Severe chest wall deformities are considered an absolute contraindication for lung transplantation. The significantly impaired chest compliance associated with pectus excavatum is thought to result ...in a high risk of postoperative respiratory complications and significant morbidity and mortality. We herein report our pooled institutional experience consisting of 3 patients who underwent bilateral lung transplantation and simultaneous correction of a pectus excavatum. Two of the patients were children and 1 patient had severe asymmetric pectus. All patients received a size‐reduced double lung transplant and the deformity was corrected by a Nuss or modified Ravitch procedure. The perioperative course was complicated by prolonged weaning requiring tracheostomy in 2 of the 3 patients. However, long‐term results were good and all 3 patients are alive in excellent clinical condition 72, 60, and 12 months after the transplantation. This case series demonstrates that patients with severe chest wall deformities should not a priori be excluded from lung transplantation, and a combined approach is feasible for selected patients.
This case series suggests that, for selected cases, lung transplantation with simultaneous correction of severe chest wall deformity may be feasible.
The introduction of the lung allocation score has brought lung transplantation (LTX) of patients on extracorporeal membrane oxygenation (ECMO) bridge into the focus of interest. We reviewed our ...institutional experience with ECMO as a bridge to LTX.
Between 1998 and 2011, 38 patients (median age 30.1 years, range 13-66 years) underwent ECMO support with intention to bridge to primary LTX. The underlying diagnosis was cystic fibrosis (n=17), pulmonary hypertension (n=4), idiopathic pulmonary fibrosis (n=9), adult respiratory distress syndrome (n=4), hemosiderosis (n=1), bronchiolitis obliterans (n=1), sarcoidosis (n=1), and bronchiectasis (n=1). The type of extracorporeal bridge was venovenous (n=18), venoarterial (n=15), interventional lung assist (n=1), or a stepwise combination of them (n=4). The median bridging time was 5.5 days (range 1-63) days. The type of transplantation was double LTX (n=7), size-reduced double LTX (n=8), lobar LTX (n=16), split LTX (n=2), and lobar LTX after ex vivo lung perfusion (n=1).
Four patients died before transplantation. Thirty-four patients underwent LTX, of them eight patients died in the hospital after a median stay of 24.5 days (range 1-180 days). Twenty-six patients left the hospital and returned to normal life (median hospital stay=47.5 days; range 21-90 days). The 1-, 3-, and 5-year survival for all transplanted patients was 60%, 60%, and 48%, respectively. The 1-, 3-, and 5-year survival conditional on 3-month survival for patients bridged with ECMO to LTX (78%, 78%, and 63%) was not worse than for other LTX patients within the same period of time (90%, 80%, and 72%, respectively, P=0.09, 0.505, and 0.344).
Transplantation of patients bridged on ECMO to LTX is feasible and results in acceptable outcome.
In patients with idiopathic pulmonary arterial hypertension, cardiac function can be impaired in the early postoperative phase after lung transplantation because the chronically untrained left ...ventricle is prone to fail. Thus, restrictive fluid management is pivotal to unload the left heart. In our institution, continuous renal replacement therapy is implemented liberally whenever a patient cannot be balanced negatively. It remains unclear whether such strategy impairs long-term kidney function.
We retrospectively reviewed our institutional database for patients with idiopathic pulmonary arterial hypertension who underwent transplantation between 2000 and 2018. The impact of postoperative continuous renal replacement therapy on long-term outcomes was investigated using a linear mixed model and multivariable Cox regression.
A total of 87 idiopathic pulmonary arterial hypertension lung transplant recipients were included in this analysis. In 38 patients (43%), continuous renal replacement therapy was started in the early postoperative period for a median of 16 days (10-22). In this group, urine production significantly decreased and patients began to acquire a positive fluid balance; however, homeostatic functions of the kidney were still preserved at the time of continuous renal replacement therapy initiation. All patients were successfully weaned from continuous renal replacement therapy and fully recovered their kidney function at the time of hospital discharge. No difference in kidney function was found between continuous renal replacement therapy and noncontinuous renal replacement therapy in patients within 5 years.
Early implementation of continuous renal replacement therapy for perioperative volume management does not impair long-term kidney function in idiopathic pulmonary arterial hypertension lung transplant recipients. Our data suggest that such a strategy leads to excellent long-term outcomes.
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Lung transplantation is the only successful treatment option for patients experiencing end-stage lung disease. Results have improved significantly in the last decade; however, the number one limiting ...factor is still the shortage of donor lungs. Due to the discrepancy between available donor lungs and patients awaiting lung transplantation, many centers have reintroduced donation after cardiac death (DCD). According to their results, DCD and donation after brain death (DBD) are comparable in terms of survival and graft function.
Currently in Hungary, donation is only allowed from DBD donors; however, due to the Eurotransplant agreement, non-heart-beating donation (NHBD) organs can be transplanted into Hungarian patients, and in some cases Hungarian transplant teams can also take part in NHBDs within the Eurotransplant region.
