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Background: The retinoblastoma (Rb) pathway, which governs cell cycle progression, is frequently genetically altered in cancer, causing deregulated expression of the E2F-1 transcription factor, which promotes DNA synthesis and cell cycle progression. Recent studies show that E2F-1 also participates in apoptosis induction in a p53 dependent or independent manner. Despite its crucial role and paradoxical effects on cell turnover, the function of E2F-1 in human cancer is unclear. Aims: To evaluate E2F-1 expression using immunohistochemistry in 43 surgically resected oesophageal squamous cell carcinoma (OSCC) specimens. Methods: This study analysed the association of E2F-1 with tumour cell proliferation and apoptosis and the upstream regulators modulating these processes, and its impact on patient outcome. Tumour cell proliferation and apoptosis were assessed as percentage of MIB-1 positive or apoptotic cells (MIB-1 labelling index (MI) and apoptotic index (AI)), respectively. Results: Entire specimens showed abnormal expression of one or more upstream regulators of pRb/E2F-1. Although E2F-1 positivity was not associated with the expression of upstream regulators, it showed a linear and positive correlation with MI but not AI. Patients with high MI, low AI, or high E2F-1 positivity had significantly shorter recurrence free survival. By multivariate analysis, high MI and low AI were independently associated with recurrence free survival, but E2F-1 was not. Conclusions: Increased cell proliferation and decreased apoptosis are associated with adverse prognosis in patients with OSCC. Although E2F-1 remains a controversial prognostic factor, its expression was closely associated with tumour cell proliferation and might influence clinical outcome, mainly via cell cycle progression.

Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.

Aims: The long-term effects of dietary diacylglycerol (DAG) on body fat and lipid metabolism were studied in patients undergoing hemodialysis (HD). Methods: Ten patients (seven males, three females) ranging in age from 40 to 64 years were enrolled. During the test period, 9.8g of DAG was ingested per day for 3 months. Results: Body mass index did not change throughout the study. The abdominal fat area measured by CT scan decreased significantly at 3 months, and increased significantly 3 months after completion of the DAG ingestion period. The serum composition of very low-density lipoprotein (VLDL) decreased significantly at 3 months and high-density lipoprotein (HDL) increased significantly at 3 months; these were determined using polyacrylamide gel electrophoresis. Serum lipoprotein (a) decreased significantly at 3 months. Conclusions: Our study showed that 3-month ingestion of DAG reduced the amount of abdominal fat and improved serum lipid profiles in free-living HD patients.

Aims: Several studies have reported that dysregulation of β catenin or k-ras mutation promotes cyclin D1 expression. This study investigated the relation between cyclin D1 expression and clinicopathological parameters in carcinoma of the ampulla of Vater (CAV), and also assessed the relation between increased cyclin D1 expression and β catenin/k-ras status in this series. Methods: Thirty CAVs were evaluated for cyclin D1 expression by immunohistochemistry in relation to patient clinicopathological features. Aberrant β catenin expression and k-ras mutation were also investigated by immunostaining and direct sequencing, and related to cyclin D1 expression. Results: Increased cyclin D1 expression was seen in 17 of 30 CAVs and was significantly correlated with tumour cell proliferation and disease free survival time (p = 0.018, p = 0.018, respectively). Nuclear accumulation of β catenin was found in nine of 30 cases, including four cases with missense mutations in exon 3 of CTNNB-1, and was significantly correlated with increased cyclin D1 expression (p = 0.003). k-ras gene mutation was detected in 12 of 30 cases, and was also significantly correlated with increased cyclin D1 expression (p = 0.026). Overall, 14 of 17 CAVs with increased cyclin D1 expression showed nuclear accumulation of β catenin and/or k-ras mutation. Conclusions: Increased cyclin D1 expression appears to be associated with tumour proliferation and poorer clinical outcome in CAV. It is also associated with both aberrant β catenin expression and k-ras mutation. These results are consistent with the in vitro data that cyclin D1 can be transactivated by activated β catenin–T cell factor/LEF and k-ras pathways.

We analysed data from 27 patients with herpes simplex virus (HSV) infections of the central nervous system (CNS) found in a 1990–1992 survey in Kyushu and Okinawa, Japan. Patients ranged in age from one year to 70 years, with peaks seen in the 20s and 50s. Temporal lobe-limbic encephalitis was the most common HSV infection (13 patients), followed by meningitis (5), diffuse encephalitis (4), disseminated encephalomyelitis (ADEM) (3) and brain stem encephalitis (2). Another three patients with non-herpetic, non-paraneoplastic acute limbic encephalitis were presented. Our study indicates that HSV infection can cause ADEM, although temporal lobe-limbic encephalitis or meningitis are more common. The early diagnosis of HSV-related ADEM is important because of the efficacy of the timely administration of corticosteroids.

