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1.
Clin Radiol ; 78(12): e975-e984, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37783612

RESUMO

AIM: To evaluate the overall diagnostic performance of magnetic resonance imaging (MRI), different image features, and different image analysis methods in predicting hepatocellular carcinoma (HCC) with cytokeratin 19 (CK19) expression. MATERIALS AND METHODS: A systematic literature search was performed to identify studies using MRI to predict HCC with CK19 expression between 2012 and 2023. Data were extracted to calculate the pooled sensitivity and specificity. Overall diagnostic performance was assessed using areas under the summary receiver operating characteristic curve (AUC). Subgroup analyses were conducted for specific image features and according to image analysis methods (traditional image feature, radiomics, and combined methods). Z-test statistics was used to analyse the differences in diagnostic performance between combined and individual methods. RESULTS: Eleven studies with 14 datasets (1,278 lesions from 1,264 patients) were included. The overall pooled sensitivity, specificity, and AUC with corresponding 95% confidence intervals were estimated to be 0.72 (0.55, 0.85), 0.88 (0.80, 0.93), and 0.89 (0.86, 0.91) for MRI in predicting HCC with CK19 expression. Combined methods had higher sensitivity than image feature methods (0.86 versus 0.54, p=0.001), with no difference in specificity (0.85 versus 0.87, p=0.641). There were no significant differences between radiomics and combined methods regarding sensitivity (p=0.796) and specificity (p=0.535), respectively. CONCLUSION: MRI shows moderate sensitivity and high specificity in identifying HCC with CK19 expression. The application of radiomics can improve the sensitivity of MRI in identifying HCC with CK19 expression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Queratina-19/análise , Imageamento por Ressonância Magnética/métodos , Sensibilidade e Especificidade , Estudos Retrospectivos
2.
Zhonghua Wei Chang Wai Ke Za Zhi ; 26(10): 940-946, 2023 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-37849264

RESUMO

Objective: To investigate the safety and efficacy of total pelvic exenteration (TPE) for treating late complications of radiation-induced pelvic injury. Methods: This was a descriptive case series study. The inclusion criteria were as follows: (1) confirmed radiation-induced pelvic injury after radiotherapy for pelvic malignancies; (2) late complications of radiation-induced pelvic injury, such as bleeding, perforation, fistula, and obstruction, involving multiple pelvic organs; (3) TPE recommended by a multidisciplinary team; (4) patient in good preoperative condition and considered fit enough to tolerate TPE; and (5) patient extremely willing to undergo the procedure and accept the associated risks. The exclusion criteria were as follows: (1) preoperative or intraoperative diagnosis of tumor recurrence or metastasis; (2) had only undergone diversion or bypass surgery after laparoscopic exploration; and (3) incomplete medical records. Clinical and follow-up data of patients who had undergone TPE for late complications of radiation-induced pelvic injury between March 2020 and September 2022 at the Sixth Affiliated Hospital of Sun Yat-sen University were analyzed. Perioperative recovery, postoperative complications, perioperative deaths, and quality of life 1 year postoperatively were recorded. Results: The study cohort comprised 14 women, nine of whom had recto-vagino-vesical fistulas, two vesicovaginal fistulas, one ileo-vesical fistula and rectal necrosis, one ileo-vesical and rectovaginal fistulas, and one rectal ulcer and bilateral ureteral stenosis. The mean duration of surgery was 592.1±167.6 minutes and the median blood loss 550 (100-6000) mL. Ten patients underwent intestinal reconstruction, and four the Hartmann procedure. Ten patients underwent urinary reconstruction using Bricker's procedure and 7 underwent pelvic floor reconstruction. The mean postoperative hospital stay was 23.6±14.9 days. Seven patients (7/14) had serious postoperative complications (Clavien-Dindo IIIa to IVb), including surgical site infections in eight, abdominopelvic abscesses in five, pulmonary infections in five, intestinal obstruction in four, and urinary leakage in two. Empty pelvis syndrome (EPS) was diagnosed in five patients, none of whom had undergone pelvic floor reconstruction. Five of the seven patients who had not undergone pelvic floor reconstruction developed EPS, compared with none of those who had undergone pelvic floor reconstruction. One patient with EPS underwent reoperation because of a pelvic abscess, pelvic hemorrhage, and intestinal obstruction. There were no perioperative deaths. During 18.9±10.1 months of follow-up, three patients died, two of renal failure, which was a preoperative comorbidity, and one of COVID-19. The remaining patients had gradual and significant relief of symptoms during follow-up. QLQ-C30 assessment of postoperative quality of life showed gradual improvement in all functional domains and general health at 1, 3, and 6 months postoperatively (all P<0.05). Conclusions: TPE is a feasible procedure for treating late complications of radiation-induced pelvic injury combined with complex pelvic fistulas. TPE is effective in alleviating symptoms and improving quality of life. However, the indications for this procedure should be strictly controlled and the surgery carried out only by experienced surgeons.


Assuntos
COVID-19 , Fístula , Obstrução Intestinal , Exenteração Pélvica , Lesões por Radiação , Humanos , Feminino , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Qualidade de Vida , Estudos Retrospectivos , COVID-19/etiologia , Pelve , Reto , Lesões por Radiação/cirurgia , Lesões por Radiação/etiologia , Complicações Pós-Operatórias/etiologia , Obstrução Intestinal/etiologia , Fístula/etiologia
3.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 58(6): 554-560, 2023 Jun 09.
Artigo em Chinês | MEDLINE | ID: mdl-37272000

