Lipid Metabolism Pathway Genes and Lung Cancer: ACADSB rs12220683G>C Is Associated with Better Survival Outcome in Patients with Non-Small Cell Lung Cancer.

INTRODUCTION: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC). METHODS: In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. The association between 176 polymorphisms of lipid metabolism pathway genes and the clinical outcomes of NSCLC patients was analyzed. RESULTS: Among the polymorphisms investigated, ACADSB rs10902859G>A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G>A was located in the repressed region and had strong linkage disequilibrium (D' = 1.00 and r2 = 0.94), with rs12220683G>C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G>C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30-0.94, p = 0.03; aHR = 0.37, 95% CI = 0.15-0.89, p = 0.03; and aHR = 0.47, 95% CI = 0.29-0.75, p = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (p = 3 × 10-5). CONCLUSION: These results suggest that ACADSB rs12220683G>C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC.

Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery. METHODS: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated. RESULTS: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes. CONCLUSIONS: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.

Ultrasound-Guided Percutaneous Needle Biopsy for Small Pleural Lesions: Diagnostic Yield and Impact of CT and Ultrasound Characteristics.

BACKGROUND. Ultrasound (US)-guided percutaneous pleural needle biopsy (PCPNB) is widely used to evaluate pleural lesions, although its diagnostic accuracy is variable. OBJECTIVE. The purpose of this study is to assess the diagnostic yield of US-guided PCPNB for small (≤ 2 cm) pleural lesions and the impact of CT and US morphologic and technical factors. METHODS. A total of 103 patients (73 men and 30 women; mean [± SD] age, 68.0 ± 13.3 years) who underwent US-guided PCPNB of a small pleural lesion performed by a single experienced operator from July 2013 to December 2019 were retrospectively analyzed. Final diagnosis was established via histopathologic results, including findings from repeat US-guided and CT-guided biopsies as well as imaging and clinical follow-up. Pleural morphology and thickness were assessed on CT and US, and needle pathway length throughout the pleura was measured on US. Accuracy, sensitivity, specificity, PPV, and NPV were calculated. The association of diagnostic yield with imaging and technical factors was evaluated. ROC curve analysis was used to determine the optimal CT pleural thickness cutoff value. Multivariable logistic regression was performed to identify independent predictors of diagnostic yield. RESULTS. The diagnostic accuracy, sensitivity, specificity, PPV, and NPV of US-guided PCPNB were 85.4%, 84.8%, 100.0%, 100.0%, and 21.1%, respectively. Diagnostic, compared with nondiagnostic, procedures more commonly (p ≤ .002) revealed nodular morphology on CT (96.4% vs 3.6%) and US (97.3% vs 2.7%,), greater pleural thickness on CT (7.5 vs 3.2 mm) and US (7.4 vs 3.0 mm), and a greater needle pathway length (11.0 vs 6.1 mm). The optimal cutoff value for pleural thickness on CT was 4.5 mm. Diagnostic yield was 96.4% for nodular lesions, 95.0% for diffuse lesions that had a thickness of 4.5 mm or greater on CT, 55.6% for diffuse lesions that had a thickness less than 4.5 mm on CT, and 100% for diffuse lesions on CT that had nodular morphology on US. Nodular morphology on US (p = .002) and needle pathway length (p = .04) were independent predictors of diagnostic yield. CONCLUSION. US-guided PCPNB has excellent diagnostic accuracy for small pleural lesions; imaging characteristics influence this accuracy. CLINICAL IMPACT. US-guided PCPNB is highly likely diagnostic for small pleural lesions with nodular morphology on either CT or US or with a pleural thickness of 4.5 mm or greater.

Serratus Anterior Plane Block and Intercostal Nerve Block after Thoracoscopic Surgery.

