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.     

Prognostic value of FDG uptake in early stage non-small cell lung cancer

Background: Non-small cell lung cancer (NSCLC) has a poor prognosis even for early stages of the disease (stage I and II). We studied the prognostic value of PET FDG in patients with completely resected stage I and II NSCLC. Methods: Retrospective study of 96 patients with NSCLC whose staging included ¹⁸F-FDG PET (fluoro deoxy glucose positron emission tomography). Histopathological stage was either stage I (75) or stage II (n = 21). FDG uptake was measured as maximal standardized uptake value for body weight (SUVmax). Mean follow-up was 45 ± 30 months (1–142 months). Overall and cancer-free survival rates were recorded. Results: SUVmax were higher for stage II than for stage I (10.5 ± 4.5 vs 8.5 ± 5, p = 0.04). Mean tumor volumes were equivalent for both stages (33 cm³, p = 0.18), excluding a partial volume effect. The median SUVmax in the whole study population was 7.8. The median survival was significantly longer in patients with a lower (SUVmax ≤ 7.8) FDG uptake (127 months vs 69 months, p = 0.001). For stage I tumors (n = 75), high FDG uptake was significantly associated with reduced median survival: 127 months if SUVmax ≤ 7.8 and 69 months if SUVmax > 7.8 (p = 0.001). For stage II tumors (n = 21), no statistical difference was observed: 72 months vs 40 months for SUVmax ≤ 7.8 and for SUVmax > 7.8, respectively (p = 0.11), although there was a clear trend towards reduced survival for highly metabolic tumors. Disease-free survival was also significantly better for lower metabolic tumors: 96.1 months vs 87.7 months (p = 0.01). Conclusion: High FDG uptake is associated with reduced overall survival and disease-free survival of patients with completely resected stage I–II NSCLC. Whether patients with highly metabolic tumors should undergo a closer postoperative surveillance or adjuvant chemotherapy has to be addressed in a properly designed prospective trial.     

Assessment of pulmonary function after lobectomy for lung cancer — upper lobectomy might have the same effect as lung volume reduction surgery

Objective: Lung volume reduction surgery (LVRS) in well-selected patients with severe emphysema results in postoperative improvement in symptoms and pulmonary function. Experience with LVRS suggests that predicted postoperative FEV_1.0 may be underestimated after lobectomy in patients with lung cancer and emphysema. As most of the patients with lung cancer have more or less emphysematous changes in the lungs, we assumed that lobectomy would achieve the same effect as LVRS even in patients without chronic obstructive pulmonary disease on the pulmonary function test. We assessed changes in pulmonary function in terms of ‘volume reduction effect’ after lobectomy for lung cancer. Methods: Forty-three patients underwent right upper lobectomy (RUL), 38 patients left upper lobectomy (LUL), 39 patients right lower lobectomy (RLL), and 38 patients left lower lobectomy (LLL). Pulmonary function tests were performed preoperatively and 6 months to 1 year after surgery. Results: Percent change in FEV_1.0 after lobectomy was −6.9 ± 16.1% in RUL group, −11.2 ± 16.9% in LUL group, −14.7 ± 9.8% in RLL group, and −12.8 ± 9.5% in LLL group. We evaluated the correlation between a preoperative FEV_1.0% of predicted and percentage change in FEV_1.0 after lobectomy. There were no significant relationships between these variables in RLL or LLL group. In contrast, there were significant negative relationships between these variables in RUL and LUL groups. Correlation coefficients were r = −0.667, p < 0.0001 for RUL and r = −0.712, p < 0.0001 for LUL. In RUL and LUL groups, patients with a higher preoperative FEV_1.0% of predicted had a more adverse percentage change in FEV_1.0 after surgery. In addition, all 13 patients with a preoperative FEV_1.0% of predicted <60% in RUL and LUL groups had an increase in FEV_1.0 postoperatively. Patients with a lower preoperative FEV_1.0% of predicted had a greater ‘volume reduction effect’ with an increase in FEV_1.0 after upper lobectomy. Conclusion: Upper lobectomy might have a volume reduction effect.     

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.     

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.     

Interleukin 6 and interleukin 1 receptor antagonist as early markers of complications after lung cancer surgery.

