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Silicon microparticles were wrapped by using well-dispersed single-walled carbon nanotubes via a facile freeze-drying method and used as an anode material in lithium-ion battery.

Verrucous carcinoma (VC) is a rare, highly keratinized, well-differentiated, low-grade squamous cell carcinoma. A 58-year-old male presented with a 5-year history of a recurrent growing hyperkeratotic mass with intermittent bloody discharge, ulceration and dystrophic nail change on the right fifth toe. Since multiple dermatologic treatments were yielding no response, punch biopsy was performed for a more accurate diagnosis and the result was consistent with verruca vulgaris. As the lesion was responding poorly despite further dermatologic treatments for verruca vulgaris, radical surgical resection was performed. Microscopic examination of the excised lesion revealed epidermis with hyperkeratosis, hypergranulosis, papillomatosis, and reticular dermis invasion, consistent with VC. Since the diagnosis changed to VC, and the resection margin was involved by the carcinoma, the patient underwent an amputation procedure at the proximal phalangeal base. This case report highlights the importance of diagnosing VC. In cases of lesions such as verruca vulgaris or onychomycosis that are not responsive to general treatment, physicians should consider VC as a differential diagnosis, to prevent delaying a proper diagnosis and progression of disease.

Background: Desmoid tumor, also known as aggressive fibromatosis, is well-characterized by abnormal Wnt/β-catenin signaling. Various therapeutic options, including imatinib, are available to efficiently treat desmoid tumor. However, molecular mechanism of why imatinib works remains poorly understood. Here, we describe the potential roles of NOTCH2 and HES1 in association with clinical response to imatinib as in genome and transcriptome levels. Methods: We identified all somatic mutations in coding and non-coding regions via whole genome sequencing using desmoid tumor samples. To validate the genetic interaction with expression level in desmoid-tumor condition, we utilized large-scale Whole-genome sequencing (WGS) and transcriptome datasets from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. RNA-sequencing was performed using prospective and retrospective cohort samples to evaluate the expressional relevance with clinical response. Results: Among 20 patients, 4 (20%) had a partial response and 14 (66.7%) had stable disease, 11 of which continued for ≥1 year. With gene-wise functional analyses, we detected significant correlation between recurrent NOTCH2 noncoding mutations and clinical response to imatinib. Based on PCAWG data analyses, NOTCH2 mutations affect its expression levels particularly in the presence of CTNNB1 missense mutations. By analyzing RNA-sequencing with additional desmoid tumor samples, we found that NOTCH2 expression was significantly correlated with HES1 expression. Interestingly, NOTCH2 had no statistical power to discriminate responders and non-responders. Instead, HES1 was differentially expressed with statistical significance between responders and non-responders Conclusions: Imatinib was effective and well tolerated for advanced desmoid tumor treatment. Our results show that HES1, regulated by NOTCH2, as an indicator of sensitivity to imatinib, which provides an important therapeutic consideration for desmoid tumor. Trial Registration: ClinicalTrials.gov, NCT02495519, Registered July 13, 2015- Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT02495519

Dupuytren's disease (DD) is a progressive fibroproliferative condition involving contractures of the fascia of the palm. Up to now, there are no relevant investigations on patients with DD in case of serum vitamin D deficiency. We hypothesized that transforming growth factor-β1 (TGF-β1) is increased in patients with DD in consequence of vitamin D deficiency, thereby leading to myofibroblast differentiation and subsequent progression of contractures.The aim of this study was to analyze serum vitamin D levels and explore possible clinical and immunohistochemical correlates with vitamin D concentrations in a group of patients with DD. Vitamin D levels were measured in all patients with DD and healthy controls. In the patient group, clinical characteristics were compared between vitamin D deficient and nondeficient subgroups. Diseased palmar fascia samples were obtained from 14 patients undergoing fasciectomy for DD. Correlations between vitamin D levels and vitamin D receptor(VDR), TGF-β1 expression levels in collected fascia samples were evaluated.Vitamin D concentrations were significantly lower in patients than in healthy controls. In addition, total extension deficit of involved fingers was higher in vitamin D deficient patients. Moreover, a positive correlation was found between vitamin D levels and expression of VDR in pathologic fascia in patients undergoing fasciectomy for contracture. Serum vitamin D levels were found to be low in patients with DD. Expression of VDR was lower in the vitamin D deficient group.The results suggest a potential link between vitamin D status and DD but causation is not yet established. The potential role of vitamin D and its interaction with VDR and the TGF-β1 signaling pathway in the pathogenesis of DD needs to be explored further.

