Francesco Leo

Lung metastases from melanoma: when is surgical treatment warranted?

Surgical treatment of lung metastases from melanoma is highly controversial as the expected outcome is much poorer than for other primary tumours and a reliable system for selecting patients is lacking. This study evaluated the long-term results of lung metastasectomy for melanoma, with the aim of defining a subset of patients with better prognosis. By reviewing the data of the International Registry of Lung Metastases (IRLM), we identified 328 patients who underwent lung metastasectomy for melanoma in the period 1945–1995. Survival was calculated by Kaplan–Meier estimate, using log-rank test and Cox regression model for statistical analysis. After complete pulmonary metastasectomy (282 patients) the 5- and 10-year survival was 22% and 16%, respectively. In this group of patients, a time to pulmonary metastases (TPM) shorter than 36 months or the presence of multiple metastases were independent unfavourable prognostic factors. There were no long-term survivors after incomplete resection (46 patients, P< 0.01). Using the IRLM grouping system, patients without risk factors (TPM > 36 months and single lesion) experienced the best survival (29% at 5 years), followed by those with one risk factor only (20% at 5 years). On the other hand, those with two risk factors or incomplete resection showed a significantly poorer survival (7% and 0% at 5 years). Surgery plays an important role in carefully selected cases of pulmonary metastatic melanoma. The prognostic grouping system proposed by the International Registry of Lung Metastases provides a simple and effective method for improving the selection of surgical candidates.

Lung cancer screening with low-dose computed tomography: A non-invasive diagnostic protocol for baseline lung nodules

BACKGROUND Indeterminate non-calcified lung nodules are frequent when low-dose spiral computed tomography (LD-CT) is used for lung cancer screening. We assessed the diagnostic utility of a non-invasive work-up protocol for nodules detected at baseline in volunteers enrolled in our single-centre screening trial, and followed for at least 1 year. METHODS 5201 high-risk volunteers, recruited over 1 year from October 2004, underwent baseline LD-CT; 4821 (93%) returned for the first repeat LD-CT. Nodules <or=5mm underwent repeat LD-CT at 1 year; nodules 5.1-8mm underwent LD-CT 3 months later; lesions >8mm received combined CT-positron emission tomography (CT-PET). A subset of nodules >8mm was studied by CT with contrast. Protocol failures were delayed diagnosis with disease progression beyond stage I, and negative surgical biopsy. RESULTS 2754 (53%) volunteers presented one or more non-calcified nodules. Ninety-two lung cancers were diagnosed: 55 at baseline and 37 at annual screening (66% stage I). Among the 37 incident cancers, 17 had a baseline nodule that remained stage I, 7 had a baseline nodule that progressed beyond stage I, and 13 presented a new malignant nodule. Baseline and annual cancers were 79 (1.5%) and 13 (0.2%), respectively. In 15 of 104 (14%) invasive diagnostic procedures, the lesion was benign. Sensitivity, and specificity were 91 and 99.7%, respectively, for the entire protocol; 88 and 93% for CT-PET; and 100 and 59% for CT with contrast. CONCLUSIONS The protocol limits invasive diagnostic procedures while few patients have diagnosis delay, supporting the feasibility of lung cancer screening in high-risk subjects by LD-CT. Nevertheless further optimization of the clinical management of screening-detected nodules is necessary.

Respiratory function changes after chemotherapy: an additional risk for postoperative respiratory complications?

BACKGROUND Patients receiving chemotherapy for lung cancer usually modify their lung function during treatment with increases in forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) and decreases in lung diffusion for carbon monoxide (DLCO). This prospective study was designed to evaluate functional changes in forced expiratory volume in 1 second, forced vital capacity, and DLCO after three courses of induction chemotherapy with cisplatinum and gemcitabine in stage IIIa lung cancer patients and to assess their impact on respiratory complications after lung resection. METHODS From March 1998 to January 2001, 30 consecutive patients with N2 nonsmall cell lung cancer had surgical resection after neoadjuvant treatment. Pre-chemotherapy and postchemotherapy results of standard respiratory function tests and DLCO were compared in patients with and without postoperative respiratory complications. RESULTS All 30 patients completed the chemotherapy protocol without respiratory complications. Significant improvements (p < 0.05) were recorded after chemotherapy in transition dyspnea score, PaO(2) (mean value from 79.8 to 86.4 mm Hg), forced expiratory volume in 1 second % (from 78.1% to 87.5%) and forced vital capacity % (from 88.1% to 103.3%). Lung diffusion for carbon monoxide was significantly impaired after chemotherapy (from 74.1% to 65.7%; p = 0.0006), as well as DLCO adjusted for alveolar volume (from 92.8% to 77.4%; p < 0.0001). One patient died after surgery and 4 patients (13.3%) experienced postoperative respiratory complications. Compared with patients without complications, these 4 patients had higher mean increase in FEV(1) after chemotherapy (+26.8% vs + 6.7%; p = 0.025), but greater mean decrease in DLCO/Va (-27.8% vs -13.6%; p = 0.03). Impact of change in DLCO on postoperative respiratory complications was not confirmed by multiple logistic regression analysis (p = 0.16). CONCLUSIONS In lung cancer patients, forced expiratory volume in 1 second and forced vital capacity assessed after neoadjuvant chemotherapy are not reliable indicators of the likelihood of respiratory complications after surgery. The risk of respiratory complication may be directly linked to loss of DLCO/Va. Lung diffusion for carbon monoxide assessed after neoadjuvant chemotherapy is probably the most sensitive risk indicator of respiratory complications after surgery. We recommend that DLCO studies be performed before and after chemotherapy in lung cancer patients undergoing induction therapy.