BACKGROUND: This study aimed to compare the postoperative analgesic effect between ultrasound-guided serratus anterior plane block (Group S, SAPB) and intercostal nerve block (Group I, ICNB) after single port video-assisted thoracoscopic surgery (S-VATS) in primary spontaneous pneumothorax. METHODS: In this prospective randomized controlled study, 54 patients were randomly assigned to two groups. Patients in Group S underwent the SAPB before the surgical drape by an anesthesiologist, and in Group I, ICNBs were performed just before the wound closure after S-VATS by an attending thoracic surgeon. The primary outcome was the numeric pain rating scale (NRS) score given by the patients for pain at the surgical incision site. NRS was assessed during resting and coughing statuses at 3, 6, and 12 hours postoperatively and at the time of the chest tube removal. The secondary outcomes included the number of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid administration until time to chest tube removal. RESULTS: There were no statistical differences between the two groups regarding age, body mass index, duration of operation, duration of anesthesia, and average NRS scores for the assigned time periods. There was no statistical significance in the number of opioid injections; however, NSAIDs were administered 2.8 times per patient in Group I, and 1.9 times per patient in Group S (p = 0.038). CONCLUSION: In the patients who underwent S-VATS with primary spontaneous pneumothorax, the SAPB provided similar postoperative pain relief with reducing the NSAIDs consumption compared with ICNB.

Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC). METHODS: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed. RESULTS: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54-0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13-4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08-1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10-3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41-1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11-6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17-2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12-6.88, p = 0.03, respectively). CONCLUSIONS: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.

Under-recognized primary spontaneous pneumothorax in ALS: a multicenter retrospective study.

Primary spontaneous pneumothorax (PSP) is not an uncommon disease, especially in patients with risk factors such as male gender, history of smoking, and low body mass index (BMI). Amyotrophic lateral sclerosis (ALS) is a rare disease caused by neurodegeneration of the motor neurons that share risk factors with PSP. The aim of this study was to determine the prevalence of PSP in ALS and find the significant risk factors related to PSP. We retrospectively reviewed the data from 86 patients with clinically probable or definite ALS from three different centers. Clinical characteristics, including age, sex, subtype, disease duration, body mass index, history of smoking, tracheostomy state, and ventilator use, were obtained. The ALS Functional Rating Scale-Revised Form (ALSFRS-R) total score and subscores were also retrieved from the medical records. In the results, six of the 86 patients (7%) had PSP. There were no statistically significant differences among the clinical characteristics and the ALSFRS-R scores between the patients with and without PSP, except for BMI and smoking (p < 0.022 and p < 0.019, respectively). A multivariate logistic regression analysis of smoking and BMI showed an odds ratio of 19.25. In conclusion, the existence of PSP in ALS may be under-recognized. Further well-designed, large studies are needed to elucidate the prevalence and pathophysiology of pneumothorax in ALS.

Risk of Primary Spontaneous Pneumothorax According to Chest Configuration.

BACKGROUND: We compared the chest configurations of patients with primary spontaneous pneumothorax (PSP) and age-sex-matched controls to determine the presence of chest wall deformities in patients with PSP. METHODS: We retrospectively enrolled 166 male patients with PSP (age, 18-19 years) and 85 age-sex-matched controls without PSP, who simultaneously underwent chest computed tomography (CT) and radiography at one of two institutes. After correcting for height, the following thoracic parameters were comparatively evaluated between the two groups: maximal internal transverse (T) and anteroposterior (W) diameters of the chest, maximal internal lung height (H), Haller index (T/W), and T/Height, T/H, W/Height, W/H, and H/Height ratios. RESULTS: Patients were taller than the control subjects (176.5 cm ± 5.9 cm versus 174.4 cm ± 5.6 cm; p = 0.007). After controlling for height, the patient group exhibited lower T and W and greater H and Haller index values than the control group (T: 95% confidence interval [CI], 24.8-25.2 cm versus 25.9-26.5; W: 95% CI, 8.9-9.2 cm versus 10.1-10.6 cm; H: 95% CI, 25.2-25.9 cm versus 23.4-24.4 cm; and Haller index, 95% CI, 2.7-2.9 versus 2.4-2.6; all, p < 0.001). The patient group also exhibited lower T/Height, T/H, W/Height, and W/H ratios and greater H/Height ratio than the control group. CONCLUSIONS: Patients with PSP have an anteroposteriorly flatter, laterally narrower, and craniocaudally taller thorax than subjects without PSP, suggesting that chest configuration is associated with the development of pneumothorax.

