Chemokine Involvement in Lung Injury Secondary to Ischaemia/Reperfusion.

INTRODUCTION: During transplant surgeries, the lung experiences an ischaemia-reperfusion (I/R)-induced damage identified as a significant cause of morbidity and mortality. However, the mechanisms by which I/R induces leucocyte accumulation and subsequent tissue damage in lung surgeries remain unknown. Therefore, the present study aims to assess the role of monocyte chemotactic protein 1 (MCP-1) and macrophage inflammatory protein 2 (MIP-2) in leucocyte chemotaxis related to lung injury secondary to I/R. METHODS: Six pigs were subjected to an orthotopic left caudal lobe lung transplantation with a subsequent 60-min graft reperfusion (Transplant group). In addition, six animals underwent to sham surgery (Sham Group). Plasma samples and lung biopsies were collected before the beginning of pneumonectomy, before starting the reperfusion, and 30 min and 60 min after the beginning of the reperfusion. Plasma levels of intercellular adhesion molecule 1 (ICAM-1) and lung expressions of MCP-1, MIP-2, myeloperoxidase (MPO), and lung oedema were measured. RESULTS: Lung I/R caused substantial damage observed as pulmonary oedema. The oedema was evident after the ischemic insult and increased after reperfusion. After reperfusion, increased levels of MPO were observed which suggests an activation and infiltration of neutrophils into the lung tissue. After 30 min of reperfusion, MCP-1, MIP-2, and ICAM-1 levels were significantly increased compared to prepneumonectomy levels (p < 0.05) and a further increase was observed after 60 min of reperfusion (p < 0.05). CONCLUSION: The present study demonstrates that activated neutrophils, as well as MCP-1, MIP-2, and ICAM-1, are involved in inflammatory response induced by ischaemia-reperfusion-induced lung injury.

Ischaemic preconditioning prevents the liver inflammatory response to lung ischaemia/reperfusion in a swine lung autotransplant model.

OBJECTIVES: Lung ischaemia/reperfusion (IR) induces a systemic inflammatory response that causes damage to remote organs. The liver is particularly sensitive to circulating inflammatory mediators that occur after IR of remote organs. Recently, remote ischaemic preconditioning has been proposed as a surgical tool to protect several organs from IR. The present study was designed to investigate a possible protective effect of lung ischaemic preconditioning (IP) against the liver inflammatory response to lung IR. METHODS: Two groups [IP and control (CON)] of 10 Large White pigs underwent lung autotransplants (left pneumonectomy, ex situ cranial lobectomy and caudal lobe reimplantation). Before pneumonectomy was performed in the study group, IP was induced with two 5-min cycles of left pulmonary arterial occlusion and a 5-min interval of reperfusion between the two occlusions. Five animals underwent sham surgery. Liver biopsies were obtained during surgery at (i) prepneumonectomy, (ii) prereperfusion, (iii) 10 min after reperfusion of the implanted lobe and (iv) 30 min after reperfusion. The expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-10 and inducible form of nitric oxide synthase (iNOS) was analysed by western blotting. The expression of mRNA for TNF-α, IL1, IL-10, monocyte chemoattractant protein-1 (MCP-1), nuclear factor kappa beta and iNOS was analysed by reverse transcription-polymerase chain reaction. Caspase-3 activity was determined by enzyme-linked immunosorbent assay. Non-parametric tests were used to compare differences between and within groups. RESULTS: Lung IR markedly increased expression of TNF-α (P = 0.0051) and IL-1 (P = 0.0051) and caspase-3 activity (P = 0.0043) in the CON group compared with the prepneumonectomy levels. A decrease of IL-10 mRNA expression was observed in the CON group after lung reperfusion. In the IP group, TNF-α (P = 0.0011) and IL-1 (P = 0.0001) expression and caspase-3 activity (P < 0.0009) were lower after reperfusion than in the CON group. IP caused reversion of the observed decrease of IL-10 mRNA expression (P = 0.016) induced in liver tissue by lung IR. Lung IR markedly increased the expression of mRNA MCP-1 after 10 min (P = 0.0051) and 30 min (P = 0.0051) of reperfusion. These increases were not observed in the IP or sham groups. CONCLUSIONS: IP prevented liver injury induced by lung IR through the reduction of proinflammatory cytokines and hepatocyte apoptosis.

