A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.

By stimulating blood lymphocytes from a renal cell carcinoma patient in vitro with the autologous tumor cells, we obtained cytolytic T lymphocyte (CTL) clones that killed several autologous and allogeneic histocompatibility leukocyte antigen (HLA)-B7 renal carcinoma cell lines. We identified the target antigen of these CTLs by screening COS cells transfected with the HLA-B7 cDNA and with a cDNA library prepared with RNA from the tumor cells. The antigenic peptide recognized by the CTLs has the sequence LPRWPPPQL and is encoded by a new gene, which we named RU2. This gene is transcribed in both directions. The antigenic peptide is not encoded by the sense transcript, RU2S, which is expressed ubiquitously. It is encoded by an antisense transcript, RU2AS, which starts from a cryptic promoter located on the reverse strand of the first intron and ends up on the reverse strand of the RU2S promoter, which contains a polyadenylation signal. This mechanism of antigen expression is unprecedented and further illustrates the notion that many peptides recognized by T cells cannot be predicted from the primary structure of the major product of the encoding gene. Antisense transcript RU2AS is expressed in a high proportion of tumors of various histological types. It is absent in most normal tissues, but is expressed in testis and kidney, and, at lower levels, in urinary bladder and liver. Short-term cultures of normal epithelial cells from the renal proximal tubule expressed significant levels of RU2AS message and were recognized by the CTLs. Therefore, this antigen is not tumor specific, but corresponds to a self-antigen with restricted tissue distribution.

Modulation of small conductance calcium-activated potassium (SK) channels: a new challenge in medicinal chemistry.

Small conductance calcium-activated potassium (SK) channels are found in many types of neurons as well as in some other cell types. These channels are selective for K(+) and open when intracellular Ca(2+) rises to omega 500 nM. In neurons, this occurs during and after an action potential. Activation of SK channels hyperpolarizes the membrane, thus reducing cell excitability for several tens or hundreds of milliseconds. This phenomenon is called a afterhyperpolarization (AHP). Three subtypes of SK channels (SK1, SK2, SK3) have been cloned and exhibit a differential localization in the brain. SK channels may play a role in physiological and pathological conditions. They may be involved in the control of memory and cognition. Moreover, they are heavily expressed in the basal ganglia (in particular in the substantia nigra, pars compacta) and in the limbic system, suggesting that they may modulate motricity and emotional behaviour. Based on these facts, SK channel subtypes may be a suitable target for developing novel therapeutic agents, but more work is needed to validate these targets. Hence, there is a great need for selective ligands. Moreover, although the risk of peripheral side-effects for SK channel modulators appears to be low, some questions remain to be investigated. Currently, different molecules are known as SK channel modulators. Apamin is a very potent peptidic agent; it produces a strong blockade of these targets which is only very slowly reversible and it has limited selectivity. Dequalinium was found to be an effective blocker. Different chemical modulations on the dequalinium structure led to the discovery of highly potent bis-quinolinium derivatives such as UCL 1684. Other bis-(2-amino-benzimidazole) derivatives are in development. On the other hand, quaternary salts of bicuculline were reported to be effective in inhibiting AHPs. More recent developments on structurally-related molecules revealed that methyl-laudanosine is a new interesting tool for exploring SK channel pharmacology. Finally, a family of compounds has been shown to facilitate SK channel opening. Such compounds may be useful in treating disorders involving neuronal hyperexcitability.

Undetectable prostate-specific antigen in aging men.

Undetectable prostate-specific antigen was found in three aging men despite the absence of any prostatic surgery or exogenous hormonal deprivation. Clinical and elementary hormonal workup revealed the presence of secondary hypogonadism. This finding confirms the hormonal dependency of this prostatic marker and may, in some cases, explain the discrepancy between prostatic volume and the value of serum prostate-specific antigen.

Laparoscopic nephrolithotomy: the value of intracorporeal sonography and color Doppler.

Laparoscopic nephrolithotomy was used as an alternative to open surgery in a patient who had failed extracorporeal shock-wave lithotripsy and whose anteriorly located stone-bearing calix precluded percutaneous extraction. Endocavitary ultrasonography and color Doppler render the procedure safe and effective; localization of the stone, selection of an optimal nephrotomy site away from large vessels and where cortical thickness is minimal, and control of fragment clearance are greatly facilitated.

Free to total prostate-specific antigen (PSA) ratio improves the discrimination between prostate cancer and benign prostatic hyperplasia (BPH) in the diagnostic gray zone of 1.8 to 10 ng/mL total PSA.

