The first tissue-engineered airway transplantation: 5-year follow-up results.

BACKGROUND: In 2008, the first transplantation of a tissue-engineered trachea in a human being was done to replace an end-staged left main bronchus with malacia in a 30-year-old woman. We report 5 year follow-up results. METHODS: The patient was followed up approximately every 3 months with multidetector CT scan and bronchoscopic assessment. We obtained mucosal biopsy samples every 6 months for histological, immunohistochemical, and electron microscopy assessment. We also assessed quality of life, respiratory function, cough reflex test, and production and specificity of recipient antibodies against donor human leucocyte antigen. FINDINGS: By 12 months after transplantation, a progressive cicatricial stenosis had developed in the native trachea close to the tissue-engineered trachea anastomosis, which needed repeated endoluminal stenting. However, the tissue-engineered trachea itself remained open over its entire length, well vascularised, completely re-cellularised with respiratory epithelium, and had normal ciliary function and mucus clearance. Lung function and cough reflex were normal. No stem-cell-related teratoma formed and no anti-donor antibodies developed. Aside from intermittent bronchoscopic interventions, the patient had a normal social and working life. INTERPRETATION: These clinical results provide evidence that a tissue-engineering strategy including decellularisation of a human trachea, autologous epithelial and stem-cell culture and differentiation, and cell-scaffold seeding with a bioreactor is safe and promising. FUNDING: European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, ALF Medicine.

Which Surgery for Stage II-III Empyema Patients? Observational Single-Center Cohort Study of 719 Consecutive Patients.

OBJECTIVE: Recent guidelines support the use of thoracoscopic surgery in stage II-III empyema; however, there is still debate regarding the best surgical approach. The aim of our study is to compare postoperative outcomes of VATS and open surgical approaches for the treatment of post-pneumonic empyema. METHODS: Observational cohort study on prospectively collected cases of post-pneumonic empyema surgically treated in a single center (2000-2020). Patients were divided into an open group (OT, posterolateral muscle sparing thoracotomy) and VATS group (VT, 2 or 3 port ± utility incision). The primary outcome of the study was empyema resolution, assessed by the recurrence rate. Secondary outcomes were mortality, complications, pain and return to daily life. All patients were followed up at 1, 3 and 6 months after surgery in the outpatient clinic with a chest radiograph/CT scan. RESULTS: In total, 719 consecutive patients were surgically treated for stage II-III empyema, with 644 belonging to the VT group and 75 to the OT group. All patients had a clinical history of pneumonia lasting no more than 6 months before surgery, and 553 (76.9%) had stage II empyema. Operative time was 92.7 ± 6.8 min for the OT group and 112.2 ± 7.4 for the VT group. The conversion rate was 8.4% (46/545) for stage II and 19.2% (19/99) for stage III. Twelve patients (1.86%) in the VT group and four patients (5.3%) in the OT group underwent additional surgery for bleeding. Postoperative mortality was 1.25% (9/719): 5.3% (4/75) in OT and 0.77% (5/644) in VT. Postoperative stay was 10 ± 6.5 days in OT and 8 ± 2.4 in VT. Overall morbidity was 14.7% (106/719): 21.3% (16/75) in OT and 13.9% (90/644) in VT. In VT, six patients (0.93%) showed recurrent empyema: five were treated with chest drainage and one with additional open surgery. CONCLUSIONS: Our findings suggest that the VATS approach, showing a 99% success rate, shorter length of stay and lower postoperative morbidity, should be considered the treatment of choice for thoracic empyema.

Post-intubation tracheal lacerations: Risk-stratification and treatment protocol according to morphological classification.

Background: Post-intubation tracheal laceration (PITL) is a rare condition (0.005% of intubations). The treatment of choice has traditionally been surgical repair. Following our first report in 2010 of treatment protocol tailored to a risk-stratified morphological classification there is now clear evidence that conservative therapy represents the gold standard in the majority of patients. In this paper we aim to validate our risk-stratified treatment protocol through the largest ever reported series of patients. Methods: This retrospective analysis is based on a prospectively collected series (2003-2020) of 62 patients with PITL, staged and treated according to our revised morphological classification. Results: Fifty-five patients with Level I (#8), II (#36) and IIIA (#11) PITL were successfully treated conservatively. Six patients with Level IIIB injury and 1 patient with Level IV underwent a surgical repair of the trachea. No mortality was reported. Bronchoscopy confirmed complete healing in all patients by day 30. Statistical analysis showed age only to be a risk factor for PITL severity. Conclusions: Our previously proposed risk-stratified morphological classification has been validated as the major tool for defining the type of treatment in PITL.

Malignant Pleural Mesothelioma Nodal Status: Where Are We at?

Due to the lack of both prospective trial and high-volume retrospective studies, the management of clinical N+ malignant pleural mesothelioma (MPM) patients remains highly debated. Node positive patients show poor survival compared with node-negative ones; thus, lymph node staging appears crucial in determining treatment strategy. Notwithstanding the improvement in pre-treatment staging and the update on lymph node classification in the 8th edition of TNM, several open controversies remain on N parameter. How should we stage suspected N+ patients? How should we treat node positive patients? Which is the definition of a "resectable patient"? Is the site or the number the main prognostic factor for node positive patients? The aim of our narrative review is to analyse the existing relevant literature on lymph node status in MPM.

