) of 36 PCa patients, three (17.6%) of 17 IPMN and one (4.8%) of 21 CP by MSP assay. Using a suitable cut-off value of 2.5 according to the receiver operating characteristic curve, the incidence of aberrant TFPI-2 methylation in the PPJ by real-time MSP was 18 (62.1%) of 29 PCa patients, one (5.1%) of 17 IPMN and three (14.3%) of 21 CP, respectively. The incidence of quantitative TFPI-2 hypermethylation in the PPJ with PCa was significantly higher than that with IPMN (P < 0.001) or CP (P < 0.001). Moreover, the aberrant methylation rate of TFPI-2 in the PPJ was 100%, as observed (6/6) in the PCa patients with liver metastasis, and 86.7% (26/30) in stages IVa + IVb of PCa by Q-MSP assay. These results suggest that promoter methylation of TFPI-2 in the PPJ may be a useful marker in the diagnosis and progression of PCa using an endoscopically feasible approach.

Adenocarcinoma, Mucinous↗
PubMed2006

Consensus of primary care in acute pancreatitis in Japan.

The incidence of acute pancreatitis in Japan is increasing and ranges from 187 to 347 cases per million populations. Case fatality was 0.2% for mild to moderate, and 9.0% for severe acute pancreatitis in Japan in 2003. Experts in pancreatitis in Japan made this document focusing on the practical aspects in the early management of patients with acute pancreatitis. The correct diagnosis of acute pancreatitis and severity stratification should be made in all patients using the criteria for the diagnosis of acute pancreatitis and the multifactor scoring system proposed by the Research Committee of Intractable Diseases of the Pancreas as early as possible. All patients diagnosed with acute pancreatitis should be managed in the hospital. Monitoring of blood pressure, pulse and respiratory rate, body temperature, hourly urinary volume, and blood oxygen saturation level is essential in the management of such patients. Early vigorous intravenous hydration is of foremost importance to stabilize circulatory dynamics. Adequate pain relief with opiates is also important. In severe acute pancreatitis, prophylactic intravenous administration of antibiotics at an early stage is recommended. Administration of protease inhibitors should be initiated as soon as the diagnosis of acute pancreatitis is confirmed. A combination of enteral feeding with parenteral nutrition from early stage is recommended if there are no clear signs and symptoms of ileus and gastrointestinal bleeding. Patients with severe acute pancreatitis should be transferred to ICU as early as possible to perform special measures such as continuous regional arterial infusion of protease inhibitors and antibiotics, and continuous hemodiafiltration. The Japanese Government covers medical care expense for severe acute pancreatitis as one of the projects of Research on Measures for Intractable Diseases.

Acute Disease↗
PubMed2006

Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells.

AIM: To investigate the expression of genes involved in the gemcitabine-induced cytotoxicity in human pancreatic cancer cells. METHODS: A human pancreatic cancer cell line, PANC-1, was cultured. 1x10(4) PANC-1 cells were plated in 96-well microtiter plates. After being incubated for 24 h, gemcitabine was added to the medium at concentrations ranging 2.5-1000 mg/L. The AlamarBlue dye method was used for cell growth analysis. DNA fragmentation was quantitatively assayed using a DNA fragmentation enzyme-linked immunosorbent assay (ELISA) kit. PAP and TP53INP1 mRNA expression was determined using the reverse transcription-polymerase chain reaction with semi-quantitative analysis. The expression of GSK-3beta and phospho-GSK-3beta proteins was examined with Western blot analysis. RESULTS: The IC50 for the drug after a 48-h exposure to gemcitabine was 16 mg/L. The growth of PANC-1 cells was inhibited by gemcitabine in a concentration-dependent manner (P<0.0001) and the cell growth was also inhibited throughout the time course (P<0.0001). The DNA fragmentation rate in the gemcitabine-treated group at 48 h was 44.7%, whereas it was 25.3% in the untreated group. The PAP mRNA expression was decreased after being treated with gemcitabine, whereas the TP53INP1 mRNA was increased by the gemcitabine treatment. Western blot analysis showed that phospho- GSK-3beta (ser9) was induced by the gemcitabine treatment. CONCLUSION: Gemcitabine suppresses PANC-1 cell proliferation and induces apoptosis. Apoptosis is considered to be associated with the inhibition of PAP and GSK-3beta, and the activation of TP53INP1 and pospho-GSK-3beta (ser9).

Antigens, Neoplasm↗
PubMed2006

Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer.

AIM: Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer. METHODS: TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed. RESULTS: TP53INP1 was expressed in 98% (139/142 cases) of non-cancerous gastric tissues and was down-expressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%). Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3% vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients). P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P=0.0006). CONCLUSION: TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may reflect the malignant grade of gastric cancer and is regarded as an adverse prognostic factor.

