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1.
Gastroenterology ; 162(3): 952-956, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35094786

RESUMO

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update Commentary is to review the available evidence and provide expert advice regarding the approach to using noninvasive colorectal cancer (CRC) screening options, including evidence for their effectiveness, selection of individuals for whom these tests are appropriate, implications of a positive non-colonoscopy screening test, and opportunities to enhance the quality of noninvasive CRC screening programs. This Clinical Practice Update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology. This expert commentary reflects recently published studies in this field, as well as the experiences of the authors who are gastroenterologists with high-level expertise in CRC screening and prevention.


Assuntos
Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , DNA/análise , Detecção Precoce de Câncer/métodos , Sangue Oculto , Adenoma/sangue , Adenoma/urina , Neoplasias Colorretais/sangue , Neoplasias Colorretais/urina , DNA/sangue , Metilação de DNA , Fezes/química , Humanos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Medição de Risco , Septinas/genética
2.
Cancer Epidemiol Biomarkers Prev ; 31(1): 293-295, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34758968

RESUMO

BACKGROUND: Sex hormones have been implicated in the etiology of colorectal neoplasia in women for over 40 years, but there has been very little investigation of the role of these hormones in men. METHODS: Using data from an adenoma chemoprevention trial, we conducted a secondary analysis to examine serum hormone levels [testosterone, androstenedione, DHEA sulfate (DHEAS), and sex hormone binding globulin (SHBG)] and risk of colorectal precursors in 925 men. Multivariable logistic regression models were fit to evaluate adjusted associations between hormone levels and risk of "low-risk" (single tubular adenoma < 1 cm) and "high-risk" lesions (advanced adenoma or sessile serrated adenoma or right-sided serrated polyp or >2 adenomas of any size). RESULTS: Overall, levels of free testosterone, total testosterone, androstenedione, DHEAS, or SHBG were not associated with either "low-risk" or "high-risk" early precursor lesions in the colorectum. CONCLUSIONS: These findings do not support the role of sex hormones in early colorectal neoplasia among men. IMPACT: This large prospective study address a missing gap in knowledge by providing information on the role of sex hormones in colorectal neoplasia in males.


Assuntos
Adenoma/sangue , Pólipos do Colo/sangue , Neoplasias Colorretais/sangue , Hormônios Esteroides Gonadais/sangue , Idoso , California , Estudos de Casos e Controles , Colonoscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
3.
Front Endocrinol (Lausanne) ; 12: 743052, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867787

RESUMO

Purpose: Determine predictive factors for long-term remission of acromegaly after transsphenoidal resection of growth hormone (GH)-secreting pituitary adenomas. Methods: We identified 94 patients who had undergone transsphenoidal resection of GH-secreting pituitary adenomas for treatment of acromegaly at the USC Pituitary Center from 1999-2019 to determine the predictive value of postoperative endocrine lab values. Results: Patients underwent direct endoscopic endonasal (60%), microscopic transsphenoidal (38%), and extended endoscopic approaches (2%). The cohort was 63% female and 37% male, with average age of 48.9 years. Patients presented with acral enlargement (72, 77%), macroglossia (40, 43%), excessive sweating (39, 42%), prognathism (38, 40%) and frontal bossing (35, 37%). Seventy-five (80%) were macroadenomas and 19 (20%) were microadenomas. Cavernous sinus invasion was present in 45%. Available immunohistochemical data demonstrated GH staining in 88 (94%) and prolactin in 44 (47%). Available postoperative MRI demonstrated gross total resection in 63% of patients and subtotal resection in 37%. Most patients (66%) exhibited hormonal remission at 12 weeks postoperatively. Receiver operating characteristic (ROC) curves demonstrated postoperative day 1 (POD1) GH levels ≥1.55ng/mL predicted failure to remit from surgical resection alone (59% specificity, 75% sensitivity). A second ROC curve showed decrease in corrected insulin-like growth factor-1 (IGF-1) levels of at least 37% prognosticated biochemical control (90% sensitivity, 80% specificity). Conclusion: POD1 GH and short-term postoperative IGF-1 levels can be used to successfully predict immediate and long-term hormonal remission respectively. A POD1 GH cutoff can identify patients likely to require adjuvant therapy to emphasize clinical follow-up.


