Multi-reoperations for lung metastases.

In this study, we investigated role and results of multi-reoperations for lung metastases. From 1986 to 2010, 113 consecutive patients (61 men and 52 women; mean age: 53.2 ± 12.8 years) underwent repeated lung metastasectomy with curative intent in our institution. Two procedures were performed in 113 patients, three in 54, four in 31, five in eight and six in three. There was no perioperative mortality. Cumulative 5-year survival was 65% and this was significantly higher than the value recorded for patients undergoing only one metastasectomy (42%; p = 0.021). Size, number of resections and probability of recurrence increased by number of operation whereas disease free interval reduced. At any metastasectomy both short disease-free interval and multiple metastases resulted in the most significant negative prognosticators. In conclusion, redo metastasectomy is worthwhile for the initial procedures, afterwards both disease-free and overall survivals decrease and surgery lose its efficacy.

Immune profiling by multiple gene expression analysis in patients at-risk and with type 1 diabetes.

There is a need for biomarkers to monitor the development and progression of type 1 DM. We analyzed mRNA expression levels for granzyme B, perforin, fas ligand, TNF-α, IFN-γ, Foxp3, IL-10, TGF-ß, IL-4, IL-6, IL-17, Activation-induced cytidine deaminase (AID) and Immunoglobulin G gamma chain (IgG) genes in peripheral blood of at-risk, new-onset and long-term type 1 DM , and healthy controls. The majority of the genes were suppressed in long-term type 1 DM compared to controls and new-onset patients. IFN-γ, IL-4 and IL-10 mRNA levels were significantly higher in new-onset compared to at-risk and long-term groups. There was decreased mRNA expression for AID and IgG and up-regulation of IFN-γ with age in controls. Data suggest an overall depressed immunity in long-term type 1 DM. Increased gene expression levels for IFN-γ, IL-4 and IL-10 in new-onset patients from at-risk patients might be used as potential markers for progression of the disease.

Variations of inflammatory mediators and alpha1-antitrypsin levels after lung volume reduction surgery for emphysema.

RATIONALE: In emphysema, chronic inflammation, including protease-antiprotease imbalance, is responsible for declining pulmonary function and progressive cachexia. OBJECTIVES: To evaluate variations of inflammatory mediators and alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared with respiratory rehabilitation. METHODS: A total of 28 patients with moderate to severe emphysema, who underwent video-assisted thoracoscopic LVRS, were compared with 26 similar patients, who refused operation and followed a standardized rehabilitation program, and to a matched healthy group. Respiratory function, body composition, circulating inflammatory mediators, and alpha(1)-antitrypsin levels were evaluated before and 12 months after treatment. Gene expression levels of inflammatory mediators and protease-antiprotease were assessed in emphysematous specimens from 17 operated patients by matching to normal tissue from resection margins. MEASUREMENTS AND MAIN RESULTS: Significant improvements were only obtained after surgery in respiratory function (FEV(1), +25.2%, P < 0.0001; residual volume [RV], -19.5%, P < 0.0001; diffusing lung capacity for carbon monoxide, +3.3%, P < 0.05) and body composition (fat-free mass, +6.5%, P < 0.01; fat mass, +11.9%, P < 0.01), with decrement of circulating inflammatory mediators (TNF-alpha, -22.2%, P < 0.001; IL-6, -24.5%, P < 0.001; IL-8, -20.0%, P < 0.001) and increment of antiprotease levels (alpha(1)-antitrypsin, +27.0%, P < 0.001). Supportive gene expression analysis demonstrated active inflammation and protease hyperactivity in the resected emphysematous tissue. Reduction of TNF-alpha and IL-6 and increment of alpha(1)-antitrypsin levels significantly correlated with reduction of RV (P = 0.03, P = 0.009, and P = 0.001, respectively), and partially with increment of fat-free mass (P = 0.03, P = 0.02, and P = 0.09, respectively). CONCLUSIONS: LVRS significantly reduced circulating inflammatory mediators and increased antiprotease levels over respiratory rehabilitation, also improving respiratory function and nutritional status. Correlations of inflammatory mediators and antiprotease levels with RV and, partly, with body composition suggest that elimination of inflammatory emphysematous tissue may explain clinical improvements after surgery.

