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1.
Comput Med Imaging Graph ; 115: 102384, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759471

RESUMO

BACKGROUND: The KRAS, NRAS, and BRAF genotypes are critical for selecting targeted therapies for patients with metastatic colorectal cancer (mCRC). Here, we aimed to develop a deep learning model that utilizes pathologic whole-slide images (WSIs) to accurately predict the status of KRAS, NRAS, and BRAFV600E. METHODS: 129 patients with left-sided colon cancer and rectal cancer from the Third Affiliated Hospital of Sun Yat-sen University were assigned to the training and testing cohorts. Utilizing three convolutional neural networks (ResNet18, ResNet50, and Inception v3), we extracted 206 pathological features from H&E-stained WSIs, serving as the foundation for constructing specific pathological models. A clinical feature model was then developed, with carcinoembryonic antigen (CEA) identified through comprehensive multiple regression analysis as the key biomarker. Subsequently, these two models were combined to create a clinical-pathological integrated model, resulting in a total of three genetic prediction models. RESULT: 103 patients were evaluated in the training cohort (1782,302 image tiles), while the remaining 26 patients were enrolled in the testing cohort (489,481 image tiles). Compared with the clinical model and the pathology model, the combined model which incorporated CEA levels and pathological signatures, showed increased predictive ability, with an area under the curve (AUC) of 0.96 in the training and an AUC of 0.83 in the testing cohort, accompanied by a high positive predictive value (PPV 0.92). CONCLUSION: The combined model demonstrated a considerable ability to accurately predict the status of KRAS, NRAS, and BRAFV600E in patients with left-sided colorectal cancer, with potential application to assist doctors in developing targeted treatment strategies for mCRC patients, and effectively identifying mutations and eliminating the need for confirmatory genetic testing.


Assuntos
Neoplasias Colorretais , GTP Fosfo-Hidrolases , Genótipo , Proteínas de Membrana , Redes Neurais de Computação , Proteínas Proto-Oncogênicas B-raf , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Aprendizado Profundo , Adulto , Mutação
2.
Nanomedicine (Lond) ; 18(12): 907-921, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37466022

RESUMO

Aim: To investigate the use of nanoparticle (NP)-encapsulated injectable thermosensitive hydrogel-formed nanogel for inhibition of postsurgical residual temozolomide (TMZ)-resistant glioblastoma (GBM) recurrence. Materials & methods: Curcumin (Cur) was coloaded with TMZ into PEG-PLGA NPs, then NPs were further encapsulated into a thermosensitive hydrogel to form a nanogel, which was injected into the resection cavity of the GBM postsurgery. Results: The prepared nanogel displayed excellent drug-loading capacity and long-term drug release. Estimated survival characteristics demonstrated that the nanogel could play a significant role in TMZ-resistant tumor inhibition with low drug-induced toxicity. The originally designed ratio of Cur/TMZ was sustained, making it an effective therapeutic outcome. Conclusion: Cur-combined TMZ-formed nanogels can be a promising candidate for the local inhibition of GBM recurrence.


In this study, the animal model used was rats suffering residual brain tumor after resection. The selected drugs were temozolomide, a first-line chemotherapeutic drug for the clinical treatment of glioma, and curcumin, an extract from the ginger plant. With the use of temozolomide, brain glioma cells gradually develop resistance, resulting in poor efficacy of temozolomide. Therefore, the purpose of this study was to construct a drug-delivery system for temozolomide-resistant brain glioma residual tumor after surgery, namely, a temperature-sensitive gel containing drug-carrying nanopreparations ­ the so-called nanogels. This drug-delivery system can directly deliver drugs to residual tumor cells in situ after surgery. In situ drug-delivery systems can reduce the dose of drugs consumed and increase their potency compared to oral or intravenous administration.


