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1.
Discov Oncol ; 13(1): 27, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35438346

RESUMO

PURPOSE: FOXP3 + and CD8 + are recognized markers of tumor-infiltrating lymphocytes (TILs) for breast cancer. FOXP3 + TILs are composed of effector Tregs (eTregs) and other subpopulations that are classified by their differences in suppressive function. In this prospective study, we evaluated Treg subpopulations and CD8 + TILs in breast cancer. METHODS: 84 patients with breast cancer were enrolled. Fresh TILs were extracted andTregs were classified into eTregs (CD4+FOXP3highCD45RA-), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4- TILs using flow cytometry. The suppression strength of each Treg subpopulation was analyzed. The association between TIL subpopulations, clinicopathological characteristics, and response to chemotherapy was evaluated. RESULTS: The mean CD8/eTreg ratio value was 7.86 (interquartile range: 4.08-12.80). The proliferation function of eTregs was significantly suppressed compared with that of the other subpopulations (proliferation rates: control: 89.3%, + naiiveTreg: 64.2%, + non-Treg: 78.2% vs eTreg 1.93%; all P < 0.05). The patients with high with a high CD8 + /eTreg ratio achieved excellent pathological complete response (pCR) rate of neoadjuvant chemotherapy (90.2%) and the CD8/eTreg ratio were independent predictive factors for pCR (odds ratio:18.7(confidence interval 1.25-279) P < 0.05). A detailed assessment of the CD8/eTreg ratio for each patient who underwent NAC revealed that high CD8/eTreg ratio showed a significantly higher pCR rate compared to patients with a low CD8/FOXP3 ratio (39.6% vs 13.3, P < 0.05) in triple negative subtype patients with stromal TILs < 50%. CONCLUSIONS: A high CD8/eTreg ratio enhances pCR rate in patients with invasive breast cancer.

2.
Mol Cell Endocrinol ; 548: 111613, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35257799

RESUMO

DNA methylation alteration is tissue-specific and play a pivotal role in regulating gene transcription during cell proliferation and survival. We aimed to detect genes regulated by DNA methylation, and then investigated whether the gene influenced cell proliferation or survival in adrenal cells. DNA methylation and qPCR analyses were performed in nonfunctioning adrenocortical adenoma (NFA, n = 12) and aldosterone-producing adenoma (APA, n = 35) samples. The VDR gene promoter was markedly hypomethylated in APA with ATP1A1 mutation, and the promoter methylation levels showed a significant inverse association with the transcripts in APA. ATP1A1 mutation led to VDR transcription in HAC15 cells, and VDR suppression abrogated ATP1A1 mutation-mediated cell proliferation in HAC15 cells. We demonstrated that APA with ATP1A1 mutation showed entire hypomethylation in the VDR promoter and abundant VDR mRNA and protein expression. VDR suppression abrogated ATP1A1 mutation-mediated cell proliferation in HAC15 cells. Abundant VDR expression would be essential for ATP1A1 mutation-mediated cell proliferation.


Assuntos
Adenoma , Adenoma Adrenocortical , Hiperaldosteronismo , Receptores de Calcitriol , ATPase Trocadora de Sódio-Potássio , Adenoma/genética , Adenoma Adrenocortical/genética , Adenoma Adrenocortical/metabolismo , Aldosterona/metabolismo , Metilação de DNA/genética , Humanos , Hiperaldosteronismo/genética , Mutação/genética , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
3.
DEN open ; 2(1): e35, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35310732

