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1.
Emerg Infect Dis ; 30(10): 2214-2217, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39320242

RESUMEN

A 61-year-old man in Japan with abdominal pain was suspected of having a renal tumor. Despite initial treatment, his condition rapidly deteriorated, leading to death. Postmortem examination revealed a renal abscess and sepsis caused by Porphyromonas gingivalis. This case underscores the need to consider atypical pathogens in renal masses.


Asunto(s)
Absceso , Infecciones por Bacteroidaceae , Hemorragia , Porphyromonas gingivalis , Humanos , Masculino , Persona de Mediana Edad , Porphyromonas gingivalis/aislamiento & purificación , Resultado Fatal , Japón , Hemorragia/etiología , Hemorragia/microbiología , Infecciones por Bacteroidaceae/microbiología , Infecciones por Bacteroidaceae/diagnóstico , Infecciones por Bacteroidaceae/tratamiento farmacológico , Absceso/microbiología , Absceso/diagnóstico , Enfermedades Renales/microbiología
2.
Neuropathology ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313445

RESUMEN

In the fifth edition of the World Health Organization's (WHO) classification of tumors of the central nervous system (CNS), molecular analysis is required for not only determining each tumor type but assessing its prognosis based on malignancy (CNS WHO grade). A notable example is the loss of tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A), and CDKN2A homozygous deletion (HD) is a novel CNS WHO grade 4 marker in isocitrate dehydrogenase gene (IDH)-mutant astrocytoma. However, incorporating molecular workup into the "routine diagnostics" of each brain tumor type remains a major challenge, especially in resource-limited settings, including low- and middle-income countries. We herein validated the usefulness of p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as potential surrogates for the assessment of CDKN2A status in 20 IDH-mutant astrocytoma cases. Of note, loss or retention of p16 and MTAP could accurately predict CDKN2A HD (p16: 87.5%, MTAP: 88.9%) or non-HD (p16: 100%, MTAP: 100%) with a single marker alone. Importantly, we revealed contributing factors to gray-zone IHC results (p16: 5-20%, MTAP: mosaic), including (1) hemizygous deletion of CDKN2A, (2) degenerative findings, and (3) intratumoral CDKN2A HD heterogeneity, the detailed histologic and molecular assessment of which would be a key to achieving integrated assessment of malignancy in IDH-mutant astrocytoma. We characterized the pitfalls of each method and provided for the first time a practical flowchart of astrocytoma grading, contributing to a normalization of WHO2021-based molecular diagnostics in resource-limited settings.

3.
Int J Urol ; 31(1): 73-81, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37798866

RESUMEN

OBJECTIVES: The objective of the study was to analyze the outcomes of patients with renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) over a 40-year span. METHODS: We retrospectively evaluated data of patients with ESRD-RCC diagnosed between 1979 and 2020 at two institutions. We assessed changes in stage, surgical approaches, and cancer-specific survival (CSS) following nephrectomy according to era between ESRD-RCC and sporadic RCC. Furthermore, perioperative outcomes in patients with ESRD-RCC were compared between laparoscopic and open surgery. RESULTS: Patients with ESRD-RCC (n = 549) were diagnosed at an earlier stage (p = 0.0276), and the ratio of laparoscopic nephrectomy was increased (p < 0.0001) according to eras. Since 2000 (i.e., after implementation of laparoscopic nephrectomy), patients with ESRD-RCC (n = 305) had significantly shorter CSS (p = 0.0063) after nephrectomy than sporadic RCC (n = 2732). After adjustment by multivariate analysis and propensity score matching, ESRD status was independently associated with shorter CSS (p = 0.0055 and p = 0.0473, respectively). Improved CSS in sporadic RCC (p < 0.0001), but not ESRD-RCC (p = 0.904), according to era contributed to this difference. Laparoscopic nephrectomy showed favorable outcomes, including shorter surgery time, lower estimated bleeding volumes, transfusion rates, and readmission rates, and shorter postoperative hospitalization than open nephrectomy (p < 0.05). CONCLUSIONS: Advances in diagnostic and treatment modalities potentially enable early diagnosis and minimally invasive surgery for patients with ESRD-RCC. As ESRD-RCC may not present indolently, careful post-operative monitoring is needed.