RESUMO

Objective: To explore an automatic landmarking method for anatomical landmarks in the three-dimensional (3D) data of the maxillary complex and preliminarily evaluate its reproducibility and accuracy. Methods: From June 2021 to December 2022, spiral CT data of 31 patients with relatively normal craniofacial morphology were selected from those who visited the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The sample included 15 males and 16 females, with the age of (33.3±8.3) years. The maxillary complex was reconstructed in 3D using Mimics software, and the resulting 3D data of the maxillary complex was mesh-refined using Geomagic software. Two attending physicians and one associate chief physician manually landmarked the 31 maxillary complex datasets, determining 24 anatomical landmarks. The average values of the three expert landmarking results were used as the expert-defined landmarks. One case that conformed to the average 3D morphological characteristics of healthy individuals' craniofacial bones was selected as the template data, while the remaining 30 cases were used as target data. The open-source MeshMonk program (a non-rigid registration algorithm) was used to perform an initial alignment of the template and target data based on 4 landmarks (nasion, left and right zygomatic arch prominence, and anterior nasal spine). The template data was then deformed to the shape of the target data using a non-rigid registration algorithm, resulting in the deformed template data. Based on the unchanged index property of homonymous landmarks before and after deformation of the template data, the coordinates of each landmark in the deformed template data were automatically retrieved as the automatic landmarking coordinates of the homonymous landmarks in the target data, thus completing the automatic landmarking process. The automatic landmarking process for the 30 target data was repeated three times. The root-mean-square distance (RMSD) of the dense corresponding point pairs (approximately 25 000 pairs) between the deformed template data and the target data was calculated as the deformation error of the non-rigid registration algorithm, and the intra-class correlation coefficient (ICC) of the deformation error in the three repetitions was analyzed. The linear distances between the automatic landmarking results and the expert-defined landmarks for the 24 anatomical landmarks were calculated as the automatic landmarking errors, and the ICC values of the 3D coordinates in the three automatic landmarking repetitions were analyzed. Results: The average three-dimensional deviation (RMSD) between the deformed template data and the corresponding target data for the 30 cases was (0.70±0.09) mm, with an ICC value of 1.00 for the deformation error in the three repetitions of the non-rigid registration algorithm. The average automatic landmarking error for the 24 anatomical landmarks was (1.86±0.30) mm, with the smallest error at the anterior nasal spine (0.65±0.24) mm and the largest error at the left oribital (3.27±2.28) mm. The ICC values for the 3D coordinates in the three automatic landmarking repetitions were all 1.00. Conclusions: This study established an automatic landmarking method for three-dimensional data of the maxillary complex based on a non-rigid registration algorithm. The accuracy and repeatability of this method for landmarking normal maxillary complex 3D data were relatively good.


Assuntos
Algoritmos , Imageamento Tridimensional , Masculino , Feminino , Humanos , Adulto , Imageamento Tridimensional/métodos , Reprodutibilidade dos Testes , Software , Tomografia Computadorizada Espiral , Pontos de Referência Anatômicos/anatomia & histologia
4.
Zhonghua Bing Li Xue Za Zhi ; 51(10): 1013-1018, 2022 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-36207915

RESUMO

Objective: To investigate the clinical features, morphological characteristics, immunophenotype, and differential diagnosis of goblet cell adenocarcinoma (GCA) in the digestive system. Methods: The clinicopathological data, morphological characteristics, immunophenotypes of 22 cases of GCA in the digestive system diagnosed from January 2010 to January 2021 were collected. Meanwhile, 25 cases of neuroendocrine neoplasm (NEN) and 24 cases of adenocarcinoma were used as controls. Relevant literature was also reviewed. Results: There were 16 males and 6 females, aged from 36 to 79 years with an average of 56 years. The anatomical sites of the 22 GCA were mostly appendix (17 cases) and occasionally extra-appendix (5 cases), including 3 cases in stomach, 1 case in duodenum and 1 case in anal. All 17 cases of appendiceal GCA were pure GCA. Among the 5 cases of extra-appendiceal GCA, One case of gastric GCA was pure, two cases of gastric GCA with NEN or adenocarcinoma, duodenal GCA with NEN and adenocarcinoma, anal GCA with NEN.Low-grade GCAs were composed of goblet, Paneth and neuroendocrine cells, which were arranged in intestinal crypt tubular or cluster structures and distributed in the wall of digestive system. The tubular and cluster structures lacked adhesion. Goblet cells were columnar, located in the base, with clear cytoplasm, small nuclei, inconspicuous atypia, and uncommon mitoses. Extracellular mucus and signet-ring cells with nuclear variations could be seen in some cases. Nerve fiber bundle invasion and tumor thrombus in vessels were often present. High-grade GCAs lacked tubular and cluster structures, and their histological structures were more complex. Tumor cells expressed mixed neuroendocrine and glandular epithelial markers. Similar to the expression patterns of synaptophysin and chromogranin A, CD200 and INSM1 were also dot-like or patch-positive in GCA. Conclusions: GCA is an infrequent tumor of the digestive system and shows the bi-directional differentiation characteristics of neuroendocrine and glandular epithelium. Accurate diagnosis and staging are related to its prognosis.


Assuntos
Adenocarcinoma , Neoplasias do Apêndice , Tumor Carcinoide , Tumores Neuroendócrinos , Adenocarcinoma/patologia , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Cromogranina A , Feminino , Células Caliciformes/metabolismo , Células Caliciformes/patologia , Humanos , Masculino , Tumores Neuroendócrinos/patologia , Proteínas Repressoras , Sinaptofisina
5.
Beijing Da Xue Xue Bao Yi Xue Ban ; 54(3): 532-540, 2022 Jun 18.
Artigo em Chinês | MEDLINE | ID: mdl-35701132

RESUMO

OBJECTIVE: To explore the amino acid metabolomics characteristics of myeloid-derived suppressor cells (MDSCs) in mice with sepsis induced by the cecal ligation and puncture (CLP). METHODS: The sepsis mouse model was prepared by CLP, and the mice were randomly divided into a sham operation group (sham group, n = 10) and a CLP model group (n = 10). On the 7th day after the operation, 5 mice were randomly selected from the surviving mice in each group, and the bone marrow MDSCs of the mice were isolated. Bone marrow MDSCs were separated to measure the oxygen consumption rate (OCR) by using Agilent Seahorse XF technology and to detect the contents of intracellular amino acids and oligopeptides through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) technology. Different metabolites and potential biomarkers were analyzed by univariate statistical analysis and multivariate statistical analysis. The major metabolic pathways were enriched using the small molecular pathway database (SMPDB). RESULTS: The proportion of MDSCs in the bone marrow of CLP group mice (75.53% ± 6.02%) was significantly greater than that of the sham group (43.15%± 7.42%, t = 7.582, P < 0.001), and the basal respiratory rate [(50.03±1.20) pmol/min], maximum respiration rate [(78.07±2.57) pmol/min] and adenosine triphosphate (ATP) production [(25.30±1.21) pmol/min] of MDSCs in the bone marrow of CLP group mice were significantly greater than the basal respiration rate [(34.53±0.96) pmol/min, (t = 17.41, P < 0.001)], maximum respiration rate [(42.57±1.87) pmol/min, (t = 19.33, P < 0.001)], and ATP production [(12.63±0.96) pmol/min, (t = 14.18, P < 0.001)] of sham group. Leucine, threonine, glycine, etc. were potential biomarkers of septic MDSCs (all P < 0.05). The increased amino acids were mainly enriched in metabolic pathways, such as malate-aspartate shuttle, ammonia recovery, alanine metabolism, glutathione metabolism, phenylalanine and tyrosine metabolism, urea cycle, glycine and serine metabolism, ß-alanine metabolism, glutamate metabolism, arginine and proline metabolism. CONCLUSION: The enhanced mitochondrial oxidative phosphorylation, malate-aspartate shuttle and alanine metabolism in MDSCs of CLP mice may provide raw materials for mitochondrial aerobic respiration, thereby promoting the immunosuppressive function of MDSCs. Blocking the above metabolic pathways may reduce the risk of secondary infection in sepsis and improve the prognosis.


