Chronic lung allograft dysfunction (CLAD) remains the major barrier to long-term success after lung transplantation. This report compares gross and microscopic features of lungs removed from patients ...receiving a redo-transplant as treatment for CLAD. Lungs donated by patients with either the bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) phenotype of CLAD and appropriate control lungs (eight per group) were air-inflated, frozen solid and kept frozen while a multi-detector computed tomography (MDCT) was obtained. The lung was then cut into 2-cm thick transverse slices and sampled for micro-CT and histopathology. The MDCT showed reduced lung volume with increased lung weight and density in RAS versus BOS and control (p<0.05). Although pre-terminal bronchioles were obstructed in both phenotypes, RAS lungs showed a reduction of pre-terminal bronchioles (p<0.01). Micro-CT and matched histopathology showed that RAS was associated with reduced numbers of terminal bronchioles/lung compared to BOS and controls (p<0.01), with expansion of the interstitial compartment and obliteration of the alveolar airspaces by fibrous connective tissue. RAS is associated with greater destruction of both pre-terminal and terminal bronchioles. Additionally, the interstitial compartments are expanded and alveolar airspaces are obliterated by accumulation of fibrous connective tissue.
The epidemiology, diagnostic methods and management of infectious complications after solid-organ transplantation (SOT) are evolving. The aim of our study is to describe current infectious ...complications in the year following SOT and risk factors for their development and outcome. We conducted a retrospective study in adult SOT recipients in a Belgian university hospital between 2018 and 2019. We gathered demographic characteristics, comorbidities leading to transplantation, clinical, microbiological, surgery-specific and therapeutic data concerning infectious episodes, and survival status up to one year post-transplantation. Two-hundred-and-thirty-one SOT recipients were included (90 kidneys, 79 livers, 35 lungs, 19 hearts and 8 multiple organs). We observed 381 infections in 143 (62%) patients, due to bacteria (235 (62%)), viruses (67 (18%)), and fungi (32 (8%)). Patients presented a median of two (1-5) infections, and the first infection occurred during the first six months. Nineteen (8%) patients died, eleven (58%) due to infectious causes. Protective factors identified against developing infection were obesity OR IC: 0.41 0.19-0.89;
= 0.025 and liver transplantation OR IC: 0.21 0.07-0.66;
= 0.007. Risk factors identified for developing an infection were lung transplantation OR IC: 6.80 1.17-39.36;
= 0.032, CMV mismatch OR IC: 3.53 1.45-8.64;
= 0.006 and neutropenia OR IC: 2.87 1.27-6.47;
= 0.011. Risk factors identified for death were inadequate cytomegalovirus prophylaxis, infection severity and absence of pneumococcal vaccination. Post-transplant infections were common. Addressing modifiable risk factors is crucial, such as pneumococcal vaccination.
Objectives We sought to evaluate the efficacy and safety of a synthetic bioresorbable pleural sealant (PleuraSeal; Covidien, Bedford, Mass) to treat air leaks after pulmonary resection. Methods ...Patients with air leaks after lung resection were randomized to treatment with pleural sealant on air leak sites after standard methods of lung closure or standard lung closure only. The primary outcome variable was the percentage of patients remaining air leak free until discharge. The secondary outcome variables were the proportion of patients with successful intraoperative air leak sealing, time to last air leak, and durations of chest tube drainage and hospitalization. Results The sealant group comprised 62 subjects, and the control group comprised 59 subjects. Most patients (98.3%) underwent open lobectomy for bronchogenic carcinoma. The overall success rates for intraoperative air leak sealing were as follows: sealant group, 71.0%; control group, 23.7% ( P < .001). For grade 2 and 3 air leaks (n = 77), the intraoperative sealing rates were as follows: sealant group, 71.7%; control group, 9.1% ( P < .001). More patients with grade 2 and 3 air leaks had their leaks remain sealed in the sealant group (43.5% vs 15.2%, P = .013). The median time from skin closure to last observable air leak was 6 hours (sealant group) versus 42 hours (control group, P = .718). No treatment-related complications were reported. No differences in drainage or hospitalization were observed. Conclusions In this multicenter study the pleural sealant was safe and effective treatment for intraoperative air leaks after lung resection. Significantly fewer patients with surgically relevant intraoperative air leaks had postoperative air leaks when the pleural sealant was applied.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary ...process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumour-propagating cell capacity, they displayed differences in cellular plasticity, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes identify the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulate EMT transition states.
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KISLJ, NUK, SBMB, UL, UM, UPUK
FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers
. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation ...and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2-CD44-SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.
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KISLJ, NUK, SBMB, UL, UM, UPUK
Endoscopic treatment of a bronchial restenosis previously treated by insertion of a partially covered self-expandable metallic stent (SEMS) can be difficult. Classically, after recanalization of the ...bronchus, the stent is removed and replaced by a more adapted one. We report on two cases of proximal bronchial restenosis treated by insertion of an additional stent inside the lumen of the previously inserted stent using the stent-in-stent (SIS) technique. The indications for the initial stent were malignancy in Patient 1 and posttransplant bronchial stenosis in Patient 2. Restenosis occurred at the proximal end of the stent within months in both cases. Stent removal and insertion of a new stent were considered, but this option was discarded because of an excessive risk of bronchial perforation and preference towards an alternative approach. In both cases, a second customized SEMS was placed using the SIS technique after ablation of the proximal end stenosis of the stent by argon plasma coagulation and/or dilation with a balloon. Recanalization of the bronchus was achieved in both cases without complications. The SIS technique is a valuable alternative to removal of SEMS in case of proximal bronchial restenosis.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES
To minimize air leak after anatomical lung resections, many video-assisted thoracic surgery (VATS) surgeons use a ‘fissureless' technique, using staplers to divide the hilar ...bronchovascular structures first and the main part of the fissure last. We describe a cohort of 198 consecutive patients operated with an alternative fissureless technique, opening the fissure completely with staplers at an early stage of the VATS anatomical lung resection.
