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No studies have examined the association of the combination of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs intake with psychological distress during pregnancy. To examine these associations, we divided Japanese pregnant women into 25 groups based on combining quintiles of n-3 PUFAs intake and quintiles of n-6 PUFAs intake. We conducted multivariable logistic regression analyses to assess the risk of psychological distress during pregnancy (Kessler Psychological Distress Scale ≥ 5 or 13). Compared to the third quintile of both n-3 PUFAs and n-6 PUFAs intake, the groups with unbalanced intake, high intake of both, and low intake of both were associated with a higher risk of both Kessler Psychological Distress Scale ≥ 5 and 13 in early and mid-pregnancy. Further research is needed to identify the precise combination of n-3 PUFAs and n-6 PUFAs intake associated with the lowest psychological distress during pregnancy.

Supplemental Digital Content is available in the text., Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of

A 28-year-old woman who complained of irregular menstruation was diagnosed as suffering from trisomy 18 mosaicism. She was karyotyped because of her characteristic face, mild mental retardation and aberrant hyperpigmentation of the skin. Her motor function was within normal range. Physical and laboratory examinations, however, revealed obesity, short stature, minor anomalies of the fingers, many areas of hyperpigmentation on the trunk and the hips, hypergonadotropinemia, diabetes mellitus, liver dysfunction, and hyperlipidemia. The ratios of normal/trisomy 18 were 4:135 in blood lymphocytes, 3:11 in a hyperpigmented area of the skin, 20:0 in a normally pigmented area of the skin, and 14:6 in ascitic cells. Laparoscopy revealed that her ovaries contained neither follicles nor germ cells.

Anaplastic thyroid carcinoma is a rapidly growing, aggressive neoplasm affecting the elderly which does not respond to most of the therapies. We established cultured cell lines from four untreated tumors. The cultures grew in a monolayer of spindle-shaped cells in three cell lines and of small polygonal cells in one line, having relatively long doubling times and chromosomal abnormalities. The xenotransplantation of the lines in athymic nude mice produced tumors with a histology similar to the original tumors. The immunocytochemical staining showed the expression of PCNA, HLA-class 1, cytokeratin, vimentin and FAS (fatty acid synthase) but not CEA, desmin or P-glycoprotein. The lines secreted TPA, IL-6, IL-8 and few or no thyroid-related hormones in the culture supernatant. One cell line produced G-CSF. The chemosensitivity assay revealed intrinsic drug resistance to nine out of 11 antineoplastic agents. The reverse transcriptase-polymerase chain reaction (RT-PCR) detected MRP (multidrug resistance-associated protein) mRNA but not mdr (multidrug resistance protein)-1 and mdr-3 mRNAs. This finding indicates that the multidrug resistance of these lines is mediated by a P-glycoprotein-unrelated mechanism. The RT-PCR also presented FAS mRNA in all the lines, and IL-6 and IL-8 mRNAs in some of the lines.

The concentrations of sCD4 and sCD8 in 69 patients with systemic sclerosis (SSc) were examined by using a sandwich enzyme-linked immunosorbent assay. The patients with SSc had significantly higher concentrations of sCD8 (mean 249.2 U/ml (SD 155.1), median 224 U/ml) than the normal subjects (mean 149.3 U/ml (SD 42.1), median 148 U/ml). The concentration of sCD4 in patients with SSc were significantly lower (mean 6.2 U/ml (SD 3.8), median 5.0 U/ml) than in the normal subjects (mean 10.9 U/ml (SD 4.1), median 10.3 U/ml). The concentration of sCD8 in patients with diffuse sclerosis tended to be higher than in those with sclerodactyly.

A newly recognized distinctive fibrous soft tissue lesion called "calcifying fibrous pseudotumor" (CFPT) was recently described in the soft tissue of the extremities, trunk, scrotum, groin, neck, or axilla. But CFPT orgining from the pleura is rare. A 44-year-old woman was admitted to our hospital for an investigation of a chest radiographic abnormality. The complete resection was performed through mini-thoracotomy utilizing video assisted thoracoscopic surgery. Microscopically, the lesion was mostly composing dense collagenous tissue and scattered calcifications. The postoperative course was uneventful and no recurrence is observed 18 months after operation. We report succsessful surgical treatment for multiple CFPTs.

The usefulness of self-measurements of blood pressure (BP) at home (home BP measurements) in hypertensive patients has been reported by many studies. Several national guidelines recommend the use of home BP measurements to achieve better hypertension control. The objective of this study was to clarify the association between home BP measurements and hypertension treatment among 2363 essential hypertensive patients taking antihypertensive drugs. Compared to the 543 (23.0%) patients who had not taken home BP measurements, the 1820 (77.0%) patients who had taken home BP measurements were significantly older, included a higher proportion of males, included a higher proportion with a family history of hypertension, took a greater number of antihypertensive drugs and alpha blockers and took antihypertensive drugs more often in the evening. Home BP measurements were associated with significantly better control of home and office BP levels. Compared to patients who had not taken home BP measurements, the adjusted odds ratios for good control of morning home BPs, evening home BPs and office BPs in patients who had taken home BP measurements were 1.46 (95% confidential interval (CI) 1.33–1.57), 1.35 (95% CI 1.21–1.47) and 1.23 (95% CI 1.06–1.37), respectively. Home BP measurements were associated with good hypertensive management. Our findings suggest that it is important that physicians recommend home BP measurements to their patients.

