JR Tokyo General Hospital

CD20-negative large B-cell lymphomas exhibit aggressive behavior and are ineligible for rituximab-containing therapy. To identify antigens targeted by treatment, we analyzed CD79B and CD19 expression in 108 samples from 75 patients with CD20-negative large B-cell lymphomas using H-score. Diffuse-strong (H-score 300) CD79B and CD19 expression was observed in 51% and 57% of samples, and low/negative (H-score ≤ 100) in 35% and 30%, respectively. CD79B expression was significantly lower in de novo CD20-negative diffuse large B-cell lymphoma (DLBCL) than in CD20-negative DLBCL changed from CD20-positive DLBCL after rituximab-containing therapy and in CD20-negative DLBCL transformed from CD20-positive low-grade B-cell lymphoma after rituximab-containing therapy (H-score ≤ 100 in 79% vs. 27% vs. 10%, p<0.001). CD19 expression was lower in de novo CD20-negative DLBCL than in transformed DLBCL (H-score ≤ 100 in 43% vs. 3%, p=0.006). Of 12 patients with plasmablastic lymphoma, CD79B and CD19 were negative in 83% and 66% of cases, respectively. Among 46 CD20-negative large B-cell lymphomas with low CD79B and/or CD19 expression, the tumor proportion score for programmed death-ligand 1 was positive (≥ 1%) in 33% of cases. The combined positive score for programmed death-ligand 1 was positive in 52% of programmed death-ligand 1 tumor proportion score-negative samples. In conclusion, CD79B and CD19 were variably expressed in CD20-negative large B-cell lymphomas, but lower in de novo DLBCL, and especially in plasmablastic lymphoma. Programmed cell death protein 1/programmed death-ligand one inhibitors may represent a treatment option.

Lymphovascular invasion (LVI) is an established adverse prognostic factor in urothelial carcinoma; however, prior studies have rarely distinguished lymphatic vessel invasion (LymVI) from blood vessel invasion (BVI). We investigated the prevalence and prognostic significance of LymVI and BVI in upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNUx), and assessed their associations with clinicopathological characteristics and metastatic patterns. We retrospectively analyzed 455 patients who underwent RNUx at Jikei University Hospital and six affiliated centers between 2012 and 2021. LVI subtype was assessed using hematoxylin-eosin staining, supplemented by D2-40, CD31, and Elastica van Gieson staining when required. Patients were categorized into four groups: no LVI, LymVI only, BVI only, and combined LymVI+BVI. Outcomes included non-urothelial tract recurrence-free survival (NUTRFS), cancer-specific survival (CSS), and overall survival (OS). Kaplan-Meier methods and Cox regression analyses were used to evaluate prognostic associations. LVI subtypes were distributed as follows: no LVI (65.1%), LymVI only (9.9%), BVI only (7.7%), and combined LymVI+BVI (17.4%). Higher pathological T and N stages were observed progressively across these groups (P<0.001). BVI only and combined LymVI+BVI were independent predictors of inferior NUTRFS (HR 4.52 and 5.01), OS (HR 2.46 and 2.73), and CSS (HR 2.85 and 4.06), whereas isolated LymVI did not significantly affect outcomes. Hematogenous metastases to the lung, liver, and bone were significantly more frequent in patients with BVI or combined LVI. Distinguishing BVI from LymVI provides refined prognostic stratification in UTUC. BVI, alone or combined with LymVI, is strongly associated with adverse survival and increased hematogenous dissemination, while isolated LymVI has limited prognostic impact. Routine pathological subclassification of vascular invasion may improve postoperative risk assessment and guide adjuvant treatment decisions.

Diabetic striatopathy (DS) is a rare neurological complication in poorly controlled diabetes mellitus. The pathogenesis of DS is thought to involve microvascular injury; however, autopsy-based histological documentation remains scarce. We report an autopsy-confirmed case of DS complicated by right cerebellar hemorrhagic infarction, in which hemichorea developed despite radiological improvement. A histological examination showed neuronal loss, reactive astrocytosis, calcification, and organizing hemorrhage with fibroblast proliferation in the basal ganglia within 82 days after the initial imaging. These findings highlight the paradox between radiological normalization and irreversible pathological injury, supporting DS as a spectrum that extends from functional disturbance to structural damage.

