Automated volumetry of meningiomas in contrast-enhanced T1-Weighted MRI using deep learning.

BACKGROUND: Meningiomas are among the most common intracranial tumors. In these tumors, volumetric assessment is not only important for planning therapeutic intervention but also for follow-up examination.However, a highly accurate automated volumetric method for meningiomas using single-modality magnetic resonance imaging (MRI) has not yet been reported. Here, we aimed to develop a deep learning-based automated volumetry method for meningiomas in MRI and investigate its accuracy and potential clinical applications. METHODS: For deep learning, we used MRI images of patients with meningioma who were referred to Osaka University Hospital between January 2007 and October 2020. Imaging data of eligible patients were divided into three non-overlapping groups: training, validation, and testing. The model was trained and tested using the leave-oneout cross-validation method. Dice index (DI) and root mean squared percentage error (RMSPE) were measured to evaluate the model accuracy. Result: A total of 178 patients (64.6 ± 12.3 years [standard deviation]; 147 women) were evaluated. Comparison of the deep learning model and manual segmentation revealed a mean DI of 0.923 ± 0.051 for tumor lesions. For total tumor volume, RMSPE was 9.5 ± 1.2%, and Mann-Whitney U test did not show a significant difference between manual and algorithm-based measurement of the tumor volume (p = 0.96). CONCLUSION: The automatic tumor volumetry algorithm developed in this study provides a potential volume-based imaging biomarker for tumor evaluation in the field of neuroradiological imaging, which will contribute to the optimization and personalization of treatment for central nervous system tumors in the near future.

The Usefulness of Surgical Titanium Microclips for Mucosal Repair in the Frontal Sinus Using ORBEYE: A Technical Note.

Bifrontal craniotomy frequently involves opening the frontal sinus and mucosal injury. We report a new technique for mucosal repair in the frontal sinus using surgical titanium microclips. Six consecutive patients who underwent bifrontal craniotomy with frontal sinus exposure and mucosal injury underwent mucosal repair using surgical titanium microclips between April 2019 and August 2022. In all cases, the frontal sinus mucosa was peeled from the inner walls of the frontal sinus to ensure sufficient mucosal margin for clipping using ORBEYE. The repair was accomplished with the microclips in all cases. We also sealed the mucosal wound using fibrin glue and sufficiently filled the frontal sinus with bone debris, resulting in zero incidence of postoperative liquorrhea in all cases. Repairing the mucosa using surgical titanium microclips using ORBEYE may be a simple and quick technique when the frontal sinus mucosa is injured during craniotomy.

A resected case of acinar cell carcinoma of the pancreas with liver metastasis following chemotherapy using modified FOLFIRINOX.

BACKGROUND: Acinar cell carcinoma of the pancreas is a rare exocrine malignancy representing less than 1% of all pancreatic neoplasms. It has been reported that it responds to treatment differently from pancreatic ductal adenocarcinoma and the treatment algorithm for acinar cell carcinoma usually depends on the stage of the respective tumor and the patient's current status. CASE PRESENTATION: A 60-year-old man presented with upper abdominal pain and anorexia. Abdominal ultrasonography showed a large-sized hepatic mass and he was referred to our hospital. Contrast-enhanced computed tomography demonstrated a 110-mm low-density area occupying the right hemi-liver and an enhanced mass of 70 × 56 mm in the tail of the pancreas, which seemed to directly infiltrate into the spleen. The case was diagnosed as acinar cell carcinoma with a simultaneous liver metastasis identified by liver biopsy. Upfront resection of pancreatic cancer with distant metastasis might not be considered as an optimal choice, and in this case chemotherapy was administered prior to curative resection. Chemotherapy using the modified FOLFIRINOX regimen was undertaken, resulting in a partial remission; the liver tumor reduced in size from 110 to 47 mm and the pancreatic tumor from 70 to 40 mm. The patient then safely underwent curative hepatic resection with distal pancreato-splenectomy. Histological examinations revealed small-sized atypical cells with large nuclei that had formed acinar patterns, and immunostaining with trypsin was positive in tumor cells, which was in accordance with acinar cell carcinoma. More than 3 years later, the patient is doing well without any recurrence. CONCLUSION: Aggressive and curative surgery in combination with chemotherapy such as FOLFIRINOX could be a treatment option to achieve long-term survival in cases of acinar cell carcinoma with liver metastases.

