[Diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery].

Objective: To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA). Methods: This is a retrospective case series study. From January 2016 to July 2023, 24 cases of high-risk AAOCA underwent surgical treatment in Department of Cardiac Surgery, Guangdong Provincial People's Hospital. There were 18 males and 6 females, operatively aged (M (IQR)) 13 (26) years (range: 0.3 to 57.0 years). They were confirmed by cardiac ultrasound and cardiac CT, all of which had anomalous coronary running between the aorta and the pulmonary artery. There were 15 cases of the right coronary artery from the left aortic sinus of Valsalva, 6 cases of left coronary artery from the right aortic sinus of Valsalva, 3 cases of the sigle coronary artery. Only 3 patients had no obvious related symptoms (2 cases were complicated with a positive exercise stress test and 1 case with other intracardiac malformations), 21 cases had a history of chest tightness, chest pain, or syncope after exercise. Three patients suffered syncope after exercise and underwent cardiopulmonary resuscitation (2 cases were treated with an extracorporeal membrane oxygenerator (ECMO)). The gap from the first symptom to the diagnosis was 4.0 (11.5) months (range: 0.2 to 84.0 months). The detection rate of coronary artery abnormalities suggested by the first cardiac ultrasound was only 37.5% (9/24). Seven patients were complicated with other cardiac diseases (4 cases with congenital heart defects, 2 cases with coronary atherosclerotic heart disease, 1 case with mitral valve disease). Results: All 24 patients underwent surgical treatment (23 cases underwent abnormal coronary artery unroofing, 1 case underwent coronary artery bypass grafting), and 5 patients underwent other intracardiac malformation correction at the same time. There were no death or surgery related complications in the hospital for 30 days after the operation. A patient with preoperative extracorporeal cardiopulmonary resuscitation was continuously assisted by ECMO after emergency AAOCA correction and had complications such as limb ischemia necrosis and renal dysfunction after the operation. During the follow-up of 2.2 (3.3) years (range: 1 month to 7.2 years), one patient who previously underwent percutaneous transluminal coronary angioplasty with a stent implant experienced significant postoperative symptomatic relief, and the other discharged patients had no related symptoms. Conclusions: The accurate rate of initial diagnosis for high-risk AAOCA is still low, but the risk of cardiovascular accidents is high. For sports-related chest pain and other symptoms, more attention should be paid to the detection of AAOCA, especially for adolescents. Exercise stress testing can be helpful in evaluating the cardiovascular risk of asymptomatic AAOCA. Instant surgical treatment can achieve satisfactory curative effects.

The efficacy and safety of immune checkpoint inhibitors in non-small cell lung cancer patients of different age groups: a meta-analysis.

BACKGROUND: Age is closely related to the efficacy of treatment for non-small cell lung cancer (NSCLC) patients. Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in NSCLC patients. However, we had no clear idea of the efficacy of them in elderly patients. So we conducted a meta-analysis to compare the efficacy of immune checkpoint inhibitors for NSCLC patients of different age groups and summarized overall treatment-related adverse events. MATERIALS AND METHODS: PubMed, EMBASE, Web of Science and the Cochrane Library were searched for all clinical trials in NSCLC until 30th of April 2019. Eligible studies included randomized controlled trials (RCTs) comparing immune checkpoint inhibitors with chemotherapy in NSCLC patients. The hazard ratio (HRs) and 95% confidence intervals (CIs) of OS, progression-free survival or adverse events (AEs) were used. RESULTS: A total of 4994 patients from 8 RCTs were included. Immune checkpoint inhibitors significantly prolonged the OS (HR, 0.73; 95% CI, 0.61-0.89) versus chemotherapy in NSCLC patients who were less than 65 years old. Also, they prolonged the OS (HR, 0.74; 95% CI, 0.59-0.93) in NSCLC patients who were more than 65 years old. However, there was no statistical significance of OS (HR, 0.87; 95% CI, 0.57-1.30) among NSCLC patients who were more than 75 years old. It also showed that the single use of immune checkpoint inhibitors had fewer all-grade AEs. CONCLUSION: Regardless of the NSCLC patients who were less or more than 65 years, immune checkpoint inhibitors could achieve better OS than chemotherapy. But there was no significant difference when NSCLC patients who were more than 75 years old. Older patient should be offered immune therapies if it is possible and the mechanism in old age treatment should be further studied.

