BACKGROUND: Endocrine pancreas tumor is a rare disease which incidence is less than 2% of all pancreatic tumors. But it comprises various types of tumor and usually secretes several hormones from one type of tumor although the patient with this tumor complains of sole symptom associated with only one hormone. The mechanism and clinical significance of multiple hormone secretion in the endocrine pancreas tumom are not yet clearly defined. METHODS: We analyzed retrospectively the clinicopathologic features of 20 cases which were operated at Seoul National University Hospital during the period between February 1989 and May 1998. RESULTS: The most common tumor was insulinoma (13 cases) and the second most common tumor was nonfunctioning tumor (6 cases). There was one case of somatostatinoma. Most of the patients with insulinoma complained of neuroglycopenic symptoms. There were 9 cases (45.0%) in which the tumors secreted more than two kinds of hormones, 7 cases in insulinoma, 2 cases in nonfunctioning tumors. Whether the tumor secreted multiple hormones was detected by the method of immunohistochemical staining. Though the tumors secreted more than two kinds of hormones, the patients with the tumors complained of symptoms which were associated with the cell type most strongly stained by immunohistochemical method. Whether or not the tumors secreted multiple hormones was not associated with the pathologic features such as tumor size, histologic patterns of the tumor, status of tumor cell differentiation and malignancy. CONCLUSION: From this results, we suggest that endocrine tumors of the pancreas secreted multiple hormones not by the mechanism of dedifferentiation from already differentiated endocrine cells but by the mechanism of neogenesis of multipotent islet stem cells. Since the relationship between the function of multiple hormone secretion in the endocrine pancreas tumors and islet stem cell would be significant, further study should be needed to find out the function of stem cells and application of stem cells to clinical use.
Cell Differentiation ; Endocrine Cells ; Humans ; Incidence ; Insulinoma ; Islets of Langerhans ; Pancreas* ; Rare Diseases ; Retrospective Studies ; Seoul ; Somatostatinoma ; Stem Cells

Inflammatory mediators, such as oxidants, TNF-alpha, and IL-6, play a major role in the systemic response to bum injury It has been known that a continuing inflammatory response cause a sepsis and subsequent multiple organ failure. Recent studies have shown that burn patients receiving recombinant human growth hormone(rhGH) therapy have an improvement of the general condition, but the mechanism by which rhGH exerts its effects has not been clearly understood. The aim of this study was to evaluate the effect of rhGH on the early bum injury. Female Sprague-Dawley rats were divided into four groups : control group, bum group, burn plus rhGH treated group, and rhGH only treated group. Animals were killed at 30min., 3, 6, 24, and 48 hours after treatment. Histology and biochemical changes including malondialdehyde(MDA) content, tissue reduced glutathione(GSH) and catalase activity in the lung and liver, and plasma TNF-alpha and IL-6 levels were examined. Lung histology in the bum plus rhGH treated group showed decreased inflammtory response such as neutrophil and lymphocyte infiltrations, interstitial thickening, and edema compared with the bum group. Liver histology in the bum group revealed mild neutrophil and lymphocyte infiltrations, vacuolization .of hepatocytes, disrupted lobular structures, and dilated sinusoids. But liver histology of the bum plus rhGH was similar to control group. Lung and liver MDA in the burn plus rhGH and rhGH only treated groups were decreased with time compared with the burn group. Lung and liver GSH and catalase activities in the bum plus rhGH and GH only treated groups remained significantly increased compared with the bum group for the 48-hours period. Plasma TNF-alpha levels in the bum group remained elevated for the 48-hours period compared with the bum plus rhGH and rhGH only treated groups. Plasma IL-6 levels in the burn group were significantly increased only at first compared with the bum plus rhGH and rhGH only treated groups. These results suggested that rhGH showed inhibitory effects on the inflammatory cell infiltration and lipid peroxidation in the lung and liver after bum injury. Increased GSH levels and catalase activities seemed to be associated with the antioxidant effect of rhGH. But the inhibitory effect of rhGH on plasma TNF- and R-6 levels was not clearly demonstrated.
Animals ; Antioxidants ; Burns ; Catalase ; Edema ; Female ; Hepatocytes ; Human Growth Hormone* ; Humans* ; Interleukin-6* ; Lipid Peroxidation* ; Liver ; Lung ; Lymphocytes ; Multiple Organ Failure ; Neutrophils ; Oxidants ; Plasma* ; Rats* ; Rats, Sprague-Dawley ; Sepsis ; Tumor Necrosis Factor-alpha*

