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Telomeric repeat-containing RNA (TERRA) is closely involved in the regulation of telomere length, which plays critical roles in tumorigenesis. However, the biological significance of TERRA in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we found that HCC cells show a frequent downregulation of TERRA and its positive regulator TTAGGG repeat binding factor-1 (TRF1), whereas the negative regulator TTAGGG repeat binding factor-1 (TRF2) was upregulated. We found that TERRA, TRF1, and TRF2 contributed to poor prognosis of HCC patients. Importantly, we found that the downregulation of TERRA significantly promoted HCC cell growth and metastasis in vitro and in vivo, whereas the upregulation of TERRA showed an opposite effect. Mechanistically, downregulation of TERRA significantly increased telomerase activity and promoted telomere elongation. Moreover, the inhibitory effects of TERRA overexpression on the growth and metastasis of HCC cells were reversed by treatment with TA-65 that activates telomerase activity. In contrast, the protumor effect of TERRA downregulation was reversed by treatment with TMPyP4 that inhibits telomerase activity. Our findings reveal that TERRA plays a critical role in HCC cell growth and metastasis, indicating that TERRA is a potential therapeutic target for HCC.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , ARN Largo no Codificante/metabolismo , Telomerasa/genética , Telómero/metabolismo , Animales , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Enfermedad , Progresión de la Enfermedad , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Hígado/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Ratones , Complejo Shelterina , Telomerasa/metabolismo , Proteínas de Unión a Telómeros/genética , Proteínas de Unión a Telómeros/metabolismo , Proteína 2 de Unión a Repeticiones Teloméricas/genética , Proteína 2 de Unión a Repeticiones Teloméricas/metabolismo , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: This study aims to identify risk factors for central nervous system (CNS) infection in elderly patients hospitalized with traumatic brain injury (TBI) and to develop a reliable predictive tool for assessing the likelihood of CNS infection in this population. METHOD: We conducted a retrospective study on 742 elderly TBI patients treated at Tangdu Hospital, China. Clinical data was randomly split into training and validation sets (7:3 ratio). By conducting univariate and multivariate logistic regression analysis in the training set, we identified a list of variables to develop a nomogram for predicting the risk of CNS infection. We evaluated the performance of the predictive model in both cohorts respectively, using receiver operating characteristics curves, calibration curves, and decision curve analysis. RESULTS: Results of the logistic analysis in the training set indicated that surgical intervention (P = 0.007), red blood cell count (P = 0.019), C-reactive protein concentration (P < 0.001), and cerebrospinal fluid leakage (P < 0.001) significantly predicted the occurrence of CNS infection in elderly TBI patients. The model constructed based on these variables had high predictive capability (area under the curve-training = 0.832; area under the curve-validation = 0.824) as well as clinical utility. CONCLUSIONS: A nomogram constructed based on several key predictors reasonably predicts the risk of CNS infection in elderly TBI patients upon hospital admission. The model of the nanogram may contribute to timely interventions and improve health outcomes among affected individuals.
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Lesiones Traumáticas del Encéfalo , Infecciones del Sistema Nervioso Central , Anciano , Humanos , Nomogramas , Estudios Retrospectivos , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico , Factores de RiesgoRESUMEN
Severe traumatic brain injury (sTBI) is a prominent contributor to both morbidity and mortality in the elderly population. The monitoring of intracranial pressure (ICP) is crucial in the management of sTBI patients. Nevertheless, the appropriate timing for the placement of ICP monitor in elderly sTBI patients remains uncertain. To determine the optimal timing for the placement of ICP monitor in elderly sTBI patients, in this retrospective cohort study, we collected data from elderly patients (> 65 years) who suffered sTBI and received ICP monitors at Tangdu Hospital, The Fourth Military Medical University, between January 2011 and December 2021. To examine the relationship between the time of ICP monitor placement and in-hospital mortality, we conducted a multi-variate-adjusted restricted cubic spline (RCS) analysis. Additionally, logistic regression analysis was applied to further analyze the influencing factors contributing to early or late ICP monitor placements. A total of 283 eligible elderly TBI patients were included in the current analysis. The in-hospital mortality rate was 73 out of 283 (26%). The RCS analysis demonstrated an inverted U-shaped curve in the relationship between the timing of ICP monitor placement and in-hospital mortality. For the elderly sTBI patient cohort, 6 h was identified as the crucial moment for the treatment strategy. In addition, the protective time window for ICP placement was less than 4.92 h for the GCS 3-5 group, and less than 8.26 h for the GCS 6-8 group. However, the clinical benefit of ICP placement decreased gradually over time. The relationship between ICP placement and in-hospital mortality was non-linear, exhibiting an inverted U-shaped curve in elderly patients with sTBI. For elderly patients with sTBI, early (≤ 6 h) ICP placement was associated with reduced in-hospital mortality. The clinical benefit of ICP placement decreased beyond the optimal time window.