Assuntos
Acromegalia/sangue , Acromegalia/cirurgia , Adenoma/sangue , Adenoma/cirurgia , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/cirurgia , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Acromegalia/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Adulto , Idoso , Estudos de Coortes , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Curva ROC , Valores de Referência , Estudos Retrospectivos , Resultado do Tratamento
4.
Medicine (Baltimore) ; 100(52): e28414, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34967378

RESUMO

RATIONALE: Syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) is a rare cause of hyperthyroidism. Thyroid-stimulating hormone (TSH) levels are usually normal or high, and triiodothyronine (FT3) and free thyroxine (FT4) levels are usually high in subjects with SITSH. PATIENT CONCERN: A 37-year-old woman had experienced galactorrhea and menstrual disorder for a couple of years before. She had undergone infertility treatment in 1 year before, hyperthyroidism was detected and she was referred to our institution. DIAGNOSIS: She was suspected of having SITSH and was hospitalized at our institution for further examination. The data on admission were as follows: FT3, 4.62 pg/mL; FT4, 1.86 ng/dL; TSH, 2.55 µIU/mL. Although both FT3 and FT4 levels were high, TSH levels were not suppressed, which is compatible with SITSH. In addition, in brain contrast-enhanced magnetic resonance imaging, nodular lesions were observed in the pituitary gland with a diameter of approximately 10 mm. In the thyrotropin-releasing hormone load test, TSH did not increase at all, which was also compatible with TSH-secreting pituitary adenoma. In the octreotide load test, the TSH levels were suppressed. Based on these findings, we diagnosed this subject as SITSH. INTERVENTIONS: Hardy surgery was performed after the final diagnosis. In TSH staining of the resected pituitary adenoma, many TSH-producing cells were observed. These findings further confirmed the diagnosis of pituitary adenoma producing TSH. OUTCOMES: Approximately 2 months after the operation, TSH, FT3, and FT4 levels were normalized. Approximately 3 months after the operation, she became pregnant without any difficulty. LESSONS: We should consider the possibility of SITSH in subjects with galactorrhea, menstrual disorders, or infertility. In addition, we should recognize that it is very important to repeatedly examine thyroid function in subjects with galactorrhea, menstrual disorder, or infertility.


Assuntos
Adenoma , Amenorreia , Galactorreia , Hipertireoidismo , Infertilidade , Neoplasias Hipofisárias , Tireotropina , Adenoma/sangue , Adenoma/diagnóstico , Adenoma/metabolismo , Adenoma/cirurgia , Adulto , Amenorreia/etiologia , Amenorreia/cirurgia , Feminino , Galactorreia/etiologia , Galactorreia/cirurgia , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/etiologia , Hipertireoidismo/metabolismo , Hipertireoidismo/cirurgia , Infertilidade/etiologia , Infertilidade/metabolismo , Infertilidade/cirurgia , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgia , Síndrome , Tireotropina/sangue , Tireotropina/metabolismo
6.
Front Endocrinol (Lausanne) ; 12: 782050, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925241

RESUMO

Objective: To assess the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperparathyroidism (PHPT), and to investigate whether MWA can improve the bone turnover and renal function. Methods: A total of 20 consecutive PHPT patients with 21 parathyroid lesions treated with MWA in our center from May 2019 to March 2021 were recruited in this study. Serum parathyroid hormone (PTH), calcium and phosphorus levels before MWA and at 20 minutes, 4 hours, 1 day, 3 months, 6 months and 12 months after MWA were measured. Bone turnover biomarkers, renal function and lesion volume with volume reduction rate (VRR) before MWA and at the last follow-up were compared. Any complication related with MWA was evaluated. The technical and clinical success rates of MWA in the treatment of PHPT were calculated. Clinical success was defined as normal serum PTH and calcium without PHPT-associated manifestations at more than 6 months after ablation. Technical success was defined as complete ablation indicated by immediate postoperative contrast-enhanced ultrasound. Results: The serum PTH, calcium and phosphorus levels at their respective follow-up time points dropped significantly after MWA (P <0.05). The volume of parathyroid lesions at the final examination was significantly reduced, compared with pre-ablation volume (P <0.001), with a median VRR reaching 89%. The technical and clinical success rates were 100% and 63.6%, respectively. Substantial changes of bone turnover biomarkers were observed before and after MWA (P <0.05), but the differences in renal function were not statistically significant. No major complications were reported in all cases. Pre-MWA serum PTH, lesion volume, maximum diameter of lesion and ablation time were significantly different between patients with successful and failed MWA. Conclusions: PHPT can be effectively and safely treated by ultrasound-guided MWA, as proven by drop in serum PTH and reduction in the volume of parathyroid adenomas. Besides, MWA can impede bone remodeling to suppress hyperparathyroidism in the condition of PHPT.


