Impacts of additional cycles of neoadjuvant immunotherapy on surgery in non-small-cell lung cancer.

OBJECTIVE: Whether cycle number influences the subsequent pathological or surgical outcomes remained unclear. This study aimed to assess the efficacy and surgical safety of neoadjuvant immunochemotherapy-based treatment in the real-world setting. METHODS: Clinical data of patients who received neoadjuvant immunochemotherapy for non-small-cell lung cancer between 2018 and 2021 were collected. Oncological outcomes such as objective response rate (ORR), major pathological response (MPR), and pathological complete response (pCR), and surgical outcomes including operating time, intraoperative bleeding, postoperative drainage, and hospital stay were analyzed. RESULTS: In total, 176 patients were included, among whom 102 cases were lung squamous carcinoma (LUSQ). After immunochemotherapy, 98 (56%) of patients achieved ORR. Notably, the ORR (63% vs. 46%, p = 0.039) and pCR (45% vs. 27%, p = 0.022) were significantly higher in patients with LUSQ. For patients who received two, three, four, and five or more cycles, the ORRs were 52%, 67%, 53%, and 50% (p = 0.36). In post hoc analysis, cycle numbers showed no significant association with MPR or pCR (p = 0.14 and p = 0.073). Treatment cycles showed no influence on operating time, postoperative drainage, and hospital stay (p = 0.79, 0.37, and 0.22). Notably, the blood loss index of patients who received more than four cycles was higher than those receiving four or fewer cycles (mean blood loss: two or fewer cycles 153.1, three cycles 113.8, four cycles 137.6, and five or more cycles 293.3, respectively). CONCLUSIONS: This study indicated that cycles of neoadjuvant immunochemotherapy had no significant effect on the feasibility and safety of surgery. Although not statistically significant, patients who received five or more cycles of treatment experienced higher intraoperative blood loss.

Artificial intelligence for stepwise diagnosis and monitoring of COVID-19.

BACKGROUND: Main challenges for COVID-19 include the lack of a rapid diagnostic test, a suitable tool to monitor and predict a patient's clinical course and an efficient way for data sharing among multicenters. We thus developed a novel artificial intelligence system based on deep learning (DL) and federated learning (FL) for the diagnosis, monitoring, and prediction of a patient's clinical course. METHODS: CT imaging derived from 6 different multicenter cohorts were used for stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. Patients with more than 3 consecutive CT images were trained for the monitoring algorithm. FL has been applied for decentralized refinement of independently built DL models. RESULTS: A total of 1,552,988 CT slices from 4804 patients were used. The model can diagnose COVID-19 based on CT alone with the AUC being 0.98 (95% CI 0.97-0.99), and outperforms the radiologist's assessment. We have also successfully tested the incorporation of the DL diagnostic model with the FL framework. Its auto-segmentation analyses co-related well with those by radiologists and achieved a high Dice's coefficient of 0.77. It can produce a predictive curve of a patient's clinical course if serial CT assessments are available. INTERPRETATION: The system has high consistency in diagnosing COVID-19 based on CT, with or without clinical data. Alternatively, it can be implemented on a FL platform, which would potentially encourage the data sharing in the future. It also can produce an objective predictive curve of a patient's clinical course for visualization. KEY POINTS: • CoviDet could diagnose COVID-19 based on chest CT with high consistency; this outperformed the radiologist's assessment. Its auto-segmentation analyses co-related well with those by radiologists and could potentially monitor and predict a patient's clinical course if serial CT assessments are available. It can be integrated into the federated learning framework. • CoviDet can be used as an adjunct to aid clinicians with the CT diagnosis of COVID-19 and can potentially be used for disease monitoring; federated learning can potentially open opportunities for global collaboration.

Minimally Invasive Carinal Reconstruction Using Bronchial Flap and Omental Flap Reinforcement.