Anesthetic management for inhibiting sympathetic activation in an adolescent patient diagnosed with catecholaminergic polymorphic ventricular tachycardia and undergoing left cardiac sympathetic denervation: A case report.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disorder in which catecholamine release during exercise or emotional stress cause fatal tachyarrhythmias. In this paper, we discuss methods to minimize the sympathetic stimulation that can occur during the perioperative period in patients undergoing left cardiac sympathetic denervation to surgically treat CPVT.

Effect of Minimum Bronchial Cuff Volume of Left-Sided Double-Lumen Tube for One-Lung Ventilation on the Change in Bronchial Cuff Pressure during Lateral Positioning in Thoracic Surgery: A Prospective Observational Study.

The minimum bronchial cuff volume (BCVmin) of a double-lumen tube (DLT) without air leaks during lung isolation may vary among individuals, and lateral positioning could increase the bronchial cuff pressure (BCP). We investigated the effect of initially established BCVmin (BCVi) on the change in BCP by lateral positioning. Seventy patients who underwent elective lung surgery were recruited and divided into two groups according to the BCVi obtained during anesthetic induction in each patient. Outcome analysis was conducted using data from 39 patients with a BCVi greater than 0 (BCVi > 0 group) and 27 with a BCVi of 0 (BCVi = 0 group). The primary outcome was a change in the value measured in the supine and lateral positions of the initially established BCP (BCPi; BCP at the time of BCVi injection), which was significantly larger in the BCVi > 0 group than in the BCVi = 0 group (1.5 (0.5-6.0) cmH2O vs. 0.0 (0.0-1.0) cmH2O; p < 0.001). BCVi was related to the left main bronchus (LMB) diameter (Spearman's rho = 0.676, p < 0.001) and the gap between the LMB diameter and the outer diameter of the bronchial cuff (Spearman's rho = 0.553, p < 0.001). Therefore, selecting a DLT size with a bronchial cuff that fits each patient's LMB may be useful in minimizing the change in BCP when performing lateral positioning during thoracic surgery. If the bronchial cuff requires unavoidable initial inflation, it is necessary to be aware that BCP may increase during lateral positioning and to monitor the BCP regularly if possible.

Ultrasound-guided lung biopsy for small (≤2 cm) subpleural lung lesions: comparison of diagnostic yield and safety with larger lesions.

Background: Ultrasound (US)-guided percutaneous core needle biopsy (PCNB) has been used to diagnose subpleural lung lesions with high diagnostic performance and acceptable complication rates. However, with regard to the role of US-guided needle biopsy for the diagnosis of small (≤2 cm) subpleural lesions, limited information is available. Methods: From April 2011 to October 2021, a total of 572 US-guided PCNBs in 572 patients were retrospectively reviewed. The lesion size, pleural contact length (PCL), lesion location, and operator's experience were analyzed. Computed tomography features including peri-lesional emphysema, air-bronchogram, and cavitary change were also included in image analysis. The patients were divided into three groups according to lesion size (lesions ≤2 cm vs. 2 cm< lesions ≤5 cm vs. lesions >5 cm). The sample adequacy, diagnostic success rate, diagnostic accuracy, and complication rate was calculated. For statistical analysis, one-way ANOVA, Kruskal-Wallis test, or the chi-square test were used. Results: The overall sample adequacy, diagnostic success rate, and diagnostic accuracy were 96.2%, 82.9%, and 90.4%, respectively. In the subgroup analysis, sample adequacy (93.1% vs. 96.1% vs. 96.9%, P=0.307), diagnostic success rate (75.0% vs. 81.6% vs. 85.7%, P=0.079), and diagnostic accuracy (84.7% vs. 90.8% vs. 90.5%, P=0.301) were not significantly different. Operator's experience (OR, 0.64; 95% CI: 0.49-0.80; P<0.001), lesion size (OR, 0.68; 95% CI: 0.54-0.83; P<0.001), PCL (OR, 0.68; 95% CI: 0.52-0.84; P=0.001), and presence of air-bronchogram (OR, 14.36; 95% CI: 4.18-48.53; P<0.001) were independently associated with complication rate. Conclusions: US-guided PCNB performed by an experienced radiologist could be an effective and safe diagnostic approach for subpleural lesions, even in small lesions.

