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1.
BMC Pulm Med ; 24(1): 84, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355540

RESUMEN

BACKGROUND: Exposure assessment is integral to the diagnosis of hypersensitivity pneumonitis (HP). Although the clinical relevance of exposed antigens is essential for the assessment, many of the previous guidelines or reports have only evaluated simple exposure histories or immunological tests. To overcome this problem, the Exposure Assessment Form (EAF) was developed as an assessment tool for classifying the exposure grade from G0 to G4. The EAF was modified from the description in the Japanese clinical practice guide 2022 for HP published by the Japanese Respiratory Society. METHODS: One hundred and seventy-two consecutive patients with interstitial lung disease who underwent multidisciplinary discussion (MDD) at our hospital were retrospectively examined. We assessed whether the use of the EAF improved the diagnostic performance of the international guideline of HP. We also evaluated whether the exposure grade affected the prognosis of HP. RESULTS: Even when a HP diagnosis was made with a confidence of 70% or higher according to the international guideline, less than half of these cases resulted in a final diagnosis of HP when the exposure grades were lower than G3. When the result of the EAF was integrated into the exposure definition of the international guideline, the specificity of the diagnostic performance improved, while sensitivity was maintained. Furthermore, HP patients with an exposure grade of G3 or higher showed a tendency to take a longer time to initiate medication. CONCLUSIONS: This is the first study to evaluate the clinical relevance of possible antigens using the EAF. Assessing the exposure grade prevents overdiagnosis and improves the diagnostic performance of the international guideline.


Asunto(s)
Alveolitis Alérgica Extrínseca , Enfermedades Pulmonares Intersticiales , Humanos , Estudios Retrospectivos , Relevancia Clínica , Alveolitis Alérgica Extrínseca/diagnóstico , Enfermedades Pulmonares Intersticiales/diagnóstico , Antígenos
2.
Rinsho Ketsueki ; 63(10): 1373-1378, 2022.
Artículo en Japonés | MEDLINE | ID: mdl-36351642

RESUMEN

We here present a 33-year-old woman who was referred to our hospital with a complaint of back pain and was found to have elevated IgG and hypercalcemia, as well as osteolytic lesions of pelvis and spines. 18F-FDG-PET/CT scan revealed numerous uptakes in the bones. An examination of the bone marrow revealed increased plasma cells (10.2%). Despite clinical similarities to multiple myeloma, any evidence of plasma cell clonal proliferation, including serum M-protein and light chain restriction, was not found. A reexamination of the bone marrow with a biopsy revealed the proliferation of abnormal cells with chromogranin A and synaptophysin expression but no expression of hematopoietic and epithelial cell markers. Based on these results together with extra-adrenal lesions, a diagnosis of malignant paraganglioma was made. Malignant paraganglioma is known to frequently cause bone metastasis and skeletal related events, whose clinical manifestations are similar to those of multiple myeloma. Since patients with osteolytic lesions, hypercalcemia, and hypergammaglobulinemia are likely to be referred to hematologists, malignant paraganglioma should be considered as a differential diagnosis.


Asunto(s)
Hipercalcemia , Mieloma Múltiple , Paraganglioma , Femenino , Humanos , Adulto , Mieloma Múltiple/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18/metabolismo , Paraganglioma/diagnóstico
3.
Cancer Sci ; 112(2): 932-944, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33275808

