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Biomedical subjects

N Sawabu

Publications and source records attributed to N Sawabu.

At least 19 recordsLinked to original sources
PubMed1999

K-ras mutations in duodenal aspirate without secretin stimulation for screening of pancreatic and biliary tract carcinoma.

BACKGROUND: K-ras mutations at codon 12 (KRM) have been detected in over 80% of tissues and pure pancreatic juice (PPJ) samples from patients with pancreatic carcinoma (PCa) and are promising genetic tumor markers. Aspirating PPJ not only requires technical skill, but is also exhausting for patients. The authors attempted to evaluate whether the detection of KRM in the duodenal aspirate (DA) obtained immediately after endoscopic retrograde cholangiopancreatography (ERCP), an easier sample-collecting method than collecting PPJ, could be useful for the diagnosis of PCa and biliary tract carcinoma (BTCa). METHODS: DA was collected endoscopically without secretin stimulation immediately after the ERCP procedure from 160 patients: 38 patients with PCa, 38 with chronic pancreatitis (CP), 22 with BTCa, 20 with adenomyomatosis of the gallbladder (AGB), 22 with cholecystolithiasis (CCL), and 20 control subjects. Mutant allele specific amplification (MASA), which is a highly sensitive method for detecting KRM, was performed, with the DNAs extracted from these samples by phenol-chloroform. RESULTS: The incidence of KRM in DA by MASA was 25 (66%) of the 38 PCa cases, 12 (32%) of the 38 CP cases, and 12 (55%) of the 22 BTCa cases. There was no patient with positive KRM in DA among the 20 cases of AGB, 22 of CCL, and 20 control subjects. The sensitivity was 62% and the specificity 88% in this study design. The KRM incidence was found to be relatively high for the patients with PCa and BTCa by MASA, which is a highly sensitive method, although the incidence of KRM in DA from the patients with PCa was not as high as the incidence in their PPJ with secretin stimulation. CONCLUSIONS: MASA showed a relatively high incidence of KRM even in the DA, which was easily obtained from the patients with PCa and BTCa without secretin stimulation immediately after ERCP. These results suggest that the detection of KRM in the DA by MASA is useful for the screening of both PCa and BTCa.

Adult↗
PubMed1999

Mucin-producing biliary papillomatosis associated with gastrobiliary fistula.

We report a case of mucin-producing biliary papillomatosis in a 78-year-old woman. Abdominal ultrasound (US) and computed tomography (CT) showed wall thickening and dilatation of the intrahepatic bile duct (IHBD), as well as a nodular lesion, 1.2 cm in diameter, in the left branch of the IHBD. Gastric endoscopy revealed excretion of bile-containing mucin on the anterior wall of the body of the stomach. Endoscopic ultrasonography (EUS) showed gastrobiliary fistula and discharge of mucin into the stomach. Needle biopsy of the biliary tumor revealed papillary proliferation, but no malignant cells were recognized histologically. Therefore this patient was diagnosed as having mucin-producing biliary papillomatosis forming gastrobiliary fistula. She did not present with obstructive jaundice, probably because of the fistula. She is alive, without obstructive jaundice, 16 months after the diagnosis without having had surgery. This is, to our knowledge, the first reported case of biliary papillomatosis forming gastrobiliary fistula and with the patient free of obstructive jaundice.

Aged↗
PubMed1999

Primary biliary cirrhosis associated with type A gastritis and chronic thyroiditis.

We report a patient with primary biliary cirrhosis (PBC) associated with type A gastritis, chronic thyroiditis, and iron deficiency anemia. The patient was a 45-year-old Japanese woman who was admitted to our hospital with severe microcytic and hypochromic anemia, abnormal results for liver function tests, and a diffuse goiter. The diagnosis of PBC (Scheuer's stage II) was confirmed by the presence of specific anti-mitochondrial antibody in high titers and histological examination showing chronic non-suppurative destructive cholangitis with bridging fibrosis. Additionally, marked atrophic mucosa throughout the body and fundus of the stomach was observed endoscopically, and there was positivity for intrinsic factor antibody, an extremely low ratio of serum pepsinogen A to C, and hypergastrinemia, indicating coexisting type A gastritis. The severe anemia was thought to be caused by failure of dietary iron absorption related to achlorhydria with this gastritis. However, the serum level of vitamin B12 was normal. She also had autoimmune thyroiditis. PBC is frequently associated with extrahepatic autoimmune diseases, including ductular lesions. However, the association of PBC with type A gastritis is quite rare, although the stomach is also an exocrine glandular structure. This particular case, in addition to previous reports, leads to a discussion of whether type A gastritis should be regarded as a possible, although uncommon, component disorder of so-called dry gland syndrome.