Peritumoral imaging features of thymic epithelial tumors for the prediction of transcapsular invasion: beyond intratumoral analysis

PURPOSE: The purpose of this study was to differentiate cases without transcapsular invasion (Masaoka-Koga stage I) from cases with transcapsular invasion (Masaoka-Koga stage II or higher) in patients with thymic epithelial tumors (TETs) using tumoral and peritumoral computed tomography (CT) features. METHODS: This retrospective study included 116 patients with pathological diagnoses of TETs. Two radiologists evaluated clinical variables and CT features, including size, shape, capsule integrity, presence of calcification, internal necrosis, heterogeneous enhancement, pleural effusion, pericardial effusion, and vascularity grade. Vascularity grade was defined as the extent of peritumoral vascular structures in the anterior mediastinum. The factors associated with transcapsular invasion were analyzed using multivariable logistic regression. In addition, the interobserver agreement for CT features was assessed using Cohen's or weighted kappa coefficients. The difference between the transcapsular invasion group and that without transcapsular invasion was evaluated statistically using the Student's t-test, Mann-Whitney U test, chi-square test, and Fisher's exact test. RESULTS: Based on pathology reports, 37 TET cases without and 79 with transcapsular invasion were identified. Lobular or irregular shape [odds ratio (OR): 4.19; 95% confidence interval (CI): 1.53-12.09; P = 0.006], partial complete capsule integrity (OR: 5.03; 95% CI: 1.85-15.13; P = 0.002), and vascularity grade 2 (OR: 10.09; 95% CI: 2.59-45.48; P = 0.001) were significantly associated with transcapsular invasion. The interobserver agreement for shape classification, capsule integrity, and vascularity grade was 0.840, 0.526, and 0.752, respectively (P < 0.001 for all). CONCLUSION: Shape, capsule integrity, and vascularity grade were independently associated with transcapsular invasion of TETs. Furthermore, three CT TET features demonstrated good reproducibility and help differentiate between TET cases with and without transcapsular invasion.

Genetic variants in key necroptosis regulators predict prognosis of non-small cell lung cancer after surgical resection.

BACKGROUND: Necroptosis is a regulated inflammatory cell death which plays a significant role in cancer development and progression. In this study, we evaluated whether genetic variants in key regulators of necroptosis may affect survival outcome of non-small cell lung cancer (NSCLC) patients after surgical resection. METHODS: A total of 674 patients who underwent curative surgery were included. Fifteen genetic variants in key regulators of necroptosis (RIPK1, RIPK3, and MLKL) were selected. The association of these variants with survival outcomes was evaluated. RESULTS: Two variants, RIPK1 rs17548629C > T and MLKL rs877375G > C, were associated with better overall survival and disease-free survival in multivariate analyses. When the patients were divided according to histology, the associations were significant only in adenocarcinoma, but not in squamous cell carcinoma. RIPK1 rs17548629 C-to-T change was associated with significantly increased luciferase activity by modulating the binding of miR-642a. Promoter assays showed a significantly increased promoter activity in MLKL rs877375C allele compared to G allele. Consistently, the mRNA expression level of RIPK1 and MLKL showed significant positive correlation with RIPK1 rs17548629C-to-T and MLKL rs877375G-to-C changes. CONCLUSION: Two genetic variants in key regulators in necroptosis, RIPK1 rs17548629C > T and MLKL rs877375G > C, may be used as biomarkers to predict survival outcomes in surgically resected NSCLC patients.

