5078 Background: This randomized trial was designed to assess the long-term efficacy of intravesical passive diffusion mitomycin-C (PD/MMC), electromotive/mitomycin-C (EMDA/MMC) and bacillus Calmette-Guerin (BCG) in carcinoma in situ (Tis) of the urinary bladder. Methods: 108 patients with Tis of the bladder were randomly assigned to: 40 mg PD/MMC for 60 min (n=36); 40 mg EMDA/MMC with 20 mA electric current for 30 min (n=36); or 81 mg BCG for 120 min (n=36). All patients were scheduled for 6 weekly treatments. Non-responders received another 6 weekly treatments while responders received 10 monthly treatments. Analyses were done by intention to treat. Results: The complete response rates at 3 months for the PD/MMC, EMDA/MMC and BCG groups were 28%, 53% and 56%, respectively (p=0.0361). At 6 months the corresponding rates rose to 31%, 58% and 64% (p=0.0123). After a median follow-up of 82.5 months (range 17.8–148.8) 32/108 patients (29.6%) were disease-free. They included 7 (19.4%) in the PD/MMC group, 12 (33.3%) in the EMDA/MMC group and 13 (36.1%) in the BCG group (p<0.0001). Median time to first recurrence was 9.1 months in the PD/MMC group, 15.0 months in the EMDA/MMC group and 17.8 months in the BCG group (p<0.0001). Progression to muscle invasive disease was reported in 37/108 patients (34.2%), who included 16 (44.4%) in the PD/MMC group, 11 (30.6%) in the EMDA/MMC group and 10 (27.8%) in the BCG group (p=0.0612). Median time to progression was 21.5 months in the PD/MMC group, 26.9 months in the EMDA/MMC group and 27.8 months in the BCG group (p=0.0612). The overall mortality rate was 50.9% (55/108). Death occurred in 19 patients (52.7%) in the PD/MMC group, 17 (47.2%) in the EMDA/MMC group and 19 (52.7%) in the BCG group (p=0.4964). 27 deaths (25%) were due to bladder cancer with 11 patients (30.5%) dying in the PD/MMC group, 8 (22.2%) in the EMDA/MMC group and 8 (22.2%) in the BCG group (p=0.4941). Conclusions: Intravesical EMDA/MMC provides a better response rate and disease-free interval than passive MMC transport. However, after all approaches, the complete response rates and times to recurrence are unreliable predictors of outcome in these high risk patients. No significant financial relationships to disclose.

5027 Background: To evaluate and compare the results of electromotive mitomycin-C (MMC) instillation administered before transurethral resection (TUR) with TUR alone or TUR plus single immediate MMC instillation on recurrence rate and time to first recurrence in patients with pTa bladder tumors. Methods: From 1994 to 2002, 167 patients with stage pTa and grade G1-G2 primary bladder tumors entered the study and were randomized to receive: TUR alone (Group-1; n=57), TUR plus one single immediate MMC 40 mg passive diffusion instillation with a dwell time of 60 minutes (Group-2; n=56) and one single immediate electromotive MMC 40 mg instillation with 20 mA electric current for 30 minutes before TUR soon after the induction of anesthesia (Group-3; n=54). All the patients were followed with ultrasound, urinary citology and cystoscopy. Clinical analyses were performed on an intent to treat basis. Results: During a median followup of 84.7 months (IQR 56.6) there was recurrence in 88/167 patients (52.7%), including 38/57 (66.7%) in Group-1, 30/56 (53.6%) in Group- 2 and 20/54 (37%) in Group-3 (p=0.007). In 58 patients with grade G1 tumors, 11 (19.0%) had recurrence, 6/20 (30%) in Group-1, 4/24 (20%) in Group-2 and 1/18 (5.6%) in Group-3 (p=0.157). In 109 patients with grade G2 tumors, 77 (70.6%) had recurrence, 32/37 (86.5%) in Group-1, 26/36 (72.2%) in Group-2 and 19/36 (52.8%) in Group-3 (p=0.007). In 71 patients with single tumors, 26 (36.6%) had recurrence, 12/24 (50%) in Group- 1, 9/24 (37.5%) in Group-2 and 5/23 (21.7%) in Group-3 (p=0.132). In 96 patients with multiple tumors 62 (64.6%) had recurrence, 26/33 (78.8%) in Group-1, 21/32 (65.6%) in Group 2 and 15/31 (48.4%) in Group-3 (p=0.039). Median time to first recurrence was 12.8 months for the Group-1, 14.7 months for the Group-2 and 36.8 for Group-3 (p=0.009). Irritative bladder symptoms were the most frequent side effects occurring in approximately 15% of patients in Group-2. Conclusions: In patients with single or multiple pTa bladder tumors one immediate preoperative intravesical instillation of electromotive MMC significantly decreases the risk of recurrence compared with TUR alone or with one immediate postoperative instillation of passive diffusion MMC. No significant financial relationships to disclose.

