Surgical prognosis of lung invasive mucinous and non-mucinous adenocarcinoma: Propensity score matched analysis.

OBJECTIVES: Invasive mucinous adenocarcinoma exhibits distinct prognostic outcomes compared to nonmucinous adenocarcinoma. This study investigated and compared the clinical outcomes and prognostic factors of invasive mucinous and nonmucinous adenocarcinoma patients. METHODS: This retrospective study included patients who underwent curative surgery for adenocarcinoma between 2011 and 2021. Patient characteristics were balanced using propensity score matching. Cumulative incidence was analysed to evaluate cancer recurrence incidence, and the Kaplan-Meier method was used to calculate overall survival for each group. RESULTS: A total of 6,101 patients were included. After matching, the nonmucinous group and mucinous groups comprised 798 and 408 patients, respectively. The patients in the mucinous group had a lower recurrence incidence than those in the nonmucinous group (p = 0.014). The recurrence incidence in the mucinous group was between those of grades 1 (p = 0.011) and 2 (p = 0.012) and the overall survival rates were comparable to those of grades 2 (p = 0.6) and 3 (p = 0.2). Multivariable analysis revealed that the maximal standardised uptake value (HR: 1.13, p = 0.11) and progressed pathological stages (pStage II, HR: 3.9, p = 0.028; pStage III, HR: 8.33, p = 0.038) served as adverse prognostic factors for the mucinous group. CONCLUSIONS: Patients with mucinous adenocarcinoma demonstrated lower recurrence incidence and similar overall survival rates compared to those with nonmucinous adenocarcinoma. The recurrence incidence of mucinous adenocarcinoma was between those of International Association for the Study of Lung Cancer grades 1 and 2, with the overall survival rates comparable to those of grades 2 and 3.

Risk prediction of multiple-station N2 metastasis in patients with upfront surgery for clinical single-station N2 non-small cell lung cancer.

To investigate long-term outcomes and develop a risk model for pathological multi-station N2 (pN2b) in patients who underwent upfront surgery for clinical single-station N2 (cN2a) non-small cell lung cancer (NSCLC). From 2006 to 2018, 547 patients who had upfront surgery for suspected cN2a NSCLC underwent analysis. A risk model for predicting pN2b metastasis was developed using preoperative clinical variables via multivariable logistic analysis. Among 547 clinical cN2a NSCLC patients, 118 (21.6%), 58 (10.6%), and 371 (67.8%) had pN0, pN1, and pN2. Among 371 pN2 NSCLC patients, 77 (20.8%), 165 (44.5%), and 129 (34.7%) had pN2a1, pN2a2, and pN2b. The 5-year overall survival rates for pN2a1 and pN2a2 were significantly higher than for pN2b (p = 0.041). Histologic type (p < 0.001), age ≤ 50 years (p < 0.001), preoperatively confirmed N2 metastasis (p < 0.001), and clinical stage IIIB (vs. IIIA) (p = 0.003) were independent risk factors for pN2b metastasis. The risk scoring system based on this model demonstrated good discriminant ability for pN2b disease (area under receiver operating characteristic: 0.779). In cN2a NSCLC patients, those with multiple N2 metastases indicate worse prognosis than those with a single N2 metastasis. Our risk scoring system effectively predicts pN2b in these patients.

Prognostic Implications of Selective Dissection of Left Lower Paratracheal Lymph Nodes in Patients with Left-Sided Non-Small Cell Lung Cancer.