New predictors of response to neoadjuvant chemotherapy and survival for invasive thymoma: a retrospective analysis.

BACKGROUND: Cell-cycle protein (p27, p21, and p53) expression can predict response to neoadjuvant chemotherapy and prognosis in some neoplasms. This study evaluated whether these markers could also be effective in invasive thymoma during a multimodality treatment. METHODS: Between 1989 and 2008, 33 patients with invasive thymoma underwent surgical resection after neoadjuvant chemotherapy. Expression of p27, p21, and p53 was assessed using immunohistochemistry in specimens retrieved pre and post chemotherapy. Factors influencing response to neoadjuvant chemotherapy and survival were investigated by univariate and multivariate analysis. Good response was defined as complete disappearance of tumor at imaging or necrosis >90% at pathologic studies. RESULTS: Twelve patients disclosed an imaging good response. Complete resection was possible in 17 patients, 9 of whom had presented imaging good response and 11 of whom had revealed pathologic good response. On univariate analysis both imaging and pathologic poor responses were significantly associated with incomplete resection (P = 0.04 and P = 0.03, respectively) and preneoadjuvant triple combination of p27 low, p21 low, and p53 high expressions (P = 0.001 and P < 0.0001, respectively), the last factor being the only one selected on logistic regression (P = 0.01 and P = 0.005, respectively). Long-term survival analysis was negatively influenced by triple combination of p27, p21, and p53 (P < 0.0001) and incomplete resection (P < 0.0001), which were also selected on Cox's regression (P = 0.004 and P = 0.02, respectively). CONCLUSIONS: The triple combination of p27 low, p21 low, and p53 high expressions was the most significant predictor of imaging and pathologic poor responses to neoadjuvant chemotherapy in invasive thymoma. This combination together with incomplete resection was also the most significant negative predictor of long-term survival.

Symptomatic and quality of life changes after extrapleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: Extrapleural pneumonectomy for malignant pleural mesothelioma is considered an aggressive procedure, but symptomatic and quality of life changes are unknown. METHODS: Between 1997 and 2004, 16 consecutive patients underwent extrapleural pneumonectomy for mesothelioma followed by chemo-radiotherapy. Tumor-related symptoms and quality of life (Short-Form-36 and St. George's questionnaires) were assessed pre, 3, 6, 12, and 24 months postoperatively. RESULTS: Thirty-day postoperative major morbidity was 31% with no mortality. At 3 months postoperatively, dyspnea improved in 10 patients (62%), pain in 12 (75%), cough in 10 (62%), fever in 11 (68%), Karnofsky-index in 10 (62%), Short-Form-36 physical-component-summary in 8, mental-component-summary in 5 and total St. George score in 8 (50%). At 1 year 10 (62%) patients were alive and majority of improved parameters were still stable. Thereafter they usually started to decline. Survival was influenced by nonepithelial histology (P < 0.01) and N2-disease (P < 0.01), which showed to be the only prognosticator at Cox regression (P < 0.0001, Odd ratio 5.4). Among symptomatic variables, a 3-month postoperative Short-Form-36 physical-component-summary above the median value correlated significantly with a better prognosis (P < 0.02). CONCLUSIONS: Extrapleural pneumonectomy may rapidly improve symptoms as well as quality of life, especially in physical domains. Other than biological factors, postoperative Short-Form-36 physical component as well, significantly influenced the prognosis.

Effects of lung volume reduction surgery for emphysema on glycolipidic hormones.

