Costas S. Bizekis

Minimally invasive mitral valve surgery: a 6-year experience with 714 patients.

BACKGROUND This study analyzes a single institutional experience with minimally invasive mitral valve operations of 6 years, reviewing short-term morbidity and mortality and long-term echocardiographic follow-up data. METHODS Seven hundred fourteen consecutive patients had minimally invasive mitral valve procedures between November 1995 and November 2001; concomitant procedures included 91 multiple valves and 18 coronary artery bypass grafts. Of these 714 patients, 561 patients had isolated mitral valve operations (375 repairs, 186 replacements). Mean age was 58.3 years (range, 14 to 96 years; 30.1% > 70 years), and 15.4% of patients had previous cardiac operations. Arterial cannulation was femoral in 79.0% and central in 21%, with the port access balloon endo-occlusion used in 82.3%. Cardioplegia was transjugular retrograde (54.1%) or antegrade (29.4%). Right anterior minithoracotomy was used in 96.6% and left posterior minithoracotomy in 2.2%. RESULTS Hospital mortality for primary isolated mitral valve repair was 1.1% and 5.8% for isolated mitral valve replacement. Overall hospital mortality was 4.2% (30 of 714). Mean cross-clamp time was 92 minutes and mean cardiopulmonary bypass time was 127 minutes. Postoperatively, median ventilation time was 11 hours, intensive care unit time was 19 hours, and total hospital stay was 6 days. Complications for all patients included permanent neurologic deficit (2.9%), aortic dissection (0.3%); there was no mediastinal infection (0.0%). Follow-up echocardiography demonstrated 89.1% of the repair patients had only trace or no residual mitral insufficiency. CONCLUSIONS This study demonstrates that the minimally invasive port access approach to mitral valve operations is reproducible with low perioperative morbidity and mortality and with late outcomes that are equivalent to conventional operations.

Local surgical, ablative, and radiation treatment of metastases.

Because local therapies directed toward a specific tumor mass are known to be effective for treating early‐stage cancers, it should be no surprise that there has been considerable historical experience using local therapies for metastatic disease. In more recent years, increasing interest in the use of local therapy for metastases likely has arisen from improvements in systemic therapy. In the absence of effective systemic therapies, such local treatments were often considered futile given both the difficulty in eliminating all sites of identifiable metastatic disease as well as realities regarding the rapid natural history of uncontrolled tumor dissemination. However, with a higher likelihood of patients surviving longer after effective systemic therapy, even if not cured, the goal of the eradication of residual metastases via potent local therapies can be rationalized. However, this rationalization should be evidence‐based so as to avoid harming patients for no established benefit. Although surgical metastectomy remains the most common and first‐line standard among local therapies, nonsurgical alternatives, including thermal ablation and stereotactic body radiotherapy, have become increasingly popular because they are generally less invasive than surgery and have demonstrated considerable promise in eradicating macroscopic tumor. Rather than eliminating the need for local therapies, improvements in systemic therapies appear to be increasing the prudent utilization of modern local therapies in patients presenting with more advanced cancer. CA Cancer J Clin 2009;59:145–170.

Off-Pump Coronary Artery Bypass Grafting Reduces Mortality and Stroke in Patients With Atheromatous Aortas: A Case Control Study

Background—Patients with severe atheromatous aortic disease (AAD) who undergo coronary artery bypass (CABG) have an increased risk of death and stroke. We hypothesized that in these high risk patients, off-pump coronary artery bypass (OPCAB) technique is associated with lower morbidity and mortality. Methods and Results—Between June 1993 and January 2002, 5737 patients undergoing CABG had routine intra-operative TEE with 913 (15.9%) found to have severe AAD in the aortic arch or ascending aorta. Of these, 211 patients who underwent OPCAB were matched with 211 on-pump CABG patients by age, ejection fraction, history of stroke, cerebrovascular disease, diabetes, renal disease, nonelective operation, and previous cardiac surgery. Hospital mortality was 11.4% (24/211) for on-pump CABG and 3.8% (8/211) for OPCAB (P =0.003). Multivariate analysis revealed that increased mortality was associated with on-pump CABG (P =0.001), acute MI (P =0.03), number of grafts (P =0.01), age (P =0.01), history of stroke or cerebrovascular disease (P =0.04), CHF (P =0.02), and peripheral vascular disease (P =0.03). Multivariate analysis showed that OPCAB technique was associated with decreased stroke (P =0.05). Freedom from any complication was 78.7% for on-pump CABG and 91.9% for OPCAB (P <0.001). At 36 month follow-up multivariate analysis revealed that increased mortality was associated with age (P =0.001), previous MI (P =0.03), and renal disease (P =0.04), whereas increased survival was associated with increased number of grafts (P =0.001) and OPCAB (P =0.01). Conclusions—OPCAB surgery in patients with severe AAD is associated with lower risk of death, stroke and complications and improved mid-term survival. Routine intra-operative TEE allows identification of these patients and directs choice of appropriate surgical technique.

