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T Obara

Publications and source records attributed to T Obara.

At least 55 records · Page 3Linked to original sources

alpha-Fetoprotein-producing adenocarcinoma of the pancreas presenting focal hepatoid differentiation.

We report a rare case of pancreatic carcinoma producing alpha-fetoprotein (AFP), showing focal hepatoid differentiation in metastatic lymph nodes. A 65-yr-old female was admitted because of abdominal pain. The serum AFP was measured at 16,170 ng/mL. Radiological examinations revealed a mass measuring 6 cm in diameter in the body and tail of the pancreas. A right supraclavicular lymphadenopathy was found and biopsied. Light microscopy showed a tumor consisting of a portion of a hepatoid area and well-differentiated adenocarcinoma, which was suggestive of a hepatoid adenocarcinoma. Immunohistochemical analysis showed that the tumor cells expressed AFP, alpha 1-antitrypsin (AT) and albumin. Although the pathological diagnosis of the primary pancreatic tumor was not obtained, this appears to be the first case of hepatoid adenocarcinoma of the pancreas.

Adenocarcinoma↗

[Surgical treatment of Graves' disease].

Surgery has a definite role in the management of patients with Graves' disease, although it may be followed by perioperative complications and postoperative thyroid dysfunction. Since alternative treatments such as antithyroid drugs or radioiodine are also available, the decision making in the management should be based on clear assessment of advantages and limitations of each strategy by both patients and physicians. As clinicians caring for patients, we have to make efforts to obtain valid and reliable evidence regarding clinical outcomes of the treatment options so that the information can be used for the decisions in daily medical practices where patients' values and preferences are also important determinants.

Graves Disease↗

Immunohistochemical estimations of growth activity to predict biological behavior of pheochromocytomas.

To determine the usefulness of immunohistochemical estimations of growth activity to predict biological behavior of pheochromocytomas (PC), 42 cases of PC (33 adrenal and nine extra-adrenal tumors) were studied by immunohistochemistry using the monoclonal antibody, MIB-1. The mean MIB-1-positive cell rate for all 42 PCs was low (1.4%). The MIB-1-positive cell rates of adrenal PCs were significantly higher in malignant tumors (mean, 3.30%) than in benign tumors (mean, 0.81%) (P = .0184). In extra-adrenal PCs, the difference between benign (mean, 0.44%) and malignant (mean, 5.10%) tumors was also statistically significant (P = .0004). Other clinicopathologic factors, including family history, age, sex, and multiple endocrine neoplasm (MEN) type II status were also examined and were not statistically significant. In conclusion, estimation of the MIB-1-positive cell rate is useful for histologic distinction between benign and malignant pheochromocytomas. Especially, it is important to note that a high MIB-1-positive cell rate (>2%) is highly suggestive of malignancy.

Adolescent↗

Proliferative potential and K-ras mutation in epithelial hyperplasia of the gallbladder in patients with anomalous pancreaticobiliary ductal union.

