Asad A. Shah

Induction Chemoradiation Is Not Superior to Induction Chemotherapy Alone in Stage IIIA Lung Cancer

BACKGROUND The optimal treatment strategy for patients with operable stage IIIA (N2) non-small cell lung cancer is uncertain. We performed a systematic review and meta-analysis to test the hypothesis that the addition of radiotherapy to induction chemotherapy prior to surgical resection does not improve survival compared with induction chemotherapy alone. METHODS A comprehensive search of PubMed for relevant studies comparing patients with stage IIIA (N2) non-small cell lung cancer undergoing resection after treatment with induction chemotherapy alone or induction chemoradiotherapy was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Hazard ratios were extracted from these studies to give pooled estimates of the effect of induction therapy on overall survival. RESULTS There were 7 studies that met criteria for analysis, including 1 randomized control trial, 1 phase II study, 3 retrospective reviews, and 2 published abstracts of randomized controlled trials. None of the studies demonstrated a survival benefit to adding induction radiation to induction chemotherapy versus induction chemotherapy alone. The meta-analysis performed on randomized studies (n=156 patients) demonstrated no benefit in survival from adding radiation (hazard ratio 0.93, 95% confidence interval 0.54 to 1.62, p=0.81), nor did the meta-analysis performed on retrospective studies (n=183 patients, hazard ratio 0.77, 95% confidence interval 0.50 to 1.19, p=0.24). CONCLUSIONS Published evidence is sparse but does not support the use of radiation therapy in induction regimens for stage IIIA (N2). Given the potential disadvantages of adding radiation preoperatively, clinicians should consider using this treatment strategy only in the context of a clinical trial to allow better assessment of its effectiveness.

Results with an algorithmic approach to hybrid repair of the aortic arch

OBJECTIVE Hybrid repair of the transverse aortic arch may allow for aortic arch repair with reduced morbidity in patients who are suboptimal candidates for conventional open surgery. We present our results with an algorithmic approach to hybrid arch repair, based on the extent of aortic disease and patient comorbidities. METHODS Between August 2005 and January 2012, 87 patients underwent hybrid arch repair by three principal procedures: zone 1 endograft coverage with extra-anatomic left carotid revascularization (zone 1; n = 19), zone 0 endograft coverage with aortic arch debranching (zone 0; n = 48), or total arch replacement with staged stented elephant trunk completion (stented elephant trunk; n = 20). RESULTS The mean patient age was 64 years, and the mean expected in-hospital mortality rate was 16.3% as calculated by the EuroSCORE II. Of operations, 22% (n = 19) were nonelective. Sternotomy, cardiopulmonary bypass, and deep hypothermic circulatory arrest were required in 78% (n = 68), 45% (n = 39), and 31% (n = 27) of patients to allow for total arch replacement, arch debranching, or other concomitant cardiac procedures, including ascending with or without hemiarch replacement in 17% (n = 8) of patients undergoing zone 0 repair. All stented elephant trunk procedures (n = 20) and 19% (n = 9) of zone 0 procedures were staged, with 41% (n = 12) of patients undergoing staged repair during a single hospitalization. The 30-day/in-hospital rates of stroke and permanent paraplegia or paraparesis were 4.6% (n = 4) and 1.2% (n = 1). Of 27 patients with native ascending aorta zone 0 proximal landing zone, three (11.1%) experienced retrograde type A dissection after endograft placement. The overall in-hospital mortality rate was 5.7% (n = 5); however, 30-day/in-hospital mortality increased to 14.9% (n = 13) owing to eight 30-day out-of-hospital deaths. Native ascending aorta zone 0 endograft placement was found to be the only univariate predictor of 30-day in-hospital mortality (odds ratio, 4.63; 95% confidence interval, 1.35-15.89; P = .02). Over a mean follow-up period of 28.5 ± 22.2 months, 13% (n = 11) of patients required reintervention for type 1A (n = 4), type 2 (n = 6), or type 3 (n = 1) endoleak. Kaplan-Meier estimates of survival at 1 year, 3 years, and 5 years were 73%, 60%, and 51%. CONCLUSIONS Hybrid aortic arch repair can be tailored to patient anatomy and comorbid status to allow complete repair of aortic pathology, frequently in a single stage, with acceptable outcomes. However, endograft placement in the native ascending aorta is associated with high rates of retrograde type A dissection and 30-day/in-hospital mortality and should be approached with caution.