RESUMEN

Intraductal papillary mucinous neoplasm (IPMN) is a precancerous lesion of pancreatic cancer. Although there are 4 types of IPMN, among which intestinal-type IPMN is likely to progress into invasive cancer known as colloid carcinoma, no information regarding the involvement of the intestinal phenotype in the carcinogenesis of IPMN exists. The present study was conducted to explore how the intestinal differentiation system is maintained during the tumor progression of intestinal-type IPMN using surgical resection specimens. Results showed that Atoh1, a critical transcriptional factor for intestinal differentiation toward the secretory lineages of intestinal epithelial cells, was expressed in an invasive-grade IPMN. To determine the function of Atoh1 in pancreatic cancer, we generated a pancreatic ductal adenocarcinoma (PDAC) cell line overexpressing Atoh1. In a xenograft model, we successfully induced an IPMN phenotype in PDAC cells via Atoh1 induction. Finally, for the first time, we discovered that GPA33 is expressed in intestinal-type IPMN, thereby suggesting a novel target for cancer therapy. In conclusion, the intestinal differentiation system might be maintained during tumor progression of intestinal-type IPMN. Further analysis of the function of Atoh1 in IPMN might be useful for understanding the molecular mechanism underlying the malignant potential during the tumor progression of IPMN.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Diferenciación Celular/fisiología , Neoplasias Intraductales Pancreáticas/patología , Anciano , Anciano de 80 o más Años , Animales , Línea Celular Tumoral , Femenino , Xenoinjertos , Humanos , Intestinos/patología , Masculino , Glicoproteínas de Membrana/metabolismo , Ratones , Persona de Mediana Edad , Neoplasias Intraductales Pancreáticas/metabolismo , Fenotipo
4.
Pathol Int ; 71(2): 147-154, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33333628

RESUMEN

Satoyoshi syndrome is a rare multisystemic disorder of unknown etiology characterized by progressive muscle spasms, alopecia and diarrhea. Multiple protruding lesions with cystic glands, namely gastroenterocolitis cystica polyposa, manifest in the gastrointestinal tract. Since the first report of these lesions in 1977, which was unique to Satoyoshi syndrome, few studies have focused on their role, and the associated clinicopathological features are not well understood. Here, we report a 64-year-old Japanese woman with Satoyoshi syndrome who presented with multiple polypoid lesions in the stomach, duodenum, jejunum, ileum and colon. Histologically, the polypoid lesions in the intestine comprised multiple heterotopic submucosal glands containing cystically dilated glands and smooth muscle fibers in the lamina propria mucosa and/or submucosa. Additionally, we observed stromal changes, such as fibrosis, discontinuous and thinning muscularis mucosae, and diffuse neural fiber proliferation in the entire intestinal tract. Furthermore, multiple foci of adenocarcinomas were identified within several heterotopic submucosal glands. We hypothesized that multiple heterotopic submucosal glands in the present case corresponded to previously reported gastroenterocolitis cystica polyposa, suggesting that these lesions are essential in the histopathology and are a unique manifestation of Satoyoshi syndrome.


Asunto(s)
Adenocarcinoma/diagnóstico , Alopecia/patología , Huesos/anomalías , Coristoma/patología , Diarrea/patología , Mucosa Intestinal , Neoplasias Intestinales/diagnóstico , Espasmo/patología , Adenocarcinoma/etiología , Adenocarcinoma/patología , Alopecia/complicaciones , Huesos/patología , Coristoma/diagnóstico , Coristoma/etiología , Diarrea/complicaciones , Femenino , Humanos , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/etiología , Enfermedades Intestinales/patología , Neoplasias Intestinales/etiología , Neoplasias Intestinales/patología , Persona de Mediana Edad , Espasmo/complicaciones
5.
Int J Mol Sci ; 22(17)2021 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-34502181

RESUMEN

Ferroptosis, a term first proposed in 2012, is iron-dependent, non-apoptotic regulatory cell death induced by erastin. Ferroptosis was originally discovered during synthetic lethal screening for drugs sensitive to RAS mutant cells, and is closely related to synthetic lethality. Ferroptosis sensitizes cancer stem cells and tumors that undergo epithelial-mesenchymal transition and are resistant to anticancer drugs or targeted therapy. Therefore, ferroptosis-inducing molecules are attractive new research targets. In contrast, synthetic lethal strategies approach mechanisms and genetic abnormalities that cannot be directly targeted by conventional therapeutic strategies, such as RAS mutations, hypoxia, and abnormalities in the metabolic environment. They also target the environment and conditions specific to malignant cells, have a low toxicity to normal cells, and can be used in combination with known drugs to produce new ones. However, the concept of synthetic lethality has not been widely adopted with ferroptosis. In this review, we surveyed the literature on ferroptosis-related factors and synthetic lethality to examine the potential therapeutic targets in ferroptosis-related molecules, focusing on factors related to synthetic lethality, discovery methods, clinical application stages, and issues in drug discovery.


