Immediate and Long-Term Effects of Hyperbaric Oxygenation in Patients with Long COVID-19 Syndrome Using SF-36 Survey and VAS Score: A Clinical Pilot Study.

(1) Background: Long COVID syndrome (LCS) is a heterogeneous long-standing condition following COVID-19 infection. Treatment options are limited to symptomatic measures, and no specific medication has been established. Hyperbaric oxygenation (HBO) has been found to have a positive impact on the treatment of COVID-19 infection. This study evaluates both the feasibility and outcome of supportive HBO in patients with LCS. (2) Methods: Within 17 months, 70 patients with proven LCS were prospectively included. Each patient underwent a cycle of 10 subsequent HBO treatment sessions administered for 75 min at 2.2 atmospheres. Evaluation of the patients was performed before the first and after the last HBO session and 3 months afterwards. Statistical evaluation was based on an intention-to-treat analysis using Fisher's exact test and Student's t-test for paired samples. (3) Results: In total, 59 patients (33 females, 26 males; mean age: 43.9 years; range: 23-74 years; median: 45.0) were evaluable. After HBO, a statistically significant improvement of physical functioning (p < 0.001), physical role (p = 0.01), energy (p < 0.001), emotional well-being (p < 0.001), social functioning (p < 0.001), pain (p = 0.01) and reduced limitation of activities (p < 0.001) was confirmed. (4) Conclusions: Physical functioning and both the physical and emotional role improved significantly and sustainably, suggesting HBO as a promising supportive therapeutic tool for the treatment of LCS.

The Prognostic Long-Term Impact of Chronic Obstructive Pulmonary Disease and Postoperative Mucostasis in Patients with Curatively Resected Non-Small Cell Lung Cancer.

Chronic obstructive pulmonary disease (COPD) serves as risk factor for the development of lung cancer and seems to have a prognostic impact after surgery for non-small cell lung cancer (NSCLC). The aim was to investigate the impact of COPD and postoperative mucostasis on the long-term survival after resected NSCLC. We retrospectively reviewed the data from 342 patients with curatively resected NSCLC. The prognostic long-term impact of COPD and postoperative mucostasis on overall survival (OS), recurrence free survival (RFS) and cancer specific survival (CSS) was calculated using univariable and multivariable Cox regression analyses. We found that 52.3% suffered from COPD and 25.4% had postoperative mucostasis. COPD was significantly more common among smokers (59.9%) compared with non-smokers (21.3%), (p < 0.001). There was a significant relationship between COPD and postoperative mucostasis (p = 0.006) and between smoking and mucostasis (p = 0.023). Patients with postoperative mucostasis had a significantly worse OS (p < 0.001), RFS (p = 0.009) and CSS (p = 0.008). The present analysis demonstrated that postoperative mucostasis, but not COPD, was associated with both worse short- and long-term outcomes for OS, RFS and CSS in curatively resected NSCLC.

Hemoptoe, thin-walled lung cysts, and spontaneous pneumothorax are features of metastatic cutaneous angiosarcoma : A case report.

We present a case of bilateral cystic lung metastases originating from cutaneous angiosarcoma (cAS) of the scalp in a 73-year-old man. He presented with hemoptysis and recurrent bilateral pneumothorax. The clinical, radiological, and histological features and a potential pathophysiological mechanism of pulmonary changes in cutaneous angiosarcoma are discussed.

Autophagy, Oxidative Stress and Cancer Development.

Autophagy is an important cellular repair mechanism, aiming at sequestering misfolded and dysfunctional proteins and damaged cell organelles. Dysfunctions in the autophagy process have been linked to several diseases, like infectious and neurodegenerative diseases, type II diabetes mellitus and cancer. Living organisms are constantly subjected to some degree of oxidative stress, mainly induced by reactive oxygen and nitrogen species. It has been shown that autophagy is readily induced by reactive oxygen species (ROS) upon nutrient deprivation. In recent years, research has increasingly focused on outlining novel therapeutic targets related to the autophagy process. With this review of the literature, we want to give an overview about the link between autophagy, oxidative stress and carcinogenesis.

