PATRI, a Genomics Data Integration Tool for Biomarker Discovery.

The availability of genomic datasets in association with clinical, phenotypic, and drug sensitivity information represents an invaluable source for potential therapeutic applications, supporting the identification of new drug sensitivity biomarkers and pharmacological targets. Drug discovery and precision oncology can largely benefit from the integration of treatment molecular discriminants obtained from cell line models and clinical tumor samples; however this task demands comprehensive analysis approaches for the discovery of underlying data connections. Here we introduce PATRI (Platform for the Analysis of TRanslational Integrated data), a standalone tool accessible through a user-friendly graphical interface, conceived for the identification of treatment sensitivity biomarkers from user-provided genomics data, associated with information on sample characteristics. PATRI streamlines a translational analysis workflow: first, baseline genomics signatures are statistically identified, differentiating treatment sensitive from resistant preclinical models; then, these signatures are used for the prediction of treatment sensitivity in clinical samples, via random forest categorization of clinical genomics datasets and statistical evaluation of the relative phenotypic features. The same workflow can also be applied across distinct clinical datasets. The ease of use of the PATRI tool is illustrated with validation analysis examples, performed with sensitivity data for drug treatments with known molecular discriminants.

The E3 ubiquitin ligase WWP1 sustains the growth of acute myeloid leukaemia.

The E3 ubiquitin ligase (E3) WWP1 is an oncogenic factor implicated in the maintenance of different types of epithelial cancers. The role of WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) in haematological neoplasms remains unknown. Acute myeloid leukaemia (AML) is characterized by the expansion of malignant myeloid cells blocked at different stages of differentiation. Here we report that the expression of WWP1 is significantly augmented in a large cohort of primary AML patients and in AML cell lines, compared with haematopoietic cells from healthy donors. We show that WWP1 inactivation severely impairs the growth of primary AML blasts and cell lines in vitro. In vivo, we observed a reduced leukaemogenic potential of WWP1-depleted AML cells upon transplantation into immunocompromised mice. Mechanistically, WWP1 inactivation induces the accumulation of its protein substrate p27Kip1, which ultimately contributes to G0/G1 cell cycle arrest of AML blasts. In addition, WWP1 depletion triggers the autophagy signalling and reduces survival of leukaemic cells. Collectively, our findings provide molecular insights into the anti-cancer potential of WWP1 inhibition, suggesting that this E3 is a promising biomarker and druggable target in AML.

PML-RARA-associated cooperating mutations belong to a transcriptional network that is deregulated in myeloid leukemias.

It has been shown that individual acute myeloid leukemia (AML) patients are characterized by one of few initiating DNA mutations and 5-10 cooperating mutations not yet defined among hundreds identified by massive sequencing of AML genomes. We report an in vivo insertional-mutagenesis screen for genes cooperating with one AML initiating mutations (PML-RARA, oncogene of acute promyelocytic leukemia, APL), which allowed identification of hundreds of genetic cooperators. The cooperators are mutated at low frequency in APL or AML patients but are always abnormally expressed in a cohort of 182 APLs and AMLs analyzed. These deregulations appear non-randomly distributed and present in all samples, regardless of their associated genomic mutations. Reverse-engineering approaches showed that these cooperators belong to a single transcriptional gene network, enriched in genes mutated in AMLs, where perturbation of single genes modifies expression of others. Their gene-ontology analysis showed enrichment of genes directly involved in cell proliferation control. Therefore, the pool of PML-RARA cooperating mutations appears large and heterogeneous, but functionally equivalent and deregulated in the majority of APLs and AMLs. Our data suggest that the high heterogeneity of DNA mutations in APLs and AMLs can be reduced to patterns of gene expression deregulation of a single 'mutated' gene network.

New positron emission tomography derived parameters as predictive factors for recurrence in resected stage I non-small cell lung cancer.