Assuntos
Neoplasias Encefálicas , Curcumina , Glioblastoma , Humanos , Temozolomida/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Nanogéis , Curcumina/farmacologia , Curcumina/uso terapêutico , Linhagem Celular Tumoral , Hidrogéis/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Am J Transl Res ; 15(6): 4390-4398, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37434812

RESUMO

OBJECTIVE: To develop and validate a simple prediction model for postoperative anastomotic leakage (AL) in patients with rectal cancer who underwent Dixon surgery by combining preoperative and intraoperative risk factors. METHODS: We conducted a retrospective study on 358 patients who underwent Dixon surgery for rectal cancer in the Affiliated Hospital of Youjiang Medical University for Nationalities (Guangxi Zhuang Autonomous Region, China). Based on logistic regression, the prediction model of AL after Dixon surgery was established and verified. RESULTS: The incidence of postoperative AL in these patients was 9.2% (33/358). The results of logistic regression analysis showed that age ≥60 years, male, Tumor-Node-Metastasis (TNM) stage ≥IIIa, preoperative obstruction, and the distance from the tumor to the anus ≤7 cm were the risk factors for AL after Dixon surgery, and intraoperative defunctioning stoma was the protective factor for AL after rectal Dixon surgery (all P<0.05). The prediction model construction: Risk score =-4.275 + 0.851 × age + 1.047 × sex + 0.851 × distance + 0.934 × stage + 0.983 × obstruction. The area under receiver operating characteristic curve (ROC-AUC) was 0.762 (95% CI: 0.667-0.856). The best cutoff, sensitivity and specificity were 0.14, 79.60%, and 83.10%, respectively. Hosmer-Lemeshow: X2=6.876, P=0.550. Clinical validation results: the sensitivity, specificity, and accuracy of the model were 82.05%, 80.06%, and 80.25%, respectively. CONCLUSIONS: Both preoperative and intraoperative risk factors were used in the prognostic model. The prediction model established on this basis was well differentiated and highly calibrated, providing a good reference for the clinical prediction model of postoperative AL in rectal cancer patients undergoing Dixon surgery.

4.
BMC Gastroenterol ; 22(1): 461, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384447

RESUMO

BACKGROUND: China is a region with a high incidence of tuberculosis, and the incidence of IBD has also been rising rapidly in recent years. Differentiating Crohn's disease(CD) from intestinal tuberculosis (ITB) has become a very challenging issue. We aimed to develop and assess a diagnostic nomogram to differentiate between CD and ITB to improve the accuracy and practicability of the model. METHODS: A total of 133 patients (CD 90 and ITB 43) were analyzed retrospectively. Univariate and multivariate logistic regression analysis was included to determine the independent predictive factors and establish the regression equation. On this basis, the nomogram prediction model was constructed. The discrimination, calibration and clinical efficiency of the nomogram were assessed using area under the curve(AUC), C-index, calibration curve, decision curve analysis (DCA) and clinical impact curve. RESULTS: T-SPOT positive, cobblestone appearance, comb sign and granuloma were significant predictors in differentiating CD from ITB. Base on the above independent predictors, a diagnostic nomogram was successfully established. The sensitivity, specificity, accuracy of the prediction model are 94.4%, 93.0%, 94.0% respectively. The AUC and the C-index of the prediction model are both 0.988, which suggest that the model had a good discrimination power. The calibration curve indicated a high calibration degree of the prediction model. The DCA and clinical impact curve indicated a good clinical efficiency of the prediction model which could bring clinical benefits. CONCLUSION: A nomogram prediction model for distinguishing CD from ITB was developed and assessed, with high discrimination, calibration and clinical efficiency. It can be used as an accurate and convenient diagnostic tool to distinguish CD from ITB, facilitating clinical decision-making.


