Intra-tumoral vascular or perineural invasion as prognostic factors for long-term survival in early stage non-small cell lung carcinoma

Objective: In recent studies focusing on the prognostic significance of histologic features of NSCLC tumors, vessel invasion was correlated to survival across all surgical stages. We similarly analyzed whether intra-tumoral permeation could affect survival in subgroups of stage I and II NSCLC. Methods: A retrospective single institution analysis of a prospectively computed database. Specimens were analyzed for intra-tumoral vascular, lymphatic and nervous permeation. Overall mortality was determined and for each stage, a Cox regression analysis of selected variables was performed. Detailed histologic information was available in all patients. Follow-up was 100% complete (median = 69 months). Results: From 1989 to 2004, out of 346 patients with stage I and II NSCLC, 253 patients with p stage I (75.7%) and 81 patients with p stage II (24.3%) underwent surgery with complete resection, for a completeness resection rate of 97% (334/346). We performed 70 pneumonectomies, 255 lobectomies and 9 lesser resections (respectively, 21%, 76.3% and 2.7%). In-hospital mortality was 2.1%. The incidence of intra-tumoral permeation was 14.4% (48/334). Permeation correlated both with T status (p = 0.04), grade of differentiation (p = 0.03) and stage (p = 0.02). Median survival and overall 5-year survival for patients with and without permeation were 42.3 months (95% CI [20–64.6]) and 72.1 months (95% CI [56.9–87.2]), respectively; and 44% and 54%, respectively (p = NS). However, intra-tumoral permeation was not a significant predictor for overall death (HR = 1.1 [95% CI = 0.74–1.66). Conclusion: In this large institutional study of early stage NSCLC, the presence of intra-tumoral permeation was correlated both to T, grade of differentiation, as well as to stage. However, in contrast to recent reports, we did not find that intra-tumoral permeation adversely affects long-term survival.     

Jugular venous valved conduit (Contegra) matches allograft performance in infant truncus arteriosus repair

Objective: Limited availability and durability of allograft conduits require that alternatives be considered. We compared bovine jugular venous valved (JVV) and allograft conduit performance in 107 infants who survived truncus arteriosus repair. Methods: Children were prospectively recruited between 2003 and 2007 from 17 institutions. The median z-score for JVV (n = 27, all 12 mm) was +2.1 (range +1.2 to +3.2) and allograft (n = 80, 9–15 mm) was +1.7 (range −0.4 to +3.6). Propensity-adjusted comparison of conduit survival was undertaken using parametric risk-hazard analysis and competing risks techniques. All available echocardiograms (n = 745) were used to model deterioration of conduit function in regression equations adjusted for repeated measures. Results: Overall conduit survival was 64 ± 9% at 3 years. Conduit replacement was for conduit stenosis (n = 16) and/or pulmonary artery stenosis (n = 18) or regurgitation (n = 1). The propensity-adjusted 3-year freedom from replacement for in-conduit stenosis was 96 ± 4% for JVV and 69 ± 8% for allograft (p = 0.05). The risk of intervention or replacement for branch pulmonary artery stenosis was similar for JVV and allograft. Smaller conduit z-score predicted poor conduit performance (p < 0.01) with best outcome between +1 and +3. Although JVV conduits were a uniform diameter, their z-score more consistently matched this ideal. JVV exhibited a non-significant trend towards slower progression of conduit regurgitation and peak right ventricular outflow tract (RVOT) gradient. In addition, catheter intervention was more successful at slowing subsequent gradient progression in children with JVV versus those with allograft (p < 0.01). Conclusions: JVV does match allograft performance and may be advantageous. It is an appropriate first choice for repair of truncus arteriosus, and perhaps other small infants requiring RVOT reconstruction.     

