Lung cancer and interstitial lung diseases: the lack of prognostic impact of lung cancer in IPF.

Lung Cancer (LC) is the first cause of death worldwide. Recently increased interest in interstitial lung diseases (ILD) has highlighted an association with lung cancer, offering interesting insights into the pathogenesis of the latter. Describe the association between lung cancer and ILD and evaluate the impact of LC on survival in these populations. We collected clinical, radiological, histologic data of 53 cases of advanced pulmonary fibrosis with lung cancer: 17 with UIP pattern (usual interstitial pneumonia, UIP/IPF-LC) and 36 with non-UIP pattern (ILD-LC). Adenocarcinoma was the most frequent histological subtype of lung cancer in all three groups and in UIP/IPF-LC developed in the lung periphery and in an advanced fibrosis context. Patients with DLCO% < 38% showed survival < 10 months, irrespective of group and development of carcinoma in UIP/IPF does not necessarily affect survival, unlike in SR-ILD. Our results confirm that the oncogenic mechanism is closely linked to fibrotic and inflammatory processes and that the development of carcinoma affects survival in SR-ILD but not in IPF.

The prognostic significance of proliferative indices in surgically resected IIIA-N2 non-small cell lung cancer after induction chemotherapy.

BACKGROUND: The aim of this study was to assess the prognostic significance of Mib1 expression, Mitosis (Mi) and Apoptosis (Ai) in residual tumour cells after induction chemotherapy in surgically resected IIIA-N2 patients. METHODS: Between January 2002 and November 2008, we reviewed 50 consecutive patients (39 males) with histologically proven stage IIIA-N2 non-small cell lung cancer (NSCLC), who underwent radical resection following induction chemotherapy. Five-year survival in the series was evaluated in relation to lymph node downstaging, histology, extent of resection, number of chemotherapy cycles, pT status, sex and age. It was then also evaluated in relation to the proliferative indexes (Mi, Ap and Mib 1 expression), dividing the patients into two groups according to whether they were above or below the 50th percentile for each parameter. The associations between mortality and the abovementioned prognostic factors were explored using the Kaplan-Meier method, the log-rank test, and Cox regression analysis. RESULTS: The monovariate analysis confirmed the positive prognostic role of lymph node downstaging in terms of 5-yr survival: 31% vs. 12% (P=0.018). However Mi and Mib1 expression under the 50th percentile were also associated with better 5-yr survival: respectively 46% vs. 5% (P=0.007) and 40% vs. 6% (P=0.017). Neither apoptosis nor the other prognostic factors showed any statistical impact on long-term survival. The multivariate analysis showed Mi to be an independent prognostic factor (P=0.005). CONCLUSIONS: Although lymph node downstaging has been considered the principal prognostic factor after induction chemotherapy and surgical resection, Mi and Mib1 expression in residual tumor can predict long-term survival more accurately.

Mortality on the Waiting List for Lung Transplantation in Patients with Idiopathic Pulmonary Fibrosis: A Single-Centre Experience.

PURPOSE: Lung transplantation (LTX) is nowadays accepted as a treatment option for selected patients with end-stage pulmonary disease. Idiopathic pulmonary fibrosis (IPF) is characterized by the radiological and histologic appearance of usual interstitial pneumonia. It is associated with a poor prognosis, and LTX is considered an effective treatment to significantly modify the natural history of this disease. The aim of the present study was to analyse mortality during the waiting list in IPF patients at a single institution. METHODS: A retrospective analysis on IPF patients (n = 90) referred to our Lung Transplant Program in the period 2001-2014 was performed focusing on patients' characteristics and associated risk factors. RESULTS: Diagnosis of IPF was associated with high mortality on the waiting list with respect to other diagnosis (p < 0.05). No differences in demographic, clinical, radiological data and time spent on the waiting list were observed between IPF patients who underwent to LTX or lost on the waiting list. Patients who died showed significant higher levels of pCO2 and needed higher flows of O2-therapy on effort (p < 0.05). Pulmonary function tests failed to predict mortality and no other medical conditions were associated with survival. CONCLUSIONS: Patients newly diagnosed with IPF, especially in small to medium lung transplant volume centres and in Countries where a long waiting list is expected, should be immediately referred to transplantation, delay results in increased mortality. Early identification of IPF patients with a rapid progressive phenotype is strongly needed.