Site of mitochondrial reactive oxygen species production in skeletal muscle of chronic obstructive pulmonary disease and its relationship with exercise oxidative stress.

Exercise triggers skeletal muscle oxidative stress in patients with chronic obstructive pulmonary disease (COPD). The objective of this research was to study the specific sites of reactive oxygen species (ROS) production in mitochondria isolated from skeletal muscle of patients with COPD and its relationship with local oxidative stress induced by exercise. Vastus lateralis biopsies were obtained in 16 patients with COPD (66 ± 10 yr; FEV(1), 54 ± 12% ref) and in 14 control subjects with normal lung function who required surgery because of lung cancer (65 ± 7 yr; FEV(1), 91 ± 14% ref) at rest and after exercise. In these biopsies we isolated mitochondria and mitochondrial membrane fragments and determined in vitro mitochondrial oxygen consumption (Mit$$\stackrel{.}{\hbox{ V }}$$o(2)) and ROS production before and after inhibition of complex I (rotenone), complex II (stigmatellin), and complex III (antimycin-A). We related the in vitro ROS production during state 3 respiration), which mostly corresponds to the mitochondria respiratory state during exercise, with skeletal muscle oxidative stress after exercise, as measured by thiobarbituric acid reactive substances.State 3 Mit$$\stackrel{.}{\hbox{ V }}$$o(2) was similar in patients with COPD and control subjects (191 ± 27 versus 229 ± 46 nmol/min/mg; P = 0.058), whereas H(2)O(2) production was higher in the former (147 ± 39 versus 51 ± 8 pmol/mg/h; P < 0.001). The addition of complexI, II, and III inhibitors identify complex III as the main site of H(2)O(2) release by mitochondria in patients with COPD and in control subjects. The mitochondrial production of H(2)O(2) in state 3 respiration was related (r = 0.69; P < 0.001) to postexercise muscle thiobarbituric acid reactive substance levels. Our results show that complex III is the main site of the enhanced mitochondrial H(2)O(2) production that occurs in skeletal muscle of patients with COPD, and the latter appears to contribute to muscle oxidative damage.

Modulation of monocyte chemoattractant protein-1 expression by ischaemic preconditioning in a lung autotransplant model.

OBJECTIVES: Monocyte chemoattractant protein-1 (MCP-1) is believed to play a crucial role in lung ischaemia-reperfusion injury (LIRI). Ischaemic preconditioning (IP) has been shown to protect several organs from ischaemia-reperfusion (IR) injury, although less is known about IP's effect on MCP-1 modulation. The objective of this study was to investigate IP's effect on MCP-1 expression in lung tissue and its relationship with oxidative stress and proinflammatory cytokine production in an experimental LIRI model. METHODS: Two groups (IP and control groups) of seven large white pigs underwent a lung autotransplant (left pneumonectomy, ex situ superior lobectomy and lower lobe reimplantation). Before pneumonectomy was performed in the study group, IP was induced with two cycles of 5 min of left pulmonary artery occlusion with a 5 min interval of reperfusion between the two occlusions. Blood samples and lung biopsies were obtained at prepneumonectomy (PPn), at prereperfusion (PRp) and up to 30 min after reperfusion of the implanted lobe (Rp-10' and Rp-30'). Haemodynamic and blood-gas measurements, evaluation of oxidative stress in lung tissue and MCP-1, tumour necrosis factor-α (TNF-α) and IL-1 protein and mRNA measurements in lung tissue were performed. Nonparametric tests were used to compare differences between groups. Data are expressed as mean ± SEM. RESULTS: In control lungs, MCP-1 protein levels were found to be higher at PRp, Rp-10' and Rp-30' than at PPn (0.59 ± 0.1 vs. 0.21 ± 0.05, 0.47 ± 0.01 vs. 0.21 ± 0.05 and 0.56 ± 0.01 vs. 0.21 ± 0.05, respectively; P < 0.05). These differences were not evident in the IP group. MCP-1 levels at PRp, Rp-10' and Rp-30' were significantly higher in the control group than in the IP group (0.59 ± 0.1 vs. 0.15 ± 0.02, 0.47 ± 0.01 vs. 0.13 ± 0.01 and 0.56 ± 0.01 vs. 0.27 ± 0.01, respectively; P < 0.05). MCP-1, TNF-α and IL-1 mRNA expressions were lower at PRp, Rp-10' and Rp-30' (control vs. IP group, P < 0.05) when IP was carried out. Lipid peroxidation metabolites and myeloperoxidase activity increase in lung tissue were prevented by IP. CONCLUSIONS: In this model, LIRI induced the expression of MCP-1 and the proinflammatory proteins TNF-α and IL-1 in control lungs. IP significantly reduced the expression of these chemokines and cytokines. These features may explain the reduction of oxidative stress observed with IP.

