A 74-year-old man was referred to our hospital because of persistent cough. A chest radiograph revealed an elevation of the right diaphragm. Computed tomography (CT) images revealed a small nodule localized on the right mediastinum. Five months later, the nodule had grown and was diagnosed as malignant pleural mesothelioma (MPM) by a CT-guided needle biopsy. The patient underwent combined chemotherapy, but the disease progressed rapidly and he passed away. On autopsy, microscopic findings and immunohistological examinations supported the diagnosis of sarcomatoid mesothelioma. Therefore, we diagnosed this rare case as localized sarcomatoid MPM showing phrenic nerve paralysis as an initial presentation.
Malignant pleural mesothelioma; Localized sarcomatoid mesothelioma; Phrenic nerve paralysis; Immunohistological examination
In order to examine which factors were important for achieving a ≥5 year survival time in non-small cell lung cancer (NSCLC) patients with distant metastasis, 268 NSCLC patients who received first-line chemotherapy between January 2004 and December 2007 were retrospectively examined. The median survival time of the patients was 14 months, with 22 surviving for ≥5 years, 48 for ≥2 years, but <5 years, and 198 surviving <2 years. Multivariate analysis determined that never having smoked, a good performance status, relapse following thoracic surgery and intra-thoracic metastasis were significantly favorable prognostic factors, while abdominal metastasis was a significantly poor prognostic factor. The ≥5 years and ≥2–5 years groups had significantly more favorable prognostic factors than the <2 years group. The never-smoked status was a particularly important factor for ≥5 years of survival. The ≥5 years and ≥2–5 years groups achieved a significantly more favorable response to first-line chemotherapy, and a greater number of regimens, total months of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and cytotoxic agent treatment cycles compared with the <2 years group. In total, ~50% of the patients received palliative radiotherapy. In the ≥5 years group, patients with EGFR drug-sensitive mutations achieved ≥5 years of survival mainly by EGFR-TKI therapy, while those without EGFR mutations achieved ≥5 years of survival by continuing effective cytotoxic agents. Achievement of >5 years of survival was found to correlate with the presence of favorable prognostic factors, response to first-line chemotherapy, provision of appropriate EGFR-TKI therapy according to genetic testing results, continuing effective cytotoxic regimens and the use of radiotherapy as local therapy.
non-small-cell lung cancer; prognostic factors; ≥5 years survival; survival post-progression
Chronic thromboembolic pulmonary hypertension (CTEPH) has been increasingly recognized as a common source of elevated pulmonary vascular resistance and pulmonary hypertension. It is clear that development of pulmonary thromboemboli is the inciting event for this process, yet it remains unclear why some patients have persistent pulmonary artery occlusion leading to distal pulmonary vascular remodeling and CTEPH. Thrombin, a serine protease, is an integral part of the common coagulation cascade, yet thrombin also has direct cellular effects through interaction with the family of PAR membrane receptors. This study is designed to determine the effects of thrombin on Akt signaling in pulmonary artery smooth muscle cells (PASMC) from normal humans and pulmonary hypertension patients. Thrombin treatment of PASMC resulted in a transient increase in Akt phosphorylation and had similar effects on the downstream targets of the Akt/mTOR pathway. Ca2+ is shown to be required for Akt phosphorylation as well as serum starvation, a distinct effect compared to platelet‐derived growth factor. Thrombin treatment was associated with a rise in intracellular [Ca2+] and enhanced store‐operated calcium entry (SOCE). These effects lead to enhanced proliferation, which is more dramatic in both IPAH and CTEPH PASMC. Enhanced proliferation is also shown to be attenuated by inhibition of Akt/mTOR in CTEPH PASMC. Thrombin has direct effects on PASMC increasing intracellular [Ca2+] and PASMC proliferation, an effect attributed to Akt phosphorylation. The current results implicate the effects of thrombin in the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) and CTEPH, which may potentially be a novel therapeutic target.
Thrombin is known to play an important role in thrombotic events including pulmonary embolism. In this manuscript, we show a direct effect of thrombin on pulmonary artery smooth muscle cells in both normal and diseased states through Akt signaling, which leads to increased store‐operated calcium entry and cellular proliferation. These direct effects of thrombin may play a role in the development and progression of chronic thromboembolic pulmonary hypertension.
