Predictive and Prognostic Value of Early Disease Progression by PET Evaluation in Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: To assess the predictive and prognostic value of progressive metabolic disease (PMD) by the use of early 18Fluorodeoxyglucose positron emission tomography (18FDG-PET) in patients with clinical stage IV non-small cell lung cancer (NSCLC) treated with first-line chemotherapy. METHODS: An 18FDG-PET performed following the first cycle of chemotherapy (PET-1) was compared with a pretreatment 18FDG-PET (PET-0) and a computed tomography (CT) scan after the third cycle (CT-3). The primary endpoint was the positive predictive value (PPV) of PMD. Secondary endpoints included the prognostic value of PMD. RESULTS: Eleven of 38 patients (29%) had a PMD by PET-1, and 15 (39%), including all patients with a PMD, experienced a progressive disease by CT-3. The PPV of PMD was 100% according to both the European Organization for Research and Treatment of Cancer (EORTC) criteria and the PET Response Criteria In Solid Tumors (PERCIST) (p value for both, <0.0001). Patients with a PMD by PET-1 had a median overall survival of 7.0 months versus 14.0 months for those without a PMD (p = 0.04, according to the EORTC criteria). CONCLUSIONS: Early 18FDG-PET assessment deserves further investigation for the identification of NSCLC patients who do not benefit from first-line chemotherapy.

Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study-The Importance of Pathological N Status, More Than We Thought.

BACKGROUND: Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial. METHODS: We retrospectively reviewed clinical records related to 195 patients affected by TC (159) or AC (36) surgically treated between 2000 and 2014, in three different centers. Survival and subtypes comparison analyses were performed to identify potential prognostic factors. RESULTS: TCs showed a lower rate of nodal involvement than ACs (N0 = 94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of resected carcinoids were significantly better in TCs than ACs with higher 5- and 10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively; p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8 and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis revealed that AC subtype [HR 4.33 (95% CI 1.72-8.03), p = 0.002], pathological nodal involvement [HR 3.05 (95% CI 1.77-5.26), p < 0.0001], and higher SUVmax [HR 4.33 (95% CI 1.03-7.18), p = 0.002] were independently and pejoratively associated with overall survival. Factors associated with a higher risk of recurrence were AC subtype [HR 6.13 (95% CI 1.13-18.86), p = 0.002]; nodal involvement [HR 5.48 (95% CI 2.85-10.51), p < 0.0001]; higher Ki67 expression level [HR 1.09 (95% CI 1.01-1.20), p = 0.047]; and SUVmax [HR 1.83 (95% CI 1.04-3.23), p = 0.035]. CONCLUSION: Surgery for lung carcinoids allows satisfactory oncological results which mainly depend on carcinoid subtype dichotomy, pathological nodal status, and SUVmax.

Histology-based Combination Induction Chemotherapy for Elderly Patients with Clinical Stage III Non-small Cell Lung Cancer.

AIM: To explore the feasibility and activity of a histology-based induction combination chemotherapy for elderly patients with clinical stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged ≥70 years with stage IIIA and IIIB lung squamous cell carcinoma (SCC) or adenocarcinoma were treated with three cycles of carboplatin and gemcitabine or pemetrexed, respectively, followed by definitive radiotherapy or surgery. The primary endpoint was the overall response rate (ORR) following induction. RESULTS: Twenty-seven patients, with a median age of 74 years (range=70-80 years) were treated for adenocarcinoma in 14 (52%) and SCC in 13 (48%), clinical stage IIIA in eight (30%) and IIIB in 19 (70%). Grade 3 or 4 toxicity was reported for five patients (18.5%). The ORR was 46% in 12 (partial responses) out of 26 assessable patients. CONCLUSION: Histology-based induction combination chemotherapy is active and feasible in elderly patients with stage III NSCLC.

Surgical treatment of superior sulcus tumors: results and prognostic factors.

