Learning curve and functional outcomes after laser enucleation of the prostate for benign prostate hyperplasia according to surgeon's caseload.

PURPOSE: To evaluate the impact of surgical caseload on safety, efficacy, and functional outcomes of laser enucleation of the prostate (LEP) applying a structured mentoring program. METHODS: Patient characteristics, perioperative data, and functional outcomes were analyzed descriptively. Linear and logistic regression models analyzed the effect of caseload on complications, functional outcomes and operative speed. Within the structured mentoring program a senior surgeon was present for the first 24 procedures completely, for partial steps in procedures 25-49, and as needed thereafter. RESULTS: A total of 677 patients from our prospective institutional database (2017-2022) were included for analysis. Of these, 84 (12%), 75 (11%), 82 (12%), 106 (16%), and 330 patients (49%) were operated by surgeons at (A) < 25, (B) 25-49, (C) 50-99, (D) 100-199, and (E) ≥ 200 procedures. Preoperative characteristics were balanced (all p > 0.05) except for prostate volume, which increased with caseload. There was no significant difference in change of IPSS, Quality of life, ICIQ, pad usage, peak urine flow, residual urine, and major complications (Group A: 8.3 to E: 7.6%, p = 0.2) depending on the caseload. Caseload was not associated (Odds ratio: 0.7-1.4, p > 0.2) with major complications in the multivariable logistic regression model. Only operating time was significantly shorter with increasing caseload in the multivariable analysis (111-55 min, beta 23.9-62.9, p < 0.001). CONCLUSION: With a structured mentoring program, the safety and efficacy of LEP can be ensured even during the learning curve with very good outcome quality. Only the operating time decreases significantly with increasing experience of the surgeon.

[Movember health care initiative 2019: prostate cancer screening at the University Hospital Frankfurt]. / Urologische Prostatakrebsvorsorge im Rahmen der Movember-Gesundheitsinitiative 2019 am Universitätsklinikum Frankfurt.

BACKGROUND: Men die earlier than women in Germany. Men also have impaired access to cancer screening compared to women. OBJECTIVES: Our Movember campaign 2019 at University Hospital Frankfurt (UKF) aimed at improving health care awareness in the context of prostate cancer checkup. MATERIALS AND METHODS: In November 2019, every male employee of the UKF with a minimum age of 45 yrs (or 40 yrs with a first degree relative with prostate cancer) was offered a free prostate cancer checkup. This checkup contained digital rectal examination (DRE), transrectal ultrasound and PSA (prostata-specific antigen) testing. RESULTS: Overall, 121/840 employees (14.4%) participated in the Movember campaign. A first degree relative with prostate cancer was reported in overall by 14% of the participants (n = 17). At least one prior prostate cancer check up had 33%. A total of 2.5% (n = 3) had one prior negative prostate biopsy. Median age was 54 yrs (interquartile range 50-58). Median PSA level was 0.9 ng/ml and median free-PSA 0.3 ng/ml. A suspicious DRE was found in 5% (n = 6). After stratification according to age (≤ 50 yrs vs. > 50 yrs), participants over 50 yrs had a significantly higher PSA level (1.0 ng/ml vs. 0.7 ng/ml, p < 0.01) and had more frequently at least one prior prostate cancer checkup in the past (42.0 vs. 12.1%, p < 0.01). All suspicious DREs were in the cohort > 50 yrs. Overall, 32.2% (n = 39) had at least a suspicious checkup. A total of 3.3% (n = 4) had suspicious PSA levels. 17.4% (n = 21) of the participants had a suspicious PSA ratio (< 20%) only. During follow-up, 6 prostate biopsies were performed, with the detection of one case of intermediate-risk prostate cancer (Gleason 3 + 4, pT3a, pPn1, pNx, R0). CONCLUSION: Overall, 121 employees participated in our Movember Prostate cancer checkup campaign with measurement of the PSA level. Suspicious results were recorded in 32.2%. One employee was diagnosed and successfully treated with an intermediate-risk prostate cancer.

[Perioperative blood pressure management : What is the optimal pressure?] / Perioperatives Blutdruckmanagement : Was ist der optimale Druck?

