Showing papers by "Hiroshi Nishihara published in 2021"
TL;DR: The use of organic radicals as building blocks is an effective approach to the production of open-shell coordination polymers (CPs) as mentioned in this paper, and two-dimensional (2D) CPs with honeycomb spin-lattices have attra
Abstract: The use of organic radicals as building blocks is an effective approach to the production of open-shell coordination polymers (CPs). Two-dimensional (2D) CPs with honeycomb spin–lattices have attra...
42 citations
TL;DR: In this paper, the effect of spin-correlated electronic and magnetic properties of organic radicals on luminescence properties has been investigated based on interplay with spins, and it has been shown that the effects of these properties on the luminance of radicals can be significant.
Abstract: Spin-correlated electronic and magnetic properties of organic radicals have been developed, but luminescence properties, based on interplay with spins, have rarely been reported. The effect of magn...
34 citations
TL;DR: The role of the magnetic field dominantly affects the spin sublevel population of radical dimers in the ground states, and the spin degree of freedom of ground-state open-shell molecules is a new key for achieving magnetic-field-controlled molecular photofunctions.
Abstract: Organic radicals are an emerging class of luminophores possessing multiplet spin states and potentially showing spin-luminescence correlated properties. We investigated the mechanism of recently reported magnetic field sensitivity in the emission of a photostable luminescent radical, (3,5-dichloro-4-pyridyl)bis(2,4,6-trichlorophenyl)methyl radical (PyBTM) doped into host αH-PyBTM molecular crystals. The magnetic field (0–14 T), temperature (4.2–20 K), and the doping concentration (0.1, 4, 10, and 22 wt%) dependence on the time-resolved emission were examined by measuring emission decays of the monomer and excimer. Quantum mechanical simulations on the decay curves disclosed the role of the magnetic field; it dominantly affects the spin sublevel population of radical dimers in the ground states. This situation is distinctly different from that in conventional closed-shell luminophores, where the magnetic field modulates their excited-state spin multiplicity. Namely, the spin degree of freedom of ground-state open-shell molecules is a new key for achieving magnetic-field-controlled molecular photofunctions.
30 citations
TL;DR: The immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes is uncovered and a workflow with optimal biomarker cut-offs for discriminating the tumour profiles of LAG-3, TIM- 3, and TIGIT is devised.
Abstract: A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs.
25 citations
TL;DR: The concordance between NGS and PCR-based testing was 98.8% (79/80) and 98.7% (74/75), respectively, for MSI-H as mentioned in this paper.
Abstract: Various malignancies exhibit high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR). The MSI-IVD kit, a polymerase chain reaction (PCR)-based method, was the first tumor-agnostic companion diagnostic to detect MSI status in MSI-H solid tumors. Recently, next-generation sequencing (NGS), which can also detect MSI-H/dMMR, has been made clinically available; however, its real-world concordance with PCR-based testing of MSI-H/dMMR remains to be investigated. The co-primary end points included the positive and negative predictive values of MSI-H/dMMR. A retrospective analysis of 80 patients who had undergone both MSI testing and NGS between July 2015 and March 2021 was conducted. Five patients were confirmed to have MSI-H in both examinations. Among the 75 patients diagnosed as microsatellite stable (MSS) by PCR-based testing, one with pancreatic cancer was diagnosed as having MSI-H after NGS. One patient with pancreatic cancer was diagnosed as having MSS in both tests was found to have a mutation in MLH1 by NGS, which was confirmed as dMMR by IHC staining. NGS had positive and negative predictive values of 100% (5/5) and 98.7% (74/75), respectively, for MSI-H. The concordance between NGS and PCR-based testing was 98.8% (79/80). Thus, NGS can be useful for evaluating MSI/MMR status in clinical practice and can be an important alternative method for detecting MSI-H/dMMR in the future.
17 citations
TL;DR: In this paper, the authors discuss the interpretation of RT-qPCR results relative to viral infectivity and propose the new concept of a "social cut-off" Ct value and risk stratification based on the correlation of Ct with infectivity.
