A comparison of sufentanil vs. remifentanil in fast-track cardiac surgery patients.

We retrospectively compared patients receiving remifentanil with patients receiving sufentanil undergoing fast-track cardiac surgery. After 1:1 propensity score matching there were 609 patients in each group. The sufentanil group had a significantly longer mean (SD) ventilation time compared with the remifentanil group; 122 (59) vs. 80 (44) min, p < 0.001 and longer mean (SD) length of stay in the recovery area; 277 (77) vs. 263 (78) min, p = 0.002. The sufentanil group had a lower mean (SD) visual analogue pain score than the remifentanil group; 1.5 (1.2) vs. 2.4 (1.5), p < 0.001 and consumed less mean (SD) piritramide (an opioid analgesic used in our hospital); 2.6 (4.7) vs. 18.9 (7.3) mg, p < 0.001. The results of our study show that although remifentanil was more effective in reducing time to tracheal extubation and length of stay in the recovery area, there was an increased requirement for postoperative analgesia when remifentanil was used.

Chromosome 20p11 gains are associated with liver-specific metastasis in patients with colorectal cancer.

OBJECTIVE: Metastatic colorectal cancer (CRC) cells have a selective preference for certain target organs that cannot be explained by circulatory patterns alone. This study aimed to identify clinicopathological features and chromosomal aberrations of primary tumours associated with organ-specific CRC metastasis. DESIGN: Clinicopathological features were investigated in patients with CRC who had exclusively hepatic (n=182) versus exclusively extrahepatic (n=139) metastases. A total of 139 primary tumours of patients with hepatic (n=85) and extrahepatic metastases (n=54) were screened for chromosomal aberrations by microarray-based comparative genomic hybridisation, and the findings were validated in an independent set of 80 primary tumours. A publicly available database was used to correlate chromosomal aberrations with gene expression. Protein expression was evaluated by immunohistochemistry on tissue microarrays. RESULTS: Patients with hepatic metastases were significantly more often male (71% vs 53% p=0.002), more often had abnormal lactate dehydrogenase activity (37% vs 14% p<0.0001), exhibited primary tumour localisation in the colon (52% vs 40% p=0.03) and had synchronous onset of metastases (70% vs 19% p<0.0001). Primary tumours of patients with hepatic metastases were more commonly T3 tumours (79% vs 63% p=0.006) and less commonly of mucinous histology (5% vs 16% p=0.02). Gain of 20p11 was more often observed in patients with hepatic metastases (p<0.05), which was confirmed in an independent dataset (p<0.05; false discovery rate <0.05). Twelve genes mapping at 20p11 were significantly overexpressed as a consequence of 20p11 copy number gain. C20orf3 showed the strongest correlation between RNA expression and DNA copy number. This was reflected in significantly higher protein expression in patients with hepatic metastases (59%; n=325) than in those with extrahepatic metastases (41%; n=256) (p=0.01). CONCLUSION: C20orf3 mapping at 20p11 is associated with hepatic-specific metastasis in patients with CRC. This gene is a candidate biomarker for liver metastases and may be of clinical value in early-stage CRC.

Near-infrared spectroscopy monitoring of the collateral network prior to, during, and after thoracoabdominal aortic repair: a pilot study.