Prognostic influence of loss of blood group A antigen expression in pathologic stage I non-small-cell lung cancer.

INTRODUCTION: In the scientific literature, contradictory results has been published on the prognostic value of the loss of expression of blood group antigen A (BAA) in lung cancer. The objective of our study was to analyze this fact in our surgical series. PATIENTS AND METHODS: In a multicenter study, 402 non-small-cell lung cancer (NSCLC) patients were included. All were classified as stage-I according to the last 2009-TNM classification. We analyzed the prognostic influence of the loss of expression of BAA in the 209 patients expressing blood group A or AB. RESULTS: The 5-year cumulative survival was 73% for patients expressing BAA vs 53% for patients with loss of expression (P=.03). When patients were grouped into stages IA and IB, statistical significance was only observed in stage I-A (P=.038). When we analyzed the survival according to histologic type, those patients with adenocarcinoma and loss of expression of BAA had a lower survival rate that was statistically very significant (P=.003). The multivariate analysis showed that age, gender and expression of BAA were independent prognostic factors. CONCLUSIONS: The loss of expression of blood group antigen A has a negative prognostic impact in stage I NSCLC, especially in patients with adenocarcinoma.

Multicenter analysis of survival and prognostic factors in pathologic stage I non-small-cell lung cancer according to the new 2009 TNM classification.

INTRODUCTION: The new 2009 TNM classification introduced important modifications in lung cancer staging. The aim of this study is to validate our series of patients with pathologic stage I non-small-cell lung cancer according to the 7th edition of the TNM classification of malignant tumors and to the factors related with prognosis. PATIENTS AND METHODS: A multicenter retrospective study was performed. Survival rates were calculated by the Kaplan-Meier method, and for multivariate analyses, Cox proportional hazards regression model was used. The following variables were analyzed: age, sex, pathologic stage, T category, histology, type of resection and tumor size. RESULTS: A total of 402 patients were included. Mean follow-up was 70.18 months. Overall 5-year survival was 68%. Males and patients over 70 had lower survival. Prognosis worsened with increasing pathologic stage, T category and tumor size. We found no statistically significant differences in prognosis for histology or type of resection. Multivariate analysis showed age, sex and pathologic stage to be independent prognostic factors. CONCLUSIONS: Survival results and the analysis of prognostic factors in our series are similar to those published in the new 2009 TNM classification. The most important prognostic factor is pathologic stage. Other adverse prognostic factors include male sex and age over 70.

Experimental Swine lung autotransplant model to study lung ischemia-reperfusion injury.