Cisplatin, Etoposide, and Bevacizumab Regimen Followed by Oral Etoposide and Bevacizumab Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer: A Single-Institution Experience.

UNLABELLED: Cisplatin and etoposide (PE) is the most used chemotherapy regimen in extensive-stage disease small-cell lung cancer (ED-SCLC), and usually achieves a high initial response rate. An intriguing maintenance strategy could be the combination of the angiogenic agent bevacizumab (Bev) with a convenient and well tolerated chemotherapy agent such as oral etoposide. Results of the current single-institutional phase II study suggest that a regimen that includes conventional PE chemotherapy combined with Bev followed by oral etoposide and Bev as maintenance treatment is feasible and effective in terms of 9-month disease control rate in patients with ED-SCLC. BACKGROUND: In the present study we evaluated the efficacy and safety of a cisplatin (P), etoposide (E), and bevacizumab (Bev) regimen followed by maintenance oral E and Bev in patients with extensive-stage disease small-cell lung cancer (ED-SCLC). PATIENTS AND METHODS: Patients were administered 3-day fractionated P 25 mg/m(2) and E 100 mg/m(2) on days 1 to 3, every 3 weeks. After 3 PE cycles, all patients whose disease did not progress continued treatment with PE combined with Bev 15 mg/kg on day 3 every 3 weeks. After completion of 3 PE/Bev cycles, patients who did not experience tumor progression continued maintenance treatment with oral E 50 mg on days 1 to 14 every 21 days combined with Bev 3 times per week until occurrence of disease progression or unacceptable toxicity. RESULTS: At our institution, 22 patients were enrolled and their median age was 66 years (range, 38-79 years). After completion of induction chemotherapy (3 PE cycles with 3 PE/Bev cycles) the objective response rate was in 17 patients (77.2%) (95% confidence interval [CI], 54.6-92.1). Twenty-one patients received maintenance treatment with oral E and Bev. The 9-month disease control rate was 8 patients (36.3%). Median progression-free survival was 7.8 months (95% CI, 7.0-11.3 months) and median overall survival was 13.2 months (95% CI, 11.8-18.7 months). Grade 3 to 4 neutropenia occurred in 12 patients (54.4%) and 14 patients (63.6%) of patients during cycles 1 to 3 and cycles 4 to 6 of induction chemotherapy, respectively. Severe adverse events during maintenance treatment were rarely observed. CONCLUSION: A PE and Bev regimen followed by oral E and Bev maintenance treatment appears feasible and effective in terms of 9-month disease control rate in patients with ED-SCLC.

Switch maintenance treatment with oral vinorelbine and bevacizumab after induction chemotherapy with cisplatin, gemcitabine and bevacizumab in patients with advanced non-squamous non-small cell lung cancer: a phase II study.

The present study evaluated the efficacy and safety of cisplatin (Cis), gemcitabine (Gem) and bevacizumab (Bev), followed by maintenance treatment with Bev and oral vinorelbine (Vnb), in patients with advanced non-squamous non-small cell lung cancer (NSCLC). The patients were administered six cycles of induction chemotherapy consisting of intravenously (i.v.) Cis 70 mg/m(2) on day 1 plus i.v. Gem 1000 mg/m(2) on days 1 and 8, plus i.v. Bev 7.5 mg/kg on day 1, every 3 weeks. Patients who did not experience tumor progression remained on maintenance treatment with Bev combined with oral Vnb 60 mg/m(2) weekly until occurrence of disease progression or unacceptable toxicity. Thirty-seven patients were enrolled: The median age was 67 years (range 38-81); 22 patients were male, and 30 patients had stage IV tumors. The response rate was 32.4 % (95 % CI 18-49.7). The 9-month disease-control rate was 45.9 %. The median PFS was 8.4 months (95 % CI 4.4-10.7), and the median OS was 18.1 months (95 % CI 15.3-20.8 months). Grade 3-4 neutropenia occurred in 6 (16.2 %) patients and grade 3-4 thrombocytopenia in four (10.8 %) patients during induction chemotherapy. Bev- or Vnb-associated toxicities were mild. Switch maintenance treatment with Bev and oral Vnb after first-line Cis, Gem and Bev is feasible in patients with non-squamous NSCLC and may achieve encouraging results in terms of PFS and OS.

