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In 2020, nearly 30,000 published references appeared in the PubMed for the search term "cardiac surgery." While SARS-CoV-2 affected the number of surgical procedures, it did not affect outcomes reporting. Using the PRISMA approach, we selected relevant publications and prepared a results-oriented summary. We reviewed primarily the fields of coronary and conventional valve surgery and their overlap with interventional alternatives. The coronary field started with a discussion on trial data value and their interpretation. Registry comparisons of coronary artery bypass surgery (CABG) and percutaneous coronary intervention confirmed outcomes for severe coronary artery disease and advanced comorbidities with CABG. Multiple arterial grafting was best. In aortic valve surgery, meta-analyses of randomized trials report that transcatheter aortic valve implantation may provide a short-term advantage but long-term survival may be better with classic aortic valve replacement (AVR). Minimally invasive AVR and decellularized homografts emerged as hopeful techniques. In mitral and tricuspid valve surgery, excellent perioperative and long-term outcomes were presented for structural mitral regurgitation. For both, coronary and valve surgery, outcomes are strongly dependent on surgeon expertise. Kidney disease increases perioperative risk, but does not limit the surgical treatment effect. Finally, a cursory look is thrown on aortic, transplant, and assist-device surgery with a glimpse into the current stand of xenotransplantation. As in recent years, this article summarizes publications perceived as important by us. It does not expect to be complete and cannot be free of individual interpretation. We aimed to provide up-to-date information for decision-making and patient information., Competing Interests: None., (Thieme. All rights reserved.)

Objectives: The aim of this study was to compare outcomes of transcatheter and surgical aortic valve implantation in chronic dialysis patients with aortic valve stenosis (AS)., Background: Chronic dialysis patients undergoing heart valve surgery are at higher risk for morbidity and mortality. Whether interventional techniques can reduce this risk is unclear because dialysis patients have thus far been excluded from randomized trials., Methods: Chronic dialysis patients with AS enrolled in the German Aortic Valve Registry (GARY) between 2012 and 2015 were analyzed to compare transcatheter aortic valve implantation (TAVI n = 661) with surgical aortic valve replacement (SAVR n = 457). Propensity scores for inverse probability of treatment weighting (IPTW) were used to adjust the comparison of the two treatment groups for potential confounders., Results: TAVI patients were older (78 ± 7.3 vs. 69 ± 10.2 years, p < 0.01, unadjusted) and had more comorbidities. Mortality at 1 year was the same (TAVI: 33.4% vs. SAVR 35.0%, p = 0.72, IPTW-adjusted) while it was lower with TAVI at 30 days (8.6% vs. 15.0%, p = 0.02, IPTW-adjusted). TAVI patients required more pacemaker implantation and showed more aortic regurgitation. SAVR patients required more blood transfusions and had longer hospital stay. Diabetes mellitus, atrial fibrillation, previous PCI, urgent procedure and EuroSCORE were associated with elevated 30-day mortality. Atrial fibrillation and older age were independent risk factor of 1-year mortality in both groups., Conclusions: Chronic dialysis patients with AS undergoing TAVI or SAVR had the same 1-year mortality, although survival at 30 days was better with TAVI. These results suggest that TAVI may improve peri-procedural outcomes.

Background: Prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) may affect survival but data are conflicting. It is assessed by relating effective orifice area (EOA) to body surface area (EOAi). EOA is patient-specific as the result of flow-velocity times area at the individual patient's outflow tract levels (LVOT A ) divided by trans-prosthetic flow velocity. However, some studies use projected EOAs (i.e., valve size associated EOAs from other patient populations) to assess how PPM affects outcome., Methods: We analyzed 76 studies addressing hemodynamic outcome and/or mortality after bioprosthetic AVR., Results: In 48 studies, projected or measured EOA for calculation of EOAi and PPM assessment was used (of which 25 demonstrated an effect on survival). We identified 28 additional studies providing measured EOA values and the corresponding Bernoulli's pressure gradients after AVR. Despite EOA being a patient-specific parameter, 77% of studies assessing a PPM impact on survival used projected EOAs. The 28 studies are providing measured EOA values and the corresponding Bernoulli's pressure gradients in patients after AVR showed a highly significant, linear relationship between EOA and Bernoulli's gradient. Considering this relationship, it is surprising that relating EOA to body surface area (BSA) (EOAi) is standard but relating pressure gradients to BSA is not., Conclusion: We conclude that the majority of studies assessing PPM have used false assumptions because EOA is a patient-specific parameter and cannot be transferred to other patients. In addition, the use of EOAi to assess PPM may not be appropriate and could explain the inconsistent relation between PPM and survival in previous studies., Competing Interests: Author T.D. received occasional honoraria from St. Jude Medical, Inc. for lectures on aortic valve topics. All other authors have nothing to disclose., (Thieme. All rights reserved.)