Objectives We sought to investigate the effectiveness of glucocorticoid administration or continuous venovenous hemodiafiltration on endothelin and corticotropin-releasing factor release or clearance during prolonged fetal cardiac bypass and on the overall performance of fetuses. Methods Circulating endothelin 1, 2, and 3 and corticotropin-releasing factor levels were measured in fetal ewes during a 60-minute cardiac bypass period performed with an inline axial flow pump. Blood samples were collected before, during, and 90 minutes after cardiac bypass. Animals were divided into 4 groups. The betamethasone group (n = 6) received maternal treatment with 12 mg of betamethasone 1 and 2 days before the experiment. The methylprednisolone group (n = 5) received fetal treatment with 40 mg/kg intravenous methylprednisolone at the beginning of cardiac bypass. The continuous venovenous hemodiafiltration group (n = 4) underwent continuous venovenous hemodiafiltration with a 0.3-m2 polysulfone filter during cardiac bypass. The final group was the control group (n = 4). Results Maternal steroid pretreatment failed to decrease endothelin or corticotropin-releasing factor production when compared with levels in the control animals. Fetal treatment with methylprednisolone produced a significant decrease in endothelin 2 production during cardiac bypass (P < .02) and endothelin 1 production at the end of the experiment (P < .02). Continuous venovenous hemodiafiltration blocked completely the increase of endothelin and corticotropin-releasing factor levels during cardiac bypass (P < .02), which was maintained 90 minutes after cardiac bypass. Acid-base balance was preserved during cardiac bypass by the continuous venovenous hemodiafiltration but worsened after disconnection of the extracorporeal circuit, whereas animals treated with methylprednisolone had better pH, Paco2, and bicarbonate levels by the end of the experiment. The overall tolerance of the procedure was better in the continuous venovenous hemodiafiltration group during cardiac bypass and in the methylprednisolone group at the end of the experiment. Conclusions Continuous venovenous hemodiafiltration provides sustained stability of endothelin levels during fetal cardiac bypass. This technique might help, in association with fetal steroid treatment, to contain the inflammatory response leading to postbypass placental dysfunction.

