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Activating antibody-dependent cellular cytotoxicity (ADCC) by targeting claudin-18 isoform 2 (CLDN18.2) using zolbetuximab, a monoclonal antibody against CLDN18.2, has been considered a promising novel therapeutic strategy for gastric cancer (GC). However, the impact of CLDN18.2 expression on natural killer (NK) cells and monocytes/macrophages-crucial effector cells of ADCC-in GC has not been fully investigated. In the present study, we assessed the impact of CLDN18.2 expression on clinical outcomes, molecular features, and the frequencies of tumor-infiltrating NK cells and macrophages, as well as peripheral blood NK cells and monocytes, in GC by analyzing our own GC cohorts. The expression of CLDN18.2 did not significantly impact clinical outcomes of GC patients, while it was significantly and positively associated with Epstein-Barr virus (EBV) status and PD-L1 expression. The frequencies of tumor-infiltrating NK cells and macrophages, as well as peripheral blood NK cells and monocytes, were comparable between CLDN18.2-positive and CLDN18.2-negative GCs. Importantly, both CLDN18.2 expression and the number of tumor-infiltrating NK cells were significantly higher in EBV-associated GC compared to other molecular subtypes. Our findings support the effectiveness of zolbetuximab in CLDN18.2-positive GC, and offer a novel insight into the treatment of this cancer type, highlighting its potential effectiveness for CLDN18.2-positive/EBV-associated GC.
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Citotoxicidade Celular Dependente de Anticorpos , Claudinas , Células Matadoras Naturais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Masculino , Feminino , Claudinas/metabolismo , Claudinas/genética , Pessoa de Meia-Idade , Idoso , Macrófagos/imunologia , Macrófagos/metabolismo , Monócitos/imunologia , Monócitos/metabolismoRESUMO
PURPOSE: To clarify the diagnostic utility and formation of the Mille-feuille sign for ovarian carcinosarcoma (OCS) on MRI, and to evaluate the other MRI findings and serum markers compared to ovarian metastases from colorectal carcinoma (OMCRC). METHOD: Three blinded radiologists retrospectively reviewed MR images of 12 patients with OCS, 18 with OMCRC, and 40 with primary ovarian carcinoma (POC) identified by the electronic database of radiology reports. The interobserver agreement was analyzed using Fleiss' kappa test. Their MRI characteristics and tumor markers were compared using Fisher's exact test and Mann-Whitney's U test. Receiver operating characteristic curve analyses were used to determine the cutoff points for the ADC value. This study was approved by the institutional ethics committee. RESULTS: Interobserver agreement analysis was moderate or higher for all MRI characteristics. The frequency of Mille-feuille sign was comparable for both OCS and OMCRC groups, and predominantly higher than that of the POC group (p < 0.001, p < 0.001), respectively. Pathologically, the Mille-feuille sign in OCS reflected alternating layers of tumor cells with stroma and necrosis or intraluminal necrotic debris. Compared to OMCRC, intratumoral hemorrhage (p = 0.02), margin irregularity (p = 0.048), unilateral adnexal mass (p = 0.02), and low ADC values (p < 0.01) were more frequently observed and serum CEA levels was significantly lower (p = 0.007) in the OCS group. Under setting of the cutoff value of ADC at 0.871 × 10-3mm2/s, the discriminative ability for OCS showed 66.7% sensitivity, 94.4% specificity, and 81.0% accuracy, respectively. CONCLUSIONS: The Mille-feuille sign was seen in both OCS and OMCRC. MR findings of intratumoral hemorrhage, margin irregularity, unilateral adnexal mass, low ADC values, and low serum CEA levels can be useful in differentiating OCS from OMCRC.