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OBJECTIVE: To explore mortality risk factors and to construct an online nomogram for predicting in-hospital mortality in traumatic brain injury (TBI) patients receiving invasive mechanical ventilation (IMV) in intensive care unit (ICU). METHODS: We retrospectively analysed TBI patients on IMV in ICU from MIMIC-â £ database and two hospitals. Least Absolute Shrinkage and Selection Operation (LASSO) regression and multiple logistic regression were used to detect predictors of in-hospital mortality and to construct an online nomogram. The predictive performance of nomogram was evaluated using area under the receiver operating characteristic curves (AUC), calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). RESULTS: 510 from MIMIC-â £ database were enrolled for nomogram construction (80%, n=408) and internal validation (20%, n=102). 185 from two hospitals were enrolled for external validation. LASSO-Logistic regression revealed predictors of in-hospital mortality among TBI patients on IMV in ICU included Glasgow Coma Scale (GCS) after ICU admission, Acute Physiology Score â ¢ (APS â ¢) after ICU admission, neutrophil and lymphocyte ratio after IMV, blood urea nitrogen after IMV, arterial serum lactate after IMV, and in-hospital tracheotomy. The AUC, calibration curves, DCA, and CIC indicated the nomogram had good discrimination, calibration, clinical benefit, and applicability. The multi-model comparisons revealed the nomogram had higher AUC than GCS, APS â ¢, and Simplified Acute Physiology Score â ¡. CONCLUSION: We constructed and validated an online nomogram based on routinely recorded factors at admission to ICU and at the beginning of IMV to target prediction of in-hospital mortality among TBI patients on IMV in ICU.
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OBJECTIVE: To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram. METHODS: Data from elderly individuals (age ≥65 years) histologically diagnosed with brain glioma were sourced from the Surveillance, Epidemiology, and End Results (SEER) database. The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio. Additionally, data obtained from Tangdu Hospital constituted an external validation cohort for the study. The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis, enabling the construction of a nomogram. Model performance was evaluated using C-index, ROC curves, calibration plot and decision curve analysis (DCA). RESULTS: A cohort of 20 483 elderly glioma patients was selected from the SEER database. Five prognostic factors (age, marital status, histological type, stage, and treatment) were found to significantly impact overall survival (OS) and cancer-specific survival (CSS), with tumor location emerging as a sixth variable independently linked to CSS. Subsequently, nomogram models were developed to predict the probabilities of survival at 6, 12, and 24 months. The assessment findings from the validation queue indicate a that the model exhibited strong performance. CONCLUSION: Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients. They can potentially assist in risk stratification and clinical decision-making.
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Neoplasias Encefálicas , Glioma , Nomogramas , Programa de VERF , Humanos , Glioma/mortalidad , Glioma/patología , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Femenino , Masculino , Factores de Riesgo , Pronóstico , Anciano de 80 o más Años , Curva ROCRESUMEN
Objective: Awake craniotomy with intraoperative brain functional mapping effectively reduces the potential risk of neurological deficits in patients with glioma invading the eloquent areas. However, glioma patients frequently present with impaired neurocognitive function. The present study aimed to investigate the neurocognitive and functional outcomes of glioma patients after awake brain mapping and assess the experience of a tertiary neurosurgical center in China over eight years. Methods: This retrospective study included 80 patients who underwent awake brain mapping for gliomas invading the eloquent cortex between January 2013 and December 2021. Clinical and surgical factors, such as the extent of resection (EOR), perioperative Karnofsky Performance Score (KPS), progression-free survival (PFS), and overall survival (OS), were evaluated. We also used the Montreal Cognitive Assessment (MoCA) to assess the neurocognitive status changes. Results: The most frequently observed location of glioma was the frontal lobe (33/80, 41.25%), whereas the tumor primarily invaded the language-related cortex (36/80, 45%). Most patients had supratotal resection (11/80, 13.75%) and total resection (45/80, 56.25%). The median PFS was 43.2 months, and the median OS was 48.9 months in our cohort. The transient (less than seven days) neurological deficit rate was 17.5%, whereas the rate of persistent deficit (lasting for three months) was 15%. At three months of follow-up, most patients (72/80, 90%) had KPS scores > 80. Meanwhile, compared to the preoperative baseline tests, the changes in MoCA scores presented significant improvements at discharge and three months follow-up tests. Conclusion: Awake brain mapping is a feasible and safe method for treating glioma invading the eloquent cortex, with the benefit of minimizing neurological deficits, increasing EOR, and extending survival time. The results of MoCA test indicated that brain mapping plays a critical role in preserving neurocognitive function during tumor resection.
