The concentration of console surgeons: prospective evaluation of the loss of attention in robotic-assisted procedures.

To prospectively evaluate the possible loss of attention among console surgeons performing robotic-assisted procedures using a validated psychological test. The concentration of one console surgeon was assessed before and after 25 robotic-assisted procedures (radical prostatectomies) using the validated d2 attention test (computer-assisted, Hogrefe test systems, Germany). Error frequency, work rate, and accuracy of task performance were evaluated as parameters of the fluctuation in concentration. Data were correlated with clinical parameters, including console times, positive surgical margin rates and the use of a nerve-sparing procedure. Pre- and post-operative test results revealed no differences in the number of items performed, but a significant decline in the error-corrected performance between the pre- and post-operative tests was observed with increasing console time (p = 0.046; median console time 123 min.). No differences in the pre-operative tests for consecutive procedures (mean time between procedures 93 min.) were found, whereas the number of errors (missed items) increased in the post-operative tests (p = 0.0025). The measured differences in test results showed no association with the positive surgical margin rate. A planned nerve-sparing procedure tended to result in a lower level of concentration found in pre-operative testing (p = 0.07). Concentration decrease and loss of attention during robotic-assisted procedures can be measured validly using the d2 attention test. Longer console times lead to loss of attention but consecutive procedures do not decrease the test or surgical performance. Further studies need to address whether similar effects apply to the comparable open or other robotic procedures or to different levels of surgeons experience.

Intensified neoadjuvant chemoradiotherapy in locally advanced rectal cancer -- impact on long-term quality of life.

AIMS: In spite of advances in rectal cancer surgery and the use of preoperative 5-fluorouracil-(5-FU) based chemoradiotherapy (CRT) in stage II and III disease distant metastases still occur in about 35-40% of the patients. Intensified preoperative CRT (ICRT) using other drugs in conjunction with 5-FU has been investigated in order to improve the pathological complete remission (pCR) rate and thereby prognosis of patients with locally advanced rectal cancer. However, acute toxicity, especially diarrhea, was reported to be high and no improvement in pCR rates has been observed in randomized trials. Long-term results of these trials are pending. In the present analysis we investigated the impact of ICRT on health related quality of life and long term toxicity. METHODS: The present study included 119 patients with locally advanced rectal cancer who underwent neoadjuvant CRT followed by surgery within controlled clinical trials. Patients received ICRT (n = 83) or standard CRT (n = 36). Evaluation of HRQoL was performed using EORTC QLQ-C30 and QLQ-CR29 questionnaires. RESULTS: The overall rating of global health status/QLQ scale of the EORTC QLQ-C30 questionnaire was identical in both patient groups but patients in the CRT group showed better results in four out of nine function scales. Concerning symptom scales, patients in the CRT arm exhibited significantly less diarrhea (p = 0.028) and less disorders with taste (0.042). CONCLUSIONS: This data suggests that higher gastrointestinal acute toxicity caused by ICRT might lead to a higher risk of long-term deterioration of "gastrointestinal QoL". Future results of randomized trials investigating ICRT versus CRT should be discussed in the light of long-term QoL data.

Dosimetric consequences of a translational isocenter correction based on image guidance for intensity modulated radiotherapy (IMRT) of the prostate.

Interfractional prostate motion during radiotherapy can have deleterious clinical consequences. It has become clinical practice to re-position the patient according to ultrasound or other imaging techniques. We investigated the dosimetric consequences of the linear translational position correction (isocenter correction) when a conformal IMRT technique with nine fields was used. Treatment plans of seven patients with empty and distended rectums were analyzed. The reference plans were calculated on the CT with an empty rectum. The treatment plans were transferred to a second CT with a distended rectum for an uncorrected setup of the patient referenced to bony anatomy and a corrected setup after translational position correction of the isocenter. The dosimetric consequences (with and without correction) were analyzed. For single treatment fractions, organ motion decreased the volume of the prostate encompassed by the 95% isodose (V95%) by up to -24%-p (percentage points). The mean rectum dose increased by up to 41%-p. Linear translational correction increased V95% of the prostate by up to 17%-p while the mean rectum dose was reduced by up to -23%-p compared to the uncorrected setup. Linear translational correction can improve radiation treatment accuracy for prostate cancer if geometrical changes are within certain limits.

[Complications and side effects of low dose rate brachytherapy for the treatment of prostate cancer: data on a 13 year follow-up study from Mannheim]. / Komplikationen und Nebenwirkungen der LDR-Brachytherapie beim Prostatakarzinom : 13-Jahresdaten aus Mannheim.

BACKGROUND: Brachytherapy (BT) is an established treatment option for low risk prostate cancer. The aim of this study was to determine the long-term complications and side effects of the procedure in an up to 13 year long single center follow-up analysis. MATERIAL: A total of 505 patients were treated by BT for prostate cancer between May 1991 and August 2005. Cohort I (n=412; May 1991 to November 2003) was evaluated by written questionnaire (modified ICS male) and patient chart evaluation in terms of side effects and secondary interventions. In cohort II (n=148; January 2002 to August 2005) perioperative complications were investigated. RESULTS: The mean follow-up was 5.5 years. Perioperative complications were present in 5.4% of patients. Transurethral resection of the prostate was a common secondary intervention, performed in 7% of cases. The rate of incontinence was 6.3% in the long-term follow-up, the rate of potency was 43.5% in those patients who were potent before BT and no hormonal manipulation was performed at any time. CONCLUSION: BT is a minimally invasive procedure for the treatment of localised "low risk" prostate cancer. Perioperative complications are rare, secondary intervention may be necessary and the patient has to be informed of possible impotence, incontinence and lack of ejaculation.