Anemia, Iron-Deficiency↗
PubMed1999

EUS and K-ras analysis of pure pancreatic juice collected via a duodenoscope after secretin stimulation for diagnosis of pancreatic mass lesion: a prospective study.

BACKGROUND: The early diagnosis of pancreatic cancer remains problematic. This prospective study assessed the utility of a combination of endoscopic ultrasound (EUS) and genetic analysis of pure pancreatic juice in the diagnosis of pancreatic mass lesions. METHODS: One hundred seventy-six patients with suspected pancreatic disease were enrolled and underwent ultrasonography (US), computed tomography (CT), endoscopic retrograde choleangiopancreatography (ERCP), and EUS. Pure pancreatic juice was collected endoscopically after secretin stimulation. K-ras point mutations at codon 12 in the juice were assayed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Thirty-six (20%) patients were found to have solid pancreatic masses including 19 with cancer (7 patients, </= 2 cm) and 17 patients with an inflammatory mass (13 patients, </= 2 cm). US and CT were both less sensitive, particularly in patients with small masses. In 13 patients, small masses (4 cancer and 9 inflammatory masses) were not delineated until EUS. The combination of EUS and K-ras analysis had a high sensitivity (100%; p < 0.05 vs. US) and its accuracy reached 94% (p < 0.01 vs. US). CONCLUSIONS: EUS and K-ras determination in pure pancreatic juice collected via a duodenoscope may be useful for the diagnosis of pancreatic mass lesions.

Adenocarcinoma↗
PubMed1999

Serum levels of pancreatitis-associated protein in digestive diseases with special reference to gastrointestinal cancers.

The serum levels of pancreatitis-associated protein (PAP) were measured in 196 patients with digestive diseases and 15 healthy subjects by an enzyme-linked immunosorbent assay. The serum PAP levels were significantly elevated in the patients with gastric, colorectal, biliary tract, hepatocellular, or pancreatic cancers compared with the healthy subjects. After curative resection of the tumor, serum PAP levels were significantly decreased. The serum PAP levels were not related to clinicopathological factors except for the tumor size of pancreatic cancer. There were some cases of PAP-positive and carcinoembryonic antigen (CEA) or carbohydrate antigen (CA) 19-9 -negative gastric and colorectal cancers. The serum PAP levels were also significantly elevated in the patients with acute pancreatitis compared with those in not only the healthy subjects but also the patients with chronic pancreatitis. The peak PAP levels were significantly correlated with the severity of acute pancreatitis and reflected the clinical healing of the disease. The peak of serum PAP was significantly delayed compared with those of other pancreatic enzymes. These results suggest that the increase of serum PAP levels in patients with gastrointestinal cancers reflects an ectopic expression of PAP in cancer cells and that increased serum levels of PAP in acute pancreatitis are correlated with the disease severity and are prolonged than those of other pancreatic markers.

Acute Disease↗
PubMed1999

Bcl-2 expression related to altered p53 protein and its impact on the progression of human pancreatic carcinoma.

p53 and Bcl-2 are two important factors related to apoptosis and tumorigenesis. In this study, a series of 52 cases of pancreatic carcinoma (PC) were investigated using an immunohistochemical assay to determine whether altered expression of Bcl-2 and p53 has an impact on the progression of this malignancy. Cytoplasmic immunoreactivity for Bcl-2 and nuclear staining of p53 was found in 12 (23.1%) and 32 (63.5%) cases of PC respectively. Furthermore, an inverse correlation between the expression of p53 and Bcl-2 existed in this series (P < 0.01). In a subgroup, the proportion of tumours showing that p53-positive and Bcl-2-negative staining was increased with increasing histological grade and clinical stage (P < 0.05), and moreover, the survival period of those patients whose tumour had this staining was shorter than those with other staining patterns of combined p53 and Bcl-2 (P < 0.05). Therefore, it is concluded that simultaneously aberrant expression of Bcl-2 and p53 may confer PC with more malignant clinicopathological characteristics.

Adenocarcinoma↗
PubMed1999

Diagnostic value of endoscopic retrograde pancreatography in chronic pancreatitis based on the new criteria proposed by the Japan Pancreas Society in 1995: comparison with the criteria proposed by the Japanese Society of Gastroenterology in 1983.