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OBJECTIVE: The classification of central nervous system (CNS) tumors has changed greatly. The Central Brain Tumor Registry of the United States (CBTRUS) and other institutions have analyzed the incidence rate and characteristics of primary CNS tumors. However, there are limited studies analyzing the incidence rate and characteristics of CNS tumors in China. To better understand CNS tumors in China, we summarized all primary CNS tumors diagnosed pathologically in a single center from 2003 to 2019. METHODS: All patients with primary CNS tumors who underwent neurosurgery at our hospital from January 2003 to December 2019 were included in this study. The data were collected from the hospital information system, including diagnosis time, age, gender, anatomic sites, and pathologic results. RESULTS: A total of 17,226 cases of primary CNS tumors were retrospectively analyzed in this study. Among all cases, the major tumor types included meningiomas, tumors of neuroepithelial tissue, and pituitary adenomas. Most tumors of neuroepithelial tissue were glioblastoma and astrocytoma. Most tumors of neuroepithelial tissue were located in the frontal lobe. However, grade 4 tumors of neuroepithelial tissue were more common in the temporal lobe. The median age of all patients was 46 years. The incidence of CNS tumors was higher in women than in men. CONCLUSIONS: Based on this data set, we analyzed various parameters of CNS tumors and found that grade 4 tumors of neuroepithelial tissue were more common in the temporal lobe, which were rarely reported in previous articles.
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Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Neoplasias Meníngeas , Masculino , Humanos , Femenino , Estados Unidos , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias del Sistema Nervioso Central/epidemiología , Neoplasias del Sistema Nervioso Central/cirugía , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/patología , China/epidemiología , IncidenciaRESUMEN
Objective: Traumatic brain injury (TBI) is a global social, economic, and health challenge that is associated with premature death and long-term disability. In the context of rapid development of urbanization, the analysis of TBI rate and mortality trend could provide abundant diagnosis and treatment suggestions, which helps to form future reference on public health strategies. Methods: In this study, as one of major neurosurgical centers in China, we focused on the regime shift of TBI based on 18-year consecutive clinical data and evaluated the epidemiological features. In our current study, a total of 11,068 TBI patients were reviewed. Results: The major cause of TBI was road traffic injuries (44.%), while the main type of injury was cerebral contusion (n = 4,974 [44.94%]). Regarding to temporal changes, a decreasing trend in TBI incidence for patients under 44 years old was observed, while an increasing trend for those aged over 45 years was indicated. Incidences of RTI and assaults decreased, while ground level fall presented increasing incidences. The total number of deaths was 933 (8.43%), with a decreasing trend in overall mortality since 2011. Age, cause of injury, GCS at admission, Injury Severity Score, shock state at admission, trauma-related diagnoses and treatments were significantly associated with mortality. A predictive nomogram model for poor prognosis was developed based on patient's GOS scores at discharge. Conclusions: The trends and characteristics of TBI patients changed with rapid development of urbanization in the past 18 years. Further larger studies are warranted to verify its clinical suggestions.
