Chronic pancreatitis with diffuse irregular narrowing of the main pancreatic duct.
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Aged↗
Biomedical subjects
N Sawabu
Publications and source records attributed to N Sawabu.
Miniprobe or ultrasound endoscope for gastric lesions?
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Endosonography↗
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↗
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↗
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↗
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↗
Undifferentiated (anaplastic) carcinoma of the pancreas showing sarcomatous change and neoplastic cyst formation.
CONCLUSION: Pancreatic undifferentiated (anaplastic) carcinoma contained two components: sarcomatous change of spindle-cell type and a neoplastic cyst. Immunohistochemical analysis suggested that both the sarcomatous and the cystic portions were of epithelial origin. This case showed a "dual" differentiation both into the sarcomatous change and into the cystic lesion. BACKGROUND: Pancreatic sarcoma or sarcomatous change is very rare. The origin of sarcomatous change is unknown. On the other hand, pancreatic adenocarcinoma sometimes shows necrosis and forms a cystic lesion during its growth, but a neoplastic cyst formation is very rare except for cystadenomas. METHODS: We report a case of pancreatic undifferentiated (anaplastic) carcinoma associated with sarcomatous change and neoplastic cyst formation. Clinicopathological and immunohistochemical analyses were performed. RESULTS: A 75-yr-old male was admitted because of low back pain and body weight loss. He died 7 d after admission presenting obstructive jaundice. Autopsy disclosed that the large mass was a poorly differentiated ductal adenocarcinoma, which mostly consisted of sarcomatous components of spindle-cell type. The cystic lesion was a neoplastic cysts with the wall composed of epithelial tumor cells. There was no necrosis or hemorrhage in the cystic cavity. Immunohistochemical analyses suggested that both the tumor and the cystic lesion were of epithelial origin. Sarcomatous changes were recognized also in the metastatic lesions in the liver and lymph nodes. The tumor is considered to be labeled undifferentiated (anaplastic) carcinoma of the pancreas.
Aged↗
Prolonged intrahepatic cholestasis in acute-onset, severe autoimmune hepatitis.
A 72-year-old woman was admitted because of jaundice and hepatocellular dysfunction. She was diagnosed with autoimmune hepatitis from laboratory test results showing high titers of antinuclear antibodies and negativity for hepatitis viral markers. Steroid i.v. pulse therapy and oral administration of prednisolone were effective in improving the liver function test results, except for hyperbilirubinemia. Elevated serum bilirubin levels, of approximately 20 mg/dl persisted for more than 6 months, despite the administration of ursodeoxycholic acid. Insulin-glucagon therapy was given for normalization of transaminases and then withdrawn 3 weeks after admission, but it was resumed at 3 months, resulting in a dramatic decrease in serum bilirubin levels, which then normalized in 2.5 months. Liver biopsy 6 months after onset showed chronic active hepatitis with bile plugs. Insulin-glucagon therapy, because of its choleretic effect, may be worth continuing even after recovery of acute hepatic failure.
Acute Disease↗
Effect of niuche-shen-qi-wan on painful muscle cramps in patients with liver cirrhosis: a preliminary report.
Twelve patients with liver cirrhosis complaining of painful muscle cramps were treated with Niuche-Shen-Qi-Wan (TJ-107). Three patients were at the decompensated state. Muscle cramps disappeared in 4 weeks on the average after oral administration of TJ-107 in all 12 patients. During the period of TJ-107 administration, there was no significant improvement of hepatic function. One patient complained of mild epigastric discomfort after taking TJ-107, but there were no other adverse effects. Our results indicate that TJ-107 is useful for treatment of painful muscle cramps in cirrhotic patients.
Administration, Oral↗
Effect of gegen-tang on painful gynecomastia in patients with liver cirrhosis: a brief report.
Four patients with liver cirrhosis and complaining of painful gynecomastia were treated with oral administration of Gegen-Tang (TJ-1). Pain disappeared in 3 patients in one week, and in one patient in 4 weeks. The size of gynecomastia did not change significantly on mammography, but palpable induration diminished or disappeared. The patients had been treated with Chaihu (saiko) group drugs for liver diseases, and TJ-1 was used in combination with these drugs. Serum levels of estrogen, progesterone, testosterone, and other sex hormones did not change significantly after TJ-1 treatment. These results suggest that TJ-1 could be used for the painful gynecomastia that is occasionally seen in cirrhotic patients.
Administration, Oral↗
Frequent loss of p16 expression and its correlation with clinicopathological parameters in pancreatic carcinoma.
