Outcomes of oncological intended thoracic surgery after lung transplantation.

Background: Lung cancer following lung transplantation (LT) may require thoracic surgery (TS). There is an urgent need for data on surgical feasibility, clinical and surgical characteristics, as well as outcome data. Methods: We reviewed the medical records of LT patients who had undergone TS at the University Hospital Leipzig between the years 2000 and 2022. Data on medical and surgical history, pulmonary function test, arterial blood gas analysis, six-minute walking distance test, and surgical approach, perioperative management, anesthesiologic, and surgical procedures were analyzed. Results: Among 248 LT patients, 13 patients (5.2%) developed lung cancer after 4.2 years on average and on 6 of them (46.2%), major TS procedure was performed for the resection of lung cancer. In one patient who underwent TS for a suspicious pulmonary nodule, it turned out to be a parenchymal scar. TS was carried out in 57.1% on the native lung and 42.9% on the transplant lung. Pneumonia and acute renal failure were predominantly observed postoperative complications. We found that the capacity of gas exchange either before or after TS was related to the degree of postoperative complications. The in-hospital survival was 71.4%. Conclusions: Incidence of lung cancer is increased after LT. Follow-up care allows early diagnosis with a comparably high share of operable tumor stage. Cancer as well as postoperative complications were more likely after single lung transplantation (SLT). Postoperative morbidity and mortality are higher in this scarce group of patients and hence, warrants a centered and experienced interdisciplinary approach.

Organotypic 3D Co-Culture of Human Pleura as a Novel In Vitro Model of Staphylococcus aureus Infection and Biofilm Development.

Bacterial pleural infections are associated with high mortality. Treatment is complicated due to biofilm formation. A common causative pathogen is Staphylococcus aureus (S. aureus). Since it is distinctly human-specific, rodent models do not provide adequate conditions for research. The purpose of this study was to examine the effects of S. aureus infection on human pleural mesothelial cells using a recently established 3D organotypic co-culture model of pleura derived from human specimens. After infection of our model with S. aureus, samples were harvested at defined time points. Histological analysis and immunostaining for tight junction proteins (c-Jun, VE-cadherin, and ZO-1) were performed, demonstrating changes comparable to in vivo empyema. The measurement of secreted cytokine levels (TNF-α, MCP-1, and IL-1ß) proved host-pathogen interactions in our model. Similarly, mesothelial cells produced VEGF on in vivo levels. These findings were contrasted by vital, unimpaired cells in a sterile control model. We were able to establish a 3D organotypic in vitro co-culture model of human pleura infected with S. aureus resulting in the formation of biofilm, including host-pathogen interactions. This novel model could be a useful microenvironment tool for in vitro studies on biofilm in pleural empyema.

Narrowing the therapeutic window?-A case-control study on the influence of the COVID-19 pandemic on the primary UICC stage of NSCLC.

Background: General clinical perception suggests a decline in the diagnosis and treatment of lung cancer during the SARS-CoV-2 pandemic. Early diagnosis of non-small cell lung cancer (NSCLC) is crucial in therapeutic regimes as early stages are potentially curable by operation alone or with combined therapy. Pandemic-triggered overload of the healthcare system may have prolonged the diagnosis of NSCLC, possibly leading to higher tumor stages at first diagnosis. This study aims to identify how COVID-19 affected the distribution of the Union for International Cancer Control (UICC) stage in NSCLC at first diagnosis. Methods: A retrospective case-control study was conducted, including all patients receiving their first diagnosis of NSCLC in the regions of Leipzig and Mecklenburg-Vorpommern (MV) between January 2019 and March 2021. Patient data were retrieved from the clinical cancer registries of the city of Leipzig and the federal state of MV. Ethical approval for this retrospective evaluation of archived, anonymized patient data was waived by the Scientific Ethical Committee at the Medical Faculty, Leipzig University. Three investigation periods were defined to study the effects of high incidences of SARS-COV-2: the curfew period as an enacted security measure, the period of high incidence rates and the period of the aftermath of high incidences. Differences in the UICC stages between these pandemic periods were studied by Mann-Whitney-U-Test. Pearson's correlation was calculated to examine changes in operability. Results: The number of patients diagnosed with NSCLC dropped substantially during investigation periods. There was a significant difference in the UICC status in the aftermath of high incidences and imposed security measures in Leipzig (P=0.016). N-status differed significantly in the aftermath of high incidences and imposed security measures (P=0.022) with a decrease of N0- and an increase of N3-status, respectively, while N1- and N2-status remained relatively unaffected. No pandemic phase showed a significant difference in operability. Conclusions: The pandemic led to a delay in the diagnosis of NSCLC in the two examined regions. This resulted in higher UICC stages upon diagnosis. However, no increase in inoperable stages was shown. It remains to be seen, how this will affect the overall prognosis of the involved patients.