Implications of the Immune Landscape in COPD and Lung Cancer: Smoking Versus Other Causes.

Cigarette smoking is reported in about one third of adults worldwide. A strong relationship between cigarette smoke exposure and chronic obstructive pulmonary disease (COPD) as well as lung cancer has been proven. However, about 15% of lung cancer cases, and between one fourth and one third of COPD cases, occur in never-smokers. The effects of cigarette smoke on the innate as well as the adaptive immune system have been widely investigated. It is assumed that certain immunologic features contribute to lung cancer and COPD development in the absence of smoking as the major risk factor. In this article, we review different immunological aspects of lung cancer and COPD with a special focus on non-smoking related risk factors.

Role of Tumor-Associated Neutrophils in the Molecular Carcinogenesis of the Lung.

Tumorigenesis is largely influenced by accompanying inflammation. Myeloid cells account for a significant proportion of pro-inflammatory cells within the tumor microenvironment. All steps of tumor formation and progression, such as the suppression of adaptive immune response, angio- and lymphangiogenesis, and the remodeling of the tumor stroma, are to some degree influenced by tumor-associated immune cells. Tumor-associated neutrophils (TANs), together with tumor-associated macrophages and myeloid-derived suppressor cells, count among tumor-associated myeloid cells. Still, the exact molecular mechanisms underlying the tumorigenic effects of TANs have not been investigated in detail. With this review of the literature, we aim to give an overview of the current data on TANs, with a special focus on lung cancer.

Survey of Molecular Mechanisms of Hyperbaric Oxygen in Tissue Repair.

For more than six decades, hyperbaric oxygen (HBO) has been used for a variety of indications involving tissue repair. These indications comprise a wide range of diseases ranging from intoxications to ischemia-reperfusion injury, crush syndrome, central nervous injury, radiation-induced tissue damage, burn injury and chronic wounds. In a systematic review, the molecular mechanisms triggered by HBO described within the last two decades were compiled. They cover a wide range of pathways, including transcription, cell-to-cell contacts, structure, adhesion and transmigration, vascular signaling and response to oxidative stress, apoptosis, autophagy and cell death, as well as inflammatory processes. By analyzing 71 predominantly experimental publications, we established an overview of the current concepts regarding the molecular mechanisms underlying the effects of HBO. We considered both the abovementioned pathways and their role in various applications and indications.

Liquid biopsy in non-small cell lung cancer-current status and future outlook-a narrative review.

Lung cancer ranks first as the cause of cancer-associated deaths gobally. The American Cancer Society estimates for 228,820 new cases and 135,720 deaths from lung cancer in the United States for the year 2020. Targeted treatment options have rapidly emerged for non-small cell lung cancer (NSCLC) within the past decade. Screening for molecular aberrations is mainly done by tissue biopsy. However, in some cases a biopsy is not possible, or patients do not consent to it. Hence, liquid biopsy remains the only option. Relevant data about the topic of liquid biopsy, with a special focus on NSCLC, was obtained via a PubMed search. We included mainly literature published from 2010 onwards, omitting older studies whenever possible. With this review of the literature, we give an overview of different liquid biopsy approaches, as well as their respective advantages and disadvantages. We have reviewed the assessment of epidermal growth factor receptor (EGFR) mutation status in particular, and go into detail with current use of liquid biopsy in everyday clinical practice. Today, liquid biopsy is still infrequently used, depending on the treatment center, but popularity is steadily increasing. Various different approaches are already available, but costs and level of sensitivity significantly differ between techniques. By using liquid biopsy more widely in selected patients, complication rates can be reduced, and constant disease monitoring is made considerably easier.

The History and Development of Hyperbaric Oxygenation (HBO) in Thermal Burn Injury.