Assuntos
Remodelação Óssea/fisiologia , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/cirurgia , Micro-Ondas/uso terapêutico , Ablação por Radiofrequência/métodos , Ultrassonografia de Intervenção/métodos , Adenoma/sangue , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Adulto , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia
7.
Nutrients ; 13(11)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34836131

RESUMO

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33-0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33-0.94)); and of a large adenoma with higher PGE2 ((0.52 (0.31-0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.


Assuntos
Adenoma/prevenção & controle , Ácido Araquidônico/sangue , Neoplasias Colorretais/prevenção & controle , Oxilipinas/sangue , Selênio/administração & dosagem , Adenoma/sangue , Idoso , Celecoxib/administração & dosagem , Neoplasias Colorretais/sangue , Suplementos Nutricionais , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
Front Endocrinol (Lausanne) ; 12: 774519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803930

RESUMO

Background: Diabetes is a risk factor for colorectal neoplasms. The association between the level of glycosylated hemoglobin (HbA1c) and the risk of colorectal adenomas (CRAs) in non-diabetic adults needs to be investigated. Methods: A cross-sectional study was performed on non-diabetic adults with normal HbA1c level who underwent colonoscopy between January 2010 and December 2016 during health check-ups in our hospital in China. The association between HbA1c level and CRAs was assessed by multiple logistic regression models stratified by age group (<40, ≥40 and <50, and ≥50 years old). The age group-specified thresholds for HbA1c on elevated risk of CRAs were estimated using the piecewise logistic regression. Results: Among the 2,764 subjects, 445 (16.1%) had CRA. The prevalence of CRA varied across the three age groups. A higher HbA1c level was found to be significantly associated with increased CRA risk in the 40-50 years group (odds ratio [OR]=1.70, 95% confidence interval [CI] 1.04-2.78, p=0.035) after adjusting for other related factors, while this association was borderline significant among the 50 years and older group (OR=1.57, 95% CI 0.97-2.54, p=0.067). Based on the piecewise logistic regression analysis results, the thresholds for HbA1c on elevated risk of CRA were 5.44% for the 40-50 years group and 4.81% for the 50 years and older group, respectively. Conclusions: Higher levels of HbA1c, even within the normal range, were associated with elevated CRA risk among non-diabetic adults. The threshold effects of HbA1c on the risk of CRA varied across different age groups, and early screening colonoscopy might be needed for individuals in their 40s and with HbA1c levels ≥5.44%.


Assuntos
Adenoma/diagnóstico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Hemoglobina A Glicada/metabolismo , Adenoma/sangue , Adenoma/epidemiologia , Adulto , Fatores Etários , Idade de Início , China/epidemiologia , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Estudos Transversais , Diabetes Mellitus , Feminino , Hemoglobina A Glicada/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
9.
Anticancer Res ; 41(11): 5517-5525, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732422

RESUMO

BACKGROUND/AIM: The present study compared the accuracy of visually analyzed (VA) and automatically analyzed (AA) ColonView (CV) quick test; a new-generation fecal immunochemical test (FIT) for hemoglobin (Hb) and hemoglobin/haptoglobin (Hb/Hp) (Biohit Oyj, Helsinki, Finland) in subjects participating in colorectal neoplasia (CRN) detection in Brazil. A traditional guaiac-based fecal occult blood test (gFOBT) test (HemoccultSENSA) was used as a reference. PATIENTS AND METHODS: A cohort of 509 colonoscopy-referral patients were asked to collect three consecutive fecal samples, to be analyzed by both CV and SENSA. RESULTS: In ROC analysis for the AA reading, the optimal cut-off value for CV Hb was ≥8.0912 and that for CV Hb/Hp was ≥1.8983. With these cut-offs, the sensitivity (Se), specificity (Sp), and efficiency of CV AA in detecting colorectal adenoma (CRA) were: 64.2%/78.6%, 53.4%/35.3%, and 58.6%/56.5%, for Hb and Hb/Hp, respectively. In the HSROC analysis, the AUC values for i) VA and ii) AA modes were as follows: i) AUC=0.551 (95%CI=0.500-0.602), ii) AUC=0.606 (95%CI=0.550-0.662). The difference between these AUC values was statistically significant (p=0.0160). CONCLUSION: The present study confirms the previous results on the applicability of the ColonView quick test in CRN screening. Of the two optional reading modes, the AA reading showed significantly better diagnostic accuracy as compared to the VA reading (or SENSA), in detecting the CRA endpoint in colonoscopy-referral patients.


