Antitumor Effects of Orally Administered Rare Sugar D-Allose in Bladder Cancer.

D-allose is a rare sugar that has been reported to up-regulate thioredoxin-interacting protein (TXNIP) expression and affect the production of intracellular reactive oxygen species (ROS). However, the antitumor effect of D-allose is unknown. This study aimed to determine whether orally administered D-allose could be a candidate drug against bladder cancer (BC). To this end, BC cell lines were treated with varying concentrations of D-allose (10, 25, and 50 mM). Cell viability and intracellular ROS levels were assessed using cell viability assay and flow cytometry. TXNIP expression was evaluated using Western blotting. The antitumor effect of orally administered D-allose was assessed using a xenograft mouse model. D-allose reduced cell viability and induced intracellular ROS production in BC cells. Moreover, D-allose stimulated TXNIP expression in a dose-dependent manner. Co-treatment of D-allose and the antioxidant L-glutathione canceled the D-allose-induced reduction in cell viability and intracellular ROS elevation. Furthermore, oral administration of D-allose inhibited tumor growth without adverse effects (p < 0.05). Histopathological findings in tumor tissues showed that D-allose decreased the nuclear fission rate from 4.1 to 1.1% (p = 0.004). Oral administration of D-allose suppressed BC growth in a preclinical mouse model, possibly through up-regulation of TXNIP expression followed by an increase in intracellular ROS. Therefore, D-allose is a potential therapeutic compound for the treatment of BC.

A rare case of BRAF V600E-mutated epithelioid glioblastoma with a sarcomatous component.

Epithelioid glioblastoma is a rare subtype of glioblastoma, but the coexistence of a sarcomatous component is even rarer. An 80-year-old woman was admitted to our hospital with somnolence. Magnetic resonance imaging revealed a cystic lesion with a solid component in the left temporal-parietal lobe. Histopathological examination of the resected tumor revealed three components; namely, typical glioblastoma, sarcomatous and epithelioid components at a ratio of about 5:3:2. All components were immunohistochemically positive for vimentin and mutated BRAF (V600E) and showed focal expression of glial fibrillary acidic protein and cytokeratin AE1/AE3, but they were negative for isocitrate dehydrogenase 1. Genetic analysis revealed that both the sarcomatous and epithelioid components harbored BRAF T1799A (V600E) mutation and homozygous deletion of cyclin-dependent kinase inhibitor 2A/B. We diagnosed this tumor as epithelial glioblastoma with a sarcomatous component. Our results indicate that even when the epithelial component is not dominant, immunohistochemical and genetic investigation of BRAF mutations is useful for the diagnosis of glioblastoma subtypes. In particular, although the prognosis of epithelial glioblastoma is poor, potentially effective targeted therapies for BRAF V600E-mutated tumors are available.

Characteristic electron-microscopic features of cryofibrinogen-associated glomerulonephritis: a case report.

BACKGROUND: Cryofibrinogenemia is a rare disorder that mainly affects the skin and occasionally the kidney. However, there are few published reports of cryofibrinogenemia-associated renal pathology. We therefore report a patient with cryofibrinogen-associated glomerulonephritis. Samples from this patient were examined by electron microscopy, laser microdissection, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). CASE PRESENTATION: A 78-year-old Japanese man presented with declining renal function, proteinuria, and gross hematuria. Kidney biopsy showed a membranoproliferative pattern with crescent formation and dominant C3c deposition in which subendothelial deposits with uniquely organized electron-microscopic features were observed. Additional ultrastructural analysis of cryoprecipitates extracted from plasma revealed similar structures of the glomerular subendothelial deposits. LC-MS/MS identified an increase in fibrinogen α, ß, and γ chains, fibronectin, filamin-A, and C3. The glomerular lesions were diagnosed as cryofibrinogen-associated glomerulonephritis on the basis of these findings. CONCLUSIONS: Although there are few reports of cryofibrinogen-associated glomerulonephritis, we believe that accurate diagnosis can be achieved by performing LC-MS/MS and ultrastructural analysis.

Characteristic findings of high-grade cervical intraepithelial neoplasia or more on magnifying endoscopy with narrow band imaging.

