[Role of coronary artery bypass grafting in the treatment of coronary artery disease - a well-balanced information of the patients and objective decision making are welcome]

Most recently discussion about the optimal treatment for different subsets of patients suffering from coronary artery disease has re-emerged, mainly because of the uncertainty caused by doctors and patients regarding the phenomenon of unpredictable early and late stent thrombosis. Surgical revascularization using multiple arterial bypass grafts has repeatedly proven its superiority compared to percutaneous intervention techniques, especially in patients suffering from left main stem disease and coronary 3-vessels disease. Several prospective randomized multicenter studies comparing early and mid-term results following PCI and CABG have been really restrictive, with respect to patient enrollment, with less than 5% of all patients treated during the same time period been enrolled. Coronary artery bypass grafting allows the most complete revascularization in one session, because all target coronary vessels larger than 1 mm can be bypassed in their distal segments. Once the patient has been turn-off for surgery, surgeons have to consider the most complete arterial revascularization in order to decrease the long-term necessity for re-revascularization; for instance patency rate of the left internal thoracic artery grafted to the distal part left anterior descending artery may be as high as 90-95% after 10 to 15 years. Early mortality following isolated CABG operation has been as low as 0.6 to 1% in the most recent period (reports from the University Hospital Berne and the University Hospital of Zurich); beside these excellent results, the CABG option seems to be less expensive than PCI with time, since the necessity for additional PCI is rather high following initial PCI, and the price of stent devices is still very high, particularly in Switzerland. Patients, insurance and experts in health care should be better and more honestly informed concerning the risk and costs of PCI and CABG procedures as well as about the much higher rate of subsequent interventions following PCI. Team approach for all patients in whom both options could be offered seems mandatory to avoid unbalanced information of the patients. Looking at the recent developments in transcatheter valve treatments, the revival of cardiological-cardiosurgical conferences seems to a good option to optimize the cooperation between the two medical specialties: cardiology and cardiac surgery.

C-Port Flex-A-assisted automated anastomosis for high-flow extracranial-intracranial bypass surgery in patients with symptomatic carotid artery occlusion: a feasibility study. Clinical article

OBJECT: Preliminary experience with the C-Port Flex-A Anastomosis System (Cardica, Inc.) to enable rapid automated anastomosis has been reported in coronary artery bypass surgery. The goal of the current study was to define the feasibility and safety of this method for high-flow extracranial-intracranial (EC-IC) bypass surgery in a clinical series. METHODS: In a prospective study design, patients with symptomatic carotid artery (CA) occlusion were selected for C-Port-assisted high-flow EC-IC bypass surgery if they met the following criteria: 1) transient or moderate permanent symptoms of focal ischemia; 2) CA occlusion; 3) hemodynamic instability; and 4) had provided informed consent. Bypasses were done using a radial artery graft that was proximally anastomosed to the superficial temporal artery trunk, the cervical external, or common CA. All distal cerebral anastomoses were performed on M2 branches using the C-Port Flex-A system. RESULTS: Within 6 months, 10 patients were enrolled in the study. The distal automated anastomosis could be accomplished in all patients; the median temporary occlusion time was 16.6+/-3.4 minutes. Intraoperative digital subtraction angiography (DSA) confirmed good bypass function in 9 patients, and in 1 the anastomosis was classified as fair. There was 1 major perioperative complication that consisted of the creation of a pseudoaneurysm due to a hardware problem. In all but 1 case the bypass was shown to be patent on DSA after 7 days; furthermore, in 1 patient a late occlusion developed due to vasospasm after a sylvian hemorrhage. One-week follow-up DSA revealed transient asymptomatic extracranial spasm of the donor artery and the radial artery graft in 1 case. Two patients developed a limited zone of infarction on CT scanning during the follow-up course. CONCLUSIONS: In patients with symptomatic CA occlusion, C-Port Flex-A-assisted high-flow EC-IC bypass surgery is a technically feasible procedure. The system needs further modification to achieve a faster and safer anastomosis to enable a conclusive comparison with standard and laser-assisted methods for high-flow bypass surgery.