Background. In Japan, living donor renal transplantation has gained momentum due to an increased number of patients with end-stage renal disease. Living donation not only provides better outcomes, but also the recipients usually need less medications, thereby increasing the quality of life and reducing the potential side effects of immunosuppression. Materials and Methods. For the past 25 years, our center had performed 140 open donor nephrectomy (OPNx) renal transplantations. Since July 2003, we changed our procurement operation to living hand-assisted laparoscopic donor nephrectomy (HALNx) in 49 cases. Our operative technique consisted of two 12-mm ports placed in the midaxillary line at the superior and inferior levels of the umbilicus. Next, a 5-cm incision was made in the midline periumbilicus and the hand port system fitted through a midline abdominal incision. Results. In 49 cases, HALNx was completed successfully; no patient required conversion to laparotomy. The estimated blood loss was 33.0 ± 43.4 g and no patient required blood transfusion. In comparison, in OPNx the blood loss was 426.5 ± 247.6 g (P

Background and purpose: Sorbin and SH3-domain-containing-1 (SORBS1) is an important adaptor protein in insulin-signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke. Methods: Genotyping was achieved by a rapid-cycle PCR and melting curve analysis using fluorescent probes in 1049 incident cases of ischaemic stroke and 1049 age- and sex-matched control subjects recruited from the Hisayama study. Results: The allele distributions of the SORBS1 T228A polymorphism were similar amongst cases and controls. The multivariate-adjusted odds ratio (OR) of the AA genotype for ischaemic stroke was 2.897 (95% CI, 0.907–8.018) compared with the TT genotype. In terms of stroke subtype, there was a trend toward a difference in the AA genotypes for lacunar infarction, compared with the TT genotype (OR = 8.740, P = 0.0510), and combined TT and TA genotypes (OR = 8.768, P = 0.0505). The other polymorphisms genotyped were not associated with any subtypes of ischaemic stroke. T228A polymorphism of SORBS1 was not associated with the prevalence of diabetes. Conclusions: The AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population.

In our department, there were 313 thoracic surgeries for primary lung cancer from January 1994 to December 2003. We clinically reviewed for the operative and hospital death (n=18, 5.8%). The patients were 16 males and 2 females (70.6 +/- 5.6 years old). The surgical procedures were 4 pneumonectomies, 13 lobectomies (3 bronchoplasties) and 1 partial resection. The mean interval until postoperative death was 122.5 +/- 156.1 days. There were 5 direct operative deaths within 30 days (1.6%). There were 4 cancer deaths, 2 hemoptyses, 2 operative bleeding, 2 thromboses, 2 cerebral hemorrhages, 1 pyothorax, 1 pneumonia, 1 respiratory failure, 1 multiple organ failure after chemotherapy and 2 unexplained deaths. The patients with pneumonectomy or aged significantly had high mortality. For postoperative complications such as hemoptysis or bleeding, perioperative management that takes these issues into consideration is needed. Furthermore, we must carefully review the preoperative evaluation and combined treatment, because there were many cancer deaths among cases showing early recurrence and metastasis.

Since radiation and chemotherapy have little impact on survival and no prospect for cure, surgery offers the best potentially option in patients with liver tumors. However, a lot of patients with liver tumors is not resectable due to stage combined with health problems, or poor liver function reserve. In this study, our preliminary clinical reports in patients with unresectable liver tumors treatment with RFA have demonstrated radiologic evidence of tumor necrosis and complications. Multielectrode, radiofrequency probes were supplied by RITA Medical Systems (Mountain View, California). This study involved a total of 28 liver tumors in 19 patients (including 17 patients with hepatomas and 2 patients with metastases). The mean age was 68.9 years old. The size of tumor was more than 3 cm in 15 patients. The approaches to the tumor were laparoscopic in 1 patients and open surgical in 18 patients. Hepatic vascular occlusion was combined with RFA in 5 cases. The reasons for unresectable were defined as total bilirubin, ICGR 15, cardiopulmonary function and multiplicity. The efficacy of this RFA therapy was evaluated by preoperative and follow-up CT scans or tumor makers. There tumor necrosis was shown in 15 patients (78.9%). The survival rates at the time up to 12 months were 84.2% in 16 patients. The present study has demonstrated that the RFA is able to provide a safe and effective means in controlling liver tumors.

