Histological analysis of trabeculotomy - An investigation on the intraocular pressure lowering mechanism.

The primary aim of trabeculotomy (TLO) and/or minimally invasive glaucoma surgery (MIGS) is to produce a direct communication between the anterior chamber (AC) and collector channels (CC), which is believed to be the process by which intraocular pressure (IOP) is normalized. However, we previously reported our finding of the large opening of the Schlemm's canal (SC) into the AC in eyes with failed TLO (Amari et al., 2015). If the routes from the AC to the CC by TLO/MIGS are direct, IOP should be stabilized at around aqueous vein pressure if the SC and CC are undamaged. However, in eyes in which TLO/MIGS is successful, IOP usually stays at around the middle or high teens post surgery. In this current study, we retrospectively investigated the specific reason for middle- or high-teens IOP following TLO/MIGS via the histological examination of trabeculectomy (TRAB) specimens that include the area of previous TLO/MIGS in eyes with failed TLO or insufficient IOP control following TLO by specifically focusing on the behavior of the SC endothelium (SCE). Patient background, maximum IOP prior to TLO/MIGS and TRAB, the number medications administered, and elapsed time between TLO/MIGS and TRAB were reviewed. In 42 TRAB specimens of 31 120-180° TLO eyes (Group A; 27 ab-externo and 4 ab-interno eyes) and 11 360° suture TLO eyes (Group B), SC length (SCL), the site of the incision in the trabecular meshwork (TM) [i.e., the center (CEN)/anterior-tip (TIP)], and TM opening into the AC [i.e., open (OPN)/closed (CLS)] were histologically investigated. The correlation between the clinical parameters of the maximum IOP of pre-TLO/MIGS, the maximum IOP of pre-TRAB, the percentage of IOP reduction (PIR), and the histological results were statistically evaluated. Our findings revealed a significant negative correlation between the maximum IOP of pre-TRAB and SCL (P = 0.0167), and a significantly higher PIR in the eyes with OPN than those with CLS in Group A (P = 0.0045). However, no significant difference in SCL was found between the OPN and CLS eyes in both groups. In comparison to Group A, a higher percentage of OPN (82%) yet a smaller SCL (P = 0.0024) was observed in Group B. No significant correlation between clinical and histological parameters was found in Group B. In both groups, the common finding was sealing of the SC openings by SC endothelium (SCE) and no direct communication between the AC and the CC. This fact indicates that the nature by which SCE seals off the opened SC lumen into the AC created by TLO may be very important for maintaining the blood-aqueous barrier. Based on these results, we concluded that accessibility for aqueous humor to the SC and preservation of the SC may be important for lowering IOP by TLO. However, the opening of the SC into the AC (OPN type) does not guarantee an adequate IOP lowering effect if the SC is widely collapsed. Thus, TLO may be improved only by eliminating the most resistant part of the TM with minimal SCE damage.

Comparisons of Schlemm's canal and trabecular meshwork morphologies between juvenile and primary open angle glaucoma.

The histologic differences in Schlemm's canal (SC) and trabecular meshwork (TM), obtained from the trabeculectomy specimens of different age-group glaucoma patients, were compared. This study involved 44 trabeculectomy specimens of 37 juvenile-onset open-angle glaucoma (JOAG) patients (Group A) and 24 trabeculectomy specimens of 24 elderly-onset primary OAG (POAG) patients (age range: 70-79 years, Group B) with no familial history of POAG. Clinical parameters of gender, maximum intraocular pressure (IOP), and the number of glaucoma medications used prior to trabeculectomy were investigated and compared between the two groups. From light microscopy photographs of hematoxylin-eosin, and immunohistochemical staining of markers for SC endothelium (SCE), the total SC length (TSC), comprised of the opened-SC length (OSC) and the closed-SC length (CSC), the percentage of CSC in TSC (%CSC), the percentage of positive SCE marker in CSC (%PinCSC), and the percentage of negative SCE marker in OSC (%NinOSC) were analyzed. Moreover, podoplanin staining patterns in the TM were investigated and compared between the two groups. Among the clinical parameters, the mean maximum IOP in Group A (33.41 ± 9.24 mmHg) was the only significant parameter when compared to that in Group B (22.96 ± 7.17 mmHg, P = 0.000003). TSC in Group A was significantly shorter than that in Group B (P = 0.00092), and %CSC (P = 0.00004) and %PinCSC (P = 0.00342) in Group B were significantly higher than those in Group A. No statistically significant difference in %NinOSC was found between Group A and Group B (P = 0.76060). Juxtacanalicular tissue (JCT) in Group A showed compact and weak staining with podoplanin, while the JCT and closed-SC area in Group B showed intense staining. In the Group A subjects, TSC (P = 0.04819) and OSC (P = 0.02867) were significantly shorter in the non-familial cases than in the familial cases. Platelet coagulations 10-37 µm in size at the defect of the SCE in the inner wall of the SC were observed in 8 eyes (18%) and 4 eyes (17%) in Group A and Group B, respectively. The platelets appeared to repair the SCE damage for maintaining the blood aqueous barrier in both groups of POAG eyes. Smaller SC diameters and accompanying TM abnormality were features observed in the young-onset JOAG patients, thus suggesting developmental abnormalities in the outflow routes. The collapse of SC lumen, presumably due to aging, was the feature observed in the elderly-onset POAG patients. In Group A, the significantly higher IOP, despite of no significant number of topical medications used prior to trabeculectomy, also suggested that JOAG eyes can be categorized as a distinct type of POAG from the eyes of elder-aged POAG patients. The SCE drop out observed in the glaucomatous eyes of the different age groups suggested that worsening of IOP control may possibly occur equally in both groups.