Asunto(s)
Ferroptosis , Animales , Antineoplásicos , Descubrimiento de Drogas , Humanos , Hierro/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Mutaciones Letales Sintéticas
6.
Gan To Kagaku Ryoho ; 47(13): 2068-2070, 2020 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-33468803

RESUMEN

The patient was a woman in her early 60s with type 4 advanced cancer which spread throughout the entire stomach. Total gastrectomy with regional lymphadenectomy was performed. She was diagnosed as Stage Ⅳ scirrhous gastric cancer with positive lavage cytology pathologically without any macroscopic peritoneal metastasis(P0CY1). S-1 plus cisplatin therapy was carried out as first-line therapy, but must be stopped after 2 courses because of appetite loss. As the second-line, ramucirumab monotherapy was administered, due to the patient's denial of alopecia and numbness as side effects of paclitaxel. Tumor marker value of CA19-9 remained high 24 months after ramucirumab chemotherapy, but gradually decreased near the normal level with no proof of distant metastasis or peritoneal dissemination. However, after 74 courses, CA19-9 value was elevated and peritoneal dissemination was detected from CT scan. Nivolumab therapy was started as third-line, but only for 5 courses because of indefinite complaints. Afterwards, no chemotherapy has been performed as the patient's request until almost 5 years after surgery. The prognosis of patients with P0CY1 gastric cancer is generally poor, but in our case long-term survival was obtained from ramucirumab therapy only. Recently, ramucirumab monotherapy is administered for advanced HCC patients and expect to be effective in AFP producing gastric cancer. There is an urgent need to elucidate potential predictive biomarkers of ramucirumab efficacy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Gástricas , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Gastrectomía , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Ramucirumab
7.
Eur Neurol ; 79(3-4): 200-205, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29587294

RESUMEN

Subicular degeneration occurs in amyotrophic lateral sclerosis (ALS) patients. However, it was unknown whether microscopic subicular degeneration could be observed as macroscopic changes and whether these changes were associated with the transactive-response DNA binding protein 43 kDa (TDP-43) pathology. Topographic differences between subicular degeneration caused by ALS and Alzheimer disease (AD) had also not been characterized. Here we investigated the subiculum and related areas in autopsied brains from 3 ALS and 3 AD patients. Macroscopic subicular thinning and corresponding astrocytosis were pronounced in ALS compared to AD. This thinning was frequently accompanied by TDP-43 pathology in the transentorhinal cortex and nucleus accumbens. The preferential susceptibility of the perforant pathway to TDP-43 deposition may be an underlying cause of subicular thinning in ALS.


Asunto(s)
Enfermedad de Alzheimer/patología , Esclerosis Amiotrófica Lateral/patología , Hipocampo/patología , Anciano , Proteínas de Unión al ADN , Femenino , Humanos , Masculino
9.
Gan To Kagaku Ryoho ; 44(12): 1835-1837, 2017 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-29394792

RESUMEN

Breast cancer in male is rare, accounting for 1%of all breast cancers.Among male breast cancers, noninvasive carcinoma is extremely rare.We experienced a case of noninvasive carcinoma of the breast in a male.A 72-year-old male was referred to our hospital with a chief complaint of the tumor and blood secretion from the left nipple.Mammography revealed a highdensity mass.Ultrasound examination revealed low echoic mass at the E area, and it measured 1.5 cm.Core needle biopsy failed to provide a definitive diagnosis, and we performed an excisional biopsy of the tumor.The pathological diagnosis was noninvasive ductal carcinoma.He underwent a mastectomy without sentinel lymph node biopsy because the resection margin was positive.The patient received no adjuvant therapy and the patient's postoperative course was uneventful for 1 year.As there have been few reports on male noninvasive ductal carcinoma, we do not have evidence for indication of the sentinel lymph nodes and postoperative adjuvant therapy such as tamoxifen.We may confuse the treatment policy.