BACKGROUND: Colposcopy, which is a standard modality for diagnosing cervical intraepithelial neoplasia (CIN), can have limited accuracy owing to poor visibility. Flexible magnifying endoscopy with narrow band imaging (ME-NBI) has excellent diagnostic accuracy for early gastrointestinal neoplasms and is expected to be highly useful for CIN diagnosis. This study aimed to determine the characteristic findings and evaluate the diagnostic ability of ME-NBI for lesions ≥ CIN 3. METHODS: A well-designed prospective diagnostic case series conducted at multiple tertiary-care centers. A total of 24 patients who underwent cervical conization with a preoperative diagnosis of high-grade squamous cell intraepithelial lesions (HSILs) or lesions ≥ CIN 3 were enrolled. Prior to conization, still images and video of ME-NBI were captured to investigate the cervical lesions. The images were reviewed based on histological examination of the resected specimens. RESULTS: The NBI-ME images revealed the following abnormal findings: (1) light white epithelium (l-WE), (2) heavy white epithelium (h-WE), and (3) atypical intra-epithelial papillary capillary loop (IPCL). Pathological examination of the resected specimens confirmed cervical lesions ≥ CIN 3 in 21 patients. The ME-NBI findings were classified into four groups: l-WE, l-WE with atypical IPCL, h-WE, and h-WE with atypical IPCL, at rates of 0, 23.8, 9.5, and 66.7%, respectively. Additionally, all 3 patients with micro-invasive carcinoma showed a strong irregularity of IPCLs. CONCLUSION: The lesions ≥ CIN 3 demonstrated characteristic ME-NBI findings of h-WE alone, or l-/h-WE with atypical micro-vessels. This study indicates that ME-NBI may have novel value for CIN diagnosis.

A Case of Idiopathic Portal Hypertension Diagnosed by Noninvasive Fibrosis Evaluation Using Elastography.

Idiopathic portal hypertension (IPH) is often misdiagnosed as liver cirrhosis. Because it is difficult to distinguish between the two using diagnostic imaging, invasive tests, such as pathology and hepatic vein pressure gradient measurement, are necessary to make a diagnosis. Several studies have shown that the measurement of liver and spleen stiffnesses using elastography is useful in the diagnosis of IPH; however, there are few concrete reports on this subject. Herein, we report the case of a 58-year-old woman with IPH in which elastography was helpful for the diagnosis.

Siglec10 Expression on Tumor-associated Macrophages Is an Independent Prognostic Factor in Stage I Lung Adenocarcinoma.

BACKGROUND/AIM: Prognostic indicators for postoperative lung adenocarcinoma are elusive. The interaction between CD24 on tumor cells and sialic-acid-binding Ig-like lectin 10 (Siglec10) on tumor-associated macrophages (TAMs) is implicated in immune evasion in distinct tumors. However, the therapeutic significance of phagocytic checkpoints in lung adenocarcinoma remains unknown. We aimed to investigate the clinical relevance and prognostic significance of phagocytosis checkpoints mediated by Siglec10 in TAMs of patients with lung adenocarcinoma who underwent curative resection. PATIENTS AND METHODS: In this single-center retrospective study, we analyzed the data of 423 patients with stage I lung adenocarcinoma resected between 1999 and 2016. Tissue microarrays were constructed, and CD24, CD68, and Siglec10 immunohistochemistry was performed. Additionally, we assessed the clinical significance and prognostic associations of these markers. RESULTS: CD24 expression was higher in the Siglec10-high expression group than that in the -low expression group. Multivariate analysis showed that combined high Siglec10 and CD24 expression was an independent predictor of recurrence-free probability. The combined high Siglec10 and CD68 expression was a significant independent predictor of overall survival. Univariate analysis demonstrated that the 5-year probability of post-recurrence survival of patients with combined high Siglec10 and CD68 expression was lower than that of the other patients. CONCLUSION: High TAM Siglec10 expression and tumor CD24 expression are correlated, and the high Siglec10+CD24 combination is a major risk factor for recurrence. CD68+Siglec10 TAMs are important prognostic factors. Siglec10 expression on TAMs is essential for tumor microenvironment immunoregulation and offers a promising new immunotherapeutic approach for lung adenocarcinoma.

Prognostic significance of tumor budding in patients with pancreatic invasive ductal carcinoma who received neoadjuvant therapy.