Some proto-oncogenes in human malignancies can be primary cause of carcinogenesis and can be correlated to histologic aggressiveness or prognosis. In this study, to define the role of c-myc and c-fos protooncogenes in multistage tumorigenesis of thyroid tumor and to correlate the expression of c-myc protooncogene with the degree of histologic aggressiveness and EORTC prognostic index in patients of thyroid carcinoma, 132 fresh specimens obtained at surgery from 71 cases of thyroid tumor were analysed by slot blot hybridization for the expression of c-myc and c-fos proto-oncogene, and 42 formalin-fixed paraffin-embedded tissues were analysed by immunohistochemical staining with monoclonal c-myc antibody and monoclonal Ki-67 antibody, and in 34 paraffin-embedded malignant tissues, the degree of histologic aggressiveness was determined, and in 42 cases of thyroid cancer, EORTC prognostic index were determined. And each item was compared to c-myc mRNA expression level. The results obtained were as follows: 1. The level of c-myc mRNA was significantly higher in malignant thyroid tissues as compared to normal or benign thyroid tissues(p=0.01). 2. The level of c-fos mRNA was similar in normal, benign and well differentiated thyroid carcinoma 3. There was no difference of c-myc mRNA expression levels between central and peripheral tumor tissues. 4. C-myc expression of normal tissues originated from cancer was higher than those from benign tumor(p=0.01) 5. A high level of c-myc mRNA in differentiated thyroid cancer corresponded to a high degree of histologic aggressiveness, although there was no statistically significant correlation between two. 6. High levels of c-myc mRNA were more frequently found in thyroid carcinoma with unfavourable prognosis, although there was no statistically significant correlation between c-myc mRNA expression and EORTC prognostic index or other prognostic factors such as age, sex, tumor size, tumor extent in thyroid carcinoma. 7. C-myc mRNA expression was statistically significantly correlated to the degree of immunohistochemical staining of monoclonal c-myc antibody(p=0.01). 8. C-myc mRNA expression was statistically significantly correlated to Ki-67 cell proliferative index score(p=0.005). On the basis of results, it can be suggested that overexpression of c-myc protooncogene in thyroid carcinoma is secondary phenotype of growth signal rather than primary cause of thyroid carcinogenesis, and expression of c-fos protooncogene was similar in normal, benign and malignant tumor tissues. C-myc may be useful prognostic indicator because there was some relationship between c-myc mRNA expression and EORTC prognostic index score or histologic aggressiveness score. And because c-myc correaltes significantly to Ki-67 cell proliferative index score, c-myc expression will be important growth signal in follicular cell of thyroid and have a role of progression of thyroid carcinoma.
Carcinogenesis ; Genes, fos ; Humans* ; Phenotype ; Prognosis ; Proto-Oncogenes ; RNA, Messenger ; Thyroid Gland* ; Thyroid Neoplasms

No abstract available.
Thyroid Gland* ; Thyroid Nodule*

PURPOSE: There are no specific clinical and histopathologic characteristics of malignant pheochromocytoma and the optimal treatment modality has not been established yet. We analyzed the clinical and histopathologic features of malignant pheochromocytoma and treatment results. MATERIALS AND METHODS: We reviewed the clinical records of 10 patients with malignant pheochromocytoma diagnosed at Seoul National University Hospital from March 1987 to June 1998. RESULTS: Nine of 10 (90%) patients had functional tumors. The biochemical laboratory findings showed elevated 24-hour urine VMA level in nine patients available. The median size of the tumors was 11x11 cm. Six of 10 (60%) patients were initially diagnosed as malignant tumors because of direct invasions to adjacent tissues or distant metastases. On the other hand, remaining 4 patients were initially diagnosed as benign, but the distant metastases developed metachronously after resection of the primary lesion. The median duration between the initial operation and the detection of metastases was 57 months (range: 47~72 months) in these patients. The liver was the most common site of metastases (60%). With regards to the histopathological features, most of the tumors (87.5%) showed capsulation, necrosis and hemorrhage. The findings of lymphatic invasion, angio-invasion, and mitosis were found in 62.5% of the cases. All but 2 patients were initially treated with radical operation for the primary lesions. The disease recurrences or metastases occurred in 7 out of 10 patients. Of these, 4 patients were treated with chemotherapy or interferon- a after recurrences. Overall, the median survival for all patients was 82 months (range: 37~143 months). Two patients is alive and only one patient is alive without recurrence. CONCLUSION: The careful follow-up for at least 5 years and the aggressive multi-disciplinary therapy may be needed for the diagnosis and the management of malignant pheochromocytoma.
Diagnosis ; Drug Therapy ; Follow-Up Studies ; Hand ; Hemorrhage ; Humans ; Liver ; Mitosis ; Necrosis ; Neoplasm Metastasis ; Pheochromocytoma* ; Recurrence ; Seoul