Three neurodegenerative diseases causing primary autonomic failure are pure autonomic failure (PAF), Parkinson's disease (PD), and multiple system atrophy (MSA). Differential diagnoses among these diseases are often difficult especially in early disease stage. For example, it may be difficult to determine whether a patient with parkinsonism and autonomic failure has PD or MSA. Recently, a decrease in myocardial uptake of meta-iodobenzylguanidine (MIBG), an analogue of norepinephrine, has been reported in PD but not in MSA using [123I]MIBG myocardial scintigraphy.1 This new imaging approach is thought to be of significance in the diagnosis and characterisation of akinetic rigid syndromes, especially PD. After that, we reported severe loss of cardiac sympathetic nerves in one patient with PD but not in one patient with MSA, which accounts for a difference in myocardial uptake of MIBG between PD and MSA.2 However, our observation was based on the study in only a single patient of each disease. In this study, we immunohistochemically examined the heart tissues from four patients with PD, three patients with MSA, and one patient with PAF, and showed the involvement of postganglionic cardiac sympathetic nerves in PD and PAF …

Although the pathogenesis of oral lichen planus (OLP) is not clear, a small proportion of cases with OLP are reported to transform to cancer. We examined the epithelial cell proliferation status of OLP to relate the labelling index to microscopic features surveyed routinely in pathology. Mucosal biopsies obtained from 44 cases diagnosed with OLP with an intact oral epithelium and 10 normal control specimens from Japanese subjects were immunohistochemically stained with MIB and p53 antibodies. The Ki67 labelling index (LI) was significantly higher in OLP compared with normal controls. A particularly large number of OLP lesions (64%) were p53 positive. No association was, however, found with p53 expression and the Ki67 LI. Atrophic and flat epithelia had a quantitatively higher LI, which did not significantly differ from acanthotic biopsies. Increased cell proliferation in OLP is likely to be a secondary phenomenon due to the damage inflicted on keratinocytes by infiltrating mononuclear cells in the submucosa.

To elucidate whether a relationship exists between the site of trauma and severity of acute hyperextension spinal cord injury without bone damage, we examined the clinical features of 25 male and 10 female patients aged 13 to 88 years. None of the patients had vertebral damage such as fracture and dislocation. The site of impact was classified as the buccal, forehead, or mandibular region. The neurological findings were assessed according to Frankel's classification at admission and at follow up after 3 months or more to assess outcome. Eleven patients suffered trauma in the buccal region, one patient in Frankel's grade B, three in grade C, and seven in grade D at admission. All 11 of these patients showed an improvement of one grade or more to an outcome of C in one patient, D in one, and E in nine. Trauma occurred at the forehead region in 18 patients, four in grade B, 10 in grade C, and four in grade D. Improvement was seen at follow up by one grade or more to C in one patient, D in 10, and E in seven. Trauma occurred at the mandibular region in six patients, four in grade B and two in grade C. Four of these patients showed improvement of one grade or more to grade B in one, grade C in four, and grade E in one. Overall, seven patients had poor outcomes, five of whom suffered trauma to the mandibular region, indicating that impact to the mandibular region tends to have an unfavorable clinical outcome. Our findings indicate that the site of trauma greatly influences the severity of hyperextension spinal cord injury.

We propose the designation 'sialolipoma' to establish and characterize a new category of benign lipomatous tumour occurring in salivary glands. Until now, these tumours have not been regarded as a distinct entity in the salivary glands.We evaluated the clinicopathological and immunohistochemical features of seven sialolipomas among 2051 surgically resected primary salivary gland tumours deposited in our files. The seven patients with sialolipoma were five men and two women, aged 20-75 years (mean: 54.4 years). Five tumours had arisen in the parotid gland, one in the soft palate, and one in the hard palate. The tumours ranged from 10 to 60 mm (mean: 38 mm) in maximum diameter. Histologically, the tumours were characterized by a well circumscribed mass composed of glandular tissue and mature adipose elements. The adipose elements in the tumours arising in the parotid gland were more abundant than those arising in the minor salivary gland. The glandular components consisted of ductal, acinar, basal and myoepithelial cells, and closely resembled the cellular and structural compositions of normal salivary gland tissues. These findings were confirmed by immunohistochemical and ultrastructural studies. These components had no atypia, except for the presence of some minor variations, e.g. ductal ectasia with fibrosis and focal oncocytic metaplasia. In all cases, cell proliferative activity, as assessed by Ki67 (MIB1) immunostaining, was low. From these findings, it is likely that our cases were lipomas with secondary entrapment of the salivary gland elements. No recurrence was seen in all cases after superficial parotidectomy, or after surgical excision in the patients with palatal tumours.We regard sialolipoma as a distinct variant of salivary gland lipoma that can occur in both the major and minor salivary glands. Superficial parotidectomy, or surgical resection in the case of palatal tumours, is an appropriate treatment for this benign tumour.