INTRODUCTION: Ischemia-reperfusion (IR) lung injury has been investigated extensively on clinical and experimental models of cold ischemia. However, relatively few studies examine the detailed biochemical changes occurring during normothermic (warm) IR. The objective of this work was to establish an experimental lung autotransplant model to be carried out on pigs in order to study the early stages of normothermic lung IR. ANIMALS Y METHODS: Six Large-White pigs underwent a lung autotransplant which entailed left pneumonectomy, ex situ cranial lobectomy, caudal lobe reimplantation and its reperfusion for 30 min. Throughout the procedure, several parameters were measured in order to identify hemodynamic, gasometric and biochemical changes. Non-parametric statistical analyses were used to compare differences between periods. RESULTS: After ischemia, a significant increase (P < 0.05) in lipid peroxidation metabolites, proinflammatory cytokines and chemokines (TNF-α, IL-1ß y MCP-1), neutrophil activation, inducible nitric oxide synthase activity and protein-kinase MAPK p38 levels were observed in lung tissue. However, constitutive nitric oxide synthase activity in lung tissue and carbon monoxide plasma levels were decrease. The same held true throughout the reperfusion period, when an increase in the constitutive heme-oxygenase activity was also shown. CONCLUSIONS: An experimental model of normothermic lung IR injury is presented and detailed changes in hemodynamic, gasometric and biochemical parameters are shown. Both the model and the studied parameters may be clinically useful in future investigations testing new therapies to prevent normothermic IR induced lung injury.

Surgery of female genital tract tumour lung metastases.

INTRODUCTION: Lung metastases originating from tumours of the female genital tract are rare. Due to this rarity and their variable histology, it has been difficult to compare different patient series. MATERIAL AND METHODS: A retrospective study of patients undergoing resection of lung metastases of female genital tract tumours (uterine and cervical cancer) during the period 01/01/1989 to 12/31/2006. Epidemiological, diagnostic and treatment data were collected. Non-parametric tests and survival analysis were performed using the Kaplan-Meier and log-rank test. RESULTS: A resection was performed on 27 patients during the study period. Disease-free interval (DFI) from initial diagnosis of lung metastases was 58 months (1-195 months). The median survival from diagnosis of metastases was 94 months. The overall survival at 5 years after diagnosis of metastasis was 84.1%. A second surgery of metastases was performed on 5 patients (18.5%). Survival after second surgery of metastases: 80.5 months. Survival from diagnosis of metastasis at five years: endometrial carcinoma 100%, cervical cancer 62.5%, uterine sarcoma 60%. Adjuvant hormonal therapy was prescribed in 15 out of 16 patients with endometrial carcinoma. There was a statistically significant difference in the survival depending on the histological type and disease free interval. CONCLUSION: Surgical treatment of lung metastases originating from female genital tract tumours (mainly endometrial carcinoma) is associated with a high long-term survival.

Early and long-term validation of an algorithm assessing fitness for surgery in patients with postoperative FEV1 and diffusing capacity of the lung for carbon monoxide < 40%.

