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W Weder

Publications and source records attributed to W Weder.

At least 37 records · Page 2Linked to original sources

Laryngeal mask airway and high-frequency jet ventilation for the resection of a high-grade upper tracheal stenosis.

The surgical resection of a high-grade tracheal stenosis presents a special case of a difficult airway. A 20-year-old male was treated for a 45-mm long tracheal stenosis with 60% reduction of the patent airway area beginning 25 mm below the glottis. To avoid manipulations of the affected segment before surgical exposure of the trachea was established, strictly supraglottic ventilation via a laryngeal mask airway was performed. During removal of the stenosis and creation of the anastomosis, transglottic high-frequency jet ventilation (HFJV) is a convenient technique that enables optimal access to the operation field. Changing from HFJV to conventional ventilation after completion of the anastomosis is not necessary, and the jet catheter can be left in place until the end of the anesthesia.

Adult↗

Thoracoscopic lobectomy for benign disease--a single centre study on 64 cases.

OBJECTIVE: Chronic lung infection is the main indication for lobectomy in benign pulmonary disease and may be technically demanding due to inflammatory changes such as adhesions, lymph node enlargement and neovascularization. The role of the thoracoscopic operation in these indications is yet ill-defined. METHODS: We retrospectively analyzed the results of patients who underwent thoracoscopic lobectomy (TL) between 1992 and June 1999 and compared this study group with patients who underwent open lobectomy (OL), all for benign disease. Data were not normally distributed, therefore, the median and range is given and nonparametric statistical analysis was applied. RESULTS: A total of 117 lobectomies for benign disease (64 TL) were analyzed. Indications included bronchiectasis (36 TL; 18 OL), chronic infections (13 TL; eight OL), tuberculosis (five TL; 15 OL), emphysema (five TL; one OL), AV-malformations (two TL; one OL), severe haemoptysis (four OL), and others (three TL; six OL). Twelve conversions to thoracotomy were necessary due to severe adhesions. One patient in the open lobectomy group died within 30 days postoperative. Drainage time was 5.0 (1-32) days in TL and 6.0 (3-21) days in OL, hospital stay was 8.5 (4-41) days and 10.0 (5-52) days, respectively. Blood loss was 0 (0-2000) ml in TL and 300 (0-6000) ml in OL. Operation time for thoracoscopic lobectomies significantly decreased from 2.5 (1-6) h for cases between 1992 and 1997 (n=49) to 1.5 (0.5-2.5) h for recent cases (n=15) (P<0.01). In addition, a trend towards less blood loss was noted (100 (0-2000) ml vs. 0 (0-400) ml; P=0.06). Drainage time and hospital stay did not differ significantly. CONCLUSIONS: Thoracoscopic lobectomy in chronic inflammatory disease can be performed safely in selected patients, especially with bronchiectasis. Conversion rate to thoracotomy is low. Operation time with this approach declined significantly over time.

Adult↗

Recipient treatment with trimetazidine improves graft function and protects energy status after lung transplantation.

