Interactive effects of alpha-interferon A/D and interleukin 2 on murine lymphokine-activated killer activity: analysis at the effector and precursor level.

Studies from our laboratory and others have demonstrated that alpha-interferon (IFN alpha) can regulate natural killer cells and lymphokine-activated killer (LAK) cell activation. In vitro experiments have shown that IFN alpha has differential effects on both natural killer cells and LAK activity when combined with interleukin 2 (IL2); IFN alpha synergized with IL2 to augment natural killer cells activity while it suppressed the IL2-induced LAK response. Here we demonstrated that IFN alpha A/D can also regulate IL2-induced LAK activity in vivo with enhanced or suppressed activity depending on the IFN alpha A/D dose. The enhanced response was observed with the combination when 80,000 units/day of IFN alpha A/D were used and was detectable in the spleen, lung, and peritoneum. When a high dose of IFN alpha A/D was combined with IL2, a moderate reduction in LAK activity was noted in the spleen and peritoneum. In contrast, a high dose IFN alpha A/D augmented IL2-induced LAK activity in the lung even though it reduced the level of cellular infiltration. We have also evaluated the effect that IL2, IFN alpha A/D, and IL2 plus IFN alpha A/D have on the frequency of LAK precursors in the spleen and lung using limiting dilution analysis. Treatment of normal mice with IL2 alone increased the frequency of LAK precursor (LAKp) in the lung. This increase was associated with an infiltration of Thy-1+, asialo-GM1+, Lyt-2- lymphocytes into the lungs. Moreover, treatment with IL2 plus IFN alpha A/D enhanced the frequency of LAKp over that observed with IL2 alone. Treatment with the combination did not change the phenotype of LAKp in the lung from that seen with IL2. The increase in LAKp frequency induced by the combined treatment may not be a direct effect of IFN alpha A/D on precursor cells since IFN alpha A/D alone did not increase the frequency of LAKp in vivo or in vitro when added to limiting dilution analysis cultures. In contrast to what occurred in the lung, a consistent increase in LAKp was not seen in the spleen after treatment with IL2 or with the combination, although LAK activity was observed. These results demonstrated that in addition to inducing lytic activity from LAK effectors in vivo, IL2 treatment increased the number of precursor cells within the lung. Moreover, IFN alpha A/D in combination with IL2 influenced the level of LAKp in situ.

Dosimetric comparison of pre-planned and or-planned prostate seed brachytherapy.

PURPOSE: To compare the dosimetry of the traditional two step procedure (volume study + treatment planning several weeks later) with that of an OR-based single procedure in which these two steps follow one another immediately. Computer generated treatment plans were used in both procedures. METHODS AND MATERIALS: Several dosimetric parameters relating to target coverage were obtained from dose volume histograms of CT-based evaluation plans developed either 1 or 3 days following seed implantation. A total of 113 patients with early stage (T1C, T2A) prostate cancer were used for this retrospective study. RESULTS: The fraction of target (prostate) covered by the prescription dose (144 Gy), 90% of the prescription dose (115 Gy), and the dose encompassing 90% of the target in the evaluation plan were all statistically significantly improved for OR-based plans compared to pre-planned cases. CONCLUSION: In our hands, there is a small but significant improvement in dose coverage of the prostate when the ultrasound volume study and treatment planning are combined into a single procedure.

Laparoscopic radical cystoprostatectomy with ileal conduit performed completely intracorporeally: the initial 2 cases.

OBJECTIVES: To present the initial 2 patients who underwent laparoscopic radical cystoprostatectomy, bilateral pelvic lymphadenectomy, and ileal conduit urinary diversion, with the entire procedure performed exclusively by intracorporeal laparoscopic techniques. METHODS: Two male patients, 78 and 70 years old, with muscle-invasive, organ-confined, transitional cell carcinoma of the urinary bladder underwent the procedure. The entire procedure, including radical cystoprostatectomy, pelvic node dissection, isolation of the ileal loop, restoration of bowel continuity with stapled side-to-side ileoileal anastomosis, retroperitoneal transfer of the left ureter to the right side, and bilateral stented ileoureteral anastomoses were all performed exclusively by intracorporeal laparoscopic techniques. Free-hand laparoscopic suturing and in situ knot-tying techniques were used exclusively. RESULTS: The surgical time was 11.5 hours in the first patient and 10 hours in the second. The respective blood loss was 1200 mL and 1000 mL. In both patients, ambulation resumed on postoperative day 2, bowel sounds on day 3, and oral intake on day 4; the hospital stay was 6 days. Narcotic analgesia comprised 108.3 mg and 16.5 mg of morphine sulfate equivalent, respectively. Pathologic examination revealed pT4N0M0 (prostate) and pT2bN0M0 transitional cell carcinoma of the bladder with the surgical margins negative for cancer in both patients. No intraoperative or postoperative complications occurred in either patient. CONCLUSIONS: To our knowledge, this is the initial report of laparoscopic radical cystoprostatectomy with intracorporeal ileal conduit urinary diversion. We believe that with further experience and refinement in the operative technique, laparoscopic radical cystoprostatectomy with ileal conduit urinary diversion may become an attractive treatment option for selected candidates with localized muscle-invasive bladder cancer.

