Retrospective comparison between definitive stereotactic body radiotherapy and radical surgery for 538 patients with early-stage non-small cell lung cancer in a single institution.

Introduction: Survival information for stereotactic body radiotherapy (SBRT) and surgery for stage I non-small cell lung cancer (NSCLC) was examined. Methods: Stage I NSCLC patients who underwent surgery or SBRT between 2012 and 2016 were retrospectively enrolled in this single-institution study. Using the Kaplan--Meier method and Cox regression model, overall survival (OS) was estimated and compared. Results: Among 538 enrolled patients, compared to the surgery group (443), the SBRT group (95) had more complications (P = 0.01), worse performance status (P = 0.001), and were older (P < 0.001). Three-year OS was 70.5% post SBRT and 90.1% postsurgery. The 3-year cancer-specific survival (CSS) and disease-free survival (DFS) post SBRT and postsurgery were 92.7% vs. 92.3% and 61.1% vs 79.3%, respectively. Three-year locoregional and distant control rates post SBRT and postsurgery were 85.6% vs. 90.1% and 82.5% vs. 86.4%, respectively. Multivariate analysis using the Cox model, including age, T-stage, CCI, and C/T ratio and treatment, showed the surgery group's OS to be significantly superior to that of the SBRT group (HR of SBRT per surgery: 1.90, 95%CI: 1.12-3.21, P = 0.017). No significant differences were observed in rates of adverse events. Conclusion: Although OS was better in the surgery group, no differences in CSS existed. This analysis suggests the need for future studies that compare specific radical surgeries and SBRT in a prospective and randomized setting.

Novel SLC9A6 Variation in Female Carriers With Intellectual Disability and Atypical Parkinsonism.

BACKGROUND AND OBJECTIVES: Variations in SLC9A6 cause the X-linked neurologic disorder Christianson syndrome in males. Meanwhile, female carriers with SLC9A6 variations may remain asymptomatic or develop intellectual disability, behavioral problems, and psychiatric illnesses. Only a few female carriers have been reported to have associated atypical parkinsonism in late life. METHODS: We present a Japanese family with a novel SLC9A6 variation identified by quad whole-exome sequencing analysis and a reverse phenotyping strategy. The molecular and cellular impacts of the W89R variation in vitro were examined. RESULTS: The missense variation (c.265T>C, p.Trp89Arg) in SLC9A6 cosegregated with atypical parkinsonism and intellectual disability in female carriers of this family. The female carriers in this family presented with bradykinesia, rigidity, and tremor, predominately on the right side. We found that the W89R variation changed membrane traffic of NHE6-harboring vesicles, indicating potential involvement in the disease pathogenesis. DISCUSSION: This study might have revealed an example of a monogenic origin of atypical parkinsonism in females with SLC9A6 variations and draw attention to this understudied female-specific phenotype in clinical practice.

Radiotherapy for symptom palliation of splenomegaly in patients with haematological malignancies.

Splenomegaly severely compromises the quality of life of those affected. The aim of the present study was to describe the clinical characteristics of patients with haematological disorders who receive radiotherapy for splenomegaly, particularly focusing on the changes in spleen volume. The present study conducted a retrospective analysis of consecutive patients with haematological disorders who underwent splenic radiotherapy with palliative intent at the Department of Radiology of the University of Tokyo Hospital between June 2008 and June 2019. Pre- and post-radiotherapy spleen volumes were measured from computed tomography images. A total of 8 patients (5 men and 3 women) with a median age of 59 years (range, 46-76 years) were included. The median total prescription and fractional doses were 4.5 Gy (range, 1.5-10 Gy) and 0.78 Gy (range, 0.5-2.0 Gy), respectively. A total of 5 patients (62.5%) experienced a reduction in spleen volume. The mean ± SD spleen sizes pre- and post-radiotherapy were 1,887±1,011 and 1,368±577 ml, respectively. The mean variation rate in spleen volume was -19.1±24.7%, and the case with the most notable improvement in the present study exhibited a -52.4% change. Of the 5 patients who experienced pain prior to radiotherapy, 3 achieved pain relief, 1 did not experience any change and 1 patient was not assessed post-radiotherapy. Therefore, the findings of the present study revealed that palliative radiotherapy for splenomegaly may achieve symptom palliation and radiological volumetric effects in patients with haematological disorders.

Significance of glomerular cell apoptosis in the resolution of acute post-streptococcal glomerulonephritis.

BACKGROUND: Glomerular hypercellularity due to resident glomerular cell proliferation and leucocyte infiltration has been described in acute post-streptococcal glomerulonephritis (APSGN). APSGN usually resolves without progression. However, the mechanism of resolution remains to be determined. METHODS: Renal biopsy tissues from 15 patients with APSGN (obtained 1-31 days after disease onset) and five control patients with minor glomerular abnormality were evaluated with respect to glomerular resolution. Apoptotic cells were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) as well as by immunostaining of single-stranded DNA (ssDNA). RESULTS: The number of glomerular cells was high in the early-phase of APSGN and decreased over time. No TUNEL+ glomerular cells were found in control subjects, whereas prominent glomerular TUNEL+ cells were observed in APSGN patients, particularly in the early phase of the disease. The number of glomerular TUNEL+ cells decreased exponentially but was still prominent in renal tissue biopsied at 31 days after disease onset. Double staining for ssDNA and glomerular cell markers showed that glomerular apoptotic cells were predominantly mesangium and endothelial cells, with some neutrophils and macrophages. CONCLUSIONS: These results suggest that apoptosis exists in the glomerulus in patients with APSGN from the early to the late stages of the disease and contributes to the resolution of glomerular hypercellularity.

Improvements in treatment strategies for patients with antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis.

The course of rapidly progressive glomerulonephritis (RPGN) caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is often life-threatening, especially in the elderly when pulmonary involvement and/or severely impaired renal function are present. Corticosteroids and cyclophosphamide are the first-line treatment, but ironically infection, not vascular events such as hemorrhage, caused by the vasculitis itself, is the most common cause of death of RPGN patients. Several new treatment strategies, such as leukocytapheresis (LCAP) and intravenous immunoglobulin (IVIg), have become available during the past decade and these treatments have made it possible to treat high-risk RPGN patients without inducing serious immunosuppressive states. In the present paper we review recent clinical trials of LCAP and IVIg therapy in patients with pauci-immune/ANCA-associated RPGN, and show improved clinical outcomes after using these new treatment strategies in our institution.