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Carcinossarcoma , Neoplasias Colorretais , Imageamento por Ressonância Magnética , Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Carcinossarcoma/diagnóstico por imagem , Carcinossarcoma/secundário , Estudos Retrospectivos , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Idoso , Imageamento por Ressonância Magnética/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Sensibilidade e Especificidade , Meios de ContrasteRESUMO
PURPOSE: Complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) share common clinical features such as female phenotype, vaginal hypoplasia, and primary amenorrhea. Magnetic resonance imaging (MRI) is performed to investigate the cause of primary amenorrhea. However, the MRI features are also similar in both disorders. They are ultimately diagnosed by chromosome testing, but there is a possibility of misdiagnosis if chromosome testing is not performed. This study aimed to identify MRI features that are useful for differentiating CAIS from MRKHS. METHOD: This multicenter retrospective study included 12 patients with CAIS and 19 patients with MRKHS. Three radiologists blindly evaluated the following features: (1) detection of vagina, (2) detection of nodular and cystic structures in the lateral pelvis; undescended testicles and paratesticular cysts in CAIS and rudimentary uteri and ovaries in MRKHS, (3) their location, (4) number of cysts in the cystic structures, and (5) signal intensity on diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) values of the nodular structures. Statistical comparisons were performed using Mann-Whitney U and Fisher's exact tests. RESULTS: Compared with MRKHS, the CAIS group showed significantly detectable vagina, more ventrally located nodular and cystic structures, fewer cysts within the cystic structures, and nodular structures with higher signal intensity on DWI and lower ADC values. CONCLUSIONS: MRI features of detectable vagina, location of nodular and cystic structures, number of cysts within the cystic structures, signal intensity on DWI and ADC values of the nodular structures were useful in differentiating CAIS from MRKHS.
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OBJECTIVES: To investigate the relationship between low kidney volume and subsequent estimated glomerular filtration rate (eGFR) decline in eGFR category G2 (60-89 mL/min/1.73 m2) population. METHODS: In this retrospective study, we evaluated 5531 individuals with eGFR category G2 who underwent medical checkups at our institution between November 2006 and October 2017. Exclusion criteria were absent for follow-up visit, missing data, prior renal surgery, current renal disease under treatment, large renal masses, and horseshoe kidney. We developed a 3D U-net-based automated system for renal volumetry on CT images. Participants were grouped by sex-specific kidney volume deviations set at mean minus one standard deviation. After 1:1 propensity score matching, we obtained 397 pairs of individuals in the low kidney volume (LKV) and control groups. The primary endpoint was progression of eGFR categories within 5 years, assessed using Cox regression analysis. RESULTS: This study included 3220 individuals (mean age, 60.0 ± 9.7 years; men, n = 2209). The kidney volume was 404.6 ± 67.1 and 376.8 ± 68.0 cm3 in men and women, respectively. The low kidney volume (LKV) cutoff was 337.5 and 308.8 cm3 for men and women, respectively. LKV was a significant risk factor for the endpoint with an adjusted hazard ratio of 1.64 (95% confidence interval: 1.09-2.45; p = 0.02). CONCLUSION: Low kidney volume may adversely affect subsequent eGFR maintenance; hence, the use of imaging metrics may help predict eGFR decline. CRITICAL RELEVANCE STATEMENT: Low kidney volume is a significant predictor of reduced kidney function over time; thus, kidney volume measurements could aid in early identification of individuals at risk for declining kidney health. KEY POINTS: ⢠This study explores how kidney volume affects subsequent kidney function maintenance. ⢠Low kidney volume was associated with estimated glomerular filtration rate decreases. ⢠Low kidney volume is a prognostic indicator of estimated glomerular filtration rate decline.
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INTRODUCTION: This study aimed to identify cases that require a three-dimensional-printed kidney model in robot-assisted partial nephrectomy. METHODS: We enrolled 93 patients undergoing robot-assisted partial nephrectomy for renal tumors at a single institution between November 2018 and May 2021. The endpoints were how often and how long the surgeon consulted the three-dimensional-printed model, determined using intraoperative video. Multivariate analyses of the endpoints were adjusted by preoperative patient and kidney characteristics, including renal vascular complexity that was defined as the number of vascular branches penetrating the surface tangential to the ventral side of the kidney. RESULTS: Of the 93 cases, the median frequency and duration of intraoperative three-dimensional-printed model consultation were four times and 39 s, respectively. The multivariate linear regression analyses showed that the frequency of intraoperative three-dimensional-printed model consultation by the surgeon was significantly related to the complexity of the arterial structure (≥4 branches), presence of hilar tumor, and high Mayo Adhesive Probability score; the regression coefficients were 1.81, 2.79, and 1.34, respectively. All p-values were ≤.03. The duration of the three-dimensional-printed model consultation was significantly related to the complexity of the arterial structure (≥4 branches) and the presence of hilar tumor; the regression coefficients were 21.6, and 29.0 s, respectively. All p-values were <.01. CONCLUSION: During robot-assisted partial nephrectomy, a three-dimensional-printed model would be helpful in cases with a complex arterial structure or hilar tumor.
