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Background and Objectives: The incidence of distant metastases in patients with head and neck cancer (HNC) is approximately 10%. Pulmonary metastases are the most frequent distant location, with an incidence of 70-85%. The standard treatment options are chemo-, immuno- and radiotherapy. Despite a benefit for long-term survival for patients with isolated pulmonary metastases, pulmonary metastasectomy (PM) is not the treatment of choice. Furthermore, many otorhinolaryngologists are not sufficiently familiar with the concept of PM. This work reviews the recent studies of pulmonary metastatic HNC and the results after pulmonary metastasectomy. Materials and Methods: PubMed, Medline, Embase, and the Cochrane library were checked for the case series' of patients undergoing metastasectomy with pulmonary metastases published since 1 January 2000. Results: We included the data of 15 studies of patients undergoing PM. The 5-year survival rates varied from 21% to 59%, with median survival from 10 to 77 months after PM. We could not identify one specific prognostic factor for long-term survival after surgery. However, at least most studies stated that PM should be planned if a complete (R0) resection is possible. Conclusions: PM showed reliable results and is supposedly the treatment of choice for patients with isolated pulmonary metastases. Patients not suitable for surgery may benefit from other non-surgical therapy. Every HNC patient with pulmonary metastases should be discussed in the multidisciplinary tumor board to optimize the therapy and the outcome.

Objectives Extracorporeal membrane oxygenation or extracorporeal life support (ECLS) in patients after cardiac surgery and postcardiotomy cardiogenic shock (PCS) is known to be associated with high mortality. Especially in patients after coronary artery bypass grafting (CABG) and PCS, ECLS is frequently established. The aim of this analysis was to evaluate factors associated with in-hospital mortality in patients treated with ECLS due to PCS after CABG. Methods Between August 2006 and January 2017, 92 consecutive patients with V-A ECLS due to PCS after isolated CABG were identified and included in this retrospective analysis. Patients were divided into survivors (S) and non-survivors (NS) and analyzed with risk factors of in-hospital mortality. Results In-hospital mortality added up to 61 patients (66%). Non-survivors were significantly older (60 +/- 812 (S) vs. 67 +/- 10 (NS); p = 0.013). Bilateral internal mammary artery graft was significantly more frequently used in S (23% (S) vs. 2% (NS); p = 0.001). After 24 h of ECLS support, median lactate levels were significantly higher in NS (1.9 (1.3; 3.5) mmol/L (S) vs. 3.5 (2.1; 6.3) mmol/L (NS); p = 0.001). NS suffered more often acute kidney injury requiring dialysis (42% (S) vs. 74% (NS); p = 0.002). Conclusion Mortality in patients with refractory PCS after CABG and consecutive ECLS support remains high. Failing end-organ recovery under ECLS despite optimized concomitant medical therapy is an indicator of adverse outcomes in this specific patient cohort. Moreover, total-arterial revascularization might be beneficial for cardiac recovery in patients suffering PCS after CABG and following ECLS.

Objective: Sublobar resection is frequently performed for Non-Small Cell Lung Cancer (NSCLC) patients with <= 2 cm nodules. Frequently, both proper staging and radical lymphadenectomy are omitted in these operations. Therefore, we decided to evaluate the number of lymph node metastases and the number of postoperative nodal upstaging in patients undergoing pulmonary resection due to NSCLC with tumors <= 2 cm at our institution. Methods: Nodal upstaging, lymphangiosis-(L1), and hemangiosis carcinomatosa (V1) were analyzed. pN0 patients were compared to patients with postoperative nodal upstaging. One-, three, and five-year survival rates were measured. Survival was also assessed by the Kaplan-Meier method. Results: 747 patients underwent surgery for NSCLC at our institution between 2012 and 2020. We retrospectively reviewed data of 236 NSCLC patients with <= 2 cm tumors. The mean tumor size was 1.4 cm +/- 0.39 in our cohort. Of our patients, 14% showed a cT1a tumor, and 86% of patients cT1b. 24.0 +/- 12.3 lymph nodes were dissected and analyzed per patient, and 0.7 +/- 2.0 of those were affected. Of our patients, 16.1% showed L1 affection, and 7.6% a V1 affection. Lymph node involvement was diagnosed in 11(4.7%) patients preoperatively. 39(16.5%) patients were upstaged due to lymph node involvement postoperatively (p < 0.001). Upstaged patients showed significantly worse 3-(upstaged: 60.6% vs. pN0: 83.2%; p = 0.01) and 5-year (upstages: 38% vs. pN0 71.5%; p = 0.02) survival rates. Conclusion: 16.5% of patients with <= 2 cm NSCLC were nodal upstaged postoperatively. These results underline that lymphadenectomy and proper staging are crucial for NSCLC patients irrespective of the tumor size and the surgical approach.