Assuntos
Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Haptoglobinas/análise , Hemoglobinas/análise , Imuno-Histoquímica , Sangue Oculto , Adenoma/sangue , Adenoma/patologia , Automação Laboratorial , Brasil , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Humanos , Valor Preditivo dos Testes , Encaminhamento e Consulta , Reprodutibilidade dos Testes
10.
Front Endocrinol (Lausanne) ; 12: 748725, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34690934

RESUMO

Objective: No accurate predictive models were identified for hormonal prognosis in non-functioning pituitary adenoma (NFPA). This study aimed to develop machine learning (ML) models to facilitate the prognostic assessment of pituitary hormonal outcomes after surgery. Methods: A total of 215 male patients with NFPA, who underwent surgery in four medical centers from 2015 to 2021, were retrospectively reviewed. The data were pooled after heterogeneity assessment, and they were randomly divided into training and testing sets (172:43). Six ML models and logistic regression models were developed using six anterior pituitary hormones. Results: Only thyroid-stimulating hormone (p < 0.001), follicle-stimulating hormone (p < 0.001), and prolactin (PRL; p < 0.001) decreased significantly following surgery, whereas growth hormone (GH) (p < 0.001) increased significantly. The postoperative GH (p = 0.07) levels were slightly higher in patients with gross total resection, but the PRL (p = 0.03) level was significantly lower than that in patients with subtotal resection. The optimal model achieved area-under-the-receiver-operating-characteristic-curve values of 0.82, 0.74, and 0.85 in predicting hormonal hypofunction, new deficiency, and hormonal recovery following surgery, respectively. According to feature importance analyses, the preoperative levels of the same type and other hormones were all important in predicting postoperative individual hormonal hypofunction. Conclusion: Fluctuation in anterior pituitary hormones varies with increases and decreases because of transsphenoidal surgery. The ML models could accurately predict postoperative pituitary outcomes based on preoperative anterior pituitary hormones in NFPA.


Assuntos
Adenoma/cirurgia , Hipopituitarismo/etiologia , Aprendizado de Máquina , Procedimentos Neurocirúrgicos/efeitos adversos , Hormônios Adeno-Hipofisários/sangue , Neoplasias Hipofisárias/cirurgia , Adenoma/sangue , Adulto , Humanos , Hipopituitarismo/sangue , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/sangue , Prognóstico , Estudos Retrospectivos
11.
J Clin Lab Anal ; 35(11): e23988, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34651346

RESUMO

BACKGROUND/AIM: This study aimed to investigate the clinical significance of changes in vitamin D [25(OH)D] levels and vitamin D receptor (VDR) mRNA expression in colorectal adenoma development. METHODS: Plasma concentrations of 25(OH)D and mRNA expression of VDR in tissues were determined by enzyme-linked immunosorbent assay (ELISA) and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, the concentration of plasma 25(OH)D and levels of VDR mRNA in tissues were compared among healthy individuals and adenoma and adenocarcinoma patients. RESULTS: Vitamin D receptor expression in colorectal adenocarcinoma tissues was significantly lower than that in para-cancerous tissues that were >5 cm away from malignant tumor sites (p < 0.01). The level of VDR expression in normal colorectal tissues from healthy individuals was significantly higher than that in colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the VDR expression was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.106). The concentration of 25(OH)D in healthy individuals was significantly higher than that in patients with colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the concentration of 25(OH)D was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.489). A low concentration of 25(OH)D was considered a risk factor for colorectal adenoma and colorectal adenocarcinoma, with odds ratios of 4.875 and 2.925, respectively. CONCLUSIONS: The 25(OH)D levels and VDR mRNA expression might be associated with the development of colorectal adenoma and its progression to adenocarcinoma.