Background: This study aimed to examine the clinical implications of selective station 4L lymph node dissection (S4L-LND) on survival in non-small cell lung cancer (NSCLC) and to evaluate its potential advantages. Methods: We enrolled patients with primary left-sided NSCLC who underwent upfront video-assisted thoracoscopic surgery with R0 resection including lobectomy and segmentectomy, with or without S4L-LND, at our institution between January 2007 and December 2021. Following 1:1 propensity score matching (PSM), we compared overall survival (OS) and recurrence-free survival (RFS) between patients with and without S4L-LND. Results: The study included 2,601 patients, of whom 1,126 underwent S4L-LND and 1,475 did not. PSM yielded 1,036 patient pairs. Among those who underwent S4L-LND, 87 (7.7%) exhibited S4L-LN involvement. Neither OS (p=0.12) nor RFS (p=0.24) differed significantly between matched patients with and without S4L-LND. In patients with S4L-LN involvement, metastases were more common in the left upper lobe (LUL) than in the left lower lobe (LLL) (3.6% vs. 2.0%, p=0.061). Metastasis became significantly more frequent with more advanced clinical N (cN) stage (cN0, 2.3%; cN1, 5.8%; cN2, 32.6%; p<0.001). Multivariate logistic regression analysis revealed that cN stage and tumor location were independently associated with S4L-LN involvement (p<0.001 for both). Conclusion: OS and RFS did not differ significantly between matched patients with and without S4L-LND. Among participants with S4L-LN involvement, metastases occurred more frequently in the LUL than the LLL, and their incidence increased significantly with more advanced cN stage. Thus, patients with LUL or advanced cN lung cancers may benefit from S4L-LND.

TIPRL Regulates Stemness and Survival in Lung Cancer Stem Cells through CaMKK2-CaMK4-CREB Feedback Loop Activation.

Frequent recurrence and metastasis caused by cancer stem cells (CSCs) are major challenges in lung cancer treatment. Therefore, identifying and characterizing specific CSC targets are crucial for the success of prospective targeted therapies. In this study, it is found that upregulated TOR Signaling Pathway Regulator-Like (TIPRL) in lung CSCs causes sustained activation of the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) signaling pathway by binding to CaMKK2, thereby maintaining stemness and survival. CaMKK2-mediated activation of CaM kinase 4 (CaMK4) leads to phosphorylation of cAMP response element-binding protein (CREB) at Ser129 and Ser133, which is necessary for its maximum activation and the downstream constitutive expression of its target genes (Bcl2 and HMG20A). TIPRL depletion sensitizes lung CSCs to afatinib-induced cell death and reduces distal metastasis of lung cancer in vivo. It is determined that CREB activates the transcription of TIPRL in lung CSCs. The positive feedback loop consisting of CREB and TIPRL induces the sustained activation of the CaMKK2-CaMK4-CREB axis as a driving force and upregulates the expression of stemness- and survival-related genes, promoting tumorigenesis in patients with lung cancer. Thus, TIPRL and the CaMKK2 signaling axis may be promising targets for overcoming drug resistance and reducing metastasis in lung cancer.

Differences in the Prognostic Impact between Single-zone and Multi-zone N2 Node Metastasis in Patients with Station-based Multiple N2 Non-Small Cell Lung Cancer.

Purpose: The International Association for the Study of Lung Cancer suggest further subdivision of pathologic N (pN) stage in non-small-cell lung cancer (NSCLC) by incorporating the location and number of involved lymph node (LN) stations. We reclassified patients with the station-based N2b disease into single-zone and multi-zone N2b groups and compared survival outcomes between the groups. Materials and Methods: This retrospective study included patients with pN2 NSCLC who underwent lobectomy from 2006 to 2019. The N2 disease was subdivided into four categories: single-station N2 without N1 (N2a1), single-station N2 with N1 (N2a2), multiple-station N2 with single zone involvement (single-zone N2b), and multiple-station N2 with multiple zone involvement (multi-zone N2b). LN zones included in the subdivision of N2 disease were upper mediastinal, lower mediastinal, aortopulmonary, and subcarinal. Results: Among 996 eligible patients, 211 (21.2%), 394 (39.6%) and 391 (39.4) were confirmed to have pN2a1, pN2a2, and pN2b disease, respectively. In multivariable analysis after adjustment for sex, age, pT stage, and adjuvant chemotherapy, overall survival was significantly better with single-zone N2b disease (n=125, 12.6%) than with multi-zone N2b disease (n=266, 26.7%) (hazard ratio 0.67, 95% confidence interval 0.49-0.90, p<0.009) and was comparable to that of N2a2 disease (1.12, 0.83-1.49, p=0.46). Conclusion: Prognosis of single-zone LN metastasis was better than that of multiple-zone LN metastasis in patients with N2b NSCLC. Along with the station-based N descriptors, zone-based descriptors might ensure optimal staging, enabling the most appropriate decision-making on adjuvant therapy for patients with pN2 NSCLC.

