Epithelial tissues have sparse stroma, in contrast to their corresponding tumours. The effect of cancer cells on stromal cells is well recognized. Increasingly, stromal components, such as endothelial and immune cells, are considered indispensable for cancer progression. The role of desmoplastic stroma, in contrast, is poorly understood. Targeting such cellular components within the tumour is attractive. Recent evidence strongly points towards a dynamic stromal cell participation in cancer progression that impacts patient prognosis. The role of specific desmoplastic stromal cells, such as stellate cells and myofibroblasts in pancreatic, oesophageal and skin cancers, was studied in bio-engineered, physiomimetic organotypic cultures and by regression analysis. For pancreatic cancer, the maximal effect on increasing cancer cell proliferation and invasion, as well as decreasing cancer cell apoptosis, occurs when stromal (pancreatic stellate cells) cells constitute the majority of the cellular population (maximal effect at a stromal cell proportion of 0.66–0.83), accompanied by change in expression of key molecules such as E-cadherin and β-catenin. Gene-expression microarrays, across three tumour types, indicate that stromal cells consistently and significantly alter global cancer cell functions such as cell cycle, cell–cell signalling, cell movement, cell death and inflammatory response. However, these changes are mediated through cancer type-specific alteration of expression, with very few common targets across tumour types. As highlighted by these in vitro data, the reciprocal relationship of E-cadherin and polymeric immunoglobulin receptor (PIGR) expression in cancer cells could be shown, in vivo, to be dependent on the stromal content of human pancreatic cancer. These studies demonstrate that context-specific cancer–stroma crosstalk requires to be precisely defined for effective therapeutic targeting. These data may be relevant to non-malignant processes where epithelial cells interact with stromal cells, such as chronic inflammatory and fibrotic conditions.
Coronary endarterectomy (CE) may provide a useful adjunct to coronary artery bypass grafting (CABG) in patients with extensive, diffuse coronary atheroma. However, concerns regarding its morbidity and mortality have created uncertainty as to the role of CE in the current era. The aim of this study was therefore to quantitatively summarize the short- and long-term outcomes of CE. Twenty observational studies were identified by systematic literature search, incorporating 54 440 patients (7366 CABG + CE; 47 074 CABG only), which were analysed using random-effects modelling. Heterogeneity, subgroup analysis, quality scoring and risk of bias were assessed. Primary end-points were 30-day mortality and perioperative and postoperative myocardial infarction (MI). Secondary end-points were postoperative morbidity, intensive care unit (ITU) stay, hospital stay and long-term graft patency. Adjunctive CE significantly increased 30-day mortality [odds ratios (OR) = 1.69, 95% confidence interval (CI) [1.49-1.92], P <0.00001], perioperative (OR = 2.10, 95% CI [1.82-2.43], P <0.00001) and postoperative MI (OR = 3.34, 95% CI [1.74-6.41], P = 0.0003) when compared with CABG alone. Furthermore, postoperative ventricular arrhythmias, pulmonary complications, renal failure and inotrope use were significantly greater in patients undergoing adjunct CE. CE also increased ITU and hospital stay and reduced angiographic patency at the last follow-up (OR = 0.57, 95% CI [0.36-0.88]). Increased 30-day morbidity and mortality continues to raise concerns over the safety of adjunct CE. Furthermore, the procedure can be associated with worse long-term graft patency. To better determine whether CE should remain a viable adjunct to CABG, novel studies must focus on collecting prospective data with homogeneous inclusion criteria for CE as well as isolating outcomes for different coronary vessels and standardizing postoperative anticoagulation.
