According to Authur Clarke’s three laws of technology: First, the only way to discover the limit of possible is to venture a little way past them into the impossible.
Second, when a scientist states that something is possible, he is almost certainly right.
When he states that something is impossible, he is very probably wrong. Third, any sufficiently advanced technology is indistinguishable from magic.
In 1940s, Blalock and Taussig developed a novel palliative surgical treatment for cyanotic congenital heart diseases. From then on, cardiac surgery gathered public attention and received new blood for further inventions. In 1953, Gibbon developed the heart-lung machine and made the first “open heart surgery” come true. Cardiac surgery once again presented a new and huge surge. Most significant achievements and well known operations were established before 1980s. However, all of them were conducted via midline full sternotomy.
Started from mid-1980s, technological advancement enabled endoscopic operations.
Laparoscopic cholecystectomy was one of the earliest and most famous examples. At that time, open cholecystectomy was a well-established operation which carried predictable and reproducible results. Most surgeons were familiar with this operation.
The endoscopic procedure was completely new to them. Surgeons from that time had no chance to palpate the lesion, although they could visualize more details. Loss of tactile feedbacks, unpredictable learning curve, and trouble-shooting were reasons why some surgeons hesitated and resisted the new procedure. However, there are always early adaptors. Some pioneers solved those obstacles and set up the standard.
Through practices, most surgeons accepted the procedure because their patients desired to have less invasive procedures. Starting from this example, more and more endoscopic or less invasive procedures were developed and replaced the conventional approaches in every surgical discipline.
Coronary artery bypass grating (CABG) is a well established treatment for
coronary artery disease. It provides more complete relief of angina and less need for repeated revascularization. However, it carries more peri-operative morbidities, including stroke and wound related complications. CABG was successful in the early era and remained unchanged as it was developed in 1960s. Full sternotomy,
cardiopulmonary bypass, cardioplegic arrest, and large leg wounds for saphenous vein harvest were all characteristics to CABG. In 1980s, the rapid development of
percutaneous interventions urged the transformation of CABG. Although CABG procedures remained in an increased trend for the past 2 decades, it did not correlate
with the significant increment of the incidence of coronary artery disease. Most patients with a newly diagnosed coronary artery disease chose to have percutaneous coronary interventions rather than the invasive counterpart-CABG. As the trend of surgical evolution, CABG per se should have modifications aiming at the reduction of the invasiveness, morbidities and potential mortalities.
The concerns of less invasive cardiac surgery remain the safety followed by efficacy. All new treatment modalities should provide “better” results. Some alternatives provide results “as good as” or “not inferior to” the conventional one.
Tremendous works focus on head-to-head comparisons and keep to persuade other practitioners as followers. Less invasive surgical approaches face the same challenges as well. Besides from patients’ satisfaction, evidence showed that less invasive
surgical approaches achieved the safety and efficacy as conventional ones. But how minimal is minimal enough? From the viewpoints of consumers, the best incision is no incision. That means we still have long way to go and will not have the true destination. In the real world, how to define the less invasive cardiac surgery? Most surgeons agree that elimination of heart lung machine and/or avoidance of sternotomy are currently available choices. The famous robotic cardiac surgeon - Chitwood stated that less invasiveness is a philosophy – a constellation of new routines, methods and techniques all directed collectively toward speedily returning patients to normalcy.
There are some impacts of less invasive cardiac surgery. The rapid growing
interventional technology drives cardiac surgeons to think alternatively. The change in patient’s risk category urges less invasiveness for higher safety. The increase of hospital number and decrease in surgeons’ volume both have negative impacts for better practices. Reduced hospital resources and reduced industry interest in cardiac surgery prevent this high-esteem surgical discipline from new inventions. Despites all these obstacles, there are many recent advances in CABG. Off-pump CABG regains popular acceptance in recent 2 decades. Off-pump CABG fits the primary concern of less invasiveness and provides better results in regards to cerebral, pulmonary and renal outcomes. The enabling technologies provide an user-friendly situation for followers to learn this approach. Endoscopic harvest of graft conduits is the milestone for cardiac surgeons to enter the endoscopic era. Using this technique, both arterial and venous conduits are available without conventional, long skin incisions. Cerebral protection is another achievement. Intraoperative monitor equipments and proximal anastomosis facilitators are all aimed for reduction in this drastic complication.
Intraoperative conduit confirmation for patency offers a safeguard for immediate revision. Fast track allows caregivers, patient, and families to predict every next step in a reasonable way. Pharmacological advances increase the long-term patency and
reduce adverse events and the need for repeated revascularization. Finally, robotic surgery offers a platform for totally endoscopic cardiac surgery. All these
breakthroughs are endorsed from our colleagues’ endeavor and intelligence.
The choice of conduits for CABG varies within patients. Arterial conduits consist of internal mammary artery, radial artery and right gastroepiploic artery. Venous conduits focus mainly on the great saphenous vein. Arterial conduits provide longevity on patency. The harvest procedures for arterial conduits are usually time consuming and technique demanding. Venous conduits are often readily available, but the long-term patency for them remains a myth. Conduit-related wound complications are not uncommon and usually underestimated or ignored because they are not life threatening. Saphenous vein related wound complications include hematoma, infection, poor healing, persistent leakage and poor cosmetic results. It has been one of the notorious consequences in CABG.