Background: We report our starting experience with parasternal minimally-invasive aortic valve replacement., Methods: From 7/14 to 8/18, 192 received classic aortic valve surgery using a 5 cm parasternal incision and percutaneous groin cannulation. Patients were selected based on anatomic feasibility judged by preoperative computed tomography-scan. Except for porcelain aorta, left-sided aortic location, or endocarditic abscess, there were no exclusions., Results: Patients were divided into two groups (first and second half of experience). Demographics were equal. Patients' mean ejection fraction was 59%, with preoperative stroke (12%), severe chronic obstructive pulmonary disorder (11%), and endocarditis (2%). All cases were elective or urgent. The Euroscore II was 3.37 ± 3.31 in the first and 3.68 ± 3.97 in the second group (n.s.). Biological prostheses were implanted in 90%. Operating times in the first group were just under 3 hours, with bypass times of 129 ± 32 minutes and clamp times of 77 ± 20 minutes. In the second group, these times changed only minimally. There were three conversions to sternotomy in the first, but only one in the second group. Similarly, three patients died in the first and one in the second group. There were fewer complications in the second group regarding revision for bleeding (7 vs 1%), stroke (4 vs 0%) dialysis (3 vs 1%), and pericardial effusions (3 vs 1%). The O/E ratio dropped from 0.93 to 0.28., Conclusions: Parasternal minimally-invasive aortic valve replacement is a feasible technique associated with a slow learning curve but the potential to achieve improved outcomes. Considering the transcatheter alternatives, the relative risk reduction may be worth investigating in future trials., (© 2020 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals, Inc.)

Background: Fractional flow reserve (FFR) is a reliable tool for the functional assessment of coronary stenoses. FFR computed tomography (CT) derived (FFR CT ) has shown to be accurate, but its clinical usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the impact of FFR CT on heart team's treatment decision-making and selection of vessels for revascularization in patients with 3-vessel coronary artery disease., Methods: The trial was an international, multicenter study randomizing 2 heart teams to make a treatment decision between percutaneous coronary interventions and coronary artery bypass grafting using either coronary computed tomography angiography or conventional angiography. The heart teams received the FFR CT and had to make a treatment decision and planning integrating the functional component of the stenoses. Each heart team calculated the anatomic SYNTAX score, the noninvasive functional SYNTAX score and subsequently integrated the clinical information to compute the SYNTAX score III providing a treatment recommendation, that is, coronary artery bypass grafting, percutaneous coronary intervention, or equipoise coronary artery bypass grafting-percutaneous coronary intervention. The primary objective was to determine the proportion of patients in whom FFR CT changed the treatment decision and planning., Results: Overall, 223 patients were included. Coronary computed tomography angiography assessment was feasible in 99% of the patients and FFR CT analysis in 88%. FFR CT was available for 1030 lesions (mean FFR CT value 0.64±13). A treatment recommendation of coronary artery bypass grafting was made in 24% of the patients with coronary computed tomography angiography with FFR CT . The addition of FFR CT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as reference, FFR CT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile., Conclusions: In patients with 3-vessel coronary artery disease, a noninvasive physiology assessment using FFR CT changed heart team's treatment decision-making and procedural planning in one-fifth of the patients., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02813473.