[Combined intrapulmonary/intramediastinal K-wire position after K-wire osteosynthesis of the clavicle : A case report]. / Kombinierte intrapulmonale/intramediastinale K-Draht-Lage nach K-Draht-Osteosynthese an der Clavicula : Ein Case Report.

BACKGROUND: Lateral clavicle fractures can be treated both conservatively and surgically depending on the fracture classification. Different surgical techniques have been described for the operative treatment. The selection of the appropriate technique is decisive for the functional outcome and healing process without complications. CASE: We report on a patient with a secondary dislocation of two Kirschner wires after Kirschner wire osteosynthesis. The secondary dislocation caused one of the wires to migrate into the mediastinum and pulmonary tissue, directly under the aortic arch. To prevent further migration with potential damage to surrounding structures, a uniportal video-assisted thoracoscopy was performed to retrieve the wire. CONCLUSION: The treatment of lateral clavicle fractures should be performed with bent Kirschner wires as they can otherwise lead to severe complications including the occurrence of pseudarthrosis or secondary migration of the material. Safe and stable surgical techniques (plate osteosynthesis, hybrid treatment) should be preferred if they are available.

[Thoracic Surgery Without Chest Tube: The Current Situation in Germany]. / Thoraxchirurgie ohne Thoraxdrainage ­ aktuelle Situation in Deutschland.

BACKGROUND: Over the last decades, several techniques have been implemented to reduce the invasiveness of thoracic surgery. Omitting chest tubes can lead to less postoperative pain and a shorter length of hospital stay. This study examines the extent to which German surgeons use the tubeless technique and what experience they have had with it. MATERIALS AND METHODS: We conducted a nationwide survey, supported by the German Society of Thoracic Surgery (DGT). A digital questionnaire was sent to all leading thoracic surgeons with DGT membership between July and September 2020. RESULTS: 63 of 161 surgeons (39%) returned the questionnaires. The tubeless technique was used in 1.9% of thoracic surgery procedures performed last year. 59% of hospitals have implemented the technique; 24% of them also performed lung resections that way. The majority of respondents (79%) believe that the tubeless technique causes less postoperative pain; 16% see no advantage. Pleural effusion was ranked as the most important contraindication (76%). All participating surgeons agree that the absence of an air fistula is a prerequisite for performing lung resections using the tubeless technique - commonly checked by an underwater leak test (73%), and/or with a digital drainage system (53%), partially under pressure controlled ventilated lungs. Almost half of the respondents (46%) have not observed any complications using the tubeless technique. CONCLUSION: Most German thoracic surgeons consider the tubeless technique safe and advantageous over the conventional technique. However, the case load is low and only 59% of the surgeons surveyed have experience with this technique. Randomised clinical trials concerning selection criteria and the procedural pathway may help increase the use.

Novel 3D organotypic co-culture model of pleura.

Pleural mesothelial cells are the predominant cell type in the pleural cavity, but their role in the pathogenesis of pleural diseases needs to be further elucidated. 3D organotypic models are an encouraging approach for an in vivo understanding of molecular disease development. The aim of the present study was to develop a 3D organotypic model of the pleural mesothelium. Specimens of human pleura parietalis were obtained from patients undergoing surgery at the University Hospital Leipzig, Germany. 3D co-culture model of pleura was established from human pleural mesothelial cells and fibroblasts. The model was compared to human pleura tissue by phase-contrast and light microscopy, immunochemistry and -fluorescence as well as solute permeation test. Histological assessment of the 3D co-culture model displayed the presence of both cell types mimicking the morphology of the human pleura. Vimentin and Cytokeratin, PHD1 showed a similar expression pattern in pleural biopsies and 3D model. Expression of Ki-67 indicates the presence of proliferating cells. Tight junctional marker ZO-1 was found localized at contact zones between mesothelial cells. Each of these markers were expressed in both the 3D co-culture model and human biopsies. Permeability of 3D organotypic co-culture model of pleura was found to be higher for 70 kDa-Dextran and no significant difference was seen in the permeability for small dextran (4 kDa). In summary, the presented 3D organoid of pleura functions as a robust assay for pleural research serving as a precise reproduction of the in vivo morphology and microenvironment.

