m6A demethylase ALKBH5 suppression contributes to esophageal squamous cell carcinoma progression.

Esophageal squamous cell carcinoma (ESCC) is a highly malignant gastrointestinal cancer with a high recurrence rate and poor prognosis. Although N6-methyladenosine (m6A), the most abundant epitranscriptomic modification of mRNAs, has been implicated in several cancers, little is known about its participation in ESCC progression. We found reduced expression of ALKBH5, an m6A demethylase, in ESCC tissue specimens with a more pronounced effect in T3-T4, N1-N3, clinical stages III-IV, and histological grade III tumors, suggesting its involvement in advanced stages of ESCC. Exogenous expression of ALKBH5 inhibited the in vitro proliferation of ESCC cells, whereas depletion of endogenous ALKBH5 markedly enhanced ESCC cell proliferation in vitro. This suggests ALKBH5 exerts anti-proliferative effects on ESCC growth. Furthermore, ALKBH5 overexpression suppressed tumor growth of Eca-109 cells in nude mice; conversely, depletion of endogenous ALKBH5 accelerated tumor growth of TE-13 cells in vivo. The growth-inhibitory effects of ALKBH5 overexpression are partly attributed to a G1-phase arrest. In addition, ALKBH5 overexpression reduced the in vitro migration and invasion of ESCC cells. Altogether, our findings demonstrate that the loss of ALKBH5 expression contributes to ESCC malignancy.

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

[Brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique for Stanford type A aortic dissection: analysis of 23 cases].

OBJECTIVE: To assess the clinical outcomes of brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique for treatment of Stanford type A aortic dissection. METHODS: Twenty-three patients with Stanford type A aortic dissection requiring arch replacement underwent brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique. The operations were performed within 72 h (20 cases) or 3-14 days (3 cases) after the onset of aortic dissection. RESULTS: There was no perioperative death in these cases. The mean extracorporeal circulation time was 209∓52 min, the aortic cross clamp time was 85∓21 min, and the mean chest tube output within the first 24 h after the operation was 570∓263 mL; none of the patients required chest reopening for management of bleeding. Postoperative acute renal failure requiring hemodialysis occurred in 3 cases, transient neurologic dysfunction in 2 cases, paraplegia in case and hematosepsis in 1 case. No such complications as permanent neurologic deficit or postoperative visceral malperfusion occurred in these cases. All the patients survived and were discharged from hospital without experiencing severe complications in the follow-up for 6-18 months. CONCLUSION: Brachiocephalic artery-sparing aortic arch repair combined with stent-graft elephant trunk technique is a safe and simple procedure with controllable bleeding and can serve as an optional procedure for aortic arch replacement.

[Effect of one lung ventilation preconditioning on oxygenation during pediatric video-assisted thoracoscopic surgery].

OBJECTIVE: To observe the effect of one lung ventilation (OLV) preconditioning on perioperative oxygenation during pediatric video-assisted thoracoscopic surgeries (VATS). METHODS: A total of 171 children aged 5 days to 11 years underwent VATS for empyema dissection and abscess excisions (n=55), mediastinal tumor resection (n=34), repair of the diaphragmatic hernia or diaphragmatic plication (n=21), pulmonary lobectomy or biopsy (n=43), or esophageal disease (n=18). Of these patients, 127 were younger than 3 years of age. A 5-Fr pediatric endobronchial blocker was used for OLV with a delivered inspired oxygen fraction (FiO(2)) of 1.0. After lateral decubitus, a sequential protocol of a 5- to 8-min OLV preconditioning and a 5-min two lung ventilation (TLV) was performed followed by OLV again before incision for VATS. In cases of a SpO(2)<95% without malposition of the blocker during OLV, a 5 cm H(2)O positive end expiratory pressure was applied; TLV was maintained for a SpO(2)<90%. RESULTS: OLV provided good surgical conditions in 160 cases. Acceptable saturations were achieved in 166 cases during OLV. In 2 cases in empyema group and 3 in esophageal disease group, the ventilation protocol was converted to intermittent TLV during the operation due to hypoxemia. In esophageal disease group, the procedure and OLV duration, postoperative ventilation time and length of stay (LOS) were the longest among the groups, and the number of cases developing postoperative atelectasis was greater than that in diaphragmatic hernia and pulmonary disease groups. In empyema and esophageal disease groups, the oxygenation index (PaO(2)/FiO(2)) after total collapse of the lung in OLV and after extubation were lower than that in mediastinal tumor group (P<0.05 or 0.01). CONCLUSION: A OLV preconditioning can maintain an acceptable oxygenation during pediatric OLV. A longer procedure and OLV duration is associated with a prolonged postoperative length of ventilation and LOS.