Recurrence Dynamics of Pathological N2 Non-small Cell Lung Cancer Based on IASLC Residual Tumor Descriptor.

Purpose: This study investigated the recurrence patterns and timing in patients with pathologic N2 (pN2) non-small cell lung cancer (NSCLC) according to the residual tumor (R) descriptor proposed by the International Association for the Study of Lung Cancer (IASLC). Materials and Methods: From 2004 to 2021, patients with pN2 NSCLC who underwent anatomical resection were analyzed according to the IASLC R criteria using medical records from a single center. Survival analysis was performed using Cox proportional hazards models. Recurrence patterns between complete (R0) and uncertain resections (R[un]) were compared. Results: In total, 1,373 patients were enrolled in this study: 576 (42.0%) in R0, 286 (20.8%) in R(un), and 511 (37.2%) in R1/R2 according to the IASLC R criteria. The most common reason for R(un) classification was positivity for the highest lymph node (88.8%). In multivariable analysis, the hazard ratios for recurrence in R(un) and R1/R2 compared to R0 were 1.18 (95% confidence interval [CI], 0.96-1.46) and 1.58 (1.31-1.90), respectively. The hazard rate curves displayed similar patterns among groups, peaking at approximately 12 months after surgery. There was a significant difference in distant recurrence patterns between R0 and R(un). Further analysis after stratification with the IASLC N2 descriptor showed significant differences in distant recurrence patterns between R0 and R(un) in patients pN2a1 and pN2a2 disease, but not in those with pN2b disease. Conclusion: The IASLC R criteria has prognostic relevance in patients with pN2 NSCLC. R(un) is a highly heterogeneous group, and the involvement of the highest mediastinal lymph node can affect distant recurrence patterns.

Expansion of tumor-infiltrating lymphocytes in non-small cell lung cancer: Clinical potential and efficacy in EGFR mutation subsets.

Our study aimed to expand tumor-infiltrating lymphocytes (TILs) from primary non-small cell lung cancers (NSCLCs) and evaluate their reactivity against tumor cells. We expanded TILs from 103 primary NSCLCs using histopathological analysis, flow cytometry, IFN-γ release assays, cell-mediated cytotoxicity assays, and in vivo efficacy tests. TIL expansion was observed in all cases, regardless of EGFR mutation status. There was also an increase in the median CD4+/CD8+ ratio during expansion. In post-rapid expansion protocol (REP) TILs, 13 out of 16 cases, including all three cases with EGFR mutations, exhibited a two-fold or greater increase in IFN-γ secretion. The cytotoxicity assay revealed enhanced tumor cell death in three of the seven cases, two of which had EGFR mutations. In vivo functional testing in a patient-derived xenograft model showed a reduction in tumor volume. The anti-tumor activity of post-REP TILs underscores their potential as a therapeutic option for advanced NSCLC, irrespective of mutation status.

Outcomes of Lung Transplantation in Patients With Right Ventricular Dysfunction: A Single-Center Retrospective Analysis Comparing ECMO Configurations in a Bridge-to-Transplant Setting.

This study aimed to assess the lung transplantation (LT) outcomes of patients with right ventricular dysfunction (RVD), focusing on the impact of various extracorporeal membrane oxygenation (ECMO) configurations. We included adult patients who underwent LT with ECMO as a bridge-to-transplant from 2011 to 2021 at a single center. Among patients with RVD (n = 67), veno-venous (V-V) ECMO was initially applied in 79% (53/67) and maintained until LT in 52% (35/67). Due to the worsening of RVD, the configuration was changed from V-V ECMO to veno-arterial (V-A) ECMO or a right ventricular assist device with an oxygenator (Oxy-RVAD) in 34% (18/67). They showed that lactic acid levels (2-6.1 mmol/L) and vasoactive inotropic score (6.6-22.6) increased. V-A ECMO or Oxy-RVAD was initiated and maintained until LT in 21% (14/67) of cases. There was no significant difference in the survival rates among the three configuration groups (V-V ECMO vs. configuration changed vs. V-A ECMO/Oxy-RVAD). Our findings suggest that the choice of ECMO configuration for LT candidates with RVD should be determined by the patient's current hemodynamic status. Vital sign stability supports the use of V-V ECMO, while increasing lactic acid levels and vasopressor needs may require a switch to V-A ECMO or Oxy-RVAD.