The Hungarian experience. A Hungarian patient received a lung from a 15-year-old uncontrolled DCD in Vienna. The donor was reanimated for 54 minutes and after lung procurement the lungs were put on ex vivo lung perfusion and later successfully implanted into the Hungarian recipient. The recovery was very successful and the patient is still alive.
The Hungarian Lung Transplantation Team was involved in a controlled Maastricht III donation in 2017. A 49-year-old female donor was reported from Ghent, Belgium. A multiorgan donation was carried out with 15 minutes of warm ischemic time in the case of the lungs.
DCD is an effective, safe, and available method to increase the donor pool. In the case of controlled donations, the necessary protocols have already been prepared. Although DBD is working very successfully in Hungary, infrastructural developments, education of professionals, and social preparations are all needed to implement a DCD protocol in Hungary.
After its initial difficulties were overcome, lung transplantation became an accepted and effective treatment for end-stage lung disease. Patients can take part in almost all kinds of sports after ...lung transplantation, including high-altitude mountaineering, which is an extreme sport even for healthy individuals. Several articles have been published about high-altitude tolerance of transplanted patients. However, this was the first high-altitude expedition that included only lung transplant patients.
The Vienna lung transplantation team organized an expedition in 2017 to conquer the peak of Mount Kilimanjaro, which consisted of 10 lung transplanted patients and 24 accompanying medical personnel. The participants were tested before and several times during the hike to evaluate their general and cardiopulmonary status, the severity of altitude sickness, and radio-morphologic changes. The results of the lung transplanted patients were compared to the results of their healthy companions.
The group started at 2360 meters and reached the 5895-meter-high summit of Mount Kilimanjaro after 6 days on June 18, 2017. Eight transplant patients and 24 escorting medical personnel reached the peak. This means that the success rate was 94%, which is significantly higher than the reported 85% for this route. The 2 transplant patients who did not make the summit turned back on the first and second day because they lacked the necessary fitness for the trip. We did not see a significant difference in the results regarding cardiopulmonary status or the severity of altitude sickness, although we observed mildly higher blood pressure and altitude sickness score results in the lung transplant group.
Based on our experiences, we can state that a stable patient after lung transplantation who attains the necessary physical fitness can achieve similar or even better physical results than an average healthy individual.
OBJECTIVES
Pulmonary metastasectomy (PM) has evolved to become a standard treatment for colorectal cancer lung metastases. However, biomarkers to estimate the prognosis after PM are currently ...missing. We therefore investigated the prognostic impact of inflammatory-related biomarkers and scores in patients undergoing curative PM for colorectal cancer.
METHODS
We analysed prospectively collected datasets of 52 patients treated in our institution between April 2009 and June 2014. Fibrinogen (cut-off 325 mg/dl), C-reactive protein (CRP, cut-off 0.5 mg/dl), the modified Glasgow prognostic score (mGPS) and the neutrophil-to-lymphocyte ratio (NLR) at the time of PM were tested for their prognostic power, and correlated to time to recurrence (TTR), time to lung-specific recurrence (TTLR) and overall survival (OS).
RESULTS
Median OS after PM of all patients (n = 52, 21 females, 31 males, mean age ± standard deviation: 62.65 ± 11.41 years) was 36 months 95% confidence interval (CI) 24.7–47.3 months, number of events: n = 20/38.5%. In univariable survival analyses, high fibrinogen hazard ratio (HR) 5.51, 95% CI 1.21–25.17, elevated CRP (HR 2.81, 95% CI 1.08–7.28), mGPS >0 (HR 2.81, 95% CI 1.08–7.28) and an NLR of 4 or higher (HR 3.05, 95% CI 1.02–9.13) was associated with poor OS. Median TTR was 15 months for all patients (number of events: n = 35/67.3%). Fibrinogen (HR 3.79, 95% CI 1.32–10.94) and NLR (HR 2.99, 95% CI 1.20–7.46) but not CRP (P = 0.102) and mGPS (P = 0.102) were found to indicate TTR. With regard to TTLR (number of events: n = 26/50%), only NLR predicted early lung recurrence (HR 3.02, 95% CI 1.06–8.564). After multivariable analyses, fibrinogen was the only significant OS predictor. However, all investigated inflammatory biomarkers and scores were prognostic for TTR in multivariable analyses. Finally, we divided the study population into an inflammatory phenotype (one or more inflammatory marker/score-elevated) and a non-inflammatory phenotype group. The inflammatory phenotype was prognostic in uni- and multivariable analyses for all three outcome parameters (OS, TTR and TTLR).
CONCLUSIONS
Inflammatory markers provided promising prognostic information in this cohort of curative PM patients after colorectal cancer. Further validation is needed to verify the prognostic role of these markers and establish them in clinical routine.
In this article we summarize the results of the first 3 years after launching the Hungarian Lung Transplantation Program.
The first lung transplant in Hungary was carried out on December 12, 2015, ...with the collaboration of the National Institute of Oncology and the Semmelweis University. Up to December 31, 2018, a total of 62 lung transplants were performed. Data were analyzed retrospectively. Patients were listed for lung transplant after the indication was established by the National Lung Transplantation Committee. Donor lungs were procured from brain-dead donors only.