The patient was a 54-year-old female with both headache and vomit presented to the emergency room. Endoscopic examination revealed an advanced esophageal cancer located on the middle thoracic esophagus. Histological analysis revealed squamous cell carcinoma. The clinical stage was diagnosed as T4N2M0 and this case was treated by the chemoradiation. She presented progressive moist cough after chemoradiotherapy. Esophagography demonstrated esophago-bronchial fistula (EBF). EBF was not detected by routine broncoscopy. To confirm fistula, we were performed the bronchoscopy which utilized an indocyanine green. Contrast media colored green were over from the superior segmental bronchus in a bronchoscope. The bronchoscope which utilized an indocyanine green is effective for EBF.

Basic principles apply to the management of all forms of acute empyema: investigation and treatment of the underlying infection, drainage of purulent collection, obliteration of the space, and treatment of the associated intercurrent medical conditions. From July 1999 to May 2001, we performed surgical treatment in 11 patients for acute empyema. There were 4 cases of the fibrinopurulent phase and 7 cases of the organizing phase. Surgical procedure was 7 open thoracotomies and 4 thoracoscopies. The mean operating time was 154.2 +/- 36.6 minutes and blood loss during surgery was 344.7 +/- 274.8 ml. There was no procedure-related morbidity. In conclusion, early aggressive surgical approach is a feasible method for treatment of acute empyema.

To estimate the dose required to counteract accelerated proliferation, gamma/alpha, of medulloblastoma (MB) cells during fractionated radiotherapy.Sixty-five patients with MB (local control rate at 5 years: 73%) treated between 1980 and 1990 at our university hospitals were analyzed. The gamma/alpha was estimated by applying the profile likelihood method to Cox's proportional hazards model including the maximum value of time-incorporated biologically effective dose, tBEDmax. The tBEDmax was conditionally calculated with various settings of alpha/beta, time to kick off accelerated proliferation, Tk, and gamma/alpha. Pretreatment T-stage, log(age+1), extent of removal, and use of chemotherapy and immunotherapy were also included in the multivariate model.When alpha/beta was taken to be 10 Gy, the estimate of gamma/alpha was 0.52 Gy/day (95% confidence limits: 0.29-0.75) for 0 day of Tk and was 0.55 Gy/day (0.30-0.80) for 21 days of Tk. The gamma/alpha values tended to be larger in the T3 subgroup and in the non-total removal subgroup than in all patients, by about 0.05 Gy/day and 0.1 Gy/day, respectively. When alpha/beta was taken to be 25 Gy, the estimated values were about 0.05 Gy/day smaller than these values.The estimated gamma/alpha values were considerably large. Therefore, it is preferable to take this consumed dose per day into consideration in planning and conducting treatments for MB.

The genetic background of the D(Va) category phenotype has been described in two Caucasian individuals. We were interested in the RHD sequence of 7 Japanese D(Va) individuals and their families.With SSP-PCR we tested exons 4, 5 and 7 of the RHD gene and used restriction enzymes for testing nucleotide associated with the D(Va) phenotype.A single RHD G667 C697 allele was present in 5 individuals with D(Va) category phenotype, and in 2 individuals we found a D-CE-D hybrid gene (exon 5 had been replaced). The D(Va)Ce gene complex was found in all families.The changes of the RHD gene described in European D(Va) individuals were also observed in Japanese families.

Adrenocortical carcinoma manifesting pure hyperaldosteronism is extremely rare. We report here a 61-year-old woman with biochemically proven primary aldosteronism due to right adrenocortical carcinoma. Computed tomographic scan showed 4.5x5.3 cm lobulated mass with tiny calcification, while there was no significant uptake of 131I-iodomethyl norcholesterol in the tumor. Immunohistochemical analysis demonstrated expression of steroidogenic enzymes in the tumor tissue: P-450scc, P-45c21, 3beta-hydroxysteroid dehydrogenase, P450(17alpha), and P-450(11beta). In addition, we could demonstrate mRNA expression of aldosterone synthase (P-450aldo:CYP11B2) in the tumor by specific ribonuclease protection assay. This is the first report of a case of primary aldosteronism due to adrenocortical carcinoma, in which expression of all sets of steroidogenic enzymes required for aldosterone synthesis was proven.

Few data are available on the fate and incidence of epithelial hyperplasia throughout the life of anomalous pancreaticobiliary ductal union (APBD) patients. The pathological study in pediatric APBD patients is less recognized.Ten resected gallbladders obtained from children with APBD and control patients without APBD were examined histologically, and immunohistochemically for the detection of Ki-67 (as a proliferative marker) and p53. K-ras mutations in codon 12 were also examined. Epithelial hyperplasia was classified into high-grade and low-grade hyperplasia.Six (60%) of 10 patients with APBD had epithelial hyperplasia of the gallbladder, whereas no patients without APBD exhibited this lesion. Diffuse epithelial hyperplasia was observed in 1 (50%) of 2 undilated-type APBD and 5 (63%) of 8 dilated-type. Two (33%) of 6 patients with epithelial hyperplasia exhibited high-grade hyperplasia. Ki-67 labeling index (LI) was significantly higher in hyperplastic mucosa than in control gallbladder mucosa. K-ras mutations and p53 overexpression were not detected in hyperplastic and normal mucosa.Epithelial hyperplasia of the gallbladder accompanied by increased proliferative activity exists at birth or is acquired in childhood with APBD patients and may be an important factor predisposing to the development of gallbladder carcinoma.

