Intrinsic pulmonary sealing, its mechanisms and impact on validity and translational value of lung sealant studies: a pooled analysis of animal studies.

Background: No validated and standardized animal models of pulmonary air leakage (PAL) exist for testing aerostatic efficacy of lung sealants. Lack of negative control groups in published studies and intrinsic sealing mechanisms of healthy animal lungs might contribute to a translational gap, leading to poor clinical results. This study aims to address the impact of intrinsic sealing mechanisms on the validity of PAL models, and investigate the conditions required for an ovine model of PAL for lung sealant testing. Methods: An ovine acute aerostasis model was developed, consisting of a bilateral thoracotomy with lesion creation, chest tube insertion and monitoring of air leaks using digital drains (≥80 minutes), under spontaneous respiration. Healthy mixed-breed adult female sheep were used and all in vivo procedures were performed under terminal anesthesia. Superficial parenchymal lesions were tested post-mortem and in vivo, extended lesions including bronchioles (deep bowl-shaped and sequential lung amputation lesions) were tested in vivo. Experiment outcomes include air leakage (AL), minimal leaking pressure (MLP) and histology. Results: Two post-mortem (N=4 superficial parenchymal lesions) and 10 in vivo experiments (N=5 superficial parenchymal and N=16 lesions involving bronchioles) were performed. In contrast to the post-mortem model, superficial parenchymal lesions in vivo showed less air leak [mean flow ± standard deviation (SD): 760±693 vs. 42±33 mL/min, P=0.055]. All superficial parenchymal lesions in vivo sealed intrinsically within a median time of 20 minutes [interquartile range (IQR), 10-75 minutes]. Histology of the intrinsic sealing layer revealed an extended area of alveolar collapse below the incision with intra-alveolar hemorrhage. Compared to superficial parenchymal lesions in vivo, lesions involving bronchioles induced significantly higher air leak post-operatively (normalized mean flow ± SD: 459±221 mL/min, P=0.003). At termination, 5/9 (55.6%) were still leaking (median drain time: 273 minutes, IQR, 207-435 minutes), and intrinsic sealing for the remaining lungs occurred within a median of 115 minutes (IQR, 52-245 minutes). Conclusions: Lung parenchyma of healthy sheep shows a strong intrinsic sealing mechanism, explained pathologically by an extended area of alveolar collapse, which may contribute to a translational gap in lung sealant research. A meaningful ovine model has to consist of deep lesions involving bronchioles of >⌀1.5 mm. Further research is needed to develop a standardized PAL model, to improve clinical effectiveness of lung sealants.

Sealing effectiveness of a novel NHS-POx based patch: experiments in a dynamic ex vivo porcine lung.

Background: Sealants are used to prevent prolonged pulmonary air leakage (PAL) after lung resections (incidence 5.6-30%). However, clinical evidence to support sealant use is insufficient, with an unmet need for a more effective product. We compared a novel gelatin patch impregnated with functionalized polyoxazolines (NHS-POx) (GATT-Patch) to commercially available sealant products. Methods: GATT-Patch Single/Double layers were compared to Progel®, Coseal®, Hemopatch® and TachoSil® in an ex vivo porcine lung model (first experiment). Based on these results, a second head-to-head comparison between GATT-Patch Single and Hemopatch® was performed. Air leakage (AL) was assessed in three settings using increasing ventilatory pressures (max =70 cmH2O): (I) baseline, (II) with 25 mm × 25 mm superficial pleural defect, and (III) after sealant application. Lungs floating on saline (37 ℃) were video recorded for visual AL assessment. Pressure and tidal volumes were collected from the ventilator, and bursting pressure (BP), AL and AL-reduction were determined. Results: Per sealant 10 measurements were performed (both experiments). In the first experiment, BP was superior for GATT-Patch Double (60±24 cmH2O) compared to TachoSil® (30±11 cmH2O, P<0.001), Hemopatch® (33±6 cmH2O, P=0.006), Coseal® (25±13 cmH2O, P=0.001) and Progel® (33±11 cmH2O, P=0.005). AL-reduction was superior for GATT-Patch Double (100%±1%) compared to Hemopatch® (46%±50%, P=0.010) and TachoSil® (31%±29%, P<0.001), and also for GATT-Patch Single (100%±14%, P=0.004) and Progel (89%±40%, P=0.027) compared to TachoSil®. In the second experiment, GATT-Patch Single was superior regarding BP (45±10 vs. 40±6 cmH2O, P=0.043) and AL-reduction (100%±11% vs. 68%±40%, P=0.043) when compared to Hemopatch®. Conclusions: The novel NHS-POx patch shows promise as a lung sealant, demonstrating elevated BP, good adhesive strength and a superior AL-reduction.