BACKGROUND: Recent studies have shown that anomalous pancreaticobiliary ductal union (APBD) is an important risk factor for the development of gallbladder carcinoma. Epithelial hyperplasia of the gallbladder is one of the characteristic changes, but it is not clear whether epithelial hyperplasia is a premalignant lesion that could lead to cancer in APBD patients. METHODS: Twenty-four APBD patients were classified into two types: patients with bile duct dilation (dilated type) (n 13) and patients without dilation (undilated type) (n = 11). Resected gallbladders obtained from APBD patients and control patients without APBD were examined histologically and with immunohistochemical techniques for the detection of p53 and Ki-67 (as a cell proliferation marker). K-ras mutations were examined using polymerase chain reaction-restriction fragment length polymorphism and direct DNA sequence analysis. The patients were also classified, according to extent of epithelial hyperplasia, as having high grade or low grade hyperplasia. RESULTS: Fifteen (63%) of 24 APBD patients had epithelial hyperplasia of the gallbladder, whereas no patients without APBD exhibited this lesion. The incidence of epithelial hyperplasia was significantly higher in the gallbladders of undilated-type APBD patients (91%) than in those of dilated-type patients (38%) (P < 0.01). Three of 24 APBD patients (13%) had gallbladder carcinoma, and 2 of the 3 gallbladder carcinomas (67%) were accompanied by diffuse epithelial hyperplasia of the gallbladder. Among 21 nonneoplastic gallbladders, diffuse epithelial hyperplasia was observed in all (100%) of the undilated-type APBD and in 4 (33%) of 12 dilated-type APBD (P < 0.001). High grade hyperplasia was observed in 7 of 11 patients (64%) with undilated-type APBD and 2 of 13 patients (15%) with dilated-type APBD (P < 0.05). The incidence of high grade hyperplasia increased with age among patients older than 35 years. Ki-67 labeling index (LI) was significantly higher in hyperplastic mucosa than in control gallbladder mucosa. High grade hyperplasia had a significantly higher Ki-67 LI than low grade hyperplasia (P < 0.001). Two (22%) of 9 high grade hyperplasia cases had K-ras mutations, whereas none of 6 low grade hyperplasia cases had. The types of K-ras mutations in codon 12 were GTT (Val) and GAT (Asp) in each case of hyperplasia; these were identical to those of concomitant carcinomas. Neither hyperplastic nor normal mucosa exhibited p53 overexpression. CONCLUSIONS: The results of this study suggest that hyperplasia of the gallbladder mucosa in APBD patients is an early change that, because of the increased proliferative activity and presence of K-ras mutations, could be considered a premalignant lesion of the gallbladder. An increased cell population of epithelial hyperplasia may predispose the mucosa to mutational events, resulting in an increased risk for the development of gallbladder carcinoma in APBD patients.

Adolescent↗

Cytologic characteristics of parathyroid carcinoma: a case report.

A 44-yr-old man with a preoperative diagnosis of malignant mediastinal goiter underwent a preoperative fine-needle aspiration (FNA) biopsy. Fine-needle aspiration biopsy showed enlarged uniform nuclei, prominent nucleoli, few mitotic figures, karyolysis, anuclear cells, hyalinized nonepithelial cell clusters with hemosiderin deposits, and a perivascular pseudorosette pattern. This study reviewed the current literature dealing with this cytologic feature of parathyroid carcinoma. To our knowledge, this is the first report of an oxyphilic cell type of parathyroid carcinoma detected by FNA in the English-language literature.

Adenocarcinoma↗

Selective cytotoxicity of farnesylamine to pancreatic carcinoma cells and Ki-ras-transformed fibroblasts.

Farnesyl protein transferase (FPTase) catalyses the post-translational modification of proteins by a farnesyl pyrophosphate. One of the substrates of this enzyme is p21ras, the product of the ras oncogene. We examined whether farnesylamine, one of the FPTase inhibitors (FTI), is selectively cytotoxic in pancreatic carcinoma cells and Ki-ras-transformed fibroblasts. Furthermore, we investigated whether the cytotoxicity of farnesylamine is caused by the induction of apoptosis in these cells. Using the FPTase assay, we found that farnesylamine inhibited FPTase in vitro. Immunoprecipitation showed that farnesylamine inhibited farnesylation of p21ras in vivo. In addition, 24 and 5 microM farnesylamine were required to achieve 50% cytotoxicity in pancreatic carcinoma cells containing activated Ki-ras and Ki-ras-transformed NIH/3T3 cells, respectively. The parental NIH/3T3 cells were resistant to the cytotoxic effect of farnesylamine at concentrations less than 100 microM. After incubation with farnesylamine, DNA fragmentation was observed in both pancreatic carcinoma cells and Ki-ras-transformed fibroblasts at cytotoxic doses of this compound but not in NIH/3T3 cells. These results indicate that the mechanism of cell death induced by farnesylamine is apoptosis, and this apoptosis occurred specifically in pancreatic carcinoma cells containing mutated Ki-ras and the Ki-ras-transformed cells. Because raf is downstream of ras (p21ras) in the ras-raf-mitogen-activated protein kinase signaling pathway, we used c-raf-1-transformed fibroblasts, which proved to be resistant to apoptosis induced by farnesylamine. This supports the theory that inhibition of ras signaling may be related to the induction of apoptosis. These data further suggest that farnesylamine could be useful as a chemotherapeutic agent in cancers that very frequently contain a Ki-ras oncogene mutation, e.g., pancreatic cancer.