Carinal reconstruction and omental flap harvesting are traditionally performed through open approaches. We report a case in which carinal reconstruction with bronchial flap and omental flap reinforcement was performed using minimally invasive approaches. The omental flap was harvested laparoscopically and wrapped around the anastomosis, which reduced the risk of airway anastomosis complications. Noncircumferential resection and reconstruction used bronchial flap, which made it easier to perform under video-assisted thoracoscopic surgery conditions. Minimally invasive carinal reconstruction with bronchial flap and omental reinforcement after neoadjuvant treatment can be safely performed.

New tubeless video-assisted thoracoscopic surgery for small pulmonary nodules.

Objectives: Problems associated with intubation, chest drainage and urinary catheterization can have a negative impact on patient's recovery after thoracic surgery. We therefore evaluated the feasibility of a new tubeless (spontaneous ventilation without tracheal intubation, urinary catheterization, and no post-operative chest drain placement) approach to perform video-assisted thoracoscopic surgery (VATS) for small pulmonary nodules (SPN) less than 2cm in diameter. Methods: From 1 January 2012 to 31 December 2014, 34 patients with SPNs were treated using tubeless VATS in our centre. To be eligible for this approach, the patient must have a body mass index (BMI) of less than 25; ASA grade of II or less; no history of prostate or renal disease and no parenchymal air leak at the end of surgery. All operations were performed via an anterior uniportal VATS under spontaneous ventilation without tracheal intubation. Results: All patients [29 male:5 females; average age: 58 ± 19 years old] completed their operation under spontaneous ventilation, without conversion to endotracheal intubation. There was good operative exposure and definite diagnosis was obtained in all patients. The anaesthesia and operating time were 23 ± 3 min and 43 ± 10 min, respectively. No major intra-operative or post-operative complications were seen. Patients recovered from their anaesthesia (fully awake) within a mean time of 18 ± 3 min after surgery, and were eating 42 normally on an average of 5 ± 1 h post-operatively. No patients had pain on deep breathing or coughing (Bruggemann Comfort Score < 2). Within 24 h after surgery, 26 patients were discharged, while the remaining 8 patients were discharged on the second day. None of the patients needed re-invention with chest drainage or urinary catheterization even after discharge. All patients remained well at a median [interquartile range] follow-up time of 3[2-5] weeks. Conclusions: Tubeless VATS approach for SPNs is feasible in carefully selected patients. Intubation, chest drainage, and/or urinary catheterization may not be necessary in all patients.

Non-intubated combined with video-assisted thoracoscopic in carinal reconstruction.

Carinal reconstruction is a difficult technique combined with video-assisted thoracoscopic surgery (VATS). It has a high requirement on the operator's skills in operating thoracoscope and meanwhile requires the close cooperation from anesthesiologists. Tracheal intubation and ventilator-assisted ventilation are key steps to ensure the success of surgery. However, tracheal intubation itself may influence the exposure of surgical field and increase the difficulty of anastomosis. In close cooperation of anesthesiologists, we did not perform tracheal intubation; rather, we carried out non-intubated complete VATS carinal reconstruction in a patient with adenoid cystic carcinoma (ACC) of the lower trachea. The awake complete VATS carinal reconstruction was successfully performed. The anastomosis lasted about 36 hours, and the whole surgical procedure lasted 230 min. The intraoperative blood loss was about 80 mL. The patient recovered well 100 min after surgery. A semi-solid diet began 6 hours following the surgery. This non-intubated anesthesia method makes the surgery easier, especially during the anastomosis of stumps. It is feasible and safe to apply this anesthesia technique in carinal reconstruction.

Video-Assisted Thoracic Surgery Resection and Reconstruction of Carina and Trachea for Malignant or Benign Disease in 12 Patients: Three Centers' Experience in China.

