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Objective Complete gastrectomy for gastric stump cancer (GSC) can be challenging due to severe adhesions; therefore, advanced techniques are required when being performed by laparoscopic surgery. This study aimed to evaluate the clinical outcomes of laparoscopic completion total gastrectomy (LCTG) for the treatment of GSC. Methods Patient records from January 2010 to October 2018 were retrospectively evaluated. The patients were classified into 2 groups depending on whether they underwent open or laparoscopic gastrectomy. We compared patient characteristics; operative, clinical, and pathological data between the groups. Results Twenty open and 17 LCTGs were performed. Laparoscopic gastrectomy resulted in a significantly longer operation time (230 versus 182.5 min; P = 0.026), lower blood loss (14 versus 105 mL; P < 0.001), and shorter period to the first flatus passage (2 versus 3 days; P < 0.001) than open gastrectomy. No significant differences in the number of retrieved lymph nodes, duration of hospital stay, complication rate, and postoperative analgesic usage between the 2 groups were observed. No patients required conversion to open surgery in the laparoscopic-treatment group. Pathologic findings revealed that the laparoscopic group had a smaller tumor size (not pathologic T category) and fewer metastatic lymph nodes than the open group, leading to an earlier distribution of the pathologic stage in the laparoscopic group. Conclusions LCTG for the treatment of GSC was safely conducted with fewer complications and mortalities than previously reported results. Advanced technologies and sophistication of laparoscopic skills may further yield minimal invasiveness with better short-term outcome.

The association between insulin resistance and lipid dysmetabolism after consuming a meal is unclear. We aimed at assessing the effects of ezetimibe on postprandial hyperlipidemia and hyperinsulinemia and to find out whether the medication improves endothelial function in obese metabolic syndrome (MetS) patients with coronary artery disease (CAD). We obtained oral fat loading test results (4 and 6 h after load) and brachial flow-mediated vasodilation (FMD) measurements before and 24 weeks after ezetimibe treatment initiation from 27 MetS patients with CAD and from 68 control patients with CAD alone. Serum triglyceride (TG) and insulin levels (2 h after the loading dose) were significantly higher in MetS patients than in control patients. The incremental areas under the curve (iAUCs) for these levels decreased significantly after ezetimibe treatment in MetS patients but not in control patients. Treatment with ezetimibe resulted in significant FMD changes in MetS patients (from 3.4 to 4.9%, P = 0.002), but not in control patients (from 5.1 to 5.4%, P = 0.216). When MetS patients were divided into two groups based on the median insulin iAUC reduction rate (higher group ≥ 34%, n = 14; lower group

Aim This study investigated whether the characteristic changes in hippocampal atrophy seen in coronal scans are useful for differentiating Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), and major depressive disorder (MDD). Methods Subjects included 58 patients with AD, 33 with aMCI, 20 with MDD, and 22 normal controls, all aged 60 years or older. For each subject, eight coronal short TI inversion recovery images perpendicular to the hippocampal longitudinal axis were obtained. Images were manually measured using the conventional region of interest method of quantitative analysis. Results The overall trend in the corrected volumes of the hippocampus was AD < aMCI < MDD < normal controls. We found atrophy in all slices in AD, atrophy centred on the hippocampal head in aMCI, and atrophy in the slice of the hippocampal body 12 mm from the amygdala in MDD. Conclusions The present study suggested that our method of comparing hippocampal atrophy by region may be useful in distinguishing AD, aMCI, MDD, and normal controls.

A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. 18F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor. Subsequently, the patient was treated with 2 more cycles of the chemotherapy. Eventually, thrombocytopenia completely resolved.

We report on two elderly patients with cognitive impairments, for whom chronic carbon monoxide (CO) exposure was suspected based on elevated carboxyhaemoglobin levels in their serum. On their initial visits, cognitive impairment and brain magnetic resonance imaging findings in both patients were compatible with the diagnosis of Alzheimer's-type dementia. However, after discontinuation of the use of a kotatsu, a charcoal-based heater, their serum carboxyhaemoglobin levels normalized and their physical symptoms resolved. Their cognitive function also slightly improved. The causal relationship between physical symptoms and cognitive impairment after chronic CO poisoning is uncertain; however, it is possible that chronic exposure to low CO levels exacerbated the clinical manifestation in our patients.