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.

The urokinase pathway of plasminogen activation is known to be involved in proteolytic degradation of the extracellular matrix during carcinoma invasion.We immunohistochemically examined 97 colorectal carcinomas for the expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) to investigate whether uPA and PAI-1 expressions could serve as prognostic parameters; the gene expression of uPA and PAI-1 in human colon cancer tissues was also analyzed using reverse transcription-polymerase chain reaction (RT-PCR).The relative expression levels of uPA and PAI-1 mRNAs were well correlated with immunoreactivities of uPA and PAI-1, respectively (p0.05). In immunohistochemical staining, diffuse specific staining was observed in the cytoplasm of carcinoma cells. uPA expression was detected in 57 carcinoma specimens (58.8%) and PAI-1 expression was detected in 36 specimens (37.1%). With regard to 5-year overall survival rate, patients whose tumors had positive uPA and negative PAI-1 immunoreactivities had a significantly poorer prognosis (p0.05). In multivariate analysis, the combined variable of uPA and PAI-1 was shown to be an independent prognostic indicator.Our results suggest that immunohistochemical combined analysis of uPA and PAI-1 may be a useful prognostic factor in colorectal carcinoma patients.

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).Restrospective study.Thirty-six (33 females and 3 males) with CS. 31 healthy controls were age- and sex-matched to CS patients.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.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, P0.0001, 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.Our findings indicated the importance of age as a factor modulating hormonal levels and possible clinical manifestations in patients with cortisol-secreting adenomas.

The purpose of this study was to evaluate the efficacy of endoscopic approaches for the diagnosis and treatment of postoperative biliary leak.Endoscopic retrograde cholangiopancreatography (ERCP) was performed in eight patients with postoperative biliary leak. Of 8 cases, 6 had biliary leak alone (4 cases with a cystic duct leak and 2 cases with a bile duct leak) and 2 cases with a bile duct leak were associated with a bile duct stricture. Endoscopic sphincterotomy (ES) and endoscopic biliary stenting (EBS) were employed in 5 patients and nasobiliary tube drainage (NBD) without ES was performed in 3 patients.In all the patients, ERCP was successfully performed and could demonstrate exact nature and site of postoperative bile duct injuries. In 2 patients with a concomitant bile duct stricture, repetitive endoprosthesis placements were required. The remaining six patients with biliary leak alone were successfully treated by temporary stenting, i.e., ES and EBS (n = 3), and NBD (n = 3).The patients with postoperative biliary leaks can be successfully diagnosed by ERCP and treated by temporary endoscopic methods. Among various endoscopic treatments, NBD alone appears to be preferable in treating patients with small bile leaks. However, cases with a concomitant bile duct stricture were intractable and required longer period of stenting.

Human thyrocytes produce vascular endothelial growth factor (VEGF), a potent angiogenic factor, also known as vascular permeability factor (VPF), which increases vascular permeability. Based on the assumption that VEGF/VPF is involved in fluid accumulation in thyroid cysts, we determined the VEGF/VPF concentration in cyst fluids of thyroid nodules from 79 patients. VEGF/VPF was found to be abundantly present in the cyst fluids (0.02-183 ng/mL). There was no significant difference of VEGF/VPF concentration in the cyst fluid obtained from thyroid adenoma or from adenomotous goiter with cystic degeneration. Immunoreactive VEGF/VPF in cyst fluid was eluted mainly at 45 kDa, and stimulated endothelial cell proliferation, which was partially blocked by anti-VEGF/VPF antibody. The VEGF/ VPF concentration in the cyst fluid obtained from patients who required repeated aspiration or underwent surgical resection because of recurrent accumulation (84.8 +/- 58.3 ng/mL, mean +/- SD, n = 18) was significantly higher than that in the cysts that regressed or disappeared after a single aspiration (4.3 +/- 4.4 ng/mL, n = 12, P0.001). These in vitro and clinical findings suggest that VEGF/VPF is at least partly involved in the accumulation of cyst fluid in thyroid nodules, and that a high VEGF/VPF concentration predicts rapid accumulation of the cyst fluid, possibly necessitating interventional treatment.