Distinguishing thymic cysts from low-risk thymomas via [18F]FDG PET/CT.

BACKGROUND: Thymic cysts are a rare benign disease that needs to be distinguished from low-risk thymoma. [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is a non-invasive imaging technique used in the differential diagnosis of thymic epithelial tumours, but its usefulness for thymic cysts remains unclear. Our study evaluated the utility of visual findings and quantitative parameters of [18F]FDG PET/CT for differentiating between thymic cysts and low-risk thymomas. METHODS: Patients who underwent preoperative [18F]FDG PET/CT followed by thymectomy for a thymic mass were retrospectively analyzed. The visual [18F]FDG PET/CT findings evaluated were PET visual grade, PET central metabolic defect, and CT shape. The quantitative [18F]FDG PET/CT parameters evaluated were PET maximum standardized uptake value (SUVmax), CT diameter (cm), and CT attenuation in Hounsfield units (HU). Findings and parameters for differentiating thymic cysts from low-risk thymomas were assessed using Pearson's chi-square test, the Mann-Whitney U-test, and receiver operating characteristics (ROC) curve analysis. RESULTS: Seventy patients (18 thymic cysts and 52 low-risk thymomas) were finally included. Visual findings of PET visual grade (P < 0.001) and PET central metabolic defect (P < 0.001) showed significant differences between thymic cysts and low-risk thymomas, but CT shape did not. Among the quantitative parameters, PET SUVmax (P < 0.001), CT diameter (P < 0.001), and CT HU (P = 0.004) showed significant differences. In ROC analysis, PET SUVmax demonstrated the highest area under the curve (AUC) of 0.996 (P < 0.001), with a cut-off of equal to or less than 2.1 having a sensitivity of 100.0% and specificity of 94.2%. The AUC of PET SUVmax was significantly larger than that of CT diameter (P = 0.009) and CT HU (P = 0.004). CONCLUSIONS: Among the [18F]FDG PET/CT parameters examined, low FDG uptake (SUVmax ≤ 2.1, equal to or less than the mediastinum) is a strong diagnostic marker for a thymic cyst. PET visual grade and central metabolic defect are easily accessible findings.

Validation Study for the N Descriptor of the Newly Proposed Ninth Edition of the TNM Staging System Proposed by the International Association for the Study of Lung Cancer.

INTRODUCTION: The aim of this study was to validate the discriminatory ability and clinical utility of the N descriptor of the newly proposed ninth edition of the TNM staging system for lung cancer in a large independent cohort. METHODS: We retrospectively analyzed patients who underwent curative surgery for NSCLC between January 2004 and December 2019. The N descriptor of patients included in this study was retrospectively reclassified based on the ninth edition of the TNM classification. Survival analysis was performed using the log-rank test and Cox proportional hazard model to compare adjacent N categories. RESULTS: A total of 6649 patients were included in this study. The median follow-up period was 54 months. According to the newly proposed ninth edition N classification, 5573 patients (83.8%), 639 patients (9.6%), 268 patients (4.0%), and 169 patients (2.5%) were classified into the clinical N0, N1, N2a, and N2b categories and 4957 patients (74.6%), 744 patients (11.2%), 567 patients (8.5%), and 381 patients (5.7%) were classified into the pathologic N0, N1, N2a, and N2b categories, respectively. The prognostic differences between all adjacent clinical and pathologic N categories were highly significant in terms of both overall survival and recurrence-free survival. CONCLUSIONS: We validated the clinical utility of the newly proposed ninth edition N classification for both clinical and pathologic stages in NSCLC. The new N classification revealed clear prognostic separation between all categories (N0, N1, N2a, and N2b) in terms of both overall survival and recurrence-free survival.