BACKGROUND: Pulmonary emphysema is associated with cachexia and disregulation of the hormones regulating the glycolipid metabolism, insulin resistance, and altered substrate utilization. This study aimed at identifying the effects of lung volume reduction surgery (LVRS) on glycolipidic hormones compared to respiratory rehabilitation (RR). METHODS: Thirty-three patients with moderate-to-severe emphysema who were undergoing video-assisted thoracoscopic LVRS were compared to 31 similar patients who refused the operation and followed a standardized RR program. All patients were evaluated before and 12 months after treatment for respiratory function, body composition, glycolipidic hormones, metabolic parameters, and insulin resistance, which was calculated using the homeostatic model assessment index for insulin resistance (HOMA-IR). These groups were compared to a matched healthy control population. RESULTS: Only after LVRS significant improvements were obtained in respiratory function (FEV1, +25.2%; p<0.0001; residual volume, -19.5%; p<0.0001), metabolic parameters (total cholesterol, +13.1%; p<0.01; high-density lipoprotein cholesterol, +11.2%; p<0.01; triglycerides, +18.4; p<0.001; nonesterified fatty acid, -19.7%; p<0.001), and body composition (fat-free mass [FFM], +6.5%; p<0.01; fat mass [FM], +11.9%; p<0.01). The leptin/FM ratio (-6.1%; p<0.01) and resistin/FM ratio (-5.6%; p<0.01) decreased, whereas the adiponectin/FM ratio (+6.9%; p<0.01) and ghrelin (+9.2%; p<0.01) increased, together with reductions in glycemia (-8.8%; p<0.01), insulin level (-20.4%; p<0.001), and HOMA-IR (-27.2%; p<0.0001). The decrement in residual volume was correlated with increment of FFM (rho=-0.49; p<0.02), FM (rho=-0.55; p<0.009), and ghrelin (rho=-0.52; p<0.01), and also with decreases in leptin corrected for FM (rho=0.50; p<0.02) and, marginally, HOMA-IR (rho=0.35; p=0.07). CONCLUSIONS: After LVRS, glycolipidic hormone levels and nutritional status significantly improved, along with insulin resistance reduction and more physiologic utilization of substrates. Correlations between residual volume and body composition as well as glycolipidic hormone levels suggest that postoperative recovery in respiratory dynamics may induce favorable clinical changes when compared to RR.

Allosensitization of islet allograft recipients.

BACKGROUND: The immune monitoring of islet transplant recipients includes the assessment of panel reactive antibodies (PRA). A negative association of PRA+ with allogeneic solid organ graft survival has been recognized, but scattered data is available for islet transplantation. METHODS: We performed a retrospective analysis of PRA status in 66 patients with type 1 diabetes mellitus recipient of islet allografts between 1985 and 2006. RESULTS: Pretransplant PRA+ was observed in 10 subjects in the old trials and associated with kidney transplantation and/or pregnancies. Thirteen subjects displayed PRA+ at follow-up, eight of whom were de novo. Overall, PRA+ did not correlate with islet graft outcome: long-term graft survival was observed in the presence of basal or persistent PRA+ and graft dysfunction occurred also in the absence of PRA+. Loss of graft function was associated with PRA+ after lowering of immunosuppression or after infection episodes. Loss of C-peptide did not affect kidney graft function even in simultaneous islet-kidney transplant recipients. Mostly, PRA remained negative under adequate immunosuppression. Patients whose immunosuppression was discontinued invariably developed PRA+. CONCLUSIONS: Monitoring of PRA under immunosuppression may have little clinical value under adequate immunosuppression in islet transplant recipients. The implications of allosensitization after discontinuation of immunosuppression need to be evaluated to define the real clinical impact in this patient population.

Analysis of cell cycle regulator proteins in encapsulated thymomas.