OBJECTIVES: To study the clinical characteristics, treatment modalities, and outcome of patients with superior sulcus tumors who underwent surgery over a 15-year period. DESIGN: Retrospective clinical study. METHODS: Clinical records of all patients operated on for superior sulcus tumors by the same surgical team between 1988 and 2002 were reviewed retrospectively. RESULTS: Sixty-seven patients were operated on in this period. All the patients underwent en bloc lung and chest wall resection. Surgical approaches were as follows: posterolateral thoracotomy according to Paulson (n = 33), combined transcervical and transthoracic approach (n = 33), and isolated transcervical approach (n = 1). Types of pulmonary resection included lobectomies (n = 59), pneumonectomies (n = 2), and wedge resections (n = 6). Pathologic stages were IIB, IIIA, and IIIB in 49 cases, 12 cases, and 6 cases, respectively. Resection was complete in 55 patients (82%). Operative mortality was 8.9% (n = 6). Postoperative treatment was administered in 53 patients (radiotherapy, n = 42; chemoradiotherapy, n = 9; and chemotherapy, n = 2). Overall 2-year and 5-year survival rates were 54.2% and 36.2%, respectively. Five-year survival was significantly higher after complete resection than after incomplete resection (44.9% vs 0%, p = 0.000065). The presence of associated major illness negatively affected the outcome (5-year survival, 16.9% vs 52%; p = 0.043). Age, weight loss, respiratory impairment, tumor size, presence of nodal disease, and histologic type did not influence the long-term outcome. At multivariate analysis, only the completeness of resection and the absence of associated major comorbidities had an independent positive prognostic value. CONCLUSIONS: Superior sulcus tumor remains an extremely severe condition, but long-term survivals may be achieved in a large percentage of cases. The presence of associated major illness and the completeness of resection are the two most important factors affecting the long-term outcome.

Outcome and prognostic factors of pleural mesothelioma after surgical diagnosis and/or pleurodesis.

OBJECTIVE: The objective of this study was to evaluate long-term survival and prognostic factors in patients with malignant pleural mesothelioma. METHODS: All consecutive patients referred for surgical diagnosis and/or pleurodesis for malignant pleural mesothelioma between 2000 and 2010 were studied. The following parameters were prospectively recorded: age, sex, tobacco consumption, asbestos exposure, type and duration of symptoms, American Society of Anesthesiologists (ASA) score, body mass index, preoperative C-reactive protein levels, white blood cells and platelet count, pachypleuritis on chest radiograph, type of diagnostic surgical procedure, histologic type, modality of pleurodesis, and chemotherapy. Survival was assessed on March 1, 2011. RESULTS: A total of 170 patients were included. For the entire population, median survival was 12 months (95% confidence interval [CI], 10-15). Two-, 5-, and 7-year overall survival was 26% (95% CI, 19-35), 11% (95% CI, 6-21), and 5% (95% CI, 9-22), respectively. Asbestos exposure, age, ASA class III versus ASA classes I and II, nonepithelioid histology, C-reactive protein levels >3 mg/L, and white cell count >12,000/mm(3) influenced outcome in univariate analysis. Multivariate analysis showed that nonepithelioid histology (hazard ratio [HR], 2.76; 95% CI, 1.50-5.08); age (HR, 1.05; 95% CI, 1.01-1.08); C-reactive protein levels between 4 and 50 mg/L, and >51 (HR, 2.28; 95% CI, 1.18-4.42; and HR, 2.69; CI, 1.29-5.60, respectively); and leukocytosis >12,000/mm(3) (HR, 2.28; 95% CI, 1.22-4.25) were independent worse survival predictors. CONCLUSIONS: Median survival in an unselected population of patients with malignant pleural mesothelioma treated nonsurgically is 12 months. Nonepithelioid histology, older age, abnormal C-reactive protein levels, and leukocytosis are independent predictors of worse survival.

Prognostic significance of vascular and lymphatic emboli in resected pulmonary adenocarcinoma.