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Neoplasias Renais , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Nefrectomia/métodos , Rim/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Renais/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Chemotherapy has the potential to induce CD8+ T-cell infiltration in the tumor microenvironment (TME) and activate the anti-tumor immune response in several cancers including esophageal squamous cell carcinoma (ESCC). The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has been known as a critical component for regulating immune cell activation in the TME. However, its effect on the infiltration of immune cells induced by chemotherapy in the ESCC TME has not been investigated. METHODS: We examined the effect of the tumor-cell intrinsic cGAS-STING pathway on the infiltration of CD8+ T cells induced by chemotherapy in ESCC using ESCC cell lines and surgically resected ESCC specimens from patients who received neoadjuvant chemotherapy (NAC). RESULTS: We found that chemotherapeutic agents, including 5-fluorouracil (5-FU) and cisplatin (CDDP), activated the cGAS-STING pathway, consequently inducing the expression of type I interferon and T-cell-attracting chemokines in ESCC cells. Moreover, the tumor cell-intrinsic expression of cGAS-STING was significantly and positively associated with the density of CD8+ T cells in ESCC after NAC. However, the tumor cell-intrinsic expression of cGAS-STING did not significantly impact clinical outcomes in patients with ESCC after NAC. CONCLUSION: Our findings suggest that the tumor cell-intrinsic cGAS-STING pathway might contribute to chemotherapy-induced immune cell activation in the ESCC TME.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Interferon Tipo I , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Linfócitos T CD8-Positivos , Neoplasias Esofágicas/tratamento farmacológico , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/uso terapêutico , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Interferon Tipo I/uso terapêutico , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Microambiente TumoralRESUMO
PURPOSE: Standardized uptake values (SUVs) derived from 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography are a crucial parameter for identifying tumors or abnormalities in an organ. Moreover, exploring ways to improve the identification of tumors or abnormalities using a statistical measurement tool is important in clinical research. Therefore, we developed a fully automatic method to create a personally normalized Z-score map of the liver SUV. METHODS: The normalized Z-score map for each patient was created using the SUV mean and standard deviation estimated from blood-test-derived variables, such as alanine aminotransferase and aspartate aminotransferase, as well as other demographic information. This was performed using the least absolute shrinkage and selection operator (LASSO)-based estimation formula. We also used receiver operating characteristic (ROC) to analyze the results of people with and without hepatic tumors and compared them to the ROC curve of normal SUV. RESULTS: A total of 7757 people were selected for this study. Of these, 7744 were healthy, while 13 had abnormalities. The area under the ROC curve results indicated that the anomaly detection approach (0.91) outperformed only the maximum SUV (0.89). To build the LASSO regression, sets of covariates, including sex, weight, body mass index, blood glucose level, triglyceride, total cholesterol, γ-glutamyl transpeptidase, total protein, creatinine, insulin, albumin, and cholinesterase, were used to determine the SUV mean, whereas weight was used to determine the SUV standard deviation. CONCLUSION: The Z-score normalizes the mean and standard deviation. It is effective in ROC curve analysis and increases the clarity of the abnormality. This normalization is a key technique for effective measurement of maximum glucose consumption by tumors in the liver.