In this paper, we study [Formula: see text]-skew McCoy rings under the [Formula: see text]-compatible or the [Formula: see text]-semicompatible conditions. We show that if [Formula: see text] is a semicommutative right or left artinian ring which is [Formula: see text]-semicompatible with an epimorphism [Formula: see text], then the Jacobson radical [Formula: see text] is [Formula: see text]-skew McCoy. As a corollary, we get that the Jacobson radical of a semicommutative artinian ring is right McCoy. We also show that every [Formula: see text]-compatible right duo ring is [Formula: see text]-skew McCoy and that for [Formula: see text]-compatible regular rings, the notions of the [Formula: see text]-skew McCoy and the right McCoy coincide. In addition, we show that every [Formula: see text]-semicompatible semicommutative ring is linearly [Formula: see text]-skew Camillo and that every matrix ring over a division ring is linearly [Formula: see text]-skew Camillo for any endomorphism [Formula: see text].

Background Autologous fat grafts are commonly used in cosmetic and reconstructive surgery, and various methods are used to improve their viability. Low-level laser therapy (LLLT) can enhance the proliferation, growth, and differentiation of various cell lines, including stem cells. Our study investigated and compared the effects of LLLT and the addition of adipose-derived stem cells (ADSCs) on the viability of fat grafts.Methods Twenty nude mice were divided into four groups: control (group 1), LLLT irradiation (group 2), ADSC addition (group 3), and LLLT irradiation+ADSC addition (group 4). ADSCs were combined with the fat tissue. LLLT irradiation was performed once daily for 1 week from the day of grafting. After 8 weeks, the weight, volume, histology, and Western blot findings of the grafted fat tissues were evaluated.Results The retention rate and volume of the fat tissue in groups 2, 3, and 4 were higher than that of group 1, but the difference was not statistically significant. The number of capillaries, histological parameters, and immunofluorescence staining analyses for CD68, CD31, fibroblast growth factor, and vascular endothelial growth factor (VEGF) showed no significant differences among the four groups. The expression level of VEGF was higher in group 2 than in the other groups, but not to a statistically significant level.Conclusions LLLT and ADSCs did not significantly improve the viability of autologous fat grafts. Therefore, further study is necessary to develop safe and effective methods to improve the viability of these grafts for clinical application.

The interleukin (IL)-23/T-helper (Th)17 axis is considered central to the pathogenesis of psoriasis, with IL-36γ considered a marker for histological differential diagnosis. However, expression data regarding key cytokines in the pathogenesis of psoriasis, as well as data on the effects of IL-23 inhibition on downstream cytokines in human psoriatic skin, are limited. We investigated the expression profile of key cytokines and the effect of ustekinumab (UST) on cytokine expression in human psoriatic tissue. Tumor necrosis factor (TNF)-α, IL-23, IL-17A, and IL-22 were highly expressed in the epidermis, dermal papillae, and upper dermis in patients with psoriasis compared with controls; IL-36γ was strongly expressed in the upper epidermis. Compared with the untreated group, expression intensity and area of IL-23 were significantly decreased in the UST group; expression areas of TNF-α, IL-17A, IL-22, and IL-36γ did not differ. This study identified the distribution and quantitative expression levels of key cytokines in psoriatic lesions and demonstrated that only IL-23 was downregulated without blocking downstream effector cytokines in recalcitrant psoriatic lesions during UST treatment. Our results suggest that, although IL-23 is inhibited, the persistent expression of IL-17 through an alternative pathway maintains the vicious cycle of the TNF-α/IL-23/IL-17 axis with IL-36γ, inducing refractory psoriatic lesions in patients with well-controlled psoriasis.

Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.