Does videomediastinoscopy with frozen sections improve mediastinal staging during video-assisted thoracic surgery pulmonary resections?

BACKGROUND: To assess if video-mediastinoscopy (VM) with frozen sections (FS) combined with a video-assisted thoracic surgery major pulmonary resection (VMPRS) is able to improve VATS mediastinal intraoperative staging. METHODS: From June 2012 to March 2015 a total of 146 patients underwent VMPRS lymphadenectomy. NCCN guidelines were followed for pre-operative staging, including VM with FS in 27 patients (19%). Procedural time, dissected nodal stations, complications related to VM and VATS lymphadenectomy and definitive histology, were evaluated. RESULTS: Operative time for VATS resection with VM (group 1) and VATS pulmonary resection alone (group 2) was 198±64 vs. 167±43 min (P=0.003). Mean/median numbers of dissected nodal stations were 4.93±1.1/5 (range, 4-8) in group 1 and 3.25±0.5/5 (range, 3-8) in group 2 (P<0.001). Group 1 vs. group 2 right-sided lymphadenectomy (n=86) was performed at station 2R/4R in 18 (90%) and 46 (69.7%); at station 3a/3p in 14 (51.8%) and 22 (31%); at station 7 in 18 (90%) and 44 (66.7%); at station 8/9 in 11 (55%) and 24 (36.4%) respectively. On the left side (n=60) group 1 vs. group 2 lymphadenectomy resulted at station 4 in 6 (85.7%) and 38 (71.7%); at station 5/6 in 6 (85.7%) and 26 (49%); at station 7 in 6 (85.7%) and 33 (62.3%), and at station 8/9 in 1 (14.3%) and 18 (34%). There were no early deaths and recurrent laryngeal nerve palsy occurred in 1 (0.8%) in group 2. Pathological upstaging (pN1; pN2) was found in 5 patients (17%) in group 1, and 13 (11%) in group 2 (P=0.23). About FS (n=29), formal paraffin histology resulted in 0% of both, false negative and false positive results. CONCLUSIONS: Based on our experience, the combination "VM with FS followed by VMPRS in sequence", seems to be effective and offers an alternative approach to improve intraoperative mediastinal staging.

Development of a video-assisted thoracoscopic lobectomy program in a single institution: results before and after completion of the learning curve.

BACKGROUND: The development of a video assisted thoracic surgery lobectomy (VATS-L) program provides a dedicated surgical team with a recognized learning curve (LC) of 50 procedures. We analyse the results of our program, comparing the LC with subsequent cases. METHODS: From June 2012 to March 2015, we performed n = 146 VATS major pulmonary resections: n = 50 (Group A: LC); n = 96 (Group B). Pre-operative mediastinal staging followed the National Comprehensive Cancer Network guidelines. All procedures were performed using a standard anterior approach to the hilum; lymphadenectomy followed the NCCN recommendations. During the LC, VATS-L indication was reserved to clinical stages I, therefore evaluated case by case. RESULTS: Mean operative time was 191 min (120-290) in Group A and 162 min (85-360) in Group B (p <0,01). Pathological T status was similar between two Groups. Lymphadenectomy included a mean of 5.8 stations in Group A and 6.6 in Group B resulting in: pN0 disease: Group A n = 44 (88 %), Group B n = 80 (83.4 %); pN1: Group A n = 3 (6 %), Group B n = 8 (8.3 %); pN2: Group A n = 3 (6 %), Group B n = 8 (8.3 %). Conversion rate was: 8 % in group A (n = 4 vascular injuries); 1.1 % in Group B (n = 1 hilar lymph node disease). We registered n = 6 (12 %) complications in Group A, n = 10 (10.6 %) in Group B. One case (1.1 %) of late post-operative mortality (90 days) was registered in Group B for liver failure. Mean hospital stay was 6.5 days in Group A and 5.9 days in Group B. CONCLUSIONS: We confirm the effectiveness of a VATS-L program with a learning curve of 50 cases performed by a dedicated surgical team. Besides the LC, conversion rate falls down, lymphadenectomy become more efficient, indications can be extended to upper stages.

Long-term changes to in vitro preserved bioengineered human trachea and their implications for decellularized tissues.

Bioengineered tissues created for transplant will be expected to survive and contribute to function over the lifetime of the individual. To evaluate potential intrinsic changes and degradation of the extracellular matrix of decellularized human tissue scaffolds, human decellularized tracheas were evaluated over a one year period in vitro. Human tracheas were decellularized and stored for one year in phosphate-buffered saline at 4 °C in the presence of antibiotics and anti-mycotics, and their structural, mechanical, and angiogenic properties compared to baseline values. Results showed that stored human decellularized tracheas were increasingly degraded resulting in a loss of extracellular matrix architecture - in particular of collagenous and elastic fiber structure -and decreased mechanical and angiogenic properties. The mechanical alterations of the extracellular matrix but not the deterioration and microstructure were not improved by using a natural cross-linking agent. These findings demonstrate that human decellularized tracheas, stored for one year in phosphate-buffered saline solution at 4 °C, would not meet the demands for a tissue engineering matrix and likely would not yield a suitable graft for lifelong implantation. The degradation phenomenon observed in vitro may be further enhanced in vivo, having clinical relevance for tissues that will be transplanted long-term and this should be carefully evaluated in pre-clinical settings.