BACKGROUND: Ischemia-reperfusion injury remains an important obstacle to successful lung transplantation. Trimetazidine is an anti-ischemic drug that restores the ability of ischemic cells to produce energy and reduces the generation of oxygen-derived free radicals. The aim of this study was to assess the protective effect of trimetazidine after prolonged ischemia in lung transplantation. METHODS: Rat single-lung transplantation was performed in 4 experimental groups (n = 5 each). In all groups, transplantation was performed after 18 hours of cold (4 degrees C) ischemia. All donor lungs were flushed with low-potassium dextran-glucose (LPDG) solution that also contained 500 microg/liter prostaglandin estradiol (E(1)). Groups studied included: Group I: flush solution was administered containing 10(-6) mol/liter trimetazidine (TMZ), neither donor nor recipient treatment given; Group II: donors were treated with 5 mg/kg intravenous TMZ 10 minutes prior to harvest, but the flush solution did not contain TMZ; Group III: recipients treated with 5 mg/kg intravenous TMZ 10 minutes before reperfusion, and flush solution contained 10(-6) mol/liter trimetazidine; Group IV: ischemic control group. After 2 hours of reperfusion, oxygenation was measured and lung tissue was frozen and assessed for adenosine triphosphate (ATP) content, myeloperoxidase (MPO) activity and thiobarbituric acid-reactive substances (TBARS). Peak airway pressure (PawP) was recorded throughout the reperfusion period. RESULTS: Group III showed significantly higher levels of ATP content (11.1 +/- 5.01 pmol vs Group I, 3.36 +/- 1.8 pmol, p = 0.008; vs Group II, 4.7 +/- 1.9 pmol, p = 0.03; vs Group IV, 0.7 +/- 0.2 pmol, p = 0.008), better oxygenation (442.5 +/- 26.5 mm Hg, vs Group I, 161.06 +/- 54.5 mm Hg; vs Group II, 266.02 +/- 76.9 mm Hg; vs Group IV, 89.4 +/- 14.7 mm Hg, p = 0.008) and reduced lipid peroxidation (TBARS) (0.15 +/- 0.03 nmol/g; vs Group I, 1.04 +/- 0.76 nmol/g; vs Group II, 0.69 +/- 0.4 nmol/g; vs Group IV, 2.29 +/- 0.4 nmol/g, p = 0.008). PawP and MPO activity were comparable in the 4 study groups. CONCLUSION: Recipient treatment with TMZ provided significant protection of energy status, better oxygenation and reduced lipid peroxidation. Our data suggest that TMZ may be an important adjunct in the prevention of post-transplant lung ischemia-reperfusion injury.

Animals↗

Trimetazidine protects the energy status after ischemia and reduces reperfusion injury in a rat single lung transplant model.

BACKGROUND: Ischemia-reperfusion injury involves free radical generation and polymorphonuclear neutrophil chemotaxis. Trimetazidine is an anti-ischemic drug that restores the ability of the ischemic cells to produce energy and reduces the generation of oxygen-derived free radicals. We evaluated the effect of trimetazidine against ischemia-reperfusion injury after lung transplantation. METHODS: Rat single lung transplantation was performed in 3 experimental groups (n = 5): (1) the immediate transplantation group was defined as animals undergoing transplantation immediately after harvest without treatment; (2) the ischemic control group was defined as animals undergoing transplantation after 18 hours of cold (4 degrees C) ischemia without treatment; and (3) the trimetazidine-treated group was defined as animals undergoing transplantation after 18 hours of cold (4 degrees C) ischemia and donor and recipient treatment with 5 mg/kg intravenous trimetazidine 10 minutes before harvest and reperfusion, respectively. All donor lungs were flushed with low-potassium dextran-glucose solution. After 2 hours of reperfusion, oxygenation was measured, and lung tissue was frozen and assessed for adenosine triphosphate content, myeloperoxidase activity, and thiobarbituric acid-reactive substances. Peak airway pressure was recorded throughout the reperfusion period. RESULTS: The trimetazidine group showed significantly higher levels of adenosine triphosphate content (1.73 +/- 0.8 pmol vs 0.72 +/- 0.2 pmol [ischemic control], P =.008), better oxygenation (238.82 +/- 113.9 mm Hg vs 89.39 +/- 14.7 mm Hg [ischemic control], P =.008), and reduced lipid peroxidation (1.28 +/- 0.1 nmol/g vs 2.09 +/- 0.4 nmol/g [ischemic control], P =.008). Adenosine triphosphate levels of the trimetazidine group were comparable with those of the immediate transplantation group (1.73 +/- 0.8 pmol vs 1.89 +/- 0.5 pmol, respectively; P =.31). Peak airway pressure and myeloperoxidase activity were comparable among groups. CONCLUSION: Donor and recipient treatment with trimetazidine provided a significant protection of the energy status, better oxygenation, and reduced lipid peroxidation in this experimental model. Our data suggest that trimetazidine may be an important adjunct to prolong ischemic time safely and to decrease lung ischemia-reperfusion injury.

Adenosine Triphosphate↗

Effects of lung volume reduction surgery for emphysema on diaphragm dimensions and configuration.