Both postprandial hyperlipidemia and hyperinsulinemia have been thought to play an important role in the development of atherosclerosis, and to be a potent risk factor for cardiovascular event. To examine effects of glycemic state on postprandial hyperlipidemia and hyperinsulinemia in patients with coronary artery disease (CAD), a total of 112 consecutive male pati ents with angiographically confirmed CAD were loaded with a high-fat and high-glucose test meal. CAD patients were divided into three groups as “non-diabetic”, “prediabetic”, and “diabetic” CAD groups. The serum triglyceride (TG) and remnant-like particle cholesterol (RLP-C) levels at the 6th hour in diabetic CAD group showed significantly higher than non-diabetic CAD group, and the incremental area under the curves (iAUCs) of these levels in diabetic CAD group were significantly greater than non-diabetic CAD group (TG, P = 0.0194; RLP-C, P = 0.0219). There were no significant differences in the iAUCs of TG or RLP-C between prediabetic and non-diabetic CAD group. The AUCs of plasma insulin levels or insulin resistance index (IRI): (AUCs of insulin) × (AUCs of glucose) as the insulin resistance marker were greater in diabetic CAD group than non-diabetic CAD group (insulin, P = 0.0373; IRI, P = 0.0228). The AUCs of serum TG or RLP-C levels showed a correlation with the AUCs of plasma insulin (AUC-TG, r = 0.5437, P

Patients with near tetraploidy/tetraploidy (NT/T)-acute myeloid leukemia (AML) are rare and generally show poor survival. A 62-year-old man was referred to our hospital with pancytopenia. A bone marrow examination revealed the proliferation of extremely large blasts, and led to the diagnosis of AML M0. A cytogenetic analysis showed an NT-karyotype of 91, XXYY, -5, add(18)(p21),del(20)(q12q13) ×2. Complete remission was achieved with single remission induction chemotherapy. Although consolidation chemotherapies were not available because of his critical condition, he remained in remission and survived for more than 40 months without cytopenia. However, repeated bone marrow examinations showed persistent clonal hematopoiesis with del(20)(q12q13) without apparent myelodysplasia.

A 65-year-old man with occlusion of the left superficial femoral artery (SFA) underwent the endovascular therapy (EVT). A successful EVT was performed with three paclitaxel-eluting peripheral stents (Zilver PTX®) implanted in the left SFA. Angiography 1 year later showed an exudation of contrast outside the stent struts, and intravascular ultrasound, and optical coherence tomography also showed incomplete stent apposition with remarkable positive vascular remodeling. Zilver PTX® stent is a polymer-free stent and it is unclear that the reason why the patient treated with Zilver PTX® stents in the SFA lesions caused the contrast stainings outside the stents. However, we need more careful long-term follow-up of this patient for late thrombosis.

This report describes a patient with autoimmune myelofibrosis accompanied by Sjögren's syndrome (SS). A 36-year-old woman was admitted due to petechiae, purpura, gingival bleeding, dyspnea on exertion, and a lack of concentration. She had pancytopenia and was diagnosed with SS. A bone marrow study showed hypercellular marrow with reticulin fibrosis. Lymphocytic infiltrates and aggregates composed of a mixture of T and B cells in the marrow were also observed. A chromosomal analysis of the marrow cells showed 47, XXX and an analysis of peripheral lymphocytes revealed 47, XXX/46, XX mosaic results. The patient's cytopenia resolved following treatment with oral prednisolone.

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM) with a poor prognosis. Nonsecretory myeloma is also a rare form of MM characterized by the absence of detectable M-protein in the serum and urine. This report describes two cases of nonsecretory PCL. The first patient was an 85-year-old man in whom the lack of monoclonal immunoglobulins made it difficult to make a diagnosis because the malignant cells showed an atypical morphology. He died of rapid disease progression before starting chemotherapy. The second patient was a 78-year-old woman whose tumor cells displayed a typical plasma cell morphology. She was successfully treated with bortezomib-containing chemotherapy.

A 67-year-old man with recent myocardial infarction underwent a total of five sirolimus-eluting stents (SES) implantation for three vessels stage by stage. A follow-up angiography showed no significant restenosis except one in the side branch. Thereafter, he had remained asymptomatic. Sixty-six months later, he had an acute myocardial infarction with cardiogenic shock due to simultaneous 3-vessel very late stent thrombosis (VLST). After successful percutaneous coronary intervention, final angiography revealed serious peri-stent contrast staining along with positive remodeling and grade V stent fracture. This rare case illustrates simultaneous 3-vessel VLST, associating with multiple SES-related problems, under continuation of aspirin and cilostazol.

Background On March 11, 2011, the Tohoku district was struck by the most powerful known earthquake to hit Japan. Although stress-induced heart diseases rise after strong psychosocial stress, little is known about the characteristics of heart failure (HF) caused by psychosocial stress related to earthquakes. Methods We examined patients admitted to our hospital for HF during a three-week period between March 11 and March 31, 2011 (Disaster group) and compared them to patients during the corresponding period of 2010 (Non-Disaster group). Results The number of patients was larger in the Disaster group (n = 30, 18 men, 12 women; mean age 77.3 ± 9.8 years) than in the Non-Disaster group (n = 16, 8 men, 8 women; mean age 77.3 ± 11.6 years). A total of 14 of 30 patients (46.7%) in the Disaster group did not have past history of admission for HF, compared to 2 patients (12.5%) in the Non-Disaster group (p = 0.02). The number of patients with hypertension was larger in the Disaster group than in the Non-Disaster group (53.3% vs. 37.5%, p = 0.04). The number of patients with atrial fibrillation was also larger in the Disaster group than in the Non-Disaster group (56.7% vs. 25.0%, p = 0.03). Left ventricular systolic ejection fraction (EF) did not differ between the Disaster and Non-Disaster groups (45.2 ± 17.8% vs. 45.6 ± 14.0%, p = 0.46), however, the proportion of patients whose EF was more than 45% were significantly higher in the Disaster group more than in the Non-Disaster group (56.7% vs. 43.8%, p = 0.04). The in-hospital mortality rate for patients in the Disaster group was higher than in the Non-Disaster group (20.0% vs. 6.3%, p = 0.04). Conclusion The incidence and in-hospital mortality rate of HF increased after the Great East Japan Earthquake, suggesting that psychosocial stress brought on by such a disaster could lead to the development of HF with preserved EF more than that with reduced EF.