Ex-vivo exploration of an endobronchial sentinel lymph node procedure in lung cancer for optimizing workflow and evaluating feasibility of novel imaging tools.

Background: Early-stage lung cancer is treated with curative intent by surgery or radiotherapy. However, upstaging is frequently seen after surgery in clinical N0 lung cancer patients, and despite curative intent, 2-year recurrence rates of 9-28% are reported. A sentinel lymph node (SLN) procedure could improve the staging accuracy. We explored the feasibility of performing a navigation bronchoscopy based SLN procedure in human ex-vivo lung cancer specimens to optimize procedural parameters and assess a novel injection tool. Methods: Ten lung resection specimens were included and allocated to either peri- or intratumoral injection of a tracer combining 99mTc-nanocolloid and indocyanine green (ICG) while varying the injection volume. A Pioneer Plus catheter with a pre-angulated 24G needle and an ultrasound (US)-element was used to perform real-time US guided transbronchial injections at multiple locations. Thereafter, single photon emission computed tomography/computed tomography (SPECT/CT)-scanning was performed to image injection depots and to assess their location relative to the tumor. Results: An average volume of 0.7 mL (range, 0.3-1.2 mL) with an average activity of 89.5 MBq 99mTc (range, 35.4-188.0 MBq) was injected. Intratumoral injections in non-solid and solid tumors were successful in 100% and 64.3% respectively, while 100% of peritumoral injections in solid tumors were successful. The US-element of the catheter allowed real-time imaging and was able to visualize all tumors and 67.4% of all injections. SPECT/CT-scanning visualized 76.7% of the injection depots. Conclusions: A navigation bronchoscopy mediated SLN procedure seems technically feasible. The Pioneer Plus is a suitable catheter to place tracer depots at multiple intra-/peri-tumoral sites, while receiving real-time feedback on the needle localization in relation to the tumor. The next step of in-vivo injections will determine if tracer drainage to the SLN can also be detected on pre- and per-operative imaging.

Long-term follow-up of voice changes after cervical mediastinoscopy.

BACKGROUND: Vocal cord palsy after cervical mediastinoscopy is usually reported at less than 1%. However, its incidence might be underestimated and no follow-up studies are available. Our study aimed to evaluate the incidence of voice changes after cervical mediastinoscopy and report on long-term outcomes, including quality of life, after at least one-year follow-up. METHODS: A retrospective cohort study was performed, considering all patients who underwent cervical mediastinoscopy in our center between January 2011 and April 2016. Patients with pre-existing voice changes, voice changes only after pulmonary resection and patients who underwent neoadjuvant chemo(radio)therapy were excluded. Voice changes with full recovery within 14 days were attributed to intubation-related causes. Follow-up questionnaires, including the standardized Voice Handicap Index, were sent to patients with documented voice changes. RESULTS: Of 270 patients who were included for final analysis, 17 (6.3%) experienced voice changes after cervical mediastinoscopy, which persisted > 2 years in 4 patients (1.5%), causing mild to moderate disabilities in daily living. Twelve patients (out of 17, 71%) were referred for otolaryngology consultation, and paresis of the left vocal cord suggesting recurrent laryngeal nerve injury was confirmed in 10 (3.7% of our total study group). Additionally, 83% of the patients who were referred for otolaryngology consultation received voice treatment. Recovery rate after vocal exercises therapy and injection laryngoplasty was respectively 71% and 33%. CONCLUSIONS: Voice changes after cervical mediastinoscopy is an underreported complication, with an incidence of at least 6.3% in our retrospective study, with persisting complaints in at least 1.5% of patients, leading to mild to moderate disabilities in daily living. These findings highlight the need for appropriate patient education for this underestimated complication, as well as the exploration of possible preventive measures.

Correlation of Preoperative State Anxiety and Pain Six Weeks After Surgical Correction of Pectus Excavatum.

