Changes in magnetic resonance imaging relaxation time on postmortem magnetic resonance imaging of formalin-fixed human normal heart tissue.

BACKGROUND: Postmortem magnetic resonance imaging (MRI) has been used to investigate the cause of death, but due to time constraints, it is not widely applied to the heart. Therefore, MRI analysis of the heart after formalin fixation was previously performed. However, the changes in MRI signal values based on the fixation time of formalin were not investigated. The objective was to investigate changes over time in the T1- and T2-values of MRI signals in normal areas of hearts removed during autopsy, hearts subsequently fixed in formalin, and heart specimens sliced for the preparation of pathological specimens. METHODS: The study subjects were 21 autopsy cases in our hospital between May 26, 2019 and February 16, 2020 whose hearts were removed and scanned by MRI. The male:female ratio was 14:7, and their ages at death ranged from 9 to 92 years (mean age 65.0 ± 19.7 years). Postmortem (PM)-MRI was conducted with a 0.3-Tesla (0.3-T) scanner containing a permanent magnet. A 4-channel QD head coil was used as the receiver coil. Scans were performed immediately after removal, post-formalin fixation, and after slicing; 7 cases were scanned at all three time points. RESULTS: The T1- and T2-values were calculated from the MRI signals of each sample organ at each scanning stage. Specimens were sliced from removed organs after formalin fixation, and the changes in T1- and T2-values over time were graphed to obtain an approximate curve. The median T1-values at each measurement time point tended to decrease from immediately after removal. The T2-values showed the same tendency to decrease, but this tendency was more pronounced for the T1-values. CONCLUSION: MRI signal changes in images of heart specimens were investigated. Formalin fixation shortened both T1- and T2-values over time, and approximation formulae were derived to show these decreases over time. The shortening of T1- and T2-values can be understood as commensurate with the reduction in the water content (water molecules) of the formalin-fixed heart.

Pathological analysis of cadavers for educational dissection by using postmortem imaging.

This study was performed primarily to clarify whether pathological analysis of cadavers for anatomical dissection is possible using postmortem imaging (PMI), and whether this is worthwhile. A total of 33 cadavers that underwent systematic anatomical dissection at our medical school also underwent PMI. Fixative solution was injected into the corpus 3-4 days after death. PMI was then performed using an 8-slice multi-detector CT scanner 3 months before dissection. Before dissection, a conference was held to discuss the findings of the PMI. First, two radiologists read the postmortem images without any medical information and deduced the immediate cause of death. Then, the anatomy instructor revealed the medical information available. Based on this information, the radiologist, anatomy instructor, and pathologists suggested candidate sampling sites for pathological examination. On the last day of the dissection period, the pathologists resected the sample tissues and processed them for pathological examination. In 12 of 33 cases, the presumed causes of death could be determined based on PMI alone, and revision of the cause of death described in the death certificate was considered in five (15.2%) cases, based on PMI and pathological analysis. This article presents a novel method of pathological analysis of cadavers for anatomical dissection using PMI without disturbing the anatomy education of medical students.

Newly recognized cerebral infarctions on postmortem imaging: a report of three cases with systemic infectious disease.