Background:  Coronary artery bypass grafting (CABG) using bilateral internal thoracic artery (BITA) is associated with the best long-term survival. However, using BITA increases the risk of sternal wound infections with conventional sternotomy. We describe here our initial results of minimally invasive CABG (MICS-CABG) using BITA., Methods:  Patients were operated through an incision similar to that of standard minimally invasive direct CABG. All operations were performed off-pump. We evaluated patient's quality of life (QoL) using the Medical Outcomes trust, 36-Item Short Form Health Survey (SF-36)., Results:  Between February 2016 and August 2017, we performed 21 cases of MICS-CABG using BITA. There was no intraoperative complication and no conversion to sternotomy or to on-pump. Two patients required reexploration through the same minithoracotomy for postoperative bleeding. Two cases of early postoperative graft failure were identified. There was no stroke or in-hospital mortality. The median duration of follow-up was 13 months, with a maximum of 19 months. Relief of angina was achieved in all patients. There was one readmission for superficial wound infection, which was conservatively treated. An 84-year-old man died 4 months after the operation. The remaining 20 patients attested good QoL with the SF-36 questionnaire., Conclusions:  Myocardial revascularization using BITA can be safely achieved off-pump through a left-sided minithoracotomy with good postoperative and short-term outcomes., Competing Interests: The authors report no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many-sometimes contradictory-observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: The 30-day and 1-year follow-up analysis of the GOPCABE trial (German Off-Pump Coronary Artery Bypass Grafting in Elderly Patients) revealed no significant difference in the composite end point consisting of death, stroke, myocardial infarction, new renal replacement therapy, or repeat revascularization. The 5-year follow-up data of this trial are reported here., Methods: From June 2008 to September 2011, a total of 2539 patients aged ≥75 years were randomly assigned to undergo off-pump or on-pump coronary artery bypass grafting (CABG) at 12 centers in Germany. The primary outcome was all-cause mortality at 5 years. The secondary 5-year outcomes were a composite of death, myocardial infarction, and repeat revascularization. Furthermore, the impact of complete versus incomplete revascularization was assessed., Results: After a median follow-up of 5 years, 361 patients (31%) assigned to off-pump CABG and 352 patients (30%) assigned to on-pump CABG had died (hazard ratio off-pump/on-pump CABG, 1.03; 95% CI, 0.89-1.19; P=0.71). The composite outcome of death, myocardial infarction, and repeat revascularization occurred in 397 (34%) after off-pump and in 389 (33%) after on-pump CABG (hazard ratio, 1.03; 95% CI, 0.89-1.18; P=0.704). Incomplete revascularization occurred in 403 (34%) patients randomly assigned to off-pump and 354 (29%) patients randomly assigned to on-pump CABG ( P<0.001). Five-year survival rates were 72% (95% CI, 67-76) with incomplete versus 76% (95% CI, 74-80) with complete revascularization (log-rank test: P=0.02) after off-pump CABG and 72% (95% CI, 67-76) versus 77% (95% CI, 74-80) after on-pump CABG (log-rank test: P=0.03), respectively. Cox regression analysis revealed a hazard ratio incomplete/complete revascularization of 1.19 (95% CI, 1.01-1.39; P=0.04)., Conclusions: In elderly patients ≥75 years of age, the 5-year survival rates and the combined outcome of death, myocardial infarction, and repeat revascularization, as well, were similar after on-pump and off-pump CABG. Incomplete revascularization was associated with a lower 5-year survival rate, irrespective of the type of surgery., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00719667.

