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Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown.We analysed expression of genes involved in OXPHOS from the livers of 14 patients with type 2 diabetes and 14 subjects with NGT using serial analysis of gene expression (SAGE) and DNA chip analysis. We evaluated the correlation between expression levels of genes involved in OXPHOS and the clinical parameters of individuals with type 2 diabetes and NGT.Both gene analyses showed that genes involved in OXPHOS were significantly upregulated in the type 2 diabetic liver. In the SAGE analysis, tag count comparisons of mitochondrial transcripts showed that ribosomal RNAs (rRNA) were 3.5-fold over-expressed, and mRNAs were 1.2-fold over-expressed in the type 2 diabetes library. DNA chip analysis revealed that expression of genes involved in OXPHOS, which correlated with several nuclear factors, including estrogen-related receptor-alpha or peroxisome proliferator-activated receptor-gamma, was a predictor of fasting plasma glucose levels, independently of age, BMI, insulin resistance and fasting insulin levels (p = 0.04). Surprisingly, genes involved in OXPHOS did not correlate with peroxisome proliferator-activated receptor-gamma coactivator-1alpha or nuclear respiratory factor 1.Our results indicate that upregulation of genes involved in OXPHOS in the liver, which are regulated by different mechanisms from genes in the skeletal muscle, is associated with fasting hyperglycaemia in patients with type 2 diabetes.

We studied MLL rearrangements in five patients with myeloid hematologic malignancies with trisomy 11. Two had acute monocytic leukemia (AMoL), one had chronic myelomonocytic leukemia, one had refractory anemia, and the other had juvenile chronic myelogenous leukemia. Only one patient, a 15-year-old boy with AMoL and simple trisomy 11, showed rearrangement of MLL. He did not respond to chemotherapy, and successfully underwent bone marrow transplantation, but suffered a relapse 22 months later. Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing analyses of bone marrow cells revealed a tandem duplication of MLL, and his relapse was predictable by sequential RT-PCR studies before it was clinically evident. Of 16 acute myeloid leukemia patients with trisomy 11 and rearrangement of MLL reported, our patient was the youngest in age and the only one with AMoL.

The AML1 gene was rearranged in leukemic cells with t(8;21)(q22;q22) or its variant, complex t(8;V;21) translocations from 33 acute myeloid leukemia (AML) patients. The AML1 rearrangement was also detected in three AML patients without t(8;21); two had a normal diploid karyotype, and one had a karyotype of 45,X, - X. The AML1 rearrangement in the t(8;21) breakpoint cluster region was not detected in leukemic cells with cytogenetic abnormalities other than t(8;21), or with normal diploidy obtained from 23 AML patients. Because leukemic cells of the five patients with complex t(8;V;21) translocations had a der(8)t(8;21) chromosome with a break in band 8q22 in common, the juxtaposition of the 5' side of AML1 to a predicted counterpart gene located in the breakpoint region of 8q22 may be an essential step in the leukemogenesis of AML with t(8;21). Our findings show that the 8;21 translocation, its variants, and the masked t(8;21) may all be detectable by the Southern hybridization method using the AML1 probes.

The purpose of this study is to evaluate usefulness of perfusion cooling for regional spinal cord hypothermia during most or all of thoracic or thoracoabdominal aneurysm repair.From 1987 to 2003, 103 patients underwent most or all of thoracic or thoracoabdominal aneurysm repair. Forty-eight patients underwent operation using distal aortic perfusion, mild hypothermia and segment sequential repair (group MH). Fifty-five patients underwent the same operation as group MH except epidural perfusion cooling and drainage of cerebrospinal fluid (CSF) [group ECCSFD]. The aorta was replaced sequentially in segment and several paris of intercostal and lumbar arteries were reconstructed in 2 groups.Cardiopulmonary bypass time of group MH and group ECCSFD was averaged 235 and 241 minutes, respectively. The lowest CSF temperature in group ECCSFD was averaged 24.7 degrees C, and the difference between nasopharyngeal and CSF temperature was averaged 6.4 degrees C. The rate of spinal cord injury of group MH and ECCSFD was 10.4% and 3.6%, respectively. Hospital mortality of group MH and ECCSFD was 8.3% and 5.5%, respectively. The incidence of spinal cord injury and hospital mortality of group ECCSFD were decreased compared to them of group MH.We conclude that the perfusion cooling of epidural space and CSF drainage are effective method in reducing postoperative spinal cord injury.

Ataxic sensory neuronopathy with Sjögren's syndrome is a devastating neurologic complication for which there is no established treatment. IV immunoglobulin (IVIG) was given to five patients with severe disabilities for an average of 12 years. Four patients showed remarkable improvement, two of whom responded after the first course. The authors conclude that IVIG is safe and effective to treat even chronically debilitated patients who have the disease, presumably because it ameliorates smoldering inflammation.

From June 1994 to July 2001, 92 consecutive patients underwent total aortic arch replacement using hypothermic selective cerebral perfusion. Forty-four patients had nondissecting fusiform or saccular aneurysms (non-ruptured 34, ruptured 10), and 48 patients had dissection (acute 37, chronic 11). Hospital mortality rate was 6.8% in the nondissecting group and 6.3% in the dissecting group. No major operative cerebral complications were observed. There were 9 late deaths in the nondissecting group and 5 late deaths in the dissecting group. The actuarial survival rate was 61.6% after 100 months in the nondissecting group and 82.5% after 86 months in the dissecting group (p = 0.5128). In the postoperative aortic accidents, there were 2 cases of the descending aortic rupture and 2 cases of cholesterol crystal embolization in the nondissecting group and 3 cases of thoracoabdominal grafting, 2 cases of re-operation in the ascending aorta and 1 case of descending aortic rupture in the dissection group. The actuarial freedom from aortic accidents was 88% after 100 months in the nondissecting group and 80% after 86 months in the dissecting group (p = 0.6908). Our surgical outcome of total aortic arch replacement using hypothermic selective cerebral perfusion are satisfactory.