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has been widely applied to both peripheral and central lung cancer treatment in many centers, there is great hesitation to adopt it for carinal or tracheal surgical procedures. The aims of this study were to explore the feasibility of VATS in the treatment of benign and malignant diseases involving the carina and trachea and to highlight relevant techniques. METHODS: Patients undergoing VATS carinal or tracheal procedures between May 2012 and July 2015 from three centers in China were included in this study. Their clinical characteristics, operative details, and postoperative course were analyzed. RESULTS: Twelve patients underwent five different types of VATS airway reconstructions with or without lobectomy: including right bronchial resection with partial carinal reconstruction (3 patients), tracheal resection and reconstruction (4 patients), tracheal or right bronchial resection with carinal reconstruction (3 patients), left bronchial resection with carinal reconstruction (1 patient), and right pneumonectomy with carinal reconstruction (1 patient). Complete resection was achieved in all patients. The mean operative time was 224 ± 78 minutes, and the median time of the first anastomosis was 41 minutes (range, 15 to 60 minutes), regardless of whether the reconstruction was a tracheal or carinal. The median estimated blood loss was 100 mL (range 10 to 1000 mL). The mean postoperative hospital stay was 12.5 ± 2.5 days. There was no perioperative mortality or major morbidity. Median duration of follow-up was 12 months (range 5 to 43 months). CONCLUSIONS: VATS resection and reconstruction of the carina or trachea are feasible, and these procedures can be safely performed using the techniques described. We believe, with the accumulation of VATS experience, these procedures could be adopted as routine approaches in tracheal surgery.

White light, autofluorescence and narrow-band imaging bronchoscopy for diagnosing airway pre-cancerous and early cancer lesions: a systematic review and meta-analysis.

BACKGROUND: We aimed to summarize the diagnostic accuracy of white light bronchoscopy (WLB) and advanced techniques for airway pre-cancerous lesions and early cancer, such as autofluorescence bronchoscopy (AFB), AFB combined with WLB (AFB + WLB) and narrow-band imaging (NBI) bronchoscopy. METHODS: We searched for eligible studies in seven electronic databases from their date of inception to Mar 20, 2015. In eligible studies, detected lesions should be confirmed by histopathology. We extracted and calculated the 2×2 data based on the pathological criteria of lung tumor, including high-grade lesions from moderate dysplasia (MOD) to invasive carcinoma (INV). Random-effect model was used to pool sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the receiver-operating characteristic curve (AUC). RESULTS: In 53 eligible studies (39 WLB, 39 AFB, 17 AFB + WLB, 6 NBI), diagnostic performance for high-grade lesions was analyzed based on twelve studies (10 WLB, 7 AFB, 7 AFB + WLB, 1 NBI), involving with totally 2,880 patients and 8,830 biopsy specimens. The sensitivity, specificity, DOR and AUC of WLB were 51% (95% CI, 34-68%), 86% (95% CI, 73-84%), 6 (95% CI, 3-13) and 77% (95% CI, 73-81%). Those of AFB and AFB + WLB were 93% (95% CI, 77-98%) and 86% (95% CI, 75-97%), 52% (95% CI, 37-67%) and 71% (95% CI, 56-87%), 15 (95% CI, 4-57) and 16 (95% CI, 6-41), and 76% (95% CI, 72-79%) and 82% (95% CI, 78-85%), respectively. NBI presented 100% sensitivity and 43% specificity. CONCLUSIONS: With higher sensitivity, advanced bronchoscopy could be valuable to avoid missed diagnosis. Combining strategy of AFB and WLB may contribute preferable diagnosis rather than their alone use for high-grade lesions. Studies of NBI warrants further investigation for precancerous lesions.

Differences in performance of five types of aortic valve prostheses: haemodynamic assessment by dobutamine stress echocardiography.

BACKGROUND: In patients being considered for aortic valve replacement, there remains controversy over which design or tissue offers the best performance. We aimed to evaluate in a single study the haemodynamic performances of five different widely used aortic valve prostheses: stentless porcine xenograft (Elan), stentless bovine pericardium (Pericarbon Freedom), stented porcine xenograft (Aspire), stented bovine pericardium (More) and mechanical (Ultracor). We also compared them with normal aortic valves and stenosed valves of variable severity. METHODS AND RESULTS: Preoperative echocardiography and dobutamine stress echocardiography at 1 year postoperatively were undertaken in 106 patients (n=18-24 from each group). Stentless bioprostheses, whether porcine or bovine, displayed superior haemodynamics across nearly all echocardiographic parameters: lower gradients, larger effective orifice area, higher dimensionless severity index (DSI) and lower resistance, when compared with stented or mechanical prostheses. Comparing both stented designs, bovine tissue performed the worst at rest, but with stress, there was no difference. The stress performances of the stentless bioprostheses were similar to the mildly stenosed native aortic valve, whereas the performances of the stented and mechanical prostheses resembled that of native valves with mild-to-moderate stenoses. Haemodynamic differences, however, did not translate into differences in left ventricular mass reduction at 1 year. CONCLUSIONS: Stentless bioprostheses displayed haemodynamics superior to stented or mechanical prostheses and had the closest performance to a normal, native aortic valve. Stress DSI data, least reliant on variable annulus/valve sizes and flow rates, provided the best haemodynamic discrimination.

