Attenuation of renal ischemia-reperfusion injury by postconditioning involves adenosine receptor and protein kinase C activation.

SUMMARY: Significant organ injury occurs after transplantation and reflow (i.e., reperfusion injury). Postconditioning (PoC), consisting of alternating periods of reperfusion and re-occlusion at onset of reperfusion, attenuates reperfusion injury in organs including heart and brain. We tested whether PoC attenuates renal ischemia-reperfusion (I/R) injury in the kidney by activating adenosine receptors (AR) and protein kinase C (PKC). The single kidney rat I/R model was used. Groups: (1) sham: time-matched surgical protocol only. In all others, the left renal artery (RA) was occluded for 45 min and reperfused for 24 h. (2) CONTROL: I/R with no intervention at R. All antagonists were administered 5 min before reperfusion. (3) PoC: I/R + four cycles of 45 s of R and 45 s of re-occlusion before full R. (4) PoC + ARi: PoC plus the AR antagonist 8-rho-(sulfophenyl) theophylline (8-SPT). (5) PoC + PKCi: PoC plus the PKC antagonist chelerythrine (Che). In shams, plasma blood urea nitrogen (BUN mg/dl) at 24 h averaged 23.2 +/- 5.3 and creatinine (Cr mg/dl) averaged 1.28 +/- 0.2. PoC reduced BUN (87.2 +/- 10 in CONTROL vs. 38.8 +/- 9, P = 0.001) and Cr (4.2 +/- 0.6 in CONTROL vs. 1.5 +/- 0.2, P < 0.001). 8-SPT and Che reversed renal protection indices after PoC. I/R increased apoptosis, which was reduced by PoC, which was reversed by 8-SPT and Che. Postconditioning attenuates renal I/R injury by adenosine receptor activation and PKC signaling.

Renal epithelial cell-derived monocyte colony stimulating factor as a local informant of renal injury and means of monocyte activation.

Monocyte accumulation in renal allografts is associated with allograft dysfunction. As monocyte influx occurs acutely following reperfusion, we investigated the effect of ischemia-reperfusion injury (IRI) on monocyte colony stimulating factor (m-CSF), a key cytokine in monocyte recruitment. We hypothesized that renal tubule epithelial cells (RTECs) could produce m-CSF in response to IRI, which could in turn promote monocyte activation. Real time PCR was used to measure levels of intragraft m-CSF transcripts in patients during IRI and clinical rejection. Also, m-CSF production by RTECs following IRI simulation in vitro was measured using ELISA. Monocyte expression of CD40 and CD80 was then analyzed using flow cytometry following co-culture with supernatants of RTECs after IRI. Monocyte expression of CD40, CD80 and HLA-DR was then examined following treatment with rh-m-CSF (10, 36, and 100 ng/ml), as was monocyte size and granularity. We found that intragraft m-CSF transcription was significantly increased postreperfusion (P = 0.002) and during clinical rejection (P = 0.002). We also found that RTECs produced m-CSF in response to IRI in vitro (P = 0.036). Monocytes co-cultured with the supernatants of postischemic RTECs became activated as evidenced by increased expression of CD40 and CD80. Also, monocytes treated with recombinant m-CSF assumed an activated phenotype exhibiting increased size, granularity and expression of CD40, CD80, CD86, and HLA-DR, and demonstrating enhanced phagocytic activity. Taken together, we suggest that renal tubular cell derived m-CSF is a stimulus for monocyte activation and may be an important target for control of IRI-associated immune activation.

Robotic Lung Resection for Non-Small Cell Lung Cancer.

Robotic-assisted pulmonary lobectomy can be considered for patients able to tolerate conventional lobectomy. Contraindications to resection via thoracotomy apply to patients undergoing robotic lobectomy. Team training, familiarity with equipment, troubleshooting, and preparation are critical for successful robotic lobectomy. Robotic lobectomy is associated with decreased rates of blood loss, blood transfusion, air leak, chest tube duration, length of stay, and mortality compared with thoracotomy. Robotic lobectomy offers many of the same benefits in perioperative morbidity and mortality, and additional advantages in optics, dexterity, and surgeon ergonomics as video-assisted thoracic lobectomy. Long-term oncologic efficacy and cost implications remain areas of study.