Asunto(s)
Carcinoma de Células Renales , Fallo Renal Crónico , Neoplasias Renales , Humanos , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/cirugía , Neoplasias Renales/complicaciones , Neoplasias Renales/cirugía , Estudios Retrospectivos , Japón/epidemiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/epidemiología , Nefrectomía
4.
BMC Cancer ; 23(1): 1206, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062416

RESUMEN

BACKGROUND: Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor; novel LAG3 immune checkpoint inhibitors (ICIs) exhibit therapeutic activity in melanoma. The role of LAG3and ICIs of LAG3 are unknown in malignant pleural mesothelioma (MPM). This study aimed to uncover the prognostic landscape of LAG3 in multiple cancers and investigate the potential of using LAG3 as an ICIs target in patients with MPM. METHODS: We used The Cancer Genome Atlas (TCGA) cohort for assessing mRNA expression and our cohort for immunohistochemical expression. TCGA cohort were analyzed using the Wilcoxon rank-sum test to compare mRNA expression between normal and tumor tissues in multiple cancers. We used 86 MPM cases from TCGA and 38 MPM cases from our cohort to analyze the expression of LAG3 in tumor-infiltrating lymphocytes. The mean LAG3 mRNA expression was set as the cut-off and samples were classified as positive/negative for immunohistochemical expression. Overall survival (OS) of patients with MPM was determined using the Kaplan-Meier method based on LAG3 mRNA and immunohistochemical expression. OS analysis was performed using the multivariate Cox proportional hazards model. The correlation of LAG3 expression and mRNA expression of tumor immune infiltration cells (TIICs) gene markers were estimated using Spearman correlation. To identify factors affecting the correlation of LAG3 mRNA expression, a multivariate linear regression model was performed. RESULTS: LAG3 mRNA was associated with prognosis in multiple cancers. Elevated LAG3 mRNA expression was correlated with a better prognosis in MPM. LAG3 expression was detected immunohistochemically in the membrane of infiltrating lymphocytes in MPM. LAG3 immunohistochemical expression was correlated with a better prognosis in MPM. The multivariate Cox proportional hazards model revealed that elevated LAG3 immunohistochemical expression indicated a better prognosis. In addition, LAG3 mRNA expression was correlated with the expression of various gene markers of TIICs, the most relevant to programmed cell death 1 (PD-1) with the multivariate linear regression model in MPM. CONCLUSIONS: LAG3 expression was correlated with prognosis in multiple cancers, particularly MPM; LAG3 is an independent prognostic biomarker of MPM. LAG3 regulates cancer immunity and is a potential target for ICIs therapy. PD-1 and LAG3 inhibitors may contribute to a better prognosis in MPM. TRIAL REGISTRATION: This study was registered with UMIN000049240 (registration day: August 19, 2022) and approved by the Institutional Review Board (approval date: August 22, 2022; approval number: 2022-0048) at Tokyo Women's Medical University.


Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Femenino , Mesotelioma/tratamiento farmacológico , Mesotelioma/genética , Mesotelioma/metabolismo , Estudios Retrospectivos , Inhibidores de Puntos de Control Inmunológico , Pronóstico , Receptor de Muerte Celular Programada 1 , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/genética , Neoplasias Pleurales/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , ARN Mensajero/genética , Biomarcadores de Tumor/análisis
5.
Pathol Int ; 73(12): 601-608, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37818800

RESUMEN

Multiple lung cysts are one of the major features of Birt-Hogg-Dubé syndrome (BHD), but little is known about their nature and pathogenesis. We report a case of a woman diagnosed with BHD lung cysts who exhibited pulmonary interstitial glycogenosis (PIG), a mesenchymal abnormality hitherto undescribed in this disease, in specimens resected at 14 and 29 years of age. Histopathologically, oval to spindle clear cells were seen in the subepithelial interstitial tissue of septal structures and the walls of the cysts. They had abundant periodic acid-Schiff-positive cytoplasmic glycogen. Immunohistochemically, these cells were positive for a few markers of mesenchymal stem cell-like lineage, including vimentin, CD44, and CD10, and negative for markers of epithelial or specific mesenchymal differentiation; these results were consistent with the reported immunophenotype of PIG cells. These PIG cells were more abundant in her specimen at age 14 years than in the second specimen from adulthood. The present case suggests that BHD lung cysts belong to a group of pulmonary developmental disorders characterized by combined PIG and alveolar simplification/cystic change. Disorders with PIG may persist until adulthood and may be of clinical and pathological significance.