A 38-year old female was admitted to our hospital for further evaluation of an incidentally found cardiac murmur. She had been in a hypertensive state for 5 years but had taken antihypertensive drugs intermittently on her own. Her history revealed that she had become amenorrheic for 7 months and had, had headaches for a few months. Physical examination revealed central obesity and a moon face, but no hirsuitism. When she first visited our hospital, her blood pressure was 260/170 mmHg and grade 2 systolic murmur was audible along the left sternal border. Laboratory studies revealed high levels of 24-hour urine-free cortisol and plasma aldosterone, but a very low level of plasma adrenocorticotropic hormone and plasma renin activity. A low-dose and a high-dose dexamethasone suppression tests, adrenal venous sampling, inferior petrosal sinus sampling, and a renin stimulation test were performed. Bilateral adrenal masses were found on computerized tomographic scanning and magnetic resonance imaging but there was no abnormality of the pituitary gland. The uncontrollable blood pressure and the elevated 24-hour urine-free cortisol and plasma aldosterone levels were corrected by a right-total and left-subtotal adrenalectomy. Pathologic findings were bilateral adrenal cortical adenomas of different cell types. These findings indicate that the adrenal cortical adenomas were tumors that functioned differently, causing Cushing's syndrome and primary aldosteronism in the same patient. A review of, the literature published in English showed that this is the first reported case, of bilateral adrenal adenomas functioning differently.
Adenoma ; Adrenalectomy ; Adrenocortical Adenoma* ; Adrenocorticotropic Hormone ; Adult ; Aldosterone ; Antihypertensive Agents ; Blood Pressure ; Cushing Syndrome* ; Dexamethasone ; Female ; Headache ; Heart Murmurs ; Humans ; Hydrocortisone ; Hyperaldosteronism* ; Magnetic Resonance Imaging ; Obesity, Abdominal ; Petrosal Sinus Sampling ; Physical Examination ; Pituitary Gland ; Plasma ; Renin ; Systolic Murmurs

BACKGROUND: The authors have developed a Digital image chart(DIC) and digital Radiotherapy Record System (DRRS). We have evaluated the DIC and DRRS for reliability, usefulness, ease of use, and efficiency. METHOD AND MATERIALS: The basic design o f the DIC and DRRS was to build an digital image database of radiation therapy patient records for a more efficient and timely flow of critical image in formation throughout the department. This system is a subunit of comprehensive radiation oncology managemert system (C-ROMS) and composed of a picture archiving and communication system (PACS), radiotherapy information database, and a radiotherapy imaging database. The DIC and DRRS were programmed using Delphi under a Windows 95 environment and is capable of displaying the digital images of patients identification photos, simulation films, radiotherapy setup, diagnostic radiology image... Gross lesion photos, and radiotherapy planning isodose charts with beam arrangements. Twenty-three clients in the department are connected by Ethernet (10 Mbps) to the central image server (Sun Ultra-sparc 1 workstation). RESULTS: From the introduction of this system in February 1998 through December 1999, we have accumulated a total of 15,732 individual images for 2,556 patients. We can organize radiation therapy in; paperless environment in 120 patients with breast cancer. Using this system, we have succeeded in the prompt, accurate, and simultaneous access to patient care information from multiple locations throughout the department. This coordination has resulted in improved operational efficiency within the department. CONCLUSION: The authors believe that the DIC and DRRS has contributed to the improvement of radiation oncology department efficacy as well as to time and resource savings by providing necessary visual information throughout the department conveniently and simultaneously. As a result, we can also achieve the paperless and filmless practice of radiation oncology with this system.
Breast Neoplasms ; Dacarbazine ; Hospital Information Systems ; Humans ; Income ; Patient Care ; Radiation Oncology* ; Radiotherapy*

PURPOSE: Axillary node involvement is the single most important prognostic variable in patients with breast cancer. If axillary lymph node status of breast cancer patients could be accurately predicted from basic clinical information and from characteristics of their primary tumors, many patients could be spared axillary lymph node dissection. With the availability of numerous histologic prognosticators and new immunochemical prognostic indicators, it is reasonable to reconsider the necessity of axillary node dissection for lesions more advanced than duct carcinoma in situ. MATERIALS AND METHODS: Six hundred fifty-six patients with Tl invasive breast cancer were evaluated. All the patients underwent axillary dissection, and the pathologic status of the nodes was known. The parameters of the primary tumor in this study were age, size, family history, tumor palpability, nuclear and histological grade, hormone receptor status, lymphatic vessel invasion (LVI), and various tumor markers (bc1-2, cathepsinD, c-erbB2, E-cadherin, p53). RESULTS: Approximately 31% of the 656 patients with Tl breast carcinoma had axillary node metastasis. Four factors were identified as significant predictors of node metastasis: age 35 or less (p=0.01), lymphatic vessel invasion (p < 0.01), tumor palpability (p=0.02), and tumor size (p<0.01). However, independent predictors of lymph node metastasis in the multivariate logistic regression analyses were tumor size (p=0.04) and LVI (p=0.03). CONCLUSION: Characteristics of the primary tumor can help assess the risk for axillary lymph node metastases in Tl breast cancer. Selected patients who have 1cm or less without lymphatic vessel invasion are considered to be at minimal risk of axillary node metastasis and might be spared routine axillary dissection.
Breast Neoplasms* ; Breast* ; Cadherins ; Carcinoma in Situ ; Humans ; Logistic Models ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Vessels ; Neoplasm Metastasis* ; Prognosis ; Biomarkers, Tumor