Study Objective. To quantify and compare neuroendocrine stress responses during and immediately after surgery by laparoscopy, minilaparotomy, and laparotomy for benign ovarian cysts.Design. Prospective study (Canadian Task Force classification II-1).Setting. Tertiary care university hospital.Patients. Thirty healthy women with no major diseases and without endocrine disorders.Interventions. Surgery for benign ovarian cysts performed by laparoscopy (10), minilaparotomy (10), or laparotomy (10).Measurements and Main Results. Venous blood samples were collected at fixed times as follows: at 8 A.M. in the ward before transferring the patient to the operating room (time 0), 30 minutes after the beginning of surgery (time 1), at the end of surgery after extubation with the patient awake (time 2), and 2 and 4 hours after the end of surgery (times 3 and 4). We evaluated intraoperative and postoperative variations of the following stress-related markers: norepinephrine (NE), epinephrine (E), adrenocorticotropic hormone (ACTH), human growth hormone (hGH), prolactin (PRL), and cortisol, and postoperative pain. No differences were present in demographic characteristics and operating times in the three groups. No anesthesiologic or surgical complications occurred. Postoperative pain was similar in the laparoscopy and minilaparotomy group but significantly higher in the laparotomy group (p <0.001). Serum levels of markers were not significantly different among the groups at baseline. In the laparoscopy group the increase of hGH was limited to intraoperative time (p <0.05); increases in NE, E, ACTH, and PRL were limited to intraoperative and early postoperative time after extubation (p <0.01), with only PRL persisting with significantly higher levels after the end of surgery (p <0.05). In the minilaparotomy group no increase was detected for hGH, a significant intraoperative increase in cortisol was present (p <0.05), and NE, E, ACTH, and PRL were significantly higher even after the end of surgery (p <0.01). In this group levels of NE, E, and hGH were significantly higher than in the laparoscopy-group 2 and 4 hours after the end of surgery (p <0.05). In the laparotomy group significant intraoperative increases were present for all stress markers and persisted until after extubation for ACTH (p <0.01) and to the postoperative period for NE (p <0.07), E (p <0.07), cortisol (p <0.01), PRL (p <0.05), and hGH (p <0.01). In this group levels of NE, E ACTH, and hGH were significantly higher than those in the laparoscopy group from the beginning (NE p <0.05, E p <0.01, ACTH p <0.05, hGH p <0.01) until after the end of surgery. Comparison of laparotomy and minilaparotomy groups showed the former to have significantly higherplasma levels of E, cortisol, and hGH in intraoperative and postoperative times (p <0.00 1); significantly higher NE at sampling times I and 2 (p <0.001) and time 4 (p <0.01), and no difference at sampling time 3; and ACTH significantly higher only during surgery (p <0.01).Conclusion. Laparoscopic surgery causes minimal activation of stress hormones, which in some instances is confined to the intraoperative period. Minilaparotomy may be a valid alternative to laparoscopy in high-risk patients who cannot tolerate abdominal distention.

The aim of the study was to assess plasma catecholamine levels in patients undergoing myocardial revascularization and relate them to pulsatile (P) and nonpulsatile (NP) normothermic cardiopulmonary bypass (CPB). Twenty-eight patients were randomly assigned to different CPB management: 15 patients were assigned to group ‘P’, 13 patients to group ‘NP’. During normothermic extracorporeal circulation, group ‘P’ received pulsatile perfusion, while group ‘NP’ received nonpulsatile perfusion. Levels of epinephrine and norepinephrine were evaluated during the operation and in the intensive care unit (ICU), at seven time points. Haemodynamic assessment was performed at four time points in the same period. Demographic and surgical data were collected, and the postoperative course was analysed. Epinephrine levels were markedly increased during CPB in both groups, while norepinephrine increased more in group NP in comparison with group P. No significant difference was found in fluid administration, transfusion, drugs usage, or postoperative complications. Normothermic pulsatile CPB seems to achieve reduced levels of norepinephrine. A clinical beneficial effect of this finding was not demonstrated during the study.