Fluorodeoxyglucose positron emission tomography improves preoperative staging of resectable lung metastasis

OBJECTIVE F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is now a procedure of proven clinical value in the staging of primary lung cancer. This study evaluated the role of PET in the preoperative assessment of resectable lung metastases. METHODS Eighty-six patients with previously treated malignancy and proven or suspected lung metastases, deemed resectable at computed tomography scan, were investigated with 89 preoperative PET procedures. Primary tumor sites were: gastrointestinal in 32 cases, sarcoma in 13, urologic in 14, breast in 8, head and neck in 7, gynecologic in 5, thymus in 5, other in 5. Seventy lung resections were performed in 68 patients of whom only 54 proved to be lung metastasis, 7 were primary lung tumors, and 9 were benign lesions. RESULTS In 19 cases (21%) lung surgery was excluded on the basis of PET scan results due to extrapulmonary metastases (11 cases), primary site recurrence (2), mediastinal adenopathy (2), or benign disease (4). All mediastinal node metastases (7 cases) were detected by PET with a sensitivity, accuracy, and negative predictive value for mediastinal staging of 100%, 96%, and 100%, respectively, versus 71%, 92%, and 95% of the computed tomography scan. In the group of patients who underwent lung resection, PET sensitivity for detection of lung metastasis was 87%. CONCLUSIONS PET scan proved to be a valuable staging procedure in patients with clinically resectable lung metastasis and changed the therapeutic management in a high proportion of cases.

Low morbidity of bronchoplastic procedures after chemotherapy for lung cancer.

OBJECTIVE To evaluate if induction chemotherapy, with or without irradiation, represents an additional risk factor for early and late morbidity and perioperative mortality in bronchoplastic procedures for lung cancers. METHODS From January 1998 to January 2001, 27 patients underwent a bronchial sleeve resection after induction treatment at the European Institute of Oncology in Milan. They represent 7% of lung cancer resections (387) and 27% of those performed after neoadjuvant treatment (100 cases). Histology was: 17 epidermoid carcinoma, 8 adenocarcinoma and 2 SCLC. Twenty-four patients (89%) received a preoperative cisplatin based polichemotherapy, and three cases (11%) a chemo-radiation therapy. A right sleeve lobectomy or bilobectomy was undertaken in 21 patients (78%) and a left lobectomy in 6 (22%). A resection of tracheal carina was associated in three cases and a vascular resection in 10 (five vena cava and five pulmonary artery). Twelve patients (44%) received adjuvant mediastinal irradiation. Perioperative morbidity of the study group (group 1) was compared with that of patients submitted to sleeve resection without neoadjuvant treatment (group 2), or standard pneumonectomy after induction treatment (group 3). RESULTS There were no postoperative deaths. A major perioperative complication occurred in two patients (7%) of group 1, one patient of group 2 (3.5%), and four in group 3 (17%). Among patients of the study group, no anastomotic dehiscence or pleural empyema were observed. Only one late anastomotic stricture occurred after postoperative radiation treatment. No significant difference in early and late complication rate was found between the three groups of patients. High rate of complete resection was achieved (93%) in patients of the study group and extent of nodal dissection was similar between sleeve resections and pneumonectomy patients. CONCLUSIONS Preoperative chemotherapy or combination of chemo-radio therapy is not associated with an additional risk of anastomotic complications in bronco and angioplastic procedures. Parenchyma sparing resection is a valid option for selected patients with locally advanced lung cancer after induction treatment. A longer follow up is necessary to evaluate efficacy of the procedure in term of survival and local control.