OBJECTIVE: To assess changes of interleukin 6 (IL-6) and interleukin 1 receptor antagonist (IL-1ra) in serum, sputum, and drained pleural fluid of patients operated on due to lung cancer. METHODS: Twenty-seven patients treated with lobectomy or pneumonectomy, including 14 with complications and 13 without complications, were analyzed. Serum IL-6 and IL-1ra concentration was measured before, at the end of surgery, and on postoperative day 1, 3, and 7, by ELISA test. Additionally, concentration of IL-6 and IL-1ra was measured in sputum at the end of surgery and in pleural fluid on postoperative day 1. RESULTS: In the entire group serum concentrations of IL-6 and IL-1ra were significantly elevated after surgery, in comparison with preoperative values. Serum IL-6 concentration was higher in patients with complications only on day 7 (median 59.0 (range: 41.25-76.65) pg/ml vs 21.5 (9.87-35.0) pg/ml; p=0.012). Patients with complications had higher concentration of IL-6 in pleural fluid (91312 (51812-94872) pg/ml vs 2006 (1926-2108) pg/ml; p=0.00008). Serum IL-1ra concentration was higher in patients with complications on day 1 (1832.4 (1144.7-2362.2) pg/ml vs 1088.4 (817.5-1312.5) pg/ml; p=0.01). Concentration of IL-1ra in drained fluid was higher in patients with complications (68128.8 (48104-108564) pg/ml vs 16470 (15930-16875) pg/ml; p=0.0003). On day 1 after surgery a significant correlation between serum and pleural fluid concentration for IL-6 as well as for IL-1ra were observed (Spearman test for IL-6: r=0.47; p=0.02; for IL-1ra: r=0.48; p=0.02). CONCLUSIONS: Elevated concentrations of IL-6 and IL-1ra in pleural fluid on postoperative day 1 are promising early markers of postoperative complications. Elevated concentrations of IL-6 and IL-1ra in serum are good early markers of severity of surgical injury and may reflect development of postoperative complications.     

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.     

Post-transplant diabetes mellitus in lung transplant recipients: incidence and risk factors

Objective: Post-transplant diabetes mellitus (PTDM) is a common and potentially serious complication after solid organ transplantation. There are only a few data, however, about the incidence of DM in patients undergoing lung transplantation. Patients and methods: The medical records of 119 consecutive patients who underwent lung transplantation from 1998 to September 2004 were reviewed. Patients were divided in three groups according to their diabetes status, including pre-transplant DM, the PTDM group and those without DM. Patient records and all laboratory data were reviewed and the clinical course of diabetes was monitored. All recipients were treated with tacrolimus based regimen. Results: Mean follow-up for all patients was 25 ± 10. Twenty-three patients had DM in the pre-lung transplantation (LTX) DM group. PTDM developed in 34 of the remaining 96 patients (35.4%) with an incidence of 20%, 23% after 6 months and 12 months post-transplant. No significant difference was noted between 12 and 24 months post-LTX. The patients who developed DM were older (57 ± 15 vs 53 ± 13 years, p = 0.009), had increased BMI (26 ± 5 vs 24 ± 4, p = 0.0001), shorter time from diagnosis to LTX (21 ± 13 vs 28 ± 18 months, p = 0.007) more cytomegalovirus infection and more acute rejection and hyperglycemia in the first month after LTX. Four patients died in the PTDM group compared to nine patients in the no-DM group (12% vs 14%; p = 0.72). Conclusions: Post-transplant diabetes is a common complication in lung transplant patients receiving tacrolimus-based immunosuppression. The risk for developing PTDM is greatest among older recipients, those obese, and among recipients with more rejections episodes.     