BACKGROUND: Postmortem imaging (PMI) refers to the imaging of cadavers by computed tomography (CT) and/or magnetic resonance imaging (MRI). Three cases of cerebral infarctions that were not found during life but were newly recognized on PMI and were associated with severe systemic infections are presented. CASE PRESENTATIONS: An 81-year-old woman with a pacemaker and slightly impaired liver function presented with fever. Imaging suggested interstitial pneumonia and an iliopsoas abscess, and blood tests showed liver dysfunction and disseminated intravascular coagulation (DIC). Despite three-agent combined therapy for tuberculosis, she died 32 days after hospitalization. PMI showed multiple fresh cerebral and cerebellar infarctions and diffuse ground-glass shadows in bilateral lungs. On autopsy, the diagnosis of miliary tuberculosis was made, and non-bacterial thrombotic endocarditis that involved the aortic valve may have caused the cerebral infarctions. A 74-year-old man on steroid therapy for systemic lupus erythematosus presented with severe anemia, melena with no obvious source, and DIC. Imaging suggested intestinal perforation. The patient was treated with antibiotics and drainage of ascites. However, he developed adult respiratory distress syndrome, worsening DIC, and renal dysfunction and died 2 months after admission. PMI showed infiltrative lung shadow, ascites, an abdominal aortic aneurysm, a wide infarction in the right parietal lobe, and multiple new cerebral infarctions. Autopsy examination showed purulent ascites, diffuse peritonitis, invasive bronchopulmonary aspergillosis, and non-bacterial thrombotic endocarditis that likely caused the cerebral infarctions. A 65-year-old man with an old pontine infarction presented with a fever and neutropenia. Despite appropriate treatment, his fever persisted. CT showed bilateral upper lobe pneumonia, pain appeared in both femoral regions, and intramuscular abscesses of both shoulders developed. His pneumonia worsened, his level of consciousness decreased, right hemiplegia developed, and he died. PMI showed a newly diagnosed cerebral infarction in the left parietal lobe. The autopsy revealed bilateral bronchopneumonia, right-sided pleuritis with effusion, an intramuscular abscess in the right thigh, and fresh multiple organ infarctions. Systemic fibrin thrombosis and DIC were also found. Postmortem cultures showed E. coli and Burkholderia cepacia. CONCLUSION: Cerebral infarction that is newly recognized on PMI might suggest the presence of severe systemic infection.

Feasibility of liver weight estimation by postmortem computed tomography images: an autopsy study.

Although organ weight gives pathologists information about the pathogenesis of diseases at autopsy, the knowledge is rarely helpful in postmortem virtual autopsy by computed tomography (CT). To investigate the feasibility of liver weight estimation based on liver volume estimated from three-dimensional CT images and the specific gravity of liver, thirty cadavers who died in the University of Fukui Hospital and whose family members agreed to postmortem CT and autopsy were prospectively enrolled. Mean specific gravity of liver was 1.054 ± 0.009 g/mL (95% confidence interval: 1.0507-1.0573 g/mL). The specific gravity was positively correlated to Hounsfield unit (HU) values of less than 40 (cases with moderate to severe fatty deposition) and remained stable between 1.05 to 1.065 g/mL for HU values greater than 40 (cases with mild or no fatty change). The liver weight estimated by our formula corresponded well to the actual liver weight, and the correlation coefficient was 0.96 (P < 1 × 10(-13) ). The estimated liver weight calculated from estimated liver volume and the specific gravity of 1.055 g/mL was highly accurate, whereas the specific gravity should be reduced by 2%-3% in patients with an HU value less than 40 due to fatty deposition.

Should prophylactic thrombolysis be routine in clinical practice? Evidence from an autopsy case of septicemia.

BACKGROUND: Central venous catheters provide easy access for intravenous infusion and nutrition, but they can bring about complications such as catheter-related infections. Infected central venous catheters often cause nosocomial bloodstream infections with high morbidity and mortality. However, most of the morphological data that have been published are derived from in vitro and in vivo studies and few reports of direct evidence obtained from patient-derived samples have been described. Here we present visual evidence of catheter-related candidemia. To our knowledge, this is the first reported conventional histopathological evidence of a Candida-infected intraluminal thrombus in a patient's central venous catheter. CASE PRESENTATION: A 62-year-old Japanese female with obstructive jaundice, gastrointestinal bleeding, and liver metastasis from pancreatic head cancer was given an implantable subcutaneous central venous port for nutrition and chemotherapy administration. High fever ensued on day 16 after the central venous port insertion and blood cultures revealed Candida albicans. Although the patient was given 300 mg/day of fosfluconazole according to the suggestion of the infection control team, she died from respiratory failure. Postmortem computed tomography revealed findings consistent with acute respiratory distress syndrome, suggesting that the patient's course was complicated by catheter-related sepsis. Autopsy revealed a subcutaneous abscess around the port, from which C. albicans was cultured. However, no catheter-adherent thrombus, thrombosis of the great central veins, or endocardial vegetations were detected in the patient. Histological analysis revealed scattered abscesses in several organs including lungs and kidneys. Hyaline membrane formation and Candida colonies were found in the lungs. The central venous port tube, together with the part of the subclavian vein into which it had been inserted, was involved in an intraluminal fibrin thrombus containing neutrophils and macrophages, indicating that the thrombus existed while the patient was alive. Histopathological examination following use of the periodic acid-Schiff reagent and the Grocott stain revealed scattered Candida in the thrombus. CONCLUSIONS: Prophylactic thrombolysis should be encouraged to prevent central venous catheter-related candidiasis in clinical practice.