Assuntos
Neoplasias Colorretais , Receptores de Calcitriol , Vitamina D/sangue , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenoma/sangue , Adenoma/genética , Adenoma/metabolismo , Colo/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue , RNA Mensageiro/genética , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo
12.
J Hematol Oncol ; 14(1): 175, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702327

RESUMO

Previous studies on liquid biopsy-based early detection of advanced colorectal adenoma (advCRA) or adenocarcinoma (CRC) were limited by low sensitivity. We performed a prospective study to establish an integrated model using fragmentomic profiles of plasma cell-free DNA (cfDNA) for accurately and cost-effectively detecting early-stage CRC and advCRA. The training cohort enrolled 310 participants, including 149 early-stage CRC patients, 46 advCRA patients and 115 healthy controls. Plasma cfDNA samples were prepared for whole-genome sequencing. An ensemble stacked model differentiating healthy controls from advCRA/early-stage CRC patients was trained using five machine learning models and five cfDNA fragmentomic features based on the training cohort. The model was subsequently validated using an independent test cohort (N = 311; including 149 early-stage CRC, 46 advCRA and 116 healthy controls). Our model showed an area under the curve (AUC) of 0.988 for differentiating advCRA/early-stage CRC patients from healthy individuals in an independent test cohort. The model performed even better for identifying early-stage CRC (AUC 0.990) compared to advCRA (AUC 0.982). At 94.8% specificity, the sensitivities for detecting advCRA and early-stage CRC reached 95.7% and 98.0% (0: 94.1%; I: 98.5%), respectively. Promisingly, the detection sensitivity has reached 100% and 97.6% in early-stage CRC patients with negative fecal occult or CEA blood test results, respectively. Finally, our model maintained promising performances (AUC: 0.982, 94.4% sensitivity at 94.8% specificity) even when sequencing depth was down-sampled to 1X. Our integrated predictive model demonstrated an unprecedented detection sensitivity for advCRA and early-stage CRC, shedding light on more accurate noninvasive CRC screening in clinical practice.


Assuntos
Adenocarcinoma/diagnóstico , Adenoma/diagnóstico , Ácidos Nucleicos Livres/genética , Neoplasias Colorretais/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenoma/sangue , Adenoma/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Detecção Precoce de Câncer , Humanos , Estudos Prospectivos
13.
Cell Death Dis ; 12(10): 897, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599156

RESUMO

The epithelial signaling pathways involved in damage and regeneration, and neoplastic transformation are known to be similar. We noted upregulation of argininosuccinate synthetase (ASS1) in hyperproliferative intestinal epithelium. Since ASS1 leads to de novo synthesis of arginine, an important amino acid for the growth of intestinal epithelial cells, its upregulation can contribute to epithelial proliferation necessary to be sustained during oncogenic transformation and regeneration. Here we investigated the function of ASS1 in the gut epithelium during tissue regeneration and tumorigenesis, using intestinal epithelial conditional Ass1 knockout mice and organoids, and tissue specimens from colorectal cancer patients. We demonstrate that ASS1 is strongly expressed in the regenerating and Apc-mutated intestinal epithelium. Furthermore, we observe an arrest in amino acid flux of the urea cycle, which leads to an accumulation of intracellular arginine. However, loss of epithelial Ass1 does not lead to a reduction in proliferation or increase in apoptosis in vivo, also in mice fed an arginine-free diet. Epithelial loss of Ass1 seems to be compensated by altered arginine metabolism in other cell types and the liver.


Assuntos
Argininossuccinato Sintase/metabolismo , Carcinogênese/patologia , Células Epiteliais/enzimologia , Intestinos/patologia , Regeneração , Adenoma/sangue , Adenoma/genética , Adenoma/patologia , Polipose Adenomatosa do Colo/sangue , Polipose Adenomatosa do Colo/genética , Aminoácidos/metabolismo , Animais , Arginina/metabolismo , Argininossuccinato Sintase/genética , Linhagem Celular Tumoral , Dieta , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Mucosa Intestinal/patologia , Fígado/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação/genética , Organoides/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/genética
14.
Horm Metab Res ; 53(8): 512-519, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34384108