Abstract: The year 2020 will be remembered for the coronavirus disease 2019 (COVID-19) pandemic, which continues to affect the whole world. Early and accurate identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is fundamental to combat the disease. Among the current diagnostic tests, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) is the most reliable and frequently used method. Herein, we discuss the interpretation of RT-qPCR results relative to viral infectivity. Although nasopharyngeal swab samples are often used for RT-qPCR testing, they require collection by trained medical staff. Saliva samples are emerging as an inexpensive and efficient alternative for large-scale screening. Pooled-sample testing of saliva has been applied for mass screening of SARS-CoV-2 infection. Current policies recommend isolating people with borderline cycle threshold (Ct) values (35
16 citations
TL;DR: In this article, the authors analyzed the association between biglycan expression in TECs in lung cancer and cancer progression in patients and showed that low BGN level in preoperative serum in patients with lung cancer might indicate low malignancy.
Abstract: Objectives In lung cancer, surgery remains the most curative treatment and limited resection is beneficial for patients with low cardiopulmonary function and low malignancy tumors. However, there are no biomarkers of low malignancy to select candidates for limited resection without compromising the outcome of treatments. Recently we identified biglycan (BGN) as a tumor endothelial cell (TEC) marker that is associated with tumor progression in various cancers. In this study, we analyzed the association between BGN expression in TECs in lung cancer and cancer progression in patients. Materials and methods First, we performed immunohistochemistry of BGN with resected lung tumor tissues of 155 patients who had undergone thoracic surgery and analyzed the correlation between BGN-positive vessel density in primary lung tumors and clinicopathological factors. Second, we measured the BGN levels in preoperative serum of other 46 patients with lung cancer by ELISA, and analyzed the correlation between BGN expression in tumor tissues and blood BGN levels. Results High BGN expression in the TECs was significantly associated with T factor, and was a significant negative predictor. BGN levels in preoperative serum of 46 patients with lung cancer was significantly correlated with BGN expression in the TECs. Preoperative serum BGN level was significantly lower in healthy volunteers and less invasive adenocarcinoma than in invasive adenocarcinoma and other lung carcinomas. These results suggest that low BGN level in preoperative serum in patients with lung cancer might indicate low malignancy. Conclusions BGN can be a potential biomarker for lung cancer.
16 citations
TL;DR: Interestingly, the FeBHT self‐powered photodetector reveals extremely high long‐term air stability, maintaining over 94% of its initial photocurrent after aging for 60 days without encapsulation, which opens the prospect of using organometallic 2D materials in commercialized optoelectronic fields.
Abstract: Organometallic two-dimensional (2D) nanosheets with tailorable components have recently fascinated the optoelectronic communities due to their solution-processable nature. However, the poor stability of organic molecules may hinder their practical application in photovoltaic devices. Instead of conventional organometallic 2D nanosheets with low weatherability, an air-stable π-conjugated 2D bis(dithiolene)iron(II) (FeBHT) coordination nanosheet (CONASH) is synthesized via bottom-up liquid/liquid interfacial polymerization using benzenehexathiol (BHT) and iron(II) ammonium sulfate [Fe(NH4)2(SO4)2] as precursors. The uncoordinated thiol groups in FeBHT are easily oxidized, but the Fe(NH4)2(SO4)2 dissociation rate is slow, which facilitates the protection of sulfur groups by iron(II) ions. The density functional theory calculates that the resultant FeBHT network gains the oxygen-repelling function for oxidation suppression. In air, the FeBHT CONASH exhibits self-powered photoresponses with short response times (<40 ms) and a spectral responsivity of 6.57 mA W-1, a specific detectivity of 3.13 × 1011 Jones and an external quantum efficiency of 2.23% under 365 nm illumination. Interestingly, the FeBHT self-powered photodetector reveals extremely high long-term air stability, maintaining over 94% of its initial photocurrent after aging for 60 days without encapsulation. These results open the prospect of using organometallic 2D materials in commercialized optoelectronic fields.
14 citations
TL;DR: In this paper, the relationship of ARID1A mutation and expression to the immunogenic profile of different histologic subtypes of ovarian cancer was defined, and the immunohistochemical status was analyzed for selecting candidates for immune checkpoint blockade in CCC.
13 citations
TL;DR: In this paper, the results of gene profiling targeting 160 cancer-related genes in breast and non-breast cancer tissue were compared with the ERBB2-estimated gene copy number (CN).