This study evaluated the new criteria for the diagnosis of chronic pancreatitis (CP) with endoscopic retrograde pancreatography (ERP) proposed by the Japan Pancreas Society in 1995 by comparing it with the older criteria of the Japanese Society of Gastroenterology proposed in 1983. No significant differences were noted between the two when the diagnostic sensitivity of ERP was considered in calcifying CP. Among 54 patients of noncalcifying CP (group I) with ERP diagnosis of moderate or advanced pancreatitis by the previous criteria, only one of 22 with the localized type was definite CP. The remaining 21 were ruled out as either definite or probable CP, and six were classified as having chronic obstructive pancreatitis based on the new criteria. In contrast, a diagnosis of definite CP was made not only for all the 32 patients with CP (group I) of diffuse type but also in 11 cases of CP (group II) with diffuse minimal pancreatitis showing irregular dilatation of the side branches with scattered distribution throughout the gland. In a series of 15 follow-up patients with CP (group II) having initial ERP diagnosis of minimal pancreatitis, CP group I developed in three of five cases of diffuse minimal pancreatitis, which is consistent with definite CP by the new criteria, whereas progression to this group of CP was found in none of the 10 patients with localized minimal pancreatitis. These results indicate that although localized CP is excluded from CP, the incidence of diffuse noncalcifying CP diagnosed by ERCP was increased with the new criteria, and detecting radiologic features with diffuse irregular dilatation of the branch ducts based on these criteria may lead to early diagnosis of CP.

Calcinosis↗
PubMed1999

Expression of pancreatitis-associated protein (PAP) in rat spontaneous chronic pancreatitis: effect of herbal medicine Saiko-keishi-to (TJ-10).

Pancreatitis-associated protein (PAP) is almost absent in the normal pancreas but is overexpressed in acute pancreatitis. However, its expression in chronic pancreatitis (CP) is unknown. An herbal medicine Saiko-keishi-to (TJ-10) has long been used clinically for CP, but there is no experimental evidence of the effect of TJ-10 on CP. The aim of this study was to analyze the expression of PAP and the effect of TJ-10 in a spontaneous chronic pancreatitis model. Four-week-old male WBN/Kob rats were fed with a special pellet diet (MB-3), and TJ-10 (80 mg/100 g body weight/day) was orally administered for 16 weeks. The rats were killed at every 4 weeks, and pancreata were histopathologically examined. PAP messenger RNA (mRNA) in the pancreas was detected with a reverse transcription/polymerase chain reaction (RT-PCR) method. The cellular localization of PAP mRNA and protein was analyzed with in situ hybridization (ISH) and immunohistochemistry (IHC). PAP mRNA was expressed from 8 weeks, when the pancreas was still pathologically normal, and reached its peak at 12 weeks, when the pancreatitis first appeared. Then the expression of PAP mRNA was decreased gradually. TJ-10 suppressed the expression of PAP mRNA completely at 8 and 12 weeks. PAP mRNA was slightly expressed at 16 and 20 weeks. ISH and IHC confirmed the PAP mRNA and protein expression in the cytoplasm of acinar cells. These results suggest that PAP mRNA appears before CP, and its peak coincides with the onset of CP. TJ-10 suppressed the PAP expression and delayed the development of CP in the WBN/Kob rat.

Acute-Phase Proteins↗
PubMed1999

Effect of Koso-san on globus pharyngeus.

Twenty-three patients with globus pharyngeus were treated with Koso-san (TJ-70) at a dose of 7.5 g/day for at least 14 days. Symptoms disappeared in 18 cases and improved in 3 cases, therefore, the effective rate was 91.3% (21/23). The symptoms disappeared on average within 13.5 days. Terasawa qi-stasis scores were significantly decreased after the treatment. TJ-70 might thus be a remedy for globus pharyngeus with qi-stasis.

Adult↗
PubMed1999

Urinary gonadotropin peptide as acute phase reactant: transient elevation after operation for digestive diseases.