Lack of ERK activation and cell migration in FGF-2-deficient endothelial cells

The formation of blood capillaries from preexisting vessels (angiogenesis) and vascular remodeling secondary to atherosclerosis or vessel injury are characterized by endothelial cell migration and proliferation. Numerous growth factors control these cell functions. Basic fibroblast growth factor (FGF‐2), a potent angiogenesis inducer, stimulates endothelial cell proliferation, migration, and proteinase production in vitro and in vivo. However, mice genetically deficient in FGF‐2 have no apparent vascular defects. We have observed that endothelial cell migration in response to mechanical damage in vitro is accompanied by activation of the extracellular signal‐regulated kinase (ERK) pathway, which can be blocked by neutralizing anti‐FGF‐2 antibodies. Endothelial cells from mice that are genetically deficient in FGF‐2 neither migrate nor activate ERK in response to mechanical wounding. Addition of exogenous FGF‐2 restores a normal cell response, which shows that impaired migration results from the genetic deficiency of this growth factor. Injury‐induced ERK activation in endothelial cells occurs only at the edge of the wound. In addition, FGF‐2‐induced ERK activation mediates endothelial cell migration in response to wounding without a significant effect on proliferation. These data show that FGF‐2 is a key regulator of endothelial cell migration during wound repair.

Late Results of Isolated Mitral Annuloplasty for “Functional” Ischemic Mitral Insufficiency

Background: Repair of functional ischemic mitral regurgitation (MR) due to annular deformity and leaflet restriction remains a challenge for the surgeon and lacks well‐documented outcomes. We investigated outcomes in the treatment of functional ischemic MR corrected by annuloplasty techniques alone. Methods: From May 1980 to July 1999, 174 patients underwent repair for functional ischemic mitral insufficiency with annuloplasty alone (128 ring annuloplasty; 46 suture annuloplasty). Acute insufficiency was present in 25 (14.4%). Concomitant procedures included CABG (n = 152;87.4%). Patients wisro studied longitudinally with annual follow‐up and echocardiograms. Results: Overall hospital mortality was 17.8% and was increased by NYHA Class 4 (23.8% vs. 8.7%; p = 0.011), diabetes (25.0% vs. 13.6%; p = 0.059), and chronic mitral insufficiency (16.4% vs. 8.0%; p = 0.070). Multiverlatis analysis revealed age (β= 0.099; p = 0.049) and ejection fraction < 30% (β= 1.260; p = 0.097) as significant predictors of hospital death. Mean postoperative mitral insufficiency was 0.84 ± 0.86 (scale of 0–4). NYHA Class 4 (β= 2.33; p = 0.034) and simple suture annuloplasty (β= 2.08; p = 0.07) were associated with increased risk of late cardiac death. Cumulative incidence of mitral reoperation was 7.7% at 5 years. At follow‐up, 89.7% of patients were in NYHA Class 1 or 2 with 83.4% having none or only mild mitral insufficiency. Conclusions: Ring annuloplasty is associated with a survival benefit when compared to simple suture repair in ischemic patients who require annuloplasty alone to correct the MR. Mitral re construction with a ring annuloplasty offers durable results in this homogeneous subset of functional ischemic MR patients. Ischemic mitral insufficiency is associated with significant late mortality.

Malignant mesothelioma 2008.

Purpose of review Mesothelioma is an aggressive malignancy of the pleura with poor survival. There will be approximately 3000 cases of mesothelioma in the United States annually. Multimodality treatment including neoadjuvant chemotherapy in selected individuals followed by extrapleural pneumonectomy and radiation has been studied in recent trials for its effects on disease free and overall survival This review provides a general overview of malignant mesothelioma with a summary of the most significant articles from within the past year as well as from the past. Recent findings Areas of recent interest include the evaluation of osteopontin and mesothelin as new tumor markers for mesothelioma. New phase III trials have been performed to evaluate the use of combined chemotherapy regimens. Summary Malignant mesothelioma is a very difficult malignancy to treat. Patients with the disease usually have an occupational asbestos exposure, and in some, viral exposure with SV40. There have been many historical treatments including combinations of local control with surgery and radiation as well as attempts to prevent systemic failure with chemotherapy. Novel therapies including intrapleural chemotherapy, photodynamic therapy and hyperthermic perfusion have also been used with some success. Finally there are several attempts at immunomodulating and targeted treatments, which are in phase I/II trials.

Severe mediastinal infection with abscess formation after endobronchial ultrasound-guided transbrochial needle aspiration.

Endobronchial, ultrasound-guided, transbronchial needle aspiration has recently been introduced as an alternative to mediastinoscopy for lymph node staging of lung cancer and the diagnosis of respiratory diseases. This procedure is less invasive and more cost-effective, and multiple large studies have reported no associated complications. In this case, an individual presented with descending mediastinitis after having this minimally invasive procedure for mediastinal lymphadenopathy.

Radiofrequency ablation for Barrett's esophagus and low-grade dysplasia in combination with an antireflux procedure: a new paradigm.