Neoadjuvant therapy is commonly used for invasive pancreatic ductal carcinoma (PDAC). Tumor budding and high podoplanin expression in cancer-associated fibroblasts (CAFs) are prognostic factors in patients with various carcinomas including PDAC who have not received neoadjuvant therapy. In this study, we investigated whether tumor budding and podoplanin-positive CAFs are associated with outcomes in Japanese PDAC patients with neoadjuvant therapy. Histopathological findings of surgically resected PDACs with neoadjuvant therapy from 2005 to 2018 were reviewed (n = 97). With reference to International Tumor Budding Consensus Conference recommendations, tumors were evaluated for budding at 20 × magnification (/0.785 mm2) and at 40 × magnification (/0.237 mm2; mean number of fields: 3) for podoplanin expression in CAFs (%). Overall survival, disease-free survival, and disease-specific survival (DSS) were analyzed using the log-rank test and Cox proportional hazards model. After adjusting for T category, N category, resection margin, and adjuvant therapy, multivariate analyses demonstrated that tumor budding at 40 × magnification was an independent prognostic factor for worse DSS (hazard ratio: 2.41, p = 0.022). Tumor budding at 20 × magnification and podoplanin-positive CAFs tended to be associated with worse DSS; however, these findings were not statistically significant. Our findings indicate that tumor budding is an independent prognostic factor in PDAC patients with neoadjuvant therapy.

Clinicopathological and Prognostic Relevance of Tumoral Suppression of Tumorigenicity 2 Expression in Patients With Surgically Resected Pancreatic Carcinoma.

BACKGROUND/AIM: The interleukin (IL)-33/suppression of tumorigenicity 2 (ST2) pathway promotes cancer development and remodels the tumor microenvironment. However, the role of tumoral ST2 expression remains controversial in some solid malignancies. In this study, we have investigated the clinicopathological and prognostic relevance of tumoral ST2 expression in patients with resected pancreatic carcinoma after neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: We analyzed data from 76 patients with surgically resected pancreatic ductal adenocarcinoma after neoadjuvant chemoradiotherapy, between 2009 and 2018. Tissue microarrays were constructed and immunohistochemical analysis was performed for ST2. Associations between variables were analyzed using chi-square tests. Disease-specific survival (DSS) and disease-free survival (DFS) were analyzed using log-rank tests. RESULTS: High expression of ST2, which was observed in 43 patients (57%), was more frequent in patients with high T status (p=0.002), lymphatic invasion (p=0.049), and ≤50% of tumor cells destroyed by chemoradiotherapy (p=0.043; Evans grade I-IIA vs. IIB). In stage I patients, DFS was significantly lower in patients with high ST2 expression (median, 10.6 months) than in those with low ST2 expression (median, 43.4 months; p=0.046). CONCLUSION: High tumoral ST2 expression is associated with high T status, lymphatic invasion, and lower histopathological response grade in patients with pancreatic carcinoma after neoadjuvant chemoradiotherapy.

CD44v6 downregulation as a prognostic factor for distant recurrence in resected stage I lung adenocarcinomas.

CD44 and CD44 variant isoforms have been reported as contributing factors to cancer progression. In this study, we aimed to assess whether CD44 and its variant isoforms were correlated with the prognostic factors for distant metastasis in stage I lung adenocarcinomas using tissue microarray and immunohistochemistry. In this single-center retrospective study, we analyzed the data of 490 patients with stage I lung adenocarcinoma resected between 1999 and 2016. We constructed tissue microarrays and performed immunohistochemistry for CD44s, CD44v6, and CD44v9. The risk of disease recurrence and its associations with clinicopathological risk factors were assessed. CD44v6 expression was significantly associated with recurrence. Patients with CD44v6-negative tumors had a significantly increased risk of developing distant recurrence than patients with CD44v6-positive tumors (5-year cumulative incidence of recurrence (CIR), 10.7% vs. 4.6%; P = 0.009). However, CD44v6-negative tumors were not associated with an increased risk of locoregional recurrence compared to CD44v6-positive tumors (5-year CIR, 6.0% vs. 4.0%; P = 0.39). The overall survival (OS) of patients with CD44v6-negative tumors was significantly lower than that of patients with CD44v6-positive tumors (5-year OS: 87% vs. 94%, P = 0.016). CD44v6-negative tumors were also associated with invasive tumor size and lymphovascular invasion. Even in stage I disease, tumors with negative-CD44v6 expression had more distant recurrences than those with positive-CD44v6 expression and were associated with poor prognosis in resected stage I lung adenocarcinomas. Thus, CD44v6 downregulation may be a prognostic factor for distant metastasis in stage I lung adenocarcinomas.

