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Background/objectives: Ocular syphilis is a vision-threatening disease that can lead to permanent blindness if left untreated. The global re-emergence of syphilis warrants greater investigations into the visual prognosis of eyes affected by this potentially devastating disease. This systematic review investigates the impact of HIV on visual acuity (VA) outcomes in ocular syphilis., Methods: A literature search of Medline, PubMed, Embase, Clinicaltrials.gov and Cochrane Reviews was conducted for studies published between 01 January 2011 and 19 March 2022, reporting non-aggregate initial and post-treatment VA data of eyes with ocular syphilis and corresponding HIV status in patients ≥ 18 years., Results: A total of 95 studies, including 364 patients and 568 eyes, were evaluated. Among people living with HIV with a diagnosis of ocular syphilis, affected eyes were more likely to have optic nerve involvement and panuveitis. However, HIV status, CD4 cell count, and HIV viral load were not predictive of VA outcomes of treated ocular syphilis. Prognostic factors of final VA worse than 1.00 logMAR were female sex, the presence of macular edema, and VA ≥ 1.00 at presentation. The strongest predictor of a worse final VA was VA ≥ 1.00 at presentation., Conclusions: This systematic review demonstrates that HIV status, CD4 cell count, and HIV viral load are not significant factors impacting VA outcomes of eyes with ocular syphilis. While visual prognosis is generally good, poor visual outcome is most strongly predicted by poor VA at presentation. This underscores the importance of early recognition and treatment prior to permanent vision loss., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

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., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2251). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio = 8.82, P = 1.18 × 10 -15 ) and replication (adjusted OR = 2.93, P = 2.22 × 10 -3 ) that is more pronounced in females (adjusted OR = 6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR = 2.61, P = 7.98 × 10 -22 ) and replication datasets (adjusted OR = 1.55, P = 0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

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., Competing Interests: CONFLICTS OF INTEREST The authors whose names are listed above certify that they have NO affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Objectives: Anatomical lobar resection and mediastinal lymphadenectomy remain the standard for the treatment of early stage non-small-cell lung cancer (NSCLC) and are preferred over procedures such as segmentectomy or wedge resection. However, there is an ongoing debate concerning the influence of the extent of the resection on overall survival. The aim of this article was to assess the overall survival for different types of resection for Stage I NSCLC., Methods: We performed a retrospective analysis of the results of the surgical treatment of Stage I NSCLC. Between 1 January 2007 and 31 December 2013, the data from 6905 patients who underwent Stage I NSCLC operations were collected in the Polish National Lung Cancer Registry (PNLCR) and overall survival was assessed. A propensity score-matched analysis was used to compare 3 groups of patients, each consisting of 231 patients who underwent lobectomy, segmentectomy, or wedge resection., Results: In the unmatched and matched patient groups, lobectomy and segmentectomy were associated with a significant benefit compared to wedge resection regarding overall survival (log-rank P  < 0.001 and P  = 0.001). The Cox proportional hazard ratio comparing segmentectomy and lobectomy to wedge resection was 0.54 [95% confidence interval (CI): 0.37-0.77) and 0.44 (95% CI: 0.38-0.50), respectively, indicating a significant improvement in survival. There was no difference in the 5-year survival of patients after lobectomy (79.1%; 95% CI: 77.7-80.4%) or segmentectomy (78.3%; 95% CI: 70.6-86.0%). The 30-day mortality rate was 1.6, 2.6 and 1.4% for lobectomy, segmentectomy and wedge resection, respectively. Wedge resection was associated with a significantly lower 5-year survival rate (58.1%; 95% CI: 53.6-62.5%) compared to segmentectomy (78.3%; 95% CI: 70.6-86.0%) and lobectomy (79.1%; 95% CI: 77.7-80.5%). The propensity score matched analysis confirmed most of the results of the comparisons of unmatched study groups., Conclusions: Wedge resection was associated with significantly lower 3-year and 5-year survival rates compared to the other methods of resection. There was no significant difference in 3-year or 5-year survival rates between lobectomy and segmentectomy. Segmentectomy, but not wedge resection, could be considered an alternative to lobectomy in the treatment of patients with Stage I NSCLC., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