Within this period our team was involved in 87 lung procurements, 61 of which resulted in bilateral lung transplant and 1 in single-sided transplant. The operative approach was unilateral thoracotomy (n = 1), bilateral thoracotomy (n = 1), or clamshell incision (n = 60) with venoarterial extracorporeal membrane oxygenation support. The underlying disease of the recipients was obstructive lung disease (n = 30), lung fibrosis (n = 11), cystic fibrosis (n = 18), primary pulmonary hypertension (n = 2), histiocytosis-X syndrome (n = 1), bronchiectasis (n = 2), lymphangioleiomyomatosis (n = 1), and retransplant because of bronchiolitis obliterans syndrome (n = 1). The youngest patient was 13 years of age, while the oldest was 65 years. Three patients died in the early postoperative phase. One-year survival was 80%.
The number of cases rises steadily in the Hungarian Lung Transplantation Program, which is exceptional compared with the start of other centrums. The incidence of complications and mortality is comparable with those of other experienced centers around the world. Our future goal is to broaden our waiting list, thus increasing the number of lung transplants carried out.
DNA methylation regulates together with other epigenetic mechanisms the transcriptional activity of genes and is involved in the pathogenesis of malignant diseases including lung cancer. In non-small ...cell lung cancer (NSCLC) various tumor suppressor genes are already known to be tumor-specifically methylated. However, from the vast majority of a large number of genes which were identified to be tumor-specifically methylated, tumor-specific methylation was unknown so far. Thus, the major aim of this study was to investigate in detail the mechanism(s) responsible for transcriptional regulation of the genes SPAG6 and L1TD1 in NSCLCs.
We analysed publically available RNA-sequencing data and performed gene expression analyses by RT-PCR. DNA methylation analyses were done by methylation-sensitive high-resolution melt analyses and bisulfite genomic sequencing. We additionally investigated protein expression using immunohistochemistry. Cell culture experiments included tumor cell growth, proliferation, viability as well as colony formation assays. Moreover, we performed xenograft experiments using immunodeficient mice.
We observed frequent downregulation of SPAG6 and L1TD1 mRNA expression in primary tumor (TU) samples compared to corresponding non-malignant lung tissue (NL) samples of NSCLC patients. We furthermore observed re-expression of both genes after treatment with epigenetically active drugs in most NSCLC cell lines with downregulated SPAG6 and L1TD1 mRNA expression. Frequent tumor-specific DNA methylation of SPAG6 and L1TD1 was detected when we analysed TU and corresponding NL samples of NSCLC patients. ROC curve analyses demonstrated that methylation of both genes is able to distinguish between TU and NL samples of these patients. Immunohistochemistry revealed a close association between SPAG6/L1TD1 methylation and downregulated protein expression of these genes. Moreover, by performing functional assays we observed reduced cell growth, proliferation and viability of pCMV6-L1TD1 transfected NSCLC cells. In addition, reduced volumes of tumors derived from pCMV6-L1TD1 compared to pCMV6-ENTRY transfected NCI-H1975 cells were seen in a xenograft tumor model.
Overall, our results demonstrate that SPAG6 and L1TD1 are tumor-specifically methylated in NSCLCs and that DNA methylation is involved in the transcriptional regulation of these genes. Moreover, in vitro as well as in vivo experiments revealed tumor-cell growth suppressing properties of L1TD1 in NSCLC cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The immunosuppressive treatment after organ transplantation highly contribute to evolve cardiovascular comorbidities like hypertension, hyperlipidemia, diabetes and kidney diseases. The ...effect of hypertriglyceri-demia could cause accelerated atherosclerosis. Previous smoking and excessive inflammatory response could increase the cardiovascular risk on those patients who were transplanted because of end-staged chronic obstructive pulmonary disease. Long term follow up needed on lung transplanted (LuTx) patient with cardiovascular risk assessment and to screen patients with vulnerable cardiovascular diseases. However, the correlation between LuTx patients and arterial stiffness is not investigated in the literature. Method: We investigated the arterial stiffness parameters in 51 LuTx and 49 healthy individuals. The arterial stiffness parameters were measured with oscillometric method (Tensiomed Arteriograph). Aortic pulse wave velocity (aoPWV), augmentation index (Aix), central systolic blood pressure (cSBP) and aortic pulse wave reflection time (RT) were determined.
Results
We found increased aoPWV and Aix values in lung transplanted (LuTx) patients than in the healthy individuals. Significant higher aoPWV (8.45 vs 7.49 m/s; p = 0.045 ), and RT (120 vs 134 ms; p = 0,0004) were found. Patients who were transplanted because of COPD and lung fibrosis the aoPWV were significantly higher versus the patient who were transplanted because of cystic fibrosis or pulmonary hypertension.
Conclusion
We strongly recommend the long term cardiovascular follow up on lung transplanted patient, because of the common systemic atherogen effect of the frequent infection and immunsupressive therapy.
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