A 72-year-old man with back pain on the left side was admitted. Imaging analysis revealed a retroperitoneal mass and a mass in the left iliocostal muscle and the left quadratus lumborum muscle. The two masses could not be resected en bloc, and were resected separately. The clinicopathological findings of these tumors revealed dedifferentiated liposarcoma. The primary dedifferentiated liposarcoma appeared to have originated from the retroperitoneal space extending into the iliocostal muscle and the quadratus lumborum muscle. Then the mass was thought to have formed accompanied with osteogenesis.

This study was aimed to evaluate the usefulness and feasibility of extracorporeal shock wave lithotripsy (ESWL) performed in elderly patients. ESWL by Triptor X-1 was used to treat 530 patients with upper urinary tract stones from 1991 to 1998. Sixty one (11.5%) of them were aged 70 years and older. The results of ESWL treatment in this elderly group were compared retrospectively with those in 122 patients aged from 20 to 39 and 243 patients aged from 40 to 59. Although the elderly had a higher incidence of preoperative risk factors, the postoperative complication rates were similar among all groups. The stone-free rate and the success rate at one month in the elderly group were 67.2% and 92.5%, respectively, which were similar to those in the younger groups. These results suggested that ESWL offered a safe and effective means of treating upper urinary tract stones in elderly patients.

We report a simultaneously operated case of a 68-year-old man with lung cancer accompanied with aortic arch aneurysm. Preoperative staging CT for lung cancer incidentally demonstrated another lesion in the para-aortic arch area, which was suspected to be rather a pleural or intrapulmonary lesion by enhanced CT and MRI. However, this lesion was intraoperatively diagnosed as a cystic small sized-aneurysm. After a left upper lobectomy with lymph node dissection for lung adenocarcinoma (T2N0) was performed, this aneurysm was tightly wrapped using PTFE felt during the course of one operation. The difficulty of peroperative diagnosis by CT and MRI for small sized-aneurysm is discussed, and surgical stragety for lung cancer accompanied with such an aortic aneurysm is also commented.

Cytogenetic and molecular-genetic characteristics in peripheral T cell lymphoma (PTL) have not been well defined, except for those in adult T cell leukemia/lymphoma (ATL/L). Translocations and inversions involving a chromosome band 14q32 were extremely common abnormalities reported in PTL and ATL/L. We studied the involvement of TCL1, a recently isolated gene located in 14q32.1, in tumor tissues from 20 patients with PTL including three with 14q32 translocations by two color fluorescent in situ hybridization (FISH) using two cosmid probes flanking the TCL1 gene. The two cosmid signals were separated in none of them, but much increased in number in one tumor without 14q32 translocation, indicating that the TCL1 genomic region was amplified in this tumor. Reverse transcription-polymerase chain reaction (RT-PCR), however, failed to detect the TCL1 transcript in the tumor. These findings suggest that an oncogene other than TCL1 may be located in 14q32.1, and its amplification may be involved in the neoplastic process of PTL.

By in situ hybridization (ISH) method using digoxygenin (DIG)-labeled RNA probe, we proved the localization and replication of hepatitis C virus (HCV) RNA not only in the hepatocytes but also in the lymphocytes of the 52 liver tissues of chronic hepatitis C. We classified the staining patterns into four groups. The pattern of signal distribution significantly correlated with serum alanine aminotransferase (ALT) level, quantity of serum HCV RNA just before liver biopsy, histological grade of inflammatory activity, and stage of fibrosis by Spearman rank correlation. Moreover, we investigated the relation between the signals in the hepatocytes or lymphocytes and the effectiveness of interferon (IFN) therapy. Therefore, we suggest that ISH is a useful tool to evaluate the activity of chronic hepatitis C associated with serological and histopathological changes and is an important marker to assess the effectiveness of IFN treatment.

We examined whether paracrine factors produced by prostate cancer cells can modulate bone metabolism in proportion to the volume of cancer cells in bone metastasis. Endocrine factors produced by prostate cancer cells affect both phosphate and 1,25-dihydroxyvitamin D metabolisms. Levels of urine pyridinoline (U-Pyr) excretion and serum carboxy-terminal propeptide of type 1 procollagen (P1CP) in patients with bone metastasis were significantly higher than those in patients without bone metastasis (P0.05). In patients with bone metastasis (n = 17), serum prostate-specific antigen (PSA) levels were significantly correlated with the levels of U-Pyr and urine deoxypyridinoline (U-dPyr) excretion, serum cross-linked carboxyterminal telopeptide of type 1 collagen (1CTP), and P1CP levels (p0.05). However, serum PSA levels were not correlated with U-Pyr, U-dPyr excretions, serum 1CTP and P1CP levels in patients without bone metastasis. Therefore, prostate cancer cells appear to have some paracrine effects on bone cells. In controls (n = 15), serum 1,25-dihydroxyvitamin D levels (1,25-(OH)2D) were inversely correlated with serum phosphorus levels (P0.01). In prostate cancer patients with bone metastasis, the ability to regulate the serum 1,25-(OH)2D levels in response to serum phosphorus levels is lost. These results suggest that endocrine factors produced by prostate cancer cells disturb the regulation of serum 1,25-(OH)2D in response to serum phosphorus levels.

We investigated the correlation between tumor angiogenesis and prognosis of T1N0M0 lung adenocarcinoma.Forty two specimens resected from patients with T1NOM0 lung adenocarcinoma were investigated by immunohistochemical staining with a monoclonal antibody to CD31. The relationship between microvessel count, clinicopathologic factors and prognosis was studied.The microvessel count was significantly higher in cases with vessel invasions than in those without. Univariate analysis showed that microvessel count was related to poorer prognosis. In patients with a high microvessel count (or = 38), prognosis was significantly poorer than in those with a low count (38). Multivariate analysis indicated that the microvessel count and mitosis are prognostic factors in patients with lung cancer, and that the microvessel count is a more important factor than mitosis.Microvessel count may be a major prognostic factor and a useful tool to predict recurrence in patients with T1N0M0 lung adenocarcinoma.