Expression of the p16 gene product in human primary pancreatic carcinoma (PC) was investigated in paraffin-embedded tissue using a monoclonal antibody against p16 protein, clone G175-405, by means of immunohistochemistry, and the correlation of results with various clinicopathological parameters was evaluated. All six cases of normal pancreas and all but 1 of 20 cases of chronic pancreatitis expressed p16 protein, whereas 37.5% (3 of 8) of cystadenomas and 41. 9% (26 of 62) of PCs lost p16 expression. There was a significant difference between chronic pancreatitis and PC for frequency of the loss of p16 expression (P < 0.01). Moreover, loss of p16 expression in pancreatic malignancy was significantly associated with histological grade (G1 versus G2 and G3, P < 0.01) but not with sex, age, clinical stage, tumor location, or resectability. The survival period was shorter and metastasis is more likely in those cases that did not show p16 expression than those that did.
Adenocarcinoma↗
Cruveilhier-Baumgarten syndrome in which venous hum disappeared following endoscopic variceal sclerotherapy.
We report a case of Cruveihier-Baumgarten syndrome associated with portal vein thrombosis that developed, slowly during a 2-year period after endoscopic variceal sclerotherapy. The thrombosis led to the disappearance of the venous hum and the dilated abdominal wall veins characteristic of this syndrome. A 73-year-old woman was hospitalized for treatment of esophageal varices in April 1988. Her spleen was markedly enlarged, and the histologic findings of her liver were not consistent with hepatic cirrhosis, but with idiopathic portal hypertension. A venous hum was audible in the upper abdomen. Superior mesenteric angiography revealed a porto-systemic shunt vessel under the abdominal wall, originating from the umbilical vein. She was injected four times with a sclerosant, and this brought about disappearance of the esophageal varices. Two years after the first admission, the venous hum was no longer audible, but there was a recurrence of the esophageal varices. More than 2 years later (4 years after the first admission), ultasonographic study, computed tomography, and angiography showed a large thrombus, which completely obstructed the portal vein at the origin of the umbilical vein, and the development of collateral vessels, seen as a "cavernous transformation."
Aged↗
Detection of K-ras point mutations at codon 12 in pure pancreatic juice for the diagnosis of pancreatic cancer by PCR-RFLP analysis.
The present study was undertaken to detect K-ras point mutations at codon 12 in pure pancreatic juice (PPJ) for the diagnosis of pancreatic cancer (PC) using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. PPJ was collected through a cannula under a duodenal fiberscope from 26 patients with PC and 32 patients with chronic pancreatitis (CP). DNA was extracted from PPJ and was used as the template for PCR. Analysis of PPJ by PCR-RFLP with BstNI revealed that the incidence of K-ras point mutations at codon 12 was 81% (21/26) in patients with PC and 6% (2/32) in those with CP. With reference to the location of PC, the incidence of K-ras mutations was 79% (11/14) in the head, 86% (6/7) in the body, and 80% (4/5) in the tail of the pancreas. The incidence of K-ras mutants was 50% (1/2) in tumor size 1 (TS1; < or = 2.0 cm in size), 71% (5/7) in TS2 (2.1 to < or = 4.0 cm), 89% (8/9) in TS3 (4.1 to < or = 6.0 cm), and 88% (7/8) in TS4 (> 6.1 cm). These results suggested that analysis of K-ras point mutations at codon 12 in PPJ using the PCR-RFLP method is a promising new genetic test for the diagnosis of PC.
Adult↗
Detection of K-ras point mutations at codon 12 in pancreatic juice for the diagnosis of pancreatic cancer by hybridization protection assay: a simple method for the determination of the types of point mutation.
The present study was undertaken to detect K-ras oncogene point mutations at codon 12 in pure pancreatic juice (PPJ) by the hybridization protection assay (HPA) method for the diagnosis of pancreatic cancer (PC). This assay can be carried out within 30 min and can determine not only the presence of a mutation, but also the mutational type of K-ras at codon 12. The minimal ratio of mutant DNA detectable by the HPA was 5-10% of the total DNA. PPJ was collected through a cannula under duodenal fiberscope control from 20 patients with PC and 20 patients with chronic pancreatitis (CP). Analysis of PPJ by the HPA revealed that the incidence of K-ras point mutations at codon 12 was 55% (11/20) in patients with PC and 0% (0/20) in those with CP. Mutational types of K-ras at codon 12 in PC were aspartic acid (Asp) in nine cases, both Asp and cysteine in one case, and arginine in one case. Analysis of K-ras point mutations at codon 12 in PPJ using the HPA method seems promising as a new genetic test for the diagnosis of PC, because the HPA method is simple, and can easily determine the mutational type.