Asunto(s)
Neoplasias de la Mama Masculina/patología , Neoplasias de la Mama Masculina/cirugía , Carcinoma Ductal de Mama/cirugía , Anciano , Biopsia con Aguja Gruesa , Humanos , Masculino , Invasividad Neoplásica
10.
Lab Invest ; 94(11): 1212-23, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25199050

RESUMEN

The bone marrow microenvironment, known as 'hematopoietic stem cell niche,' is essential for the survival and maintenance of hematopoietic stem cells. Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell diseases, which eventually result in leukemic transformation (acute myelogenous leukemia with myelodysplasia-related changes, AML-MRC). However, the precise components and functions of the MDS niche remain unclear. Recently, CXCL12-abundant reticular cells were shown to act as a hematopoietic stem cell niche in the murine bone marrow. Using immunohistochemistry, we show here that CXCL12(+) cells were located in the cellular marrow or perivascular area, and were in contact with CD34(+) hematopoietic cells in control and MDS/AML-MRC bone marrow. MDS bone marrow exhibited higher CXCL12(+) cell density than control or AML, not otherwise specified (AML-NOS) bone marrow. Moreover, AML-MRC bone marrow also exhibited higher CXCL12(+) cell density than control bone marrow. CXCL12(+) cell density correlated positively with bone marrow blast ratio in MDS cases. CXCL12 mRNA level was also higher in MDS bone marrow than in control or AML-NOS bone marrow. In vitro coculture analysis revealed that overexpression of CXCL12 in stromal cells upregulated BCL-2 expression of leukemia cell lines. Triple immunostaining revealed that the CD34(+) hematopoietic cells of MDS bone marrow in contact with CXCL12(+) cells were BCL-2-positive and TUNEL-negative. In the bone marrow of MDS cases, CXCL12-high group showed significantly higher Bcl-2(+)/CD34(+) cell ratio and lower apoptotic cell ratio than CXCL12-low group. Moreover, CXCL12-high refractory cytopenia with multilineage dysplasia (RCMD) cases had a greater tendency to progress to refractory anemia with excess blasts (RAEBs) or AML-MRC than CXCL12-low RCMD cases. These results suggest that CXCL12(+) cells constitute the niche for CD34(+) hematopoietic cells, and may be associated with the survival/antiapoptosis of CD34(+) hematopoietic cells and disease progression in MDS. Thus, CXCL12(+) cells may represent a novel MDS therapeutic target.


Asunto(s)
Médula Ósea/metabolismo , Quimiocina CXCL12/metabolismo , Células Madre Hematopoyéticas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Síndromes Mielodisplásicos/etiología , Células 3T3 , Animales , Antígenos CD34/metabolismo , Apoptosis , Médula Ósea/patología , Estudios de Casos y Controles , Progresión de la Enfermedad , Humanos , Células K562 , Leucemia Mieloide Aguda/patología , Ratones , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
11.
Intern Med ; 63(4): 513-519, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37380459

RESUMEN

Malignant pericardial mesothelioma (MPM) is extremely rare, and peritoneal dissemination has not yet been reported. There is no consensus regarding appropriate pharmacological treatment for MPM, including immune checkpoint inhibitors (ICIs). We herein report a 36-year-old man with MPM diagnosed by peritoneal dissemination and treated with an ICI. Cytology of the ascites revealed malignant peritonitis, and a re-evaluation of a pericardial biopsy performed at the previous hospital led to a diagnosis of MPM. The patient was treated with nivolumab and showed a clinical response despite several complications, such as renal dysfunction and performance status deterioration. This case report provides suggestive information for the diagnosis and ICI therapy of a rare type of mesothelioma.


Asunto(s)
Mesotelioma Maligno , Mesotelioma , Masculino , Humanos , Adulto , Nivolumab/uso terapéutico , Mesotelioma Maligno/complicaciones , Mesotelioma/diagnóstico por imagen , Mesotelioma/tratamiento farmacológico , Ascitis/tratamiento farmacológico , Biopsia
12.
Respir Investig ; 62(6): 1027-1033, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39236513