OBJECTIVE: In order to characterize urinary gonadotropin peptide (UGP) as an acute phase reactant, we focused on the UGP levels after surgical operation. DESIGN: Fifty cases of gastrointestinal cancer, 4 cases of cancers of other organs and 13 cases of benign digestive diseases were enrolled into this study. METHODS: UGP levels were measured using an enzyme immunoassay before and after surgery. RESULTS: Fifty-four (80.6%) of the 67 cases studied showed transient elevations of UGP. Both urinary interleukin (IL)-6 and LH levels were also increased transiently in 49 cases (73.1%). All of these three factors were increased in 38 cases (56.7%), and in 32 (84.2%) of these 38 cases, the order of peak appearance was as follows: IL-6, LH, and UGP. The UGP levels in the group of total gastrectomy were significantly higher than those in the group of partial gastrectomy. CONCLUSIONS: These results suggest that UGP shows a transient peak after surgery, correlating with levels of cytokines such as IL-6. UGP may be an acute phase reactant, and its levels are correlated with the grade of surgical stress.

Acute-Phase Reaction↗
PubMed1999

Detection of mutations of p53 tumor suppressor gene in pancreatic juice and its application to diagnosis of patients with pancreatic cancer: comparison with K-ras mutation.

Because of the difficulty in obtaining biopsy specimens from pancreatic cancer patients, K-ras mutation analysis in pancreatic juice has been used for specific diagnosis. But recently, false positives have been obtained with this method. To improve the genetic diagnosis of pancreatic cancer, detection of p53 gene mutation in pancreatic juice was studied. Pancreatic juice was sampled endoscopically. Single-strand conformation polymorphism analysis was used for p53 mutation analysis. Furthermore, K-ras mutations at codon 12 were also studied in the same pancreatic cancer patients. Of 26 cases of pancreatic cancer, p53 mutations were detected in 11 (42.3%). No mutations were seen in the cases with mucin-producing adenoma nor with chronic pancreatitis. K-ras mutations were detected in 84.0% of cases by RFLP analysis, which has high sensitivity, and in 65.3% by hybridization protection assay, which has high specificity. Using a combination assay with both genes, genetic abnormalities were detected in 92.0% by RFLP and 73.1% by hybridization protection assay including two cases in which p53 alone was positive by both methods. The specificity of p53 mutation for pancreatic cancer is very high. Therefore, simultaneous analysis of p53 and K-ras mutation is suggested to enhance the genetic diagnosis of pancreatic cancer.

Aged↗
PubMed1998

Expression of pancreatitis-associated protein (PAP) mRNA in gastrointestinal cancers.

CONCLUSION: Pancreatitis-associated protein (PAP) mRNA is expressed in some cases of gastric and colorectal cancers resulting from an ectopic expression in dedifferentiated cancer cells. BACKGROUND: The PAP gene is identical to the hepatoma-intestine-pancreas (HIP) gene, which is expressed in hepatoma. Expression in cancer might be another characteristic of PAP. METHODS: Fresh surgical specimens of 100 gastrointestinal cancers, 14 benign digestive diseases, and six normal organs were studied with nonisotopic in situ hybridization (ISH) using biotin-labeled cDNA probe. RESULTS: PAP mRNA was detected in 10% (6/60) of gastric cancers, 21.4% (6/28) of colorectal cancers, 20.0% (1/5) of pancreatic cancers and 0% of biliary tract (three), esophageal (one), and hepatocellular cancers (three). Reverse transcription-polymerase chain reaction (RT-PCR) detected PAP mRNA in these ISH-positive cases. PAP mRNA was not detected in noncancerous portions, benign disease tissues, or normal organs except for the small intestine. There was no relationship between PAP mRNA expression and any clinicopathological factors.

Acute-Phase Proteins↗
PubMed1998

Pancreatic cancer associated with granulocyte-colony stimulating factor production confirmed by immunohistochemistry.

We report an 83-year-old man with pancreatic body cancer of 4.5 cm in diameter. Peripheral leukocyte count was 15,700/microl and the serum concentration of granulocyte-colony stimulating factor (G-CSF) was 123 pg/ml (normal, 6.0-21.9 pg/ml) on admission. Furthermore, not only K-ras codon 12 (GGT --> GAT) but also p53 at codon 247 (CGG --> CCG) mutations were identified in the pancreatic juice aspirated endoscopically. We performed chemotherapy with two courses of 5-fluorouracil, pirarubicin hydrochloride, and mitomycin-C, resulting in no beneficial effect. After the second course the patient developed interstitial pneumonia, probably caused by anticancer drugs, and died 4 months after the tumor was detected. In the autopsy tissue, the tumor macroscopically occupied the pancreas body and was 7 x 6 x 5 cm in size. Histopathologic diagnosis of the tumor was poorly differentiated adenosquamous carcinoma. Immunohistochemical staining of the autopsy tissue showed that pancreatic cancer cells were positive for G-CSF. This is the first case report of G-CSF-positive pancreatic cancer confirmed by immunohistochemistry.