Objectives: We report the first use of a biorestorative valved conduit (Xeltis pulmonary valve-XPV) in children. Based on early follow-up data the valve design was modified; we report on the comparative performance of the two designs at 12 months post-implantation. Methods: Twelve children (six male) median age 5 (2 to 12) years and weight 17 (10 to 43) kg, had implantation of the first XPV valve design (XPV-1, group 1; 16 mm (n = 5), and 18mm (n = 7). All had had previous surgery. Based on XPV performance at 12 months, the leaflet design was modified and an additional six children (five male) with complex malformations, median age 5 (3 to 9) years, and weight 21 (14 to 29) kg underwent implantation of the new XPV (XPV-2, group 2; 18 mm in all). For both subgroups, the 12 month clinical and echocardiographic outcomes were compared. Results: All patients in both groups have completed 12 months of follow-up. All are in NYHA functional class I. Seventeen of the 18 conduits have shown no evidence of progressive stenosis, dilation or aneurysm formation. Residual gradients of >40 mm Hg were observed in three patients in group 1 due to kinking of the conduit (n = 1), and peripheral stenosis of the branch pulmonary arteries (n = 2). In group 2, one patient developed rapidly progressive stenosis of the proximal conduit anastomosis, requiring conduit replacement. Five patients in group 1 developed severe pulmonary valve regurgitation (PI) due to prolapse of valve leaflet. In contrast, only one patient in group 2 developed more than mild PI at 12 months, which was not related to leaflet prolapse. Conclusions: The XPV, a biorestorative valved conduit, demonstrated promising early clinical outcomes in humans with 17 of 18 patients being free of reintervention at 1 year. Early onset PI seen in the XPV-1 version seems to have been corrected in the XPV-2, which has led to the approval of an FDA clinical trial.

OBJECTIVES: Bovine and porcine pericardial patches are frequently used in cardiothoracic and vascular surgery. There are no guidelines recommending the usage of these patches for particular surgical approaches. However, these 2 materials supposedly possess different properties. The clinical advantage of porcine compared with bovine patches remains controversial. In this experimental study, we analysed the incorporation and vascularization of bovine and porcine pericardial patches during the initial phase after implantation. METHODS: Bovine and porcine pericardial patches were implanted into the dorsal skinfold chamber of C57BL/6 mice (n = 8 per group) to study vascularization and inflammation at the implantation site using repetitive intravital fluorescence microscopy over a 14-day period. At the end of the in vivo experiments, CD-31-positive cells were determined to evaluate the vascularization by immunohistochemistry. Furthermore, cell proliferation and apoptosis were analysed immunohistochemically. RESULTS: Implanted bovine patches exhibited an enhanced vascularization, as indicated by a significantly higher number of CD-31-positive cells and micro-vessels (23.2 +/- 4.3 vs 16.5 +/- 5.8 mm(-2); P=0.001). Furthermore, bovine patches showed a slightly but not significantly higher functional capillary density. Both patches induced a moderate leukocytic inflammatory host tissue response, and neither bovine nor porcine patches significantly affected apoptosis and cell proliferation at the implantation site. CONCLUSIONS: Bovine and porcine pericardial patches are similarly suitable for surgery. Bovine patches exhibited an improved vascularization during the first 14 days after implantation. This may result in a quicker and improved incorporation into the surrounding tissue compared with porcine pericardial patches.