Fate of pulmonary arteries following Norwood Procedure

Objective: This study evaluated the requirement for surgical reoperation and catheter-based reintervention to central pulmonary arteries (CPAs) following Norwood Procedure (NP). We sought to identify the influence of various surgical techniques employed during NP on subsequent interventions. Methods: Between 1993 and 2004, 226 patients underwent Stage II following NP. Ninety-eight patients (43%) had completion of Fontan circulation (Stage III) and a further 107 (47%) are on course for Fontan completion with 21 (9%) inter-stage deaths. During NP, the aortic arch was reconstructed without additional material (n = 91, 40%) or with a pulmonary homograft patch (n = 135, 60%). Pulmonary blood flow was supplied by modified Blalock–Taussig shunt (n = 177, 78%) or right ventricle to pulmonary artery conduit (RV-PA; n = 49, 22%). The CPAs defect was closed directly (n = 69, 31%) or with a patch (n = 157, 69%). Complete resection of coarctation was performed in 126 patients (56%). Results: Ninety-seven patients (43%) required surgical reoperation to CPAs during Stage II. Actuarial freedom from reoperation was 60 ± 3%, 52 ± 4% and 50 ± 4% at 1, 5 and 10 years, respectively. On multivariable analysis, NP with RV-PA increased risk of reoperation (LR 8.3, 5.3–13.2; p < 0.001). Forty-one patients (18%) required catheter-based reintervention on CPAs. Actuarial freedom from reintervention was 98 ± 1%, 72 ± 4% and 58 ± 6% at 1, 5 and 10 years, respectively. CPA problems were almost exclusively limited to the proximal Left pulmonary artery. On multivariable analysis, catheter-based reintervention became more common with time. Complete resection of coarctation increased risk of reintervention (LR 3.9, 1.6–9.6; p < 0.005). Arch reconstruction and CPAs repair techniques did not affect risk of reoperation or reintervention on CPAs. Conclusions: CPA stenoses and hypoplasia need surgical attention in approximately half of all patients undergoing the NP. The need for reoperation is increased when using the RV-PA conduit technique (although the majority of these are performed as part of the Stage II procedure). Catheter reinterventions are almost exclusively confined to the left CPA and are increased when the arch is shortened by resection of the coarctation tissue at time of NP.     

Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

The effects of therapeutic sulfide on myocardial apoptosis in response to ischemia–reperfusion injury

Objective: Ischemia–reperfusion (I/R) injury, often encountered clinically, results in myocardial apoptosis and necrosis. Hydrogen sulfide (H₂S) is produced endogenously in response to ischemia and thought to be cardioprotective, although its mechanism of action is not fully known. This study investigates cardioprotection provided by exogenous H₂S, generated as sodium sulfide on apoptosis following myocardial I/R injury. Methods: The mid-LAD coronary artery in Yorkshire swine (n = 12) was occluded for 60 min, followed by reperfusion for 120 min. Controls (n = 6) received placebo, and treatment animals (n = 6) received sulfide 10 min prior to and throughout reperfusion. Hemodynamic, global, and regional functional measurements were obtained. Evans blue/TTC staining identified the area-at-risk (AAR) and infarction. Serum CK-MB, troponin I, and FABP were assayed. Tissue expression of bcl-2, bad, apoptosis-inducing-factor (AIF), total and cleaved caspase-3, and total and cleaved PARP were assessed. PAR and TUNEL staining were performed to assess apoptotic cell counts and poly-ADP ribosylation, respectively. Results: Pre-I/R hemodynamics were similar between groups. Post-I/R, mean arterial pressure (mmHg) was reduced by 30.2 ± 4.3 in controls vs 8.2 ± 6.9 in treatment animals (p = 0.01). +LV dP/dt (mmHg/s) was reduced by 1308 ± 435 in controls vs 403 ± 283 in treatment animals (p = 0.001). Infarct size (% of AAR) in controls was 47.4 ± 6.2% vs 20.1 ± 3.3% in the treated group (p = 0.003). In treated animals, CK-MB and FABP were lower by 47.0% (p = 0.10) and 45.1% (p = 0.01), respectively. AIF, caspase-3, and PARP expression was similar between groups, whereas cleaved caspase-3 and cleaved PARP was lower in treated animals (p = 0.04). PAR staining was significantly reduced in sulfide treated groups (p = 0.04). TUNEL staining demonstrated significantly fewer apoptotic cells in sulfide treated animals (p = 0.02). Conclusions: Sodium sulfide is efficacious in reducing apoptosis in response to I/R injury. Along with its known effects on reducing necrosis, sulfide's effects on apoptosis may partially contribute to providing myocardial protection. Exogenous sulfide may have therapeutic utility in clinical settings in which I/R injury is encountered.     