Early impact of aortic wrapping on patients undergoing aortic valve replacement with mild to moderate ascending aorta dilatation.

BACKGROUND: The management of mild to moderate dilatation of the ascending aorta of less than 5 cm is controversial, particularly when concomitant surgical correction of aortic valve is required. We investigate the impact of a simple method of aorta reduction using Dacron graft wrapping during aortic valve replacement on the rest of the aorta. METHODS: We studied 14 patients who had ascending aorta dilatation of 4-5 cm before undergoing aortic wrapping during their aortic valve replacement and compared with their post-operative imaging within a month. RESULTS: The diameters of the ascending aorta wrapped with the Dacron graft were significantly reduced within 4 weeks after surgery from 44.7 +/- 2.6 to 33.6 +/- 3.9 mm (p < 0.001). This was associated with significant reduction in the diameter of rest of ascending aorta: coronary sinuses (from 37.9 +/- 4.9 mm to 33.3 +/- 6.1 mm; p < 0.001), sinotubular junction (from 33.2 +/- 4.7 mm to 30.6 +/- 4.4 mm, p = 0.02), and aortic arch (from 34.7 +/- 4.3 mm to 32.6 +/- 4.1 mm, p = 0.03). CONCLUSIONS: Reduction of ascending aortic dilatation by wrapping with a Dacron graft in this preliminary study is associated with favourable early reversed aortic remodelling. This supports the hypothesis that correction of mild-moderate dilatation of the ascending aorta with Dacron wrapping at the time of aortic valve surgery may prevent the progression of the dilatation, although the long-term study on a larger population is needed to confirm its benefits.

Limitations of conventional approaches to identify myocyte nuclei in histologic sections of the heart.

Accurate nuclear identification is crucial for distinguishing the role of cardiac myocytes in intrinsic and experimentally induced regenerative growth of the myocardium. Conventional histologic analysis of myocyte nuclei relies on the optical sectioning capabilities of confocal microscopy in conjunction with immunofluorescent labeling of cytoplasmic proteins such as troponin T, and dyes that bind to double-strand DNA to identify nuclei. Using heart sections from transgenic mice in which the cardiomyocyte-restricted alpha-cardiac myosin heavy chain promoter targeted the expression of nuclear localized beta-galactosidase reporter in >99% of myocytes, we systematically compared the fidelity of conventional myocyte nuclear identification using confocal microscopy, with and without the aid of a membrane marker. The values obtained with these assays were then compared with those obtained with anti-beta-galactosidase immune reactivity in the same samples. In addition, we also studied the accuracy of anti-GATA4 immunoreactivity for myocyte nuclear identification. Our results demonstrate that, although these strategies are capable of identifying myocyte nuclei, the level of interobserver agreement and margin of error can compromise accurate identification of rare events, such as cardiomyocyte apoptosis and proliferation. Thus these data indicate that morphometric approaches based on segmentation are justified only if the margin of error for measuring the event in question has been predetermined and deemed to be small and uniform. We also illustrate the value of a transgene-based approach to overcome these intrinsic limitations of identifying myocyte nuclei. This latter approach should prove quite useful when measuring rare events.

Randomized controlled trial on the cardioprotective effect of bone marrow cells in patients undergoing coronary bypass graft surgery.