RESUMEN

BACKGROUND: The importance of multidisciplinary discussion (MDD) for diagnosing interstitial lung disease (ILD) is emphasized by several international guidelines. While initial diagnoses are often provisional and require periodic re-evaluation, there is a lack of literature regarding the role of follow-up MDD in clinical practice. METHODS: From September 2020 to January 2022, patients underwent an initial MDD (MDD1) based on clinical, radiological, and pathological evaluations. Each diagnosis was assigned a confidence level. One year later, a second MDD (MDD2) was conducted for re-evaluation, based on subsequent clinical and radiological information. Changes in diagnosis and confidence levels between MDD1 and MDD2 were assessed. RESULTS: Among 52 patients enrolled in both MDDs, the diagnosis for 13 (25%) was revised at MDD2. Of these, 10 patients were initially diagnosed with unclassifiable ILD, and 3 received a low confidence diagnosis of either idiopathic pulmonary fibrosis or idiopathic nonspecific interstitial pneumonia. The most common diagnostic revision was due to the deterioration after antigen exposure or improvement after antigen avoidance, which resulted in a revised diagnosis of HP at MDD2. CONCLUSIONS: Our findings underscore the importance of periodic reassessment of MDD to improve the accuracy of ILD diagnosis. This study highlights the significance of longitudinal clinical and radiological evaluation for diagnostic revision, even in situations when rebiopsy is not feasible.

13.
JTCVS Open ; 20: 183-193, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39296452

RESUMEN

Introduction: TP53 is a strong tumor suppressor gene; its deactivation contributes to carcinogenesis and influences clinical outcomes. However, the prognostic influence of p53 deactivation on early relapse in patients with surgically resected non-small cell lung cancer remains unclear. Materials and methods: A cohort of 170 patients with primary stage I through III lung adenocarcinoma (LADC) and lung squamous cell carcinoma who underwent complete resection at Tokyo Medical and Dental University was screened for TP53 mutations using panel testing, and association studies between TP53 mutations and clinical data, including histology and postoperative recurrence, were performed. The association between TP53 mutations and postoperative recurrence was validated using data from 604 patients with MSK-IMPACT from The Cancer Genome Atlas. Additional immunohistochemistry for p53 was performed on some subsets of the Tokyo Medical and Dental University population. Results: Mutations in TP53 were recurrently observed (35.9%; 61 out of 170) in the Tokyo Medical and Dental University cohort. In the histology-stratified analysis, patients with LADC histology showed TP53 mutations that were associated with poor relapse-free survival (log-rank test; P = .020), whereas patients with lung squamous cell carcinoma histology showed TP53 mutations that were not (P = .99). The poor prognosis of TP53 mutation-positive LADCs was validated in The Cancer Genome Atlas-LADC cohort (log-rank test; P = .0065). Additional immunohistochemistry for p53 in patients with LADC histology in the Tokyo Medical and Dental University cohort showed a significant correlation between TP53 mutations and abnormal IHC pattern of p53 (Cramer's correlation coefficient V = 0.67). Conclusions: TP53 mutation is a potential marker for worse prognosis in surgically resected LADC; immunohistochemistry for p53 could be a surrogate method to identify patients with LADC with a worse prognosis.

14.
Intern Med ; 63(18): 2543-2546, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38346738

RESUMEN

We herein report a rare case of hypersensitivity pneumonitis (HP) that was initially demonstrated as solitary pure ground-glass opacity (GGO) on chest computed tomography (CT). A 51-year-old woman with a history of breast cancer underwent follow-up CT, which revealed solitary pure GGO. The patient developed exertional dyspnea after two years, and CT revealed diffuse centrilobular nodules in addition to GGO, which had increased in size. An antigen avoidance test was performed to diagnose HP, leading to the resolution of CT abnormalities, including the GGO. Our findings suggested that nonfibrotic HP can present as solitary pure GGO.


Asunto(s)
Alveolitis Alérgica Extrínseca , Tomografía Computarizada por Rayos X , Humanos , Alveolitis Alérgica Extrínseca/diagnóstico por imagen , Alveolitis Alérgica Extrínseca/diagnóstico , Femenino , Persona de Mediana Edad , Pulmón/diagnóstico por imagen , Pulmón/patología , Diagnóstico Diferencial
15.
Histopathology ; 62(3): 414-20, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23339364

