[SARS-CoV-2-associated pneumothorax, pneumomediastinum and soft tissue emphysema. Clinical implications based on a case series]. / SARS-CoV-2-assoziierter Pneumothorax, Pneumomediastinum und Weichteilemphysem. Klinische Implikationen anhand einer Fallserie.

The new coronavirus (SARS-CoV-2) that arose in 2019 causes a wide spectrum of symptoms and different courses of disease. Pneumothorax, pneumomediastinum and soft tissue emphysema are rare complications in patients with pulmonary involvement. They are the sequelae of severe, virus-induced structural changes of the pulmonary architecture. High pressure artificial ventilation aggravates the problem. Hence pneumothorax and ectopic air in soft tissues are indicators of extensive pulmonary damage. Therefore, efforts should be made to treat even very small or multiply recurrent pneumothorax by drainage procedures.

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.

Prognostic value of cyclin A2 and B1 expression in lung carcinoids.

Carcinoid classification in the lung is still based on morphological criteria. Although there are many studies investigating the role of Ki-67 proliferation index in the classification of lung neuroendocrine tumours, it is still not used in routine diagnostics. Interestingly, cyclins, which have a crucial role in controlling the cell cycle, have not been thoroughly studied in lung neuroendocrine tumours. The aim of our study was to investigate the correlation of cyclin A2 and B1 expression with prognosis, Ki-67 proliferation index, and carcinoid morphology. A cohort of 134 resected typical and atypical carcinoids was stained with antibodies against Ki-67, cyclin A2 and B1. The positive nuclear reaction was assessed in hot spot areas and expressed as the percentage of tumour cells. Univariate analyses found the highest relative hazard between low and high cyclin A2 expression both with respect to overall survival [hazard ratio (HR)=16; 95% confidence interval (CI) 4.8-51; p=0.0000054], and relapse (HR=8; 95% CI 3.1-21; p=0.00002). In multivariate analysis for overall survival cyclin A2 (HR=10; 95% CI 2.5->100; p=0.0082) and B1 (HR=6.5; 95% CI 1.5-35; p=0.02) remained significant when adjusted for other risk factors, whereas Ki-67 was no longer significant (HR=0.64; 95% CI 0.003-5.5; p=0.65). This suggests that Ki-67 is closer to conventional risk factors for survival than cyclin A2 and B1. Furthermore, the analysis revealed 4 mitoses per 2 mm2 as a more powerful prognostic cut-off than currently accepted 2 mitoses. We have clearly demonstrated that application of cyclin A2 and cyclin B1 might bring additional value regarding the overall and progression-free survival of patients with carcinoids of the lung.

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.

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.

Application of Hyperbaric Oxygen Reduce Oxidative Damage of Plasmatic Carbonyl Proteins and 8-OHdG by Activating Glutathion Peroxidase.

BACKGROUND: It is postulated that application of hyperbaric oxygenation may induce the production of radicals after HBO. Higher oxygenation and transport of oxygen increase the mitochondrial energy turnover, whereas inner mitochondrial radical formation decreases. METHODS: Several markers of oxidative stress in healthy volunteers (n = 21), including plasma carbonyl proteins (CP), malondialdehyde (MDA), oxidized LDL (oxLDL), 8-hydroxy-deoxyguanosine (8-OHdG), and erythrocyte glutathione peroxidase (GPx) activity are measured before, during, and after HBO. RESULTS: Median plasma concentrations of CP decreased significantly during HBO compared to CP levels before HBO (from 77.1 to 61.7 pmol/mg; p < 0.001) and increased again after HBO (to 78.1 pmol/mg; p = 0.035). 8-OHdG decreased significantly during HBO (8.1 ng/mL; p < 0.001) and remained constant after HBO (8.1 ng/mL) compared to "before HBO" (9.4 ng/mL). MDA increased significantly from 0.92 µM (before HBO) to 1.26 µM (during HBO, p < 0.01) and decreased again to 1.00 µM (after HBO, p = 0.023). Erythrocyte GPx activity also increased significantly during HBO (26.5 ± 14.7; p = 0.005), but not after HBO (25.6 ± 17.2 IU/mg). A negative correlation was observed between GPx and MDA only during HBO (r = -0.518; p = 0.016). CONCLUSIONS: We assume that higher oxygen consumption decreases, on the one hand, the inner mitochondrial generation of free radicals and, on the other, RONS by activation of detoxifying enzymes like GPx.

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.

Surgical therapy of primary malignant bone tumours and soft tissue sarcomas of the chest wall: a two-institutional experience.

PURPOSE: Primary malignant bone tumours and soft tissue sarcomas of the chest wall are exceedingly rare entities. The aim of this study was a retrospective two-institutional analysis of surgical therapy with respect to the kind and amount of the resection performed, the type of reconstruction and the oncological outcome. METHODS: Between September 1999 and August 2010 31 patients (seven women and 24 men) were treated due to a primary malignant bone tumour or soft tissue sarcoma of the chest wall in two centres. Eight low-grade sarcomas were noted as well as 23 highly malignant sarcomas. The tumours originated from the sternum in six cases, from the ribs in 12 cases, from the soft tissues of the thoracic wall in 11 cases and from a vertebral body and the clavicle in one case each. RESULTS: In 26 cases wide resection margins were achieved, while four were intralesional and one was marginal. In all 31 cases the defect of the chest wall was reconstructed using mesh grafts. At a mean follow-up of 51 months 20 patients were without evidence of disease, three were alive with disease, seven patients had died and one patient was lost to follow-up. One recurrence was detected after wide resection of a malignant triton tumour. CONCLUSIONS: Primary malignant bone tumour or soft tissue sarcoma of the chest wall should be treated according to the same surgical oncological principles as established for the extremities. Reconstruction with mesh grafts and musculocutaneous flaps is associated with a low morbidity.