Aged↗
PubMed1998

Quantitative determination of K-ras mutations in pancreatic juice for diagnosis of pancreatic cancer using hybridization protection assay.

K-ras mutations at codon 12 (KRM) have been detected in approximately 80% of samples of pure pancreatic juice (PPJ) from patients with pancreatic cancer (PCa) and are a promising potential tumor marker. However, the frequent presence of KRM was reported in PPJ from noncancerous patients as determined by a highly sensitive method, raising questions as to the cancer specificity of this marker. Therefore we evaluated whether the hybridization protection assay (HPA), which can quantitatively determine KRM in PPJ, is useful for the diagnosis of PCa, differentiating from chronic pancreatitis (CP). PPJ was collected endoscopically from 29 patients with PCa, 26 patients with CP, and the 11 cases as the control group. Polymerase chain reaction (PCR) and HPA using an acridinium ester-labeled DNA probe for KRM were performed with DNA extracted from these samples. The results were compared with those obtained by PCR-restriction fragment length polymorphism (RFLP). The mean + 2 SD of chemiluminescence in the control group was 11,020 RLUs. When 11,020 RLUs was taken as the cut-off value, KRM was detected by PCR-HPA in 19 (66%) of 29 of PCa and one (4%) of 26 of CP cases. Analysis of PPJ by PCR-RFLP demonstrated KRM in 22 (79%) of 28 of PCa and five (19%) of 26 of CP cases. However, four of five patients with CP who were KRM-positive by PCR-RFLP were defined as negative by PCR-HPA, suggesting that PCR-HPA is superior to PCR-RFLP for the discrimination between PCa and CP. These findings indicate that quantitative analysis of KRM in PPJ using the PCR-HPA method is a promising approach for the diagnosis of PCa, differentiating from CP with a suitable cut-off value, as in the case with the use of conventional serum tumor marker.

Aged↗
PubMed1998

Infrequent expression of p21 is related to altered p53 protein in pancreatic carcinoma.

This study is designed to investigate the expression of p21 and its relation to altered p53 protein in pancreatic carcinoma (PC). Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue sections of PC was performed using a monoclonal antibody against p21 (187), with a parallel examination of altered p53 protein. The expression of p21 was only found in 12 of 58 (20.7%) PCs and, moreover, was mainly restricted to the well-differentiated ductal epithelium. Sixty-four % (37 of 58) of PCs showed positive p53 staining, and this change was significantly related to the absence of p21 expression (P < 0.01). In a subgroup, the proportion of the undetectable p21 expression and the expression of p53 were increased with increasing tumor grade but decreased with advancing clinical stage. The results of the present study suggest that the absence of p21 expression is very common in PCs and appears to relate to altered p53 protein. Moreover, the abnormalities involving the expression of p21 and p53 may play a more important role in the development than in the progression of this malignancy.

Adult↗
PubMed1997

Sclerosing pancreatitis showing rapidly progressive changes with recurrent mass formation.

CONCLUSION: Sclerosing pancreatitis might develop repeatedly or might rapidly extend to the whole pancreas with recurrent mass formation. BACKGROUND: Nothing is known concerning course or development of sclerosing pancreatitis. METHODS: A 63-yr-old male was followed up for 2.5 yr. RESULTS: The patient was admitted because of a tumor in the body and tail of the pancreas. Serum pancreatic enzymes were transiently elevated, but tumor markers were all negative. Imaging studies showed a tumor 7 cm in size. The main pancreatic duct was normal in the head and obstructed at the body on endoscopic retrograde pancreatography (ERCP). The K-ras oncogene mutation was positive in pure pancreatic juice. Distal pancreatectomy was performed because pancreatic cancer was highly suspected. Pathological findings showed that the tumor was a densely fibrotic mass without malignant cells. Inflammatory cell infiltration was observed in the stroma. One year later, another mass 3 cm in size was noted in the remnant pancreatic head. ERCP revealed diffuse irregular narrowing of the main pancreatic duct, its branches, and the common bile duct. Liver dysfunction improved and an elevation of serum pancreatic enzymes subsided without any specific treatment, and the mass diminished in size. The patterns of various imaging studies on the second tumor were the same as those of the previous resected mass. Corticosteroid was not administered.

Genes, ras↗