Assuntos
Doença de Crohn , Enterite , Peritonite Tuberculosa , Tuberculose Gastrointestinal , Humanos , Doença de Crohn/diagnóstico , Diagnóstico Diferencial , Nomogramas , Estudos Retrospectivos , Tuberculose Gastrointestinal/diagnóstico , Peritonite Tuberculosa/diagnóstico , Enterite/diagnóstico
5.
Molecules ; 27(12)2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35744822

RESUMO

Eucommia ulmoides Oliver (E. ulmoides) is a popular medicinal herb and health supplement in China, Japan, and Korea, and has a variety of pharmaceutical properties. The neuroendocrine-immune (NEI) network is crucial in maintaining homeostasis and physical or psychological functions at a holistic level, consistent with the regulatory theory of natural medicine. This review aims to systematically summarize the chemical compositions, biological roles, and pharmacological properties of E. ulmoides to build a bridge between it and NEI-associated diseases and to provide a perspective for the development of its new clinical applications. After a review of the literature, we found that E. ulmoides has effects on NEI-related diseases including cancer, neurodegenerative disease, hyperlipidemia, osteoporosis, insomnia, hypertension, diabetes mellitus, and obesity. However, clinical studies on E. ulmoides were scarce. In addition, E. ulmoides derivatives are diverse in China, and they are mainly used to enhance immunity, improve hepatic damage, strengthen bones, and lower blood pressure. Through network pharmacological analysis, we uncovered the possibility that E. ulmoides is involved in functional interactions with cancer development, insulin resistance, NAFLD, and various inflammatory pathways associated with NEI diseases. Overall, this review suggests that E. ulmoides has a wide range of applications for NEI-related diseases and provides a direction for its future research and development.


Assuntos
Eucommiaceae , Hipertensão , Doenças Neurodegenerativas , China , Suplementos Nutricionais , Eucommiaceae/química , Humanos
6.
Gastroenterology ; 162(7): 1948-1961.e7, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35202643

RESUMO

BACKGROUND & AIMS: Hepatocellular nodular lesions (HNLs) constitute a heterogeneous group of disorders. Differential diagnosis among these lesions, especially high-grade dysplastic nodules (HGDNs) and well-differentiated hepatocellular carcinoma (WD-HCC), can be challenging, let alone biopsy specimens. We aimed to develop a deep learning system to solve these puzzles, improving the histopathologic diagnosis of HNLs (WD-HCC, HGDN, low-grade DN, focal nodular hyperplasia, hepatocellular adenoma), and background tissues (nodular cirrhosis, normal liver tissue). METHODS: The samples consisting of surgical and biopsy specimens were collected from 6 hospitals. Each specimen was reviewed by 2 to 3 subspecialists. Four deep neural networks (ResNet50, InceptionV3, Xception, and the Ensemble) were used. Their performances were evaluated by confusion matrix, receiver operating characteristic curve, classification map, and heat map. The predictive efficiency of the optimal model was further verified by comparing with that of 9 pathologists. RESULTS: We obtained 213,280 patches from 1115 whole-slide images of 738 patients. An optimal model was finally chosen based on F1 score and area under the curve value, named hepatocellular-nodular artificial intelligence model (HnAIM), with the overall 7-category area under the curve of 0.935 in the independent external validation cohort. For biopsy specimens, the agreement rate with subspecialists' majority opinion was higher for HnAIM than 9 pathologists on both patch level and whole-slide images level. CONCLUSIONS: We first developed a deep learning diagnostic model for HNLs, which performed well and contributed to enhancing the diagnosis rate of early HCC and risk stratification of patients with HNLs. Furthermore, HnAIM had significant advantages in patch-level recognition, with important diagnostic implications for fragmentary or scarce biopsy specimens.


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo , Hiperplasia Nodular Focal do Fígado , Neoplasias Hepáticas , Inteligência Artificial , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia
7.
Front Immunol ; 13: 1029092, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36733399

