Treatment-related cardiovascular events in patients with non-small cell lung cancer: Evidence from real-world data with a competing risks approach.

BACKGROUND: Understanding cancer treatment-related cardiovascular (CV) events is important for cancer care; however, comprehensive evaluation of CV events in patients with lung cancer is limited. This study aimed to assess the cumulative incidence and associated risks of various CV event types in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 7868 individuals aged 40 years and older, recently diagnosed with NSCLC (2007-2018), were assessed with data obtained from the National Cancer Center, Korea. This study included nine types of CV events. A 2-year cumulative incidence function (CIF) of CV events was estimated, with death as a competing event. The associated risks were assessed by subdistribution hazard ratio (sHR) in the Fine-Gray competing risks model. RESULTS: CV events were observed in 7.8% of patients with NSCLC, with the most frequently observed types being atrial fibrillation and flutter (AF) (2.7%), venous thromboembolic disease (2.0%), and cerebrovascular disease (CeVD) (1.5%). Overall, all CV events were highest in the group treated with systemic therapy (CIF, 10.6%; 95% confidence interval [CI], 9.5%-11.8%), followed by those treated with surgery (CIF, 10.0%; 95% CI, 8.6%-11.6%); the incidence of AF (CIF, 5.7%; 95% CI, 4.6%-7.0%) was highest in patients treated with surgery. Individuals treated with systemic therapy were found to exhibit a higher CeVD risk than those treated with surgery (sHR, 4.12; 95% CI, 1.66-10.23). Among the patients who underwent surgery, those with lobectomy and pneumonectomy had a higher AF risk (vs. wedge resection/segmentectomy; sHR, 7.79; 95% CI, 1.87-32.42; sHR, 8.10; 95% CI, 1.60-40.89). CONCLUSIONS: These findings revealed treatment-related CV event risks in patients with NSCLC, which suggests that the risk of AF in surgery and CeVD in systemic therapy should be paid more attention to achieve a better prognosis and improve cancer survivorship outcomes. PLAIN LANGUAGE SUMMARY: Atrial fibrillation and flutter (AF) is the most common cardiovascular event, particularly at a high risk in patients with non-small cell lung cancer (NSCLC) undergoing surgery. Patients receiving surgery with poor performance status, diagnosed with regional stage, and undergoing lobectomy or pneumonectomy are at a high risk of AF. Systemic/radiotherapy is associated with cerebrovascular and ischemic heart disease in patients with NSCLC.

Clinical Outcomes after Upfront Surgery in Clinical Stage I-IIA Small Cell Lung Cancer.

Background: Upfront surgery followed by systemic treatment is recommended to treat clinical stage I-IIA small cell lung cancer (SCLC), but data on the clinical outcomes are sparse. Thus, this study evaluated the stage migration and long-term prognosis of surgically treated clinical stage I-IIA SCLC. Methods: We retrospectively reviewed 49 patients with clinical stage I-IIA SCLC who underwent upfront surgery between 2000 and 2020. Additionally, we re-evaluated the TNM (tumor-node-metastasis) staging according to the eighth edition of the American Joint Committee on Cancer staging system for lung cancer. Results: The clinical stages of SCLC were cIA in 75.5%, cIB in 18.4%, and cIIA in 6.1% of patients. A preoperative histologic diagnosis was made in 65.3% of patients. Lobectomy and systematic lymph node dissection were performed in 77.6% and 83.7% of patients, respectively. The pathological stages were pI in 67.3%, pII in 24.5%, pIII in 4.1%, and pIV in 4.1% of patients. The concordance rate between clinical and pathological stages was 44.9%, and the upstaging rate was 49.0%. The 5-year overall survival (OS) rate was 67.8%. No significant difference in OS was found between stages pI and pII. However, the OS for stages pIII/IV was significantly worse than for stages pI/II (p<0.001). Conclusion: In clinical stage I-IIA SCLC, approximately half of the patients were pathologically upstaged, and OS was favorable after upfront surgery, particularly in pI/II patients. The poor prognosis of pIII/IV patients indicates the necessity of intensive preoperative pathologic mediastinal staging.

Outcomes of Single-Incision Thoracoscopic Surgery Using the Spinal Needle Anchoring Technique for Primary Spontaneous Pneumothorax.