Incidental finding of extramammary Paget's disease during active surveillance for early-stage prostate cancer in a prostate biopsy.

Introduction: Skin tissue contamination within transcutaneous visceral organ biopsies is seldom found. We encountered a rare case of extramammary Paget's disease incidentally diagnosed by prostate biopsy during active surveillance for prostate cancer. Case presentation: A 71-year-old Japanese patient was diagnosed with prostate cancer, and active surveillance was selected. After 1 year, prostate biopsy was performed by a transperitoneal approach, and 16 biopsy cores were taken. One biopsy core contained skin tissue showing extramammary Paget's disease. Careful skin examination confirmed the presence of an extramammary Paget's disease lesion in the left perineum, and curative surgical resection was performed. Recurrence and metastasis did not occur after 6 months of follow-up. Conclusion: Although the perianal region is a common site of extramammary Paget's disease, early-stage extramammary Paget's disease is often asymptomatic. Thus, during a transcutaneous biopsy, it is important to consider the appearance of the skin and the pathological features of migrating skin tissue.

MMP-7 expression is associated with a higher rate of tumor spread through air spaces in resected lung adenocarcinomas.

OBJECTIVES: The spread through air spaces (STAS) of adenocarcinoma (ADC) is a unique pattern for local invasion, which comprises the spread of tumor cells within air spaces beyond the tumor edge without a direct connection with the primary tumor. Matrix metalloproteinase-7 (MMP-7), a secreted proteolytic enzyme that degrades various extracellular matrix components and other substrates, regulates several pathophysiological processes as well as the occurrence and development of cancers in humans. Here, we retrospectively analyzed a cohort of Japanese patients with treatment-naive, surgically-resected lung ADC to assess whether MMP-7 is associated with STAS development and if it could be used as a predictor of STAS. MATERIALS AND METHODS: We performed histological evaluation using hematoxylin and eosin staining and immunohistochemical analysis using microarrays. Thereafter, we scored the examined tissues for immune markers to identify significant tumor STAS predictors. RESULTS: We identified that high MMP-7 expression is an independent predictor of a high STAS incidence. Multivariate analysis revealed that MMP-7 expression was correlated with tumor behavior and poor prognosis. Furthermore, STAS remained significantly associated with a higher risk of ADC recurrence. CONCLUSION: The development of tumor STAS could be promoted by the functioning of MMP-7. This study could be a crucial basis for future investigations on the detection of tumor STAS.

P53 immunolabeling in EUS-FNA biopsy can predict low resection rate and early recurrence in resectable or borderline resectable pancreatic cancer treated with neoadjuvant therapy.

PURPOSE: KRAS, P16, TP53, and SMAD4/DPC4 mutations are common in pancreatic ductal adenocarcinoma (PDAC). The study aimed to evaluate the association between gene mutations in pre-treatment endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples and clinical outcomes of patients with PDAC. METHODS: There were 43 patients with resectable (R) PDAC and 41 patients with borderline resectable (BR) PDAC. CDKN2A/p16, TP53, and SMAD4/DPC4 were evaluated through immunohistochemistry (IHC) of pretreatment EUS-FNA (n = 84) and resected specimens (n = 71). All patients received neoadjuvant therapy. RESULTS: IHC of EUS-FNA specimens revealed p16 loss in 61 (73%), abnormal p53 in 61 (73%), and Smad4 loss in 38 (45%) patients. Abnormal p53 was associated with a lower resection rate (p = .017). Abnormal p53 and Smad4 loss were associated with recurrence within 6 months post-pancreatectomy (p = .03, p = .03, respectively). Univariate Cox regression analysis was conducted to reveal that abnormal p53 (p = .07), p16 loss and abnormal p53 (p = .04), and Smad4 and p16 loss (p = .03) were associated with poor prognosis. CONCLUSIONS: Pre-treatment abnormal labeling of p53 in EUS-FNA specimen was associated with a lower resection rate and an early recurrence in R or BR PDAC cases.

