Evolution of induction chemotherapy for non-small cell lung cancer over the last 30 years: A surgical appraisal.

BACKGROUND: Induction chemotherapy (ICT) is supposed to reduce the risk of micrometastatic progression and improve resectability of non-small cell lung cancer (NSCLC). However, best indications for ICT strategy remain unclear in published meta-analyses. Based on this observation, an evaluation of daily practice is of importance. Therefore, we reviewed indications and efficacy time trends in our 30-year series. METHODS: A database including all patients with NSCLC who underwent surgical resection in two French centers from 1980 to 2009 (n = 5563) was prospectively set and retrospectively reviewed. The indications, clinical and pathologic response rates, and overall survival of ICT patients (n = 732) were analyzed during three successive time-periods: P1 from 1980 to 1989, P2 from 1990 to 1999, and P3 from 2000 to 2009. RESULTS: The proportion of patients who benefited from ICT increased over time, from 2.8% (n = 35) in P1 to 12.5% (n = 274) in P2, and 20.2% (n = 423) in P3. Indications evolved over time with more N2 patients (n = 211; 49.8%) and less initially unresectable patients (n = 72; 17%) in P3. The clinical response rate between P1 and P2 increased. Five and 10-year survival rates of ICT patients were 35.2% and 21.5%, respectively. In multivariate analysis, time-period, age, type of resection, histology, and pathologic response to chemotherapy were significant prognostic factors. CONCLUSIONS: Our report on the off-trial use of induction therapy during the last 30 years demonstrates an increased use of ICT, a progressive focus on N2 disease, and improved response rates.

Postoperative morbidity and mortality after pneumonectomy: a 30-year experience of 2064 consecutive patients.

OBJECTIVES: We examined whether the changes in clinical practice with time correlated with the changes in the 90-day mortality following pneumonectomy. METHODS: The clinical records of consecutive patients undergoing pneumonectomy in two French centres from 1980 to 2009 were prospectively collected. The 90-day postoperative course was retrospectively studied according to clinical characteristics, underlying diseases, type of surgery and time-period (1980-1989; 1990-1999 or 2000-2009). RESULTS: Pneumonectomy was performed in 2064 patients (right n = 948, males n = 1758, mean age 60 ± 10 years). Indications were non-small-cell lung cancer (n = 1805, 87%), mesothelioma (n = 39, 1.8%), other tumours (n = 132, 6.3%) and non-tumour disease (n = 88, 4.2%). The 30- and 90-day mortality were 17.4 and 7.2% in the first decade, 22.3 and 9% in the second decade and 26.4 and 7.3% in the third decade, respectively. In multivariate analysis, older age, right-sided resection, T3-T4 and N2 lung cancer disease were significantly associated with increased overall 90-day mortality, whereas surgery during the last decade was associated with a better outcome when compared with the first decade (RR: 0.63, 95% confidence interval: 0.50-0.80, P = 0.045). When focusing on patients with non-small-cell lung cancer (NSCLC), the 90-day mortality following induction therapy and pneumonectomy decreased from 21.9% in the 1980s to 8.2% in the 2000s (P = 0.038), while such decrease was not found in patients without induction therapy or in patients undergoing a lobectomy. CONCLUSIONS: The overall 90-day mortality after pneumonectomy was not significantly modified over the last 30 years, while the 90-day mortality after induction therapy followed by pneumonectomy for NSCLC decreased significantly.

Is the lymphatic drainage of lung cancer lobe-specific? A surgical appraisal.