Primary glioblastoma develops de novo without clinical or histological evidence of a low-grade precursor lesion, whereas secondary glioblastoma develops from a low-grade glioma. The present report describes an extraordinary case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma. A 31-year-old female had a surgical history of IDH-mutant diffuse astrocytoma on the left frontal lobe six years before. Magnetic resonance imaging revealed new infiltrative lesions in the left frontal lobe adjacent to the previous lesion. The patient underwent tumourectomy, and the new infiltrative lesion was diagnosed as glioblastoma. Interestingly, the IDH-1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing. ATRX (p.Gln1670Ter) and TP53 (p.His193Arg) mutations were found in both lesions. Additionally, the PTEN (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the IDH mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the IDH mutation to develop from low grade glioma with IDH mutation. However, this case showed that the other genetic mutations can be initiated before the IDH mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma.

Subependymoma is a slow-growing, exophytic, intraventricular glial neoplasm that commonly arises in the ventricular system. However, a report found that the frequency of intracerebral subependymoma was 0.4% in 1000 routine autopsies. To the best of our knowledge, only seven cases of intracerebral subependymoma have been reported. We report a rare case of intracerebral subependymoma in a child. An 11-year-old girl with generalized tonic-clonic seizures visited the emergency room and had an intraparenchymal tumor on the left frontal lobe on magnetic resonance imaging (MRI). Craniotomy with gross total removal was performed without any perioperative morbidities. The tumor was finally histopathologically diagnosed as a subependymoma.

Background Pleomorphic xanthoastrocytoma (PXA) is a rare type of astrocytoma with a peak incidence from 10 to 19 years of age. PXA is found most commonly in the supratentorium. When it is present in atypical areas such as the infratentorium, it is often overlooked as a potential differential diagnosis. Case Description This report discusses the case of an 18-year-old woman with a pure PXA in the left cerebellum. The case consists of interesting pathologic and molecular features which do not align with the literature about PXA: a positive finding for BRAF V600E mutation and a negative finding for cluster of differentiation 34 expression. A review of pure PXA cases in the infratentorium has also been completed. Conclusions To our knowledge, this is the first case of PXA in the infratentorium with BRAF V600E mutation. The case also highlights the clinical relevance of including PXA as a differential diagnosis for lesions of the infratentorium.

AIMS The importance of programmed cell death ligand 1 (PD-L1) expression has emerged in clinical trials of PD-L1 target therapy in renal cell carcinoma (RCC). This study compares PD-L1 assays in RCC. METHODS AND RESULTS Two US Food and Drug Administration-approved PD-L1 assays (22C3 and SP142) and one research-use only antibody (E1L3N) were used in a retrospective cohort of 591 patients with RCC. PD-L1 positivity on tumour cells (TCs) and immune cells (ICs) and combined positive score (CPS) were evaluated. With the 22C3, SP142 and E1L3N assays, positive PD-L1 expression on TCs ≥1% was observed in 24 (4.1%), 12 (2.0%) and 16 (2.7%) cases and on ICs ≥1% was observed in 132 (22.3%), 120 (20.3%) and 65 (11.0%) cases, respectively. PD-L1 expression scores among the three assays showed moderate-high positive correlation (ρ = 0.599-0.835, P

Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy.

BACKGROUND Chordomas, which are rare malignant neoplasms arising from notochordal remnants, often cause gradually progressive clinical symptoms. Intradural cranial chordomas (ICCs) are extremely rare and generally have a favorable prognosis. However, the authors reported the case of a primary ICC originating in the pineal gland presenting with recurrent thalamic hemorrhage and displaying an aggressive postoperative clinical course. OBSERVATIONS A 41-year-old man arrived at the emergency department with morning headaches and recurrent syncope that had lasted several months. Computed tomography and magnetic resonance imaging (MRI) revealed a pineal gland mass causing obstructive hydrocephalus and a subacute hematoma in the right thalamus. Three weeks after an endoscopic third ventriculostomy was performed, recurrent hemorrhage was observed in the right thalamus. The tumor was promptly removed surgically. The yellowish-white tumor did not exhibit abundant bleeding. No evidence of intratumoral hemorrhage around the hematoma pocket was found. Histopathological examination revealed the characteristics of a chordoma with minimal vascularity. MRI performed 10 weeks postoperatively for worsening headaches revealed abnormal enhancement of multiple cranial nerves, suggesting leptomeningeal seeding (LMS) of the tumor. LESSONS Despite radiotherapy and intrathecal chemotherapy, the patient’s neurological status worsened; he died 2 years postoperatively. A pineal ICC may cause recurrent thalamic hemorrhage and potentially fatal LMS, even in the early postoperative period.

