Increasing frequency of non-smoking lung cancer: Presentation of patients with early disease to a tertiary institution in the UK.

BACKGROUND: Never-smokers with lung cancer often present late as there are no established aetiological risk factors. The aim of the study is to define the frequency over time and characterise clinical features of never-smokers presenting sufficiently early to determine if it is possible to identify patients at risk. METHODS: We retrospectively analysed data from a prospectively collected database of patients who underwent surgery. The frequency was defined as number of never-smokers versus current and ex-smokers by year. Clinical features at presentation were collated as frequency. RESULTS: A total of 2170 patients underwent resection for lung cancer from March 2008 to November 2014. The annual frequency of developing lung cancer in never-smokers increased from 13% to 28%, attributable to an absolute increase in numbers and not simply a change in the ratio of never-smokers to current and ex-smokers. A total of 436 (20%) patients were never-smokers. The mean age was 60 (16 SD) years and 67% were female. Presenting features were non-specific consisting of cough in 34%, chest infections in 18% and haemoptysis in 11%. A total of 14% were detected on incidental chest film, 30% on computed tomography, 7% on positron-emission tomography/computed tomography and 1% on MRI. CONCLUSIONS: We observed more than a double of the annual frequency of never-smokers in the last 7 years. Patients present with non-specific symptoms and majority were detected on incidental imaging, a modality that is likely to play an increasingly important role for early detection in this cohort that does not have any observable clinical risk factors.

Selection for adjuvant chemotherapy in completely resected stage I non-small cell lung cancer: external validation of a Chinese prognostic risk model.

BACKGROUND: The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub-group. Liang et al. recently published a nomogram to predict post-operative survival in patients undergoing lung cancer surgery. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I. METHODS: Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively. RESULTS: A total of 1,238 patients were included for analysis. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI: 0.58 to 0.67). When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. CONCLUSIONS: Our results of external validation suggested lower survival discrimination than reported by the original group; however discrimination between survival remained evident for stage I.

Beware of arteria lusoria during lymph node dissection of the right paratracheal fossa for lung cancer surgery.

An asymptomatic elderly woman presented with a solitary right upper lobe mass revealed to be non-small cell lung cancer following routine surveillance post mastectomy. Upon review of CT with contrast in preparation for rigid bronchoscopy and right upper lobectomy, we noticed that the patient had a rare case of arteria lusoria. This is the presence of an aberrant right subclavian artery extending from the left side of the aortic arch, crossing posteriorly across the midline to supply the upper limb. We suggest that with a documented 100% diagnostic sensitivity on 64 multislice computed tomography, the presence of arteria lusoria within the posterior paratracheal fossa may cause life-threatening complications in the unaware during systematic lymph node dissection for non-small cell lung cancer (NSCLC).

New predictors of response to neoadjuvant chemotherapy and survival for invasive thymoma: a retrospective analysis.

BACKGROUND: Cell-cycle protein (p27, p21, and p53) expression can predict response to neoadjuvant chemotherapy and prognosis in some neoplasms. This study evaluated whether these markers could also be effective in invasive thymoma during a multimodality treatment. METHODS: Between 1989 and 2008, 33 patients with invasive thymoma underwent surgical resection after neoadjuvant chemotherapy. Expression of p27, p21, and p53 was assessed using immunohistochemistry in specimens retrieved pre and post chemotherapy. Factors influencing response to neoadjuvant chemotherapy and survival were investigated by univariate and multivariate analysis. Good response was defined as complete disappearance of tumor at imaging or necrosis >90% at pathologic studies. RESULTS: Twelve patients disclosed an imaging good response. Complete resection was possible in 17 patients, 9 of whom had presented imaging good response and 11 of whom had revealed pathologic good response. On univariate analysis both imaging and pathologic poor responses were significantly associated with incomplete resection (P = 0.04 and P = 0.03, respectively) and preneoadjuvant triple combination of p27 low, p21 low, and p53 high expressions (P = 0.001 and P < 0.0001, respectively), the last factor being the only one selected on logistic regression (P = 0.01 and P = 0.005, respectively). Long-term survival analysis was negatively influenced by triple combination of p27, p21, and p53 (P < 0.0001) and incomplete resection (P < 0.0001), which were also selected on Cox's regression (P = 0.004 and P = 0.02, respectively). CONCLUSIONS: The triple combination of p27 low, p21 low, and p53 high expressions was the most significant predictor of imaging and pathologic poor responses to neoadjuvant chemotherapy in invasive thymoma. This combination together with incomplete resection was also the most significant negative predictor of long-term survival.