OBJECTIVES: Nowadays, early-stage lung cancers are more frequently encountered. Selective lymph node (LN) dissection based on lobe-specific lymphatic pathway has been proposed. Our aim was to study nodal involvement according to tumour location. METHODS: We reviewed 1779 lobectomized patients and analysed their pathological characteristics according to tumour location: Group 1 (G1), right upper lobe; Group 2 (G2), right middle lobe; Group 3 (G3), right lower lobe; Group 4 (G4), left upper division; Group 5 (G5), lingula; Group 6 (G6), left lower lobe. The pN status was recorded for each group to analyse the lymphatic spread of non-small-cell lung cancer (NSCLC) according to tumour location. RESULTS: The numbers and proportions of lobectomies in each group were 613 patients in G1 (59.2%), 64 in G2 (6.4%), 359 in G3 (34.6%), 404 in G4 (54.3%), 54 in G5 (7.3%) and 286 in G6 (38.4%). The rates of pN2 involvement were similar, whatever the group was, even when deciphering single- and multistation diseases. on the right side, single-station N2 disease was mainly found in the superior mediastinum (SM) for G1 (95%), and in the inferior for G3 (90%). On the left side, single-station N2 was mainly found in the SM in G4 (94%), and the inferior in G6 (48%). Whatever the side, in case of two-station involvement, both mediastina were concerned in 40% (in G4) to 81% of the case (in G3). Long-term survival rates were different in skip metastasis, single- and multistation involvement, but not between lobes. CONCLUSIONS: Tumour location is not a predictor of nodal metastasis pattern. In surgical treatment of NSCLC, complete systematic mediastinal LN dissection remains the only acceptable procedure from an oncological point of view.

Number of mediastinal lymph nodes in non-small cell lung cancer: a Gaussian curve, not a prognostic factor.

BACKGROUND: It has been proposed that examining a greater number of lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) treated by surgical resection may increase the likelihood of proper staging and affect outcome. Our purpose was to evaluate the interindividual variability and prognostic relevance of the number of LNs harvested during complete pulmonary and mediastinal lymphadenectomy performed for NSCLC. METHODS: We prospectively collected and retrospectively reviewed the data from 1,095 patients who underwent lung cancer resection in association with systematic lymphadenectomy and pulmonary and mediastinal LN counts from 2004 to 2009. We analyzed the interindividual variability and prognostic impact of the number of LNs on overall survival (OS). RESULTS: The mean number of harvested pulmonary and mediastinal LNs was 17.4±7.3 (range, 1-65) and was higher in male patients, right lung surgical procedures, lobectomy and pneumonectomy, N2 disease, and pIII stage. The mean number of harvested mediastinal LNs was 10.7±5.6 and was normally distributed (range, 0-49; median, 10). The 5-year survival rate was 53.8%. Overall survival was influenced by the number of involved stations (single-station versus multi-station disease, 5-year survival rates 31.5% versus 16.9%, respectively; p=0.041) but not by the number of harvested LNs, the number of harvested mediastinal LNs, or the number of positive mediastinal LNs. CONCLUSIONS: After lung cancer resection and complete lymphadenectomy, the number of LNs is subject to normally distributed interindividual variability, with no significant impact on OS. Recommending an optimal number of nodes is therefore arbitrary. Instead, our recommendation is to perform a complete systematic pulmonary and mediastinal lymphadenectomy following established anatomical boundaries.

Long-term survival of patients with pN2 lung cancer according to the pattern of lymphatic spread.

BACKGROUND: N2 involvement has dramatic consequences on the prognosis and management of patients with non-small cell lung cancer (NSCLC). N2-NSCLC may present with or without N1 involvement, constituting non-skip (pN1N2) and skip (pN0N2) diseases, respectively. As the prognostic impact of this subclassification is still a matter of debate, we analyzed the prognosis of pN2 patients according to the pN1-involvement and the number of N2-stations concerned. METHODS: The medical records of consecutive patients who underwent surgery for pN2-NSCLC in 2 French centers between 1980 and 2009 were prospectively collected and retrospectively reviewed. Patients undergoing induction therapy, exploratory thoracotomy, incomplete mediastinal lymphadenectomy, or incomplete resections were excluded. The prognoses of pN1N2 and pN0N2 patients were first compared, and then deciphered according to the number of N2 stations involved (single-station: 1S, multi-station: 2S). RESULTS: All together, 871 patients underwent first-line complete surgical resection for pN2-NSCLC during the study period, including 258 pN0N2 (29.6%) and 613 pN1N2 (70.4%) patients. Mean follow-up was 72.8±48 months. Median, 5- and 10-year survivals were, respectively, 30 months, 34%, and 24% for pN0N2 and 20 months, 21%, and 14% for pN1N2 patients (p<0.001). Multivariate analysis revealed 3 different prognostic groups; ie, favorable in pN0N2-1S disease, intermediate in pN0N2-2S and pN1N2-1S diseases, and poor in pN1N2-2S disease (p<0.001). CONCLUSIONS: Among pN2 patients, the combination of N1 involvement (pN0N2 vs pN1N2) and number of involved N2 stations (1S vs 2S) are independent prognostic factors. These results might be taken into consideration to sub-classify the heterogeneous pN2-NSCLC group of patients.

