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.

[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.

IGFBP3 inhibits tumor growth and invasion of lung cancer cells and is associated with improved survival in lung cancer patients.

The insulin-like growth factor (IGF)-pathway is involved in tumor cell proliferation, metastasis, and survival. We aimed to find out what effects IGF binding protein 3 (IGFBP3) exerted on H1299 lung cancer (LC) cells in terms of tumor growth and invasion and whether IGFBP3 was associated with clinical and pathological parameters in a prospective cohort of LC patients. H1299 cells were transfected with an IGFBP3-expressing vector. Its influence on apoptosis induction via flow cytometry annexin V FITC assay, cell proliferation in 2D and 3D cell culture, and invasion were examined. Expression of several matrix metalloproteinases (MMPs) and inhibitors (TIMP-1) were also investigated in IGFBP3-transfected LC cells. Further, data on LC patients (n = 131), tumor characteristics, and survival were prospectively collected and correlated with IGFBP3 plasma levels. IGFBP3 did not influence apoptosis induction and 2D cell proliferation. However, both spheroid growth (3D proliferation) and invasion of IGFBP3-transfected cells planted in an extracellular matrix-based gel were significantly inhibited. IGFBP3 inhibited MMP-1 release, and the total MMP activity. In LC patients, higher IGFBP3 plasma levels correlated with both lower clinical tumor stage, grading, Ki-67 staining, and the absence of necrosis (P < 0.05, respectively). Increased IGFBP3 plasma levels were associated with improved overall survival (hazard ratio 0.37, P = 0.01). In conclusion, overexpressed IGFBP3 in a LC cell line inhibited tumor growth and invasion. Translating from bench to bedside, investigation of clinicopathological parameters confirmed these experimental results showing that higher IGFBP3 plasma levels were associated with less aggressive tumor growth, reduced tumor spread, and improved survival of LC patients.

The role of virtual reality simulation in surgical training in the light of COVID-19 pandemic: Visual spatial ability as a predictor for improved surgical performance: a randomized trial.

INTRODUCTION: Due to the current COVID-19 pandemic, surgical training has become increasingly challenging due to required social distancing. Therefore, the use of virtual reality (VR)-simulation could be a helpful tool for imparting surgical skills, especially in minimally invasive environments. Visual spatial ability (VSA) might influence the learning curve for laparoscopic surgical skills. However, little is known about the influence of VSA for surgical novices on VR-simulator training regarding the complexity of different tasks over a long-term training period. Our study evaluated prior VSA and VSA development in surgical trainees during VR-simulator training, and its influence on surgical performance in simulator training. METHODS: In our single-center prospective two-arm randomized trial, VSA was measured with a tube figure test before curriculum training. After 1:1 randomization, the training group (TG) participated in the entire curriculum training consisting of 48 different VR-simulator tasks with varying difficulty over a continuous nine-day training session. The control group (CG) performed two of these tasks on day 1 and 9. Correlation and regression analyses were used to assess the influence of VSA on VR-related surgical skills and to measure procedural abilities. RESULTS: Sixty students (33 women) were included. Significant improvements in the TG in surgical performance and faster completion times were observed from days 1 to 9 for the scope orientation 30° right-handed (SOR), and cholecystectomy dissection tasks after the structured 9-day training program. After training, the TG with pre-existing low VSA scores achieved performance levels similar to those with pre-existing high VSA scores for the two VR simulator tasks. Significant correlations between VSA and surgical performance on complex laparoscopic camera navigation SOR tasks were found before training. CONCLUSIONS: Our study revealed that that all trainees improved their surgical skills irrespective of previous VSA during structured VR simulator training. An increase in VSA resulted in improvements in surgical performance and training progress, which was more distinct in complex simulator tasks. Further, we demonstrated a positive relationship between VSA and surgical performance of the TG, especially at the beginning of training. Our results identified pre-existing levels of VSA as a predictor of surgical performance.

Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-ß.

Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-ß (TGF-ß) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-ß, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-ß signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-ß.

Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition.