Simultaneous quantitation of alpha-ketoglutaric acid and 5-hydroxymethylfurfural in plasma by HPLC with UV and fluorescence detection.

Alpha-ketoglutaric acid (KG) and hydroxymethylfurfural (HMF) are currently being investigated in clinical trials as an approach in targeted cancer therapy. Hence, a method for the simultaneous determination of KG and HMF in plasma has been developed. Due to the strongly discriminative chemical properties of KG and HMF, SPE purification is performed using an ion-exchange cartridge to separate KG, and a hydrophobic polymeric cartridge to separate HMF. The cartridges are connected together for several steps, thus resulting in a quicker approach for the purification of plasma samples. The derivatization step is based on the reaction of the carbonyl groups of KG and HMF with dansylhydrazine (DNSH) catalyzed by trifluoroacetic acid. The formed derivatives could be separated by reversed-phase LC on a C8-column, and analyzed by UV and fluorescence detection in a single run using a gradient program. The obtained results show good reproducibility, specificity, and detection limits down to the low picomole range.

Management of esophageal perforation in 120 consecutive patients: clinical impact of a structured treatment algorithm.

INTRODUCTION: The therapy of esophageal perforation is still challenging. The aim of this study was to assess the etiology, specific treatment, and outcome of esophageal disruption in order to generate an optimal therapeutic approach to improve patient's outcome. METHODS: We reviewed the cases of 120 consecutive patients with esophageal perforation treated within 10 years. RESULTS: Iatrogenic perforation was the most frequent cause of esophageal perforation (58.3 %); Boerhaave's syndrome was detected in 15 cases (6.8 %). Surgery was performed in 66 patients (55 %), 17 (14 %) patients received conservative treatment and 37 (31 %) patients underwent endoscopic stenting after tumorous perforation. Statistically significant impact on mean survival had Boerhaave's syndrome (p = 0.005), initial sepsis (p = 0.002), pleural effusion/empyema (p = 0.001), mediastinitis (p = 0.003), peritonitis (p = 0.001), and redo-surgery (p = 0.000). Overall mortality rate was 11.7 %, in the esophagectomy group 17 % and in the patients with Boerhaave's syndrome 33.3 %. CONCLUSIONS: An approach considering etiology and extent of perforation, diagnostic delay, and septic status is required to improve patient's outcome. Primary repair is feasible in patients without intrinsic esophageal disease and evidence of sepsis. The greater the diagnostic delay, the more the destruction of the esophageal wall especially in the case of septic esophageal disease, thus the stronger the argument for esophagectomy if anatomically and/or oncologically possible.

Multimodal therapy of malignant pleural mesothelioma: is the replacement of radical surgery imminent?

OBJECTIVES: Malignant pleural mesothelioma (MPM) remains an aggressive thoracic malignancy associated with poor prognosis. There is no standard treatment regimen, and particularly, the impact of radical surgery remains controversial. The main goal of our retrospective single-centre study was to evaluate the surgical and non-surgical treatment modalities applied at our division regarding their effect on the patient's survival. METHODS: During the last decade, 82 patients with histologically confirmed MPM were treated at our division. The complete clinical records of 61 patients were eligible for statistical evaluation. RESULTS: There were 14 women (23%) and 47 men (77%) with a mean age of 63.7 years. Epitheloid subtype was found in 48 patients (78.7%), sarcomatoid in 3 (4.9%) and biphasic in 10 (16%). Surgery as the first treatment modality was performed in 44 patients (72.1%). Pleurectomy/decortication was done in 28 cases (45.9%), extended pleurectomy/decortication was performed in 13 (21.3%) and extrapleural pneumonectomy in 3 (4.9%). Additional intraoperative photodynamic therapy was administered in 20 patients, 34 underwent chemotherapy (55.7%) and 12 had radiotherapy (19.7%). Mean survival time for the collective was 18.3 months. Five-year survival was 17% in the epitheloid histology group, where patients treated with chemotherapy alone yielded a significant increase in survival (P = 0.049), and those with other subtypes survived for a maximum of 20.6 months. CONCLUSIONS: Chemotherapy and pleurectomy/decortication can extend the survival time of patients with MPM remarkably. The adequate treatment options have to be tailored to the specific particular needs of each patient considering histological subtype, tumour stage and patient's individual functional assessment as well as comorbidity.

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.

Method development and validation for the analysis of a new anti-cancer infusion solution via HPLC.

A fast and simple HPLC method has been developed and validated for the quantification of a completely new anti-cancer drug during the manufacturing process. The combination of four compounds including α-ketoglutaric acid, hydroxymethylfurfural, N-acetyl-L-methionine and N-acetyl-L-selenomethionine, administered intravenously, is still in test phase but has already shown promising results in cancer therapy. HPLC separation was achieved on an RP-18 column with a gradient system. However, the highly different concentrations of the compounds required a variation in the detection wavelength within one run. In order to produce a chromatogram where peaks were comparable on a similar range scale, detection at absorption maxima for the two most concentrated components was avoided. After optimization of the gradient program it was possible to detect all four substances within 14 min in spite of their strongly different chemical structure. The method developed was validated for accuracy, repeatability, reproducibility and robustness in relation to temperature and pH of buffer. Linearity as well as the limit of detection and quantification were determined. This HPLC method was found to be precise, accurate and reproducible and can be easily used for in-line process control during the manufacture of the anti-tumour infusion solution.