Abstract: Assessing Erb-b2 receptor tyrosine kinase 2 (ERBB2) amplification status in breast and gastric cancer is necessary for deciding the best therapeutic strategy. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are currently used for assessing protein levels and gene copy number (CN), respectively. The use of next-generation sequencing (NGS) to measure ERBB2 CN in breast cancer is approved by the United States Federal Drug Administration as a companion diagnostic. However, a CN of less than 8 is evaluated as “equivocal”, which means that some ERBB2 amplification cases diagnosed as “HER2 negative” might be false-negative cases. We reviewed the results of gene profiling targeting 160 cancer-related genes in breast (N = 90) and non-breast (N = 19) cancer tissue, and compared the ERBB2 CN results with the IHC/FISH scores. We obtained an estimated CN from the measured CN by factoring in the histological proportion of tumor cells and found that an ERBB2-estimated CN of 3.2 or higher was concordant with the combined IHC/FISH outcome in 98.4% (88/90) of breast cancer cases, while this was not always evident among non-breast cancer cases. Therefore, NGS-estimated ERBB2 CN could be considered a diagnostic test for anti-HER2 therapy after the completion of adequate prospective clinical trials.
12 citations
TL;DR: In this article, a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of renal cell carcinoma (RCC) was performed to clarify the effects of the AXL/GAS6 axis on RCC.
Abstract: Background Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis. Methods To clarify the effects of the AXL/GAS6 axis on RCC, we herein performed a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of RCC. We further applied genome-wide mutation analyses and methylation arrays. Results Varying patterns of AXL and GAS6 expression were observed throughout primary RCC tumours and metastases. Scoring individual AXL/GAS6 levels in the tumour centre and invasive margin, namely, the AXL/GAS6 score, showed a good ability to predict the prognosis of clear cell RCC. Metastasis- and histological subtype-specific differences in the AXL/GAS6 score existed since lung metastasis and the papillary subtype were weakly related to the AXL/GAS6 axis. Cell-by-cell immunohistological assessments clarified an immunosuppressive environment in tumours with high AXL/GAS6 scores. Genomic alterations in the PI3K-mTOR pathway and DNA methylation profiling revealed distinct differences with the AXL/GAS6 score in ccRCC. Conclusion The AXL/GAS6 scoring system could predict the outcome of prognosis and work as a robust biomarker for the immunogenomic state in RCC.
TL;DR: Immunohistologic analyses suggested that an allergic reaction played an important role in the etiology of Kimura disease in this case.
Abstract: A 52-year-old man with a 2-year history of left buccal swelling was admitted to our department. An elastic hard oral mass was palpated under the intact buccal mucosa. A CT scan with enhancement revealed a solid mass measuring 2.0 × 1.5 × 1.3 cm between the left masseter muscle and the maxilla. Laboratory examination showed elevated peripheral blood eosinophil count of 1070/μL (12.3%) and serum immunoglobulin (Ig)E level of 1374 IU/mL. Histologic examination of transorally excised mass revealed lymphoid follicular hyperplasia with reactive germinal centers and eosinophilic infiltration with eosinophilic micro-abscesses in the germinal centers. Abundant IgE deposition in a reticular fashion was observed in the germinal centers and c-kit positive mast cells was observed in the paracortical area in the excised mass. The patient was diagnosed with Kimura disease (KD) and treated with oral prednisolone, tapering from 10 mg/day for approximately 8 months. Eosinophil count and serum IgE level decreased to 435/μL (5%) and 520 IU/dL, respectively. He is free from symptoms at the time of this submission. KD, a rare, benign, and chronic inflammatory disorder, occurs predominantly in young male adults in Asia. Patients with KD who presents with buccal mass are relatively rare. Immunohistologic analyses suggested that an allergic reaction played an important role in the etiology of KD in this case.
TL;DR: In this article, liquid-liquid interfacial reactions between FeSO4 (aq.) and benzenehexathiol (BHT) in chloroform at room temperature and at 45 °C give bis(dithiolato)iron nanosheets 1-RT and 1-H, respectively.
Abstract: Liquid-liquid interfacial reactions between FeSO4 (aq.) and benzenehexathiol (BHT) in chloroform at room temperature and at 45 °C give bis(dithiolato)iron nanosheets 1-RT and 1-H, respectively. Nan...
