Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population.

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.

Use the Lower Limit of Normal, Not 80% Predicted, in Judging Eligibility for Lung Resection.

BACKGROUND: Impaired lung function (LF) is a well-known risk factor for perioperative complications in patients qualified for lung resection surgery. The recent European guidelines recommend using values below 80% predicted as indicating abnormal LF rather than the lower limit of normal (LLN). OBJECTIVES: To assess how the choice of a cut-off point (80% predicted vs. LLN at -1.645 SD) affects the incidence of functional disorders and postoperative complications in lung cancer patients referred for lung resection. METHODS: Preoperative spirometry and the transfer factor for carbon monoxide (TL,CO) were retrospectively analysed in 851 consecutive lung cancer patients after resectional surgery. RESULTS: Airway obstruction was diagnosed in 369 (43.4%), and a restrictive pattern in 41 patients (4.8%). The forced expiratory volume in 1 s (FEV1) or TL,CO was below the LLN in 503 patients (59.1%), whereas the FEV1 or TL,CO was <80% predicted in 620 patients (72.9%; χ2 test: p < 0.0001). In all, 117 out of 851 patients had LF indices <80% predicted but not below the LLN. Odds ratios (ORs) for perioperative complications were higher in patients with impaired LF indices defined as below the LLN (1.59, p = 0.0005) with the exception of large resections (>5 segments). In patients with test results above the LLN and <80% predicted, the OR for perioperative complications was not different (1.14, p = 0.5) from that in patients with normal LF. CONCLUSIONS: LF impairments are common in candidates for lung resection. Using the LLN instead of 80% predicted diminishes the prevalence of respiratory impairment by 14% and allows for safe resectional surgery without additional function testing.

Clinically important pulmonary vascular variations: a narrative review.

Background and Objective: Pulmonary vascular variations are a major factor in thoracic surgeries. Minimally invasive techniques, such as video-assisted thoracic surgery (VATS) used in non-small lung cancer treatment, have a limited field of view and no haptic feedback. Additionally, new studies suggest that segmentectomies are beneficial for patients. Accurate knowledge of vascular patterns and variants is crucial for conducting such procedures safely. The aim of this review was to systematize data in a useful manner from studies and case reports concerning pulmonary vascular variations and patterns. Methods: We conducted a search on the PubMed and Embase databases. We used classifications of Nagashima, Yamashita, Boyden, Maciejewski, and Shimizu. Key Content and Findings: The analysis showed that more data on the incidence rate and vascular patterns of certain bronchopulmonary segments are needed. Venous variations are a major factor in segmental resections, but additional data regarding incidence and pattern types are needed. Surgeons need to be aware of vascular variations as they can influence procedures in seemingly unrelated areas. The majority of studies emphasize the use of three-dimensional (3D) reconstruction of computed tomography (CT) for accurate planning of any thoracic procedures. Conclusions: Abnormal vessels pose a risk in various procedures performed within the thorax, and the data in this review could be valuable in different medical areas in this regard.

The absence of lymph nodes removed (pNx status) impacts survival in patients with lung cancer treated surgically.

OBJECTIVES: We aimed to study the clinical significance of the lack of lymph node assessment (pNx status) and its impact on survival in non-small-cell lung cancer patients. METHODS: We retrospectively analysed the Polish Lung Cancer Study Group database. pNx status was defined as 0 lymph nodes removed. We included 17,192 patients. RESULTS: A total of 1080 patients (6%) had pNx status. pNx patients were more likely to be younger, be female, have a different pT distribution, have squamous cell carcinoma, undergo open thoracotomy, be operated on in non-academic hospitals, and have a lower rate of some comorbidities. pNx was more likely to be cN0 than pN1 and pN2 but less likely than pN0 (p < 0.001). pNx patients were less likely to undergo preoperative invasive mediastinal diagnostics than pN1 and pN2 patients but more likely than pN0 patients (p < 0.001). Overall, the five-year overall survival rates were 64%, 45%, 32% and 50% for pN0, pN1, pN2 and pNx, respectively. In pairwise comparisons, all pN descriptors differed significantly from each other (all p < 0.0001 but pNx vs. pN1 p = 0.016). The placement of the pNx survival curve and survival rate depended on histopathology, surgical approach and pT status. In multivariable analysis, pNx was an independent prognostic risk factor (HR = 1.37, 95%CI: 1.23-1.51, p < 0.01). CONCLUSION: The resection of lymph nodes in lung cancer remains a crucial step in the surgical treatment of this disease. The survival of pNx patients is similar to that of pN1 patients. pNx survival curve placement depends on the other variables which could be useful in clinical decisions.