PURPOSE: Although survival of encapsulated thymomas is usually good, some patients present a higher incidence rate of recurrence and a shorter long-term survival. Abnormalities in the components of cell cycle checkpoints are extremely common among virtually all neoplasms. In this study, three components of the cell cycle machinery (i.e., p21, p27 and p53) were examined in a series of well-characterized encapsulated thymoma specimens to analyze coregulation and influence on recurrence and survival. EXPERIMENTAL DESIGN: Sixty-eight consecutive patients with thymoma were operated in our center from 1987 to 2000. Expression of p53, p21, and p27 was studied in specimens from 25 encapsulated thymomas using immunohistochemistry. Generic factors and gene expression influencing the probability of recurrence were studied. Positive expression was dichotomized defining positive when present in more than 5% of tumor cells. Mean follow up was 85.9 months; clinical data about recurrence were recorded. RESULTS: Univariate analysis suggests that positive p53 (P < 0.05), negative p21 (P = 0.01), and especially negative p27 expressions (P = 0.001) significantly correlate with poor prognosis for disease-free survival. Multivariate Cox regression analysis suggests that negative p27 immunohistology is the only significant variable for poor prognosis (P = 0.03; odds ratio, 0.08; 95% confidence interval, 0.01-0.88). CONCLUSIONS: These results show that loss of control of cell cycle checkpoints is a common occurrence in thymomas and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumor suppression.

Results of unilateral lung volume reduction surgery in patients with distinct heterogeneity of emphysema between lungs.

OBJECTIVE: This study was undertaken to analyze the comprehensive outcome of unilateral lung volume reduction in patients with distinct heterogeneity of emphysema between lungs assessed by a visual radiologic scoring system. METHODS: Ninety-seven patients who underwent intentional unilateral lung volume reduction because of distinct heterogeneity of emphysema between lungs (asymmetric ratio of emphysema >/=1.1) between 1995 and 2003 were evaluated. Baseline median measures were 0.83 L for forced expiratory volume in 1 second, 5.0 L for residual volume, 380 m for 6-minute walking test distance, 0.50 for maximal incremental treadmill test score, and 25 for physical functioning domain score assessed by the Short Form-36 Quality of Life questionnaire. RESULTS: Median follow-up was 34 months. Significant improvements occurred for as long as 36 months in forced expiratory volume in 1 second (+24%), residual volume (-12%), Short Form-36 Quality of Life questionnaire physical functioning domain score (+100%), 6-minute walking test distance (+18%), and maximal incremental treadmill test score (+200%). A direct correlation was found between asymmetric ratio of emphysema and change in forced expiratory volume in 1 second ( r = 0.65, P < .00001). At 60 months, residual volume (-6.2%), maximal incremental treadmill test score (+100%), and Short Form-36 Quality of Life questionnaire physical functioning domain score (+70%) were still significantly improved. Five-year survival was 82%; 5-year freedom from contralateral lung volume reduction was 70%. CONCLUSIONS: In this series, significant, long-lasting improvements and satisfactory survival were seen after intentional unilateral lung volume reduction. Heterogeneity of emphysema between lungs was directly correlated with improvement at 36 months in forced expiratory volume in 1 second. Our results suggest that unilateral lung volume reduction is a suitable option for patients with distinct heterogeneity of emphysema between lungs.

Bone mineral density improvement after lung volume reduction surgery for severe emphysema.

