Repair of a fistula between the aorta and right ventricular outflow tract secondary to infective endocarditis of a unicuspid aortic valve and previously repaired ventricular septal defect.

BACKGROUND: Infective endocarditis of the aortic valve can result in a wide range of destructive pathology beyond the valve leaflets and annulus which require careful surgical planning to provide appropriate debridement and reconstruction. Failure to do so can result in a failure of surgical treatment, recurrent infection and cardiac failure with concomitant high morbidity and mortality. CASE REPORT: We describe the case of a 45-year-old male with previous patch repair of a ventricular septal defect, who was diagnosed with sub-acute bacterial endocarditis of the native aortic valve and developed a new fistula from the aorta to the right ventricular outflow tract which. This was managed surgically. CONCLUSION: This unique case highlights another spectrum of infective endocarditis with a unique approach to repair and management.

Extensive Spontaneous Coronary Artery Dissection Associated With Thrombosis: A Surgical Challenge.

Spontaneous coronary artery dissection is an uncommon cause of myocardial ischemia. Conservative management is the mainstay, although a few patients will require revascularization. We present a case of a 31-year-old woman whose extensive dissection necessitated coronary artery bypass grafting requiring an extended arteriotomy for excision of the thrombus and dissection flap. (Level of Difficulty: Advanced.).

Precise endoballoon positioning for High-Risk sternal re-entry in an ascending aortic pseudoaneurysm with patent coronary grafts.

Redo cardiac surgery can present a unique set of challenges even to the experienced surgeon. Although outcomes have steadily improved in the modern era; if an intraoperative adverse event occurs, there is a 5% incidence of mortality and 19% incidence of myocardial infarction, stroke or death. Overall, the modern incidence of mortality at reoperation varies but be segregated into low and higher risk cohorts depending on the planning computed tomography imaging and risk to substernal structures on re-entry. Patients with ascending aortic or root pseudoaneurysms represent a particularly difficult subset of high-risk patients requiring reoperative cardiac surgery due to the danger of exsanguination and air embolization. The gold standard for management of such cases remains the use of deep hypothermic circulatory arrest (DHCA) to achieve safe re-entry in such cases however this can result in unpredictable DHCA duration depending on the degree of pericardial adhesions. We report a case of aortic pseudoaneurysm in a patient with patent coronary grafts managed using an endoballoon precisely positioned relative to the proximal anastomoses resulting in a safe surgical re-entry and shorter DHCA time.

Examining the forgotten valve: outcomes of tricuspid valve surgery, a 15-year experience.

BACKGROUND: We have entered an era of renewed interest in novel approaches to surgical intervention and minimally invasive and transcatheter technique. With an aging population, isolated tricuspid valve regurgitation incidence is rising; however, referral for surgical intervention remains low. AIMS: We undertook this retrospective review to assess outcomes and challenges associated with tricuspid valve intervention. METHODS: A comprehensive retrospective review of all patients undergoing tricuspid valve intervention in our institution between 2004 and 2018 was carried out. RESULTS: A total of 259 patients who underwent a tricuspid intervention between 2004 and 2018 were identified. Of those, 229 underwent a repair and 30 underwent a replacement. Median survival for repair was 3124 days, and replacement was 2294 days. In-patient mortality was 12% for those undergoing repair and 7% for the replacement patients. Of those undergoing redo tricuspid valve intervention, eight patients (61.5%) were alive at most recent follow-up. Eight patients required intraoperative pacemakers, 2 required postoperative pacemakers. Of those who had intraoperative epicardial pacing systems placed, 5 of the 8 remained pacing dependent on most recent follow up. CONCLUSION: Beyond technical challenges, decision making regarding pacemaker requirement requires further exploration. Redo tricuspid valve surgery carries a significant mortality risk and consideration should be given to earlier intervention in this context.

Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.