A review of 250 ten-year survivors after pneumonectomy for non-small-cell lung cancer.

OBJECTIVES: During the last decades, pneumonectomy has been increasingly seen as a risky procedure, first reserved for tumours not amenable to lobectomy, and now discouraged even in advanced stages of non-small-cell lung cancer (NSCLC). Our purpose was to assess the long-term survival following pneumonectomy for NSCLC and its prognostic factors. METHODS: We set a retrospective study including every patient who underwent a pneumonectomy for NSCLC in 2 French centres from 1981 to 2002. We then described the demographic and pathological characteristics of patients who survived >10 years, and studied the prognostic factors of long-term survival. RESULTS: During the study period, 1466 pneumonectomies were performed for NSCLC, including 1121 standard and 345 extended, and accounted for the overall population. Postoperative complications occurred in 396 patients (27%), including 93 deaths (6.3%). Five- and 10-year survival rates were 32 and 19%, respectively. Two-hundred and fifty patients survived >10 years after surgery, and accounted for the study group. The study group included a majority of males (n = 230, 92%), a mean age of 57 ± 9.2 years and a majority of clinical stage IIIA (n = 117, 46.8%). Induction, right-sided pneumonectomy, extended resection and adjuvant therapy were performed in 41 (16.4%), 109 (43.6%), 40 (16%) and 97 patients (38.8%), respectively. Histology revealed a majority of squamous cell carcinoma (n = 181, 72.4%), T2 tumours (n = 117, 36.8%) and N1 disease (n = 105, 42%). In multivariate analysis, factors associated with adverse outcomes included older age, advanced stage, extended resection, non-lethal postoperative complication, adenocarcinoma, lymphatic vessel microinvasion, N1 and N2 disease and R1 and R2 resection. CONCLUSIONS: During the last 30 years, pneumonectomy was effectively performed for advanced NSCLC, allowing a 10-year survival rate of 19%. Such results have not been reported with other non-surgical treatments and confirm that pneumonectomy is still an essential weapon in the armamentarium against lung cancer.

Is the rate of pneumonectomy higher in right middle lobe lung cancer than in other right-sided locations?

BACKGROUND: Historically, right middle lobe (RML) non-small cell lung cancer (NSCLC) has been reported to be associated with a higher rate of pneumonectomy than other right-sided locations. Because this would discourage minimally invasive approaches in RML-NSCLC, we sought to update this assertion through the study of a large surgical series. METHODS: Clinical records of patients who underwent operations for right-sided NSCLC in 2 French surgical centers were prospectively entered and retrospectively reviewed. Demographic and pathologic characteristics of RML NSCLC were compared with other right-sided NSCLC. RESULTS: This study included 3,234 right-sided and 211 RML (6.5%) NSCLC patients. After exclusion of 14 patients who underwent exploratory thoracotomy, patients were a mean age of 61.5 years, most RML resections occurred in men (134 [72.8%]), and most were lobectomies (wedge, n=4; lobectomy, n=102; bilobectomy, n=22; pneumonectomy, n=56). Pathologic analysis revealed adenocarcinoma in 88 patients (47.8%) and squamous cell carcinoma in 80 (43.5%). pStaging was stage I in 86 patients (46.7%), II in 42 (22.8%), III in 47 (25.5%), and IV in 9 (4.9%). Superior and inferior mediastinal N2 were found in 45.4% and 54.6% of patients, respectively, when 1 station was involved. When compared with other right-sided NSCLC, RML was characterized by higher T status and higher rates of bilobectomy (10.9% vs 5.6%, p=0.0017) and pneumonectomy (30.3% vs 22.3%, p=0.0071) but similar 5-year survival (47.4%). CONCLUSIONS: Compared with other right-sided NSCLC, RML location is associated with a higher albeit limited rate of pneumonectomy.

High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients.

Long-term survival with surgery as part of a multimodality approach for N3 lung cancer.