OBJECTIVES: Improved discrimination between prostate cancer (PC) and benign prostatic hyperplasia (BPH) is clearly needed. Our aim in this study was to evaluate whether the free to total prostate-specific antigen (PSA) ratio would be useful in the gray zone of 1.8-10 ng/mL total PSA range. METHODS: In a consecutive series of 435 clinic patients referred for prostate evaluation, 308 had a total PSA < 10 ng/mL (92 had PC and 216 BPH). Free and total PSA were measured, and the free to total PSA ratio calculated. RESULTS: Total PSA values were significantly different between the two groups. For the 200 patients with a total PSA < 6 ng/mL, no significant difference in total PSA values were seen (P = 0.411), whereas free to total PSA ratios remained statistically different (P < 0.001). Receiver operating characteristic (ROC) curve analysis comparing the performances of total PSA over the ratio of free to total PSA showed a clear advantage for the ratio at all sensitivity levels. CONCLUSIONS: These data demonstrate that in a significant number (n = 308) of prostatic patients in the diagnostic gray zone of 1.8-10 ng/mL total PSA, the routine use of free to total PSA might be advantageous in discriminating between cancer and benign hyperplasia. This advantage remained for total PSA < 4 ng/mL. Further study is warranted to confirm these findings in an unselected population.

Efficacy of laser prostatectomy at 2-years' follow-up.

A total of 32 patients with symptomatic benign prostatic hyperplasia were treated with the right-angle firing neodymium:YAG laser fiber at a 60 W power setting. All these patients represented a high operative risk (ASA score > or = 3) and were excluded by the anesthesiologist for classic surgical treatment. Twenty-six patients were followed at least 24 months; the six remaining patients died of intercurrent disease. Efficacy of treatment was assessed at 3, 6, 12, 18, and 24 months postoperatively by International Prostatic Symptom Scores, peak urinary flow rates, prostatic volume, and radiographic or endoscopic imaging of the prostatic urethra. The mean preoperative symptom score was 25, the mean peak urinary flow rate 7.6 mL/sec, and mean prostatic volume 31 cc. At 2 years postoperatively, the mean symptom score was 5, the mean peak urinary flow rate was 19.3 mL/sec, and the mean prostatic volume was 18 cc. In two elderly patients, in spite of a significant improvement of symptomatology and peak flow rate, a surprisingly obstructed prostatic urethra was found endoscopically.

Transurethral ultrasound-guided laser-induced prostatectomy: a critical evaluation.

We evaluated 38 patients with a follow-up of 30 months after transurethral ultrasound-guided laser-induced prostatectomy (TULIP) for benign prostatic hyperplasia. The mean symptom score decreased by 54%, and peak urinary flow increased by 112%. For the entire series, 43.6% of the patients had an improved symptom score and 41% better urinary flow, but only 28.2% had improvement in both. Six patients (16%) required reoperation, two underwent a radical prostatectomy, and one patient presented total urinary incontinence. Also, 19% presented postoperative impotence, and 47% presented retrograde ejaculation. Although one third of the patients are improved with the TULIP procedure, the rate of complications is significantly higher than for TURP, which remains the most effective treatment of obstructive BPH.

Vessels around the ureteropelvic junction: significance and imaging by conventional radiology.

We studied the influence of vessels crossing the ureteropelvic junction and of the grade of hydronephrosis in 86 patients who underwent endoureteropyelotomy. With a follow-up ranging from 1 to 12 years, the presence of crossing vessels had a significant negative influence on the outcome and recurrence rate of the procedure. The success rate was 82% when no vessels were present but only 33% when crossing vessels were documented. In 13 of 15 failures (87%), a crossing vessel was found at open pyeloplasty. The degree of hydronephrosis was a less potent detrimental factor, with an 81% success rate in low-grade and 54% in high-grade hydronephrosis. The best results (90% success) were obtained in patients with no crossing vessels and low-grade hydronephrosis and the worst (30% success) in those with high-grade hydronephrosis in the presence of crossing vessels. Selection of patients according to those prognostic factors is recommended. Conventional intravenous urographic imaging techniques proved insufficient, and only angiography provided diagnostic accuracy; less-invasive methods are desirable.

Blunt renal traumas: contribution of spiral CT with three dimensional reconstruction to the surgical decision process?