BACKGROUND: The incidence of vascular and lymphatic emboli in a specimen of resected non-small cell lung cancer is variable according to different authors' experience as well as prognostic significance in patients treated by surgery. We aimed at evaluating these factors in an unselected population of patients with primary pulmonary adenocarcinoma treated by major surgical resection. METHODS: Clinical and pathology records of all patients treated by lobectomy or pneumonectomy and nodal dissection for pulmonary adenocarcinoma between June 2001 and June 2006 were retrospectively reviewed. Impact on survival of age, sex, tobacco use, history of chronic obstructive pulmonary disease, extent of resection, pathologic stage, and presence of vascular and lymphatic emboli was studied by univariate analysis and multivariate analysis (for factors significantly associated with survival at univariate analysis). RESULTS: Five hundred three patients underwent lobectomy or pneumonectomy with nodal dissection for pathologically proven lung adenocarcinoma. There were 355 men and 148 women; mean age was 61.1 years, and 181 patients were 65 years old or older; 87% were current or former smokers; 90.3% had pulmonary lobectomy; and 9.7% had pneumonectomy. Pathologic stages were I, II, and III/IV in 45%, 17.9%, and 37.1%, respectively. Vascular emboli and lymphatic emboli were found in 183 of 503 patients (36.4%) and 149 of 503 (29.6%), respectively. Overall 5-year survival for the whole population was 50.7%. At univariate analysis, age more than 65 years (p=0.0019), chronic obstructive pulmonary disease (p=0.042), extent of resection (p=0.047), pathologic stage (p<0.0000001), T size (p=0.0020), T and N variables (p=0.0000016 and p<0.0000001, respectively), presence of vascular emboli (p=0.026), and presence of lymphatic emboli (p=0.000021) were associated with worse prognosis. At multivariate analysis, age more than 65 years (p=0.0047, relative risk 1.5), stage I versus II versus III versus IV (p=0.00000032), and presence of lymphatic emboli (p=0.05, relative risk 1.34) were identified as independent negative prognostic factors. CONCLUSIONS: In an unselected population of patients with pulmonary adenocarcinoma treated by lobectomy or pneumonectomy, the presence of lymphatic emboli is an independent negative prognostic factor.

Thoracoplasty in the current practice of thoracic surgery: a single-institution 10-year experience.

BACKGROUND: We retrospectively reviewed our recent experience with thoracoplasty to define its role in the context of current surgical practice. METHODS: Twenty-six patients underwent thoracoplasty in the last 10 years with the aim of obliterating a residual pleural space or pulmonary cavity. Twenty-one patients had a postresectional empyema, 3 had a primary empyema and 2 had a cavernostomy performed for a pulmonary aspergilloma. A bronchopleural fistula was present in 10 cases. Infection had been previously controlled in all cases by intercostal drainage, open-window thoracostomy, or cavernostomy (in 4, 20, and 2 patients, respectively). Twenty-two extramuscoloperiosteal thoracoplasties, 3 thoracomyoplasties, and 1 Andrews thoracoplasty were performed. Intrathoracic flap transposition followed thoracoplasty in 9 cases; a second step of the Clagett procedure followed thoracoplasty in 2 cases. RESULTS: One patient died postoperatively (3.8%). Thoracoplasty alone (n=6) or combined with a procedure to fill the residual space (n=14) was successful in achieving complete obliteration of the residual space in 77% of patients (n=20). In 4 patients thoracoplasty alone reduced the residual cavity but filling procedures were not feasible. In 1 patient thoracoplasty failed to obliterate the cavity and infection recurred. Three patients experienced chronic thoracic sequelae. CONCLUSIONS: Thoracoplasty remains an option for the treatment of residual pleural or pulmonary spaces (with or without bronchopleural fistula) once infection has been controlled, when other more conservative procedures are not effective or feasible. In our experience it was effective both when used alone in favorable conditions and when combined with other procedures to fill the residual cavity.

Primary chordoma of the lung.

We report the case of a 79-year-old woman referred to our institution for persistent cough and right-sided chest pain. A computed tomographic scan revealed a 2-cm round nodule in the right lower lobe. A wedge resection of the lesion was achieved by video-assisted thoracic surgery. Pathologic examination was consistent with the diagnosis of chordoma. Magnetic resonance imaging of the whole spine and skull basis was normal. Therefore, a diagnosis of primary lung chordoma, an exceptional condition, could be established.

Lobectomy with pulmonary artery resection: morbidity, mortality, and long-term survival.