Drug-induced hypersensitivity syndrome caused by minodronic acid hydrate.

BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings. CASE PRESENTATION: An 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test. CONCLUSIONS: We described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.

Diagnosis and outcome of resected solitary pulmonary nodules after liver transplantation.

OBJECTIVE: Solitary pulmonary nodules after liver transplantation are challenging clinical problems. Herein, we report the causes and clinical courses of resected solitary pulmonary nodules in patients who underwent liver transplantation. METHODS: We retrospectively obtained medical records of 68 patients who underwent liver transplantation between March 2009 and June 2016. This study mainly focused on patients with solitary pulmonary nodules observed on computed tomography scans during follow-ups that were conducted until their deaths or February 2019. RESULTS: Computed tomography scans revealed solitary pulmonary nodules in 7 of the 68 patients. Definitive diagnoses were obtained using video-assisted lung resection in all seven patients. None experienced major postoperative complications. The final pathologic diagnoses were primary lung cancer in three patients, pulmonary metastases from hepatocellular carcinoma in one patient, invasive pulmonary aspergillosis in one patient, post-transplant lymphoproliferative disorder in one patient, and hemorrhagic infarction in one patient. The three patients with lung cancer were subsequently treated with standard curative resection. CONCLUSIONS: Solitary pulmonary nodules present in several serious but potentially curable diseases, such as early-stage lung cancer. Patients who present with solitary pulmonary nodules after liver transplantation should be evaluated by standard diagnostic procedures, including surgical biopsy if necessary.

Oxidized regenerated cellulose induces pleural thickening in patients with pneumothorax: possible involvement of the mesothelial-mesenchymal transition.

PURPOSE: The pleural covering technique, i.e., wrapping a part of or the entire surface of the lung with oxidized regenerative cellulose (ORC), reinforces visceral pleura through pleural thickening for patients with pneumothorax and cystic lung diseases. However, it remains undetermined how ORC induces pleural thickening. METHODS: A histopathological examination was performed for lung specimens from patients who had recurrent pneumothoraces after pleural covering and re-operation (n = 5). To evaluate the influence of ORC on the pleura in vitro, we used MeT-5A cells (a human pleural mesothelial cell line). RESULTS: Pleural thickening was confirmed in all lung specimens examined. Three months after covering, the thickened pleura showed inflammatory cell infiltration, proliferation of myofibroblasts, and expression of fibronectin and TGF-ß. However, after 1 year, those findings virtually disappeared, and the thickened pleura was composed mainly of abundant collagen. When MeT-5A cells were cultured in ORC-immersed medium, their morphology changed from a cobblestone to spindle-shaped appearance. The expression of E-cadherin decreased, whereas that of N-cadherin, α-smooth muscle actin, and fibronectin increased, suggesting mesothelial-mesenchymal transition (Meso-MT). CONCLUSIONS: Our results suggest that Meso-MT may be involved as a mechanism of pleural thickening induced by pleural covering with ORC.

Histological analysis of vasculopathy associated with pulmonary hypertension in combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis or emphysema alone.