BACKGROUND: In patients with severe emphysema, bone mineral density (BMD) is reduced and the risk of osteoporosis is increased. STUDY OBJECTIVES: To identify the impact of lung volume reduction surgery on BMD. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Forty emphysematous patients, all receiving oral steroid therapy, underwent bilateral lung volume reduction surgery. Thirty similar patients, who refused the operation, followed a standard respiratory rehabilitation program. MEASUREMENTS: All subjects were evaluated pretreatment and 12 months posttreatment for respiratory function, nutritional status, and bone-related biochemical parameters. BMD was assessed by dual-energy radiograph absorptiometry. RESULTS: After surgery, we observed significant improvements in respiratory function (FEV1, + 18.8% [p < 0.01]; residual volume [RV], -29.6% [p < 0.001]; diffusing capacity of the lung for carbon monoxide [Dlco], + 21.6% [p < 0.01]) nutritional parameters (fat-free mass, + 6.0% [p < 0.01]), levels of bone-related hormones (free-testosterone, + 20.5% [p < 0.01]; parathormone, -11.2% [p < 0.01]), bone turnover markers (osteocalcin, -12.7% [p < 0.05]; bone-alkaline-phosphatase, -14.0% [p < 0.05]; beta-crosslaps, -33.6% [p < 0.001]), BMD (lumbar, + 8.8% [p < 0.01]; femoral, + 5.5% [p < 0.01]), and T-score (lumbar, + 21.0% [p < 0.01]; femoral, + 12.4% [p < 0.01]) with reduction in osteoporosis rate (50 to 25%). Nineteen patients who had undergone surgery were able to discontinue treatment with oral steroids. These subjects showed a more significant improvement in BMD (lumbar, + 9.6%; femoral, + 6.8%; p < 0.001) and T-score (lumbar, + 27.3%; femoral, + 14.3%; p < 0.001). The remaining 21 patients who had undergone surgery experienced significant improvement compared to respiratory rehabilitation subjects despite continued therapy with oral steroids (BMD: lumbar, + 4.5% vs -0.7%, respectively [p < 0.01]; femoral, + 2.7% vs -1.1%, respectively [p < 0.05]; T-score: lumbar, + 14 vs -2.1, respectively [p < 0.01]; femoral, + 7.4 vs -2.7, respectively [p < 0.01]). The increase in lumbar BMD was correlated with the surgical reduction of RV (p = 0.02) and with the increase in Dlco (p = 0.01) and fat-free mass (p = 0.01). CONCLUSIONS: Lung volume reduction surgery significantly improves BMD compared to respiratory rehabilitation therapy, even in patients requiring oral steroids. The increase in BMD correlates with RV, Dlco, and fat-free mass, suggesting that the restoration of respiratory dynamics, gas exchange, and nutritional status induces improvement in bone metabolism and mineral content.

Plasma von Willebrand factor antigen levels in non-small cell lung cancer patients.

BACKGROUND: To analyze the behavior of circulating von Willebrand factor antigen (vWf:Ag) in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Pre-surgical vWf:Ag levels were measured in 64 patients with histologically diagnosed NSCLC compared to 64 patients with benign pulmonary diseases, as well as 64 age- and sex-matched controls. RESULTS: Patients with NSCLC had mean vWf:Ag concentrations lower than either controls or benign patients (p =0.001). CEA was the only variable predictive of low vWf:Ag levels (p<0.01). Five of the 64 NSCLC patients had abnormally low vWf:Ag concentrations (<36 IU/dL). When these patients were excluded from the analysis, the vWf:Ag levels of NSCLC patients did not differ from those of controls (p=0.19). CONCLUSION: The vWf antigen levels of NSCLC patients are not substantially altered. A small subset of these patients will have a depletion of circulating vWf:Ag, probably because of a paraneoplastic process associated with an advanced stage of disease.

Awake one stage bilateral thoracoscopic sympathectomy for palmar hyperhidrosis: a safe outpatient procedure.