Part of the functional benefit provided by lung volume reduction surgery (LVRS) may be related to improvement in respiratory muscle function resulting from changes in diaphragm dimension and configuration. To study these changes, we obtained 3D reconstructions of the muscle using spiral computed tomography in 11 patients with severe emphysema before and 3 mo after surgery, and in 11 normal subjects matched for sex, age, height, and weight. Bilateral LVRS was performed by thoracoscopy in eight patients and by sternotomy in three patients. Acquisitions were made in the supine posture at relaxed FRC, midinspiratory capacity, and TLC. On average, LVRS produced a 51 +/- 11% increase in FEV(1) and a 30 +/- 4% decrease in FRC. The total surface area of the diaphragm (A(di)) and of the zone of apposition (A(ap)) at FRC increased by 17 +/- 4% and 43 +/- 8%, respectively, but the surface area of the dome did not change. Compared with the values recorded in the normal subjects, postoperative values of A(di) and A(ap) at FRC were reduced by 11% (p < 0.05) and 24% (p < 0.005), respectively. The curvature of the dome increased at TLC in the left sagittal plane, but was otherwise unaffected by the procedure. We conclude that LVRS substantially increases A(di) and A(ap), but does not significantly improve diaphragm configuration at FRC.

Anthropometry↗

[Indications for lung transplantation in advanced cystic fibrosis].

Lung transplantation has become a valid therapeutic option for cystic fibrosis patients with end-stage lung disease. The indication for transplantation does not rely on strict criteria only but must be evaluated case by case. In particular, the dynamics of the clinical course need to be considered with regard to impaired physical performance, recurrent infections, decline in pulmonary function and weight loss. Important risk factors are a poor nutritional status, osteoporosis, liver involvement, previous pleurodesis and the occurrence of multiresistant bacteria. Management and assessment of cystic fibrosis patients for lung transplantation is complex. Therefore patients should be referred to specialised centres at an early stage.

Bacterial Infections↗

[Special problems after lung transplantation: walking a tightrope between infection and graft rejection].

Between November 1992 and September 1999 84 lungs have been transplanted at University Hospital Zurich. Currently the 1-year survival rate is up to 85%. However, long-term success is limited by the development of chronic rejection in the form of bronchiolitis obliterans. The risk factors are repeated episodes of acute rejection and infections, due to cytomegalovirus in particular. Both can occur in asymptomatic patients and are sometimes detected only by transbronchial lung biopsy. At the Zurich Lung Transplant Centre biopsies are performed as surveillance biopsies in asymptomatic patients in the first 6 months after transplantation, for clinical indications and as follow-up biopsies after a pathological result. Open lung biopsies are performed for special indications only. We evaluated 408 transbronchial biopsies taken between November 1992 and September 1999. Relevant findings were present in 46% of biopsies in symptomatic patients. Relevant acute rejection episodes were diagnosed in 15% of surveillance biopsies. Overall, 72% of acute rejection episodes requiring therapy and 33% of biopsies detecting cytomegalovirus were found in surveillance biopsies. 7 of 11 late (> 45 days postoperative) and 1 of 5 early (< or = 45 days postoperative) open lung biopsies revealed new diagnoses. Transbronchial biopsy after lung transplantation is at present the gold standard for diagnosis of acute rejection and cytomegalovirus pneumonia of the lung.

Adult↗

Osteonecrosis after lung transplantation: cystic fibrosis as a potential risk factor.

BACKGROUND: Osteonecrosis is a known complication after transplantation of solid organs. The incidence of osteonecrosis after lung transplantation is not well documented. METHODS: We investigated the incidence of symptomatic osteonecrosis in lung transplant recipients, transplanted between November 1992 and June 1998 at our institution. For the detection of osteonecrosis, all patients complaining of musculoskeletal pain underwent magnetic resonance imaging. Demographic characteristics, time after transplantation, etiology of underlying lung disease, and the number of steroid pulses for rejection episodes were compared for patients with and without osteonecrosis. RESULTS: Of 63 transplant recipients, all 49 with a follow-up of >3 months were included for analysis. Of seven symptomatic transplant recipients, five cases of osteonecrosis (10%) were detected at a median duration of 216 days (range 44-600) after transplantation. Patients with osteonecrosis have been treated with the same immunosuppressive regimen and with an equal number of steroid pulses for acute rejection episodes (1.4+/-1.1 vs. 1.4+/-1.5, P=0.69), but were younger (26+/-8 vs. 40+/-11 years, P<0.01) than other transplant recipients. Symptomatic osteonecrosis was detected in four of 14 patients (29%) with cystic fibrosis (CF), compared with one osteonecrosis among 35 patients (3%) with other underlying diseases (P<0.02). Within the group of CF patients, specific clinical and demographic characteristics correlating with the risk for subsequent osteonecrosis could not be found. CONCLUSION: In lung transplant recipients, CF may be a risk factor for the development of symptomatic osteonecrosis.