Background: Limited information is available regarding the lymphatic vasculature during pneumonia. Objective: To characterize lymphatic vasculatures in autopsied cadavers with pneumonia. Methods: Paraffin-embedded lung tissues obtained from 20 autopsied cadavers with complicated pneumonia and 10 control cadavers without pneumonia were used for immunohistochemical analyses using primary antibodies against podoplanin, vascular endothelial growth factor receptor-3 (VEGFR-3), CD34, vascular endothelial growth factor (VEGF)-C, VEGF-D, CD73, and CD163. Results: There was no difference in the vascular density of podoplanin+ usual lymphatics between the individuals with and without pneumonia. In half of the cadavers with pneumonia, however, a network of podoplanin+ cells lying together in a side-by-side bead-like arrangement appeared along the alveolar septa; however, this was absent in the control cadavers. The podoplanin+ cells in the network were characterized by a weaker expression of podoplanin, rel...

We report two autopsy cases of primary pulmonary adenocarcinoma associated with unusual pleural spread. Both patients had confirmed history of asbestos exposure. In the first patient the tumor was localized in one pulmonary lobe with marked infiltration into pleura, chest wall and diaphragm. In the second patient the entire right lung was covered by irregularly thickened tumor. Both tumors were mainly located in the extrapulmonary area and the intrapulmonary portions represented only minor components. Histologically, tumor cells demonstrated glandular and papillary growth patterns associated with focal hobnail-like features. Immunohistochemical evaluation revealed diffuse and marked immunoreactivity of TTF-1, CEA, CD15 and MOC31 in both cases, while calretinin, CK5/6, vimentin, thrombomodulin and HBME-1 were broadly positive in one case. D2-40 was not detected in either case. Examination using electron microscopy revealed the presence of sparse and short microvilli in tumor cells. All of the above findings are consistent with adenocarcinoma of the lung. Primary adenocarcinoma with a characteristic pleural extention grossly resembling malignant mesothelioma has been previously reported in the literature as pseudomesotheliomatous adenocarcinoma. This is the first report of pseudomesotheliomatous adenocarcinoma displaying variable immunoprofile with a diagnosis using electron microscopical examination. Additionally, we performed quantitative analysis of asbestos bodies in pseudomesotheliomatous adenocarcinoma.

A 76-year-old woman with sarcoidosis who had an implantable pacemaker for complete atrioventricular block was admitted with syncope. Electrocardiogram revealed ventricular pacing failure, and a marked rise in the ventricular pacing threshold. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) indicated increased uptake of FDG in the ventricular septum. Three days after steroid therapy, the ventricular pacing threshold reverted to normal, and FDG-PET showed decreased FDG uptake in the ventricular septum. In this case report, we demonstrate that a sudden deterioration in the ventricular pacing threshold due to worsening cardiac sarcoidosis can be reversed with early steroid therapy.

Little is known regarding the relationship between insulin resistance and lipid dysmetabolism after consuming a meal. We aimed to assess the effect of ezetimibe on postprandial hyperlipidemia and hyperinsulinemia, and whether it improves endothelial function in obese metabolic syndrome (MetS)

The distribution of adult T-cell leukemia/lymphoma (ATLL) is typically systemic. In addition to peripheral blood (PB) and lymph nodes, extranodal sites such as the skin, lung, liver, gastrointestinal tract, and central nervous system are frequently involved. We report a unique case of ATLL in which the patient presented with prolonged fever. A 65-year-old man had high-grade fever lasting for 2 weeks. He showed no lymphadenopathy, hepatosplenomegaly, skin lesions, or PB involvement. Bone marrow examination showed widespread infiltration of ATLL cells. (18)F-fluorodeoxy glucose positron emission tomography (FDG-PET) revealed that the disease was confined to the bone marrow.