OBJECTIVE: The aim of this study was to evaluate the feasibility of non-invasive monitoring of the paraspinous collateral network (CN) oxygenation prior to, during, and after thoracoabdominal aortic repair in a clinical series. METHODS: Near-infrared spectroscopy optodes were positioned bilaterally-over the thoracic and lumbar paraspinous vasculature-to transcutaneously monitor muscle oxygenation of the CN in 20 patients (age: 66 ± 10 years; men = 11) between September 2010 and April 2012; 15 had open thoracoabdominal aortic repair (Crawford II and III), three had thoracic endovascular aortic repair (TEVAR; Crawford I), and two had a hybrid repair (Crawford II). CN oxygenation was continuously recorded until 48 hours postoperatively. RESULTS: Hospital mortality was 5% (n = 1), 15% suffered ischemic spinal cord injury (SCI). Mean thoracic CN oxygenation saturation was 75.5 ± 8% prior to anesthesia (=baseline) without significant variations throughout the procedure (during non-pulsatile cooling on cardiopulmonary bypass and with aortic cross-clamping; range = 70.6-79.5%). Lumbar CN oxygenation (LbS) dropped significantly after proximal aortic cross-clamping to a minimum after 11.7 ± 4 minutes (74 ± 13% of baseline), but fully recovered after restoration of pulsatile flow to 98.5% of baseline. During TEVAR, stent-graft deployment did not significantly affect LbS. Three patients developed relevant SCI (paraplegia n = 1/paraparesis n = 2). In these patients LbS reduction after aortic cross-clamping was significantly lower compared with patients who did not experience SCI (p = .041). CONCLUSIONS: Non-invasive monitoring of CN oxygenation prior to, during, and after thoracoabdominal aortic repair is feasible. Lumbar CN oxygenation levels directly respond to compromise of aortic blood circulation.

Experience with anatomically orientated devices for transapical aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is a new technology, which is rapidly growing to a routine procedure amenable for patients with symptomatic aortic valve stenosis and higher than average risk for conventional aortic valve surgery. The crucial disadvantage of TAVI remains the not well foreseeable risk of more than trivial degree of paravalvular leakage and a high rate of atrioventricular block and consecutive pacemaker implantation. In addition, current implantation techniques do not allow controlling the rotation of first-generation devices that might be beneficial regarding optimal physiological valve performance, optimal coronary flow and avoidance of placement of covered commissures in front of the coronary ostia. These shortcomings had pushed the development of second-generation self-expandable nitinol-based devices for subcoronary implantation that aim a reduction of paravalvular leak and AV-block by anatomical orientated positioning into the aortic root. This review focuses on the description of three different TAVI concepts, which are presently under early clinical evaluation, or have recently received commercial approval, using the transapical approach.

Acute aortic dissection type A.

BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular emergency. Clinical presentation ranges from pain related to the acute event, collapse due to aortic rupture or pericardial tamponade, or manifestations of organ or limb ischaemia. The purpose of this review was to clarify important clinical issues of AADA management, with a focus on diagnostic and therapeutic challenges. METHODS: Based on a MEDLINE search the latest literature on this topic was reviewed. Results from the German Registry for Acute Aortic Dissection Type A (GERAADA) are also described. RESULTS: Currently, the perioperative mortality rate of AADA is below 20 per cent, the rate of definitive postoperative neurological impairment approaches 12 per cent and the long-term prognosis after surviving the acute phase of the disease is good. Many pathology- and therapy-associated factors influence the outcome of AADA, including prompt diagnosis with computed tomography and better cerebral protection strategies during aortic arch reconstruction. Endovascular technologies are emerging that may lead to less invasive treatment options. CONCLUSION: AADA is an emergency that can present with a wide variety of clinical scenarios. Advances in the surgical management of this complex disease are improving outcomes.

Beyond KRAS mutation status: influence of KRAS copy number status and microRNAs on clinical outcome to cetuximab in metastatic colorectal cancer patients.

BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Novel predictive markers are required to further improve the selection of patients for this treatment. We assessed the influence of modification of KRAS by gene copy number aberration (CNA) and microRNAs (miRNAs) in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab. METHODS: Formalin-fixed paraffin-embedded primary tumour tissue was used from 34 mCRC patients in a phase III trial, who were selected based upon their good (n = 17) or poor (n = 17) progression-free survival (PFS) upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene copy number at the KRAS locus was assessed using high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR. RESULTS: Copy number loss of the KRAS locus was observed in the tumour of 5 patients who were all good responders including patients with a KRAS mutation. Copy number gains in two wild-type KRAS tumours were associated with a poor PFS. In KRAS mutated tumours increased miR-200b and decreased miR-143 expression were associated with a good PFS. In wild-type KRAS patients, miRNA expression did not correlate with PFS in a multivariate model. CONCLUSIONS: Our results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS might further optimize the selection of mCRC eligible for anti-EGFR therapy.

KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients.

BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. METHODS: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. RESULTS: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. CONCLUSION: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

Prediction of the annuloplasty ring size in patients undergoing mitral valve repair using real-time three-dimensional transoesophageal echocardiography.

AIMS: We sought to investigate the additional value of real-time three-dimensional transoesophageal echocardiography (RT 3D TOE)-guided sizing for predicting annuloplasty ring size during mitral valve repair. METHODS AND RESULTS: In 53 patients undergoing elective mitral valve repair, an RT 3D TOE was performed pre- and post-operatively. The digitally stored loops were imported into a software for mitral valve assessment. The annuloplasty ring size was predicted by superimposing computer-aided design (CAD) models of annuloplasty rings onto Live 3D zoom loops, measurement of the intercommissural distance, or the height of the anterior mitral leaflet. The surgeon implanted the annuloplasty ring according to the usual surgical technique and was blinded to the echocardiographic measurement results. Pre-operative correlation between the selected ring size with mitral valve assessment and the actual implanted annuloplasty ring size was 0.91. The correlation for measurement of the intercommissural distance was 0.55 and for measurement of the height of the anterior mitral leaflet 0.75. The post-operative correlation with the actual implanted ring size was 0.96 for mitral valve assessment, 0.92 for intercommissural distance, and 0.79 for the anterior mitral leaflet height. CONCLUSION: Superimposition of annuloplasty ring CAD models on the Live 3D zoom loops of the mitral valve using mitral valve assessment is superior to two-dimensional measurements of the intercommissural distance or the height of the anterior mitral leaflet in predicting correct annuloplasty ring size.

Life-threatening hemothorax resulting from lung hernia after minimally invasive mitral valve surgery.

Lung hernia following minimally invasive mitral valve surgery is an uncommen entity. We report the case of a male patient who developed a lung hernia as a sequela to limited access mitral valve surgery. Two months after discharge, the patient presented with a bulge in the region of the lateral thoracotomy related to respiration which could be provoked by a Valsalva maneuver. In the night following admission the patient had acute cardiovascular decompensation with worsening dyspnea, pallor and hypotension. The patient was quickly transferred to the ICU, where a chest X-ray revealed the presence of a large hemothorax with compression of the entire right lung. We transferred the patient to the operation room, evacuated the hemothorax and reconstructed the 15-cm long and 3-cm wide dehiscence using a GoreTex patch adapted in a special technique.

Late onset Takotsubo cardiomyopathy after mitral valve replacement.

We report a case of delayed onset Takotsubo cardiomyopathy (TC) in a 69-year-old woman, associated with minor stressors, two weeks after mitral valve replacement. After suffering several minor complications she had fully recovered and her discharge was planned. On the 14th postoperative day she had to be resuscitated due to cardiogenic shock. TC was diagnosed based on reduced ventricular function with apical ballooning and normal coronaries. Treatment with catecholamines and intra-aortic balloon pump led to full recovery. She continues to do well two years after surgery. TC should be considered as a potential cause of delayed ventricular dysfunction in postcardiac surgery patients.

Dislocation of a transapically implanted aortic valve prosthesis with a functionally bicuspid aortic valve and ascending aortic aneurysm.