BACKGROUND: Measurement of blood pressure is part of standard monitoring procedures in anesthesia, in addition to the other vital parameters of heart frequency and peripheral oxygen saturation. In recent years the relevance of the duration and extent of perioperative episodes of hypotension for the occurrence of postoperative complications or even increased mortality have become the focus of scientific investigations. OBJECTIVE: The aim of this review is to briefly recapitulate the physiological aspects of blood pressure and to describe the pathophysiology and risk factors of perioperative hypotension. It describes which potential organ damage can be caused by hypotension and discusses which perioperative blood pressure values are acceptable without harming the patient. METHODS: Review and analysis of the currently available literature. RESULTS: Perioperative hypotension is defined by either absolute systolic arterial pressure (SAP) or mean arterial pressure (MAP) thresholds and by relative blood pressure declines from an individual preoperative baseline value. For the definition of absolute and relative thresholds it needs to be considered that the ultimate target is an adequate perfusion pressure (and not the MAP) and that the preinduction blood pressure is a poor reflection of the patients' normal blood pressure profile. Risk factors for an intraoperative drop in blood pressure are advanced age, higher American Society of Anesthesiologists (ASA) status, low blood pressure prior to induction of anesthesia, the premedication, e.g. angiotensin-converting enzyme (ACE) inhibitors, the anesthesia technique (combination of general and epidural anesthesia) and emergency surgery. The lowest tolerable intraoperative blood pressure should be defined according to the individual patient's preoperative blood pressure and risk profile. Individual thresholds should be determined for the severity and duration of intraoperative hypotension. Empirically, MAP values <65 mm Hg and relative pressure declines of >20-30% are often recommended as thresholds. Below critical blood pressure values the risk of postoperative organ damage (myocardium, kidneys and central nervous system) and mortality increases with longer duration of hypotension. Older people and high-risk patients (e.g. patients in vascular surgery) have a poorer and shorter tolerance of low blood pressure. Postoperative organ complications can be minimized by maintenance of an adequate intraoperative blood pressure CONCLUSION: Anesthesiologists should avoid extensive and prolonged hypotension by timely interventions in order to improve the postoperative outcome of patients.

What predicts the outcome in patients with intestinal ischemia? A single center experience.

BACKGROUND: Acute mesenteric ischemia (AMI) is associated with a mortality of 60-80%. Early diagnosis and rapid treatment have a decisive influence on therapy. The aim of this study was to evaluate the prognostic value of AMI markers on mortality, in order to better anticipate the clinical course and to initiate therapeutic steps at an early stage. STUDY DESIGN: An analysis from our prospective database of 302 consecutive patients with AMI who were treated surgically in the Department of General Surgery between February 2003 and October 2014 was performed. Uni- and multivariate analysis of risk factors for mortality have been performed in the total cohort and in two subgroups according to their stay in intensive care unit (ICU) at the time of AMI diagnosis. RESULTS: Of the 302 patients with AMI, 115 were in ICU at the time of diagnosis. Totally, 203 patients underwent computed tomography scan (CT-scan) of the abdomen for diagnosis and 68% of them showed specific signs of AMI. A total of 63 (21%) embolectomies were performed during the surgical procedure. The post-operative mortality rate was 68% (204 patients). Among survivors, 85 (87%) patients developed a short bowel syndrome in the post-operative course. Multivariate analysis showed a significant association between mortality and preoperative lactate>3mmol/L, C-reactive protein>100mg/L and ICU stay at the time of AMI diagnosis. CONCLUSION: Mortality of patients with AMI remains high. Elevated lactate, elevated C-reactive protein and ICU stay are factors associated with increased mortality. Their presence in a patient with suspicion of AMI should trigger a multidisciplinary management in emergency.

Lipid droplet motility and organelle contacts.