28 Jun 2021
TL;DR: In this article, the authors performed comprehensive genomic testing with either their original in-house CLHURC system or with OncoPrime, and found that TP53, PIK3CA, AKT1, ESR1, and MYC were the most frequently mutated genes.
Abstract: Clinical targeted sequencing allows for the selection of patients expected to have a better treatment response, and reveals mechanisms of resistance to molecular targeted therapies based on actionable gene mutations. We underwent comprehensive genomic testing with either our original in-house CLHURC system or with OncoPrime. Samples from 24 patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer underwent targeted sequencing between 2016 and 2018. Germline and somatic gene alterations and patients' prognosis were retrospectively analyzed according to the response to endocrine therapy. All of the patients had one or more germline and/or somatic gene alterations. Four patients with primary or secondary endocrine-resistant breast cancer harbored germline pathogenic variants of BRCA1, BRCA2, or PTEN. Among somatic gene alterations, TP53, PIK3CA, AKT1, ESR1, and MYC were the most frequently mutated genes. TP53 gene mutation was more frequently observed in patients with primary endocrine resistance compared to those with secondary endocrine resistance or endocrine-responsive breast cancer. Recurrent breast cancer patients carrying TP53-mutant tumors had significantly worse overall survival compared to those with TP53-wild type tumors. Our 160-gene cancer panel will be useful to identify clinically actionable gene alterations in breast cancer in clinical practice.
TL;DR: The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.
Abstract: We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11 C-MET or 18 F-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11 C-MET PET and 18 F-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.
01 Jan 2021
TL;DR: In this article, the authors reported the first Japanese case of a metastatic abiraterone acetate-resistant castration-resistant prostate cancer accompanied by BRCA2 mutation.
Abstract: Introduction Most metastatic prostate cancers acquire the capacity for androgen-independent growth and become resistant to androgen deprivation therapy. A patient-focused treatment strategy is needed for aggressive castration-resistant prostate cancer. Case presentation We report the case of a 62-year-old man who presented with prostatic adenocarcinoma who was treated by radiation and combined androgen blockade. After completion of first-line therapy, he was diagnosed with multiple metastatic castration-resistant prostate cancer in the lung. Second-line therapy with abiraterone acetate resulted in partial remission of the lung metastases. Thoracic surgery was performed to remove the single lung metastasis remaining. Next-generation sequencing of the specimens demonstrated homozygous loss of BRCA2. We note in this case a heterogeneous response to abiraterone acetate may be related to the somatic BRCA2 deletions. Conclusions We present the first Japanese case of a metastatic abiraterone acetate-resistant castration-resistant prostate cancer accompanied by BRCA2 mutation.
TL;DR: In this paper, an efficient and convenient electrochemical method was developed to synthesize π-conjugated redox metal-complex linear polymer wires composed of azobenzene-bridged bis(terpyridine) units covalently immobilized on glassy carbon (GC).
Abstract: We developed an efficient and convenient electrochemical method to synthesize π-conjugated redox metal-complex linear polymer wires composed of azobenzene-bridged bis(terpyridine)metal (2-M, M = Fe, Ru) units covalently immobilized on glassy carbon (GC). Polymerization proceeds by electrochemical oxidation of bis(4′-(4-anilino)-2,2′:6′,2″-terpyridine)metal (1-M) in a water–acetonitrile–HClO4 solution, affording ultralong wires up to 7400 mers (corresponding to ca. 15 μm). Both 2-Fe and 2-Ru undergo reversible redox reactions, and their redox behaviors indicate remarkably fast redox conduction. Anisotropic hetero-metal-complex polymer wires with Fe and Ru centers are constructed via stepwise electropolymerization. The cyclic voltammograms of two hetero-metal-complex polymer wires, GC/[2-Fe]–[2-Ru] (3) and GC/[2-Ru]–[2-Fe] (4), show irreversible redox reactions with opposite electron transfer characteristics, indicating redox diodelike behavior. In short, the present electrochemical method is useful to synthesize polymer wire arrays and to integrate functional molecules on carbon.