Impact of interstitial lung disease on short-term and long-term survival of patients undergoing surgery for non-small-cell lung cancer: analysis of risk factors.

OBJECTIVES: The study aimed to determine the impact of interstitial lung disease (ILD) on postoperative morbidity, mortality and long-term survival of patients with non-small-cell lung cancer (NSCLC) undergoing pulmonary resection. METHODS: We performed a retrospective chart review of 775 consecutive patients who had undergone lung resection for NSCLC between 2000 and 2009. ILD, defined by medical history, physical examination and abnormalities compatible with bilateral lung fibrosis on high-resolution computed tomography, was diagnosed in 37 (4.8%) patients (ILD group). The remaining 738 patients were classified as non-ILD (control group). We also attempted to identify the predictive factors for early and late survival in patients with ILD following pulmonary resection. RESULTS: There was no significant difference between the two groups in terms of age (69 vs 66 years), sex (79 vs 72% male), smoking history (93 vs 90% smokers), forced expiratory volume in 1 s % of predicted (89 vs 84%), predicted values of forced vital capacity (FVC)% (92 vs 94%), types of surgical resection and histology. Patients with ILD had a higher incidence of postoperative acute respiratory distress syndrome (ARDS; 13 vs 1.8%, P < 0.01) and higher postoperative mortality (8 vs 1.4%, P < 0.01). The overall 5-year survival rate was 52% in the ILD and 65% in the non-ILD patients, respectively (P = 0.019). In the ILD group, at the median follow-up of 26 months (range 4-119), 19 (51%) patients were still alive and 18 (49%) had died in the ILD group. The major cause of late death was respiratory failure due to the progression of fibrosis (n = 7, 39%). In the ILD group, lower preoperative FVC% (mean 77 vs 93%, P < 0.01) and lower diffusing capacity of the lung for carbon monoxide (DLCO%; 47 vs 62%; P < 0.01) were significantly associated with postoperative ARDS. CONCLUSIONS: In conclusion, major lung resection in patients with NSCLC and ILD is associated with an increased postoperative morbidity and mortality. Patients with a low preoperative FVC% should be carefully assessed prior to undergoing surgery, particularly in the presence of a lower DLCO%. Long-term survival is significantly lower when compared with patients without ILD, but still achievable in a substantial subgroup. Thus, surgery can be offered to properly selected patients with lung cancer and ILD, keeping in mind the risk of respiratory failure during the evaluation of such patients.

Surgical treatment of synchronous multiple lung cancer located in a different lobe or lung: high survival in node-negative subgroup.

BACKGROUND: The International Association for Study of Lung Cancer Staging Committee proposes for the next revision of TNM (tumour, nodes, metastases) classification that additional nodules in a different lobe of the ipsilateral lung moves from an M1 designation to T4, while additional nodule(s) in the contralateral lung should be classified as M1a, because of poorer survival. We analysed the survival after surgery of patients presenting with synchronous lung cancers located in a different lobe or lung. METHODS: A database of 1551 patients operated on for non-small-cell lung cancer (NSCLC) between 1990 and 2007 was evaluated for unilateral (other lobe) (n=15) and bilateral (n=28) synchronous multiple lung cancers. The relationships among the location of tumours, histology, date of surgery (before and after 2000), lymph node metastasis, type of surgery, adjuvant therapy and survival were analysed. RESULTS: The 5-year survival for all synchronous multiple lung cancers (n=43) was 34%, with a median survival of 32 months. Postoperative mortality was 7%. On univariate analysis, only lymph node metastasis and surgery before the year 2000 affected the overall survival adversely, and both prognostic factors maintained a statistical significance on multivariate analysis. The 5-year survivals were 57% and 0% for patients without (n=25) and with (n=18) lymph node metastasis, respectively (p=0.004), and were 43% and 18% for patients operated upon after (n=27) and before (n=16) the year 2000, respectively (p=0.01), perhaps reflecting a better selection process related to the extensive use of positron emission tomography (PET) scanning. The 5-year survival was not different between bilateral (43%) and unilateral (27%) synchronous lung cancers (p=n.s.). CONCLUSIONS: Our data support complete surgical resection of synchronous multiple lung cancers in patients with node-negative NSCLC. Even patients with bilateral lung cancer should not be treated as metastatic disease. Provided there is no evidence of node and distant metastasis, after an extensive preoperative work-up, including PET scanning and mediastinoscopy, bilateral surgical resection should be performed in fit patients.