[Sudden blast crisis of chronic myeloid leukemia after a 13-year durable remission following allogeneic bone marrow transplantation and donor lymphocyte infusion].

We describe a rare case of sudden blast crisis of chronic myeloid leukemia that occurred after a 13-year durable remission, following allogeneic bone marrow transplantation and donor lymphocyte infusion. A 55-year-old Japanese man was diagnosed with chronic-phase chronic myeloid leukemia 24 years previously. He underwent allogeneic bone marrow transplantation 2 years after diagnosis. Although the disease recurred 6 years after transplantation, the patient achieved remission again by a donor lymphocyte infusion. Despite a 13-year durable remission, the disease later relapsed into a sudden blast crisis. Prednisolone and vincristine combined with imatinib mesylate effectively achieved a major molecular response. However, the disease relapsed repeatedly with central nervous system infiltration. Dasatinib and intrathecal methotrexate, cytarabine, and dexamethasone administration via the Ommaya reservoir controlled disease progression. Nevertheless, the disease became refractory to treatment with the emergence of a T315I Bcr-Abl gene mutation. The patient eventually died 43 months post crisis.

Domain transformation using semi-supervised CycleGAN for improving performance of classifying thyroid tissue images.

PURPOSE: A large number of research has been conducted on the classification of medical images using deep learning. The thyroid tissue images can be also classified by cancer types. Deep learning requires a large amount of data, but every medical institution cannot collect sufficient number of data for deep learning. In that case, we can consider a case where a classifier trained at a certain medical institution that has a sufficient number of data is reused at other institutions. However, when using data from multiple institutions, it is necessary to unify the feature distribution because the feature of the data differs due to differences in data acquisition conditions. METHODS: To unify the feature distribution, the data from Institution T are transformed to have the closer distribution to that from Institution S by applying a domain transformation using semi-supervised CycleGAN. The proposed method enhances CycleGAN considering the feature distribution of classes for making appropriate domain transformation for classification. In addition, to address the problem of imbalanced data with different numbers of data for each cancer type, several methods dealing with imbalanced data are applied to semi-supervised CycleGAN. RESULTS: The experimental results showed that the classification performance was enhanced when the dataset from Institution S was used as training data and the testing dataset from Institution T was classified after applying domain transformation. In addition, focal loss contributed to improving the mean F1 score the best as a method that addresses the class imbalance. CONCLUSION: The proposed method achieved the domain transformation of thyroid tissue images between two domains, where it retained the important features related to the classes across domains and showed the best F1 score with significant differences compared with other methods. In addition, the proposed method was further enhanced by addressing the class imbalance of the dataset.

Low-frequency maternal novel MYH7 mosaicism mutation in recurrent fetal-onset severe left ventricular noncompaction: a case report.

Background: Left ventricular noncompaction (LVNC) is a rare inherited cardiomyopathy with a broad phenotypic spectrum. The genotype-phenotype correlations in fetal-onset LVNC have not yet been fully elucidated. In this report, we present the first case of severe fetal-onset LVNC caused by maternal low-frequency somatic mosaicism of the novel myosin heavy chain 7 (MYH7) mutation. Case presentation: A 35-year-old pregnant Japanese woman, gravida 4, para 2, with no significant medical or family history of genetic disorders, presented to our hospital. In her previous pregnancy at 33 years of age, she delivered a male neonate at 30 weeks of gestation with cardiogenic hydrops fetalis. Fetal echocardiography confirmed LVNC prenatally. The neonate died shortly after birth. In the current pregnancy, she again delivered a male neonate with cardiogenic hydrops fetalis caused by LVNC at 32 weeks of gestation. The neonate died shortly after birth. Genetic screening of cardiac disorder-related genes by next-generation sequencing (NGS) was performed which revealed a novel heterozygous missense MYH7 variant, NM_000257.3: c.2729A > T, p.Lys910Ile. After targeted and deep sequencing by NGS, the same MYH7 variant (NM_000257.3: c.2729A > T, p.Lys910Ile) was detected in 6% of the variant allele fraction in the maternal sequence but not in the paternal sequence. The MYH7 variant was not detected by conventional direct sequencing (Sanger sequencing) in either parent. Conclusions: This case demonstrates that maternal low-frequency somatic mosaicism of an MYH7 mutation can cause fetal-onset severe LVNC in the offspring. To differentiate hereditary MYH7 mutations from de novo MYH7 mutations, parental targeted and deep sequencing by NGS should be considered in addition to Sanger sequencing.