This report describes a patient with extramedullary relapse of acute myeloid leukemia (AML) without involving bone marrow. A 57-year-old man was diagnosed as having acute monoblastic leukemia with t(9;11)(p22;q23) and trisomy 8. Ten months after achieving complete response (CR) with chemotherapy, masses developed in his left forearm and in the back of his thigh, preceded by enigmatic peripheral neurological symptoms. Aspiration from the forearm showed leukemic relapse, and fluorescence in situ hybridization (FISH) revealed that the majority of the cells had 11q23 anomaly and tetrasomy 8. Bone marrow or meningeal relapse was not observed. To our knowledge, this is the first case report of clonal evolution associated with the development of myeloid sarcoma as a relapse in AML.

Summary An abnormal healing process is believed to be involved in lung tissue damage in pulmonary fibrosis. Lymphangiogenesis has been determined to play a role in structural remodeling in diffuse alveolar damage. However, the mechanism of lymphangiogenesis remains unclear. The aim of this study is to investigate the cellular mechanisms of lymphangiogenesis in diffuse alveolar damage, focusing on the roles of macrophages. Formalin-fixed and paraffin-embedded lung tissues from 13 autopsy cases with idiopathic diffuse alveolar damage were used. Antibodies specific for D2-40 and CD68 were mainly used as the markers for lymphatics and macrophages, respectively, and immunohistochemical examinations and morphometric analyses were performed. Immunohistochemistry showed the aggregation of numerous CD68 + macrophages around newly formed lymphatics in the intraalveolar fibrotic lesions in the proliferative stage, and some of the CD68 + macrophages were colocalized with the lymphatic endothelium. These macrophages were characterized by the expression of vascular endothelial growth factor-C. Among the 3 stages of diffuse alveolar damage, the number of Ki-67 + cells on the lymphatic endothelium tended to increase in newly formed lymphatics of the proliferative stage. In addition, the number of CD68 + macrophages on the lymphatic endothelium was significantly increased in the newly formed lymphatics of the proliferative stage more than those of the fibrotic stage. The CD68 + macrophages around the newly formed lymphatics coexpressed CCR7. Dual immunostaining showed the coexpression of CCL19—a ligand for CCR7—on the lymphatic endothelium. Thus, macrophages may participate in lymphangiogenesis in diffuse alveolar damage, which is facilitated by CCL19 and CCR7.

There is limited information regarding the process of tissue remodeling in fibroblastic foci associated with idiopathic pulmonary fibrosis. The aim of this study was to identify the different pathologic stages of tissue remodeling in fibroblastic foci based on the histopathologic differences in the glycosaminoglycan distribution and collagen deposition. In addition, we also aimed at clarifying the stage-specific characteristics by taking into consideration the expression pattern of matrix metalloproteinase and angiogenesis. Lung biopsies of 16 patients with idiopathic pulmonary fibrosis were used. The presence of glycosaminoglycans was detected by Alcian blue staining, and type I collagen was detected by immunohistochemical analysis with a primary antibody specific to the cross-linked carboxyterminal telopeptide of type I collagen. The fibroblastic foci characterized by the expression intensity of Alcian blue and telopeptide of type I collagen were divided into 3 groups, namely, Alcian blue(+)telopeptide of type I collagen(weak), Alcian blue(+)telopeptide of type I collagen(+), and Alcian blue(weak)telopeptide of type I collagen(+); consequently, 3 new stages were defined--stages I, II, and III, respectively. A significant inverse correlation was observed between the area densities of Alcian blue(+) and telopeptide of type I collagen(+) in fibroblastic foci. Stage I was characterized by the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloprotease-2 in fibroblasts and the overlying epithelium of fibroblastic foci, and also the absence of capillary angiogenesis. In contrast, the expression of these proteins was attenuated in stage III, except for that of matrix metalloproteinase-2 in fibroblasts. In stages II and III, capillary angiogenesis was observed. Lymphangiogenesis was undetected in all the 3 stages. Thus, pathologic staging helps understand the roles of the factors involved in tissue remodeling in idiopathic pulmonary fibrosis.

To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients.

Background: Sequential changes in the hemodynamic effect of chronic epoprostenol therapy raise the following questions. Does an increase in cardiac output (CO) precede lowering of the pulmonary artery pressure (PAP) over the time course of improvement? What are the characteristics of good responders to chronic epoprostenol treatment? Methods and Results: Hemodynamics were evaluated by catheter examination. Most patients still alive after >1 year showed an increase in CO either with no change in mean PAP or accompanied by a decrease in mean PAP during increased dosing of epoprostenol. Immediately before cessation of the increase in epoprostenol dose in good responders, the ratio of total pulmonary resistance to total systemic resistance was low, and the pulmonary artery wedge pressure minus right atrial pressure was high compared with the newest data in poor responders. One year after fixing at the best dose of epoprostenol, the mean PAP further decreased. Conclusions: In good responders, pulmonary selectivity to epoprostenol is high, and the blood returning to the left-sided heart through the pulmonary circulation increases. Hemodynamics further improve, even after fixing at the best dose of epoprostenol. The present data did not show that an increase in CO precedes lowering of the PAP over the course of improvement. (Circ J 2009; 73: 523 - 529)