Genetic variants in LKB1/AMPK/mTOR pathway are associated with clinical outcomes of chemotherapy in non-small cell lung cancer.

This study was conducted to investigate the relationship between genetic variants in LKB1/AMPK/mTOR pathway and treatment outcomes of patients with non-small cell lung cancer (NSCLC) treated with chemotherapy. A total of 379 patients with NSCLC who underwent first-line paclitaxel-cisplatin chemotherapy was enrolled. The associations between 19 single nucleotide variants (SNVs) in the LKB1/AMPK/mTOR pathway and the chemotherapy response and overall survival (OS) were analyzed. Among the SNVs analyzed, AKT1 rs2494750G>C and TSC1 rs2809244C>A were associated with clinical outcomes after chemotherapy in multivariate analyses. The AKT1 rs2494750G>C was significantly associated with a better response to chemotherapy (adjusted odds ratio [aOR]: 1.92, 95% confidence interval [CI]: 1.02-3.62, p = 0.04). The TSC1 rs2809244C>A were significantly associated with better OS (adjusted hazard ratio [aHR]: 0.79, 95% CI: 0.62-0.99, p = 0.04). When stratified by tumor histology, AKT1 rs2494750G>C exhibited a significant association with the chemotherapy response only in adenocarcinoma and TSC1 rs2809244C>A was also significantly associated with OS only in adenocarcinoma. This result suggests that the AKT1 rs2494750G>C and TSC1 rs2809244 C>A may be useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.

Comparison of costs for video-assisted thoracic surgery lobectomy and open lobectomy for non-small cell lung cancer.

BACKGROUND: To promote the broad use of video-assisted thoracic surgery (VATS) for lobectomy (VATSL) in the management of lung cancer, it should be proved cost-effective, especially in the current cost-sensitive climate. This study evaluated and compared the costs of VATSL and open lobectomy (OL) and analyzed how the surgeon's experience level with VATSL affected the cost. METHODS: In this study, 86 patients in a VATSL group and 97 patients in an OL group underwent surgery for lung cancer. Cost comparisons were performed for the VATSL and OL groups between patients who had no complications and patients with and without complications according to tumor location and the learning period of the surgeon. RESULTS: Postoperative complications occurred for 56 patients (30.6%) (14 VATSL vs 42 OL patients; p < 0.05). Patients who underwent VATSL had significant reductions in both chest tube duration (5.4 vs 9.1 days; p = 0.000) and length of hospital stay (7.1 vs 12.0 days; p = 0.000). The mean operation time for VATSL was not significantly longer than for OL (145.8 vs 136.4 min; p = 0.782). The total hospital cost (i.e., that paid by the patient and national insurance combined) was lower for VATSL than for OL according to comparisons both among all patients ($5,391 vs $5,593, respectively) and among only noncomplicated patients ($4,684 vs $4,769, respectively). In terms of tumor location, the total hospital cost for the VATSL group was lower than for the OL group when the surgery was performed on the right lower lobe (RLL), left upper lobe (LUL), and left lower lobe (LLL). The costs were not significantly different between the two learning periods of the surgeons, except for the cost of anesthesia. CONCLUSIONS: In Korea, VATSL for lung cancer had lower complication rates, shorter hospital stays, and lower total hospital costs than OL.

Transpedal lymphatic embolization for lymphorrhea at the graft harvest site after coronary artery bypass grafting.