RESUMO

Cuproptosis, a newly identified form of programmed cell death, plays vital roles in tumorigenesis. However, the interconnectivity of cuproptosis and ferroptosis is poorly understood. In our study, we explored genomic alterations in 1162 lung adenocarcinoma (LUAD) samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) cohort to comprehensively evaluate the cuproptosis regulators. We systematically performed a pancancer genomic analysis by depicting the molecular correlations between the cuproptosis and ferroptosis regulators in 33 cancer types, indicating cross-talk between cuproptosis and ferroptosis regulators at the multiomic level. We successfully identified three distinct clusters based on cuproptosis and ferroptosis regulators, termed CuFeclusters, as well as the three distinct cuproptosis/ferroptosis gene subsets. The tumor microenvironment cell-infiltrating characteristics of three CuFeclusters were highly consistent with the three immune phenotypes of tumors. Furthermore, a CuFescore was constructed and validated to predict the cuproptosis/ferroptosis pathways in individuals and the response to chemotherapeutic drugs and immunotherapy. The CuFescore was significantly associated with the expression of miRNA and the regulation of post-transcription. Thus, our research established an applied scoring scheme, based on the regulators of cuproptosis/ferroptosis to identify LUAD patients who are candidates for immunotherapy and to predict patient sensitivity to chemotherapeutic drugs.


Assuntos
Adenocarcinoma de Pulmão , Apoptose , Ferroptose , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/terapia , Ferroptose/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Prognóstico , Microambiente Tumoral/genética , Cobre
8.
Ann Palliat Med ; 10(7): 7173-7183, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34154359

RESUMO

BACKGROUND: The pathogenesis of gastric cardiac polyps is not yet clear, and there is little research on their clinical and histopathologic characteristics and correlation with gastroesophageal reflux. Early detection and treatment of premalignant lesions in this area can prevent the development of cancer. We aimed to evaluate the clinical and histopathologic characteristics and risk factors of gastric cardiac polyps to improve the current understanding of the disease. METHODS: Patients diagnosed with gastric cardiac polyps at the Third Affiliated Hospital of Sun Yat-Sen University between January 1, 2010, and December 31, 2019, were sought for the study. The exclusion criteria were missing clinical data, insufficient pathological reports, gastric malignancy, or a previous history of gastroduodenal surgery. Ultimately, 140 patients were included in the case group, while 140 patients diagnosed with chronic superficial gastritis from the same 10-year period were identified randomly and selected as a control group. The exclusion criteria for this group were the same as those for the case group. Patients in both groups were matched in age and gender to ensure comparability between the two groups. We evaluated and compared the demographic and clinical data and endoscopic impressions of each group and analyzed the endoscopic, histologic features of gastric cardiac polyps. RESULTS: Gastroesophageal reflux was significantly associated with a higher risk of gastric cardiac polyps after adjustment for other covariates [adjusted odds ratio (OR) =2.809; 95% confidence interval (CI): 1.178-6.697; P=0.020]. Most gastric polyps were single (97.9%), sessile (92.8%), and small polyps with a diameter less than 1 cm (88.6%). Most were located in the gastroesophageal junction region (65.0%) with a smooth surface (56.4%) or surface congestion (30.0%). Hyperplastic (inflammatory) polyps (88.0%) were the most common pathological type and comprised gastric-type foveolar epithelium, squamous epithelium, or admixture of the two epithelia, with a minority showing intestinal metaplasia, mild, or moderate epithelial dysplasia. CONCLUSIONS: Gastroesophageal reflux was associated with a significantly higher incidence of gastric cardiac polyps with a 2.8-fold increased risk. Most gastric cardiac polyps were found to be benign lesions and had a favorable prognosis in the clinic despite their malignant potential.


Assuntos
Refluxo Gastroesofágico , Neoplasias Gástricas , Estudos de Casos e Controles , Junção Esofagogástrica , Refluxo Gastroesofágico/complicações , Humanos , Metaplasia , Neoplasias Gástricas/etiologia
9.
Inflammation ; 44(5): 2044-2053, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34041646