PSMA-PET/CT in Patients with Recurrent Clear Cell Renal Cell Carcinoma: Histopathological Correlations of Imaging Findings.

PET/CT with prostate-specific membrane antigen (PSMA)-targeted tracers has been used in the diagnosis and staging of patients with clear cell renal cell carcinoma (ccRCC). For ccRCC primary tumors, PET parameters were shown to predict histologic grade and features. The aim of this study was to correlate PSMA PET/CT with histopathological findings in patients with metastatic recurrence of ccRCC. Patients with ccRCC who underwent PSMA-targeted PET/CT and subsequent histopathological evaluation of suspicious lesions were included. Specimens underwent immunohistochemical marking. Lesion diameter, volume and tracer uptake were correlated with the extent and intensity of molecular PSMA expression and with clinical findings. Twelve PET-positive lesions of nine patients were evaluated. Eleven ccRCC metastases and one prostate carcinoma were detected histopathologically. Molecular PSMA expression was detected in all lesions, which intensity and distribution did not correlate with PET parameters. PSMA-targeted PET/CT is a feasible tool for the evaluation of patients with ccRCC but cannot reliably predict histologic features of metastases. PSMA may also be expressed in malignant lesions other than ccRCC, leading to incidental detection of these tumors.

[Robot-Assisted Lung Surgery]. / Roboterassistierte Lungenchirurgie.

Anatomical lung resection is the standard treatment for patients with early-stage lung cancer. The conventional surgical techniques are thoracotomy and video-assisted thoracic surgery, but new methods have been added as technology has developed. The latest technological development is the robot-assisted anatomical lung resection. In this technique, a robot is used to perform an anatomical lobectomy or segmentectomy as well as lymph node dissection, as determined by oncological criteria. Comparison between the robot-assisted and video-assisted thoracic surgery is still of the greatest interest, since both minimally invasive approaches have their advantages and disadvantages. The aim of this work is to describe the development and performance of robot-assisted thoracic surgery, as well as the comparison with other surgical methods.

[Videoassisted Thoracoscopy with Preserved Spontaneous Breathing - an Anaesthesiological Perspective]. / Videoassistierte Thorakoskopie unter Erhalt der Spontanatmung ­ eine anästhesiologische Perspektive.

INTRODUCTION: Video-assisted thoracoscopic procedures with preserved spontaneous breathing (NI-VATS = conscious video-assisted thoracic surgery) have enjoyed a revival in recent years. However, there have been few reports on proper patient selection, as well as surgical or anaesthesiologic management for these procedures in Germany. Therefore, we present our experience with NI-VATS procedures in the form of a case study and discuss the results with a current survey and the current literature. METHOD: Retrospective evaluation of all NI-VATS procedures at our local institution. RESULTS: From June 2018 to January 2020 n = 17 (9 male and 8 female) patients underwent NI-VATS at our institution. Median age of patients was 68 [61 - 79] years. Fourteen patients suffered from progressive cancer as the underlying disease, leading to thoracic surgery. All patients had a number of comorbidities and were classified according to the ASA categories III (n = 9) or IV (n = 8). Surgical procedures were of short duration (in median 18 [15 - 27] min) and included 82% pleural procedures (pleurectomy, decortication or insertion of pleural drainage). All patients tolerated the surgical procedures under local anaesthesia and conscious sedation very well. Eleven patients could therefore be transferred to the normal ward after surgery, while the remaining patients underwent prolonged and intensified postoperative monitoring. Five of the 17 patients died within the hospital, in median 8 [3.0 - 33.5] days after surgery, in context of the underlying disease. None of the deaths could be associated with the surgical procedures. DISCUSSION: In a well selected patient cohort and with our local experience, NI-VATS is a safe and practicable alternative to standard thoracotomy in general anaesthesia and one-lung ventilation. In our local institution, multimorbid patients with interventions of short duration and reasonable extent underwent successful NI-VATS and emerged as good candidates for this procedure. Careful patient selection and knowledge of the procedure and its side effects present important milestones for successful NI-VATS.

[How severe is the effect of the coronavirus pandemic on the department of surgery of a university hospital? : An analysis of the first 7 weeks]. / Wie stark trifft die Corona-Pandemie die chirurgische Klinik eines universitären Maximalversorgers? : Eine Analyse der ersten 7 Wochen.

