Hyperbaric oxygen (HBO2) therapy in thermal burn injury revisited. Pressure does matter. Review.

For over five decades, many experimental and clinical studies have shown predominantly positive but controversial results on the efficacy of hyperbaric oxygen (HBO2) therapy in burns. The study aimed to define a common denominator or constellations, respectively, linked to the effects of HBO2 in burns with a special focus on dosage parameters. Based on original work since 1965, species, number of individuals, type of study, percentage of total body surface area (TBSA), region, depth of burn, causative agent, interval between burn and first HBO2 session, pressure, duration of individual session, number of HBO2 sessions per day, cumulative number of HBO2 sessions and type of chamber were assessed. Out of 47 publications included, 32 were animal trials, four were trials in human volunteers, and 11 were clinical studies. They contained 94 experiments whose features were processed for statistical evaluation. 64 (67.4%) showed a positive outcome, 16 (17.9%) an ambiguous one, and 14 (14.7%) a negative outcome. The only factor independently influencing the results was pressure with ATA (atmospheres absolute) lower than 3 ATA being significantly associated with better outcomes (p=0.0005). There is a dire need for well-designed clinical studies in burn centers equipped with hyperbaric facilities to establish dedicated treatment protocols.

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.

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.

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.

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.

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.

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.

The influence of elevated levels of C-reactive protein and hypoalbuminemia on survival in patients with advanced inoperable esophageal cancer undergoing palliative treatment.

BACKGROUND AND OBJECTIVES: Inflammation perpetuates individual tumor progression resulting in decreased survival in cancer patients. The aim of our study was to evaluate the influence of elevated levels of C-reactive protein (CRP) as well as low levels of albumin on patients with inoperable esophageal carcinoma. METHODS: The data of 218 patients with advanced esophageal cancer, who were treated at a single center within 12 years, were evaluated retrospectively. Patient's age, gender, body weight, dysphagia, plasma levels of CRP and albumin, the Glasgow Prognostic Score (GPS) combining both indicators, and survival were assessed for statistical evaluation. RESULTS: Thirty-nine (18.2%) had hypoalbuminemia and 161 (73.9%) had elevated CRP levels. Patients with hypoalbuminemia (P = 0.001) as well as patients with increased CRP levels (P = 0.001) showed a significantly shorter survival. Weight loss was correlated to elevated plasma CRP (P = 0.022), to diarrhea (P = 0.021), and to dysphagia (P = 0.008). Increasing GPS was significantly associated with poor survival (P = 0.001). CONCLUSIONS: Elevated CRP levels and hypoalbuminemia are significantly associated with reduced survival and are considered to be an appropriate predictor for poor outcome in advanced esophageal carcinoma. The GPS provides additional detailed prognostication and should be therefore taken into consideration when the individual palliative strategy has to be scheduled.

Esophageal perforation with near fatal mediastinitis secondary to Th3 fracture.

A 74-year-old male patient was referred with signs of sepsis 5 days after having been diagnosed with a rib fracture following a fall out of bed. Novel hypodensities were visible on thoracic X­rays and laboratory tests revealed elevated inflammatory parameters. Subsequently performed thoracic computed tomography (CT) scan showed burst fracture of the 3rd thoracic vertebra, posttraumatic esophageal rupture at the same level and mediastinitis. Furthermore, marked degenerative changes of the spinal column (diffuse idiopathic skeletal hyperostosis) were present. The patient underwent emergency thoracotomy and esophagectomy. Gastric pull-up with esophagogastrostomy was postponed for 3 days. After 14 days on the intensive care unit (ICU) and 12 days of i.v. antibiotics, the patient was transferred to the general ward and 7 weeks after trauma the patient was infection-free without difficulties in swallowing. Up to the latest follow-up 41 months following injury, several endoscopic dilations with a bougie due to constrictions at the anastomosis have been performed. Similar to previous cases in the literature, esophageal injury was diagnosed delayed, with the patient already having developed severe complications. This extremely seldom injury should be suspected in young patients following high-energy trauma, but also in older patients after low-energy trauma but known degenerative changes of the vertebral column.

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.

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.

Individualized, multimodal palliative treatment of inoperable esophageal cancer: clinical impact of photodynamic therapy resulting in prolonged survival.

BACKGROUND AND OBJECTIVE: In esophageal carcinoma palliative treatment is often required due to advanced tumor stage or patient-related factors. The main goal of our retrospective single center study was to evaluate the effect of an individualized multimodal palliative treatment, focusing on the efficacy of different treatment options. MATERIALS AND METHODS: Between 1999 and 2009, 640 patients suffering from esophageal carcinoma were referred to our division. Two hundred fifty out of those (39.1%) were treated with palliative intention by using a individualized, multimodal concept including endoscopic dilatation, photodynamic therapy (PDT), endoluminal brachytherapy, external radiation, chemotherapy, stenting, feeding tube, and palliative resection. RESULTS: There were 37 women (14.9%) and 211 men (85.1%). The treatment included PDT in 171 cases (in 118 as first measure), stenting in 124 (38), dilatation in 83 (24), endoluminal brachytherapy in 92 (20), feeding enterostomy in 40 (14), external radiation in 67 (23), chemotherapy in 57 (29), and palliative resection in 3 patients. The mean number of palliative treatments per patient was 2.6. Mean survival time for the collective was 34 months. Distant metastases and nodal positivity were connected with a significantly reduced survival. If PDT was used in the first place, median survival was 50.9 months compared to 17.3 months if other options were used as initial modality (P = 0.012). CONCLUSION: By using an individualized multimodal approach, an acceptable mean survival time can be achieved in advanced esophageal cancer treated with palliative intention. PDT, if used as initial endoluminal treatment in patients without gross tumor infiltration into the mediastinum, the great vessels or the tracheo-bronchial tree, enables a considerable beneficial effect in the palliative setting.

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.

Systemic arterial supply of the right lung with venous drainage to the pulmonary arterial circuit.

In a girl suffering from "Scimitar syndrome", a rerouting of the scimitar vein was performed at the age of 6 years, but no embolisation of the aberrant systemic vessel was done. She presented with recurring respiratory problems 13 years later. An angiography revealed an invert flow from the aberrant systemic vessel via the right pulmonary artery into the left pulmonary artery. After pneumonectomy, she recovered well.

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.

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.

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.