In 1982, the Fourth International Workshop on Chromosomes in Leukemia reviewed data prospectively collected on 716 patients with acute myeloid leukemia (AML) diagnosed between 1980 and 1982. The present study examined the extended follow-up on these patients.The analyses included cytogenetic and clinical data, with a median follow-up of 14.7 years, from 54 patients with treatment-associated AML and 628 with de novo AML. Of these patients, 291 received induction therapy that would be considered standard by today's criteria; no patient received high-dose cytarabine (HiDAC) intensification.Among the patients with treatment-associated AML, the only long-term survivor in retrospect appears to have had de novo AML. Among the patients with de novo AML, achievement of complete remission and survival varied significantly based on cytogenetic classification among all 628 patients as well as among those who did and did not receive standard induction therapy. The remission rate and survival were significantly better with standard induction therapy for patients with t(15;17) and normal cytogenetics. Multivariate analyses showed that karyotype was an independent predictor of survival for all patients and those receiving standard induction therapy. Only 8.9% of patients were alive 5 years following diagnosis, but 5 years of continuous remission was synonymous with cure. Even among 5-year survivors who had suffered a previous relapse, 41% appeared to be cured. Survival among patients in continuous remission foror = 10 years varied significantly by cytogenetic classification. In the absence of HiDAC intensification, no complete responders with t(8;21) and only 7% with normal cytogenetics survived continuously 10 years disease free.Cure of AML following specific therapies must be evaluated in the context of cytogenetics. A meta-analysis incorporating cytogenetic data is indicated for patients withor = 10 years of follow-up.

Phase II study of combination chemotherapy with cisplatin, carboplatin and etoposide (CPVP) was conducted in 46 patients with unresectable non-small cell lung cancer. In the previous paper, we showed that CPVP produced a satisfactory response rate without major toxicities. In the present paper, survival time and prognostic factors were analyzed. The median survival time (MST), 1- and 2-year survival of 46 patients (III A4, III B15, IV 27) were 14.1 months, 57.0% and 18.2%, respectively. In prognostic analysis, responders survived significantly longer than non-responders (MST: 15.8 vs 11.0 months, p0.05). Large cell carcinoma and stage IV have proven to be indicators of poor prognosis. Females and patients less than 60 years old tended to do better. With regard to the relationship between the time from initiation of treatment to response and survival time, late responders (response after 3 or 4 courses) survived significantly (p0.05) longer than early responders (response after 1 or 2 courses). The CPVP regimen is not only practical, but also very effective. It deserves further study to reveal its advantages compared to the other platinum compound containing regimens.

Background and Study Aims : The correct histological diagnosis of gastric borderline adenomas is often difficult, especially in excluding malignancy, since the usual diagnostic methods, such as radiography and histological examination of forceps biopsy specimens, are of limited accuracy. The aim of this study was to retrospectively analyze the value of endoscopic mucosal resection in establishing the correct diagnosis of boderline adenomas. Patients and Methods : Fifty patients diagnosed as having borderline adenomas of the stomach were included in the study. None of the tumors had a conclusive diagnosis of carcinoma on endoscopic biopsy. Following endoscopic mucosal resection, the histological results of biopsy and resected specimens were analyzed. Results : Fourteen borderline adenomas were finally diagnosed as containing early gastric cancer type IIa (well-differentiated tubular adenocarcinoma) after endoscopic mucosal resection, of the remaining 36 tubular adenomas, six represented mild dysplasia, 24 moderate dysplasia, and six severe dysplasia. Most parts of the 14 adenomas containing early gastic cancers had regions of structural atypia, and cellular atypia was moderate in all. Seven of 14 cancers were completely resected, all patients being tumor-free after a follow-up of 33-61 months. Conclusions : These results suggest that diagnosing borderline adenoma on the basis of radiographic and endoscopic-bioptic findings is generally unreliable, because biopsy specimens may not be representative of the entire lesion. Borderline adenomas of the stomach should be completely resected by endoscopic mucosal resection to obtain a final diagnosis and - depending on the size and type of the lesion - possibly also definitive treatment.

This study was carried out to clarify if there has been any improvement in the outcome of patients with aneurysmal subarachnoid hemorrhage during the past 20 years. Because elderly patients have apparently poorer prognoses than younger patients, patients older than 70 years were analyzed separately in the following article.Five hundred seventy-one patients with aneurysmal subarachnoid hemorrhage, under 70 years, who were consecutively admitted to Kagawa Prefectural Central Hospital from July 1972 to December 1992, were reviewed. These patients were divided into four groups according to the time of admission. The ultimate outcome was evaluated by means of Glasgow Outcome Scale 6 months after the ictus.Changes in treatment protocol in this period included the induction of early surgery and the invention of a variety of modalities for the treatment of cerebral vasospasm. This resulted in a distinct increase in patients who actually underwent direct aneurysm clipping. Outcome has been significantly improved during this period, especially in patients with Hunt and Kosnik grade III (p0.05, chi2). Patients in good clinical condition at follow-up (Glasgow Outcome Scale: good recovery) increased from 8.7% to 60.7%. Mortality decreased from 28.7% to 10.7%.Current therapeutic modalities have significantly improved the outcome of patients with aneurysmal subarachnoid hemorrhage. Rebleeding before early surgery remains as a major cause of unfavorable outcome and further progress on this subject is mandatory.