RESUMO

Objectives: There are some endoscopic resection (ER) methods for neuroendocrine tumors (NETs), however, which method is most useful remains unclear. This study aimed to compare the outcomes of different ER techniques, such as conventional endoscopic mucosal resection (cEMR), endoscopic submucosal dissection (ESD), and endoscopic submucosal resection with a ligation device (ESMR-L) for rectal NETs. Methods: We retrospectively analyzed 96 consecutive patients with 102 rectal NETs of less than 10 mm in diameter who underwent ER between January 2001 and December 2019 at Hiroshima University Hospital. We compared the clinical outcomes of each ER method (cEMR 60 lesions, ESD 21 lesions, and ESMR-L 21 lesions), divided according to the treatment periods, and evaluated the risk factors for vertical margin (VM) positivity in relation to clinicopathological and endoscopic characteristics. Results: As for the mean procedure time, ESD took significantly longer to perform than the other methods. The histological complete resection rate was 80% (48/60) for cEMR, 85.7% (18/21) for ESD, and 100% (21/21) for ESMR-L, and the VM positive rate was 20% (12/60) for cEMR, 14.3% (3/21) for ESD, and 0% (0/21) for ESMR-L, with no significant difference. However, the tumor-front-to-VM distance was significantly longer in the ESMR-L group than in the cEMR and ESD groups. cEMR and ESD were both significant risk factors for VM positivity. No perforation or local recurrence was observed in all methods. Conclusions: ESMR-L is the most useful ER method for small rectal NETs.

4.
BMC Ophthalmol ; 22(1): 142, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35346121

RESUMO

BACKGROUND: A hypertrophic limbal mass lesion is an uncommon finding of vernal keratoconjunctivitis; it normally occurs in eyes with severe papillae formation in the tarsal conjunctiva. We present a case with a limbal mass lesion in a patient with relatively mild allergic findings in the tarsal conjunctiva. CASE PRESENTATION: A 12-year-old Japanese boy displaying allergic conjunctivitis presented with a mass lesion at the inferior limbus in the left eye. Relatively mild papillae formation was found on the tarsal conjunctiva in both eyes. We diagnosed that the mass lesion resulted from limbal vernal keratoconjunctivitis and resected it for therapeutic purposes. Histopathological examination showed that eosinophils, lymphocytes, and fibroblasts were present in the subepithelial lesion and the substantia propria of the mass lesion. Immunohistochemical staining detected diffuse and rich infiltration of CD3-positive T lymphocytes and a relatively small number of CD20-positive B lymphocytes and CD138-positive plasma cells that tended to aggregate. The histopathologic features suggested that the limbal mass lesion had similar structures to the papillae at the tarsal conjunctiva of vernal keratoconjunctivitis. CONCLUSION: The limbal mass lesion as a finding of vernal keratoconjunctivitis can occur even if the papillae formation at the patient's tarsal conjunctiva is mild.


Assuntos
Conjuntivite Alérgica , Linfócitos B/patologia , Criança , Túnica Conjuntiva/patologia , Conjuntivite Alérgica/diagnóstico , Humanos , Hiperplasia/patologia , Linfócitos/patologia , Masculino
5.
Surg Oncol ; 41: 101725, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35189516

RESUMO

BACKGROUND: The tumor-infiltrating lymphocyte (TIL)-ultrasonography (US) score determined through characteristic US findings has predictive performance of lymphocyte-predominant breast cancer (LPBC). This study aimed to investigate whether the TIL-US score before neoadjuvant chemotherapy (NAC) can predict the pathological complete response (pCR). METHODS: We evaluated patients with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (n = 55) and triple-negative breast cancer (TNBC) (n = 24) who underwent surgery after NAC from November 2012 to April 2019. Pre-NAC biopsy examination was performed to examine stromal TILs; the cutoff value for predicting pCR was defined as ≥50% stromal TILs. The TILs-US score was calculated from the pre-NAC US findings. Based on previous data, the cutoff value for predicting pCR was set at ≥4 points. RESULTS: Forty-six patients achieved pCR. The TIL-US score was significantly associated with the pCR rate (p = 0.003) but not the pre-NAC biopsy findings (p = 0.055). Multivariate logistic regression analysis revealed that a TILs-US score ≥4 and HER2 positivity were significant pCR predictors (odds ratio [OR] 3.69; p = 0.031; OR 8.74; p = 0.025). CONCLUSIONS: TILs-US scores can be used to evaluate the therapeutic effect of NAC, and may be used as a non-invasive, convenient, and an alternative method to assess stromal TILs in pre-treatment biopsies.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Feminino , Humanos , Terapia Neoadjuvante/métodos , Prognóstico , Receptor ErbB-2/metabolismo , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Ultrassonografia
6.
Pancreatology ; 22(3): 414-420, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35219581