Background: Isolated tricuspid valve (TV) surgery is considered a high risk-procedure. The optimal surgical approach is controversial. We analyzed our experience with isolated TV redo surgery performed either minimally invasively (redo-MITS) or through sternotomy., Methods: We retrospectively analyzed all patients with previous cardiac surgery who underwent redo-MITS ( n  = 26) and compared them to redo-Sternotomy ( n  = 17). A group of primary-MITS ( n  = 61) served as control., Results: The redo-MITS approach consisted of a right anterolateral mini-thoracotomy, transpericardial right atrial access, and beating heart TV surgery without caval occlusion. Redo-MITS patients were oldest and had the most comorbidities (EuroScore II: 9.83 ± 6.05% versus redo-Sternotomy: 8.42 ± 7.33% versus primary-MITS: 4.15 ± 4.84%). There were no intraoperative complications or conversions to sternotomy in both MITS groups. Redo-Sternotomy had the highest 30-day mortality (24%), the poorest long-term survival, and the highest perioperative complication rate. Redo-MITS did not differ in perioperative outcome from primary-MITS. Multivariable logistic regression analysis identified redo-Sternotomy (odds ratio [OR] = 9.76; 95% confidence interval [CI] 1.88-63.26), liver cirrhosis (OR = 9.88; 95% CI 2.20-54.20), and body mass index (BMI) (OR = 1.16; 95% CI 1.02-1.35) as independent predictors of 30-day mortality. The Cox model revealed redo-Sternotomy (hazard ratio [HR] = 2.67; 95% CI 1.18-6.03), liver cirrhosis (HR = 3.31; 95% CI 1.45-7.58), and pulmonary hypertension (HR = 2.26; 95% CI 1.04-4.92) as risk factors for poor long-term survival. TV surgery significantly reduces NYHA class., Conclusion: Minimally invasive, isolated TV surgery as reoperation without caval occlusion and on the beating heart can be safe and may improve clinical outcome., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Coronary artery bypass grafting (CABG) without cardiopulmonary bypass (off-pump CABG) may reduce severe adverse events including stroke., Methods: In the German Off-Pump Coronary Artery Bypass Grafting in Elderly patients trial, the rate of major adverse cardiovascular events was compared in 2,394 elderly (≥ 75 years) patients undergoing CABG with (on-pump) or without (off-pump) cardiopulmonary bypass. This exploratory post-hoc analysis investigated the impact of surgical aortic manipulation on the rate of stroke., Results: There was no significant difference in the rate of stroke within 30 days after surgery between both groups (off-pump: 2.2%; on-pump: 2.7%; odds ratio [OR]: 0.83 [0.5-1.38]; p  = 0.47). Within the off-pump group, different degrees of aortic manipulation did not lead to significant different stroke rates (tangential clamping: 2.3%; OR 0.86 [0.46-1.60]; clampless device: 1.8%; OR 0.67 [0.26-1.75]; no aortic manipulation: 2.4%; OR 0.88 [0.37-2.14]). An aggregate analysis including more than 10,000 patients out of the four recent major trials also yielded comparable stroke rates for on- and off-pump CABG (off-pump: 1.4%; on-pump: 1.7%; OR 0.87 [0.64-1.20])., Conclusion: Within recent prospective randomized multicenter trials off-pump CABG did not result in lower stroke rates. The possible intrinsic benefit of off-pump CABG may be offset by the complexity of the operative therapy as well as the multiple pathomechanisms involved in perioperative stroke., Competing Interests: All authors declare that there was no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work, (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Infective endocarditis (IE) is often associated with multiorgan dysfunction and mortality. The impact of perioperative liver dysfunction (LD) on outcome remains unclear and little is known about factors leading to postoperative LD., Methods: We performed a retrospective, single-center analysis on 285 patients with left-sided IE without pre-existing chronic liver disease referred to our center between 2007 and 2013 for valve surgery. Sequential organ failure assessment (SOFA) score was used to evaluate organ dysfunction. Chi-square, Cox regression, and multivariate analyses were used for evaluation., Results: Preoperative LD (Bilirubin >20 μmol/L) was present in 68 of 285 patients. New, postoperative LD occurred in 54 patients. Hypoxic hepatitis presented the most common origin of LD, accompanied with high short-term mortality. In-hospital mortality was higher in patients with preoperative and postoperative LD compared to patients without LD (51.5, 24.1, and 10.4%, respectively, p < 0.001). 5-year survival was worse in patients with pre- or postoperative LD compared to patients without LD (20.1, 37.1, and 57.0% respectively). A landmark analysis revealed similar 5-year survival between groups after patient discharge. Quality of life was similar between groups when patients survived the perioperative period. Logistic regression analysis identified duration of cardiopulmonary bypass and S. aureus infection as independent predictors of postoperative LD., Conclusions: Perioperative liver dysfunction in patients with infective endocarditis is an independent predictor of short- and long-term mortalities. After surviving the hospital stay, 5-year prognosis is not different and quality of life is not affected by LD. S. aureus and duration of cardiopulmonary bypass represent risk factors for postoperative LD.