BACKGROUND: Pain is a major concern in the early postoperative phase after correction of pectus excavatum. Most studies only focus on pain management in the first days after surgery and describe methods to alleviate the pain immediately postoperatively. The severity of postoperative pain may be influenced by anxiety. So far, few studies have looked into the relationship between anxiety and postoperative pain after pectus excavatum correction. OBJECTIVES: This study aimed to investigate the correlation between preoperative anxiety and late postoperative pain scores. METHODS: This was a prospective cohort study. Anxiety was assessed with the State and Trait Anxiety Inventory questionnaire. Visual analogue scale (VAS) for pain scores assessed the pain at rest and activity. Anxiety was measured before surgery and pain scores six weeks after surgery. A hierarchical linear regression analysis was performed to investigate the correlation between baseline anxiety and pain measurements six weeks after surgery. RESULTS: In this study, 136 patients were included. State anxiety was not associated with postoperative pain (mean of pain on activity and in rest), only with pain on activity after six weeks. Age and sex were not effect modifiers in any of the models. Relevant confounding factors, although not significant, consisted of trait, sex, minor complications, epidural duration, major complications, and the number of stabilizer plates. The explained variance of state anxiety on VAS for pain scores was minimum after 6 weeks. CONCLUSIONS: Preoperative anxiety does not appear to influence postoperative pain after PE correction.

The Outcome of the Single Step Questionnaire in Pectus Excavatum Patients is Phase Dependent.

INTRODUCTION: Pectus excavatum (PE) is the most common chest wall deformity. Patients with PE may have cosmetic complaints, restricted physical capabilities, or both and may seek surgical correction. One method to assess satisfaction after surgery is the single step questionnaire (SSQ). Although the developers state that the SSQ produces a stabile score and only needs to be used once, we hypothesized that the score may depend on point in time after surgery. MATERIALS AND METHODS: One hundred and eight patients from a longitudinal cohort of patients undergoing a Nuss bar placement for PE were selected. Mean age was 16.0 years (range: 12-29). SSQ was completed at 6 weeks, 6 months, 1 year, and 2 years postoperatively. Mean and median scores per question and total scores were calculated on each measurement moment. Overall scores were tested using the Friedman test. RESULTS: There were significant differences in overall SSQ scores (p < 0.009) throughout the postoperative period, especially between 6 weeks and 6 months (p = 0.006). Scores on general health, exercise capacity, impact on social life, pain during hospital stay, and after discharge changed also significant in the first 2 years after Nuss bar placement. CONCLUSION: There were significant differences in total SSQ score depending on the time of application postoperatively. However, the most clinical relevant difference was between 6 weeks and 6 months. Assessment of the overall satisfaction postoperative with the SSQ questionnaire should not be done with a single measurement but rather at different postoperative time intervals before and after 6 months postoperatively.

Platelet-leukocyte rich gel application in the prevention of deep sternal wound problems after cardiac surgery in obese diabetic patients.

BACKGROUND: Deep sternal wound problems (DSWP) are a rare, but serious complication following cardiac surgery requiring extensive medical treatment and resulting in increased mortality. Cardiac surgery patients presenting with both obesity and diabetes mellitus type 2 (DM 2) showed an increased incidence of DSWP in our clinic. As platelets upon activation have been shown to excrete growth factors and attractants for tissue stem cells, thus potentially promoting tissue healing, we investigated whether activated platelets could reduce the incidence of DSWP. METHODS: We applied activated autologous platelet rich plasma (PRP), forming a gel (PLG), between the sternal halves immediately prior to closure in obese [body mass index (BMI) >30] DM 2 cardiac surgery patients. The reference group constituted of all elective patients with a BMI >30 and DM 2 operated upon in the 2-year period before the application of PLG. RESULTS: The PLG treated group (n=144) showed a significant decrease in DSWP compared to the reference group (n=118), 6 DSWP vs. 13 DSWP respectively, P=0.03. In these groups the application of PLG was associated with a risk reduction for DSWP from 11% to 4.2%. CONCLUSIONS: These results suggest PLG application could be beneficial to prevent DSWP following cardiac surgery in a high-risk population.

Spontaneous leaflet fracture resulting in embolization from mechanical valve prostheses.

Spontaneous leaflet fracture of mechanical heart valve prostheses is very rare. We describe a case of spontaneous leaflet embolization 31 years after aortic valve replacement with an Edwards-Duromedics prosthesis (Baxter Healthcare Corp., Edwards Division, Santa Ana, CA). We review the literature on this subject to increase awareness and recognition for this potentially life-threatening complication.