Assuntos
Células Supressoras Mieloides , Sepse , Trifosfato de Adenosina/metabolismo , Alanina/metabolismo , Animais , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Cromatografia Líquida , Glicina/metabolismo , Malatos/metabolismo , Camundongos , Células Supressoras Mieloides/metabolismo , Sepse/complicações , Espectrometria de Massas em Tandem
6.
Ann Oncol ; 33(8): 836-844, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35715285

RESUMO

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.


Assuntos
COVID-19 , Neoplasias , COVID-19/epidemiologia , Humanos , Oncologia , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , Estudos Prospectivos
7.
Lancet Haematol ; 9(6): e434-e444, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35576960

RESUMO

BACKGROUND: Primary analyses of cohort 1a of the REFINE trial showed that addition of navitoclax to ruxolitinib induced a 35% or greater reduction in spleen volume (SVR35) and reduced symptoms in patients with myelofibrosis no longer benefiting from ruxolitinib. Here, we report the exploratory post-hoc biomarker analyses from cohort 1a. METHODS: REFINE is a phase 2, multicentre, open-label trial designed to assess the activity and safety of navitoclax alone or in combination with ruxolitinib in patients with primary or secondary (post-polycythaemia vera or post-essential thrombocythaemia) myelofibrosis. Cohort 1a of the study included patients who had disease progression or suboptimal response on stable ruxolitinib monotherapy. Patients in cohort 1a, who had previously received ruxolitinib for 12 weeks or more, continued their current stable dose, and navitoclax was orally administered at 50 mg per day and escalated weekly to a maximum of 300 mg per day, based on tolerability. The primary activity endpoint was SVR35 at week 24 from baseline. Secondary endpoints were a 50% or greater reduction in total symptom score (TSS50) at week 24 from baseline as measured by the Myelofibrosis Symptom Assessment Form (version 4.0), anaemia response assessed according to International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet criteria, and change in grade of bone marrow fibrosis according to the European consensus grading system; and exploratory endpoints included overall survival and changes in inflammatory cytokines. Exploratory analyses investigated potential prognostic biomarkers of the benefit of navitoclax-based combination treatment, including bone marrow fibrosis and variant allele frequency, in patients with a suboptimal response to ruxolitinib. This study is registered with ClinicalTrials.gov (NCT03222609) and is ongoing. FINDINGS: Between Nov 14, 2017, and April 10, 2019, 34 patients in cohort 1a received at least one dose of navitoclax plus ruxolitinib. 23 (68%) patients were male, with 32 (94%) being White. At data cutoff (May 6, 2021), the median follow-up for survivors was 26·2 months (IQR 21·9-32·3). 33 patients were evaluable for biomarker analyses; 19 (58%) had high molecular risk mutations. Five (31%) of 16 patients had SVR35 at week 24 in the high molecular risk group, as did four (31%) of 13 in the non-high molecular risk group. Four (36%) of 11 patients in the high molecular risk group had TSS50 at week 24 compared with two (25%) of eight in the non-high molecular risk group; seven (39%) of 18 in the high molecular risk group had an improvement in fibrosis by at least one grade compared with five (36%) of 14 in the non-high molecular risk group; and four (28%) of 14 had reductions in variant allele frequency of 20% or greater in the high molecular risk group compared with two (17%) of 12 in the non-high molecular risk group. Patients with improvements in fibrosis of one grade or more and a reduction of 20% of more in variant allele frequency had improved overall survival (median overall survival not reached) compared with those who did not achieve fibrosis improvement or a reduction in variant allele frequency (median overall survival 28·5 months [95% CI 19·6-not estimable] for both), suggesting potential disease modification. Additionally, changes in concentrations of ß-2-microglobulin (week 12: r=0·57; week 24: r=0·57), TIMP metallopeptidase inhibitor 1 (week 12: r=0·47; week 24: r=0·54), TNF receptor type II (r=0·55; week 24: r=0·40), and vascular cell adhesion molecule-1 (r=0·58; week 24: r=0·50) were positively associated with changes in spleen volume. INTERPRETATION: These biomarker analyses reveal clinically meaningful splenic responses independent of high molecular risk mutation status in patients treated with navitoclax plus ruxolitinib who were not benefiting from ruxolitinib monotherapy. Furthermore, the overall survival benefit observed in those with an improvement in fibrosis or a reduction in variant allele frequency is suggestive of disease modification, implying the therapeutic potential of adding navitoclax to ruxolitinib for patients with myelofibrosis who had disease progression or suboptimal response to ruxolitinib monotherapy. FUNDING: AbbVie.


Assuntos
Mielofibrose Primária , Compostos de Anilina , Biomarcadores , Progressão da Doença , Feminino , Fibrose , Humanos , Masculino , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Pirazóis , Pirimidinas , Sulfonamidas
8.
Zhonghua Zhong Liu Za Zhi ; 44(5): 402-409, 2022 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-35615796

RESUMO

Objective: To compare the prognostic evaluation value of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in rectal cancer patients. Nomogram survival prediction model based on inflammatory markers was constructed. Methods: The clinical and survival data of 585 patients with rectal cancer who underwent radical resection in the First Affiliated Hospital of Xi'an Jiao tong University from January 2013 to December 2016 were retrospectively analyzed. The optimal cut-off values of NLR, PLR, LMR, and SII were determined by the receiver operating characteristic (ROC) curve. The relationship between different NLR, PLR, LMR and SII levels and the clinic pathological characteristics of the rectal cancer patients were compared. Cox proportional risk model was used for univariate and multivariate regression analysis. Nomogram prediction models of overall survival (OS) and disease-free survival (DFS) of patients with rectal cancer were established by the R Language software. The internal validation and accuracy of the nomograms were determined by the calculation of concordance index (C-index). Calibration curve was used to evaluate nomograms' efficiency. Results: The optimal cut-off values of preoperative NLR, PLR, LMR and SII of OS for rectal cancer patients were 2.44, 134.88, 4.70 and 354.18, respectively. There was statistically significant difference in tumor differentiation degree between the low NLR group and the high NLR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative carcinoembryonic antigen (CEA) level between the low PLR group and the high PLR group (P<0.05). There was statistically significant difference in tumor differentiation degree between the low LMR group and the high LMR group (P<0.05), and there were statistically significant differences in T stage, N stage, TNM stage, tumor differentiation degree and preoperative CEA level between the low SII group and the high SII group (P<0.05). The multivariate Cox regression analysis showed that the age (HR=2.221, 95%CI: 1.526-3.231), TNM stage (Ⅲ grade: HR=4.425, 95%CI: 1.848-10.596), grade of differentiation (HR=1.630, 95%CI: 1.074-2.474), SII level (HR=2.949, 95%CI: 1.799-4.835), and postoperative chemoradiotherapy (HR=2.123, 95%CI: 1.506-2.992) were independent risk factors for the OS of patients with rectal cancer. The age (HR=2.107, 95%CI: 1.535-2.893), TNM stage (Ⅲ grade, HR=2.850, 95%CI: 1.430-5.680), grade of differentiation (HR=1.681, 95%CI: 1.150-2.457), SII level (HR=2.309, 95%CI: 1.546-3.447), and postoperative chemoradiotherapy (HR=1.837, 95%CI: 1.369-2.464) were independent risk factors of the DFS of patients with rectal cancer. According to the OS and DFS nomograms predict models of rectal cancer patients established by multivariate COX regression analysis, the C-index were 0.786 and 0.746, respectively. The calibration curve of the nomograms showed high consistence of predict and actual curves. Conclusions: Preoperative NLR, PLR, LMR and SII levels are all correlated with the prognosis of rectal cancer patients, and the SII level is an independent prognostic risk factor for patients with rectal cancer. Preoperative SII level can complement with the age, TNM stage, differentiation degree and postoperative adjuvant chemoradiotherapy to accurately predict the prognosis of rectal cancer patients, which can provide reference and help for clinical decision.