Cardiopulmonary bypass reduces atrial Na+-K+-ATPase expression in children

Cardiopulmonary bypass (CPB) may induce serious side effects, potentially leading to myocardial failure. The Na(+)-K(+)-ATPase is a key component for myocardial function. Due to its developmental regulation, results from adult studies cannot be adopted to the situation in childhood. Right atrial myocardium from patients with left-to-right shunts at atrial level (VO, n=8) and those without (NO, n=8) was excised during heart surgery before and after CPB. Na(+)-K(+)-ATPase isoforms ATP1A1 (p=0.008) and ATP1A3 (p=0.038) decreased during CPB, which decrease was restricted to the VO group. This study highlights the importance of the underlying heart defect for susceptibility to the effects of CPB, showing a reduced Na(+)-K(+)-ATPase mRNA expression only in patients with left-to-right shunts on the atrial level. This seemed to be an early molecular event, as apart from one, none of the patients showed heart failure before or after surgery.

Myoglobin as a prognostic indicator for outcome in dogs with gastric dilatation-volvulus

OBJECTIVE: To determine whether myoglobin (Mb) is a useful prognostic indicator for outcome and to investigate any relationship between Mb and mortality in dogs with gastric dilatation-volvulus (GDV). DESIGN: Prospective study. SETTING: Veterinary teaching hospital. ANIMALS: Seventy-two dogs with GDV. INTERVENTIONS: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Mb levels were measured at the time of diagnosis (Mbt0), 24 hours (Mbt1), and 48 hours (Mbt2) after signs of GDV were recognized. Fifty-seven dogs survived (group I) and 15 dogs did not survive (group II). Mbt0 differed significantly between groups (P=0.04). Mbt0 in group I ranged from <30 to >700 ng/mL (n=57, median 74 ng/mL), and in group II from 34 to >700 ng/mL (n=15, median 238 ng/mL). Analysis of a receiver operating characteristic curve of Mbt0 suggested that the best single cutpoint would be 168 ng/mL (sensitivity 60.0%, specificity 84.2%). Fifty percent of dogs with Mbt0>168 ng/mL were euthanized, while 88.9% with Mbt0<168 ng/mL survived. Mbt1 and Mbt2 differed significantly between groups I and II. Mbt1 in group I ranged from 32 to >700 ng/mL (n=55, median 123 ng/mL), and Mbt1 in group II ranged from 131 to 643 ng/mL (n=7, median 343 ng/mL) (P=0.006). Mbt2 in group I ranged from 30 to 597 ng/mL (n=54, median 101 ng/mL), and in group II from 141 to >700 ng/mL (n=8, median 203 ng/mL) (P=0.02). CONCLUSIONS: In this study, Mbt0 is a moderately sensitive and specific prognostic indicator. Almost 90% of the dogs below the cutpoint survived to discharge, whereas 50% with Mbt0 above the cutpoint did not survive.

Oesophageal and gastric endoscopic foreign body removal: complications and follow-up of 102 dogs

OBJECTIVES: To assess complication rate, risk factors for complications and outcome in dogs with oesophageal and gastric endoscopic foreign body (FB) removal. METHODS: Medical records of 102 dogs undergoing endoscopic removal of oesophageal and/or gastric FBs from March 2001 to November 2006 were retrospectively reviewed. All owners were contacted by telephone to provide follow-up information. RESULTS: West Highland white terriers, Yorkshire terriers and Bernese mountain dogs were over-represented compared to the hospital population. Endoscopy alone was successful in 92/102 dogs (90.2 per cent), whereas gastrotomy (but no oesophagotomy) was required in 10 dogs (9.8 per cent). Complications in 13/102 dogs (12.7 per cent) were perforation (8), oesophageal stricture (1), oesophageal diverticula (1), perioesophageal abscess (1), pneumothorax and pleural effusion (1) and respiratory arrest (1). Six dogs (all weighing <10 kg) had complications resulting in death or euthanasia. Bone FBs, bodyweight of less than 10 kg, and oesophageal or gastric FB in place for more than three days were significant risk factors for complications. Of the dogs available for follow-up (75/96), 92 per cent had no complications after discharge. CLINICAL SIGNIFICANCE: Endoscopic FB removal is associated with a low overall complication rate with bone FBs and bodyweight of less than 10 kg as significant risk factors.