Exploration of sepsis assisting parameters in hospital autopsied-patients: a prospective study.

Although Sepsis-3 doesn't require evidence of bacteremia to diagnose sepsis, clinicians often want to identify the causative pathogen at autopsy. In principle, if the blood cultures are the same at ante- and postmortem, the cause of death is obvious. However, interpretations of postmortem blood cultures are often difficult due to discordance, negativity, mixed infection, and contamination, of pathogens occupying ≥ 50% of the tests. To increase specificity identifying agonal phase sepsis in the situations where blood cultures are discordant, multiple or negative at postmortem, we established a scoring system using blood cultures, procalcitonin (PCN) showing highest sensitivity and specificity for postmortem serum, and bone marrow polyhemophagocytosis (PHP). Histological sepsis showed significantly higher levels of culture score (2.3 ± 1.5 vs. 0.4 ± 0.5, p < 0.001), PHP score (2.5 ± 0.8 vs. 1.0 ± 1.1, p < 0.001), and PCN score (1.8 ± 0.8 vs. 0.8 ± 0.6, p < 0.01) than non-septic patients. Receiver operating characteristic curve analysis indicated that estimation of three scores was the most reliable indicator for recognizing agonal phase sepsis. These findings suggest that the combination of these three inspections enables to determine the pathological diagnoses of sepsis even it is not obvious by discordant, mixed or negative blood cultures.

Improved artificial intelligence discrimination of minor histological populations by supplementing with color-adjusted images.

Despite the dedicated research of artificial intelligence (AI) for pathological images, the construction of AI applicable to histopathological tissue subtypes, is limited by insufficient dataset collection owing to disease infrequency. Here, we present a solution involving the addition of supplemental tissue array (TA) images that are adjusted to the tonality of the main data using a cycle-consistent generative adversarial network (CycleGAN) to the training data for rare tissue types. F1 scores of rare tissue types that constitute < 1.2% of the training data were significantly increased by improving recall values after adding color-adjusted TA images constituting < 0.65% of total training patches. The detector also enabled the equivalent discrimination of clinical images from two distinct hospitals and the capability was more increased following color-correction of test data before AI identification (F1 score from 45.2 ± 27.1 to 77.1 ± 10.3, p < 0.01). These methods also classified intraoperative frozen sections, while excessive supplementation paradoxically decreased F1 scores. These results identify strategies for building an AI that preserves the imbalance between training data with large differences in actual disease frequencies, which is important for constructing AI for practical histopathological classification.

A novel reaction force-fluorescence measurement system for evaluating pancreatic juice leakage from an excised swine pancreas during distal pancreatectomy.

BACKGROUND: Resection using a stapler is a popular approach to distal pancreatectomy. However, the resulting leakage of pancreatic juice represents a serious problem. We have developed a force-fluorescence measurement as a first step towards the quantitative evaluation of pancreatic leakage due to tissue tearing under compression. METHODS: The system comprises a testing machine with an indenter, similar in size to a stapler, which controls compression speed and measures reaction force, and a fluorescence measurement system to measure pancreatic juice leakage. Pancreatic juice leakage is measured as the maximum value of the increasing rate of fluorescence intensity (max value). Ten excised swine pancreases were compressed at a speed of 500, 100, and 10 mm/min until their thicknesses became 2 mm. RESULTS: A strong positive correlation (0.804) was observed between the increase in max value before and after compression and the amount of reaction force drop due to tissue destruction. No pancreatic juice leakage was observed when compressed slowly (10 mm/min). CONCLUSIONS: We have successfully developed a novel force-fluorescence measurement system that can detect and quantify pancreatic juice leakage caused by tissue tearing. This system can determine the optimal compression conditions for preventing pancreatic juice leakage.

Tenascin C interacts with ecto-5'-nucleotidase (eN) and regulates adenosine generation in cancer cells.