Spiral CT has proved to be a valuable tool by providing various kinds of three-dimensional (3D) images of the studied structures. Such 3D images, which offer a more realistic depiction of the lesions, could be of interest for surgeons who are attempting to treat conservatively blunt abdominal traumas and lead to less inappropriate triage between conservative and operative management particularly for renal trauma. A good working relationship between surgeons and radiologists allowed us to perform an early follow-up 3D spiral CT on a commercially available spiral CT scanner. In the first adult patient, the 3D CT demonstrated minor spleen injury associated with severe lacerations of the left kidney with complete separation of the kidney lower pole. A delayed partial lower nephrectomy was performed. For the second 12-year-old patient presenting with severe spleen trauma and macroscopic hematuria, the 3D CT accurately documented the spleen and renal lesions that were safely amenable to nonoperative treatment. For hemodynamically stable patients, 3D CT is a potentially helpful addition to conventional axial CT for quantifying blunt renal traumas and for making the strategic choice between nonoperative, emergency or delayed surgical treatment.

[Aggressive aneurysmal bone cyst of the humerus in a child]. / Evolution inhabituelle d'un kyste osseux anévrismal de l'humerus.

A 9-year-old child presented an aggressive aneurysmal bone cyst of the humerus. Despite multiple treatments (intracystic steroid injections, curettage, Ethibloc injection), the lesion continued to progress. Surgical treatment was undertaken at the age of 19 years and enabled total tumor resection associated with reconstruction with a vascularized fibular flap. Five years later, the patient was free of recurrence. The graft was well integrated and shoulder function was normal. We present the diagnostic difficulties encountered in this case and discuss the therapeutic options. Biopsy is indispensable before instituting treatment.

[The value of using a facilitating dose of papaverine chlorhydrate during cavernometry]. / Intérêt de l'utilisation d'une dose facilitatrice de chlorhydrate de papavérine lors de la cavernométrie.

In order to establish diagnostic cavernometric criteria, we selected 63 patients who did not respond positively to visual sexual stimulation. They were subjected to the following protocol including Rigiscan monitoring of 2 or 3 nights erections for, hormonal assays, penile doppler, cavernometry and cavernography. Intracorporeal injection of 8 mg of papaverine was performed during the hemodynamic tests. Our results showed that the erection maintenance blood flow and the maintenance index are statistically reliable diagnostic criteria for venous leaks (the maintenance index is more accurate). The use of 8 mg of papaverine reduces the incidence of false positive results without significant hemodynamic changes. In order to exclude psychogenic false positive patients, it is recommended to select the candidates for cavernometry after papaverine tests and nocturnal penile tumescence and rigidity monitoring.

[Ureteral lithiasis. Development of the therapeutic strategy and the place of endoscopic treatment]. / Lithiases urétérales. Evolution de la stratégie thérapeutique et place du traitement endoscopique.

In order to evaluate the impact of endourological techniques and extracorporeal lithotripsy on the management of ureteral calculi, we reviewed the charts of 838 patients requiring hospitalization for this pathology from 1982 till 1987. 314 patients were managed conservatively and 524 required intervention therapy: 52 with blind endoscopic techniques, 93 with open surgery, 122 with retrograde ureteroscopy, 168 with percutaneous extraction and 92 with ESWL. Evolution of the therapeutic strategy is discussed and our present approach to ureteral stone management is outlined.

[Urinary continence after radical prostatectomy: importance of the vesico-urethral anastomosis. Objective evaluation]. / Continence urinaire après prostatectomie radicale: importance de l'anastomose vésico-urétrale. Evaluation objective.

Urinary continence after radical prostatectomy is frequently evaluated subjectively. The authors describe their technique of vesicourethral anastomosis and report their method of objective evaluation of postoperative urinary continence. At the 6th postoperative week, 15% of patients presented with severe incontinence. This percentage fell to 3.3% by the 16th postoperative week.

Germ cell tumors of the testis: the place of surgery.

Optimal management of testicular cancer requires a multidisciplinary approach. This paper reviews the present role of surgery at three different stages of therapy. Radical inguinal orchidectomy is the treatment of the primary tumor, retroperitoneal lymphadenectomy is an essential tool in staging and treatment of low stage non-seminomatous germ cell cancer, and cytoreductive surgery is an indispensable adjunct in post-chemotherapeutic residual masses. These surgical aspects are placed in the perspective of modern therapeutic strategies.

Tamoxifen for retroperitoneal fibrosis.