(Pro)renin Receptor Down-regulation Is Associated With a Higher Risk of Recurrence in Lung Adenocarcinoma.

BACKGROUND/AIM: The (pro)renin receptor [(P)RR] plays a role not only in cardiovascular and renal diseases, but also in tumorigenesis. (P)RR contributes to the activation of the Wnt/ß-catenin signaling pathway, independent of the renin-angiotensin system. Accumulating evidence has shown that (P)RR is expressed in various human cancers. However, its clinical impact in lung carcinomas remains unclear. This study aimed to clarify the associations between (P)RR expression and clinical outcomes in patients with non-small cell lung carcinoma (NSCLC). PATIENTS AND METHODS: We analyzed the data of 913 patients with NSCLC who underwent resection between 1999 and 2016. Tissue microarrays were constructed and the expression of (P)RR and ß-catenin was investigated using immunohistochemistry. Recurrence-free probability and overall survival were analyzed using a log-rank test and Cox proportional hazards model. RESULTS: In adenocarcinomas, (P)RR down-regulation correlated significantly with high-grade tumors (p=0.026) and a higher risk of recurrence in all patients (p=0.001). Among patients with (P)RR-positive tumors, the nuclear expression of ß-catenin was associated with a higher risk of recurrence (p=0.001). Multivariate analysis revealed that (P)RR down-regulation was an independent predictor of disease recurrence (p=0.031). Conversely, in squamous cell carcinoma, (P)RR was not associated with patient outcomes. CONCLUSION: (P)RR down-regulation is associated with a higher risk of recurrence in lung adenocarcinomas, thereby characterizing a prognostic subset within high-grade tumors.

High-grade tumor classified by new system is a prognostic predictor in resected lung adenocarcinoma.

OBJECTIVES: A grading system for pulmonary adenocarcinoma has not been established; hence, the International Association for the Study of Lung Cancer (IASLC) pathology panel developed a new grading system for invasive adenocarcinoma. We aimed to evaluate the prognostic significance of the IASLC grading system for invasive pulmonary adenocarcinoma. METHODS: We conducted a retrospective analysis of 471 Japanese patients with resected lung adenocarcinoma. Tumors were classified in accordance with the IASLC grading system and 2015 World Health Organization classification. We analyzed recurrence-free probability (RFP) and overall survival (OS) using the log-rank test and compared the two grading systems using the Cox proportional hazards model. RESULTS: Grade 3 tumors of the IASLC system and high-grade tumors of the 2015 World Health Organization classification were present in 38% and 17% of patients, respectively. The 5-year RFP was lower in patients with IASLC Grade 3 tumors (45%) than in patients with IASLC Grade 1 and 2 tumors (91% and 83%, respectively). The 5-year RFP of patients with IASLC Grade 2 tumors (83%) was higher than of those with 2015 World Health Organization intermediate tumors (69%). On multivariate analysis for recurrence, IASLC Grade 3 was an independent prognostic factor of worse RFP. We showed similar results on analysis for the OS. CONCLUSIONS: The prognostic significance of IASLC Grade 3 tumors on recurrence-free probability was confirmed through both univariate and multivariate analyses. Thus, the IASLC Grade 3 tumor is an independent factor of poor prognosis in patients with resected lung adenocarcinoma.

Tumor-associated CD163+ macrophage as a predictor of tumor spread through air spaces and with CD25+ lymphocyte as a prognostic factor in resected stage I lung adenocarcinoma.