Asunto(s)
Síndrome de Birt-Hogg-Dubé , Quistes , Enfermedad del Almacenamiento de Glucógeno , Enfermedades Pulmonares Intersticiales , Enfermedades Pulmonares , Neumotórax , Humanos , Femenino , Adulto , Adolescente , Síndrome de Birt-Hogg-Dubé/complicaciones , Síndrome de Birt-Hogg-Dubé/genética , Neumotórax/diagnóstico , Neumotórax/etiología , Neumotórax/patología , Proteínas Proto-Oncogénicas/genética , Proteínas Supresoras de Tumor/genética , Enfermedades Pulmonares/patología , Pulmón/patología , Enfermedades Pulmonares Intersticiales/patología , Quistes/complicaciones , Quistes/genética , Enfermedad del Almacenamiento de Glucógeno/complicaciones , Enfermedad del Almacenamiento de Glucógeno/patología
6.
Rinsho Ketsueki ; 64(2): 119-124, 2023.
Artículo en Japonés | MEDLINE | ID: mdl-36990731

RESUMEN

The patient, a 56-year-old lady, also exhibited numerous lymphadenopathy, hepatosplenomegaly, hyperleukocytosis (167,200/µl, aberrant lymphocytes 91.5%), and fever. A lymph node biopsy revealed follicular lymphoma (FL), grade 1. Peripheral blood tumor cells did not express CD10, which was a distinctive characteristic of the lymph node specimen. To prevent tumor lysis syndrome (TLI), CHOP was delivered without an anti-CD20 antibody, but afterward, residual lymphoma cells were found in peripheral blood (>80%). As a result, obinutuzumab (Obi) was given on day 8 following the second round of CHOP, and the tumor cells in the peripheral blood vanished without any major side effects like TLI. She underwent six chemotherapy sessions before receiving maintenance therapy with Obi and achieving a full metabolic response. According to reports, leukemic FL exhibits negative CD10 expression in peripheral blood lymphoma cells, while leukemic mantle cell lymphoma also shows this trait. Therefore, it is important not to confuse the two types in diagnosis. Leukemic FL with significant leukocytosis is reportedly uncommon and has a bad prognosis. Our case indicates that CHOP with Obi would be a good alternative for cases like yours, however, there have been a few cases recorded. Further case accumulation or investigation is warranted.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Femenino , Humanos , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Prednisolona/uso terapéutico , Prednisona/uso terapéutico , Rituximab/uso terapéutico , Vincristina/uso terapéutico
7.
J Biol Chem ; 295(6): 1704-1715, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-31882535

RESUMEN

The influenza A (H1N1)pdm09 outbreak in 2009 exemplified the problems accompanying the emergence of novel influenza A virus (IAV) strains and their unanticipated virulence in populations with no pre-existing immunity. Neuraminidase inhibitors (NAIs) are currently the drugs of choice for intervention against IAV outbreaks, but there are concerns that NAI-resistant viruses can transmit to high-risk populations. These issues highlight the need for new approaches that address the annual influenza burden. In this study, we examined whether palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI) effectively antagonize (H1N1)pdm09 infection. POPG and PI markedly suppressed cytopathic effects and attenuated viral gene expression in (H1N1)pdm09-infected Madin-Darby canine kidney cells. POPG and PI bound to (H1N1)pdm09 with high affinity and disrupted viral spread from infected to noninfected cells in tissue culture and also reduced (H1N1)pdm09 propagation by a factor of 102 after viral infection was established in vitro In a mouse infection model of (H1N1)pdm09, POPG and PI significantly reduced lung inflammation and viral burden. Of note, when mice were challenged with a typically lethal dose of 1000 plaque-forming units of (H1N1)pdm09, survival after 10 days was 100% (14 of 14 mice) with the POPG treatment compared with 0% (0 of 14 mice) without this treatment. POPG also significantly reduced inflammatory infiltrates and the viral burden induced by (H1N1)pdm09 infection in a ferret model. These findings indicate that anionic phospholipids potently and efficiently disrupt influenza infections in animal models.