Objective: An analysis of subglottic stenosis (SGS) occurrence frequency in patients with granulomatosis with polyangiitis (GPA) based on the time of appearance of clinical symptoms, and an assessment of treatment effectiveness, in particular with the intratracheal dilation-injection technique (IDIT)., Methods: Review and treatment with IDIT of 34 patients with SGS associated with GPA., Results: SGS developed in 34 of 250 patients with GPA (13.6%) and was not reflective of disease activity in the organs in 15 of 34 patients (44%): 11 cases after and 4 cases during immunosuppressive therapy (IST) when patients did not have organ symptoms. All patients underwent IDIT and in total, the treatment resulted in immediate improvement. In addition, in 21 cases, IST was applied because of other organ involvement or of the lack of longterm efficacy of IDIT. The median time of response was 37 months and the median interval between sessions was 5 months. None of the patients required tracheostomy after beginning IDIT in our hospital., Conclusion: SGS often occurs independently of other features of active GPA. IDIT is a safe and effective technique in the treatment of GPA-related SGS. It should be performed in all patients with GPA who develop significant SGS and in those with multiorgan disease concomitantly with IST. In patients with isolated SGS, IDIT also makes IST and tracheostomy unnecessary.

Purpose: This study aimed to determine whether three preoperative cycles of gemcitabine plus cisplatin followed by radical surgery provides a reduction in the risk of progression compared with surgery alone in patients with stages IB to IIIA non-small-cell lung cancer (NSCLC)., Patients and Methods: Patients with chemotherapy-naive NSCLC (stages IB, II, or IIIA) were randomly assigned to receive either three cycles of gemcitabine 1,250 mg/m(2) days 1 and 8 every 3 weeks plus cisplatin 75 mg/m(2) day 1 every 3 weeks followed by surgery, or surgery alone. Randomization was stratified by center and disease stage (IB/IIA v IIB/IIIA). The primary end point was progression-free survival (PFS). Results The study was prematurely closed after the random assignment of 270 patients: 129 to chemotherapy plus surgery and 141 to surgery alone. Median age was 61.8 years and 83.3% were male. Slightly more patients in the surgery alone arm had disease stage IB/IIA (55.3% v 48.8%). The chemotherapy response rate was 35.4%. The hazard ratios for PFS and overall survival were 0.70 (95% CI, 0.50 to 0.97; P = .003) and 0.63 (95% CI, 0.43 to 0.92; P = .02), respectively, both in favor of chemotherapy plus surgery. A statistically significant impact of preoperative chemotherapy on outcomes was observed in the stage IIB/IIIA subgroup (3-year PFS rate: 36.1% v 55.4%; P = .002). The most common grade 3 or 4 chemotherapy-related adverse events were neutropenia and thrombocytopenia. No treatment-by-histology interaction effect was apparent., Conclusion: Although the study was terminated early, preoperative gemcitabine plus cisplatin followed by radical surgery improved survival in patients with clinical stage IIB/IIIA NSCLC.

Aim: To prospectively assess the cardiopulmonary morbidity and quality of life in patients with non-small cell lung cancer (NSCLC) treated with postoperative radiotherapy (PORT) in comparison to those not receiving PORT., Materials and Methods: From 2003 to 2007, 291 patients entered the study; 171 pN2 patients received 3D-planned PORT (PORT group), 120 pN1 patients (non-PORT group) did not. One month after surgery, all patients completed EORTC QLQ C-30 questionnaire and had pulmonary function tests (PFT); cardiopulmonary symptoms were assessed by modified LENT-SOM scale. Two years later, disease-free patients repeated the same examinations. The differences between baseline values and values recorded at two years in QLQ, LENT-SOM and the PFT of the two groups were compared., Results: In the whole cohort, the rate of non-cancer related deaths was 5.3% and 5.0% in PORT and non-PORT group, respectively. Ninety-five patients (47 - PORT group, 48 - non-PORT group) were included into the final analysis. The differences in the QLQ and cardiopulmonary function (LENT/SOM, PFT) between both groups were insignificant. The forced expiratory volume in one second was on average 12.2% and 1.3% better in the PORT and the non-PORT group, respectively, p=0.2., Conclusions: Our findings support the hypothesis about insignificant morbidity of 3D-planned PORT., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The resectability of NSCLC is determined by its stage. The surgical treatment in stage I and II NSCLC remains a golden standard. Stage IIIA NSCLC constitutes a non-homogenous group, and many patients are potentially non-resectable. The patients in stage IIIA NSCLC also constitute a non-homogenous group. The patients in stage T3N1 usually undergo surgical resection, but many patients with N2 disease are disqualified from surgical treatment due to the negative prognostic factors. The negative prognostic factors comprise: (1) metastases to upper paratracheal (no 2), anterior paratracheal (no 3), and subcarinal (no 7) lymph nodes; (2) metastases to multiple mediastinal lymph nodes; (3) occurrence of the so called 'bulky disease'; (4) capsular lymph node invasion. The occurrence of one of these negative prognostic factors disqualifies the patient with N2 disease from radical surgical treatment. In more advanced cases, i.e. stage IIIB, and stage IV NSCLC, patients are rarely operated. It regards the patients in stage T4 N1, and in M1 disease with a single metastasis (mainly to CNS) accompanied by the stage I, or II, of the primary focus. In these cases N2 disease always constitutes the contraindication to the surgical treatment. Multidisciplinary approach in the treatment of NSCLC is supposed to improve the results of the treatment of NSCLC.