BACKGROUND: The recurrence rate for stage I non-small cell lung cancer is high, with 20-40% of patients that relapse after surgery. The aim of this study was to evaluate new F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) derived parameters, such as standardized uptake value index (SUVindex), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as predictive factors for recurrence in resected stage I non-small cell lung cancer. METHODS: We retrospectively reviewed 99 resected stage I non-small cell lung cancer patients that were grouped by SUVindex, TLG and MTV above or below their median value. Disease free survival was evaluated as primary end point. RESULTS: The 5-year overall survival and the 5-year disease free survival rates were 62% and 73%, respectively. The median SUVindex, MTL and TLG were 2.73, 2.95 and 9.61, respectively. Patients with low SUVindex, MTV and TLG were more likely to have smaller tumors (p ≤ 0.001). Univariate analysis demonstrated that SUVindex (p = 0.027), MTV (p = 0.014) and TLG (p = 0.006) were significantly related to recurrence showing a better predictive performance than SUVmax (p = 0.031). The 5-year disease free survival rates in patients with low and high SUVindex, MTV and TLG were 84% and 59%, 86% and 62% and 88% and 60%, respectively. The multivariate analysis showed that only TLG was an independent prognostic factor (p = 0.014) with a hazard ratio of 4.782. CONCLUSION: Of the three PET-derived parameters evaluated, TLG seems to be the most accurate in stratifying surgically treated stage I non-small cell lung cancer patients according to their risk of recurrence.

The surgical treatment of lung cancer in patients with previous lymphoproliferative disorders: a historical cohort study.

OBJECTIVES: We undertook a historical cohort study to compare, in terms of morbidity, mortality and long-term survival associated with lung cancer resection, a group of patients with previous lymphoproliferative disorders and a group without a hematological history. METHODS: We identified 29 patients with a previous lymphoproliferative disorder who underwent lung cancer resection. These subjects (Group-A) were matched with 87 patients without a hematological history who underwent pulmonary resection during the same period (Group-B). RESULTS: We found no significant difference between the two groups in length of hospitalization, comorbidities, spirometric parameters, type of surgery, histology, neoadjuvant chemotherapy, morbidity, mortality, median survival (Group-A = 37 months; Group-B = 52 months) and 5-year survival (Group-A = 37%; Group-B = 42%). The mean age of Group-A patients was significantly lower than that of Group-B patients (62 vs 66 years; p = 0.024). Group-A patients had a well differentiated lung cancer more frequently than Group-B patients (p = 0.001). Group-A patients had transitory bacteraemies more frequently than Group-B patients (p = 0.005). Multivariate Cox regression analysis showed that age (p = 0.01) and lung cancer stage (p = 0.04) were significantly associated with survival. CONCLUSIONS: Patients with lymphoproliferative disorders had a lower age and more differentiated lung cancers than those without lymphoproliferative disorders. Patients with lymphoproliferative disorders and those without a hematological history had similar morbidity, mortality and long-term survival after pulmonary resection. Distinguishing patients with and without a lymphoproliferative disorder seems to be of limited value in the decision-making process of evaluating the indications for surgical treatment of lung cancer.

Combined treatment of non-small cell lung cancer with synchronous brain metastases: a single center experience.

AIM: The aim of this study was to analyze our experience with combined treatment of non-small cell lung cancer with synchronous brain metastases. METHODS: Between 1992 and 2008, 31 patients were treated by performing neurosurgery (or stereotactic radiosurgery) and lung surgery. Patients were divided into two groups according to their preoperative mediastinal work-up: group A (CT scan) and group B (FDG-PET scan). RESULTS: Twenty-six patients had one brain metastasis and five had two. Neurosurgery was performed in 10 patients, stereotactic radiosurgery in 20 and both approaches in 1. Seven patients underwent chemotherapy after cerebral procedure. Pulmonary resection was complete in 27 cases and incomplete in 4. Histological findings showed: adenocarcinoma in 19 cases, squamous cell carcinoma in 8 and large cell carcinoma in 4. All patients underwent adjuvant chemotherapy. Overall 1, 2 and 5-year survival rates were 83%, 47% and 21%, respectively. The median survival was 22 months. Univariate analysis showed a better prognosis for complete resection (P=0.008), adenocarcinomas (P=0.015), N0 disease (P=0.038), and Group B (P=0.045). Multivariate analysis showed that only the radicality of the resection (P=0.027) and Group B (P=0.047) were independent prognostic factors. CONCLUSION: Our experience confirms that selected patients with non-small cell lung cancer and synchronous brain metastases may be effectively treated by combined therapy. Complete resection, adenocarcinoma histology and N0 disease were prognostic factors. The incorporation of FDG-PET scan into the preoperative work-up may translate into a survival benefit.

Surgical treatment of multiple primary adenocarcinomas of the lung.