PIM kinases are constitutively active proto-oncogenic serine/threonine kinases that play a role in cell cycle progression, metabolism, inflammation and drug resistance. PIM kinases interact with and stabilize p53, c-Myc and parallel signaling pathway PI3K/Akt. This study evaluated PIM kinase expression in NSCLC and in response to PI3K/mTOR inhibition. It investigated a novel preclinical PI3K/mTOR/PIM inhibitor (IBL-301) in vitro and in patient-derived NSCLC tumor tissues. Western blot analysis confirmed PIM1, PIM2 and PIM3 are expressed in NSCLC cell lines and PIM1 is a marker of poor prognosis in patients with NSCLC. IBL-301 decreased PIM1, c-Myc, pBAD and p4EBP1 (Thr37/46) and peIF4B (S406) protein levels in-vitro and MAP kinase, PI3K-Akt and JAK/STAT pathways in tumor tissue explants. IBL-301 significantly decreased secreted pro-inflammatory cytokine MCP-1. Altered mRNA expression, including activated PIM kinase and c-Myc, was identified in Apitolisib resistant cells (H1975GR) by an IL-6/STAT3 pathway array and validated by Western blot. H1975GR cells were more sensitive to IBL-301 than parent cells. A miRNA array identified a dysregulated miRNA signature of PI3K/mTOR drug resistance consisting of regulators of PIM kinase and c-Myc (miR17-5p, miR19b-3p, miR20a-5p, miR15b-5p, miR203a, miR-206). Our data provides a rationale for co-targeting PIM kinase and PI3K-mTOR to improve therapeutic response in NSCLC.

Permanent pacemaker implantation rates following cardiac surgery in the modern era.

AIMS: The aim of this study was to evaluate the incidence of permanent pacemaker (PPM) implantation after cardiac surgery in our institution and investigate risk factors for PPM dependency to provide patients with accurate incidence figures at the time of consent for surgery. METHODS: Data was collected retrospectively from a single tertiary institution from October 2018 to April 2019 inclusive of 403 patients. Incidence of PPM implantation after various cardiac operations was evaluated. A univariate analysis was carried out to identify the independent risk factors related to PPM implantation. RESULTS: Ten patients required a PPM (2.48%). The most common indication for PPM implantation post-cardiac surgery was complete heart block (N = 7, 70%) followed by bradycardia/pauses (N = 2, 20%) and sick sinus syndrome (N = 1, 10%). PPM implantation after coronary artery bypass graft (CABG) surgery was the lowest (0.63%), while combined CABG and valve operations had the highest incidence (5.97%). Independent risk predictors for PPM implantation included female gender (p = 0.03), rheumatic heart disease (p = 0.008), pulmonary hypertension (p = 0.01), redo operations (p = 0.002), mitral valve procedures (p = 0.001), tricuspid valve procedures (p = 0.0003) and combined mitral and tricuspid valve procedures (p = 0.0001). Average length of intensive care unit (ICU)/high-dependency unit (HDU) stay was significantly prolonged for patients who required a PPM post-cardiac surgery. CONCLUSION: As clinicians, it can be challenging to provide our patients with accurate information on the risk of PPM implantation relative to their operation. A unit-specific data may be a more accurate method of informing our patients on this risk.

A systematic review of robotic versus open and video assisted thoracoscopic surgery (VATS) approaches for thymectomy.

BACKGROUND: Median sternotomy has been the most commonly used approach for thymectomy to date. Recent advances in video-assisted thoracoscopic surgery (VATS) and robotic access with CO2 insufflation techniques have allowed more minimally invasive approaches. However, prior reviews have not compared robotic to both open and VATS thymectomy. METHODS: A systematic review was conducted in accordance with the PRISMA guidelines using PubMed, Embase and Scopus databases. Original research articles comparing robotic to VATS or to open thymectomy for myasthenia gravis, anterior mediastinal masses, or thymomas were included. Meta-analyses were performed for mortality, operative time, blood loss, transfusions, length of stay, conversion to open, intraoperative and postoperative complication rates, and positive/negative margin rates. RESULTS: Robotic thymectomy is a valid alternative to the open approach; advantages include: reduced blood loss [weighted mean difference (WMD): -173.03, 95% confidence interval (95% CI): -305.90, -40.17, P=0.01], fewer postoperative complications (odds ratio: 0.37, 95% CI: 0.22, 0.60, P<0.00001), a shorter hospital stay (WMD: -2.78, 95% CI: -3.22, -2.33, P<0.00001), and a lower positive margin rate (relative difference: -0.04, 95% CI: -0.07, -0.01, P=0.01), with comparable operative times (WMD: 6.73, 95% CI: -21.20, 34.66, P=0.64). Robotic thymectomy was comparable with the VATS approach; both have the advantage of avoiding median sternotomy. CONCLUSIONS: While randomized controlled studies are required to make definitive conclusions, current data suggests that robotic thymectomy is superior to open surgery and comparable to a VATS approach. Long-term follow-up is required to further delineate oncological outcomes.