OBJECTIVES: The extension of non-small-cell lung cancer (NSCLC) to supraclavicular (SC) and contralateral (CL) mediastinal lymph nodes is termed N3 and usually forbids surgical resection. However, scarce surgical series have reported encouraging results, and we sought to analyse our experience with this particular subgroup of patients. METHODS: We retrospectively reviewed the charts of 5857 patients undergoing surgery for NSCLC during the last 30 years in two French centres. Eleven patients presenting with pathological-N3 were found, and more closely analysed concerning lymphatic spread, surgical indication and prognosis. RESULTS: N3 consisted of tumoural extension to the SC (n = 5), CL mediastinal (n = 5) or both (SC + CL, n = 1) stations. Patients underwent induction treatment with chemotherapy alone (n = 4), chemoradiotherapy (n = 3) or first-line surgery (n = 4). All patients underwent a complete surgical resection of the tumour associated with ipsilateral systematic mediastinal lymph node dissection. Additional resection of N3 lymph nodes was performed in 8 cases. Adjuvant treatment included chemoradiotherapy (n = 6), chemotherapy alone (n = 1) or radiation therapy alone (n = 1). All 5 patients with SC-N3 presented with ipsilateral disease; 3 of them survived 5 years. Four patients with CL-N3 presented with left-sided tumour and nodal extension to the 4R station, and none of them survived. CONCLUSIONS: Some N3-patients with specific anatomical location may benefit from multimodality treatment including surgery. These results support further prospective studies for selected N3-patients.

Adenosquamous carcinoma of the lung: surgical management, pathologic characteristics, and prognostic implications.

BACKGROUND: Adenosquamous carcinoma (ASC) is a mixed glandular and squamous cell carcinoma with a more aggressive behavior than the other histologic subtypes of lung cancer. We revisited the pathologic characteristics and surgical results associated with ASC. METHODS: Patients who underwent surgical resection of non-small cell lung cancer in two French centers were retrospectively reviewed. Patients presenting with ASC (n=141) were compared to those with adenocarcinomas (AC, n=2415) and squamous cell carcinomas (SCC, n=2662) regarding preoperative data, histologic characteristics, and outcome. RESULTS: The frequency of ASC and SCC decreased over time. ASC patients were similar to AC patients regarding age, sex, and smoking habits. The type of resections performed in ASC patients was intermediary between SCC (more pneumonectomy) and AC (more lobectomy) patients. ASC was associated with larger size, more frequent visceral pleura invasion, microinvasion of the lymphatic vessels, and ipsilateral second nodules, compared with SCC and AC. Among the 135 patients with documented ASC, 48% presented with a combination of AC and SCC tumor cells ranging between 40% and 60% of each component, and 55% of cases were associated with undifferentiated large cells. ASC was associated with a lower 5-year survival rate (37%) than SCC and AC (43.4% and 42.8%, respectively, p=0.017). For ASC patients, survival was better during the last decade or in cases of balanced AC/SCC components. CONCLUSIONS: ASC is characterized by both histologic aggressiveness and adverse prognosis. In this setting, the impact of adjuvant therapies needs to be reevaluated.

Prognosis of lung cancer resection in patients with previous extra-respiratory solid malignancies.

OBJECTIVES: Non-small-cell lung cancer (NSCLC) following pulmonary or pharyngolaryngeal malignancies has been widely studied, but only a few articles have focussed on lung cancers following other solid malignancies. Our purpose was to compare the characteristics and prognosis of patients with NSCLC according to the medical history of the extra-pulmonary and extra-pharyngolaryngeal solid malignancy. METHODS: Patients who underwent surgery for NSCLC from January 1980 to December 2009 in two French thoracic centres were reviewed. We compared patients with no history of cancer (Group 1) and patients with a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy (Group 2). RESULTS: There were 4992 patients: 4603 (92%) in Group 1 and 389 (8%) in Group 2. In comparison with Group 1, Group 2 showed an increasing incidence over the last 3 decades (2-8%), an older population (65.9 vs 61 years, P < 0.001), a higher proportion of women (34 vs 18%, P < 0.001), non-smokers (20 vs 10%, P < 0.001), adenocarcinomas (53 vs 40%, P < 0.001), T1 (16 vs 14%, P = 0.047) and second nodule in the same lobe (4 vs 2%, P < 0.001). The overall survival was not significantly different between the two groups (P = 0.09). In multivariate analysis, older age, male gender, pneumonectomy, higher T, higher N, incomplete resection and history of extra pulmonary-extra pharyngolaryngeal solid malignancy were significantly associated with a worse prognosis. CONCLUSIONS: Despite an earlier diagnosis, a history of extra-pulmonary and extra-pharyngolaryngeal solid malignancy is associated with a worse prognosis in patients with NSCLC undergoing surgical resection. Overall survival is particularly low after a history of bladder and upper gastrointestinal malignancies.