INTRODUCTION: The incidence of lung adenocarcinomas has steadily increased over the last decades. The aim of this study was to assess the results of surgical treatment of multiple primary adenocarcinomas of the lung (MPAL) analyzing the radiological and histological features. METHODS: From 1988 to 2005, 26 patients underwent surgical treatment for MPAL at our department, for a total of 52 tumors. Three patients had synchronous and 23 had metachronous tumors. RESULTS: Thirty-seven tumors were classified as solid, two as ground-glass opacities (GGO) and 13 as mixed solid/GGO tumors on the basis of CT scan evaluation. Histology revealed 26 adenocarcinomas, five adenocarcinomas with a bronchioloalveolar (BAC) pattern and 21 BAC. There was no postoperative mortality. Five-year survival of patients with synchronous tumors was 66 %. Survival of patients with metachronous tumors was 95 % and 70 % from the first and second operation. Patients with stage II and III a tumors had significantly reduced survival rates ( P < 0.05). Survival was 60 % after lobectomy and 78 % after wedge resection. CONCLUSIONS: Surgical treatment of MPAL is associated with favorable results. Sublobar resections, when technically feasible, provide adequate oncological management.

Preoperative assessment in patients with postintubation tracheal stenosis : Rigid and flexible bronchoscopy versus spiral CT scan with multiplanar reconstructions.

BACKGROUND: Postintubation stenosis remains the most frequent indication for tracheal surgery. Rigid bronchoscopy has traditionally been considered the technique of choice for the preoperative diagnostic assessment. However, this technique is not routinely available, and new techniques such as flexible videobronchoscopy and spiral computed tomography (CT) scan with multiplanar reconstructions have been proposed as alternatives to rigid bronchoscopy. The aim of this study was to compare these techniques in the diagnostic assessment of patients with tracheal stenosis submitted to surgical treatment. METHODS: Twelve patients who underwent airway resection and reconstruction for postintubation tracheal and laryngotracheal stenosis were preoperatively evaluated with rigid and flexible bronchoscopy and with spiral CT scan with multiplanar reconstructions. The following parameters were examined: involvement of subglottic larynx, length of the stenosis, and associated lesions. The results were compared with the intraoperative findings. RESULTS: The accuracy of rigid bronchoscopy, flexible bronchoscopy, and CT scan in the evaluation of the involvement of subglottic larynx was, respectively, 92%, 83%, and 83%. The evaluation of the length of the stenosis was correct in 83%, 92%, and 25% of the patients, respectively, with rigid bronchoscopy, flexible bronchoscopy, and CT scan. A significant correlation was observed between the length of the stenosis measured intraoperatively and preoperatively with rigid (p < 0.001) and flexible bronchoscopy (p < 0.05) but not with CT scan (p = 0.08). The three techniques correctly showed the presence of an associated tracheoesophageal fistula in two patients, but CT scan did not correctly show the exact location of the fistula in relation to the airway. Flexible bronchoscopy was the only effective technique in the assessment of laryngeal function. CONCLUSIONS: Rigid bronchoscopy remains the procedure of choice in the evaluation of candidates for tracheal resection and reconstruction for postintubation stenosis, and it should be available in centers that perform surgery of the airway. Flexible bronchoscopy and CT scan have to be considered complementary techniques in the evaluation of laryngeal function and during follow-up.

Neoadjuvant chemotherapy and pneumonectomy in a lung cancer patient on hemodialysis.

Major pulmonary resections are rarely performed in non-small cell lung cancer patients on hemodialysis. To date only two cases of pneumonectomy performed in such patients are reported in the literature. Moreover, chemotherapy, as a treatment for advanced non-small cell lung cancer, is not routinely administered to patients with end-stage renal disease requiring hemodialysis. We present the case of a stage IIIB non-small cell lung cancer patient on hemodialysis who successfully underwent neoadjuvant chemotherapy followed by pneumonectomy. To our knowledge, this is the first case of non-small cell lung cancer patient on hemodialysis reported in the literature who successfully underwent this type of combined therapy.

Thoracoscopic treatment of a pericardial diverticulum.

A 35-year-old female patient presented with a history of recurrent chest pain. On chest x-ray, a regularly shaped lesion at the right cardiophrenic angle was observed. The lesion appeared smaller on a subsequent x-ray. Magnetic resonance imaging showed a cystic lesion that could be differentiated from the pericardium only in its lower part. Thoracoscopy revealed a pericardial diverticulum. Resection of the lesion was performed thoracoscopically, with complete remission of the symptoms.

Surgical tracheostomy versus percutaneous dilatational tracheostomy. A prospective-randomized study with long-term follow-up.