Stereotactic radiosurgery (SRS) for brain metastasis results in a high local control rate. But cystic metastatic tumor should have been a contraindication for SRS. Because it is often found that a cyst is too large to be irradiated, the tumor does not exist in the center of the irradiation field. Between 1995 and 1998, 8 consecutive patients underwent linear accelerator-based SRS for cystic brain metastases identified by computed tomography or magnetic resonance image scan. Stereotactic cyst aspiration is carried out after placement of the BRW frame under local anesthesia. All of the patients except one were confirmed to have sufficient reduction of the cysts. 5-7 days after stereotactic cyst aspiration, SRS was performed. The dose range was 25-30 Gy. In follow-up MRI, local recurrences and enlargement of cysts were not noted. Six patients with neurological symptoms recuperated satisfactorily. Median survival was 30 weeks from the date of radiosurgery. All of the patients died and the causes of death were related with the primary lesion. We conclude that our technique, a combination of stereotactic cyst aspiration and SRS is an effective measure which leads to palliation of neurologic symptoms and is a low risk treatment for patients with cystic brain metastasis.

Measurement of 99mTc-MAG3 plasma clearance (CLmag) based on one-compartment model (MPC method) was applied to renal transplantation and evaluated for the factors which might affect the calculated results, especially concerning renal depth. Correlation coefficient of CLmag between MPC method using real renal depth and Russell or Bubeck single sampling method was good (r = 0.852 or 0.876, respectively). Regression equation between MPC method and Russell method was y = 1.044x - 3.0 and was more closer to y = x than that between MPC method and Bubeck method. CLmag of MPC method calculated by estimated renal depth from the abdominal thickness was also similar to that by real renal depth. Even if the fixed renal depth, 4 cm, was applied, the coefficient and regression equation between MPC method and Russell method were r = 0.884 and y = 1.004x - 10.2. In conclusion, MPC method is applicable to the evaluation of renal transplants. Though measuring renal depth is best, calculation with fixed renal depth of 4 cm might be practically acceptable.

Association between lymphocyte-sensitivity to immunosuppressants in transplant recipients in vitro and clinical outcomes has been demonstrated. In general, renal transplant recipients are treated with a combination of immunosuppressants such as either glucocorticoid/cyclosporin A (CsA) or glucocorticoid/tacrolimus (FK506) but the pharmacological complementarity of these drugs is still controversial. We examined relationships between the lymphocyte-sensitivities to these immunosuppressants.We examined lymphocyte-sensitivities to prednisolone (PSL), CsA, and FK506 in vitro in a total of 190 chronic renal failure (CRF) patients and 140 healthy subjects. The lymphocyte-sensitivity was evaluated from the IC50 value against mitogen-stimulated lymphocyte-blastogenesis in vitro.Statistically significant correlations of the IC50 values in CRF patients between the following pairs of drugs were observed: PSL and CsA (P0.0001; n=129, r=0.419), PSL and FK506 (P0.001; n=54, r=0. 441), and CsA and FK506 (P0.0001; n=45, r=0.608). Similar correlations were also observed in lymphocytes from healthy subjects. The population of CRF patients who exhibited high IC50 values (low sensitivities) to PSL and FK506 was significantly larger than that of healthy subjects (P0.05).Patients who showed low lymphocyte-sensitivity to either of the drugs also may exhibit low sensitivity to the others, and thus they may have a high risk of unsatisfactory outcome under combination therapy after renal transplantation. To overcome this risk, the selection of immunosuppressants is recommended to be restricted according to individual lymphocyte-sensitivities to these drugs in vitro, or alternatively, by addition of other drugs with different mechanisms for immunosuppression.

Variable clinical courses have been recognized in patients with idiopathic pulmonary fibrosis (IPF), but the disease is known to have a fundamentally unfavorable outcome. In addition, we have yet to fully understand whether the regional or population differences are negligible or not. Therefore, we analyzed the clinical outcomes in Japanese IPF patients in a hospital-based historical cohort study.A questionnaire was used to collect records for retrospective analysis of the IPF patients. We analyzed data collected from 51 hospitals and clinics in Japan on 234 Japanese IPF patients (males 170, females 64) with IPF who had been followed up after diagnosis.1. Five and ten years after the detection of exertional dyspnea, the overall survival rates were 41.0% and 20.1%, respectively. A higher age at the time of detection (over 59) was related to a decrease in survival rates. 2. The incidence of complications was no higher in the corticosteroid-treated cases than in the untreated cases. The effects of corticosteroid treatment on survival was not confirmed in this type of study.The survival rates of histologically proven Japanese patients with IPF were similar to the rates previously reported in different populations. Age at the detection of exertional dyspnea was critical in terms of the survival rate.