Intrapyloric botulinum injection increases postoperative esophagectomy complications.

BACKGROUND: Intrapyloric botulinum toxin injection has emerged as a possible alternative to standard pyloric drainage procedures. Possible advantages include decreased operative time and less postoperative dumping and bile reflux symptoms. However, data are lacking to show its effectiveness versus standard drainage procedures. The purpose of this review is to compare the results in a prospective cohort of patients who received pyloric botulinum injection versus patients who received pyloromyotomy or pyloroplasty with esophagectomy. METHODS: We performed a retrospective review of a prospective database of all patients who underwent an open esophageal resection at a single institution from 2005 through 2010. Three hundred twenty-two patients were divided into 3 groups for analysis: botulinum injection (n = 78), pyloromyotomy (n = 45), and pyloroplasty (n = 199). We compared these groups with respect to duration of the procedure, presence of delayed gastric emptying on postoperative swallow studies, requirement of anastomotic dilation, requirement of pyloric dilation, use of postoperative promotility agents, and patient experience of postoperative symptoms of reflux or dumping, or both. RESULTS: Patients receiving botulinum injections experienced similar delayed gastric emptying on postoperative radiologic evaluation as did patients undergoing pyloromyotomy and pyloroplasty (16% versus 5% and 13%, respectively; p = 0.14). Mean operative time was significantly shorter for the patients receiving botulinum as expected (239 minutes versus 312 minutes and 373 minutes, respectively; p < 0.001). However, more patients receiving botulinum and pyloric dilation (22% versus 4% and 2%, respectively; p < 0.001) experienced postoperative reflux symptoms (32% versus 12% and 13%, respectively; p = 0.001) and used postoperative promotility agents (22% versus 5% and 15%, respectively; p = 0.04). There was no statistical difference between the groups regarding postoperative dumping. CONCLUSIONS: Use of intrapyloric botulinum injection significantly decreased operative time. However, the patients receiving botulinum experienced more postoperative reflux symptoms, had increased use of promotility agents as well as a requirement for postoperative endoscopic interventions, and postoperative dumping was not reduced by the reversible procedure. Intrapyloric botulinum injection should not be used as an alternative to standard drainage procedures. Pyloromyotomy appears to be the drainage procedure of choice to accompany an esophagectomy.

Cervical tracheal resection: new lessons learned.

BACKGROUND: Cervical tracheal stenosis can be a difficult condition to manage. Depending on the etiology, location, and extent of the stenosis, tracheal or cricotracheal resection may be required. Intraoperative decisions may predict outcome. METHODS: We performed a retrospective chart review of all patients undergoing cervical tracheal or cricotracheal resection from April 2000 through March 2008. RESULTS: One hundred and five patients underwent 108 tracheal or cricotracheal resections. Median age was 65 years (range, 15 to 78); 68% were women. Indication for operation included postintubation tracheal stenosis (38), idiopathic (31), tracheostomy stenosis (19), invasive thyroid cancer (9), and other (8). Median length of trachea resected was 2.7 cm (range, 1.5 to 6.0 cm); 48 patients (46%) underwent extended cricotracheal resections. Twenty-six patients (25%) had an intraoperative chin stitch placed. Hospital stay was a median of 4 days (range, 2 to 33). Operative mortality was (1%); 1 patient died of myocardial infarction on postoperative day 3. Four patients (4%) had hoarseness or vocal cord immobility. Median follow-up was 36 months (range, 1 to 79). Eighteen patients (17%) required dilation postoperatively. Seven patients (7%) required tracheostomy; 2 (2%) are tracheostomy dependent. Three patients (3%) underwent a re-resection for recurrent stenosis. Multivariate analysis of indication for resection, type of resection, length of resection, anastomotic technique, and use of chin stitch did not predict the need for postoperative dilation, tracheostomy, or reoperation. CONCLUSIONS: Cervical tracheal resection can be performed safely with low morbidity and mortality. Only 5% of patients required a long-term tracheostomy or re-resection for recurrent tracheal stenosis. Specific intraoperative decisions did not predict long-term success.