BACKGROUND: Although classical multi-port video-assisted thoracic surgery has been widely performed, single-incision thoracoscopic surgery (SITS) is a popular surgical technique for the treatment of primary spontaneous pneumothorax (PSP). However, the inconvenient alignment of instruments and the limited field of view occasionally make surgeons convert from SITS to multi-port surgery or extend the incision. This study aimed to present an easy and safe SITS technique for PSP using a spinal needle. METHODS: In total, 139 patients underwent SITS between May 2011 and December 2017. We used a spinal needle to hook the bulla or bleb, and wedge resection was performed through a small incision. Patients' medical records were reviewed retrospectively, and a telephone survey was conducted to investigate the recurrence rate. RESULTS: The mean age of the 139 patients was 23.62±9.60 years. The mean operative time was 36.69±14.64 minutes, and multi-port conversion was not performed. The mean postoperative hospital stay was 3.00±0.78 days, and the mean indwelling chest tube duration was 1.97±0.77 days. No complications were observed. In the mean follow-up period of 86.75±23.20 months, recurrence of pneumothorax was found in 3 patients. CONCLUSION: We suggest that SITS for PSP with the aid of a spinal needle to replace a grasper is a safe and easy technique that only requires a small incision.

Diaphragmatic Hernia with Stomach Rupture after Blunt Chest Trauma at a Short Interval: A Case Report.

Diaphragmatic hernias have been reported in 0.8%-1.6% of patients who experience blunt chest trauma. The hernia is assumed to form as a result of direct diaphragmatic violation or significant intraabdominal or intrathoracic pressure caused by the trauma. Some reports have described cases of delayed diaphragmatic hernia and subsequent stomach perforation that occurred a few days to several years after an accident. We report an extremely rare case of diaphragmatic herniation in which the process from initial blunt trauma to visceral organ perforation took only 2 days, without any evidence of herniation on the initial X-ray or computed tomography. Delayed diaphragmatic herniation and subsequent visceral organ perforation should not be missed during the period immediately after blunt chest trauma.

Isolation and Genomic Analysis of Single Circulating Tumor Cell Using Human Telomerase Reverse Transcriptase and Desmoglein-2.

As epithelial cells in the circulation are considered to originate from the tumor, the epithelial cell adhesion molecule has been commonly used as a standard marker for circulating tumor cells (CTCs) isolation. However, it seems to disappear after the epithelial-mesenchymal transition that most cancer cells undergo for intravasation. Thus, more advanced techniques for CTC detection are needed to better understand the clinical significance of CTCs. A cancer cell-specifically-infecting or replicating virus that codes a fluorescent monitor gene can be a solution to efficiently detect CTCs. Thus, the authors designed an adenovirus to bind to desmoglein-2, which is highly expressed in most cancer cells. A cancer-specific human telomerase reverse transcriptase promoter is inserted to control a viral E1 region. The adenovirus is utilized to compare the number of CTCs from renal cell carcinoma and prostate cancer patients before and after surgery. The isolated two or three CTCs are eligible for whole genome sequencing. The genomic analysis proves the difference of variants between primary tumors and CTCs. Taken together, it is a fast and exact serial method for CTC isolation and the enriched genome sequencing may be used to determine the prognosis and as a point-of-care system for patients with cancer.

Electromagnetic Navigation Bronchoscopy-Guided Dye Marking for Localization of Pulmonary Nodules.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB)-guided dye marking is a useful localization method for small pulmonary nodules. This study evaluated the efficacy and safety of intraoperative full virtual ENB-guided dye marking. METHODS: Patients who underwent full virtual ENB-guided dye marking without adjunct intraoperative imaging (fluoroscopy or cone-beam computed tomography) for small pulmonary nodules were investigated retrospectively. Efficacy was evaluated on the basis of the success rates of dye marking (visible dye mark) and nodule localization, and safety was evaluated on the basis of the rate of ENB-related complications. RESULTS: ENB-guided dye marking was performed on 164 nodules in 134 patients. Twenty-seven patients (20.1%) had multiple nodules. The total number of dye marking attempts was 241, and the mean number of markings per nodule was 1.5 ± 0.7. The mean ENB procedure duration was 29.4 ± 15.7 minutes. No ENB-related complications were observed. The success rate of dye marking was 86.7% (209 of 241) and that of localization was 94.5% (155 of 164). Among 63 nodules with multiple dye marking attempts, 62 (98.4%) were successfully localized. In 101 nodules with a single dye marking attempt, 87 (86.1%) were localized with the visceral pleural dye mark. In addition, 6 nodules (5.9%) could be localized with the needle hole on the visceral pleura. The number of dye marking attempts was a significant factor in the success of localization (1.5 ± 0.7 vs 1.1 ± 0.3, P = .01). CONCLUSIONS: Full virtual ENB-guided dye marking was effective and safe for the localization of small pulmonary nodules. A multiple dye marking strategy is recommended to achieve a high success rate.