AIMS: To evaluate pulmonary vasculopathy in an autopsy series of patients with combined pulmonary fibrosis and emphysema (CPFE), and compare these findings with those of patients with idiopathic pulmonary fibrosis (IPF) alone and emphysema alone. METHODS AND RESULTS: We retrospectively analysed the clinical, radiological and pathological features of 26 patients with CPFE, 11 with IPF, and 23 with emphysema. We evaluated pulmonary vascular, venous-venular and arteriolar tissue changes in the fibrotic, emphysematous and relatively unaffected (preserved) areas by using the Heath-Edwards scoring system. We found moderate-to-severe vasculopathy in the CPFE group, but no significant differences in the fibrotic and emphysematous areas among the three groups. However, in the preserved area, the grading was significantly different among the three groups (P < 0.001), and vasculopathy in the CPFE group was the most severe. Although venous-venular and arteriolar changes in almost all fibrotic and emphysematous areas in the three groups showed no significant differences, there were significant differences in venous-venular (P = 0.004) and arteriolar (P < 0.001) changes in the preserved area among the three groups, which were most prevalent in the CPFE group. In the CPFE group, venous-venular changes and vasculopathy by Heath-Edwards grading were highest in the fibrotic area and lowest in the preserved area. CONCLUSIONS: These results imply that pulmonary vasculopathy in patients with CPFE could occur in the whole lung tissue. This may explain the tendency for it to lead to the development of pulmonary hypertension in CPFE cases.

Efficacy and safety of stereotactic body radiotherapy using CyberKnife in Stage I primary lung tumor.

BACKGROUND: CyberKnife® (CK) is a new, advanced radiotherapy technique. This study aimed to evaluate its efficacy and toxicity in Japanese patients with early-stage primary lung tumor who were medically unfit and inoperable. METHODS: This retrospective study investigated patients who received CK treatment for medically inoperable Stage І primary lung tumor at the Japanese Red Cross Medical Center between June 2011 and September 2016. Each patient received a total of 36-48 Gy (median, 43 Gy) administered by CK in 4-5 fractions. RESULTS: Totally, 40 patients (T1a, n = 19; T1b, n = 15; T2a, n = 6) were included. Their median age was 86 (range, 56-95) years. Tracking required the use of fiducial markers in 28 patients and the Xsight Spine Tracking System in 12. The median follow-up was 14.5 (range, 1-51) months. Local recurrence occurred in seven (17.5%) patients. The local progression-free survival rates at 1 and 2 years were 83.9% and 74.0%, respectively. Distant recurrence occurred in regional lymph nodes (n = 5), the lung outside the radiation field (n = 3), and the bone (n = 1). Seven patients died. Overall survival rates at 1 and 2 years were 93.6% and 73.1%, respectively. Radiation pneumonitis was identified in 28 (70%) patients (Grade 1, n = 25; Grade 2, n = 2; Grade 5, n = 1). CONCLUSIONS: CK showed good local control with limited toxicity and could be an alternative treatment modality in medically inoperable patients with Stage І primary lung tumor.

Adenovirus Type 7 Pneumonia in Children Who Died from Measles-Associated Pneumonia, Hanoi, Vietnam, 2014.

During a 2014 measles outbreak in Vietnam, postmortem pathologic examination of hospitalized children who died showed that adenovirus type 7 pneumonia was a contributory cause of death in children with measles-associated immune suppression. Adenovirus type 7 pneumonia should be recognized as a major cause of secondary infection after measles.

Benign clear cell "sugar" tumor of the lung in a patient with Birt-Hogg-Dubé syndrome: a case report.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene. Here we report, for the first time to our knowledge, a patient with BHD syndrome who was complicated with a clear cell "sugar" tumor (CCST) of the lung, a benign tumor belonging to perivascular epithelioid cell tumors (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1) or 2 (TSC2) gene. CASE PRESENTATION: In a 38-year-old Asian woman, two well-circumscribed nodules in the left lung and multiple thin-walled, irregularly shaped cysts on the basal and medial area of the lungs were disclosed by chest roentgenogram and computer-assisted tomography (CT) during a preoperative survey for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed large polygonal cells with clear cytoplasm proliferating in a solid pattern. Immunohistochemistry revealed that these tumor cells were positive for microphthalmia-transcription factor, S100, and CD1a but negative for HMB45, indicating that the tumor was a CCST. Genetic testing indicated that the patient had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7 nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon 12 using genomic DNA obtained from her microdissected CCST cells clearly revealed loss of the wild-type FLCN sequence, which confirmed complete functional loss of the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2-associated genetic region was demonstrated. CONCLUSION: To our knowledge, this is the first report of CCST of the lung in a patient with BHDS, indicating that CCST should be added to the spectrum of pulmonary manifestations of BHDS.

Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib.

A 56-year-old woman, a never-smoker, had postoperative recurrence of anaplastic lymphoma kinase rearranged lung cancer. She achieved a partial response to treatment with an anaplastic lymphoma kinase tyrosine kinase inhibitor, crizotinib. After the tumor regrowth, crizotinib was switched to alectinib; once again a partial response was observed. At the second recurrence, transbronchial needle aspiration of the right paratracheal node was performed, which revealed cytological findings of small-cell carcinoma. While treatment with cisplatin-irinotecan chemotherapy made reduction of some tumor shadows, including the biopsied mediastinal lymph nodes, new, small, nodular shadows, highly suggestive of pulmonary metastases, were detected in both lung fields. This case may show proof of the transformation to small-cell lung cancer as a mechanism of resistance to anaplastic lymphoma kinase tyrosine kinase inhibitors in anaplastic lymphoma kinase rearranged tumor. However, this transformation may also be only one part of the resistance mechanism of the heterogeneous tumor.

Presence of Citrullinated Histone H3-Positive Neutrophils in Microscopic Polyangiitis from the Early Phase: An Autopsy Proven Case.

A 76-year-old man was admitted with general fatigue, weight loss, fever, headache, renal failure, and a high serum level of myeloperoxidase-antineutrophil cytoplasmic antibody. Biopsy revealed citrullinated histone H3 (citH3)-positive neutrophils adherent to the temporal artery endothelium. Three days after completing pulse steroid therapy, he suffered from a sudden disturbance of consciousness and died. On autopsy, the kidneys showed the most severe vasculitis with dense infiltration of citH3-positive neutrophils. The lungs showed intra-alveolar hemorrhage due to capillaritis. Severe brain hemorrhage was found in the left frontal lobe and putamen with uncal herniation. No vasculitis or thrombi was observed in the brain. The right dura mater was thickened due to fibrosis and inflammation. In conclusion, autopsy revealed systemic vasculitis with infiltration of abundant citH3-positive neutrophils, suggesting that the neutrophil extracellular trap formation and citH3 might play important roles in the early phases and development of microscopic polyangiitis.

Telomere Length of Human Adult Bronchial Epithelium and Bronchogenic Squamous Cell Carcinoma Measured Using Tissue Quantitative Fluorescence in situ Hybridization.

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes. Chromosomal and genomic instability due to telomere dysfunction has been known to play an important role in the carcinogenesis of some organs. OBJECTIVES: The aim of this study was to examine the correlation between smoking and the telomere length of human bronchial epithelial cells in individuals with and without lung cancer. PATIENTS AND METHODS: We examined 68 non-lung cancer adult autopsy cases and 24 surgically resected cases of lung squamous cell carcinoma. Telomere lengths of the basal cells of bronchial epithelium were measured using the tissue quantitative fluorescence in situ hybridization method and were expressed in normalized telomere-to-centromere ratios (NTCRs). RESULTS: The autopsied individuals included 27 current smokers (CuS), 33 never-smokers (NeS), and 8 ex-smokers (ExS). The NTCRs in the central bronchi of CuS, NeS, and ExS were 1.515, 1.372, and 1.204, respectively. The bronchial epithelial telomeres of CuS were significantly longer than those of non-CuS (NeS + ExS). When the analysis was conducted separately for females and males, a significant difference between CuS and NeS + ExS was recognized only for males. The NTCRs of the bronchial epithelium of lung cancer cases and lung cancer tissue are 1.514 and 1.385, respectively. CONCLUSIONS: Our findings suggest that smoking causes telomeric elongation in the bronchial epithelium. Therefore, it appears that the mechanism of carcinogenesis in smoking-related carcinomas may differ from that of many other carcinomas in which genetic instability due to aging-related telomeric shortening is assumed to play a role.

[Brentuximab vedotin and cord blood transplantation for primary refractory Hodgkin lymphoma following autologous hematopoietic stem cell transplantation].

We report a 26-year-old man with primary refractory nodular sclerosis Hodgkin lymphoma against ABVD, ICE and autologous peripheral blood stem cell transplantation (auto-PBSCT), presenting with multiple epidural spinal cord compressions, paraplegia, and generalized lymphadenopathy. We administrated four cycles of brentuximab vedotin to achieve a complete response, and then conducted cord blood transplantation. This case raises the possibility of a new strategy for refractory Hodgkin lymphoma showing residual lesions after auto-PBSCT.

