Faculty Bibliography

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

According to the American Cancer Society, there will be an estimated 14,520 new cases of esophageal cancer and 174,470 new cases of lung cancer in 2005. Close to 60% of these patients with esophageal cancer will present at an advanced stage not amenable to cure, but still will require palliation of their dysphagia. Conventional plastic stents (CPS) were used initially, and with continuous improvement in technology, insertion of self-expanding metal stents (SEMS) has become the palliative treatment of choice in the majority of these patients. SEMS are effective in palliating malignant dysphagia in 85%-100% of patients. More recently, a new self-expanding plastic stent (SEPS) has been designed which in early studies has been very effective in palliating dysphagia. Similarly, the majority of patients with lung cancer will present at an advanced stage and approximately 20% of these patients will have an endobronchial component requiring some form of palliation for relief of airway obstruction. Currently airway stents are either made of self-expanding metal for more permanent use, orl silicone if a more temporary solution is needed. Complications similar to the esophageal stents may arise. The purpose of this article is to provide an evidence based review of stents in the palliative setting for esophageal and lung cancer and briefly explore their potential use and expanding indications in the neoadjuvant setting

Most complications after surgery for GERD can be avoided by experience and proper surgical technique. Often, what is termed a 'slipped' or 'twisted' wrap is one that was not properly constructed during the initial surgery. These technical errors can be avoided by complete mobilization of the stomach and esophagus, removal of the epigastric fat pad to identify esophageal shortening, and preservation of both vagus nerves. It is critical to avoid these errors, because an improperly constructed wrap will probably condemn the patient to significant dysphagia, recurrent reflux, and the need for reoperation. Should reoperation be required, the wrap should be completely dismantled so the technical error can be identified and a proper antireflux mechanism created

BACKGROUND: We have previously reported our experience with minimally invasive esophagectomy. Our standard approach involves laparoscopic and thoracoscopic mobilization of the esophagus with a cervical esophagogastric anastomosis. In the present study we report our early experience with a modification of this technique, in which a high intrathoracic anastomosis is performed. METHODS: From 2002 to 2005, a minimally invasive Ivor Lewis esophagectomy was performed in 50 patients. The planned approach included a totally laparoscopic abdominal procedure and either a minithoracotomy or thoracoscopy. Indications for esophagectomy included short segment Barrett's esophagus with high-grade dysplasia or resectable adenocarcinoma of the gastroesophageal junction (GEJ) with minimal proximal esophageal extension. . RESULTS: The median age was 62.3 years (range, 38 to 79). Twenty-five patients (50%) received either preoperative chemotherapy or chemoradiation. There was one nonemergent conversion to an open procedure during laparoscopy. Planned minithoracotomy was successful in 35 patients; an additional 15 patients had the entire thoracic component performed thoracoscopically. A circular stapled anastomosis was performed in all patients. The operative mortality was 6%. Three patients (6%) developed an anastomotic leak; all were successfully managed nonoperatively. Four patients (8%) developed postoperative pneumonia. There were no recurrent laryngeal nerve injuries. CONCLUSIONS: Minimally invasive Ivor Lewis esophagectomy was technically feasible and resulted in good initial results in our center, which is experienced in minimally invasive and open esophagectomy. This approach minimizes the degree of gastric mobilization, almost eliminates recurrent laryngeal nerve injury and pharyngeal dysfunction, and allows additional gastric resection margin in the case of cardia extension of GEJ tumors

OBJECTIVE: Vascular injury results in activation of the mitogen-activated protein kinases-extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38(MAPK)-which have been implicated in cell proliferation, migration, and apoptosis. The goal of this study was to characterize mitogen-activated protein kinase activation in arterialized vein grafts. METHODS: Carotid artery bypass using reversed external jugular vein was performed in 29 dogs. Vein grafts were harvested after 30 minutes and 3, 8, and 24 hours, and 4, 7, 14, and 28 days. Contralateral external jugular vein and external jugular vein interposition vein-to-vein grafts were used as controls. Vein graft extracts were analyzed for extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38(MAPK) activation. Proliferating cell nuclear antigen expression was investigated as a parameter of cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling staining and intimal hyperplasia by morphometric examination of tissue sections. RESULTS: Significant intimal hyperplasia was observed at 28 days. Over the time points studied, vein graft arterialization resulted in bimodal activation of both extracellular-signal regulated kinase and p38(MAPK) (30 minutes through 3 hours; 4 days) but did not induce activation of c-jun N-terminal kinase. Proliferating cell nuclear antigen expression increased from days 1 through 28, and apoptosis increased between 8 and 24 hours. CONCLUSION: Vein graft arterialization induces bimodal activation of extracellular-signal regulated kinase and p38(MAPK); however, in contrast with what is described in arterial injury, it does not induce c-jun N-terminal kinase activation. These results provide the first comprehensive characterization of the mitogen-activated protein kinase signaling pathways activated in vein graft arterialization and identify mitogen-activated protein kinases as potential mediators of vein graft remodeling and subsequent intimal hyperplasia

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.

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