History of multiple previous malignancies should not be a contraindication to the surgical resection of lung cancer.

BACKGROUND: Patients with a history of previous malignancy are often encountered in a discussion of surgical resection of non-small-cell lung cancer (NSCLC). The outcome of patients with 2 or more previous cancers remains unknown. METHODS: We performed a retrospective study including all patients undergoing resection for NSCLC from January 1980 to December 2009 at 2 French centers. We then compared the survival of patients without a history of another cancer (group 1), those with a history of a single malignancy (group 2), and those with a history of 2 or more previous malignancies (group 3). RESULTS: There were 5,846 patients: 4,603 (78%) in group 1, 1,147 (20%) in group 2, and 96 (2%) in group 3. The proportion of patients included in group 3 increased from 0.3% to 3% over 3 decades. Compared with groups 1 and 2, group 3 was associated with older age, a larger proportion of women, earlier tumor stage, less induction therapy, and fewer pneumonectomies. Despite this, postoperative complications and mortality were similar in groups 2 and 3, and higher than in group 1. Five-year survival rates were 44.6%, 35.1%, and 23.6% in groups 1, 2, and 3, respectively (p < 0.000001 for comparison between 3 groups; p = 0.18 for comparison between groups 2 and 3). In multivariate analysis, male sex, higher T stage, higher N stage, incomplete resection, and study group were significant predictors of adverse prognosis. CONCLUSIONS: Despite earlier diagnosis and acceptable long-term survival, patients operated on for NSCLC after 2 or 3 previous malignancies carried a worse prognosis than did those undergoing operation after 1 malignancy or if there was no previous diagnosis of cancer.

Unexpected extensions of non-small-cell lung cancer diagnosed during surgery: revisiting exploratory thoracotomies and incomplete resections.

OBJECTIVES: Only patients with a complete resection of non-small-cell lung cancer (NSCLC) may expect long-term survival. Despite the recent progress in imaging and induction therapy, a thoracotomy may remain exploratory or with incomplete resection (R2). Our purpose was to revisit these situations. METHODS: A total of 5305 patients who underwent surgery for NSCLC between 1980 and 2009 were reviewed. We compared the epidemiology, pathology, causes and prognosis characteristics of exploratory thoracotomy (ET) and R2 resections. RESULTS: ET and R2 resections were observed in 223 (4%) and 197 (4%) patients, respectively. The frequency of ET decreased with time, while the frequency of R2 resection remained almost stable. The indications for ET and R2 resections were not significantly different. In comparison with ET, R2 resections were characterized by a significantly higher frequency of induction therapy (22 vs 17%, P < 10(-3)), adenocarcinomas (49 vs 15%, P < 10(-6)), T1-T2 (53 vs 29%, P < 10(-6)) and N0-N1 extension (67 vs 42%, P = 10(-6)). R2 resections were also characterized by a higher rate of postoperative complications (19.1 vs 9.9%, P = 0.014), with no significant difference in postoperative mortality (6.9 vs 4.9%, P = non significant). R2 resections resulted in a higher 5-year survival compared with ET (11.1 vs 1.2%, P = 10(-3)). There was no long-term survivor after ET, except during the last decade. CONCLUSIONS: ET and R2 remain unavoidable. In comparison with ET, R2 resection is associated with a higher rate of postoperative complications, but a higher long-term survival.

Characteristics and prognostic value of lymphatic and blood vascular microinvasion in lung cancer.