RESUMO

The majority of incidentally discovered adrenal tumors are later characterized as non-producing adrenocortical adenomas (NPA). We asked whether laboratory abnormalities in parameters that reflect glucocorticoid action can be found in patients with NPA despite their nature of being clinically unapparent. Since glucocorticoids are potent immunosuppressants we studied blood counts and differential blood counts along with corticotropin and dehydroepiandrostenedione sulfate (DHEAS) blood concentrations, as well as cortisol values before and after an overnight 1 mg dexamethasone suppression test. We compared the results of normal individuals, of patients with adrenal adenomas and normal hormone profiles and with subclinical autonomous glucocorticoid hypersecretion, as well as overt cortisol excess. We found that almost all indices of the blood counts were significantly different between the patients groups. In particular, patients with adrenal non-producing adenomas already showed signs of glucocorticoid excess, including relative lymphocytopenia, lowered DHEAS, and ACTH concentrations than control individuals. We also found that the extent of lymphocytopenia correlated with the concentrations of DHEAS and ACTH, and DHEAS correlated well with ACTH. We conclude that the basal ACTH and DHEAS values along with the differential blood counts give good information on the extent of glucocorticoid excess and that silent adrenal adenomas seem to oversecrete glucocorticoids at concentrations that already alter these parameters.


Assuntos
Adenoma/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Sulfato de Desidroepiandrosterona/sangue , Glucocorticoides/metabolismo , Adenoma/sangue , Neoplasias das Glândulas Suprarrenais/sangue , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Contagem de Células Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
PLoS One ; 16(7): e0254505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242355

RESUMO

BACKGROUND AND AIMS: Resting heart rate is an independent predictor of colorectal cancer (CRC) development and CRC-related mortality. However, little is known about the relationship between resting heart rate and colorectal adenoma development. We aimed to investigate this association in a population who underwent screening colonoscopy. METHODS: Among 39,021 patients who underwent both electrocardiogram and screening colonoscopy during routine health examinations at the Seoul National University Bundang Hospital, Health Promotion Center, Korea from January 2014 to July 2019, 1,344 patients had advanced adenoma. We performed 1:1 propensity score (PS) matching to establish a control group that mitigated the confounding effects of age and sex. We performed multivariate logistic regression analyses to identify the independent risk factors of advanced adenoma development. RESULTS: Resting heart rate was significantly higher in the advanced adenoma group than in the control group. The prevalence of advanced polyp increased across the quartiles of resting heart rate. Patients with higher resting heart rates were more likely to be older, smokers, and have increased blood pressure and DM and less likely to engage in active exercises than those with lower resting heart rates. Patients with higher resting heart rates had higher serum glucose, triglyceride, hemoglobin A1C, and insulin levels and lower high-density lipoprotein cholesterol levels. Patients with resting heart rate in the highest quartile (≥71 bpm) still showed significantly increased odds ratio (OR) of advanced adenoma development (OR: 1.379, 95% confidence interval: 1.099-1.731, p = 0.006). CONCLUSIONS: High resting heart rate was a meaningful independent risk factor of advanced adenoma development.


Assuntos
Adenoma/fisiopatologia , Neoplasias Colorretais/fisiopatologia , Descanso/fisiologia , Adenoma/sangue , Idoso , Pólipos do Colo/sangue , Pólipos do Colo/fisiopatologia , Colonoscopia , Neoplasias Colorretais/sangue , Frequência Cardíaca , Humanos , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Triglicerídeos/sangue
16.
BMC Cardiovasc Disord ; 21(1): 350, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294029

RESUMO

BACKGROUND: Primary aldosteronism (PA), as a cause of secondary hypertension, can cause more serious cardiovascular damage than essential hypertension. The aldosterone-to-renin ratio (ARR) is recommended as the most reliable screening method for PA, but ARR screening is often influenced by many factors. PA cannot be easily excluded when negative ARR. CASE PRESENTATION: We report the case of a 45-year-old Chinese man with resistant hypertension. Three years ago, he underwent a comprehensive screening for secondary hypertension, including the ARR, and the result was negative. After that, the patient's blood pressure was still poorly controlled with four kinds of antihypertensive drugs, the target organ damage of hypertension progressed, and hypokalaemia was difficult to correct. When the patient was hospitalized again for comprehensive examination, we found that aldosterone levels had significantly increased, although the ARR was negative. An inhibitory test with saline was further carried out, and the results suggested that aldosterone was not inhibited; therefore, PA was diagnosed. We performed a unilateral adenoma resection for this patient, and spironolactone was continued to control blood pressure. After the operation, blood pressure is well controlled, and hypokalaemia is corrected. CONCLUSION: When the ARR is negative, PA cannot be easily excluded. Comprehensive analysis and diagnosis should be based on the medication and clinical conditions of patients.