Akt signaling; chronic thromboembolic pulmonary hypertension; pulmonary hypertension; store‐operated calcium entry; thrombin
The optimal suction pressure during endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) remains to be determined. The aim of this study was to compare suction pressures for performance in collecting sufficient tissue specimens from mediastinal and hilar lymph nodes during EBUS-TBNA.
Retrospective analysis of consecutive patients with mediastinal and hilar lymphadenopathy who underwent EBUS-TBNA over a 3-year period. Results from patients who underwent EBUS-TBNA using a dedicated 20-mL VacLoc (Merit Medical Systems, Inc, South Jordan, UT) syringe (conventional method, group C) were compared with results from patients in whom a disposable 30-mL syringe (high pressure group, group H) was used. The yield for sufficient histologic specimen retrieval and amount of tissue obtained were compared between the 2 groups.
Of 178 patients who underwent EBUS-TBNA, 131 had lung cancer confirmed by EBUS-TBNA: 35 in group C and 96 in group H. There were 7 patients in group C and 6 in group H who received final diagnoses by cytology alone. There were 28 in group C and 90 in group H who were diagnosed by both cytology and histology. There was a statistically significant difference between the groups in terms of the rate of sufficient sampling for histological specimens (p = 0.04). The H group revealed a tissue area approximately twice that of the C group (p = 0.003). There were no major procedure-related complications in either group.
Higher suction pressures with larger syringe volumes during EBUS-TBNA may be useful for safely collecting sufficient tissue specimens.
For patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the relationship between the dose or duration of treatment with tyrosine kinase inhibitor (TKI) and overall survival remains unclear. Here, we analyzed clinical data of 39 patients who were diagnosed with EGFR mutation-positive non-small cell lung cancer and treated with TKI, but subsequently died. Several parameters were measured in this study: overall survival; first, second, and overall TKI therapy durations; first TKI intensity (actual dose/normal dose); and TKI rate (overall TKI therapy duration/overall survival). The response rate to TKI therapy was 50%, and the median survival was 553 days. After TKI therapy failed, 38.5% patients were re-challenged with TKI. We observed a moderate relationship [r = 0.534, 95% confidential interval (CI) = 0.263 to 0.727, P < 0.001] between overall TKI therapy duration and overall survival. However, we found no relationship between overall survival and first TKI intensity (r = 0.073, 95% CI = -0.380 to 0.247, P = 0.657) or TKI rate (r = 0.0345, 95% CI = -0.284 to 0.346, P = 0.835). Non-small cell lung cancer patients with mutation-positive tumors remained on TKI therapy for, on average, 33% of the overall survival time. These findings suggest that patients with EGFR mutation-positive tumors should not stick to using TKIs.
Tyrosine kinase inhibitor; gefitinib; erlotinib; non-small cell lung cancer; epidermal growth factor receptor mutation
Influenza virus is a common respiratory tract viral infection. Although influenza can be fatal in patients with chronic pulmonary diseases such as chronic obstructive pulmonary disease, its pathogenesis is not fully understood. The Nrf2-mediated antioxidant system is essential to protect the lungs from oxidative injury and inflammation. In the present study, we investigated the role of Nrf2 in protection against influenza virus-induced pulmonary inflammation after cigarette smoke exposure with both in vitro and in vivo approaches. For in vitro analyses, peritoneal macrophages isolated from wild-type and Nrf2-deficient mice were treated with poly(I:C) and/or cigarette smoke extract. For in vivo analysis, these mice were infected with influenza A virus with or without exposure to cigarette smoke. In Nrf2-deficient macrophages, NF-κB activation and the induction of its target inflammatory genes were enhanced after costimulation with cigarette smoke extract and poly(I:C) compared with wild-type macrophages. The induction of antioxidant genes was observed for the lungs of wild-type mice but not those of Nrf2-deficient mice after cigarette smoke exposure. Cigarette smoke-exposed Nrf2-deficient mice showed higher rates of mortality than did wild-type mice after influenza virus infection, with enhanced peribronchial inflammation, lung permeability damage, and mucus hypersecretion. Lung oxidant levels and NF-κB-mediated inflammatory gene expression in the lungs were also enhanced in Nrf2-deficient mice. Our data indicate that the antioxidant pathway controlled by Nrf2 is pivotal for protection against the development of influenza virus-induced pulmonary inflammation and injury under oxidative conditions.