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Fluordesoxiglucose F18 , Neoplasias , Humanos , Compostos Radiofarmacêuticos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias/diagnóstico por imagem , Fígado/diagnóstico por imagemRESUMO
Gene therapy using adeno-associated virus (AAV)-based vectors has become a realistic therapeutic option for hemophilia. We examined the potential of a novel engineered liver-tropic AAV3B-based vector, AAV.GT5, for hemophilia B gene therapy. In vitro transduction with AAV.GT5 in human hepatocytes was more than 100 times higher than with AAV-Spark100, another bioengineered vector used in a clinical trial. However, liver transduction following intravenous injection of these vectors was similar in mice with a humanized liver and in macaques. This discrepancy was due to the low recovery and short half-life of AAV.GT5 in blood, depending on the positive charge of the heparin-binding site in the capsid. Bypassing systemic clearance with the intra-hepatic vascular administration of AAV.GT5, but not AAV-Spark100, enhanced liver transduction in pigs and macaques. AAV.GT5 did not develop neutralizing antibodies (NAbs) in two of four animals, while AAV-Spark100 induced serotype-specific NAbs in all macaques tested (4 of 4). The NAbs produced after AAV-Spark100 administration were relatively serotype specific, and challenge with AAV.GT5 through the hepatic artery successfully boosted liver transduction in one animal previously administered AAV-Spark100. In summary, AAV.GT5 showed different vector kinetics and NAb induction compared with AAV-Spark100, and intra-hepatic vascular administration may minimize the vector dose required and vector dissemination.
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In order to develop a biomarker predicting the efficacy of treatments for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT). Fifty-five ESCC patients were enrolled in this study, and peripheral blood samples were collected before and after CT or CRT and during NT. Frequencies of memory, differentiated, and exhausted T cells were evaluated using flow cytometry among cStages, treatment strategies, pathological responses of CT/CRT, and during NT. The frequencies of PD-1+ or TIM-3+CD4+ T cells were significantly higher in patients with cStage IV. PD-1+CD4+ and TIM-3+CD8+ T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4+ and CD8+ CD45RA-CD27+CD127+ central memory T cells (TCM) were significantly decreased during the course of NT in the progressive disease group. Taken together, the alteration in frequency of CD45RA-CD27+CD127+ TCM during NT may be a biomarker to predict its therapeutic response in ESCC patients.
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The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment, thereby contributing to a more favorable response to immune checkpoint inhibitors (ICI) in colorectal cancer (CRC). However, the impact of the expression of cGAS-STING in tumor cells on the infiltration of CD8+ T cells and clinical outcomes in mismatch repair proficient/microsatellite stable (pMMR/MSS) CRC remains largely unknown. Our findings reveal that 56.8% of all pMMR CRC cases were cGAS-negative/STING-negative expressions (cGAS-/STING-) in tumor cells, whereas only 9.9% of all pMMR CRC showed cGAS-positive/STING-positive expression (cGAS+/STING+) in tumor cells. The frequency of cGAS+/STING+ cases was reduced in the advanced stages of pMMR/MSS CRC, and histone methylation might be involved in the down-regulation of STING expression in tumor cells. Since the expression level of cGAS-STING in tumor cells has been associated with the infiltration of CD8+ and/or CD4+ T cells and the frequency of recurrence in pMMR/MSS CRC, decreased expression of cGAS-STING in tumor cells might lead to poor immune cell infiltration and worse prognosis in most pMMR/MSS CRC patients. Our current findings provide a novel insight for the treatment of patients with pMMR/MSS CRC.
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M2 tumor-associated macrophages (M2-TAMs) promote cancer cell proliferation and metastasis in the TME. Our study aimed to elucidate the mechanism of increased frequency of M2-TAMs infiltration in the colorectal cancer (CRC)-TME, focusing on the resistance to oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In this study, we evaluated the correlation between M2-TAM signature and mRNA expression of antioxidant related genes using public datasets, and the expression level of antioxidants in M2-TAMs by flow cytometry and the prevalence of M2-TAMs expressing antioxidants by immunofluorescence staining using surgically resected specimens of CRC (n = 34). Moreover, we generated M0 and M2 macrophages from peripheral blood monocytes and evaluated their resistance to oxidative stress using the in vitro viability assay. Analysis of GSE33113, GSE39582, and The Cancer Genome Atlas (TCGA) datasets indicated that mRNA expression of HMOX1 (heme oxygenase-1 (HO-1)) was significantly positively correlated with M2-TAM signature (r = 0.5283, r = 0.5826, r = 0.5833, respectively). The expression level of both Nrf2 and HO-1 significantly increased in M2-TAMs compared to M1- and M1/M2-TAMs in the tumor margin, and the number of Nrf2+ or HO-1+M2-TAMs in the tumor stroma significantly increased more than those in the normal mucosa stroma. Finally, generated M2 macrophages expressing HO-1 significantly resisted to oxidative stress induced by H2O2 in comparison with generated M0 macrophages. Taken together, our results suggested that an increased frequency of M2-TAMs infiltration in the CRC-TME is related to Nrf2-HO-1 axis mediated resistance to oxidative stress.