Assuntos
Adenoma/complicações , Neoplasias das Glândulas Suprarrenais/complicações , Aldosterona/sangue , Hiperaldosteronismo/sangue , Hipertensão/etiologia , Renina/sangue , Adenoma/sangue , Adenoma/diagnóstico , Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/etiologia , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
17.
J Pediatr Endocrinol Metab ; 34(11): 1469-1473, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34284528

RESUMO

OBJECTIVES: To describe the case of a 12-year-old girl with a rare plurihormonal pituitary macroadenoma secreting prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), and alpha subunit (α-SU). CASE PRESENTATION: The patient experienced recurrent headaches and progressing loss of vision in one eye. During the examination, abnormalities such as tall stature, coarse facial features, enlarged feet and hands, tachycardia, hand tremor, hyperhidrosis, galactorrhea, and goiter were observed. Head magnetic resonance imaging (MRI) revealed a solid tumor in the anterior and middle cranial fossa, measuring 80 × 50 × 55 mm. A stereotactic biopsy revealed plurihormonal Pit-1 positive pituitary adenoma secreting PRL, GH, and TSH. A pituitary hyperfunction with PRL, GH, TSH, and α-SU excess was diagnosed. The patient was successfully treated pharmacologically with dopamine agonists and somatostatin analogue, and a decrease of tumor volume (30%) was achieved. CONCLUSIONS: When neurosurgery is not possible, long-term pharmacological treatment of plurihormonal pituitary macroadenoma can be a safe and relatively effective alternative.


Assuntos
Adenoma/diagnóstico por imagem , Neoplasias Hipofisárias/diagnóstico por imagem , Adenoma/sangue , Adenoma/patologia , Criança , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/patologia , Prolactina/sangue , Tireotropina/sangue
18.
Mol Oncol ; 15(9): 2480-2490, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34288395

RESUMO

Association studies have linked alterations of blood-derived microRNAs (miRNAs) with colorectal cancer (CRC). Here, we performed a microarray-based comparison of the profiles of 2549 miRNAs in 80 blood samples from healthy donors and patients with colorectal adenomas, colorectal diverticulitis and CRC at different stages. Confirmation by quantitative real-time PCR (RT-PCR) was complemented by validation of identified molecules in another 36 blood samples. No variations in miRNA levels were observed in samples from patients with colorectal adenomas and diverticulitis or from healthy donors. However, there were 179 CRC-associated miRNAs of differential abundance compared to healthy controls. Only three - miR-1225-5p, miR-1207-5p and miR-4459 - exhibited increased levels at all CRC stages. Most deregulated miRNAs (128/179, 71%) specifically predicted metastatic CRC. Pathway analysis found several cancer-related pathways to which the miRNAs contribute in various ways. In conclusion, miRNA levels in blood vary throughout CRC progression and affect cellular functions relevant to haematogenous CRC progression and dissemination. The identified biomarker and therapeutic candidates require further confirmation of their clinical relevance.


Assuntos
Adenoma/sangue , Adenoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , MicroRNAs/sangue , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Biologia Computacional , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos
19.
J Steroid Biochem Mol Biol ; 212: 105924, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34089832