Coronary artery bypass grafting (CABG) on a beating heart has been successfully performed for high risk patients, and is known to be less invasive than conventional CABG using cardiopulmonary bypass (CPB). We expanded the indication of beating-heart CABG in patients requiring emergency coronary revascularization.A retrospective chart review was performed for patients who had undergone emergency CABG on a beating heart (EM-BH group), elective CABG on a beating heart (Elective-BH group) and emergency CABG under CPB (EM-CPB group), between January 1, 1997 and June 30, 1998.Four cases (1 male and 3 females with a mean age of 67.8 +/- 5.4) in the EM-BH group, 67 cases (48 males and 19 females with mean age of 67.3 +/- 7.8) in the Elective-BH group, and 41 cases (29 males and 12 females with mean age of 63.3 +/- 10.4) in the EM-CPB group were analyzed. The number of the grafts was 1.75 +/- 0.50 in EM-BH group, 1.37 +/- 0.55 in the Elective-BH group, and 2.95 +/- 1.07 in the EM-CPB group. The intubation period, ICU stay, and the postoperative hospital stay were significantly shorter in the EM-BH group (6.0 hours intubation, 1.5 days ICU stay, and 11.5 days postoperative hospital stay) and Elective-BH group (6.8 +/- 11.0 hours intubation, 1.6 +/- 1.5 days ICU stay, and 12.7 +/- 5.2 days postoperative hospital stay) than in the EM-CPB group (20.1 +/- 22.5 hours intubation, 3.6 +/- 2.4 days ICU stay, and 21.8 +/- 14.9 days postoperative hospital stay).The postoperative recovery period for EM-BH patients was almost the same as that for elective cases of beating-heart CABG, and was significantly shorter than that of conventional emergency CABG under CPB. Selected patients with coronary ischemia can be safely treated by beating-heart surgery.

Cystic partially differentiated nephroblastoma (CPDN) is an uncommon renal multicystic tumour, usually affecting early infants. To our knowledge, this report describes the first case of CPDN occurring in an adult.A 45-year-old man was found incidentally to have a left renal cystic tumour, measuring 20 mm in diameter, at the lower pole far from the pelvis. The tumour was composed of multilocular cystic spaces of variable size and intervening septa without solid nodular areas. The cysts were lined by a single layer of flattened, hobnail, or columnar epithelium. The septa were made of mesenchymal cells, which were admixed with small numbers of loosely aggregated blastemal cells, occasional tubular structures in various stages of development, and a few glomeruloid structures. The tumour cells had no anaplasia, and mitoses were rare. Immunohistochemical and lectin histochemical studies revealed that the cyst lining epithelium and the tubular structures in the septa expressed predominantly the markers for distal tubules and collecting ducts. Ultrastructurally, the cyst lining cells closely resembled collecting duct cells while some tubular structures showed an immature nephrogenic morphology. The patient was alive and well without evidence of recurrence 11 months after surgery.CPDN does occur in adults, as experienced in Wilms' tumour, though its incidence is extremely low. This study suggests that CPDN may show maturation intermediate between cystic nephroma and Wilms' tumour, even in adult cases.

Malignant transformation of Warthin's tumour (WT) is a rare event. We present two cases of mucoepidermoid carcinoma (MEC) arising in WT in the parotid gland.Two cases of MEC arising in WT, which were found in 185 cases of WT of the parotid gland, were investigated by light and electron microscopy, and immunohistochemistry. Both cases had largely similar macroscopic and histological features with some differences. Histologically, the tumours consisted mainly of WT with multilayered hyperplastic arrangements of oncocytic cells and focal squamous and goblet cell metaplasia. In the same tumour mass, however, the features of MEC were observed with invasion to adjacent adipose tissue. A transitional zone between WT and MEC was evident. Both patients were alive and well without evidence of recurrence 30 and 34 months after surgery, respectively. Electron microscopy revealed that cyst lining epithelial cells in WTs had abundant mitochondria whereas some of the MEC cells contained numerous tonofilaments and mucinous granules. Immunohistochemically, oncocytic cells of WTs were strongly positive for mitochondria and SalylTn was extensively stained in MECs. The labelling index for Ki67 was obviously higher in the carcinoma cells than the epithelial cells of WT.Our cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.

In this report, we discuss the findings of a 1994 retrospective study concerning the rate of inhibitor formation in Japanese hemophiliacs. The study was the second of its kind, following on the first in 1991 (Kamiya et al. 1995 Int. J. Hematology). The records of 77 medical institutions were examined. Inhibitors were found in 6.50% (140 of 2154) of the patients with hemophilia A (HA), and 5.21% (22 of 422) of those with hemophilia B (HB). The median age for antibody formation was 10.7 years in patients with HA, and 4.5 years in those with HB. The median period (exposure period) from initial plasma factor concentrates exposure to inhibitor formation was 46 days and 20 days, respectively, in the HA and HB patients. Among the HA inhibitor patients, those with a large deletion or a nonsense mutation were aged 17.4 years or less (0.58, 1.7, 3.5, 5.5, 7.0 and 17.4), whereas those with intron 22 inversion were aged 55.7 years or less (1.3, 1.3, 1.8, 33.0, 36.1, 37.7, 43.9, 47.9 and 55.7).

