An Evaluation of the Efficacy of Preoperative Therapy for Thoracic Esophageal Carcinoma Using Endoscopic Ultrasonography

Abstract: We performed endoscopic ultrasonography (EUS) to assess the therapeutic efficacy of thoracic esophageal carcinoma treatment and compared this assessment with that of histology. The subjects were 43 patients who underwent surgical resection following preoperative chemotherapy for advanced thoracic esophageal carcinoma. The region of maximal thickness and the cross-sectional area of the tumor were measured, and the percent reduction was taken to be the degree of reduction. Total assessment of metastatic lymph nodes was made on the basis of the degree of reduction in the major axis and cross-sectional area, and the three elements of morphology, border echo and inner echo. The histological findings were classified into Grades 0 through 3 according to criteria for the management of esophageal carcinoma and compared with the EUS findings. The reduction in tumor thickness was 30% or less in 16 patients, 14 (87.5%) of whom had Grades of 0 to 1. The degree of reduction was greater than 50% in 17 patients, 15 (88.2%) of whom had Grades 2 to 3. The degree of reduction was 60% or greater in eight patients, six (75%) of whom had a Grade of 3. Reduction in the cross-sectional area was less than 50% in 19 patients, 16 (84.2%) of whom had Grades of 0 to 1. Of the 19, all who showed a reduction of 30% or less had Grades of 0 to 1. The reduction in cross-sectional area was greater than 50% in 24 patients, 20 (83.3%) of whom had Grades of 2 to 3. A significant difference was noted in the correlation between reduction in thickness and histological assessment between Grades 0 to 1 and Grade 2 (p<0.01) and between of Grades 2 and 3 (p<0.02). The correlation between reduction in cross-sectional area and histological assessment was similar to that for reduction in thickness. None of the methods produced satisfactory results in relation to assessment of metastatic lymph nodes. Assessment of accuracy by down-staging did not prove useful.     

Use of inhaled fluticasone propionate to control respiratory manifestations of relapsing polychondritis

Effective management of respiratory tract involvement is very important in improving the prognosis of relapsing polychondritis (RPC). This case report describes a 19-year-old patient with RPC, who required frequent hospitalization due to recurrent exacerbations of airway obstruction. Use of high-dose fluticasone propionate effectively reduced the amount of oral corticosteroid necessary to control inflammation of the airway mucosa and dramatically decreased the patient's obstructive airway impairment. This report is the first illustrating the effectiveness and safety of inhaled corticosteroids in the control of the respiratory manifestations of RPC.     

TNF-α, nitric oxide and IFN-γ are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii

We previously reported that genetic susceptibility of mice to peroral infection with T. gondii is associated with CD4+ T cell-dependent, interferon (IFN)-gamma-mediated necrosis of their small intestine. We examined the role of tumour necrosis factor (TNF)-alpha and nitric oxide (NO), in addition to IFN-gamma. At 7 days after infection, a marked increase in CD4+ T cells was observed in lamina propria mononuclear cells (LPC) of the small intestine as compared with normal mice, and significantly greater amounts of mRNA for IFN-gamma, TNF-alpha, and inducible NO synthase (iNOS) were detected in LPC of the small intestine of infected than uninfected animals. Treatment of infected mice with anti-TNF-alpha monoclonal antibody (mAb) or the iNOS inhibitor, aminoguanidine, prevented necrosis and prolonged time to death. Infected iNOS-targeted mutant mice did not develop the disease whereas infected, control mice did. Treatment with anti-TNF-alpha mAb did not affect the expression of IFN-gamma in the LPC but inhibited expression of iNOS in the infected mice, indicating the role of TNF-alpha in the induction of iNOS. These results suggest that NO induced by a combination of IFN-gamma and TNF-alpha through activation of iNOS is a critical mediator of intestinal pathology and contributes to early mortality in genetically susceptible mice.     