Retroperitoneal fibrosis, either idiopathic or associated with aortic inflammatory aneurysm, is a chronic fibrotic disease that causes progressive obstruction of ureters and vessels around the lower abdominal aorta. Treatment is often difficult (surgery) or hazardous (steroids). We report a case of a woman with retroperitoneal fibrosis associated with aortic inflammatory aneurysm, who was successfully treated with oral tamoxifen.

Massive bone allografts in children.

A group of ten children and adolescents with malignant bone tumours (eight osteosarcomas, two Ewing's tumours) were treated with chemotherapy and resection with allograft reconstruction. Intercalary grafts were used in three cases and terminal osteoarticular grafts at the knee in seven. The mean follow up was 22 months. Functional results were satisfactory, but there were some complications related to the graft. Although these are early results, we believe that the method is justified and is preferable to the use of an endoprosthesis, particularly in children.

[Severe and unexpected occurrence of water-electrolyte disorders in the postoperative period]. / Désordres hydro-électrolytiques sévères et inattendus survenus en période post-opératoire.

Unexpected severe electrolyte imbalance in the postoperative period. Report two cases. Two cases of inappropriate secretion of antidiuretic hormone are reported. In each patient, the physiopathology is reviewed. Differential diagnosis and treatment of hyponatremia is discussed.

Direct carbon dioxide insufflation of the retroperitoneum under laparoscopic control for renal and adrenal surgery.

OBJECTIVE: Assessment of the videoscopic approach to the retroperitoneal space in the vicinity of the kidney and the adrenal gland. DESIGN: Open study. SETTING: University hospital, Belgium. SUBJECTS: 10 patients who underwent 11 operations (adrenalectomy, n = 3, nephrectomy, n = 5, partial nephrectomy, n = 2, and renal cystectomy, n = 1). INTERVENTIONS: Direct CO2 insufflation of the retroperitoneal space in order to obtain a convenient retroperitoneal working space for renal and adrenal surgery. OUTCOME MEASURES: Feasibility, morbidity and mortality. RESULTS: 8 patients were operated on exclusively by the retroperitoneoscopic approach; 2 required the retroperitoneal and transperitoneal routes to be combined to complete an adrenalectomy. No patients required blood transfusion and no patient died. Median postoperative stay was 3 days. CONCLUSION: The CO2 insufflation technique of the retroperitoneum is safe and reproducible. Nevertheless, far from excluding each other, both approaches-laparoscopic and retroperitoneoscopic-are complementary in difficult cases, particularly for adrenal endoscopic surgery and for larger renal lesions.

Transitional cell carcinoma involving the prostate: a clinicopathological retrospective study of 76 cases.

PURPOSE: We reviewed the degree to which extension from transitional cell carcinoma into the prostate affects survival. We also compared whether prostatic stromal invasion occurring via direct extension through the bladder wall differs from stromal invasion arising intraurethrally. MATERIALS AND METHODS: A total of 76 men who underwent radical cystectomy for transitional cell carcinoma also had prostate involvement. Patients were separated into group 1-18 with primary bladder tumor extending transmurally through the bladder wall to invade the prostate and group 2-58 with prostate involvement arising from within the prostatic urethra. In the latter group the degree of prostate invasion was classified as urethral mucosal involvement, ductal/acinar involvement and stromal invasion. RESULTS: The 5-year overall survival and recurrence-free rate were 22% and 28% in group 1 versus 43% and 45% in group 2, respectively. In group 2 survival rates were similar in those with prostatic urethral and ductal tumors (without stromal invasion). Five-year overall survival rates without and with stromal invasion were 49% and 25%, respectively (p = 0.024). Prostate involvement decreased survival, which varied according to primary bladder stages (Pis, P1, P2a/b and P3a/b, p = 0.004) or superficial (Pis, Pa and P1) and muscle invasive (P2a/b and P3/b, p = 0.045), disease in 2 groups. Those with positive lymph nodes experienced poorer outcomes in each group. The 5-year overall survival rate in the 19 men with positive lymph nodes was 13% and it was 44% with negative lymph nodes (p = 0.034). The major prognostic factors were age, degree of prostate invasion and lymph node involvement. CONCLUSIONS: The invasion pathways of prostate invasion in patients with transitional cell bladder carcinoma have a statistically significant prognostic role in survival. Transitional cell carcinoma of the bladder extending into the prostate through the bladder wall and bladder carcinoma that did not directly infiltrate the prostate through the bladder wall are 2 distinct clinicopathological entities that should not be included in the same staging grade.