Impact of postoperative complications on long-term survival in bladder cancer patients.

OBJECTIVE: To determine the impact of postoperative complications on long-term survival outcomes in patients with bladder cancer undergoing radical cystectomy. METHODS: This retrospective multi-institutional study included 766 bladder cancer patients who underwent radical cystectomy between 2011 and 2017. Patient characteristics, perioperative outcomes, all complications within 90 days after surgery and survival outcomes were collected. Each complication was graded based on the Clavien-Dindo system, and grouped using a standardized grouping method. The Comprehensive Complication Index, which incorporates all complications into a single formula weighted by their severity, was utilized. Overall survival and recurrence-free survival (local, distant or urothelial recurrences) were stratified by Comprehensive Complication Index (high: ≥26.2; low: <26.2). A multivariate model was utilized to identify independent prognostic factors. RESULTS: The incidence of any and major complications (≥Clavien-Dindo grade III) was 70 and 24%, respectively. In terms of Comprehensive Complication Index, 34% (261/766) of the patients had ≥26.2. Patients with Comprehensive Complication Index ≥ 26.2 had shorter overall survival (4-year, 59.5 vs. 69.8%, respectively, log-rank test, P = 0.0037) and recurrence free survival (51.9 vs. 60.1%, respectively, P = 0.0234), than those with Comprehensive Complication Index < 26.2. The Cox multivariate model identified the age, performance status, pT-stage, pN-stage and higher CCI (overall survival: HR = 1.35, P = 0.0174, recurrence-free survival: HR = 1.26, P = 0.0443) as independent predictors of both overall survivial and recurrence-free survival. CONCLUSIONS: Postoperative complications assessed by Comprehensive Complication Index had adverse effects on long-term survival outcomes. Physicians should be aware that major postoperative complications can adversely affect long-term disease control.

Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer.

Androgen deprivation therapy is given to suppress prostate cancer growth; however, some cells continue to grow hormone-independently as castration-resistant prostate cancer (CRPC). Sulfated glycosaminoglycans promote ligand binding to receptors as co-receptors, but their role in CRPC remains unknown. Using the human prostate cancer cell line C4-2, which can proliferate in hormone-dependent and hormone-independent conditions, we found that epidermal growth factor (EGF)-activated EGFR-ERK1/2 signaling via 3-O-sulfated heparan sulfate (HS) produced by HS 3-O-sulfotransferase 1 (HS3ST1) is activated in C4-2 cells under hormone depletion. Knockdown of HS3ST1 in C4-2 cells suppressed hormone-independent growth, and inhibited both EGF binding to the cell surface and activation of EGFR-ERK1/2 signaling. Gefitinib, an EGFR inhibitor, significantly suppressed C4-2 cell proliferation and growth of a xenografted C4-2 tumor in castrated mouse. Collectively, our study has revealed a mechanism by which cancer cells switch to hormone-independent growth and identified the key regulator as 3-O-sulfated HS.

Mice lacking nucleotide sugar transporter SLC35A3 exhibit lethal chondrodysplasia with vertebral anomalies and impaired glycosaminoglycan biosynthesis.