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Introduction: Secondary gliosarcomas (SGS) are rare malignancies that are diagnosed subsequent to pre-existing glioma. Clinical features and optimal treatment strategies for SGS have not been conclusively established. This study aimed to assess the clinicopathological features and outcomes of SGS. Methods: We assessed the clinicopathological features and outcomes of SGS via retrospective analysis of data for SGS patients at Tangdu Hospital. Data from SGS patients in prior publications were also analyzed in accordance with PRISMA guidelines. Results: Eighteen SGS patients who had been treated at Tangdu Hospital between 2013 and 2020 were enrolled in this study. Additional 89 eligible SGS patients were identified from 39 studies. The median age for the patients was 53 years old, and the most common location was the temporal lobe. The most common initial diagnosis was glioblastoma (GBM) (72.0%). Radiology revealed enhanced masses in 94.8% (73/77) of patients. Ten patients (10/107, 9.35%) had extracranial metastases at or after SGS diagnosis. Patients with initial diagnosis of non-GBM and who were younger than 60 years of age were significantly associated with a long duration of disease progression to SGS. After SGS diagnosis, patients with initial non-GBM diagnosis, gross total resection and chemoradiotherapy exhibited prolonged survival outcomes. Patients who had been initially diagnosed with GBM and received both chemoradiotherapy and active therapy after disease progression to SGS, had a significantly longer overall survival than patients who did not. Conclusion: Initial diagnosis of GBM was a poor prognostic factor for SGS. Patients who underwent gross total resection and chemoradiation had better overall survival outcomes than those who did not. However, during treatment, clinicians should be cognizant of possible extracranial metastases.
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Background: CNS tumors, particularly gliomas, are associated with a high rate of disability and lethality, and are typically diagnosed with histopathology and immunohistochemistry. Our research aims to develop a minimally invasive method for diagnosing, grading and molecular typing glioma. Methods: We collected patients who underwent surgery for glioma, Trigeminal neuralgia/Hemifacial spasm, schwannoma, pituitary adenomas and meningioma at our hospital from June 2019 to June 2021. Preoperative WBCs, neutrophils, lymphocytes, monocytes, platelet counts and albumin levels were collected. Preoperative NLR, dNLR, PLR, LMR and PNI were calculated, and the correlation between them and glioma diagnosis as well as grading was analyzed. We also evaluated the diagnostic significance of NLR, dNLR, PLR, LMR, PNI and their combinations for gliomas, particularly GBM, as well as the diagnostic significance of IDH molecular typing of gliomas. Results: There were 182 healthy samples and 3101 diseased samples in our study. Compared with other groups, glioma patients had significantly higher preoperative NLR, dNLR and PLR values, but lower LMR and PNI values. Further analysis showed that NLR, dNLR, and PLR were positively correlated with glioma grading, while LMR and PNI were negatively correlated with glioma grading. For the diagnosis of glioma, NLR showed a maximum AUC value of 0.8099 (0.7823-0.8374). For GBM, NLR showed a maximum AUC value of 0.9585 (0.9467-0.9703). In the combination, NLR+dNLR showed the highest AUC value of 0.8070(0.7849-0.8291). NLR showed significant statistical significance in all grades of glioma IDH molecular typing, while PLR did not show statistical significance. Conclusions: NLR has the greatest value for the diagnosis, differential diagnosis, grading and molecular typing of gliomas. The NLR+dNLR combination also showed high sensitivity and specificity. We believe that inflammatory parameters may serve as economical and specific markers for glioma diagnosis, grading, molecular typing, and progression.
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Objective: To design a multidisciplinary enhanced recovery after surgery (ERAS) protocol for glioma patients undergoing elective craniotomy and evaluate its clinical efficacy and safety after implementation in a tertiary neurosurgical center in China. Methods: ERAS protocol for glioma patients was developed and modified based on the best available evidence. Patients undergoing elective craniotomy for treatment of glioma between September 2019 to May 2021 were enrolled in a randomized clinical trial comparing a conventional neurosurgical perioperative care (control group) to an ERAS protocol (ERAS group). The primary outcome was postoperative hospital length of stay (LOS). Secondary outcomes were 30-day readmission rate, postoperative complications, duration of the drainage tube, time to first oral fluid intake, time to ambulation and functional recovery status. Results: A total of 151 patients were enrolled (ERAS group: n = 80; control group: n = 71). Compared with the control group, postoperative LOS was significantly shorter in the ERAS group (median: 5 days vs. 7 days, p<0.0001). No 30-day readmission or reoperation occurred in either group. The time of first oral intake, urinary catheter removal within 24 h and early ambulation on postoperative day (POD) 1 were earlier and shorter in the ERAS group compared with the control group (p<0.001). No statistical difference was observed between the two groups in terms of surgical- and nonsurgical-related complications. Functional recovery in terms of Karnofsky Performance Status (KPS) scores both at discharge and 30-day follow-up was similar in the two groups. Moreover, no significant difference was found between the two groups in the Hospital Anxiety and Depression Scale (HADS) scores. Conclusion: The implementation of the ERAS protocol for glioma patients offers significant benefits over conventional neurosurgical perioperative management, as it is associated with enhancing postoperative recovery, without additional perioperative complications and risks. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=42016), identifier ChiCTR1900025108.