We have reported improvement in the outcome of the younger patients with aneurysmal subarachnoid hemorrhage in the preceding article. The purpose of this article is to study if the same management protocol has simultaneously benefited the elderly patients.One hundred twenty-nine patients with aneurysmal subarachnoid hemorrhage, over 70 years old, who were consecutively admitted to Kagawa Prefectural Central Hospital from July 1972 to December 1992, were reviewed. Patient grouping and outcome evaluation were the same as those of younger patients.Changes in treatment protocol in this period, which were similar to those of the younger counterparts, resulted in an increased number of patients who actually underwent aneurysm clipping. Although the outcome evaluated at 6 months after initial hemorrhage was significantly poorer than that of the younger counterparts, there have been some improvements during the study period. Patients in good clinical condition at 6 months' follow-up (Glasgow Outcome Scale: Good Recovery) increased from 37.5% to 42.9% in grades I-II and from 0% to 23.1% in grade III, respectively.The improvement in the outcome of elderly patients was less remarkable than that observed in younger patients. Significantly higher incidence of preoperative rebleeding and postoperative symptomatic vasospasm has proven to be the major cause of mortality and major morbidity at present. More careful and sophisticated perioperative care is required in elderly patients with aneurysmal subarachnoid hemorrhage.

MMP-9 degrades type IV collagen, gelatin, type V collagen, and type XI collagen. We measured proMMP-9 and proMMP-9/TIMP-1 complex in sera and joint fluids by sandwich ELISA, and examined immunohistochemically the expression of these proteins in joint tissue from patients with rheumatoid arthritis (RA). ProMMP-9 was purified by the three chromatographic steps from the culture medium of HT1080 cells. Purified proMMP-9 and activated MMP-9 by APMA showed a single band of Mr92000, Mr67000, resectively on gelatin-zymography. We raised two monoclonal antibody colones 2G9, 8G7 against proMMP-9 with BALB/c mice. 2G9 and 8G7 reacted with proMMP-9 on Western blotting, and these clones reacted proMMP-9 and proMMP-9/TIMP-1 complex on sandwich ELISA, specifically. ProMMP-9 concentration in 86 sera (749.4+/-940.2 ng/ml) and 54 joint fluids (4539.9+/-7681.5 ng/ml) from patients with RA was significantly higher than those of patients with osteoarthritis and control. Immunohistochemistry with 2G9 showed that in rheumatoid synovium proMMP-9 localized in neutrophils and monocytes diffusely infiltrated the sublining layer. In addition, osteoclasts in rheumatoid subchondral bone were intensively stained. ProMMP-9 concentration in joint fluids from 39 RA patients was not correlated to stage and class of Steinbrocker and to clinical laboratorial data. But, it was positively correlated to the number of proMMP-9 positive cells in RA synovium (r=0.607) and the score of Roony's diffuse infiltrates of lymphocytes (r=0.720). Our results suggest a role of MMP-9 in joint destraction of RA throughout neutrophils and monocytes, and a regulation of this enzyme by lymphocytes.

Bone mineral density (BMD) of the radius was measured in 181 female patients with rheumatoid arthritis (RA) and 255 control subjects using dual energy X-ray absorptiometry (DXA). The BMD of RA patients was assessed according to patients' age and menopause and was compared with age-matched controls for various activity factors of RA and duration of the disease that might correlate with BMD. At stages I and II of premenopausal RA, generalised osteoporosis was not observed. At stages III and IV, the BMD decreased considerably in premenopausal RA patients at age of 45 years or older. There were significant correlations between the BMD of postmenopausal RA and all factors examined, many of which did not affect premenopausal RA. These results suggest that osteoporosis of female patients with RA is influenced only slightly by the disease itself, but it is secondary osteoporosis induced by decreased activities of daily living due to RA.

1. We analysed the expression of neurofibromin mRNAs, encoded by the gene responsible for neurofibromatosis type 1, and of neurofibromin protein in nine soft tissue tumours by S1 nuclease mapping and Western blot analyses. Four tumours were obtained from patients with neurofibromatosis type 1, comprising two neurofibromas, one fibrolipoma and one malignant schwannoma, and five neurogenic tumours were obtained from non-neurofibromatosis type 1 patients. 2. All tumours, except for a malignant schwannoma, similarly expressed three species of mRNA encoding neurofibromin, an isoform with the insertion of 21 amino acids in the domain related to ras GTPase-activating protein, and an N-terminal isoform lacking this domain. 3. Western blot analysis demonstrated deficiency of neurofibromin in the tumours derived from three out of the four neurofibromatosis type 1 patients: a fibrolipoma, a malignant schwannoma and a neurofibroma. In contrast, reduction in neurofibromin was not detected in the five tumours obtained from non-neurofibromatosis type 1 patients. Furthermore, the expression of ras GTPase-activating protein was detected in all nine tumours examined. 4. The undetectable or reduced level of neurofibromin in the tumours obtained from neurofibromatosis type 1 patients suggests that this deficiency is closely related to their tumourigenesis.

Phase I/II study of combination regimen composed of cisplatin (CDDP), carboplatin (CBDCA) and etoposide (VP-16) [CPVP] was conducted for small cell lung cancer. The dose level of VP-16 was fixed at 100 mg/m2, while the dosages of CDDP and CBDCA administered at each of the 4 steps were 50/200, 60/200, 60/250 and 70/250 mg/m2, respectively. Nine patients were allocated to each step dose group. Toxicities were evaluated in the first 2 courses to determine the maximum tolerated dose (MTD). As a result, step 3 dosages proved to be MTD, and the dose limiting factor (DLF) was hematotoxicity, but gastro-intestinal toxicity was tolerated. The response (CR+PR) was found in 21 out of 23 patients with evaluable lesions (91%). In the 22 patients who had not received pretreatment, median survival time (M ST) was 16.4 months. These results suggest that the recommended dose is step 2, and that the CPVP regimen is both more tolerable and more effective than the standard regimen. The CPVP regimen warrants further study in phase III trials.

We treated a patient with von Recklinghausen's disease and angiosarcoma. This combination has not been reported in Japan to the best of our knowledge. An emergency operation for massive gastrointestinal bleeding was performed on a 68-year-old woman with von Recklinghausen's disease, who had been known to have a retroperitoneal tumor; The bleeding was controlled and the tumor was also resected. Postoperative course was uneventful also but one month after operation intra-abdominal and intrathoracic bleeding developed, and the patient died of respiratory failure. Autopsy showed hemorrhagic lesions, which were diagnosed pathologically metastatic angiosarcoma. The possibility of hemorrhagic lesions in the patients with von Recklinghausen's disease should be kept in mind.