Effect of Ascites on Bone Density Measurement in Cirrhosis

Cirrhosis is an independent risk factor for the development of osteoporosis. The presence of ascites in patients with cirrhosis may affect the accuracy of bone density measurement in the spine. Twenty cirrhotic patients had bone mineral density (BMD) measurements of the lumbar spine, femoral neck, hip, and total body using dual-energy X-ray absorptiometry (DXA; Lunar Prodigy) before and after large-volume paracentesis. To establish short-term precision of DXA measurement, 28 healthy adults also had duplicate BMD measurements on the same day. After paracentesis (6.4 ± 2.0 L), there was a significant increase in the spine BMD of 4.2% (p = 0.003) and in the total hip BMD of 1.3% (p = 0.002), but there was no change in the femoral neck or total body. No significant differences (p > 0.1) were seen in duplicate BMD measurements at any site among the healthy cohort. Within-patient changes in spine (p = 0.001) and total hip (p = 0.001) BMD measurements were significantly greater in patients with ascites than in the healthy cohort. These changes in BMD measurements were not associated with age, gender, amount of fluid removed, or time interval between measurements. These results suggest that ascites cause a fluid artifact in the soft tissue and bone interface that can falsely lower BMD measurements, particularly in the spine.     

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.     

Retrograde flush following topical cooling is superior to preserve the non-heart-beating donor lung

Objective: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. Formation of microthrombi after circulatory arrest, however, is a major concern for the development of reperfusion injury. We looked at the effect and the best route of pulmonary flush following topical cooling in NHBD. Methods: Non-heparinized pigs were sacrificed by ventricular fibrillation and divided into three groups (n = 6 per group). After 1 h of in situ warm ischaemia and 2.5 h of topical cooling, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted following an anterograde flush (AF) through the pulmonary artery with 50 ml/kg Perfadex^® (6 °C). Finally, in group III, lungs were retrieved after an identical but retrograde flush (RF) via the left atrium. Flush effluent was sampled at intervals to measure haemoglobin concentration. Performance of the left lung was assessed during 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) of both lungs was calculated as an index of pulmonary oedema. IL-1ß and TNF- protein levels in bronchial lavage fluid from both lungs were compared between groups. Results: Haemoglobin concentration (g/dl) was higher in the first effluent in RF versus AF (3.4 ± 1.1 vs 0.6 ± 0.1; p < 0.05). Pulmonary vascular resistance (dynes × s × cm⁻⁵) was 975 ± 85 RF versus 1567 ± 98 AF and 1576 ± 88 NF at 60 min of reperfusion (p < 0.001). Oxygenation (mmHg) and compliance (ml/cmH₂O) were higher (491 ± 44 vs 472 ± 61 and 430 ± 33 NS, 22 ± 3 vs 19 ± 3 and 14 ± 1 NS, respectively) and plateau airway pressure (cmH₂O) was lower (11 ± 1 vs 13 ± 1 and 13 ± 1 NS) after RF versus AF and NF, respectively. No differences in cytokine levels or in W/D ratios were observed between groups after reperfusion. Histology demonstrated microthrombi more often present after AF and NF compared to RF. Conclusion: Retrograde flush of the lung following topical cooling in the NHBD results in a better washout of residual blood and microthrombi and subsequent reduced pulmonary vascular resistance upon reperfusion.     

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.     

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.     

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.     

Thoracoscopic localization techniques for patients with solitary pulmonary nodule: hookwire versus radio-guided surgery

Objective: Our aim was to evaluate the best intrathoracoscopic localization technique between hookwire and radio-guided surgery, in patients with pulmonary nodule. Methods: From January 2000 to January 2005 we enrolled in this study 50 patients with a solitary pulmonary nodule, prospective randomized in two groups, well matched for diameter and depth of the pulmonary lesion. In 25 patients we performed the hookwire technique (Group A), whereas in the other 25 patients radio-guided localization was adopted (Group B). In both groups the localization technique was compared with finger palpation. In Group A, 9 lesions were in the left and 16 in the right lung; in Group B, 14 nodules were in the left lung and 11 in the right one. In both groups, the distance of the nodule from the pleural surface with lung inflated was 2.5 cm (1.5–2.5 cm in 12 patients, and >2.5 cm for the remaining 13). The mean size of the nodules in both groups was 1.1, range 0.6–1.9 (≤1 cm n = 18 patients, and >1 cm n = 7 patients). Results: All patients underwent thoracoscopic wedge resection, and 23 patients with a primary pulmonary lesion underwent thoracotomy for lobectomy and radical mediastinal lymphadenectomy. In Group A the hookwire technique localized the nodule in 21 of 25 patients (84%) whereas finger palpation localized it in 7 of 25 patients (28%). In Group B, radio-guided surgery localized the nodule in 24 of 25 patients (96%) whereas finger palpation localized it in 6 of 25 (24%). In Group A we registered 6 cases of pneumothorax compared to 1 case observed in the radio-guided group. Postoperative hospital stay required an average of 4 days in both groups. Conclusions: In our experience radio-guided surgery has therefore been proven efficacious in the diagnosis of solitary pulmonary nodule and video-assisted thoracoscopic surgery allows the removal of pulmonary nodules without complications. Hookwire was also shown to be efficacious but demonstrated complications linked primarily to external technical factors.     

