Different Role of TRF1 and TRF2 Expression in Non-Small Cell Lung Cancers.

Background: TRF1, TRF2, and TERT (Telomerase reverse transcriptase) are telomere-associated factors that regulate telomere length. Genetic changes in these genes may be associated with cancer pathogenesis; however, this relationship has not yet been comprehensively elucidated in lung cancer. Aim: : Exploring the clinicopathologic and prognostic values of TRF1, TRF2, and TERT mRNA expression in non-small cell lung cancers (NSCLC). Methods: : The clinical significance of TRF1, TRF2, and TERT expression in 141 patients with NSCLC was investigated. Additionally, these findings were supported by the open big data from The Cancer Genome Atlas (TCGA). Results: : TRF1 and TRF2 expression levels tended to be associated with smoking, and TERT expression was positively correlated with age. The survival analysis showed that TRF1 expression predicted a better prognosis for squamous cell carcinoma (SCC), whereas TRF2 expression was associated with a shorter survival in adenocarcinoma. TCGA data also showed a better prognosis for SCC with TRF1 expression. However, the TRF2 results were not in agreement with our data. Conclusions: : We present the clinical and prognostic values of TRF1, TRF2, and TERT expression in NSCLC tissues and TCGA. Our findings suggest that TRF1 expression is a possible prognostic marker for NSCLC, particularly SCC.

Clinical impact of pleural fluid carcinoembryonic antigen on therapeutic strategy and efficacy in lung adenocarcinoma patients with malignant pleural effusion.

BACKGROUND/AIMS: Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. METHODS: This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10-100 ng/mL, 100-500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. RESULTS: This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. CONCLUSION: High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.

Clinical characteristics and course of pulmonary artery stump thrombosis following lung cancer surgery: A retrospective study from tertiary care hospital.

The data regarding pulmonary artery stump thrombosis (PAST) after lung cancer surgery are insufficient. The aim of the present study was to evaluate the incidence, clinical characteristics, and prognosis of PAST. We retrospectively investigated the incidence and clinical characteristics of PAST among patients who underwent lung resection for lung cancer at 2 institutions. We compared the clinical parameters between PAST and pulmonary embolism (PE) and examined the clinical course of patients with PAST. Of the 1885 patients, PAST was found in 36 patients (1.9%). Right lower lobectomy (n = 13) and middle-lower bilobectomy (n = 9) were the most common types of surgery. The median time interval from lung resection to the detection of PAST was 3.8 months. Immobilization and a history of cerebrovascular disease were not observed in the PAST group. Most of the patients with PAST (91.7%) were diagnosed incidentally, whereas many patients with PE (75.9%) were symptomatic at the time of diagnosis. During the follow-up, one patient (2.8%) had contralateral PE complications. However, no patients in the PAST group experienced pulmonary thromboembolism-related in-hospital death or adverse outcomes. There was no difference in the prognosis of patients with PAST according to the administration of anticoagulation. PAST was rarely detected in lung cancer patients on follow-up chest computed tomography after lung resection. Patients with PAST were asymptomatic in most cases and had relatively favorable clinical outcomes. However, these patients are at risk of contralateral PE, despite its rarity.

Bilateral Cardiac Sympathetic Denervation as a Safe Therapeutic Option for Ventricular Arrhythmias.

Background: The recurrence of ventricular arrhythmias (VAs) in patients who have already undergone treatment with antiarrhythmic medication, catheter ablation, and the insertion of implantable cardioverter defibrillators is not uncommon. Recent studies have shown that bilateral cardiac sympathetic denervation (BCSD) effectively treats VAs. However, only a limited number of studies have confirmed the safety of BCSD as a viable therapeutic option for VAs. Methods: This single-center study included 10 patients, who had a median age of 54 years (interquartile range [IQR], 45-65 years) and a median ejection fraction of 58.5% (IQR, 56.2%-60.8%), with VAs who underwent video-assisted BCSD. BCSD was executed as a single-stage surgery for 8 patients, while the remaining 2 patients initially underwent left cardiac sympathetic denervation followed by right cardiac sympathetic denervation. We evaluated postoperative complications, the duration of hospital stays, and VA-related symptoms before and after surgery. Results: The median hospital stay after surgery was 2 days (IQR, 2-3 days). The median surgical time for BCSD was 113 minutes (IQR, 104-126 minutes). No significant complications occurred during hospitalization or after discharge. During the median follow-up period of 13.5 months (IQR, 10.5-28.0 months) from surgery, no VA-related symptoms were observed in 70% of patients. Conclusion: The benefits of a short postoperative hospitalization and negligible complications make BCSD a safe, alternative therapeutic option for patients suffering from refractory VAs.