Periprostatic local anesthesia eliminates pain of office-based transrectal prostate biopsy.

Up to 96% of patient who undergo prostate biopsy report pain. We performed periprostatic local anesthesia injection in an effort to improve patient acceptance of prostate biopsy. Sixty patients were randomized to receive either local injection of lidocaine in the periprostatic nerves or no anesthetic. Lidocaine was injected through a 7-inch spinal needle placed through a transrectal ultrasound biopsy guide. Ten-core biopsies were immediately performed. Following biopsy, all patients gave a Visual Analog Scale (VAS) assessment of their pain experienced during biopsy.A majority of patients reported Visual Analog Scale (VAS) scores in the moderate (28.6%) or severe (28.6%) ranges unless local anesthesia was given. Only one of 27 patients (3.7%) receiving local anesthetic reported moderate pain, and none reported severe pain. Mean VAS pain scores were 1.4 in the anesthetic group and 4.5 in the control group (P<0.0001). No difficulty was encountered from scarring in the five patients who underwent nerve spring radical retropubic prostatectomy following local anesthetic injection. Periprostatic injection of local anesthetic essentially eliminates pain from prostate biopsy. Nerve-sparing radical retropubic prostatectomy is not more difficult as a result.

The spectrum of ureteropelvic junction obstructions occurring in duplicated collecting systems.

The authors reviewed four cases of ureteropelvic junction obstruction (UPJ) in duplicated systems. Associated abnormalities included contralateral duplication, vesicoureteral reflux, and a case of ipsilateral upper pole ectopic ureter with a dysplastic upper pole moiety. Surgical management included dismembered pyeloplasty, ureteral reimplantation, end-to-side pyeloureterostomy to the upper-pole ureter, and upper-pole heminephrectomy with lower-pole dismembered pyeloplasty. UPJ obstructions occurring in duplicated systems often are associated with other anomalies.

Laser bladder perforation from photoselective vaporization of prostate resulting in rhabdomyolysis induced acute renal failure.

Hyponatremia and its related comorbidities remain a concern after traditional transurethral resection of the prostrate (TURP). Photoselective vaporization of the prostate (PVP) laser coagulation therapy is a new, relatively bloodless procedure for treatment of benign prostatic hyperplasia (BPH). Perceived benefits with PVP laser TURP include excellent visualization of the operative field during urethral prostatic tissue vaporization and the reduced incidence of laser penetration through the prostatic capsular fibers once the capsule is reached. Theoretically, this would provide a low risk method of perforation during laser TURP. After literature review, we report this as the first case of laser bladder perforation as a complication arising from PVP therapy. This case report discusses the management of acute hyponatremic induced rhabdomyolysis with acute renal failure (ARF) and the recommendation to use sodium chloride vs. sterile water for bladder irrigation during PVP TURP procedures.

Biology of metastasis and its clinical implications: renal-cell cancer.

The ability of malignant cells to metastasize from a primary tumor and from secondary lesions is the most life-threatening aspect of cancer. Reported factors enabling this metastatic cascade to occur include reduced levels or an absence of cell-adhesion molecules, proteolytic enzymes, and angiogenic factors. The metastatic cell must also escape immune destruction. Defects in lymphocytes from renal-cell carcinoma patients with abnormalities in their proliferation, receptor structure, and signal transduction are present. The pathologic stage has been the most consistent single prognostic factor to influence survival. Other factors include the performance status, age, and histology grade and may include serum interleukin 6 (IL-6) levels and ploidy. Current and future therapeutic approaches that interfere with this metastatic cascade include applications of cytokines, antiadhesion-molecule strategies, and antisense nucleotides. An improvement in our understanding of the biology of metastases is essential before a significant increase in the cure rate can be realized.

Successful outcomes in pheochromocytoma surgery in the modern era.