Background and Objectives: Hyperbaric oxygenation (HBO) denotes breathing of 100% oxygen under elevated ambient pressure. Since the initiation of HBO for burns in 1965, abundant experimental and clinical work has been done. Despite many undisputedly positive and only a few controversial results on the efficacy of adjunctive HBO for burn injury, the method has not yet been established in clinical routine. Materials and Methods: We did a retrospective analysis of the literature according to PRISMA-guidelines, from the very beginning of HBO for burns up to present, trying to elucidate the question why HBO is still sidelined in the treatment of burn injury. Results: Forty-seven publications (32 animal experiments, four trials in human volunteers and 11 clinical studies) fulfilled the inclusion criteria. Except four investigators who found little or no beneficial action, all were able to demonstrate positive effects of HBO, most of them describing less edema, improved healing, less infection or bacterial growth and most recently, reduction of post-burn pain. Secondary enlargement of burn was prevented, as microvascular perfusion could be preserved, and cells were kept viable. The application of HBO, however, concerning pressure, duration, frequency and number of treatment sessions, varied considerably. Authors of large clinical studies underscored the intricate measures required when administering HBO in severe burns. Conclusions: HBO unquestionably has a positive impact on the pathophysiological mechanisms, and hence on the healing and course of burns. The few negative results are most likely due to peculiarities in the administration of HBO and possibly also to interactions when delivering the treatment to severely ill patients. Well-designed studies are needed to definitively assess its clinical value as an adjunctive treatment focusing on relevant outcome criteria such as wound healing time, complications, length of hospital stay, mortality and scar quality, while also defining optimal HBO dosage and timing.

A nomogram illustrating the probability of anastomotic leakage following cervical esophagogastrostomy.

BACKGROUND: Early diagnosis of anastomotic dehiscence following cervical esophagogastrostomy may become difficult. Estimation of an individual probability could help to establish preventive and diagnostic measures. The predictive impact of epidemiological, surgery-related data and laboratory parameters on the development of anastomotic dehiscence was investigated in the immediate perioperative period. METHODS: Retrospective study in 412 patients with cervical esophagogastrostomy following esophagectomy. Epidemiological data, risk factors, underlying disease, pre-treatment- and surgery-related data, C-reactive protein and albumin levels pre-and post-operatively were evaluated. We applied univariable and multivariable logistic regression analysis and developed a nomogram for individual risk assessment. RESULTS: There were 345 male, 67 female patients, mean aged 61.5 years; 284 had orthotopic, 128 retrosternal gastric pull-up; 331 patients had carcinoma, 81 non-malignant disease. Mean duration of operation was 184 min; 235 patients had manual, 113 mechanical and 64 semi-mechanical suturing; 76 patients (18.5%) developed anastomotic dehiscence clinically evident at mean 11.4 days after surgery. In univariable testing young age, retrosternal conduit transposition, manual suturing, high body mass index, high ASA and high postoperative levels of C-reactive protein were predictors for anastomotic leakage. These six parameters which had yielded a p < 0.1 in the univariable analysis, were entered into a multivariable analysis and a nomogram allowing the determination of the patient's individual risk was created. CONCLUSION: By using the nomogram as a supportive measure in the perioperative management, the patient's individual probability of developing an anastomotic leak could be quantified which may help to take preventive measures improving the outcome.

Hazard Curves for Tumor Recurrence and Tumor-Related Death Following Esophagectomy for Esophageal Cancer.

BACKGROUND: The knowledge of both patterns and risk of relapse following resection for esophageal cancer is crucial for establishing appropriate surveillance schedules. The aim of this study was to evaluate the pattern of hazards for tumor recurrence and tumor-related death in the postoperative long-term follow-up after esophagectomy. METHODS: Retrospective single-center analysis of 362 patients, with resected esophageal cancer. Multivariate Cox proportional hazard model was used. RESULTS: A total of 192 (53%) had postoperative tumor recurrence. The relapse patterns of adenocarcinoma and squamous-cell carcinoma showed that each had a single peak, 12 months after surgery. After induction there was one peak at 5 months, the non-induced patients peaked 11 months, postoperatively. At 18 months, the recurrence hazard declined sharply in all cases. The hazard curves for tumor-related death were bimodal for adenocarcinoma, with two peaks at 6 and 22 months and one single peak for squamous-cell carcinoma at 18 months after surgery, showing pronounced decline later on. CONCLUSION: In curatively resected esophageal cancer, both tumor recurrence hazard and hazard for tumor-related death showed distinct, partly bimodal patterns. It could be justified to intensify the surveillance during the first two postoperative years by initiating a close-meshed follow-up to detect and treat tumor recurrence, as early as possible.