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.     

Improving the surgery for sigmoid achalasia: long-term results of a technical detail

Objective: Heller myotomy results for the treatment of sigmoid achalasia are worse than those achieved for fusiform achalasia. We retrospectively examined two groups of sigmoid achalasia patients, in which we performed (1) the standard Heller–Dor procedure (no pull-down) and (2) the Heller–Dor plus a technique apt to obtain the verticality of the oesophageal axis (pull-down). We verified whether the latter technique improved long-term results. Materials and methods: We considered 33 patients affected by primitive oesophageal sigmoid achalasia operated upon consecutively (1979–2005). Diagnosis was based on symptoms, manometry, radiology and endoscopy. After 1987, we routinely isolated 360° of the gastro-oesophageal junction and the lower oesophagus and applied U stitches at the right side of the lower oesophagus to pull down and rotate the gastro-oesophageal junction toward the right. Fifteen patients underwent the no pull-down and 18 patients underwent the pull-down technique. Postoperative follow-up included objective clinical and instrumental evaluation (questionnaire filled by a surgeon including the assessment of symptoms and endoscopic reflux oesophagitis according to a semi-quantitative scale) and subjective evaluation (self-evaluation SF-36 questionnaire). Results: The mean follow-up period was 89 months (range 12–261 months). The postoperative dysphagia score was significantly improved in the entire group. Excellent results were present in 12 patients (36.4%), good in 11 (33.3%), fair in 3 (9.1%) and insufficient in 7 patients (21.2%). No statistically significant differences were observed between the two groups with regard to the postoperative symptoms and oesophagitis. Postoperative radiological measurements of oesophageal diameter and residual barium column were significantly improved in the whole group and within each group with respect to the radiological variables measured preoperatively (p = 0.000). In the comparison of the two groups, statistically significant differences were observed with regard to mean oesophageal diameter (p = 0.030) (pull-down, 4 ± 0.9 cm; no pull-down, 4.7 ± 0.6 cm) and residual barium column (p = 0.048) (pull-down, 6.2 ± 3.4 cm; no pull-down, 9.6 ± 5.8 cm). Conclusions: The Heller–Dor operation is effective in the presence of sigmoid achalasia. The clinical objective and subjective evaluations show a trend toward the improvement of results with the pull-down technique. Stronger statistical significance would probably be obtained from a larger case series.     

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.     

The "lively" cytokines network in beta-Thalassemia Major-related osteoporosis

Osteoporosis affects approximately 40–50% of adult patients with β-Thalassemia Major (βTM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of βTM-osteoporosis. OPG/RANKL system acts downstream from IL-1, IL-6 and TNF- and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in βTM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in βTM patients.

IL-1, IL-6 and TNF-, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17β-estradiol, and free-testosterone levels were measured in 30 well treated βTM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients.

βTM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P < 0.0001), decreased osteocalcin (BGP) concentrations (< 0.0001) and significantly lower lumbar (P = 0.001) and femoral (P < 0.05) BMD values as compared to controls. Circulating levels of IL-1 (P < 0.0001), TNF- (P < 0.0001) and IL-6 (P < 0.05) were all increased in βTM patients as compared with controls. In βTM patients, IL-1 was significantly related with D-PYR (r = 0.5; P < 0.05), RANKL (r = 0.7; P = 0.03) and IL-6 (r = 0.3; P = 0.006); IL-6 was also significantly correlated with D-PYR (r = 0.5; P < 0.05) and EPO levels (r = 0.3; P = 0.03); TNF- showed a negative correlation with L2L4 BMD (r = − 0.4; P < 0.05).

Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in βTM-patients, suggesting their involvement in the pathogenesis of βTM-osteoporosis.     

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.