Ultrastructural study on the follicle-associated epithelium of nasal-associated lymphoid tissue in specific pathogen-free (SPF) and conventional environment-adapted (SPF-CV) rats

Membranous (M) cells in follicle-associated epithelium (FAE) play an important role in the mucosal immunity through transport of a variety of foreign antigens to the underlying mucosa-associated lymphoid tissue (MALT). We aimed to investigate the ultrastructure of M cells in the FAE covering nasal-associated lymphoid tissue (NALT) both in specific pathogen-free (SPF) rats and in conventional environment-adapted (SPF-CV) rats aged 8–38 wk. In NALT of both SPF and SPF-CV rats, FAE included the nonciliated microvillous cell, which appears to be an analogue of M cell previously described in other MALT. In SPF rats, M cells increased in number only slightly with age, and they maintained morphological uniformity irrespective of age. In SPF-CV rats, M cells selectively increased in number resulting in prominent expansion of FAE surface area in parallel with the duration of maintenance in a conventional environment. In addition, M cells in SPF-CV rats showed heterogeneity in their surface morphology such as the length and number of microvilli and cell surface area and outline. In addition, the FAE was stratified by various subtypes of M cells, which were characterised by several subcellular alterations including the presence of many keratin filaments, homogeneous dark bodies and extensive cytoplasmic interfoliation with wide intercellular spaces filled with amorphous proteinaceous material. These characteristics of M cells in SPF-CV rat were intimately related with a preferential influx of immunocompetent cells into the FAE, which was not seen or was very rare in SPF rats irrespective of age. The results suggest the possibility that NALT may effectively carry out the mucosal immune response against antigenic stimuli of different magnitude through the unique dynamics of M cells which seem to be influenced by the infiltration of immunocompetent cells.     

ORIGINAL ARTICLE: Detection of early amnestic mild cognitive impairment without significantly objective memory impairment: a case‐controlled study

Background: We encountered eight early amnestic mild cognitive impairment (aMCI) patients (early MCI group) who did not fulfill the diagnostic criteria for aMCI. We compared the scores of neuropsychological examinations as well as the cerebral metabolic rate for glucose consumption (CMRglc) decrease on ¹⁸F‐FDG PET examination between the early MCI group and 10 aMCI patients (MCI group) or six normal elderly subjects (normal group), to examine whether the current diagnostic criteria can detect early‐stage aMCI. Methods: The three groups underwent Mini‐Mental State Examination (MMSE), Wechsler Adult Intelligence Scale – Third Edition (WAIS‐III), Wechsler Memory Scale Revised (WMS‐R), magnetic resonance imaging and 18F‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) examinations. Results: The early MCI group did not show significant memory impairment of 1.0 SD or other cognitive dysfunctions on neuropsychological examinations, and did not fulfill the diagnostic criteria of aMCI. With one‐way anova and Tukey's HSD post‐hoc test, the early MCI group showed the highest scores for WAIS‐III, whereas the MCI group showed the lowest scores for WMS‐R, although there were no significant differences between the early MCI and normal groups. In order to show a discrepancy in scores between WAIS‐III and WMS‐R, we subtracted the scores of WMS‐R from WAIS‐III. Consequently, the normal group showed significantly smaller differences in scores than the other groups, although there were no significant differences between the early MCI and MCI groups. ¹⁸F‐FDG PET recognized a CMRglc decrease in the posterior cingulate gyrus and/or part of the parietotemporal area in both the MCI and early MCI groups, of which the extent and magnitude were weaker in the early MCI group. The normal group did not show a significant CMRglc. Conclusions: The early MCI group should be included in aMCI not only based on the discrepancy between intelligence and memory scores, but also based on the ¹⁸F‐FDG PET findings. The combination of these examinations would make it possible to diagnose early‐stage aMCI.     

Superoxide dismutase in psoriasis, squamous cell carcinoma and basal cell epithelioma: an immunohistochemical study

Monoclonal antibodies against human Cu,Zn-superoxide dismutase (SOD) and Mn-SOD were used to stain frozen sections of normal and abnormal human skin. In normal human epidermis, the Cu,Zn-SOD antibody almost exclusively stained the basal cells. Mn-SOD antibody weakly stained the whole of the epidermis but more predominantly the basal cell layer. In psoriasis, Cu,Zn-SOD antibody mainly stained the basal cells of the lowest parts of the elongated rete ridges. Basal cells corresponding to the tip of the dermal papillae were weakly stained. Mn-SOD staining was considerably decreased in the psoriatic epidermis. In squamous cell carcinoma, staining with both Cu,Zn-SOD and Mn-SOD antibodies was decreased, and single cells positive for Cu,Zn-SOD were scattered throughout the tumour nests. In basal cell epithelioma, Cu,Zn-SOD staining was intense and diffusely distributed throughout the tumour nests, while Mn-SOD staining was absent.     