Staged total abdominal debranching and thoracic endovascular aortic repair for thoracoabdominal aneurysm

OBJECTIVE Thoracoabdominal aortic aneurysms (TAAAs) occur most commonly in elderly individuals, who are often suboptimal candidates for open repair because of significant comorbidities. The availability of a hybrid option, including open visceral debranching with endovascular aneurysm exclusion, may have advantages in these patients who are at high-risk for conventional repair. This report details the evolution of our technique and results with complete visceral debranching and endovascular aneurysm exclusion for TAAA repair in high-risk patients. METHODS Between March 2005 and June 2011, 47 patients (51% women) underwent extra-anatomic debranching of all visceral vessels, followed by aneurysm exclusion by endovascular means at a single institution. A median of four visceral vessels were bypassed. The debranching procedure was initially performed through a partial right medial visceral rotation approach, leaving the left kidney posterior in the first 22 patients, and in the last 25 by a direct anterior approach to the visceral vessels. The debranching and endovascular portions of the procedure were performed in a single operation in the initial 33 patients and as a staged procedure during a single hospital stay in the most recent 14. RESULTS Median patient age was 71.0 ± 9.8 years. All had significant comorbidity and were considered suboptimal candidates for conventional repair: 55% had undergone previous aortic surgery, 40% were American Society of Anesthesiologists (ASA) class 4, and baseline serum creatinine was 1.5 ± 1.3 mg/dL. The 30-day/in-hospital rates of death, stroke, and permanent paraparesis/plegia were 8.5%, 0%, and 4.3%, respectively, but 0% in the most recent 14 patients undergoing staged repair. These patients had significantly shorter combined operative times (314 vs 373 minutes), decreased intraoperative red blood cell transfusions (350 vs 1400 mL), and were more likely to be extubated in the operating room (50% vs 12%) compared with patients undergoing simultaneous repair. Over a median follow-up of 19.3 ± 18.5 months, visceral graft patency was 97%; all occluded limbs were to renal vessels and clinically silent. There have been no type I or III endoleaks or reinterventions. Kaplan-Meier overall survival is 70.7% at 2 years and 57.9% at 5 years. CONCLUSIONS Hybrid TAAA repair through complete visceral debranching and endovascular aneurysm exclusion is a good option for elderly high-risk patients less suited to conventional repair in centers with the requisite surgical expertise with visceral revascularization. A staged approach to debranching and endovascular aneurysm exclusion during a single hospitalization appears to yield optimal results.

Primary Chest Wall Tumors

Patients with chest wall tumors present diagnostic and therapeutic challenges. The differential diagnosis of these tumors is broad, because they can represent a heterogeneous spectrum of diseases from primary benign or malignant tumors to metastases; local extension of adjacent tumors of the lung, mediastinum, pleura or breast; nonneoplastic infectious or inflammatory conditions; or even local manifestations of systemic disease. Primary chest wall tumors are best classified according to their tissue of origin, bone or soft tissue, and further subclassified according to whether or not they are benign or malignant. Most of these tumors are uncommon, with information garnered from individual case reports or institutional case series. Chest wall tumors are more commonly either metastases or local invasion of an underlying adjacent tumor. Primary chest wall tumors account for only 0.04% of all new cancers diagnosed and 5% of all thoracic neoplasms. The list of potential tumors is broad (Table 1), with nomenclature that is frequently overlapping and sometimes contradictory in the literature. Primary benign lesions of the chest wall can behave in a latent, active, or aggressive manner. Approximately 60% of primary chest wall tumors are malignant. Although primary chest wall tumors are diagnosed in every age group, they are more likely malignant in the extremes of age: in the young and the elderly. Certain tumors present predominantly in one age group. For example, Ewing sarcoma is

Metabolic profiles predict adverse events after coronary artery bypass grafting

OBJECTIVE Clinical models incompletely predict the outcomes after coronary artery bypass grafting. Novel molecular technologies can identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting. METHODS The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected before surgery. Principal components analysis and Cox proportional hazards regression modeling were used to assess the relation between the metabolite factor levels and a composite outcome of postcoronary artery bypass grafting myocardial infarction, the need for percutaneous coronary intervention, repeat coronary artery bypass grafting, and death. RESULTS During a mean follow-up period of 4.3 ± 2.4 years, 126 subjects (26.4%) experienced an adverse event. Three principal components analysis-derived factors were significantly associated with an adverse outcome on univariate analysis: short-chain dicarboxylacylcarnitines (factor 2, P = .001); ketone-related metabolites (factor 5, P = .02); and short-chain acylcarnitines (factor 6, P = .004). These 3 factors remained independently predictive of an adverse outcome after multivariate adjustment: factor 2 (adjusted hazard ratio, 1.23; 95% confidence interval, 1.10-1.38; P < .001), factor 5 (odds ratio, 1.17; 95% confidence interval, 1.01-1.37; P = .04), and factor 6 (odds ratio, 1.14; 95% confidence interval, 1.02-1.27; P = .03). CONCLUSIONS Metabolic profiles are independently associated with adverse outcomes after coronary artery bypass grafting. These profiles might represent novel biomarkers of risk that can augment existing tools for risk stratification of coronary artery bypass grafting patients and might elucidate novel biochemical pathways that mediate risk.