A topical application of a nonsteroidal anti-inflammatory drug (NSAID) may induct an adverse reaction of photoallergic contact dermatitis. The occlusive usage may provoke concomitant photoallergic sensitizations to an NSAID and other ingredients. We describe a 58-year-old woman with photoallergic contact dermatitis from ketoprofen and hydrogenated rosin glycerol ester in the applied compress. Our case indicates that photopatch testing with all ingredients is required to verify the actual photoallergen(s).
Photoallergic contact dermatitis; Ketoprofen; Hydrogenated rosin glycerol ester; Compress
Primary effusion lymphoma (PEL) was once defined as a body cavity‐based lymphoma without identifiable contiguous tumour mass, but is now recognised as an independent clinicopathological entity. The case of a 67‐year‐old Japanese woman with PEL is reported, in which the clinical findings showed a pericardial effusion and multiple erythema on the hypogastrium and inguinal region. The histopathological findings showed a diffuse infiltration of large neoplastic B cells from the dermis to the subcutis. After the disappearance of pericardial effusion without any treatment, she received several rounds of chemotherapy to resolve the skin eruption, but she finally died from multiple organ failure. No tumour mass was observed during the course of her disease.
The biological, medical and environmental roles of trace elements have attracted considerable attention over the years. In spite of their relevance in nutritional, occupational and toxicological aspects, there is still a lack of consistent and reliable measurement techniques and reliable information on reference values. In this review our understandings of the urinary profilings of boron, lithium and strontium are summarized and fundamental results obtained in our laboratory are discussed.
Over the past decade we have successfully used inductively coupled plasma emission spectrometry for the determination of reference values for urinary concentrations of boron, lithium and strontium. Taking into account the short biological half-life of these elements and the fact that their major excretion route is via the kidney, urine was considered to be a suitable material for monitoring of exposure to these elements. We confirmed that urinary concentrations of boron, lithium and strontium follow a lognormal distribution. The geometric mean reference values and 95% confidence intervals were 798 μg/l (398–1599 μg/l) for boron, 23.5 μg/l (11.0–50.5 μg/l) for lithium and 143.9 μg/l (40.9–505.8 μg/l) for strontium. There were no discrepancies between our values and those previously reported. Our reference values and confidential intervals can be used as guidelines for the health screening of Japanese individuals to evaluate environmental or occupational exposure to these elements.
boron; lithium; strontium; log-normal distribution; reference values
The pathological features of lung disease in nine patients with systemic sclerosis (SSc) were evaluated. The patients comprised one man and eight women, with a median age of 58 years. SSc was diagnosed according to the criteria of the American Rheumatism Association. In all patients, high resolution computed radiographic scanning of the lungs (HRCT) was performed, and apparent honeycomb formation was seen in four patients. Pathologically, four patients were diagnosed with usual interstitial pneumonia (UIP), three with non-specific interstitial pneumonia (NSIP) group II, one NSIP group II-III, and one NSIP group II with diffuse alveolar damage. HRCT showed no apparent honeycomb formations in patients diagnosed with NSIP. This is the first report describing NSIP as a pulmonary complication of SSc.
Visual processing and its conscious awareness can be
dissociated. To examine the extent of dissociation between ability to read characters or words and to be consciously aware of their forms,
reading ability and conscious awareness for characters were examined
using a tachistoscope in an alexic patient. A right handed woman with
14 years of education presented with incomplete right hemianopia,
alexia with kanji (ideogram) agraphia, anomia, and amnesia. Brain MRI
disclosed cerebral infarction limited to the left lower bank of the
calcarine fissure, lingual and parahippocampal gyri, and an old
infarction in the right medial frontal lobe. Tachistoscopic examination
disclosed that she could read characters aloud in the right lower
hemifield when she was not clearly aware of their forms and only noted
their presence vaguely. Although her performance in reading kanji was
better in the left than the right field, she could read kana
(phonogram) characters and Arabic numerals equally well in both fields.
By contrast, she claimed that she saw only a flash of light in 61% of
trials and noticed vague forms of stimuli in 36% of trials. She never
recognised a form of a letter in the right lower field precisely. She
performed judgment tasks better in the left than right lower hemifield
where she had to judge whether two kana characters were the same or different. Although dissociation between performance of visual recognition tasks and conscious awareness of the visual experience was
found in patients with blindsight or residual vision, reading (verbal
identification) of characters without clear awareness of their forms
has not been reported in clinical cases. Diminished awareness of forms
in our patient may reflect incomplete input to the extrastriate cortex.