RESUMO

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is extremely useful for pathological diagnosis of pancreatic ductal adenocarcinoma (PDAC); however, puncturing is difficult in some cases, and there is a risk of needle tract seeding. This study evaluated the indications for endoscopic retrograde pancreatography-based (ERP)-based cytology for the preoperative diagnosis of PDAC. METHODS: This study included 267 patients with PDAC who underwent preoperative ERP. The diagnostic performance of ERP-based cytology for PDAC was evaluated based on the sample collection method (pancreatic juice cytology [PJC] during ERP, brush cytology, PJC via endoscopic nasopancreatic drainage [ENPD] catheter), lesion site (pancreatic head, body/tail), and lesion size (≤10 mm, 10-20 mm, >20 mm), and compared with the diagnostic performance of EUS-FNA. RESULTS: The overall sensitivity of ERP-based cytology was 54.9%; sensitivity by the sampling method was 34.7% for PJC during ERP, 65.8% for brush cytology, and 30.8% for PJC via an ENPD catheter. The sensitivity of EUS-FNA was 85.3%. Brush cytology and PJC via an ENPD catheter were performed more often in pancreatic body/tail lesions than in head lesions (P = 0.016 and P < 0.001, respectively), and the overall sensitivity of ERP-based cytology was better for body/tail lesions (63.2% vs. 49.0%, P = 0.025). The sensitivities of ERP-based cytology and EUS-FNA in diagnosing PDAC ≤10 mm were 92.3% and 33.3%, respectively. Post-ERP pancreatitis was observed in 22 patients (8.2%) and significantly less common with ENPD catheters (P = 0.002). CONCLUSIONS: ERP-based cytology may be considered the first choice for pathological diagnosis of PDAC ≤10 mm and in the pancreatic body/tail.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos
7.
Am J Clin Pathol ; 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35157005

RESUMO

OBJECTIVES: This study aimed to develop reliable biomarkers that improve the ability of bile cytology to diagnose cholangiocarcinoma vs benign biliary lesions. METHODS: Many studies indicate that microRNAs (miRNAs) are potential candidates for the early diagnosis of cancer. We analyzed the expression of five tumor-associated miRNAs (miR-31-5p, miR-122-5p, miR-378d, miR-182-5p, and miR-92a-3p) in cytology samples using quantitative reverse transcription polymerase chain reaction. We collected 52 surgically resected tissue samples, 84 cytologic specimens from smears (53 cases of cancer and 31 cases of noncancer), and 40 residual sediments after smearing for routine cytology at Hiroshima University Hospital. RESULTS: The expression of miR-31-5p, miR-378d, and miR-122-5p was significantly higher in cancer tissues than those in normal tissues, while miR-182-5p expression was lower. The expression of miR-31-5p, miR-378d, miR-182-5p, and miR-92a-3p was significantly higher in detached cell samples from smears of cholangiocarcinoma cases than in those from noncancer cases. CONCLUSIONS: These results suggest that the analysis of miRNAs in bile cytologic specimens is a promising auxiliary tool for distinguishing cholangiocarcinoma from benign biliary lesions.

8.
Cureus ; 14(1): e21341, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35186599

RESUMO

The neoplastic cells of mantle cell lymphoma (MCL) usually express CD5 and not CD10. However, cases of MCL with aberrant expression of CD10 have been seldom reported. A 71-year-old man presented multiple lymphadenopathies with a bulky tumor of the abdomen. He received the biopsies from the left cervical lymph node and the duodenum. The former specimen showed MCL with CD5-positive and CD10-negative, but the latter showed MCL with CD5-positive and CD10-positive. After receiving induction therapy, he developed convulsions, and lymphoma cells expressing CD5-positive and CD10-positive were detected in cerebrospinal fluid (CSF). CD10-positive MCL has some significant clinical characteristics. And it shows worse overall survival compared with CD10-negative MCL when it has aggressive features such as blastoid and pleomorphic morphology, high-Ki-67 index, and high mantle cell lymphoma international prognostic index (MIPI). Therefore, physicians and pathologists must carefully discriminate against cases having this aberrant expression.