Disease-specific cutoffs are essential for accurately assessing low muscle mass. We aimed to determine calf circumference cutoffs for identifying low muscle mass in older patients with subacute stroke and to compare their diagnostic accuracy with those used across various disease-specific criteria. This single-center, cross-sectional study included older patients with subacute stroke using consecutive sampling. Low muscle mass was defined as an appendicular skeletal muscle mass index of less than 7.0 kg/m² in men and less than 5.7 kg/m² in women. Calf circumference was measured on the nonparetic side, and the maximum value was used. We assessed the diagnostic accuracy of the derived cutoffs using sensitivity, specificity, predictive values, likelihood ratios, and Matthews correlation coefficient (MCC). The study adhered to the Standards for Reporting Diagnostic Accuracy 2015 guidelines. Among 253 participants, 188 met the inclusion criteria. The optimal cutoffs were 31 cm for men and 30 cm for women. These cutoffs yielded a sensitivity of 0.78 [95% confidence interval (CI): 0.69-0.85], specificity of 0.71 (95% CI: 0.59-0.82), positive likelihood ratio of 2.73 (95% CI: 1.86-4.00), and MCC of 0.47 (95% CI: 0.36-0.62). Compared with criteria used across-disease groups, the newly derived cutoffs yielded higher specificity, a greater positive likelihood ratio, and an improved MCC. These cutoffs provide acceptable diagnostic accuracy for identifying low muscle mass in this patient population and may offer a practical screening option in clinical settings.

Background:The meniscus-bone angle (MBA), defined as the angle formed by the lateral meniscus with respect to the lateral tibial slope, has recently been identified as an intrinsic factor associated with primary anterior cruciate ligament (ACL) injuries. However, no studies have investigated the influence of MBA and other intrinsic factors excluding the influence of extrinsic factors, especially the level of sports activity.Purpose/Hypothesis:The purpose was to evaluate the intrinsic factors of primary ACL injury while controlling for the effect of sports activity level. It was hypothesized that the MBA would be a significant factor associated with ACL deficiency, irrespective of the sports activity level.Study Design:Cross-sectional study; Level of evidence, 3.Methods:A total of 143 knees in 139 patients with ACL injuries (group A) and matched controls (matched by age, sex, and Tegner Activity Scale score), 143 knees in 143 patients without ACL injuries (group N), were evaluated. Patient height, body weight, body mass index, lateral posterior tibial slope angle (LPTSA), medial posterior tibial slope angle (MPTSA), MBA of the lateral meniscus, and relative posterior inclination angle (RPIA; MBA – LPTSA) were evaluated between the 2 groups.Results:The MBA (group A: 22.3°± 4.5°; group N: 29.1°± 3.7°) and RPIA (group A: 15.0°± 6.1°; group N: 24.1°± 4.1°) were significantly (P < .001) smaller in group A, whereas LPTSA (group A: 7.3°± 3.4°; group N: 5.0°± 2.7°) and MPTSA (group A: 7.1°± 3.0°; group N: 5.6°± 2.4°) were significantly (P < .001) larger. Logistic regression analysis with ACL injury as the dependent variable showed significant differences in MBA (OR, 0.645; 95% CI, 0.579-0.718; P < .01) and LPTSA (OR, 1.3; 95% CI, 1.14-1.48; P < .001) between the 2 groups. The receiver operating characteristic curves for the MBA showed a sensitivity of 76.2% and a specificity of 83.9% with the cutoff value of 25.2° (area under the curve, 0.88).Conclusion:A low MBA with a cutoff value of 25.2° was the most significant independent factor associated with primary ACL injury when controlling for differences in sports activity level.

Objectives: This study aimed to assess the prognostic impact of the C-reactive protein-albumin-lymphocyte index in older patients with colorectal cancer and to evaluate the superiority of this new system. Methods: Of the patients who received initial treatment for colorectal cancer at our hospital between 2014 and 2021 (n=269), older patients aged ≥65 years who had undergone curative resection for colorectal cancer during the study period were included. We retrospectively investigated the relationship between the preoperative C-reactive protein-albumin-lymphocyte index and overall and recurrence-free survival rates. Univariate and multivariate analyses were performed to identify the independent prognostic factors after curative resection in older patients with colorectal cancer. Results: One-hundred-seventy-eight patients underwent initial curative resection during the study period. The median survival times for patients with C-reactive protein-albumin-lymphocyte (CALLY) indices <1.2 and ≥1.2 were 42.6 and 68.3 months, respectively (p=0.01). Multivariate analysis identified the following independent risk factors associated with poor prognosis: age ≥75 years (hazard ratio 1.64, 95% confidence interval 1.03-2.62, p=0.03), T stage 3 or 4 (hazard ratio 1.66, 95% confidence interval 1.06-2.61, p=0.02), laparotomy surgical approach (hazard ratio 2.09, 95% confidence interval 1.29-3.38, p<0.01), and C-reactive protein-albumin-lymphocyte index <1.2 (hazard ratio 1.75, 95% confidence interval 1.05-2.92, p=0.03). Conclusions: Our study suggests that the CALLY index is an independent prognostic factor in older patients with colorectal cancer and may facilitate multidisciplinary decision-making.