The effectiveness of surgical treatment of lung cancer in Polish academic and nonacademic centers.

Background: The theoretical advantage of academic hospitals over nonacademic are: more qualified surgeons, adequate diagnostic facilities and infrastructure, including intensive care units. The aim of the study was to compare the effectiveness of surgical lung cancer treatment in academic (ACA) and nonacademic (non-ACA) centers. Methods: This was a retrospective analysis of data from 31,777 patients surgically-treated for lung cancer during the period from 2007 to 2020 in 9 ACA and 21 non-ACA centers. The analysis considered the clinical data of patients, the effectiveness of preoperative diagnostics, the type of procedures performed, the complications, the postoperative mortality and the long-term survival. Results: The median number of anatomical lung resection procedures was 1,218 for ACA and 550 for non-ACA centers. In the ACA group, resection using the video-assisted thoracic surgery (VATS) technique was performed significantly more often than in the non-ACA group (23.6% vs. 14.2%, P<0.001). The pN feature analysis showed significantly lower proportions of pNX (9.2%) in the ACA group than those in the non-ACA group (17.1%) (P<0.001). The rates of postoperative complications in the ACA and non-ACA groups were 30.7% and 33.8%, respectively (P<0.001). There were no significant differences in 5-year survival between the ACA and non-ACA groups (56% and 56%, respectively) (P=0.2). Conclusions: The present study showed that ACA centers are characterized by better preoperative diagnostics, a higher percentage of VATS lobectomies, a lower percentage of postoperative complications and a shorter hospitalization period than non-ACA centers, but there was no impact on 5-year survival.

Ninety-Day Mortality of Thoracoscopic vs Open Lobectomy: A Large Multicenter Cohort Study.

BACKGROUND: Studies have demonstrated a lower incidence of complications after video-assisted thoracoscopic surgery (VATS) lobectomy compared with thoracotomy, but the data on in-hospital and 90-day mortality are inconclusive. This study analyzed whether surgical approach, VATS or thoracotomy, was related to early mortality of lobectomy in lung cancer and determined the differences between in-hospital and 90-day mortality. METHODS: Data of all patients with non-small cell lung cancer who underwent lobectomy between January 1, 2007, and July 30, 2018, were retrieved from Polish National Lung Cancer Registry. Included were 31 433 patients who met all study criteria. After propensity score matching, 4946 patients in the VATS group were compared with 4946 patients in the thoracotomy group. RESULTS: Compared with thoracotomy, VATS lobectomy was related to lower in-hospital (1.5% vs 0.9%, P = .004) and 90-day mortality (3.4% vs 1.8%, P < .001). Mortality at 90 days was twice as high as in-hospital mortality in both the VATS (1.8% vs 0.9%, P < .001) and thoracotomy groups (3.4% vs 1.5%, P < .001). Postoperative complications were less common after VATS compared with thoracotomy (23.6% vs 31.8%, P < .001). CONCLUSIONS: VATS lobectomy is associated with lower in-hospital and 90-day mortality compared with thoracotomy and should be recommended for lung cancer treatment, if feasible. Patients should also be closely monitored after discharge from the hospital, because 90-day mortality is significant higher than in-hospital mortality.

Effect of 3A lymph node resection on survival in patients with right-sided NSCLC: a retrospective, multicentre, propensity-score matching study.