Tenascin C is expressed in invasive human solid tumors; however its specific role in cancer biology remains obscure. Previously, we have found that ecto-5'-nucleotidase (eN) is a marker of ER (-) breast carcinoma and elevated expression correlates with invasive mesenchymal cell phenotype. To investigate for the potential relationship between eN and protein components of the extracellular matrix (ECM) we measured adenosine generation from AMP in cells incubated with soluble ECM proteins. We found that tenascin C was the only ECM component that strongly inhibited ecto-5'-nucleotidase (eN) activity in situ and adenosine generation from AMP (75% inhibition, p < 0.01). The inhibition was comparable to that induced by concanavalin A, a well-defined and strong inhibitor of eN. Resin immobilized tenascin C, but not collagen, and only weakly fibronectin, specifically and quantitatively bound cell-extracted eN. We further developed breast cancer cell line with reduced eN expression and tested changes in cell adhesion on different ECM. Breast cancer cells expressing reduced eN attached 56% weaker (p < 0.05) to immobilized tenascin C. This difference was not detected with other ECM proteins. Finally, control breast cancer cells migrated slower on tenascin C when compared with clone with reduced eN expression. These data suggest that eN is a novel and specific receptor for tenascin C and that the interaction between these proteins may influence cell adhesion and migration and also lead to decreased generation of local adenosine.

Advanced bladder cancer with malignant psoas syndrome: A case report with a focus on physical findings and complications.

Malignant psoas syndrome (MPS) is a rare clinical condition caused by cancer invasion of the iliopsoas muscle and has very poor prognosis. We report a case involving a 58-year-old woman with bilateral MPS caused by advanced bladder cancer. Rapid progress of a severe crouching posture with multiple deep venous thromboses was an important symptom of this case. Although 4 cycles of chemotherapy were administered, the patient died 8 months following disease onset. Since, these noteworthy symptoms have never been previously reported, in this report, we present the characteristic physical findings using photographs and cancer-related events that occur in MPS.

Binding of monosodium urate crystals with idiotype protein efficiently promote dendritic cells to induce cytotoxic T cells.

Monosodium urate (MSU) crystals have been reported to evoke specific cell immunity and to work as an adjuvant in a mouse model. The crystals also have another unique characteristic to bind with positively charged proteins, which could help to deliver some antigens into human dendritic cells (DC). We focused on the application of MSU crystals as not only an adjuvant but also as a carrier of positively charged antigenic protein to induce human cytotoxic T cells (CTL) efficiently in vitro. We selected human leukocyte antigen (HLA)-A2 expressing the multiple myeloma IM-9 cell line and its product idiotype (Id) protein as one of the best pairs of target cells and positively charged tumor-specific antigen, respectively. Following the sensitization of DC derived from HLA-A2-positive volunteers pulsed with tumor-specific monoclonal immunoglobulin G-Fab fragments (IM-9 Fab) attached to MSU crystals, the DC-stimulated CD8(+) T cells killed significantly more target cells (40.1 +/- 1.7%) than those stimulated by DC pulsed with MSU crystals alone (6.2 +/- 8.6%, P < 0.01) or IM-9 Fab alone (4.7 +/- 8.1%, P < 0.01). These cytotoxic effects of the DC-stimulated CD8(+) cells were reduced when MSU crystals were precoated with fetal bovine serum. In addition, we confirmed that MSU crystals facilitated human DC to express the maturation marker, CD83 and deliver (Fab')(2), attaching to the crystals by flow cytometer analysis. MSU crystals have distinct advantages of a protein carrier binding with positively charged proteins and delivering antigenic protein into DC, as well as an adjuvant promoting DC maturation and inducing CTL.

Multiple inflammatory cytokine-productive ThyL-6 cell line established from a patient with thymic carcinoma.