Background: Over the past two decades, minimally invasive techniques for classic heart valve surgery and isolated bypass surgery have been developed that enable access to the heart via partial sternotomy for most aortic valve procedures and via sternotomy-free mini-thoracotomy for other procedures., Methods: We review the current evidence on minimally invasive cardiac surgery on the basis of pertinent randomized studies and database studies retrieved by a selective search in the MEDLINE and PubMed Central databases, as well as by the Google Scholar search engine., Results: A PubMed search employing the search term "minimally invasive cardiac surgery" yielded nearly 10 000 hits, among which there were 7 prospective, randomized, controlled trials (RCTs) on aortic valve replacement, with a total of 477 patients, and 3 RCTs on mitral valve surgery, with a total of 340 patients. Only limited reports of specified centers are currently available for multiple valvular procedures and multiple coronary artery bypass procedures. The RCTs reveal that the minimally invasive techniques are associated with fewer wound infections and faster mobilization, without any difference in survival. Minimally invasive procedures are technically demanding and have certain anatomical prerequisites, such as appropriate coronary morphology for multiple bypass operations and the position of the aorta in the chest for sternotomy-free aortic valve procedures. The articles reviewed here were presumably affected by selection bias, in that patients in the published studies were preselected, and there may have been negative studies that were not published at all., Conclusion: Specialized surgeons and centers can now carry out many cardiac valvular and bypass operations via minithoracotomy rather than sternotomy. According to current evidence, these minimally invasive techniques yield results that are at least as good as classic open-heart surgery.

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., (© Georg Thieme Verlag KG Stuttgart · New York.)

We would like to present our experience of surgical excision of intracardiac tumors using a video-assisted minimally-invasive cardiac surgery (MIC) technique. An 83-year-old female patient received video-assisted cardiac surgery for excision of a left atrial tumor. The surgery was performed through a right anterior submammary minithoracotomy and guided by video-assisted endoscopic techniques by projected images on a video monitor while under femoro-femoral bypass. The myocardium was protected by single-dose antegrade crystalloid cardioplegia. The tumor was excised completely recording a 61-minute bypass time and a 103-minute total operative time. Histopathological examination revealed left atrial myxoma. Transthoracic echocardiography examination showed good ventricular function and the absence of residual tumors. The patient was satisfied by the cosmetic healing of the wound and was discharged eight days after the surgery. Video-assisted MIC surgery is technically feasible and could be applied as a routine access in all left atrial tumors without the fear of inadequate intraoperative exposure and its drawbacks.

Aims: Left ventricular hypertrophy is a risk factor for heart failure. However, it also is a compensatory response to pressure overload, accommodating for increased workload. We tested whether the changes in energy substrate metabolism may be predictive for the development of contractile dysfunction., Methods and Results: Chronic pressure overload was induced in Sprague-Dawley rats by aortic arch constriction for 2, 6, 10, or 20 weeks. Contractile function in vivo was assessed by echocardiography and by invasive pressure measurement. Glucose and fatty acid oxidation as well as contractile function ex vivo were assessed in the isolated working heart, and respiratory capacity was measured in isolated cardiac mitochondria. Pressure overload caused progressive hypertrophy with normal ejection fraction (EF) at 2, 6, and 10 weeks, and hypertrophy with dilation and impaired EF at 20 weeks. The lung-to-body weight ratio, as marker for pulmonary congestion, was normal at 2 weeks (indicative of compensated hypertrophy) but significantly increased already after 6 and up to 20 weeks, suggesting the presence of heart failure with normal EF at 6 and 10 weeks and impaired EF at 20 weeks. Invasive pressure measurements showed evidence for contractile dysfunction already after 6 weeks and ex vivo cardiac power was reduced even at 2 weeks. Importantly, there was impairment in fatty acid oxidation beginning at 2 weeks, which was associated with a progressive decrease in glucose oxidation. In contrast, respiratory capacity of isolated mitochondria was normal until 10 weeks and decreased only in hearts with impaired EF., Conclusion: Pressure overload-induced impairment in fatty acid oxidation precedes the onset of congestive heart failure but mitochondrial respiratory capacity is maintained until the EF decreases in vivo. These temporal relations suggest a tight link between impaired substrate oxidation capacity in the development of heart failure and contractile dysfunction and may imply therapeutic and prognostic value.