For future cell-based therapies for liver diseases, the shortage of cell sources must be resolved. Immortalized human hepatocytes are expected to be among the new sources. In addition to telomerase activation by the introduction of human telomerase reverse transcriptase (hTERT), inactivation of the p16/RB pathway and/or p53 by E6/E7 of human papillomavirus type 16 (HPV16) has been shown to be useful for efficient immortalization of several human cell types. Here we report the immortalization of human hepatocytes by the introduction of HPV16 E6/E7 and hTERT. Human adult hepatocytes were lentivirally transduced with HPV16 E6/E7 and hTERT. Two human immortalized hepatocyte cell lines were established and were named HHE6E7T-1 and HHE6E7T-2. Those cells proliferated in culture beyond 200 population doublings (PDs). Albumin synthesis and expression of liver-enriched genes were confirmed, but gradually decreased as passages progressed. Karyotype analysis showed that HHE6E7T-1 cells remained near diploid but that HHE6E7T-2 cells showed severe aneuploidy at 150 PDs. Subcutaneous injection of these cells into severe combined immunodeficiency (SCID) mice did not induce tumor development. Intrasplenic transplantation of dedifferentiated HHE6E7T-1 cells over 200 PDs significantly improved the survival of acetaminophen-induced acute liver failure SCID mice. In conclusion, we successfully established immortalized human hepatocytes that retain the characteristics of differentiated hepatocytes. We also showed the reduction of hepatocyte-specific functions in long-term culture. However, the results of intrasplenic transplantation to SCID mice with acetaminophen-induced acute liver failure showed the possibility of HHE6E7T-1 serving as a cell source for hepatocyte transplantation.

Article, CIRCULATION JOURNAL. 71(11): 1765-1770 (2007)

Background Septic and amniotic fluid emboli are rare sources of pulmonary embolism (PE), so the present study sought to elucidate the background of these cases. Methods and Results A total of 11,367 PE cases were identified from 396,982 postmortem examinations. The incidence of septic PE was 247 (2.2%) of the total. The origin of infection was found in 85.6% of the cases. Fungal embolus was detected more often than bacterial embolus. The most frequently detected fungus was aspergillus (20.8%). The primary disease associated with fungal embolus was leukemia (43.2%). The incidence of PE cases associated with pregnancy and/or delivery was 89 (0.8%) of the total PE cases. Among them, amniotic fluid embolism was found in 33 (73.3%) of 45 PE cases with vaginal delivery, and in 7 (21.2%) of 33 PE cases with cesarean delivery (p

A mass was identified in the atrial septum by clinical imaging in a patient who had multiple large lipomas of the skin. Multislice computed tomography and magnetic resonance imaging indicated that the interatrial mass was a fatty infiltration. In order to discriminate the myocardial lesion from myxoma and other benign conditions and malignant tumors, percutaneous transvenous biopsy was performed. Microscopic examination demonstrated the cardiac mass to be lipomatous hypertrophy of the interatrial septum (LHIS), and the skin lesions, simple lipomas. The LHIS is itself a rare condition, and its development in patients having multiple ponderous lipomas, or lipomatosis, could not be found in a previous report. This may be the first published case of LHIS, which likely represents cardiac involvement of lipomatosis.

Epstein-Barr virus (EBV) associated lymphoproliferative disorder (LPD) after immunosuppressive therapy for aplastic anemia (AA) is extremely rare in a nontransplant setting and has not been well described. This report describes a severe AA patient in whom fatal EBV-LPD developed after being treated with rabbit antithymocyte globulins (ATG) and cyclosporine A (CsA). An 81-year-old man was diagnosed as having severe AA. He was started on CsA followed by administration of ATG for five consecutive days. One month after the start of ATG, persistent fever which was not responsive to antibiotics or antifungal agents developed and atypical lymphocytes emerged in peripheral blood. Repeated blood cultures were negative. An extremely high level of EBV virus in his peripheral blood plasma was detected by means of a quantitative real-time PCR assay. Even after the cessation of CsA, the fever persisted and the peripheral atypical lymphocytes proliferated rapidly. The patient suffered from respiratory failure, liver dysfunction, and metabolic acidosis. Rituximab was administered without success and he died.

Dementia, gait disturbance and urinary incontinence were noted in two elderly patients, and diagnosed as idiopathic normal pressure hydrocephalus (iNPH). Case 1 was a 79-year-old man in whom dementia symptoms appeared 2 years ago. Gait disturbance and urge incontinence of urine developed later, and the patient visited our hospital. Walking was wide-based and frozen gait was noted at the time of visiting our hospital. The mini-mental state examination (MMSE) score was 11. A head MRI detected expansion of the cerebral ventricles and sylvian fissures, and narrowing of the cerebral fissures and the subarachnoid space in the higher convexity region. The diagnosis of iNPH was made based on the clinical symptoms and imaging findings, and a shunt operation (cerebrospinal fluid shunt) was performed in the neurosurgery department. Gait disturbance and cognitive function slightly improved after the operation. Case 2 was an 81-year-old woman who had had brachybasia for 1 year, and swayed from side to side while walking. Since disorientation and urge incontinence transiently occurred, the patient visited our hospital. The MMSE score was 24. Head MRI findings were similar to those in case 1. The cerebrospinal tap test was performed, and walking improved in the 1-week course observation. iNPH is not very well recognized, compared to secondary NPH, and is likely to be overlooked because differentiation from Alzheimer's disease and vascular dementia based on symptoms and imaging is difficult in elderly patients. As iNPH is treatable by accurate diagnosis and therapy, the accumulation of cases indicated for shunt operation may be necessary.