Objective: The invention of the mechanical suture of the bronchial stump resulted in the significant decrease of the incidence of bronchial fistulas. Bronchial fistula constitutes the most dangerous complication of the pulmonary resection. In connection with some negative opinions in world literature regarding the safety of applying some types of mechanical suture, the multi-factor analysis of efficacy of bronchial stump closure following the total pneumonectomy by two different types of stapling devices was performed., Methods: The experimental study was performed on 22 sheep. Each sheep underwent left pneumonectomy. In group I the bronchus was closed by the hinged-jaw stapling device (TA-Premium, Auto-Suture). In group II the bronchus was closed by the stapling device of parallel pattern (RLV 30 Ethicon). The macroscopic parameters (i.e. linear structure of staples, degree of staples closure, the symmetry of staples closure in the medial and lateral part of bronchial stump) as well as microscopic parameters (i.e. degree of inflammatory reaction, degree disorder in collagen fibers system, degree of disorders in cartilaginous system, degree of vascular proliferation and nervous regeneration) were evaluated., Results: In three cases of group I the serious abnormalities in staples closure in the medial part of the bronchial stump were revealed. Abnormalities were found also in microscopic evaluation of the specimens. In the whole group the inflammatory reaction predominated in the medial part of bronchial stump near the hinge of the cartridge (P value <0.05). The disorder in the collagen fibers system as well as in the stratified structure of muscular fibers and cartilaginous system was proved. On the other hand, in group II all staples were properly closed in adequate linear structure, without any symmetry in both medial and lateral end of the bronchial stump. The microscopic findings were only the subtle inflammatory process and a slight disarrangement in muscular, collagen and cartilaginous systems., Conclusion: The listed abnormalities of mechanical, hinged-jaw suture of bronchial stump seem to be due to the inaccurate placement of staples, their incomplete closure, and excessive damage to the sutured tissues. We conclude that the application of the hinged-jaw mechanical suture of the bronchial stump might result in higher incidence of bronchial fistula after pneumonectomy.

A case of asymptomatic pulmonary leiomyoma diagnosed by routine chest radiography and treated by lobectomy is reported. There is no particular clinical pattern that distinguishes this lesion, and diagnostic maneuvers to identify its nature are generally unrewarding except for biopsy. Resection is the recommended treatment.

Sixteen patients with far-advanced neoplastic lesions in the trachea and main-stem bronchi were studied. Ten of them were admitted to the ward in extremely poor general condition with marked cyanosis and dyspnea at rest. Palliative intubation was undertaken with two types of tubes: a Neville tracheal prosthesis and a Tracheoflex tracheostomy tube. Both types of tubes had to be specially prepared, as they had originally been designed for other purposes. The tubes were placed in the stenotic sections of the trachea and, depending on anatomical relations, within the right or left main bronchus as well. Intubation of the bronchus in the case of changes involving only the trachea was necessary to properly position and fasten the tube in the bronchial tree and to prevent displacement of the prosthesis inside the trachea. In two patients the esophagus was intubated as well. An improvement in the general condition of all patients was observed. Intubation resulted in reexpansion of a completely collapsed lung in two patients. The longest time of intubation was 9 months. The method is simple, and every physician experienced in endoscopy can use it. The results obtained encourage its further and wider application.