Despite novel immunotherapies being approved and established for the treatment of non-small cell lung cancer (NSCLC), ex vivo models predicting individual patients' responses to immunotherapies are missing. Especially immune modulating therapies with moderate response rates urge for biomarkers and/or assays to determine individual prediction of treatment response and investigate resistance mechanisms. Here, we describe a standardized ex vivo tissue culture model to investigate individual tumor responses. NSCLC tissue cultures preserve morphological characteristics of the baseline tumor specimen for up to 12 days ex vivo and also maintain T-cell function for up to 10 days ex vivo. A semi-automated analysis of proliferating and apoptotic tumor cells was used to evaluate tissue responses to the PD-1 inhibitor nivolumab (n = 12), from which two cases could be successfully correlated to the clinical outcome. T-cell responses upon nivolumab treatment were investigated by flow cytometry and multispectral imaging. Alterations in the frequency of the Treg population and reorganization of tumor tissues could be correlated to nivolumab responsiveness ex vivo. Thus, our findings not only demonstrate the functionality of T cells in NSCLC slice cultures up to 10 days ex vivo, but also suggests this model for stratifying patients for treatment selection and to investigate in depth the tumor-associated T-cell regulation.

Procedural times in early non-intubated VATS program - a propensity score analysis.

BACKGROUND: Non-intubated video-assisted thoracic surgery (NiVATS) has been introduced to surgical medicine in order to reduce the invasiveness of anesthetic procedures and avoid adverse effects of intubation and one-lung ventilation (OLV). The aim of this study is to determine the time effectiveness of a NiVATS program compared to conventional OLV. METHODS: This retrospective analysis included all patients in Leipzig University Hospital that needed minor VATS surgery between November 2016 and October 2019 constituting a NiVATS (n = 67) and an OLV (n = 36) group. Perioperative data was matched via propensity score analysis, identifying two comparable groups with 23 patients. Matched pairs were compared via t-Test. RESULTS: Patients in NiVATS and OLV group show no significant differences other than the type of surgical procedure performed. Wedge resection was performed significantly more often under NiVATS conditions than with OLV (p = 0,043). Recovery time was significantly reduced by 7 min (p = 0,000) in the NiVATS group. There was no significant difference in the time for induction of anesthesia, duration of surgical procedure or overall procedural time. CONCLUSIONS: Recovery time was significantly shorter in NiVATS, but this effect disappeared when extrapolated to total procedural time. Even during the implementation phase of NiVATS programs, no extension of procedural times occurs.

Thoracotomy for emergency repair of iatrogenic tracheal rupture: single center analysis of perioperative management and outcomes.

BACKGROUND: Iatrogenic tracheal ruptures are rare but life-threatening airway complications that often require surgical repair. Data on perioperative vital functions and anesthetic regimes are scarce. The goal of this study was to explore comorbidity, perioperative management, complications and outcomes of patients undergoing thoracotomy for surgical repair. METHODS: We retrospectively evaluated adult patients who required right thoracotomy for emergency surgical repair of iatrogenic posterior tracheal ruptures and were admitted to a university hospital over a 15-year period (2004-2018). The analyses included demographic, diagnostic, management and outcome data on preinjury morbidity and perioperative complications. RESULTS: Thirty-five patients who met the inclusion criteria were analyzed. All but two patients (96%) presented with critical underlying diseases and/or emergency tracheal intubations. The median time (interquartile range) from diagnosis to surgery was 0.3 (0.2-1.0) days. The durations of anesthesia, surgery and one-lung ventilation (OLV) were 172 (128-261) min, 100 (68-162) min, and 52 (40-99) min, respectively. The primary airway management approach to OLV was successful in only 12 patients (34%). Major complications during surgery were observed in 10 patients (29%). Four patients (11%) required cardiopulmonary resuscitation, one of whom received extracorporeal membrane oxygenation, and another one of these patients died during surgery. Major complications were associated with significantly higher all-cause 30-day mortality (p = 0.002) and adjusted mortality (p = 0.001) compared to patients with minor or no complications. CONCLUSIONS: Surgical repair of iatrogenic tracheal ruptures requires advanced perioperative care in a specialized center due to high morbidity and potential complications. Airway management should include early anticipation of alternative OLV approaches to provide acceptable conditions for surgery.

Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis.

BACKGROUND: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. AIM: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT). METHODS: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine-mediated cancer pathways inclusive of MAPK and NF-kappa B were tested. RESULTS: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1-40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12-0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029). CONCLUSIONS: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells.

Surgical therapy of chronic pancreatitis: clinical results and health-related quality of life.