RESUMEN

AIMS: Multidrug resistance (MDR) in B-cell lymphomas still constitutes a major obstacle to the effectiveness of chemotherapy even in the anti-CD20 antibody therapy era. The aim of this study was to investigate the expression of MDR-associated molecules in reactive lymphadenopathy (RL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). METHODS AND RESULTS: The expression of mRNA for ABC-transporter family genes was determined by real-time RT-PCR in lymph nodes from RL, FL, and DLBCL cases. MDR1 exhibited significantly stronger expression in RL, FL, and DLBCL than Raji B-cell lymphoma cells. RL and FL showed significantly higher expression than DLBCL. Immunohistochemically, MDR1 positive cells were localized in the germinal centers of RL and center of the nodular lesions of FL showing associations with CD21 positive follicular dendritic cells (FDCs). Raji cells were co-cultured with FDC sarcoma-derived cells and the expression of MDR1 and drug resistance were analyzed. The co-culture of Raji cells with FDCs induced strong expression of MDR1 and introduced resistance to doxorubicin-induced apoptosis. CONCLUSIONS: These results suggest that FDCs induce MDR1 expression in reactive as well as neoplastic B-cells. Inhibition of the interaction of FDCs with B-cells may provide a novel strategy for treating the chemotherapy resistant fraction.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Células Dendríticas Foliculares/metabolismo , Resistencia a Antineoplásicos/genética , Linfoma de Células B/genética , Apoptosis/fisiología , Linfocitos B/metabolismo , Línea Celular Tumoral , Técnicas de Cocultivo , Resistencia a Múltiples Medicamentos/fisiología , Humanos , Inmunohistoquímica , Linfoma de Células B/metabolismo , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
Front Immunol ; 14: 1208590, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38152406

RESUMEN

Background: Chronic granulomatous disease (CGD) is an inborn immune disorder in which the phagocytic system cannot eradicate pathogens, and autoinflammation occurs. Approximately half of the patients have associated gastrointestinal symptoms. Although most cases with CGD-associated colitis present nonspecific histology, colonoscopy in some cases shows brownish dots over a yellowish oedematous mucosa, which is termed a "leopard sign". However, the significance of these signs remains unclear. Methods: We collected data from patients with CGD whose colonoscopic findings showed the leopard sign. Results: Three patients with CGD and leopard signs were enrolled in this study. One patient underwent colonoscopy for frequent diarrhoea and weight gain failure, and another for anal fistula. The third patient was without gastrointestinal symptoms and underwent colonoscopy as a screening test before allogeneic haematopoietic cell transplantation (HCT). Endoscopic findings showed a mild leopard sign in the first case; however, non-contiguous and diffuse aphthae were observed throughout the colon. The other two cases were unremarkable except for the leopard sign. All the patients achieved remission with oral prednisolone or HCT. One patient underwent colonoscopy after HCT; results revealed improvements in endoscopy (including the leopard sign) and histological findings. However, another patient underwent colonoscopy after prednisolone treatment; this revealed no change in the leopard sign. Conclusion: The leopard sign in the colon may be a characteristic endoscopic finding of CGD, even in patients who do not develop severe gastrointestinal symptoms; however, it does not reflect the severity of CGD-associated colitis.


Asunto(s)
Colitis , Enfermedades Gastrointestinales , Enfermedad Granulomatosa Crónica , Humanos , Enfermedad Granulomatosa Crónica/complicaciones , Enfermedad Granulomatosa Crónica/diagnóstico , Enfermedad Granulomatosa Crónica/terapia , Colitis/etiología , Colitis/complicaciones , Colonoscopía , Enfermedades Gastrointestinales/complicaciones , Prednisolona
17.
Thorac Cancer ; 14(20): 1991-2000, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37253418

RESUMEN

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. METHODS: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. RESULTS: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. CONCLUSIONS: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.


Asunto(s)
Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Humanos , Nivolumab/farmacología , Nivolumab/uso terapéutico , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos/metabolismo , Estudios Retrospectivos , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Mesotelioma/patología , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/patología , Microambiente Tumoral
18.
Endocr Pathol ; 33(4): 506-518, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36029394