Assuntos
Inflamação , Nomogramas , Neoplasias Retais , Biomarcadores Tumorais , Antígeno Carcinoembrionário , Humanos , Inflamação/classificação , Linfócitos , Neutrófilos , Período Pré-Operatório , Prognóstico , Neoplasias Retais/cirurgia , Estudos Retrospectivos
9.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(6): 513-522, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34148316

RESUMO

Objective: To explore clinical features and prognosis of anastomotic leak (AL) after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients. Methods: A retrospective cohort study was performed. Data were retrieved from colorectal cancer database of the Sixth Affiliated Hospital, Sun Yat-sen University. The clinical data of 470 patients with rectal cancer who underwent anterior resection after neoadjuvant chemoradiotherapy at our department from September 2010 to December 2018 were enrolled. Clinical features and outcome of postoperative AL were analyzed. The primary outcomes were the short-term and long-term incidence and severity of AL (ISREC grading standard was adopted). The secondary outcomes were the prognostic indicators of AL, including the secondary chronic presacral sinus, anastomotic stenosis and persistent stoma. Patients received regular follow-up every 3-6 months after surgery, including physical examination, blood test, colonoscopy and image; those received follow-up once a year after postoperative 2-year; those who did not return to our hospital received telephone follow-up. Data of this study were retrieved up to January 2020. Univariate χ(2) test and multivariate logistic analysis were used to identify risk factors of AL and prognostic factors of persistent stoma. Results: There were 331 males (70.4%) with the average age of (53.5±11.6) years. Distance from tumor to anal verge ≤ 5 cm was found in 228 (48.5%) patients. The diverting stoma was performed in 440 (93.6%) patients. After a median follow-up of 28 months, AL was found in 129 (27.4%) patients, including 67 (14.3%) patients with clinical leak (ISREC grade B-C). The median time for diagnosis of AL was 70 days (2-515 days) after index surgery. Common symptoms included sacrococcygeal pain (27.9%, 36/129), purulent discharge through anus (25.6%, 33/129), and rectal irritation (17.8%, 23/129). Sixty five point one percent (84/129) of the defect site was at the posterior wall of the anastomosis. Transanal incision and drainage or lavage (27.9%, 36/129) and percutaneous drainage under ultrasound or CT (17.1%, 22/129) were the most common management. Chronic presacral sinus tract could not be evaluated in 12 patients because imaging was performed more than 1 year after the operation. Evaluation beyond 1 year showed that 73 of 458 eligible patients (15.9%) were found with chronic presacral sinus, accounting for 62.4% (73/117) of patients with AL; 69 of 454 (15.2%) were diagnosed with anastomotic stenosis, of whom 49 were secondary to AL; 59 of 470 (12.6%) had persistent stoma due to AL. Univariate analysis showed that male, operative duration > 180 minutes, intraoperative blood loss >150 ml, and pelvic radiation injury were associated with AL (all P<0.05). Multivariate analysis showed that male (OR=1.72, 95% CI: 1.04-2.86, P=0.036), intraoperative blood loss > 150 ml (OR=1.82, 95% CI: 1.11-2.97, P=0.017), and pelvic radiation injury (OR=4.90, 95% CI: 3.09-7.76, P<0.001) were independent risk factors of AL after anterior resection. For patients with AL, clinical leak (ISREC grade B-C) (OR=9.59, 95% CI: 3.73-24.69, P<0.001), age ≤55 years (OR=3.35, 95% CI: 1.35-8.30, P=0.009), distance from tumor to anal verge ≤ 5 cm (OR=3.33, 95% CI: 1.25-8.92, P=0.017), and pelvic radiation injury (OR=3.29, 95% CI: 1.33-8.14, P=0.010) were independent risk factors of persistent stoma. Conclusions: AL after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients is common. Among patients with AL, the proportion of those needing persistent stoma is high. Pelvic radiation injury is significantly associated with occurrence of AL and subsequent persistent stoma. Sphincter-preserving surgery for rectal cancer should be selectively used based on the risk of pelvic radiation injury, which is beneficial to reduce the incidence of AL and improve the quality of life.


Assuntos
Fístula Anastomótica , Neoplasias Retais , Adulto , Idoso , Anastomose Cirúrgica , Quimiorradioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Prognóstico , Qualidade de Vida , Neoplasias Retais/cirurgia , Estudos Retrospectivos
10.
Dev Comp Immunol ; 121: 104102, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33862099

RESUMO

CD63 is a member of the four-transmembrane-domain protein superfamily and is the first characterized tetraspanin protein. In the present study, we cloned the common carp (Cyprinus Carpio) CD63 (ccCD63) sequence and found that the ccCD63 ORF contained 711 bp and encoded a protein of 236 amino acids. Homology analysis revealed that the complete ccCD63 sequence had 84.08% amino acid similarity to CD63 of Sinocyclocheilus anshuiensis. Subcellular localization analysis revealed that ccCD63 was localized in the cytoplasm. Quantitative real-time PCR (qRT-PCR) analysis indicated that ccCD63 was expressed in the gill, intestine, liver, spleen, brain and kidney, with higher expression in spleen and brain tissues than in the other examined tissues. After koi herpesvirus (KHV) infection, these tissues exhibited various expression levels of ccCD63. The expression level was the lowest in the liver and highest in the brain; the expression level in the brain was 8.7-fold higher than that in the liver. Furthermore, knockdown of ccCD63 promoted KHV infection. Moreover, ccCD63 was correlated with the regulation of RIG-I/MAVS/TRAF3/TBK1/IRF3 and may be involved in the antiviral response through the RIG-I viral recognition signalling pathway in a TRAF3/TBK1-dependent manner. Taken together, our results suggested that ccCD63 upregulated the interaction of KHV with the host immune system and suppressed the dissemination of KHV.