Background and Objectives: Pediatric extracorporeal membrane oxygenation (ECMO) support is often the ultimate therapy for neonatal and pediatric patients with congenital heart defects after cardiac surgery. The impact of lactate clearance in pediatric patients during ECMO therapy on outcomes has been analyzed. Materials and Methods: We retrospectively analyzed data from 41 pediatric vaECMO patients between January 2006 and December 2016. Blood lactate and lactate clearance have been recorded prior to ECMO implantation and 3, 6, 9 and 12 h after ECMO start. Receiver operating characteristic (ROC) analysis was used to identify cut-off levels for lactate clearance. Results: Lactate levels prior to ECMO therapy (9.8 mmol/L vs. 13.5 mmol/L; p = 0.07) and peak lactate levels during ECMO support (10.4 mmol/L vs. 14.7 mmol/L; p = 0.07) were similar between survivors and nonsurvivors. Areas under the curve (AUC) of lactate clearance at 3, 9 h and 12 h after ECMO start were significantly predictive for mortality (p = 0.017, p = 0.049 and p = 0.006, respectively). Cut-off values of lactate clearance were 3.8%, 51% and 56%. Duration of ECMO support and respiratory ventilation was significantly longer in survivors than in nonsurvivors (p = 0.01 and p < 0.001, respectively). Conclusions: Dynamic recording of lactate clearance after ECMO start is a valuable tool to assess outcomes and effectiveness of ECMO application. Poor lactate clearance during ECMO therapy in pediatric patients is a significant marker for higher mortality.

Background: Application of extracorporeal membrane oxygenation in pediatric patients with severe heart failure steadily increases. Differentiation of outcomes and survival of diverse pediatric groups is of interest for adequate therapy. Methods: Between January 2008 and December 2016, a total of 39 pediatric patients needed veno-arterial extracorporeal membrane oxygenation support in our department. Patients were retrospectively divided into three groups: neonates (<30 days), infants (>30 days/<1 year), and toddlers/preadolescents (>1 year). Early outcomes as well as mid- and long-term survival up to 7-year follow-up were analyzed. Results: Basic demographics significantly differed in terms of age, height, and weight among the groups in accordance with the intended group categorization (p < 0.05). Survival after 30 days of extracorporeal membrane oxygenation application was equally distributed among the groups, and 44% of all patients survived. In terms of survival to discharge, no significant differences were found among groups. In total, 28% of patients survived up to 7 years. Infants were significantly more likely to undergo elective surgery (p < 0.001) and were predominantly weaned off extracorporeal membrane oxygenation, whereas need for urgent surgery (p < 0.001) was significantly higher in neonate group in comparison to other groups. Multinominal logistic regression analysis revealed significantly higher odds for need for re-exposure in infant group in comparison to toddler/preadolescent group as well as for incidence of neurological impairment of toddler/preadolescent group in comparison to neonate group (odds ratio = 14.67, p = 0.009 and odds ratio = 34.67, p = 0.004, respectively). Kaplan-Meier survival estimation analysis revealed no significant differences in terms of mid- and long-term survival among the groups (Breslow p = 0.198 and log-rank p = 0.213, respectively). Conclusion: Veno-arterial extracorporeal membrane oxygenation is a lifesaving therapeu

Background: Mortality and morbidity after surgical repair for complex congenital heart defects and severe cardiopulmonary failure on extracorporeal membrane oxygenation (ECMO) support remain high despite significant advances in medical management and technological improvements. We report on outcomes and factors after using ECMO in our surgical pediatric population including short- and long-term survival. Methods: A total of 45 neonatal and pediatric patients were identified who needed ECMO in our department between January 2008 and December 2016. In 41 cases (91%) a vaECMO (ECLS) was implemented, whereas 4 patients (9%) received vvECMO treatment for respiratory failure. In 33 cases vaECMO was implanted following cardiac surgery for congenital heart disease (CHD), whereas in 8 patients ECMO was utilized by means of extracorporeal cardiopulmonary resuscitation (eCPR) following refractory cardiac arrest. The primary endpoint of the present study was survival to discharge and long-term survival free from neurological impairments. Univariate and bivariate analysis was performed to address predictors for outcome. Kaplan-Meier survival analysis was used to address mid- and long-term survival. Results: Median [IQR] duration of ECMO support was 3 [2, 5] days (range, 1-17 days). Median age at ECMO implantation was 128 [14, 1,813] days, median weight of patients was 5.4 [3.3, 12] kg. Totally 10 patients included in this study were diagnosed with concomitant genetic conditions. A total of 20 (44%) patients were successfully weaned off ECMO (survived >24 h after ECMO explantation), whereas 15 (33%) of them survived to discharge. Single ventricle (SV) repair was performed in 14, biventricular repair in 19 patients. Neonates (<30 days of age), female patients, patients with genetic conditions, SV repair patients, and eCPR patient cohort showed lower odds of survival on ECMO. Failed myocardial recovery (P=0.001), profound circulatory failure despite a high dose of catecholamines (P