Adolescent↗

Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection.

The interaction between Fas and its ligand (FasL) induces apoptosis in the Fas-expressing cell. We hypothesized that liposome-mediated FasL gene transduction to the lung allograft, in addition to low-dose immunosuppression, might reduce acute rejection. Orthotopic left lung allotransplantation was performed in male rats (Brown Norway to Fischer F344). FasL gene transfer was performed by use of the plasmid pBCMGSNeo carrying the gene coding for murine FasL and the cationic liposome GL#67:DOPE. Six hundred and sixty micrograms of DNA in 250 microl H2O and 0.5 micromol GL#67 in 250 microl H2O were diluted to 5 ml with saline solution. This emulsion (20 degrees C) was instilled retrogradely through the left pulmonary vein after flushing with LPD solution (20 ml, at 4 degrees C). Subsequently, the graft was stored at 10 degrees C for 3 h. A single dose of cyclosporine A (CsA; 2.5 mg/kg i.m.) was given to all groups 48 h after the transplantation. In group 1 (n = 6), FasL/GL#67 was instilled as described. In group 2 (n = 5), GL#67 was given without DNA. Group 3 (n = 5) animals received CsA only. Five days after transplantation, gas exchange was assessed after exclusion of the contralateral native lung (FiO2 = 1.0). Grafts were flushed with saline solution and fixed in formaldehyde for histological evaluation. No statistical difference in gas exchange (PaO2) between the two control groups 2 (6.4 +/- 0.4 kPa) and 3 (7.4 +/- 0.4 kPa) could be detected 5 days postoperatively (P = 0.9). In contrast, grafts transduced with FasL (group 1) had significantly better gas exchange on postoperative day 5 (PaO2: group 1 37.0 +/- 10.6 kPa vs group 2 6.4 +/- 0.41 kPa; P = 0.002). Two animals in group 1 revealed no or only minimal improvement in gas exchange. Histologically, all lung specimen of all groups showed signs of acute rejection (A2). Leukocyte infiltrates, rated by two independent observers, were less severe in all group 1 animals. Liposome-mediated FasL gene transfer at the time of harvest in combination with low-dose CsA reduces acute rejection in four out of six animals in this model of rat lung allotransplantation.

Animals↗

Apoptosis induced by ischemia and reperfusion in experimental lung transplantation.

BACKGROUND: Apoptosis is a distinct form of single-cell death in response to injury. Time course of apoptosis in lung parenchymal cells during posttransplant reperfusion and the influence of oxygen content during preservation on apoptosis of parenchymal cells are studied. METHODS: Orthotopic syngenic single left lung transplantation was performed in male Fischer (F344) rats after 18 hours of cold ischemia (n = 5 in all groups). Apoptotic cells were stained by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique. Strictly TUNEL-positive pneumocytes were counted on anonymized slides by a pathologist on 100 fields (x400) per specimen (mean +/- SEM). RESULTS: The peak of apoptotic pneumocytes occurred 2 hours after reperfusion (16.8 +/- 2.2 pneumocytes/100 fields [p/100f]; p = 0.000012 vs controls, lungs fixed after 18 hours of ischemia), whereas the lowest level of apoptotic pneumocytes was seen in lungs fixed after harvest (1.4 +/- 0.51 p/100f) and lungs not undergoing reperfusion (2.8 +/- 0.49 p/100f). Four hours after reperfusion, the number of apoptotic pneumocytes was lower than 2 hours after reperfusion (13.6 +/- 3.1 p/100f; p = 0.00032 vs controls), with a further decline at 8 hours (6.4 +/- 1.5 p/100f) and 12 hours after reperfusion (4.0 + 1.2 p/100f). Interestingly, lungs inflated with N2 before storage revealed a significantly lower level of TUNEL-positive pneumocytes 2 hours after reperfusion (8.8 2.0 p/100f) compared with lungs inflated with 100% O2 (p = 0.0052). CONCLUSIONS: Apoptosis of pneumocytes after posttransplant lung reperfusion is a very early event. Prolonged hypothermic preservation without reperfusion, however, does not lead to an elevated rate of apoptotic pneumocytes in lung grafts.