Asunto(s)
Antivirales/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Fosfatidilgliceroles/uso terapéutico , Fosfatidilinositoles/uso terapéutico , Animales , Antivirales/farmacología , Modelos Animales de Enfermedad , Perros , Femenino , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/patología , Fosfatidilgliceroles/farmacología , Fosfatidilinositoles/farmacología , Surfactantes Pulmonares/farmacología , Surfactantes Pulmonares/uso terapéutico
8.
Cancer Sci ; 112(4): 1417-1428, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33539630

RESUMEN

Chimeric antigen receptor (CAR)-T cell therapy has shown salient efficacy in cancer immunotherapy, particularly in the treatment of B cell malignancies. However, the efficacy of CAR-T for solid tumors remains inadequate. In this study, we displayed that c-met is an appropriate therapeutic target for papillary renal cell carcinoma (PRCC) using clinical samples, developed an anti-human c-met CAR-T cells, and investigated the anti-tumor efficacy of the CAR-T cells using an orthotopic mouse model as pre-clinical research. Administration of the anti-c-met CAR-T cells induced marked infiltration of the CAR-T cells into the tumor tissue and unambiguous suppression of tumor growth. Furthermore, in combination with axitinib, the anti-tumor efficacy of the CAR-T cells was synergistically augmented. Taken together, our current study demonstrated the potential for clinical application of anti-c-met CAR-T cells in the treatment of patients with PRCC.


Asunto(s)
Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Neoplasias Renales/inmunología , Neoplasias Renales/terapia , Proteínas Proto-Oncogénicas c-met/inmunología , Receptores Quiméricos de Antígenos/inmunología , Linfocitos T/inmunología , Anciano , Animales , Anticuerpos/inmunología , Antígenos de Neoplasias/inmunología , Línea Celular Tumoral , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Humanos , Inmunoterapia/métodos , Masculino , Ratones , Ratones Endogámicos NOD , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
9.
Ann Surg Oncol ; 28(13): 8804-8812, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34086123

RESUMEN

BACKGROUND: Although conventional one-step nucleic acid amplification (OSNA) is a useful molecular-staging method, its complexity hinders its use in clinical practice. A pooled approach for OSNA (pOSNA) has been evaluated for its feasibility in pathologically node-negative colon cancer (pNNCC) for molecular staging of lymph node metastasis in clinical practice. METHODS: Subjects were patients diagnosed with clinical stage II-IIIA colon cancer between January 2017 and September 2018. pOSNA involved harvesting pericolic lymph nodes from fresh surgical specimens, cutting them in half, placing 50% of the nodes in a single test tube, and performing the OSNA assay. The remaining halved pericolic, intermediate, and main lymph nodes were submitted for histopathologic examination, with metastasis determined by hematoxylin and eosin staining of a cut surface of each node. RESULTS: Of the 98 enrolled patients, 92 formed the analysis set. The mean number of harvested lymph nodes per case was 24.3 (range 5-66) and the mean number of lymph nodes used for pOSNA analysis was 6.9 (range 1-35). The concordance rate, sensitivity, and specificity between methods were 89.1%, 84.6% (95% confidence interval [CI] 0.80-0.91), and 90.9% (95% CI 0.88-0.94), respectively. The pOSNA upstaging rate for node-negative patients was 9.1% (6/66), and pOSNA returned false-negative results in 15.4% of node-positive cases (4/26). CONCLUSIONS: pOSNA demonstrated an upstaging rate for pNNCC equivalent to that in previous studies, suggesting its feasibility for molecular staging of pNNCC in clinical practice.