Aims. Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) have become a promising tool in cardiovascular safety pharmacology. Immaturity of iPS-CMs remains an ongoing concern. We compared electrophysiological and contractile features of cardiac bodies (hiPS-CBs) derived from human-induced pluripotent stem cells and human neonatal and infantile myocardial slices relevant for drug screening. Methods and Results. Myocardial tissue slices were prepared from biopsies obtained from patients undergoing surgery for hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). Electrophysiological features and response to I-k,I-r blockade as well as contractile properties were investigated using microelectrodes and isometric force measurements and were compared to hiPS-CBs. Both native myocardial tissue slices as well as hiPS-CBs showed action potential prolongation after I-k,I-r blockade, but early afterdepolarisations could be observed in native myocardial tissue slices only. The force-frequency relationship (FFR) varied at lower frequencies and was negative throughout at higher frequencies in hiPS-CBs. In contrast, native myocardial tissue slices exhibited positive, negative, and biphasic FFRs. In contrast to native myocardial tissue slices, hiPS-CBs failed to show an inotropic response to ss-adrenergic stimulation. Although all groups showed ss-adrenergic induced positive lusitropy, the effect was more pronounced in myocardial tissue slices. Conclusion. hiPS-CBs were able to reproduce AP prolongation after I-k,I-r blockade, but to a lesser extent compared to human neonatal and infantile myocardial tissue slices. Early afterdepolarisations could not be induced in hiPS-CBs. Contractile force was differently regulated by -adrenergic stimulation in hiPS-CBs and the native myocardium. If used for cardiotoxicity screening, caution is warranted as hiPS-CBs might be less sensitive to pharmacologic targets compared to the native myocardium of neonates and infan

Nowadays, an increasing number of neonatal and pediatric patients with severe heart failure benefits from extracorporeal membrane oxygenation (ECMO) support. A total of 39 pediatric patients needed venoarterial ECMO (vaECMO) support in our department between January 2008 and December 2016. Patients were retrospectively divided in two groups: 30-day survivor group (17 patients) and 30-day nonsurvivor group (22 patients). Outcome and factors predictive for 30-day mortality and mid- as well as long-term survival up to 7-year follow-up were analyzed by univariate analysis and Kaplan-Meier survival estimation. Basic demographics and preoperative characteristics did not differ between groups (P > 0.05). 67% of patients were successfully weaned off ECMO and 44% survived 30-day after ECMO application. After 7-year follow-up 28% of pediatric patients were alive. Thirty-day survivors were significantly more likely to undergo elective cardiac surgery (P = 0.001), whereas significantly more 30-day nonsurvivors underwent urgent surgery (P = 0.004). Odds of incidence of catecholamine refractory circulatory failure, failed myocardial recovery, and cerebral edema was significantly higher in 30-day nonsurvivor group (41.6-fold, 16-fold, and 2.5-fold, respectively). Kaplan-Meier survival estimation analysis revealed significant differences in terms of mid- and long-term survival among neonates, infants, toddlers, and preadolescents (Breslow P = 0.037 and Log-Rank P = 0.028, respectively). vaECMO provides an efficient therapy option for life-threatening heart disorders in neonates and pediatric patients being at high risk for myocardial failure leading to circulatory arrest. Urgency of surgery effected on higher mortality, but there was no difference in terms of mortality in 30-day survivor group in comparison to 30-day nonsurvivor group among neonates, infants, toddlers, and preadolescents.

