The critical role of axillary ultrasound and aspiration biopsy in the management of breast cancer patients with clinically negative axilla.

BACKGROUND: Sonographic evaluation of the axilla can predict node status in a significant proportion of clinically node-negative patients. This review focuses on the value of ultrasound followed by ultrasound-guided cytology in assessing the need for sentinel node mapping and conservative versus complete axillary dissections. DESIGN: Breast primaries from 168 sentinel node candidates were prospectively assessed for clinicopathologic variables associated with increased incidence of axillary metastases. Patients were classified accordingly, and those at a higher risk underwent ultrasound of their axillae, followed by aspiration biopsy if needed. Sentinel node mapping was performed in all low-risk patients, and in high-risk patients with normal axillary ultrasounds or negative cytology. Final axillary status was compared in terms of nodal stage, number of positive nodes, and size of metastasis. RESULTS: 112 patients were at high risk for nodal disease (67%), with a statistically significant lower probability for remaining node-negative and a statistical significantly higher risk for having more than one positive node. All patients with more than three positive nodes were detected by ultrasound-guided cytology. High-risk patients with final positive axillae missed by ultrasound or ultrasound guided cytology had tumor deposits measuring

Continent ileocecal augmentation cystoplasty.

OBJECTIVES: To evaluate the use of the ileocecal bowel segment for bladder augmentation in a select group of patients who need a low pressure, high capacity urinary storage mechanism and a continent, catheterisable, cutaneous stoma that, because of their physical limitations, is easier to catheterize than their native urethra. METHODS: We reviewed records of 23 continent ileocecal augmentation cystoplasties performed over the last 5 1/2 years. The goals of the operation, patient selection criteria, pre-operative evaluation, operative technique, and post-operative evaluation with results were studied. RESULTS: Twenty-three patients underwent the procedure with the average follow-up being 26.9 months (range 3-67 months). Bladder capacity was increased by an average of 276.8 milliliters (ml). No metabolic problems have been detected, and 95% (22/23 patients) are continent via their urethra and stoma. CONCLUSIONS: This unique modification of the Indiana continent urinary reservoir is not technically difficult to create and is relatively free of complications. The bladder capacity is greatly increased and post-operative continence rates are excellent. Finally, the quality of life for these patients has been significantly improved by their ability to access the augmented bladder independently via an abdominal stoma.

Ileovesicostomy as an alternative form of bladder management in tetraplegic patients.

OBJECTIVES: Bladder management in tetraplegic patients traditionally has been intermittent catheterization by a caretaker, placement of indwelling suprapubic or urethral catheters, sphincterotomy and external catheter drainage, or supravesical urinary diversion with an ileal conduit. The aim of this study was to examine the ileovesicostomy as an alternative form of bladder management in such patients. METHODS: We report our experience with ileovesicostomy as an incontinent cutaneous urinary diversion not requiring ureteral reimplantation. Six tetraplegic patients who had experienced significant morbidity with their preoperative form of bladder management were managed with an ileovesicostomy fashioned like a funnel from the bladder dome to the right lower quadrant. All patients underwent preoperative and postoperative fluoroscopic and urodynamic evaluations. Patients were evaluated preoperatively and followed postoperatively with serum chemistries, upper urinary tract imaging, and urine bacteriologic studies. RESULTS: There were no perioperative complications. Postoperative urodynamics demonstrated subjects to have a mean stomal leak-point pressure of 7.7 cm H2O (range 5 to 10). Radiographically, patients carried low urinary residuals (less than 100 cc) and did not exhibit vesicoureteral reflux. In follow-up of 12 to 15 months, no patient has demonstrated calculus formation, hydronephrosis, autonomic dysreflexia, or worsening renal function. CONCLUSIONS: This procedure successfully creates continuous urinary drainage without catheterization, while maintaining the native antireflux mechanism of the ureterovesical junction and avoiding indwelling foreign materials in the urinary tract. Longer follow-up with more cases will be necessary to confirm these findings and to support a recommendation of the incontinent ileovesicostomy as a standard method for managing the neurogenic bladder in tetraplegic patients.

Urodynamics and multiple sclerosis.

Multiple sclerosis is an enigmatic and devastating neurologic disease. Voiding dysfunction is common and the irritative and obstructive symptoms can be disabling to the patient. Voiding symptoms alone are unreliable predictors of bladder and urethral dysfunction secondary to multiple sclerosis. This article focuses on the central role played by urodynamic studies in the initial assessment and management of the lower urinary tract. Detrusor hyperreflexia is the most common urodynamic finding. However, a variety of urodynamic patterns can be seen and voiding function may change over time with this chronic neurologic disorder.

Retrograde nephrostomy: advantages, disadvantages, and the learning curve.

Establishment of a nephrostomy tract is a prerequisite for many endourologic procedures of the upper urinary tract. We reviewed our initial experience with 31 retrograde nephrostomies to determine the advantages and disadvantages and the learning curve for the procedure. All but one of the attempts were successful, and no complications were attributable to the nephrostomy puncture. The procedure time averaged 21.1 minutes in nondilated collecting systems but 32.0 minutes in hydronephrotic kidneys (P < 0.01). The mean procedure time in our first 10 successful cases was 36.2 minutes, but it decreased to 22.6 minutes in the second 10 successful cases (P < 0.02). Radiation exposure was also minimized early, with a mean fluoroscopy time of 3.5 minutes in our first 10 successful cases and 1.5 minutes in our second 10 successful cases (P < 0.02). Similarly, both procedure and fluoroscopy times decreased further in the most recent 10 successful cases. Retrograde nephrostomy is a safe procedure, is easier in a nondilated collecting system, and can be mastered with a short learning curve with minimal radiation exposure.