Surgical Catheterization for Continuous Serratus Anterior Plane Block after Thoracoscopic Lobectomy: A Report of 3 Cases.

Serratus anterior plane block (SAPB) has been used for perioperative pain control during video-assisted thoracoscopic surgery (VATS), and the effects of continuous SAPB have been studied. This procedure is usually performed by the anesthesiologist; however, it could be performed more simply and safely by the thoracic surgeon through the use of meticulous finger dissection to create a space in the deep serratus anterior plane during surgery. We describe 3 cases of surgical catheterization for continuous SAPB in patients with lung cancer during VATS lobectomy, in which postoperative pain was effectively reduced.

Pulmonary vein stump thrombosis after lung resection for lung cancer: clinical features and outcome.

Pulmonary vein stump thrombosis (PVST) is uncommonly encountered postoperative in-situ thrombosis in the stump of pulmonary veins after lung resection. Data regarding the incidence and clinical behaviour of PVST are scarce. Thus, this study aims to investigate the incidence, clinical characteristics and outcome of PVST after lung resection in patients with lung cancer. Follow-up enhanced chest computed tomography (CT) scans acquired after the surgery were retrospectively reviewed to determine PVST presence for patients with lung cancer who underwent lung resection in two tertiary referral centres. Out of the 1885 patients with lung cancer who underwent lobectomy or more extensive lung resection, PVST was observed in 37 patients (2.0%) on their follow-up chest CT. Most stump thrombi were observed in the left superior pulmonary vein [35 (94.6%)] and in patients who underwent left upper lobectomy [34 (91.9%)]. At the last CT follow-up of each patient, 33 (89.2%) exhibited complete resolution, three partial resolution and one stabilization. Eleven (29.7%) patients received anticoagulant therapy after the diagnosis. The rate of complete PVST resolution did not differ significantly between the anticoagulation and nonanticoagulation groups. None of the PVST patients experienced systemic embolic events, regardless of anticoagulation. The PVST incidence diagnosed at routine chest CT follow-up following lung cancer surgery was 2%. PVST was characterized by a benign clinical course without progression and systemic embolization, regardless of anticoagulation. However, further studies are required to determine individualized therapeutic strategies, including anticoagulation.

Prognostic Value of Telomeric Zinc Finger-Associated Protein Expression in Adenocarcinoma and Squamous Cell Carcinoma of Lung.

Background and Objectives: Telomeric zinc finger-associated protein (TZAP) is a telomere regulation protein, previously known as ZBTB48. It binds preferentially to elongated telomeres, competing with telomeric repeat factors 1 and 2. TZAP expression may be associated with carcinogenesis, however; this study has not yet been performed in lung cancer. In this study, we examined the clinicopathological and prognostic values of TZAP expression in non-small cell lung cancer (NSCLC). Materials and Methods: Data were collected from The Cancer Genome Atlas. The clinical and prognostic values of TZAP for NSCLC were examined in adenocarcinoma (AD) and squamous cell carcinoma (SCC). Results: TZAP expression significantly increased in NSCLC tissues compared with normal tissues. In AD, TZAP expression was lower in patients with higher T stage (p = 0.005), and was associated with lymph node stage in SCC (p = 0.005). Survival analysis showed shorter disease-free survival in AD patients with lower TZAP expression (p = 0.047). TZAP expression did not have other clinical or prognostic value for AD and SCC. Conclusions: TZAP expression is a potential prognostic marker for NSCLC, especially in patients with AD.