Long-term outcomes following partial atrioventricular septal defect (AVSD) repair in Ireland.

BACKGROUND: We describe the long-term results of partial atrioventricular septal defect (AVSD) repair in a single centre encompassing a 22-year period. Described are rates of survival, reoperation and complications. METHODS: We performed a retrospective review of 556 patients undergoing AVSD repair to identify the 51 patients who underwent partial AVSD repair in Our Lady's Children's Hospital, Crumlin, Ireland, between 1993 and 2015 with long-term follow-up where available. RESULTS: A total of 29 (56.8%) of patients were male and mean age at operation was 3.32 years. Mean weight was 13.2 kg. Trisomy 21 was present in 29 (56.8%). Five patients (9.6%) had undergone prior surgery. Mean cardiopulmonary bypass time was 89 ± 36 min and mean aortic cross-clamp time was 57 ± 28 min. One patient underwent partial AVSD repair and concomitant tracheal resection and extracorporeal membrane oxygenation decannulation. One patient was managed with suture atrial septal defect (ASD) closure, the remainder with patch repair of ASD and mitral cleft closure. The length of hospital stay was 9 ± 5 days. Median follow-up was 6.06 years (IQR, 1.65-10.2 years). There were no early mortalities. One patient died 1 year following surgery (1.9%). One patient required reoperation at an interval of 2 years for severe mitral regurgitation (1.9%). CONCLUSIONS: Short- and long-term survival following partial AVSD repair in Ireland revealed excellent results compared with other published series. Reoperation incidence also compared excellently with other reports published in the literature.

Limax Nd:YAG laser-assisted thoracoscopic resection of pulmonary metastases; a single centre's initial experience.

INTRODUCTION: Pulmonary metastasectomy and indeed redo-pulmonary metastasectomy are now commonly performed thoracic surgical procedures. The air-sealant, haemostatic, and necrotic properties of the KLS Martin Limax Nd:YAG laser at 1.318 µm make it an ideal tool for limited lung resection such as metastasectomy. We present our initial experience of thoracoscopic laser metastasectomy. METHODS: We reviewed data from the first seven patients in our unit to undergo thoracoscopic laser metastasectomy, in particular, patient age, gender, primary malignancy, primary treatment, complications, length of stay (LOS), and final histopathology. All procedures were performed using a two- or three-port thoracoscopic technique with some lesions requiring CT-guided wire localisation. A single drain was inserted via the camera port site and was removed upon confirmation that there was no air leak. RESULTS: Seven patients underwent thoracoscopic laser wedge metastasectomy of eight lesions in our centre between February 2017 and October 2017. The median age was 61 years. The primary disease was colorectal carcinoma in five cases, eccrine carcinoma in one case, and high-grade uterine leiomyosarcoma in one case. Only one patient had a prolonged air leak in the other six cases; the drain was removed on post-operative day 1. The median post-operative LOS was 1 day. All patients had confirmed metastatic disease with clear resection margins on histopathology. CONCLUSION: In our early experience, thoracoscopic laser wedge metastasectomy is a safe and efficient method for performance of pulmonary metastasectomy. We experienced a low complication rate and a short post-operative stay.

A systematic review and meta-analysis of robotic versus open and video-assisted thoracoscopic surgery approaches for lobectomy.

OBJECTIVES: A number of meta-analytical and database studies have sought to compare open, video-assisted thoracoscopic surgery (VATS) and robotic operative approaches to lobectomy, often with conflicting results. Our objective was to perform a comprehensive review of these meta-analytical and database studies published to date. METHODS: A systematic review was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines using the PubMed and Scopus databases. Primary outcome was short-term mortality, and secondary outcomes were operative time, blood loss or transfusion rate, hospital stay, conversions, lymph node yield and complications. Meta-analyses of the primary and secondary outcomes were performed. RESULTS: Robotic lobectomy is a valid alternative to the VATS approach and is superior to the open approach with respect to complications [OR 0.67, 95% CI 0.58-0.76, P < 0.00001] and duration of hospital stay (WMD -1.4, 95% CI -1.96-0.85, P < 0.00001). It is inferior to both VATS and open with respect to operative duration (robotic vs. VATS; WMD 4.98, 95% CI 2.61-7.36, P < 0.001, robotic vs. open WMD 65.56, 95% CI 53.66-77.46, P < 0.00001). Robotic approach is superior with respect to 30-day mortality compared to VATS (OR 0.61, 95% CI 0.45-0.83, P = 0.001 and open approaches (OR 0.53, 95% CI 0.33-0.85, P = 0.008). CONCLUSIONS: This is the largest published systematic review and meta-analysis to date qualifying the robotic lobectomy as a reasonable alternative to VATS and open surgery. Short-term survival is superior in the robotic cohorts. No definitive conclusions on long-term outcomes can be drawn until a randomized controlled trial comparing approaches is conducted.