Hazards of Recurrence, Second Primary, or Other Tumor at Ten Years After Surgery for Non-Small-Cell Lung Cancer.

INTRODUCTION: Better treatment options entail the risk of multiple tumors in a patient's lifetime. We studied the incidence, risk factors, and prognostic impact of second primaries and other malignancies in patients with operated non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively analyzed 342 consecutive patients with curatively resected NSCLC between 2003 and 2007. RESULTS: Among the 342 patients analyzed, 172 (50.3%) developed locoregional and/or distant recurrence; 25 (7.3%) had a second primary lung cancer, 97 (28.3%) had 1 or more malignancies other than NSCLC either in their history (n = 61; 17.8%) or following resection (n = 64; 18.7%). One hundred fifteen patients (33.6%) had a malignancy other than primary NSCLC. Eight patients developed both a second primary lung cancer and another malignancy. Older age and lower N-stage were significantly correlated with the occurrence of an additional tumor, as shown by a logistic regression nomogram. Whereas the risk of recurrence decreases over time, the risk of developing a second tumor, particularly a second primary lung cancer, remains high during up to 10 years of follow-up. One hundred seventy patients (49.7%) died of the primary (n = 158; 46.2%) or second primary (n = 12; 3.5%) NSCLC, 23 (6.7%) died of another malignancy, and 66 (19.3%) died due to unrelated causes (overall 10-year survival, 33.3%). CONCLUSIONS: Second primary lung cancer or other malignancy occurs in 33% of patients with NSCLC; 26% of patients are affected within 10 years after resection of lung cancer. With curative treatment of secondary tumors, there is no negative influence on long-term prognosis of NSCLC; therefore, follow-up beyond 5 years is strongly advisable.

Preoperative Peak Oxygen Consumption: A Predictor of Survival in Resected Lung Cancer.

The peak oxygen consumption (VO2 peak) serves as a prognostic factor in cardio-respiratory diseases and plays an important role in cancer patients. The long-term prognostic relevance of VO2 peak in lung cancer patients has not been investigated extensively. The aim of this study was to evaluate the impact of the preoperative VO2 peak on the postoperative long-term survival in patients with operated lung cancer. Retrospective analysis of 342 patients with curatively resected non-small-cell lung cancer using a multivariate Cox proportional hazard model. Results: Preoperative VO2 peak ranged from 10.2 to 51.8 mL/kg/min (mean: 18.3 ± 4.6), VO2 peak % of predicted ranged from 32 to 172% (mean: 65.2 ± 18.0%). Overall 10-year survival was 23%. A Log-rank test comparing predicted VO2 peak ≥ 60% with predicted VO2 peak < 60% showed overall survival of 30% and 17%, respectively (p < 0.001) and non-tumour-related survival of 71% and 51% (p = 0.001) at 10 years. In multivariable Cox analysis, overall 10-year survival correlated with a high predicted VO2 peak% (p = 0.001) and low N-stage corresponding to N0 and N1 (p < 0.001). Non-tumour-related death correlated with low VO2 peak% of predicted (p = 0.001), and age (p < 0.001). Low preoperative VO2 peak was associated with both decreased postoperative overall survival and decreased non-tumour-related survival during the 10-year follow-up.

Prediction of Postoperative Clinical Outcomes in Resected Stage I Non-Small Cell Lung Cancer Focusing on the Preoperative Glasgow Prognostic Score.