[Effects of selective left lower lobar blockade by Coopdech endobronchial blocker tube on intrapulmonary shunt and arterial oxygenation: a comparison with double-lumen endobronchial tube].

OBJECTIVE: To compare the differences in intrapulmonary shunt (Qs/Qt) and arterial oxygenation between selective left lower lobar blockade by Coopdech endobronchial blocker tubes (BB) and one lung ventilation (OLV) by left-sided double-lumen endobronchial tubes (DLT) in patients with normal pulmonary function. METHODS: Thirty-six patients (aged 32-64 years) scheduled for lower esophageal surgery were allocated randomly into BB and DLT groups (n=18). Anesthesia was induced and maintained with Propofol by target controlled infusion with intravenous administration of sufentanil and cisatracurium if needed. A 35 to 39 French tube was placed in the DLT group, and an 8.0-mm (internal diameter) single-lumen endotracheal tube was used in the BB group where a 9 French Coopdech BB was advanced into the left lower lobar bronchus guided by a fiberoptic bronchoscope. The variables recorded were blood gas analysis data from the venous and arterial blood samples at 20 min after two-lung ventilation in supine position (T(1)), 20 min after initiation of one-lung ventilation or selective left lower lobar blockade by inflating BB balloons in the right lateral decubitus position (T(2)), total collapse of the left lung or the left lower lobe after the pleura was opened (T(3)), and before tracheal extubation (T(4)). Qs/Qt was calculated using a standard formula based on the three-compartment model. Upon pleura opening, the effectiveness of lung collapse was evaluated by the surgeon who performed the surgery. Chest radiograph and arterial blood gas analyses were performed the day after the operation. RESULTS: Both of the groups were similar with regard to rank of the surgical exposure, pH, PaCO(2), hemoglobin from T(1) to T(4), Qs/Qt, PaO(2), PO(2), and oxygenation index at T1. In BB group, a significant reduction of Qs/Qt and greater improvements in PaO(2), PO(2), oxygenation index at T(2), T(3) and T(4) were observed in comparison with those in DLT group (P<0.05 or <0.01). No lobe collapse was observed postoperatively in BB group, but 2 patients in DLT group showed left lower lobe atelectasis. The patients in BB group showed better postoperative arterial oxygenation and shorter postoperative hospital stay (P<0.01). CONCLUSION: Selective left lower lobar blockade by Coopdech endobronchial blocker tube during lower esophageal surgery provides a lower intraoperative intrapulmonary shunt and a better intra- and postoperative arterial oxygenation..

[Design and experimental application of a device for direct vision intracardiac operation without cardiopulmonary bypass].

OBJECTIVE: To design a device for direct vision intracardiac operation without cardiopulmonary bypass, and assess its applicability preliminarily. METHODS: The device was designed according to the clinical needs of intracardiac operation and used in operations for repairing atrial septal defect in 5 ex vivo porcine heart models. The practical applicability of this device was thoroughly tested and the results of the operations were evaluated. RESULTS AND CONCLUSION: Direct vision operation for repairing atrial septal defect was successfully performed using this device, which can be a well applicable in some intracardiac operations, but its clinical effects need further evaluation.

[Evaluation of ultramicroporous expanded polytetrafluoroethylene mitral valve under pulsatile flow condition in vitro].

OBJECTIVE: To test 25# and 27# ultramicroporous expanded polytetrafluo-roethylene mitral valve (UPMV) under pulsatile flow condition in vitro. METHODS: Six 25# and six 27#UPMV were tested using TH-1200 HV Prosthesis Pulsatile Flow Tester in vitro at the cycling rate of 70 cycle/min, with the systolic pressure maintained at about 16 kPa (120 mmHg), diastolic pressure at 10.7 kPa (80 mmHg), and the percentage of mean forward flow at 35%. The stimulant cardiac output was maintained at 2, 3, 4, 5 and 6 L/min, respectively, for the testing. RESULTS: The mean pressure difference for the 25#UPMV under stimulant cardiac output of 2, 3, 4, 5 and 6 L/min was 2.488-/+0.378, 4.427-/+0.240, 5.460-/+0.449, 6.776-/+0.391 and 8.327-/+0.490 mmHg, and its effective valvular orifice was 1.430-/+0.333, 1.993-/+0.208, 2.260-/+0.477, 3.204-/+0.174 and 3.652-/+0.158 cm(2), respectively. The regurgitant fraction of the 25#UPMV under each stimulant cardiac output was (5.731-/+0.643) %, (5.431-/+0.312) %, (5.059-/+0.708) %, (3.545-/+0.097) % and (2.615-/+0.125) %, respectively. The mean pressure difference of the 27#UPMV under each stimulant cardiac output was 1.618-/+0.497, 3.448-/+0.440, 4.825-/+0.434, 5.494-/+0.446 and 7.482-/+0.455 mmHg, effective valvular orifice was 1.773-/+0.364, 2.113-/+0.305, 2.409-/+0.295, 3.326-/+0.417 and 4.522-/+0.445 cm(2), and regurgitant fraction was (5.357-/+0.509) %, (5.407-/+0.110) %, (4.999-/+0.182) %, (4.010-/+0.254) % and (2.584-/+0.114)%, respectively. CONCLUSION: The mean pressure difference, effective valvular orifice and regurgitant fraction of the UPMVs can measure up to the national criteria for artificial heart valve prosthesis of China.