RESUMO

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an independent risk factor for mortality in patients with sepsis. In this study, we attempt to investigate the molecular mechanism of circANKRD36 underlying sepsis-induced ALI/ARDS in vitro. We first detected the altered circRNAs in serums of patients with sepsis-induced ARDS using circRNAs microarray. CircANKRD36 expression in serums and LPS-stimulated RAW264.7 cells was measured using qRT-PCR. CCK-8, cell migration, ELISA, and qRT-PCR were applied to the evaluation of cell biological behavior and inflammation reaction. The results showed that circANKRD36 expression was significantly elevated in serum of patients with sepsis-induced ARDS. Knockdown of circANKRD36 inhibited cell viability and migration and alleviated inflammation of lipopolysaccharide-stimulated (LPS-stimulated) RAW264.7 cells. Bioinformatic analysis demonstrated that circANKRD36 serves as a sponge for miR-330 and ROCK1 was directly targeted by miR-330. Furthermore, knockdown of circANKRD36 repressed ROCK1 expression by targeting miR-330. In short, circANKRD36 knockdown suppressed cell viability and migration of LPS-stimulated RAW264.7 cells in vitro via sponging miR-330, which may provide new ideas for the treatment of sepsis-induced ARDS.


Assuntos
Movimento Celular/fisiologia , Técnicas de Silenciamento de Genes/métodos , Lipopolissacarídeos/toxicidade , MicroRNAs/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Animais , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , MicroRNAs/genética , Proteínas Nucleares/biossíntese , Proteínas Nucleares/genética , Células RAW 264.7 , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/metabolismo
10.
Int J Pediatr Otorhinolaryngol ; 134: 110058, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32388082

RESUMO

INTRODUCTION: Otitis media with effusion (OME) is one of the most common pediatric diseases worldwide. Several studies have analyzed the diversity of the microbiomes found in the middle ear effusions (MEEs) of populations from developed countries. However, no microbiological studies of MEEs from Chinese children with OME have been reported. This study investigated the middle ear and adenoid microbiological profiles of children with OME, and compared the microbial flora of the adenoid between children with and without otitis media. METHODS: MEEs and adenoid swabs were acquired from 15 children undergoing ventilation tube insertion and adenoidectomy. Adenoid swabs from 15 patients with no ear disease were used as controls. Samples were analyzed by 16S rRNA sequencing. Operational taxonomic units (OTUs) abundance information were normalized. Alpha diversity analyses were used to assess the richness and diversity of the microbial community for each sample. Beta diversity analyses were used to determine the inter-group variability between microbiome structure. RESULTS: Based on the mean relative abundance, the MEEs were dominated by Haemophilus (14.75%), Staphylococcus (9.37%) and Halomonas (7.85%), and the bacterial compositions of the adenoids in the OME groups were dominated by Haemophilus (21.87%), Streptococcus (19.65%), and Neisseria (5.8%). The bacterial compositions in the adenoids of the controls were dominated by Haemophilus (15.96%), Streptococcus (13.33%), and Moraxella (12.28%). Alpha diversity analyses showed that there were no significant differences in microbiome richness or diversity between the middle ear effusions (TM) and adenoids (TA) of OME subjects. Adenoid samples from OME patients (TA) and control patients (CA) were also similar. Beta diversity analyses showed that the microbiomes of the adenoids in OME patients were also similar to that of controls. However, the microbiome structure of middle ear effusions was dissimilar to those of the adenoids in OME patients according to beta diversity analyses. CONCLUSIONS: Our results confirmed the microbial diversity of MEEs among Chinese children. However, the dissimilar microbiome composition between samples taken from the surface of the adenoids and from the middle ear effusions challenges the conventional theory that the adenoid serves as a microbial reservoir in children with otitis media with effusion.


Assuntos
Tonsila Faríngea/microbiologia , Orelha Média/microbiologia , Otite Média com Derrame/microbiologia , Tonsila Faríngea/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Orelha Média/patologia , Feminino , Haemophilus/isolamento & purificação , Halomonas/isolamento & purificação , Humanos , Hipertrofia/microbiologia , Masculino , Microbiota , Moraxella/isolamento & purificação , Neisseria/isolamento & purificação , Otite Média com Derrame/cirurgia , Staphylococcus/isolamento & purificação , Streptococcus/isolamento & purificação
11.
Clin Cancer Res ; 26(14): 3760-3770, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32234760

RESUMO

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.