Long-term experiences on cardiac retransplantation in adults

Background: It remains disputed whether cardiac retransplantation should be performed. This study aimed to evaluate our long-term experiences on cardiac retransplantation in adults. Patients and methods: Between March 1989 and December 2004, 2% (28/1290) of cardiac retransplantations were performed. Results: The reasons for cardiac retransplantation were cardiac allograft vasculopathy (n = 13; 47%), primary graft failure (n = 11; 39%), and refractory acute rejection (n = 4; 14%). The 30-day mortality risk was 29% (acute rejection: 50%; primary graft failure: 36%; cardiac allograft vasculopathy: 15%, p = 0.324), compared to 8.5% for primary cardiac transplantation (p < 0.001). The causes of early death were acute rejection (n = 3; 37%), multiorgan failure (n = 3; 37%), primary graft failure (n = 1; 13%), and right ventricular failure (n = 1; 13%). The late mortality rate was 96/1000 patient-years. The causes of late death were acute rejection (n = 4; 50%), cardiac allograft vasculopathy (n = 2; 25%), multiorgan failure (n = 1; 13%), and infection (n = 1; 13%). The 1-, 5-, 10-, and 15-year survival was respectively 78, 68, 54, and 38% (primary cardiac transplantation), and 46, 41, 32, and 32% (cardiac retransplantation) (p = 0.003). The short-term survival for cardiac retransplantation due to cardiac allograft vasculopathy was likely better than primary graft failure and refractory acute rejection (p = 0.09). Conclusion: The overall outcomes of cardiac retransplantation are significantly inferior to primary cardiac transplantation. Cardiac retransplantation should be only performed for selected patients.     

Immunohistochemistry-detected microscopic tumor spread affects outcome in en-bloc resection for T3-chest wall lung cancer

Objective: This study is aimed at analyzing the effect of immunohistochemistry-detected microscopic tumor spread on long-term survival after en-bloc lung and chest wall resection for T3-chest wall non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed 47 patients (mean age 64.4 ± 7.1 years, range 48–77) who underwent radical en-bloc lung and chest wall resection for NSCLC between 1987 and 2000. Resection margins, invasion depth, and lymph nodes were re-assessed by immunohistochemistry with AE1/AE3 anti-cytokeratin and anti-CEA monoclonal antibodies. Results: Operative mortality and morbidity were 2.1% and 34%, respectively. At immunohistochemistry analysis, five patients (10.6%) revealed microinfiltration of the resection margins that was significantly correlated with the development of local recurrence (p < 0.005). Nodal micrometastases were found in 4 out of 33 N0 patients (12.1%), and correlated with distant relapse (p < 0.001). Overall and disease-free survivals were significantly influenced by N-status (p < 0.001), especially after re-evaluation of micrometastases (p < 0.0001), and resection margins microinfiltration (p < 0.0001) being these last two the only significant prognostic factors at Cox regression analysis. Five-year overall survival in radically resected patients was 73%. Conclusions: In this study immunohistochemical analysis allowed to identify patients at higher risk of recurrence following en-bloc resection for T3-chest wall NSCLC.     

Inhaled iloprost to control residual pulmonary hypertension following pulmonary endarterectomy

Objective: Pulmonary endarterectomy (PEA) is the standard therapy for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In the immediate postoperative period, persistent pulmonary hypertension increases the risk of acute respiratory or right heart failure. In pulmonary arterial hypertension, prostanoid inhalation has been found to improve pulmonary hemodynamics, right ventricular function, gas exchange, and clinical outcome. We report the results of a double-blinded randomized trial with the aerosolized prostacyclin analogue iloprost in patients with residual pulmonary hypertension after PEA. Methods: Twenty-two patients (age, 55 ± 13 years; 8 females; propofol- and sufentanil-based anesthesia; pressure-controlled mechanical ventilation) were randomized to receive either a single dose of 25 μg aerosolized iloprost (iloprost group; n = 11) or normal saline (placebo group; n = 11) immediately after postoperative ICU admission. Primary endpoints were changes in gas exchange, pulmonary and systemic hemodynamics, and clinical outcome. Results: Iloprost significantly enhanced cardiac index (CI) and reduced mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance [PVR (dyn s cm⁻⁵)] in contrast to placebo. Placebo: pre-inhalation 413 ± 195 versus post-inhalation 404 ± 196 at 30 min (p = 0.051), 415 ± 189 at 90 min (p = 0.929). Iloprost: pre-inhalation 503 ± 238 versus post-inhalation 328 ± 215 at 30 min (p = 0.001), 353 ± 156 at 90 min (p = 0.003). Blood oxygenation remained unchanged. Conclusion: In addition to the effect of PEA, iloprost reduces residual postoperative pulmonary hypertension, decreases right ventricular afterload and may facilitate the early postoperative management after PEA.     