Cardiovascular and metabolic effects of adenosine A1-receptor agonists in streptozotocin-treated rats.

Because one manifestation of diabetes is an enhancement of the lipolytic process, we evaluated the antilipolytic effects of adenosine A1 agonists in vitro and in vivo in streptozotocin (STZ)-treated diabetic rats. In vitro, we examined the responses to norepinephrine (NE) and adenosine deaminase (ADA), as well as several adenosine A1 agonists, in isolated adipocytes from normal and diabetic rats. Both NE and ADA caused dose-dependent stimulation of lipolysis, elevating glycerol release twofold to threefold over baseline. The sensitivity to both NE and ADA was significantly enhanced in adipocytes from STZ-treated as compared with normal rats. N-5'-ethyl-N(6)(cyclopentyl) adenosine-5'-uronamide (RG14202) was by far the most potent A agonist in inhibiting NE-stimulated lipolysis [50% effective concentration (EC50): 0.014 +/- 0.0008 nM), approximately 1 and 2 log units more potent than N(6)-cyclopentyladenosine (CPA) and N(6)-cyclohexyl-2'-O-methyladenosine (SDZ WAG 994), respectively. In vivo we established a model for evaluating the therapeutic utility of adenosine A1 agonists, emphasizing duration of action. In STZ rats instrumented with telemetry transmitters, the metabolic effects of CPA, RG14202, and SDZ WAG 994 were assessed 6 h after oral administration. Under those conditions, RG14202 and SDZ WAG 994, but not CPA, significantly reduced triglycerides (TRIs) and TRI/free fatty acids (FFAs), respectively. However, all three A1 agonists dose-dependently reduced mean arterial pressure (MAP) and heart rate (HR) concurrently. Thus adenosine A1 agonists can inhibit lipolysis in vitro and in vivo; however, oral administration produces long-lasting beneficial metabolic effects only at doses that also produce a significant bradycardia.

Water-in-oil microemulsions containing medium-chain fatty acids/salts: formulation and intestinal absorption enhancement evaluation.

PURPOSE: Water-in-oil (w/o) microemulsions have been developed which, in addition to non-ionic medium-chain glycerides, incorporate ionic lipids, primarily medium-chain fatty acids, such as caprylic (C8) capric (C10) and lauric (C12) acids and their corresponding sodium salts. The absorption enhancing activity of w/o microemulsions incorporating these lipids was evaluated in the rat using Calcein (MW = 623) a water-soluble and poorly absorbed marker molecule. METHODS: Phase diagrams were constructed where C8/C10 or C12 fatty acids were treated as lipophilic surfactants and their sodium salts as hydrophilic ones. The anesthetised rat model was employed to evaluate Calcein absorption upon a single intraduodenal administration from a solution and the various w/o microemulsions. RESULTS: A wide range of clear and transparent w/o microemulsions were obtained at ambient temperature either in liquid or solid form when a fixed blend of medium chain fatty acid/salt was titrated by a fixed ratio of the oil containing the oil-soluble mono- and diglycerides and deionized water or physiological saline. Upon intraduodenal administration in the anesthetised rat, the absorption of Calcein was improved from about 2% in aqueous solution up to about 37% in w/o microemulsions. Solid and liquid formulations were equally effective in improving bioavailability. The absorption enhancement activity of the fatty acids/salts followed the order C8 approximately C10 > C12. Absorption enhancement of Calcein was significantly reduced in the absence or presence of low levels of C8/C10 mono-/diglycerides. CONCLUSIONS: These results further support the use of medium-chain glycerides and fatty acids/salts in microemulsion formulations to improve intestinal absorption of water-soluble compounds.

Characterization of the renal effects and renal elimination of sulotroban in the dog.

The renal effects and renal handling of the nonprostanoid thromboxane receptor antagonist, sulotroban (4-[2-(phenylsulfonylamino)ethyl]phenoxyacetic acid), were characterized in dogs. Sulotroban was infused i.v. at 0.06, 0.2, 0.6 and 1.0 mg kg-1 min-1 (plus prime) for 180 min. Arterial blood pressure was reduced significantly during infusion of the 1.0 mg kg-1 min-1 dosage only. Diuresis, characterized by increases in both fractional and absolute urinary excretion of sodium, potassium, chloride and calcium, and decreases in urine osmolality occurred at each of the sulotroban dosages tested. The renal clearance of sulotroban exceeded the glomerular filtration rate, suggesting renal secretion of sulotroban. The transport maximum for sulotroban secretion was approximately 160 micrograms kg-1 min-1. Renal cortical slices from naive dogs accumulated [14C]sulotroban against a concentration gradient. Sulotroban accumulation was blocked by metabolic inhibitors (dinitrophenol and sodium azide) and inhibitors of organic anion transport (probenecid and p-aminohippurate), but not by inhibitors of organic cation transport (cyanine and tetraethylammonium), suggesting that tubular secretion of sulotroban is mediated by an organic anion transport system. It was concluded that: 1) decreases in blood pressure occurred only after high dosages and were associated with high plasma sulotroban concentrations; 2) diuresis occurred at all dosages and may represent a separate pharmacological action unrelated to thromboxane receptor antagonism; and 3) renal excretion of sulotroban in the dog occurs by both filtration and tubular secretion with secretion occurring via an organic acid transporter.