BACKGROUND: The corona pandemic poses enormous financial challenges for hospitals. Using the example of a clinic for visceral, transplantation, thorax and vascular surgery (VTTG), the performance development of inpatient care in the first 7 weeks in comparison to the previous year as well as an evaluation of the compensation measures laid down by law were evaluated. METHODOLOGY: Based on the performance figures, a comparison was made between the period from 16 March to 3 May 2019 and the same period in 2020. Changes in the number of cases, case mix, case mix index and day mix index as well as the bed occupancy days were recorded. The monetary measures from the COVID-19 Hospital Relief Act were applied to these changes and the adequacy was evaluated. RESULTS: Compared to the previous year there was a decrease in inpatient admissions of 120 patients during the observation period. As a result there was a decrease of 370 points in case mix and 1433 days of occupancy. For the whole VTTG this resulted in a decrease in revenue of approximately 0.8 million €, which was completely compensated by the flat rate payment for empty beds. The individual areas of the VTTG showed a heterogeneous picture in relation to the compensation for the loss of revenue. Elective units in particular showed a shortfall up to 128,163 € with respect to inpatient treatment for 7 weeks. CONCLUSION: The measures taken by the Government are an important support for the economic security of German hospitals. The lack of differentiation of measures by specialty leads to a heterogeneous picture in compensation for VTTG revenues and has to be understood as an alarm signal especially for elective surgical healthcare.

[Robotics in thoracic surgery]. / Robotik in der Thoraxchirurgie.

The number of interventions using robot-assisted thoracic surgery (RATS) is increasing in Germany, following the previous international development. Robot-assisted surgery provides some technical advantages and can overcome existing limitations of video-assisted thoracic surgery (VATS), especially in the case of extended resections, thus enabling the proportion of minimally invasive operations to be further increased. The safety of the procedure, even in extended resections, has repeatedly been demonstrated but whether there are clinically relevant benefits from RATS is currently the subject of scientific discussions. In addition, a further technical evolution of the RATS can be postulated by the upcoming market introduction of new robotic systems.

Current status and evolution of robotic-assisted thoracic surgery in Germany-results from a nationwide survey.

BACKGROUND: Robot-assisted surgery has made a significant entry into surgical practice within Germany, including thoracic surgery. As no published data exists regarding robotic-assisted thoracic surgery (RATS), we conducted a survey to investigate its current status. METHODS: We performed a nationwide survey of all centers active in RATS, using a standardized questionnaire. The annual number of operations, mean duration of surgery, docking time, length of hospital stay(s), conversions, chest tube duration, the RATS program start date, robot system used, operating room capacity, and staplers and instruments used were recorded. RESULTS: Of the 22 centers contacted, 14 responded. In total, 786 RATS interventions were recorded. Most were anatomical lung resections, comprising 372 (bi-) lobectomies and 80 segmentectomies. During the study period, eight bronchoplastic procedures were performed robotically. There were 93 wedge lung resections, 148 thymectomies, 26 sympathectomies, and 59 other RATS procedures, and a single-center series of around 1,000 RATS thymectomies (excluded from statistical analysis). The average incision-suture time of the RATS lobectomy was 245 (range, 80-419) minutes, average residence time seven days. The conversion rate was 6.7% across all interventions, with significant inter-intervention differences. All surveyed centers plan to further expand RATS, with OR capacity being a frequent impediment. Five RATS interventions were performed in Germany in 2013, versus 320 in 2018. CONCLUSIONS: Overall, RATS is becoming more established in everyday clinical practice in Germany. The number of operations, active centers, and trained RATS surgeons has increased steadily since 2013. A German-speaking operation course for entry into RATS already exists. Even extended resections can be carried out safely, and RATS has become standard procedure in some centers.

Second- and further-line therapy with erlotinib in patients with advanced non-small-cell lung cancer in daily clinical practice.