Assuntos
Ilhas de CpG/genética , Metilação de DNA , Recidiva Local de Neoplasia/epidemiologia , Nomogramas , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tomada de Decisão Clínica/métodos , Intervalo Livre de Doença , Proteína 7 com Repetições F-Box-WD/genética , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/prevenção & controle , Seleção de Pacientes , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Valor Preditivo dos Testes , Receptor Notch1/genética , Estudos Retrospectivos , Medição de Risco/métodos
12.
World J Clin Cases ; 8(6): 1116-1128, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32258082

RESUMO

BACKGROUND: Hepatoid carcinoma (HC) is an extremely rare neoplasm that is morphologically similar to hepatocellular carcinoma. HC has been described in various organs; however, HC of the pancreas is extremely rare. To our knowledge, only 38 cases have been reported. We present a case of HC of the pancreas in a 36-year-old male patient. CASE SUMMARY: A 36-year-old cachexic man with no significant past medical history was transferred to our hospital with a history of painless jaundice, elevated blood glucose and significant weight loss. Lab tests showed elevated serum transaminases, bilirubin and alpha-fetoprotein levels. Magnetic resonance imaging of the upper abdomen showed a diffusely enlarged pancreas, appearing "sausage-shaped". Magnetic resonance cholangiopancreatography showed upstream ductal dilation secondary to stricture of the main pancreatic duct and the common bile duct, which were not visible. Immunohistochemistry of biopsied tissue from a percutaneous pancreatic biopsy showed tumor cell positivity for HepPar1, polyclonal carcinoembryonic antigen and CK19, suggestive of HC of the pancreas. The characteristics of 39 patients with HC of the pancreas were reviewed. CONCLUSION: HC of the pancreas is more prevalent in males, and patients have a median age of 57 years. It is most commonly asymptomatic or presents as abdominal back pain, and the pancreatic tail is the most common location. At the time of diagnosis, liver metastasis is often present.

13.
Leukemia ; 34(9): 2392-2404, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32080345

RESUMO

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Transcriptoma , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Estudos Retrospectivos
14.
Leukemia ; 33(10): 2454-2465, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30953029

RESUMO

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.


Assuntos
MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Indução de Remissão/métodos
15.
Endosc Int Open ; 7(4): E615-E620, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30993166

RESUMO

Background and study aims Gastrointestinal ulcers are responsible for a wide spectrum of diseases. Infection, drug-induced enteritis, malignancy, vasculitis and Inflammatory bowel disease are the most common causes; their clinical expression often varies according to the site and severity of intestinal involvement. We report on a 68-year-old male presenting with dyspepsia and melena and multiple gastrointestinal ulcers on endoscopy. We could not establish diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) despite multiple biopsies taken on several endoscopic sessions, and cytomegalovirus (CMV) infection was documented by presence of inclusion bodies on pathology. The immunohistochemical study showed a mixture of B lymphocytes and predominantly T lymphocytes, negative for cluster of differentiation (CD)7. Southern blot gene rearrangement was positive for T-cell receptor beta. Our patient eventually expired from a massive gastrointestinal hemorrhage following four cycles of chemotherapy. We wish to emphasize that a CMV infection, as a comorbidity, can potentially mask and delay diagnosis of PTCL-NOS, especially in cases with aberrant immunophenotype presentation.