Animals↗

Buttressing the staple line in lung volume reduction surgery: a randomized three-center study.

BACKGROUND: The intention of buttressing the staple line in lung volume reduction surgery is to reduce air leaks and to shorten the hospital stay. A randomized three-center study was carried out to test this hypothesis. METHODS: Sixty-five patients with a mean age of 59.2 +/- 1.2 years underwent bilateral lung volume reduction surgery by video-assisted thoracoscopy using endoscopic staplers (ET 45B; Ethicon Endo-Surgery, Cincinnati, OH) either without or with bovine pericardium for buttressing (Peri-Strips Dry; Bio-Vascular, Inc, Saint Paul, MN). There were no differences between the control and treatment groups in lung function, degree of dyspnea, and arterial blood gases before and 3 months after LVRS. RESULTS: Seven patients (3 in the treatment group) needed a reoperation because of persistent air leak. The median duration of air leaks was shorter in the treatment group (0.0 day [range, 0 to 28 days versus 4 days [range, 0 to 27 days); p < 0.001), confirmed by a shorter median drainage time in this group (5 days [range, 1 to 35 days] versus 7.5 days [range, 2 to 29 days); p = 0.045). Hospital stay was comparable between the two groups (9.5 days [range, 6 to 44 days] versus 12.0 days [range, 5 to 46 days]; p = 0.14). CONCLUSIONS: Buttressing the staple line significantly shortens the duration of air leaks and the drainage time. As hospital stay did not differ significantly between the two groups, cost-effectiveness may depend on the local situation.

Adult↗

Redo lung volume reduction surgery in a patient with alpha1-antitrypsin deficiency.

Lung volume reduction surgery is a palliative procedure that improves dyspnea and pulmonary function in selected patients with advanced emphysema. Postoperative benefit is sustained for an individual period and depends on the emphysema morphology, the surgical technique, and other not yet well-defined factors. The question whether lung volume reduction surgery can be performed a second time on the same thoracic cavity is often raised but experience in this regard is lacking. We describe a patient who has undergone a successful redo operation 2 years after the initial lung volume reduction surgery.

Humans↗

Early and long-term complaints following video-assisted thoracoscopic surgery: evaluation in 173 patients.

OBJECTIVE: Minimal invasive surgical techniques have gained high acceptance in thoracic surgery during the last 10 years. However, up to now, only scant information exists on chronic postoperative pain and discomfort in patients who underwent video-assisted thoracoscopy. Therefore, a retrospective study was performed with the aid of a self-reported questionnaire. METHODS: Two hundred and thirteen patients (of whom 79 females) with a mean age of 48 (range 15-88) years were operated on for a total of 225 procedures. Thoracoscopy was performed for pneumothorax (n=70), pulmonary nodules (n=44), interstitial lung diseases (n=20), pleural effusion (n=20), and empyema (n=19). Various indications included therapeutic or diagnostic procedures in bullous disease, mediastinal tumors, carcinoma, inflammatory lung disease, hyperhidrosis mani and bronchiectasis. RESULTS: Mean drainage time was 6.0+/-4.7 days and hospital stay 8.4+/-6.6 days. One patient died on the ninth postoperative day after lobectomy for bronchial carcinoma due to cardiac failure, five patients needed a short period of reintubation due to acute respiratory failure. In two patients, thoracoscopic reoperation was necessary for closure of bronchopleural fistula. The self-reported questionnaire was returned by 173 (81%) of all patients within a mean follow-up of 18 (3-38) months. More than half of the patients (53%) reported no thoracic pain as early as 2 weeks after the procedure. At 2 weeks after the operation, 13% of patients suffered from localized pain and 31% from diffuse discomfort. Twelve percent needed pain medication regularly, and 3% occasionally. At 6 months postoperatively, three quarters of the patients had no complaints, 5% suffered from scar pain, and 20% had diffuse chest discomfort. One year after the procedure, 86% of the patients had no complaints, 9% suffered from minimal pain, and 5% from moderate pain. Two years after the procedure, 96% of the patients had no complaints at all. One hundred and twenty-five of the 140 patients (89%) working preoperatively went back to work within 2 weeks after the operation. Fifteen patients did not work between 3 and 16 weeks; 14 due to chest pain, one due to shoulder pain. CONCLUSION: Video-assisted thoracoscopy permits very early recovery with rapid reintegration into the working process. Long-term complaints after videothoracoscopy are rare.