BACKGROUND: The prognostic value of vascular microinvasion (VMI) in non-small cell lung cancer (NSCLC) has been a matter of discussion in recent decades. The last T N M classification does not take VMI into account, but many points remain questionable. METHODS: A retrospective study was performed of patients undergoing operations for NSCLC during a 20-year period. Lymphatic VMI (LVMI) was classified as group (G) 1, blood VMI (BVMI) as G2, LVMI and BVMI as G3, and no VMI as G4. The demographic, pathologic, T N M characteristics, and long-term survival of each group were analyzed. RESULTS: A total of 3,868 patients (G1, 334; G2, 642; G3, 172; G4, 2,720), mean age 61.9 ± 10.1 years, underwent different types of resection, with complete lymphadenectomy in 88.5%. Adenocarcinomas were more frequent in G1 and G3, and squamous cell carcinomas in G2. In G2, more N1 tumors needed more extensive resections. G1 was equally distributed regardless of tumor size, but G2 prevalence increased with augmenting size. Nodules in the same lobe were significantly more frequent in LVMI than in BVMI. After exclusion of patients with R1 and R2 resections, multivariate analysis confirmed that LVMI and BVMI were independent prognostic factors as well as age, sex, type of resection, T extension, and N involvement. CONCLUSIONS: VMI is generally associated with a poorer prognosis. LVMI is less frequent than BVMI but has lower survival rates. The benefit of adjuvant therapy in VMI patients needs to be evaluated.

Risk factors and characteristics of respiratory and allergic phenotypes in early childhood.

BACKGROUND: Unsupervised approaches can be used to analyze complex respiratory and allergic disorders. OBJECTIVE: We investigated the respiratory and allergic phenotypes of children followed in the Pollution and Asthma Risk: An Infant Study (PARIS) birth cohort. METHODS: Information on respiratory and allergic disorders, medical visits, and medications was collected during medical examinations of children at 18 months of age; biomarker data were also collected (total and allergen-specific IgE levels and eosinophilia). Phenotypes were determined by using latent class analysis. Associated risk factors were determined based on answers to questionnaires about environmental exposures. RESULTS: Apart from a reference group, which had a low prevalence of respiratory symptoms or allergies (n=1271 [69.4%]), 3 phenotypes were identified. On the basis of clinical signs of severity and use of health care resources, we identified a mild phenotype (n=306 [16.7%]) characterized by occasional mild wheeze and 2 severe phenotypes separated by atopic status. The atopic severe phenotype (n=59 [3.2%]) included 49 (83%) children with wheezing and was characterized by a high prevalence of atopy (61% with allergenic sensitization) and atopic dermatitis (78%). In contrast, atopy was rare among children with the nonatopic severe phenotype (n=195 [11%]); this group included 88% of the children with recurrent wheezing. Risk factors for respiratory disease included parental history of asthma, male sex, siblings, day care attendance, exposure to tobacco smoke or molds, indoor renovations, and being overweight, although these factors did not have similar affects on risk for all phenotypes. CONCLUSION: Atopy should be taken into account when assessing the risk of severe exacerbations (that require hospital-based care) in wheezing infants; precautions should be taken against respiratory irritants and molds and to prevent children from becoming overweight.

Evolving characteristics of lung cancer: a surgical appraisal.

OBJECTIVE: Lung cancer management has changed due to emergence of new imaging techniques and of multimodal therapies. Our purpose was to analyse how lung cancer evolved in surgical practice. METHODS: The records of patients who underwent surgical resection for lung cancer from 1983 to 2006 in two centres were reviewed. Data were split into four time periods of 6 years. We analysed and compared the epidemiological, pathological and prognostic characteristics of each period. RESULTS: There were 832, 1148, 1493 and 1195 patients during the periods 1983-88, 1989-94, 1995-2000 and 2001-06, respectively. The main changed characteristics were increasing numbers of older patients, females, past history of another cancer and/or cardio-vascular disease, adenocarcinomas and undifferentiated large-cell carcinomas, smaller tumour size, T1-T2, N0 (47.2-61.2%) and neoadjuvant therapy (NAT) (3.8-24.9%). There were also a decreasing number of exploratory thoracotomies, pneumonectomies and adjuvant therapy (AT) (48.5-30%). The 5-year survival rates improved (34.5-46.3%, P < 10(-6)), mainly after lobectomy, and in the case of adenocarcinoma, N0 and N2 patients. Multivariate analysis confirmed that time trend was an independent factor of prognosis (P < 10(-6)), just as important as N involvement, complete resection (R0), tumour size, age, another cancer history and more significant than the type of resection, histology, NAT and AT. CONCLUSIONS: During the last 25 years, the clinico-pathological features of operated patients have progressively changed and the results following surgery improved. Earlier stage diagnosis might explain overall survival improvement, and play a more major role than associated peri-operative treatments. Therefore, it is advisable to consider the time-related factor in future studies on lung cancer surgery.