Changes in Forced Expiratory Volume in 1 Second after Anatomical Lung Resection according to the Number of Segments.

BACKGROUND: Although various methods are already used to calculate predicted postoperative forced expiratory volume in 1 second (FEV1) based on preoperative FEV1 in lung surgery, the predicted postoperative FEV1 is not always the same as the actual postoperative FEV1. Observed postoperative FEV1 values are usually the same or higher than the predicted postoperative FEV1. To overcome this issue, we investigated the relationship between the number of resected lung segments and the discordance of preoperative and postoperative FEV1 values. METHODS: From September 2014 to May 2020, the data of all patients who underwent anatomical lung resection by video-assisted thoracoscopic surgery (VATS) were gathered and analyzed retrospectively. We investigated the association between the number of resected segments and the differential FEV1 (a measure of the discrepancy between the predicted and observed postoperative FEV1) using the t-test and linear regression. RESULTS: Information on 238 patients who underwent VATS anatomical lung resection at Kyung Hee University Hospital at Gangdong and by DH. Kim for benign and malignant disease was collected. After applying the exclusion criteria, 114 patients were included in the final analysis. In the multiple linear regression model, the number of resected segments showed a positive correlation with the differential FEV1 (Pearson r=0.384, p<0.001). After adjusting for multiple covariates, the differential FEV1 increased by 0.048 (95% confidence interval, 0.023-0.073) with an increasing number of resected lung segments (R2=0.271, p<0.001). CONCLUSION: In this study, after pulmonary resection, the number of resected segments showed a positive correlation with the differential FEV1.

Life-Threatening Subglottic Stenosis of Granulomatosis with Polyangiitis: A Case Report.

Granulomatosis with polyangiitis (GPA) is an autoimmune disease characterized by necrotizing granulomatous inflammation. Subglottic stenosis, which is defined as narrowing of the airway below the vocal cords, has a frequency of 16-23% in GPA. Herein, we present the case of a 39-year-old woman with subglottic stenosis manifesting as life-threatening GPA, which was recurrent under systemic immunosuppressive therapy. The patient underwent an emergency tracheostomy, intratracheal intervention, such as carbon dioxide (CO2) laser surgery and intralesional steroid injection via laryngomicroscopic surgery, and laryngotracheal resection with remodeling. Severe subglottic stenosis treatment requires active intratracheal intervention, surgery, and systemic immunosuppressive therapy.

Recurrent Aortobronchial Fistula after Endovascular Stenting for Infected Pseudoaneurysm of the Proximal Descending Thoracic Aorta: Case Report.

Aortobronchial fistula (ABF) induced by an infected pseudoaneurysm of the thoracic aorta is a life-threatening condition. As surgical treatment is associated with significant mortality and morbidity, thoracic endovascular aneurysm repair (TEVAR) may be an alternative for the treatment of ABF. However, the long-term durability of this intervention is largely unknown and the recurrence of ABF is a potential complication. We experienced a case of recurrent ABF after stent grafting as an early procedure for an infected pseudoaneurysm of the thoracic aorta. Remnant ABF, bronchial and/or aortic wall erosion, vasa vasorum connected with ABF, and recurrent local inflammation of the thin aortic wall around ABF might cause recurrent hemoptysis. As a result, we suggest that TEVAR should be considered as a bridge therapy for the initial treatment of ABF resulting from an infected pseudoaneurysm, and that several options, such as second-stage surgery, should be considered to prevent the recurrence of ABF.

A Case of Lymphocyte-Rich Hepatocellular Carcinoma in a Patient Who Was Treated for Colon Cancer.