Lipid droplets (LDs) are fat storage organelles integral to energy homeostasis and a wide range of cellular processes. LDs physically and functionally interact with many partner organelles, including the ER, mitochondria, lysosomes, and peroxisomes. Recent findings suggest that the dynamics of LD inter-organelle contacts is in part controlled by LD intracellular motility. LDs can be transported directly by motor proteins along either actin filaments or microtubules, via Kinesin-1, Cytoplasmic Dynein, and type V Myosins. LDs can also be propelled indirectly, by hitchhiking on other organelles, cytoplasmic flows, and potentially actin polymerization. Although the anchors that attach motors to LDs remain elusive, other regulators of LD motility have been identified, ranging from modification of the tracks to motor co-factors to members of the perilipin family of LD proteins. Manipulating these regulatory pathways provides a tool to probe whether altered motility affects organelle contacts and has revealed that LD motility can promote interactions with numerous partners, with profound consequences for metabolism. LD motility can cause dramatic redistribution of LDs between a clustered and a dispersed state, resulting in altered organelle contacts and LD turnover. We propose that LD motility can thus promote switches in the metabolic state of a cell. Finally, LD motility is also important for LD allocation during cell division. In a number of animal embryos, uneven allocation results in a large difference in LD content in distinct daughter cells, suggesting cell-type specific LD needs.

Evaluation of the MDACC clinical classification system for pancreatic cancer patients in an European multicenter cohort.

BACKGROUND: The MDACC group recommends to extend the current borderline classification for pancreatic cancer into three groups: type A patients with resectable/borderline tumor anatomy, type B with resectable/borderline resectable tumor anatomy and clinical findings suspicious for extrapancreatic disease and type C with borderline resectable and marginal performance status/severe pre-existing comorbidity profile or age>80. This study intents to evaluate the proposed borderline classification system in a multicenter patient cohort without neoadjuvant treatment. METHODS: Evaluation was based on a multicenter database of pancreatic cancer patients undergoing surgery from 2005 to 2016 (n = 1020). Complications were classified based on the Clavien-Dindo classification. χ2-test, Kaplan-Meier estimator and Cox regression hazard model were used for statistical analysis. RESULTS: Most patients (55.1%) were assigned as type A patients, followed by type C (35.8%) and type B patients (9.1%). Neither the complication rate, nor the mortality rate revealed a correlation to any subgroup. Type B patients had a significant worse progression free (p < 0.001) and overall survival (p = 0.005). Type B classification was identified as an independent prognostic marker for progression free survival (p = 0.005, HR 1.47). CONCLUSION: The evaluation of the proposed classification in a cohort without neoadjuvant treatment did not justify an additional medical borderline subgroup. A new subgroup based on prognostic borderline patients might be the main target group for neoadjuvant protocols in future.

Drosophila KASH-domain protein Klarsicht regulates microtubule stability and integrin receptor localization during collective cell migration.

During collective migration of the Drosophila embryonic salivary gland, cells rearrange to form a tube of a distinct shape and size. Here, we report a novel role for the Drosophila Klarsicht-Anc-Syne Homology (KASH) domain protein Klarsicht (Klar) in the regulation of microtubule (MT) stability and integrin receptor localization during salivary gland migration. In wild-type salivary glands, MTs became progressively stabilized as gland migration progressed. In embryos specifically lacking the KASH domain containing isoforms of Klar, salivary gland cells failed to rearrange and migrate, and these defects were accompanied by decreased MT stability and altered integrin receptor localization. In muscles and photoreceptors, KASH isoforms of Klar work together with Klaroid (Koi), a SUN domain protein, to position nuclei; however, loss of Koi had no effect on salivary gland migration, suggesting that Klar controls gland migration through novel interactors. The disrupted cell rearrangement and integrin localization observed in klar mutants could be mimicked by overexpressing Spastin (Spas), a MT severing protein, in otherwise wild-type salivary glands. In turn, promoting MT stability by reducing spas gene dosage in klar mutant embryos rescued the integrin localization, cell rearrangement and gland migration defects. Klar genetically interacts with the Rho1 small GTPase in salivary gland migration and is required for the subcellular localization of Rho1. We also show that Klar binds tubulin directly in vitro. Our studies provide the first evidence that a KASH-domain protein regulates the MT cytoskeleton and integrin localization during collective cell migration.

[Pediatric anesthesia for proton radiotherapy : medicine remote from the medical centre]. / Kinderanästhesie zur protonenbestrahlung : medizin fernab der klinik.