Which metastasis management allows long-term survival of synchronous solitary M1b non-small cell lung cancer?

UNLABELLED: OBJECTIVES; Patients with extrathoracic synchronous solitary metastasis and non-small cell lung cancer (NSCLC) are rare. The effectiveness of both tumour sites resection is difficult to evaluate because of the high variability among clinical studies. We reviewed our experience regarding the management and prognosis of these patients. METHODS: The charts of 4668 patients who underwent lung cancer surgery from 1983 to 2006 were retrospectively reviewed. We analysed the epidemiology, treatment, pathology and prognostic characteristics of those with extrathoracic synchronous solitary metastasis amenable to lung cancer surgery on a curative intend. RESULTS: There were 94 patients (sex ratio M/F 3.2/1, mean age 56 years). Surgery included pneumonectomy (n = 27), lobectomy (n = 65) and exploratory thoracotomy (n = 2). Pathology revealed adenocarcinomas (n = 57), squamous cell carcinoma (n = 20), large cell carcinoma (n = 14) and other NSCLC histology (n = 3). Lymphatic extension was N0 (n = 46), N1 (n = 17) and N2 (n = 31). Metastasis involved the brain (n = 57), adrenal gland (n = 12), bone (n = 14), liver (n = 5) and skin (n = 6). Sixty-nine metastases were resected. Five-year survival rate was 16% (median 13 months). Induction therapy, adenocarcinoma, N0 staging and lobectomy were criteria of better prognosis, but metastasis resection was not. CONCLUSIONS: These results suggest that extrathoracic synchronous solitary metastasis of pN0 adenocarcinoma may achieve long-term survival in the case of lung resection with or without metastasis resection. This pattern may reflect a specific tumour biology whose solitary metastasis benefits both from surgical or non-surgical treatment.

Lung cancer invading the fissure to the adjacent lobe: more a question of spreading mode than a staging problem.

OBJECTIVES: Lung cancer invading beyond the interlobar pleura, classified as T2a in the new TNM, is a rare entity with a poor outcome. Our purpose was a better understanding of the mechanisms of this particular behaviour and its prognostic value. METHODS: Patients who underwent surgery between 1984 and 2007 were reviewed. We focused on T1 and T2 tumours. Tumours not traversing the pleural elastic layer were defined as PL0, extending through the layer as PL1 and extending to the surface of the visceral pleura as PL2. We considered three groups: group 1, tumours invading the lobar fissure, group 2, PL0-tumours and group 3, PL1 + PL2 tumours and studied their pathology and prognostic characteristics. RESULTS: The distribution was as follows: group 1 n = 154, group 2 n = 2310 and group 3 n = 651. Pneumonectomy was necessary in 55.2% and bilobectomy in 19.5% of group 1, and N-involvement was present in 55.8% (significantly more than other groups). The mean tumour size (42.7 ± 12 mm) was bigger in group 1. Post-operative mortality was as follows: -5.2, -3.5 and 3.2% in groups 1, 2 and 3, respectively (P = 0.49). Five-year survival rates were: group 1: 38.9%, group 2: 52.5% and group 3: 43.4%; P = 0.00002. Survival was not different between groups concerning pN1 and pN2, but poorer in groups 1 and 3 than in group 2 in pN0 patients, P = 0.0057. Survival was 48.1, 37.9 and 38.4% for tumours between 31 and 70 mm in groups 2, 1 and 3, respectively, P = 0.0024 (but P = 0.65 between groups 1 and 3). Pneumonectomy was a poor prognostic factor in all groups, but survival between pneumonectomy and bilobectomy was not different in group 1. Multivariate analysis confirmed intralobar invasion to be an independent factor of poor prognosis, as well as visceral pleura invasion. CONCLUSIONS: Tumours invading through the fissure have a significant effect on long-term survival in the first stages of lung cancer but also in all stages because of their size and important locoregional spread. Their prognostic value is due to pleural invasion, whose role in lung cancer dissemination is worth further research.