Usual and unusual locations of intrathoracic mesothelial cysts. Is endoscopic resection always possible

OBJECTIVE Mesothelial intrathoracic cysts are congenital lesions classically located in the anterior cardiophrenic angle (pleuro-pericardial cysts). Locations elsewhere in the thorax are infrequent. The aim of the study was to describe a 10-year, single-institution experience with endoscopic management of mesothelial cysts by video-assisted thoracoscopy (VT) or video-assisted mediastinoscopy (VM), regardless of their location. METHODS From January 1992 to December 2002, 13 patients (four males and nine females, mean age 49.9 years, range 22-75) underwent surgery for a mesothelial cyst. Information on past history, clinical and radiological presentation, indications for surgery, the surgical procedure and postoperative outcome were collected retrospectively and inserted in a dedicated database. A follow-up visit was performed on December 2002 in all of the patients. RESULTS In five patients the cyst was in the right cardio-phrenic angle, in three cases it was in the left cardiophrenic angle. Five cysts were located in the mediastinum (right paratracheal space in two cases, anterior mediastinum in one case, paravertebral mediastinum in two cases). Mean lesion diameter was 7.5 cm (+/-4) x 5 cm (+/-2). Cyst density ranged between 1 and 10 Hounsfield units (HU) in 11 patients. It was respectively 38 and 52 UH in the other two patients. All patients were classed ASA 1 or 2 according to the guidelines of the American Society of Anesthesiologists (ASA). Indications for surgery included the presence of symptoms, uncertain diagnosis, practice of a particular sport or professional activity, and radiological evidence of compression of the superior vena cava (namely for the two paratracheal lesions). Eleven patients were operated on by VT. Two patients with a right paratracheal lesions were operated on by VM. Mean operating time was 60+/-14 min (range 45-80). No postoperative complications were recorded. The mean postoperative stay was 4.3+/-1.2 days (5 days for VT and 2.5 days for VM). Pathology studies confirmed the diagnosis of mesothelial cyst in all cases. CONCLUSIONS Mesothelial cysts have a heterogeneous distribution within the thorax, and nearly 40% are located elsewhere than in the cardiophrenic angle. Endoscopic resection by VT or VM can be proposed as the treatment of choice even for mesothelial cysts in unusual locations.

Difficulties encountered managing nodules detected during a computed tomography lung cancer screening program

OBJECTIVE The main challenge of screening a healthy population with low-dose computed tomography is to balance the excessive use of diagnostic procedures with the risk of delayed cancer detection. We evaluated the pitfalls, difficulties, and sources of mistakes in the management of lung nodules detected in volunteers in the Cosmos single-center screening trial. METHODS A total of 5201 asymptomatic high-risk volunteers underwent screening with multidetector low-dose computed tomography. Nodules detected at baseline or new nodules at annual screening received repeat low-dose computed tomography at 1 year if less than 5 mm, repeat low-dose computed tomography 3 to 6 months later if between 5 and 8 mm, and fluorodeoxyglucose positron emission tomography if more than 8 mm. Growing nodules at the annual screening received low-dose computed tomography at 6 months and computed tomography-positron emission tomography or surgical biopsy according to doubling time, type, and size. RESULTS During the first year of screening, 106 patients underwent lung biopsy and 91 lung cancers were identified (70% were stage I). Diagnosis was delayed (false-negative) in 6 patients (stage IIB in 1 patient, stage IIIA in 3 patients, and stage IV in 2 patients), including 2 small cell cancers and 1 central lesion. Surgical biopsy revealed benign disease (false-positives) in 15 cases (14%). Positron emission tomography sensitivity was 88% for prevalent cancers and 70% for cancers diagnosed after first annual screening. No needle biopsy procedures were performed in this cohort of patients. CONCLUSION Low-dose computed tomography screening is effective for the early detection of lung cancers, but nodule management remains a challenge. Computed tomography-positron emission tomography is useful at baseline, but its sensitivity decreases significantly the subsequent year. Multidisciplinary management and experience are crucial for minimizing misdiagnoses.

Impact of limited pulmonary function on the management of resectable lung cancer.

AIMS Limited pulmonary function (LPF) related to obstructive disease and emphysema or due to significant lung toxicity resulting from chemotherapy regimens are frequent co-morbidity factors in lung cancer patients. Purpose of this study was to investigate the frequency of LPF in lung cancer and its impact of on surgical eligibility and postoperative outcome. MATERIALS AND METHODS We analyzed a series of 255 consecutive patients with otherwise resectable lung cancer, admitted to our department between January 1998 and December 1999. Patients were considered affected by LPF if their forced expiratory volume in one second (FEV1%) and/or diffusing lung capacity for carbon monoxide (DLCO%) was less than 50% of predicted normal values. Perioperative mortality, major and minor complications were analysed according to lung function status. RESULTS A total of 42 (16.5%) patients presented with significant limitations of the pulmonary function (LPF). Of these, 11 (26%) cases were excluded from surgery because of the severity of pulmonary disease. In the group of 244 patients who underwent surgery, the 31 LPF cases showed a slightly higher frequency of preoperative induction therapies (42 vs. 30%) and sublobar resections (33 vs. 8%) in comparison with the other 213 resected cases. However, no difference was observed in median hospital stay (7 days in both groups), major morbidity (13 vs. 11%) or mortality (0 vs. 1.4%). CONCLUSIONS A strict and careful selection of patients, guided by concurrent analysis of different functional tests, allowed to offer surgery with a very low complication rate to the majority of patients with limited pulmonary function. A volume reduction effect was evident in selected patients with severe emphysema.