Thymic epithelial cells can produce many kinds of cytokines, and interleukin (IL)-6-producing thymic carcinoma cases have been reported. However, a cytokine-producing human thymic tumor cell line has not previously been established. In this paper, we report a novel, multiple inflammatory cytokine-productive cell line that was established from a patient with thymic carcinoma. This cell line, designated ThyL-6, positively expressed epithelial membrane antigen, cytokeratins, vimentin intermediate filament and CD5, although hematological markers were not present in the cells. Cytokine antibody array analysis showed that the cells secreted several cytokines including IL-1alpha, IL-6, IL-8, RANTES, soluble TNFalpha-receptor 1, VEGF and CTLA into the culture medium. The addition of ThyL-6-cultured supernatant supported the growth of human myeloma ILKM-3 cells, which require the presence of IL-6 in the culture medium for the maintenance of cell growth, suggesting that the secreted IL-6 from ThyL-6 cells was biologically active. Chromosome analysis demonstrated that ThyL-6 cells had complex karyotype anomalies, including der(16)t(1;16); the latter has been recognized in thymic squamous cell carcinoma and thymic sarcomatoid carcinoma cases, as well as in several other kinds of malignancies. Heterotransplantation of the cells into nude mice showed tumorigenesis with neutrophil infiltration and liquefactive necrosis. These findings suggest that ThyL-6 cells will provide us with a new experimental tool for investigating not only the pathogenesis, biological behavior, chromo-somal analysis and therapeutic reagents of human thymic carcinoma, but also for studying cytokine-chemokine network systems.

Frequent detection of multidrug-resistant pneumonia-causing bacteria in the pneumonia lung tissues of patients with hematological malignancies.

Pneumonia is a critical issue during the agonal phase, and often becomes lethal in the absence of pathogen detection. Autopsy is a powerful tool for analyzing the cause of a patient's death, progression of the disease, and the therapeutic response. However, it is frequently limited to the identification of bacterial strains. To elucidate the pathogenesis during the agonal phase of pneumonia, intrapulmonary sputum was harvested by directly inserting a swab into a resected lung, and the bacterial composition was analyzed using both pathological and microbiological techniques from 15 patients with hematological malignancies, and the results were compared with those from 25 patients with other medical and surgical diseases. Among the 54 bacteria strains isolated from the 40 patients, multidrug-resistant strains were significantly more prevalent in hematological group than in other diseases (16/21 versus 11/33, P = .002). Enterococcus faecium was preferentially isolated from the hematological patients, whereas the methicillin-resistant Staphylococcus aureus was predominantly found in the nonhematological group. Two coagulase-negative Staphylococcus epidermidis strains in hematological diseases may be diagnosed as causative bacteria of pneumonia by both bacterial and pathological techniques. Although the results of this study may not be directly applicable for clinical diagnosis, this approach has a potential to become not only a diagnostic method for bacterial pneumonia, but may be also useful for the analysis of multidrug-resistant pathogens.

Combined low-dose cytarabine, melphalan and mitoxantrone for older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.

BACKGROUND: Low-dose cytarabine (ara-C) has been used to treat older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), but has resulted in complete remission for <20% of cases. A pilot study of the efficacy of a combination chemotherapy using low-dose ara-C, melphalan (Mel), and mitoxantrone (Mit) was conducted. PATIENTS AND METHODS: The treatment comprised ara-C (10 mg/m2) twice daily, melphalan (2 mg/body) every other day, and mitoxantrone (3 mg/m2) every 3 days. The treatment was discontinued if the nuclear cell count was <15,000/microl with <20% blast count in the bone marrow. The primary end-points were initial response and tolerability. RESULTS: The study comprised 9 patients with AML or high-risk MDS (median age, 75 years). Complete remission was achieved in 3 patients. All the patients displayed grade 4 neutropenia and thrombocytopenia. One patient died from sepsis. CONCLUSION: The present regimen was more effective and displayed similar safety, compared with low-dose ara-C alone.

Lipid rafts remodeling in estrogen receptor-negative breast cancer is reversed by histone deacetylase inhibitor.