Adenocarcinoma↗
PubMed2006

Preproenkephalin hypermethylation in the pure pancreatic juice compared with p53 mutation in the diagnosis of pancreatic carcinoma.

BACKGROUND: Aberrant methylation of CpG islands is a common mechanism for the dysregulation of tumor suppressor genes in a variety of human malignancies. Preproenkephalin ppENK) hypermethylation is recognized in 90% of pancreatic carcinoma (PCa) tissues, but not in normal pancreas. We analyzed ppENK hypermethylation in pure pancreatic juice (PPJ) in patients with PCa, intraductal papillary mucinous neoplasms (IPMN), and chronic pancreatitis (CP), and elucidated its usefulness as a marker in the diagnosis of PCa compared with p53 mutation. METHODS: PPJ was collected endoscopically from 28 patients with PCa, 15 patients with IPMN, and 20 patients with CP. DNA was extracted from the supernatant and the sediment of PPJ. Methylation-specific polymerase chain reaction was performed for hypermethylation analysis of ppENK. In addition, single-strand conformation polymorphism and direct sequencing were performed simultaneously to identify p53 mutations. RESULTS: The incidence of ppENK hypermethylation in the supernatant and/or the sediment of PPJ was 50% (14 of 28) in patients with PCa. In contrast, the incidence of ppENK hypermethylation was 26.7% (4 of 15) in patients with IPMN, and 5% (1 of 20) in patients with CP (P < 0.002). The incidence of p53 mutations in the PPJ was 42.9% (12 of 28) in patients with PCa and 0% (0 of 20) in patients with CP. Furthermore, the incidence of ppENK hypermethylation and/or p53 mutations in the PPJ was enhanced to 67.9% (19 of 28) in patients with PCa in the combination assay. CONCLUSIONS: These results suggest that ppENK hypermethylation in PPJ is specific for cancer, and the combination assay with p53 enhances the genetic diagnosis of PCa.

Adult↗
PubMed2006

Successful cystic fenestration for a macrocystic serous cystadenoma of the pancreas causing obstructive jaundice: report of a case.

A 72-year-old man was admitted to our hospital for investigation of jaundice. We made a preoperative diagnosis of macrocystic serous cystadenoma (SCA) of the pancreas, but did not perform palliative choledochojejunostomy because aspiration of the pancreatic cystic fluid caused the cysts to shrink and relieved the compressive stenosis of the common bile duct (CBD) during the operation. Frozen sections of the cyst wall taken by incision biopsy showed no signs of malignancy. Therefore, we performed fenestration of the cystic wall after fixing the inner epithelium of the cyst with 100% ethanol and aspirating the cystic fluid. Cholangiography after the cystic fenestration showed resolution of the CBD stenosis and abdominal computed tomography (CT) confirmed the disappearance of the pancreatic cysts. No recurrence of cystic swelling or obstructive jaundice has been detected by abdominal CT or laboratory data for more than 2 years since the cystic fenestration. Thus, cystic fenestration may be a better palliative option for treating benign compressive tumors such as macrocystic SCA of the pancreas causing obstructive jaundice.

Aged↗
PubMed2006

Autoimmune pancreatitis in young patients.

GOALS: To examine whether there is a difference in the autoimmune pancreatitis (AIP) seen in young and elderly patients. BACKGROUND: AIP has a preponderance for elderly males, although the reason is unknown. STUDY: A total of 64 patients with AIP were divided into a young (<40 y old) group and a middle-aged or elderly group (> or =40 y old) according to the age at diagnosis. The clinical findings of each group were compared. RESULTS: The young group consisted of 6 patients (3 men, 3 women) with a mean age of 33.0 (range, 28 to 37) years. In the middle-aged or elderly group, there were 58 patients with a mean age of 66.4 (range, 46 to 83) years; males predominated (79%). Abdominal pain as the presenting symptom was significantly more frequent in the young group than in the middle-aged or elderly group (100% vs. 43%, P<0.05). Obstructive jaundice was detected in only 17% (1/6) of patients in the young group compared with 59% (34/58) of patients in the middle-aged or elderly group. Serum amylase elevations were detected more frequently in the young group than in the middle-aged or elderly group (83% vs. 40%, P<0.05). One young patient also had ulcerative colitis. CONCLUSIONS: Although rare in Japan, young patients with AIP show different clinical features from middle-aged or elderly patients with AIP; young patients are more likely to have abdominal pain and serum amylase elevations.