The time-lag/sequential/step by step chemotherapy by fosfomycin plus sulbactam/cefoperazone including a short time small dose of steroid was done for 27 severely infected patients suffered from various cancer or other severe basal diseases. And the staggered "intensive" chemotherapy with added arbekacin or vancomycin to the previous staggered chemotherapy was done against 13 severely infected patients having MRSAs among their infecting pathogens. 1. Bacteriological effects Pseudomonas aeruginosa 6/8, Staphylococcus epidermidis 5/5, Enterococcus faecalis 3/6, Acinetobacter calcoaceticus 2/2, Klebsiella pneumoniae 2/2, MRSA 2/2, Xanthomonas maltophilia 2/3 and other 10/10 were eradicated (84.2%) by the staggered chemotherapy and MRSA 7/13, P. aeruginosa 3/4, E. faecalis 3/5, A. calcoaceticus 2/2, X. maltophilia 1/1 and others 2/2 were eradicated (53.8% in MRSA, 78.6% in others and 66.7% in total) and 3 of MRSAs were colonized. 2. Clinical effects 1) Staggered chemotherapy: Excellent 18/27, good 8/27, fair 1/27, poor 0/27 (96.3%). 2) Staggered "intensive" chemotherapy: Excellent 6/13, good 4/13, fair 2/13, poor 1/13 (76.9%) in total: excellent 60.0%, efficacy rate 90.0%.

We sought to assess whether serum levels of hyaluronate (HA) in patients with rheumatoid arthritis (RA) are elevated and correlated with grade of joint destruction and with laboratory data. Circulating HA levels were determined by protein binding assay of serum from 236 patients and 19 healthy controls. The greatest elevations of HA were seen in RA patients (350.7 +/- 689.5 ng/ml) than controls (33.7 +/- 24.2 ng/ml). Their levels showed only weak correlation values of CRP in laboratory data. Although HA levels of sera in stage III and IV in Steinbrocker's classification revealed significantly higher on average than ones in stage I and II (p0.01), there were many cases with low HA levels even in stage III and IV. Comparing HA levels between the cases with progressive and non-progressive type of hip or knee joint destruction within a year, the former (1143.6 +/- 1746.0 ng/ml median 480.1 ng/ml) presented significantly higher HA levels than the latter (245.3 +/- 255.8 ng/ml median 140.0 ng/ml) (p0.01). Further, one of 7 cases followed by 4 years with extremely high levels of HA showed progression of joint destruction from grade III to IV in Larsen Grade in bilateral knee joints during these times, though there were no significant correlations between HA levels and laboratory data. From above results, levels of circulating HA in the sera of patients with RA correspond to the joint destruction, not to a result of one.

Forty five patients with complicated urinary tract infections were treated with tosufloxacin (TFLX) in the initial antibacterial treatment. Excellent and moderate responses were obtained in 39 patients (86.7%). No side effects were seen. Clinical efficacy and safety of long-term preventive administration of TFLX (150mg, a day) were also examined in 39 patients who showed an excellent or a moderate response in the initial treatment. The period of the administration ranged from 28 to 112 days (average; 55 days). The rate of preventing recurrence of urinary tract infection was 92.3% on the last day of treatment. These findings suggested that TFLX was useful not only in treating the patients with complicated urinary tract infections but also in preventing recurrence of urinary tract infection.

Pseudomonas aeruginosa has been a major bacterial partner when MRSA (Methicillin-resistant Staphylococcus aureus) is isolated clinically. Hence, we studied the in vitro combined effect of fosfomycin (FOM) plus sulbactam/cefoperazone (SBT/CPZ) against mixed infections of MRSA and P. aeruginosa. The combined effect of FOM plus SBT/CPZ was observed through an FIC index using the checkerboard method, log reduction of colony counts on the time killing curve, and morphological changes observed using scanning electron micrography. Under serum concentration at 3 hours after administration in consider of pharmacokinetics, the combination effect was also evaluated. Furthermore, we evaluated a time-lag combination therapy in which FOM is administered 60 minutes before SBT/CPZ administration for mixed infections. Synergistic effects of FOM plus SBT/CPZ were clearly observed against mixed infections of MRSA and P. aeruginosa. Log reduction of colony counts on the time killing curve seemed to be an appropriate indicator in the evaluation of synergistic effects.

Thymoma with thrombocytopenia has rarely been reported. We recently encountered a case of operated invasive thymoma with thrombocytopenia. A 74-year-old woman was admitted to our hospital with the chief complaint of 'shortness of breath' and general fatigue. Chest X-ray, CT and MRI showed a mass 5 x 5 cm in size at the anterior mediastinum. In hematological test, a significant decrease in platelets count (1.6 x 10(4)/mm3) and a increase in PA-IgG (134.5 ng/10 cells) were found. This finding suggests that thrombocytopenia is due to immunological abnormality. Steroid therapy (prednisolone 60 mg) was begun but was not effective and then, extended thymectomy was performed. After operation, prednisolone (30 mg) therapy was continued. Although prednisolone therapy was gradually decreased and stopped, platelets count was gradually increased 10.8 x 10(4)/mm3. Extended thymectomy and steroid therapy were effective.

We studied the dietary habits of 113 upper urinary tract stone formers and 24-h urine specimens before and after dietary control. Protein intake was decreased in male patients after dietary control but urinary risk factors were not changed significantly. The excretion of urinary risk factors (calcium, uric acid and oxalate) was decreased in the patients who had calcium excretion of more than 250 mg per day or uric acid excretion more than 650 mg per day or oxalate excretion more than 45 mg per day before the control. The daily protein intake was significantly correlated to urinary uric acid, calcium, and phosphate excretion and the daily vitamin C intake to urinary citrate excretion. There was a negative correlation between the daily calcium intake and urinary oxalate. The mean stone episode rate of these patients was significantly decreased from 0.174 to 0.059 stones per year by dietary control (p0.005).