[Prediction model for survival in patients with biliary tract cancer: a development and validation study].

Objective: The aim of the present study was to investigate the survival rate and its prognostic factors for patients with biliary tract cancer, and then a prognostic risk prediction model was constructed to predict the survival probability of patients. Methods: A total of 14 005 patients with biliary tract cancer (including gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer), who were diagnosed between 2010 and 2015 in the US National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) were included in the development cohort. The prognostic risk factors of biliary tract cancer were investigated using multivariate Cox regression models. The predictive nomograms were then constructed to predict the overall survival probability of 1, 3, and 5 years, and the predictive discrimination and calibration ability of the nomograms were further evaluated. Meanwhile, 11 953 patients who were diagnosed during 2004 to 2009 from SEER Program were then selected to validate the external predictive accuracy of the prediction models. Results: The 1, 3 and 5-year cumulative survival rates of patients with biliary tract cancer were 41.9%, 20.4% and 15.3%, respectively, in the development cohort. Age greater than 50 years, African Americans and Native Americans and Alaska Natives, higher T, N and M stage and poor histological differentiation grade were risk factors for death, while married status, Asia-Pacific Islanders, insured status and surgery on primary site were protective factors. Gender was not significantly associated with the overall survival. The C statistic of the prediction model was 0.73 (95%CI: 0.72-0.74), and the calibration curve showed that the interaction curves of predictive and actual survival rates of 1, 3 and 5 years were close to the 45 degree diagonal. Results in the validation cohort were similar with those in the construction cohort, with a C statistic of 0.70 (95%CI: 0.69-0.72), indicating high external applicability of the prediction model. Findings from gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer are in consistent with the overall biliary tract cancer. Conclusions: The survival rate of patients with biliary tract cancer is relatively poor, and the survival prediction model based on prognostic factors has high prediction accuracy. In the future, this prognostic prediction model could be applied to clinical practice to guide individualized treatment for patients with biliary tract cancer.

[Short and midterm results of surgical treatment of interrupted aortic arch].

Objective: To analyze the early and midterm results of surgical treatment of interrupted aortic arch (IAA) with double-ventricular procedure. Methods: The data of the 68 cases with the main diagnosis of IAA with biventricular structure from June 2009 to June 2017 at Department of Cardiac Surgery, Guangdong General Hospital was collected, including 46 cases of type A, 22 cases of type B. There was no type C case. Except for 5 cases without patent ductus arteriosus or other intracardiac malformations, the remaining 63 cases were combined with intracardiac deformity. The age of operation was 8 days to 18 years, including 28 cases(41.2%) of newborns, 32 cases(47.1%) within 1 year old, 6 cases(8.8%) from 1 to 15 years old, and 2 cases(2.9%) above 15 years old. Of the 5 patients with no intracardiac malformations, 4 patients were treated with a left-posterior thoracic lateral incision for primary surgical correction with end-to-side anastomosis, and 1 adult patient was treated with a median sternotomy incision to complete the anastomosis with the assist of extracorporeal circulation. Of the 63 patients with intracardiac malformation, 2 underwent reconstruction of the aortic arch via posterolateral left thoracic incision merely; 2 patients underwent staged surgery to correction the IAA and intracardiac malformation; the remaining 59 patients underwent the one-stage procedure of IAA and intracardiac malformation correction with deep hypothermic circulatory arrest and 43 cases of selective cerebral perfusion. A total of 55 cases of end-to-end or end-to-side anastomosis were performed in all aortic arch reconstruction. There were 6 cases of connection the arch to descending aorta with autogenous pulmonary artery conduit, and 1 case with homemade bovine pericardial conduit. And there were 5 cases of anastomosis enlargement with autogenous pulmonary artery patch, and 1 case with left subclavian artery flap patch. There were 1 case performed with D. K.S. operation for the severe hypogenetic aortic valve and ascending aorta, and 1 case with left ventricular double outlet channel operation for the severe subvalvular aortic stenosis. Results: Follow-up to 9 years, 4 deaths (5.9%) related to circulatory system diseases: 3 cases died within 30 days after surgery (1 case was neonatal, 2 cases were 1 to 12 months old); one died 8 months after surgery for low cardiac output syndrome. In the early postoperative period, 11 cases (16.2%) of residual aortic arch obstruction (pressure gradient >30 mmHg) were observed, of which 3 cases were moderate (4.4%); follow-up to 5 years after operation was residual obstruction in 3 cases and moderate in 2 cases. There were 3 cases with aortic valve and subvalvular obstruction (differential pressure >30 mmHg), 3 cases were followed up to 5 years after aortic valve and subvalvular obstruction, and 2 cases were moderate or above. To date, 5 patients have undergone 6 reoperations of the cardiovascular system: 3 cases because of pulmonary artery stenosis, 2 cases because of severe aortic arch stenosis, and 1 case because of aortic subvalvular obstruction. Conclusions: One-stage surgical repair of IAA is safe and clinically effective in the neonatal and infant. But some patients still requires reoperation for re-obstruction from subvalvular or aorta arch. For some patients, the choice of aortic arch reconstruction depends on the specific situation.