Background: We aimed to assess the clinical significance and impact on survival of prevascular mediastinal lymph nodes (3A) in patients with right-sided lung cancer. Methods: Prospective data of 6,348 patients, who underwent lung resection from 2005 to 2015, were retrospectively analysed. There were 221 patients who underwent 3A dissection (3ALN+), while 6,127 did not (3ALN-). We performed propensity score matching (PSM) to decrease selection bias (221 vs. 221). Results: The incidence of 3A metastasis was 8%, and it elevated with pT stage. Between pT1c and pT2a, there was a significant increase in the 3A metastasis incidence, which doubled from 4% to 9%. For pT4, the incidence was 15%. The highest incidence was found among patients undergoing pneumonectomy (10%) and in the N2b1 and N2b2 subgroups (33% and 64%). In univariable analysis, we found no differences in 5-year survival between 3ALN+ and 3ALN- (51% vs. 51%, P=0.74). But, non-metastatic 3ALN+, 3ALN-, and metastatic 3ALN+ differed significantly (P<0.0001). pN2 subgroups (pN2a1, pN2a2, pN2b1, pN2b2) within PSM analysis did not differ significantly in terms of survival. 3A metastasis failed to be an independent prognostic factor in the multivariable analysis of matched pN2 subgroups. Conclusions: Regardless of 3A lymph nodes failing to be an independent prognostic factor in our cohort, the incidence of metastases in lymph nodes increases notably in advanced stages. 3A metastasis rate is comparable to other lymph node stations. Therefore, superior mediastinal lymphadenectomy in advanced cancers may improve from resections of the 3A lymph node station.

Sex differences in clinico-pathologic characteristics and long-term survival among 17,192 surgically treated NSCLC patients: Nationwide population-based propensity score-matching study.

INTRODUCTION: More information is needed on gender differences in lung cancer surgery. Thus, we conducted a retrospective study on thoracic treatment of non-small cell lung cancer (NSCLC) patients between 2007 and 2020 in Poland. The aim was to characterize sex differences in survival after complete surgical resection and to compare postoperative complications between Polish men and women. The main aspects that were compared between women and men were as follows: type of surgery and postoperative staging, morbidity and mortality, thoracic surgery complications, comorbidities, and overall survival based on a univariate analysis including propensity score matching (PSM) and a multivariate analysis. MATERIALS AND METHODS: Data were collected retrospectively from the Polish Lung Cancer Study Group database. Patients who were surgically treated for NSCLC between 2007 and 2020 (n = 17,192) were included in the study. RESULTS: The univariate analysis showed significantly better survival in women than in men. Women had better 5-year survival compared to men both for adenocarcinoma and squamous cell carcinoma (66% vs. 53%, p < 0.0001 and 65% vs. 51%, p<0.0001%, respectively), for both smokers and non-smokers (65% vs. 52%, p < 0.0001 and 65% vs. 51%, p < 0.0001, respectively), all age groups, and all stages (IA1 to III B). In the PSM analysis, statistically significant differences in favor of women were found for lower lobectomy (67% vs. 50%, p < 0.0001) and upper lobectomy (67% vs. 56%, p < 0.0001). Overall, postoperative complications occurred in 33.1% of patients and were observed more often in men than in women (35.8% vs. 28.6%, p < 0.001). CONCLUSIONS: Women with NSCLC who were treated surgically had a better long-term outcome compared to men, with no significant difference in disease severity. In addition to gender, the histological type, comorbidities, and type of surgery and surgical approach are also important.

The clinico-pathological characteristics of surgically treated young women with NSCLC.