In recent years, catheter-based aortic valve interventions have become established procedures for the treatment of high-risk and advanced age patients with aortic valve pathologies. One of the limitations of the widespread applicability of this procedure is the annulus size. Until recently, no prosthesis was available to treat patients with a large annulus. We report on a patient with high-grade aortic stenosis (AS) and a 27-mm annulus, who underwent transapical implantation (TAP) of an Edwards SAPIEN® 29-mm prosthesis (Edwards LifeScience, Irvine, CA, USA). Due to insufficient dilation of his heavily calcified, functionally bicuspid aortic valve leaflets during balloon aortic valvuloplasty (BAV), the TAP prosthesis did not anchor adequately. This was determined during follow-up as he developed progressive aortic insufficiency and orthopnea, and an echocardiography revealed that the valve had been displaced into the LVOT. A conventional aortic valve replacement and ascending aorta replacement were performed, at which time the TAP prosthesis was removed. The patient recovered uneventfully, and was discharged with a well-functioning aortic bioprosthetic valve and in good general condition.

Pacemaker-associated thrombotic occlusion of the inferior vena cava causing liver failure.

Pacemaker implantation using endocardial leads can give rise to thrombotic venous occlusion. We report the case of a 23-year-old male with transposition of the great arteries, who had previously undergone a Senning repair at the age of one year. A sick sinus syndrome required pacemaker implantation with subsequent multiple lead revisions. Following the implantation of the last lead, the patient developed complete occlusion of the inferior vena cava (IVC) with stenosis of the superior vena cava (SVC) with pacemaker leads in both lesions. Liver failure, ascites and esophageal varices developed. Thrombolytic treatment was ineffective; finally the patient was listed for liver transplantation. We explanted the lead embedding the thrombosis, together with some lead remnants. The stenosis of the SVC and the occlusion of the IVC were dilatated and stabilized with four stents. Over a follow-up period of 4 months, NYHA class improved from NYHA III to NYHA I-II, the hepatic function showed complete remission, and a liver transplantation was not necessary.

Mitral valve re-replacement in a patient with osteogenesis imperfecta.

A 34-year-old patient with osteogenesis imperfecta (OI) underwent previous double-valve replacement in the aortic and mitral valve position. Bioprostheses were implanted because of an elevated risk of daily injury. Five years later the patient underwent re-replacement of the stenotic stentless mitral valve prosthesis. A right anterolateral mini-thoracotomy was used for operative access during both procedures, in order to preserve thorax stability. Patients with OI may benefit from minimally invasive valve surgery for primary procedures or reoperation.

Computerized whole slide quantification shows increased microvascular density in pT2 prostate cancer as compared to normal prostate tissue.

BACKGROUND: Contrast enhanced imaging enables powerful, non-invasive diagnostics, important for detection and staging of early prostate cancer. The uptake of contrast agent is increased in prostate cancer as compared to normal prostate tissue. To reveal the underlying physiological mechanisms, quantification of tissue components in pathology specimens may yield important information. Aim of this study was to investigate whether microvascularity is increased in prostate confined cancer (pT2). METHODS: Radical prostatectomy specimens of 26 patients were selected for organ confined peripheral zone tumors which were restricted to one side of the prostate. Microvessels were visualized by immunohistochemistry against CD31. Specimens were scanned using a computer controlled microscope and scanning stage and vessels were recognized automatically. Pseudocolor mappings were produced showing number of vascular profiles (MVD), vascular area (MVA) and perimeter (MVP) in an overview of the entire prostate transection. MVD is a common measure for vascularity, whereas MVA represents the 3D vascular volume and MVP the perfused surface area. Mean, coefficient of variation and 75th percentile of these parameters were calculated automatically in manually indicated areas, consisting of the entire tumor area and the corresponding normal area in the contra lateral side of the prostate. RESULTS: The mappings clearly indicate areas of increased vascularity in prostate transections. In tumor tissue an increase was found compared to normal tissue of 81%, 49%, and 62% for mean MVD, mean MVA and mean MVP, respectively (P < 0.001 for all comparisons). In contrast, the heterogeneity in tumor vasculature was significantly decreased as compared to normal prostate (P < 0.001). CONCLUSIONS: Characteristics of microvasculature deviated significantly in pT2 prostate tumor as compared to normal tissue.

Mutational Signature Analysis Reveals NTHL1 Deficiency to Cause a Multi-tumor Phenotype.