The molecular pathology underlying the development and progression of ductal pancreatic adenocarcinoma is poorly understood relative to that of other major cancers in industrialized societies. The frequency, nature, and distribution of p53 abnormalities, their temporal relationship to the metastatic and clinicopathologic phenotypes of sporadic and familial pancreatic cancer, and their consequent effects on the genetics and expression of critical wild-type p53-regulated genes (mdm-2 and p21/WAF-1) warrant examination in pancreatic adenocarcinoma. This molecular and immunochemical study of the p53, mdm-2, and p21/ WAF-1 genes and gene products examined the largest series of nonneoplastic, neoplastic, and metastatic ductal pancreatic lesions reported to date in relation to clinicopathologic profile.Histologically confirmed specimens of primary (n = 136) and metastatic (n = 23) sporadic and familial ductal pancreatic adenocarcinoma lesions were subjected to immunochemical analyses of p53 expression in which a panel of 3 antibodies was utilized. A panel of nonneoplastic but histologically abnormal pancreatic lesions (n = 77) from individuals with varied histories of cigarette smoking were subjected to similar immunohistochemical examinations. In addition, 3 specimens from patients with chronic pancreatitis, 2 specimens of normal fetal pancreata, and 16 specimens of normal adult pancreata were examined as control tissues. Suitable frozen and archival microdissected tumor lesions were evaluated for mutations in exons 4-9 of the p53 gene by single strand conformation polymorphism (SSCP) and dideoxy sequencing analyses in which two distinct sets of outer and nested intron-based amplification primers were used for each exon. A subset of 25 tumor specimens and 18 tumor-derived cell lines for which the p53 mutation status was known were examined for amplification and/or overexpression of the mdm-2 gene; amplification was determined by Southern hybridization and overexpression by immunohistochemical and Western blot analyses. Similarly, mutations in the coding region of p21/WAF-1 gene were examined by SSCP and DNA sequence analyses, and steady-state expression of the p21/WAF-1 protein was assessed by Western blot analysis in these subsets of tumors and tumor-derived cell lines.Positive ductal nuclear p53 immunostaining was demonstrated in 56% of primary tumors and 54% of metastatic lesions. The frequency did not differ significantly between sporadic and familial lesions, and immunostaining was not observed in ductal, acinar, or islet cell elements of normal pancreata or histologically abnormal benign pancreatic lesions from cigarette smokers. A total of 70% of tumor samples revealed reproducible SSCP abnormalities for p53; 42% of these were found in exons 7 and 8. DNA sequence analysis of cases with greater than 35% epithelial cellularity (n = 25) revealed 17 missense mutations, 12 of which were transitions. Seventy-five percent of these transitions were of G:C--A:T type. A total of 22% of the p53 mutations identified were microdeletions, along with one insertional mutation at exon 8. None of the normal pancreata from sporadic or familial lesions revealed germ-line p53 alterations. Moreover, the frequency and spectra of p53 alterations exhibited no clear, statistically significant association with tumor grade, TNM stage, or patients' cigarette-smoking histories. The mdm-2 gene was neither amplified nor overexpressed immunochemically in a subset of ductal adenocarcinomas, and there was no clear relationship between the p53 mutation status and the status of the mdm-2 gene or protein. Similarly, SSCP and DNA sequence analysis of the p21/WAF-1 gene revealed only 2 genetic abnormalities in a series of 25 primary tumors and 15 tumor-derived cell lines; 1 of the cell lines also revealed the absence of immunoreactive p21/WAF-1 protein...

To determine the diagnostic implications of measuring the serum thyroglobulin level in patients with a solitary follicular thyroid tumor, a retrospective study was conducted on 122 consecutive patients with a solitary follicular thyroid nodule who underwent thyroidectomy. Data for eight variables were collected: the serum thyroglobulin (Tg) level (microgram/l), age, maximum diameter of the nodule, gender, histopathologic type, presence or absence of metastases, macroscopic characteristics of the cut surface of the resected tumor, and smoking habit. Multiple regression analyses were used to investigate the relationships between the serum Tg level and the seven other variables. The diagnostic value of serum Tg was examined by means of receiver operating characteristic (ROC) curves. There were significant correlations between the serum Tg level and the maximum diameter of the nodule, the macroscopic characteristics, and the smoking habit. The sensitivity and specificity of the serum Tg level with a cut-off value of 1,000 micrograms/l were 57% and 86%, respectively. The likelihood ratio favouring follicular carcinoma associated with the serum Tg1,000 micrograms/l was 4.41. Measuring the level of serum Tg may be useful in discriminating follicular carcinoma from follicular adenoma, but since there may be some biases in this retrospective study, the results are less definitive. Further research activities are mandatory to obtain valid evidence.

Retrospective analysis has been performed in 404 patients, undergoing initial operation for primary hyperparathyroidism for differences in clinical presentation, laboratory data, pathological findings and outcome of surgery. In elderly patients (= 60 years of age, n = 116), neuromuscular and psychic symptoms, hypertension, cholelithiasis and pseudogout were significantly more common, while renal stones were less common than in younger patients. There were no significant difference in preoperative laboratory findings, parathyroid pathology and surgical cure rate. Parathyroidectomy could be safely performed under local anesthesia, particularly in elderly patients in whom general anesthesia was involved with an increased operative risk. An attack of pseudogout was the most common postoperative complication. Hence, immediate calcium supplementation after operation is recommended in patients with a radiologic finding of chondrocalcinosis.

Therapeutic efficacy of Elental and Enterued as home enteral nutrition (HEN) for the maintenance of remission in 32 patients with quiescent Crohn's disease was studied retrospectively. Their cumulative rates of continuous remission and non hospitalization were statistically compared in relation to following five factors; type of disease, history of bowel resection, duration of disease, oral bile acid tolerance test (OBATT) and radiological lesion score (RLS). As to the cumulative rates of continuous remission and non hospitalization, there was no significant difference between two groups treated with Elental and Enterued. In patient with ileocolitis type,or = 5-year history, and a high score of RLS, few cases could continuously maintain remission following a long-term HEN. Especially, patients with low absorption in OBATT had a significantly lower cumulative rate of continuous remission than those with normal absorption in OBATT. The present results suggest that above factors may be useful in the application of HEN to patients with Crohn's disease.