SLC35A3 is considered an uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) transporter in mammals and regulates the branching of N-glycans. A missense mutation in SLC35A3 causes complex vertebral malformation (CVM) in cattle. However, the biological functions of SLC35A3 have not been fully clarified. To address these issues, we have established Slc35a3-/-mice using CRISPR/Cas9 genome editing system. The generated mutant mice were perinatal lethal and exhibited chondrodysplasia recapitulating CVM-like vertebral anomalies. During embryogenesis, Slc35a3 mRNA was expressed in the presomitic mesoderm of wild-type mice, suggesting that SLC35A3 transports UDP-GlcNAc used for the sugar modification that is essential for somite formation. In the growth plate cartilage of Slc35a3-/-embryos, extracellular space was drastically reduced, and many flat proliferative chondrocytes were reshaped. Proliferation, apoptosis and differentiation were not affected in the chondrocytes of Slc35a3-/-mice, suggesting that the chondrodysplasia phenotypes were mainly caused by the abnormal extracellular matrix quality. Because these histological abnormalities were similar to those observed in several mutant mice accompanying the impaired glycosaminoglycan (GAG) biosynthesis, GAG levels were measured in the spine and limbs of Slc35a3-/-mice using disaccharide composition analysis. Compared with control mice, the amounts of heparan sulfate, keratan sulfate, and chondroitin sulfate/dermatan sulfate, were significantly decreased in Slc35a3-/-mice. These findings suggest that SLC35A3 regulates GAG biosynthesis and the chondrodysplasia phenotypes were partially caused by the decreased GAG synthesis. Hence, Slc35a3-/- mice would be a useful model for investigating the in vivo roles of SLC35A3 and the pathological mechanisms of SLC35A3-associated diseases.

Cisplatin resistance driver claspin is a target for immunotherapy in urothelial carcinoma.

Bladder cancer is a major and fatal urological disease. Cisplatin is a key drug for the treatment of bladder cancer, especially in muscle-invasive cases. In most cases of bladder cancer, cisplatin is effective; however, resistance to cisplatin has a significant negative impact on prognosis. Thus, a treatment strategy for cisplatin-resistant bladder cancer is essential to improve the prognosis. In this study, we established a cisplatin-resistant (CR) bladder cancer cell line using an urothelial carcinoma cell lines (UM-UC-3 and J82). We screened for potential targets in CR cells and found that claspin (CLSPN) was overexpressed. CLSPN mRNA knockdown revealed that CLSPN had a role in cisplatin resistance in CR cells. In our previous study, we identified human leukocyte antigen (HLA)-A*02:01-restricted CLSPN peptide by HLA ligandome analysis. Thus, we generated a CLSPN peptide-specific cytotoxic T lymphocyte clone that recognized CR cells at a higher level than wild-type UM-UC-3 cells. These findings indicate that CLSPN is a driver of cisplatin resistance and CLSPN peptide-specific immunotherapy may be effective for cisplatin-resistant cases.

Growth risk classification and typical growth speed of convexity, parasagittal, and falx meningiomas: a retrospective cohort study.

OBJECTIVE: Meningiomas are the most common primary intracranial tumors, and their clinical and biological characteristics vary by location. Convexity, parasagittal, and falx meningiomas account for approximately 50%-65% of intracranial meningiomas. Focusing only on these locations, the aim of this study was to determine the typical speed of tumor growth, to assess the growth risk, and to show the possible tumor volume that many lesions can reach after 5 years. METHODS: Patients with radiologically suspected convexity, parasagittal, or falx meningiomas at the authors' institution were studied retrospectively. The relative growth rate (RGR) and annual volume change (AVC) were calculated from MRI at more than 3-month intervals. Based on sex, age, and signal intensity on T2-weighted MRI, the cases were classified into three groups: extremely high-growth, high-growth, and low-growth groups. RESULTS: The data of 313 cases were analyzed. The median RGR and AVC for this entire cohort were 6.1% (interquartile range [IQR] 2.4%-16.0%) and 0.20 (IQR 0.04-1.18) cm3/year, respectively. There were significant differences in sex (p = 0.018) and T2-weighted MRI signal intensity (p < 0.001) for RGR, and T2-weighted MRI signal intensity (p < 0.001), tumor location (p = 0.025), and initial tumor volume (p < 0.001) for AVC. The median RGR and AVC were 17.5% (IQR 8.3%-44.1%) and 1.05 (IQR 0.18-3.53) cm3/year, 8.2% (IQR 2.9%-18.6%) and 0.33 (IQR 0.06-1.66) cm3/year, and 3.4% (IQR 1.2%-5.8%) and 0.04 (IQR 0.02-0.21) cm3/year for the extremely high-growth, high-growth, and low-growth groups, respectively, with a significant difference among the groups (p < 0.001). A 2.24-times, or 5.24 cm3, increase in tumor volume over 5 years was typical in the extremely high-growth group, whereas the low-growth group showed little change in tumor volume even over a 5-year follow-up period. CONCLUSIONS: For the first time, the typical speed of tumor growth was calculated, focusing only on patients with convexity, parasagittal, and falx meningiomas. In addition, the possible tumor volume that many lesions in these locations can reach after 5 years was shown based on objective indicators. These results may allow clinicians to easily detect lesions that require frequent follow-up or early treatment by determining whether they deviate from the typical range of the growth rate, similar to a growth chart for children.