Biallelic germline mutations affecting NTHL1 predispose carriers to adenomatous polyposis and colorectal cancer, but the complete phenotype is unknown. We describe 29 individuals carrying biallelic germline NTHL1 mutations from 17 families, of which 26 developed one (n = 10) or multiple (n = 16) malignancies in 14 different tissues. An unexpected high breast cancer incidence was observed in female carriers (60%). Mutational signature analysis of 14 tumors from 7 organs revealed that NTHL1 deficiency underlies the main mutational process in all but one of the tumors (93%). These results reveal NTHL1 as a multi-tumor predisposition gene with a high lifetime risk for extracolonic cancers and a typical mutational signature observed across tumor types, which can assist in the recognition of this syndrome.

[Efficacy and safety of various energy sources and application techniques for the surgical treatment of atrial fibrillation]. / Experimentelle Evaluierung verschiedener Energiequellen und Applikationsverfahren zur chirurgischen Therapie des Vorhofflimmerns.

We investigated efficacy and safety of different energy sources and application techniques for the treatment of atrial fibrillation in an experimental acute sheep model. In particular, we focused on thermal damage to the adjacent structures and tissues. We also attempted to evaluate the efficacy of different application techniques such as endocardial or epicardial approaches. Overall 64 young Merino sheep were examined. It could be shown that endocardial ablation with different energy sources on cardiopulmonary bypass consistently caused histomorphologically and electrophysiologically transmural lesions. Depending on the energy source, different amounts of endocardial damage were induced. Cryoapplication produces the smallest endocardial laceration without thrombus formation. Dry radiofrequency energy and microwave produced very wide and diffuse endocardial damage with carbonisation and disruption of the endothelium. Epicardial ablation on a beating heart (off-pump) with bipolar radiofrequency was consistently effective. Due to the energy flow between the two jaws of the bipolar clamp, no collateral damage was observed. All other energy sources were unable to produce transmural lesions epicardially (off-pump) because the nearby blood flow rewarmed or recooled the myocardium and caused the so called "heat sink phenomenon". Depending on the energy source, different histomorphological changes in the esophagus could be observed. Changes in intraluminal-measured esophageal temperatures were not observed during ablation.

Surgical therapy of ventricular arrhythmias.

Since the advent of implantable cardioverters/defibrillators (ICD) and percutaneous ablation, surgery for the treatment of ventricular arrhythmia has decreased tremendously. Nevertheless, surgical treatment of ventricular arrhythmias is still required, especially for cases where ICD discharge occurs very frequently or in patients with other indications for surgery. The choice of surgical therapy may range from radiofrequency- or cryoablation of a single focus (identified either intra- operatively or percutaneously) to more extensive surgical procedures such as surgical ventricular reconstruction with endocardial resection or even resection of the right ventricle and the creation of a cavo-pulmonary circulation for malignant arrhythmias and right ventricular failure in patients with arrhythmogenic right ventricular dysplasia. However, the choice of surgical procedure should be made based on the pathomechanism of the arrhythmia. This is important because any incision in the left or right ventricle or percutaneous ablation may also be the cause for ventricular arrhythmia. In this short review we will describe the most common underlying substrates for ventricular arrhythmia, indications for surgery, the techniques used for treatment and the results achieved. We will conclude that for most cases of patients with ventricular arrhythmia undergoing surgery, ischemia and the presence of a scar after myocardial infarction is the underlying cause and revascularization plus surgical ventricular reconstruction with endocardial resection may be the best treatment option.

The changing pattern of reoperative coronary surgery: trends in 1230 consecutive reoperations.