OBJECTIVE: To verify the feasibility and compare the results of thoracoscopic sympathectomy under local anaesthesia (LA) and spontaneous breathing vs. general anaesthesia (GA) with one-lung ventilation. METHODS: Two groups of consecutive patients underwent one stage bilateral T2-T3 thoracoscopic sympathectomy under LA (n=15) and GA (n=30) by the same surgical team for treatment of primary palmar hyperhidrosis. The groups were homogeneous for relevant demographic, physiological and clinical data, including pulmonary function. In both groups, patient's satisfaction was evaluated 24h after surgery by a simple interview and scored into five grades (1=very poor to 5=excellent), while quality of life (QOL) was evaluated by SF-36 and Nottingham's Health Profile questionnaires before and 6 months after surgery. A cost comparison between groups concerning devices, drugs, global in operating room time, medical personnel and hospital stay was also carried out. RESULTS: No operative mortality was recorded. The overall in operating room time for the whole bilateral procedure under LA was 63.55+/-10.58 vs. 86.05+/-5.75 under GA (P<0.01) and temperature increased in all patients from a baseline of 25.42+/-0.56 up to 32.15+/-0.84 degrees C. All patients undergone LA were discharged the same day after a chest roentgenogram and a short stay in the outpatient clinic. Among them three patients (20%) experienced a minimal (<30%) pneumothorax that required no treatment, while five (33.3%) had a trunk compensatory sweating that spontaneously resolved on the long run. Patients undergoing GA were discharged after a mean stay of 1.38+/-0.6 days. Among these, eight (26.6%) had prolonged trunk compensatory sweating that did not persist longer than 3 months. At a follow-up of 7.16+/-2.97 months, QOL was significantly improved with no difference between groups. The overall rate of satisfaction was greater in the LA group (P<0.05). CONCLUSIONS: In our study, awake one stage bilateral thoracoscopic sympathectomy for palmar hyperhidrosis could be safely and effectively performed as an outpatient procedure in patients refusing GA. Postoperative quality of life was equal to that in patients undergone the same procedure under GA, while patient satisfaction was better and cost were significantly reduced.

The Arg972 variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients.

The insulin receptor substrate-1 (IRS-1) gene has been considered a candidate for insulin resistance, type 2 diabetes, and coronary artery disease. To investigate the relationship between the common Gly(972)Arg IRS-1 variant and the presence of cardiovascular risk factors, 153 glucose-tolerant, unrelated offspring of type 2 diabetic patients were studied. There were no differences between Arg(972) IRS-1 carriers and noncarriers in age, gender, body mass index, waist/hip ratio, body composition, fasting glucose and insulin levels, and glucose or insulin levels during the oral glucose tolerance test. Insulin sensitivity, assessed by hyperinsulinemic-euglycemic clamp, was significantly reduced in carriers of Arg(972) IRS-1 (P < 0.03). Carriers of Arg(972) IRS-1 displayed many features of the insulin resistance syndrome, including higher values for serum triglycerides (P < 0.01), total/high density lipoprotein cholesterol ratio (P < 0.01), free fatty acid levels (P < 0.04), systolic blood pressure (P < 0.04), microalbuminuria (P < 0.003), and intima-media thickness (P < 0.02). These results suggest that the Arg(972) IRS-1 variant could contribute to the risk for atherosclerotic cardiovascular diseases associated with type 2 diabetes by producing a cluster of insulin resistance-related metabolic abnormalities.

Body weight and nutritional changes after reduction pneumoplasty for severe emphysema: a randomized study.

BACKGROUND: The impact of reduction pneumoplasty on body weight and nutritional status has not previously been tested in a controlled study. METHODS: We investigated 60 patients with severe emphysema who were randomly assigned to receive either reduction pneumoplasty (n = 30) or a 6-week respiratory rehabilitation program (n = 30). Nutritional status was evaluated by means of body mass index, triceps skin fold measurement, midarm muscle circumference, and biochemical blood values. Fat mass and fat-free mass were calculated by bioelectric impedance. Two treatment-related deaths occurred after reduction pneumoplasty and 1 death occurred after respiratory rehabilitation. RESULTS: Functional and subjective improvements were significantly showed in reduction pneumoplasty group. Despite insignificant differences in energy intake, the reduction pneumoplasty group showed significant gain (P <.0001) relative to the respiratory rehabilitation group in mean weight changes at 3 months (1.82 +/- 2.63 kg vs -0.57 +/- 2.25 kg), 6 months (2.87 +/- 3.79 kg vs -1.11 +/- 2.64 kg), and 12 months (3.29 +/- 4.01 kg vs -0.95 +/- 1.90 kg). Both fat mass and fat-free mass increased after surgery, but only fat-free mass had a significant improvement (P =.001). Six-month weight gain in the reduction pneumoplasty group was significantly correlated with low baseline weight (rho = -0.437, P =.02) and residual volume reduction (rho = -0.446, P =.01). Total proteins (P =.003), albumin (P =.03), transferrin (P =.04), cholesterol (P =.003), hemoglobin (P =.01), triceps skin fold measurement (P <.0001), and midarm muscle circumference (P <.0001) were significantly increased only in the reduction pneumoplasty group. Conversely, in the respiratory rehabilitation group no nutritional index was significantly increased at 6 months after rehabilitation. CONCLUSIONS: Body weight and nutritional status improved only after reduction pneumoplasty and not after respiratory rehabilitation, and this was significantly related to fat-free mass increment. In the reduction pneumoplasty group, the residual volume result was significantly correlated with postoperative weight gain.