BACKGROUND: To compare surgical tracheostomy (ST) versus percutaneous dilatational tracheostomy (PDT) in terms of complication rates. In particular we specifically studied the late tracheal complications of both methods by means of endoscopic controls of patients up to 6 months after the procedures. DESIGN: prospective-randomized clinical study. SETTING: University-affiliated tertiary care referral hospital. PATIENTS: 50 consecutive translaryngeally intubated patients with respiratory failure were randomized to undergo either ST (25 patients) or endoscopic guided PDT (25 patients). RESULTS: ST was performed in 41+/-14 min versus 14+/-6 min for PDT (p<0.0001). There was no procedure-related death. In the ST group there were no intraoperative complications. In the PDT group 2 intraoperative complications (minor hemorrhages) were observed. In the ST group 9 early postoperative complications occurred: one minor bleeding, 7 stomal infections and one accidental decannulation. In the PDT group only one early postoperative complication (minor bleeding) occurred. Early postoperative complication rates were 36% for ST and 4% for PDT. In the ST group there were no late tracheal complications. In the PDT group 2 late tracheal complications (one segmental malacia and one stenosis at the level of the stoma) were observed. CONCLUSIONS: This study confirms that PDT is a simpler and quicker procedure than ST and that it has a lower rate of early postoperative complications. Late tracheal complications were more frequent, although the difference was not statistically-significant, in the PDT group. Further investigations of long-term outcome following PDT are therefore necessary.

Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma.

One-hundred and twenty-one cases of malignant pleural mesothelioma (MPM) seen between 1986 and 1999 at the authors' Institution were reviewed. Histotype was epithelial in 88 patients (73%), sarcomatous in 21 (17%) and mixed in 12 (10%). Ninety-one patients received a treatment (38 palliative pleurectomy and no further therapy, 16 palliative pleurectomy followed by chemotherapy, 37 chemotherapy alone), while 30 were referred to supportive care only. Median survival of the whole population was 10.5 months. The 1-, 2- and 3-year survival were 40, 17 and 8%, respectively. Univariate analysis of subgroups showed that poor performance status (PS), non-epithelial histotype, Butchart stage>I and International Mesothelioma Interest Group (IMIG) stage>I were individually associated with lower survival. Patients receiving any therapy survived longer than patients treated with supportive care only (P=0.0004). Treatment modality had an independent prognostic value (P=0.00005), with a survival advantage for patients receiving surgery and adjuvant chemotherapy. Multivariate analysis confirmed the independent prognostic value of PS (P=0.001; HR=2.48) and treatment modality (P=0.003; HR=1.38). The prognostic role of PS (P=0.02) and treatment modality (P=0.01) was confirmed in the subset of patients with epithelial histology. On the contrary, therapy had no impact on survival in patients with sarcomatoid MPM (P=0.74). Despite the predicted bias of a retrospective non-randomized evaluation of treatment-related factors, patients with good PS and epithelial histology seemed to have a survival benefit from surgery or multimodality therapy, as opposite to patients with poor PS or non-epithelial histotype. However, these results must be confirmed in a larger prospective trial with uniform treatment.

[Treatment of malignant pleural mesothelioma]. / Il trattamento del mesotelioma pleurico maligno.

BACKGROUND: In this study all patients observed between January 1993 and October 1997 with malignant pleural mesothelioma (MPM) have been analyzed in order to describe the impact of treatment modality on survival. METHODS: Medical records of 56 patients with MPM (44 male, 12 female, median age = 59 yrs) were reviewed. In 34 cases the histotype was epithelial, in 4 sarcomatoid, in 4 mixed, in 3 desmoplastic, and in 11 not specified. Four treatment modalities were identified: 1) Surgery (subtotal pleurectomy) = 20 patients; 2) Chemotherapy = 19 patients; 3) Surgery+Chemo-therapy = 8 patients; 4) Supportive care = 9 patients. RESULTS: The median survival was: 1) Surgery = 12.4 months; 2) Chemotherapy = 7.5 months; 3) Surgery+Chemotherapy = 12 months; 4) Supportive care = 11.4 months. Using univariate analysis, 8 prognostic factors were studied (age, sex, asbestos exposure, side, histotype, performance status, stage, treatment). Among these, only the stage and the performance status had shown a prognostic value on survival (p<0.05), while the treatment modality had not significantly influenced the prognosis. Using multivariate analysis only performance status showed to be significatively associated with survival (p=0.01 and odds ratio = 1.9, I.C. 1.2-3.2). CONCLUSIONS: Despite the limits of a retrospective study, personal experience confirms the ineffectiveness of current therapeutical approaches to MPM. A better understanding of MPM is required to develop new therapeutical approaches and alter the dismal prognosis of this disease.