AIMS: This randomized study investigates whether bone marrow cells (BMCs) can reduce ischaemic injury during cardiac surgery. METHODS AND RESULTS: Forty-four elective coronary artery bypass grafting patients were randomized to control group or BMCs group (whereby autologous BMCs were administered with each dose of cardioplegia antegradely into the coronaries). Troponin I and CK-MB were measured during the first 48 h after surgery and were not significantly different between the control and BMCs groups. The role of cardiopulmonary bypass (CPB) on the cardioprotective effects of BMCs was also studied using an in vitro model of stimulated ischaemia and reoxygenation on right atrial appendages obtained from controls either before or 10 min after the initiation of CPB. Bone marrow cells significantly reduced myocardial injury in muscles obtained prior to CPB. This effect was comparable with ischaemic preconditioning (IP), although their combination did not afford additional benefit. However, when muscles were harvested after CPB, myocardial injury in the ischaemic group alone was less, and BMCs or IP did not exert further protection. CONCLUSION: Bone marrow cells did not afford additional benefit when used as an additive to cardioplegia during CPB. However, BMCs offer cardioprotection as potent as IP, when the heart is not subjected to stress, such as CPB, that per se can precondition the myocardium.

Randomized, controlled trial of intramuscular or intracoronary injection of autologous bone marrow cells into scarred myocardium during CABG versus CABG alone.

BACKGROUND: Studies of the transplantation of autologous bone marrow cells (BMCs) in patients with chronic ischemic heart disease have assessed effects on viable, peri-infarct tissue. We conducted a single-blinded, randomized, controlled study to investigate whether intramuscular or intracoronary administration of BMCs into nonviable scarred myocardium during CABG improves contractile function of scar segments compared with CABG alone. METHODS: Elective CABG patients (n = 63), with established myocardial scars diagnosed as akinetic or dyskinetic segments by dobutamine stress echocardiography and confirmed at surgery, were randomly assigned CABG alone (control) or CABG with intramuscular or intracoronary administration of BMCs. The BMCs, which were obtained at the time of surgery, were injected into the mid-depth of the scar in the intramuscular group or via the graft conduit supplying the scar in the intracoronary group. Contractile function was assessed in scar segments by dobutamine stress echocardiography before and 6 months after treatment. RESULTS: The proportion of patients showing improved wall motion in at least one scar segment after BMC treatment was not different to that observed in the control group (P = 0.092). Quantitatively, systolic fractional thickening in scar segments did not improve with BMC administration. Furthermore, BMCs did not improve scar transmurality, infarct volume, left ventricular volume, or ejection fraction. CONCLUSION: Injection of autologous BMCs directly into the scar or into the artery supplying the scar is safe but does not improve contractility of nonviable scarred myocardium, reduce scar size, or improve left ventricular function more than CABG alone.

Lineage tracing of cardiac explant derived cells.

AIMS: Cultured cardiac explants produce a heterogeneous population of cells including a distinctive population of refractile cells described here as small round cardiac explant derived cells (EDCs). The aim of this study was to explore the source, morphology and cardiogenic potential of EDCs. METHODS: Transgenic MLC2v-Cre/ZEG, and actin-eGFP mice were used for lineage-tracing of EDCs in vitro and in vivo. C57B16 mice were used as cell transplant recipients of EDCs from transgenic hearts, as well as for the general characterisation of EDCs. The activation of cardiac-specific markers were analysed by: immunohistochemistry with bright field and immunofluorescent microscopy, electron microscopy, PCR and RT-PCR. Functional engraftment of transplanted cells was further investigated with calcium transient studies. RESULTS: Production of EDCs was highly dependent on the retention of blood-derived cells or factors in the cultured explants. These cells shared some characteristics of cardiac myocytes in vitro and survived engraftment in the adult heart in vivo. However, EDCs failed to differentiate into functional cardiac myocytes in vivo as demonstrated by the absence of stimulation-evoked intracellular calcium transients following transplantation into the peri-infarct zone. CONCLUSIONS: This study highlights that positive identification based upon one parameter alone such as morphology or immunofluorescene is not adequate to identify the source, fate and function of adult cardiac explant derived cells.

Mitral valve injury by cardiotomy suction during aortic valve replacement--a near miss.