The therapeutic response of 131I-MIBG was evaluated in 4 patients with malignant pheochromocytoma who had been treated with 131I-MIBG and followed-up over 5 years. The patients were 2 men and 2 women with ages ranging from 41 to 69 years old (mean 53 years). The primary tumors in 3 of 4 patients had been resected four to eight years before 131I-MIBG treatment. One patient was diagnosed as adrenal pheochromocytoma, and two were retroperitoneal paraganglioma. And in one patient, the resection of primary mediastinal tumor was not performed due to the adhesion to pericardium but the diagnosis of paraganglioma was obtained by biopsy of bone lesion. All patients showed the clear accumulation of 131I-MIBG in tumor on scintigraphy. The number of doses of 131I-MIBG ranged from one to three times with 3.7 GBq per administration and a cumulative activity from 3.7 to 11.1 GBq. Treatment effect was obvious in one patient with lung, bone, and lymph node metastases whose cumulated absorbed dose with 11.1 GBq of 131I-MIBG exceeded over 150 Gy. At the present time, the duration of survival since the beginning of initial 131I-MIBG therapy is over 5 yrs. The other three patients, however, showed little effects, and died with the disease in 2.6 to 4.1 years after the initial 131I-MIBG therapy. 131I-MIBG will become a promising agent for therapy in patients with malignant pheochromocytoma with high degree of accumulation.

Eight cases of thymic carcinoma (mean age 62 years, 5 males and 3 females) were treated in our hospital from Apr. 1988 to Mar. 1993, which were 21% of thymic epithelial tumors. The histologic subtypes of thymic carcinoma were 3 squamous, 4 undifferentiated, and 1 adenocarcinoma, respectively. Computed tomography showed extrathymic metastases to the mediastinal lymph nodes in 6 cases. All cases underwent thoracotomy, and postoperative radiotherapy or chemotherapy were performed. A case of squamous cell carcinoma in stage II who underwent total resection followed by irradiation is alive and disease free 5 years after surgery. However, the remaining 7 cases died of the disease within 29 months. 8 cases of thymic carcinoma and 7 of thymoma were studied immunohistologically on the formalin-fixed and paraffin-embedded tissues. Higher positivity of EMA in thymic carcinoma was noted comparing to ordinary thymoma, suggesting that EMA is a useful parameter of potential malignancy of the thymic epithelial neoplasms.

Alterations in the p53 tumor suppressor gene are involved in the pathogenesis of diverse human cancers. Immunohistochemical detection of the p53 protein has been strongly correlated with mutations in the p53 gene. Fifty-four human exocrine pancreatic tumors of American, Japanese, and Senegalese origin and six xenotransplanted human pancreatic carcinoma cell lines were investigated immunohistochemically with monoclonal anti-p53 antibodies pAb 1801 and BP53-12. Positive nuclear p53 immunoreactivity was detected in 37% of paraffin-embedded primary tumors (21.8% in the Japanese group, 52.6% in the American group) and in 50% of xenotransplanted carcinoma cell lines. Since several intraductal papillary adenocarcinomas exhibited positive p53 immunostain, it seems probable that alterations in this tumor suppressor gene occur relatively early in the process of pancreatic carcinogenesis. No clear correlation was established between p53-positive immunohistochemical staining and tumor stage and histologic appearance, nor with patient age, sex, or survival time. In contrast to ductal carcinomas and intraductal papillary adenocarcinomas, none of the mucinous or adenosquamous pancreatic carcinomas exhibited positive nuclear staining for p53. The fact that more than half of the ethanol-fixed fine-needle aspirates were positive for p53 suggests that this type of immunostain may be of potential diagnostic significance. An investigation of a large series of pancreatic tumors is needed to further evaluate the relationship between p53 alterations and clinicopathologic features in human pancreatic cancer.

Clinicopathological studies were carried out in 35 cases of mucin-producing tumor of the pancreas. In addition, natural history and serial pancreatogram changes were studied in 12 long-term follow-up cases. 83% of the main duct type and branch duct type greater than 4 cm were malignant, whereas hyperplasia cases were found in the branch duct type of 3 cm or less in size without marked dilation of the main duct and excrescent nodules. 33% of carcinoma cases were accompanied by parenchymal invasion and all those cases were of polypoid type of 2.5 cm or more in size. In long-term follow-up cases, all 3 cases of the main duct type showed progression of pancreatograms. In contrast, 8 of 9 cases of the branch duct type remained unchanged. These results suggest that surgical resection is mandatory in the main duct type and that the branch duct type where hyperplasia is highly suspected can be followed up.

To investigate the clinical significance of pulmonary uptake of 99mTc-HM PAO, we studied the effect of cigarette smoking on pulmonary uptake of 99mTc-HM PAO. This study included 14 volunteers: 4 nonsmokers and 10 smokers (Brinkmann indexes 544 +/- 270.8). Following injection of 99mTc-HM PAO into the antecubital vein, time-activity curve was obtained with the regional activity of one frame/min. for 30 minutes and 64 x 64 matrices. Characteristics of pulmonary clearance curve, described as C(t) = A exp-kt, and lung/liver uptake ratio (Lu/Li index) at 30 min. after injection were determined, and groups of non-smokers and smokers were compared. In smokers, 99mTc-HM PAO clearance was delayed and k was smaller significantly. Lu/Li index was also higher in smokers. Brinkmann index correlated both with k (r = -0.815, p0.01) and Lu/Li index (r = 0.911, p0.01). In conclusion, the delayed clearance and retention of 99mTc-HM PAO in the lung may indicate metabolic disorders of the lung due to cigarette smoking.