Background: Non-small cell lung cancer diagnosed in young patients is rare. Younger patients with lung cancer are mostly female and have a more advanced stage at initial diagnosis. To our knowledge, no studies have compared single-surgical treatment in different age groups among women. Our study aimed to elucidate the clinicopathological characteristics and the best strategies for surgically treating young women with non-small-cell lung cancer. Methods: The data were collected retrospectively from the Polish Lung Cancer Study Group database. Women who were surgically treated for non-small-cell lung cancer between 2007 and 2020 were included in the study. The participants (n=11,460) were divided into two subgroups: aged ≤55 and >55 years. Results: Statistically significant differences were found for grades IB, IIA, IIIA, and IIIB (22.8% vs. 24.5%, 5.3% vs. 7.5%, 19.3% vs. 15.8%, 5.8% vs. 3.2%, for younger and older women, respectively, all P<0.001). The univariate analysis showed a higher percentage of 5-year survival in the group of younger women than in older women (0.67 vs. 0.64, P=0.00076). Regarding the stage of advancement, statistically significant differences in survival were found for stages IA1, IA2, and IIIA (0.95 vs. 0.86, P=0.047; 0.88 vs. 0.79, P=0.003; 0.5 vs. 0.42, for younger and older women, respectively, all P=0.01). Postoperative complications were more common in older than younger women (27.6% vs. 23.1%, P<0.001). However, there were no statistically significant differences in the number of hospitalization days since surgery and postoperative 30-day mortality. Conclusions: Younger women treated surgically were characterized by a lower percentage of comorbidities, were treated in a more advanced stage of the disease and had a lower percentage of postoperative complications, which, however, did not affect the hospitalization time. Despite the more advanced stage of the disease, survival in selected stages was much better than in the group of older women.

[Reexpansion pulmonary edema and pleural bleeding after suction drainage of pneumothorax]. / Rozprezeniowy obrzek pluca i krwawienie oplucnowe po leczeniu drenazem ssacym odmy oplucnowej.

We present a case of 26 years old man with large spontaneous pneumothorax of about 5 days duration. Application of suction drainage was complicated by unilateral reexpansion pulmonary edema (REPE) and hemothorax developed during first 24 hours of treatment. On thoracotomy multifocal superficial pleural bleeding was seen which was probably attributed to the pathomechanisms similar to suggested in reexpansion pulmonary edema. The patient received supplemental oxygen therapy and completely recovered during next few days. The patient presented typical risk factors of REPE including: young age, large and prolonged pneumothorax. In such cases chest tube should be initially left off suction to prevent REPE.

The influence of the number of lymph nodes removed on the accuracy of a newly proposed N descriptor classification in patients with surgically-treated lung cancer.

INTRODUCTION: The International Association for the Study of Lung Cancer has proposed a new classification of N descriptor based on the number of metastatic lymph nodes (LNs) stations, including skip metastasis. The aim of the study was to determine the effect of removed LNs on the adequacy of this new classification. MATERIALS AND METHODS: The material was collected retrospectively based on the database of the Polish Lung Cancer Group, including information on 8016 patients with non-small cell lung cancer operated in 23 thoracic surgery centers in Poland. The material covered the period from January 2005 to September 2015. We divided patients into two groups: ≤6LNs and >6LNs removed. RESULTS: In the whole group, an average of 13.4 nodes and 4.54 nodal stations were removed. 5-year survivals in the >6LNs group vs ≤ 6LNs group were: 62.3% and 55.1% (N0), 44.5% and 35.9% (N1a), 34.1% and 31,7% (N1b), 37.3% and 26.3% (N2a1), 32.4% and 26.7% (N2a2), 29.4% and 29.2% (N2b1), and 22.0% and 23.0% (N2b2), respectively. Comparing these groups, we detected significant differences at N0 (p < 0.001) and N2a1 (p = 0.022). In the ≤6LNs group, the survival curves for N2a1, N2a2, N2b1, and N2b2 overlapped (p > 0.05). In the >6LNs group, the survival curves were significantly different between grades, with survival for N2a1 better than N1b (p = 0.232). CONCLUSION: The proposed classification N descriptor is potentially better at differentiating patients into different stages. The accuracy of the classification depends on the number of lymph nodes removed. Therefore, the extent of lymphadenectomy has a significant impact on the staging of surgically-treated lung cancer.