Saphenous vein was harvested in open method since it was used for grafting procedures. The abundance of adipose tissue prohibits adequate healing. Therefore, early in these practices, bridged skin incisions were used to reduce wound-related complications. Following the trend of endoscopic surgery, endoscope was applied in saphenous vein harvest in late 1990s. Endoscopic saphenous vein harvest started from an idea to a prototype. The instrument was applied from the animal experiment to the human trial. FDA approved it for clinical use in 2001 (Guidant Vasoview system).
Since them, it was rapid adopted by cardiac surgeons and welcome by patients.
Following the initial success of one company, there are several followers in the market.
Briefly speaking, endoscopic vein harvest (EVH) consists of several steps using specially designed instruments. A 2-cm skin incision was made over the saphenous vein near the knee area. Following an initial local dissection, a balloon trocar was inserted and a cone dissector was used to spread the surrounded tissue over the saphenosu vein. Carbon dioxide was insufflated at a given pressure to open up the subcutaneous tract and facilitate the dissection. The remaining branches were divided using endoscopic scissors incorporated with cauterization. After proximal ligation and division were completed, the saphenous vein could be pulled out through the first incision.
The clinical benefits are obvious. Several case-control and prospective, randomized, controlled trials show that EVH results in decreased infection rate, fewer observed morbidities, fewer mean days to ambulation, reduced total length of stay, improved
cosmetic results and overall patients’ satisfaction. Traditional longitudinal saphenectomy is a multivariable risk factor for development of leg wound complications. Regardless of harvest techniques, double blinded histological
assessment involved endothelial, elastic lamina, and smooth muscle continuity as well as medial and adventitial connective tissue uniformity are not significantly different.
The effect of endoscopic technique on endothelial cell viability is comparable to that of the open technique. Electron microscopic evaluation using scanning and
transmission electron microscopy for endoscopic and conventional methods reveals similar damages in endothelial cell edema, separation, detachment, basement membrane exposure and collagen exposure. Even molecular studies were done.
Endoscopic and open saphenous vein harvest are comparable in their effects on synthesis of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and the levels of interleukin-1, interleukin-2 and interleukin-10. But are all these experimental benefits translated into better patients’ outcomes?
There are two important articles dealing with patency studies comparing
endoscopic and conventional approaches. One prospective, randomized study shows that EVH is not a risk factor for vein graft occlusion or vein graft disease. The overall patency rate depends on target and vein-related variables and patient characteristics rather than the method of vein harvesting. The other prospective, randomized study shows that five-year actual event-free survival is similar in patients with either an endoscopic or traditional vein-harvesting procedures. Long-term patency and event-free survival are our ultimate goals to evaluate the new approach. However, there are lots of confounding factors. Since direct evidence of patency is lacking, we propose the following studies to evaluate the endothelial functions and refer as supporting evidence for long-term outcomes.
During the last 6 years, we collected more than 1400 cases of EVH in our institute.
Our clinical experience modified the initial way of our approach. We reduced the need for two skin incisions. In order to achieve proximal ligation and division, a
percutaneous stitch was used to encircle the proximal saphenous vein from outside under the endoscopic vision. After gentle ligation, saphenous vein was divided from inside using endoscopic scissors. Preoperative mapping of saphenous vein is also one of the keys to success. Duplex ultrasound scanning localizes vein segment precisely, optimizes incision sites, eliminates blind exploration and also improves conduit planning. Some varicosities could be identified prior to surgery and EVH could be abandoned to reduce the cost.
Early in our clinical practices, a rare complication – carbon dioxide embolism
happened as an incidence. Due to routine application of transesophageal
echocardiography in CABG, a prospective, observational study was conducted. Our objectives were to determine the incidence, severity and the time course of the carbon dioxide embolism during EVH using carbon dioxide insufflation. Four hundred three consecutive patients scheduled for off-pump coronary artery bypass surgery or peripheral artery bypass surgery were studies. Multiplane transesophageal
echocardiography with a new trnasgastric view was used to monitor bubbles in the inferior vena cava and hepatic vein. The overall carbon dioxide embolism occurred in 17.1% of patients. Whereas, mild. moderate, and massive carbon dioxide embolism occurred in 13.1%, 3.5% and 0.5%, respectively. The occurrence of moderate and massive carbon dioxide embolism was frequently associated with the surgical manipulation of branches of saphenous veins. No significant risk factors were identified in multiple logistic regression analysis. Our report first addressed the occurrence of un-notified entity and gave the idea of incidence of occurrence. In the clinical scenario of massive carbon dioxide embolism, circulatory collapse, high pulmonary artery pressure, high central venous pressure, and desaturation happened without anticipation. Rapid commence of cardiopulmonary bypass was the only way to save the patient. For beginners who struggled with the learning curve, we identified a potential missed, but dangerous complication. Cautious hemodynamic monitor and careful manipulation were helpful.