Assuntos
Carpas/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Infecções por Herpesviridae/veterinária , Tetraspanina 30/metabolismo , Animais , Carpas/genética , Carpas/virologia , Clonagem Molecular , DNA Viral , Doenças dos Peixes/virologia , Proteínas de Peixes/genética , Técnicas de Silenciamento de Genes , Brânquias , Herpesviridae/imunologia , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Interações Hospedeiro-Patógeno/imunologia , Transdução de Sinais/imunologia , Tetraspanina 30/genética
11.
Folia Biol (Praha) ; 67(5-6): 183-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35439851

RESUMO

Apolipoprotein J (clusterin) is a component of high-density lipoproteins, the high level of which is reversely correlated with the risk of coronary heart disease. In addition, it exerts anti-inflammatory and anti-apoptotic effects on endothelial cells and inhibits smooth muscle cell migration and proliferation, indicating that it may play a protective role in cardiovascular disease. However, the exact mechanisms by which this occurs remain unclear. This study aimed to clarify these underlying protective mechanisms by researching the inhibitory effects of apolipoprotein J via the NOD-like receptor protein 3 pathway on the inflammation induced by cholesterol crystals in THP­1 macrophages. In culture, THP-1 macrophages were infected with adenoviral vectors containing apolipoprotein J genes and subsequently treated with cholesterol crystals. The inflammatory cytokines interleukin­1ß, interleukin 18 and tumour necrosis factor α were quantitatively measured with ELISA kits. NOD-like receptor protein 3, cysteinyl aspartate specific proteinase 1 and interleukin 1ß were evaluated by Western blot and PCR analysis. As a result, apolipoprotein J expression was found to remarkably decrease the levels of inflammatory cytokines, including tumour necrosis factor α, interleukin 18 and interleukin 1ß, secreted by THP­1 macrophages. It was also found capable of inhibiting the levels of NOD-like receptor protein 3, cysteinyl aspartate-specific proteinase 1 and interleukin 1ß both at the protein and mRNA levels. In the current study, we revealed that over-expression of apolipoprotein J attenuated the inflammation induced by cholesterol crystals through inhibition of the NOD-like receptor protein 3 inflammasome pathway.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ácido Aspártico/metabolismo , Ácido Aspártico/farmacologia , Colesterol/metabolismo , Clusterina/metabolismo , Clusterina/farmacologia , Citocinas/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Inflamação/patologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
12.
J Physiol Pharmacol ; 71(4)2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33316771

RESUMO

This study aims to evaluated the prognostic and predictive roles of DNA mismatch repair status in colon cancer patients treated with oxaliplatin-based chemotherapy. From 2005 to 2008, patients who underwent curative surgical resection for high-risk stage II or stage III colon cancer were recruited in this study. These patients had been received oxaliplatin-based chemotherapy. A total 324 patients were included (41.7% at stage II and 58.3% at stage III), and 59 patients (18.2%) exhibited mismatch repair-deficient (dMMR). The prognostic analysis revealed an increase in disease-free survival (DFS) for dMMR patients versus proficient MMR (pMMR) patients (81.4% versus 64.2%, P = 0.009), and overall survival (OS) (86.4% versus 69.1%, P = 0.004). Among the 82 patients who did not receive adjuvant therapy, the 5-year DFS was significantly higher in patients with dMMR (81.3%) than in patients with pMMR (49.7%, P = 0.040). In the multivariate models, dMMR was independently associated with improved DFS (HR = 2.171, 95% CI: 1.108 - 4.253, P = 0.024) and OS (HR = 2.521, 95% CI: 1.190 - 5.339, P = 0.016). In the predictive analysis, it was observed that the benefit of treatment significantly differed according to the DNA MMR status (P = 0.020). Compared with surgery alone, oxaliplatin-based adjuvant chemotherapy improved the 5-year DFS (69.9% versus 56.2%, P = 0.024) among patients with pMMR in the multivariable analysis (HR = 0.794, 95% CI = 0.646 - 0.976, P = 0.029). In contrast, the oxaliplatin-based chemotherapy in the group with dMMR had no benefit in DFS (83.1% versus 81.8%, HR 1.040, 95% CI: 0.276 - 3.922, P = 0.954). Patients with dMMR colon cancer are associated with improved survival rates, compared with pMMR colon cancer. MMR status is an independent prognostic biomarker for DFS in patients with high-risk stage II and stage III colon cancer. Oxaliplatin-based adjuvant chemotherapy mainly benefits patients with pMMR, but may not benefit patients with tumors exhibiting dMMR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Neoplasias do Colo/tratamento farmacológico , Reparo de Erro de Pareamento de DNA , Enzimas Reparadoras do DNA/análise , Oxaliplatina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Colectomia , Neoplasias do Colo/química , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
13.
Zhonghua Zhong Liu Za Zhi ; 42(8): 629-634, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867453

RESUMO

Objective: To investigate the effect of esculin on the proliferation of triple negative breast cancer cells and its molecular mechanism. Methods: MDA-MB-231 cells were treated with 28, 56, 112, 225, 450 and 900 µmol/L of esculin for 24, 48 and 72 h, respectively, and the cell viability was detected by cell counting kit 8 (CCK-8) assay. In addition, MDA-MB-231 cells were treated with 0, 225, 450 and 900 µmol/L of esculin for 48 h. And then the changes in cell morphology were observed by inverted microscope. The clone-forming ability was detected by colony formation assay. The mRNA expression levels of FBI-1, p53 and p21 were detected using real-time fluorescence quantitative polymerase chain reaction. The protein expression levels of FBI-1, p53, p21 and Ki67 were detected by western blot. Results: Compared with the blank control group, the cell viability of MDA-MB-231 cells that treated with esculin significantly decreased in a dose-dependent and time-dependent manners. After treatment with esculin, MDA-MB-231 cells shrunk, flattened, adhered poorly to the culture dish and the cell spacing became larger. Meanwhile, shedding and incomplete cells appeared, of which 900 µmol/L of esculin treatment group showed the most dramatic changes. In addition, the colony formation ratios were decreased to (77.18±5.13)%, (65.94±4.98)% and (45.92±3.70)% in the 225, 450 and 900 µmol/L of esculin treatment groups compared with blank control, respectively (P<0.01). Furthermore, the mRNA and protein expressions of FBI-1 increased, while the levels of p53 and p21 mRNA and protein, as well as the protein expression of Ki67 decreased in a concentration-dependent manner (P<0.01). Conclusion: Esculin may regulate cell cycle-related p53-p21 pathway via FBI-1 mediated DNA replication, thus inhibit the proliferation of triple negative breast cancer cells.