Hepatocellular carcinoma (HCC) primarily originates in the liver with hepatic differentiation. However, HCCs are not homogenous, and approximately 35% of HCC cases are classified as histopathological variants that present distinct pathologic characteristics. In particular, the lymphocyte-rich variant is the rarest subtype accounting for less than 1% of HCCs, which is not well known to date about molecular features and pathophysiology. Herein, we present a case of a patient who was suspected of metastatic liver cancer and confirmed as lymphocyte-rich HCC pathologically. A 78-year-old woman who underwent a right hemicolectomy for colon cancer was referred to our hospital for a newly detected liver mass. We could not make a decision because of insufficient evidence for diagnosis from imaging studies. After resection, we found that it was a lymphocyte-rich HCC. The pathologic features and prognostic trends of this subtype are also discussed.

The robotic thymectomy via the subxiphoid approach: technique and early outcomes.

OBJECTIVES: Robotic thymectomy via the subxiphoid approach (RTX) is a recently introduced surgical approach. This study aimed to report on the surgical technique and early outcomes of RTX in our institute. METHODS: RTX was performed using the 3-arm technique in the da Vinci robotic surgical system. The camera was inserted into a subxiphoid port, and 2 robotic arms were inserted in bilateral intercostal ports. A complete dissection of both cervical poles up to the thyroid gland was conducted, and bilateral phrenic nerves were identified in all cases. Radical combined resection of adjacent organs, including the lung, pericardium, phrenic nerve and the innominate vein, was performed if necessary. The resected specimen could be retrieved through the subxiphoid port site. RESULTS: A total of 110 patients underwent RTX in our institute from October 2016 to August 2019. Thymoma was the most common diagnosis (60.9%), and the mean size of the tumours was 4.9 ± 2.4 cm. Combined resection was performed in the lung (n = 9, 8.1%), pericardium (n = 6, 5.5%) and innominate vein (n = 5, 4.5%). There were 2 minor postoperative complications (1.8%), and the mean length of hospital stay was 2.2 ± 1.4 days. For the cumulative sum curve analysis of the learning curve using operative time, 50 cases were necessary to gain proficiency. CONCLUSIONS: RTX was a safe and feasible surgical approach, even in advanced thymic epithelial tumours. It should be considered one of the valuable surgical options in minimally invasive thymectomy.

Synthetic Anion Transporters as Endoplasmic Reticulum (ER) Stress Inducers.

Cl--ion transporters (2a-2h) were synthesized based on the binding motifs of prodigiosin. Transporter 2e clearly displays Cl--ion transportation activity across both model and live cell membranes. Furthermore, 2e can disrupt Ca2+ homeostasis and increase the intracellular concentration of Ca2+ in the DLD-1 cell. This disruption can lead to Caspase-dependent apoptosis supported by CHOP expression (a marker of ER stress) and the appearance of the cleaved forms of Caspase 3 and PARP.

Primary Extraskeletal Osteosarcoma in the Anterior Mediastinum: A Case Report and Review.

Extraskeletal osteosarcoma (ESOS) is a malignant soft tissue neoplasm producing osteoid, without any continuity with the bone or periosteum. Primary ESOS presenting in the mediastinum is an extremely rare, yet aggressive malignant tumor associated with a poor prognosis. We report a case of primary ESOS arising from the thymus in a 63-year-old male patient.

Electromagnetic navigation bronchoscopic dye marking for localization of small subsolid nodules: Retrospective observational study.

Thoracoscopic resection of small subsolid nodules is challenging and requires preoperative localization. We investigated the efficacy, safety, and factors affecting accuracy in localizing pulmonary nodules with electromagnetic navigation bronchoscopy (ENB)-guided dye marking.Patients with small subsolid nodule(s) who underwent thoracoscopic resection after ENB-guided dye marking were retrospectively reviewed. Dye marking was performed at the nearest pleura and the localized nodule(s) was resected thoracoscopically. Efficacy was evaluated by success rates of dye marking and resection of nodules. Navigation accuracy was represented by target distance, which was the closest distance between target and the tip of locatable guide. Factors affecting target distance were evaluated by linear regression analyses.Twenty-nine ENB-guided dye markings were done for 24 nodules in 20 patients. The success rate of the dye marking and nodule localization were 93.1% (27/29) and 95.8% (23/24), respectively. Twenty-three nodules were completely resected thoracoscopically without conversion. There were no ENB-related complications: pneumothorax or bronchopulmonary hemorrhage. Nine targets were in the upper, 14 in the middle, and 6 in the lower zone. Even though navigation time was longer in the upper zone, target distance showed no significant inter-zone difference. Approach angle was the only significant predictor for target distance (0-45°, estimate = -1.24, P = .01; 45-90°, estimate = -1.26, P = .006; reference = ≥90°).Localization with ENB-guided dye marking is effective and safe for thoracoscopic resection of small subsolid nodules. For better performance, a pathway with smaller approach angle (<90°) should be selected to increase the navigation accuracy.