Following the identification of carbon dioxide embolism, another clinical study was proposed to reduce this complication. The carbon dioxide insufflation was the
keystone to enable the endoscopic techniques.Of course, there were several
modifiable factors. Careful manipulation and complete seal-off of those vein branches were important with no doubt. The techniques to divide vein branches varied and could not be well controlled for study. The duration of carbon dioxide insufflation certainly played an important role. But it seemed not reasonable to limit the harvest time in order to prevent this complication. Therefore, we focus on the insufflation pressure. Four hundred and ninety eight consecutive patients scheduled for elective off-pump CABG were prospectively studied. These patients were randomly assigned into high or low pressure groups in which 15 and 12 mmHg carbon dioxide
insufflation pressure were used during EVH, respectively. Multiplane transesophageal echocardiography with transgastric inferior vena cava view was used to monitor the appearance of carbon dioxide bubbles. The incidence of carbon dioxide embolism in the high pressure group was significantly higher than that in the low pressure group.
(13.3% vs 6.5%, p<0.05) Two episodes of emergent cessation of carbon dioxide insufflation were required in the high pressure group in order to prevent further hemodynamic compromise. No massive carbon dioxide embolism with significant
hemodynamic alterations occurred in either group. In comparison with our previous experience (17.1%), the overall incidence of carbon dioxide embolism was reduced.
Meticulous manipulation of vein branches played a role. Reduction of carbon dioxide insufflation pressure was indeed the major determinant. From this result, we
concluded that the incidence of carbon dioxide embolism during EVH could be reduced with a lower insufflation pressure, which, in combination with increased surgical expertise and continuous transesophageal echocardiography monitoring helps to reduce the risks of massive carbon dioxide embolism. The first clinical
observational study and the second prospective, randomized, controlled study were novel for all those EVH practioners. These reports highlighted the importance of the systemic side effect and add safe margins for beginners in this practice.
Besides from our clinical experience, several basic studies were proposed to evaluate the clinical benefits of EVH. The functional integrity of endothelium in venous conduits play a critical role in early or late graft occlusion. Vein trauma after saphenectomy may influence the progression of medial and intimal hyperplasia and ultimately affect the graft patency. The aims of our basic researches were to
investigate the impact of the different vein-harvesting procedures: EVH and open vein harvest, on the endothelial integrity and function of saphenous veins. We started from the morphological evaluation. CD31, so called platelet endothelial cell adhesion molecule, was targeted for this study. CD31 is highly expressed on endothelial cells.
Immunohistochemical staining for CD31 was used to localize this molecule and so was the location of endothelial cells. Patients proposed to have cornary artery bypass surgery were enrolled for this survey. A pair of saphenous vein segment was harvested in each patient. The segments harvested with endoscopic technique and open
technique were compared for the immunohistochemical staining. Our results showed the endoscopic technique preserved more of the endothelial cells than conventionally open harvest technique. This result encouraged us to continuous our works.
Following the morphological evaluation, endothelial function was our next target.
Endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), and cyclooxygenase-2 (Cox-2) were selected to represent endothelial function. These 3 molecules were famous and crucial for endothelial functions, including platelet aggregation, vascular tone, thrombogenicity, smooth muscle cell proliferation, etc. Initially, we tried to understand the protein amounts of those molecules after two different procedures. We failed in quantification of these proteins using Western blotting. Then, we shifted to ELISA techniques. After serial calibrations, significant variations existed in different individuals for these proteins which could not reach the statistically significant difference. At least, the protein expression showed that the new endoscopic method
was not inferior to the old open method.
However, it seemed not reasonable that there would be difference in protein expression if our manipulation or intervention was less than 30 minutes. Usually, it took more than 30 minutes from a mechanical stimulus, through signal transduction, gene expression (from DNA transcription, RNA translation) to the final
product-protein. Therefore, we repeated our study targeting on the RNA of these 3 molecules. First of all, primers were constructed for real-time PCR. The results showed that there was no difference in RNA amount of eNOS and Cox-2, but higher ET-1 RNA was identified in the saphenous vein segment of open harvest group. As we know, ET-1 was highly related to vasoconstriction and smooth muscle cell
proliferation. Endoscopic harvest technique seemed favorable in this context.
Although the evidence was not solid enough in RNA analysis, we concluded that endocopic technique was better than conventional way when taking both
morphological and functional evaluations.
Current practices are expected to base on evidence. Minimally invasive surgery per se is favorable in clinical outcomes. Like endoscopic saphenous vein harvest, it provides less recovery time, shorter length of stay, shorter time to return to work, less complications and higher satisfaction. But we still expect more! We still expect for the better long-term patency from the less invasive way, since the patency translates to better long-term outcomes-less repeated revascularization and better survival.
However, there is no available data yet. Indirect evidences derived from endothelial studies like our works reveal favorable results. Thus, we have better reasons to continue our works. Indeed, it is lonely to be a pioneer. The pioneer is responsible for uncertainty and responsible to answer unknown questions and face new challenges.
Hopefully, we can have more evidence to persuade followers and benefit our patients.
We will try to answer those unanswered questions.