Rationale:Bevacizumab—an inhibitor of vascular endothelial growth factor—is effective against various advanced cancers. However, it is associated with the development of hypertension and high-grade proteinuria during thrombotic microangiopathy of the kidney. In addition, there are several reports of immunoglobulin A deposition in the glomeruli, but the etiology is unclear.Patient concerns:A 67-year-old Japanese man with metastatic rectal cancer underwent low anterior rectal resection, followed by treatment with bevacizumab and SOX (S-1 plus oxaliplatin). Six months later, the patient developed hematuria, nephrotic syndrome, and purpura.Diagnoses:Renal biopsy revealed endocapillary proliferative glomerulonephritis. Immunofluorescence analyses showed granular mesangial deposition of galactose-deficient immunoglobulin A1. Skin biopsy revealed leukocytoclastic vasculitis.Interventions:We ceased bevacizumab treatment, while continuing the remaining chemotherapy regimen, as we suspected bevacizumab-induced nephropathy.Outcomes:Proteinuria and purpura improved immediately after cessation of bevacizumab. We identified this as a case of bevacizumab-induced immunoglobulin A vasculitis with nephritis.Lessons:To our knowledge, this is the first case of bevacizumab-related immunoglobulin A vasculitis with nephritis, as evidenced by galactose-deficient immunoglobulin A1. When a patient's urine tests are abnormal during bevacizumab treatment, clinicians should consider not only thrombotic microangiopathy but also vasculitis.

An 85-year-old woman presented with ataxia and deterioration of cognitive functions. She had no history of autoimmune diseases or viral infections. Magnetic resonance imaging showed a solitary mass lesion at the cerebral falx on contrast-enhanced T1-weighted imaging. Gross total resection of the lesion involving the dura mater was performed by bifrontal craniotomy. Histological examination showed diffuse infiltration of small lymphocytes and plasma cells. There was also some proliferation of large lymphocytes with folded nuclei, high-density chromatin, and inconspicuous nucleoli. The large atypical B lymphocytes did not demonstrate diffuse dense sheet findings. Meningothelial components were not detected. Immunohistochemistry was positive for pan B-cell antigens. The analysis of the kappa/lambda ratio indicated kappa immunoglobulin light chain-restricted B-cell proliferation. The final histopathological diagnosis was mucosa-associated lymphoid tissue lymphoma. Systemic screening examinations were then performed. Histological findings of the bone marrow showed normal findings without atypical lymphocytes. A chromosomal study of the bone marrow showed 46, XX. 18F fluoro-2-deoxyglucose positron emission tomography showed high accumulations at the left pterygoid muscle and the right transverse processes of the thoracic vertebrae, and mild accumulation at the right ilium bone, which indicated disseminated lesions. One year later, thickening of the dura mater was detected. Therefore, gamma knife surgery was performed. Two years later, she was alive without neurological deterioration, and magnetic resonance imaging showed no evidence of recurrence.

BACKGROUND:The information about long-term risks of hemorrhage and late adverse radiation effects (AREs) after stereotactic radiosurgery for brain arteriovenous malformations (AVMs) is lacking.OBJECTIVE:To evaluate the long-term risks of hemorrhage and late ARE rates in patients with AVM treated with Gamma Knife surgery (GKS).METHODS:We examined 1249 patients with AVM treated with GKS. The Spetzler–Martin grade was I in 313 patients (25%), II in 394 (32%), III in 458 (37%), and IV/V in 84 (7%). The median treatment volume was 2.5 cm3, and the median marginal dose was 20 Gy.RESULTS:The median follow-up period was 61 months. The 5- and 10-year nidus obliteration rates were 63% and 82%, respectively. The 5- and 10-year cumulative hemorrhage rates were 7% and 10%, respectively. The annual hemorrhage rate was 1.5% for the first 5 years post-GKS, which decreased to 0.5% thereafter. During the follow-up period, 42 symptomatic cyst formations/chronic encapsulated hematomas ([CFs/CEHs], 3%) and 3 radiation-induced tumors (0.2%) were observed. The 10- and 15-year cumulative CF/CEH rates were 3.7% and 9.4%, respectively.CONCLUSION:GKS is associated with reduced hemorrhage risk and high nidus obliteration rates in patients with AVM. The incidence of late AREs tended to increase over time. The most common ARE was CF/CEH, which can be safely removed; however, careful attention should be paid to the long-term development of fatal radiation-induced tumors.

Background/Aim: The aim of this study was to elucidate the relationship between the progression of bladder cancer (BCa) and TLR4 expression. Materials and Methods: The relationship between TLR4 expression and prognosis of BCa patients was analyzed using a publicly available database and immunohistochemical staining of clinical samples. The effect of TLR4 knockdown was also examined on the invasive capabilities of BCa cells. Finally, to investigate the biological function of TLR4, the gene expression profile of TLR4-depleted BCa cells was analyzed by microarray analysis. Results: Expression of TLR4 was inversely associated with prognosis of patients with invasive BCa, and depletion of TLR4 significantly enhanced the invasive capability of BCa cells. Gene expression profiling revealed that depletion of TLR4 led to high expression of epithelial differentiation genes. Furthermore, expression of TLR4 was found to be extremely low in areas of squamous differentiation. Conclusion: Low TLR4 expression was correlated with tumor progression.

OBJECTIVE The aim of this study was to evaluate whether endovascular embolization prior to stereotactic radiosurgery (SRS) has a negative impact on nidus obliteration for patients with arteriovenous malformations (AVMs). METHODS A total of 704 eligible patients with AVM who did not undergo prior surgery or radiotherapy were evaluated. Of these patients, 593 were treated with SRS only, and 111 were treated with embolization followed by SRS (E+SRS). Most patients in the E+SRS group (88%) underwent embolization with n-butyl-2-cyanoacrylate. In the comparison of radiosurgical outcomes between patients treated with SRS only and E+SRS, these groups were matched in a 1:1 ratio using propensity score matching to eliminate differences in basic characteristics. The primary outcome was to compare the nidus obliteration rates between the SRS-only and E+SRS groups. The secondary outcomes were the comparison of cumulative hemorrhage rates and the incidence of cyst formation or chronic encapsulated hematoma after SRS between these groups. RESULTS In the unmatched cohorts, the actuarial 3-, 5-, and 8-year nidus obliteration rates after a single SRS session were 49.6%, 69.4%, and 74.1% in the SRS-only group, respectively, and 30.7%, 50.9%, and 68.6% in the E+SRS group, respectively (p = 0.001). In the matched cohort of 98 patients in each group, the rates were 47.1%, 62.0%, and 69.6% in the SRS-only group and 32.5%, 55.3%, and 75.0% in the E+SRS group, respectively (p = 0.24). There was no significant difference in either cumulative hemorrhage or the incidence of cyst formation or chronic encapsulated hematoma between the groups. CONCLUSIONS Pre-SRS embolization did not affect nidus obliteration rates, cumulative hemorrhage rates, or the incidence of cyst formation or chronic encapsulated hematoma as late adverse radiation effects in patients with AVM treated with SRS.