Anesthesia care for infants and young children for proton beam radiotherapy demands great technical and vocational skills from the anesthesia team and also a high degree of competence in soft skills. The anesthesia team should be experienced and regularly trained in pediatric anesthesia, especially as the children are often in a reduced general condition. The infrastructure should be established according to the current standards in anesthesiology. Monitoring of vital data, thorax excursions and inadvertent movements of the remotely positioned and sedated patient need to be under constant technical and optical surveillance. Propofol is an ideal hypnotic for the sedation of children under spontaneous breathing for proton beam radiation therapy. It is well tolerated even when given on a daily basis over several weeks. A close cooperation between the pediatric oncologist, radiation oncologist and anesthetist is important in order to manage additional medical problems in an optimal way. The special needs of oncology patients must be taken into consideration when planning anesthesia care.

[Erythrocyte transfusion: update of the guidelines "therapy with blood components and plasma derivatives"]. / Erythrozytentransfusion : Update zu den Leitlinien "Therapie mit Blutkomponenten und Plasmaderivaten"

The new version of the guidelines, which have now been renamed Cross-sectional guidelines on therapy with blood components and plasma derivatives, is distinguished by focusing on key recommendations. In each section clear recommendations for the selection and indications for the use of each blood product are presented and these recommendations are classified with respect to their strength and evidence level. The most important recommendations in section 1 "Erythrocyte concentrates", which is especially important for the faculty of anesthesiology, will be presented in this article with special reference to the data on which the recommendations are based.

Molecular motors: a traffic cop within?

Intracellular transport along microtubules is often bidirectional, employing multiple plus- and minus-end directed motors. How cells regulate such transport in time and space is a fundamental but unsolved question in cell biology. A recent paper presents a new modeling approach to predict how much of transport can be understood just from our knowledge of the motors involved. The model can generate strikingly complex patterns of motion, mimicking key aspects of cargo transport in vivo. Previous studies had inferred that plus-end motors on bidirectional cargoes are usually turned off when the minus-end motors are engaged (and vice versa). In the model, such motor coordination can arise from motors competing in a tug-of-war, without help from additional regulators. This new theoretical framework should stimulate much research that will help unravel whether regulation of intracellular transport is dominated by higher-order control mechanisms or is achieved simply by tuning basic properties of the motors themselves.

Evaluation of sympathetic blockade after intrathecal and epidural lidocaine in rats by laser Doppler perfusion imaging.

The widespread use of neuraxial anaesthesia increases the need for animal models to evaluate therapeutic prospects, mechanisms and risks of this technique. As a methodological prerequisite, we characterised the sympathetic blockade after different modes of neuraxial anaesthesia with regard to segments supplying the splanchnic region. Under haemodynamic monitoring, lidocaine 2% or saline were infused via intrathecal (10 microl), lumbar epidural (10 and 30 microl) or thoracic epidural (10 and 30 microl) catheters. Segmental spread of neuraxially infused local anaesthetic was assessed using methylene blue. Mean arterial blood pressure decreased more severely after neuraxial lidocaine in thoracic epidural (10 and 30 microl) compared to high-volume (30 microl anaesthesia animals. Determination of the sympathetic blockade by means of laser Doppler perfusion imaging was restricted to the paws due to a higher density of subcutaneous blood vessels as compared to the abdominal wall (mean +/- SD: 3.93 +/- 0.06 vs. 1.35 +/- 0.05/384 mm(2), p < 0.05). Only high-volume (30 microl) lumbar and thoracic epidural anaesthesia (10 and 30 microl) increased skin perfusion in both hind and front paws. This extensive sympathetic blockade was demonstrated to include splanchnic segments using thermography. Segmental spread of methylene blue did not closely correspond to laser Doppler findings and should be interpreted as minimum rather than exact epidural spread of local anaesthetic.

Searching the ideal inhaled vasodilator: from nitric oxide to prostacyclin.

Today, the technique to directly administer vasodilators via the airway to treat pulmonary hypertension and to improve pulmonary gas exchange is widely accepted among clinicians. The flood of scientific work focussing on this new therapeutic concept had been initiated by a fundamental new observation by Pepke-Zaba [1]and Frostell in 1991 [2]: Both scientists reported, that inhalation of exogenous nitric oxide (NO) gas selectively dilates pulmonary vessels without a concomittant systemic vasodilation. No more than another decade ago NO was identified as an important endogenous vasodilator [3]while having merely been regarded an environmental pollutant before that time. Although inhaled NO proved to be efficacious, alternatives were sought-after due to NO's potential side-effects. In search for the ideal inhaled vasodilator another group of endogenous mediators -- the prostanoids -- came into the focus of interest. The evidence for safety and efficacy of inhaled prostanoids is -- among a lot of other valuable work -- based on a series of experimental and clinical investigations that have been performed or designed at the Institute for Surgical Research under the guidance and mentorship of Prof. Dr. med. Dr. h.c. mult. K. Messmer [4-19]. In the following, the current and newly emerging clinical applications of inhaled prostanoids and the experimental data which they are based on, will be reviewed.