OBJECTIVE: Lung cancer can spread in numerous ways, including spread through air spaces (STAS). A high number of CD68+ tumor-associated macrophages (TAMs), which creates a favorable microenvironment for tumor progression, is an independent predictor of increased STAS rate and is used as a pan-macrophage marker, whereas CD163 is used as an M2 macrophage marker. A high number of CD25+ tumor-infiltrating lymphocytes (TILs) is associated with the frequency of STAS. This study investigated the influence of M2 macrophages and CD25+ TILs on STAS and postoperative recurrence in patients with stage I lung adenocarcinoma who underwent curative resection. METHODS: We analyzed data from 485 patients with stage 0-I lung adenocarcinoma who underwent resection between 1999 and 2016. Tissue microarrays were constructed, and immunohistochemical analysis was performed for CD3, CD4, CD8, CD45RO, CD25, CD20, CD68, and CD163. Three tumor areas with the highest density of immune cells were photographed, and the immune cells were quantified. Associations between variables were analyzed using chi-square tests and Mann-Whitney U tests. Recurrence-free probability (RFP) was analyzed using log-rank tests and Cox proportional hazards models. RESULTS: CD163+ TAMs were identified as an independent predictor of a higher rate of STAS (P < 0.001). Analysis of biologically relevant immune cell combinations revealed that patients with high CD25+ TILs and high CD163+ TAMs had a significantly lower RFP (5-year RFP, 74%) than those with other combinations of CD25 and CD163 (5-year RFP, 90%; P < 0.001). Multivariate analysis showed that high CD25+/high CD163+ immune cell infiltration was an independent predictor of RFP. CONCLUSION: We demonstrated that a higher density of M2 macrophages is an independent predictor of a higher STAS incidence. A high CD25+/high CD163+ immune cell infiltration ratio is a significant prognostic factor for stage 0-I lung adenocarcinoma.

Prognostic impact of tumor-infiltrating lymphocytes and neutrophils in resected non-small cell lung carcinoma.

The prognostic impact of tumor-infiltrating lymphocytes (TILs) has been determined in non-small cell lung carcinoma; however, there is no standardized method for counting TILs. In this report, we applied the method proposed by the International Immuno-Oncology Biomarkers Working Group for the assessment of TILs to count the number of tumor-infiltrating neutrophils (TINs). We then analyzed the association between TIL counts, TIN counts, and clinicopathological factors in lung cancer. We retrospectively analyzed a series of 1191 Japanese patients with resected lung adenocarcinoma and squamous cell carcinoma, which were restaged according to the eighth edition of the TNM staging system. Tumors were classified according to the 2015 WHO classification of lung carcinoma. Recurrence-free probability (RFP) and overall survival (OS) were analyzed using the log-rank test and Cox proportional hazard model. Using multivariate analysis for patient outcome in patients with adenocarcinoma, high TIN counts were an independent prognostic factor for worse RFP (hazard ratio [HR]: 1.94, p < 0.001) and worse OS (hazard ratio [HR]: 1.75, p = 0.006). On the other hand, TIL counts were not related to patient outcome. We have demonstrated that high TINs are unfavorable prognostic markers for resected lung adenocarcinoma. In resected lung squamous cell carcinoma, TIL and TIN counts were not related to patient prognosis. It has been suggested that the immune response to cancer cells may differ depending on the histological type. An understanding of how neutrophils are programmed to perform protumor activities is necessary for the future design of targeted immunotherapies.

Correlation of epidermal growth factor receptor mutation status and PD-L1 expression with [18F]FDG PET using volume-based parameters in non-small cell lung cancer.

OBJECTIVE: We investigated the relationship between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET using volume-based parameters and epidermal growth factor receptor (EGFR) mutation status, programmed death-ligand-1 (PD-L1) expression level, and their combination, in pretreated non-small cell lung cancer (NSCLC). METHODS: FDG PET findings and EGFR mutation status and PD-L1 expression level were investigated retrospectively in 93 patients with newly diagnosed NSCLC (77 adenocarcinomas, 16 squamous cell carcinomas). Tumors were divided into six groups: EGFR mutant/negative PD-L1, EGFR mutant/low PD-L1, EGFR mutant/high PD-L1, EGFR wild/negative PD-L1, EGFR wild/low PD-L1, and EGFR wild/high PD-L1. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumor were measured from PET images. The EGFR mutation status and PD-L1 expression level were estimated in tumor tissue specimens and compared with the PET parameters. RESULTS: None of the PET parameters differed significantly between EGFR-mutated and wild-type EGFR. According to the PD-L1 level, significant differences were detected in SUVmax (P = 0.001) and TLG (P = 0.016), but not MTV. Comparing all six groups, significant difference was detected in only SUVmax (P = 0.011). CONCLUSION: Based on the preliminary results of this study, FDG PET may help in the prediction of PD-L1 expression level, but not EGFR mutation status, in patients with newly diagnosed NSCLC. The SUVmax rather than MTV or TLG, may be of value in predicting the six groups according to the combination of EGFR mutation status and PD-L1 expression level.

Peroxisome proliferator-activated receptor-α expression is associated with histological type in human gastric carcinoma.