Aims—To investigate the clinicopathological differences among gastric low grade MALT lymphomas (low MALT), large B cell lymphomas with low grade components (secondary high grade MALT lymphomas, high MALT), and diffuse large B cell lymphomas without low grade features (primary high grade MALT lymphomas, DLL).
Methods—Clinicopathological and morphological characters of 126 gastric lymphoma cases were studied: 82 cases of low MALT lymphoma including 40 that were surgically resected, 17 cases of high MALT lymphoma including 13 surgically resected, and 27 cases of DLL including 12 surgically resected.
Results—Age ranges were as follows: low MALT lymphoma, 34 to 85 years (mean 59.9); high MALT lymphoma, 53 to 88 years (mean 68.5); DLL, 29 to 83 years (mean 62.3). The average age for low and high MALT lymphomas was significantly different (p < 0.05), but there were no differences in other comparisons. There was a female predominance of low MALT lymphoma patients (female to male ratio, 47/35), while for high MALT patients the ratio was almost even (8/9), and for DLL patients there was a male predominance (11/16). Examination of surgically resected material showed that MALT lymphomas had a wider distribution in the gastric wall than DLL.
Conclusions—The findings suggest that at least some of the high grade gastric lymphomas, especially in patients younger than the fifth decade, do not originate from high grade transformation of low MALT lymphomas. It seems to take about one decade at least for high grade transformation of low MALT lymphomas.
Key Words: MALT lymphoma • stomach • transformation
BACKGROUND—It has been suggested that the humoral
immune system plays a role in the pathogenesis of cryptogenic fibrosing
alveolitis (CFA). Although circulating autoantibodies to lung
protein(s) have been suggested, none of the lung proteins have been
characterised. The purpose of this study was to determine the antigen
to which the serum from patients with pulmonary fibrosis reacted.
METHODS—The anti-A549 cell antibody was
characterised in a patient with CFA using Western immunoblotting and
immunohistochemical staining of A549 cells. As we identified that one
of the antibodies against A549 cells was anti-cytokeratin 8, the
expression of mRNA of cytokeratin 8 in A549 cells was evaluated. In
addition, we attempted to establish an enzyme linked immunosorbent
assay to measure the levels of anti-cytokeratin 8 antibody in the serum
of patients with CFA and pulmonary fibrosis associated with collagen
vascular disorders (PF-CVD).
RESULTS—Initially two anti-A549 cell antibodies
were detected in the serum of patients with pulmonary fibrosis, one of
which was characterised as anti-cytokeratin 8 antibody by Western
immunoblotting. We were able to establish an ELISA to measure
anti-cytokeratin 8 antibody and found significantly higher levels in
patients with CFA and PF-CVD than in normal volunteers, patients with
sarcoidosis, pneumonia, and pulmonary emphysema.
CONCLUSIONS—One of the anti-A549 cell antibodies
in the serum of patients with CFA was against cytokeratin 8. The serum
levels of anti-cytokeratin 8 antibody were increased in patients with
CFA and PF-CVD. These results suggest that anti-cytokeratin 8 antibody
may be involved in the process of lung injury in pulmonary fibrosis.
It has been reported that cytokeratin 8 (CK8) is expressed in all non-small-cell lung cancers (NSCLC). We hypothesized that antigenic changes of CK8 may occur in some NSCLC cell lines. To prove this, Western immunoblot analysis using anti-human CK8 monoclonal antibodies as well as immunohistological staining of CK8 were performed in NSCLC cell lines. As a result, CK8 which had a higher molecular weight than recombinant CK8 was demonstrated in two of eight NSCLC cell lines. In addition, this CK8 contained antigenic epitopes of CA19–9. This CK8 with higher molecular weight, may have played a role in the process of invasion or metastasis of NSCLC. © 1999 Cancer Research Campaign
antibody; CA19–9; cytokeratin 8; non-small-cell lung cancer
OBJECTIVES—Memory impairment is not only the
earliest clinical symptom but a central and prominent feature
throughout the course of Alzheimer's disease. Alzheimer related
pathological alterations in the medial temporal structures may account
for the memory impairments in patients with Alzheimer's disease. The
aim of this study was to elucidate the role of the medial temporal
structures in memory impairment caused by Alzheimer's disease.