Background The specific incidence of thrombotic pulmonary embolism (PE), tumor PE and tumor invasion into large veins according to tumor type and tumor site remains unclear. Methods and Results A total of 65,181 cancer patients were identified from 98,736 postmortem examinations. Thrombotic PE occurred in 2.32% of all cancer patients and comprised 88.6% of the total number of all PE events. The incidence of thrombotic PE was high in those with adenocarcinoma, leukemia and large cell carcinoma, and was low in those with hepatic cell carcinoma. The incidence of PE was high when tumor was present in hematogenous tissue, lungs, ovaries, pancreas and the biliary system, and was low when tumor was present in the liver. The incidence of tumor PE was high with large cell carcinoma, hepatic cell carcinoma and adenocarcinoma, and was also high when tumor was present in the lungs, ovaries, kidneys and liver. There was a significant correlation between the incidence of tumor PE and the incidence of tumor invasion into large veins. Conclusion The incidence of thrombotic PE, tumor PE and tumor invasion into large veins varies significantly according to tumor histopathology and tumor site. (Circ J 2006; 70: 744 - 749)

A 75-year-old male was diagnosed as prostate cancer (serum PSA: 4,772 ng/ml, Gleason score: 4 + 4 = 8) with multiple bone metastases. And he noticed a painless mass of the frontal neck a month before the diagnosis. Computed tomography of the neck showed a tumor in the thyroid cartilage. Biopsy of the neck tumor revealed metastasis of prostate cancer by positive PSA staining. Metastasis of malignant tumor to cartilaginous tissue is extremely rare because there are usually no vessels in it. Only 4 cases of the metastasis of prostate cancer to the thyroid cartilage have been reported. It was thought that tiny bone marrows were formed in the ossified cartilage and it caused hematogenous metastasis.

A 45-year-old woman was admitted to our hospital because of high fever and malaise. She also presented abnormal urine findings including macrohematuria and proteinuria with transient renal insufficiency. Salmonella Typhi was isolated from her blood and stool culture, and then she was diagnosed as having typhoid fever. Salmonella enterica serotype typhi infection can be complicated by renal involvement, although rare. In Japan, few cases have been reported about acute nephritic syndrome in typhoid fever. Here, we report a case of endemic acquired typhoid fever associated with acute renal failure probably due to acute nephritic syndrome successfully treated with levofloxacin.

Idiopathic abnormal bodily sensations, or cenesthesic symptoms, are exhibited in a wide variety of mental illnesses. In Japan, patients with abnormal bodily sensations are often diagnosed with cenesthopathy. This study reviewed recent case reports of cenesthopathy. Of the 100 identified cases, young patients were more commonly men with predominant bodily cenesthesic symptoms, while older patients (≥40 years) were more commonly women with cenesthesic symptoms restricted to the oral cavity (oral cenesthopathy).

Objective The incidence of pulmonary thromboembolism (PTE) is much lower in Japan than in the United States. The number of deaths from PTE, however, has gradually increased. The present study was designed to investigate the incidence and characteristics of PTE in Japan. Methods and Materials We sent 5, 582 questionnaires to inquire about the number of new cases of PTE between August 1, 2000 and September 30, 2000. Results We received 1, 702 replies and 205 new cases were registered. The number of new cases per year was 4, 022 (95% confidence interval: 3, 704-4, 305) and the incidence was 32 (95% confidence interval: 29.2-33.9) patients per 1, 000, 000 people per year. Main risk factors were immobilization, surgery, trauma, and malignancy. The mortality within a month and 6 months was 16% and 20%, respectively. Half of the deaths within a month occurred on the diagnosis day. Conclusion The results showed that the incidence of PTE in Japan 2000 tended to increase compared with that in 1996, but it was still much lower than that in the United States.(Internal Medicine 42: 1090-1094, 2003)

The right ventricular ejection fraction (RVEF) can be shown theoretically as a mathematical function of the percent shortening in the 3 axial dimensions of the right ventricular cavity (the septum-free wall dimension (SF), the anterior-posterior dimension (AP), and the tricuspid valve-apex dimension (TA) or the long axis dimension (LA)). There is a need to decide which mechanism is the most important for the RVEF in cases with neither obvious regional wall motion abnormalities of the left ventricle nor right ventricular overload. Forty-four consecutive subjects (34 males/10 females) were enrolled: 16 had normal hemodynamic parameters without significant coronary artery stenosis, 15 had hypertrophic cardiomyopathy and 13 had dilated cardiomyopathy. Biplane right ventricular cineangiography was performed and the percent shortening of the SF, AP, and TA or LA were measured. The percent shortening in the SF (34.8+/-14.7%) was larger than that of the AP, TA, and LA (23.2+/-8.5, 21.0+/-8.3 and 18.3+/-7.0, respectively; all p