Lymph node isolated tumor cells and micrometastases in pathological stage I non-small cell lung cancer: prognostic significance

Objective: To determine the prevalence and prognostic significance of lymph node micrometastases and isolated tumor cells (ITC) in patients submitted for radical resection for pathological stage I non-small cell lung cancer (NSCLC). Methods: From January 1998 through December 2005, 87 consecutive pT1-2, pN0 NSCLC patients were enrolled. Surgical specimens were submitted to pathological routine examinations to define histotype, grade, stage, vascular invasion, necrosis and tumor proliferative index. A total of 694 regional lymph nodes were examined by means of serial sections stained with hematoxylin and eosin and labelled by immunohistochemistry (antibody AE1/AE3, DAKO). Relationships between these parameters and patients’ prognosis were investigated. Results: By histological examination, there were 36 squamous-cell carcinoma, 38 adenocarcinoma and 13 large-cell carcinoma. Micrometastases and ITC were detected in 19 lymph nodes (2.7%) of 14 patients (16%). Significant correlation was observed between micrometastases or ITC and adenocarcinoma (p = 0.03) and the absence of necrosis (p = 0.05). No relationship was demonstrated between micrometastases or ITC and T-status, vascular invasion or proliferative index (p > 0.05). Median follow-up was 3.2 (range 0.25–8.6) years. Two- and 5-year disease-free survival was similar for patients with and without micrometastases or ITC (79% and 64% vs 81% and 64%, respectively). Recurrence occurred in three patients with (two local, 66%) and in 21 patients without micrometastases or ITC (three local, 14%) (p = 0.186). By multivariate analysis only T-status was demonstrated to be a significant prognostic factor. Discussion: Micrometastases or ITC to regional lymph nodes are demonstrated to be not a rare aspect of pathological stage I resected lung cancer. In our series, the presence of lymph nodes micrometastases does not affect long-term disease-free survival.     

Quality assessment of distal SAS connector anastomosis by 13 MHz epicardial ultrasound

Objective: During application of a distal coronary bypass connector, we employed 13 MHz epicardial ultrasound to evaluate quantitative caliper measurements for vessel size matching and to assess anastomosis quality after connector deployment. Methods: Two S²AS connector anastomoses were constructed on ex vivo pressure-perfused porcine hearts. Epicardial ultrasound measurements of the connector ring and anastomosis were compared to intravascular ultrasound measurement and cast dimensions. In 21 pigs, anastomotic sites with internal diameter of 2.25–3.0 mm (internal mammary artery, IMA) and 1.8–2.2 mm (left anterior descending coronary artery, LAD) were selected using external caliper and epicardial ultrasound measurements. Anastomoses were visualized and assessed intraoperatively (beating heart, n = 21) and at 3 and 6 months’ follow-up (explanted heart, n = 10 each). Results: Epicardial ultrasound underestimated connector dimension by ≤5% versus intravascular ultrasound and deviated ≤13% from cast dimensions for other anastomotic measurements. Caliper estimates of internal IMA and LAD diameter differed from ultrasound by −3 ± 6% and −2 ± 7% (mean ± SD), respectively. Intraoperatively, the anastomotic orifice was flawless in all animals. It remained fully patent at 3 and 6 months by ultrasound, which was confirmed by histology. The connector to LAD percentage diameter stenosis changed from −12 ± 5% intraoperatively to −1 ± 7% at 3 months and from −5 ± 6% intraoperatively to −16 ± 13% at 6 months, in the growing pig model. Conclusions: In the pig, external caliper measurements provided a reliable quantitative estimate of inner graft and coronary diameter for connector size matching. Epicardial 13 MHz ultrasound is a promising method to assess coronary anastomosis quality even when connector metal is present.     