Adolescent↗

8-Br-cyclic GMP given during reperfusion improves post-transplant lung edema and free radical injury.

UNLABELLED: Substitution of the NO-pathway reduces ischemia/reperfusion injury following lung transplantation. 8-Br-cGMP is a membrane permeable analogue of cGMP, the second messenger of NO. In this study the effect of continuous administration of 8-Br-cGMP on early graft function was evaluated. METHODS: Unilateral left lung transplantation was performed in 10 weight-matched pigs (23-30 kg). Donor lungs were flushed with 1.51 cold (1 degree C) LPD solution and preserved for 20 hours. In Group I (n = 5), 8-Br-cGMP (0.2 mg/kg/h) was given continuously over the entire observation time starting 15 min before reperfusion. Group II served as control, no 8-Br-cGMP was administered. In both groups, 250 microg PGE1 was injected into the pulmonary artery (PA) before flush. One hour after reperfusion the recipients contralateral right PA and bronchus were ligated to assess isolated graft function only. Extravascular lung water index (EVLWI), pulmonary vascular resistance, mean PA pressure, mean systemic arterial pressure and gas exchange were assessed during a 5-hour observation period. Lipid peroxidation as indicator for free radical mediated injury and neutrophil migration to the allograft were measured at the end of the assessment. RESULTS: EVLWI was significantly reduced in animals treated with 8-Br-cGMP (overall difference P = 0.024) with a peak 2 hours after reperfusion (Group I, 8.2+/-0.3 mg/ml vs Group II, 10.1+/-0.6 mg/ml; P = 0.039). Also in Group I the free radical mediated tissue injury was significantly lower when compared to Group II (Group I, 61.8+/-12.3 pmol/g vs Group II, 120.7+/-7.2 pmol/g; P = 0.006). A tendency towards a reduced neutrophil migration after 8-Br-cGMP infusion was shown; however, the changes in comparison to the control animals were not statistically significant (Group I, 1.0+/-0.2 deltaOD/mg/min vs Group II, 1.7+/-0.3 deltaOD/mg/min; P = 0.13). Pulmonary- and systemic hemodynamics, and allograft gas exchange did not differ between groups. CONCLUSIONS: The results indicate that substitution of the NO pathway by administration of the second messenger cGMP at the time of reperfusion improves post-transplant lung allograft function.

Animals↗

Lung volume reduction surgery: a survey on the European experience.

STUDY OBJECTIVE: To evaluate the activity and evolution in the field of lung volume reduction surgery (LVRS) performed at surgical centers in Europe. BACKGROUND: LVRS is a novel surgical therapy with the potential to improve lung function, exercise performance, and quality of life in selected patients suffering from severe pulmonary emphysema. METHODS: Questionnaire addressed to 75 European thoracic surgical centers presumed to perform LVRS, and review of the literature. RESULTS: Of 45 responding centers, 42 centers in 17 countries covering a population of 423 million reported performing LVRS. Until the end of 1998, 1,120 patients were reported to have undergone LVRS, corresponding to 2.6 patients/million inhabitants. Thirty-one of 40 centers (78%) perform the operation bilaterally. Most centers (83%) evaluate their activity prospectively. The average perioperative mortality rate of 4.1% is moderate. The most commonly utilized technique is video-assisted thoracoscopy, which is most frequently performed bilaterally. Two thirds of the centers treat patients with alpha(1)-antitrypsin deficiency, and half of the centers will consider patients with homogenous morphology of emphysema on CT scan for LVRS. Half of the centers also perform lung transplantation. The five largest centers have operated on 49% of all LVRS patients assessed by this survey. CONCLUSIONS: LVRS is performed at few thoracic surgical centers throughout Europe, with a large variation in the operative activity between different regions. Half of the centers also perform lung transplantation. Between 1995 and 1997, the number of LVRS procedures performed per year nearly tripled but has reached a plateau since then. As five centers perform nearly half the total number of operations, an optimal exchange of knowledge with smaller centers seems important.

Europe↗