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.

Serratus anterior plane block versus intercostal nerve block for postoperative analgesic effect after video-assisted thoracoscopic lobectomy: A randomized prospective study.

BACKGROUND: Serratus anterior plane block (SAPB) and intercostal nerve block (ICNB) are attractive options for multimodal analgesia in patients undergoing thoracoscopic surgery, but which block is superior remains unclear. OBJECTIVE: The present study aimed to assess the effect of SAPB versus ICNB on reducing postoperative pain after video-assisted thoracoscopic surgery (VATS) for lobectomy. METHODS: This prospective, randomized, active-intervention-controlled, subject-assessor-blinded, single-center, parallel-group trial allocated 18- to 80-year-old patients with American Society of Anesthesiologists status I to III to receive either SAPB or ICNB in a 1:1 ratio. The primary outcome was numerical pain rating scale (NRS) scores during the first 24 hours postoperatively. The secondary outcomes were postoperative cumulative doses of ketorolac and fentanyl, and the occurrence of postoperative adverse effects. RESULTS: Among the 57 patients assessed for eligibility, 50 were randomly assigned in a 1:1 ratio. Due to conversion to open thoracotomy and patient-controlled analgesia pump failure, 4 patients were excluded and 46 were analyzed. The intergroup differences in NRS scores were not statistically significant at any time point. Cumulative consumptions of fentanyl and ketorolac were also not significantly different. No perioperative adverse events occurred. Postoperative complications were also absent, except for nausea (2/23 patients [8.7% in both groups]). CONCLUSION: Results of the present study do not clarify whether SAPB or ICNB has a superior effect on reducing pain after VATS, thereby suggesting they may exert similar analgesic effects.

Anatomical resection of lung cancer with isolated left bronchial isomerism: a case report with long-term follow-up.

An isolated bronchial isomerism without accompanying malformations is known to be very rare and has little clinical problems. There are a few case reports demonstrating that the bronchial isomerism is incidentally found during lung cancer evaluations or surgeries, but none of them have reported the long-term outcomes after lung cancer surgeries. Thoracic surgeons should fully identify the anatomical details of the bronchial isomerism preoperatively to avoid unexpected resection of the wrong bronchi or pulmonary vessels. Herein, we report a rare case of an isolated left bronchial isomerism that was diagnosed preoperatively; the patient safely underwent anatomical pulmonary resection due to lung cancer in the right upper lobe and who has been followed up for >5 years.

Patch aortoplasty and anatomical lung resection in a patient with aortobronchial fistula due to aortic psuedo-aneurysm.

Aortobronchial fistula (ABF) is a rare and devastating complication, if left untreated. Its main clinical manifestation is hemoptysis, and there are no defined guidelines for its treatment yet. Herein, we present the case of a 74-year-old male who complained of back pain and hemoptysis. The patient was diagnosed with pseudo-aneurysm and ABF, and he underwent hybrid thoracic endovascular aortic repair. However, hemoptysis recurred. With patch aortoplasty and anatomical lung resection, successful management of ABF was achieved, with no relapse for 5 years.

The Prognostic Significance of TERT Locus Polymorphism (rs36115365) in Surgically Resected Non-Small Cell Lung Cancer.

OBJECTIVE: Telomere length is an important factor for the development of non-small cell lung cancer (NSCLC), and current articles focused on telomere associated genes. We studied the clinicopathological and prognostic implications of rs36115365 polymorphism of the TERT-CLPTM1L locus in NSCLC. The association between rs36115365 and telomere length was investigated in 176 NSCLCs. METHODS: DNA was extracted from NSCLC tissues and polymorphism and telomere length were analyzed. RESULTS: The rs36115365 polymorphism showed the following frequencies according to the genotype: G/G in 81.8% of the patients, G/C in 14.2%, and C/C in 4.0%. Average telomere length in the tumor tissues were 3.06-fold longer than telomeres in paired non-tumor tissues (SD=1.87), and telomere length was not significantly different according to rs36115365 (p=0.134). The rs36115365 polymorphism did not have any relationships with clinicopathological characteristics. A poor overall survival result was found in NSCLC with C allele carriers than that with G/G allele (p=0.034). However, disease free survival rate was not different statistically (p=0.938). CONCLUSIONS: These findings suggest that rs36115365 may contribute to the progression of NSCLC.

Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival.

The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named "double-agent" genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 "double-agent" genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels of Ccna genes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development.

Idiopathic Pleural Effusions: Characteristics and Discrimination From Cytology-Negative Malignant Pleural Effusions.

BACKGROUND: The etiology of pleural effusions often remained unknown notwithstanding surgical pleural biopsy and further clinical observation. A better understanding of clinical characteristics of patients with idiopathic pleural effusion (IPE) may improve the ability to differentiate between IPEs and cytology-negative malignant pleural effusions (MPEs) and facilitate the identification of patients requiring invasive investigation. However, little is known about the clinical factors that can help distinguish patients with IPE from those with cytology-negative MPE. MATERIALS AND METHODS: Patients who were diagnosed with IPE or cytology-negative MPE between 2010 and 2017 were enrolled in this retrospective study. Clinical, laboratory and radiologic characteristics were compared between patients with IPE and cytology-negative MPE. Diagnostic performances of predictors for IPE were assessed using receiver operating characteristic curves. RESULTS: Of 146 patients undergoing pleural biopsy owing to cytology-negative pleural effusion of uncertain cause, MPE was confirmed in 54 patients. IPE was ultimately diagnosed in 22 patients. Multivariate analysis demonstrated that a minimal amount of pleural effusion (odds ratio [OR] = 12.41, P = 0.039), presence of pleural nodularity (OR = 0.01, P < 0.001) and pleural fluid carcinoembryonic antigen levels less than 14 ng/mL (OR = 87.59, P = 0.002) were independent factors for distinguishing IPEs from cytology-negative MPEs. A combination of the absence of pleural nodularity with pleural fluid carcinoembryonic antigen levels less than 14 ng/mL yielded an area under the curve of 0.94 (sensitivity = 91% and specificity = 96%). CONCLUSIONS: Using these readily available parameters to identify IPE in patients with cytology-negative exudative effusion of unknown cause can help guide decision-making when choosing to perform an invasive pleural biopsy or to take a conservative approach.

Characteristics and survival impact of polymorphonuclear leucocyte-predominant malignant pleural effusions secondary to lung cancer.

INTRODUCTION: In comparison with mononuclear leucocyte (MNL)-predominant malignant pleural effusions (MPEs), polymorphonuclear leucocyte (PMNL)-predominant MPEs have rarely been investigated and may be associated with a poorer prognosis. OBJECTIVES: To investigate the characteristics and survival impact of PMNL-predominant MPEs secondary to lung cancer. METHODS: This retrospective study included patients with MPE secondary to lung cancer, which were classified into the PMNL- and MNL-predominant groups according to cellular predominance in the pleural fluid. Clinical, hematological, radiological, and pleural fluid data were compared between the groups, and the survival impact of PMNL predominance in MPE was evaluated. RESULTS: Of the 193 MPEs included, 37 (19%) were characterised by PMNL predominance. Compared to the MNL-predominant group, the PMNL-predominant group showed significantly poorer patient performances (P = .001), higher white blood cell counts (P = .009), higher neutrophil counts, higher blood neutrophil-to-lymphocyte ratio (P = .046), higher serum C-reactive protein (P = .003), lower serum albumin (P < .001), lower pleural fluid pH (P = .002) and higher pleural fluid lactate dehydrogenase (P = .029) levels. In contrast, most clinical and radiological findings, including the duration of symptoms, showed no significant intergroup differences. A shift towards MNL predominance was observed in only 38% of the PMNL-predominant patients who underwent repeat thoracentesis. Overall survival of the PMNL-predominant group was significantly shorter than the MNL-predominant group (P = .003). CONCLUSIONS: PMNL predominance in MPEs secondary to lung cancer may be observed in variable phases with respect to the duration of symptoms and the time of thoracentesis. Overall, PMNL-predominant MPEs were associated with more advanced stages and poorer survival outcomes, compared to MNL-predominant MPEs.