BACKGROUND:During cardiopulmonary bypass (CPB) an intracellular ATP deficit could theoretically play a role in changes of erythrocyte shape and deformability caused by mechanical trauma. We therefore studied erythrocyte energy metabolism in 12 patients undergoing normothermic CPB for myocardial revascularization. METHODS:Blood samples were collected prior to and 45 minutes after CPB beginning and analyzed for erythrocyte ATP, ADP, and AMP and their metabolites, erythrocyte NAD and NADP, plasma and whole blood lactate (Lact(p) and Lact(b) respectively), and whole blood pyruvate (Pyr(b)). RESULTS:Values were expressed as mean +/- standard deviation or median (lower and higher quartiles) on the ground of a test for normality. During CPB erythrocyte nucleotides and their metabolites did not change significantly (ATP: 60.2+/-12.1 vs. 68.3+/-13.0; ADP: 12.2+/-3.6 vs. 12.0+/-3.1; AMP: 0.43+/-24 vs. 0.44+/-0.26; adenosine: 0.063 (0.034-0.203) vs. 0.77 (0.032-0.221); inosine: 0.064 (0.023-0.072) vs. 0.075 (0.025-0.111); hypoxanthine: 0.330+/-0.272 vs. 0.367+/-0.223; xanthine: 0.193+/-0.090 vs. 0.220+/-0.095; NAD: 3.149+/-0.743 vs. 3.358+/-0.851; values in microM/mM packed red blood cell hemoglobin) while NADP increased (2.110+/-0.390 vs. 2.433+/-0.288 microM/mM packed red blood cell hemoglobin; p<0.05). Ringer lactate, with which the extracorporeal circuit was primed, caused Lact(p) to increase (1.87+/-0.81 vs. 3.27+/-1.15 mM/l; p<0.01). Some lactate entered erythrocytes since Lact(p)/Lact(b) ratio did not change (1.09+/-0.25 vs. 1.07+/-0.23) and some was transformed into pyruvate since Pyr(b) increased [62.9 (30.3-73.3) vs. 100.5 (61.0-146.9) microM/l; p<0.01]. Lact(b)/Pyr(b) ratio did not change significantly [22.6 (16.1-40.5) vs. 27.9 (17.5-35.2)] so that NAD/NADH ratio and, consequently, the rate of glycolysis were unlikely to change too. CONCLUSIONS:Erythrocyte energy metabolism is not affected by CPB, at least during the period of time taken into account in this study.

Cardiac surgery is often associated with a postoperative increase in the patient's metabolic rate; surface rewarming has been suggested to decrease the energy expenditure by preventing hypothermia. Thirty patients, undergoing coronary revascularization, were randomly divided into two groups; after surgery group A was rewarmed by a new device that acts by both conduction and convection, while group B was just covered with cotton blankets. Blood, oesophagus and skin (thigh and foot) temperatures were recorded on admission to the intensive care unit (ICU) and 30, 60, 90, 180, 270, and 450 min later. Haemodynamic parameters, oxygen delivery, calculated oxygen consumption, and plasma lactate concentration were assessed as well. Group A warmed up quicker than group B as far as the skin was concerned while the core temperature was unaffected. Group A was also characterized by lower cardiac indices and oxygen consumption. As the occurrence of a dependence of oxygen consumption on delivery could be reasonably ruled out in warmed patients because blood lactate levels were lower than in the controls, we conclude that surface rewarming might have some positive effect in decreasing metabolic demand after cardiac surgery even if the patient's core temperature is little affected. The inhibition of skin temperature receptors could possibly explain this finding.

Pheochromocytoma (Pheo) is an uncommon neoplasm producing blood pressure troubles and it may be undiagnosed in chronic dialyzed patients in whom hypertension is a common finding. The symptoms in Pheo syndrome depends on the prevalent catecholamine released, the most common being epinephrine (E) and norepinephrine (NE). Recently, a particular clinical picture has been described for dopamine (DA)-producing Pheos, in whom a normo-hypotensive status is more often observed. The authors report a case of mainly dopamine-producing Pheo in a long-term dialyzed patient, successfully treated with adrenalectomy. The main steps in diagnosis and preoperative management are described and debated also in view of the particular background produced by the end-stage renal failure. The common imaging techniques adopted for adrenal medullary neoplasms (US, CT, MIBG scintiscan) confirmed to be decisive for diagnosis; HPLC assay of plasma catecholamines is the only biochemical test available in these patients although its significance is questionable due to the poor knowledge of catecholamine metabolism in chronic renal failure. The clinical findings observed in this case seem in disagreement with those already reported in DA producing Pheos. Pheo in hemodialyzed patients is a rare event and it may be hidden by other more common causes of hypertension. However, more awareness from the medical staff allows to diagnose the neoplasm correctly by the currently available methods and to plan a safe surgical therapy also in high-risk patients.