RESUMO

Endogenous Cushing syndrome (CS) is an endocrine disorder marked by excess cortisol production rendering patients susceptible to visceral obesity, dyslipidemia, hypertension, osteoporosis and diabetes mellitus. Adrenal CS is characterized by autonomous production of cortisol from cortisol-producing adenomas (CPA) via adrenocorticotropic hormone-independent mechanisms. A limited number of studies have quantified the steroid profiles in sera from patients with CS. To understand the intratumoral steroid biosynthesis, we quantified 19 steroids by mass spectrometry in optimal cutting temperature compound (OCT)-embedded 24 CPA tissue from patients with overt CS (OCS, n = 10) and mild autonomous cortisol excess (MACE, n = 14). Where available, normal CPA-adjacent adrenal tissue (AdjN) was also collected and used for comparison (n = 8). Immunohistochemistry (IHC) for CYP17A1 and HSD3B2, two steroidogenic enzymes required for cortisol synthesis, was performed on OCT sections to confirm the presence of tumor tissue and guided subsequent steroid extraction from the tumor. LC-MS/MS was used to quantify steroids extracted from CPA and AdjN. Our data indicated that CPA demonstrated increased concentrations of cortisol, cortisone, 11-deoxycortisol, corticosterone, progesterone, 17OH-progesterone and 16OH-progesterone as compared to AdjN (p < 0.05). Compared to OCS, MACE patient CPA tissue displayed higher concentrations of corticosterone, 18OH-corticosterone, 21-deoxycortisol, progesterone, and 17OH-progesterone (p < 0.05). These findings also demonstrate that OCT-embedded tissue can be used to define intra-tissue steroid profiles, which will have application for steroid-producing and steroid-responsive tumors.


Assuntos
Adenoma/metabolismo , Neoplasias do Córtex Suprarrenal/metabolismo , Síndrome de Cushing/metabolismo , Esteroides/metabolismo , Adenoma/sangue , Neoplasias do Córtex Suprarrenal/sangue , Adulto , Cromatografia Líquida , Síndrome de Cushing/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Progesterona Redutase/metabolismo , Esteroide 17-alfa-Hidroxilase/metabolismo , Esteroides/sangue , Espectrometria de Massas em Tandem
20.
Medicine (Baltimore) ; 100(20): e25968, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011079

RESUMO

INTRODUCTION: Primary hyperparathyroidism (PHPT) in pregnancy is rare and unrecognized because the maternal physiological adaptations blurs the symptoms. There is no standard treatment strategy for maternal PHPT. Early diagnosis and interventions can prevent catastrophic consequences to the mother and fetus. PATIENT CONCERNS: A 31-year-old Chinese woman was admitted, due to a lump on the left lower leg for 4 months. The patient complained of mild pain in the left lower leg following exercise that could be relieved after a short rest. The patient was at 18 weeks of gestation, and the growth of the fetus was normal. The patient has a 3-year history of hypercalcemia and a 2-year history of nephrolithiasis. No family history of hypercalcemia and endocrine tumors were present. DIAGNOSIS: Laboratory tests demonstrated high serum calcium level of 3.84 mmol/L, parathyroid hormone 1393 pg/mL, alkaline phosphatase 488 µ/L. Ultrasound showed a 22.4 mm × 7.8 mm solid nodule in the left lower lobe of the thyroid gland. Based on these findings, the patient was diagnosed with PHPT. INTERVENTIONS: The patient accepted continuous renal replacement to reduce ironized calcium level. Parathyroidectomy was performed at the 19th week of gestation. Threatened abortion occurred 2 days after the surgery, and magnesium sulfate was used to prevent the abortion. Calcium gluconate, calcium carbonate and vitamin D3 were used to treat the hypocalcemia that occurred 5 days after the surgery. OUTCOMES: Pathology examination demonstrated the parathyroid adenoma. Abortion was prevented using magnesium sulfate and hypocalcemia was cured with calcium gluconate, calcium carbonate and vitamin D3. At 38-week of gestation, the patient (ionized calcium level: 2.16 mmol/L) delivered a healthy female baby weighing 2700 g with 10/10 Apgar. Till now, both the mother and infant showed no complications. CONCLUSION: Maternal PHPT is rare and challenging to diagnose, causing life-threatening complications to mother and fetus. Any decision regarding surgery for a pregnant woman with primary hyperparathyroidism is more complex than in men or nonpregnant women. The decision should be made based on the severity of hypercalcemia and symptoms.


Assuntos
Adenoma/diagnóstico , Hipercalcemia/etiologia , Hiperparatireoidismo Primário/diagnóstico , Neoplasias das Paratireoides/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Aborto Espontâneo/prevenção & controle , Adenoma/sangue , Adenoma/cirurgia , Adulto , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/diagnóstico , Hipercalcemia/cirurgia , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/cirurgia , Recém-Nascido , Nascido Vivo , Sulfato de Magnésio/administração & dosagem , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Gravidez , Complicações Neoplásicas na Gravidez/sangue , Complicações Neoplásicas na Gravidez/cirurgia , Segundo Trimestre da Gravidez , Índice de Gravidade de Doença , Ultrassonografia
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