Early troponin T and prediction of potentially correctable in-hospital complications after coronary artery bypass grafting surgery

BACKGROUND Peak levels of troponin T (TnT) reliably predict morbidity and mortality after cardiac surgery. However, the therapeutic window to manage CABG-related in-hospital complications may close before the peak is reached. We investigated whether early TnT levels correlate as well with complications after coronary artery bypass grafting (CABG) surgery. METHODS A 12 month consecutive series of patients undergoing elective isolated CABG procedures (mini-extra-corporeal circuit, Cardioplegic arrest) was analyzed. Logistic regression modeling was used to investigate whether TnT levels 6 to 8 hours after surgery were independently associated with in-hospital complications (either post-operative myocardial infarction, stroke, new-onset renal insufficiency, intensive care unit (ICU) readmission, prolonged ICU stay (>48 hours), prolonged need for vasopressors (>24 hours), resuscitation or death). RESULTS A total of 290 patients, including 36 patients with complications, was analyzed. Early TnT levels (odds ratio (OR): 6.8, 95% confidence interval (CI): 2.2-21.4, P=.001), logistic EuroSCORE (OR: 1.2, 95%CI: 1.0-1.3, P=.007) and the need for vasopressors during the first 6 postoperative hours (OR: 2.7, 95%CI: 1.0-7.1, P=.05) were independently associated with the risk of complications. With consideration of vasopressor use during the first 6 postoperative hours, the sum of specificity (0.958) and sensitivity (0.417) of TnT for subsequent complications was highest at a TnT cut-off value of 0.8 ng/mL. CONCLUSION Early TnT levels may be useful to guide ICU management of CABG patients. They predict clinically relevant complications within a potential therapeutic window, particularly in patients requiring vasopressors during the first postoperative hours, although with only moderate sensitivity.

Protective autophagy is involved in resistance towards MET inhibitors in human gastric adenocarcinoma cells

MET, also known as hepatocyte growth factor receptor (HGFR), is a receptor tyrosine kinase with an important role, both in normal cellular function as well as in oncogenesis. In many cancer types, abnormal activation of MET is related to poor prognosis and various strategies to inhibit its function, including small molecule inhibitors, are currently in preclinical and clinical evaluation. Autophagy, a self-digesting recycling mechanism with cytoprotective functions, is induced by cellular stress. This process is also induced upon cytotoxic drug treatment of cancer cells and partially allows these cells to escape cell death. Thus, since autophagy protects different tumor cells from chemotherapy-induced cell death, current clinical trials aim at combining autophagy inhibitors with different cancer treatments. We found that in a gastric adenocarcinoma cell line GTL-16, where MET activity is deregulated due to receptor overexpression, two different MET inhibitors PHA665752 and EMD1214063 lead to cell death paralleled by the induction of autophagy. A combined treatment of MET inhibitors together with the autophagy inhibitor 3-MA or genetically impairing autophagy by knocking down the key autophagy gene ATG7 further decreased cell viability of gastric cancer cells. In general, we observed the induction of cytoprotective autophagy in MET expressing cells upon MET inhibition and a combination of MET and autophagy inhibition resulted in significantly decreased cell viability in gastric cancer cells.

Chronic critical leg ischemia: revascularization of the isolated popliteal segment in comparison with femoro-distal bypass

Several patients with chronic critical limb ischemia show angiographically an isolated popliteal segment (IPS) and a single calf vessel (SCV) with no direct communication to the former. In this situation a bypass can be inserted from the common femoral artery to the IPS or to the SCV. The results of 73 bypass procedures--40 to an isolated popliteal segment and 33 to a single calf vessel for limb salvage--were prospectively evaluated. Eighty percent of the grafts were performed with an autogenous saphenous vein (ASV), the rest with a thin wall polytetrafluoroethylene (PTFE) prosthesis. The mean age of our patients was 75 years and many suffered from cardiovascular disease. The operative mortality rate was 3% and the mean postoperative survival 32 months. Three year patency and limb salvage rates for ASV grafts was 83% and 87% (IPS) respectively 77% and 76% (MCV); for PTFE grafts 58% and 88% (IPS) respectively 17% and 50% (MCV). There was no significant difference found in patency and limb salvage rates of the two procedures if the graft was an autogenous saphenous vein (p > 0.05). The PTFE prosthesis was only suitable for grafts inserted to the isolated popliteal segment.