Early cost-utility estimation of the surgical correction of pectus excavatum with the Nuss bar.

OBJECTIVES: The surgical correction of pectus excavatum (PE) with a Nuss bar provides satisfactory outcomes, but its cost-effectiveness is yet unproven. We prospectively analysed early outcomes and costs for Nuss bar placement. METHODS: Fifty-four patients aged 16 years or older (6 females and 48 males; mean age, 17.9 years; range 16.0-29.4 years) with a PE filled out a Short Form-36 Health Survey (SF-6D) preoperatively and 1 year after a Nuss procedure. Costs included professional fees and fees for the operating room, materials and hospital care. Changes in the responses to the SF-36 or its domains were compared using the Wilcoxon signed rank test and the utility test results were calculated preoperatively and postoperatively from the SF-6D. The quality-adjusted life years (QALYs) were calculated from the results of these tests. RESULTS: Significant improvements in physical functioning, social functioning, mental health and health transition (all P < 0.05) were noted. The other SF-36 subgroups showed improvement; however, the improvement was not significant. The SF-6D utility showed improvement from 0.76 preoperatively to 0.79 at the 1-year follow-up (P = 0.096). The mean direct costs were €8805. The 1-year discounted QALY gain was 0.03. The estimated cost-utility ratio was €293 500 per QALY gained. CONCLUSIONS: Despite a significant improvement in many domains of the SF-36, the results of the SF-6D cost-utility analysis showed only a small improvement in cost-effectiveness (> €80 000/QALY) for patients with PE 1 year after Nuss bar placement. Based on this discrepancy, general health outcome measurements as the basis for cost-utility analysis in patients with PE may not be the best way forward.

Sports activity in adolescents in the Netherlands with a pectus excavatum; the impact of surgery.

PURPOSE: Pectus excavatum (PE) is the most common chest wall deformity in adolescents. The main complaint is cosmetic, but many patients also complain about exertional dyspnea. This may lead to the patient seeking surgery of the thoracic wall deformity (TWD). The assumption is that both, appearance and physical complaints will have a negative effect on being able or wanting to engage in sport activity. METHODS: In December 2011 a prospective registration of sport activity in pectus excavatum patients started. Sport activity was assessed using questionnaires (CHQ, SF-36 and PEEQ). Measurements were taken before corrective surgery (preoperatively) and 12 months postoperatively. RESULTS: 127 patients have been included. The number of patients who were active in sports preoperatively and after 12 months remained steady. The type of sport activity, individual sport or team sport showed no significant change. The CHQ showed that physical activity caused fewer complaints (p < 0.001). The PEEQ showed a decrease in difficulties with sports activity performance after 12 months (p < 0.001). CONCLUSIONS: Twelve months after surgical correction of PE there was no significant increase in the number of patients performing sport activities. However there was a significant decrease of complaints or difficulties during sport compared to preoperatively. LEVEL OF EVIDENCE: Level IV.

Aortic allografts: final destination?-a summary of clinical tracheal substitutes.

The patient population in desperate need for an airway substitute are individuals with long segment tracheal defects that are considered, technically, inoperable. Regardless of the underlying etiology, benign or malignant growing processes, this patient category enters a palliative setting or require tracheal transplantation. Different airway substitutes have been categorized by Grillo as follows; tracheal transplantation, autogenous tissue, non-viable tissue, tissue-engineering and foreign materials. These fields have been explored in the past in animal models and in clinical patients. Research on airway replacement has been exposed to a level of controversies in the past years. The field has been turbulent and apocryphal. In particular, the area of tissue-engineering using stem cells has suffered from a major set-back leaving scientists, clinicians and ethical committees skeptical. Recently, a hopeful study emerged using aortic allografts as tracheal substitutes in patients with airway defects. The initial results seem promising and reliable. The developments of the field at this point seem striking and hopeful. The focus of this review is to shed light on developments in the field of aortic allografts as substitute for tracheal replacement.

Tracheal rupture after intubation and placement of an endotracheal balloon catheter (A-view®) in cardiac surgery.