Asunto(s)
Neoplasias del Colon , Ácidos Nucleicos , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Estudios de Factibilidad , Humanos , Queratina-19/genética , Ganglios Linfáticos/patología , Estadificación de Neoplasias , Técnicas de Amplificación de Ácido Nucleico , Estudios Prospectivos , Biopsia del Ganglio Linfático Centinela
10.
Eur Radiol ; 31(8): 5990-5997, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33559699

RESUMEN

OBJECTIVES: To retrospectively evaluate whether the early dark cortical band (EDCB) on CT can be a predictor to differentiate clear cell renal cell carcinoma (ccRCC) from fat poor angiomyolipoma (Fp-AML) and to detect peritumoral pseudocapsules in ccRCC. METHODS: The EDCBs, which are comprised of unenhanced thin lines at the tumor-renal cortex border in the corticomedullary phase, on the CT images of 342 patients who underwent partial nephrectomy were evaluated. Independent predictors among the clinical and CT findings for differentiating ccRCC from Fp-AML were identified using multivariate analyses. The diagnostic performance of the EDCB for diagnosing peritumoral pseudocapsule in ccRCC and differentiating ccRCC from Fp-AML was calculated. RESULTS: The EDCB was observed in 157 of 254 (61.8%) ccRCCs, 4 of 31 (12.9%) chromophobe RCCs, 1 of 21 (4.8%) papillary RCCs, 3 of 11 (27.3%) clear cell papillary RCCs, 3 of 8 (37.5%) oncocytomas, and 0 of 17 (0%) Fp-AMLs. There was substantial interobserver agreement for the EDCB (k = 0.719). The EDCB was a significant predictor for differentiating ccRCC from Fp-AML (p < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of the EDCB for differentiating ccRCC from Fp-AML were 61.8%, 100%, 100%, and 14.9%, respectively, and those for detecting pseudocapsule in 236 ccRCCs were 62.3%, 68.8%, 96.5%, and 11.7%, respectively. CONCLUSION: Although diagnostic accuracy of the EDCB for detecting peritumoral pseudocapsule in RCC is inadequate, it can be a predictor for differentiating ccRCC from Fp-AML with high specificity and PPV. KEY POINTS: • The early dark cortical band (EDCB) sign is observed in nearly two-thirds of clear cell renal cell carcinoma (ccRCC) that are treated by partial nephrectomy and have substantial interobserver agreement. • The EDCB is a significant predictor for differentiating ccRCCs from fat poor angiomyolipomas, with a high specificity and positive predictive value. • Diagnostic accuracy of the EDCB for detecting peritumoral pseudocapsule in ccRCC is inadequate, though better than those in the nephrographic and excretory-phase images.


Asunto(s)
Angiomiolipoma , Carcinoma de Células Renales , Neoplasias Renales , Angiomiolipoma/diagnóstico por imagen , Carcinoma de Células Renales/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Neoplasias Renales/diagnóstico por imagen , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X
11.
J Pharmacol Sci ; 147(2): 176-183, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34384565

RESUMEN

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic disease. SGL5213, which is minimally absorbed and is restricted to the intestinal tract, is a potent intestinal sodium-glucose cotransporter 1 (SGLT1) inhibitor. In this study, we investigated the protective effect of SGL5213 in a rodent model of NAFLD. METHODS: Using a rodent model of NAFLD, we compared SGL5213 efficacy with miglitol, which is an α-glucosidase inhibitor. We used a high-fat and high-sucrose diet-induced NAFLD model. RESULTS: SGL5213 and miglitol improved obesity, liver dysfunction, insulin resistance, and the NAFLD severity. To further investigate the effects of SGL5213, we analyzed the mRNA expression of genes involved in lipid metabolism, inflammation, and liver fibrosis, and cecal pH levels. SGL5213 and miglitol treatment significantly decreased mRNA expression of factors involved in inflammation and liver fibrosis. SGL5213 treatment significantly decreased cecal pH levels, which did not occur with miglitol. CONCLUSIONS: SGL5213 had a protective effect on the pathogenesis of NAFLD in a rodent model. We considered that inhibiting glucose absorption and increasing glucose content in the gastrointestinal tract with SGL5213 might have contributed to the protective effect in NAFLD. SGL5213 is a promising therapeutic agent for NAFLD with obesity and insulin resistance.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Transportador 1 de Sodio-Glucosa/antagonistas & inhibidores , Sorbitol/análogos & derivados , 1-Desoxinojirimicina/administración & dosificación , 1-Desoxinojirimicina/análogos & derivados , Animales , Enfermedad Crónica , Dieta Alta en Grasa/efectos adversos , Sacarosa en la Dieta/efectos adversos , Modelos Animales de Enfermedad , Absorción Gastrointestinal/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , Resistencia a la Insulina , Masculino , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/tratamiento farmacológico , Gravedad del Paciente , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transportador 1 de Sodio-Glucosa/genética , Transportador 1 de Sodio-Glucosa/metabolismo , Sorbitol/administración & dosificación , Sorbitol/farmacología
12.
Pathol Int ; 71(6): 406-414, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33783928