3T3 Cells↗

Multifocal serous cystadenoma of the pancreas. A case report and review of the literature.

Serous cystadenoma of the pancreas is usually unifocal; multifocal tumors are rare. We report a case of multifocal serous cystadenoma of the pancreas in a 48-yr-old female complaining of general malaise. Serum tumor markers, such as CA 19-9, DUPAN-2, and Span-1, were elevated. Abdominal ultrasound (US) and computed tomography (CT) scans revealed two distinct cystic masses in the head and body of the pancreas, respectively. The patient underwent total pancreatectomy. The resected pancreas contained two discrete cystic masses in the head and body; no solid components were observed. Microscopically, the inner surfaces of the cysts were evenly lined by a single layer of low cuboidal or significantly attenuated epithelial cells containing clear cytoplasm and abundant glycogen without other morphological alterations. The histogenesis of serous cystadenoma is not clear; multicentric tumors may be helpful in understanding histogenesis.

Abdomen↗

Efficacy of single-voided urine metanephrine and normetanephrine assay for diagnosing pheochromocytoma.

Urinary catecholamines (CAs) and their metabolites are usually measured during the process of diagnosing pheochromocytoma (pheo), but a 24-hour urine collection is not convenient for outpatients. Since 1987 we have utilized "spot" urine metanephrine (MN) and normetanephrine (NMN) assays for management of patients with pheo or adrenal incidentaloma. MN and NMN were measured by radioimmunoassay in 82 patients with surgically proved pheo and 15 patients with incidentaloma. In 10 patients with pheo, MN and NMN were measured with fractional every-3-hour urine samples, which were accumulated and then measured as a 24-hour urinary specimen. Fractions of 3-hour MN and NMN excretion were constant (MN 98.5 +/- 9.6%, NMN 97.6 +/- 10.8%; 24-hour MN and NMN 100%). The average levels of MN and NMN in patients with pheo were 6801 ng/mg creatinine (Cr) (range 93-88,248, median 1426) and 5627 ng/mg Cr (range 219-31,528, mean 3190), whereas the MN and NMN levels in patients with incidentaloma were 123 ng/mg Cr (range 36-246, mean 133) and 251 ng/mg Cr (range 84-472, mean 220), respectively. When we selected a cutoff value for MN + NMN of 1000 ng/mg Cr, the sensitivity was 97.6% and the specificity 100% for diagnosing pheo. When the standard was set as > 500 ng/mg Cr for either MN or NMN, both the sensitivity and specificity were 100%. The assay for MN and NMN is simple and effective, not only for screening but for diagnosing pheo and managing incidentaloma.

Adrenal Gland Neoplasms↗

Segmental groove pancreatitis accompanied by protein plugs in Santorini's duct.

