Role of SMAD proteins in colitis-associated cancer: from known to the unknown.

Small mothers against decapentaplegic (SMAD) proteins are a family of signal transduction molecules in transforming growth factor ß (TGFß) ligand pathways that have been found to have a key role in the pathogenesis of inflammatory bowel disease (IBD). Long standing IBD predisposes individuals to colitis-associated colorectal cancer (CAC), an entity that possess unique characteristics compared to hereditary and sporadic cancer. The ligands of the TGFß super family along with SMADs have also been implicated in several aspects of colorectal cancer formation. SMAD proteins are shown to be involved in a number of potentially carcinogenic mechanisms such as altering gene transcription, controlling stem cell differentiation to causing epigenetic changes. Modulation of these proteins has emerged as a novel therapeutic intervention for IBD although its effect on carcinogenesis remains elusive. This account reviews available evidence linking SMAD proteins to CAC and explores the potential areas for future research in this area.

Supracoronary myotomy for myocardial bridges in the setting of hypertrophic cardiomyopathy: off-pump experience.

Myocardial bridges (MB) are rarely observed but well known pathology of the major epicardial coronary arteries which are embedded in the overlying myocardial tissue. It is most frequently found in young patients with hypertrophic cardiomyopathy (HCM). Myocardial bridges are associated with myocardial ischemia and infarction, cardiac arrhythmias and sudden death. The present case series report the outcomes of three symptomatic patients with hypertrophic cardiomyopathy who underwent myocardial muscle debridges. They were operated using beating heart technique without cardiopulmonary bypass. The authors conclude that off-pump supracoronary muscle myotomy is a feasible treatment modality in the young age group with non-obstructive hypertrophic cardiomyopathy.

Should minimally invasive aortic valve replacement be restricted to primary interventions?

BACKGROUND: The role of minimally invasive aortic valve replacement in cardiac reoperations has not yet been defined. The purpose of this study is to report our experience with this technique. METHODS: Nineteen consecutive patients underwent aortic valve replacement via J-sternotomy as a reoperative cardiac procedure between 1999 and 2005. The mean age was 73.6 +/- 11.4 years. Previous cardiac operations included 12 (63.2 %) coronary artery bypass graftings, 6 (31.5 %) aortic valve replacements and 1 (5.2 %) mitral valve replacement. Mean follow-up was 23.6 +/- 19.7 months. The medical records were retrospectively analyzed. RESULTS: All procedures were successful. Mean aortic cross-clamping time and cardiopulmonary bypass time were 87.4 +/- 32.7 and 133.1 +/- 54.4 minutes, respectively. Cannulation sites were: ascending aorta (52.6 %), femoral artery (47.4 %), femoral vein (94.8 %) and right atrium (5.2 %). Myocardial protection was obtained by selective coronary osteal cold crystalloid cardioplegia and systemic cooling (mean 26.2 +/- 4 degrees C). Average intubation time was 1.5 +/- 1.4 days. Mean intensive care unit stay and postoperative hospital stay was 2.9 +/- 2.6 and 12.9 +/- 5.7 days, respectively. Median chest tube output was 550 ml. There were 4 revisions for bleeding. There were 2 late deaths and one non-incision related hospital death (5 %). This patient, who was already being treated for chronic dialysis, died on day 22 due to a cerebrovascular accident. CONCLUSIONS: Minimally invasive aortic valve replacement is feasible as a reoperative procedure. Its major advantage is avoidance of cardiac reexposure with potential damage to coronary grafts. We think this technique deserves more widespread application.

Robotically enhanced minimally invasive direct coronary artery bypass surgery: a winning strategy?

AIM: Minimally invasive direct coronary artery bypass (MIDCAB) through a small anterolateral thoracotomy on the beating heart can be considered as the better approach for treating isolated lesions on the left anterior descending (LAD) artery. This original MIDCAB procedure, however, involves a larger and often painful thoracotomy due to rib spreading. We describe our experience with robotically enhanced harvesting of one or both internal mammary arteries (IMAs), and with anastomosis performed under direct vision on a beating heart through a very small thoracotomy without rib retraction. METHODS: Between February 2001 and January 2006, 146 consecutive patients underwent robotically enhanced MIDCAB surgery. Perioperative and early follow-up data were analyzed. RESULTS: In all, 144 left and 13 right IMAs were harvested. The mean extubation time was 11.3 h, the mean intensive care (ICU) stay was 30.3 h, the mean hospital stay 8 days. There were no in-hospital deaths, postoperative myocardial infarctions or renal failures. Systematic control angiograms performed in the first 64 patients showed a 96.3% patency rate of the investigated anastomoses. CONCLUSION: Robotically assisted takedown of the IMA and direct off-pump anastomosis through a small anterolateral thoracotomy with no rib retraction appears to be safe, with minimal morbidity, little blood loss, and a reasonable ventilation time, ICU and hospital stay. It is recommended as the preferred method of revascularization for a growing number of indications and certainly an acceptable alternative to percutaneous transluminal coronary angioplasty.