Validation of the Japanese version of the Body Image Scale for bladder cancer patients.

The Body Image Scale (BIS) is a 10-item tool that measures the body images of cancer patients. This study aims to validate the Japanese version of the BIS for bladder cancer patients. A multicenter cross-sectional survey was used to identify the participants, which included Japanese bladder cancer patients. The percentage of missing responses, internal consistency, and known-group validity were evaluated. The correlations between the BIS and two HRQOL instruments (the Bladder Cancer Index and the SF-12) were assessed to determine convergent validity. Among 397 patients, 221 patients were treated by transurethral resection of bladder tumor (TURBT) endoscopically, 49 patients underwent cystectomy with neobladder, and 127 patients underwent cystectomy involving stoma. The percentage of missing responses in the BIS ranged from 8.1 to 15.6%. Cronbach's α coefficient was 0.924. Higher BIS scores indicate negative body image, and the median BIS score for patients with native bladders after TURBT (0.5) was significantly lower than those of the patients with neobladder (4.0) and stoma formation (7.0), which indicated the discriminatory ability of the BIS. Each domain of the Bladder Cancer Index and the role summary score of the SF-12 correlated to the BIS scores, which confirmed the convergent validity. A range of BIS scores were identified among patients who reported similar physical summary scores and mental summary scores of the SF-12. This study confirmed the reliability and validity of the Japanese version of the BIS for bladder cancer patients.

Circulating miRNA profiles in mice plasma following flavonoid intake.

BACKGROUND: Polyphenols, including flavonoids, have been the focus of numerous studies that have revealed diverse health benefits. MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that function as posttranscriptional regulators of gene expression. miRNAs can be detected in the blood and these so-called circulating miRNAs are potential biomarkers of various diseases. This study aimed to explore circulating miRNAs in plasma as a means to predict the biological effects of functional food ingredients. METHODS AND RESULTS: We used miRNA microarray analysis to compare plasma miRNA levels in mice orally administered three flavonoids (daidzein, quercetin, and delphinidin). Several miRNAs were differentially expressed in plasma from mice in each treatment group compared with the vehicle-treated group. The plasma levels of miR-25-5p, miR-146b-5p, and miR-501-3p were increased in the flavonoid-treated and the plasma levels of miR-148b-3p, miR-669e-5p, and miR-3962 were decreased. CONCLUSIONS: Our findings suggested that flavonoids alter miRNA expression in plasma and identified promising plasma miRNAs for assessing the functionality of flavonoids.

Cerebellopontine angle metastasis of a neuroendocrine tumor mimicking vestibular schwannoma: A case report.