Background: The Glasgow Prognostic Score (GPS), which consists of albumin and C-reactive protein (CRP), may predict overall survival (OS) in cancer patients. The aim of this retrospective analysis was to evaluate the clinical impact of the preoperative GPS on patients with resected early stage non-small cell lung cancer (NSCLC). Methods: 300 patients with curatively resected stage I NSCLC were followed-up for OS, recurrence-free survival (RFS), cancer-specific survival (CSS), and death from other causes. Results: 229 patients (76%) had a preoperative GPS of 0, and 71 (24%) a GPS ≥ 1. The three-year probabilities of RFS, OS, CSS, and death from other causes were 81%, 84%, 88%, and 96% in patients with GPS = 0, and 79%, 74%, 91%, and 82% in patients with a GPS ≥ 1, respectively. GPS ≥ 1 was significantly associated with a higher risk of death from other causes (p = 0.022), serving as an independent predictor of death from other causes (p = 0.034). Pathologically elevated CRP levels (CRP > 5 mg/L) were found in 91 patients (30%). The mean CRP level was 7.88 ± 15.80 mg/L (0.5-135.6 mg/L). Pre-treatment CRP level was significantly associated with coronary heart disease (p < 0.0001), histology (p = 0.013), tumor size (p = 0.018), tumor stage (p = 0.002), and vascular invasion (p = 0.017). Conclusion: The preoperative GPS predicts adverse survival outcomes in patients with resected stage I NSCLC.

Interposition of Retrosternal Pedicled Jejunum After Hypopharyngolaryngo-Esophagogastrectomy.

Reconstruction of the upper gastrointestinal tract presents a surgical challenge after esophagogastrectomy, especially when it includes hypopharyngolaryngectomy. Reconstruction is generally undertaken with interposed colon as a substitute conduit, but it carries several risks. Alternative reconstruction of the foregut with pedicled retrosternal jejunum anastomosed at the level of the base of the tongue is described.

Pseudoachalasia as First Manifestation of a Malignancy.

Pseudoachalasia is a condition in which symptoms, radiologic, endoscopic, and manometric findings mimick idiopathic achalasia. About 4% of patients with a typical constellation for idiopathic achalasia will turn out to have pseudoachalasia, posing a major diagnostic challenge. A large spectrum of underlying causes of pseudoachalasia has been described. However, in about 70% of affected patients, this condition is caused by a malignancy (mostly adenocarcinoma of the esophagogastric junction or cardia). We describe a 16-year-old high school student referred for management of achalasia who turned out to have pseudoachalasia due to adenocarcinoma of the cardia. He was cured with preoperative chemotherapy followed by radical surgery. Therapy of pseudoachalasia secondary to neoplasia is directed against the tumor or may be palliative to keep the lumen open. Other causes of pseudoachalasia include esophageal motility disturbances as a paraneoplastic phenomenon (e.g., with small cell lung cancer), post fundoplication or post bariatric surgery, in association with a thoracic aortic aneurysm, or with sarcoidosis or amyloidosis. Therapy is directed accordingly to eliminate or correct the underlying cause.

Hyperbaric oxygen in patients with ischemic stroke following cardiac surgery: a retrospective observational trial.

BACKGROUND: Hyperbaric oxygenation (HBO2) involves breathing 100% oxygen under elevated ambient pressure in a hyperbaric chamber, thereby dissolving oxygen in the plasma. This results in an increase of arterial partial pressure of oxygen (pO2). Though well established in experimental studies, HBO2 treatment for ischemic stroke is still under discussion. METHODS: From 2002-2014 HBO2 (2.2 bar, 90 minutes one/day; average number per patient: 4.7) was applied in 49 consecutive patients (32 males, 17 females, mean age: 68.8 years, range 31.2 - 83.9) with acute neurological deficit following cardiac surgery (CABG 15; combined surgery 14; valve surgery 11; aneurysm repair 8; malformation 1). Patients' history including TIA or stroke and carotid artery pathology were documented. Both degree and type of neurological deficit was evaluated by a scoring system (0-4) before and after HBO2 treatment. RESULTS: Before HBO2 therapy, the average motor deficit score was 2.45 and the average speech disorder score was 0.55, as compared with an average motor deficit of 1.12 and an average speech disorder of 0.27 afterward (α=0.0001, α=0.009). The majority of patients had an overall improvement of 2 score-points after HBO2 therapy (n=23 patients). Probit analysis showed that for a 50% response/probability (LC50) of having an overall outcome of ≥2 scoring points, an estimate of 4.3 HBO2 therapy sessions is necessary. CONCLUSIONS: HBO22 therapy was associated with significant improvement in patients with acute neurological deficits due to ischemic stroke following cardiac surgery. Though this fact suggests gas embolism as the most likely cause of stroke in this collective, other underlying pathologies cannot be ruled out. Randomized studies are needed for further evaluation.