The concentrations of soluble CD4 (sCD4) and soluble CD8 (sCD8) were determined in 64 patients with polymyositis/dermatomyositis (PM/DM). The patients with PM/DM had significantly higher concentrations of sCD8, though the concentrations of sCD4 did not significantly increase. Patients with high concentrations of sCD8 tended to have too high concentrations of soluble interleukin-2 receptor (sIL-2R). The patients with high levels of myogenic enzymes tended to have high concentrations of sCD8. The results of a serial study indicated that the concentrations of sCD8 decreased simultaneously with the decrease of the myogenic enzymes. These results may suggest that the activation of CD8+ cells are related to muscular involvement.

Unfavorable characteristics of early postoperative recurrence of hyperthyroidism were studied in patients with Graves' disease after subtotal thyroidectomy. We examined 338 patients who underwent subtotal thyroidectomy during a 9-year period from 1981 to 1989. Thyroid functional status was determined biochemically and the following variables were collected and divided into two categories for each patient: sex, age at operation, indication for surgery, serum titer of antimicrosomal hemagglutination antibody, weight of resected thyroid tissue and size of remnant thyroid tissue relative to body surface area. Early postoperative recurrence was defined as relapse of the disease within one year after surgery, necessitating medication or radioiodine therapy. Logistic regression analysis disclosed that the most important characteristics were age20 yr, relatively large thyroid remnant and weight of resected thyroid tissueor = 100g, the odds ratios for these variables being 20.6, 16.7 and 3.4, respectively (p0.05). Although candidates for surgical treatment of Graves' disease are likely to be younger and to have a large goiter, these characteristics are unfavorable, since they predict the early recurrence of hyperthyroidism. One alternative is to leave a smaller than usual thyroid remnant thyroid in these patients, even if the risk of postoperative hypothyroidism is high.

We estimated the concentration of soluble IL-2R (sIL-2R) in the serum of patients with systemic lupus erythematosus (SLE) and examined the relationship between the serum levels of sIL-2R and clinical features or laboratory data. We found that elevated levels of sIL-2R were present in the serum of SLE patients with discoid rash, and sIL-2R concentrations were correlated with the soluble CD4 and soluble CD8 concentrations but not with classical serological marker, anti-DNA antibody or complement titer.

The clinical features and changes of the pancreatic duct system in nine patients with mucin-producing tumor of the pancreas were serially studied to clarify the natural history and evolution of pancreatograms. The observation periods ranged from 6 to 50 months (mean, 30 months), and all patients were examined by endoscopic retrograde pancreatography two or more times. Four of the nine cases exhibited obvious progression of pancreatic duct dilation in association with increased amounts of mucin in the dilated duct, whereas five did not show apparent progression of ductal changes. Changes in the pancreatograms of mucin-producing tumor occurred when mucin secretion by the tumor became prominent, and such cases frequently presented with abdominal pain and pancreatitis. In contrast, most of the branch duct type remained unchanged; all three cases of main duct type showed progression of pancreatograms. There was no apparent relationship between degree and progression of ductal changes and the tumor malignancy.

We evaluated the diagnostic capability of technetium-99m-diethylene triamine pentaacetic acid-human serum albumin (99mTc-DTPA-HSA) lymphoscintigrapy in a patient with protein-losing gastroenteropathy. 99mTc-DTPA-HSA (total 740 MBq) was injected subcutaneously into the digital webs of the both feet. With a gamma camera, whole-body and abdominal lymphoscintigrams were obtained after the injection of the radioisotope: early images and delayed images taken 5-15 min and 50-60 min, respectively, after the injection. A few days later, the dynamic lymphoscintigraphy was also performed. Lymph fluid leakage into the small bowel and the sites of the leakage were detected. It was concluded that lymphoscintigraphy with 99mTc-DTPA-HSA was a useful diagnostic tool in patients with protein-losing gastroenteropathy.

Unilateral adrenalectomy was performed in 63 patients with primary aldosteronism. During a mean follow-up time of 4.1 years, none of the patients showed recurrence of hyperaldosteronism. However, 24 patients (38%) had persistent hypertension. The purpose of this study was to determine factors responsible for postoperative persistent hypertension.A stepwise multivariate logistic regression analysis was performed to assess the combined predictive effects of the clinicopathologic variables.Age, sex, and pathologic findings were the best predictive factors of postoperative persistent hypertension. For a patient aged 50 years or more, the odds of persisting hypertension are 10.6:1, compared with those of a patient under 40 years of age. A male patient appears to have a greater chance of hypertension than a female patient; the odds ratio is 5.9:1. Persistent hypertension develops in patients with multiple adenomas or with an adenoma associated with macronodules more frequently than in those patients with a solitary adenoma; the odds ratio is 8.1.This study suggests that early surgical intervention at a younger age results in a more favorable outcome for patients with primary aldosteronism. The presence of macronodules in association with an adenoma is a cautious predictor of persistent hypertension after adrenalectomy.