Clinical advantages of using mini-bypass systems in terms of blood product use, postoperative bleeding and air entrainment: an in vivo clinical perspective

Objective: In an effort to minimize the effect of extracorporeal circulation (ECC), mini-bypass is gaining clinical acceptance in routine coronary artery bypass grafting (CABG). These small circuits target combine the clinical advantages of reduced prime, 100% bio-coating and suction blood separation. We demonstrate that the use of mini-bypass in routine CABG reduces homologous blood product use and postoperative bleeding. Our goal was to also demonstrate that these small systems are effective in gaseous microemboli (GME) management as compared to a conventional extracorporeal system. Methods: Prospective, randomized study comparing 30 mini-bypass (Dideco ECC.O™) to 30 conventional systems (n = 30, Dideco 903 Avant™). Study included CABG cases only, independent of preoperative coagulative status; clinic ethical committee approval and informed patient consent was obtained before initiating study. Results: There were no statistical differences in terms of patient demographics. Statistically significant differences were seen in transfusion frequency (27% of the study group vs 43% in the control group, p = 0.05), transfused volume (133.3 ± 244.5 ml vs 325 ± 483.1 ml, p < 0.05), fresh frozen plasma (0 unit vs 3 units, p < 0.001), postoperative bleeding (301.8 ± 531.9 ml vs 785.5 ± 1000.4 ml, p < 0.05) and GME activity post-arterial filter (0.14 μl vs 5.32 μl, p < 0.05). Conclusions: The adoption of mini-bypass significantly potentially reduces hemodilution, donor blood usage, postoperative bleeding and exposure to GME in routine CABG patients as compared to the use of conventional extracorporeal circulation circuits.     

Effects of pre-natal and early post-natal undernutrition on adult internal thoracic artery function

Objective: Previous studies in humans and animals have suggested that undernutrition in utero and in early post-natal life may lead to altered vascular function in a number of peripheral arteries. We investigated the effect of pre- and post-natal nutrient restriction on the vascular reactivity of the left internal thoracic artery using a sheep model. Methods: Welsh mountain ewes were mated and assigned to three dietary groups: (1) 100% of total nutritional requirements (control, n = 6); (2) 50% of total nutritional requirements during the first 31 days of gestation (n = 6); and (3) 50% nutritional restriction during the first 31 days of gestation, followed by a restriction in the diet of their offspring 12–25 weeks post-natally, designed to produce a 15% reduction in growth trajectory (n = 7). The male offspring were sacrificed at 130 weeks; the left internal thoracic artery was mounted onto a wire myograph and the reactivity of the vessel to various agonists measured. Results: The offspring of animals who underwent an early gestation nutrient restriction had a significantly increased basal tone (0.41 ± 0.25 vs 6.34 ± 1.35, p = 0.015) and sensitivity to phenylephrine (log EC₅₀: −6.23 ± 0.04 M vs −5.74 ± 0.17 M, p = 0.036) as compared with control animals. However, this phenomenon was not seen in animals that underwent both pre- and post-natal nutrient restriction. Conclusions: Pre-natal undernutrition increases the basal tone and sensitivity of the left internal thoracic artery to phenylephrine. This effect is significantly attenuated by continued undernutrition in early post-natal life. These experiments suggest that in utero and early post-natal undernutrition may be important determinants of graft function in later life.     

Concurrent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response

Introduction: Optimal preoperative treatment of stage IIB (Pancoast)/III non-small cell lung cancer (NSCLC) remains undetermined and a subject of controversy. The goal of our study is to confirm feasibility and pathological response rates after induction chemoradiation (CRT) in our community-based treatment center. Patients and methods: Patients were selected according to functional and resectability criteria. Induction treatment comprised 3D conformal 4500 cGy radiotherapy delivered to the primary tumor and pathologic hilar and/or mediastinal lymph nodes on CT scan with an extra-margin of 1–1.5 cm. Concurrent chemotherapy regimen was cisplatinum 20 mg/m² d1–d5 and etoposide 50 mg/m² d1–d5, d1–5 d29–33. Within 3–4 weeks after CRT completion, operability was re-assessed accordingly. Surgery was performed 4–6 weeks after CRT completion in patients (pts) deemed resectable. Inoperable pts were referred for a 20–25 Gy boost ±1 extra-cycle of cisplatinum + etoposide. Results: From 1996 to 2005, 107 pts were initially selected for treatment and received induction chemoradiation (stage IIB-Pancoast 18, IIIA 58 and IIIB 31, squamous cell carcinoma 48%, adenocarcinoma 44%, large-cell undifferentiated carcinoma 14%). After preoperative evaluation, 72 pts (67%) had a thoracotomy (pneumonectomy 21, lobectomy 45, bilobectomy 5) and all but one (unresectable tumor) had a macroscopic complete resection. During the 3-month postoperative time, five patients (6.9%) died, four after pneumonectomy (right 3, left 1). The analysis of tumoral samples showed a pathological complete response rate or microscopic residual foci of 39.5%. Median follow-up time was 22.3 months (survivors: 36.8 months), 2-year and 3-year overall survival rates were 55% and 40%, respectively (median = 26.7 months) for all the intention-to-treat population (n = 107), 62% and 51% (median = 36.5 months) for 71 resected pts, 41% and 16% for 36 non-resected pts (median = 19.1 months). On multivariate analysis, surgical resection and tumoral necrosis >50% (or pathological complete response) were the most pertinent predictive factors of the risk of death (hazard ratio = 0.50 and 0.48, p = 0.006 and 0.038, respectively). Conclusion: Surgery was feasible after induction chemoradiation, particularly lobectomy in PS 0–1, stage IIB (Pancoast)/III NSCLC pts but pneumonectomy carries a high risk of postoperative death (particularly, right pneumonectomy). Pathological response to induction chemoradiation was complete in 39.5% of patients and was a significant predictive factor of overall survival.     