Assuntos
Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Esculina/farmacologia , RNA Mensageiro/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias da Mama/metabolismo , Ciclo Celular , Linhagem Celular Tumoral , Proteínas de Ligação a DNA , Regulação para Baixo/efeitos dos fármacos , Feminino , Humanos , Fatores de Transcrição , Neoplasias de Mama Triplo Negativas/patologia
14.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(8): 745-751, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32810945

RESUMO

Objective: To preliminarily evaluate the feasibility and safety of laparoscopic Parks procedure for chronic radiation proctopathy (CRP). Methods: A descriptive cohort study was carried out. The clinical and follow-up data of 19 patients who received laparoscopic Parks procedure due to CRP in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2013 to March 2019 were retrospectively analyzed. Inclusion criteria: (1) serious late complications occurred after pelvic radiotherapy, e.g.serious intractable hematochezia (hemoglobin <70 g/L), intractable anal pain (numerical rating scale >7), rectostenosis, perforation, and fistula. (2) imaging examinations including colonoscopy, pelvic MRI and/or chest, abdomen and pelvic CT were performed before surgery to confirm the lesions. Exclusion criteria: (1) preoperative or intraoperative diagnosis of tumor recurrence; (2) only ostomy was performed after laparoscopic exploration; (3) after neoadjuvant radiotherapy for rectal cancer; (4) incomplete medical records. Surgical procedures: (1) Laparoscopic exploration: tumor recurrence was excluded, and the range of radioactive damage in the intestine was determined. Marks were made on the proximal sigmoid colon without grossly obvious edema, thickening or radioactive injuries. (2) Abdominal operation: the right mesentery of sigmoid colon and rectum was opened, inferior mesenteric vein and inferior mesenteric artery were divided and the Toldt gap was expanded inwards and cephalad. The outside of left hemicolon was freed, the gastrocolic ligament was opened, the splenic flexure was fully mobilized, and the rectum was separated from the rear, side and front to the lowest point. Then perineal operation was performed. (3) Perineal operation: the whole layer of rectum wall was cut thoroughly at 1cm below the lesion's lower margin, the space around the rectum was fully separated, the rectum and sigmoid colon was pulled out through the anus and cut off at the site of the grossly normal intestine, the diseased bowel was removed and a coloanal anastomosis was made. (4) A protective stoma was performed. Conditions of operation, complication and symptom relief were summarized. A descriptive statistic method was used to analyze the results. Results: All the 19 patients were female with a median age of 53 (interquartiles, 50, 56) years old, of whom 18 patients had primary cervical cancer. Surgical indications: 9 cases were rectovaginal fistula; 9 cases were intractable anal pain, among whom 7 were complicated with deep rectal ulcer; and 1 case was intractable hematochezia with deep rectal ulcer. Eighteen cases completed laparoscopic Parks procedure, while 1 case was converted to laparotomy. The median operative time was 215 (131, 270) minutes, the median bleeding volume was 50 (50, 100) ml, and the median hospital stay was 12 (11, 20) days. There was no perioperative death. Ten cases had postoperative complications, including 3 cases of serious complications (CD grade IIIb and above) within 30 days after operation, of whom one case developed pelvic infection caused by rectovaginal, rectovesical and rectourethral fistula and acute renal failure (IVa); 2 cases developed orifice prolapse and parastomal hernia (IIIb). Seven cases had anastomosis-related complications, including 4 cases of grade A anastomotic leakage and 3 cases of anastomotic stenosis. Symptoms of CRP in the whole group were significantly relieved or disappeared after one year of the operation. Five cases achieved stoma closure. Conclusions: Laparoscopic Parks procedure for chronic radiation proctopathy is safe and feasible, and can effectively improve symptoms. However, the incidence of anastomotic complications is high, so the surgical indications should be strictly controlled.


Assuntos
Laparoscopia , Lesões por Radiação , Doença Crônica , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Retais , Estudos Retrospectivos
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(4): 370-376, 2020 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-32306605

RESUMO

Objective: To evaluate the feasibility, safety and efficacy of robotic-assisted lateral lymph node dissection for mid-low advanced rectal cancer. Methods: A retrospective cohort study was performed. Inclusion criteria: (1) age between 18 and 80 years old; (2) rectal adenocarcinoma diagnosed by pathology; (3) without distant metastasis by preoperative CT or MRI; (4) patients underwent robotic-assisted total mesorectal resection (TME). Exclusion criteria: (1) conversion to open surgery; (2) multiple primary tumors; (3) patients underwent combined multiple organ resection. According to the above criteria, 137 patients undergoing robotic-assisted mid-low rectal cancer resection in the First Affiliated Hospital of Xi'an Jiaotong University from December 2016 to April 2019 were enrolled. Ninety-seven cases underwent robotic-assisted total mesorectal excision (TME group) and 40 underwent robotic-assisted total mesorectal resection with lateral lymph node dissection (LLND) (TME+LLND group, pelvic LLND was performed with neurovascular guidance to retain pelvic autonomic nerves in the order of the left side the first and then the right side). The propensity score matching of 1:1 was performed with R software, based on age, sex, BMI, ASA classification, distance from tumor to the anal verge, preoperative chemoradiotherapy history, preoperative abdominal surgery history, the size of tumors and TNM stage. The operative indicators, postoperative recovery, pathology and postoperative complications within 30 days were compared between the two groups. Results: A total of 72 cases were successfully matched (36 in each group), and there were no statistically significant differences in baseline data between the two groups (all P>0.05). The operation time of TME+LLND group was significantly longer than that of TME group [275.0 (180-405) minutes vs. 220.0 (140-320) minutes, Z=-3.680, P<0.001], while there were no statistically significant differences in blood loss during operation, time to postoperative first flatus, postoperative hospital stay, total hospital cost, tumor differentiation, and distal resection length of margin (all P>0.05). Circumferential resection margin was all negative in both groups. The number of harvested lymph modes in the TME+LLND groups was higher than that in the TME group [26 (18-37) vs. 14 (9-36), Z=-6.407, P<0.001]. In addition, there were no statistically significant differences in postoperative morbidity and Clavien-Dindo classification of complication within 30 days between the two groups (both P>0.05). Conclusions: Although robotic lateral lymph node dissection requires longer operation time, it is a feasible, safe and effective procedure.