RESUMEN

Monoclonal tubular basement membrane immune deposits (TBMID) are associated with progression of interstitial injury in renal allograft. However, the significance of monoclonal and polyclonal TBMID in the native kidney remains unclear. We retrospectively analyzed 1894 native kidney biopsies and 1724 zero-hour biopsies performed between 2008 and 2018 in our institution. The rate of immunoglobulin G (IgG) TBMID was found to be 8.4% among native kidney biopsies and 0.4% among zero-hour biopsies. Polyclonal TBMID is common in IgG4-related tubulointerstitial nephritis (37.5%), diabetic nephropathy (31.3%) and lupus nephritis (25.5%). Monoclonal IgG TBMID was identified in seven cases, including three zero-hour biopsies. The combination of IgG1κ was observed in two cases, IgG1λ in three, and IgG2κ in two. Electron microscopy revealed powdery electron-dense deposits in all cases. Monoclonal gammopathy of undetermined significance was diagnosed in one case. Although one patient with focal segmental glomerulosclerosis developed renal failure, all others exhibited stable renal function. Monoclonal IgG TBMID in the native kidney is not associated with renal prognosis. However, this may be an interesting immunopathological finding that would help clarify the pathogenesis of TBM immune deposits. Further study for both monoclonal and polyclonal TBMID is required in the future.


Asunto(s)
Inmunoglobulina G/metabolismo , Trasplante de Riñón , Riñón , Membrana Basal/patología , Biopsia , Femenino , Humanos , Riñón/patología , Riñón/ultraestructura , Masculino , Estudios Retrospectivos
13.
Clin Exp Nephrol ; 25(6): 674-682, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33641007

RESUMEN

BACKGROUND: The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited. METHODS: Patients diagnosed with advanced RCC on maintenance dialysis therapy (ESRD-RCC) and treated with tyrosine kinase inhibitors (TKIs) were retrospectively evaluated. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after initiation of first-line TKI therapy in ESRD-RCC patients were compared to those in RCC arising in the general population (sporadic RCC). RESULTS: A total of 36 and 240 patients were diagnosed with advanced ESRD-RCC and sporadic RCC, respectively. PFS and OS were significantly shorter in patients with ESRD-RCC than in those with sporadic RCC (p = 0.0004 and p = 0.0045). After adjusting for histopathological type, MSKCC risk and liver metastasis status, ESRD status (ESRD-RCC vs. sporadic RCC) was not an independent risk factor for PFS or OS (both, p > 0.05). The ORR tended to be lower in patients with ESRD-RCC than in those with sporadic RCC (11% vs. 28%, p = 0.0833). In 34 patients with ESRD-RCC treated with sorafenib, longer duration of dialysis was an independent prognostic factor for shorter OS (hazard ratio 3.21, p = 0.0370). CONCLUSIONS: Outcome of advanced ESRD-RCC was poorer than that of sporadic RCC, but this finding was affected by other prognostic factors. Nevertheless, the study suggested that advanced ESRD-RCC was not an indolent disease. Additionally, patients with a longer duration of dialysis therapy might require careful monitoring.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Anciano , Antineoplásicos/efectos adversos , Carcinoma de Células Renales/etiología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Bases de Datos Factuales , Duración de la Terapia , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Neoplasias Renales/etiología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/efectos adversos , Diálisis Renal , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
14.
World J Surg Oncol ; 19(1): 269, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34479591