9.
Intern Med ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35022344

RESUMO

A 69-year-old man with advanced non-small-cell lung cancer was treated with pembrolizumab for 4 months. Three months after pembrolizumab was discontinued, computed tomography showed enlargement of the pancreatic head, with hypoattenuating areas in the pancreatic head to body. On endoscopic ultrasonography, the entire pancreatic parenchyma was hypoechoic. Endoscopic retrograde cholangiopancreatography showed narrowing of the main pancreatic duct at the pancreatic head. Endoscopic ultrasound-guided fine-needle aspiration showed inflammatory cell infiltration in the stroma but no neoplastic lesions. CD8-positve T cells were dominant over CD4-positive T cells in the infiltrating lymphocytes, and the patient was diagnosed with pembrolizumab-induced pancreatitis.

10.
Surg Endosc ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020058

RESUMO

BACKGROUND: Vertical tumor margin-negative T1 colorectal carcinoma (CRC) is an absolute curative condition following complete endoscopic resection (ER). However, the influence on prognosis in relation to vertical tumor margin is unclear. Therefore, we evaluated the influence of the distance from vertical tumor margin to resected specimen edge (vertical margin distance) of ER for T1b (submucosal invasion depth > 1000 µm) CRC on the prognosis of patients undergoing additional surgery after ER. METHODS: In total, 215 consecutive patients with T1b CRC who underwent additional surgery after ER at Hiroshima University Hospital between February 1992 and June 2019 were enrolled. We assessed 191 patients without lymph node metastases at the additional surgery. The specimens resected by ER were classified into three groups based on the vertical margin distance: patients with a vertical margin distance of ≥ 500 µm (Group A); patients with a vertical margin distance of < 500 µm (Group B); and patients with a positive vertical tumor margin (Group C). Subsequently, we evaluated the prognosis of the patients in relation to the clinicopathological characteristics among the three groups. RESULTS: There were no significant differences in clinicopathological characteristics among the three groups. Group A had a significantly higher recurrence-free 5-year survival rate than Groups B and C (100%, 84.5%, and 81.8%, respectively). Similarly, Group A had a significantly higher disease-specific 5-year survival rate than Group C (100% vs. 95.5%). CONCLUSIONS: Complete en bloc resection with sufficient submucosal layer from the invasive front (vertical margin distance > 500 µm) by ER for T1 CRC reduces the risk of metastatic recurrence after additional surgery.

11.
Cancer Discov ; 12(3): 692-711, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34880079

RESUMO

The neuroendocrine carcinoma of the gastrointestinal system (GIS-NEC) is a rare but highly malignant neoplasm. We analyzed 115 cases using whole-genome/exome sequencing, transcriptome sequencing, DNA methylation assays, and/or ATAC-seq and found GIS-NECs to be genetically distinct from neuroendocrine tumors (GIS-NET) in the same location. Clear genomic differences were also evident between pancreatic NECs (Panc-NEC) and nonpancreatic GIS-NECs (Nonpanc-NEC). Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic features. Alterations in TP53 and RB1 proved common in GIS-NECs, and most Nonpanc-NECs with intact RB1 demonstrated mutually exclusive amplification of CCNE1 or MYC. Alterations of the Notch gene family were characteristic of Nonpanc-NECs. Transcription factors for neuroendocrine differentiation, especially the SOX2 gene, appeared overexpressed in most GIS-NECs due to hypermethylation of the promoter region. This first comprehensive study of genomic alterations in GIS-NECs uncovered several key biological processes underlying genesis of this very lethal form of cancer. SIGNIFICANCE: GIS-NECs are genetically distinct from GIS-NETs. GIS-NECs arising in different organs show similar histopathologic features and share some genomic features, but considerable differences exist between Panc-NECs and Nonpanc-NECs. In addition, Panc-NECs could be classified into two subgroups (i.e., "ductal-type" and "acinar-type") based on genomic and epigenomic features. This article is highlighted in the In This Issue feature, p. 587.