OBJECTIVE: We noted an increasing risk profile of patients undergoing reoperative coronary surgery. We evaluated the risk compared with primary procedures, our results over a 16-year span, and the predictors of hospital outcomes after redo surgery. METHODS: We analyzed 20,614 patients undergoing isolated coronary surgery at our institution from 1982 to 1997. Of these, 1230 (6.0%) were undergoing reoperation. Independent predictors of outcomes were identified by multivariable regression. RESULTS: The prevalence of reoperation peaked in 1994 at 8.2%. Patients undergoing reoperation were more likely to be male, to have left ventricular dysfunction and worse symptoms, and to require an urgent operation than patients undergoing a primary operation (P <.0001). Perioperative myocardial infarctions (3.7% vs 7.4%), low-output syndrome (9.0% vs 24.0%), and death (2.4% vs 6.8%) were more common in patients undergoing reoperation (all P <.0001). Over the years, the risk profile of patients undergoing reoperation increased. Age, left ventricular dysfunction, severity of symptoms, extent of coronary artery disease, left main stenosis, and requirement for urgent or emergency operations increased with time (P <.05). However, mortality, myocardial infarction, and low-output syndrome have remained constant. The independent predictors of mortality after reoperative surgery were increased age, greater Canadian Cardiovascular Society symptom class, earlier year of operation, and greater left ventricular dysfunction. After 1990, analysis of an expanded data set also identified peripheral vascular disease and failure to use retrograde cardioplegia as predictors of mortality. CONCLUSIONS: Improving results of reoperative surgery have been offset by an increasing patient risk profile. Meticulous operative technique and retrograde cardioplegia may permit good results in these high-risk patients.

Is profound hypothermia required for storage of cardiac allografts?

BACKGROUND: Improved methods of cardiac allograft protection are required to expand the pool of potentially available organs and to enhance the recovery of grafts subjected to prolonged ischemia. We have previously demonstrated that limited coronary perfusion provided by donor blood harvested at the time of organ procurement can improve both metabolic and functional recovery after transplantation. In this study we evaluated the hypothesis that limited coronary perfusion may enable prolonged cardiac storage while avoiding the potentially detrimental effects of profound hypothermia. METHODS: Fourteen orthotopic cardiac transplants were performed in female Yorkshire pigs by using donor blood perfusion during 5 hours of either tepid (25 degrees C) or cold (4 degrees C) storage. Assessments of myocardial metabolism and function were performed at baseline and after 45 minutes of normothermic (37 degrees C) reperfusion. RESULTS: Hearts protected with tepid perfusion displayed improved recovery of myocardial function (89% +/- 18% vs 63% +/- 25%, P =.05). Diastolic compliance was adversely affected in both groups after transplantation. Aerobic myocardial metabolism was better preserved in the tepid group. CONCLUSIONS: Profound hypothermia results in depressed myocardial metabolic and functional recovery after transplantation. Limited coronary perfusion with shed donor blood can permit cardiac allograft storage at tepid temperatures, resulting in improved myocardial performance.

Insulin cardioplegia for elective coronary bypass surgery.

BACKGROUND: Improved methods of myocardial preservation are required to reduce the morbidity and mortality of coronary bypass surgery for high-risk subgroups. Metabolic stimulation with insulin, glucose solutions, or both has been proposed as a method to preserve the ischemic myocardium. We performed a prospective, double-blind, randomized trial to evaluate the effects of insulin and glucose as cardioplegic additives when used as part of a tepid continuous blood cardioplegic strategy. METHODS: We randomized 56 male patients undergoing elective isolated coronary bypass surgery to 1 of 4 cardioplegic groups containing either 42 or 84 mmol/L glucose with or without 10 IU/L of insulin. Perioperative assessments of myocardial metabolism and left ventricular function were performed. RESULTS: Insulin-enhanced cardioplegia was associated with beneficial effects on both myocardial metabolic and functional recovery after cardioplegic arrest. Insulin's effect was independent of the ambient glucose concentration. CONCLUSIONS: Cardioplegic formulations containing a 42 mmol/L concentration of glucose and a 10 IU/L concentration of insulin provide significant benefit to patients undergoing isolated coronary bypass surgery. The clinical effect of these formulations will need to be assessed in high-risk subgroups of patients, such as those with unstable angina, recent myocardial infarction, or poor left ventricular function.