Comparison of Fluid Types for Resuscitation in Acute Hemorrhagic Shock and Evaluation of Gastric Luminal and Transcutaneous P co 2 in Leghorn Chickens

The objective of this study was to compare the effects of 3 different fluid types for resuscitation after experimentally induced hemorrhagic shock in anesthetized chickens and to evaluate partial pressures of carbon dioxide measured in arterial blood (Paco2), with a transcutaneous monitor (TcPco2), with a gastric intraluminal monitor (GiPco2), and by end tidal measurements (Etco2) under stable conditions and after induced hemorrhagic shock. Hemorrhagic shock was induced in 40 white leghorn chickens by removing 50% of blood volume by phlebotomy under general anesthesia. Birds were divided into 4 groups: untreated (control group) and treated with intravenous hetastarch (haes group), with a hemoglobin-based oxygen carrier (hemospan group), or by autotransfusion (blood group). Respiratory rates, heart rates, and systolic arterial blood pressure (SAP) were compared at 8 time points (baseline [T0]; at the loss of 10% [T10%], 20% [T20%], 30% [T30%], 40% [T40%], and 50% [T50%] of blood volume; at the end of resuscitation [RES]; and at the end of anesthesia [END]). Packed cell volume (PCV) and blood hemoglobin content were compared at 6 time points (T0, T50%, RES, and 1, 3, and 7 days after induced hemorrhagic shock). Measurements of Paco2, TcPco2, GiPco2, and Etco2 were evaluated at 2 time points (T0 and T50%), and venous lactic acid concentrations were evaluated at 3 time points (T0, T50%, and END). No significant differences were found in mortality, respiratory rate, heart rate, PCV, or hemoglobin values among the 4 groups. Birds given fluid resuscitation had significantly higher SAPs after fluid administration than did birds in the control group. In all groups, PCV and hemoglobin concentrations began to rise by day 3 after phlebotomy, and baseline values were reached 7 days after blood removal. At T0, TcPco2 did not differ significantly from Paco2, but GiPco2 and Etco2 differed significantly from Paco2. After hemorrhagic shock, GiPco2 and TcPco2 differed significantly from Paco2. The TcPco2 or GiPco2 values did not differ significantly at any time point in birds that survived or died in any of the groups and across all groups. These results showed no difference in mortality in leghorn chickens treated with fluid resuscitation after hemorrhagic shock and that the PCV and hemoglobin concentrations increased by 3 days after acute hemorrhage with or without treatment. The different CO2 measurements document changes in CO2-values consistent with poor perfusion and may prove useful for serial evaluation of responses to shock and shock treatment.

Interim endoscopy results during neoadjuvant therapy for gastric cancer correlate with histopathological response and prognosis

BACKGROUND Neoadjuvant chemotherapy for locally advanced gastric cancer leads to major histopathological response in less than 30 % of patients. Data on interim endoscopic response assessment do not exist. This exploratory prospective study evaluates early endoscopy after 50 % of the chemotherapy as predictor for later response and prognosis. METHODS Forty-seven consecutive patients were included (45 resected; 33 R0 resections). All patients received baseline endoscopy and CT scans, after 50 % of their chemotherapy (EGD-1, CT-1) and after completion of chemotherapy (EGD-2, CT-2). Interim endoscopic response (EGD-1) was assessed after having received 50 % (6 weeks) of the planned 12 weeks of neoadjuvant chemotherapy. Post-chemotherapy response was clinically assessed by a combination of CT scan (CT-2) and endoscopy (EGD-2). Histopathological response was determined by a standardized scoring system (Becker criteria). Endoscopic response was defined as a reduction of >75 % of the tumor mass. RESULTS Twelve patients were responders at EGD-1 and 13 at EGD-2. Nine patients (19.1 %) were clinical responders and 7 patients (15.6 %) were histopathological responders after chemotherapy. Specificity, accuracy, and negative predictive value of the interim EGD-1 for subsequent histopathological response were 31/38 (82 %), 36/47 (76 %), and 31/33 (93 %); and for recurrence or death, 28/30 (93.3 %), 38/47 (80.9 %), and 28/35 (80.0 %). Response at EGD-1 was significantly associated with histopathological response (p = 0.010), survival (p < 0.001), and recurrence-free survival (p = 0.009). CONCLUSIONS Interim endoscopy after 6 weeks predicts response and prognosis. Therefore, tailoring treatment according to interim endoscopic assessment could be feasible, but the findings of this study should be validated in a larger patient cohort.