Selective ERP and EPB were employed in the diagnosis of mucin-producing tumor (MPT) of the pancreas and their usefulness was evaluated. Thirty five cases of MPTs were subdivided into three subtypes, i.e., 1) main duct type, 2) branch duct type and 3) peripheral type (mucinous cystadenoma/cystadenocarcinoma). Selective ERP was proved to be useful in demonstrating precise and whole pancreatograms, especially in revealing multiple lesions, when compared with standard ERP. Selective ERP could demonstrate communication between cystic tumors of the peripheral type and the pancreatic duct in seven (88%) of eight cases of the peripheral type, which suggests high frequency of the communication in the peripheral type. For preoperative tissue diagnosis, EPB was shown to be a useful method to yield sufficient tissue materials for histopathological evaluation and may be used as an adjunction method to diagnose the intraductal extent of the tumorous lesion.

Nineteen patients were surgically treated for hyperparathyroidism associated with multiple endocrine neoplasia type 1 syndrome. Fourteen patients (74%) had removal of three or more parathyroid glands at the first operation, and five (26%) by removal of 2 1/2 or fewer glands. Two patients had recurrent hypercalcemia during the mean follow-up period of 65 months. One had a recurrence 10 years after subtotal parathyroidectomy. Reexploration in this patient revealed enlargement of the remaining tissue in the neck and an enlarged supernumerary gland in the aorticopulmonary window. The other patient had persistent hypercalcemia after removal of two hyperplastic parathyroid glands until after another 1 1/2 more glands were removed. After reoperation the patient was normocalcemic for 10 years before hypercalcemia was again noticed. The patient subsequently died from renal carcinoma metastases, which might have been the cause of the hypercalcemia before death.

A novel monoclonal anti-human coagulation factor XIII (F. XIII) antibody (2C3 antibody) raised in BALB/c mice was established by Kohler and Milstein methods. The monoclonal antibody recognized F. XIII of 85 KD demonstrated by western blotting analysis. Plasma F. XIII-IR levels measured by ELISA with 2C3 antibody were significantly lower in active disease than in quiescent disease in a total of 21 Crohn's disease (CD) patients. Plasma F. XIII levels were significantly lower on admission in CD with fistulas than in CD without fistulas. Relationships between activities of CD and plasma F. XIII levels were shown. No significant relationships, however, were observed between F. XIII-IR levels and nutritional states assessed by TP, ALB, TF, PA, RBP, %IBW. Low levels of F. XIII in active CD patients with fistulas may occur regardless of hyponutrition. By using 2C3 antibody, global functions of F. XIII will become clarified as well as pathologic and diagnostic roles of plasma F. XIII in CD.

We report our experience with nine patients with "mucin-producing tumor of the pancreas," in which abundant mucin secreted by the tumor cells played a major role in the characteristic alterations of the pancreatic duct system. Four of nine patients presented with pancreatitis. Ultrasound and computed tomography demonstrated a well-defined cystic mass and dilated main pancreatic duct. Endoscopic retrograde pancreatography showed ductectatic character, i.e., diffuse dilatation of main duct and/or cystic dilatation of the branch ducts with filling defects of mucin. Ultrasound proved to be a good screening test. However, the diagnosis was confirmed on endoscopic retrograde pancreatography. Nine of our cases had no peripancreatic invasion or metastasis, resulting in a good prognosis after pancreatectomy. Mucin-producing tumor of the pancreas is a unique clinical entity that should be distinguished from "common" pancreatic carcinomas, and a favorable prognosis can be expected after surgical operation.

It has been suggested that the presence of ischemic heart disease correlates with an increased risk of cardiac infarction and fatal arrhythmia following noncardiac operations. To prevent these complications, coronary arteriographies were performed on 55 patients before pulmonary surgery for the assessment of the risk of perioperative cardiac complications. A coronary artery obstruction, with a 50% or greater reduction in the internal diameter was recognized on 21 patients (Group 1) and the other 34 patients showed no significant coronary stenotic lesions (Group 2). Discriminant analysis revealed that cardiac index (p less than 0.025), blood sugar level (p less than 0.05), hyperlipidemia (p less than 0.05) and postoperative cardiac failure (p less than 0.005) correlated independently with coronary artery stenosis. Postoperative cardiac complications were observed in the form of atrial arrhythmias (11%), ventricular arrhythmias (16%) and ischemic ECG findings (17%) in all cases. The rate of occurrence of these complications were not different between the two groups. However, the need for therapeutic procedures for perioperative circulatory failure (18%) was much greater in group 1 (p less than 0.005). This study supports the merits of preoperative coronary arterial angiography and the estimation of the left ventricular function in reducing pulmonary perioperative risk.

The expression of epidermal growth factor receptor (EGFR) was studied immunohistochemically in 92 colorectal carcinomas: 21 early and 71 advanced. EGFR immunoreactivity was detected in 15 cases (16.3%) of colorectal carcinomas. All EGFR-positive cases was advanced carcinomas, while no EGFR immunoreactivity was found in early carcinomas. EGFR-positive cases were macroscopically 3.4 type and more than 2 cm in diameter. No significant correlation of EGFR expression with tumor location, stage, lymph node metastasis, degree of differentiation, and prognosis was found. All EGFR-positive cases was synchronous positive for the expression of EGF. These results suggest that EGFR may play an important role in tumor progression in cooperation with EGF.