Cerebral Emboli Generation During Off-Pump Coronary Artery Bypass Grafting With a Clampless Device versus Partial Clamping of the Ascending Aorta.

OBJECTIVE: : It is not known whether use of a clampless facilitating device during proximal graft anastamosis decreases intraoperative cerebral emboli in patients with mild atherosclerotic ascending aorta (AAA) having off-pump coronary artery bypass. METHODS: : After intraoperative epiaortic ultrasound showed no more than mild (grade I-II) atherosclerotic ascending aorta, 20 patients were randomized to receive either partial clamping (PC, n = 10) or the HEARTSTRING clampless device (HS, n = 9) for proximal graft construction on the ascending aorta. Continuous transcranial Doppler monitoring, with capability to discern gaseous from solid particulates, was used intraoperatively to monitor high-intensity transient signals (HITS) in the middle cerebral arteries. Postoperative diffusion-weighted brain magnetic resonance imaging documented old and new ischemic brain lesions. RESULTS: : There were no significant differences between the groups in the number of proximals (P = 0.14), distals (P = 0.4), or intraoperative cell saver transfusions (P = 0.69). The total number of HITS was not significantly different between the PC and HS groups (P = 0.2). However, the number of solid HITS was significantly lower in the HS than in the PC group (2.7 ± 2.6 versus 14.0 ± 8.1; P < 0.001). The number of gaseous emboli in the HS group was fourfold greater when a mister-blower rather than a suction device was used to clear blood away from the HS site. Postoperatively, there were no deaths, myocardial infarctions, or clinical strokes observed in either group. Diffusion-weighted cerebral magnetic resonance imaging revealed no statistical difference between groups for new infarct lesions. CONCLUSIONS: : Use of the HS device during off-pump coronary artery bypass was associated with significantly fewer intraoperative solid emboli in the middle cerebral artery than PC of the ascending aorta.

Long-Term Outcomes After CABG With Concomitant CO2 Transmyocardial Revascularization in Comparison With CABG Alone.

OBJECTIVES: : Transmyocardial revascularization (TMR) has been used as an isolated or adjunctive revascularization therapy in patients presumed to have nonbypassable coronary artery disease. The purpose of this study is to evaluate the short- and midterm mortality for patients with complete revascularization using TMR and coronary artery bypass grafting (CABG) compared with those patients with incomplete CABG revascularization and to document long-term follow-up in patients receiving TMR + CABG. METHODS: : Seventy TMR + CABG patients were cohort matched with 70 patients undergoing isolated CABG with circumflex coronary artery disease, but with no bypassable distal targets, from 1999 to 2005 at Emory University Hospital. The data were retrospectively reviewed from a database after being prospectively entered. Results are presented in mean ± standard deviation, and Kaplan-Meier curves were created for long-term all-cause mortality. RESULTS: : The TMR + CABG patients had a similar incidences to the CABG only group for preoperative ejection fraction (50.9 ± 11.2% vs. 50.7 ± 10.3%, P = 0.93), number of grafts (2.6 ± 1.1 vs. 2.5 ± 1.3, P = 0.5), and number of diseased vessels (2.8 ± 0.3 vs. 2.9 ± 0.4, P = 0.26). Off-pump surgery was used more often in the CABG alone group versus the TMR combined with CABG group (74.3% vs. 41.4%, P < 0.001). Postoperatively, there was no statistical difference among the TMR + CABG and the CABG alone groups for intensive care unit length of stay (4.3 ± 7.8 days vs. 2.6 ± 3.4 days, P = 0.026), postsurgical length of stay (7.6 ± 6.1 days vs. 6.8 ± 4.5 days, P = 0.31), stroke events (1.4% vs. 1.4%, P = 1.00), myocardial infarction (4.3% vs. 2.9%, P = 0.65), and 30-day mortality (5.7% vs. 4.3%, P = 0.70). Long-term survival rate was not statistically significant. In addition, 4-year follow-up in the TMR + CABG group had symptom improvement with reduction in New York Heart Association classification for class III/IV (P < 0.0001, baseline vs. 4-year follow-up). CONCLUSIONS: : The combination of TMR and CABG for complete revascularization is safe and carries no further risk to patients compared with CABG only. CABG + TMR patients tend to have increased resource utilization. Long-term follow-up shows similar survival between the groups. TMR can be a useful adjunct to CABG for complete revascularization.