BACKGROUND: There is evidence in the literature that the incidence of pulmonary complications and mortality is fair enough in patients with lower pulmonary function than conventionally accepted. In this article, we validate in patients with low baseline lung function (ie, FEV(1) or diffusing capacity of the lung for carbon monoxide [DLCO] < 80%) an algorithm to evaluate anatomic lung surgery in patients with low predicted postoperative lung function (ie, either FEV(1)-postoperative estimated [ppo] or DLCO-ppo < 40% or both between 30% and 40% predicted) if peak oxygen uptake (VO(2)peak)-ppo > 10 mL/kg/min. METHODS: We prospectively studied 126 consecutive patients evaluated for anatomic resection of lung tumors by thoracotomy. RESULTS: Ninety-two patients were operated on: age 67 (8 SD) years; FEV(1) 63 (14)% pp; DLCO 71 (19)% pp; VO(2)peak 71 (19)% predicted; and 2-year Kaplan-Meier conditional probability of survival (CPS) 0.62 (0.06). Thirty-day perioperative mortality was 6.4%. Thirty-four patients were not functionally fit, or rejected the procedure: age 69 (8) years; FEV(1) 58 (16)% predicted; DLCO 67 (26)% predicted; VO(2)peak 66 (16)% predicted. In this group, 2-year CPS was 0.18 (0.08), P < .01. Subgroups A (FEV(1)-ppo and DLCO-ppo > 40% predicted) and B (either FEV(1)-ppo or DLCO-ppo < 40% predicted or both between 30% and 40% predicted) were comparable in terms of perioperative morbidity; however, they were different in terms of 30-day mortality (A, 1/53 [1.9%]; B, 5/37 [13.5%]; P = .047; relative risk, 7.2; 95% CI 1.1-27.7). The survival functions of both subgroups were significantly different (P < .01) from nonsurgical subjects. CONCLUSIONS: Adherence to the proposed algorithm results in a reasonable preoperative mortality in patients with low preoperative lung function. Although perioperative mortality is significantly higher when predicted postoperative lung function is low, 2-year survival of patients is better than if such patients had not undergone surgery.

[Detection of lymph node involvement and surgical treatment of pulmonary neoplastic processes. Current state of diagnostic and therapeutic procedures]. / Detección de la afectación ganglionar y tratamiento quirúrgico de los procesos neoplásicos pulmonares. Estado actual de distintos procederes diagnósticos y terapéuticos.

An analysis is made of different publications associated with the surgical staging and treatment of primary and metastasic pulmonary neoplastic processes. A suitable treatment program is essential to determine lymph node involvement in patients with bronchogenic carcinoma. The indication and sequence of the procedure to use (CT-PET, transbronchial puncture, videomediastinoscopic ultrasound guided transbronchial needle aspiration) is evaluated in accordance to the sensitivity, specificity and positive and negative predictive value of the different methods. Another interesting challenge is to define the criteria for indicating a sublobar resection in certain tumours and patients. Different factors, age, lung function, tumour location and type of sublobar resection, are analysed. Levels of evidence and recommendations of the procedure are also considered. Surgical resection is an accepted therapeutic option in the treatment of colorectal cancer lung metastases. Its indication is based on acceptable survival rates and knowledge of the impact of various factors (interval free of disease, number of metastases, presence of liver metastasis, presence of lymph node involvement, or increased pre-operative levels of carcinoembryonic antigen), is analysed in detail.

[Pulmonary epithelioid hemangioendothelioma]. / Hemangioendotelioma epiteloide pulmonar.

Epithelioid hemangioendothelioma is a multifocal tumor that rarely metastasizes. It is difficult to diagnose and is most often an incidental finding in young asymptomatic women. It has a heterogeneous radiologic pattern. The most important diagnostic information is histologic confirmation of Weibel-Palade bodies or immunohistochemistry based on specific tumor markers such as factor VIII and CD34. We report the case of a 73-year-old woman in whom multiple pulmonary nodules detected by chance in a radiograph were subsequently diagnosed as epithelioid hemangioendothelioma.

Thoracic paravertebral block after thoracotomy: comparison of three different approaches.

BACKGROUND: Thoracic paravertebral block (TPVB) is a regional block technique increasingly used for the early management of post-thoracotomy pain. We compare three different postoperative analgesic approaches based on TPVB: anesthetist, anesthetist plus surgeon, and surgeon. MATERIALS AND METHODS: We randomized 54 patients undergoing elective thoracotomy to three different postoperative analgesia groups: paravertebral percutaneous catheter (PVA group), paravertebral percutaneous catheter plus incisional (subcutaneous) catheter (PVA+Inc), and paravertebral catheter under direct vision (PVS group). During early postoperative 48h, we measured pain intensity, intravenous morphine afforded by the patient-controlled analgesia pump, and the spirometric test. RESULTS: There were no statistically significant differences among the collected preoperative data. No significant differences were observed on postoperative spirometric values. Analgesic quality was better in PVA+Inc group at 12 and 24 postoperative hours. In this group, intravenous morphine use to improve analgesia was significantly lower from 8h until 48h postoperative. CONCLUSIONS: Association of thoracic paravertebral block to continuous infusion of a local anesthetic in the surgical incision area affords a better pain relief than paravertebral block alone (introduced by the surgeon or the anesthetist).