Assuntos
Carcinoma Neuroendócrino , Tumores Neuroendócrinos , Carcinoma Neuroendócrino/genética , Exoma , Humanos , Recém-Nascido , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Sequenciamento Completo do Exoma
12.
PLoS One ; 16(10): e0258856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34673800

RESUMO

Hypoxia is a common pathway to the progression of end-stage kidney disease. Retinoic acid-inducible gene I (RIG-I) encodes an RNA helicase that recognizes viruses including SARS-CoV2, which is responsible for the production of interferon (IFN)-α/ß to prevent the spread of viral infection. Recently, RIG-I activation was found under hypoxic conditions, and klotho deficiency was shown to intensify the activation of RIG-I in mouse brains. However, the roles of these functions in renal inflammation remain elusive. Here, for in vitro study, the expression of RIG-I and IFN-α/ß was examined in normal rat kidney (NRK)-52E cells incubated under hypoxic conditions (1% O2). Next, siRNA targeting RIG-I or scramble siRNA was transfected into NRK52E cells to examine the expression of RIG-I and IFN-α/ß under hypoxic conditions. We also investigated the expression levels of RIG-I and IFN-α/ß in 33 human kidney biopsy samples diagnosed with IgA nephropathy. For in vivo study, we induced renal hypoxia by clamping the renal artery for 10 min in wild-type mice (WT mice) and Klotho-knockout mice (Kl-/- mice). Incubation under hypoxic conditions increased the expression of RIG-I and IFN-α/ß in NRK52E cells. Their upregulation was inhibited in NRK52E cells transfected with siRNA targeting RIG-I. In patients with IgA nephropathy, immunohistochemical staining of renal biopsy samples revealed that the expression of RIG-I was correlated with that of IFN-α/ß (r = 0.57, P<0.001, and r = 0.81, P<0.001, respectively). The expression levels of RIG-I and IFN-α/ß were upregulated in kidneys of hypoxic WT mice and further upregulation was observed in hypoxic Kl-/- mice. These findings suggest that hypoxia induces the expression of IFN-α/ß through the upregulation of RIG-I, and that klotho deficiency intensifies this hypoxia-induced expression in kidneys.


Assuntos
Glucuronidase/metabolismo , Hipóxia/metabolismo , Interferon-alfa/metabolismo , Rim/metabolismo , RNA Helicases/metabolismo , Regulação para Cima , Animais , Glucuronidase/genética , Hipóxia/genética , Camundongos , Camundongos Knockout , RNA Interferente Pequeno , Ratos
13.
Int J Mol Sci ; 22(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34681640

RESUMO

The molecular mechanisms by which ATP1A1 mutation-mediated cell proliferation or tumorigenesis in aldosterone-producing adenomas (APAs) have not been elucidated. First, we investigated whether the APA-associated ATP1A1 L104R mutation stimulated cell proliferation. Second, we aimed to clarify the molecular mechanisms by which the ATP1A1 mutation-mediated cell proliferated. We performed transcriptome analysis in APAs with ATP1A1 mutation. ATP1A1 L104R mutation were modulated in human adrenocortical carcinoma (HAC15) cells (ATP1A1-mutant cells), and we evaluated cell proliferation and molecular signaling events. Transcriptome and immunohistochemical analysis showed that Na/K-ATPase (NKA) expressions in ATP1A1 mutated APA were more abundant than those in non-functioning adrenocortical adenoma or KCNJ5 mutated APAs. The significant increase of number of cells, amount of DNA and S-phase population were shown in ATP1A1-mutant cells. Fluo-4 in ATP1A1-mutant cells were significantly increased. Low concentration of ouabain stimulated cell proliferation in ATP1A1-mutant cells. ATP1A1-mutant cells induced Src phosphorylation, and low concentration of ouabain supplementation showed further Src phosphorylation. We demonstrated that NKAs were highly expressed in ATP1A1 mutant APA, and the mutant stimulated cell proliferation and Src phosphorylation in ATP1A1-mutant cells. NKA stimulations would be a risk factor for the progression and development to an ATP1A1 mutant APA.