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Neoplasias Colorretais , Macrófagos Associados a Tumor , Humanos , Macrófagos Associados a Tumor/metabolismo , Antioxidantes/metabolismo , Peróxido de Hidrogênio , Microambiente Tumoral , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Neoplasias Colorretais/patologia , RNA Mensageiro/metabolismoRESUMO
INTRODUCTION: This study aimed to evaluate whether it is useful for junior physicians to use a three-dimensional (3D) kidney model when evaluating the R.E.N.A.L. nephrometry score. MATERIALS AND METHODS: An expert and four urology residents retrospectively evaluated the R.E.N.A.L. nephrometry scores of 64 renal tumors (62 patients) that underwent robot-assisted partial nephrectomy at our hospital. The expert evaluated 64 R.E.N.A.L. nephrometry scores with computed tomography (CT), whereas four residents evaluated 32 cases using CT alone and the other 32 cases using CT and a 3D kidney model. The consistency between the expert and residents was assessed by Cohen's kappa score. Patient-specific 3D kidney models were created in a gird style using a 3D printer based on CT or magnetic resonance imaging of the patient. RESULTS: For all four residents, the accuracy of the overall R.E.N.A.L. nephrometry score was significantly higher with the 3D model and CT than with CT alone (P < .001). Regarding the individual components of the R.E.N.A.L. nephrometry score, the accuracy rates of "E," "N," "A," and "L" scores were higher with the 3D model and CT than with the CT alone (P = .020-.089). CONCLUSION: Patient-specific 3D-printed kidney models could improve the resident's understanding of the renal tumor complexity and could be an important educational tool for residents.
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Neoplasias Renais , Rim , Humanos , Estudos Retrospectivos , Rim/diagnóstico por imagem , Rim/cirurgia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Impressão TridimensionalRESUMO
A 70-year-old male patient was diagnosed with advanced gastric cancer with para-aortic lymph node metastasis. After diagnostic laparoscopy, the patient received 2 courses of neoadjuvant chemotherapy. Subsequently, distal gastrectomy, D2 plus para-aortic lymph node dissection, and Roux-en-Y reconstruction were performed. An enlarged lymph node(No. 16b2)was identified during surgery. The histopathological diagnosis revealed ypT4b, ypN3b, cM1(LYM; No. 16), Stage â £B. Chemotherapy with ramucirumab plus nab-paclitaxel was administered at 6 weeks postoperatively. However, after 2 courses of chemotherapy, the patient developed an abscess discharge from the wound, which was confirmed by an abdominal CT scan and diagnosed as an intra-abdominal abscess derived from duodenal perforation. The abscess was drained percutaneously. Subsequently, chemotherapy with nab-paclitaxel, nivolumab, and trifluridine/tipiracil hydrochloride was administered. After the appearance of brain metastases, the treatment was shifted to palliative care. The patient died 2 years and 7 months later from the primary disease.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Gástricas , Idoso , Humanos , Masculino , Abscesso/cirurgia , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Duodeno/patologia , Gastrectomia , Paclitaxel , Ramucirumab , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologiaRESUMO
Decidualization can originate in ovarian endometrioma by elevated serum progesterone levels during pregnancy, which mimics malignancy on ultrasonography. Moreover, decidualized ovarian endometrioma may rupture and cause acute abdominal pain during pregnancy. Magnetic resonance imaging (MRI) is reportedly useful in differentiating decidualized ovarian endometriomas from malignancies. However, to our knowledge, serial MRI of decidualized ovarian endometrioma before and after rupture has not been reported. Herein, we report the case of a 39-year-old woman with a ruptured decidualized ovarian endometrioma in which serial MRI was useful for adequate management. She had a history of right ovarian endometrioma. Transvaginal ultrasonography at 20 weeks of gestation showed the known right ovarian endometrioma with mural nodules that were not evident before pregnancy. MRI for further evaluation showed ovarian endometrioma with mural nodules with signals similar to those of the placenta. Based on the MRI findings, we diagnosed a decidualized ovarian endometrioma. At 27 weeks of gestation, she complained of sudden abdominal pain, for which MRI was performed. MRI showed disappearance of the ovarian endometrioma and bloody ascites, based on which we diagnosed a ruptured ovarian endometrioma. The abdominal pain subsided immediately, and a conservative observational treatment approach was taken. At 37 weeks of gestation, right ovarian cystectomy was performed simultaneously with an elective cesarean section, which revealed a ruptured decidualized ovarian endometrioma. Our findings demonstrate that the accurate diagnosis of a ruptured decidualized ovarian endometrioma on serial MRI can contribute to its management.