Surgery for bronchogenic cysts: always easy?

A few cases of major complications after surgery for bronchogenic cyst have been reported. The purpose of this study was to analyze the complicated and unusual cases among 30 consecutive patients with bronchogenic cysts treated surgically at our institution between 1975 and 2007. There were 3 cases of mediastinal bronchogenic cyst characterized by significant surgical complications or very unusual pathological findings. The operations were performed through a thoracotomy in 25 patients, and by video-assisted thoracoscopic surgery in 5. Two patients suffered iatrogenic injury of the contralateral main bronchus during excision of a mediastinal cyst; in one of them, late development of foreign body granuloma was related to migration towards the bronchial wall of cyanoacrylate used to reinforce suturing of the bronchial tear. Histological examination of one resected specimen showed a large-cell anaplastic carcinoma arising from the wall of a mediastinal bronchogenic cyst. Bronchogenic cysts should be excised before they become symptomatic or infected, which leads to more difficult surgery and complications. The small risk of developing malignancy within a bronchogenic cyst also justifies early intervention.

Long-term respiratory functional results after pneumonectomy.

INTRODUCTION: The aim of this study is to evaluate the long-term respiratory outcome of patients who underwent pneumonectomy for non-small cell lung cancer (NSCLC), analysing functional tests. MATERIALS AND METHODS: Twenty-seven consecutive patients who were candidates for pneumonectomy performed spirometry before and at least 24 months after surgery in the same laboratory. Diffusion of carbon monoxide and the most common dynamic and static lung volumes were evaluated in percentage of predicted and compared. RESULTS: A significant inverse correlation was observed between the preoperative FEV1 (%) and FVC (%) and their postoperative loss, respectively r=-641 (p<0.0001) and r=-789 (p<0.0001). Also the correlation between the RV/TLC ratio and the FEV1 loss confirmed a better postoperative outcome in patients with major airway obstruction (p=0.02). To investigate these data, the series were divided into two groups: group A included BPCO patients with a FEV1 lower than 80%, the others were considered group B. Group B showed a significant major postoperative FEV1 (%) and FVC (%) impairment, 31% versus 12%, p=0.005, and FVC (%) loss, 37% versus 16% (p=0.02), meanwhile group A showed a significant major postoperative RV (%) reduction, 43% versus 17%, p=0.03. Despite being significantly higher preoperatively in BPCO patients, the RV% becomes similar between the two groups in the postoperative. CONCLUSIONS: In our experience patients with major preoperative airway obstruction who underwent pneumonectomy had lower impairment in FEV1% at almost one year after surgery than those with normal respiratory function. The resection of a certain amount of non-functional parenchyma associated with the mediastinal shift, with an improvement of the chest cavity for the remaining lung, could give a reduction volume effect in BPCO/emphysematous patients.

Abscess of residual lobe after pulmonary resection for lung cancer.

Abscess of the residual lobe after lobectomy is a rare but potentially lethal complication. Between January 1975 and December 2006, 1,460 patients underwent elective pulmonary lobectomy for non-small-cell lung cancer at our institution. Abscess of the residual lung parenchyma occurred in 5 (0.3%) cases (4 bilobectomies and 1 lobectomy). Postoperative chest radiography showed incomplete expansion and consolidation of residual lung parenchyma. Flexible bronchoscopy revealed persistent bronchial occlusion from purulent secretions and/or bronchial collapse. Computed tomography in 3 patients demonstrated lung abscess foci. Surgical treatment included completion right pneumonectomy in 3 patients and a middle lobectomy in one. Complications after repeat thoracotomy comprised contralateral pneumonia and sepsis in 1 patient. Residual lobar abscess after lobectomy should be suspected in patients presenting with fever, leukocytosis, bronchial obstruction and lung consolidation despite antibiotic therapy, physiotherapy and bronchoscopy. Computed tomography is mandatory for early diagnosis. Surgical resection of the affected lobe is recommended.