Assuntos
Adenoma/patologia , Aldosterona/metabolismo , Proliferação de Células , ATPase Trocadora de Sódio-Potássio/genética , Adenoma/metabolismo , Adenoma Adrenocortical/metabolismo , Adenoma Adrenocortical/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocromo P-450 CYP11B2/genética , Citocromo P-450 CYP11B2/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Humanos , Mutação , Ouabaína/farmacologia , Fosforilação/efeitos dos fármacos , Pontos de Checagem da Fase S do Ciclo Celular , ATPase Trocadora de Sódio-Potássio/metabolismo , Transcriptoma , Quinases da Família src/metabolismo
14.
Sci Rep ; 11(1): 20163, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635790

RESUMO

Systemic sclerosis (SSc) is characterized by fibrosis of the skin and various internal organs. However, there is limited knowledge concerning small-bowel lesions. We evaluated the clinical state of patients with SSc according to the capsule endoscopy (CE) findings. Sixty-five consecutive patients with SSc (61 females; mean age, 64.3 years) underwent CE at Hiroshima University Hospital between April 2012 and December 2019. SSc was subclassified into diffuse and limited cutaneous SSc. Among the 65 patients, 55 (51 females; mean age, 64.5 years; diffuse cutaneous SSc, 27 patients) were evaluated for the presence of fibrosis in the gastrointestinal tract by biopsy. Small-bowel lesions were detected in 27 (42%) patients with SSc. Type 1b angioectasia (Yano-Yamamoto classification) was more frequent in limited cutaneous SSc patients (p = 0.0071). The average capsule transit time of the esophagus was significantly longer in diffuse cutaneous SSc patients (p = 0.0418). There were more cases of Type 1a angioectasia in SSc patients without fibrosis. The average capsule transit time of the esophagus was significantly longer in SSc patients with fibrosis. Thus, this study revealed that the frequency of small-bowel angioectasia and gastrointestinal motility in patients with SSc differed depending on SSc subclassification and the presence of fibrosis.


Assuntos
Endoscopia por Cápsula/métodos , Gastroenteropatias/diagnóstico , Motilidade Gastrointestinal , Escleroderma Sistêmico/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
15.
BMC Cancer ; 21(1): 1077, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34610807

RESUMO

BACKGROUND: The benefits of postoperative chemotherapy in patients with estrogen receptor (ER)-positive breast cancer remain unclear. The use of tumor grade, Ki-67, or ER expression failed to provide an accurate prognosis of the risk of relapse after surgery in patients. This study aimed to evaluate whether a multigene assay Curebest™ 95GC Breast (95GC) can identify the risk of recurrence and provide more insights into the requirements for chemotherapy in patients. METHODS: This single-arm retrospective multicenter joint study included patients with ER-positive, node-negative breast cancer who were treated at five facilities in Japan and had received endocrine therapy alone as adjuvant therapy. The primary lesion specimens obtained during surgery were analyzed using the 95GC breast cancer multigene assay. Based on the 95GC results, patients were classified into low-risk (95GC-L) and high-risk (95GC-H) groups. RESULTS: The 10-year relapse-free survival rates were 88.4 and 59.6% for the 95GC-L and 95GC-H groups, respectively. Histologic grade, Ki-67, and PAM50 exhibited a significant relationship with the 95GC results. The segregation into 95GC-L and 95GC-H groups within established clinical factors can identify subgroups of patients using histologic grade or PAM50 classification with good prognosis without receiving chemotherapy. CONCLUSIONS: Based on the results of our retrospective study, 95GC could be used to evaluate the long-term prognosis of ER-positive, node-negative breast cancer. Even though further prospective validation is necessary, the inclusion of 95GC in clinical practice could help to select optimal treatments for breast cancer patients and identify those who do not benefit from the addition of chemotherapy, thus avoiding unnecessary treatment.