A prospective analysis of the inter-relationship between lung volume reduction surgery and body mass index

Objectives: LVRS is thought to result in significant improvements in BMI. Patients with a higher BMI at the time of diagnosis of COPD are known to have better survival, and those with a low BMI prior to LVRS have significantly worse perioperative morbidity. We aimed to assess the influence of BMI on the outcome of LVRS in our own experience. Methods: Complete preoperative BMI data was available in 114 of 131 consecutive patients who have undergone LVRS since 1995. These patients were arbitrarily classified into three categories: underweight (BMI ≤ 19 kg/m²), normal (BMI 20–25 kg/m²) and overweight (BMI > 26 kg/m²). The in-hospital course and perioperative change in BMI at 3, 6, 12, 24 and 36 months were prospectively recorded for each category and compared. Results: There were no significant differences in preoperative variables except BMI. There were significantly more postoperative ITU admissions among the lowest two BMI groups (12/29, 18/58 and 3/27 patients, respectively, p = 0.02), and significantly shorter hospital stay in overweight patients [16 days (5–79) vs 18 days (6–111) vs 13 days (6–25), respectively, p = 0.005, expressed as median (range)]. However, there was no difference in survival between the three groups (p = 0.21). Postoperative physiological improvements in the first year were related to preoperative BMI for both FEV₁ (r = 0.29, p = 0.02) and DLCO (r = 0.33, p = 0.02). Postoperative BMI significantly increased in the underweight yet significantly decreased in the overweight at all time points. Conclusions: The perioperative course of LVRS and its physiological benefits are influenced by preoperative BMI. Whilst the treatment of the underweight is more complicated, LVRS may be the only way of increasing their BMI. Future work is needed to explore the roles of changing energy requirements and body composition following LVRS.     

Staging and resection of lung cancer with minimal invasion of the adjacent lobe

Objective: Correct staging, optimal resection type, and prognosis for non-small cell lung cancer (NSCLC) with invasion of the adjacent lobe through the fissure have seldom been reported. Methods: We retrospectively evaluated 351 completely resected NSCLC patients between 1994 and 2004. Of these, 152 patients had T2 and 139 had T3 NSCLC confined in one lobe and 60 patients had T2 NSCLC that shows a limited growth through the interlobar fissure into the adjacent lobe (NSCLC-ALI). Types of resections performed in patients who have NSCLC-ALI were: pneumonectomy in 40, bilobectomy in 10, and lobectomy plus partial adjacent lobe resection (LPR) in 10. Survival rates of all patients were determined and factors affecting the survival were evaluated by univariate and multivariate analyses. A multivariate survival analysis of NSCLC-ALI patients including the resection type as a prognostic factor was also performed. Results: Survival of the patients with NSCLC-ALI was not statistically different from those with T3 disease (p = 0.67, log rank test) but was significantly poorer than remaining patients with simple T2 disease (p = 0.049, log-rank test). T status was found as a prognostic factor at multivariate analysis too (p = 0.037). The survival of patients who underwent pneumonectomy was significantly worse than the patient group who underwent bilobectomy or LPR (p = 0.04). There was no statistically significant difference between survival of the patients who underwent LPR and the patient group who underwent pneumonectomy or bilobectomy (p = 0.16). Hospital mortality was 6.6% (4/60) and they all underwent a pneumonectomy. During follow-up there was no local recurrence encountered in patients in LPR group. Conclusions: The prognosis of NSCLC with limited invasion of an adjacent lobe was found to be similar with that of T3 tumors. A resection type lesser than a pneumonectomy may be considered in these tumors.     

