Predictive Parameters in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan for Unresectable Liver Metastases from Uveal Melanoma: A Retrospective Pooled Analysis.

PURPOSE: The aim of this study was to identify positive predictors for survival in uveal melanoma (UM) patients treated with percutaneous hepatic perfusion with melphalan (M-PHP), by retrospectively pooling data from three centers. MATERIALS AND METHODS: Retrospective analysis including patients ([Formula: see text] 18 years) treated with M-PHP between February 2014 and December 2019 for unresectable liver-dominant or liver-only metastases from UM. Predictors for OS were assessed using uni- and multivariate analyses. Other study outcome measures were response rate, progression-free survival (PFS), liver progression-free survival (LPFS), overall survival (OS) and complications according to CTCAEv5.0. RESULTS: In total, 101 patients (47.5% males; median age 59.0 years) completed a minimum of one M-PHP. At a median follow-up time of 15.0 months, complete response (CR), partial response (PR), stable disease (SD) and progressive disease were seen in five (5.0%), 55 (54.5%), 30 (29.7%) and 11 (10.9%) patients, respectively, leading to a 89.1% disease control rate. Median PFS, LPFS and OS were 9.0, 11.0 and 20.0 months, respectively. Survival analyses stratified for radiological response demonstrated significant improved survival in patients with CR or PR and SD category. Treatment of the primary tumor with radiotherapy, ≥ 2 M-PHP and lactate dehydrogenase (LDH) < 248 U/L were correlated with improved OS. Thirty-day mortality was 1.1% (n = 2). Most common complication was hematological toxicity (self-limiting in most cases). CONCLUSION: M-PHP is safe and effective in patients with UM liver metastases. Achieving CR, PR or SD is associated with improved survival. Primary tumor treatment with radiotherapy, normal baseline LDH and > 1 M-PHP cycles are associated with improved OS.

[Anesthesia and bariatric surgery]. / Anästhesie bei bariatrischer Chirurgie.

Today obesity is accepted as an independent disease. The WHO describes obesity as an epidemic disease occurring worldwide and associated comorbidities affect all organ systems. Bariatric operations lead to an improvement or even complete remission of obesity-correlated comorbidities. Bariatric operations are conducted as restrictive, malabsorptive, or mixed procedures. The preoperative anesthetic evaluation of comorbidities is carried out with a special focus on preexisting impairments of cardiac and lung function (e.g. cardiomyopathy, obstructive respiratory dysfunctions). Extremely obese patients are at risk of aspiration. Airway management at anesthesia induction includes normal intubation or, if additional risk factors are present, either fiber optic awake intubation or rapid sequence induction. The pharmacokinetics of all applicable drugs are altered in extremely obese patients and they are at risk for developing postoperative thromboembolic complications with a high mortality rate. Therefore early and sufficient thrombotic prophylaxis is important.

Ventricular tachycardia during hyperthermic intraperitoneal chemotherapy.

SUMMARY: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is used for selected gastrointestinal carcinomas. We report a case of ventricular tachycardia during HIPEC with cisplatin that persisted as long as the chemotherapy solution remained in the intra-abdominal cavity. We hypothesise that high plasma levels of cisplatin with concomitant low magnesium levels caused the arrhythmia.

Audit of motor weakness and premature catheter dislodgement after epidural analgesia in major abdominal surgery.

In a quality improvement audit on epidural analgesia in 300 patients after major abdominal surgery, we identified postoperative lower leg weakness and premature catheter dislodgement as the most frequent causes of premature discontinuation of postoperative epidural infusion. Lower limb motor weakness occurred in more than half of the patients with lumbar epidural analgesia. In a second period monitoring 177 patients, lumbar catheter insertion was abandoned in favour of exclusive thoracic placement for epidural catheters. Additionally, to prevent outward movement, the catheters were inserted deeper into the epidural space (mean (SD) 5.2 (1.5) cm in Period Two vs 4.6 (1.3) cm in Period One). Lower leg motor weakness declined from 14.7% to 5.1% (odds ratio 0.35; 95% confidence interval 0.16-0.74) between the two periods. Similarly, the frequency of premature catheter dislodgement was reduced from 14.5% to 5.7% (odds ratio 0.35; 95% confidence interval 0.17-0.72). With a stepwise logistic regression model we demonstrated that the odds of premature catheter dislodgement was reduced by 43% for each centimetre of additional catheter advancement in Period Two. We conclude that careful audit of specific complications can usefully guide changes in practice that improve success of epidural analgesia regimens.