Base Sequence↗
[Kinds of cancer-associated antigens and their properties].
Although a number of substances have been reported to be tumor markers, no substance can be completely cancer-specific, but only a cancer-associated antigen (CAA). Now, CAA is considered to be a substance by which malignancies are distinguishable by a quantitative increase or qualitative change, even though it may be present or be produced in small quantities in normal cell as well. The following is a classification of CAAs chiefly on the basis of their origins. Group 1: ectopic CAA that is produced in a large amount in cancer cell, but can also be present or be produced in small amounts in its original normal cell. Group 2: ectopic CAA that is not present in the original normal cell, but can be produced by its carcinogenesis, though it can exist or be produced in other organs as well. Group 3: heterophile CAA that is not present in the human normal cell, but is produced by its carcinogenesis, though it can exist in other species. Group 4: fetal CAA that can be expressed in the fetal stage of the normal cell and vanishes after birth, but reappears with its carcinogenesis. This group includes oncofetal proteins, and carbohydrate antigens of which most are referred to as differentiation or developmental antigens. Based on the above classification, properties of each CAA are reviewed and discussed.
Antigens, Neoplasm↗
[Isoenzyme].
Expression of cancerous isoenzymes in various malignant tumors has been extensively studied using different biochemical techniques. Cancerous alkaline phosphatase (ALP) isoenzymes, such as placental ALP and variant ALP, are detected from sera of patients with various malignant diseases. Variant ALP is a specific tumor marker for hepatocellular carcinoma (HCC). The positive rate of each ALP isoenzyme is, however, low except for a high positivity of placental ALP in seminoma. Novel gamma-glutamyltranspeptidase (gamma-GTP) isoenzyme is specifically found in about 60% of the sera from patients with HCC but in only 3% of those from patients with benign liver diseases, suggesting a high specificity for HCC. Thus, cancerous isoenzymes are available for diagnosis of various malignant tumors.
Alkaline Phosphatase↗
[Sensitivity and specificity of tumor markers in cancer diagnosis].
Each serum tumor marker has its own sensitivity and specificity. The sensitivity is the true positive rate in malignant cases, and the specificity is the true negative rate in benign cases. We should ascertain various benign diseases or triggers which tend to show false-positivity, especially in the measuring of CA19-9, CA125, and acute phase reactants, such as, IAP and TPA. Cancer-specificity is high in sialyl-stage-specific embryonic antigen-I, sialyl-Tn antigen, and NCC-ST-439, etc. Organ-specificity is considerably high in the case of some markers, such as, alpha-fetoprotein, elastase-I, and neuron-specific enolase, etc. On the other hand, the organ-specificity of carcinoembryonic antigen is low. Therefore, the combination of different categories of tumor markers is of great importance. Recently, molecular diagnosis of cancer is being developed. However, even K-ras oncogene mutations at codon 12 are not absolutely specific to pancreatic cancer from genetic analysis of pancreatic juice endoscopically aspirated from patients with pancreatic diseases. Improvement of sensitivity and specificity is still one of the most important issues in the research and development of tumor markers.
Biomarkers, Tumor↗
Preoperative diagnosis of mucinous gastric adenocarcinoma by endoscopic ultrasonography.
OBJECTIVES: The aims of this study were to investigate the characteristic features of mucinous gastric carcinoma on endoscopic ultrasonography (EUS) and to demonstrate the usefulness of EUS in the preoperative diagnosis of this disease. METHODS: Twelve patients with mucinous gastric carcinoma who underwent EUS examination between April 1984 and April 1995 were enrolled in this study. All patients subsequently underwent surgery. Histopathologically, tumors were classified according to the mucin content (high or moderate) and the glandular formation of the tumor cells (well or poorly differentiated). Finally, the histological and endosonographic features were compared. RESULTS: In all patients, the infiltrated wall appeared echogenic because of diffusely distributed, reticular, highly echoic speckles in the submucosa and muscularis propria. The presence of mucinous lakes surrounded by reactive fibrous tissue correlated well with reticular, highly echoic speckles on EUS. There was an increase in echogenicity and thickness of the muscularis propria, depending on the invasion of the mucin. Although the boundary between submucosa and muscularis propria was distinct and the five-layered gastric wall structure was generally preserved, the mucosal layer was not discriminated in patients with poorly differentiated mucinous carcinoma with high mucin content. CONCLUSIONS: As a preoperative diagnostic procedure, EUS may be useful in recognizing the mucinous component of gastric tumors and may facilitate the differentiation of mucinous carcinoma from other gastric epithelial tumors.
Adenocarcinoma, Mucinous↗