OBJECTIVE Radiofrequency ablation for Barretts esophagus in combination with an antireflux procedure has not been widely documented. We report our initial experience with radiofrequency ablation in association with antireflux procedure for Barretts metaplasia and low-grade dysplasia. METHODS A total of 14 patients (10 male and 4 female patients) presented with Barretts metaplasia (n=11) or low-grade dysplasia (n=3). Median age was 60 years (38-80 years). The severity of Barretts esophagus was classified by length (in centimeters), appearance (circumferential/noncircumferential), and histology (1, normal; 2, Barretts metaplasia; and 3, low-grade dysplasia). Radiofrequency ablation was performed with the HALO 360 degrees or 90 degrees systems (BARRX Medical, Sunnyvale, Calif). RESULTS Median follow-up was 17 months. The mean number of ablative procedures undertaken was 2.6 (range, 1-6). There was no mortality, but there were 2 perioperative complications after the antireflux procedure (pneumonia, 1; atrial fibrillation, 1). One patient had mild dysphagia requiring a single dilation 2 months after ablation. The mean length of Barretts esophagus decreased from 6.2 to 1.2 cm after treatment (P=.001). Barretts grade decreased significantly (P=.003). Before therapy, circumferential Barretts esophagus was present in 13 patients. At last endoscopy, only 1 patient had circumferential Barretts esophagus present. The number of radiofrequency ablation treatments was significantly (P < .05) associated with success. All patients receiving 3 or more treatments had complete resolution of Barretts metaplasia. CONCLUSIONS Radiofrequency ablation performed either before or after an antireflux procedure is safe. This approach is effective for reducing or eliminating metaplasia and dysplasia. Long-term studies will be necessary to determine whether this approach can provide durable control of both reflux and Barretts esophagus.

Initial experience with endobronchial ultrasound in an academic thoracic surgery program.

BACKGROUND Mediastinoscopy is considered the gold standard for evaluating mediastinal lymph nodes. However, endobronchial ultrasound-guided transbronchial needle aspiration has lately offered a less invasive alternative, with the ability to obtain nodal samples under direct visualization. Recent literature found an early learning curve for this technique. We present the initial experience of 4 thoracic surgeons with the procedure. MATERIALS AND METHODS A retrospective chart review was performed on the first 51 patients on whom an endobronchial ultrasound-guided transbronchial needle aspiration was performed from January 5, 2007, to July 24, 2008. This group included 43 patients with a history or known diagnosis of malignancy as well as 8 patients with a presumed sarcoidosis diagnosis. All negative results were confirmed with mediastinoscopy. The techniques sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were assessed. RESULTS A total of 73 lymph nodes underwent biopsy in 51 patients. These individuals included 34 men and 17 women, with an average age of 62 years (range, 21-89 years). No surgical or postoperative complications were noted. Overall, a correct diagnosis was established in 88% of the patients (45 of 51). After the first 25 cases (a mean of 6 cases per surgeon), a technique modification was adapted to increase diagnostic yield. The first 25 cases had a 72.22% sensitivity and 80% accuracy, whereas the last 26 cases had a 95.45% sensitivity and 96.15% accuracy (P = .07). CONCLUSION Endobronchial ultrasound-guided transbronchial needle aspiration is a quickly mastered technique that offers a safe, minimally invasive, and accurate means to evaluate mediastinal lymph nodes.

Activation of mitogen-activated protein kinases during preparation of vein grafts and modulation by a synthetic inhibitor

OBJECTIVE Long-term durability of saphenous vein grafts used for coronary artery bypass grafting is limited by neointimal formation. Arterial vascular injury is known to activate intracellular mitogen-activated protein kinases, including extracellular signal-regulated kinases and c-jun N-terminal kinases, that affect cell differentiation, proliferation, migration, and apoptosis. This study tests the hypothesis that these mitogen-activated protein kinases are activated in saphenous veins during preparation for coronary artery bypass grafting. METHODS Saphenous veins were harvested from 10 patients undergoing coronary artery bypass grafting. A specimen from each vein was placed in ice-cold lysis buffer immediately after harvesting (t = 0). The remaining tissue was incubated at room temperature in normal saline, 0.1% dimethylsulfoxide (vehicle), or 50 mmol/L PD98059 (mitogen-activated protein kinase kinase-1/2 inhibitor) until the vein was grafted (mean 50 minutes). To study kinetics of intracellular signaling pathways, canine saphenous veins were harvested, and mitogen-activated protein kinases and PI-3 kinase pathways were studied after different incubation time intervals. Extracted proteins were analyzed by Western blotting or in vitro kinase assay. RESULTS The human saphenous veins showed elevated levels of active extracellular signal-regulated kinase after harvesting (t = 0) and prior to implant (t = 1). Incubation with PD98059 resulted in decreased activation of extracellular signal-regulated kinase. Kinetics of canine saphenous veins showed extracellular signal-regulated kinase and c-jun N-terminal kinase activation, in a time-dependent manner, along with activation of the growth factor-regulated PI3 kinase pathway. CONCLUSIONS This study characterizes activation of extracellular signal-regulated kinases and c-jun N-terminal kinases during vein graft preparation and demonstrates the ability to inhibit extracellular signal-regulated kinase activation by simple incubation with a specific inhibitor. Further studies are needed to evaluate the significance of these findings with respect to graft durability.