Characterization of pulmonary cysts in Birt-Hogg-Dubé syndrome: histopathological and morphometric analysis of 229 pulmonary cysts from 50 unrelated patients.

AIMS: To characterize the pathological features of pulmonary cysts, and to elucidate the possible mechanism of cyst formation in the lungs of patients with Birt-Hogg-Dubé syndrome (BHDS), a tumour suppressor gene syndrome, using histological and morphometric analyses. METHODS AND RESULTS: We evaluated 229 lung cysts from 50 patients with BHDS and 117 from 34 patients with primary spontaneous pneumothorax (PSP) for their number, size, location and absence or presence of inflammation. The BHDS cysts abutted on interlobular septa (88.2%) and had intracystic septa (13.6%) or protruding venules (39.5%) without cell proliferation or inflammation. The frequencies of these histological characteristics differed significantly from those seen in the lungs of patients with PSP (P < 0.05). Although the intrapulmonary BHDS cysts were smaller than the subpleural BHDS cysts (P < 0.001), there was no difference in size between them when there was no inflammation. The number of cysts diminished logarithmically and the proportion of cysts with inflammation increased as their individual sizes became greater (P < 0.05). CONCLUSIONS: These results imply that the BHDS cysts are likely to develop in the periacinar region, an anatomically weak site in a primary lobule, where alveoli attach to connective tissue septa. We hypothesize that the BHDS cysts possibly expand in size as the alveolar walls disappear at the alveolar-septal junction, and grow even larger when several cysts fuse.

An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features.

BACKGROUND: Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. METHODS: Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. RESULTS: All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p=0.001). The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions. Honeycombing with emphysema was also observed in 11 CPFE patients. CONCLUSIONS: TWCLs were only observed in the CPFE patients. They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE.

Diagnostic yields and safety of thoracoscopic cryobiopsies in Japan: A single-center retrospective observational study.

BACKGROUND: Thoracoscopy is useful for diagnosing unexplained pleural effusions. A sufficient specimen volume is often difficult to obtain using forceps biopsies (FBs) but can be obtained with pleural cryobiopsies (CBs). This study aimed to assess the utility and safety of CB during thoracoscopy in the Japanese population. METHODS: Patients who underwent thoracoscopic CBs at the Japanese Red Cross Medical Center between January 2017 and August 2023 were included in the study. Data were retrospectively analyzed, including clinical data, thoracoscopic findings, specimen size, diagnostic yield, and complications. The number of collected specimens and the freezing time were left to the discretion of the attending physician. RESULTS: Twenty-six patients underwent thoracoscopic CB. Specimens obtained by CB were larger than those obtained by FB. Primary lung cancer was the most common cause of pleural effusion, followed by malignant pleural mesothelioma. CB contributed to the diagnosis in 24 of 26 cases (92.3%) and FB contributed to the diagnosis in 11 of 18 cases (61.1%). Severe fibrosis could be diagnosed in all 3 cases by CB, but not by FB. The common complications of CB included bleeding at the biopsy site and atelectasis, but no severe complications occurred. CONCLUSIONS: The utility and safety of thoracoscopic CB for diagnosing pleural effusions in Japan were verified. The diagnostic yield, specimen size, and safety profile of CB support the diagnostic utility of this method.

Comparison of Schlemm's Canal Morphology Parameters Between Propensity Score-Matched Primary Open-Angle Glaucoma and Exfoliation Glaucoma.

Purpose: This study aimed to histologically compare the status of Schlemm's canal (SC) and Schlemm's canal endothelial (SCE) cells between trabeculectomy specimens from patients with primary open-angle glaucoma (POAG) and exfoliation glaucoma (EXG). Methods: A total of 182 eyes from 152 patients with POAG and 138 eyes from 116 patients with EXG underwent immunohistochemical staining for thrombomodulin. Equal numbers of cases were selected from both groups using propensity score matching. The following parameters were evaluated: total SC length, staining positive and negative SC length (PSC and NSC, respectively), opened and closed SC length, staining positive and opened SC length, staining positive and closed SC length, staining negative and opened SC length (NOSC), and staining negative and closed SC length. Results: After matching for age and gender, 87 cases were selected in each group. The EXG group had significantly higher preoperative IOP and medication scores. PSC was significantly longer in the POAG group, while NSC and NOSC were longer in the EXG group. Multiple regression analysis of these 174 cases revealed that PSC was significantly shorter in the EXG group. After matching for age, gender, preoperative IOP, and medication score, 64 cases were selected in each group, and NOSC was significantly longer in the EXG group. Conclusions: These findings suggest that in EXG, SCE loss occurs independently of background factors such as aging and medication use. The loss of SCE may have a more critical impact on IOP elevation in EXG compared to POAG.