Mitral valve injury due to cardiotomy suckers during aortic valve surgery has never been reported. We highlight the possibility of such injury experienced in our unit. We also discuss its preventive measures.

Repair of the damaged heart by bone marrow cells: from experimental evidence to clinical hope.

Heart failure remains the leading cause of death in developed countries in spite of improvements in medical and surgical treatments. However, recent observations in experimental studies that bone marrow cells may repair cardiac tissue have offered renewed hopes for the treatment of heart failure. This optimism is further supported by encouraging results from some clinical trials, although the degree of benefits, the underlying mechanisms, and the cell types involved remain to be elucidated. This review summarizes the relevant experimental and clinical studies supporting the use of bone marrow cells in myocardial repair, as well as the controversies and challenges encountered.

Massive CO2 embolism in cardiopulmonary bypass circuit - a near miss.

OBJECTIVES: We report a case of massive air embolism in the cardiopulmonary bypass (CPB) circuit to highlight the principle of its immediate management and its preventive measures. METHODS: The air embolism was caused by the accidental connection of carbon dioxide (CO(2)) supply to the monitoring arm of the retrograde cardioplegia delivery system. The CPB ceased, resulting in cardiac arrest requiring immediate internal cardiac massage. Cerebral protective measures were also instituted instantaneously and the air embolism was purged from the CPB circuit. The cause of air embolism was identified after high initial arterial CO(2) concentration was detected in the blood gas analysis. The CO(2) supply was disconnected, and CPB was restarted. Spontaneous cardiac activities resumed shortly after, and the operation was completed uneventfully. RESULTS: The patient had no immediate post-operative sequel and remained well at 6 weeks follow-up. CONCLUSION: Massive air embolism in cardiopulmonary bypass (CPB) circuit is a life-threatening emergency. Immediate cerebral protective manoeuvres and rectification of the cause of air embolism are vital for favourable outcome. However, high degree of vigilance and cooperation amongst all teams involved are paramount to prevent its occurrence in the first place.

Twenty months' routine use of a new percutaneous tracheostomy set using controlled rotating dilation.

After a favorable trial period, we introduced the new percutaneous tracheostomy set, PercuTwist, in February of 2002 for our routine procedures. Over the next 20 mo, 90 procedures were performed with minimal complications. To prospectively evaluate this experience, we collected information on reasons for unit admission, operators' previous experience, the duration of prior tracheal intubation, the time needed for the procedure, the grading of the difficulty, the amount of bleeding, and the complications of the procedure. Twenty-two of 90 (24.4%) procedures were performed by senior consultants with experience; 68 of 90 (75.6%) were safely performed by intensive care residents under close bedside supervision. The mean time needed for the procedure was 13 min 7 s. In only one procedure during the entire study was any difficulty observed during the insertion process. This occurred because the initial skin incision was too small. However, no major bleeding or complications were encountered.

Intrapleural tumor dissemination after video-assisted thoracoscopic surgery metastasectomy.

In a 34-year-old woman extensive intrapleural disease developed within 1 year of video-assisted thoracoscopic surgery (VATS) removal of two pulmonary metastases from a previously treated synovial sarcoma. She underwent a successful complete pleurectomy through a left thoracotomy to excise the pleural tumor and remains well 6 months later. This case highlights tumor dissemination as one of the pitfalls of VATS metastasectomy and raises concerns about using VATS in this situation.

Primary pulmonary pleomorphic adenoma. An immunohistochemical study and review of the literature.

Primary pleomorphic adenoma of the lung is an uncommon condition. We present a case of primary pulmonary pleomorphic adenoma and its immunohistologic features. The presence of immunoreactivity to both anticytokeratin and antivimentin antibodies for its epithelial components is suggestive of a primary pulmonary lesion. Its high proliferation index and its immunoreactivity to tumor regulatory gene p16(INK4A) are features that, to our knowledge, have not been reported previously. They may have a role in the frequent recurrence of these tumors many years after their apparently complete excision. Detailed genetic investigation and long-term follow-up of this rare tumor will aid in the characterization of its biologic profile.