Abdominal Pain↗
PubMed2006

Aberrant methylation of secreted apoptosis-related protein 2 (SARP2) in pure pancreatic juice in diagnosis of pancreatic neoplasms.

OBJECTIVE: Secreted apoptosis-related protein (SARP) families are considered to counteract the oncogenic Wnt signaling pathway, and inactivation of this gene may aid cancer development and progression. Recently, the aberrant methylation of SARP2 was detected frequently in pancreatic carcinoma (PCa) tissue, but not in normal pancreatic tissue. We evaluated the hypermethylation of SARP2 in pure pancreatic juices (PPJ) aspirated endoscopically from patients with PCa, intraductal papillary mucinous neoplasm of the pancreas (IPMN), chronic pancreatitis (CP), and a control group who were consequently free of pancreatic diseases according to the differential diagnosis of PCa. METHODS: We investigated the aberrant methylation of SARP2 in 9 human PCa cell lines and in the PPJ samples from 33 patients with PCa, 20 with IPMN, 19 with CP, and 10 control patients. DNAs extracted from not only sediment, but also the supernatant of the PPJ and PCa cell lines were treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction (PCR) (MSP). Moreover, real-time MSP was also performed for the melting curve analysis and the quantitative analysis of SARP2 in the PPJ. RESULTS: The incidence of the aberrant methylation of SARP2 using MSP was 8/9 (89%) in PCa cell lines, 26/33 (79%) in the PPJ with PCa, and 17/20 (85%) with IPMN. However, it was only 1/19 (5%) in the PPJ with CP, and 0/10 (0%) in the PPJ of the control patients, respectively. The incidences of aberrant methylation of SARP2 in the PPJ with PCa and IPMN were significantly higher than that in the PPJ with CP (P < 0.001, P < 0.001). Melting curve analysis by real-time MSP revealed that the incidences of aberrant methylation of SARP2 in PPJ was 28/33 (85%) with PCa, 9/11 (82%) with the malignant group of IPMN, 5/9 (56%) with the benign group of IPMN and 5/19 (26%) with CP. In this analysis, there were significant differences between PCa and CP (P < 0.001), and between the malignant group of IPMN and CP (P < 0.005). In the quantitative analysis by real-time MSP with a suitable cut-off value, the incidences of aberrant methylation of SARP2 in the PPJ with PCa, the malignant group of IPMN, the benign group of IPMN, and CP were 19/33 (58%), 6/11 (55%), 3/9 (33%), and 2/19 (11%), respectively. The incidence of the aberrant methylation of SARP2 in the PPJ was significantly different between PCa and CP and between the malignant group of IPMN and CP (P < 0.005 and P < 0.05, respectively). CONCLUSIONS: Hypermethylation of SARP2 in the PPJ may be a highly sensitive and useful marker for the detection of pancreatic neoplasms, including PCa and the malignant group of IPMN.

Adult↗
PubMed2005

Herbal medicine Ninjinyoeito ameliorates ribavirin-induced anemia in chronic hepatitis C: a randomized controlled trial.

AIM: Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when used in combination with interferon. However, RBV-induced anemia is a major problem in this therapy. It would be of great clinical importance to ameliorate the anemia without reducing the RBV dose. We report here that, Ninjinyoeito (NYT), a herbal medicine can reduce the RBV-induced anemia. METHODS: Twenty-three patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV with (NYT group) or without (control group) NYT by a randomized selection. Eighteen patients completed the treatment schedule, and hemato-biochemical and virological effects were evaluated. RESULTS: There was no significant difference in biochemical and virological responses between the two groups. However, anemia was significantly reduced in the NYT group compared with the control group. The maximal decrease of Hb in the NYT group (2.59+/-1.10 g/dL) was significantly (P = 0.026) smaller than that in the control group (3.71+/-0.97 g/dL). There was no significant difference in serum glutathione peroxidase activity, serum RBV concentration, and Th1/Th2 balance between the two groups. There was no specific adverse effect in NYT administration. CONCLUSION: These results suggest that NYT could be used as a supportive remedy to reduce the RBV-induced anemia in the treatment of chronic hepatitis C.

Anemia↗
PubMed2005

Duct-narrowing chronic pancreatitis without immunoserologic abnormality: comparison with duct-narrowing chronic pancreatitis with positive serological evidence and its clinical management.