Pharmacokinetics, safety, and tolerability of flosequinan in patients with hepatic dysfunction.

The pharmacokinetics of flosequinan and its active metabolite, flosequinoxan, were investigated following a single 100-mg oral dose in 10 patients with compromised hepatic function. Plasma and urine samples were collected for up to 144 h postdose and analyzed by HPLC. All 10 patients provided analyzable data even though one patient withdrew before the 144-h sample because of an adverse event unrelated to the study medication. Interpatient variability was appreciable for the plasma and urine concentrations was well as for the calculated pharmacokinetic parameters. Relative to a comparative cohort of normal subjects, flosequinan concentrations in the study patients were elevated, showing increases in mean AUC0-t (62.8 +/- 49.4 vs 3.4 +/- 1.5 micrograms.h/mL), AUC0-infinity (70.2 +/- 58.3 vs 3.8 +/- 1.6 micrograms.h/m:), Cmax (2.43 +/- 0.56 vs 1.30 +/- 0.39 micrograms/mL), and t1/2 (20.7 +/- 16.8 vs 1.7 +/- 0.5 h). The mean systemic clearance decreased (47.3 +/- 46.5 vs 544 +/- 279 mL/min), along with the elimination rate constant (0.066 +/- 0.069 vs 0.44 +/- 0.13 h-1). Mean flosequinoxan AUC0-t and AUC0-infinity values were unaffected by hepatic dysfunction. The mean time to peak was longer (36.4 +/- 27.4 vs 7.0 +/- 3.1 h) and Cmax was less (0.98 +/- 0.52 vs 1.84 +/- 0.26 micrograms/mL) than in normal subjects. These findings are consistent with a decrease in the rate of flosequinan metabolism to flosequinoxan. Five patients reported adverse events, which included headache (three patients) and syncope (one patient).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic profile of flosequinan in patients with compromised renal function.

The pharmacokinetics of flosequinan and its major active metabolite (BTS 53,554, 7-fluoro-1-methyl-3 methylsulfinyl-4-quinolone, 1) were investigated following a single oral dose of 100 mg of flosequinan in 20 patients with severe renal dysfunction (creatinine clearance, < or = 25 mL/min). Plasma and urine samples were collected for 144 h post-dose and analyzed by high-performance liquid chromatography. Flosequinan was well absorbed and rapidly eliminated, reaching mean peak concentrations in plasma of 1.37 +/- 0.67 micrograms/mL at 1.6 +/- 1.4 h post-dose. As in healthy volunteers, approximately 1% of the administered dose of flosequinan was excreted unchanged in urine. Renal clearance of flosequinan was decreased by an average of 20% relative to healthy volunteers. The active metabolite 1 reached mean peak concentrations in plasma of 2.22 +/- 0.58 micrograms/mL at 10.9 +/- 5.9 h post-dose and yielded mean areas under the curve of concentration in plasma versus time twice that of healthy volunteers. Elimination rates for 1 decreased by half, and the mean elimination half-life increased to 68.5 +/- 24.2 h compared with 34.5 +/- 6.7 h for healthy volunteers. The decrease in elimination rate resulted in higher exposure to total active drug substance (flosequinan plus metabolite) for renal patients than for healthy volunteers. These results suggest dosage adjustments may be necessary in patients with severe renal dysfunction to prevent excessive accumulation of 1 with repeated dosage of flosequinan.

Flurbiprofen in post-partum women: plasma and breast milk disposition.

The plasma and milk disposition of flurbiprofen (FB) was assessed in healthy women during the early post-partum period after multiple doses of FB. The results confirmed that a pragmatic study design is an attainable requirement for definitive statements about the excretion of FB in transitional milk. Nine doses of FB (50 mg per dose) were administered during three days. Paired milk and plasma samples were obtained during this period of dosing as well as after the last dose. The plasma data were used to derive an equation, which was then used to simulate cumulative plasma profiles for multiple doses given at unequal time intervals. The observed data corresponded to the simulated cumulative profiles of FB in plasma. The plasma elimination half-life of FB during early lactation was slightly prolonged (mean 4.8 hrs) as compared to reported values for normal adult men. The peak plasma concentrations of FB were comparable to those reported for healthy volunteers. In 10 of 12 women (3-5 days post-partum) the FB concentration in breast milk was less than 0.050 micrograms/ml. In two women the milk concentrations of FB were 0.06, 0.07 and 0.07 micrograms/ml as found in only three samples. We conclude that, on the basis of dose found in milk, FB is safe for women breast feeding their infants in the early post-partum period.

Pharmacologic factors contributing to variance in the milk to plasma ratio for acetaminophen in the goat.

A single-point estimate of the milk to plasma (M/P) drug ratio presupposes an invariant ratio. This may lead to erroneous conclusions about the amount of drug excreted in breast milk. A variance of the M/P ratio with regard to time has been shown for acetaminophen under standardized biologic conditions in the lactating goat. This ratio is potentially confounded by such factors as route of administration, dose amount and duration of exposure to the drug. Each factor was evaluated by computer simulations of the M/P ratio and by derivation of a ratio from empirical data in the goat. Route of administration was found to influence both the pattern and magnitude of the M/P ratio after acetaminophen dosing in the goat. Similar, but less, effects were found for duration of dosing. Dose itself did not influence the ratio. A temporal basis exists for each confounding factor. We thus propose that the M/P ratio is fundamentally variant with time under a standard set of biologic conditions. The contributing variance of confounding factors must be assessed if drug in milk dosing of the infant is to be accurately evaluated by use of the M/P ratio.