TL;DR: Xia et al. as discussed by the authors analyzed the expression profiles of OX40 and other relevant molecules, such as CD4, CD8, and Foxp3, in tumor stroma and cancer nest using immunohistochemistry and investigated their association with survival.
Abstract: OX40 (CD134) is a co-stimulatory molecule mostly expressed on activated T lymphocytes. Previous reports have shown that OX40 can be an immuno-oncology target and a clinical biomarker for cancers of various organs. In this study, we collected formalin-fixed paraffin-embedded tumor samples from 124 patients with small-cell lung cancer (SCLC) who had undergone surgery. We analyzed the expression profiles of OX40 and other relevant molecules, such as CD4, CD8, and Foxp3, in tumor stroma and cancer nest using immunohistochemistry and investigated their association with survival. High infiltration of OX40+ lymphocytes (OX40high) in tumor stroma was positively associated with relapse-free survival (RFS) and overall survival (OS) compared with low infiltration of OX40+ lymphocytes (OX40low) (RFS, median, 26.0 months [95% confidence interval (CI), not reached (NR)-NR] vs 13.2 months [9.1-17.2], p = .024; OS, NR [95% CI, NR-NR] vs 29.8 months [21.3-38.2], p = .049). Multivariate analysis revealed that OX40high in tumor stroma was an independent indicator of prolonged RFS. Moreover, RFS of patients with OX40high/CD4high in tumor stroma was significantly longer than that of patients with OX40low/CD4low. The RFS of patients with tumor stroma with OX40high/CD8high was significantly longer than that of patients with tumor stroma with OX40low/CD8high, OX40high/CD8low, or OX40low/CD8low. These findings suggest that OX40+ lymphocytes in tumor stroma play a complementary role in regulating the relapse of early-stage SCLC. Reinforcing immunity by coordinating the recruitment of OX40+ lymphocytes with CD4+ and CD8+ T cells in tumor stroma may constitute a potential immunotherapeutic strategy for patients with SCLC.
TL;DR: A 74-year-old Japanese woman with a 1-year history of right preauricular pain and a 2-month history of bleeding from the right ear was admitted to our department as discussed by the authors.
Abstract: A 74-year-old Japanese woman with a 1-year history of right preauricular pain and a 2-month history of bleeding from the right ear was admitted to our department. Tumor was observed in the anterior...
TL;DR: An organ-agnostic basket trial, which covers a variety of solid cancers harboring HER2 amplification, and the primary endpoint is the objective response rate, and secondary endpoints are progression-free survival, overall survival, duration of response, and safety.
Abstract: TPS3141Background: The human epidermal growth factor receptor 2 (HER2) gene amplification and mutations have emerged as oncogenic drivers and therapeutic targets not limited to breast and gastric c...
05 May 2021
TL;DR: Genomic profiling provides useful information for diagnosis, treatment, and prognosis, and detection of certain defects can possibly lead to optimal treatment, but this testing has not been widely used to inform prostate cancer treatment.
Abstract: Introduction Genomic profiling provides useful information for diagnosis, treatment, and prognosis, and detection of certain defects, such as DNA repair gene aberrations or microsatellite instability, can possibly lead to optimal treatment, but this testing has not been widely used to inform prostate cancer treatment. Case presentation A 55-year-old man sequentially treated for prostate cancer was diagnosed as neuroendocrine prostate cancer from prostate specimens resected because of urinary retention. Subsequently, he received five cycles of platinum-based chemotherapy in total and responded well. We also performed next-generation sequencing of a sample from the prostate specimen and identified a breast cancer susceptibility gene mutation with Murine Double Minute 2 amplification and loss of heterozygosity in retinoblastoma 1. Conclusion We report a neuroendocrine prostate cancer patient with Murine Double Minute 2 amplification who experienced an aggressive course and for whom platinum-based chemotherapy was effective, and one of the reasons for the good response might be the breast cancer susceptibility gene mutation.
20 Oct 2021
TL;DR: In this paper, the first case of ductal adenocarcinoma having a neuroendocrine phenotype was presented, where the authors performed transurethral resection of the prostate, and the diagnosis was ductal carcinoma with a Gleason score of 5 + 4.