RESUMEN

BACKGROUND: Pedunculated polyps are more likely to be amenable to complete resection than non-pedunculated early colorectal cancers and rarely require additional surgery. We encountered a patient with a pedunculated early colorectal cancer that consisted of poorly differentiated adenocarcinoma with lymphatic invasion. We performed an additional bowel resection and found nodal metastasis. CASE PRESENTATION: A 43-year-old woman underwent colonoscopy after a positive fecal occult blood test. The colonoscopist found a 20-mm pedunculated polyp in the descending colon and performed endoscopic resection. Histopathologic examination revealed non-solid type poorly differentiated adenocarcinoma. The lesion invaded the submucosa (3500 µm from the muscularis mucosa) and demonstrated lymphatic invasion. In spite of the early stage of this cancer, the patient was considered at high risk for nodal metastasis. She was referred to our institution, where she underwent bowel resection. Although there was no residual cancer after her endoscopic resection, a metastatic lesion was found in one regional lymph node. The patient is undergoing postoperative adjuvant chemotherapy, and there has been no evidence of recurrence 3 months after the second surgery. CONCLUSIONS: Additional bowel resection is indicated for patients with pedunculated polyps and multiple risk factors for nodal metastasis, such as poorly differentiated adenocarcinoma and lymphatic invasion. We encountered just such a patient who did have a nodal metastasis; herein, we report her case history with a review of the literature.


Asunto(s)
Adenocarcinoma , Neoplasias Colorrectales , Adenocarcinoma/cirugía , Adulto , Colonoscopía , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Recurrencia Local de Neoplasia , Pronóstico
15.
Pol J Pathol ; 72(3): 197-199, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35048631

RESUMEN

The disease entity of TFEB-amplified renal cell carcinoma (RCC) has been recently established. In this article, we review such cases. Clinically, the age of patients ranged from 28 to 83 years with a mean age of 62.8 years. The size of the tumor ranged from 1.9 to 19.5 cm with a mean size of 8.7 cm. The tumor demonstrated a variety of architectural patterns such as solid, alveolar, papillary, pseudopapillary, nested or tubular. The International Society of Urological Pathology (ISUP) grade usually corresponds to grade 3 or 4. Cytomorphology shows eosinophilic, clear, amphophilic or even oncocytic cytoplasm. Necrosis can be frequently observed. Neoplastic cells with TFEB-amplified RCC show diffuse or patchy positivity for TFEB. Fluorescence in situ hybridization frequently show the amplification of more than 10 or 20 copies of the TFEB gene. Most TFEB-amplified RCCs behave in an aggressive fashion. Metastasis frequently occurs. In conclusion, this tumor seems to be characterized by occurrence in older patients, frequent necrosis, papillary/pseudopapillary growth pattern, high-grade nuclear grade, TFEB gene amplification, and aggressive clinical behavior. In order to clarify whether this tumor is a distinct entity from previously described renal tumors or not, a further examination in a large scale study will be required in the future.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Adulto , Anciano , Anciano de 80 o más Años , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Humanos , Hibridación Fluorescente in Situ , Neoplasias Renales/genética , Persona de Mediana Edad
16.
Cancer Sci ; 111(1): 15-22, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31777168

RESUMEN

Birt-Hogg-Dubé (BHD) syndrome is associated with the development of hereditary renal cell carcinoma (RCC) and is caused by a germline mutation in the folliculin gene. Most cases of BHD syndrome-associated RCC (BHD-RCC) are less aggressive than sporadic clear cell RCC and multifocal. Therefore, it is critical to distinguish BHD-RCC from its sporadic counterparts to identify and monitor affected families and to preserve renal function for as long as possible. The World Health Organization/International Society of Urological Pathology consensus classification defined distinct entities for certain hereditary RCC; however, BHD-RCC was not included in this classification. Although the clinical features and molecular mechanisms of BHD-RCC have been investigated intensively over the last two decades, pathologists and urologists occasionally face difficulties in the diagnosis of BHD-RCC that require genetic testing. Affected patients usually have miscellaneous benign disorders that often precede renal carcinogenesis. In the present review, we summarize the current understanding of the histopathological features of BHD-RCC based on our epidemiological studies of Japanese families and a literature review. Pathological diagnostic clues and differential diagnosis of BHD-RCC from other hereditary RCC are also briefly discussed.