Quality of life after tailored combined surgery for stage I non-small-cell lung cancer and severe emphysema.

BACKGROUND: We analyzed the early and long-term quality of life changes occurring in 16 patients undergoing tailored combined surgery for stage I non-small-cell lung cancer (NSCLC) and severe emphysema. METHODS: Mean age was 65 +/- 5 years. All patients had severe emphysema with severely impaired respiratory function and quality of life. Tumor resection was performed with sole lung volume reduction (LVR) in 5 patients, separate wedge resection in 3 patients, segmentectomy in 2 patients, and lobectomy in 6 patients. A bilateral LVR was performed in 5 patients. Quality of life was assessed at baseline and every 6 months postoperatively by the Short-form 36 (SF-36) item questionnaire. RESULTS: Mean follow-up was 44 +/- 21 months. All tumors were pathologic stage I. There was no hospital mortality nor major morbidity. Significant improvements occurred for up to 36 months in the general health (p = 0.02) domain and for up to 24 months in physical functioning (p = 0.02), role physical (p = 0.005), and general health (p = 0.01) SF-36 domains. Associated improvements regarded dyspnea index (-1.3 +/- 0.6) forced expiratory volume in one second (+0.28 +/- 0.2L), residual volume (-1.18 +/- 0.5L) and 6-minute-walking test distance (+86 +/- 67 m). Actuarial 5-year survival was similar to that of patients with no cancer undergoing LVRS during the same period (68% vs 82%, p = not significant). CONCLUSIONS: Our study suggests that selected patients with stage I NSCLC and severe emphysema may significantly benefit from tailored combined surgery in terms of long-term quality of life and survival.

Longterm results after resection of simultaneous and sequential lung and liver metastases from colorectal carcinoma.

BACKGROUND: Although simple lung or liver metastasectomy from colorectal cancer have proved effective in selected patients, the value of simultaneous biorgan metastasectomies is still debated. STUDY DESIGN: Of 155 patients who underwent operation for lung or liver colorectal metastases between March 1987 and December 1998, we retrospectively reviewed 29 patients who presented simultaneous (n = 12) or sequential liver-->lung (n = 10) and lung-->liver (n = 7) metastases. All metastases were successfully resected in a total of 56 separate procedures. In 35 thoracic procedures, 45 metastases were removed by wedge resection (n = 36) or lobectomy (n = 9). In addition, 47 liver metastases were resected with wedge (n = 24), segmentectomy (n = 13), or lobectomy (n = 10). There were no perioperative deaths and the morbidity rate was low (10.7%). All patients were followed for a minimum of 3 years. Factors possibly influencing survival were evaluated by univariate and subsequently by multivariate analyses. RESULTS: Median survival from the second metastasectomy was 41 months, with a 5-year survival rate of 51.3%. Risk factor distribution among the three metastastic pattern groups was insignificant. Premetastasectomy elevated levels of both CEA and CA19-9 (p = 0.0001), and mediastinal or celiac lymph node status (p = 0.03) were significantly associated with survival in the univariate analysis, although number of metastasectomies, disease-free interval, and simultaneous versus sequential diagnosis were not. In the multivariate analysis, only elevated CEA plus CA19-9 (p = 0.01) was significantly associated with survival. CONCLUSIONS: We conclude that either simultaneous or sequential lung and liver metastasectomy can be successfully treated by surgery. Poor results were obtained in the presence of high levels of CEA plus CA19-9.