The endotracheal balloon catheter (A-view®) is a device developed to locate atherosclerotic plaques of the ascending aorta (AA) in cardiac surgery to prevent stroke. The saline-filled balloon is located in the trachea and combines the advantages of transoesophageal echocardiography (e.g. used before performing the sternotomy) and intraoperative epiaortic ultrasound scanning (e.g. complete view of the AA). We report the first severe complication after the use of A-view®. This is a case of a 66-year old woman who underwent elective myocardial revascularization complicated by an intraoperative iatrogenic tracheal rupture of 6 cm, after uncomplicated intubation and the use of an endotracheal balloon catheter (A-view®), which required direct surgical repair with a posterolateral thoracotomy after the myocardial revascularization was completed, weaning from bypass and closure of the median sternotomy.

Mediastinal staging in daily practice: endosonography, followed by cervical mediastinoscopy. Do we really need both?

OBJECTIVES: In patients with lung cancer, endosonography has emerged as a minimally invasive method to obtain cytological proof of mediastinal lymph nodes, suspicious for metastases on imaging. In case of a negative result, it is currently recommended that a cervical mediastinoscopy be performed additionally. However, in daily practice, a second procedure is often regarded superfluous. The goal of our study was to assess the additional value of a cervical mediastinoscopy, after a negative result of endosonography, in routine clinical practice. METHODS: In a retrospective cohort study, the records of 147 consecutive patients with an indication for mediastinal lymph node staging and a negative result of endosonography were analysed. As a subsequent procedure, 124 patients underwent a cervical mediastinoscopy and 23 patients were scheduled for an intended curative resection directly. The negative predictive value (NPV) for both diagnostic procedures was determined, as well as the number of patients who needed to undergo a mediastinoscopy to find one false-negative result of endosonography (number needed to treat (NNT)). Clinical data of patients with a false-negative endosonography were analysed. RESULTS: When using cervical mediastinoscopy as the gold standard, the NPV for endosonography was 88.7%, resulting in a NNT of 8.8 patients. For patients with fluoro-2-deoxyglucose positron emission tomography positive mediastinal lymph nodes, the NNT was 6.1. Overall, a futile thoracotomy could be prevented in 50% of patients by an additional mediastinoscopy. A representative lymph node aspirate, containing adequate numbers of lymphocytes, did not exclude metastases. CONCLUSIONS: In patients with a high probability of mediastinal metastases, based on imaging, and negative endosonography, cervical mediastinoscopy should not be omitted, not even when the aspirate seems representative.

Efficiency, efficacy, and safety of EZ-blocker compared with left-sided double-lumen tube for one-lung ventilation.

BACKGROUND: Double-lumen tubes (DLTs) or bronchial blockers are commonly used for one-lung ventilation. DLTs are sometimes difficult or even impossible to introduce, and the incidence of postoperative hoarseness and airway injuries is higher. Bronchial blockers are more difficult to position and need more frequent intraoperative repositioning. The design of a Y-shaped bronchial blocker, the EZ-Blocker (Teleflex Life Sciences Ltd., Athlone, Ireland) (EZB), combines some advantages of both techniques. The objective of this study was to assess whether EZB performs clinically better than left-sided DLTs (Broncho-cath; Mallinckrodt, Athlone, Ireland) without causing more injury. Primary outcome was the frequency of initial malpositions. METHODS: Eligible patients were adults scheduled for surgery requiring one-lung ventilation who met criteria for placement of both devices. In this parallel trial, 100 consecutive and blinded patients were assigned randomly using a computer-generated list to two groups. The incidence of malposition and ease and time of placement were recorded. Blinded assessors investigated quality of lung deflation, postoperative complaints, and damage to the airway. RESULTS: Placement of a DLT was unsuccessful twice. The incidence of initial malposition was high and comparable between EZBs (37 of 50) and DLTs (42 of 49) (P = 0.212). Placing single-lumen tubes and EZBs took more time but was rated easier. Quality of lung deflation was comparable. Fewer patients in the EZB group complained of sore throat at day 1. There was a higher incidence of tracheal hematoma and redness and bronchial hematoma in the DLT group. CONCLUSIONS: The EZB is an efficient and effective device for one-lung ventilation and causes less injury and sore throat than a DLT.

Circumferential disruption of the ventriculo-aortic junction due to infective endocarditis: surgical repair with custom-made, accurately sized, pericardial tube.

Repair of circumferential ventriculo-aortic annular disruption following infective endocarditis is technically challenging. We present an approach for systematic repair and describe a technique for preparation of an accurately sized pericardial tube graft.