Lung cancer surgery in the elderly.

Non-small cell lung cancer (NSCLC) is a typical disease of the elderly, and is becoming increasingly more common as a result of the gradual aging of the population. Although patient age is known to be an independent prognostic factor of postoperative survival, lung resection should not be denied on the basis of age alone. In patients of this kind, careful evaluation and selection is very important. In early-stage NSCLC, surgery is the treatment of choice. In the advanced stages of the disease treatment usually comprises primary radiotherapy or combined radio-chemotherapy. Preoperative preparation and postoperative care are very important in chest surgery, and particularly in elderly patients. The 5-year survival rate in octogenarians exceeds 40%, but is much lower in pneumonectomized patients (close to 10%). In conclusion, elderly patients should be offered the best treatment possible, bearing in mind that surgery offers the best results when the disease is resectable.

Neuroendocrine tumors of the lung.

PURPOSE OF REVIEW: The aim of this article is to answering different questions related to the treatment and prognosis of neuroendocrine lung tumors. RECENT FINDINGS: In neuroendocrine lung tumors, regardless of the grade of tumoral malignancy, the general growth during the past years of the nodal involvement percentage detected in lung neuroendocrine tumors might be explained by accepting surgical treatment as the norm and a complete mediastinal nodal dissection. Among non-small-cell carcinomas, large cell neuroendocrine carcinoma is the tumor with the worst prognosis. Nodal invasion clearly decreases the possibility of long-term survival in these patients, confirming the importance of preoperative and perioperative staging. A definitive survival advantage for postoperative adjuvant therapy has yet to be reported; tumoral genetics studies may contribute to specifying its indication. The importance of neuroendocrine differentiation in non-small-cell lung carcinomas for the treatment and prognosis of these tumors is a reason to intensify research. SUMMARY: In the surgical treatment of lung neuroendocrine carcinomas, nodal mediastinal dissection should always be performed. In the large neuroendocrine carcinoma, experience confirms the possibility of surgical treatment in early stages; in all cases, adjuvant treatment should always be established. The presence of synaptophysin in squamous carcinoma tumors and adenocarcinoma tumors in stage I seems to be associated with a worse prognosis.

[Trends in prognostic factors for neuroendocrine lung tumors]. / Tendencias en los factores pronósticos de los tumores pulmonares neuroendocrinos.

OBJECTIVE: The aim of this study was to analyze trends in a variety of prognostic factors for neuroendocrine lung carcinomas through analysis of 2 groups of surgically treated patients. PATIENTS AND METHODS: Group A contained the first 361 patients, treated between 1980 and 1997. That group was analyzed retrospectively and contained 261 patients with typical carcinoid tumors, 43 with atypical carcinoid tumors, 22 with large-cell neuroendocrine carcinoma, and 35 with small-cell neuroendocrine carcinoma. Group B contained 404 patients enrolled prospectively between 1998 and 2002: 308 with typical carcinoid tumors, 49 with atypical carcinoid tumors, 18 with large-cell neuroendocrine carcinoma, and 29 with small-cell neuroendocrine carcinoma. The following clinical variables were considered: sex, mean age, tumor site, tumor size, lymph node involvement, stage, metastasis, and local recurrence. The 1997 TNM classification was used for staging of lung cancer and survival analysis was performed along with assessment of factors influencing survival. Statistical analysis of the data involved univariate and multivariate analysis. RESULTS: In both groups, significant differences were observed between patients with typical and atypical carcinoid tumors in terms of mean age, tumor size, node involvement, and recurrence. In group A, female sex, node involvement, and recurrence differed between patients with atypical carcinoid tumors and those with large-cell neuroendocrine carcinoma; the same was true for group B, with the exception of lymph node involvement. Node involvement differed between patients with small-cell versus large-cell neuroendocrine carcinoma in group A but not group B. Both groups displayed significant differences in overall survival and survival of patients with lymph node involvement between patients with typical and atypical carcinoid tumors and between patients with atypical carcinoid tumors and those with large-cell neuroendocrine carcinoma; no differences were observed between patients with large-cell versus small-cell neuroendocrine carcinoma. Histological type and lymph node involvement had the greatest influence on prognosis in the multivariate analysis. CONCLUSIONS: A well-defined trend is observed in prognostic factors for neuroendocrine lung tumors. Histological type and lymph node involvement show the greatest influence on survival.