STUDY OBJECTIVE:To evaluate the stress hormone response after pelvic surgery performed by laparoscopy versus laparotomy.DESIGN:Prospective study.SETTING:A tertiary care university hospital.PATIENTS:Ten women were scheduled to undergo laparoscopic surgery and 10 laparotomy for either tubal disease or endometriosis.INTERVENTIONS:Surgical procedures were performed by laparoscopy or laparotomy for stage III-IV endometriosis, pelvic adhesions, or distal tubal occlusion. The following hormones were measured before the induction of anesthesia in the ward, 60 minutes after the beginning of surgery, at the end of surgery after extubation, and 2 hours and 6 hours after the end of the operation: norepinephrine (NE), epinephrine (E), dopamine (D), adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), and GH.MEASUREMENTS AND MAIN RESULTS:The mean duration of surgery was not significantly different between the two groups. Surgery-related adrenergic activation (E, NE, D) appears more pronounced in the laparotomy group (p<0.005) during surgery and in the postoperative period. More elevated values for laparotomy were observed also for the other stress hormones (ACTH, cortisol, PRL, GH), even though statistical significance was not always reached.CONCLUSIONS:Compared with laparotomy, activation of stress-related factors during laparoscopy seems to be less intense and of shorter duration.

The anesthetic management of a hemodialyzed patient with a dopamine producing pheochromocytoma is described. A 56-years old man underwent surgical procedure the day after hemodialysis. Prior to intervention adrenal cortex hormones were normal as well as other endocrine variables (T3-T4-TSH-cortisol-ACTH-parathyroid hormone); epinephrine and norepinephrine, were in a normal range while dopamine was elevated (185 pg/ml). Preoperatively the patient was alpha-blocked with oral phenoxybenzamine (20 mg/day). A balanced anesthesia was performed (isoflurane and fentanyl). Plasma catecholamines were determined. During the induction of anesthesia and before tracheal intubation phentolamine and labetalol were injected till 3.4 mg and 50 mg total dose respectively. During surgical manipulation a nitroglycerin infusion was started (1.5 gamma/kg/min) and after tumor resection dopamine was given till 15 gamma/kg/min. Hormonal values increased in presence of unchanged hemodynamic parameters, likely due to alpha and/or beta blockade. In this case report our problem was especially fluid replacement after tumor resection, because of renal failure. On the basis of CVP and PCWP values, fluid treatment and dopamine infusion allowed to achieve an adequate preload. A sufficient level of analgesia and an efficient alpha blockade may assure hemodynamic stability also in a so compromised patient status.

The changes of erythrocyte Na, K, C1, and Mg during open-heart surgery were studied in 10 patients undergoing aorto-coronary bypass and in 10 patients undergoing valvular replacement and chronically treated with digitalis and diuretics. The results showed: initial Mg levels lower in both groups of patients than in 10 healthy subjects utilized as controls (p less than .01); higher initial Na levels in patients treated with digitalis and diuretics than in controls (p less than .001); no electrolyte change during extracorporeal circulation; significantly increased Na values at the end of surgery and in the 1st postoperative day, that were probably caused by erythrocyte damage during CPB. The increase was observed following the CPB because of the slow rate of erythrocyte Na changes.

Fifty consecutive patients were monitored during cardiac surgery. Cardiac index (CI), O2 delivery (O2 del), O2 uptake (VO2) and blood lactates were collected: before surgery (1); at the end of surgery (II); at the first hour in the Intensive Care Unit (ICU) (III); at the sixth hour in ICU (IV). Time variations were significant for all the parameters studied. Progressive lactate increase up to time I occurred simultaneously with a progressive CI and O2 del decrease, even though the latter values were greater than the critical levels for patients under anesthesia or sedation. Positive correlations at time III, especially between CI and lactates and between O2 del and lactates, indicate than an O2 debt had already begun to develop, probably during CPB. At time IV, blood lactate decrease accompanied by CI, O2 del and VO2 increase, indicated metabolic and O2 debt improvement. Negative correlations at this time further explained this trend. Failure to normalize blood lactate was due to the continually low O2 del value compared to time I. As result of this findings it seems important to continue to rigorously support and monitor CPB patients in the ICU during the first critical postoperative hours.