PURPOSE: We describe our experience with surgical management, complications and treatment outcome of histologically confirmed pheochromocytoma. MATERIALS AND METHODS: The records of 113 patients who underwent surgical excision of pheochromocytoma were reviewed and assessed for preoperative medical treatment, intraoperative findings, postoperative hospitalization and complications. RESULTS: There were no surgical mortalities. Average length of stay in the intensive care unit was 1.2 days. There were only 6 major cardiovascular complications all of which occurred in patients who received preoperative medications, including 5 with alpha blockade. Patients receiving no preoperative alpha blockade required an average of 956 cc less in total intraoperative fluids, which approached statistical significance, and 479 cc less fluids on postoperative day 1, which was statistically significant. CONCLUSIONS: Preoperative alpha-adrenergic blockade is not essential in pheochromocytoma patients. Calcium channel blockers are just as effective and safer when used as the primary mode of antihypertensive therapy. Surgery for pheochromocytoma is safe in the modern era.

Cost comparison of radical prostatectomy and transperineal brachytherapy for localized prostate cancer.

OBJECTIVES: To compare perioperative costs associated with radical retropubic prostatectomy (RRP) to transperineal brachytherapy (BXRT) with iodine-125 (125I) seeds in the treatment of localized prostate cancer. METHODS: Actual costs per case for the perioperative period were compiled prospectively for 583 consecutive patients undergoing RRP or BXRT between January 1, 1997 and October 30, 1998 using a hospital-wide cost accounting system. The total cost per case included both technical and professional components. The technical costs included those incurred for anesthesiology, laboratory medicine, medicine, pharmacy, nursing, radiology, 125I seeds, and BXRT technicians. Professional costs included fees from anesthesiology, laboratory, medicine, urology, radiation oncology, and physics. Cases were divided into three groups for analysis: group 1, RRP (n = 404); group 2, BXRT with planning ultrasound performed in the office setting before implantation (n = 107); and group 3, BXRT with planning ultrasound performed in the operating room at the time of implantation (n = 72). Results are reported as relative cost ratios, with RRP assigned a relative cost of 1.0. RESULTS: The total relative perioperative cost for BXRT exceeded that for RRP by 85% to 105%. Technical cost, exclusive of 125I seeds, was substantially lower for BXRT (relative cost 0.36 to 0.42) but was more than offset by the cost of the seeds when comparing total cost with RRP. Performance of the planning ultrasound in the operating room (group 3) increased the total cost by 20%. The categorical technical costs for both BXRT groups were significantly lower for anesthesiology, laboratory medicine, medicine, pharmacy, and nursing but were significantly higher for radiology. The total professional costs were similar for all groups. CONCLUSIONS: Perioperative costs of BXRT with 125I seeds are substantially higher than RRP in the treatment of localized prostate cancer, primarily because of the cost of the seeds.

Interferon-gamma production by T lymphocytes from renal cell carcinoma patients: evidence of impaired secretion in response to interleukin-12.

Interleukin-12 (IL-12) is a heterodimeric cytokine that enhances the cytolytic activity, proliferation, and interferon-gamma (IFN-gamma) production by T lymphocytes and natural killer cells, and has significant antitumor activity in a variety of murine tumor models. The induction of interferon (IFN)-gamma by IL-12 in tumor-bearing mice plays an important role in its antitumor activity. We therefore examined the effects of IL-12 on IFN-gamma production by T cells derived from patients with renal cell carcinoma (RCC), including freshly isolated tumor infiltrating lymphocytes (T-TIL), matched peripheral blood T cells (T-PBL), and RCC-specific TIL lines. IL-12 alone induced IFN-gamma secretion by T cells from normal individuals and appeared to act synergistically with either IL-2 or anti-CD3 antibody. In contrast, it failed to stimulate significant IFN-gamma secretion by T-PBL and T-TIL from RCC patients. This unresponsive state in T-PBL appeared selective because IFN-gamma was produced when cells were stimulated with either phytohemagglutinin or anti-CD3 antibody. Moreover, costimulation through the T-cell receptor (TCR)/CD3 complex or with IL-2 made T-PBL from RCC patients responsive to IL-12, possibly secondary to the upregulation of IL-12R (beta chain). A selective loss of IL-12-dependent production of IFN-gamma was also consistently observed in two of three established RCC-specific TIL lines. Although these cell lines did not respond to any concentration of IL-12, they did produce IFN-gamma after ligation of the TCR/CD3 or stimulation with IL-2, IL-12 also acted either syngeristically or additively with IL-2, anti-CD3 antibody, or autologous tumor cells to induce IFN-gamma production. The observed decreases in IFN-gamma production in response to IL-12 may have a negative effect on the development of T-cell immunity. The clinical importance of these findings during in vivo administration of IL-12 remains to be determined.