To assess how the immunological events occur in the colonic mucosa in patients with ulcerative colitis, it is thought to be important to evaluate the subpopulations and/or subsets of mucosal lymphocytes. In this point of view, we assayed those by lymphocyte isolation techniques and two color flow cytometry. Although our results showed no disease-specific abnormalities of the percentages of CD3, CD4, CD8, CD20, and HLA-DR (+) cells in PBL (peripheral blood lymphocyte) nor CML (colonic mucosal lymphocyte), these subsets of CML appeared to be altered according to the grade of severity of inflammation. In our cases, the HLA-DR (+) cell and CD4 population were larger in severely inflamed mucosa. Furthermore, fluorescence intensities of HLA-DR antigen of CD20 population in CML were greater than those in PBL. These results suggest that the B cell-mediated mechanisms may play an important role in maintaining the severe inflammation, and the clinical significance of these studies are discussed.

The expression of epidermal growth factor (EGF) was studied immunohistochemically in a total of 92 human colorectal cancers to examine whether EGF was expressed in relation to its degrees of malignancy. Significantly high incidence of EGF was observed in advanced cancers than in early cancers. In the tissues of advanced cancers, tumor cells having EGF-immunoreactivity tended to be more frequently and intensely observed in deeply invasive tumor cells than in superficial tumor cells. Regarding macroscopic and histologic types, incidence of EGF-immunoreactivity was significantly higher in infiltrating types and in differentiated types than in localized types and in poorly differentiated types, respectively. Cases with poor prognosis and in advanced stages showed high positive rate of EGF-immunoreactivity. These results suggest that the expression of EGF may serve as a biologic marker for the degree of malignancy in human colorectal cancers.

A flow cytometric DNA analysis of papillary thyroid carcinomas has been performed on paraffin-embedded specimens, in order to determine the clinical usefulness of this method by defining the degree of the biological malignancy. Fifty-eight patients with papillary carcinomas were followed from 2 to 8 years. They were classified according to their prognosis into three groups: non-recurrent (47 patients), recurrent (5 patients), and a deceased group (6 patients). Aneuploidy was found in 6 (10.3%) of the total 58 patients. It was more frequently detected in the recurrent (40%) and in the deceased (33.3%) groups than in the non-recurrent group (4.3%). Higher proliferating index values were observed in the deceased group than in the recurrent and non-recurrent groups. These results indicate that a DNA analysis, using routine paraffin-embedded materials, is a useful adjunct in the determination of the degree of the biological malignancy of a papillary carcinoma.

A 8 month old infant with pulmonary artery sling and partial anomalous pulmonary venous drainage was reported. The patient was seen initially with severe stridor. Diagnosis was made by barium swallow study, echocardiography, bronchoscopy, and pulmonary arteriography. The patient was operated on through a median sternotomy; the left pulmonary artery was dissected deep between the trachea and esophagus, and then reimplanted to the side of the main pulmonary artery. Systemic heparinization and microsurgical technique were used. Simultaneous intracardiac repair was carried out by means of extracorporeal circulation. The patient improved dramatically after operation. Postoperative pulmonary arteriogram revealed a wide patent left pulmonary artery, and postoperative perfusion lung scan confirmed improved perfusion of the left lung. It is concluded that pulmonary artery sling should be treated surgically as soon as diagnosed. From the surgical point of view, the left pulmonary artery should be anastomosed to the main pulmonary artery with micro-surgical technique to avoid late occlusion of the left pulmonary artery.

Although the benign counterpart of medullary carcinoma of the thyroid has never been indicated in textbooks, we propose that C cell adenoma is a rare but distinct clinical entity. Two patients, a 43-year-old man and a 53-year-old woman, had similar thyroid tumors, both about 4 cm in diameter. The cut surfaces of the resected tumors were indistinguishable from a common microfollicular adenoma of the thyroid. Microscopically, the tumors were uniformly composed of fusiform cells without any follicle formation. Neither amyloid deposition nor calcification was found. Although some kind of C cell tumors were suggested, the exact nature was debatable. However, extremely high levels of calcitonin (1330 and 2065 pg/ml, respectively; normal level, less than 170 pg/ml) were found in the stored sera taken preoperatively. Serum levels of carcinoembryonic antigen (CEA) were normal in both patients. Immunohistochemically, the tumor tissues were positive for calcitonin and neuron-specific enolase but negative for CEA with a monoclonal anti-CEA antibody. No somatostatin, glucagon, or adrenocorticotropic hormone activity was found. It is highly probable that such tumors have not been closely studied and have been regarded as eccentric adenomas of the thyroid or simply as the so-called medullary carcinomas of the thyroid.

Three cases of pseudogout associated with primary hyperparathyroidism are reported. Preoperative radiological studies revealed association of pseudogout. Considering the frequent development of acute pseudogout attack following parathyroidectomy, prevention of a sudden decrease in the serum calcium concentration was attempted using calcium supplement therapy starting on the first postoperative day in all three cases. Serum calcium slowly decreased to the normal range, and the postoperative courses were uneventful. From these experiences, we advocate that calcium supplement therapy is worth trying for the prevention of acute pseudogout attack following parathyroidectomy.