[Mastocytosis. A challenge in anaesthesiology]. / Mastozytose. Herausforderung in der Anästhesie.

Mastocytosis is a general term for a heterogeneous group of rare disorders. Many agents used in anaesthesia can trigger mast cell degranulation with release of histamine, prostaglandin, tryptase and heparin. Therefore, patients with mastocytosis are high-risk patients when undergoing anaesthesia. The management of these patients in anaesthesia will be discussed on the basis of the literature and illustrated with the discussion of three case reports. A premedication with antihistamines and a glucocorticoid is recommended. For induction of general anaesthesia propofol, etomidate, ketamine, a fentanyl-type opioid, cis-atracurium or pancuronium are recommended. Anaesthesia can be maintained either by a total intravenous technique or with a volatile anaesthetic such as sevoflurane.

Elimination of linezolid by an in vitro extracorporeal circuit model.

Linezolid is an oxazolidinone antibiotic with activity against important grampositive aerobic bacteria, including nosocomial pathogens. It is not known whether dosage adjustments are necessary in patients treated with continuous renal replacement therapies. This in vitro study was conducted to investigate the elimination of linezolid in an in vitro continuous hemo(dia)filtration model using different filter materials (polysulfone, polyacrylonitrile, polyamide), surface areas, and different modes of renal replacement therapies. Linezolid was measured using HPLC with UV-detection. No adsorption of linezolid to any of the tested membranes was detected. Recovery of linezolid in the ultrafiltrate was 98.2 +/- 10.5% in the filtration mode. During dialysis, recovery was significantly less (87.6 +/- 16.1%; p = 0.02). Linezolid elimination was not altered by filter size, when polysulfone filters with surface areas of 0.7 m2 and 1.3 m2 were tested. In conclusion, the dosage recommendations for linezolid are independent of the filter materials. However, the elimination is significantly higher during hemofiltration compared to dialysis.

Elimination of meropenem by continuous hemo(dia) filtration: an in vitro one-compartment model.

Meropenem is a carbapenem antibiotic with a wide spectrum of activity against most gram positive and gram negative bacteria including anaerobes. Dose adjustments are necessary during continuous renal replacement therapies of acute renal failure. This in vitro study was conducted to investigate the influence of different filter materials, surface areas (AN-69 0.6 m2 and 0.9 m2, polysulfone 0.75 m2, polyamide 0.6 m2), and increasing flow rates (from 3.3 - 26.7 ml/min) on the elimination of meropenem in an in vitro continuous hemo(dia)filtration model. Meropenem was measured using HPLC with UV-detection. While the clearance increased proportionally to increasing dialysate flow rates in filters with a surface area of 0.9 m2, a peak clearance was reached in the small filters at flow rates of 10.0 ml/min (polyamide 0.6 m2) and 18.3 ml/min (AN-69 0.6 m2), when tested under the same conditions. This indicated incomplete dialysate saturation due to the diminished time available for meropenem to equilibrate with the dialysate solution. No adsorption to either of the tested membranes was detected. Dosage recommendations derived from clinical studies might be appropriate when different filter materials, but similar operational settings of the continuous replacement therapy, are applied. Reduction of the recommended dose might be necessary, when renal replacement therapies with lower flow rates and/or filters with smaller surface areas are carried out.

Effect of tracheal intubation or laryngeal mask airway insertion on intraocular pressure using balanced anesthesia with sevoflurane and remifentanil.

STUDY OBJECTIVES: To study the effect of tracheal intubation or laryngeal mask airway (LMA) insertion on intraocular pressure (IOP) in strabismus patients undergoing balanced anesthesia with sevoflurane and remifentanil. DESIGN: Open, prospective, randomized study. SETTING: Tertiary care academic medical institution. PATIENTS: 40 adult ASA physical status I and II patients scheduled for elective strabismus surgery. INTERVENTION: Patients were randomized to receive either tracheal intubation or LMA insertion following mask induction with sevoflurane in combination with IV remifentanil. MEASUREMENTS: Intraocular pressure, mean arterial pressure (MAP), and heart rate (HR) were measured before induction, immediately following induction, and after airway insertion. MAIN RESULTS: Intraocular pressure after tracheal intubation or LMA insertion did not differ significantly from preoperative baseline values. Mean arterial pressure and HR did not significantly differ between groups at any time point. CONCLUSIONS: Remifentanil and sevoflurane are not associated with an increase in IOP response during tracheal intubation or LMA insertion above baseline in healthy patients undergoing ophthalmic surgery.