Lung cancer with chest wall involvement: predictive factors of long-term survival after surgical resection.

UNLABELLED: Multimodal management of lung cancer extending to chest wall and type of surgical procedure to be performed are still debated. The aim of this retrospective analysis was to analyze the predictive factors of long-term survival after surgery, focusing on depth of infiltration, type of surgical intervention and possible role of preoperative therapies, comparing survival of these patients with that of a group of patients affected by a Pancoast tumour and surgical treated in the same period. MATERIALS AND METHODS: We reviewed records of 83 consecutive patients with NSCLC in stage T3 (owing to direct extension to chest wall), who underwent surgical resection in our Thoracic Surgery Unit between January 1994 and December 2003. Patients were classified in two groups: pancoast tumours (PT) or chest wall extending tumours (CW): survival and prognostic factors of each category were analyzed. RESULTS: In the CW group we had 68 patients: 45 were in stage IIB (pT3N0), 23 in stage IIIA (pT3-N1-2). Histology revealed adenocarcinoma in 23 cases, squamous cell carcinoma in 34, large cells anaplastic carcinoma in 8, adenosquamous carcinoma in 3. An involvement of chest wall tissues beyond the endothoracic fascia was found in 21 patients, while in the remaining 47 the invasion of chest wall tissues was confined to the parietal pleura. An extrapleural dissection was performed in 48 patients while combined pulmonary and chest wall en bloc resection was required in 20 patients. Resection was incomplete in three cases. In the PT group we had 15 patients: 11 were in stage IIB and 4 in stage IIIA. Histological type was adenocarcinoma in 10 cases, squamous cell carcinoma in 4 and adenosquamous carcinoma in 1. A univariate analysis performed in the CW group showed that survival was significantly affected by nodal status, stage, extension of chest wall invasion, type of lung resection and residual disease. In a multivariate analysis we found that nodal status, completeness of resection and extension of chest wall involvement maintained a significant prognostic value. There was no difference between the survival curve of CW and PT group: considering the two subset of CW patients, on the basis of depth of infiltration, survival of PT patients was significantly better than that of CW patients with involvement of muscular tissues and ribs (p=0.02). CONCLUSION: Nodal status, radical resection and depth of chest wall infiltration are the main predictive factors affecting long-term survival, while surgical procedure does not impact on it if margins of resection are free from disease. The better survival observed in PT patients let us to hypothesize that an induction chemo-radiation therapy, as routinely administered to PT patients, could have a potential benefit in survival of patients with CW tumour extending beyond parietal pleura.

Cardiac angiosarcoma arising from pulmonary artery: endovascular treatment.

We report a case of unusual origin of cardiac angiosarcoma rising from the pulmonary trunk. The tumor caused severe obstruction of the right ventricular outflow tract with serious symptoms of right ventricular failure and tricuspid insufficiency. The angiosarcoma was surgically unresectable because of infiltration of the pulmonary artery and cardiac structures. To relieve the patient's symptoms we chose an endovascular stent treatment to dilate the right ventricular outflow tract obstruction. Consequently this palliative treatment changed the short-term prognosis of the patient, improving his quality of life, and at 6 months follow-up he remains asymptomatic.

Impact of size, histology, and gender on stage IA non-small cell lung cancer.

The aim of this study was to assess which prognostic factors could influence survival in surgically treated stage IA non-small cell lung cancer. The records of 224 consecutive patients with pathological stage IA after radical surgery were reviewed retrospectively. Overall 1, 3 and 5-year survival rates were 89%, 76%, and 66%. Nearly half of the deaths were unrelated to the original cancer. There was no difference in survival attributable to preoperative pulmonary function, age at operation, or extent of resection. However, patients with limited resections had a higher rate of local recurrence. Survival was better with a smaller size of tumor (= 2 cm), in the female sex, and in cases of bronchoalveolar adenocarcinoma.