We reviewed the clinical features and clinical course of patients with duct-narrowing chronic pancreatitis who were negative for immunoserologic test results (n = 16) in comparison with the findings for serological test-positive patients (n = 20) in order to determine an adequate treatment for those who had typical morphology of autoimmune pancreatitis in the absence of immunoserologic abnormality. No significant differences were found between the two groups of patients in clinical profiles including associated autoimmune-related diseases, pancreatic histology, and response to steroid therapy. Of the seronegative patients, eight who showed an improvement in narrowing of the main pancreatic duct with steroid therapy and three who did no show an improvement or who relapsed after surgical resection without this therapy had stenosis of the common bile duct with increased levels of serum hepatobiliary enzymes, except for two patients with affected sites limited to the body or tail of the gland. For the remaining five patients, who showed an improvement in pancreatic duct changes or long-term remission after surgery without steroid administration, normal biochemistry test results for liver functions were obtained, with no abnormal cholangiographic findings in the three patients examined. Duct-narrowing chronic pancreatitis without immunoserologic abnormality overlaps in clinical features with that fulfilling the immunoserologic criteria for a diagnosis of autoimmune pancreatitis. In particular, the disease with bile duct involvement should be treated clinically as autoimmune pancreatitis, for which steroid therapy is recommended, even if an autoimmune mechanism is not demonstrated serologically.

Adult↗
PubMed2005

A pilot study of individualized maximum repeatable dose (iMRD), a new dose finding system, of weekly gemcitabine for patients with metastatic pancreas cancer.

OBJECTIVES: We developed and established a new dose-finding system, the individualized maximum repeatable dose (iMRD), suitable to induce prolonged TTP rather than tumor shrinkage. METHODS: We applied this system in weekly gemcitabine therapy for 18 metastatic pancreas cancer patients. We determined the iMRD at the 5th week, after weekly dose adjustments. We started at 500 mg/m2 (1/2 maximum tolerated dose) of gemcitabine and repeated the treatment with an increase or a decrease of 100 mg/m each week, if toxicity was 0 or more than grade 1, respectively. RESULTS: The iMRD of weekly gemcitabine was 300 mg/m2 in 2 patients, 400 mg/m2 in 3 patients, 500 mg/m2 in 5 patients, 600 mg/m2 in 6 patients, and 700 mg/m2 in 2 patients, demonstrating significant differences among individual patients. Grade 3 marrow depression occurred in only 1 patient (5.6%). Of these 18 patients, 3 (16.7%), 13 (72.2%) and 2 (11.1%) patients showed partial response, stable disease, and progressive disease, respectively. The median of times to progressive disease and survival were 4.5 and 9.5 months, respectively. There were no significant differences in 1-year survival time and more than 50% reduction rate of serum CA19-9, a tumor marker for pancreatic cancer, between patients with lower (500 mg/m2 or less) and higher (600 mg/m2 or more) iMRD. CONCLUSION: These results suggest that iMRD is a simple method to determine an individual's tailored dose for chemotherapy and could be the optimal dose for patients with noncurable cancers such as metastatic pancreas cancer.

Aged↗
PubMed2005

Expression of mesothelin mRNA in pure pancreatic juice from patients with pancreatic carcinoma, intraductal papillary mucinous neoplasm of the pancreas, and chronic pancreatitis.

OBJECTIVES: In the gene expression analysis of pancreatic carcinoma (PCa) using serial analysis of gene expression (SAGE) according to Ryu et al, the tag for the mesothelin mRNA transcript was present in 7 of 8 SAGE libraries derived from PCa but not in the 2 SAGE libraries derived from normal pancreatic duct epithelial cells. Mesothelin mRNA expression was confirmed with in situ hybridization in all 4 resected primary PCa tumors and with RT-PCR in 18 of 20 PCa cell lines, whereas mesothelin protein expression was confirmed with immunohistochemistry in all 60 resected primary PCa tissues by Argani et al. We evaluated mesothelin mRNA expression in pure pancreatic juice (PPJ) obtained from patients with PCa, chronic pancreatitis (CP), and intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: We evaluated mesothelin mRNA expression in the PPJ obtained from 21 patients with PCa, 22 with CP, and 11 with IPMN with reverse transcriptase PCR (RT-PCR). The PCR products were analyzed with agarose gel electrophoresis. DNase I treatment before RT-PCR and direct sequencing of the RT-PCR bands were performed for the analysis of the RT-PCR bands. RESULTS: Two products, of 308 and 226 bp, were obtained with RT-PCR, and the 308-bp RT-PCR product was confirmed as being that derived from the genomic DNA by direct DNA sequencing. Mesothelin mRNA expression was discovered using RT-PCR in 11 (52%) of 21 patients with PCa, 5 (45%) of 11 with IPMN, and 3 (14%) of 22 with CP. Fisher's exact test revealed significant differences between PCa and CP for mesothelin mRNA (P < 0.01). Moreover, the RT-PCR product (226 bp) of mesothelin mRNA in the PPJ samples with PCa was generally stronger than that in the PPJ samples with IPMN. CONCLUSION: Expression of mesothelin mRNA in PPJ was not strictly specific to PCa and was apt to be stronger in PCa than in IPMN. Quantitative detection of mesothelin mRNA in PPJ may have potential diagnostic implications for pancreatic tumors.