Background: Neuroendocrine tumors (NETs) are uncommon neoplasms arising from neuroendocrine cells and are rarely associated with intracranial metastases. Case Description: We discuss the case of a 74-year-old woman with a right CPA tumor. She had a history of retroperitoneal NET, but was diagnosed with vestibular schwannoma due to a right-sided hearing loss and a right CPA tumor along the VII and VIII nerves. After a 3-year follow-up, she presented with repetitive vomiting, a 1-month history of gait instability, and a 3-month history of general fatigue. Brain imaging revealed tumor growth and edematous changes in the right cerebellum. She underwent retrosigmoid craniotomy and partial resection. Histopathological examination revealed metastatic NET. She underwent stereotactic radiosurgery for residual lesion and, at 11 months of follow-up, the lesion was confirmed to have shrunk on magnetic resonance imaging (MRI). Conclusion: This is the first case to report the natural course of cerebellopontine metastasis of a NET. The differential diagnosis of CPA tumors is diverse, and, in our case, we suspected a vestibular schwannoma because of the typical symptoms and imaging features. However, the tumor grew relatively faster than expected and showed intratumoral hemorrhage during the 3-year follow-up. Therefore, in patients with a history of a NET, a careful follow-up is advisable even for lesions highly suspected to be another benign tumor on MRI. Careful follow-up imaging and appropriate treatment strategies were useful to manage the brain metastasis. Although NETs metastasizing to the CPA are extremely rare, this possibility should be considered when patients with NETs have intracranial lesions.

Sesame lignans upregulate glutathione S-transferase expression and downregulate microRNA-669c-3p.

Oxidative stress is associated with aging and pathologies such as cardiovascular diseases, Alzheimer's disease, and cancer. Glutathione S-transferase (GST), a family of detoxification enzymes, plays a crucial role in countering oxidative stress. Therefore, there is a need for the development of physiologically functional foods and agricultural products, which enhance GST activity. Sesamin and episesamin are major lignans in refined sesame oil that exhibit beneficial properties including antioxidative stress effects. A previous study showed that sesamin upregulated GST activity. This study aimed to elucidate the mechanism underlying the GST activity enhancement elicited by sesame lignans. C57BL/6J mice were orally administered 20 mg/kg body weight sesame lignans (sesamin:episesamin=1:1) for 7 days. Oral administration of sesame lignans increased the GST activity in the mouse liver. Furthermore, the lignans upregulated GSTA1, GSTA4, and GSTM4 protein expression. Microarray analysis revealed that sesame lignans changed the expression of various microRNAs (miRNAs) (84 upregulated, 19 downregulated). We also found 16 miRNAs, including miR-669c-3p, that may negatively regulate GST expression among the 19 miRNAs with reduced expression caused by the sesame lignans. miR-669c is reportedly negatively correlated with GST. Additionally, we transfected NMuLi cells with an miR-669c-3p mimic and evaluated the effect of miR-669c-3p on GST mRNA and protein expressions. The results showed that the miR-669c-3p mimic suppressed the mRNA and protein levels of GSTA4 and GSTM4. In conclusion, sesame lignans increased GST protein expression and activity and downregulated miRNAs, including miR-669c-3p, which is a possible suppressor of GST.

Favorable response to pembrolizumab in granulocyte colony-stimulating factor-producing upper urinary tract urothelial carcinoma.

INTRODUCTION: Granulocyte colony-stimulating factor-producing upper urinary tract urothelial carcinoma is rare, with a poor prognosis. Advanced urothelial carcinoma is currently treated with immune checkpoint inhibitors, whose efficacy for granulocyte colony-stimulating factor-producing upper urinary tract urothelial carcinoma remains unclear. CASE PRESENTATION: A 66-year-old male diagnosed with clinical stage T3N1M0 urothelial carcinoma of the right ureter with giant hydronephrosis underwent right radical nephroureterectomy. Local recurrence, leukocytosis, and elevated serum granulocyte colony-stimulating factor levels were observed approximately 3 months after surgery. Chemotherapy was started but failed to control the disease. Therefore, pembrolizumab was chosen as the second-line treatment. After this treatment, the blood leukocyte count rapidly normalized, and a clinically favorable response was achieved. There was no recurrence 10 months after the beginning of pembrolizumab treatment, which is still ongoing. CONCLUSION: Pembrolizumab may be a treatment option for advanced granulocyte colony-stimulating factor-producing upper urinary tract urothelial carcinoma.