METHODS
To open the incomplete fissure first and with staplers, a tunnel dissection is started anterior between the triangle of pulmonary veins and the parenchyma. After identification of the pulmonary artery, the anvil of a first stapler is placed on top of the artery and the anterior part of the fissure is divided. Dissection between artery and parenchyma is continued until the fissure is completely stapled. From a prospectively managed single institution database, we retrieved 405 patients scheduled for VATS anatomical resection between October 2009 and December 2014. The patients were categorized in four consecutive periods: a learning curve with the first 50 cases of VATS lobectomy technique (LC), a period of consecutive ‘hilum first, fissure last’ (HF), a transition group (TG) during which both techniques were used and a period of consecutive ‘fissure first, hilum last’ (FF).
RESULTS
No significant differences in operating time, frequency of prolonged air leak or hospital stay were observed between HF (n = 45) and FF (n = 198). Chest tubes were removed earlier in the FF period (6.9 vs 5.2 days, P = 0.025). Excluding the learning curve, we found 2 patients (2.8%) operated ‘hilum first’ with an intraoperative complication that potentially could have been avoided by a ‘fissure first’ technique.
CONCLUSIONS
By making a tunnel between the bronchovascular structures and parenchyma from anteriorly to posteriorly, one can open the fissure completely with staplers at an early stage of an anatomical lung resection. This combines the advantages of both the ‘fissureless' hilum first technique and classic (open) fissure first dissection, i.e. minimal air leak and optimal anatomical overview before bronchovascular structures are divided, potentially avoiding inadvertent transections. A cohort of 198 consecutive patients operated with this alternative fissureless technique demonstrates the feasibility and non-inferiority regarding hospital stay, chest tube duration, operation time and complications in comparison with the hilum first technique.
OBJECTIVE
Video-assisted thoracoscopic surgery (VATS) lobectomy has been gradually accepted as an alternative surgical approach to open thoracotomy for selected patients with non-small-cell lung ...cancer (NSCLC) over the past 20 years. The aim of this project was to standardize the perioperative management of VATS lobectomy patients through expert consensus and to provide insightful guidance to clinical practice.
METHODS
A panel of 55 experts on VATS lobectomy was identified by the Scientific Secretariat and the International Scientific Committee of the '20th Anniversary of VATS Lobectomy Conference-The Consensus Meeting'. The Delphi methodology consisting of two rounds of voting was implemented to facilitate the development of consensus. Results from the second-round voting formed the basis of the current Consensus Statement. Consensus was defined a priori as more than 50% agreement among the panel of experts. Clinical practice was deemed 'recommended' if 50-74% of the experts reached agreement and 'highly recommended' if 75% or more of the experts reached agreement.
RESULTS
Fifty VATS lobectomy experts (91%) from 16 countries completed both rounds of standardized questionnaires. No statistically significant differences in the responses between the two rounds of questioning were identified. Consensus was reached on 21 controversial points, outlining the current accepted definition of VATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions.
CONCLUSION
The present Consensus Statement represents a collective agreement among 50 international experts to establish a standardized practice of VATS lobectomy for the thoracic surgical community after 20 years of clinical experience.
Summary
Objective
The use of thyroid lobectomy in the treatment of unilateral, benign nodules is limited by the potential of nodular recurrence in the remaining lobe. This study aimed to assess the ...rate and clinical impact of nodular recurrence in the contralateral lobe after thyroid lobectomy and to identify predictive factors of recurrence.
Design
Single‐centre retrospective study.
Patients
Records of patients that underwent lobectomy for unilateral thyroid nodules between 1991 and 2010 were reviewed and 270 patients were included. Exclusion criteria were: presence of contralateral nodule(s) ≥5 mm on preoperative ultrasound, diagnosis of cancer necessitating completion thyroidectomy or pseudonodules. Recurrence was defined as the occurrence of nodule(s) ≥5 mm in the remaining lobe on at least one postoperative ultrasound. A set of clinical, imaging, histological and biochemical parameters was tested as predictors of recurrence using logistic regression.
Results
After a median follow‐up of 78 months (range, 12–277 months), the global recurrence rate was 42% and recurrence of nodules of a size ≥1 cm occurred in 19%. Reoperation rate was 1·1%. 90% of patients were treated postoperatively by levothyroxine. Median time to nodular recurrence was 4 years. Preoperative contralateral lobe volume and resected thyroid weight were identified as significant predictors of recurrence (P = 0·045 and P = 0·03 respectively).
Conclusions
Thyroid lobectomy is an effective therapeutic strategy for unilateral, benign nodules, resulting in a low rate of clinically relevant nodular relapse in a mildly iodine‐deficient area. Patients with uninodular disease and a contralateral lobe of normal size are particularly good candidates for lobectomy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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