Clinical impact of pre-existing acute exacerbation in patients with interstitial lung disease who underwent lung transplantation.

BACKGROUND: Acute exacerbation of interstitial lung disease (AE-ILD) significantly impacts prognosis, leading to high mortality rates. Although lung transplantation is a life-saving treatment for selected patients with ILD, its outcomes in those presenting with AE-ILD have yielded conflicting results compared with those with stable ILD. This study aims to investigate the impact of pre-existing AE on the prognosis of ILD patients who underwent lung transplantation. METHOD: We conducted a single-center retrospective study by reviewing the medical records of 108 patients who underwent lung transplantation for predisposing ILD at Asan Medical Center, Seoul, South Korea, between 2008 and 2022. The primary objective was to compare the survival of patients with AE-ILD at the time of transplantation with those without AE-ILD. RESULTS: Among the 108 patients, 52 (48.1%) experienced AE-ILD at the time of lung transplantation, and 81 (75.0%) required pre-transplant mechanical ventilation. Although the type of ILD (IPF vs. non-IPF ILD) did not affect clinical outcomes after transplantation, AE-ILD was associated with worse survival outcomes. The survival probabilities at 90 days, 1 year, and 3 years post-transplant for patients with AE-ILD were 86.5%, 73.1%, and 60.1%, respectively, while those for patients without AE-ILD were higher, at 92.9%, 83.9%, and 79.6% (p = 0.032). In the multivariable analysis, pre-existing AE was an independent prognostic factor for mortality in ILD patients who underwent lung transplantation. CONCLUSIONS: Although lung transplantation remains an effective treatment option for ILD patients with pre-existing AE, careful consideration is needed, especially in patients requiring pre-transplant mechanical respiratory support.

Pre-operative clonal hematopoiesis is related to adverse outcome in lung cancer after adjuvant therapy.

BACKGROUND: Clonal hematopoiesis (CH) frequently progresses after chemotherapy or radiotherapy. We evaluated the clinical impact of preoperative CH on the survival outcomes of patients with non-small cell lung cancer (NSCLC) who underwent surgical resection followed by adjuvant therapy. METHODS: A total of 415 consecutive patients with NSCLC who underwent surgery followed by adjuvant therapy from 2011 to 2017 were analyzed. CH status was evaluated using targeted deep sequencing of blood samples collected before surgery. To minimize the possible selection bias between the two groups according to CH status, a propensity score matching (PSM) was adopted. Early-stage patients were further analyzed with additional matched cohort of patients who did not receive adjuvant therapy. RESULTS: CH was detected in 21% (86/415) of patients with NSCLC before adjuvant therapy. Patients with CH mutations had worse overall survival (OS) than those without (hazard ratio [95% confidence interval] = 1.56 [1.07-2.28], p = 0.020), which remained significant after the multivariable analysis (1.58 [1.08-2.32], p = 0.019). Of note, the presence of CH was associated with non-cancer mortality (p = 0.042) and mortality of unknown origin (p = 0.018). In patients with stage IIB NSCLC, there was a significant interaction on OS between CH and adjuvant therapy after the adjustment with several cofactors through the multivariable analysis (HR 1.19, 95% CI 1.00-1.1.41, p = 0.041). CONCLUSIONS: In resected NSCLC, existence of preoperative CH might amplify CH-related adverse outcomes through adjuvant treatments, resulting in poor survival results.

What is the benefit of preserving the superior segment in anatomical thoracoscopic resections of the lower lobe?