Radiofrequency ablation of Barrett's esophagus: short-term results.

BACKGROUND: The presence of Barrett's esophagus (BE) increases the risk of esophageal cancer. Total regression of BE is uncommon with medication or laparoscopic fundoplication, and endoscopic techniques to obliterate BE have varied results. This study evaluated the early results of a balloon-based catheter radiofrequency ablation (RFA) system in patients with medically refractory reflux symptoms and biopsy-proven BE. METHODS: The medical records of 27 consecutive patients who underwent RFA for BE from March 2005 through January 2007 were reviewed. Esophagogastroduodenoscopy was performed before ablation to document presence of BE and no cancer and at 8 weeks after the RFA to assess the presence of residual BE. RESULTS: Mean patient age was 53.6 +/- 12.5 years; 16 (59%) were men. The average length of the Barrett segment treated was 4.6 +/- 4.7 cm. Two patients (7.4%) had low-grade dysplasia. No patient had high-grade dysplasia and cancer. There was no periprocedural morbidity or at follow-up, no postprocedure dysphagia or stricture. In all patients, the BE was completely replaced with normal squamous epithelium. Symptoms regressed in 16 patients (60%) with RFA and proton pump inhibitor therapy. Eleven required an antireflux procedure for persistent symptoms. CONCLUSIONS: Short-term results show that RFA for BE is safe and achieves 100% replacement of intestinal metaplasia. RFA of BE combined with fundoplication may be offered to patients with BE and medically refractory reflux symptoms. Long-term endoscopic surveillance is needed to determine if the risk of cancer is reduced with this bimodality therapy.

Deep hypothermic circulatory arrest for repair of the brachiocephalic artery and aorta after a gunshot wound to the chest.

The incidence of penetrating trauma to the brachiocephalic artery and aortic arch is not known, because most patients die of hemorrhage before they receive adequate treatment. Furthermore, when torrential hemorrhage from penetrating trauma is present, the anatomy of the thoracic vasculature can present a challenge for gaining adequate exposure, achieving vascular control, and performing proper repair. We describe the case of a patient with a gunshot wound to the anterior chest; he was placed under cardiopulmonary bypass and deep hypothermic circulatory arrest while we performed a patch repair of the proximal brachiocephalic artery and aortic arch.

The risk of esophageal resection after esophagomyotomy for achalasia.

BACKGROUND: Esophagomyotomy is the mainstay of treatment for achalasia with proven long-term success. However, in patients with a significantly dilated esophagus, many advocate esophageal resection thus forgoing an esophagomyotomy. The purpose of this study is to determine the esophagomyotomy failure rate in patients with achalasia. METHODS: A retrospective review of all patients with achalasia who underwent an esophagomyotomy from 1996 to 2006; 272 patients were divided into three groups based on their preoperative degree of esophageal dilation for comparison. The endpoint for esophagomyotomy failure was persistent symptoms requiring any intervention. RESULTS: The preoperative characteristics were comparable except for the severely dilated esophagus patients who had a longer duration of preoperative symptoms. Group I (mild dilatation) had 162 patients with 7 failures requiring intervention. Group II (moderate dilatation) had 74 patients with 4 failures and group III (severe dilatation) had 36 patients with 5 patients requiring intervention. For the entire cohort, median follow-up was 37 months (range, 8 to 144 months). There was no statistically significant difference among the groups in the number of patients requiring reintervention. The overall esophagectomy rate was only 2%. However, there was a significantly higher (p = 0.02) esophagectomy rate in the severely dilated patients. CONCLUSIONS: The degree of esophageal dilatation associated with achalasia does not influence the success of an esophagomyotomy. Of the entire patient population in this study, only 6 patients required an esophagectomy. The majority of patients with the most severely dilated esophagus did not require an esophagectomy. Esophagomyotomy should be the first treatment option for patients with achalasia no matter what the degree of esophageal dilatation.