Assuntos
Neoplasias da Mama/genética , Expressão Gênica , Recidiva Local de Neoplasia/genética , Receptores de Estrogênio , Análise Serial de Tecidos/métodos , Adulto , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/classificação , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Japão , Antígeno Ki-67/análise , Linfonodos , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Risco , Taxa de Sobrevida , Fatores de Tempo
16.
BMC Gastroenterol ; 21(1): 324, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425746

RESUMO

BACKGROUND: In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years. METHODS: ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months. RESULTS: The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients. CONCLUSIONS: ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Idoso , Idoso de 80 Anos ou mais , Colonoscopia , Neoplasias Colorretais/cirurgia , Dissecação , Ressecção Endoscópica de Mucosa/efeitos adversos , Humanos , Mucosa Intestinal/cirurgia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
17.
Technol Cancer Res Treat ; 20: 15330338211027901, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34191660

RESUMO

Signet ring cell carcinoma (SRCC) of the stomach is a rare type of cancer with a slowly rising incidence. It tends to be more difficult to detect by pathologists, mainly due to its cellular morphology and diffuse invasion manner, and it has poor prognosis when detected at an advanced stage. Computational pathology tools that can assist pathologists in detecting SRCC would be of a massive benefit. In this paper, we trained deep learning models using transfer learning, fully-supervised learning, and weakly-supervised learning to predict SRCC in Whole Slide Images (WSIs) using a training set of 1,765 WSIs. We evaluated the models on two different test sets (n = 999, n = 455). The best model achieved a ROC-AUC of at least 0.99 on all two test sets, setting a top baseline performance for SRCC WSI classification.


Assuntos
Carcinoma de Células em Anel de Sinete/classificação , Carcinoma de Células em Anel de Sinete/patologia , Aprendizado Profundo , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Área Sob a Curva , Carcinoma de Células em Anel de Sinete/diagnóstico , Biologia Computacional , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Curva ROC , Neoplasias Gástricas/diagnóstico , Aprendizado de Máquina Supervisionado
18.
PLoS One ; 16(5): e0241454, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34014970

RESUMO

The current understanding of clinicopathological features and genomic variants of small-bowel cancer is limited, in part due to the rarity of the disease. However, understanding of these factors is necessary for the development of novel therapeutic agents for small-bowel cancer. Thus, we aimed to identify the clinicopathological features and genomic variants associated with its prognosis and recurrence. We retrospectively examined 24 consecutive patients with primary small-bowel cancer surgically treated between May 2005 and August 2018 and collected 29 tumor specimens. The 29 lesions were subjected to mismatch repair status evaluation, using immunohistochemistry (IHC), and targeted genomic sequencing, after which they were analyzed using a panel of 90 cancer-related genes. IHC revealed that 45% (13/29) of the lesions exhibited deficient mismatch repair. The most common genomic variants in small-bowel cancers were in TP53 (48%, 13/27), followed by KRAS (44%, 12/27), ARID1A (33%, 9/27), PIK3CA (26%, 7/27), APC (26%, 7/27), and SMAD4, NOTCH3, CREBBP, PTCH1, and EP300 (22%, 6/27 each). Overall survival and disease-specific survival of patients with tumor mutational burden (TMB) ≥10 mutations/Mb (n = 17) were significantly better than those of patients with TMB <10 mutations/Mb (n = 6). Additionally, patients with a mutant SMAD4 had poorer recurrence-free survival than those with wild-type SMAD4. Our results suggested that TMB and SMAD4 mutations were associated with the prognosis of small-bowel cancer patients. Thus, cancer genomic analysis could be useful in the search for biomarkers of prognosis prediction in small-bowel cancers.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Íleo/genética , Neoplasias do Jejuno/genética , Mutação , Adulto , Idoso , Proteína de Ligação a CREB/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Neoplasias do Íleo/patologia , Neoplasias do Jejuno/patologia , Masculino , Pessoa de Meia-Idade , Receptores Notch/genética , Proteínas Smad/genética , Análise de Sobrevida , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética , Proteínas ras/genética
19.
J Cancer Res Clin Oncol ; 147(12): 3709-3718, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33796913