INTRODUCTION: The aim of this retrospective study was to examine effect of erlotinib in patients with advanced non-small cell lung cancer (NSCLC) in second-line and further therapy in daily clinical practice. METHODS: Patients with histologically or cytologically proven NSCLC (n = 84) treated with erlotinib in second-line (n = 34), third-line (n = 36), and more-line therapy (n = 14) were examined for progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of therapy, and adverse effects. RESULTS: Median PFS of all lines was 83 days (CI 70.0-96.0), OS was 7 months (CI 4.7-9.3), DCR was 66.2% (CI 55-77%), and 1-year survival rate was 33% (CI 22-43%), with no significant difference between therapy lines. Median duration of treatment was 76 days (IQR 39-139.5). Patients with epidermal growth factor receptor mutation (EGFR-M) reached the highest PFS (204 days), as did patients with good performance status (ECOG 0-1: 94 versus ECOG 2-3: 65 days, P = 0.035). Patients with EGFR-M also revealed a DCR of 100%. The most frequent side effects were rash (69%) and diarrhoea (41%), without any significant difference between therapy lines. In 24 patients, the treatment dose was reduced and in 18, the therapy was paused. CONCLUSION: Erlotinib works in all therapy lines without any significant differences in efficacy and side effects.

Expression and regulation of CD97 in colorectal carcinoma cell lines and tumor tissues.

The expression of CD97, a member of the EGF-TM7 family with adhesive properties, is proportional to the aggressiveness and lymph node involvement in thyroid tumors. CD97 has never been systematically investigated in other tumors. First, we examined colorectal carcinoma cell lines (n = 18) for CD97 expression and regulation. All cell lines were CD97-positive. The level of CD97 in each line correlated with migration and invasion in vitro. This result was confirmed in CD97-inducible Tet-off HT1080 cells. Transforming growth factor-beta, which inhibits proliferation in transforming growth factor-beta-sensitive LS513 and LS1034 cells, down-regulated CD97 in these cell lines. Examining CD97 during sodium butyrate-induced cell differentiation of Caco-2 cells, we could demonstrate a CD97-decreasing effect. Second, we screened 81 colorectal adenocarcinomas by immunohistology for expression of CD97. Normal colorectal epithelium is CD97-negative. Seventy-five of 81 of the carcinomas expressed CD97. The strongest staining for CD97 occurred in scattered tumor cells at the invasion front compared to cells located within solid tumor formations of the same tumor. Carcinomas with more strongly CD97-stained scattered tumor cells showed a poorer clinical stage as well as increased lymph vessel invasion compared to cases with uniform CD97 staining. In summary, CD97 expression correlates with dedifferentiation, migration, and invasion in colorectal tumor cell lines. Moreover, more strongly CD97-stained tumor cells at the invasion front of colorectal carcinomas indicate the involvement of the molecule in tumor migration and invasion.

CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric, pancreatic, and esophageal carcinomas.

CD97 expression is related closely to the dedifferentiation and tumor stage in thyroid carcinomas. We systematically examined the role of CD97 and its closest relative, EMR2, in normal and malignant gastric, esophageal, and pancreatic tissue. The normal tissues were EMR2-, whereas CD97 was expressed slightly in the parietal cells of gastric mucosa and in exocrine pancreatic cells. Interestingly, intralobular and interlobular pancreatic ducts were CD97+. All tumors were EMR2-. CD97 was expressed by 44 of 50 gastric, 14 of 18 pancreatic, and 10 of 13 esophageal carcinomas. Of the 44 gastric cancers, 27 showed disseminated or scattered tumor cells at the invasion front with stronger CD97 expression than tumor cells located in solid tumor formations. There was no correlation between CD97 levels in the tumors or soluble CD97 in the serum samples and the clinicopathologic features of the patients. Taken together, significant numbers of gastric, esophageal, and pancreatic carcinomas are CD97+, whereas its homolog, EMR2, does not have any role in such tumors.

Successful resection of a re-occurred pulmonary myosarcoma in a patient with turner syndrome mosaic.

We describe a patient who underwent thoracic radiation therapy for biopsy-proven pulmonary spindle cell sarcoma in the left lower lobe, 15 months after birth. At the age of 37 she developed shoulder pain, fatigue, and progressive exertion dyspnoea. Chest X-ray revealed a pulmonary mass in the left lower lobe due to a cytology-proven malignant tumour.The patient underwent left pneumonectomy. Histology revealed a myosarcoma of the lung, similar to the previous sarcoma. Furthermore, the patient was diagnosed to have Turner syndrome mosaic and chromosomal analysis revealed a translocation t(1;13) in 3/50 metaphases. However a germline mutation of the p53 tumour suppressor gene was excluded. After 2 years of follow-up the patient is stable and there are no signs of recurrence of the tumour.We conclude a re-occurrence of this very rare malignant disorder of the lung after a 36-year interval in a patient with Turner syndrome mosaic. Following initial curative radiation therapy, with a remission over 36 years, lung resection was now successfully performed.