OBJECTIVE: We report our experience with 93 consecutive pulmonary artery reconstructions during pulmonary lobectomy with regard to morbidity, mortality, and long-term survival. METHODS: Clinical records of all patients who underwent lobectomy with partial or circumferential pulmonary artery resection in a single institution during an 8-year period were reviewed retrospectively. RESULTS: Lobectomy with partial (n = 90) or circumferential (n = 3) pulmonary artery resection was carried out in 93 patients. Indications for surgical intervention were non-small cell lung cancer in 87 patients and other malignancy in the remaining 6 patients. Bronchial sleeve resection was associated in 23 patients. Neoadjuvant chemotherapy had been administered in 34 cases because of cN2 disease. Operative mortality was 5.4%. Postoperative complications occurred in 27 (29.0%) patients. All the patients underwent contrast-enhanced computed tomographic scanning 6 to 8 weeks postoperatively, which always showed patency of the pulmonary arteries. In the whole population median and 5-year survivals were 40 months and 39.4%, respectively. Disease-free survival was 41.4% at 5 years. Among patients with non-small cell lung cancer, at univariate analysis, tumor size of less than 3 cm; presence of vascular peritumoral emboli, intratumoral emboli, or both; and dyspnea influenced 5-year survival. Multivariate analysis showed that the size of the primary tumor and the presence of vascular emboli were independent factors of worse outcome. CONCLUSIONS: Lobectomy with arterial sleeve resection has acceptable mortality and no specific complications. Late results in terms of survival are satisfactory.

Should we change antibiotic prophylaxis for lung surgery? Postoperative pneumonia is the critical issue.

BACKGROUND: The recommended antibiotic prophylaxis by second-generation cephalosporins reduces the incidence of wound infection and empyema, but its effectiveness on postoperative pneumonias (POPs) after major lung resection lacks demonstration. We investigated risk factors and characteristics of POPs occurring when antibiotic prophylaxis by second-generation cephalosporin or an alternative prophylaxis targeting organisms responsible for bronchial colonization was used. METHODS: An 18-month prospective study on all patients undergoing lung resections for noninfectious disease was performed. Prophylaxis by cefamandole (3 g/24 h, over 48 hours) was used during the first 6 months, whereas amoxicillin-clavulanate (6 g/24 h, over 24 hours) was used during the subsequent 12 months. Intraoperative bronchial aspirates were systematically cultured. Patients with suspicion of pneumonia underwent bronchoscopic sampling for culture. RESULTS: Included were 168 patients in the first period and 277 patients in the second period. The incidence of POP decreased by 45% during the second period (P = 0.0027). A significant reduction in antibiotic therapy requirement for postoperative infections (P = 0.0044) was also observed. Thirty-day mortality decreased from 6.5% to 2.9% (P = 0.06). Multivariate analysis showed that type of resection, intraoperative colonization, chronic obstructive pulmonary disease, gender, body mass index, and type of prophylaxis were independent risk factors of POP. A case control-study that matched patients of the two periods according to these risk factors (except for antibiotic prophylaxis) confirmed that the incidence of POP was lowered during the second period. CONCLUSIONS: Targeted antibiotic prophylaxis may decrease the rate of POPs after lung resection and improve outcome.

Postoperative pneumonia after major lung resection.

BACKGROUND: Postoperative pneumonia (POP) is a life-threatening complication of lung resection. The incidence, causative bacteria, predisposing factors, and outcome are poorly understood. DESIGN: Prospective observational study. METHODS: A prospective study of all patients undergoing major lung resections for noninfectious disease was performed over a 6-mo period. Culture of intraoperative bronchial aspirates was systematically performed. All patients with suspicion of pneumonia underwent bronchoscopic sampling and culture before antibiotherapy. RESULTS: One hundred and sixty-eight patients were included in the study. Bronchial colonization was identified in 31 of 136 patients (22.8%) on analysis of intraoperative samples. The incidence of POP was 25% (42 of 168). Microbiologically documented and nondocumented pneumonias were recorded in 24 and 18 cases, respectively. Haemophilus species, Streptococcus species, and, to a much lesser extent, Pseudomonas and Serratia species were the most frequently identified pathogens. Among colonized and noncolonized patients, POP occurred in 15 of 31 and 20 of 105 cases, respectively (p = 0.0010; relative risk, 2.54). Death occurred in 8 of 42 patients who developed POP and in 3 of 126 of patients who did not (p = 0.0012). Patients with POP required noninvasive ventilation or reintubation more frequently than patients who did not develop POP (p < 0.0000001 and p = 0.00075, respectively). POP was associated with longer intensive care unit and hospital stay (p < 0.0000001 and p = 0.0000005, respectively). Multivariate analysis showed that chronic obstructive pulmonary disease, extent of resection, presence of intraoperative bronchial colonization, and male sex were independent risk factors for POP. CONCLUSIONS: Pneumonia acquired in-hospital represents a relatively frequent complication of lung resections, associated with an important percentage of postoperative morbidity and mortality.