Background: The beneficial effect of preserved superior segment (S6) after common basal segmentectomy remains unknown. We aimed to evaluate the effect of preserved superior segment on lung volume and function. Methods: Among 671 segmentectomies and 2,249 lobectomies for clinical stage IA lung cancer between 2004 and 2020, 48 patients who received thoracoscopic common basal segmentectomy were included and compared with 96 patients who received thoracoscopic lower lobectomy after propensity score matching. The variables analyzed were age, sex, comorbidity, smoking history, preoperative forced expiratory volume in one second (FEV1), clinical T stage, histology, and tumor location. Lung volume was assessed using a three-dimensional (3D) computed tomography (CT)-based volumetric method. Results: There were no significant differences between common basal segmentectomy (segmentectomy group) and lower lobectomy (lobectomy group) (4,183.8±1,114.9 versus 3,850.7±1,132.1 mL; P=0.10) in terms of preoperative CT-measured total lung volume. At the immediate postoperative median follow-up period (6.4 months), the reduced percentage of CT-measured total lung volume in the segmentectomy group was significantly larger than that in the lobectomy group (-16.2% versus -6.5%; P=0.004). The percentage of CT-measured contralateral lung volume expansion in the segmentectomy group was significantly smaller than that in the lobectomy group (-0.7% versus +8.9%; P=0.006). At the last median follow-up period (43.1 months), the reduced percentage of CT-measured total lung volume in the segmentectomy group remained larger than that in the lobectomy group (-13.0% versus -3.0%; P=0.01). The reduced percentage of postoperative FEV1 in the segmentectomy group did not differ from that in the lobectomy group (-9.9% versus -11.5%, P=0.63). Conclusions: Preserving the superior segment might not provide beneficial effect on the preservation of postoperative lung volume and function after common basal segmentectomy compared with lower lobectomy.

E3 ligase SOCS3 regulates NOD2 expression by ubiquitin proteasome system in lung cancer progression.

PURPOSE: Despite lung cancer is one of the leading causes of cancer-related deaths, it remains hard to discover effective diagnostic and therapeutic approaches. Moreover, the five-year survival rate is relatively lower than other tumors. So urgent needs for finding a new theranostic target to treat lung cancer effectively. This study aims to present SOCS3 and NOD2 proteins as novel targets for diagnosis and therapy. METHODS: We first confirmed SOCS3 expression level in patients' tissues. Then, we applied knockdown and overexpression of SOCS3 on lung cancer cell lines and performed proliferation, migration, and invasion assay. After that, we found NOD2 is a target of SOCS3 and introduced overexpression of NOD2 to A549 for verifying reduced tumorigenicity of lung cancer cells. RESULTS: We identified protein expression level of SOCS3 was frequently higher in tumor tissues than adjacent normal tissues. Truly, overexpression of SOCS3 promoted proliferation, migration, and invasion capacity of lung cancer cells. We found that SOCS3 interacts with NOD2 and SOCS3 ubiquitinates NOD2 directly. Furthermore, lung cancer tissues with higher SOCS3 expression showed lower NOD2 expression. We confirmed overexpression of NOD2 leads to suppressed tumorigenicity of lung cancer cells, and these effects occurred through MAPK pathway. CONCLUSION: Collectively, our work reveals novel roles of SOCS3 in lung tumorigenesis and proposes SOCS3 as a promising biomarker candidate for therapeutic and diagnostic target for lung cancer.

[18F]fluorodeoxyglucose positron emission tomography/computed tomography characteristics of primary mediastinal germ cell tumors.