Basal cell adenocarcinoma (BCAC) of the salivary gland is a rare tumor and recently described entity. Eleven cases of BCAC are presented here and compared with basal cell adenoma (BCA) through assessment of cell proliferative activity, apoptosis, and expression of p53, bcl-2, and epidermal growth factor receptor (EGFR) because these two tumors show close similarity in some cytologic and architectural characteristics.Formalin fixed, paraffin embedded sections of 11 cases of BCAC and 9 cases of BCA, selected from the authors' files of 1851 primary tumors of the major salivary gland, were examined using immunostaining for Ki-67 (MIB-1), p53, bcl-2, and EGFR. In addition, apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling.The incidence of BCAC was 0.6% among patients with major salivary gland tumors in the current series. Nine cases of BCAC arose in the parotid gland and two were of submandibular gland origin. Approximately 50% of the patients had recurrences, but no patient developed metastases or died of disease. Vascular involvement (75%), perineural invasion (36%), and necrosis (45%) were common features. Cell proliferative activity, including mitotic count, Ki-67 labeling index (LI), and apoptotic index were significantly higher in BCAC than BCA. More than four mitotic figures per ten high-power fields or a Ki-67 LI5% appeared to be limited to cases of BCAC. Considering those cases expressing p53 or EGFR in10% of tumor cells as positive, 6 of the 11 BCAC cases were positive for p53 and 3 were positive for EGFR. In contrast, all BCA cases were negative for p53 and EGFR. Although all cases of BCA were strongly positive for bcl-2 (50% of tumor cells), 3 of 11 cases of BCAC were completely negative.BCAC is a rare salivary gland tumor with a relatively high recurrence rate. Examination of cell proliferation, apoptosis, and expression of p53, bcl-2, and EGFR were found to be useful in distinguishing malignant basal cell tumors from their benign counterparts arising in the salivary gland.

Cell proliferation has a crucial importance in biologic potentialities of tumor cells. Several methods to measure S-phase fraction in tumor samples have been developed, with considerable limitations in practical applications. Histones are nucleosomal proteins that are responsible for packaging chromosomal DNA into nucleosomes. The expression of histone genes is a fundamental step constituting the process of cell proliferation. Because histone H3 mRNA accumulates in the cytoplasm during S-phase, and then decreases as cells approach G2-phase, demonstration of histone H3 mRNA expression in a tumor cell population may represent responsible S-phase fraction. Thus, we have assessed S-phase fraction by nonisotopic in situ hybridization for histone H3 mRNA in paraffin sections of hepatocellular carcinomas (HCCs); then, we compared this with the histologic grades and other cell proliferative markers. In contrast to radioisotopic detection, signals were distinctly visualized, and quantitation of the stained-cells was easily carried out. Histone H3 labeling index (LI) significantly correlated with other cell proliferative markers, including Ki-67 (MIB-1) and PCNA immunostainings, and mitotic index. In addition, a statistically significant correlation was seen between histone H3 LI and histologic grades of differentiation, i.e., histone H3 LI being higher in less-differentiated HCCs. Furthermore, histone H3 LI/Ki-67 LI ratio was significantly higher in the moderately and poorly differentiated subtypes (including one case of the undifferentiated subtype) than in well-differentiated HCCs. By using this nonisotopic in situ hybridization technique, it becomes possible to assess rapidly, retrospectively, safety, and easily a malignant potentiality of HCCs in paraffin-embedded tissues.

Since 1986, annual screening for oral cancer and precancer by postal invitation has been undertaken among 60-year-old residents of Tokoname city, Japan. Clinical examination of the oral soft tissues is performed by groups of four different, specially trained general dental practitioners in the city health centre on one day each year. Following screening each subject receives an individual consultation with an oral medicine specialist. Individuals considered to need full diagnostic follow up or treatment are advised to attend a secondary care referral facility. Between 1986 and 1993, 802 out of 5187 eligible residents (15.5 per cent) were screened of whom 38 (4.7 per cent) were designated by the screeners as positive for oral cancer, erythroplakia, leukoplakia, lichen planus or chronic candidosis. Of these, 32 were referred and 25 attended for follow up examination in hospital departments by specialists with full diagnostic back up facilities. Twenty subjects were confirmed as having a potentially malignant lesion. For these referred patients only, the proportion of correct decisions by the screeners out of all oral cancer/precancer screening decisions was 81 per cent. Positive and negative predictive values for those attending for follow up were 0.80 and 0.82 respectively. Ways of improving the effectiveness and adequacy of the programme are considered.