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Glioma is the most common primary malignant brain tumor in adults with very poor prognosis. The limited new therapeutic strategies for glioma patients can be partially attributed to the complex tumor microenvironment. However, knowledge about the glioma immune microenvironment and the associated regulatory mechanisms is still lacking. In this study, we found that, different immune subtypes have a significant impact on patient survival. Glioma patients with a high immune response subtype had a shorter survival compared with patients with a low immune response subtype. Moreover, the number of B cell, T cell, NK cell, and in particular, the macrophage in the immune microenvironment of patients with a high immune response subtype were significantly enhanced. In addition, 132 genes were found to be related to glioma immunity. The functional analysis and verification of seven core genes showed that their expression levels were significantly correlated with the prognosis of glioma patients, and the results were consistent at tissue levels. These findings indicated that the glioma immune microenvironment was significantly correlated with the prognosis of glioma patients and multiple genes were involved in regulating the progression of glioma. The identified genes could be used to stratify glioma patients based on immune subgroup analysis, which may guide their clinical treatment regimen.
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Neoplasias Encefálicas , Glioma , Adulto , Neoplasias Encefálicas/patología , Glioma/patología , Humanos , Inmunofenotipificación , Pronóstico , Microambiente Tumoral/genéticaRESUMEN
Intradural extramedullary bronchogenic cysts (IEBC) are rare congenital cystic lesions. The clinical manifestations, radiological characteristics, especially the optimal treatment regimen are not well-understood. We retrospectively analyzed a series of patients with confirmed IEBC in Tangdu hospital and reviewed the published works to gain a comprehensive understanding of IEBC. In our institution, nine consecutive patients had pathologically confirmed IEBC between 2005 and 2018. We also identified 27 patients from previous studies. The most common presentations on magnetic resonance imaging (MRI) were hypointensity on T1-weighted images (T1WI), hyperintensity on T2-weighted images(T2WI), and no improvement on T1WI contrast-enhanced with gadolinium (94.4%). All patients in our center and the patients we reviewed received surgical resection; gross total resection (GTR) and partial resection (PR) were achieved in 20 (55.6%) and 16 (44.4%) patients, respectively. The symptom remission rate of patients who underwent GTR was 100%, which was similar to those who underwent PR (93.8%) (P = 0.457). The recurrence rate was 12.5% in the group who underwent PR and nil after GTR (P = 0.202). According to our current investigation, the surgical resection degree is irrelevant to the symptom remission rate. Therefore, we suggest that total resection should not be recommended for cases with tight adhesion. For patients with PR, longer follow-up will be necessary to determine the long-term outcome.
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Glioblastoma (GBM) is the most common primary malignant intracranial tumor and the median age at diagnosis is 65 years. However, elderly patients are usually excluded from clinical studies and age is considered as an independent negative prognostic factor for patients with GBM. Therefore, the best treatment method for GBM in elderly patients has remained controversial. Elderly GBM patients (≥ 60 years old) treated between January 2015 and December 2019 were enrolled in this study. Medical records were reviewed retrospectively, and clinicopathological characteristics, treatments, and outcomes were analyzed. A total of 68 patients were included, with a median age of 65.5 years (range: 60-79). The median preoperative Karnofsky performance scale (KPS) score was 90 (range 40-100) and median postoperative KPS score was 80 (range 0-90). Univariate analysis results showed that age, gender, comorbidities, preoperative KPS < 90 and MGMT promoter methylation were not significantly associated with PFS and OS. On the other hand, total resection, postoperative KPS ≥ 80, Ki67 > 25%, and Stupp-protocol treatment were significantly associated with prolonged PFS and OS. Moreover, multivariate analysis found that postoperative KPS ≥ 80, total resection, and Stupp-protocol treatment were prognostic factors for PFS and OS. The findings of this study have suggested that, on the premise of protecting function as much as possible, the more aggressive treatment regimens may prolong survival for elderly patients with GBM. However, further studies, particularly prospective randomized clinical trials, should be conducted to provide more definitive data on the appropriate management of elderly patients, especially for patients with MGMT promoter methylation.