Polarized cell movement represents an essential prerequisite for the progression and metastasis of malignant diseases. Protein kinase C (PKC) which physically associates with integrins has been implicated in the promotion of a migratory cell phenotype. In order to identify a direct link between PKC and integrins in renal cell carcinoma (RCC) the influence of PKC isoforms on integrin expression and possible consequences on proliferation and cell migration was analyzed in RCC cells. The constitutive expression of the PKC isoforms alpha, betaI, betaII, gamma, delta, epsilon, eta, theta, xi, lambda and micro was determined in the RCC cell line CCF-RC1. In addition, the influence of PKC inhibitors RO31-8220, GF109203X and GO6976 on the beta1, beta2 and beta3 integrin expression and cell proliferation of RCC cells was investigated by flow cytometry and by BrdU incorporation, respectively. Furthermore, the motility of CCF-RC1 cells was assessed through chamber chemotaxis analysis. All PKC isoforms tested were expressed in CCF-RC1 cells with the exception of PKClambda and theta. The PKC inhibitor RO31-8220 reduced beta1 integrin expression by 92% and inhibited proliferation by 42% of untreated cells, whereas cell migration remained uninfluenced by RO31-8220. GF109203X and GO6976 reduced beta1 integrin expression to approximately 50% of untreated cells. In contrast, beta2 and beta3 integrins were only weakly affected by RO31-8220, GF109203X and GO6976 treatment. The most significant influence on beta1 integrin expression was obtained by the PKC inhibitor RO31-8220. This leads to the assumption that PKCepsilon is involved in the regulation of beta1 integrin expression. Downregulation of beta1 integrins by RO31-8220 was associated with reduced proliferation, but did not influence migration. These findings provide a conceptual basis for treatment of renal cell carcinoma by interfering with tumor cell proliferation.

Background: The expression of all eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue was quantified. A possible association of PKC-isoforms with histopathological parameters was examined., Materials and Methods: Proteins were isolated from tumor and normal tissue of 43 patients with ccRCC. Expression of PKC-isoforms were quantified by Western blot analysis., Results: In both, ccRCCs and the corresponding normal renal tissue, all PKC-isoforms apart from PKC gamma and theta were detectable. Striking associations between PKC-isoforms and histopathological parameters were observed: (i) a 3-fold increase in PKC eta of grade 3 and 4 versus grade 1 and 2 tumors (p = 0.025), (ii) a decrease of PKC alpha in tumor versus normal tissue of 18% (p = 0.020) and (iii) a 20% increase of PKC zeta in grade 3 and 4 versus grade 1 and 2 tumors (p = 0.092)., Conclusion: The major result is a clear correlation of PKC eta expression with tumor progression. This observation-is in agreement with the known oncogenic properties of PKC eta. Similarly, oncogenic PKC zeta also increased with tumor progression. PKC alpha, with known tumor-suppressor properties, was decreased in ccRCC versus normal tissue. These findings may become important for both classification and treatment of ccRCC.