Prognostic Implications of Postoperative Infectious Complications in Non-Small Cell Lung Cancer.

BACKGROUND: Few studies have evaluated the long-term impact of postoperative infectious complications in patients with non-small cell lung cancer (NSCLC). We aimed to determine the impact of infectious complications on long-term outcomes after surgical resection for NSCLC. METHODS: We performed a retrospective study of 1,380 eligible patients who underwent pulmonary resection for NSCLC from 2003 to 2012. Complications were divided into infectious complications and non-infectious complications. Kaplan-Meier survival analysis was used to compare unadjusted 5-year cancer-specific survival (CSS) rates and recurrence-free survival (RFS) rates. Cox regression was used to determine the impact of infectious complications on 5-year CSS and RFS. RESULTS: The rate of total complications and infectious complications was 24.3% and 4.3%, respectively. In the node-negative subgroup, the 5-year CSS and RFS rates were 75.9% and 57.1% in patients who had infectious complications, compared to 87.9% and 78.4% in patients who had no complications. Infectious complications were a negative prognostic factor for 5-year RFS (hazard ratio, 1.92; 95% confidence interval, 1.00-3.69; p=0.049). In the node-positive subgroup, the 5-year CSS rate and RFS were 44.6% and 48.4% in patients who had infectious complications, compared to 70.5% and 48.4% for patients who had no complications. CONCLUSION: Postoperative infectious complications had a negative impact on CSS and RFS in node-negative NSCLC. Our findings may help improve risk assessment for tumor recurrence after pulmonary resection for node-negative NSCLC.

Extracardiac Conduit Fontan Operation with Reduction Aortoplasty for Left Pulmonary Artery Compression after a Norwood Procedure in a Patient with Double-Inlet Left Ventricle.

Patients with double-inlet left ventricle usually have a small ascending aorta. In the Norwood procedure, which involves a staged operation, a neoaorta is constructed with a homograft, and the pulmonary artery plays a role in the systemic circulation. Dilatation or aneurysmal changes can occur over time due to the exposure of the neoaorta to systemic pressure, which may induce adverse effects on adjacent structures. We report a rare case of surgical repair for neoaortic root dilataiton with aortic regurgitation, compressing the left pulmohary artery, in a patient who underwent the Norwood procedure.

A case of levocetirizine-induced liver injury.

Levocetirizine is a second-generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease. There was only one case report of levocetirizine-induced liver toxicity, but a liver biopsy was not performed. In this article, we present the first case of levocetirizine-induced liver injury with histologic findings. A 48-year-old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis. Laboratory findings revealed acute hepatitis with cholestasis. A liver biopsy demonstrated portal inflammation and hepatitis with apoptotic hepatocytes. The patient fully recovered 3 weeks after withdrawing levocetirizine. Although levocetirizine is safe and effective, physicians should be aware of its potential hepatotoxicity.

New morphological features for grading pancreatic ductal adenocarcinomas.

Pathological diagnosis is influenced by subjective factors such as the individual experience and knowledge of doctors. Therefore, it may be interpreted in different ways for the same symptoms. The appearance of digital pathology has created good foundation for objective diagnoses based on quantitative feature analysis. Recently, numerous studies are being done to develop automated diagnosis based on the digital pathology. But there are as of yet no general automated methods for pathological diagnosis due to its specific nature. Therefore, specific methods according to a type of disease and a lesion could be designed. This study proposes quantitative features that are designed to diagnose pancreatic ductal adenocarcinomas. In the diagnosis of pancreatic ductal adenocarcinomas, the region of interest is a duct that consists of lumen and epithelium. Therefore, we first segment the lumen and epithelial nuclei from a tissue image. Then, we extract the specific features to diagnose the pancreatic ductal adenocarcinoma from the segmented objects. The experiment evaluated the classification performance of the SVM learned by the proposed features. The results showed an accuracy of 94.38% in the experiment distinguishing between pancreatic ductal adenocarcinomas and normal tissue and a classification accuracy of 77.03% distinguishing between the stages of pancreatic ductal adenocarcinomas.