PURPOSE: H rthle cell neoplasm of the thyroid gland is a rare disease. The reported cases in Korea are not so many; thus, there has been a lack of common therapeutic and prognostic guidance. METHODS: The cases of 15 patients with a H rthle cell neoplasm of the thyroid gland, hospitalized at Seoul National University Hospital from Nov. 1981 to Feb. 1998, were retrospectively reviewed. RESULTS: There were 4 males and 11 females. The ages varied from 23 to 69 years old (mean: 46.3 years old). Among them, 13 had neck masses with a mean size of 3.3 cm (1.2-6.0 cm), and the mean duration of the symptom was 4 years (5 months-8 years). Of the other two, one had laryngeal discomfort for 2 months, and the other one was diagnosed through a fine needle aspiration follow-up. One of the 15 patients had hyperthyroidism whereas the others had euthyroidism. The thyroid scans for 10 of them showed cold nodules. The operations consisted of a unilateral lobectomy in 2 cases, a unilateral lobectomy and isth mectomy in 11 cases, a unilateral lobectomy, isthmectomy and contralateral partial lobectomy in 1 case, and a total thyroidectomy and neck lymph node dissection in the 1 case that was combined with a papillary carcinoma. Thirteen patients (86.7%) had a H rthle cell adenoma, and two of them (13.3%) had a H rthle cell carcinoma. The mean duration of follow-up was 33 months (range 1 month-12 years), and no recurrence or death occurred during the follow-up period. CONCLUSIONS: The incidence of H rthle cell neoplasms is higher in women and the sex ratio is 1:2.8. The incidence of H rthle cell carcinomas among H rthle cell neoplasms is 13.3% (2/15). We found no specific clinical features for differentiating a H rthle cell adenoma from a H rthle cell carcinoma and no factors for adequate operative methods and prognosis due to the rarity of the condition and the short duration of the follow-up. Because of the low incidence of H rthle cell neoplasms and our limited experience, not only co-research of centers but also pathologic research is needed.
Adenoma ; Aged ; Biopsy, Fine-Needle ; Carcinoma, Papillary ; Female ; Follow-Up Studies ; Humans ; Hyperthyroidism ; Incidence ; Korea ; Lymph Node Excision ; Male ; Neck ; Prognosis ; Rare Diseases ; Recurrence ; Retrospective Studies ; Seoul ; Sex Ratio ; Thyroid Gland* ; Thyroidectomy

PURPOSE: Histopathological classification of invasive breast carcinoma with its earliest phases is fraught with pitfalls. We were willing to clarify the biology and clinicopathological features of microinvasive carcinoma which is not fully understood in comparison with those of in situ cancer. Particular attention is paid to identifying the novel markers which can be representative of the microinvasive carcinoma. METHODS: From January 1986 to December 1996, a total of 72 microinvasive carcinomas, defined as in situ carcinomas with invasion present in less than 10% of the histological section, were found out. Their paraffin blocks were chosen for immunohistochemical staining against four molecules. RESULTS: Microinvasive carcinoma was greater in primary tumor size (2.66?0.17cm vs 2.21?0.19cm, P=0.045) and metastatic axillary nodes (0.21?0.25 vs 0.06?0.16, P=0.019) than DCIS. In terms of nuclear grade(P=0.198) and comedo type(P=0.562), there was no statistical significance between microinvasive carcinoma and DCIS. Among three primary tumor features(size, comedo component, and nuclear grade), the tumor size> or =2.5cm had marginal significance affecting the incidence of axillary node metastasis in microinvasive carcinoma(P=0.081). Of investigational prognostic factors, determined by immunohistochemical staining, p53 expression was observed more frequently in microinvasive disease entity from in situ to invasive from than DCIS(P=0.031). CONCLUSION: Microinvasive carcinoma is thought to be transitional disease entity from in situ to invasive form. The microinvasive carcinoma of 2.5cm could be indication for axillary node dissection. In addition, p53 mutation might play a important biological role in progression from noninvasive to invasive form and these results provide further evidence that p53 mutation could have potential use as a molecular marker.
Biology ; Breast Neoplasms ; Carcinoma, Intraductal, Noninfiltrating ; Classification ; Incidence ; Neoplasm Metastasis ; Paraffin