[The reasonable use of right ventricular protection strategy in right ventricular outflow tract reconstruction].

As a result of right ventricular outflow tract reconstruction, which is the important and basic step of complex cardiac surgery, the blood flow of right ventricular outflow tract is unobstructed, while pulmonary valve regurgitation and right heart dysfunction could be happened. These problems are often ignored in early days, more and more cases of right heart dysfunction need clinical intervention, which is quite difficult and less effective. How to protect effectively the right ventricular function is the focus. At present main methods to protect the right ventricular function include trying to avoid or reduce length of right ventricular incision, reserving or rebuilding the function of the pulmonary valve, using growth potential material for surgery. The protection of the right ventricular function is a systemic project, it involves many aspects, single measures is difficult to provide complete protection, only the comprehensive use of various protection strategy, can help to improve the long-term prognosis.

Clinical value of combined tests for tumor markers for gastric cancer.

To study the clinical diagnostic value of treating gastric cancer (GC) with combined tests for tumor markers (CEA, CA199, CA242 and CA724), fifty healthy subjects, 50 patients with GC at different stages and 50 patients with benign GC were randomly selected from our hospital. These subjects were divided into a normal group A, an experimental group B and a control group C. Venous blood was drawn and tested for four serum tumor markers. The SPSS 18.0 analytic system was then used to analyze the data. Tumor markers for GC at different stages, different pathological patterns and tumor incidence are discussed. The difference in expression levels of tumor markers between group C and group A was not statistically significant (P>0.05). The differences in expression levels between group B in stage I and stage II and those of groups A and C was statistically significant (P less than 0.05). At the same time, the differences in expression levels of group B in stage III and stage IV and those of groups A and C were also statistically significant (P less than 0.01). For different sizes of tumors, taking 5 cm as a maximum, normal expression and abnormal expression of the four tumor markers was different (P less than 0.05). The tumor incidence of the combined test for the four tumor markers was conspicuously higher than that of single tests. Moreover, the difference between the tumor incidence of the combined test in stages I, II and III and that of single tests in the same stages was of statistical significance (P less than 0.05); however, the difference was not statistically significant in stage IV (P>0.05). The combined testing for tumor markers is useful for clinical diagnosis of GC.

[Surgical treatment and early-mid follow-up results of complete atrioventricular septal].