Adenocarcinoma, Mucinous↗
PubMed2005

Long-term prognosis of duct-narrowing chronic pancreatitis: strategy for steroid treatment.

OBJECTIVES: The purpose of this study was to assess the long-term prognosis in patients with duct-narrowing chronic pancreatitis (DNCP) and determine the indications for steroid therapy. METHODS: We evaluated clinical and imaging outcomes in patients with DNCP classified into 3 groups (A, B, and C) according to the treatment given. Group A included 6 patients who underwent surgical resection. Groups B and C included 21 and 10 patients treated medically with and without steroid therapy, respectively. RESULTS: In group A, 2 patients relapsed in the remnant pancreas. In group B, pancreatic swelling was resolved in all the patients, and moreover, both the irregular narrowing of the main pancreatic duct (MPD) and the strictures of the common bile duct (CBD) improved after initiation of corticosteroid therapy in all but 1 of the patients, including 5 without immunoserologic abnormality. However, clinical recurrences occurred in 4 patients (19%) during or after the maintenance therapy. In group C, all the patients showed an improvement in swelling of the gland, while only 5 showed improvement of pancreatic duct involvement. Four of these 5 patients did not show any serologic data suggesting autoimmune abnormality or CBD involvement. In all the other 5 patients in whom MPD irregularities did not improve, bile duct strictures or positive immunoserologic test results were noted. CONCLUSIONS: Steroid therapy is effective for improving pancreatic duct and bile duct lesions in patients with DNCP and is indicated particularly in those with CBD strictures or immunoserologic abnormality, although some patients have recurrences.

Adrenal Cortex Hormones↗
PubMed2005

[DU-PAN-2, SPan-1].

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Antigens, Neoplasm↗
PubMed2004

A yeast one-hybrid system to detect methylation-dependent DNA-protein interactions.

We developed a method for site-selective CpG methylation of the budding yeast genome. The method recruits LexA-fused M.SssI DNA methyltransferase to LexA operator sequences integrated adjacent to the target site. Microarray analysis of methylated DNAs indicated that the tethered enzyme selectively methylates the region around the target site. Exploiting this method to methylate bait DNA in the one-hybrid system, we demonstrated methylation-dependent DNA binding of methyl-CpG binding proteins, MBD1 and Kaiso, in vivo. This methylation-dependent one-hybrid system would provide a versatile tool for the search and analysis of proteins that recognize methylated DNA to participate in epigenetic regulation.

Base Sequence↗
PubMed2004

Detection of p53 gene mutations in the supernatant of pancreatic juice and plasma from patients with pancreatic carcinomas.

AIM: The sensitivity of pure pancreatic juice (PPJ) cytology for the diagnosis of pancreatic carcinoma (PCa) is still low. The usefulness of genetic analyses of PPJ seems to be limited because of insufficient sensitivity or false positivity. To improve the molecular diagnosis of PCa, we analyzed mutations of p53 together with K-ras in DNA extracted not only from the sediment but also from the supernatant of PPJ samples. METHOD: Polymerase chain reaction-single-strand conformation polymorphism and direct sequencing were used for analyses of p53 mutations in exons 5-8. K-ras mutations at codon 12 were examined by mutant allele-specific amplification. RESULTS: In PPJ supernatant from patients with PCa, p53 and K-ras mutations were detected in 42.9% (9 of 21) and 81.0% (17 of 21) of cases, respectively. The incidence of p53 and K-ras mutations in the sediment was 28.6% and 71.4%, respectively. By a combination assay with supernatant and sediment, p53 mutations were detected in 52.4% (11 of 21) of PCa cases. Moreover, p53 mutations were detected in 7 of 15 (46.7%) cases of PCa in which the cytologic diagnosis was negative. Among 25 patients with chronic pancreatitis (CP), none harbored mutant p53, although K-ras mutations were detected at an incidence of 28% (7 of 25) in the supernatant and 20% (5 of 25) in the sediment. In addition, mutant bands of p53 in plasma were detected in 2 of 11 patients with PCa in whom p53 mutations were detectable in PPJ. CONCLUSION: These results suggest that the sensitivity of detection for p53 mutations with high cancer specificity could be improved by using the Sup in PPJ samples of PCa. Genetic analysis of p53 could complement PPJ cytology. p53 mutations were detectable in PCa from plasma samples.

Adult↗