Primary mediastinal germ cell tumor (MGCT) is an uncommon tumor. Although it has histology similar to that of gonadal germ cell tumor (GCT), the prognosis for MGCT is generally worse than that for gonadal GCT. We performed visual assessment and quantitative analysis of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) for MGCTs. A total of 35 MGCT patients (age = 33.1 ± 16.8 years, F:M = 16:19) who underwent preoperative PET/CT were retrospectively reviewed. The pathologic diagnosis of MGCTs identified 24 mature teratomas, 4 seminomas, 5 yolk sac tumors, and 2 mixed germ cell tumors. Visual assessment was performed by categorizing the uptake intensity, distribution, and contour of primary MGCTs. Quantitative parameters including the maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum diameter were compared between benign and malignant MGCTs. On visual assessment, the uptake intensity was the only significant parameter for differentiating between benign and malignant MGCTs (p = 0.040). In quantitative analysis, the SUVmax (p < 0.001), TBR (p < 0.001), MTV (p = 0.033), and TLG (p < 0.001) showed significantly higher values for malignant MGCTs compared with benign MGCTs. In receiver operating characteristic (ROC) curve analysis of these quantitative parameters, the SUVmax had the highest area under the curve (AUC) (AUC = 0.947, p < 0.001). Furthermore, the SUVmax could differentiate between seminomas and nonseminomatous germ cell tumors (p = 0.042) and reflect serum alpha fetoprotein (AFP) levels (p = 0.012). The visual uptake intensity and SUVmax on [18F]FDG PET/CT showed discriminative ability for benign and malignant MGCTs. Moreover, the SUVmax may associate with AFP levels.

Cancer-Related Dysfunctional Beliefs About Sleep Mediate the Influence of Sleep Disturbance on Fear of Progression Among Patients With Surgically Resected Lung Cancer.

BACKGROUND: Lung cancer is associated with significant psychological distress, including fear of progression (FoP). Because insomnia and depression are highly prevalent and associated with FoP, we examined the association between FoP, insomnia, and depression in cancer patients. Furthermore, we tested the mediation effect of cancer-related dysfunctional beliefs about sleep (C-DBS) on this association. METHODS: We analyzed data collected from patients with surgically resected non-small cell lung cancer from a single-center randomized controlled study investigating digital healthcare applications. Baseline demographic and clinical variables were collected. In addition, self-reported questionnaires including the Fear of Progression Questionnaire-Short Form, Patients Health Questionnaire-9 items (PHQ-9), Insomnia Severity Index, and C-DBS were administered. RESULTS: Among the 320 enrolled patients with lung cancer, a regression model showed that FoP was predicted by age (ß = -0.13, P = 0.007), PHQ-9 (ß = 0.35, P < 0.001), and C-DBS (ß = 0.28, P < 0.001). Insomnia did not directly influence FoP, but C-DBS mediated the association. Depression directly influenced FoP, but C-DBS did not mediate this association. CONCLUSION: Among patients with surgically resected lung cancer, C-DBS mediated the effects of severity of insomnia on FoP. Depression directly influenced FoP, but C-DBS did not influence this association. To reduce FoP among patients with lung cancer, C-DBS should be addressed in the cognitive behavioral therapy module.

Prognostic significance of extranodal extension in patients with pathologic N1 non-small cell lung cancer undergoing complete resection.

Background: The prognostic significance of extranodal extension (ENE) remains unclear in patients with pathologic N1 (pN1) non-small-cell lung cancer (NSCLC) undergoing surgery. We evaluated the prognostic impact of ENE in patients with pN1 NSCLC. Methods: From 2004 to 2018, we retrospectively analyzed the data of 862 patients with pN1 NSCLC who underwent lobectomy and more (lobectomy, bilobectomy, pneumonectomy, sleeve lobectomy). According to their resection status and the presence of ENE, patients were classified into R0 without ENE (pure R0) (n=645), R0 with ENE (R0-ENE) (n=130), and incomplete resection (R1/R2) groups (n=87). The primary and secondary endpoints were 5-year overall survival (OS) and recurrence-free survival (RFS), respectively. Results: The prognosis of the R0-ENE group was significantly worse than the pure R0 group for both OS (5-year rate: 51.6% vs. 65.4%, P=0.008) and RFS (44.4% vs. 53.0%, P=0.04). According to the recurrence pattern, a difference of RFS was found only for distant metastasis (55.2% vs. 65.0%, P=0.02). The multivariable Cox analysis revealed that the presence of ENE was a negative prognostic factor in patients who did not undergo adjuvant chemotherapy [hazard ratio (HR) =1.58; 95% confidence interval (CI): 1.06-2.36; P=0.03], but it was not in those with adjuvant chemotherapy (HR =1.20; 95% CI: 0.80-1.81; P=0.38). Conclusions: For patients with pN1 NSCLC, the presence of ENE was a negative prognostic factor for both OS and RFS, regardless of resection status. The negative prognostic effect of ENE was significantly associated with an increase in distant metastasis and was not observed in patients who underwent adjuvant chemotherapy.