溶血性貧血,アレルギー性皮膚炎,高γグロブリン血症など多彩な免疫反応を伴ったIBL-like T cell lymphomaを経験した.症例は63歳男性.発熱,全身リンパ節腫脹,全身性皮疹が著明となり入院. Hb 10.1g/dl, reticulocyte 42‰, haptoglobin

CD66a is a member of the carcinoembryonic antigen family and has been suggested to function as an intercellular adhesion molecule and cell growth regulator. Expression of CD66a in myeloma cells was examined with mAb TS135 against CD66a transfectants of murine‐transformed fibroblasts. The reactivity of mAb TS135 with CD66a, CD66c, and CD66e was revealed. CD66a in myeloma cells was considered to be detectable with this mAb, since CD66c and CD66e are not expressed in them. CD66a was detected in three myeloma cell lines and an IgM‐producing B‐cell line. In clinical bone marrow specimens, including 18 multiple myeloma, two primary macroglobulinemia, and a case of CLL‐like chronic lymphoproliferation with monoclonal IgG production, CD66a and three conventional myeloma cell markers (PCA‐1, CD38, and CD56) were examined by indirect immunofluorescence assay. The results showed that 18 out of 21 cases (86%) were CD66a(+), and PCA‐1 showed the highest correlation with CD66a among conventional markers. Primary macroglobulinemia and chronic lymphoproliferation were also CD66a(+). Two‐dimensional flow cytometry with mAbs TS135 and CD38 confirmed the reactivity of TS135 with myeloma cells in those bone marrow specimens. The findings suggest that CD66a is expressed in multiple myeloma with high frequency. J. Clin. Lab. Anal. 16:79–85, 2002. © 2002 Wiley‐Liss, Inc.

MUC1 mucin serves as a tumor-associated antigen in various carcinomas. We have reported the expression of MUC1 in multiple myeloma (MM) cells and the establishment of an HLA-unrestricted cytotoxic T lymphocyte (CTL) that recognized MUC1 from peripheral lymphocytes in a patient with MM. In this study, we successfully induced MUC1-specific CTLs from bone marrow cells in two MM patients. Both CTLs lysed MUC1-positive cell lines with different kinds of HLA, and the cytotoxicity was inhibited by anti-CD3, anti-αβ T cell receptor and anti-MUC1 monoclonal antibodies. The treatment with O-glycosylation inhibitor augmented the cytotoxicity of the CTLs. These data showed that HLA-unrestricted CTLs that recognize the underglycosylated form of MUC1 could be induced from MM patients. MUC1 is also an important factor in cancer metastasis. We previously reported that MUC1 mucin has anti-adhesion effects that contribute to the separation of tumor cells from the primary site. We next investigated the involvement of MUC1 in tumor invasion that is a second step of metastasis. MUC1-transfectants transplanted subcutaneously into nude mice invaded the muscular layer. The treatment with O-glycosylation inhibitor abolished these effects of MUC1. Our data indicated that MUC1 mucin increases the invasive ability of tumor cells, while O-glycan plays an essential role.

We describe a 47-year-old woman with severe aplastic anemia with genital bleeding who developed acute severe hepatitis after the administration of danazol while she was receiving cyclosporin. She had been diagnosed with severe aplastic anemia 1 year previously and, while hospitalized, had received methyl prednisolone pulse therapy, which was not successful. She was then referred to our hospital. She was treated with antithymocyte globulin, cyclosporin, granulocyte colony-stimulating factor, and methyl prednisolone; a good response was achieved after 3 months of this therapy. Subsequently, oral administration of cyclosporin was continued, but she was readmitted to our hospital when pancytopenia gradually developed and the genital bleeding recurred. Danazol was administered for pancytopenia and endometriosis. Four days after the first administration of danazol, epigastric pain occurred, and the danazol was stopped. Eighteen days after the first danazol administration, very severe hepatic injury occurred abruptly. The patient died of hepatic failure. Postmortem examination revealed centrilobular massive necrosis of the liver. Danazol was implicated as the agent responsible for causing the hepatic failure. Drug interactions between danazol and cyclosporin may cause adverse effects.

Since malignant melanoma is a rare malignancy in Japan, little is known about the cytogenetic abnormalities in Japanese patients. We report a case of malignant melanoma showing complex chromosomal abnormalities. A 70-year-old woman was admitted to our hospital because of anorexia, delirium, and right hemiplegia. Cranial CT disclosed several metastatic brain tumors. Multiple subcutaneous and intra-abdominal metastases were also found. A diagnosis of metastatic malignant melanoma was made by biopsy of a subcutaneous tumor. Chromosomal analysis of the tumor cells disclosed complex karyotypic abnormalities including novel unbalanced whole arm translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10).

Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion of unknown etiology and is often accompanied by fever. Unexplained persistent fever unresponsive to antibiotics developed in a 70-year-old man suffering from intractable recurrent gouty arthritis. 67Ga-scintigraphy disclosed intense focal uptake in the upper abdomen. The lesion in the left lobe of the liver was an ill-defined hypodensity mass on computed tomographic scan and was enhanced on dynamic magnetic resonance imaging. The tumor was surgically removed and a diagnosis of IPT was made. Fever and arthritis resolved completely after surgery. Possible interaction between IPT of the liver and gouty arthritis was suggested.

The increased susceptibility to infection following splenectomy has been well documented. We report here, a case of brain abscess developed five years after splenectomy in a patient with idiopathic thrombocytopenic purpura (ITP). A 65-year-old woman was admitted to our hospital because of fever, mental disorientation, and weakness in August, 1999. She had been followed with diagnoses of essential hypertension and type 2 diabetes mellitus (DM) since 1988. The patient was diagnosed as having ITP in 1992, and then underwent splenectomy in 1994. Monoclonal gammopathy of undetermined significance (MGUS) of IgG, lambda type was found in February 1999. Though high grade fever persisted after admission, blood cultures were negative. Antibiotics were given without a satisfactory effect. Right hemiparesis and worsening of consciousness developed subsequently. Contrast enhanced cranial computed tomography (CT) disclosed a ringed enhanced low density mass in the left parieto-occipital lobe compatible with a diagnosis of brain abscess. Surgical drainage was performed and 20 ml of pus was obtained. No primary infectious focus of the brain abscess was detected with intensive examinations.

Ulcerative colitis (UC) is an inflammatory bowel disease of undetermined etiology. Mucins, mainly produced by goblet cells, protect colon cells from various kinds of stress. Alteration in the quality or quantity of mucins may be the cause of the disease. Another possible cause is immune reactions to colonic cells. Anti-MUC1 antibodies were detected in the sera of patients with UC. Antibodies would destroy the colonic cells through antibody-dependent cell-mediated cytotoxicity. We reviewed the significance of mucins as well as humoral and cellular immunity in the pathogenesis of UC.

There are patients with congenital heart disease and fatal pulmonary hypertension in whom the medial hypertrophy of the small pulmonary arteries is quite beyond the extent of ordinary cases of hypertension, a condition described as pulmonary hypertension with extremely thickened media of small pulmonary arteries (PH/ETM). Lungs from 6 infants, all younger than 2 years of age, who had congenital heart disease and fatal pulmonary hypertension, were analyzed by accurately measuring the media using Suwa's method. In PH/ETM, the media of the small pulmonary arteries was shown to be not only unusually thick, but extending toward the periphery, whereas the intimal changes were unexpectedly mild. In the PH/ETM group, the % wall thickness at a diameter of 50 microm (%Tw(50)), determined from regression analysis, was 23.2+/-1.3%, which was significantly higher than in either the control (10.3+/-1.2%) or ventricular septal defect group (18.9+/-1.6%). In persistent pulmonary hypertension of the newborn (PPHN), it was 22.3+/-1.8%, not significantly different from PH/ETM. The striking medial hypertrophy in PH/ETM and PPHN was apparently confined to small pulmonary arteries and in both conditions is likely to be the result of maldevelopment of these arteries. Surgical intervention may trigger a critical elevation of the pulmonary arterial resistance.

Objective. We have established immortalized human hepatocytes by transduction of HPV16 E6/E7 and hTERT (HHE6E7T-1). The cells retained the characteristics of differentiated hepatocytes, but the functional characteristics such as albumin secretion, ureogenesis, and glyconeogenesis decreased gradually as the passages progressed beyond 200 population doublings (PDs). In this report, we transplanted minimally differentiated HHE6E7T-1 cells into the spleens of acute liver failure severe combined immunodeficiency (SCID) mice to examine the potential of the cells to redifferentiate in vivo. Materials and Methods. Acute liver failure was induced in SCID mice by intraperitoneal injection of 400 mg/kg acetaminophen. Two hours later, HHE6E7T-1 cells at 200 PDs were transplanted: group 1 (n = 10) 50 μL phosphate-buffered saline (PBS); group 2 (n = 9), lysate of 1 X 10 6 HHE6E7T-1 cells at 200 PDs resuspended in 50 μL PBS; and group 3 (n = 8), 1 X 10 6 HHE6E7T-1 cells. Survival rates at 7 days after transplantation were compared. Blood glucose levels, plasma ammonia levels, and spleen histology were examined at 24 hours after transplantation. Results. Survivals in each group were: 30% for group 1, 33% for group 2, and 100% for group 3. The survival of group 3 was significantly higher than groups 1 or 2 (P