Hubert Schelzig

Reduction of postoperative pulmonary complications after lung surgery using a fast track clinical pathway

BACKGROUND Fast track programs, multimodal therapy strategies, have been introduced in many surgical fields to minimize postoperative morbidity and mortality. In terms of lung resections no randomized controlled trials exist to evaluate such patient care programs. METHODS In a prospective, randomized controlled pilot study a conservative and fast track treatment regimen in patients undergoing lung resections was compared. Main differences between the two groups consisted in preoperative fasting (6h vs 2h) and analgesia (patient controlled analgesia vs patient controlled epidural analgesia). Study endpoints were pulmonary complications (pneumonia, atelectasis, prolonged air leak), overall morbidity and mortality. Analysis was performed in an intention to treat. RESULTS Both study groups were similar in terms of age, sex, preoperative forced expiratory volume in one second (FEV(1)), American Society of Anesthesiologists score and operations performed. The rate of postoperative pulmonary complications was 35% in the conservative and 6.6% in the fast track group (p=0.009). A subgroup of patients with reduced preoperative FEV(1) (<75% of predicted value) experienced less pulmonary complications in the fast track group (55% vs 7%, p=0.023). Overall morbidity was not significantly different (46% vs 26%, p=0.172), mortality was comparable in both groups (4% vs 3%). CONCLUSION We evaluated an optimized patient care program for patients undergoing lung resections in a prospective randomized pilot study. Using this fast track clinical pathway the rate of pulmonary complications could be significantly decreased as compared to a conservative treatment regimen; our results support the implementation of an optimized perioperative treatment in lung surgery in order to reduce pulmonary complications after major lung surgery.

The PARP-1 inhibitor INO-1001 facilitates hemodynamic stabilization without affecting DNA repair in porcine thoracic aortic cross-clamping-induced ischemia/reperfusion

Inhibition of poly (ADP-ribose) polymerase 1 (PARP-1) improved hemodynamics and organ function in various shock models induced by sepsis or ischemia/reperfusion. PARP-1, however, is also referred to play a pivotal role for the maintenance of genomic integrity. Therefore, we investigated the effect of the PARP-1 blocker INO-1001 on hemodynamics, kidney function, and DNA damage and repair during porcine thoracic aortic cross-clamping. The animals underwent 45 min of aortic cross-clamping after receiving vehicle (n = 9) or i.v. INO-1001 (n = 9; total dose, 4 mg·kg−1, administered both before clamping and during reperfusion), data were recorded before clamping, before declamping, and 2 and 4 h after declamping. During reperfusion, continuous i.v. norepinephrine was incrementally adjusted to maintain blood pressure greater than or equal to 80% of the preclamping level. The plasma INO-1001 levels analyzed with high-pressure liquid chromatography were 1 to 1.4 &mgr;mol/L and 0.4 to 0.6 &mgr;mol/L before and after clamping, respectively. Although INO-1001-treated animals required less norepinephrine support, kidney function was comparable in the 2 groups. There was no intergroup difference either in the time course of DNA damage and repair (comet assay) as assessed both in vivo in whole blood before surgery, before clamping, before declamping, 2 h after declamping, and ex vivo in isolated lymphocytes (Ficoll gradient) sampled immediately before clamping and analyzed before, immediately, and 1 and 2 h after exposure to 4 bar 100% O2 for 2 h. There was no difference either in the expression of the cyclin-dependent kinase inhibitor gene, p27, in the kidney (immunohistochemistry). The reduced norepinephrine requirements during reperfusion suggest a positive inotropic effect of INO-1001, as demonstrated by other authors. In our model, INO-1001 proved to be safe with respect to DNA repair.

Technical and clinical success after endovascular therapy for chronic type B aortic dissections.