Abstract: Background Ductal adenocarcinoma and neuroendocrine cancer are rare subtypes of prostate cancer with poor prognosis and limited therapeutic options. We present the first case of ductal adenocarcinoma having a neuroendocrine phenotype. Case presentation A 63-year-old man presented with gross hematuria and urinary retention, and his serum prostate-specific antigen level was 4.58 ng/mL. We performed transurethral resection of the prostate, and the diagnosis was ductal adenocarcinoma with a Gleason score of 5 + 4 for acinar adenocarcinoma. Magnetic resonance imaging showed local invasion of left lobe of the prostate and bone metastasis of the left trochanteric section of the femur. Multidisciplinary treatments such as androgen deprivation therapy, chemoradiation therapy, and surgery for metastatic lesions have led to long-term survival. Since next-generation sequencing revealed PTEN and RB1 co-loss and TP53 mutations, we re-evaluated the immunohistochemistry and he was found to be positive for synaptophysin. Conclusions This is the first Japanese case of ductal adenocarcinoma with a neuroendocrine phenotype. Genetic analysis may help not only guide the therapeutic strategies, but also sometimes with the diagnosis.
TL;DR: In this paper, a 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC.
Abstract: Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient's family was advised to undergo genetic counseling to consider additional RCC screening.
17 Mar 2021
TL;DR: Ductal adenocarcinoma of the prostate is a rare prostate cancer variant and associated with higher stage and greater risk of mortality and optimal systemic therapy is not known.
Abstract: Introduction Ductal adenocarcinoma of the prostate is a rare prostate cancer variant and associated with higher stage and greater risk of mortality. Optimal systemic therapy for metastatic ductal adenocarcinoma is not known. Case presentation A 67-year-old man presented with ductal adenocarcinoma of the prostate accompanied by multiple lung metastases and advanced bone metastases. We performed channel transurethral resection of the prostate and confirmed the diagnosis of ductal adenocarcinoma of the prostate. DNA sequencing identified a TP53 somatic point mutation (p.Gly245Ser) as the pathogenic variant. Furthermore, a homozygous deletion was observed in mitogen-activated protein kinase kinase kinase 1. The patient received enzalutamide but deceased 5 months after presenting to our institution. Conclusion To our knowledge, this is the first report of ductal adenocarcinoma of the prostate with a mitogen-activated protein kinase kinase kinase 1 homozygous deletion. Accumulation of whole-exome sequencing data is expected to inform future advances in therapy development.
TL;DR: A 71-year-old woman underwent excisional biopsy of a breast mass after a conclusive diagnosis was unable to be obtained from core needle biopsy showing an AdCC-like pattern, and results were supportive of spiradenoma.
Abstract: Breast spiradenoma is extremely rare, with only 4 cases reported previously. We describe an instructive case of breast spiradenoma resembling adenoid cystic carcinoma (AdCC). A 71-year-old woman underwent excisional biopsy of a breast mass after a conclusive diagnosis was unable to be obtained from core needle biopsy showing an AdCC-like pattern. Histopathologically, the lesion demonstrated solid and cribriform foci comprising basaloid cells, luminal cells, and eosinophilic hyaline material, reminiscent of solid-basaloid AdCC, alongside convoluted lumens, stromal edema, lymphocytic infiltration, and c-kit negativity. On molecular analysis, neither MYB fusion genes nor CYLD gene abnormalities were identified. These results were supportive of spiradenoma. Salivary gland- and skin adnexal-type tumors are challenging to diagnose due to morphological overlaps. This case, highlighting histopathological and molecular features, shows that breast spiradenoma can be a diagnostic pitfall among the differential diagnoses of AdCC.
27 Mar 2021
TL;DR: A rare case of localized prostate cancer with BRCA2 and RB1 co-loss was reported in this article, which is usually found at a more advanced stage with a poor prognosis.
Abstract: We report a rare case of localized prostate cancer with BRCA2 and RB1 co-loss, which is usually found at a more advanced stage with a poor prognosis. A 59-year-old male with prostate cancer was referred to our hospital for surgical treatment. He had schizophrenia that was well controlled by medicine. He had no family history of prostate cancer, breast cancer, or ovarian cancer. His initial PSA was 4.5 ng/mL, and Gleason score 3 + 4 adenocarcinoma was detected in one of 12 needle biopsy cores. Imaging studies demonstrated the clinical stage to be cT2aN0M0. Therefore, robot-assisted laparoscopic radical prostatectomy (RALP) with bilateral nerve sparing was performed. Based on histopathological analysis, the Gleason score was 4 + 3 and the pathological stage was pT2N0M0 with a negative surgical margin. Genetic sequencing identified BRCA2 and RB1 co-loss with limited loss of heterogeneity (LOH). At 12 months after surgery, his PSA level remained < 0.01 ng/mL. This case suggests the importance of early detection of prostate cancer and the possibility of cure for prostate cancer with high malignant potential.