Results with selective preoperative lumbar drain placement for thoracic endovascular aortic repair.

BACKGROUND The optimal use of lumbar cerebrospinal fluid drainage for the prevention of spinal cord ischemia (SCI) with thoracic endovascular aortic repair (TEVAR) remains unclear. Here, we report our experience with selective preoperative lumbar drain placement with TEVAR. METHODS Between May 2002 and January 12, 381 TEVAR procedures were performed at a single referral institution. Preoperative lumbar drains were placed selectively in patients considered high-risk for SCI due to planned long-segment aortic coverage with a history of prior aortic intervention or planned hybrid Crawford extent I to III thoracoabdominal aortic aneurysm repair. RESULTS Preoperative lumbar drains were placed in 81 patients (21%); of these, drain placement in 38 (47%) was for procedures involving long-segment descending thoracic aortic coverage in the setting of prior descending thoracic or infrarenal aortic repair, and in 43 (53%) was for hybrid thoracoabdominal aortic aneurysm repair. SCI occurred in 12 patients (14.8%) who received a preoperative lumbar drain, transient in 6 (7.4%) and permanent in 6 (7.4%), whereas SCI occurred in 13 patients (4.3%) who did not receive a preoperative lumbar drain, 12 transient (4.0%) and 1 permanent (0.3%). A lumbar drain complication occurred in 9 drain patients (11.1%), although none resulted in permanent disability. Age, postoperative hypotension, and the number of endografts implanted were independently associated with SCI. Preoperative lumbar drain placement was not associated with reduced SCI. CONCLUSIONS Restricted use of preoperative lumbar drains for patients at high-risk of SCI undergoing TEVAR appears safe and leads to low rates of SCI in nondrained patients. However, the utility of preoperative lumbar drains in preventing SCI with TEVAR remains questionable and should be weighed against the risk of drain complications.

Results of Thoracic Endovascular Aortic Repair 6 Years After United States Food and Drug Administration Approval

BACKGROUND Since United States Food and Drug Administration approval in 2005, the short-term safety and efficacy of thoracic endovascular aortic repair (TEVAR) have been established. However, longer-term follow-up data remain lacking. The objective of this study is to report 6-year outcomes of TEVAR in clinical practice. METHODS A prospective cohort review was performed of all patients undergoing TEVAR at a single referral institution between March 2005 and May 2011. Rates of reintervention were noted. Overall and aortic-specific survival were determined using Kaplan-Meier methods. Log-rank tests were used to compare survival between groups. RESULTS During the study interval, 332 TEVAR procedures were performed in 297 patients. Reintervention was required after 12% of procedures at a mean of 8 ± 14 months after initial TEVAR and was higher in the initial tercile of patients (15.0% vs 9.9%). The 6-year freedom from reintervention was 84%. Type I endoleak was the most common cause of reintervention (5%). Six-year overall survival was 54%, and aorta-specific survival was 92%. Long-term survival was significantly lower than that of an age- and sex-matched United States population (p < 0.001). Survival was similar between patients requiring a reintervention vs those not (p = 0.26). Survival was different based on indication for TEVAR (p = 0.007), and patients with degenerative aneurysms had the lowest survival (47% at 6 years). Cardiopulmonary pathologies were the most common cause of death (27 of 93 total deaths). CONCLUSIONS Long-term aortic-related survival after TEVAR is high, and the need for reintervention is infrequent. However, overall long-term survival is low, particularly for patients with degenerative aneurysms, and additional work is needed to identify patients unlikely to derive a survival benefit from TEVAR.