Effective strategy in the treatment of aortobronchial fistula with recurrent hemoptysis.

Aortobronchial fistula (ABF) involves the formation of an abnormal connection between the thoracic aorta and the central airways or the pulmonary parenchyma and is associated with an increased risk of mortality. An ABF typically manifests clinically with symptoms of hemoptysis, and currently, there is a lack of defined guidelines for its treatment. Here, we report the cases of two patients who suffered from recurrent hemoptysis due to ABF with pseudoaneurysm. We propose that removal of the aorta with concomitant lung resection and coverage of the aorta using the pericardial membrane is a definite treatment to lower recurrence of ABF and persistent infection.

Infarction of torsed extralobar pulmonary sequestration in adolescence.

Torsion of pulmonary extralobar sequestration is extremely rare in childhood and adolescence, and as it presents with a variety of symptoms ranging from intermittent pain to fever from infarction, differential diagnosis is necessary. Herein, we report a rare case of 13-year-old girl who presented with abdominal pain and fever was diagnosed as infarction of torsed extralobar pulmonary sequestration. Torsed extralobar pulmonary sequestration was removed by thoracoscopic surgery, and the patient remained in good clinical condition.

The Prognostic Value of Measuring PD-L1 mRNA Expression Levels in Surgically Resected Non-Small Cell Lung Cancer.

The expression of programmed cell death 1-ligand 1 (PD-L1) by tumor cells acts as an immune-checkpoint when it interacts with its receptor on immune cells, effectively preventing the immune system from attacking the tumor. Inhibitors against PD-L1 have shown remarkable therapeutic activity in non-small cell lung cancer (NSCLC); however, the prognostic value of this potential biomarker has yet to be conclusively shown. To investigate the clinicopathological and prognostic value of PD-L1 expression, we examined PD-L1 mRNA levels in surgically resected NSCLC. We compared PD-L1 mRNA expression in tumor and adjacent normal tissue from 71 NSCLC patient samples using real-time polymerase chain reaction. To validate PD-L1 mRNA expression by this method, PD-L1 protein expression by immunohistochemistry was analyzed and their strong correlation was confirmed (r=0.728, P=0.041). PD-L1 mRNA expression was significantly increased in tumor tissue as compared to adjacent normal tissue (P<0.001). Tumor tissue on average expressed 3.72 fold higher levels of PD L1 mRNA compared to normal tissue counterparts, and higher expression levels were found in 25.4% (18/71) of NSCLC samples. PD-L1 mRNA expression levels were not associated with clinicopathological characteristics of NSCLC. However, NSCLC patients with increased PD-L1 mRNA expression have a better prognosis than patients with low levels of PD-L1 mRNA (63.49 months vs. 98.53 months, χ2=3.73, p=0.053). Disease-free survival was 82.23 months and 45.68 months in patients with and without high levels of PD-L1 expression, respectively, although this difference was not significant (χ 2= 3.23, p=0.073). These results suggest that PD-L1 mRNA expression correlates to alterations in NSCLC disease progression; therefore, further comprehensive analyses should be performed.

Successful Treatment Using Endoluminal Vacuum Therapy after Failure of Primary Closure in Boerhaave Syndrome.

Boerhaave syndrome is a transmural perforation of the esophagus and typically occurs after forceful emesis. Boerhaave syndrome is a destructive disease with a high mortality rate, though surgical intervention within 24 hours has a beneficial effect. On the other hand, late surgical intervention is associated with poorer prognoses. Several therapeutic strategies, ranging from medical to surgical management, are available for Boerhaave syndrome. Recently, endoscopic endoluminal vacuum therapy (EVT) was introduced as a treatment option. Here, we report the case of a 56-year-old male patient with Boerhaave syndrome who was successfully treated by EVT after primary closure failure. The patient recovered without complication.