Characteristics of false-positive lesions in evaluating colorectal liver metastases on gadoxetic acid-enhanced magnetic resonance imaging.

PURPOSE: Gadoxetic acid-enhanced MRI (Gd-EOB-MRI) shows higher sensitivity for colorectal liver metastases (CRLM) than contrast-enhanced computed tomography (CECT). However, the details of false-positive lesions for each imaging modality are unknown. METHODS: Cases undergoing hepatectomy for CRLM following a preoperative evaluation with both CECT and Gd-EOB-MRI between July 2008 and December 2016 were reviewed. The false-positive and false-negative rates were assessed for each modality, and the characteristics of false-positive lesions were evaluated. RESULTS: We evaluated 275 partial hepatectomies in 242 patients without preoperative chemotherapy. Among the 275 hepatectomies, 546 lesions were recognized by CECT and/or Gd-EOB-MRI. The false-positive rates for CECT and Gd-EOB-MRI were 4% (18/422) and 7% (37/536), respectively. The size of false-positive lesions was significantly smaller than that of correctly diagnosed lesions (median: 28 mm [3-120 mm] vs 7.6 mm [320 mm], P < 0.001). Compared with the 233 correctly diagnosed lesions ≤ 20 mm in diameter, false-positive lesions were more frequently located near the liver surface or vasculobiliary structures than true lesions (33/37 [89%] vs 149/233 [64%], respectively; P = 0.0021). CONCLUSION: Gd-EOB-MRI had a 7% false-positive rate. A small size and tumor location near the surface or near vasculobiliary structures were associated with false positivity.

Distribution of Amniotic Epithelial Cells After Intraportal Infusion in a Rat Model.

BACKGROUND: Human amniotic epithelial cells (hAECs) are increasingly gaining attention as novel sources for cell transplantation. In clinical practice, intraportal infusion is considered one of the leading approaches for transplantation; however, this has not yet been validated for in vivo transplantation of hAECs. Thus, this study aims to investigate the distribution of hAECs post intraportal infusion and compare this distribution with other cell administration routes. METHODS: Wistar/ST rats were divided into 4 groups (n = 3 for each) based on cell administration route: group 1, intraportal; group 2, the spleen; group 3, tail veins; and group 4, penile veins. Subsequently, hAECs (1 × 107) stained with XenoLight DiR were infused into each recipient. Cell distribution was evaluated using an in vivo imaging system. RESULTS: DiR signals were detected in the rat livers of groups 1 and 2 with those in group 2 being much weaker than those in group 1. Necrosis of small intestine was observed in 2 cases in group 2. DiR signals were detected in the lungs in groups 3 and 4 because of systemic circulation; however, all the animals died within 20 minutes of infusions. CONCLUSIONS: Intraportal infusion is potentially applicable for safe and efficient transplantation of hAECs into the liver, whereas hAECs administration via the spleen carries a risk of thrombosis in a narrow portal vein system. Our results also indicate that hAECs administration via the systemic circulation could cause pulmonary embolism in clinical settings.

[A CASE OF URETEROARTERIAL FISTULA REQUIRING SURGICAL TREATMENT AFTER ENDOVASCULAR STENT PLACEMENT].