[Accelerated fatigue test in vitro of expanded polytetrafluoroethylene artificial heart valve].

OBJECTIVE: To study the durability of expanded polytetrafluoroethylene artificial heart valve (ePTFE AHV). METHODS: Six ePTFE AHVs were tested for 400 million times against accelerated fatigue using TH-2200 artificial heart valve exosomatic accelerated fatigue instrument. Hydromechanical parameters of fore-and-aft accelerated fatigue test of the 6 AHVs were obtained by TH-1200 artificial heart valve exosomatic pulsatile stream instrument. RESULTS AND CONCLUSION: The mean gradient pressure spanning the valve and the effective orific area of ePTFE AHVs did not undergo significant changes after fore-and-aft the fatigue test, but the regurgitation volume and regurgitation rate of ePTFE AHVs were reduced after the accelerated fatigue test, suggesting good durability of ePTFE AHV.

[Calcification and biomechanics in vivo of ultra-microporous expanded polytetrafluoroethylene in rabbits].

OBJECTIVE: To study in vivo calcification and biomechanics of the ultra-microporous expanded polytetrafluo- roethylene (UePTFE) in rabbits in comparison with glutaral-treated bovine pericardium (BP), so as to assess the potential of UePTFE as a material for cardiac valve prosthesis. METHODS: Factorial analysis was adopted in the experiment. UePTFE and glutaral-treated BP of appropriate sizes were embedded beneath skin of young New Zealand rabbits, and at 0, 1, 3 and 6 months following the implantation, the materials were measured for the content of calcium and biomechanics properties. RESULTS: Lower level of calcification of the UePTFE occurred after the implantation, as compared with BP, and the biomechanics indices of the former UePTFE were obviously suprior to those of the latter. CONCLUSION: UePTFE is a better material than BP for cardiac valve prosthesis.

Experience in using three different minimally invasive approaches in cardiac operations.

BACKGROUND: In order to reach a clear understanding of minimally invasive approaches in cardiac operations, the authors review clinical experience in using three such approaches: inferior partial median sternotomy, right anterolateral minor thoracotomy, and the right parasternal approach. MATERIAL/METHODS: Sternotomy and the three different minimally invasive approaches were applied in and 2431 and 323 patients respectively. The approaches were selected according to the circumstances of the individual case. Both external and internal cardiac structures were observed during the operations. The length of the incision, the postoperative drainage, operative time, and cardiopulmonary bypass time were investigated. The postoperative complications occurring after minimally invasive approaches were observed. RESULTS: In inferior partial median sternotomy, all structures except for the ascending aorta could be exposed well. In right anterolateral minor thoracotomy, only the structures on the right side of the heart could be exposed, but the mitral valve could also be exposed well. The exposure of the right parasternal approach was similar to that of right anterolateral minor thoracotomy. There were statistically significant differences between sternotomy and the minimally invasive approaches in terms of incision length and postoperative drainage, but no difference in operative time and cardiopulmonary bypass time. The postoperative complications of MIAs included air embolism (n = 3), chest pain (n = 9), chest wall malacia (n = 1), rib fracture (n = 2), and sternum fracture (n = 2). The total incidence of complications in minimally invasive approaches was 5.3%. CONCLUSIONS: The minimally invasive approaches can have satisfactory clinical results if the approaches are correctly chosen and performed.

[Surgical treatment of ascending aortic aneurysm by Bentall's procedure: report of 14 cases].

