Luca Luzzi

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.

Introduction We report the results of the first prospective international randomized control trial to compare the perioperative outcome and surgical radicality of the robotic approach with those of traditional video-assisted surgery in the treatment of early-stage lung cancer. Methods Patients with clinical stage T1–T2, N0–N1 non-small cell lung cancer (NSCLC) were randomly assigned to robotic-assisted thoracoscopic surgery (RATS) or video-assisted thoracic surgery (VATS) resection arms. The primary objective was the incidence of adverse events including complications and conversion to thoracotomy. The secondary objectives included extent of lymph node (LN) dissection and other indicators. Results This trial was closed at 83 cases as the probability of concluding in favor of the robot arm for the primary outcome was null according to the observed trend. In this study, we report the results of the analysis conducted on the patients enrolled until trial suspension. Thirty-nine cases were randomized in the VATS arm and 38 in the robotic arm. Six patients were excluded from analysis. Despite finding no difference between the two arms in perioperative complications, conversions, duration of surgery, or duration of postoperative stay, a significantly greater degree of LN assessment by the robotic technique was observed in regards to the median number of sampled LN stations [6, interquartile range (IQR) 4–6 vs . 4, IQR 3–5; p = 0.0002], hilar LNs (7, IQR 5–10 vs . 4, IQR 2–7; p = 0.0003), and mediastinal LNs (7, IQR 5–10 vs . 5, IQR 3–7; p = 0.0001). Conclusions The results of this trial demonstrated that RATS was not superior to VATS considering the perioperative outcome for early-stage NSCLC, but the robotic approach allowed an improvement of LN dissection. Further studies are suggested to validate the results of this trial. Clinical Trial Registration clinicaltrials.gov, identifier NCT02804893.

OBJECTIVE: At the time of lung transplant, we routinely perform bronchoalveolar lavage (BAL) of the donor lungs on the recipient operating table immediately before implantation, for bacterial and fungal cultures. We sought to determine whether the results correlate with the outcome. METHODS: We retrospectively analysed 115 consecutive cadaveric lung transplants (single lung: 42; bilateral lung: 63; heart-lung: 10) performed over 4 years. RESULTS: Fifty-three (46%) grafts had positive BAL (bacteria: 33; fungus: 10; mixed: 10) and 62 (54%) were negative. Recipients with donor BAL culture positive for bacteria had lower mean oxygenation index in the first 6 h compared with those with negative bacterial culture (36.5+/-14.73 vs. 44.1+/-16.79 kPa) (P=0.019). They also had longer median intensive treatment unit stay (2.5 vs. 1.5 days) (P=0.035), and median time of mechanical ventilation (37.5 vs. 23.0 h) (P=0.008), as well as inferior 6-month, 1-year, 2-year and 4-year cumulative survival (79, 77, 74, 60% vs. 93, 92, 88, 79% respectively) (P=0.04). There was no difference in the above parameters between recipients with Gram-negative (n=18) and recipients with Gram-positive bacteria (n=19) in the donor BAL. Incidence of acute rejection within the first 2 weeks and time of onset of bronchiolitis obliterans syndrome (BOS) were similar in the bacteria-positive and bacteria-negative groups. Recipients with donor BAL positive for fungi alone had similar outcome with the negatives. There was no difference in the donor oxygenation index and age, recipient age, transplant type and ischaemic time between compared groups. There was a significant difference in the median length of donor mechanical ventilation between donors with Gram-positive and donors with Gram-negative bacteria in the BAL (24 vs. 48 h) (P=0.01), as well as between donors with fungi alone in the BAL and donors with negative BAL (67 vs. 48 h) (P=0.04). CONCLUSIONS: Donor lungs with lower airways colonized with bacteria result in inferior recipient outcome. Bacterial colonization of the donor lower airways could therefore be used as a marker of donor lung injury, but evidence from a prospective study is necessary.

OBJECTIVE: Chemotherapy of stage IIIA non-small cell lung cancer (NSCLC) using second generation, cisplatin-based combinations has shown to improve the results; however, the distant relapses remain the major problem. Encouraging results in the treatment of stage IV NSCLC with newer agents (gemcitabine, placlitaxel) has encouraged us to use them in stage III. The aim of this study was to assess feasibility and efficacy of induction chemotherapy with cisplatin and gemcitabine followed by surgery for patients with stage IIIA (N2) NSCLC. METHODS: From February 1996 to December 1999, 36 consecutive patients with mediastinoscopically staged N2 NSCLC received three cycles of cisplatin (80 mg/m(2), day 2) and gemcitabine (1200 mg/m(2), day 1+8) followed by surgery in responding patients. Patients with stable disease or even local progression received radiotherapy. All patients had clinical N2 disease (mediastinal lymph nodes metastasis) observed on CT scan. RESULTS: No major complications of the chemotherapy occurred. Twenty-five patients (70%) had a clinical partial response and were surgically explored, with 18 complete resections (70%). There were no in-hospital deaths, although four (16%) major complications: bronchopleural fistula (two), respiratory insufficiency (one), oesophagospleural fistula (one). In the total group of 36 patients, 3-year survival was 20%. So far, no patient without surgery has survived longer then 27 months; median survival was 8 months. In the group of the 25 patients who underwent surgery 3-year survival was 30%, with a median survival of 21 months. The difference is significant (P=0.0027). In the surgical group, the survival of patients with down staged disease (56%) was greater than that of patients with persistent N2 disease (44%) after chemotherapy (3-year survival of 59 and 0%, respectively; P=0.0013). CONCLUSION: induction chemotherapy with cisplatin and gemcitabine resulted in major tumour regression in a large percentage of patients with clinical N2 disease. In responding patients both the complete respectability rate and survival were higher when compared to historical controls. Survival was significantly better in patients down-staged to a mediastinal negative disease.

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.