Recently, we have found dramatic overexpression of ecto-5'-nucleotidase (or CD73), a glycosylphosphatidylinositol-anchored component of lipid rafts, in estrogen receptor-negative [ER-] breast cancer cell lines and in clinical samples. To find out whether there is a more general shift in expression profile of membrane proteins, we undertook an investigation on the expression of selected membrane and cytoskeletal proteins in aggressive and metastatic breast cancer cells. Our analysis revealed a remarkably uniform shift in expression of a broad range of membrane, cytoskeletal, and signaling proteins in ER- cells. A similar change was found in two in vitro models of transition to ER- breast cancer: drug-resistant Adr2 and c-Jun-transformed clones of MCF-7 cells. Interestingly, similar expression pattern was observed in normal fibroblasts, suggesting the commonality of membrane determinants of invasive cancer cells with normal mesenchymal phenotype. Because a number of investigated proteins are components of lipid rafts, our results suggest that there is a major remodeling of lipid rafts and underlying cytoskeleton in ER- breast cancer. To test whether this broadly defined ER- phenotype could be reversed by treatment with differentiating agent, we treated ER- cells with trichostatin A, an inhibitor of histone deacetylase, and observed reversal of mesenchymal and reappearance of epithelial markers. Changes in gene and protein expression also included increased capacity to generate adenosine and altered expression profile of adenosine receptors. Thus, our results suggest that during transition to invasive breast cancer there is a significant structural reorganization of lipid rafts and underlying cytoskeleton that is reversed upon histone deacetylase inhibition.

Postmortem CT is more accurate than clinical diagnosis for identifying the immediate cause of death in hospitalized patients: a prospective autopsy-based study.

Despite 75 to 90 % physician accuracy in determining the underlying cause of death, precision of determination of the immediate cause of death is approximately 40 %. In contrast, two thirds of immediate causes of death in hospitalized patients are correctly diagnosed by postmortem computed tomography (CT). Postmortem CT might provide an alternative approach to verifying the immediate cause of death. To evaluate the effectiveness of postmortem CT as an alternative method to determine the immediate cause of death in hospitalized patients, an autopsy-based prospective study was performed. Of 563 deaths from September 2011 to August 2013, 50 consecutive cadavers undergoing hospital autopsies with consent for additional postmortem CT at the University of Fukui were enrolled. The accuracy of determination of the immediate cause of death by postmortem CT was evaluated in these patients. Diagnostic discrepancy was also compared between radiologists and attending physicians. The immediate cause of death was correctly diagnosed in 37 of 50 subjects using postmortem CT (74 %), concerning 29 cases of respiratory failure, 4 of hemorrhage, 3 of liver failure and 1 of septic shock. Six cases of organ failure involving 13 patients were not identified as the cause of death by postmortem CT. Regarding the immediate cause of death, accuracy of clinical diagnosis was significantly lower than that of postmortem CT (46 vs 74 %, P < 0.01). Postmortem CT may be more useful than clinical diagnosis for identifying the immediate cause of death in hospitalized patients not undergoing autopsy.

Risk factor analysis for bone marrow histiocytic hyperplasia with hemophagocytosis: an autopsy study.

The excessive release of inflammatory cytokines occasionally induces life-threatening hemophagocytosis referred to as hemophagocytic syndrome (HPS). A similar condition, histiocytic hyperplasia with hemophagocytosis (HHH), is often seen in bone marrow collected during autopsy. Unlike HPS, the pathogenesis of HHH remains unclear. Therefore, we performed a clinicopathological analysis of HHH from 70 autopsy cases at the University of Fukui Hospital. HHH was detected in 29 of 70 autopsies (41.4 %) and was significantly complicated with hematological diseases (p < 0.05) and sepsis (p < 0.05). The percentage of macrophages in bone marrow (BM) nucleated cells was significantly increased in HHH (p < 0.001). Data from medical records indicated no significant changes, except for the minimum values of white blood cell counts (p < 0.05) and platelet counts (p < 0.05) in HHH patients as compared with non-HHH patients. Concentrations of inflammatory mediators including IL-1ß, IL-6, and IL-8 were significantly increased in HHH patients. Multivariate risk factor analysis identified hematological diseases (odds ratio (OR), 11.71), ≥ 15 % BM macrophages (OR, 9.42), sepsis (OR, 7.77), and high serum IL-6 levels (OR, 1.00) as independent risk factors for HHH. HHH with hypocellular BM, the most aggressive form of HHH, was recognized in 8 of 29 HHH patients and was associated with ≥ 25 % BM macrophages (p < 0.001), leukocytopenia (p < 0.05), and high IL-8 levels (p < 0.05). None of the HHH patients fulfilled the diagnostic criteria of HPS. These findings suggest that HHH is a different entity from HPS and that it preferentially develops under conditions of excessive inflammation and its associated risks, such as hematological diseases and sepsis.