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PURPOSE: Glioma is one of the most common tumors of the central nervous system, and many patients suffer from recurrence even after standard comprehensive treatment. However, little is known about the molecular markers that predict the recurrence patterns of glioma. This study aimed to demonstrate the correlations between molecular markers and glioma recurrence patterns, which included local/nonlocal recurrence and paraventricular/nonparaventricular recurrence. METHODS: Immunohistochemical techniques were used to assess the molecular markers of 88 glioma tissues following surgical resection. The recurrence patterns were divided into local recurrence, marginal recurrence, distant recurrence, multirecurrence, and subarachniod recurrence, with the last four recurrence patterns being collectively called nonlocal recurrence. According to whether the recurrence invaded ventricles, the nonlocal recurrence patterns were divided into paraventricular and nonparaventricular recurrence. Then, we compared the different recurrence patterns and their clinical characteristics, focusing on the expression of molecular markers. RESULTS: More patients in the nonlocal recurrence group received combined radiotherapy and chemotherapy than patients in the local recurrence group (p=0.019). Sex, age, extent of surgery, time to recurrence, tumor location, size, and WHO grade were not different in the defined groups (P>0.05). Recurrent tumor volume and WHO grade were significantly different between the paraventricular and nonparaventricular recurrence groups (p=0.046 and 0.033). The expression of Ki-67, P53, and PCNA in the nonlocal recurrence group was significantly higher than that in the local recurrence group (p=0.015, 0.009, and 0.037), while the expression of S-100 in the nonlocal recurrence group was significantly lower than that in the local recurrence group (p=0.015). Cox regression indicated hazard ratio (HR) for high expression level of PCNA associated with non-local recurrence was 3.43 (95% CI, 1.15, 10.24), and HR for high expression level of MGMT associated with paraventricular recurrence was 2.64 (95% CI, 1.15,6.08). CONCLUSIONS: Ki-67, P53, PCNA, and MGMT might be important clinical markers for nonlocal recurrence and paraventricular recurrence.
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PURPOSE: Diffuse midline gliomas (DMG) with H3K27M mutations have been identified as a rare distinctive entity with unique genetic features, varied molecular alterations, and poor prognosis. The current study aimed to evaluate the clinical characteristics and profile of molecular markers on patients with a DMG harboring H3K27M mutations, and explore the impact of this genetic makeup on overall survival. METHODS: We retrospectively analyzed 43 consecutive patients diagnosed with a DMG harboring H3K27M mutations (age range 3 to 75 years) and treated in a tertiary institution within China between January 2017 to December 2019. Various clinical and molecular factors were evaluated to assess their prognostic value in this unique patient cohort. RESULTS: The median overall survival (OS) was 12.83 months. Preoperative Karnofsky Performance Score (KPS) and adjuvant radiotherapy were found to be independent clinical parameters influencing the OS by multivariate analysis (p = 0.027 and p < 0.001 respectively). Whereas extent of tumor resection failed to demonstrate statistical significance. For molecular markers, P53 overexpression was identified as a negative prognostic factor for overall survival by multivariate analysis (p = 0.030). CONCLUSION: Low preoperative KPS, absence of radiotherapy and P53 overexpression were identified as predictors of a dismal overall survival in patients with DMG and H3K27M mutations.