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus.

Signal transducers and activator of transcription (STAT)-3 is activated in cancers, where it promotes growth, inflammation, angiogenesis, and inhibits apoptosis. Tissue microarrays were generated using tissues from 154 patients, with oesophageal adenocarcinoma (OAC) (n = 116) or squamous cell carcinoma (SCC) (n = 38) tumours. The tissues were stained for pSTAT3 and IL-6R using immunohistochemistry. The OE33 (OAC) and OE21 (SCC) cell lines were treated with the STAT3 inhibitor, STATTIC. The Univariate cox regression analysis revealed that a positive pSTAT3 in SCC was adversely associated with survival (Hazard ratio (HR) 6.382, 95% CI 1.266⁻32.184), while a protective effect was demonstrated with the higher pSTAT3 levels in OAC epithelium (HR 0.74, 95% CI 0.574⁻0.953). The IL-6R intensity levels were higher in the SCC tumours compared with the OAC tumours for the core and leading edge tumour tissue. The pSTAT3 levels correlated positively with the IL-6R levels in both the OAC and SCC. The treatment of OE21 and OE33 cells with the STAT3 inhibitor STATTIC in vitro resulted in decreased survival, proliferation, migration, and increased apoptosis. The pSTAT3 expression was associated with adverse survival in SCC, but not in the OAC patients. The inhibition of STAT3 in both of the tumour subtypes resulted in alterations in the survival, proliferation, migration, and apoptosis, suggesting a potential role for therapeutically targeting STAT3.

Extratumoral PD-1 blockade does not perpetuate obesity-associated inflammation in esophageal adenocarcinoma.

Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continues to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells with anti-PD-1 (clone EH12.2H7) did not enhance inflammatory cytokine expression or proliferation, but transiently increased CD107a expression by CD8+ T cells. Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post neoadjuvant chemoradiotherapy, suggesting that combination with specific conventional treatments may severely impair the efficacy of anti-PD-1 immunotherapy. This study provides evidence that systemically administered anti-PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated inflammation outside the tumor in obesity-associated cancers, such as EAC. Furthermore, our data suggests that studies are required to identify the negative impact of concomitant therapies on PD-1 expression in order to boost overall response rates.

HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients.

Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (<50%) HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.

Impact of the inflammatory microenvironment on T-cell phenotype in the progression from reflux oesophagitis to Barrett oesophagus and oesophageal adenocarcinoma.

The incidence of oesophageal adenocarcinoma (OAC), arising from reflux-induced Barrett oesophagus (BO), is increasing dramatically. T-cells have recently been implicated in the initiation of oesophagitis; however, their role in the progression from oesophagitis to BO and OAC has not been fully elucidated. Previous studies have examined the secreted cytokines from oesophageal tissue during disease progression but this study is the first to examine the activation phenotype and the inflammatory profile of CD4(+) and CD8(+) T-cells in human oesophagitis, BO and OAC tissue. Results demonstrated significantly higher levels of IL-4 producing CD4(+) T-cells and secreted levels of IL-6, confirming a Th2 phenotype in BO. In OAC tissue, both pro- and anti-inflammatory cytokines were secreted, with significantly higher levels of IL-6, IL-1ß, TNF-α, IFN-γ, IL-2 and IL-10 compared with normal oesophageal tissue. In addition, CD4(+) T-cells infiltrating OAC tissue displayed a decreased activation profile, with significantly lower CD45RO and CD69 expression compared with normal tissue. Data from this study suggest that factors in the tissue microenvironment may alter T-cell phenotype and function early during oesophageal disease progression and may represent targets for immune intervention.