16.
Eur Arch Otorhinolaryngol ; 276(5): 1291-1299, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30747317

RESUMO

PURPOSE: Our study investigated correlations between clinical characteristics, particularly hearing recovery, interval time between onset and three-dimensional fluid attenuation inversion recovery magnetic resonance imaging (3D-FLAIR MRI), and the signal intensity of post-contrast 3D-FLAIR MRI in patients with idiopathic sudden sensorineural hearing loss (SSNHL). METHODS: The study enrolled 100 SSNHL patients. The signal intensities and asymmetry ratios of the inner ear structures, including the cochleae, vestibules and vestibulocochlear nerve, were evaluated and calculated. The relationships between the clinical characteristics and MRI findings were assessed. RESULTS: After intravenous gadolinium (Gd) injection, 3D-FLAIR revealed high signal intensities in 65 patients. The corrected asymmetry ratios of cochlea correlated closely with interval time between onset and MRI. The asymmetry ratios of the inner ear structures were significantly lower in patients with final complete to partial hearing recovery. The corrected asymmetry ratios of the inner ear structures correlated with initial/final pure tone audiometry (PTA) and hearing recovery in the affected ear. Notably, it was shown that the corrected asymmetry ratios identified a poor prognosis for hearing recovery, with a sensitivity and specificity of 67.9% and 75.0% in the cochlea, 83.3% and 75.0% in the vestibule, and 52.4% and 81.2% in the vestibulocochlear nerve, respectively. CONCLUSIONS: Post-contrast 3D-FLAIR after intravenous Gd injection in SSNHL can be used to assess the permeability of the blood-labyrinth and blood-nerve barriers. The asymmetry ratios of the inner ear structures may identify patients with poor prognosis for hearing recovery. Signal characteristics are closely related to interval time between onset and MRI.


Assuntos
Perda Auditiva Neurossensorial/diagnóstico por imagem , Perda Auditiva Súbita/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Audiometria de Tons Puros , Cóclea , Meios de Contraste/administração & dosagem , Feminino , Gadolínio/administração & dosagem , Humanos , Imageamento Tridimensional , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Vestíbulo do Labirinto , Nervo Vestibulococlear
17.
Clin Anat ; 32(3): 439-445, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30664277

RESUMO

Urogenital complications due to pelvic autonomic nerve damage frequently occur following rectal surgery. We investigated whether total mesorectal excision (TME) with preservation of the Denonvilliers' fascia (DVF) can effectively prevent the removal of pelvic autonomic nerves through microscopy. Twenty consecutive male patients with mid-low rectal cancer who received TME with preservation or resection of the Denonvilliers' fascia (P and R groups, respectively) were included. Serial transverse sections from surgical specimens were studied histologically. Nerve fibers at the surfaces of the mesorectum were counted. Clinical correlation between the amount of nerve fibers removed and post-operative sexual function was analyzed. Nerve fibers closely localized to the DVF in the R group displaying rich erectile activity (positive anti-nNOS immunostaining). At the anterior surface of the mesorectum, the mean numbers of nNOS-positive nerve fibers per specimen in the P group were significantly lower than the R group (3.0 ± 1.8 vs. 5.0 ± 2.3, P < 0.05). Compared to the R group, patients in the P group had higher IIEF scores and better erectile function at 3 and 6 months post-operatively. The DVF is a key risk zone for pelvic denervation during laparoscopic TME. Preservation of the DVF can prevent the removal of autonomic nerves and protect post-operative erectile function. Clin. Anat. 32:439-445, 2019. © 2019 Wiley Periodicals, Inc.


Assuntos
Fáscia/inervação , Neoplasias Retais/cirurgia , Reto/inervação , Adulto , Idoso , Vias Autônomas/cirurgia , Disfunção Erétil/etiologia , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Tratamentos com Preservação do Órgão/métodos , Pelve/inervação , Períneo/inervação , Reto/cirurgia
18.
Zhongguo Zhong Yao Za Zhi ; 43(22): 4397-4403, 2018 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-30593230

RESUMO

The plants of Bletilla are one of the groups in Orchidaceae with the highest economic value. As the traditional Chinese medicinal material, Bletillae Rhizoma exhibits excellent efficacy in hemostatic, antibiosis, detumescent, anticancer activities and regenerating tissue to heal wound, which has great development potential. However, Bletillae Rhizoma is mainly collected from wild resources. At present, the quantity of wild resources of Bletilla plants has sharply decreased and is far from meeting the needs. Resource appraisal and breeding and cultivation of excellent germplasms of Bletilla plants are important for scientific utilization of the resources of the genus. This paper reviewed the following researches of Chinese Bletilla resources: species and distribution, genetic diversity, active ingredient evaluation, breeding, as well as seeding production and cultivation techniques. Suggestions were also provided in further researches on the resources evaluation, sustainable development and efficient utilization of Chinese Bletilla plants.