May cyclooxygenase-2 (COX-2), p21 and p27 expression affect prognosis and therapeutic strategy of patients with malignant pleural mesothelioma?

OBJECTIVES: The expression of cyclooxygenase-2 (COX-2) and cell-cycle proteins (p21 and p27) proves useful in predicting prognosis and orientating therapy in many malignant tumours. Malignant pleural mesothelioma is an uncommon and lethal cancer for which there are limited treatment options. In this study, we evaluated the impact on prognosis and the influence on therapeutic strategy of immunohistochemical expression of COX-2, p21 and p27 in specimens from patients treated for malignant pleural mesothelioma. METHODS: We retrospectively reviewed immunohistochemical expression of COX-2, p21 and p27 dichotomised into high and low expression from specimens of 77 consecutive patients undergoing biopsy-plus-pleurodesis (n=6), pleurectomy-decortication (n=44) or extrapleural pneumonectomy (n=27) operations for malignant pleural mesothelioma between 1987 and 2007. Histology was of epithelioid (n=50), biphasic (n=17) and sarcomatoid (n=10) subtypes. Tumour node metastasis (TNM)-stage was I (n=21), II (n=36) and III (n=20). Therapies used were sole adjuvant radiotherapy (n=17), adjuvant radio-chemotherapy (n=56) and neo-adjuvant chemotherapy plus adjuvant radiotherapy (n=4). From 2005 on, preoperative maximal standard uptake value (SUV(MAX)) was also measured by fluorodeoxyglucose positron-emission-tomography. Significance was investigated by Kaplan-Meier survival and Cox regression analysis. RESULTS: The median survival was 10 months. Survival was negatively influenced by histology (epithelioid vs biphasic vs sarcomatoid) (p=0.009), positive macroscopic resection margins (p=0.016), metastatic mediastinal lymph nodes (p=0.016), high COX-2 (p=0.0001) expression, low p21 (p=0.0001) expression and low p27 (p=0.001) expression. Conversely, neither the type of surgery (biopsy-plus-pleurodesis vs pleurectomy-decortication vs extrapleural pneumonectomy), nor preoperative SUV(MAX) (> or = 6.0 vs <6.0), or combined therapies (sole radiotherapy vs adjuvant radio-chemotherapy vs neo-adjuvant chemotherapy plus adjuvant radiotherapy) reached a significant level of difference. Cox regression analysis showed that only immunohistochemical triple combination of high COX-2 and low p21 and p27 expression influenced survival (p=0.0001, hazard ratio 4.7, 95% confidence intervals 3-11) regardless of type of treatment. CONCLUSIONS: At Cox regression analysis, a combination of high COX-2 and low p21 and p27 expression resulted in the only negative prognosticator of malignant pleural mesothelioma. With this combination, less aggressive surgical options might be preferred.

Variations of inflammatory mediators and alpha1-antitrypsin levels after lung volume reduction surgery for emphysema.