Among readers of this journal are two (not necessarily disjoint) groups of scholars who will benefit, albeit to differing degrees, from this book: first, those interested in the history and methodo...

Intraosseous myoepithelial tumors are very rare. Due to the low incidence and diverse histologic features, accurate diagnosis is challenging, necessitating ancillary immunohistochemistry. Moreover, genetic abnormality in this tumor was not revealed until recently. Although EWSR1 translocation is involved in half of the cases of intraosseous myoepithelioma, only a few cases have indicated its counterpart gene. We herein describe a case of intraosseous myoepithelioma with a novel localization in the fourth metatarsal bone of a 36-year-old female. Cytogenetic analysis using next generation sequencing detected a rare EWSR1-PBX3 fusion. Next generation sequencing could be useful in understanding the cytogenetic characteristics of intraosseous myoepithelioma, and in obtaining an accurate diagnosis of this rare condition.

Background Artificial intelligence (AI) research is highly dependent on the nature of the data available. With the steady increase of AI applications in the medical field, the demand for quality medical data is increasing significantly. We here describe the development of a platform for providing and sharing digital pathology data to AI researchers, and highlight challenges to overcome in operating a sustainable platform in conjunction with pathologists. Methods Over 3000 pathological slides from five organs (liver, colon, prostate, pancreas and biliary tract, and kidney) in histologically confirmed tumor cases by pathology departments at three hospitals were selected for the dataset. After digitalizing the slides, tumor areas were annotated and overlaid onto the images by pathologists as the ground truth for AI training. To reduce the pathologists’ workload, AI-assisted annotation was established in collaboration with university AI teams. Results A web-based data sharing platform was developed to share massive pathological image data in 2019. This platform includes 3100 images, and 5 pre-processing algorithms for AI researchers to easily load images into their learning models. Discussion Due to different regulations among countries for privacy protection, when releasing internationally shared learning platforms, it is considered to be most prudent to obtain consent from patients during data acquisition. Conclusions Despite limitations encountered during platform development and model training, the present medical image sharing platform can steadily fulfill the high demand of AI developers for quality data. This study is expected to help other researchers intending to generate similar platforms that are more effective and accessible in the future.

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH., Graphical Abstract

In recent years, molecular tests have become essential to diagnose brain tumor. Although numerous molecular studies of glioblastoma have been conducted, pathogenesis of glioblastoma has not been fully identified. Present report is an extraordinary case of glioblastoma, IDH-wild type with BCR-ABL1 fusion. The BCR-ABL1 fusion is also called ‘Philadelphia gene’ and have never been found in solid tumors other than hemato-lymphoid malignancies. A 63-year-old man presented with clumsy and inappropriate word symptoms a week ago. Magnetic resonance imaging test revealed a 6.6 x 5.0 cm heterogeneously enhancing mass in the left temporal lobe and the patient underwent tumorectomy. Microscopically, tumor showed increasing cellularity, marked nuclear atypia and brisk mitosis. Microvascular proliferation and necrosis was present that can be diagnosis as glioblastoma. In addition, tumor showed strong GFAP positivity which indicated the glial differentiation. There is no evidence of diagnosis as another tumor including metastatic carcinoma or hemato-lymphoid malignancy. Interestingly, BCR-ABL1 fusion was detected in next generation sequencing test. The BCR-ABL1 fusion was a novel finding in glioblastoma, thus additional fluorescence in situ hybridization tests were conducted for confirmation BCR-ABL1 fusion and the same alteration was found. The patient had no leukemic presentation in the blood test, radiologic test and clinical symptom. Notably, this is the first case report that glioblastoma has the BCR-ABL1 fusion.