Relationship of Circulating Total Homocysteine and C-Reactive Protein to Trabecular Bone in Postmenopausal Women

Homocysteine (Hcy) and C-reactive protein (CRP) are novel risk factors for osteoporosis. The purpose of this analysis was to determine the relationship of Hcy and CRP to volumetric trabecular bone, but also to assess their relationship to areal composite bone in healthy postmenopausal women (N = 184). We used peripheral quantitative computed tomography to assess volumetric bone at the distal tibia and dual-energy X-ray absorptiometry to assess areal composite bone at the proximal femur and lumbar spine. Multiple regression revealed that 22% of the variability in trabecular bone mineral content (F = 9.59, p ≤ 0.0001) was accounted for by weight (12.4%; p ≤ 0.0001), hemoglobin (5.5%; p = 0.0006), uric acid (4.2%; p = 0.003), and blood glucose (1.5%; p = 0.07). Multiple regression revealed that 5.4% of the variability in trabecular bone mineral density (F = 3.36; p = 0.020) was accounted for by hemoglobin (4.2%; p = 0.006) and Hcy (1.5%; not significant, p = 0.10). Total Hcy and CRP were not significantly related to trabecular bone, perhaps because these were nonosteoporotic women. However, our results suggested a weak but negative relationship between Hcy and trabecular bone. Further investigation is needed to examine the relationship of Hcy as an endogenous bioactive molecule to trabecular bone loss in early postmenopausal women and the response of trabecular bone to dietary intervention.     

Preliminary experience with inhaled milrinone in cardiac surgery

Background: Inhaled administration of milrinone reduces pulmonary artery pressure. Pulmonary hypertension (PH) and right heart failure are associated with difficult separation from cardiopulmonary bypass (CPB). Therefore, inhaled milrinone could facilitate separation from CPB. Objective: To determine the impact and timing of administration of inhaled milrinone. Methods: A retrospective analysis of our experience on high-risk patients receiving inhaled milrinone was conducted to evaluate the postoperative course after administration of the drug. Results: Seventy-three patients received inhaled milrinone from June 2002 to February 2005. Mean age was 64 ± 13 years, with a mean preoperative Parsonnet score of 27 ± 14. Inhaled milrinone (5 mg) was administered before (n = 30) or after (n = 40) CPB, three patients had off-pump procedures and were excluded. CPB time was 145 ± 78 min with cross-clamping times of 91 ± 56 min without any significant difference between groups. Fifty-four patients (74%) had difficult separation from CPB, 14 patients (19%) required an intra-aortic balloon pump and 10 patients (14%) needed emergency reinitiation of CPB for hemodynamic instability. Ten patients died in the perioperative period (13.7%). Patients receiving inhaled milrinone prior to CPB initiation had a lowering pulmonary artery pressure after CPB (p < .01) and had less emergency reinitiation of CPB after weaning (3% vs 23%, p = .02) as compared to those with administration after CPB. No detectable side effects were directly linked to the administration of the drug. Conclusion: In this high-risk cohort, use of inhaled milrinone was well tolerated. Administration before initiation of CPB could help weaning from CPB.     

Comparison of on pump and off pump coronary surgery: risk factors for neurological outcome