Structural lung damage after chemotherapy fact or fiction

BACKGROUND The hypothesis that chemotherapy increases morbidity after pneumonectomy remains under debate, as the results of previous surgical series remain controversial. The hypothesis of the study is that patients who received preoperative chemotherapy may have subclinical parenchymal damage, increasing their risk of respiratory complications. METHODS The study population was composed of 10 patients who underwent pneumonectomy after chemotherapy for lung cancer (cisplatin+gemcitabine) randomly selected from our database and compared with 10 matched patients who underwent pneumonectomy without previous chemotherapy during the same period. Healthy lung tissue was obtained from surgical specimens, processed according to standard methods and evaluated on ematossilin and eosin-stained sections. Two pathologists without information on the preoperative treatment were asked to review the slides in order to reach a consensus on the type and extent of lung damage. Relevant information was then compared with functional tests and postoperative outcome. RESULTS Severe and diffuse (more than 50% of lung parenchyma) interstitial alterations were detected in the lungs of eight patients, seven of which belonged to the chemotherapy group (70%, p 0.02). Six of these patients developed postoperative respiratory complications. In the chemotherapy group, patterns of interstitial involvement were variable interstitial inflammation and fibrosis associated with obliterative bronchiolitis [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885-8], bronchiolitis obliterans-organizing pneumonia [Leo F, Solli P, Veronesi G, et al. Does chemotherapy increase the risk of respiratory complications after pneumonectomy? J Thorac Cardiovasc Surg 2006;132:519-23], diffuse alveolar damage [Novoa N, Varela G, Jimenez MF. Morbidity after surgery for non-small cell lung carcinoma is not related to neoadjuvant chemotherapy. Eur J Cardiothor Surg 2001;20:700-4], DIP (desquamative interstitial pneumonia)-like reaction [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885-8] and UIP (usual interstitial pneumonia)-like changes [Roberts JR, Eustis C, Devore R, et al. Induction chemotherapy increases perioperative complications in patients undergoing resection for non-small cell lung carcinoma. Ann Thorac Surg 2001;72:885-8]. The only preoperative clinical predictor of severe diffuse damage was preoperative diffusion by carbon monoxide (Dlco). CONCLUSIONS Preoperative chemotherapy is associated with an increased risk of severe and diffuse pulmonary disease even in the presence of normal spirometric parameters. These alterations may play an important role in the occurrence of postoperative respiratory complications.

Adjuvant Surgery after Carboplatin and VP16 in Resectable Small Cell Lung Cancer

Introduction: The real benefit of surgical treatment of small cell lung cancer (SCLC) has never been demonstrated, mainly because of the rarity of surgical cases and the difficulty in comparing surgical and medical series for the different classifications systems used by surgeons (tumor, node, metastasis) and medical oncologists and radiotherapists (Veterans Administrations Lung Cancer Study Group). Materials and Methods: We prospectively assessed the utility of surgery after chemotherapy (carboplatin plus VP16 with or without ifosfamide) with or without radiotherapy in 23 patients with preoperative diagnosis of resectable stage I to IIIA SCLC. A median of three (range: three to six) courses of chemotherapy were administered. Five pneumonectomies, 12 lobectomies (seven sleeve resections), and two segmentectomies were performed, and all except one received radical lymph node dissection. Four (17%) patients received exploratory thoracotomy. Nine (39%) patients received postoperative thoracic radiotherapy. Results: Pathological stages were complete response in four patients, stage I in seven patients, stage II in seven patients, and stage III in five patients. Thirty-day morbidity and mortality were 9% and 0%, respectively. Surgery-related mortality at 90 days was 9%. Median follow-up was 19 months. Overall and local relapse rates were 52% and 17%, respectively. Median overall and disease-free survival were 24 and 12 months. Patients with complete response or pathological stage I had a significantly better Kaplan–Meier survival and lower incidence of relapse than those with more advanced pathological stage (p = 0.025 and 0.027, respectively, log rank). Conclusions: Survival after chemotherapy and surgery in the series correlated with pathological but not pretreatment stage. Only patients with pathological stage 0 or I disease seem to benefit from surgical resection.