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Aims: To assess the feasibility, safety, 1-year postoperative quality of life, and 2-year postoperative local recurrence of b-shaped laparoscopic dual anastomosis (bSLDA) technique in laparoscopic anterior resection (LAR) for mid-low rectal cancer. Methods: In this case-matched study, we retrospectively reviewed the database of 120 patients with mid-low rectal cancer who underwent LAR in Tangdu hospital between June 2014 and January 2017. The database included baseline characteristics, operative data and short-term outcomes, specimen, and pathological results. Among all the participants, 60 patients underwent bSLDA and 60 patients underwent conventional laparoscopic dual anastomosis (CLDA). After lymph node dissection and rectal dissociation, patients in the bSLDA group received the operation as follows: (1) the rectum distal end was closed vertically instead of horizontally; (2) the anastomosis was conducted in an end-lower corner of rectal stump. We also performed at least 2 years of follow-up (the median follow-up was 36 months, ranging from 24 to 54 months), including 2-year recurrence scores, 1-year low anterior resection syndrome (LARS) scores, and QLQ-C30 scores. Results: In this case-matched study, there were no differences between bSLDA group and CLDA group in operative data and short-term outcomes, which suggested that bSLDA and CLDA were equally safe. Furthermore, compared with CLDA group, bSLDA group had no statistical difference in the rate of anastomotic leakage (AL), but there was a trend that the rate in bSLDA was lower. In postoperative specimen data, the maximum and minimum edge distances of the ring from the rectal stump are longer in the bSLDA group. What is more, in the EORTC QLQ-C30 (version 3.0), the diarrhea score in bSLDA group was statistically lower (better) than in CLDA group (P = .043). Although bSLDA group had no significant differences in the LARS scores with CLDA group, there was a trend that the LARS scores were lower in bSLDA. At last, the 2-year local recurrence rate in both groups was not significantly different. Conclusions: The bSLDA technique is safe and accessible, which may reduce the incidence of AL to some extent. Therefore, it could be an alternative to laparoscopic proctectomy for mid-low rectal cancer and may also improve postoperative quality of life for many patients.
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Fuga Anastomótica/prevención & control , Laparoscopía/métodos , Estadificación de Neoplasias , Neoplasias del Recto/cirugía , Recto/cirugía , Adolescente , Anciano , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/epidemiología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Neoplasias del Recto/diagnóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To investigate the application value of the Overlap method in digestive tract reconstruction of totally laparoscopic left colectomy(TLLC) and its potential advantage. METHODS: The retrospective cohort study was adopted. Clinicopathological data of 16 patients with left colon cancer who underwent TLLC and Overlap anastomosis between August 2016 and August 2017 at Tangdu Hospital were retrospectively collected as Overlap group. Twenty-one patients who underwent laparoscopic assisted left colectomy (LALC) between January 2015 and July 2016 at Tangdu Hospital were used as control (traditional group). The intraoperative and postoperative data were compared between the two groups. During digestive tract reconstruction in the Overlap group, the proximal colon and distal colon were lined up side by side; a side-to-side anastomosis was conducted on colic band with a 60 mm linear stapler; and the common entry hole was closed using running suture. While in traditional group, the bowel was pulled out of abdominal wall through the assisted incision; the sample was resected and a proximal and distal end-to-end anastomosis was performed. RESULTS: In Overlap group, 10 cases were male and 6 cases were female, with a mean age of (66.4±4.8) years and a BMI of (23.6±2.3) kg/m2; the tumor located in distal transverse colon in 1 case, in splenic flexure in 2 cases, in descending colon in 4 cases, in upper sigmoid colon in 9 cases. TLLC was successfully completed in all the cases without conversion to laparotomy. In traditional group, 12 cases were male and 9 cases were female, with mean age of (65.9±5.8) years and BMI of (22.7±2.8) kg/m2; the tumor located in the distal transverse colon in 1 case, in the splenic flexure in 3 cases, in the descending colon in 6 cases, in the upper sigmoid colon in 11 cases. No statistically significant differences in baseline data were found between the two groups (all P>0.05). Compared to the traditional group, the total operation time was shorter [(143.4±11.1) minutes vs. (166.4±16.5) minutes, t=4.792, P=0.000], the anastomosis time was prolonged [(44.3±3.3) minutes vs. (22.4±3.0) minutes, t=-20.948, P=0.000], the amount of bleeding was reduced [(46.6±13.6) ml vs. (70.5±20.0) ml, t=4.106, P=0.000], and the incision length was shorter [(3.9±0.9) cm vs. (6.7±1.3) cm, t=7.056, P=0.000] in the Overlap group. There were no significant differences in lymph nodes harvested (17.3±2.9 vs. 15.5±3.0), time to flatus [(2.8±1.3) days vs. (2.6±1.0)days], postoperative complications [6.2%(1/16) vs. 9.5%(2/21)] and postoperative hospitalization [(4.6±1.4) days vs.(4.7±1.2) days] between the two groups (all P>0.05). CONCLUSION: The Overlap reconstruction method in totally laparoscopic left colectomy is a safe and feasible procedure, and provides less injury and better cosmetic outcome of abdominal wall.