Objective: To discuss the surgical treatment and early-mid follow-up results of complete atrioventricular septal defect (CAVSD). Methods: The clinic data of 235 cases of CAVSD underwent surgical treatment at Department of Cardiac Surgery, Guangdong General Hospital from June 2009 to June 2016 was analyzed retrospectively (104 male and 131 female patients). The patients were aged 18 days to 58 years (mid age 8.9 months) at surgery, and 2 cases of newborns (0.9%), 24 cases of 1 to 3 months (10.2%), 56 cases of 4 to 6 months (23.8%), 66 cases of 7 to 12 months (28.1%), 36 cases of 1 to 3 years (15.3%), 37 cases of 4 to 18 years (15.7%), and 14 cases above 18 years (6.0%). There were 129 cases of Rastelli type A (54.89%), 16 cases of type B (6.8%), 25 cases of type C (10.6%) and 65 cases of transitional type (27.7%). The patients were combined with 7 cases of unroofed coronary sinus syndrome, 5 cases of coarctation of aorta, 4 cases of tetralogy of Fallot, 3 cases of double outlet right ventricle, 1 case of transposition of the great arteries, 1 case of multiple ventricular septal defect, 1 case of pulmonary artery sling. The CAVSD correction operations were performed in 199 cases with modified single patch technique (84.7%), 26 cases with two patch technique (11.1%), 10 cases with conventional single patch technique (4.3%), and the corrective surgeries of other anomalies were performed in the meantime. Generalized Estimated Equation was used to statistical analysis of postoperative regurgitation level of mitral valve and tricuspid valve. Results: Followed-up for 1 to 7 years, 18 cases (7.7%) died overall and 15 cases (6.4%) died within 30 days post-operation.The mortality of little infant (operation age ≤3 months) was much highest(26.9%). The mortality of different operation age had significant difference(P=0.007). There was no difference among the mortality with three techniques. Seven cases (3.0%) suffered from the re-operation for severe mitral regurgitation. A total of 217 patients survived more than 1 year after initial surgery, and there were 11 cases (5.1%) with severe mitral regurgitation and 7 cases (3.2%) with severe tricuspid valve regurgitation at 1 year post-operation.The degree of mitral regurgitation after operation decreased at 1 week to 6 months, and slightly higher after 1 year postoperatively.The ratios of severe mitral regurgitation in different operative age group was statistically significant difference(P=0.017), mainly from 3 months group and 1 to 3 years group.The degree of tricuspid regurgitation decreased significantly after operation, and decreased gradually in the follow-up period. The ratio of postoperative residual severe tricuspid regurgitation was the highest in surgical aged >18 years old, less in 3 years group, the lowest in 3 to 18 years group. Conclusions: The mortality and the ratio of patients with serious mitral regurgitation were higher in infants less 3 months than elder patients. The infants need more frequently follow-up and medicine treatment after operation. The modified one patch technique is effective for all age groups.

MINA controls proliferation and tumorigenesis of glioblastoma by epigenetically regulating cyclins and CDKs via H3K9me3 demethylation.

It is generally known that histone demethylases regulate gene transcription by altering the methylate status on histones, but their roles in cancers and the underlying molecular mechanisms still remain unclear. MYC-induced nuclear antigen (MINA) is reported to be a histone demethylase and highly expressed in many cancers. Here, for the first time, we show that MINA is involved in glioblastoma carcinogenesis and reveal the probable mechanisms of it in cell-cycle control. Kaplan-Meier analysis of progression-free survival showed that high MINA expression was strongly correlated with poor outcome and advancing tumor stage. MINA knockdown significantly repressed the cell proliferation and tumorigenesis abilities of glioblastoma cells in vitro and in vivo that were rescued by overexpressing the full-length MINA afterwards. Microarray analysis after knockdown of MINA revealed that MINA probably regulated glioblastoma carcinogenesis through the predominant cell-cycle pathways. Further investigation showed that MINA deficiency led to a cell-cycle arrest in G1 and G2 phases. And among the downstream genes, we found that cyclins and cyclin-dependent kinases were directly activated by MINA via the demethylation of H3K9me3.

Direct effects of Bmi1 on p53 protein stability inactivates oncoprotein stress responses in embryonal cancer precursor cells at tumor initiation.

Embryonal cancer can arise from postnatally persistent embryonal remnant or rest cells, which are uniquely characterized by the absence of p53 mutations. Perinatal overexpression of the MycN oncoprotein in embryonal cancer precursor cells causes postnatal rests, and later tumor formation through unknown mechanisms. However, overexpression of Myc in adult tissues normally activates apoptosis and/or senescence signals as an organismal defense mechanism against cancer. Here, we show that perinatal neuroblastoma precursor cells exhibited a transiently diminished p53 response to MycN oncoprotein stress and resistance to trophic factor withdrawal, compared with their adult counterpart cells from the TH-MYCN(+/+) transgenic mouse model of neuroblastoma. The adult stem cell maintenance factor and Polycomb group protein, Bmi1 (B-cell-specific Moloney murine leukemia virus integration site), had a critical role at neuroblastoma initiation in the model, by repressing p53 responses in precursor cells. We further show in neuroblastoma tumor cells that Bmi1 could directly bind p53 in a complex with other Polycomb complex proteins, Ring1A or Ring1B, leading to increased p53 ubiquitination and degradation. Repressed p53 signal responses were also seen in precursor cells for other embryonal cancer types, medulloblastoma and acute lymphoblastic leukemia. Collectively, these date indicate a general mechanism for p53 inactivation in some embryonal cell types and consequent susceptibility to MycN oncogenesis at the point of embryonal tumor initiation.