TL;DR: A 15-year-old Japanese male with a 2-month history of swelling of his left subauricular area was admitted to the hospital and a thumb-sized, hard mass with mild tenderness was palpated on the left parotid gland as mentioned in this paper.
Abstract: A 15-year-old old Japanese male with a 2-month history of swelling of his left subauricular area was admitted to our department. A thumb-sized, hard mass with mild tenderness was palpated on the left parotid gland. Ultrasonography revealed a well-circumscribed, hypoechoic mass exhibiting heterogeneity in the left parotid gland measuring 1.7 × 1.5 × 1.3 cm. Computed tomography scan revealed a well-circumscribed, solid mass exhibiting slight peripheral enhancement in the left parotid gland. Magnetic resonance imaging revealed a hypointense mass in the left parotid gland on both T1- and T2-weighted images. Clinicoradiologic findings suggested a benign or low-grade malignant parotid tumor. The patient underwent left superficial parotidectomy with adequate safety margins. The facial nerve was identified and preserved. Neither facial paralysis nor tumor recurrence was observed as of 1 year postoperatively. Histologically, the nodule consisted of a vaguely nodular arrangement of variably sized ducts and acini in a hyalinized fibrous background with focal myxoid changes. The ductal/acinar component exhibited a bilayered arrangement of cuboidal luminal and flattened abluminal cells exhibiting a variety of epithelial proliferative patterns, including micropapillary and cribriform. Areas of oncocyte-like changes with intracellular coarse eosinophilic granules, apocrine-like feature, foamy/vacuolated changes, and clear cells were noted in the proliferating epithelium. Immunohistologically, the luminal cells were positive for gross cystic disease fluid protein-15. The Ki-67 labeling index was 2–3%. The histologic features and immunohistologic profile were consistent with sclerosing polycystic adenosis. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations in PTEN, PIK3CA, or PIK3R1.
Journal Article•
TL;DR: In the experience, the ICG fluorescence imaging system seems to be simple, safe, and effective, however, the use of ICg fluorescence in endoscopic tattooing necessitates the exploration of additional information such as the volume of the ICg solution and the timing of theICG injection.
Abstract: AIM: We assessed whether indocyanine green (ICG) fluorescence is effective for endoscopic tattooing in colorectal cancer surgery using a photodynamic eye (PDE) camera and fluorescent endoscope. METHODS: Between June 2014 and February 2018, 39 patients-17 patients with early and 22 patients with advanced colorectal cancer respectively-were enrolled and underwent preoperatively colonoscopic tattooing using 0.5 mL/time (n = 28 cases) or 0.3 mL/time (n = 11 cases) of ICG three days before laparotomy or laparoscopic surgery. We observed lesions using a PDE camera or a fluorescent endoscope during laparotomy or laparoscopic surgery. Moreover, we assessed the fluorescent luminance and fluorescent size of resected lesions intra- and post-operatively, respectively. Patients’ medical records and operation videos were retrospectively assessed to evaluate the visibility, duration, and adverse effects of tattooing. RESULTS: It was possible to obtain a useful fluorescent image with ICG fluorescent labeling and to determine the resection range in all cases. No difference regarding the distance from cancer’s oral margin to the ICG oral margin according to the volume of ICG (0.5 mL/time vs. 0.3 mL/time) was observed, but a significant difference concerning the distance from cancer’s oral margin to the ICG oral margin between early colorectal cancer and advanced cancer was noted (p = 0.0038). CONCLUSION: In our experience, the ICG fluorescence imaging system seems to be simple, safe, and effective. However, the use of ICG fluorescence in endoscopic tattooing necessitates the exploration of additional information such as the volume of the ICG solution and the timing of the ICG injection.