Downregulation of human leukocyte antigen (HLA) class I has been postulated to be a mechanism of adaptive immune escape in various tumors, especially microsatellite instability–high (MSI‐H) colorectal cancer (CRC). In this study, we aimed to investigate HLA class I and β2‐microglobulin (β2M) expression in MSI‐H and microsatellite‐stable (MSS) CRCs and determine its prognostic impact. The representative areas from the tumor center (TC) and tumor periphery (TP) from 300 CRCs, including 161 MSI‐H and 139 MSS cases, were selected to construct a tissue microarray. Immunohistochemistry (IHC) for HLA A/B/C, β2M, CD3, and CD8 was performed. Reduced HLA A/B/C expression was detected in 113 (70.2%) MSI‐H and 54 (38.8%) MSS cases, while reduced β2M expression was observed in 69 (42.9%) MSI‐H and 17 (12.2%) MSS cases. Although reduced β2M expression was associated with higher pathological tumor (pT) stage in MSI‐H CRC with borderline significance, no association was found between HLA A/B/C and β2M expression and survival. Interestingly, reduced HLA A/B/C expression in MSS was associated with higher stage, and reduced HLA A/B/C and β2M expression was an independent prognostic factor in multivariate analysis. In conclusion, reduced HLA A/B/C and β2M expression was frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitor. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor prognosis in MSS cancers. Overall, IHC for HLA A/B/C and β2M might be a feasible predictive or prognostic tool in CRC., Reduced HLA A/B/C and β2M expression is frequently observed in immunotherapy‐naive MSI‐H CRC, suggesting the possibility of primary resistance to immune checkpoint inhibitors. Interestingly, downregulation of HLA A/B/C and β2M was associated with poor survival in MSS cancers, but not in MSI‐H tumors, indicating that cell‐mediated antitumoral immune response may also play an important role in MSS CRC. Together, IHC for HLA A/B/C and β2M can be a predictive or prognostic tool in CRC.

BACKGROUND High-quality learning materials are needed for artificial intelligence (AI) development, but are not practically available; this situation is especially poor in the medical field. In particular, annotating medical images (e.g., annotation for tumor area by pathologists) is massive as well as expensive, and subject to privacy protection. These are major limitations for AI developers to approach and reproduce medical image data. OBJECTIVE This study aimed to reduce barriers for AI researchers to access medical image datasets by collating and sharing high-quality medical images with pathologists, and to find applicable ways to apply diagnostic AI assistance to reduce the pathologists’ workload. METHODS Pathology slides of tumors of five organs (liver, colon, prostate, pancreas and biliary tract, and kidney) from histologically confirmed cases were selected for this study. After scanning the slides to obtain whole slide digital images, the patient information was de-identified, and annotation for the tumor area was performed by the pathologist. Next, an AI-assisted annotation process was used in parallel to improve the annotation workload of pathologists and to draw complex lesion boundaries more accurately. This allowed all the data to include the annotations confirmed by experienced pathologists, and to be used as an AI learning dataset. RESULTS A web-based data-sharing platform for AI learning was built, and was unveiled in 2019. In total, 3,100 massive datasets of 5 organ carcinomas were shared through this platform, and were accessible to all researchers. The platform had the advantage that users could search data visually and intuitively; except for commercial purposes, all researchers made free use of the provided dataset for their research. Finally, the platform also provided five image data pre-processing algorithms that could help AI modeling learners. CONCLUSIONS We built and operated a web-based data-sharing platform for AI researchers providing a high-quality digital pathology dataset personally annotated by pathologists. We hope that our experience will help researchers who want to build such a platform in future, by sharing issues gained from collecting and sharing these valuable data.

Combined anti-VEGF/anti-programmed death ligand 1 (PD-L1) therapy synergistically improves treatment outcomes in advanced renal cell carcinoma (RCC) compared with anti-PD-L1 or anti-vascular endothelial growth factor (VEGF) monotherapy. Here, we analyzed the expression of VEGF and PD-L1 (SP142) in a retrospective cohort of 513 patients with clear-cell (cc) RCC. PD-L1 expression on tumor cells (TCs) and immune cells (ICs) was evaluated by immunohistochemistry (IHC) with a positive threshold value of ≥1%. Positive staining for PD-L1 on ICs and TCs was found in 115 (22.4%) and 7 (1.4%) cases, respectively. Moderate or strong staining for VEGF on TCs was found in 217 (42.3%) patients. PD-L1 expression on ICs and TCs was positively associated with VEGF expression on TCs. Both VEGF and PD-L1 (IC) positivity (VEGF/PD-L1 [IC]: +/+) was observed in 65 (12.7%) cases. Patients in this subgroup exhibited more aggressive clinicopathologic features, including older age, higher World Health Organization/International Society of Urological Pathology (ISUP) grade, angiolymphatic invasion, tumor necrosis, and sarcomatoid differentiation (P 0.05). Kaplan-Meier analysis indicated that expression of VEGF and PD-L1 on ICs was positively correlated with tumor recurrence (P 0.001), whereas expression of PD-L1 on TCs was not (P = 0.554). Tumors with positivity for both antibodies (VEGF/PD-L1 [IC]: +/+) exhibited the worst recurrence-free survival (P 0.001), and double positivity independently predicted tumor recurrence in ccRCC. The present study provides comprehensive and basic information about VEGF and PD-L1 expression for new combined therapy in primary ccRCC.