METHODS—Using high resolution MRI and a
semiautomated image analysis technique, volumes of the medial temporal
structures (amygdaloid complex, hippocampal formation, subiculum,
and parahippocampal gyrus) were measured, and correlations between
atrophy of each structure and memory dysfunction in patients with
Alzheimer's disease were examined.
RESULTS—Patients with Alzheimer's disease showed
poor performance on verbal and non-verbal memory tests, and MRI
volumetry showed a significant volume reduction of the medial temporal
lobe structures. Volumes of the amygdaloid complex and of the subiculum
correlated with memory performance. Stepwise regression analyses
disclosed that the volume of the right amygdaloid complex specifically
predicted visual memory function and to some extent verbal memory
function, and that the volume of the left subiculum specifically
predicted verbal memory function. Atrophy of the hippocampus did not
predict severity of memory impairment.
CONCLUSIONS—The presence of perihippocampal
damage involving the amygdala proper, its surrounding cortex, and the
subiculum further increased the severity of memory impairment
attributable to hippocampal damage in Alzheimer's disease.
OBJECTIVE: To investigate the relation between atrophy of the hippocampus and parahippocampal gyrus (the % hippocampal area) and cerebral metabolic rate for glucose (CMRGlc) in Alzheimer's disease. METHODS: 13 patients with probable Alzheimer's disease by NINCDS-ADRDA criteria (six men; seven women, mean age 71 years, mini mental state 13.8 (SD 4.6)) and age matched controls were studied. T1 weighted MRI (0.5T) images were used for evaluation of the hippocampal area. With a digitiser system, a percentage of the hippocampal area to the brain (the % hippocampal area) was calculated. Eight patients received another T1 weighted MRI (1.5T) for further evaluation of the minimum thickness of the hippocampus. Regional CMRGlc (rCMRGlc) was measured using PET and the FDG technique. RESULTS: The hippocampal area in patients with Alzheimer's disease was significantly lower than that of controls (P < 0.01). All the cortical rCMRGlc values in patients with Alzheimer's disease were lower than those of controls (P < 0.01). A significant correlation (P < 0.05) was found between the % hippocampal area and rCMRGlc in the temporal lobe, temporoparieto-occipital (TPO) region, and frontal lobe in Alzheimer's disease. There was a significant correlation between minimal hippocampal thickness and ipsilateral TPO metabolism on both sides. CONCLUSION: The ipsilateral correlation between hippocampal atrophy and decreased TPO metabolism in Alzheimer's disease suggests a functional relation and the asymmetries show that Alzheimer's disease is an asymmetric disease in its early stages.
A patient is described who presented with a disturbance of body cognition confined to the left side of the body. She showed difficulties in naming the left fingers and in moving the named left fingers. She also showed great difficulty in pointing to named parts of the body with her left hand. Earlier in the course of the disease she showed a personification phenomenon of the left hand. Brain MRI showed involvement of the entire corpus callosum, probably due to occlusion of a branch of the anterior cerebral artery. It is speculated that this syndrome is caused by disconnection of the right hemisphere from the left hemispheric body schema.
In right middle cerebral territory infarction a new sign, excessive closure of the right eye ipsilateral to the lesion and mild closure of the left eye on command, was noted. The excessive ipsilateral eye closure was not observed on spontaneous eye closure.
Fifteen patients with epilepsy and hypergraphia were compared with 32 patients with epilepsy but without hypergraphia. The number of previous psychiatric episodes, the number of Washington Psychosocial Seizure Inventory (WPSI) items indicating emotional maladjustment, and the number of CT scan abnormalities were significantly greater in the hypergraphic patients than in the non-hypergraphic patients. Cognitive performance, EEG laterality and the scores of WPSI items related to the psychological stress of seizures did not differ significantly between the two groups. Hypergraphia reflects changes in emotional responsiveness secondary to organic temporal lobe lesions.
A patient with MRI confirmed lesions in the corpus callosum and the left cingulate gyrus had a rare syndrome of crossed avoiding reaction of the left hand. With the right hand she could reach a stimulus object in whatever space it was presented. With the left hand, however, she could not mobilise it to reach a stimulus presented in the right hemispace relative to her body axis. In the left hemispace relative to her body axis her left hand reached an object without any difficulty. This left unilateral difficulty in the right unilateral space may be related to a unique spatial function that controls manual space, which is represented differentially in the two hemispheres. In the left hemisphere this function covers bilateral hemispace and is operated by the right hand. In the right hemisphere this function covers only the left hemispace and is operated by the left hand.