The side of pneumonectomy influences long-term survival in stage I and II non-small cell lung cancer.

BACKGROUND: The impact of pneumonectomy as an independent factor on long-term survival after lung resection for centrally or locally advanced non-small cell lung cancer (NSCLC) remains controversial. The aim of this paper is to study the impact of pneumonectomy, and the influence of side of surgery, on long-term survival in patients with pathologic stage I and II NSCLC. METHODS: A retrospective review of a prospective multi-institutional database of patients operated on for lung cancer was undertaken. In all, 1,475 patients with pathologic stage I or II NSCLC were studied (421 underwent pneumonectomy; 1,054 had a lobectomy/bilobectomy). Survival and impact of side of surgery for pneumonectomy and lesser resection groups were analyzed and compared using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: Median survival was worse after pneumonectomy than after less extensive resections for patients overall (33 versus 57 months) and for those with stage I NSCLC (38 versus 70 months); however, median survival was better after pneumonectomy for stage II left tumors (55 versus 19 months). Pneumonectomy was an independent adverse determinant of survival for both stage I right tumors (p < 0.001) and stage I left tumors (p < 0.001), but was associated with improved survival for stage II left tumors (p = 0.009). CONCLUSIONS: Pneumonectomy was found to be an independent determinant of survival in patients with stage I and II NSCLC, but results differed for right- and left-sided tumors. Further studies of survival comparing pneumonectomy with lesser resections should differentiate between right and left procedures.

Prognostic significance of synaptophysin in stage I of squamous carcinoma and adenocarcinoma of the lung.

BACKGROUND: The prognostic significance of the presence of a neuroendocrine marker (synaptophysin, SY) was analyzed in stage I of squamous carcinoma and adenocarcinoma of the lung. METHODS: A multicentric retrospective study was conducted with immunohistochemical staining in a single center of 318 patients resected for squamous carcinoma or adenocarcinoma in pathologic stage I. RESULTS: In all, 162 cases of squamous carcinoma and 156 cases of adenocarcinoma were identified, which included 105 patients in stage IA (50 patients with squamous carcinoma and 55 patients with adenocarcinoma) and 213 in stage IB (112 with squamous carcinoma and 101 with adenocarcinoma). Eighty-six tumors showed a presence of SY+ (27%). Univariate analysis showed lower survival rates at 5 years for those patients older than 70 years of age compared with those patients younger than 70 years of age (60.35% vs 70.57%; P = .007) and for those patients with SY+ compared with those with SY- (52.48% vs 72.68%; P = .0017). Patients with SY+ tumors showed a higher rate of recurrence than patients with SY- tumors (50% vs 33.6%; P = .008). Multivariate analysis showed that those patients greater that 70 years of age (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.14-2.65) and the presence of SY (HR, 2.15; 95% CI, 1.40-3.30) were significant independent prognostic factors associated with a poor outcome. CONCLUSIONS: Stage I of squamous carcinoma and adenocarcinoma of the lung with SY+ has a poor prognosis, with a higher frequency of recurrence and lower survival rates.