[Selection criteria for peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) in peritoneal carcinomatosis]. / Selektion zur Peritonektomie mit hyperthermer intraoperativer Chemotherapie (HIPEC) bei Peritonealkarzinose.

BACKGROUND: Cytoreductive peritonectomy with hyperthermic intraoperative chemotherapy (HIPEC) is an established therapy for patients with gastrointestinal, gynaecological metastasised peritoneal carcinomatosis as well as primary peritoneal carcinomatous tumours. METHODS: On the basis of a literature review and our personal experience, selection criteria for peritonectomy are discussed. RESULTS: Computed tomography (CT) scans and diagnostic laparoscopy are not sufficient for the diagnosis of peritoneal carcinomatosis. The combination of fluorodeoxyglucose positron emission tomography (FDG-PET) and CT seems to be the most reliable diagnostic imaging method. In our institution, all patients undergo PET / CT prior to peritonectomy. CONCLUSION: The PET / CT scan may play an important role in forecasting the operability of patients with peritoneal carcinomatosis.

Rhabdomyolysis in an obese patient after total knee arthroplasty.

We report the case of a morbidly obese patient who developed rhabdomyolysis with acute renal failure, hepatic dysfunction, and an increase of cardiac troponin-1 after total knee arthroplasty. Postoperative rhabdomyolysis has a wide range of triggers and differential diagnoses that should be considered by the anaesthesiologist and surgeons. We would like to emphasize that morbidly obese patients have an increased risk of developing postoperative rhabdomyolysis potentially leading to life-threatening disease. Intensified postoperative observation seem justified in these patients.

Remifentanil or sufentanil for coronary surgery: comparison of postoperative respiratory impairment.

BACKGROUND AND OBJECTIVE: High-dose opioid anaesthesia contributes to decreasing metabolic and hormonal stress responses in patients undergoing cardiac surgery. However, the increase in context-sensitive half-life of opioids given as a high-dose regimen can affect postoperative respiratory recovery. In contrast, remifentanil can be given in high doses without prolonging context-sensitive half-life due to its rapid metabolism. Therefore, we performed a prospective, randomized trial to compare anaesthesia consisting of propofol/remifentanil or propofol/sufentanil with regard to postoperative respiratory function and outcome. METHODS: Patients undergoing coronary artery bypass grafting were randomized to a propofol/remifentanil (0.5-1.0 microg kg(-1) min(-1)) or propofol/sufentanil (30-40 ng kg(-1) min(-1)) based anaesthetic. Carbon dioxide response, forced expiratory volume in one second, vital capacity, and functional residual capacity were measured 1 day prior to the operation, 1 h before extubation, 1, 24 and 72 h after extubation. In addition, the incidence of atelectasis, pulmonary infiltrates, intensive care unit and postoperative length of stay were compared. Patients and physicians were blinded to the treatment group. RESULTS: Twenty-five patients in each treatment group completed the study. There was no difference between patients of the treatment groups regarding demographics, risk- or pain scores. In all patients, carbon dioxide response, forced expiratory volume in one second, vital capacity and functional residual capacity were decreased postoperatively compared to baseline. Patients randomized to remifentanil had less depression of carbon dioxide response, less atelectasis and shorter postoperative length of stay (12 d vs. 10 d) than after sufentanil (P < 0.05). CONCLUSIONS: Intraoperative use of high-dose remifentanil for coronary artery bypass grafting may be associated with improved recovery of pulmonary function and shorter postoperative hospital length of stay than sufentanil.

[Effects of reduced shear stress on inflammatory reactions in vitro. Effects of pathological flow conditions on leukocyte-endothelial interactions and monocyte tissue factor expression in human cell cultures]. / Einfluss verminderter Scherkräfte auf Entzündungsreaktionen in vitro Effekte pathologischer Strömungsbedingungen auf Leukozyten-Endothel-Interaktionen und monozytäre "Tissue-factor-Expression" in humanen Zellkulturen.