Primary malignant lymphoma originating in the laryngeal tissue is rare. A 61-year-old woman was admitted to our hospital with hoarseness and mild dyspnea for three weeks. The fiberscopic examination revealed slight edema around the vocal cords. Despite four weeks of inhaled steroid therapy, progressive worsening of the subglottic lesion led to increasing airway obstruction, and due to diagnostic uncertainty and the risk to the airway, emergent tracheostomy was performed. Fiberscopic findings through the tracheostomy stoma revealed multiple tumors around the anterior tracheal wall and a submucosal bulge around the posterior tracheal wall in the subglottic area, so biopsies from both areas were performed. Histological examination revealed a low-grade B-cell lymphoma (probable CD5-positive mucosa-associated lymphoid tissue (MALT) lymphoma, unclassifiable). As a further biopsy would have required general anesthesia and might still have yielded insufficient tissue for definitive subclassification, treatment was initiated for an unclassifiable low-grade B-cell lymphoma, with a plan to perform a repeat biopsy at recurrence for diagnostic confirmation. The patient subsequently received chemotherapy with bendamustine and rituximab and has sustained a complete response for seven years.

Abstract BACKGROUND Current technology has been developed to analyze tumor-derived circulating cell free DNA (ccfDNA) in cerebrospinal fluid (CSF) as a substitute for genomic DNA obtained directly from glioma tissue. However, the amount of ccfDNA obtained from low-grade gliomas and tumors not in contact with the cerebrospinal space is extremely small, making genetic analysis difficult. Here, we report a new assay to identify IDH1 mutations from CSF-derived ccfDNA (below the measurement sensitivity) obtained from patients with low-grade gliomas with IDH1 mutations. MATERIAL AND RESULTS The subjects were five patients with astrocytoma, IDH1-mutant, grade 2 with a confirmed histological diagnosis. CSF was collected by lumbar puncture, extracted with a ccfDNA extraction kit, and DNA was quantified using the Qubit assay. In all cases, the concentration was below the detection limit (0.2 ng/μl). IDH1 mutations could not be detected by the conventional HRM (High Resolution Melting) method. Next, 10 additional cycles of PCR amplification were added to the HRM method, a positive curve indicating a mutation was clearly drawn in all cases, and the IDH1 R132H mutation was confirmed using DNA sequence analysis of the PCR products. By a similar method, it was also possible to analyze H3.3 K27M mutation and BRAFV600E mutation. CONCLUSION Molecular target inhibitors have been developed for IDH-mutated and BRAFV600E-mutated gliomas, and chemotherapy with these inhibitors has become promising. If an assay could be established that can detect gene mutations from cerebrospinal fluid in a minimally invasive manner, even with trace amounts of DNA, it would provide useful information for selecting new treatment methods.

Coronary artery aneurysms (CAAs) are rare. Giant CAAs are defined as those exceeding 2 cm in diameter. An 82-year-old woman was referred to our institution for surgery after coronary 3D computed tomography (CT) and transthoracic echocardiography (TTE) revealed CAAs and a coronary-to-pulmonary artery fistula. Coronary angiography identified four aneurysms, ranging from 10 to 45 mm in diameter, in the right coronary artery (RCA), left anterior descending (LAD) artery, and left circumflex (LCx) artery. The Qp/Qs ratio was 1.34. The surgical approach involved median sternotomy and was performed under cardiopulmonary bypass (CBP) on a beating heart. The aneurysms originating from the RCA and LAD artery measured 30 and 45 mm, respectively, and were easily visible. After isolating the feeding vessels, the aneurysms were opened, and their inflow and outflow vessels were sutured closed. Additionally, the feeding vessels were ligated at their origins, and the aneurysm walls were sutured. The locations of the small aneurysms were confirmed using direct echocardiography and treated similarly. There were no signs of damage to the normal coronary arteries, and revascularization was not required. The fistula was closed after opening the pulmonary artery. The patient was weaned off CBP without difficulty, and her postoperative course was uneventful. Postoperative 3D CT confirmed the disappearance of blood flow in the aneurysms and abnormal vessels. We report a case of multiple CAAs with complex feeding vessels that were successfully treated on a beating heart without revascularization.