Implantations of automatic implantable cardioverter defibrillator were performed in five patients with life-threatening ventricular tachyarrhythmias. Preoperative diagnoses of arrhythmias were sustained ventricular tachycardia (VT) in two cases, ventricular fibrillation (VF) in two cases and sustained VT+VF in one case. Four of five cases had basic diseases respectively (broad anterior myocardial infarction, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy), and the other case was idiopathic. Preoperative CTR were 43-65% (mean 57.4%) and left ventricular ejection fraction were 26-76% (mean 51.2%). Implantation of AICD was indicated for patients who survived circulatory arrest or life-threatening VT. Median sternotomy (3) or left antero-lateral thoracotomy (2) were performed for implantation of large-small patch electrodes for defibrillation. AICD generators were implanted in the pocket under abdominal rectal muscle in all cases. Postoperatively myocardial insufficiency, pericarditis, pleuritis occurred in three cases respectively. In the follow-up periods (2-25 months, mean 13 months), AICD worked effectively in two patients with spontaneous VT (6 months, 1 year after operation) and no cardiac death was experienced. We concluded that AICD system is effective for the life-threatening ventricular tachyarrhythmias, although the further estimation in longer follow-up periods are warranted.

A solution of 0.5 g of meropenem (MEPM) in 100 ml of saline was administered to adult patients before the orthopaedic surgery via intravenous drip infusion for 30 minutes. Eleven samples of bone marrow blood, 13 bone, 8 joint fluid and 8 joint tissues obtained from 15 clinical cases were analyzed for MEPM levels. At the same time, blood samples were taken from peripheral veins and serum served as control was analyzed. The concentration of MEPM in the marrow blood at 30 minutes after administration of MEPM reached 15.4 micrograms/ml, which was above 50% of the maximum concentration in serum. Ratios of concentration in bone marrow to that in serum were between 93% and 105% at that time. MEPM levels were 5.74-0.40 micrograms/g in bones, 20.3-4.55 micrograms/ml in joint fluid and 18.2-4.05 micrograms/g in joint tissues at 30 to 75 minutes after administration. In joint fluid and joint tissues, the concentration above 50% of maximum level in serum were maintained for more than an hour. MEPM is thought to be useful for the treatment of bone and joint infections and also prophylaxis of infections in cases of major surgery of skeletal tissue in the field of orthopaedic surgery.

The response of 50 patients who underwent hepatectomy for hepatocellular carcinoma measuring 3 cm or less (at the time of surgery) to transcatheter oily chemoembolization was evaluated. The response was assessed in 5 categories, A: complete necrosis (100%), B: necrosis of at least 95%, C: at least 80%, but less than 95%, D: at least 50% but less than 80%, and E: less than 50% of the tumor cells. Response A was observed in 19 patients (38%), B in 7 (14%), C in 9 (18%), D in 7 (14%), and E in 8 (16%). These results were classified with respect to the histological degree of tumor differentiation, the WHO histological classification, the microscopic patterns of tumor growth, and macroscopic classification. The response was evaluated in relation to the histological grade of tumor differentiation and the WHO histological classification in all categories of response except response A, and there was no significant difference between the categories. The response was obviously better with the expansive type than with the replacing type. Single nodular type lesions were more responsive than the single nodular type lesions with extranodular growth and the contiguous multinodular type. Pretreatment estimation of the microscopic patterns of tumor growth and macroscopic classification appears to be valuable in predicting prognosis.

A variation of the extracranial-intracranial arterial bypass, using a long saphenous vein graft, is presented. The saphenous vein graft was inserted from the contralateral external carotid artery to the distal middle cerebral artery to replace the common and internal carotid arteries in a patient with a large neck tumor that invaded the common and internal carotid arteries, the esophagus, and the trachea. The patient had a positive balloon Matas' test. The saphenous vein was covered with an artificial vascular graft so that turning of the head or movement of the mandible did not displace or compress the graft. A large volume of flow began immediately after anastomosis. A description of the case and the operative technique is presented herein.

The chromosome der(1;7) (q10;p10) is a derivative chromosome consisting of the short arm of chromosome 7 and the long arm of chromosome 1. We observed this abnormality in three patients with acute myeloblastic leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative disorder (MPD). Case 1 was a 76-yr-old male with a history of IgG myeloma treated with melphalan, cyclophosphamide, vincristine, and prednisolone (MEVP). AML-M1 developed one and half years after discontinuation of the MEVP therapy. Case 2 was a 39-yr-old male with MDS. Case 3 was a 56-yr-old male with refractory anemia with excess of blasts in transformation that evolved from primary myelofibrosis. Chromosome analyses revealed der(1;7) (q10;p10) in bone marrow cells of the three patients. All patients failed to respond to chemotherapy, and died within four months after the diagnosis. Thus, der (1;7) (q10;p10) may indicate a very poor prognostic outcome in patients with malignant hematologic disorders.

The authors report six cases of non-Hodgkin's lymphoma (NHL) (3B-cell type, one T-cell type, one non-T non-B cell type, one unclassified type) occurring subsequently to autoimmune diseases. The patients were females aged 43 to 70 (median 61). Rheumatoid arthritis was most frequent as the preceding autoimmune disease, and the intervals from the onset of an autoimmune disease to that of NHL were 10 to 36 years (median 20). Polyclonal hypergammaglobulinemia was seen in 4 cases, lymphocytopenia in 3 cases, and conversion to negative PPD reaction in 2 cases. Only one patient had been given corticosteroids, and immunosuppressive agents may not contribute much to the development of lymphoma in patients with autoimmune diseases.

In a multicenter clinical trial, the efficacy and usefulness of the BPAA Patch in the treatment of extremity trauma were evaluated in 64 patients and the safety was tested in 70 patients. In 89.1% of the patients studied, the final overall improvement was rated "moderate" or better, and no adverse reactions were reported. The results of this study indicate that the BPAA Patch is a highly useful topical antiinflammatory-analgesic agent for use in the treatment of pain and inflammatory symptoms following trauma.