Hirudin versus heparin for anticoagulation in continuous renal replacement therapy.

OBJECTIVE: To compare the efficacy and safety of hirudin and heparin for anticoagulation during continuous renal replacement therapy (CRRT) in critically ill patients. DESIGN: Prospective, randomized controlled pilot study. SETTING: Single centre; interdisciplinary intensive care unit at a university hospital. PATIENTS: Seventeen patients receiving CRRT. INTERVENTIONS: Patients were randomly allocated to two groups. Heparin group (nine patients): continuous administration of 250 IU/h heparin; dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180-210 s. Hirudin group (eight patients): continuous infusion of 10 micrograms/kg/h hirudin, dose was adjusted in 2 micrograms/kg/h steps with a targeted ecarin clotting time (ECT) of 80-100 s. Observation time was 96 h. MEASUREMENTS AND MAIN RESULTS: Measured filter run patency and haemofiltration efficacy did not significantly differ between the two groups. Three bleeding complications were observed in the hirudin group, none in the heparin group (P < 0.01). At the onset of bleeding, which occurred 60 or more hours after the start of therapy, only one patient was still under continuous hirudin administration but levels were either in therapeutic range or below. CONCLUSIONS: Hirudin can be used efficiently for anticoagulation in CRRT. Late bleeding complications may have been caused by possible hirudin accumulation, but this was not evident from hirudin plasma and ECT levels. Since bleeding complications were observed only in the presence of documented coagulation disorders, not only adequate drug monitoring but also the plasmatic and cellular coagulation status of the patient should be taken into consideration for adjusting hirudin dosage.

Local secretion of TNF-alpha from the liver does not correlate with endotoxin, IL-6, or organ function in the early phase after orthotopic liver transplantation.

Hepatic ischemia/reperfusion leads to an excessive release of proinflammatory cytokines, which promotes local and remote cell damage. The value of cytokine measurement in humans for predicting graft function after orthotopic liver transplantation (OLT) remains unclear. Therefore, in this study, tumor-necrosis-factor-alpha (TNF-alpha), interleukin-6 (IL-6), and endotoxin (ET) levels were determined in the blood taken from the hepatic veins of 31 patients who underwent OLT. Peak levels of TNF-alpha in hepatic venous blood were measured shortly after reperfusion and were significantly higher than concentrations in the systemic circulation. IL-6 concentrations, peaking 90 min after reperfusion, only correlated with postoperative pulmonary dysfunction. ET was detectable in 21 patients, but levels did not correlate with either IL-6 or TNF-alpha concentrations. Additionally, serum cytokine levels did not correlate with the duration of ischemia or with histological changes seen in liver biopsies. In general, our study suggests that local secretion of cytokines does not predict liver function in the early posttransplant phase.

Thoracic epidural anesthesia combined with general anesthesia: the preferred anesthetic technique for thoracic surgery.