Histochemical localisation of versican, aggrecan and hyaluronan in the developing condylar cartilage of the fetal rat mandible

We investigated the histochemical localisation of versican, aggrecan and hyaluronan in the developing condylar cartilage of the fetal rat mandible at d 15–17 of gestation. At d 15 of gestation, immunostaining for versican was detected in the anlage of the future condylar process (condylar anlage), although the staining intensity showed a considerable regional variation. At d 16 of gestation, a metachromatically stained matrix firstly appeared in the condylar anlage. Aggrecan, hyaluronan and versican were simultaneously detected in this newly formed condylar cartilage. At d 17 of gestation, immunostaining for versican became restricted to the perichondrium and was barely detected in the cartilage. Colocalisation of versican and aggrecan was also seen in the cranial base cartilage at d 14 of gestation. These results indicate that although versican is replaced by aggrecan during the transition from prechondrogenic tissue to cartilage, both molecules were temporally colocalised in the newly formed cartilage. A hyaluronan-rich, low-versican area was identified in the posterior end of the condylar anlage during d 15–17 of gestation. The existence of this area is a unique structural feature of the developing condylar cartilage.     

Regulatory mechanisms of C4b‐binding protein (C4BP)α and β expression in rat hepatocytes by lipopolysaccharide and interleukin‐6

Summary. Background: C4b‐binding protein (C4BP), a multimeric protein structurally composed of α chains (C4BPα) and a β chain (C4BPβ), regulates the anticoagulant activity of protein S (PS). Patients with sepsis have increased levels of plasma C4BP, which appears to be induced by interleukin (IL)‐6. However, it is not fully understood how lipopolysaccharide (LPS) and IL‐6 affect the plasma C4BP antigen level and C4BPα and C4BPβ expression in hepatocytes. Objectives: To assess the effect of LPS and IL‐6 on plasma C4BP, PS–C4BP complex levels, PS activity, and C4BP expression by rat liver in vivo and on C4BP expression by isolated rat hepatocytes in vitro. Results: Plasma C4BP antigen level transiently decreased from 2 to 12 h after LPS (2 mg kg^?1) injection, and then it abruptly increased up to 24 h after LPS injection. Plasma C4BP antigen level increased until 8 h after IL‐6 (10 μg kg^?1) injection, and then gradually decreased up to 24 h after IL‐6 injection. LPS significantly decreased the protein and mRNA expression of both C4BPα and C4BPβ in rat hepatocytes, and this effect was inhibited by NFκB and MEK/ERK inhibitors. IL‐6 mediated increase in C4BPβ expression in rat hepatocytes, which leads to increased plasma PS–C4BP complex level and to decreased plasma PS activity, was inhibited by inhibition of STAT‐3. Conclusion: LPS decreases both C4BPα and C4BPβ expression via the NFκB and MEK/ERK pathways, whereas IL‐6 specifically increases C4BPβ expression via the STAT‐3 pathway, causing an increase in plasma PS–C4BP complex, and thus decreasing the anticoagulant activity of PS.     

Marked Reduction of Cerebral Vasospasm with Intrathecal Urokinase Infusion Therapy after Endovascular Coil Embolization of the Aneurysmal Subarachnoid Hemorrhage: A Case Series

Delayed cerebral vasospasms after subarachnoid hemorrhage (SAH) are a risk factor for poor prognosis after successful treatment of ruptured intracranial aneurysms. Different strategies to remove clots from the subarachnoid space and prevent vasospasms have different outcomes. Intrathecal urokinase infusion therapy combined with endovascular treatment (EVT) can reduce the incidence of symptomatic vasospasms. To analyze the relationship between symptomatic vasospasms and residual SAHs after urokinase infusion therapy, we retrospectively reviewed the records of 348 consecutive patients managed with EVT and intrathecal urokinase infusion therapy for aneurysmal SAH at our institution between 2010 and 2021. Among them, 163 patients met the study criteria and were classified into two groups according to the presence of residual SAH in the cisterns, Sylvian fissures, and frontal interhemispheric fissure. The incidence of symptomatic vasospasms and the clinical outcomes were assessed. In total, eight (5.0%) patients developed symptomatic vasospasms. Patients with symptomatic vasospasms had a significantly higher incidence of residual SAH in the Sylvian or frontal interhemispheric fissures than those without (P <.0001). No patient with SAHs resolved by urokinase infusion therapy developed symptomatic vasospasms. However, the two groups did not differ significantly in terms of modified Rankin scale scores at discharge. Treatment with intrathecal urokinase infusion after EVT for aneurysmal SAH can substantially reduce the risk of clinically evident vasospasms.