An MR study was performed in 73 clinically diagnosed cirrhotic patients to determine correlations among the demonstration of small low intensity nodules (SLINs), secondary changes due to cirrhosis, and serological data. In 32 patients, liver cirrhosis was proved histologically. SLINs were observed in 38 of the 73 patients on gradient echo (GRE) images and in 28 patients on T2-weighted SE images. Patho-MR correlation study of the liver in the 32 histologically proved cirrhotic patients revealed that SLINs were seen on GRE images only in patients with iron deposits in regenerating nodules (RNs). There was no significant correlation between secondary changes due to liver cirrhosis and the demonstration of SLINs. Serological data indicating liver cell injury and iron store in the body were significantly higher in patients with iron deposits in RNs than in those without iron deposits.

Karyotypes of 107 cases with adult T-cell leukemia/lymphoma (58 male, 49 female; 81 acute or lymphoma type, 26 chronic or smoldering type) were reviewed by a panel of cytogeneticists and were correlated with the subtypes of the disease. Clonal chromosome abnormalities were found in 103 (96%) cases, of which four had hypotetraploidy. Of 184 numerical abnormalities in the remaining 99 cases with near- or pseudodiploidy, trisomies for chromosomes 3 (21% of cases), 7 (10%), and 21 (9%), monosomy for X chromosome (38%) in the female, and loss of a Y chromosome (17%) in the male were more frequent than expected (P less than 0.01). Of 373 structural abnormalities in all the 103 aneuploid cases, translocations involving 14q32 (28%) or 14q11 (14%) and deletion of 6q (23%) were most frequent, followed by deletion of 10p (9%), 3q (8%), 5q, 9q, and 13q (7% each), and 1p and 7p (6% each). The proportion of cases with aneuploid clones (with greater than or less than 46 chromosomes), the average numbers per case of both numerical and structural abnormalities, and marker chromosomes were larger in the aggressive acute or lymphoma type than in the nonaggressive chronic or smoldering type (P less than 0.01). The combination of rearrangement in 14q32 and monosomy X (seven cases) or deletion of 10p (six cases), and that of trisomy 3 and deletion in 6q21 (six cases), occurred only in the acute or lymphoma type and may be associated with the aggressiveness in adult T-cell leukemia/lymphoma.

The association of recurrent chromosomal abnormalities with certain types of non-Hodgkin's lymphomas (NHLs) provides important clues to their classification and pathogenesis. The t(11;14), an uncommon abnormality, has been reported in a variety of B-cell lymphomas, including the intermediately differentiated lymphocytic lymphoma (IDLL). The authors report here the histologic, immunophenotypic, and cytogenetic findings in four additional patients with such translocation. They represent 8% of 51 patients with NHL studied by cytogenetics in a provincial hospital of Western mainland Japan. Three of the patients had IDLL and one a follicular lymphoma of large cell type. These findings strengthen the association between t(11;14) and IDLL. Furthermore, the occurrence of t(11;14) in a follicular lymphoma, as the sole abnormality, along with histogenetic considerations, suggests the possible existence of a rarer subset of follicular lymphoma, not associated with the t(14;18) and histogenetically related to IDLL.

To establish clearly the pathologic basis for small low-intensity nodules seen on MR images of the cirrhotic liver, we obtained MR images in 26 patients with cirrhosis in whom partial hepatectomy for hepatoma (15 patients), laparoscopy for cirrhosis (10 patients), or autopsy (one patient) was subsequently performed. Small low-intensity nodules were seen on gradient-echo images with short TEs (10-13 msec) in 13 of the 26 patients. In 12 of these 13 patients, small low-intensity nodules appeared larger and clearer as the TE was prolonged (14-25 msec). On T2-weighted spin-echo images, small low-intensity nodules were seen in 12 of the 13 patients, but not seen as well as on gradient-echo images. Pathologic correlation in these 13 patients revealed that the nodules on the MR images corresponded to iron deposits in regenerating nodules. Small low-intensity nodules were observed only on T2-weighted spin-echo images in two of the remaining 13 patients, in whom microscopic examination of the liver revealed marked inflammatory cell infiltration in the fibrous septa and no iron deposition. We conclude that small low-intensity nodules observed on MR images are caused by iron deposits in regenerating nodules, and that gradient-echo images with short and prolonged TEs are useful to confirm the presence of iron deposits in regenerating nodules.

Eleven patients harboring recurrent or deep-seated malignant gliomas were treated by interstitial brachytherapy with 192Ir seed assembly, between June 1987 and September 1989. Implantations for the afterloaded catheter were performed using the Brown-Roberts-Wells (BRW) CT guided stereotactic system. The number of seeds and the distribution of the implants were chosen in such a way that the minimum tumor dose of 30-50Gy could be delivered to the surface or 1cm beyond the rim of the contrast enhancement. The radioactive sources were held in the afterloaded catheters that were removed after the desired dose had been delivered. Response to therapy was measured by serial CT scans and clinical examination. Tumor regressions were seen by CT scans made 2 or 3 months after implantation. One tumor showed complete regression (CR), four showed partial response (PR), one showed minor response (MR) and 5 showed no change (NC). Overall response rate was 54%. Six patients died 3 to 18 months following implantation, and five are still alive 7 to 27 months after implantation. No complications such as infection or hemorrhage were observed during the treatment. A patient harboring large (6.5cm in diameter) recurrent glioblastoma in the rt. parietal robe required a craniotomy due to the mass growing for one and half month after implantation, and radiation necrosis of the entire tumor mass was documented. The technique of stereotactic interstitial implantation was clinically well tolerated and easily reproducible and our preliminary results seemed encouraging. Technical improvement to achieve an adequate isodose distribution to cover the tumor volume might lead to improved survival rates.