Clinical impact of interleukin 6 as a predictive biomarker in the early diagnosis of postoperative systemic inflammatory response syndrome after major thoracic surgery: A prospective clinical trial.

BACKGROUND: Postoperative systemic inflammatory response syndrome and sepsis are associated with high morbidity and mortality rates. Early detection of postoperative systemic inflammatory response syndrome improves the outcome. The aim of this study was to evaluate the feasibility of interleukin 6 as a predictive biomarker in the early diagnosis of postoperative systemic inflammatory response syndrome after a major thoracic operation. METHODS: A total of 94 patients were enrolled in this prospective, clinical, single-center study. The enrolled subjects underwent either lung resection or esophageal operation. Interleukin 6, procalcitonin, C-reactive protein, and leucocytes were measured sequentially before, during, and after the operation. These levels were compared between patients who developed postoperative systemic inflammatory response syndrome and those who did not. RESULTS: The enrollees who completed the study included of 55 males (79.7%) and 14 females (20.3%) with a mean age of 60.9 years. Twenty patients (29.0%) developed systemic inflammatory response syndrome at a median time of 33.0 hours postoperatively. In cases of postoperative systemic inflammatory response syndrome, interleukin 6 was the most predictive biomarker, showing a striking increase on the day of operation and preceding the median onset of postoperative systemic inflammatory response syndrome, which occurred the next day (P ≤ .001). Peak procalcitonin and C-reactive protein occurrence were significantly delayed at 24 hours (P = .012) and 48 hours (P = .012). There was no mortality 30 days postoperatively. CONCLUSION: Interleukin 6 is a reliable predictor of postoperative systemic inflammatory response syndrome, and it is able to detect postoperative system inflammatory response syndrome before the onset of related clinical symptoms. When identifying patients at high risk, it would be beneficial to include interleukin 6 in conventional postoperative monitoring, particularly after extended surgical resection.

Stage-based treatment for thymoma in due consideration of thymectomy: a single-center experience and comparison with the literature.

BACKGROUND: Thymomas represent an uncommon and heterogeneous group of intrathoracic malignancies which require different treatments corresponding to their individual tumor stage. The objective of this study was to review the efficacy of our applied stage-based treatment for thymoma in due consideration of thymectomy. METHODS: This is a single-center, institutional review board-approved retrospective study of 50 consecutive patients with thymoma treated at our division within 10 years. RESULTS: There were 29 women (58 %) and 21 men (42 %), mean age 58.3 years. Twenty nine (58 %) had clinical symptoms and 14 (28 %) had myasthenia gravis. Forty-five patients (90 %) underwent thymectomy and complete resection was done in 42 cases (93.3 %). Histologic results were 6 subtype A, 5 AB, 8 B1, 12 B2, 12 B3, and 7 C. The Masaoka staging system revealed 20 stage I, 18 stage II, 6 stage III, and 6 stage IV. Two patients had neoadjuvant therapy and 25 received postoperative treatment. Five (11.1 %) had tumor recurrence, treated with re-resection. The 5-year disease-free survival was 91.5 %. Two patients died of tumor progression and three died of other causes (10 %). The 5-year overall survival was 82.3 % and the median survival time was 92.1 months. The 5-year survival rate after thymectomy was 87.2 % and the median survival was 92.1 months. CONCLUSIONS: Complete resection still remains the mainstay in the treatment of non-metastatic thymoma and should be performed whenever feasible. Close multidisciplinary teamwork is mandatory to optimize the neurologic outcome and to prolong postoperative survival.