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Colectomía , Neoplasias del Colon/cirugía , Laparoscopía , Anciano , Femenino , Humanos , Laparotomía , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the application value of the clearance of No.253 lymph nodes with priority to fascial space and preserving left colic artery (LCA) in patients undergoing laparoscopic radical proctectomy. METHODS: From August 2015 to August 2016, 97 consecutive middle-low rectal cancer patients underwent laparoscopic radical proctectomy using the clearance of No.253 lymph nodes with priority to fascial space and preserving LCA at Department of General Surgery, Tangdu Hospital. Among 97 patients, 45 were females , 52 were males, mean age was (64.3±5.5) years and mean BMI was (22.4±1.8) kg/m2. Brief steps of this clearance: traditional medial approach was the commencement of the dissection at the membrane bridge line in front of iliac vascular bifurcation, then entering into the Toldt's space; superior rectal artery served as the top of the tent and the Toldt's space was extended as far as possible; blunt separation was developed caudally (reaching 2 cm below the sacral promontory), cephalad (reaching the lower part of the pancreas), left laterally (reaching Toldt's line), dextrally (reaching abdominal aorta); after giving priority to fascias space, from the root of inferior mesenteric artery, LCA was exposed and No.253 lymph nodes were dissected. This regimen was suitable for the rectal adenocarcinoma patients without distant metastasis. RESULTS: There was no tension in the intestine and mesenteria after anastomosis in all the 97 patients. One patient received LCA ligation during the clearance, because of thinner LCA resulting in bleeding. The other 96 cases completed the clearance and operation successfully. The mean No.253 lymphadenectomy time was 11-27(17.1±5.3) minutes. The mean number of harvested No.253 lymph node was 0-6(4±2). The No.253 lymph nodes of 6 patients were positive. No.253 regional mesentery was complete in 95 patients. The total harvested number of lymph node was 11-26(17.3±5.3). Six patients with positive lymph nodes aged from 68 to 72 years old and all of them underwent TME operation 6-8 weeks after neoadjuvant chemoradiotherapy. The mean operative time was 89-189(125±35) minutes. The mean estimated blood loss was 10.5-38.6(22.4±10.5) ml. The first exhaust time was 3.0-6.0(5.6±2.1) days. The mean time to extracting the drainage tube was 3.0-5.0(4.5±2.5) days. Anastomotic fistula appeared in 1 case and hemorrhage appeared in 1 case, and these 2 cases were cured by conservative treatment. No perioperative death occurred. The mean postoperative hospital stay was 3.0-10.0(3.6±2.6) days. CONCLUSION: The clearance of No.253 lymph nodes with priority to fascial space and preserving LCA in laparoscopic radical proctectomy is safe and feasible.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Escisión del Ganglio Linfático , Arteria Mesentérica Inferior/cirugía , Neoplasias del Recto/cirugía , Anciano , Femenino , Humanos , Laparoscopía , Ganglios Linfáticos , Masculino , Persona de Mediana EdadRESUMEN
Growing evidence has indicated that single-stranded DNA-binding proteins 1 (SSBP1) is involved in tumor initiation and progression. However, effects of single nucleotide polymorphisms (SNPs) in SSBP1 gene on gastric cancer (GC) prognosis are still unknown. In present study, two functional SNPs from SSBP1 were selected and genotyped in a large cohorts of 1030 resected GC patients (326 in the training set, 704 in the validation set) to explore the association of SNPs with patients' survival. The rs6976500 G allele (CG/GG) genotypes were found significantly associated with both worse overall survival (OS) and recurrence-free survival (RFS) in the training and the independent validation set when compared to C allele genotype, which reaching a more robust statistical significance in the pooled analysis. Furthermore, integration of rs6976500 genotypes and TNM stage significantly improved the prognosis prediction models based on TNM stage alone. In addition, only carriers with at least one G allele of rs6976500 gained significant survival benefit from FOLFOX-based ACT. Mechanistically, SNP rs6976500 G allele genotype could significantly decrease promoter transcriptional activity and markedly reduce expression level of SSBP1 compared with the C allele genotype in GC cells. This was further substantiated by immunohistochemical assay in 70 GC tissue samples. Our study presents the first evidence that SNP rs6976500 G allele genotypes might contribute to GC prognosis by attenuating SSBP1 promoter activity and gene expression, and provides the guidance in refining therapeutic decisions of GC patients. Further exploration on its function is needed to clarify the exact biological mechanism behind.