Minimally invasive aortic root replacement: a bridge too far?

AIM: Minimally invasive aortic valve surgery has been studied widely with outcomes comparable or better than standard sternotomy. We recently reported on decreased blood loss, cross clamp time and length of hospital stay when compared to conventional full sternotomy. We expanded the indication to aortic root surgery and report here our 8 years experience. METHODS: From December 1997 to November 2005, 35 patients (mean age 51.3+/-15 years) underwent aortic root replacement, through a partial upper J-sternotomy. A homograft was implanted in 26 (74.3%) patients; the remainder received a valved (4 bioprosthesis, 5 mechanical) conduit. Mean preoperative euroscore was 7+/-2.7 and mean predicted mortality was 11.5+/-13.8%. Mean and median follow-up time was 51+/-31 and 66 months, respectively. RESULTS: Mean aortic cross clamp and cardiopulmonary bypass time were 126+/-25 and 182+/-61 min respectively. Revision for bleeding was necessary in 1 (2.9%) patient. Mean extubation time was 10.4+/-4.8 hours. No postoperative strokes occurred. Intensive care unit stay ranged from 1 to 42 days (2.7+/-7.4 days, median 1). There were 3 (8.5%) early deaths (sepsis, multi-organ failure and low cardiac output) and 2 late non-cardiac deaths. Hospital morbidity included acute renal failure (n=3), pacemaker implantation (n=3), and prolonged ventilation (n=3). Eleven (31.4%) patients experienced atrial fibrillation. No other reoperations were performed. Actuarial survival at 99 months was 74.4% (n=30). CONCLUSIONS: Our results indicate that minimally invasive aortic root replacement is a challenging but feasible procedure with a lower observed mortality than predicted mortality. We continue to perform this procedure in good risk patients.

In vitro set-up of modified Blalock Taussig shunt: vascular resistance-flow relationship.

BACKGROUND: A modified Blalock-Taussig (mBT) shunt is an anastomosis created between the systemic and pulmonary arterial tree in order to improve pulmonary blood flow in neonates and children with congenital heart disease. The aim of this study was to assess vascular resistance-flow relationship in an in vitro set-up of a modified Blalock Taussig shunt. METHODS: A shunt set-up was constructed with the vessels of a sheep. A modified BT shunt was anastomosed between an innominate (brachiocephalic) and a right pulmonary artery. A Medos pump (ventricular assist device) was used to create pulsatile flow. Three different mean pulmonary artery flow rates (Q PA ) were applied. Once mean pulmonary and mean aortic flows (Q AO ) were fixed, shunt flow rates for twelve different pulmonary vascular resistances (R p ) were investigated. RESULTS: For all three pulmonary flow rates, the shunt flow decreased with increasing pulmonary resistance. In addition, systemic flow decreased compared to pulmonary flow. When pulmonary flow rate was set at 800 ml/min and aorta flow rate at 900 ml/min, the distribution of flow between pulmonary and systemic organs flow rates ranged between 69% - 70% and 30% - 31% respectively. Similarly, when both pulmonary and aorta flow rates were set at 900 ml/min, pulmonary and systemic organ flows ranged between 73% - 77% and 23% - 27% respectively. For pulmonary and aorta flow rates of 1000 ml/min and 900 ml/min, respectively, the distribution of flow between pulmonary and systemic organ flow rates varied between 79% - 83% and 17% - 21% respectively. CONCLUSION: Knowledge of the relationship between vascular resistances and flow in this surgically created in vitro mBT shunt set-up may be helpful in the clinical management of the patients whose survival is crucially dependent on the blood flow distribution between the pulmonary and systemic circulation.