Arterial injection therapy for lung cancers is concentrated on the bronchial arteries, because they are reported by the main feeders of lung cancers. In the present study, we attempted intermittent arterial injection therapy with implantable port system. In the cases of lung cancers, in the present study, tumors were mainly fed by bronchial arteries originating from intercostal-bronchial arteries in right lungs, and those directly originating from aorta in the left lungs. However, in the processes of BAI (Bronchial Arterial Injection Therapy), main feeders often were obstructed and the new feeders originated from branches of subclavian arteries, such as thyro-cervical truncks, internal mammary arteries, thoraco-acromial arteries and intercostal arteries. They formed networks surrounding the lungs. Adequate study of the feeding arteries should be performed in the course of arterial injection therapy of lung cancers.

A clinical study was undertaken to evaluate the nutritional and immunological status of patients with malignant obstructive jaundice with serum bilirubin level of 5mg/dl or greater (N = 22). Healthy volunteers (N = 9) and patients with cholecystolithiasis (N = 26) were assessed as non-icteric control, as well as patients with obstructive jaundice due to choledocholithiasis (N = 3) were used as icteric control. We also evaluated the time-course of five patients with malignant obstructive jaundice before and after PTCD and surgery. Nutritional status was assessed by prognostic nutritional index (PNI), blood chemistry and rapid turnover protein. Cellular and humoral immunity were assessed by peripheral lymphocyte count, lymphocyte stimulation test, antibody dependent cell-mediated cytotoxicity, and serum immunoglobulins. The following results were obtained. 1) Nutritional and immunological status of patients with malignant obstructive jaundice were severely depressed. 2) Nutritional and immunological status were not improved by preoperative biliary decompression such as PTCD. 3) The immunological indices recovered postoperatively. However, the nutritional indices did not recover by the time of discharge. Intensive nutritional support before and after surgery may be mandatory for patients with malignant obstructive jaundice.

A 59-year-old female with splenomegaly was admitted in November, 1989. Her WBC was 7,900/microliters with 51% myeloblasts and 10% megakaryoblasts. Analysis of the surface markers showed that 56.5% were CD13 positive and 66.8% carried platelet GpIIb/IIIa. The Ph1 chromosome was 100% positive. VPM therapy was started but proved ineffective, as was subsequent MCNU therapy. The patient was given intramuscular human lymphoblastoid interferon-alpha (1.2 million IU daily) for more than 20 months. She had improved to the accelerated phase after INF-alpha therapy for 13 months. Thus there appears to be a relationship between INF-alpha and myelo-megakaryoblastic crisis.

Seven patients with brain abscess underwent CT-guided stereotactic aspiration using Iseki's stereotactic apparatus. Three of them were under the age of fifteen and four were older than thirty. The lesions were single and round in four cases, multilobular in two and multiple in one patient. Operations were performed after systemic administration of antibiotics for more than two weeks and after capsule formation was confirmed on CTs. Preoperative volume of the abscesses was estimated from CTs. The target point chosen was the center of the ring of the largest diameter in the enhanced lesion. Abscess was aspirated under monitoring with intraoperative CT scan. No continuous drainage was performed and no antibiotics were given directly into the abscess cavity. In all cases the center of the abscess was punctured with a single trial. Average volume of the preoperative brain abscesses was 18.8ml. Aspirated volume at the time of the operation averaged 16.9ml and all the abscesses decreased to unmeasurable size on CTs. In five of seven patients abscesses were cured after a single aspiration, and in one case after the second operation. One case required extirpation of the lesion. During the follow-up period of four months to five and a half years six patients showed no recurrence. One patient died of unrelated cause four and a half years after the operation. No operative complication was noted. There was no operative morbidity or mortality. Using a CT guided stereotactic method, brain abscess is punctured so accurately, regardless of its location and size, that damage to the surrounding brain during operation can be minimized. Therefore it is highly possible to aspirate abscesses completely.(ABSTRACT TRUNCATED AT 250 WORDS)

We present a case of intrahepatic cystic cholangiocarcinoma with unusual radiologic appearance. Computed tomography, ultrasonography, and magnetic resonance imaging showed a cystic mass with thick wall, that mimicked liver abscess, and cystic or necrotic metastasis. The fluid in the cyst was not mucinous and was negative bacteriologically. Histologic examination showed cholangiocarcinoma with large cavities resulting from necrosis.

Danazol was administered orally at a dosage of 50 mg/day to 17 patients (11 females and 6 males) with idiopathic thrombocytopenic purpura refractory to steroids and/or splenectomy. The patients had not been treated with conventional dosages of danazol. The drug was suspended in four patients because of adverse effects of danazol. In 13 patients (8 females and 5 males, mean age 44 y. o.) who received the danazol therapy for more than 6 months, there were no patients with an excellent response, and one patient had a good response to the therapy. The rest of the patients did not respond to danazol.