UNLABELLED: Thoracic epidural anesthesia (TEA) combined with general anesthesia (GA) as well as total-IV anesthesia (TIVA) are both established anesthetic managements for thoracic surgery. We compared them with respect to hypoxic pulmonary vasoconstriction, shunt fraction and oxygenation during one-lung ventilation. Fifty patients, ASA physical status II-III undergoing pulmonary resection were randomly allocated to two groups. In the TIVA group, anesthesia was maintained with propofol and fentanyl. In the TEA group, anesthesia was maintained with TEA (bupivacaine 0.5%) combined with low-dose concentration 0.3-0.5 vol% of isoflurane (end-tidal). Changing from two-lung ventilation to one-lung ventilation caused a significant increase in cardiac output (CO) in the TIVA group, whereas no change was observed in the TEA group. One-lung ventilation caused significant increases in shunt fraction in both groups which was associated per definition with a significant decrease in PaO(2) in both groups but PaO(2) remained significantly increased in the TEA group (P < 0.05). We conclude that both anesthetic regimens are safe intraoperatively. However, TEA in combination with GA did not impair arterial oxygenation to the same extent as TIVA, which might be a result of the changes in CO. Therefore, patients with preexisting cardiopulmonary disease and impaired oxygenation before one-lung ventilation might benefit from TEA combined with GA. IMPLICATIONS: Fifty patients underwent lung surgery through the opened chest wall requiring ventilation of only one lung. Patients were randomly assigned to receive either general anesthesia alone or in combination with regional anesthesia via a catheter in the back. Oxygen content in the blood and blood pressure was better maintained in the group receiving the combination of general with regional anesthesia.

Dynein-mediated cargo transport in vivo. A switch controls travel distance.

Cytoplasmic dynein is a microtubule-based motor with diverse cellular roles. Here, we use mutations in the dynein heavy chain gene to impair the motor's function, and employ biophysical measurements to demonstrate that cytoplasmic dynein is responsible for the minus end motion of bidirectionally moving lipid droplets in early Drosophila embryos. This analysis yields an estimate for the force that a single cytoplasmic dynein exerts in vivo (1.1 pN). It also allows us to quantitate dynein-mediated cargo motion in vivo, providing a framework for investigating how dynein's activity is controlled. We identify three distinct travel states whose general features also characterize plus end motion. These states are preserved in different developmental stages. We had previously provided evidence that for each travel direction, single droplets are moved by multiple motors of the same type (Welte et al. 1998). Droplet travel distances (runs) are much shorter than expected for multiple motors based on in vitro estimates of cytoplasmic dynein processivity. Therefore, we propose the existence of a process that ends runs before the motors fall off the microtubules. We find that this process acts with a constant probability per unit distance, and is typically coupled to a switch in travel direction. A process with similar properties governs plus end motion, and its regulation controls the net direction of transport.

N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study.

OBJECTIVE: In septic shock, decreased splanchnic blood flow is reported, despite adequate systemic hemodynamics. Aacetylcysteine (NAC) was found to increase hepatosplanchnic blood flow in experimental settings. In septic shock patients, NAC improved the clearance of indocyanine green and the relationship of systemic oxygen consumption to oxygen demand. We investigated the influence of NAC on liver blood flow, hepatosplanchnic oxygen transport-related variables, and liver function during early septic shock. DESIGN: Prospective, randomized, double-blind study. SETTING: Septic shock patients admitted to an interdisciplinary surgical intensive care unit. PATIENTS: We examined 60 septic shock patients within 24 hrs after onset of sepsis. They were conventionally resuscitated with volume and inotropes and were in stable condition. A gastric tonometer was inserted into the stomach and a catheter into the hepatic vein. Microsomal liver function was assessed by using the plasma appearance of monoethylglycinexylidide (MEGX). INTERVENTIONS: Subjects randomly received either a bolus of 150 mg/kg iv NAC over 15 mins and a subsequent continuous infusion of 12.5 mg/kg/hr NAC over 90 mins (n = 30) or placebo (n = 30). MEASUREMENTS AND MAIN RESULTS: Measurements were performed before (baseline) and 60 mins after beginning the infusion (infusion). After NAC, a significant increase in absolute liver blood flow index (2.7 vs. 3.3 L/min/m2; p = .01) and cardiac index (5.0 vs. 5.7 L/min/m2; p = .02) was observed. Fractional liver blood flow index (cardiac index-related liver blood flow index) did not change. The difference between arterial and gastric mucosal carbon dioxide tension decreased (p = .05) and MEGX increased (p = .04). Liver blood flow index and MEGX correlated significantly (r(s) = .57; p < or = .01). CONCLUSIONS: After NAC treatment, hepatosplanchnic flow and function improved and may, therefore, suggest enhanced nutritive blood flow. The increase of liver blood flow index was not caused by redistribution to the hepatosplanchnic area, but by an increase of cardiac index. Because of its correlation with liver blood flow index, MEGX may be helpful in identifying patients who benefit from NAC treatment in early septic shock.