INTRODUCTION: There are several well-established surgical procedures for the treatment of chronic pancreatitis (CP). The present study seeks to evaluate the perioperative and long-term outcome of these procedures. METHODS: All patients who had undergone pancreaticoduodenectomy (PD), duodenum-preserving pancreatic head resection (DPPHR), and distal pancreatectomy (DP) for CP were retrospectively analyzed with regards to the perioperative outcome and long-term survival. Health-related quality of life (HRQoL) was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: There were 145 patients available for analysis. Major complications (grade IIIb-V) occurred in 19 %, in-hospital mortality was 4.2 %, and 90-day mortality was 3 % with no differences between the different resection groups (all p > 0.05). Ten-year survival was 58 % and was highest in the DP group (100 %) but without statistical significance (p = 0.72). The response rate of the HRQoL assessment was 45 % (65 of 145). There was a significant improvement with regards to pain and HRQoL of all resection groups compared to the preoperative group (all p < 0.05). With respect to HRQoL and pain relief, the PD, DPPHR, and DP did not differ significantly. DISCUSSION: Surgical therapy of CP can be performed safely. The 3 different types of resection performed equally with regards to complications and HRQoL.

Primary liver transplantation and liver retransplantation: comparison of health-related quality of life and mental status - a cross-sectional study.

BACKGROUND: Liver Retransplantation (Re-LT) procedures are associated with an increased risk of morbidity and mortality. Up to date, there is no knowledge on the health-related quality of life and the mental status of these patients. METHODS: Health-Related Quality of Life (HRQoL) was assessed by using the Short Form 36 (SF-36) Health Survey and Mental Status was assessed by using the Hospital Anxiety and Depression Scale (HADS). The patients were examined in different assessments: During regular check-up examinations in the LT outpatient department in 2011 (Survey 1) and in a postal survey in 2013 (Survey 2). Their medical data was collected by using an established database. RESULTS: We received eligible surveys of 383 patients (55.6%) with a history of LT, of which 15 (3.9%) had undergone Re-LT (Re-LT group). These patients were compared to a group of 60 patients who had undergone only one LT. With regard to their HRQoL, the Re-LT group had significantly lower scores on the scales of physical function (PF, p = 0.026), their role-physical (RP, p = 0.008), their vitality (VIT, p = 0.040), and their role-emotional (RE, p = 0.005). The scores for anxiety and depression did not differ significantly between the groups. In a multiple regression analysis, chronic kidney disease was found to be an independent risk factor for decreased scores of PF (p = 0.023). CONCLUSIONS: Patients who have to undergo Re-LT procedures are faceing impairments in physical aspects of a HRQoL. Together with clinical results from other studies, the findings of the present examination underline the need for an optimized organ distribution strategy since not all patients listed for Re-LT appear to benefit from it.

Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model.

In patients, acute kidney injury (AKI) is often due to haemodynamic impairment associated with hepatic decompensation following extended liver surgery. Mesenchymal stem cells (MSCs) supported tissue protection in a variety of acute and chronic diseases, and might hence ameliorate AKI induced by extended liver resection. Here, 70% liver resection was performed in male pigs. MSCs were infused through a central venous catheter and haemodynamic parameters as well as markers of acute kidney damage were monitored under intensive care conditions for 24 h post-surgery. Cytokine profiles were established to anticipate the MSCs' potential mode of action. After extended liver resection, hyperdynamic circulation, associated with hyponatraemia, hyperkalaemia, an increase in serum aldosterone and low urine production developed. These signs of hepatorenal dysfunction and haemodynamic impairment were corrected by MSC treatment. MSCs elevated PDGF levels in the serum, possibly contributing to circulatory homeostasis. Another 14 cytokines were increased in the kidney, most of which are known to support tissue regeneration. In conclusion, MSCs supported kidney and liver function after extended liver resection. They probably acted through paracrine mechanisms improving haemodynamics and tissue homeostasis. They might thus provide a promising strategy to prevent acute kidney injury in the context of post-surgery acute liver failure.

Outcome and complications of combined liver and pancreas resections: a retrospective analysis.

BACKGROUND: Combined resections of the liver and pancreas are related to high complication and mortality rates. The present study assessed the outcome of these procedures and identified specific risk factors for morbidity and mortality. METHODS: Between January 2001 and April 2012, 28 combined liver/pancreas resections were performed at our institution. All patients were retrospectively analysed using a database with regards to baseline characteristics, surgical procedures, complications and survival. RESULTS: Among the pancreatic resections, there were 12 (42.9%) Kausch-Whipple (KW), 9 (32.1%) pylorus-preserving pancreaticoduodenectomy (PPPD), 6 (21.4%) distal pancreatectomies (DP) and 1 (3.6%) total pancreaticoduodenectomy (TPD). In 12 (48.9%) cases, major complications (grade IIIb-V) were observed. Overall survival was 35 months (SD = 40.5) and the 3-year survival rate was 35.7% (1-year survival rate: 50%). DISCUSSION: Combined resections of the liver and pancreas are associated with high complication rates, especially if major liver resections are performed. Therefore, it is mandatory to do a thorough evaluation of potential patients.