Pathological study of archival lung tissues from five fatal cases of avian H5N1 influenza in Vietnam.

Highly pathogenic avian H5N1 influenza virus (H5N1) infection in humans causes acute respiratory distress syndrome, leading to multiple organ failure. Five fatal cases of H5N1 infection in Vietnam were analyzed pathologically to reveal virus distribution, and local proinflammatory cytokine and chemokine expression profiles in formalin-fixed, paraffin-embedded lung tissues. Our main histopathological findings showed diffuse alveolar damage in the lungs. The infiltration of myeloperoxidase-positive and/or CD68 (clone KP-1)-positive neutrophils and monocytes/macrophages was remarkable in the alveolar septa and alveolar spaces. Immunohistochemistry revealed that H5N1 mainly infected alveolar epithelial cells and monocytes/macrophages in lungs. H5N1 replication was confirmed by detecting H5N1 mRNA in epithelial cells using in situ hybridization. Quantitation of H5N1 RNA using quantitative reverse transcription PCR assays revealed that the level of H5N1 RNA was increased in cases during early phases of the disease. We quantified the expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8, regulated on activation normal T-cell expressed and secreted (commonly known as RANTES), and interferon-gamma-inducible protein of 10 kDa (IP-10) in formalin-fixed, paraffin-embedded lung sections. Their expression levels correlated with H5N1 RNA copy numbers detected in the same lung region. Double immunofluorescence staining revealed that TNF-α, IL-6, IL-8 and IP-10 were expressed in epithelial cells and/or monocytes/macrophages. In particular, IL-6 was also expressed in endothelial cells. The dissemination of H5N1 beyond respiratory organs was not confirmed in two cases examined in this study.

Invasion of histiocytic sarcoma into the spinal cord of HTLV-1 tax transgenic mice with HTLV-1-associated myelopathy/tropical spastic paraparesis-like disease.

Human T-cell leukemia virus type 1 (HTLV-1) can cause an aggressive malignancy known as adult T-cell leukemia/lymphoma (ATLL) as well as inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Transgenic (Tg) mice expressing HTLV-1 Tax also develop T-cell leukemia/lymphoma and an inflammatory arthropathy that resembles rheumatoid arthritis. We found that 8 of 297 Tax-Tg mice developed HAM/TSP-like disease with symmetrical paraparesis of the hind limbs, but these symptoms were absent in non-Tg littermates and in other mice strains at our animal facilities. We could perform detailed evaluations for five of these mice. These evaluations showed that the disease was not inflammatory, unlike that in HAM/TSP patients, but instead involved the invasion of histiocytic sarcoma cells into the lumbar spinal cord from the bone marrow where they had undergone extensive proliferation.

Immunohistochemical analysis of thoracic endometriosis.

Thoracic endometriosis is a rare disease responsible for catamenial pneumothorax. The immunohistochemical features of thoracic endometriosis are not well understood. An immunohistochemical examination of 84 diaphragmatic specimens of catamenial pneumothorax using antibodies against estrogen receptor (ER), progesterone receptor (PgR), CD10 and smooth muscle actin (SMA) was conducted. The endometrial tissue was small, and focally located around the chasm of the tendon on the side of the thoracic cavity. Endometrial stroma were detected in 84/84 (100%) of the specimens, endometrial glands were detected in 21/84 (25%) and smooth muscle was detected in 1/84 (1.2%). The endometrial stroma exhibited positive staining for ER in 74/84 (88.1%) of the specimens, PgR in 84/84 (100%), CD10 in 74/84 (88.1%) and SMA in 46/84 (54.8%). Because thoracic endometriosis is small in size, and only 25% of the resected tissue specimens were accompanied with the endometrial gland, an immunohistochemical analysis can be useful for their detection. The fact that over half of the thoracic endometrial stroma showed positive staining for SMA, and the existence of thoracic endometriosis accompanied by smooth muscle, indicated that some part of the thoracic endometriosis may have the ability to differentiate into smooth muscle, although further studies are needed to confirm this hypothesis.