OBJECTIVE To analyze early technical success and late clinical success after endovascular entry sealing for chronic type B dissection with special emphasis on reintervention, false lumen thrombosis, and aortic remodeling. METHODS Retrospective analysis of a prospective database. From September 1999 to January 2011, 19 patients with chronic type B dissections were treated by endovascular entry sealing. Median age was 60 years. Median time between onset of acute dissection and surgical intervention was 36 (1 to 60) months. Median follow-up was 13 months (1 to 124). RESULTS The endografts used were: Medtronic Captivia (5), Medtronic Valiant (5), Gore TAG (6), Gore C-TAG (2), and Cook Zenith (1). In four patients, revascularization of the left subclavian artery was performed prior to entry sealing. Primary technical success rate (entry sealing, absence of type I leak) was 18/19 (94.7%). In-hospital mortality was 0%. Spinal cord injury with persistent paraplegia occurred in 1/19 (5.2%) patients. After a maximal follow-up of 124 months, reinterventions in 9/19 (47.3%) were necessary: distal/proximal extension of stent graft (8), replacement of the aortic arch due to retrograde dissection (1), and open infrarenal aneurysm repair (1). During follow-up, none of the patients died due to stent-related complications. CONCLUSION Endovascular treatment (EVT) in chronic type B dissections has a high technical success rate and low mortality/morbidity. However reintervention rates are not negligible which might reduce the clinical success of EVT. Future investigations should aim at identifying patients who benefit from EVT at better defining the timing of EVT and at determining if entry sealing alone is sufficient.

Use of integrated FDG-PET/CT in sarcoidosis

We studied five patients with mediastinal lymph node enlargement suggestive of malignant lymphoma, lung cancer, or sarcoidosis. Integrated [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) was performed on all patients. Sarcoidosis can be a pitfall in PET/CT imaging, which may lead to false-positive results of malignancy. Increased FDG uptake in mediastinal lymph nodes is often comparable with malignant lymphoma or lymph node metastases. Histological confirmation of the lesions should be mandatory, except for patients in whom sarcoidosis can be accurately confirmed by other diagnostic methods.

Comparison of Clinical and Surgical-Pathological Staging in IIIA Non-Small Cell Lung Cancer Patients

BackgroundThe heterogeneous group of IIIA NSCLC patients requires careful preoperative clinical staging as tumor size and lymph node involvement guide treatment. The purpose of our study was to analyze the correctness of clinical staging in IIIA patients.MethodsRetrospective analysis of all patients resected due to lung cancer that had been staged IIIA either clinically using invasive and noninvasive techniques or surgical-pathologically after surgical resection. Correctness, sensitivity, specificity, and positive and negative predictive values of clinical staging were calculated.ResultsFrom our tumor database, 49 patients who met the inclusion criteria were identified. The histology of the primary tumor included adenocarcinoma (53%), squamous cell carcinoma (41%), and other (6%). Preoperative clinical staging consisted of computed tomography (CT), integrated positron emission tomography–CT (PET–CT), bronchoscopy, and mediastinoscopy. The predominant surgical procedures performed were lobectomies (57%) and pneumonectomies (29%). Clinical staging for UICC, T and N stage was correct in 36.7, 38.7, and 40.8%, respectively. In terms of T4 stage, sensitivity was 28.5%, specificity was 80.9%, positive predictive value was 20%, and negative predictive value was 87.1%. As for N2 involvement, we found a sensitivity of 66.6% and a specificity of 35.7%. Positive and negative predictive values for N2 involvement were 43.7 and 58.8% in that order.ConclusionsDespite multimodal preoperative invasive and noninvasive staging techniques, the correctness of clinical staging in IIIA NSCLC patients is low. Hence, in doubt more invasive staging or probatory thoracotomy should be performed not to deny potentially curative surgery in those patients.

Hybrid Procedures for Complex Thoracoabdominal Aortic Aneurysms: Early Results and Secondary Interventions

Background: Hybrid procedures for thoracoabdominal aortic aneurysms (TAAA) have been previously described as an attractive alternative to open reconstruction. Patients and Methods: Between 1999 and 2009, 16 patients with a median age of 67years underwent hybrid repair of a TAAA (Crawford type I: 3, type II: 3, type III: 1, and type IV: 9). In 94%, 3 and more severe comorbidities were present, with previous aortic surgery in 56% of the patients; elective/urgent repair was done in 10 and emergent surgery in 6 patients. Results: Primary technical success was 100%, with 31 vessels grafted. Elective/urgent mortality was 20% (2 of 10) and emergent mortality 50% (3 of 6). During follow-up time (median: 12 months) 2 patients died and 2 patients had to undergo secondary interventions. Conclusion: In high-risk patients especially after prior aortic surgery hybrid repair of TAAA is feasible. However, due to high mortality rates especially in the emergent situation this procedure should be reserved only for decidedly selected patients.