Erythrocyte osmotic resistance recovery after lung volume reduction surgery.

OBJECTIVES: Alteration of erythrocyte osmotic resistance, with increment of reticulocytes, is common in emphysema. This fragility is probably due to an altered fatty acid membrane composition from lipid peroxidation, a reaction triggered by the disease-related increment of reactive oxidative species. We analysed the effects of lung volume reduction surgery (LVRS) on this anomaly compared with respiratory rehabilitation (RR) therapy. METHODS: We retrospectively compared 58 male patients with moderate-to-severe emphysema who underwent LVRS with 56 similar patients who underwent standardized RR. Respiratory function parameters, erythrocyte osmotic resistance and antioxidant enzymes levels were evaluated before and 6 months after treatments. RESULTS: Significant improvements in respiratory function, exercise capacity, unsaturated fatty acid content (+10.0%, P = 0.035), erythrocyte osmotic resistance (hyperosmolar resistance -21.0%, P = 0.001; hyposmolar resistance -18.0%, P = 0.007) and erythrocyte antioxidant enzymes [superoxide dismutase (SOD) +60.0%, P < 0.001; glutathione peroxidase +39.0%, P = 0.004 and glutathione reductase +24.5%, P = 0.008] were observed after surgery. In the RR group, we did not find any significant improvements in osmotic resistance, although respiratory and functional parameters were significantly improved. Correlation analysis in the surgical group showed that the reduction in residual volume (RV) significantly correlated the normalization of hyperosmotic (P = 0.019) and hyposmotic resistances (P = 0.006), the decrease in the absolute number of reticulocytes (P = 0.037) and increase in SOD (P < 0.001). CONCLUSIONS: LVRS improved unsaturated fatty acid content, erythrocyte osmotic resistance and levels of erythrocyte antioxidant enzymes compared with RR. Correlations between erythrocyte osmotic resistance and antioxidant intracellular enzymes with RV suggest that reduction in lung hyperinflation with the elimination of inflammatory emphysematous tissue may explain such improvements after surgery.

The impact on quality of life after en-bloc resection for non-small-cell lung cancer involving the chest wall.

BACKGROUND: En-bloc resection for non-small cell lung cancer with chest-wall involvement may achieve a 5-year survival rate higher than 40%, but the impact on postoperative quality of life is not yet known. METHODS: Twenty-six patients undergoing en-bloc lung resections were included. Life quality ratings were assessed through a Short-Form 36 questionnaire preoperatively and at six, 12, 18 and 24 month follow-up visits. The degree of dyspnea, pain level, and flow-volume curves were also obtained at the same time periods. Changes occurring over time were analyzed by means of repeated-measure ANOVA. RESULTS: As a whole, the Physical Component Summary score declined six months postoperatively (P < 0.0001) and failed to improve thereafter. Patients with preoperative Forced Expiratory Volume in one second (FEV1 ), <80% predicted (P = 0.029), resected ribs >2 (P = 0.03), and chest wall defect ≥50 cm2 (P = 0.007) experienced a greater and lasting impairment. Net postoperative decrease in FVC (P = 0.02; r = 0.48) and dyspnea worsening (P = 0.03; r =-043 at six months, P = 0.05; r =-0.39 at 12 months) were also correlated with the extent of physical deterioration, whereas age (P = 0.92), gender (P = 0.51), type of resection (P = 0.71), and adjuvant therapy (P = 0.68) did not. The Physical Component Summary didn't change significantly in patients with high pain levels (VAS >7). The Mental Component Summary score increased slightly at six months, with no difference in any patients' subgroup. CONCLUSIONS: The extent of chest wall resection, preoperative FEV1 , and postoperative decline in FVC were the main indicators of quality of life impairment after en-bloc resection for lung cancer. The impact upon quality of life should be considered in a cost-to-benefit ratio of planning this surgery in suboptimal candidates.