A case report of chronic recurrent pulmonary embolism treated by embolectomy and Günther vena caval filter. A 62-year-old man had suffered from dyspnea on effort for 4 years, and his feeling of dyspnea had gradually increased during the past 3 months. On the day of admission he was in a preshock state, and his pulmonary artery pressure was very high at 90/30 mmHg. Pulmonary blood perfusion scintigraphy showed multiple defects of isotope uptake. Immediately after the scintigraphy, pulmonary embolectomy was performed while using extracorporeal circulation. The operation was successful and his physical activity was markedly improved. After the operation, anti-coagulant and anti-platelet therapies were continued, but recurrence of pulmonary emboli was detected by scintigraphy, and some thrombi were found by venography in deep veins of the lower parts of both legs. To prevent recurrent pulmonary embolism, a Günther vena caval filter was inserted into the inferior vena cava. We considered this case as an acute worsening of chronic recurrent pulmonary embolism and we had the impression that pulmonary embolectomy is a very effective therapeutic method for serious pulmonary embolism, and that insertion of the Günther vena caval filter is a very easy and safe procedure.

A long-term follow-up study of rostral mesencephalic reticulotomy (RMR) for pain relief is presented. 34 patients (24 males and 10 females) were operated. Ages ranged from 18 to 65 years. The follow-up period was 1–70 months. The overall effectiveness of RMR showed good relief of pain in 23 patients (67%). The study of effectiveness of RMR according to type of pain showed good relief of pain in 5 out of 6 patients (83%) with nondenervation pain, whereas satisfactory pain relief was obtained in 18 out of 28 patients (64%) with denervation pain.

Prostaglandin (PG) E1 is a potent vasodilator on the peripheral vessels and also has an inhibitory action of platelet aggregation. Lipo PGE1, the lipid emulsified PGE1 has much longer half life time in the circulation than PGE1 which is rapidly inactivated in the lung. The purpose of this investigation was to study the clinical and hemodynamic effect of Lipo PGE1 on the 15 patients with acute or subacute focal cerebral ischemia. Of these patients, five had evidence of internal carotid artery occlusion, and ten had either occlusion or severe stenosis of middle cerebral artery. Lipo PGE1 containing 15 micrograms of PGE1 was administered within 12 days of onset of ischemic events. Before the first Lipo PGE1 administration, regional cerebral blood flow (rCBF) of the affected middle cerebral artery (MCA) territory was 41.8 +/- 8.4 ml/100 g/min and on the non-affected side was 60.0 +/- 9.4 ml/100 g/min. Immediately after the Lipo PGE1 treatment, rCBF of the MCA region was increased by 6% on the affected side and by 11% on the non-affected side. rCBF of the affected MCA territory was increased more than 15% in five cases (Group 1) and was changed less than +/- 15% in seven cases (Group 2) by the first Lipo PGE1 treatment. Lipo PGE1 was administered every 8 hours for 10 to 14 days in these 12 cases. By the continuous Lipo PGE1 treatment, rCBF of the affected MCA territory increased by 18% in the Group 1 and by 3% in the Group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

The occurrence of epileptic seizures is not rare after craniotomy. The authors examined the incidence of postoperative epilepsy in 150 patients of intracranial aneurysm. Anticonvulsants were given to all patients after operation, but in 12 cases anticonvulsants were discontinued because of liver dysfunction. One hundred and eight out of 138 cases (78%) were prescribed polypharmaceutically, and 30 of 138 cases (22%) were monopharmaceutically. The daily dose of anticonvulsants was as follows; diphenylhydantoin (DPH) was 150-300 mg, phenobarbital (PB) was 50-100 mg, valproic acid (VPA) was 600-1200 mg, and carbamazepin (CBZ) was 200-600 mg. Postoperative epilepsy occurred in 14 of 150 cases (9.3%); 13 cases with anticonvulsants, and 1 case without anticonvulsants. The site of aneurysm was as follows; 6 cases (10.3%) of AC aneurysm, 3 cases (9.7%) of MC aneurysm, 1 case (2.4%) of IC aneurysm, and 4 cases (21.1%) of multiple aneurysm. The interval between operation and epileptic seizure was ranged 2 to 57 months (mean 19.8 months); in 7 cases (50%) within 1 year, and in 13 cases (93%) within 3 years. The authors emphasize that prophylactic use of anticonvulsants is effective to control subclinical epileptic seizures, prescribing anticonvulsants to all patients after craniotomy in general. The medication of anticonvulsants for 3 years would be necessary for avoiding postoperative epileptic seizure.