Endovascular Repair of Aortic Isthmus Coarctation With a Self-Expanding Covered Stent

BACKGROUND Coarctation is one of the most often seen congenital aortal defects. In the majority, diagnosis will be made in newborns. Endovascular repair is critical in children owing to their growth, but in adult patients, it is an interesting alternative. METHODS A 31-year-old man presenting with hypertension of upper extremities and pulseless lower extremities was admitted to our hospital. Systolic blood pressure was 190 mm Hg, although a triple antihypertensive medication was administered. Computed tomographic angiography showed a nearly total occlusion of the aortic isthmus. Coarctation was treated by an endovascular approach with a self-expanding covered stent-graft (Medtronic Talent; Medtronic World Medical, Sunrise, FL) after predilatation with a Reliant balloon (Medtronic World Medical, Sunrise, FL). RESULTS After a follow-up of 40 months, the patient is normotensive and antihypertensive medication could be reduced. Lower extremities showed normal pulses and normal ankle-brachial index. Computed tomographic scans showed unchanged stent-graft position, with constant slight waist. DISCUSSION Endovascular repair of atresia or coarctation of the thoracic aorta is a minimal invasive debatable option. Not only reduction of blood pressure but also reduction of left ventricular mass and prolongation of life expectancy can be achieved by endovascular treatment.

Langzeitverlauf nach endovaskulärer Versorgung einer aortoenterischen Fistel

ZusammenfassungDie Versorgung von aortoenteralen Fisteln stellt aufgrund der lokalen Infektsituation und den zumeist schwerkranken Patienten eine besondere Herausforderung dar. Die konventionelle offene Chirurgie ist mit hohen Komplikations- und Mortalitätsraten behaftet. Bei endovaskulären Therapieansätzen bleibt die persistierende bzw. rezidivierende Infektion das Hauptproblem.Wir berichten vom elfjährigen Krankheitsverlauf eines Patienten mit primär endovaskulär versorgter massiver Arrosionsblutung der Aorta bei retroperitonealem Infekt nach onkologischer Lymphknotendissektion.AbstractThe treatment of aortoenteric fistulas represents a special challenge due to the local infection situation and usually severely ill patients. Therefore, conventional surgical treatment is associated with high rates of complications and mortality. In endovascular approaches, recurrent infection remains the major concern.We present the case of a patient with an 11-year history of primarily endovascularly treated massive arrosive bleeding of the aorta caused by retroperitoneal infection after oncological lymph node dissection.

ERYTHROPOIETIN DURING AORTIC BALLOON-OCCLUSION-INDUCED ISCHEMIA-REPERFUSION INJURY

TOWARDS RESOLVING THE CHALLENGE OF SEPSIS DIAGNOSTIC. Thomas Herget* and Thomas Joos . *Merck KGaA, Darmstadt, Germany; NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany Biomarkers have proven to be very useful in clinical conditions such as heart attack, stroke and cancer. There are characteristics linked to sepsis like in blood pressure, body temperature and heart rate. Efforts over the last decade to improve diagnosis for infectious inflammation have been unsuccessful in identifying a single and universal biomarker that provides sufficiently high sensitivity and specificity. In gramnegative septicemia and following major abdominal trauma, the determination of endotoxin continues to be a leading candidate which could become adopted into clinical practice. The importance of endotoxin measurement continues to grow as more clinicians recognize the added value of measuring endotoxin in critically ill patients and with the emergence of major pharmaceutical trials directly targeting endotoxin in the bloodstream. However, hundreds of other candidates potentially serving as biomarker for sepsis have been recently described, e.g. cysteinyl-leukotriene (LTC4) generation, procalcitonin (PCT) and C-reactive protein (CRP). However, none of them fulfils the criteria requested by clinicians, namely being specific and sensitive. The presentation will discuss criteria for a sepsis biomarker, will give an overview of obtaining samples from appropriate cell systems and from patients. Furthermore, tools will be described to identify marker candidates on genetic-, proteinand metabolite level. The integration of these data sets covering e.g. signal transduction, protein : protein interaction, gene expression with the help of bioinformatics and systems biology will help to validate such candidates. The final goal is manufacturing a robust diagnostic device for clinical routine work. A solid sepsis diagnostics method will be beneficial for patients, but also for the healthcare systems and will open challenges for the pharmaceutical industry.