OBJECTIVE: To review our experience in surgical treatment of ascending aortic aneurysm (AAA) with aortic insufficiency in 14 cases of by Bentall's procedure. METHODS AND RESULTS: All the patients underwent replacement of the ascending aorta and aortic valve with composite valved vascular prosthesis and received direct implantation of the aortic graft of the coronary orifices (Bentall's procedure) with satisfactory results. Five patients had ascending aortic dissection and 4 had typical Marfan's syndrome. All the patients suffered severe aortic insufficiency while 2 had mitral insufficiency. Coronary orifices were implanted in situ in 13 cases while in 1 case, Cabrol's method was adopted. No death occurred during the surgery and in the subsequent follow-up, and all the patients had good recovery. CONCLUSION: Bentall's procedure can be effective in the treatment of AAA with aortic insufficiency.

Hydrodyamical assessment of valve prosthesis made of expanded ultra-microporous Teflon in vitro.

OBJECTIVE: To assess the hydrodynamical performance of the valve prosthesis made of expanded ultra-microporous Teflon in vitro. METHOD: Sheets of the expanded ultra-microporous Teflon were sewn onto flexible bracket to prepare artificial valve prosthesis. The leakage and steady flow of the valve prosthesis was tested in vitro with Baxter valve prosthesis as control. RESULTS: The rate of leakage of this new valve prosthesis was similar to that of Baxter valve prosthesis (P>0.05), and the systolic pressure gradient of the former was much lower than control(P<0.05). CONCLUSION: This new artificial valve prosthesis has good in vitro hydrodynamical properties, which are superior to Baxter valve.

Coronary artery bypass grafting with simultaneous mitral valve replacement: report of one case.

Coronary artery bypass grafting and mitral valve replacement was performed simultaneously under cardiopulmonary bypass in a patient suffering from both coronary artery disease and severe mitral incompetence. The operation was completed smoothly with uneventful postoperative recovery of the patient. The author called for due attention to the importance of precise preoperative diagnosis and addressed the issues of the operation procedure and protection of myocardium.

[Diagnosis and management of spontaneous rupture of the esophagus].

OBJECTIVE: To explore guidelines of the diagnosis and management for spontaneous rupture of the esophagus. METHODS: Of the 15 patients suffering spontaneous rupture of the esophagus, 11 received surgical treatment while the other 4 received non-operative treatment. RESULTS: Eleven patients recovered smoothly and death occurred in 4 cases, with the total cure rate of 73%. CONCLUSION: Early diagnosis and operation are crucial for management of spontaneous rupture of the esophagus, and in cases of delayed diagnosis, indications for operation need to be extended.

[Evaluation of left parasternal approach for cardiac surgery].

OBJECTIVE: To provide a systemic evaluation of left parasternal approach (LPSA) for its clinical application. METHODS: LPSA was performed in 6 randomly-chosen formalin-preserved adult cadavers and the excisions were evaluated in external light of the external appearance, extent of traumatic injury and exposure of the structures in the thoracic cavity. RESULTS: LPSA left only short and less obvious skin incisions, thus causing minimal exterior appearance impairment. With a small operative field and only a few structures injured by this approach, LPSA had acceptable traumatic lesions and when the adequate intercostal level was chosen, the lateral structures on the left of the heart could be well exposed. CONCLUSION: LPSA is less invasive and involves acceptable external appearance impairment. Though satisfactory in exposing the structures on the left of the heart, LPSA can not properly expose the structures on the right side.

[Coronary artery bypass grafting without cardiopulmonary bypass: report of 6 cases].

OBJECTIVE: To explore the approach for coronary artery bypass grafting without cardiopulmonary bypass and assess the feasibility and safety of this procedure. METHODS: The clinical data of 6 patients receiving coronary artery bypass grafting without cardiopulmonary bypass were reviewed. RESULTS: No death occurred in these patients during the operation and the follow-up visit for 3 to 12 months found no incidence of angina pectoris, and the life quality of the patient was obviously improved. CONCLUSION: Coronary artery bypass grafting without cardiopulmonary bypass is applicable in patients with multiple coronary artery disease, especially those at high risk for cardiopulmonary bypass procedures.

Combined valve operations with transection of ascending aorta.

To facilitate combined aortic and mitral valve operations, a new approach was developed. It was employed in 50 patients with both aortic and mitral valve disease. The ascending aorta was transected 1.5 cm above the aortic annulus, and the roof of the left atrium was incised. The damaged valves were replaced or repaired. Both aortic and mitral valves could be exposed satisfactorily by this approach. All patients recovered smoothly after the operation. Complications comprised intraoperative bleeding from the distal end of the ascending aorta in 1 patient and hoarseness in 3 postoperatively. The approach was considered quick and easy for combined valve operations.