Concurrent Killian-Jamieson and Zenker's Diverticula.

Pharyngoesophageal diverticula are rare causes of dysphagia. Zenker's diverticulum is the most common type, followed by Killian-Jamieson diverticulum. A 44-year-old male presented to our clinic with a longstanding history of dysphagia and globus sensation. Bilateral pharyngoesophageal diverticula were confirmed by imaging CT and esophagogastroscopy. He underwent transcervical resection, and a right Killian-Jamieson diverticulum was observed during surgery. The left diverticulum was found to originate above the cricopharyngeus muscle and was labeled as Zenker's diverticulum. Bilateral pharyngoesophageal diverticula are rare, and physicians should be aware of the variable clinical presentations and management options for pharyngoesophageal diverticula.

Total En Bloc Spondylectomy of C7 Vertebrae for Primary Bone Tumors: The Efficacy of Autologous Sternal Structural Grafts.

AIM: To evaluate the efficacy and safety of total en bloc spondylectomy with autologous sternal structural graft, subaxial pedicle screws, and 5.5 mm titanium rods in primary bone tumor surgery. MATERIAL AND METHODS: From January 2019 to February 2020, two patients with lower cervical spine (C7) primary bone tumor underwent total en bloc spondylectomy, interbody fusion with sternal structural autograft, and posterior instrumentation using subaxial pedicle screws. The medical records and radiographic findings of the patients were reviewed. RESULTS: C7 total en bloc spondylectomy was successfully performed; the anterior column was reconstructed with an autologous sternal structural graft with posterior instrumentation using subaxial pedicle screws and 5.5 mm titanium rods. After surgery, the VAS scores of neck and radiating arm pain in both patients were relieved considerably. Bony fusion was achieved in all patient by 6 months after surgery. There were no postoperative complications associated with the donor site. CONCLUSION: Structural bone obtained from the sternum is safe and provides a viable alternative to cervical fusion for patients with primary bone tumor. It confers the advantages of autograft fusion without the complications associated with donor site morbidities.

Evaluation of Chylothorax Using Dynamic Contrast-Enhanced Magnetic Resonance Lymphangiography After Lung Cancer Surgery.

Background: To determine the role of dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) in the management of postoperative chylothorax after lung cancer surgery. Methods and Results: Between July 2017 and November 2021, patients who developed postoperative chylothorax following pulmonary resection and mediastinal lymph node dissection were assessed and those who underwent DCMRL for the evaluation of chyle leak were evaluated. The findings of DCMRL and conventional lymphangiography were compared. The incidence of postoperative chylothorax was 0.9% (50/5587). Among the patients with chylothorax, a total of 22 patients (44.0% [22/50]; mean age, 67.6 ± 7.9 years; 15 men) underwent DCMRL. Treatment outcomes were compared between patients with conservative management (n = 10) and those with intervention (n = 12). The patients demonstrated unilateral pleural effusion, ipsilateral to the operation site, and showed right-sided dominance. The most frequent site of thoracic duct injury showing contrast media leakage was visualized at the subcarinal level. No DCMRL-related complication occurred. DCMRL showed comparable performance to conventional lymphangiography in visualizing the central lymphatics, including cisterna chyli (DCMRL vs. conventional lymphangiography, 72.7% vs. 45.5%, p = 0.25) and thoracic duct (90.9% vs. 54.5%, p = 0.13), and in localizing thoracic duct injury (90.9% vs. 54.5%, p = 0.13). On follow-up, the amount of chest tube drainage after lymphatic intervention showed a significant difference over time from that after medical treatment only (p = 0.02). Conclusion: DCMRL can provide detailed information about the leak site and the central lymphatic anatomy in patients with chylothorax after lung cancer surgery. The findings of DCMRL can guide subsequent treatment planning for optimal outcomes.