RESUMO

PURPOSE: The clinicopathological or genetic features related to the prognosis of mucinous adenocarcinoma are unknown because of its rarity. The clinicopathological or targetable features were investigated for better management of patients with mucinous adenocarcinoma of the lung. METHODS: We comprehensively evaluated the clinicopathological and genetic features of 60 completely resected mucinous lung adenocarcinomas. Targetable genetic variants were explored using nCounter and polymerase chain reaction, PD-L1 and TTF-1 expression were evaluated using immunohistochemistry. We analyzed the prognostic impact using the Kaplan-Meier method and log-rank test. RESULTS: Of the 60 enrolled patients, 13 (21.7%) had adenocarcinoma in situ/minimally invasive adenocarcinoma, and 47 (78.3%) had invasive mucinous adenocarcinoma (IMA). Fifteen patients (25%) showed a pneumonic appearance on computed tomography (CT). CD74-NRG1 fusion, EGFR mutations, and BRAF mutation were detected in three (5%), four (6.7%), and one (1.7%) patient(s), respectively. KRAS mutations were detected in 31 patients (51.7%). Two patients (3.5%) showed immunoreactivity for PD-L1. No in situ or minimally invasive cases recurred. IMA patients with pneumonic appearance had significantly worse recurrence-free survival (RFS) and overall survival (OS) (p < 0.001). Furthermore, IMA patients harboring KRAS mutations had worse RFS (p = 0.211). Multivariate analysis revealed that radiological pneumonic appearance was significantly associated with lower RFS (p < 0.003) and OS (p = 0.012). KRAS mutations served as an unfavorable status for RFS (p = 0.043). CONCLUSION: Mucinous adenocarcinoma had a low frequency of targetable genetic variants and PD-L1 immunoreactivity; however, KRAS mutations were frequent. Pneumonic appearance on CT imaging and KRAS mutations were clinicopathological features associated with a worse prognosis.


Assuntos
Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos
20.
Int J Surg Case Rep ; 80: 105676, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33652367

RESUMO

INTRODUCTION: Extraskeletal Ewing sarcoma (EES) of the extremity is uncommon, and only a small number of reported cases have been devoted to the upper-extremity. PRESENTATION OF CASE: A 65-year-old woman presented with a recurrent EES, a highly malignant tumor, involving the ulnar nerve at the right elbow region which was initially suspected as a benign soft tissue tumor, schwannoma, thus marginal excision had been performed. Due to its malignant behaviour, we treated the recurrent lesion with wide excision and reconstruction combined with chemotherapy. Histological evaluation revealed a monotonous small round cells appearance. DISCUSSION: EES of the extremity involving the ulnar nerve is fairly uncommon. The tumor was often smaller in the adult than in the child population which was consistent with the present case, thus may mimic a benign tumor. Because of the overlapping histopathological features of EES with other tumors, other investigations such as immunohistochemistry and cytogenetic studies must be performed to allow definitive diagnosis. The result of our study was negative for the EWSR1-FLI-1 and CIC-DUX4 fusion gene, however, other less frequent translocations could be found in this case which does not exclude the diagnosis of Ewing sarcoma family. CONCLUSION: Few cases of EES involving the ulnar nerve have been previously reported. The correct diagnosis of EES involving the ulnar nerve has become particularly important in order to enable the initiation of comprehensive management that have the potential to reduce disease progression and the avoidance of improper and potentially harmful surgical therapy.

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