BACKGROUND: During malperfusion and inflammation leukocyte adhesion is common. The purpose of this study was to examine the effects of reduced shear stress on leukocyte-endothelial interactions and subsequent inflammatory reactions such as up-regulation of tissue factor. METHODS: Isolated neutrophils and monocytes were co-incubated with human umbilical venous endothelium at 0-3 dynes/cm(2) in a flow chamber. Adhesion and tissue factor expression on adherent leukocytes were examined at various flow conditions. RESULTS: At 2-3 dynes/cm(2) adhesion occurred only on TNFalpha-activated endothelium. Below 1 dyne/cm(2) similarly increased adhesion was also observed on non-activated endothelium. As was observed for leukocyte adhesion, these shear stress-dependent cell interactions also resulted in an up-regulation of tissue factor on adherent monocytes from non-activated co-cultures. CONCLUSION: Apart from additional activators of inflammation, reduced shear forces may directly contribute to inflammation.

Lack of adherence of clinical isolates of Pseudomonas aeruginosa to asialo-GM(1) on epithelial cells.

Numerous studies have reported that asialo-GM(1), gangliotetraosylceramide, or moieties serve as epithelial cell receptors for Pseudomonas aeruginosa. Usually this interaction is confirmed with antibodies to asialo-GM(1). However, few, if any, of these reports have evaluated the binding of fresh clinical isolates of P. aeruginosa to asialo-GM(1) or the specificity of the antibodies for the asialo-GM(1) antigen. We confirmed that asialo-GM(1) dissolved in dimethyl sulfoxide could be added to the apical membrane of Madin-Darby canine kidney cells growing as a polarized epithelium on Transwell membranes (J. C. Comolli, L. L. Waite, K. E. Mostov, and J. N. Engel, Infect. Immun. 67:3207-3214, 1999) and that such treatment enhanced the binding of P. aeruginosa strain PA103. However, no other P. aeruginosa strain, including eight different clinical isolates, exhibited enhanced binding to asialo-GM(1)-treated cells. Studies with commercially available antibodies to asialo-GM(1) showed that these preparations had high titers of antibody to P. aeruginosa antigens, including whole cells, purified lipopolysaccharide (LPS), and pili. Inhibition studies showed that adsorption of an antiserum to asialo-GM(1) with P. aeruginosa cells could remove the reactivity of antibodies to asialo-GM(1), and adsorption of this serum with asialo-GM(1) removed antibody binding to P. aeruginosa LPS. Antibodies in sera raised to asialo-GM(1) were observed to bind to P. aeruginosa cells by immunoelectron microscopy. Antibodies to asialo-GM(1) inhibited formation of a biofilm by P. aeruginosa in the absence of mammalian cells, indicating a direct inhibition of bacterial cell-cell interactions. These findings demonstrate that asialo-GM(1) is not a major cellular receptor for clinical isolates of P. aeruginosa and that commercially available antibodies raised to this antigen contain high titers of antibody to multiple P. aeruginosa antigens, which do not interfere with the binding of P. aeruginosa to mammalian cells but possibly interfere with the binding of P. aeruginosa cells to each other.

Methemoglobinemia after axillary block with bupivacaine and additional injection of lidocaine in the operative field.

Methemoglobinemia may occur after the administration of various drugs, including some local anesthetics. We report a patient with chronic renal failure and ischemic heart disease who developed clinically significant methemoglobinemia after an axillary block with bupivacaine and additional injection of lidocaine in the operative field. Although the two local anesthetics usually do not cause methemoglobinemia, we suspect that the displacement of lidocaine from protein binding by bupivacaine, in combination with metabolic acidosis and treatment with other oxidants, was the reason for the development of methemoglobinemia.

[Transesophageal echocardiography: perioperative evaluation of valvular function]. / Transösophageale Echokardiographie. Perioperative Beurteilung der Herzklappen.

Since its introduction into the operating room, transesophageal echocardiography (TEE) has proven to be an invaluable diagnostic tool for perioperative patient management. TEE allows direct visualization of structural and functional cardiac abnormalities. Therefore, it has become the most important imaging technique to evaluate valular function. Pressure gradients across a stenotic valve can be calculated by measuring the blood flow velocity within the valve. Additionally, the area of the valve can be estimated by using the continuity equation. The severity of regurgitant blood flow across an incompetent valve can be assessed using color flow, continuous or pulsed-wave Doppler. Surgical patients experience significant changes in blood pressure, intrathoracic pressures and volume status in the perioperative period. Therefore, the interaction between these parameters and valvular function is the focus of recent clinical studies and might in future contribute to the perioperative as well as anesthesiological management of patients with valvular dysfunction.