A 36-year-old woman was operated on at the age of 29 years for cervical cancer, and bilateral ureteral stents were inserted during radical hysterectomy. Subsequently, total pelvic irradiation and para-aortic lymph node irradiation were administered as postoperative radiation therapy. Four years following the surgery, the patient visited previous hospital for ureteral stent replacement; however, following this visit, there was no further contact with her. Seven years after the surgery, the patient presented with gross hematuria. Removal of right ureteral stent led to the observation of severe bleeding. The patient was, thus, transferred to our hospital because of suspected right ureteroarterial fistula. Angiography and intravascular ultrasonography showed a pseudoaneurysm at the distal end of the right common iliac artery. Thus, an endovascular stent graft was placed in the right common iliac artery, which led to resolution of the gross hematuria. One month after discharge, the patient developed right pyelonephritis and hydronephrosis; thus, she underwent right nephrostomy. Six months after undergoing right nephrostomy, the patient developed a fever of 39°C and started bleeding from the site of the right nephrostomy. A computerized tomography scan revealed a pseudoaneurysm in the right common iliac artery, and the endovascular stent graft was seen sliding into the artery. Thus, endovascular stent graft removal, pseudoaneurysm resection, and femoral-femoral artery bypass surgeries were performed. Thereafter, the patient showed no recurrence of infection or hematuria and no evidence of blood flow disorder to the lower extremities. In recent years, endovascular treatment for ureteroarterial fistulas is considered as the first-line treatment modality. However, in cases with infection, there is a possibility of vascular wall weakening, resulting in the formation of pseudoaneurysms, and sliding of the endovascular stent graft.

GRIK2 is a target for bladder cancer stem-like cell-targeting immunotherapy.

Recent studies have revealed that treatment-resistant cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) can be targeted by cytotoxic T lymphocytes (CTLs). CTLs recognize antigenic peptides derived from tumor-associated antigens; thus, the identification of tumor-associated antigens expressed by CSCs/CICs is essential. Human leucocyte antigen (HLA) ligandome analysis using mass spectrometry enables the analysis of naturally expressed antigenic peptides; however, HLA ligandome analysis requires a large number of cells and is challenging for CSCs/CICs. In this study, we established a novel bladder CSC/CIC model from a bladder cancer cell line (UM-UC-3 cells) using an ALDEFLUOR assay. CSCs/CICs were isolated as aldehyde dehydrogenase (ALDH)-high cells and several ALDHhigh clone cells were established. ALDHhigh clone cells were enriched with CSCs/CICs by sphere formation and tumorigenicity in immunodeficient mice. HLA ligandome analysis and cap analysis of gene expression using ALDHhigh clone cells revealed a distinctive antigenic peptide repertoire in bladder CSCs/CICs, and we found that a glutamate receptor, ionotropic, kainite 2 (GRIK2)-derived antigenic peptide (LMYDAVHVV) was specifically expressed by CSCs/CICs. A GRIK2 peptide-specific CTL clone recognized GRIK2-overexpressing UM-UC-3 cells and ALDHhigh clone cells, indicating that GRIK2 peptide can be a novel target for bladder CSC/CIC-targeting immunotherapy.

Comparative study of postoperative complications after radical cystectomy during the past two decades in Japan: Radical cystectomy remains associated with significant postoperative morbidities.

OBJECTIVES: During the past 2 decades, in order to improve perioperative and oncological outcomes, a minimally invasive approach, neoadjuvant chemotherapy (NAC), and an enhanced postoperative recovery program after surgery have been introduced into routine clinical practice of radical cystectomy (RC). Our aim was to examine the differences in clinical practice and postoperative complications after RC by comparing our previous and current cohorts. MATERIALS AND METHODS: A retrospective multi-institutional study. We collected all complications within 90 days after surgery between 2011 and 2017 (current cohort), and categorized them according to a standardized methodology. Then, we compared the outcomes with those in our previous study (previous cohort, 1997-2010). A multivariate logistic regression model was utilized to determine predictors of complications in the current cohort. RESULTS: A total of 838 patients were newly collected (current cohort), and 919 from the previous cohort were included in the subsequent analyses. In the current cohort, the rate of performing NAC was significantly higher (13% vs. 4%, respectively, P < 0.0001), and 26% (222/838) underwent laparoscopic RC (LRC, without robotic assistance: n = 210, with robotic assistance: n = 12). There was no significant difference in the overall complication [69% (580/838) vs. 68% (629/919), respectively, P = 0.7284] or major complication (Grades 3-5) [25% (211/838) vs. 22% (201/919), respectively, P = 0.1022] rates between the 2 cohorts. In both cohorts, the most frequent categories were infectious, gastrointestinal, wound-related, and genitourinary. In the current cohort, the performance status (odds ratio, OR = 2.11, P = 0.0013) and operative time (OR = 1.003, P = 0.0016) remained significant predictors of major complications. NAC was not associated with any or major complications. CONCLUSIONS: Surgical complications related to RC still remain significant problems, despite the recent improvements in surgical techniques and perioperative care. NAC did not increase the complications.