Gastric carcinoma is one of the most common types of cancer worldwide and a leading cause of cancer-related mortality. Gastric carcinoma is histologically subdivided into differentiated and undifferentiated carcinoma, with the latter including poorly differentiated carcinoma and signet ring cell carcinoma (SRCC). Poorly differentiated carcinoma and SRCC have a worse prognosis compared with differentiated carcinoma. Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and the PPAR-α subtype regulates important cellular functions, including cell proliferation, energy metabolism, oxidative stress, immune responses and cell differentiation. The aim of the present study was to elucidate the associations between clinicopathological factors and PPAR-α expression in patients with gastric carcinoma. The immunohistochemical staining of specimens obtained from 57 patients showed that PPAR-α expression was slightly weaker in undifferentiated carcinoma than in differentiated carcinoma (P<0.01). PPAR-α expression also significantly differed between poorly differentiated carcinoma (both positive and negative: 14/20, 70%) and SRCC (not expressed: 0/7, 0%) (P<0.01). However, PPAR-α expression was not significantly affected by age, lymph node invasion, venous invasion, lymph node metastasis, depth of invasion or stage. Collectively, the present results demonstrated that the downregulated expression of PPAR-α may play a key role in the biological transformation of tumors. Therefore, PPAR-α appears to be an important protein related to histology and may hold promise as a prognostic marker. Further studies with a larger number of subjects are needed to elucidate the relationship between PPAR-α expression and tumor progression and to analyze long-term clinical survival.

Association between expanded criteria for living kidney donors and renal biopsy findings.

BACKGROUND: There are certain criteria for selecting living kidney donors. However, the association between clinical characteristics of these criteria and kidney biopsy findings in living kidney donors have not yet been elucidated. Thus, we investigated the association between kidney biopsy findings and clinical characteristics defined in the Japanese guidelines for living kidney donors. METHODS: A retrospective multicentre study was conducted on donors and their recipients who underwent kidney transplantation between July 2014 and June 2017. Multiple linear regression analysis and multiple logistic regression analysis were performed to investigate the association between biopsy findings and clinical characteristics. RESULTS: A total of 240 donors and 240 recipients were included. Age was significantly correlated with global glomerulosclerosis and intimal thickening in multiple linear regression analysis and multiple logistic regression analysis, whereas diabetes was correlated with tubular atrophy in multiple linear regression analysis after multiple imputation and multiple logistic regression analysis. CONCLUSIONS: Amongst the clinical factors investigated in our study, age was positively correlated and diabetes was possibly correlated with kidney tissue injury in living kidney donors. Age and diabetes may be more important for selecting suitable living kidney donors than other clinical factors.

Systemic lupus erythematosus with various clinical manifestations in a patient with hereditary angioedema: a case report.

BACKGROUND: Hereditary angioedema (HAE) is an inherited disease characterized by recurrent angioedema without urticaria or pruritus. The most common types of HAE are caused by deficiency or dysfunction in C1 esterase inhibitor (C1-INH-HAE). The association between C1-INH-HAE and systemic lupus erythematosus (SLE) is known; however, variations in the underlying pathophysiology, disease course, and treatment in this population remain incompletely understood. CASE PRESENTATION: A 31-year-old Japanese woman with a prior diagnosis of HAE type 1 based on the episodes of recurrent angioedema, low C1 inhibitor antigen levels and function, and family history presented with new complaints of malar rash, alopecia, and arthralgias in her hands and elbows. She later developed fever, oral ulcers, lupus retinopathy, a discoid rash localized to her chest, and malar rash. Investigations revealed positive antinuclear antibody, leukopenia, thrombocytopenia, hypocomplementemia, and nephritis. Based on these findings, she was diagnosed with SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria. There did not appear to be a correlation between HAE disease activity and the timing of presentation with SLE, because HAE disease activity had been stable. The patient was able to achieve and maintain remission with immunosuppressive therapy including prednisolone, hydroxychloroquine, and tacrolimus. CONCLUSIONS: Our patient presented with a variety of symptoms, including fever and cytopenia in addition to mucocutaneous, joint, ocular, and renal lesions. It is important to better characterize the clinical characteristics of SLE in patients with C1-INH-HAE, and to clarify the mechanisms of SLE in this population.