To evaluate the correlation between the histological grade and the prognosis, we reviewed 100 cases of prostatic cancer according to the Japanese General Rules of Prostatic Cancer (JGRPC) and Gleason grading system. The study led to the following results: (1) There was a close relation between the JGRPC grade and Gleason score (GS). (2) The JGRPC grade and Gleason score were equally concerned with the clinical stage. (3) There were significant differences in survival rate between well and moderately, well and poorly differentiated groups by the JGRPC grading system, and between GS 2-4 and GS 5-7, GS 2-4 and GS 8-10 groups by Gleason score. (4) In proportion to the JGRPC grade, the cancer death rate increased linearly in each stage. (5) When the patients were grouped according to their JGRPC grades of main lesion and accompanied lesion, the cancer death rate increased in the cases with lower differentiated elements. We conclude that the JGRPC grading system is easily comprehensible, and equal with the Gleason grading system to predict the prognosis of prostatic cancer.

The subjects were 231 patients aged 16 to 75 years with osteoarthritis of the knee joint. Each patient received 20 mg of piroxicam daily as a suppository administered before sleep; 75% of the patients were treated for 14 days or longer. Overall treatment outcome was excellent in 34% according to physicians' ratings and in 36% according to the patients' self-ratings, good in 39% and 41%, fair in 22% and 17%, and unimproved in 5% and 7%, respectively. Side effects were reported by 3% of the patients. It is concluded that treatment of osteoarthritis with piroxicam suppositories is safe and effective.

Clonal chromosomal abnormalities were found in tumor tissue of 43 (84%) of 51 patients with non-Hodgkin's lymphoma (B-cell, 32; T-cell, 15) from an adult T-cell leukemia/lymphoma-nonendemic area in western mainland Japan. Four tumors were tetraploid, and the other 39 had a chromosome number in the diploid range. Trisomies 3, 5, 7, 18, and X, monosomy 13, and loss of an X in female and a Y in male were found in more than three patients each. Structural abnormalities in arms 1p, 1q, 2q, 3q, 13q, 14q, and 18q were found in eight or more patients each. Clustering of breaks occurred in 3q25-29 (ten patients, nine of whom with a B-cell tumor), 11q13 (five patients), dir dup(12)(q13-15----q21-24) (four patients), 14q32 (12 patients), and 18q21 (seven patients). The 14q32 translocations were all associated with B-cell tumors. t(8;14) was seen in a small noncleaved cell lymphoma, t(11;14)(q13;q32) in one follicular and three intermediately differentiated lymphocytic lymphomas, and t(14;18)(q32;q21) in two follicular lymphomas and one diffuse small cleaved cell tumor. The translocation partner of 14q could not be determined in the other four patients, three of whom had der(18)t(18;?)(q21;?). The seven 18q21 abnormalities, including a novel translocation t(2;18)(p11;q21.3), all occurred in B-cell tumors; even in the absence of t(14;18), they were closely associated with lymphomas of follicular center cell origin (six of seven).

The effect of intravesical combination chemotherapy on superficial bladder tumors was analyzed. Seventy-two patients were treated with intravesical instillation of the following anticancer drugs. MMC group: Mitomycin C (MMC) 10 mg and cytosine arabinoside (CA) 300 mg. ADM group: Adriamycin (ADM) 30 mg and CA 300 mg. PEP group: Peplomycin (PEP) 30 mg and CA 300 mg. MAC group: MMC 10 mg, ADM 30 mg and CA 300 mg. Antitumor effects in the MMC, ADM, PEP and MAC groups were evaluated in 16, 18, 17 and 21 patients and objective response (CR + PR) of tumor was observed in 87.5%, 50.0%, 35.3% and 28.6% of these patients. The papillary tumors, small tumors and low grade tumors responded better to these intravesical chemotherapies than the non-papillary tumors, the middle grade tumors and the high grade tumors. The recurrence rate in 72 patients was 6.9, 14.6 and 26.8% within 1, 2 and 3 years. No significant difference in the recurrence rate was observed between the MMC, ADM, PEP and MAC group, but the MMC group tended to have a lower recurrence rate than the other groups. The recurrence rate for the low grade tumors and the middle grade tumors was significantly lower than that for the high grade tumors and the small tumors. The major side effect of instillation therapy with these drugs was bladder irritation which appeared in 16.7% of all the patients (78 cases). In conclusion, intravesical chemotherapy is a useful approach for controlling superficial urinary bladder tumors, especially the combination of MMC and CA.

Six hundred and eighty-four cases with non-Hodgkin's lymphomas (NHL) in Osaka, Japan were reviewed, using current histopathological classification to obtain a general feature of Japanese lymphomas. There were no remarkable differences in the distribution of age, sex and the location of primary tumors between Japanese NHL and the disease in Western races. Histologically, however, several differences were present; in particular, the lower frequencies of nodular lymphomas of nodal origin and lymphocytic type of nodal and extranodal origin in the present cases. About 10% of the cases show a peculiar histology characteristic for adult T cell lymphomas. From this study, it appears that the ratio of low-grade malignant NHL in Japan is much lower than in the Western countries.

To evaluate further the prognostic significance of karyotype at diagnosis of acute myelogenous leukemia (AML), we have made a follow-up study of 711 patients who were diagnosed between January 1, 1980, and March 31, 1982, and who were originally reported by the Fourth International Workshop on Chromosomes in Leukemia (4IWCL). Three different chromosomal classifications were evaluated, including presence of normal and abnormal metaphases (NN-AN-AA classification), a modification of the Chicago classification, and a complexity classification. All three chromosomal classifications were shown to correlate significantly with outcome in patients with de novo AML. Furthermore, the NN-AN-AA classification and the complexity classification had independent prognostic significance when age, sex, and FAB morphology were also considered in multivariate analyses of survival. These data provide further evidence that karyotype is an important factor in predicting the outcome of patients with AML.

A multidisciplinary treatment for hepatocellular carcinoma including preoperative chemo-embolization with resection treatment was introduced. Recent attempts at combining lipiodol with chemo-embolization have been quite promising. An ideal multidisciplinary treatment should include an effective device using the transportal approach.