Association between HSP90 and Her2 in gastric and gastroesophageal carcinomas

BACKGROUND Her2 expression and amplification occurs in a significant subset of gastro-esophageal carcinomas. Her2 is a client protein of molecular chaperones, e.g. heat shock protein (HSP) 90, rendering targeted therapies against Her2/HSP90 an interesting approach. This study aimed to investigate the role and relationship of Her2 and HSP90 in gastric and gastro-esophageal adenocarcinomas. MATERIAL AND METHODS Immunohistochemical determination of HSP90 and Her2 expression was performed on 347 primary resected tumors. Her2 amplification was additionally determined by fluorescence in situ hybridization for all cases. Expression and amplification results were correlated with pathologic parameters (UICC pTNM category, tumor grading) and survival. RESULTS Elevated Her2 copy numbers were observed in 87 tumors, 21 of them showing amplification. 174 tumors showed Her2 immunoreactivity/expression. HSP 90 immunoreactivity was found in 125 tumors. There was no difference between gastric carcinomas and carcinomas of the gastroesophageal junction regarding Her2 or HSP90. Both high HSP90 and Her2 expression/amplification were associated with earlier tumor stages (p<0.01), absence of lymph node metastases (p<0.02) and Laurens intestinal type (p<0.001). HSP90 correlated with Her2 expression and amplification (p<0.001 each). Expressions of HSP90 and Her2, but not Her2 amplification were associated with better prognosis (p=0.02; p=0.004; p=0.802). Moreover, Her2 expression was an independent prognostic factor for overall survival in the subgroup of gastric carcinoma patients (p=0.014) besides pT category, pN category and distant metastases. CONCLUSION Her2 expression and gene amplification occurred in a significant subset of cases. Our results suggest a favorable prognostic impact of Her2 expression. This warrants further investigations regarding the significance of Her2 non-amplified tumors showing Her2 immunoreactivity and the definition of Her2 status in gastric cancers. Moreover, the correlation of Her2 expression with the expression of Her2 chaperoning HSP90 may indicate a synergistic regulation. Targeting HSP90 with or without Her2 may offer additional therapeutic options for gastric carcinoma treatment.

Prognostic implications of the seventh edition of the international union against cancer classification for patients with gastric cancer: the Western experience of patients treated in a single-center European institution

PURPOSE Validity of the seventh edition of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems for gastric cancer has been evaluated in several studies, mostly in Asian patient populations. Only few data are available on the prognostic implications of the new classification system on a Western population. Therefore, we investigated its prognostic ability based on a German patient cohort. PATIENTS AND METHODS Data from a single-center cohort of 1,767 consecutive patients surgically treated for gastric cancer were classified according to the seventh edition and were compared using the previous TNM/UICC classification. Kaplan-Meier analyses were performed for all TNM stages and UICC stages in a comparative manner. Additional survival receiver operating characteristic analyses and bootstrap-based goodness-of-fit comparisons via Bayesian information criterion (BIC) were performed to assess and compare prognostic performance of the competing classification systems. RESULTS We identified the UICC pT/pN stages according to the seventh edition of the AJCC/UICC guidelines as well as resection status, age, Lauren histotype, lymph-node ratio, and tumor grade as independent prognostic factors in gastric cancer, which is consistent with data from previous Asian studies. Overall survival rates according to the new edition were significantly different for each individual's pT, pN, and UICC stage. However, BIC analysis revealed that, owing to higher complexity, the new staging system might not significantly alter predictability for overall survival compared with the old system within the analyzed cohort from a statistical point of view. CONCLUSION The seventh edition of the AJCC/UICC classification was found to be valid with distinctive prognosis for each stage. However, the AJCC/UICC classification has become more complex without improving predictability for overall survival in a Western population. Therefore, simplification with better predictability of overall survival of patients with gastric cancer should be considered when revising the seventh edition.

Lesions of the gastric mucosa in adult horses of different disciplines: a review

The prevalence of gastric mucosal lesions in the thoroughbred race horse has been the subject of numerous studies. The frequency of gastric ulcer diseases in the adult horse of other sport disciplines are less well investigated. Recent data show that gastric mucosal lesions in non thoroughbred racehorses occur considerably more frequently than previously thought. Prevalences of up to 93 % in endurance horses, of up to 87 % in standardbreds, of 40 % in western horses, of 63 % in show-jumping horses, of 71 % in broodmares and of 53 % in leisure horses are reported. Since the introduction of gastroscopy in equine medicine in the 1990s, numerous scoring-systems to describe the number, the severity and the localisation of the lesions have been used. Unfortunately, no standardized scoring system is generally accepted to date. A direct comparison of results from different studies is therefore difficult. Comparison and interpretation of data is further hampered by the heterogenicity of the study populations which consist of horses of different age-groups, breeds and exercise intensity.