The impact of left lower paratracheal (4L) lymph node dissection on survival in patients with surgically treated left-sided NSCLC.

OBJECTIVES: We aimed to investigate the clinical significance of left lower paratracheal nodes (#4L) and their impact on survival in patients with left-sided lung cancer. METHODS: This was a retrospective analysis of prospective data. The study included 5369 patients who underwent surgery between 2005 and 2015. Six hundred fifty-nine patients underwent #4L dissection (4LND+), and 4710 did not (4LND-). Propensity score matching was used to minimize analytic error (659 vs 659). RESULTS: The percentage of #4L metastasis increased with tumour size. Between pT2a and pT2b, it nearly doubled from 8% to 14%. The mean percentage of #4L metastasis in the pN2 group was 46, which was higher in left upper lobectomy compared to left lower lobectomy (63% vs 43%, respectively, P < 0.001). In univariable analysis, no differences in 5-year survival were observed between 4LND+ and 4LND- (48% vs 50%, respectively, P = 0.65). However, we detected a significant difference among non-metastatic 4LND+, 4LND- and metastatic 4LND+ (P < 0.0001). After propensity score matching, there were no significant differences in survival among the pN2 subgroups (pN2a1, pN2a2, pN2b1, pN2b2). Multivariable analysis after propensity score matching for each pN2 subgroup did not confirm the effect of #4L metastasis as an independent prognostic factor. CONCLUSIONS: Despite #4L nodes not being an independent prognostic factor in lung cancer, the percentage of nodal metastases notably increases above pT2a grade and is comparable to the percentage of #5 and #7 metastasis. Therefore, lymphadenectomy in advanced stages of cancer could benefit from resections of the #4L nodes.

Video-assisted versus open thoracotomy lobectomy: comparison on lymphadenectomy and survival in early stage of lung cancer.

BACKGROUND: Video-assisted thoracic surgery (VATS) is increasingly used in the surgical treatment of early lung cancer, but the oncological benefits are still controversial. We aimed to compare video-assisted lobectomy and open thoracotomy lobectomy in terms of lymphadenectomy and long-term survival depending on the location of lobectomy. METHODS: A retrospective, multicenter study was based on the Polish Lung Cancer Study Group and included patients with stage I lung cancer who were surgically treated between 2007 and 2015. We included 1410 patients after video-assisted lobectomy and 4,855 after open thoracotomy. RESULTS: The average number of lymph nodes removed in video-assisted lobectomy was 10.9 and in open thoracotomy lobectomy was 12.9 (P<0.001). The 5-year survival was better in the video-assisted lobectomy group (78.6%) compared to open thoracotomy (73.8%) (P=0.002). Significant differences were found in the case of left lower lobe and left upper lobe lobectomies. Multivariable analysis showed that the prognostic factors for open thoracotomy relative to video-assisted lobectomy are: age over 60 [HR (95% CI): 1.55 (1.17-2.05), P=0.002], female [HR (95% CI): 1.57 (1.07-2.29), P=0.02], squamous cell carcinoma [HR (95% CI): 1.63 (1.12-2.37), P=0.011], left lower lobe [HR (95% CI): 2.69 (1.37-5.27), P=0.004] and left upper lobe [HR (95% CI): 1.53 (1.01-2.33), P=0.047]. CONCLUSIONS: The study showed that the number of lymph nodes removed during video-assisted lobectomy is significantly lower than in the open thoracotomy group. The long-term video-assisted lobectomy results were significantly better compared to open thoracotomy. Better long-term results were achieved on the left side of lobectomy.

The 6-min walk test in the functional evaluation of patients with lung cancer qualified for lobectomy.