Back ground Intracranial germinomas are one of the most radiosensitive tumors and are curable by radiotherapy (RT) alone. RT-only therapy without chemotherapy is effective. But, as patients with germinoma can expect long-term survival, the adverse effects of RT and late sequelae in survivors are of most concern. So, recently, standard treatment protocol of combination with chemotherapy and reduced dose of RT could be widely acceptable. Case presentation We report a patient with germinoma who developed RT-induced glioblastoma. He was diagnosed as biopsy-proven germinoma at the age of 12. Postoperatively, he underwent RT alone without chemotherapy and remained free of tumor without recurrence during long-term follow up. However, after almost 20 year, he developed RT-induced glioblastoma. Conclusions Although RT has the highest priority among treatments on intracranial germinomas, RT-only therapy with full dose for germinoma can have delayed severe complications. So, chemotherapy prior to reduced dose RT is more desirable.

PURPOSE Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. MATERIALS AND METHODS We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. RESULTS The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar's test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. CONCLUSION Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

Programmed cell death ligand‐1 (PD‐L1) detection assays have not been standardized for patients with colorectal cancer, and the prognostic value of PD‐L1 expression is unclear. We compared the PD‐L1 expression patterns in colorectal cancer samples using various immunohistochemical assays using 3 primary PD‐L1 antibodies (assay 1, MIH1; assay 2, E1L3; and assay 3, 22C3) and investigated the prognostic implication of PD‐L1 expression using each. Additionally, PD‐L1 gene amplification was evaluated using FISH. The percentage scorings and positivity rates of the 3 assays differed; the degrees of correlation and concordance between assays 2 and 3 were relatively high, whereas assay 1 was an outlier. Multivariate analyses indicated that PD‐L1 positivity in tumor cells and its negativity in tumor‐infiltrating lymphocytes were independent predictors of poorer overall and disease‐free survival in patients with colorectal cancer. PD‐L1 gene amplification was found in 2 patients (PD‐L1/CEP ratio, 5.60 and 5.84, respectively); both had strong PD‐L1 expression according to immunohistochemistry. Overall, our study showed that PD‐L1 expression status in tumor and immune cells is an independent prognostic factor in patients with colorectal cancer. Standardizations of both PD‐L1 detection using immunohistochemistry and the cut‐off for positivity are necessary. Finally, PD‐L1 gene amplification was found in a small fraction of samples, suggesting the possibility of an ancillary test for PD‐L1 evaluation.

We propose silicone implants capable of the local, controlled release of a glucocorticoid drug, triamcinolone acetonide (TA), for the prevention of fibrosis. The shells of these silicone implants were coated with two different loading amounts of TA, which could release the drug in a sustained manner for 12 weeks. The drug-loaded implants were inserted into the subcutaneous space in living rats, and the tissues were biopsied at scheduled times during 12 weeks. For the drug-coated implants, the capsule thickness and collagen density decreased compared with those of the non-coated implant. Because of the effect of TA, inflammation and the expression of pro-inflammatory cytokines were downregulated, thereby decreasing the number of monocytes during acute inflammation. This effect in turn decreased the number of macrophages at the later stage of inflammation, leading to the expression of less TGF-β and consequently fewer fibroblasts and myofibroblasts. Our findings also revealed that with an appropriate dose control, skin and muscle atrophy, major side effects of TA, could be avoided while still effectively reducing fibrosis. Therefore, we conclude that the local, sustained release of an appropriate dose of a glucocorticoid drug can be a promising strategy for safely preventing fibrosis around silicone implants.