Asunto(s)
Síndrome de Birt-Hogg-Dubé/diagnóstico , Síndrome de Birt-Hogg-Dubé/patología , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Animales , Diagnóstico Diferencial , Humanos
17.
Cancer Sci ; 111(11): 4276-4287, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32860304

RESUMEN

End-stage renal disease (ESRD) patients on dialysis therapy have a higher incidence of renal cell carcinomas (RCCs), which consist of 2 major histopathological types: clear-cell RCCs (ESRD-ccRCCs) and acquired cystic disease (ACD)-associated RCCs. However, their genetic and epigenetic alterations are still poorly understood. Here, we investigated somatic mutations, copy number alterations (CNAs), and DNA methylation profiles in 9 ESRD-ccRCCs and 7 ACD-associated RCCs to identify their molecular alterations and cellular origins. Targeted sequencing of 409 cancer-related genes, including VHL, PBRM1, SETD2, BAP1, KDM5C, MET, KMT2C (MLL3), and TP53, showed ESRD-ccRCCs harbored frequent VHL mutations, while ACD-associated RCCs did not. CNA analysis showed that ESRD-ccRCCs had a frequent loss of chromosome 3p while ACD-associated RCCs had a gain of chromosome 16. Beadarray methylation analysis showed that ESRD-ccRCCs had methylation profiles similar to those of sporadic ccRCCs, while ACD-associated RCCs had profiles similar to those of papillary RCCs. Expression analysis of genes whose expression levels are characteristic to individual segments of a nephron showed that ESRD-ccRCCs and ACD-associated RCCs had high expression of proximal tubule cell marker genes, while chromophobe RCCs had high expression of distal tubule cell/collecting duct cell marker genes. In conclusion, ESRD-ccRCCs and ACD-associated RCCs had mutation and methylation profiles similar to those of sporadic ccRCCs and papillary RCCs, respectively, and these 2 histopathological types of RCCs were indicated to have originated from proximal tubule cells of the nephron.


Asunto(s)
Epigénesis Genética , Predisposición Genética a la Enfermedad , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/genética , Neoplasias Renales/etiología , Neoplasias Renales/patología , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Adulto , Anciano , Carcinoma de Células Renales/etiología , Carcinoma de Células Renales/patología , Variaciones en el Número de Copia de ADN , Epigenoma , Femenino , Perfilación de la Expresión Génica , Genotipo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Mutación , Transcriptoma
18.
Hum Mol Genet ; 27(15): 2712-2724, 2018 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-29767721

RESUMEN

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer, which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming toward upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics that are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.


Asunto(s)
Síndrome de Birt-Hogg-Dubé/patología , Ensamble y Desensamble de Cromatina/genética , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Supresoras de Tumor/genética , Síndrome de Birt-Hogg-Dubé/genética , Variaciones en el Número de Copia de ADN , Mutación de Línea Germinal , Humanos , Neoplasias Renales/patología , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Secuenciación del Exoma
19.
Semin Dial ; 33(4): 316-321, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32557805

RESUMEN

PURPOSE: To investigate the impact of hemodialysis on survival in renal cell carcinoma (RCC) patients. METHODS: We studied 388 patients who underwent radical or partial nephrectomy for RCC at Toranomon Hospital from 2005 to 2013. Survival curves were drawn according to the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to assess the prognostic influence of hemodialysis on cancer-specific survival. RESULT: Of the 388 patients, 66 were on hemodialysis and 322 were not on dialysis. In the hemodialysis patients, incidental diagnosis of RCC was less frequent than in the non-dialysis patients. In addition, RCC was more likely to be multicentric (41% vs 1.2%), bilateral (14% vs 0.6%), and papillary (18% vs 7%) in hemodialysis patients. Moreover, tumors were smaller, the stage was lower, and the Fuhrman nuclear grade was higher in the patients on hemodialysis. The 5-year cancer-specific survival rate was 82.8% for hemodialysis patients and 93.5% for nondialysis patients. Multivariate analysis indicated that hemodialysis, stage, and Fuhrman nuclear grade were independent prognostic factors for RCC. CONCLUSIONS: This study suggested that hemodialysis was an independent prognostic factor for cancer-specific survival in RCC patients, along with the tumor stage and Fuhrman nuclear grade.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/terapia , Estadificación de Neoplasias , Nefrectomía , Pronóstico , Diálisis Renal , Estudios Retrospectivos
20.
Jpn J Clin Oncol ; 50(11): 1313-1320, 2020 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-33089867

RESUMEN

OBJECTIVES: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC. METHODS: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features. RESULTS: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years. CONCLUSION: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.


Asunto(s)
Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/patología , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Diagnóstico Diferencial , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad
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