Sporadic failure of botulinum toxin treatment in usually responsive patients with adductor spasmodic dysphonia.

Botulinum toxin (BT) injections into vocalis (thyroarytenoid) muscle is currently considered the first-choice treatment for adductor spasmodic dysphonia, producing improvement for an average period of 3 months. In our experience, sporadic failure of BT efficacy can occur even in patients usually responsive to this therapy. The reasons for these episodes have not been clarified. In a retrospective, open trial, we investigated the effect toxin preparation (Botox or Dysport) and injection monitoring (electromyography or laryngoscopy) on the success rate of BT treatment. We studied 15 patients with adductor dysphonia usually responsive to BT therapy. BT was administered into the vocalis muscle in 112 and 36 injections under electromyographic or laryngoscopic guidance, respectively. Botox and Dysport were used in 106 and 42 sessions, respectively. In 29% of all injections, no subjective or objective changes, nor side effects were observed. Failure rate did not differ using electromyographic (28.6%) or laryngoscopic (30.5%) guidance. Failure rates with Botox and Dysport were 30.2% and 26.2%, respectively, but this difference was not statistically significant. These data suggest that treatment failure may occur regardless of the method of injection and of the drug preparation used, possibly due to mislocalisation of vocal folds.

[Pleomorphic adenoma: a case treated by laryngotracheal resection and reconstruction]. / Un caso di adenoma pleomorfo trattato con resezione e ricostruzione laringo-tracheale.

Benign Pleomorphic Adenoma (PA) is a tumor rarely found in tracheal and laryngotracheal sites. A review of the literature published since 1922 has revealed only 30 certain cases of which 3 presented simultaneous involvement of both larynx and trachea. The present work describes the thirty-first case (the fourth with a laryngotracheal localization), diagnosed in a white, 40-year-old male who had been complaining of acute dyspnea for the last three years. Initially these symptoms had been interpreted as asthmatic crises. During one of these episodes, the patient underwent emergency tracheotomy and a laryngotracheoscopy revealed a rounded cricotracheal lesion with smooth surface and approximately 4 cm in cranio-caudal diameter. The mass occupied 90% of the air space and originated from the posterolateral right portion of the cricoid, and from the first 3 tracheal rings. CT and esophagoscopy ruled out its transmural invasion into the esophagus. Under rigid bronchoscopy, assisted NdYAG laser debulking was performed for biopsy purposes. The histological diagnosis was benign AP. For this reason a Grillo cricotracheal resection was performed with exeresis of the cricoid arch, mucosa of the cricoid plate and the first 4 tracheal rings. Reconstruction of the respiratory tract was achieved through termino-terminal cricothyrotracheal anastomosis. The initial diagnosis was confirmed and the resection edges were without evidence of neoplasm. Post-operative recovery proceeded without complications and the patient was discharged 7 days after surgery. Endoscopic and radiological follow-up after 30 months is still negative for any neoplastic recurrences. The laryngo-tracheal lumen is within the norm and cord motility has been preserved. The authors then describe the clinical, anatomopathological and radiological elements which prove useful in evaluating tracheal neoplasms and they underline the problems of differential diagnosis between benign AP and adenoid-cystic carcinoma. In addition, the various therapeutic options are discussed with special attention being focused on surgery through external approaches. Given the location of the AP described, the Grillo procedure-most commonly used in cases of inflammatory cricotracheal stenoses-proved well suited to the loco-regional control of the neoplasm. Stringent respect for some parts of this surgical technique make it possible to reduce post-operative complications to a minimum.

18-FDG positron emission tomography in the evaluation of malignant pleural diseases - a pilot study.