Assuntos
Protectomia/métodos , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos , Humanos , Laparoscopia , Excisão de Linfonodo , Mesentério/cirurgia , Pontuação de Propensão , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(12): 1152-1158, 2019 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-31874531

RESUMO

Objective: To investigate the effect of tumor deposits (TD) on the prognosis of patients with stage III colon cancer, and to explore whether TD number included into regional lymph node count can predict the prognosis more accurately. Methods: A retrospective cohort study was carried out. Case inclusion criteria: (1) primary colon cancer; (2) undergoing colon cancer radical operation; (3) definite pathological diagnosis; (4) colon cancer stage III according to AJCC 8th edition; (5) complete follow-up data; (6) without preoperative neoadjuvant treatment. Clinicopathological data of 296 patients undergoing colon cancer radical operation from January 2005 to December 2008 in the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively collected. The effect of TD and its amount on the prognosis was evaluated. Colon cancer TNM staging method based on the 8th edition of AJCC was compared with the modified TNM staging (mTNM) adjusted by the number of TD. The differences of the disease-free survival (DFS) and overall survival (OS) between groups were also examined. The Kaplan-Meier curve was used to analyze the survival, and prognostic factors were analyzed by Cox univariate and multivariate analyses. Results: Among 296 patients with stage III colon cancer, 78 patients had TD. The median number of TD was 2 (1-10). Tumor T stage, N stage, vascular tumor thrombus and preoperative carcinoembryonic antigen (CEA) were associated with TD in patients with colon cancer (all P<0.05). The right hemicolon appears likely to have TD than left hemicolon, but the difference was not statistically significant (P=0.059). The median follow-up of the whole group was 71 (6-102) months. During the follow-up period, 129 patients (43.6%) had recurrence or metastasis, and 111 patients died (37.5%). The 5-year DFS in TD group was 44.9%, which was lower than that in the non-TD group (60.6%), with statistically significant difference (P=0.003). The 5-year OS in TD group was 50.0%, which was also lower than 67.0% in the non-TD group, and the difference was statistically significant (P=0.002). According to TD number, patients were divided into 3 groups: 1 TD (25 cases), 2-3 TD (32 cases), ≥4 TD (21 cases). The 5-year DFS in these 3 groups was 68%, 56.3%, and 0, respectively (P<0.001), and 5-year OS was 76%, 59.4%, and 4.8% respectively (P<0.001). Univariate analysis showed that TD presence (95% CI: 1.234-2.694, P=0.003) and TD number (95% CI: 3.531-14.138, P<0.001) were associated with the prognosis of patients with stage III colon cancer. At the same time, age, tumor N stage, tumor location, chemotherapy, and preoperative CEA elevation were also associated with the prognosis of stage III colon cancer patients (all P<0.05). Multivariate analysis revealed that TD presence (HR=1.957, 95%CI: 1.269-3.017, P=0.002) and TD number (HR=8.020, 95% CI: 3.414-18.842, P<0.001) were still independent risk factors for the prognosis of patients with stage III colon cancer.According to the TD number counted as metastatic lymph nodes, in 78 patients with TD, 24 patients were upstaged in N stage, and 16 patients upstaged from TNM stage IIIB to stage IIIC. For 16 stage IIIB cases with staging modification, 30 unadjusted stage IIIB cases with TD, and 148 stage IIIB cases without TD, the 5-year OS was 37.5%, 73.3% and 76.4%, respectively with significant difference (P<0.001). However, for 16 patients adjusted as stage IIIC (mTNM), 32 patients with unchanged stage IIIC with TD (TNM, AJCC 8th edition), and 63 stage IIIC cases without TD, the 5-year OS was 37.5%, 36.4%, and 41.3%, respectively without significant difference (P=0.707). Conclusions: TD presence and TD number are independent risk factors for prognosis of stage III colon cancerpatients. TNM staging evaluation with lymph node number including TD number can predict the prognosis of patients more accurately.


Assuntos
Neoplasias do Colo/patologia , Extensão Extranodal/patologia , Estadiamento de Neoplasias/métodos , Neoplasias do Colo/cirurgia , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
17.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(11): 1034-1040, 2019 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-31770834

RESUMO

Objective: To investigate the safety and efficacy of surgical treatment for chronic radiation intestinal injury. Methods: A descriptive cohort study was performed. Clinical data of 73 patients with definite radiation history and diagnosed clinically as chronic radiation intestinal injury, undergoing operation at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 1, 2012 to February 28, 2019, were reviewed and analyzed retrospectively. Patients did not undergo operation or only received adhesiolysis were excluded. All the patients had preoperative examination and overall evaluation of the disease. According to severity of intestinal obstruction and patients' diet, corresponding nutritional support and conservative treatment were given. Surgical methods: The one-stage bowel resection and anastomosis was the first choice for surgical treatment of chronic radiation intestinal injury. Patients with poor nutritional condition were given enterostomy and postoperative enteral nutrition and second-stage stoma closure and intestinal anastomosis if nutritional condition improved. For those who were unable to perform stoma closure, a permanent stoma should be performed. Patients with severe abdominal adhesion which was difficult to separate, enterostomy or bypass surgery after adhesiolysis would be the surgical choice. For patients with tumor metastasis or recurrence, enterostomy or bypass surgery should be selected. Observation parameters: the overall and major (Clavien-Dindo grades III to V) postoperative complication within 30 days after surgery or during hospitalization; mortality within postoperative 30 days; postoperative hospital stay; time to postoperative recovery of enteral nutrition; time to removal of drainage tube. Results: Of the 73 patients who had been enrolled in this study, 10 were male and 63 were female with median age of 54 (range, 34-80) years. Preoperative evaluation showed that 61 patients had intestinal stenosis, 63 had intestinal obstruction, 11 had intestinal perforation, 20 had intestinal fistula, 3 had intestinal bleeding, and 6 had abdominal abscess, of whom 64(87.7%) patients had multiple complications. Tumor recurrence or metastasis was found in 15 patients. A total of 65(89.0%) patients received preoperative nutritional support, of whom 35 received total parenteral nutrition and 30 received partial parenteral nutrition. The median preoperative nutritional support duration was 8.5 (range, 6.0-16.2) days. The rate of one-stage intestine resection was 69.9% (51/73), and one-stage enterostomy was 23.3% (17/73). In the 51 patients undergoing bowel resection, the average length of resected bowel was (50.3±49.1) cm. Among the 45 patients with intestinal anastomosis, 4 underwent manual anastomosis and 41 underwent stapled anastomosis; 36 underwent side-to-side anastomosis, 5 underwent end-to-side anastomosis, and 4 underwent end-to-end anastomosis. Eighty postoperative complications occurred in 39 patients and the overall postoperative complication rate was 53.4% (39/73), including 39 moderate to severe complications (Clavien-Dindo grade III-V) in 20 patients (27.4%, 20/73) and postoperative anastomotic leakage in 2 patients (2.7%, 2/73). The mortality within postoperative 30 days was 2.7% (2/73); both patients died of abdominal infection, septic shock, and multiple organ failure caused by anastomotic leakage. The median postoperative hospital stay was 13 (11, 23) days, the postoperative enteral nutrition time was (7.2±6.9) days and the postoperative drainage tube removal time was (6.3±4.2) days. Conclusions: Surgical treatment, especially one-stage anastomosis, is safe and feasible for chronic radiation intestine injury. Defining the extent of bowel resection, rational selection of the anatomic position of the anastomosis and perioperative nutritional support treatment are the key to reduce postoperative complications.