RATIONALE: In emphysema, chronic inflammation, including protease-antiprotease imbalance, is responsible for declining pulmonary function and progressive cachexia. OBJECTIVES: To evaluate variations of inflammatory mediators and alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared with respiratory rehabilitation. METHODS: A total of 28 patients with moderate to severe emphysema, who underwent video-assisted thoracoscopic LVRS, were compared with 26 similar patients, who refused operation and followed a standardized rehabilitation program, and to a matched healthy group. Respiratory function, body composition, circulating inflammatory mediators, and alpha(1)-antitrypsin levels were evaluated before and 12 months after treatment. Gene expression levels of inflammatory mediators and protease-antiprotease were assessed in emphysematous specimens from 17 operated patients by matching to normal tissue from resection margins. MEASUREMENTS AND MAIN RESULTS: Significant improvements were only obtained after surgery in respiratory function (FEV(1), +25.2%, P < 0.0001; residual volume [RV], -19.5%, P < 0.0001; diffusing lung capacity for carbon monoxide, +3.3%, P < 0.05) and body composition (fat-free mass, +6.5%, P < 0.01; fat mass, +11.9%, P < 0.01), with decrement of circulating inflammatory mediators (TNF-alpha, -22.2%, P < 0.001; IL-6, -24.5%, P < 0.001; IL-8, -20.0%, P < 0.001) and increment of antiprotease levels (alpha(1)-antitrypsin, +27.0%, P < 0.001). Supportive gene expression analysis demonstrated active inflammation and protease hyperactivity in the resected emphysematous tissue. Reduction of TNF-alpha and IL-6 and increment of alpha(1)-antitrypsin levels significantly correlated with reduction of RV (P = 0.03, P = 0.009, and P = 0.001, respectively), and partially with increment of fat-free mass (P = 0.03, P = 0.02, and P = 0.09, respectively). CONCLUSIONS: LVRS significantly reduced circulating inflammatory mediators and increased antiprotease levels over respiratory rehabilitation, also improving respiratory function and nutritional status. Correlations of inflammatory mediators and antiprotease levels with RV and, partly, with body composition suggest that elimination of inflammatory emphysematous tissue may explain clinical improvements after surgery.

Effects of lung volume reduction surgery for emphysema on glycolipidic hormones.

BACKGROUND: Pulmonary emphysema is associated with cachexia and disregulation of the hormones regulating the glycolipid metabolism, insulin resistance, and altered substrate utilization. This study aimed at identifying the effects of lung volume reduction surgery (LVRS) on glycolipidic hormones compared to respiratory rehabilitation (RR). METHODS: Thirty-three patients with moderate-to-severe emphysema who were undergoing video-assisted thoracoscopic LVRS were compared to 31 similar patients who refused the operation and followed a standardized RR program. All patients were evaluated before and 12 months after treatment for respiratory function, body composition, glycolipidic hormones, metabolic parameters, and insulin resistance, which was calculated using the homeostatic model assessment index for insulin resistance (HOMA-IR). These groups were compared to a matched healthy control population. RESULTS: Only after LVRS significant improvements were obtained in respiratory function (FEV1, +25.2%; p<0.0001; residual volume, -19.5%; p<0.0001), metabolic parameters (total cholesterol, +13.1%; p<0.01; high-density lipoprotein cholesterol, +11.2%; p<0.01; triglycerides, +18.4; p<0.001; nonesterified fatty acid, -19.7%; p<0.001), and body composition (fat-free mass [FFM], +6.5%; p<0.01; fat mass [FM], +11.9%; p<0.01). The leptin/FM ratio (-6.1%; p<0.01) and resistin/FM ratio (-5.6%; p<0.01) decreased, whereas the adiponectin/FM ratio (+6.9%; p<0.01) and ghrelin (+9.2%; p<0.01) increased, together with reductions in glycemia (-8.8%; p<0.01), insulin level (-20.4%; p<0.001), and HOMA-IR (-27.2%; p<0.0001). The decrement in residual volume was correlated with increment of FFM (rho=-0.49; p<0.02), FM (rho=-0.55; p<0.009), and ghrelin (rho=-0.52; p<0.01), and also with decreases in leptin corrected for FM (rho=0.50; p<0.02) and, marginally, HOMA-IR (rho=0.35; p=0.07). CONCLUSIONS: After LVRS, glycolipidic hormone levels and nutritional status significantly improved, along with insulin resistance reduction and more physiologic utilization of substrates. Correlations between residual volume and body composition as well as glycolipidic hormone levels suggest that postoperative recovery in respiratory dynamics may induce favorable clinical changes when compared to RR.