The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) encodes a dual specific protein and phospholipid phosphatase that affects cell proliferation, apoptosis and migration. In our study, we examined protein expression of PTEN in renal carcinogenesis. PTEN protein levels were examined in 42 clear cell renal cell carcinomas (ccRCC) and oncocytomas as well as in the corresponding normal renal tissue of the same patients using Western blot analysis. Cellular localization was analyzed by immunohistochemistry. PTEN was highly expressed in all investigated normal renal tissue specimens. Immunohistochemical analysis showed an almost exclusive staining of proximal tubulus epithelial cells known to be precursor cells of ccRCC. Within the proximal tubulus cells, PTEN exhibited a membrane predominant immunostaining pattern. In ccRCCs PTEN expression was markedly reduced to an average of less than 10% compared with normal tissue as evidenced by Western blot analysis (p < 0.001). The degree of reduction was similar in highly differentiated (G1) carcinomas and in less differentiated (G2-G4) carcinomas. These observations were reproduced by immunohistochemical studies, which revealed a loss of the characteristic membrane predominant immunostaining pattern in ccRCC. In contrast to the PTEN positive proximal tubulus epithelial cells, the distal tubulus epithelial cells, which are precursor cells of the benign oncocytomas, exhibited only a very weak PTEN expression. Compared with the distal tubulus epithelial cells, no downregulation of PTEN was seen in oncocytomas. We conclude that PTEN expression and PTEN membrane localization are lost during early renal cell carcinogenesis and may therefore be a valuable RCC tumor marker., (Copyright 2002 Wiley-Liss, Inc.)

Prostaglandin E2 and F2 alpha were measured in ejaculates from 10 fertile and 55 infertile men. Prostaglandin F2 alpha was negatively correlated with motility (r = 0.77; p less than 0.01) in normal men. In patients with disturbed fertility, prostaglandin F2 alpha was always higher than in the controls, while prostaglandin E2 was elevated only in patients with persisting varicocele and in those with very low sperm counts and severely impaired motility. There was neither de novo synthesis of prostaglandins in spermatozoa nor were binding sites for prostaglandin E2 and F2 alpha detectable. Inactivation of seminal prostaglandins by incubation with prostaglandin 15-hydroxydehydrogenase resulted in a dramatic fall in motility. The results suggest that prostaglandin F2 alpha act on motility, but the action is not mediated by receptors.

A double-blind cross-over study was carried out in five healthy male volunteers to investigate the renal tolerance of 40 mg penbutolol, a receptor-specific beta-blocking agent, during exercise and to compare its effects with a placebo. The effects of exercise were compared with a resting state after a medication on the placebo. Urine was collected in fractions for seven hours on each trial day. The urine volume and the excretion of alanine aminopeptidase (AAP), N-acetyl-beta-D-glucosaminidase (NAG) and gamma glutamyltransferase (GGT) per fraction were determined. The findings for the kidney enzymes AAP, NAG and GGT show that the renal tolerance of penbutolol was good. Physical exercise per se did not cause any increase in the excretion of the above-mentioned enzymes. Slight diurnal variation was seen in the excretion of the renal enzymes after both the placebo and penbutolol.

A double-blind crossover trial was carried out in 7 healthy male volunteers to investigate the effects of penbutolol and a placebo on plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) levels before and after exercise. Each subject underwent several bicycle ergometric exercises lasting 6 min before and after the application of test medications. Ergometric exercises were performed before medication, and at 2, 5, 9 and 24 hours after medication. Blood samples for ANP and ADH levels were drawn before, after 15 min, after 2 hours (immediately after ergometry) and 5, 7, 9, and 24 hours after medication (immediately before ergometry). Urine was collected as follows: -2 to 0, 0 to 2, 2 to 4, 4 to 7, 7 to 14 and 14 to 24 hours after medication, and the volume as well as sodium excretion were documented. Penbutolol caused suppression of the exercise-induced increase in ANP. The 2 to 4 hour fractional sodium excretion was significantly decreased from 12.1 +/- 4.9 mmol/fraction after placebo treatment to 7.8 +/- 3.0 mmol/fraction after penbutolol application (p less than 0.03). There were no differences in the urinary outputs between penbutolol and placebo until 4 hours after medication, but penbutolol caused the total urinary output to increase from 1390 +/- 388 ml/24 hr during placebo treatment to 1725 +/- 549 ml/24 hr (p less than 0.02) due to the last collection fraction. Blood pressure and pulse rate both decreased during exercise after penbutolol. As opposed to the suppressing influence of penbutolol on ANP, ADH plasma levels were increased after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)