Assuntos
Enteropatias/cirurgia , Lesões por Radiação/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Fístula Anastomótica/etiologia , Doença Crônica , Enterostomia , Feminino , Humanos , Enteropatias/etiologia , Intestinos/efeitos da radiação , Intestinos/cirurgia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estado Nutricional , Lesões por Radiação/complicações , Estudos Retrospectivos , Resultado do Tratamento
18.
Acta Endocrinol (Buchar) ; -5(1): 25-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31149056

RESUMO

OBJECTIVE: In this study we investigated the effect of dorsomedial hypothalamus (DMH) neuropeptide Y (NPY) knock-down on hepatic insulin sensitivity in high-fat (HF) diet-fed rats. METHODS: Forty-eight Sprague-Dawley rats were randomly assigned to receive bilateral DMH injections of adeno-associated virus AAVshNPY or AAVshCTL and then accessed to regular chow. Five weeks after viral injection, half rats in each group were given access to the HF diet. At 16 weeks, rat livers were collected. Insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) mRNA expression was measured by qRT-PCR. Blood glucose levels were measured by the oxidase method, serum insulin, triglyceride, and TC levels were measured by Elisa. Pathological changes in the liver were assessed by hematoxylin-eosin (HE) staining. AKT, p-AKT, and GSK-3 levels were measured by western blotting. RESULTS: Compared with AAVshCTL-injected rats, AAVshNPY-injected rats showed a significant decrease in blood glucose concentrations; serum insulin, triglyceride, and TC; HOMA-IR; and IRS-1 and PI3K mRNA levels (P<0.05). ISI, GSK-3, and p-AKT levels were significantly increased (P<0.05). HE staining showed that AAVshNPY-injected rats fed the HF diet had mild fatty degeneration. CONCLUSION: These results suggest that DMH NPY knock-down improves hepatic insulin sensitivity in HF diet-fed rats by activating the hepatic PI3K/AKT insulin signalling pathway.

19.
Zhonghua Zhong Liu Za Zhi ; 41(5): 346-350, 2019 May 23.
Artigo em Chinês | MEDLINE | ID: mdl-31137167

RESUMO

Objective: To explore the feasibility of 7, 12-dimethylbenz[a] anthracene (DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods: A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg/kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg/kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg/kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor (PR), cytokeratin5/6 (CK5/6) and human epidermal factor receptor-2 (HER-2) was detected by immunohistochemical staining. Results: In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0% (4/20) tumor formation rate. The success rate of mammary cancer modeling was 10.0% (2/20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0% (9/20) tumor formation rate. The success rate of mammary cancer modeling was 40.0% (8/20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P>0.05) between the two groups (all P>0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P<0.05), whereas the tumor formation time was markedly shorter than that in the gavage group (P<0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER-2 but positive expression of ER, PR and CK5/6 with varying degrees. Conclusion: Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.


Assuntos
9,10-Dimetil-1,2-benzantraceno/toxicidade , Neoplasias da Mama/patologia , Modelos Animais de Doenças , Neoplasias Mamárias Experimentais/induzido quimicamente , 9,10-Dimetil-1,2-benzantraceno/administração & dosagem , Administração Oral , Animais , Neoplasias da Mama/induzido quimicamente , Carcinógenos/administração & dosagem , Carcinógenos/toxicidade , Feminino , Injeções , Distribuição Aleatória , Tupaiidae
20.
Zhonghua Yi Xue Za Zhi ; 98(46): 3751-3755, 2018 Dec 11.
Artigo em Chinês | MEDLINE | ID: mdl-30541216

RESUMO

Objective: To investigate the expression of factor that binds to inducer of short transcripts-1 of HIV (FBI-1)in breast cancer pre- and pro-neoadjuvant chemotherapy and explore the relationship between FBI-1 expression and treatment efficacy. Methods: We collected 50 patients with breast cancer who received neoadjuvant chemotherapy before operation in the Affiliated Tumor Hospital of Guangxi Medical University from January, 2010 to December, 2014. The expression of FBI-1 in breast cancer tissues pre- and pro-neoadjuvant chemotherapy was detected by immunohistochemical staining. We compared the level of FBI-1 expression pre- and pro-neoadjuvant chemotherapy, and tried to explore its relationship with patient and tumor characteristics and treatment efficacy. Results: (1) The rate of upregulated expression of FBI-1 in breast cancer tissues was 70% (35/50). The upregulated expression of FBI-1 was related to the higher clinical stage and trend of lymph node metastasis (P<0.05), whereas not related to the age and expression of ER, PR, Ki-67, and Her-2(P>0.05); (2) the setting of FBI-1 lower expression pre-neoadjuvant chemotherapy had superior treatment outcome than the high expression setting based on either clinical assessment (86.7% vs 51.4%, P=0.027) or pathological assessment(80.0% vs 28.6%, P=0.001); (3) the rate of upregulated FBI-1 expression was significantly decreased post-neoadjuvant chemotherapy(70.0% vs 38.0%, P=0.004), with FBI-1 expression of 22 patients downregulated (62.9%); (4) the expression of FBI-1 in responded setting was significantly decreased than that in the non-responded setting based on either clinical (77.4% vs 26.3%, P=0.001) or pathological (72.7% vs 39.3%, P=0.024) assessment. The downregulation of FBI-1 was correlated to either clinical efficacy (r=0.440, P<0.01) or pathological efficacy (r=0.491, P<0.05) of neoadjuvant chemotherapy. Conclusion: In breast cancer patients receiving neoadjuvant chemotherapy, the upregulated expression of FBI-1 in breast cancer lesion is associated with clinical stage and lymph node metastasis. The neoadjuvant chemotherapy can significantly reduce the expression of FBI-1. The upregulated expression of FBI-1 may be predictive of resistance to chemotherapeutic drugs, and has predictive value for the efficacy of neoadjuvant chemotherapy in breast cancer patients.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/terapia , China , Feminino , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Receptor ErbB-2
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