Dysbiosis of Gut Microbiome Is Associated With Rupture of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Environmental factors are important with respect to the rupture of cerebral aneurysms. However, the relationship between the gut microbiome, an environmental factor, and aneurysm rupture is unclear. Therefore, we compared the gut microbiome in patients with unruptured intracranial aneurysms (UIAs) and ruptured aneurysms (RAs) to identify the specific bacteria causing the rupture of cerebral aneurysms. METHODS: A multicenter, prospective case-control study was conducted over one year from 2019 to 2020. The fecal samples of patients with stable UIAs and RAs immediately after onset were collected. Their gut microbiomes were analyzed using 16S rRNA sequencing. Subsequently, a phylogenetic tree was constructed, and polymerase chain reaction was performed to identify the specific species. RESULTS: A total of 28 RAs and 33 UIAs were included in this study. There was no difference in patient characteristics between RAs and UIAs: age, sex, hypertension, dyslipidemia, diabetes status, body mass index, and smoking. No difference was observed in alpha diversity; however, beta diversity was significantly different in the unweighted UniFrac distances. At the phylum level, the relative abundance of Campylobacter in the RA group was larger than that in the UIA group. Furthermore, the gut microbiome in the RA and UIA groups exhibited significantly different taxonomies. However, Campylobacter was focused on because it is widely known as pathogenic among these bacteria. Then, a phylogenetic tree of operational taxonomic units related to Campylobacter was constructed and 4 species were identified. Polymerase chain reaction for these species identified that the abundance of the genus Campylobacter and Campylobacter ureolyticus was significantly higher in the RA group. CONCLUSIONS: The gut microbiome profile of patients with stable UIAs and RAs were significantly different. The genus Campylobacter and Campylobacter ureolyticus may be associated with the rupture of cerebral aneurysms.

How Much Tumor Volume Is Responsible for Development of Clinical Symptoms in Patients With Convexity, Parasagittal, and Falx Meningiomas?

Purpose: Meningiomas are the most common primary intracranial neoplasms and clinical symptom appearance depends on their volume and location. This study aimed to identify factors that influence clinical symptoms and to determine a specific threshold tumor volume for the prediction of symptomatic progression in patients with convexity, parasagittal, and falx meningiomas. Materials and Methods: We retrospectively studied patients with radiologically suspected convexity, parasagittal, or falx meningiomas at our institution. Results: The data of three hundred thirty-three patients were analyzed. We further divided patients into two groups based on clinical symptoms: an asymptomatic group (250 cases) and a symptomatic group (83 cases). Univariate analysis revealed significant differences between the groups in terms of sex (p = 0.002), age at the time of volumetric analysis (p < 0.001), hyperintense lesions on T2-weighted images (p = 0.029), peritumoral edema (p < 0.001), maximum tumor diameter (p < 0.001), and tumor volume (p < 0.001). Further multivariate analysis revealed significant differences between the groups in terms of age at the time of volumetric analysis (p = 0.002), peritumoral edema (p < 0.001), and tumor volume (p < 0.001). The receiver operating characteristic curve revealed a threshold tumor volume of 21.1 ml for predicting whether a patient would develop symptoms (sensitivity 0.843, specificity 0.880, an area under the curve 0.919 [95% confidence interval: 0.887-0.951]). Conclusion: We identified factors predictive of clinical symptoms in patients with convexity, parasagittal, and falx meningiomas and determined the first-ever threshold tumor volume for predicting symptomatic progression in such patients.