RESUMEN

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are non-epithelial neuroendocrine neoplasms originating from the adrenal medulla and paraganglion of the sympathetic and parasympathetic nervous system, respectively. PCCs and PGLs show histological similarities with other epithelial neuroendocrine neoplasms and olfactory neuroblastomas (ONBs), and the differential diagnosis of PGLs is particularly difficult. Therefore, we compared the sensitivity of PHOX2A, PHOX2B, and tyrosine hydroxylase (TH) in the histopathological diagnosis of PCCs and PGLs immunohistochemically using the tissue microarrays of 297 neoplasms including PCCs, PGLs, neuroblastomas, ganglioneuromas, epithelial neuroendocrine neoplasms, and ONBs. Using cutoff values of 25%, 5%, and 5% of tumor cells expressing PHOX2A, PHOX2B, and TH, respectively, as positive, 40 of 51 PCCs, 32 of 33 parasympathetic/head and neck PGLs (HNPGLs), 17 of 19 sympathetic/thoracoabdominal PGLs (TAPGLs), and 12 of 152 epithelial neuroendocrine neoplasms, including 123 well-differentiated and 29 poorly differentiated neuroendocrine neoplasms, were PHOX2A-positive. All 51 PCCs, 33 HNPGLs, and 19 TAPGLs were PHOX2B-positive, while all 152 epithelial neuroendocrine neoplasms were PHOX2B-negative. Moreover, 50 of 51 PCCs, 13 of 33 HNPGLs, all TAPGLs, and 12 of 152 epithelial neuroendocrine neoplasms were TH-positive. All ONBs were negative for PHOX2A, PHOX2B, and TH. PHOX2B was the most sensitive and specific diagnostic marker for PCCs and PGLs among PHOX2A, PHOX2B, and TH. PHOX2B can facilitate identification of PCCs and PGLs from epithelial neuroendocrine neoplasms and ONBs, especially in the case of HNPGLs, in which TH is often negative.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales , Paraganglioma Extraadrenal , Paraganglioma , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico , Feocromocitoma/patología , Paraganglioma/diagnóstico , Paraganglioma/patología , Neoplasias de las Glándulas Suprarrenales/diagnóstico , Neoplasias de las Glándulas Suprarrenales/patología , Factores de Transcripción , Biomarcadores
19.
Biopsychosoc Med ; 15(1): 7, 2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33743774

RESUMEN

BACKGROUND: An oral burning sensation with unidentified cause in patients with preexisting psychosocial conditions is usually diagnosed as burning mouth syndrome. However, unexpected organic lesions may be detected in rare cases. CASE PRESENTATION: A 35-year-old woman had chief complaints of a burning sensation and numbness of the right side of the lip and tongue, as well as a dry sensation of the mouth with a taste disturbance of the right side of the tongue. The symptoms were continuous and did not show any daily fluctuations. The symptoms started without any recognizable triggering factor six months before her first visit to our clinic,. No abnormality was detected in her mouth. MRI images revealed an approximately 30 × 30 mm well-defined mass localized in the right cerebropontine angle compressing the trigeminal nerve, which was diagnosed as schwannoma of the right auditory nerve. CONCLUSIONS: It is important for clinicians to consider the possibility of brain tumors in their differential diagnosis of BMS. Although it is not always easy to eliminate all diseases that may cause an oral burning sensation in patients with BMS-like symptoms, more attention and careful examination based on the patient's psychosomatic background features and other possible causes are needed to rule out organic diseases.

20.
Eur J Hybrid Imaging ; 5(1): 8, 2021 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-34181162

RESUMEN

BACKGROUND: SMARCA4-deficient thoracic tumor (SMARCA4-DTT) is a distinct entity of undifferentiated thoracic malignancies newly introduced in 2015. Due to its unique clinical characteristic with aggressive thoracic tumor mostly observed in heavy smoker man with emphysema, with poor prognosis, many physicians are becoming increasingly aware of the disease; however, reports on 2-deoxy-2-[18F] fluoroglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) have been limited; thus, this disease is not yet widely known to nuclear medicine clinicians. As a first step in discussing the usefulness of [18F]FDG PET/CT for this disease, we present a case in which [18F]FDG PET/CT played a clinically important role. CASE: A 74-year-old heavy smoker man with an anamnesis of severe emphysema characterized by pleural thickening and abnormal enhancement in CT underwent 18F-FDG PET/CT for further examination. [18F]FDG-avid pleural nodules infiltrating into the chest wall were detected and pathologically diagnosed as SMARCA4-DTT with biopsy. CONCLUSION: SMARCA4-deficient thoracic tumor should be considered in a [18F]FDG-avid aggressive thoracic tumor in heavy smoker men with emphysema.

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