Lymphorrhea is a rare but potentially severe complication that occurs after various surgical procedures. Untreated lymphorrhea may lead to wound dehiscence, infection, and prolonged hospital stay. Currently, there is no standard effective treatment. Early management usually includes leg elevation, drainage, and pressure dressing. However, these methods are associated with prolonged recovery and high recurrence rates. We report a case of lymphorrhea from a calf wound after endoscopic great saphenous vein (GSV) harvesting for coronary artery bypass grafting (CABG). The patient presented with intractable oozing from the postoperative wound on the right calf. Lymphorrhea perGsisted for 6 weeks despite negative-pressure wound therapy with a long-acting somatostatin. We performed unilateral pedal lymphangiography that confirmed wound lymphorrhea, followed by glue embolization. No recurrence was observed after 8 months of follow-up. This case report demonstrates the successful use of lymphangiography with glue embolization in the control of lymphorrhea after GSV harvesting for CABG.

Genetic variants in histone modification regions are associated with the prognosis of lung adenocarcinoma.

We investigated the association between genetic variants in the histone modification regions and the prognosis of lung adenocarcinoma after curative surgery. Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The SNPs were analyzed in a discovery set (n = 166) and a validation set (n = 238). The associations of the SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. A total of 279 SNPs were selected for genotyping. Among these, CAPN1 rs17583C>T was significantly associated with better OS and DFS (P = 0.001 and P = 0.007, respectively), and LINC00959 rs4751162A>G was significantly associated with worse DFS (P = 0.008). Luciferase assays showed a significantly lower promoter activity of CAPN1 in the rs17583 T allele than C allele (P = 0.008), and consistently the CT + TT genotypes had significantly lower CAPN1 expression than CC genotype (P = 0.01) in clinical samples. The rs4751162 G allele had higher promoter activity of GLRX3 than A allele (P = 0.05). The motif analyses and ChIP-qPCR confirmed that the variants are located in the active promoter/enhancer regions where transcription factor binding occurs. This study showed that genetic variants in the histone modification regions could predict the prognosis of lung adenocarcinoma after surgery.

Clinical implication of minimal presence of solid or micropapillary subtype in early-stage lung adenocarcinoma.

BACKGROUND: We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA. METHODS: We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP-, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP-. RESULTS: The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP- group (P < 0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P < 0.001, all comparisons for S/MP+ vs. S/MP-; P ≤ 0.01, all comparisons for S/MP5 vs. S/MP-). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer-related death than the S/MP- group(P < 0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA. CONCLUSIONS: The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed. KEY POINTS: Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma. WHAT THIS STUDY ADDS: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.

Over-the-wire deployment techniques of option elite inferior vena cava filter: 3D printing vena cava phantom study.

PURPOSE: To compare filter tilt and filter jumping during Option inferior vena cava (IVC) filter deployment with 3 different wires techniques using a 3-dimensional (3D) printing vena cava phantom. MATERIALS AND METHODS: An IVC 3D printed vena cava phantom was made from a healthy young male's computed tomographic data. Option IVC filters were deployed with 3 different wires: i) original push wire, ii) hydrophilic stiff wire, and iii) bent stiff wire. Right internal jugular and right femoral access were used 5 times with each wire. Filter tilt angle, tilt ratio, jumping, and tip abutment to the IVC wall were analyzed. RESULTS: The transfemoral approach with original push wire had significantly higher tilt angle than did the transjugular approach (6.1˚ ± 1.9 vs. 3.5˚ ± 1.3, p = 0.04). Mean tilt ratio was significantly lower with the bent wire with transfemoral access (0.49 ± 0.13 vs. 0.78 ± 0.18 [original push-wire] and 0.67 ± 0.08 [stiff wire], p = 0.019). The ratio was lower also with original push wire with transjugular access (0.34 ± 0.19 vs. 0.57 ±0.11 [stiff wire] and 0.58 ±0.17 [bent wire], p = 0.045). Filter jumping occurred more often with the transjugular approach with original push wire than with stiff or bent-wire delivery. Filter tip abutment to the IVC wall occurred only with the transfemoral approach. CONCLUSIONS: Bent wire with transfemoral access and original push wire with transjugular access had lower filter tilt ratio at Option IVC filter deployment. However, filter jumping was common using the original push wire with transjugular access.