Objective: Cerebrovascular accidents (CVA) are devastating complications after coronary artery bypass grafting (CABG). The reported incidence of neurological complications after conventional CABG (CCABG) is 3–6%. Off-pump coronary bypass grafting (OPCAB) has been associated in recent studies to a decreased morbidity and risk of perioperative stroke. Nevertheless, uncertainty still surrounds the relative benefits of OPCAB. We investigated whether, in our experience, OPCAB was associated with lower neurological morbidity than conventional CABG approach. Methods: Eight thousand and two patients underwent isolated CABG at our institution between January 1998 and January 2005. OPCAB operation was performed on 1415 patients. Data were prospectively collected. A multiple logistic regression analysis was used to evaluate the influence of the two different surgical techniques on the neurological outcomes. Results: Patients in the OPCAB group were significantly older (66.2 vs 63.5%, p < 0.0001), had a higher incidence of renal injury (5.4 vs 2.4%, p < 0.0001), and were more redo interventions (6.95 vs 1.53%, p < 0.0001). The CCABG patients were more urgent at operation (5.46 vs 3.26, p = 0.0007), were less hypertensive (57.6 vs 63% of the patients, p = 0.0003) more diabetics (22 vs 20.6%, NS), and had an ejection fraction less than 0.40 (10.4 vs 9.6%, NS). CVA incidence was similar in both groups (Type I outcome: OPCAB = 0.70% vs CCABG = 0.68%, p = 0.91; Type II outcome OPCAB = 0.70% vs CCABG = 0.83%, p = 0.63). Conclusions: In our experience patients undergoing CCABG were not exposed to a grater risk of neurological adverse events when compared to OPCAB patients.     

Mitral valve repair by Alfieri''s technique does not limit exercise tolerance more than Carpentier''s correction

Objective: The main goal of this study was to evaluate if the edge-to-edge mitral repair could be a limiting factor for exercise tolerance and to compare these results to those of classical techniques. Methods: Between 2000 and 2002, 54 consecutive patients were operated on for mitral valve regurgitation (MR). Twenty-five patients were operated with Alfieri's technique (group A) and 29 patients with Carpentier's technique (group C). The mean age was 63.9 years in group A and 63.8 years in group C (p = 0.98). After a mean follow-up of 16.2 ± 12 months, survivor patients were seen at the outpatient clinic, by the same physician for a clinical evaluation, an echocardiogram at rest and at peak exercise, and received a cardiorespiratory exercise testing with maximal oxygen uptake (VO₂ max) recording. Results: Clinical status improved with 0% of the patients in class NYHA III or IV in either group postoperatively versus 77% preoperatively. There was no significant MR in 80% of cases in group A versus 89.6% in group C (p = 0.54). The mean mitral valve area was 2.5 and 2.9 cm² in groups A and C, respectively (p = 0.018). The mitral gradient at rest was 3.8 and 3.3 mmHg (p = 0.31) and the mitral gradient at peak exercise was 8.5 and 9.7 mmHg (p = 0.22) in groups A and C, respectively. Cardiorespiratory exercise testing showed a mean VO₂ max of 73.7 ± 15% of normal value in group A versus 79.6 ± 13.1% in group C (p = 0.18). Conclusion: Alfieri's technique has the same efficiency on improvement of MR and clinical status than classical repair. Despite a higher restriction of mitral valve area at rest in group A, gradient and mean VO₂ max at peak exercise were similar in both groups.     

Risk factors for reoperation after relief of congenital subaortic stenosis

Background: Congenital subaortic stenosis entails a lesion spectrum, ranging from an isolated obstructive membrane, to complex tunnel narrowing of the left outflow associated with other cardiac defects. We review our experience with this anomaly, and analyze risk factors leading to restenosis requiring reoperation. Methods: From 1994 to 2006, 58 children (median age 4.3 years, range 7 days–13.7 years) underwent primary relief of subaortic stenosis. Patients were divided into simple lesions (n = 43) or complex stenosis (n = 15) associated with other major cardiac defects. Age, pre- and postoperative gradient over the left outflow, associated aortic or mitral valve insufficiency, chromosomal anomalies, arteria lusoria, and operative technique (membrane resection (22) vs associated myectomy (34) vs Konno (2)) were analyzed as risk factors for reoperation (Kaplan–Meier, Cox regression). Results: There was no operative mortality. Median follow-up spanned 2.7 years (range 0.1–10), with one late death at 4 months. Reoperation was required for recurrent stenosis in 11 patients (19%) at 2.6 years (range 0.3–7.5) after initial surgery. Risk factors for reoperation included complex subaortic stenosis (p = 0.003), younger age (p = 0.012), postoperative residual gradient (p = 0.019), and the presence of an arteria lusoria (p = 0.014). For simple lesions, no variable achieved significance for stenosis recurrence. Conclusions: Surgical relief of congenital subaortic stenosis, even with complex defects, yields excellent results. Reoperation is not infrequent, and should be anticipated with younger age at operation, complex defects, residual postoperative gradient, and an arteria lusoria. Myectomy concomitant to membrane resection, even in simple lesions, does not provide enhanced freedom from reoperation, and should be tailored to anatomic findings.