"Groove pancreatitis", a form of segmental pancreatitis affecting the head of the pancreas, is localized within the "groove" between pancreas head, duodenum, and common bile duct. Differentiation between groove pancreatitis and pancreatic head carcinoma is often difficult. We report a case of groove pancreatitis in which a hypoechoic mass between the duodenal wall and pancreas was clearly imaged, and narrowing of the second portion of the duodenum and bile duct stenosis were also found. The diagnosis was confirmed by surgery (pylorus-preserving pancreato duodenectomy). The patient was relieved from abdominal pain post operation. Up to the present, the patient has been good condition. We review the clinicopathologic and radiologic features of groove pancreatitis in the Japanese literature and discuss the possible role of Santorini's duct in its pathogenesis. We consider that impacted protein plugs in Santorini's duct are a pathogenic factor in the development of groove pancreatitis. Therefore, the findings of Santorini's duct on endoscopic retrograde pancreatography are very important in the diagnosis of groove pancreatitis. Groove pancreatitis presents various clinical features, such as biliary stenosis, duodenal stenosis, and pancreatic mass, and often masquerades as pancreatic head carcinoma. This condition should be kept in mind in the differential diagnosis of pancreatic head carcinoma.

Cholangiopancreatography, Endoscopic Retrograde↗

Invasion depth diagnosis of depressed type early colorectal cancers by combined use of videoendoscopy and chromoendoscopy.

BACKGROUND: Depressed type early colorectal cancers are found less frequently than other polypoid cancers although they have a higher submucosal invasion rate. Recently videocolonoscopy and chromoendoscopy have become available and precise descriptions of these lesions are now routine. Because endoscopic mucosal resection is designated for intramucosal and focally extended submucosal (m-sm1) cancers, an evaluation of the characteristic findings indicating invasion depth with these modalities is important. METHODS: Between January 1991 and March 1996, 64 depressed type early colorectal cancers were detected and treated. When a faint abnormality of the mucosa was suspected by routine videocolonoscopy, 0.1% of indigo carmine solution was sprayed on the mucosal surface (chromoendoscopy). Colonoscopic findings of m-sm1 cancers and moderately and massively extended submucosal (sm2-3) cancers were retrospectively reviewed and compared with confirmed histologic findings. RESULTS: Characteristic colonoscopic findings needed for surgical operation were as follows: (1) expansion appearance, (2) deep depression surface, (3) irregular bottom of depression surface, and (4) folds converging toward the tumor. By using these findings, the invasion depth of depressed type early colorectal cancers could be correctly determined in 58 of 64 lesions (91%). CONCLUSIONS: Characteristic colonoscopic findings obtained by a combination of videocolonoscopy and chromoendoscopy are useful for determination of the invasion depth of depressed type colorectal cancers, an essential factor in choosing a treatment modality.

Colon↗

Age-dependent decline in cortisol levels and clinical manifestations in patients with ACTH-independent Cushing's syndrome.

OBJECTIVE: Adrenocortical cells change with age in both subcellular morphology and level of steroidogenesis. This study evaluates the influence of aging on hypercortisolism and clinical manifestations in patients with ACTH-independent Cushing's syndrome due to a cortisol-secreting adrenal adenoma (CS). DESIGN: Restrospective study. PATIENTS: Thirty-six (33 females and 3 males) with CS. 31 healthy controls were age- and sex-matched to CS patients. MEASUREMENT: Patient age at diagnosis was compared to the degree of hypercortisolism and clinical manifestations. The degree of hypercortisolism was estimated using serum cortisol levels and urinary free cortisol excretion. Positive clinical manifestations were quantified using 12 symptoms and signs which resulted in a clinical score for each patient. Endogenous creatinine clearance, estimated disease duration and gender were analysed as possible factors affecting adenoma-secreated cortisol. RESULTS: Patient age correlated negatively with serum cortisol level (r = -0.417, P = 0.0107, n = 36) and urinary excretion of free cortisol (r = -0.613, P = 0.0002, n = 31). Analysis of Spearman's rank correlation showed that the clinical score decreased with age (rho = -0.631, P = 0.0004, n = 33). Oedema, weakness/myopathy, hirsutism, striae and psychological changes were infrequent symptoms in the elderly. Using stepwise multiple regression analysis, we estimated the clinical score (Y) by factors of serum cortisol levels (X1:nmol/l), age (X2: years of age) and gender (X3: gender; female = 1, male = 0), i.e. Y = 4.771 + 0.004 X1 - 0.064 X2 + 2.548 X3 (r = 0.743, P < 0.0001, n = 33). Results suggested that aging both suppressed cortisol secretion and repressed manifestations directly as an independent factor, although its direct effect may be weak. CONCLUSIONS: Our findings indicated the importance of age as a factor modulating hormonal levels and possible clinical manifestations in patients with cortisol-secreting adenomas.