Predictors of massive transfusion with thoracic aortic procedures involving deep hypothermic circulatory arrest

OBJECTIVE Massive perioperative blood product transfusion may be required with thoracic aortic operations and is associated with poor outcomes. We analyzed independent predictors of massive transfusion in thoracic aortic surgical patients undergoing deep hypothermic circulatory arrest. METHODS The study consisted of 168 consecutive patients undergoing open thoracic aortic procedures involving deep hypothermic circulatory arrest between July 2005 and August 2008. We identified 26 preoperative and procedural variables as potentially related to blood product use, tested for association with total blood products transfused by multivariate linear regression model, and constructed logistic regression model for massive transfusion (requiring ≥ 5 units of transfused packed red blood cells between incision and 48 postoperative hours). RESULTS Multivariate linear regression determined that 6 significant variables accounted for 42% of variation in total blood products transfused: age (P = .008), preoperative hemoglobin (P = .04), weight (P = .02), cardiopulmonary bypass time (P < .0001), emergency status (P < .0001), and resternotomy (P < .0001). Final predictive logistic regression model included 1-g/dL increase in preoperative hemoglobin (odds ratio, 0.54; 95% confidence interval, 0.43-0.69; P < .0001), 10-minute increase in cardiopulmonary bypass time (odds ratio, 1.15; 95% confidence interval, 1.05-1.26; P = .0026), and emergency status (odds ratio, 4.02; 95% confidence interval, 1.53-10.55; P = .0047. CONCLUSIONS Cardiopulmonary bypass time, emergency status, and preoperative hemoglobin were independent predictors of massive transfusion. These variables, along with weight, age, and resternotomy, were associated with total blood product use in thoracic aortic operations involving deep hypothermic circulatory arrest.

Outcomes After Surgical Management of Synchronous Bilateral Primary Lung Cancers

BACKGROUND Distinguishing between synchronous primary lung cancers and metastatic disease in patients with bilateral lung masses is often difficult. The objective of this study is to examine outcomes associated with a strategy of performing staged bilateral resections in patients without N2 disease based on invasive mediastinal staging and without distant metastases. METHODS Patients undergoing resections of bilateral synchronous primary lung cancer at our institution between 1997 and 2010 were reviewed. Perioperative complications were graded according to National Cancer Institute guidelines. Survival was estimated using the Kaplan-Meier method and compared using a log-rank test. End points included overall survival, disease-free survival, operative death, cancer recurrence, and postoperative complications. RESULTS Resections of bilateral synchronous primary lung cancers were performed in 47 patients. Forty-five patients (96%) had at least a unilateral thoracoscopic approach; 28 (60%) had bilateral thoracoscopic approaches. The median postresection length of stay was 3 days. Thirteen patients (28%) had a postoperative complication; only 3 (6%) were grade 3 or higher. There was 1 perioperative death (2%). Eleven patients received adjuvant therapy; only 3 patients in whom adjuvant therapy was indicated did not receive the recommended treatment. The overall 3-year survival was 35%. Survival of patients whose bilateral tumors had identical histology did not differ from patients whose histology was different (p = 0.57). Three-year disease-free survival was 24%. CONCLUSIONS Aggressive surgical treatment of apparent synchronous bilateral primary lung cancer can be performed with low morbidity. Most patients tolerate the bilateral surgeries and adjuvant therapy. Overall survival is sufficiently high to support this aggressive approach.

Cardiac catheterization within 1 to 3 days of proximal aortic surgery is not associated with increased postoperative acute kidney injury

OBJECTIVE Cardiac catheterization shortly before coronary artery bypass grafting or valve surgery has been associated with increased postoperative acute kidney injury. The relationship between catheterization timing and acute kidney injury after proximal aortic surgery remains unknown. METHODS Between August 2005 and February 2011, a total of 285 consecutive patients underwent cardiac catheterization before elective proximal aortic surgery with cardiopulmonary bypass at a single institution. The association between timing of catheterization and postoperative acute kidney injury (defined as postoperative increase in serum creatinine ≥ 50% of baseline) was assessed using logistic regression analysis. RESULTS Of 285 patients, 152 (53%) underwent catheterization on preoperative days 1 to 3 and 133 (47%) underwent catheterization on preoperative day 4 or before. Acute kidney injury occurred in 88 (31%) patients, 3 (1.1%) requiring dialysis. Acute kidney injury occurred in 37 (24%) patients catheterized on preoperative days 1 to 3, and 51 (38%) patients catheterized on preoperative day 4 or before. Catheterization on preoperative days 1 to 3 was not associated with an increased risk of acute kidney injury relative to catheterization on preoperative day 4 or before (unadjusted odds ratio, 0.52; 95% confidence interval, 0.31-0.86; P = .01; adjusted odds ratio, 0.35; 95% confidence interval, 0.17-0.73; P = .005). CONCLUSIONS Cardiac catheterization within 1 to 3 days of elective proximal aortic surgery appears safe and should be considered acceptable practice for patients at low risk of acute kidney injury.