Assuntos
Medicamentos de Ervas Chinesas , Hemostáticos , Orchidaceae , Plantas Medicinais , Melhoramento Vegetal , Rizoma
19.
J BUON ; 23(3): 659-664, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30003734

RESUMO

PURPOSE: To observe the infection rates of Helicobacter pylori (HP) in bile reflux gastritis (BRG) and gastric cancer and the clinical significance of HP eradication in BRG and gastric cancer patients complicated with HP. METHODS: 248 patients diagnosed with BRG and gastric cancer via gastroscopy were enrolled in this study. HP detection and infection rates of HP were evaluated. Then, BRG and gastric cancer patients complicated with HP were randomly divided into BRG group 1, BRG group 2, gastric cancer group 1 and gastric cancer group 2. BRG group 1 and gastric cancer group 1 were treated with conventional anti-inflammatory drugs for 10 days, and BRG group 2 and gastric cancer group 2 were treated with anti-HP drugs in addition to conventional anti-inflammatory drugs. One month after drug withdrawal, the infection rates of HP in each group were evaluated, and prognostic follow-up was performed to record the post-therapy patient conditions. RESULTS: HP infection rate was 35.8% (57/159) in the BRG group and 73.0% (65/89) in the gastric cancer group, with statistically significant difference (p<0.01). In patients treated with anti-HP drugs had the HP infection rate effectively reduced. The treatment effective rates of patients with BRG and gastric cancer complicated with HP infection after eradication of HP were 82.8 and 68.8%, respectively, while those of patients with non-eradicated HP were only 46.4 and 37.5 %, respectively. The differences between the two groups were statistically significant (p<0.05). CONCLUSION: HP is directly and closely related to the occurrence of gastric diseases, HP infection rate in patients with gastric cancer is significantly higher than that in patients with BRG, and the treatment of HP can effectively improve the rehabilitation rate in patients with gastric diseases.


Assuntos
Refluxo Biliar/microbiologia , Gastrite/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Neoplasias Gástricas/microbiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia
20.
Cancer Cell Int ; 18: 3, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29308052

RESUMO

BACKGROUND: Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied. METHODS: We investigated the clinicopathological features of PMLP and the significance of CRMP4 methylation in PMLP. The clinical data and diagnosis information of 10 patients with PMLP were retrospectively analyzed. The CRMP4 promotor methylation level in paraffin-embedded tissues of the 10 patients with PMLP were determined and then compared to limited prostate cancer (LPCa) and its negative lymph node tissue [LPCa-LN (-) (10 cases)] and also to metastatic prostate adenocarcinoma (mPCa) and its positive lymph node tissue [mPCa-LN (+) (10 cases)]. Methylation of the CRMP4 promotor in each group was analyzed statistically. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CRMP4 methylation in PMLP. RESULTS: The average methylation value of CRMP4 in 10 PMLP patients, 20 cases of prostate adenocarcinoma tissue, 10 cases LPCa-LN (-) and 10 cases mPCa-LN (+) were 42.3, 30.6, 6.7 and 20.3%, respectively. A Kruskal-Wallis test showed that the difference of CRMP4 methylation was significant (X2 = 38.0, P < 0.001). An ROC curve analysis found that CRMP4 methylation > 40.9% could diagnose PMLP. This method had 90% sensitivity and 95% specificity under conditions of CRMP4 methylation > 40.9%. The area under the curve (AUC) was 0.957. CONCLUSIONS: Methylation of the CRMP4 gene was significantly increased in PMLP, and it is expected to become a new predictor for PMLP.

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