Objectives An unobstructed extracardiac conduit (ECC) is essential for optimal Fontan haemodynamics. We aimed to evaluate the feasibility and results of percutaneous transcatheter stenting of the ECC in paediatric patients with a significant Fontan pathway obstruction. Methods Our institutional database was searched to identify all Fontan patients who had a stent placed in their ECC. Medical records, cardiac catheterisation data and echocardiographic investigations were reviewed. Vessel diameters were normalised to account for differences in body surface area. Results Nineteen Fontan patients (age 6.5+/-3.2 years; male 78.9%) with a significant stenosis of their Dacron ECC graft were identified. Seven patients presented with protein-losing enteropathy (36.8%). An ECC obstruction was suspected on echocardiography in only 6/19 patients (31.6%). The mean minimum diameter of the ECC was 8.3+/-2.4 mm. A stenosis of >45% was seen in the majority of patients (n=12, 63.1%). Significant correlations between the severity of the ECC obstruction and Fontan pathway vessel diameters were found (all p<0.05). Stenting was successful in all children. The ECC diameter increased significantly after stenting (p<0.0001). An acute clinical benefit of ECC stenting was observed in 18/19 (94.7%) patients. ECC patency was good during a mean follow-up of 1.8+/-0.9 years. Conclusions The feasibility and acute results of percutaneous transcatheter ECC stenting are promising and may provide a good alternative to postpone surgery to a later age. The mechanisms contributing to the development of ECC stenoses are likely multifactorial.

Background-The postnatal development of myofibrillar mechanics, a major determinant of heart function, is unknown in pediatric patients with tetralogy of Fallot and related structural heart defects. We therefore determined the mechanical properties of myofibrils isolated from right ventricular tissue samples from such patients in relation to the developmental changes of the isoforms expression pattern of key sarcomere proteins involved in the contractile process. Methods and Results-Tissue samples from the infundibulum obtained during surgery from 25 patients (age range 15 days to 11 years, median 7 months) were split into half for mechanical investigations and expression analysis of titin, myosin heavy and light chain 1, troponin-T, and troponin-I. Of these proteins, fetal isoforms of only myosin light chain 1 (ALC-1) and troponin-I (ssTnI) were highly expressed in neonates, amounting to, respectively, 40% and 80%, while the other proteins had switched to the adult isoforms before or around birth. ALC-1 and ssTnI expression subsequently declined monoexponentially with a halftime of 4.3 and 5.8 months, respectively. Coincident with the expression of ssTnI, Ca2+ sensitivity of contraction was high in neonates and subsequently declined in parallel with the decline in ssTnI expression. Passive tension positively correlated with Ca2+ sensitivity but not with titin expression. Contraction kinetics, maximal Ca2+-activated force, and the fast phase of the biphasic relaxation positively correlated with the expression of ALC-1. Conclusions-The developmental changes in myofibrillar biomechanics can be ascribed to fetal-to-adult isoform transition of key sarcomeric proteins, which evolves regardless of the specific congenital cardiac malformations in our pediatric patients.

Percutaneous replacement of the tricuspid valve with a bovine jugular venous valve (melody valve) was successfully undertaken in a 9-year-old boy. The patient had a previous history of bacterial endocarditis of the native tricuspid valve in infancy. Initially, a pericardial patch valve was created, followed by surgical replacement of the valve using a biological tissue valve at 4 years of age. Progressive stenosis and regurgitation of the biological valve, with severe venous congestion and resulting hepatic dysfunction prompted percutaneous valve replacement.

We describe transcatheter therapy for early onset occlusion or stenoses of extracardiac conduits in three children who had undergone Fontan completion. Successful stent implantation was associated with complete resolution of symptoms.

A vein of Galen malformation - a rare cause of cardiac insufficiency in neonates - is sometimes associated with coarctation of the aorta, two diseases requiring urgent therapy in the neonatal period. We report on a term neonate in whom we first palliated the coarctation by stent implantation, providing time to treat the vein of Galen malformation by endovascular embolisation. Following this, the coarctation was surgically repaired and the stent was explanted.