OBJECTIVE: The diagnostic approach to pleural diseases may be difficult. The CT scan, which is the current diagnostic technique, has limited accuracy both in the differentiation between benign and malignant pleural diseases and in the diagnosis of primary and metastatic pleural neoplasms. Invasive procedures, such as thoracoscopy, are therefore frequently required to complete the diagnostic approach. The increasing incidence of malignant pleural mesothelioma has led to the development of new treatment strategies, which still need to be fully validated. There is, therefore, a need for new diagnostic techniques that can lead to a definite diagnosis and a satisfactory evaluation of the response to treatment. Encouraging results have been reported with the F-18-labeled analogue of 2-deoxyglucose (18-FDG) positron emission tomography (PET) in the evaluation of chest tumors such as lung cancer. The aim of this study was to evaluate the role of 18-FDG PET in the diagnostic assessment of pleural diseases. METHODS: Patients with CT scan evidence of pleural thickening, or fluid, entered a study to evaluate the accuracy of 18-FDG PET in diagnosing pleural diseases. Image analysis was performed both with visual interpretation and using a semiquantitative method, standardized uptake values (SUV), on coronal, sagittal and axial reconstructions. The results of PET imaging were compared to histological data. PET was also performed before and after treatment in patients who underwent chemotherapy to evaluate the accuracy of this technique in the assessment of the response. RESULTS: Fourteen patients entered the study. Histology demonstrated a malignant pleural disease in 13 patients; malignant pleural mesothelioma in ten patients, adenocarcinoma in two and liposarcoma in one. Benign pleural disease was diagnosed in the remaining patient. PET assessment demonstrated significant 18-FDG uptake in 12 of the 13 patients with a malignant disease, also revealing distant metastases in two of them. A false-negative result was observed in a patient with an epithelial mesothelioma. The overall accuracy was 92%. A benign pleural disease without significant uptake was correctly diagnosed in another patient. An aspecific uptake was observed in two patients who had undergone pleurectomy and intrapleural chemotherapy. A decreased tracer uptake was observed after chemotherapy in four patients. CONCLUSIONS: These preliminary results demonstrate that 18-FDG PET may have a great potential, both in the differential diagnosis of pleural diseases and in the evaluation of the response to treatment. At present, however, histological thoracoscopic diagnosis remains mandatory before planning treatment. Further studies in larger groups of patients are needed to draw definite conclusions on the role of PET in the assessment of pleural diseases.

[Laryngotracheal resection and reconstruction by Grillo's technic for postintubation stenosis]. / Resezione e ricostruzione laringotracheale secondo Grillo per stenosi postintubazione.

BACKGROUND: Tracheal resection and reconstruction is the standard treatment for postintubation stenosis. However, when the stenosis extends proximally to the subglottic larynx surgical treatment is particularly difficult. Specific surgical techniques have to be used in order to preserve the recurrent laryngeal nerves. The aim of this study is to evaluate the results obtained at our Department with laryngotracheal resection and reconstruction with the Grillo technique for postintubation stenosis. METHODS: From January 1984 to December 1997, 83 patients with tracheal and laryngotracheal lesions underwent surgical treatment. Eighteen patients had postintubation stenosis of the upper trachea and subglottic larynx and underwent single-stage laryngotracheal resection and reconstruction. Mean stenosis length was 3.5 cm (range 3-5 cm). Twelve patients underwent anterolateral laryngotracheal reconstruction, and 6 patients had a circumferential laryngotracheal reconstruction. A Montgomery suprahyoid laryngeal release was required in 4 cases. RESULTS: There was no surgical mortality. Surgical results were excellent or good in 17 cases and satisfactory in one case. No recurrence of stenosis has been observed. CONCLUSIONS: Cricoid cartilage involvement in postintubation stenosis should not be considered a contraindication to surgical treatment. However, laryngotracheal resection and reconstruction is technically difficult and should be performed only in selected cases.

Surgical treatment of non-small cell lung cancer in patients 70 years of age or older.

BACKGROUND: Indications to surgical treatment of lung cancer in the elderly are still being discussed. The aim of this study was to evaluate postoperative complications and survival after surgery for non-small cell lung cancer (NSCLC) in patients 70 years of age or older. METHODS: During a 4 year and 6 month period, 76 patients (67 men and 9 women) entered the study. RESULTS: Postoperative complications occurred in 15 cases (19.7%) and the 30-day operative mortality was 1.3%. The overall 54 month actuarial survival was 53%. Mortality at 12 months wasn't related to stage of disease, histology or lobectomy versus wedge resection but was higher in those patients who had had postoperative cardiopulmonary complications. Results of preoperative spirometry, blood gas and cardiac status were predictive of mortality at twelve months (p < 0.05). CONCLUSIONS: Surgery for NSCLC in the elderly should not be denied on the basis of age alone. Postoperative outcome is mainly related to concomitant cardiopulmonary disease.