Adenoma↗

A large germline deletion of the MEN1 gene in a family with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a familial cancer syndrome inherited as an autosomal dominant trait. Various heterozygous germline mutations of the responsible gene, MEN1, have been identified within its exons in many, but not all, affected individuals. We here demonstrate, by DNA polymorphism analysis and gene dosage analysis with polymerase chain reaction (PCR), a large heterozygous germline MEN1 deletion in a kindred with MEN1, in whom no mutation could be detected in the PCR-amplified exons. The deletion spanned an at least 7 kb region containing the entire MEN1 gene. These findings indicate that a large germline deletion of the MEN1 gene, which escapes detection in PCR-based sequence analysis, should be considered as a potential cause of MEN1.

Chromosome Deletion↗

Association between anomalous pancreaticobiliary ductal union and adenomyomatosis of the gall-bladder.

A frequent association of biliary tract carcinoma and anomalous pancreaticobiliary ductal union (APBD) is well recognized, especially gall-bladder carcinoma in undilated type APBD. However, little is known about the presence and incidence of adenomyomatosis (AMT) of the gall-bladder, a presumed premalignant lesion, in patients with APBD. This retrospective study was conducted to elucidate the clinical features and incidence of AMT in APBD patients with relation to undilated type and dilated type APBD. We reviewed the clinicopathological records of 30 patients with APBD (28 women and two men) encountered during the past 10 years. Among them, 22 patients underwent cholecystectomy and the resected specimens were subjected to histopathological examinations. Eleven cases of APBD patients were undilated type and 11 cases were dilated type. Adenomyomatosis was found in six (55%) of 11 undilated type and one (9%) of 11 dilated type, and fundal type was predominantly observed in six (86%) of seven AMT. An overall incidence of AMT in APBD patients was 32%. An undilated type of APBD is frequently associated with AMT and we believe, therefore, that clinicians should be aware of a possible coexistence of APBD and AMT.

Adenomyoma↗

Solitary true cyst of the pancreas in two adults: analysis of cyst fluid and review of the literature.

Solitary true cyst of the pancreas in adults is extremely rare. We report two adult cases of solitary true cyst of the pancreas. In a 53-yr-old woman there was discovered, incidentally, a unilocular cyst of 7.0 x 6.5 cm in size in the tail of the pancreas that was noted on abdominal US and CT scan. A 16-yr-old boy presented with abdominal pain, and an abdominal US and CT scan revealed a 6.5 cm cystic mass located in the tail of the pancreas. Both patients underwent distal pancreatectomy. Histologically, the cyst was lined with flattened cuboidal and squamous epithelium without morphological alterations. Analysis of the cyst fluid revealed high CA 19-9 (>100,000 U/L) and Span-1 levels (>60,000 U/L) in both cases. Immunohistochemically, the lining epithelial cells of true cyst were positive for CA 19-9 staining. The clinicopathological features of solitary true cyst of the pancreas in adults are briefly reviewed.

Adolescent↗

Cardiac malignant pheochromocytoma with bone metastases.

A patient with malignant cardiac pheochromocytoma with bone metastases is described. The primary tumor was located between the pulmonary trunk and the left atrium, while metastatic lesions were found in the iliac bones. Treatments with antihypertensive agents, alpha-methylparatyrosine, and combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine partially improved the patient's symptoms, catecholamine levels, and the metastatic lesion of the iliac bones. However, the primary tumor in the heart progressively increased in size and the patient died of disseminated intravascular coagulation and other various complications about 4 years after the diagnosis of the disease.

Antineoplastic Combined Chemotherapy Protocols↗