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Deficient mismatch repair (dMMR)/microsatellite instability (MSI) colorectal cancer (CRC) has high immunogenicity and better prognosis compared with proficient MMR (pMMR)/microsatellite stable (MSS) CRC. Although the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has been considered to contribute to the high number of CD8+ TILs, its role in dMMR/MSI CRC is largely unknown. In this study, to examine the role of the cGAS-STING pathway on the recruitment of CD8+ TILs in dMMR/MSI CRC, we used public datasets and clinical tissue samples in our cohorts to evaluate the expression of cGAS, STING, and CD8+ TILs in pMMR/MSS and dMMR/MSI CRCs. According to the analysis of public datasets, the expression of cGAS-STING, CD8 effector gene signature, and CXCL10-CCL5, chemoattractants for CD8+ TILs which regulated by the cGAS-STING pathway, was significantly upregulated in dMMR/MSI CRC, and the expression of cGAS-STING was significantly associated with the expression of CD8 effector gene signature. Immunohistochemistry staining of the clinical tissue samples (n = 283) revealed that cGAS-STING was highly expressed in tumor cells of dMMR CRC, and higher expression of cGAS-STING in tumor cells was significantly associated with the increased number of CD8+ TILs. Moreover, we demonstrated that the downregulation of MMR gene in human CRC cell lines enhanced the activation of the cGAS-STING pathway. Taken together, for the first time, we found that dMMR/MSI CRC has maintained a high level of cGAS-STING expression in tumor cells, which might contribute to abundant CD8+ TILs and immune-active TME.
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Neoplasias Colorretais , Reparo de Erro de Pareamento de DNA , Fatores Quimiotáticos , Neoplasias Colorretais/patologia , Humanos , Interferons , Proteínas de Membrana , Instabilidade de Microssatélites , Nucleotidiltransferases/genética , Microambiente TumoralRESUMO
The definition of sarcopenia assessed by computed tomography (CT) varies among different reports, and few studies have examined the effect of muscle mass loss on the prognosis of post-hematopoietic cell transplantation (HCT). We retrospectively evaluated 172 patients who underwent an initial allogeneic HCT for acute leukemia at our institution. They were divided into 3 groups according to muscle mass measured at the third lumbar vertebra as assessed by CT. Patients with low muscle mass had a worse performance status, higher comorbidity index and higher disease risk. There was a significant difference in 2-year overall survival between the 3 groups, and worse overall survival (OS) was associated with lower muscle mass (p = 0.005). Muscle mass loss did not affect non-relapse mortality (p = 0.238) but was significantly associated with relapse (p = 0.067). Pre-transplant muscle mass loss may therefore reflect a poor prognosis for the primary disease.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Doenças Musculares , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Músculos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Transplante HomólogoRESUMO
Ectopic adrenocortical tissue can arise along the path of embryonic migration, such as the celiac axis, broad ligament, adnexa of the testis, and spermatic cord. Occasionally, ectopic adrenocortical tissues undergo marked hyperplasia and develop into ectopic adrenocortical adenomas. This report describes the case of a 60-year-old man who was incidentally found to have a lipid-containing mass with early enhancement and delayed washout in the right renal hilum. A renal cell carcinoma was suspected, and robot-assisted partial nephrectomy was performed, but the final diagnosis was an ectopic adrenocortical adenoma. We should include ectopic adrenocortical adenoma in the differential diagnosis when we find a lipid-containing tumor adjacent to the kidney.