A Meta-Analysis Examining Differences in Short-Term Outcomes Between Sutureless and Conventional Aortic Valve Prostheses.

OBJECTIVE: Sutureless aortic valve prostheses are anchored by radial force in a mechanism similar to that of transcatheter aortic valve implantation. Transcatheter aortic valve implantation is associated with an increased permanent pacemaker (PPM) requirement in a significant proportion of patients. We undertook a meta-analysis to examine the incidence of PPM insertion associated with sutureless compared with conventional surgical aortic valve replacement. METHODS: A systematic review was conducted in accordance with the Prisma guidelines. All searches were performed on August 10, 2014. Studies between 2007 and 2014 were included in the search. RESULTS: A total of 832 patients were included in the sutureless group and 3,740 in the conventional group. Aortic cross-clamp (39.8 vs 62.4 minutes; P < 0.001) and cardiopulmonary bypass (64.9 vs 86.7 minutes; P = 0.002) times were shorter in the sutureless group. Permanent pacemaker implantation rate was higher in the sutureless cohort (9.1% vs 2.4%; P = 0.025). CONCLUSIONS: Sutureless aortic valve prostheses are associated with significantly shorter cardiopulmonary bypass and aortic cross-clamp times and a higher incidence of PPM insertion than conventional. Further investigation of the prognostic significance is required.

The effect of obesity on acute kidney injury after cardiac surgery.

OBJECTIVE: Postoperative acute kidney injury is a frequent and serious consequence of cardiac surgery. We undertook to investigate the association of obesity and the risk of acute kidney injury development after cardiac surgery. METHODS: A total of 432 patients who underwent cardiac surgery with cardiopulmonary bypass between October 2009 and August 2010 were included in the final retrospective analysis. Obesity was defined as body mass index 30 kg/m(2) or greater. Acute kidney injury was defined as a creatinine increase of 25% or more from baseline at 48 hours after surgery. RESULTS: The overall incidence of acute kidney injury was 29.9% (n = 129). There was an increased incidence of postoperative renal impairment in the obese versus nonobese cohort; however, this was not statistically significant (39% vs 25.9%, P = .007). Multivariate logistic regression revealed that body mass index 30 kg/m(2) or greater was independently associated with the development of postoperative acute kidney injury (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.27-3.54; P = .004), as were age (OR, 0.98; 95% CI, 0.96-1.0; P = .04) and cardiopulmonary bypass time (OR, 0.99; 95% CI, 0.98-1.0; P = .048). CONCLUSIONS: Obesity with body mass index 30 kg/m(2) or greater is independently associated with an increased risk of acute kidney injury after cardiac surgery. Further understanding of the molecular basis of this association is critical to the design of preventative strategies.

The Combined Impact of Surgical Team Education and Chlorhexidine 2% Alcohol on the Reduction of Surgical Site Infection following Cardiac Surgery.

BACKGROUND: The use of 2% chlorhexidine in 70% alcohol (CHG) has been associated with reduction in catheter-related bloodstream infections and surgical site infection (SSI) in general surgery. Also, improved awareness of best practice from the perspective of the operative team is likely to result in reductions in SSI rates. METHODS: This is an ambispective cohort study of patients undergoing elective cardiac surgery. Between January 2010 and December 2010, patients underwent surgical preparation using Alcohol Povidone Iodine (API). Between January 2011 and December 2011, the surgical team received education and switched to CHG for surgical preparation. Univariate analysis was performed to identify the impact of known risk factors for SSI. A logistic regression model was then fit to estimate the effect of education and CHG in the reduction of SSI in 2011, controlling for known SSI risk factors. RESULTS: There was a substantial reduction in overall SSI rate in 2011 following staff education and the introduction of CHG. The overall unadjusted SSI rate was 4.67% versus 2.08% (p<0.05) for 2010 and 2011 respectively. Using a logistic regression model, the combined effect of education and CHG in 2011 was a 63% reduction in SSI in cardiothoracic surgery (OR 0.37, 95% CI: 0.17-0.83, p=0.016), controlling for age, major co-morbidities, and SSI risk factors. CONCLUSIONS: Using CHG as pre-operative antiseptic in cardiothoracic surgery in a risk-adjusted cohort with education of the surgical team is associated with significantly lower SSI infection rates when compared with API. Emphasis must be placed on the multifactorial approach required to prevent postoperative wound infections.