Innominate artery (IA) aneurysms represent 3% of all arterial aneurysms. Due to the risk of thromboembolic complications and spontaneous rupture, surgical repair is usually recommended on an early elective basis. We present the case of 81-year-old Caucasian male presenting with atypical anterior chest pain secondary to a large innominate artery aneurysm who underwent successful open surgical repair at our institution. In our experience, open correction via median sternotomy with extension into the right neck provides excellent exposure and facilitates rapid reconstruction with good short and long-term outcomes. Minimally invasive and endovascular approaches provide emerging alternatives to open IA aneurysm repair, however further research is required to better define optimal patient selection criteria and determine the long-term outcomes of these novel therapies.
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether open coronary endarterectomy (CE) and coronary artery bypass grafting (CABG) compares favourably with closed endarterectomy and CABG in the myocardial revascularization of patients presenting with diffuse coronary artery disease (DCAD). One hundred and fifty-five articles were identified by a systematic search, of which 10 best answered the clinical question incorporating a total of 1203 patients (915 open-CE, 288 closed-CE). All were observational studies. Two were comparative and the remaining eight were case series. The authors, journal, date, country of publication, patient group, study type, relevant outcomes and results were recorded. The open technique involved removal of atheroma under direct vision through an arteriotomy along the length of diffusely stenotic artery, whereas the closed technique involved a smaller arteriotomy and removal via traction on the proximal plaque. The overall postoperative mortality rate associated with open-CE ranged from 2.3 to 10.5%. Both comparative studies demonstrated at least equivalent 30-day mortality between open-CE and closed-CE. Notably, the four studies with highest overall postoperative mortality used a saphenous vein (SV) graft in the majority of patients. Furthermore, two-vessel CE was associated with higher mortality rates. Among these best evidence series, the overall incidence rate of postoperative myocardial infarction (MI) was 7.3% (88/1203). Whether open-CE or the use of internal thoracic artery (ITA) conduit over SV affects postoperative MI rates remains inconclusive. Mid-term and long-term graft patency, and 3-, 4- and 5-year survival rates are all improved when open-CE is combined with the ITA bypass conduit, when compared with closed-CE or open-CE using another conduit. In summary, open-CE with CABG in the setting of DCAD may carry lower 30-day mortality than closed-CE with CABG. Utilization of ITA appears to improve mortality, whereas the SV conduit and multivessel CE may worsen clinical outcome. Furthermore, the ITA may also improve graft patency when combined with open-CE. There is currently insufficient evidence to determine the effect of open-CE on MI incidence. Future large, prospective studies are now required with defined subgroups, stratifying technique, number and territory of the endarterectomy and conduit type in order to determine the patients in whom open-CE may confer the greatest benefit.
Interest in minimally invasive and off-pump cardiac surgical techniques has promoted the development of automated distal anastomotic devices (DADs) to facilitate construction of coronary artery anastomosis. Several DADs have been proposed for potential use in coronary surgery. However, a number of technical failures and uncertainty around both short-term morbidity and long-term patency have limited the generalized uptake of these devices. A systematic literature search identified 28 studies, incorporating 970 patients who underwent coronary artery bypass grafting using a DAD. Eight different devices were identified including Heartflo, St Jude, U-clip, vessel closure system, C-port, magnetic vascular positioner and coronary anastomosis coupler. Thirty-day mortality, cardiac-specific mortality and myocardial infarction were equal between DADs and hand-sewn cases (1.3, 0.3 and 0.8%, respectively). The overall proportion of postoperative haemorrhage was higher in the anastomotic device group (2.3%) than in the group with hand-sewn anastomoses (1.5%) although not statistically significant. Overall graft patency was 97.2% at <1 month, 94.6% at 1-3 months and 92.3% at >3 months. Of the currently available systems, the U-clip device was found to provide the best overall postoperative outcomes, which included a patency of 96.1% at >3months. The current literature is limited by its predominantly observational study design and lack of directly comparative studies. Furthermore, inter-study variation in patient selection, anticoagulation strategies and follow-up periods prevents quantitative comparison. Future research necessitates multicentre randomized, controlled studies to provide a direct comparison of current and future anastomotic device systems with established hand-sewn techniques in both the short and long term.
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