OBJECTIVES: The American College of Chest Physicians guidelines recommend low-technology exercise tests in the functional evaluation of patients with lung cancer considered for resectional surgery. However, the 6-min walk test (6MWT) is not included, because the data on its clinical value are inconsistent. Our goal was to evaluate the 6MWT in assessing the risk of cardiopulmonary complications in candidates for lung resection. METHODS: We performed a retrospective assessment of clinical data and pulmonary function test results in 947 patients, mean age 65.3 (standard deviation 9.5) years, who underwent a single lobectomy for lung cancer. In 555 patients with predicted postoperative values ≤60%, the 6MWT was performed. The 6-min walking distance (6MWD) and the distance-saturation product (DSP), which is the product of the 6MWD in metres, and the lowest oxygen saturation registered during the test were assessed. RESULTS: A total of 363 patients with predicted postoperative values <60% and a 6MWT distance (6MWD) ≥400 m or DSP ≥ 350 m% had a lower rate of cardiopulmonary complications than patients with shorter 6MWD or lower DSP values [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.35-0.81] and 0.47 (95% CI 0.30-0.73), respectively. This result was also true for patients with predicted postoperative values <40%, ORs 0.33 (95% CI 0.14-0.79) and 0.25 (95% CI 0.10-0.61), respectively. CONCLUSIONS: The 6MWT is useful in the assessment of operative risk in patients undergoing a single lobectomy for lung cancer. It helps to stratify the operative risk, which is lower in patients with 6MWD ≥400 m or DSP ≥350 m% than in patients with a shorter 6MWD or lower DSP values.

Alternative methods of lymph node staging in lung cancer: a narrative review.

The nodal status indicator in non-small cell lung cancer is one of the most crucial prognostic factors available. However, there are still many arguments among scientists regarding whether the currently used nodal status descriptor should be changed in the forthcoming editions of the Tumor Node Metastasis classification or whether it is precise enough and should be maintained as is. We reviewed studies concerning nodal factor classifications to evaluate their accuracy in non-small cell lung cancer patients and to address the previously mentioned challenge. We reviewed the PubMed database regarding the following classifications: ongoing 8th edition of the Tumor Node Metastasis classification, number of positive lymph nodes, number of negative lymph nodes, number of dissected lymph nodes, lymph node ratio, nodal chains, log odds of positive lymph nodes, zone-based classification and one that is based on the number of lymph node stations involved. Moreover, we analysed data regarding various combinations of these classifications. Our analysis showed that the present nodal staging may not accurately categorize every lung cancer patient. The number of positive lymph nodes and lymph node ratio or the log odds of positive lymph nodes (as the mathematical modification of lymph node ratio) are more legitimate, as they possess very robust data and should be considered initially as additional factors that can be incorporated in ongoing nodal staging systems. Forthcoming non-small cell lung cancer staging systems could benefit from the addition of quantitative-based parameters. Additionally, the minimal extent of lymphadenectomy should be established as staging benefits from it. International, prospective validation studies need to be performed to optimize the cut-off values and prognostic groups and to confirm the superiority of the newly suggested descriptors in non-small cell lung cancer nodal staging.

Pulmonary veins variations with potential impact in thoracic surgery: a computed-tomography-based atlas.

BACKGROUND: Pulmonary veins (PVs) are important during segmentectomy. Many case reports prove that they may be the source of bleeding during surgery, especially when anatomical variants are present. We decided to describe venous variations and prepare a computed tomography based atlas of our observations. METHODS: The study was conducted using 135 chest computed tomography studies with intra venous iodine contrast injection. The study population contained 86 females and 49 males, mean age was 60. Thirteen people had atrial fibrillation. Images were analysed using radiological workstation. RESULTS: The variations were divided into three categories: atypical topography of the PV, atypical venous outflow to the left atrium (LA), atypical venous vascularization of the lung bronchopulmonary segment. Retrobronchial course of the vein of the posterior segment of the right upper lobe was observed in 8.15%. The most common variant of atrial venous outflow was the direct outflow of the middle lobe vein, observed in 25.19% of cases and the long common trunk of left PVs in 11.11%. The split drainage from the middle lobe into the right superior pulmonary vein (RSPV) and the right inferior pulmonary vein (RIPV) was observed in 9.63% as the full drainage into the RIPV in 2.96%. CONCLUSIONS: Long common trunk of left PVs and numerous variants of venous vascularisation of the middle lobe are the variations that may pose potential problems during thoracic surgeries. The frequency is high enough to justify the routine assessment of pulmonary vessels with computed tomography before surgery.

Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development.

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.

[Analysis of prognostic factors and efficacy of surgical treatment for non-small cell lung cancer: department of surgery NTLDRI (1998-1999)]. / Analiza czynników rokowniczych oraz ocena skutecznosci chirurgicznego leczenia niedrobnokomórkowego raka pluca w Klinice Chirurgii IGiChP w latach 1998-1999.

INTRODUCTION: Surgical resection is the mainstay of curative treatment for non-small cell lung cancer. MATERIAL AND METHODS: A retrospective analysis of the efficacy of this treatment, based on 431 patients operated from 1998 to 1999 in the Department of Surgery of the National Tuberculosis and Lung Diseases Research Institute, was accomplished. In 218 cases (51%) lobectomy was performed, in 21 cases (5%) - bilobectomy, in 188 cases (44%) - pneumonectomy and in 4 cases (1%) - wedge resection. The pIA stage was diagnosed in 70 cases (16%), pIB - in 112 (26%), pIIA - in 22 (5%), pIIB - in 110 (26%), pIIIA - in 88 (20%), pIIIB - in 13 (3%) and pIV - in 16 (4%). RESULTS: The five-year survival rate for the whole group was 49.1%. Statistical analysis revealed better survival in patients younger than 50 (p = 0.03), in women (p = 0.01, HR = 0.63) and in cases with less extensive surgery, i.e. lobectomy, (p < 0.05). Long-term survival was significantly dependent on the disease stage (p < 0.005). Five-year survival of patients in stage IA was 81.7%, IB - 62.2%, IIA - 59.1%, IIB - 38%, IIIA - 21.3%, IIIB - 8.3% and IV - 8.3%. Tumour status (p < 0.005) and histological subtype (p < 0.005) had a significant influence on long-term survival. Five-year survival of patients with squamous cell carcinoma was 53.4%, with adenocarcinoma - 38.3%, with large cell carcinoma - 37.5%, with carcinoid - 94.7% and with other types of cancer - 39.1%. The decreased preoperative Hb level (p < 0.005, HR = 1.52), as well as blood transfusion in postoperative period (p = 0.03), were negative prognostic factors. Significantly worse prognosis was observed in the cases of R1 or R2 categories (p = 0.01) and M1 category (p < 0.005). Additionally, in multivariate Cox analysis, a decreased FEV1 lower than 80% (HR = 1.46) was a negative prognostic factor, and lack of symptoms, except cough (HR = 0.73), was a positive one. CONCLUSIONS: Univariate analysis revealed several factors worsening prognosis: male sex, age older than 50 years, lowered preoperative Hb concentration, extended surgery, advanced stage, adenocarcinoma and large cell carcinoma, T status, N status, R status, M status and blood transfusion in postoperative period. In multivariate Cox analysis lowered preoperative Hb concentration, decreased FEV1 lower than 80% pred., extended surgery (pneumonectomy), advanced stage and adenocarcinoma were negative prognostic factors. Female sex and lack of symptoms, except coughing were positive prognostic factors.

Carinal Resection and Reconstruction.

The carinal resection is still considered a real challenge, both for a thoracic surgeon and an anesthesiologist. Depending on the indications and the degree of local advancement of the neoplasm, there are 2 techniques of carinal resection and reconstruction. The first one consists of the isolated resection with formation of a new bifurcation, whereas the second one is a combination of anatomic resection of lung parenchyma together with the bifurcation and the subsequent reconstruction. Long-term outcomes after carinal resection procedures, with clear postoperative margins, depend to a large extent on the stage of advancement of the primary disease.