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Cancer immunotherapy, which is attracting attention as a fourth treatment strategy for cancer therapy, eliminates cancer cells using own immune system. Therefore, the state of tumor immune responses is very important to elicit the efficacy of cancer immunotherapy. Recently, the association between the efficacy of cancer immunotherapy using immune checkpoint inhibitors and certain intestinal bacteria has been reported. It is suggested that certain intestinal bacteria may regulate tumor immune responses. We also reported that intestinal bacteria such as Bifidobacterium, Bacteroides, and Faecalibacterium (genus level)were increased in patients with high frequency of infiltrating effector regulatory T cells in the tumor microenvironment of advanced colorectal cancer. In this article, we presented the association between intestinal bacteria and tumor infiltrating immune cells, such as regulatory T cells and tumor associated macrophages, in the tumor microenvironment of advanced colorectal cancer, focusing on results of our research. Subsequently, we introduced the possibility of clinical application of intestinal bacteria based on the review of reported articles.
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Neoplasias Colorretais , Microambiente Tumoral , Bactérias , Neoplasias Colorretais/terapia , Humanos , Imunoterapia , Linfócitos do Interstício Tumoral , Linfócitos T ReguladoresRESUMO
Liver cirrhosis is frequently complicated by spontaneous portosystemic shunt (SPSS) due to portal hypertension. Shunt embolization is considered when symptoms related to SPSSs are refractory to endoscopic and/or medical therapies. However, little information is available on the treatment of patients with multiple and large SPSS. We report a successfully managed case in which patient with such SPSS received two embolization procedures within 6 months. A 57-year-old man with alcoholic liver cirrhosis was transferred to our hospital due to a ruptured gastric varix. CT examination showed gastrorenal and splenorenal shunts of 8 mm and 11 mm in diameter, respectively. In addition, multiple hepatocellular carcinomas (HCCs) were noted. First, balloon-occluded retrograde transvenous obliteration (BRTO) was performed for the gastrorenal shunt, resulting in the disappearance of the varix, followed by transcatheter arterial chemoembolization (TACE) for HCCs. However, the hepatic encephalopathy worsened after the BRTO and TACE, and the splenorenal shunt enlarged to 18 mm in diameter. Although the shunt was tortuous and had another drainage vein, we completed the embolization for the shunt using metallic coils without any events. The patient's hepatic encephalopathy and hepatic function were ameliorated after embolization for the splenorenal shunt, and the patient was free from hepatic encephalopathy.
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Oclusão com Balão , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Varizes Esofágicas e Gástricas , Encefalopatia Hepática , Hipertensão Portal , Neoplasias Hepáticas , Derivação Portossistêmica Transjugular Intra-Hepática , Pré-Escolar , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/terapia , Humanos , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: Anastomotic leakage (AL) is one of the most devastating complications of rectal cancer surgery. Not only does AL result in reduced quality of life, extended hospitalization and impaired defecatory function, it also has a high local recurrence rate. In this study, we investigated risk factors for AL as it may help to decrease its occurrence and improve patient outcomes. METHODS: This study was a retrospective, single-institution study of rectal cancer patients who underwent elective low anterior resection between April 2002 and February 2018 at Fukushima Medical University Hospital. Patients were divided into two groups according to the presence of AL. Patient-, tumor-, and surgery-related variables were examined using univariate and multivariate analyses. RESULTS: One hundred sixty-one patients, average age 63.5±11.5 years, were enrolled in the study. The overall AL rate was 6.8% (11/161). In the univariate analysis, modified Glasgow Prognostic Score (mGPS)=2 (p=0.003), use of multiple staplers (≥3 firings) for rectal transection (p=0.001) and intraoperative bleeding (≥250 g) were significantly associated with AL incidence. Multivariate analysis identified that mGPS = 2 (odds ratio [OR]: 19.6, 95% confidence interval [CI]: 2.96-125.00, p=0.002) and multiple firings (OR: 18.19, CI: 2.31-111.11, p=0.002) were independent risk factors for AL. CONCLUSION: Higher mGPS score and multiple firings were independent risk factors for AL.