Luc Baert

Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer

The expression of fatty acid synthase (FAS), a key lipogenic enzyme and potential target for antineoplastic therapy, was analyzed in 87 frozen needle biopsies of prostate cancer using a highly sensitive immunohistochemical detection technique (Envision). In comparison to normal or benign, hyperplastic glandular structures, which were all negative for FAS staining, immunohistochemical signal was evident in 24/25 low grade prostatic epithelial neoplasia (PIN) lesions, in 26/26 high grade PIN lesions and in 82/87 invasive carcinomas. Staining intensity tended to increase from low grade to high grade PIN to invasive carcinoma. Cancers with a high FAS expression had an overall high proliferative index. No correlation was found between FAS expression and lipid accumulation. These findings indicate that increased FAS expression is one of the earliest and most common events in the development of prostate cancer, suggesting that FAS may be used as a general prostate cancer marker and that antineoplastic therapy based on FAS inhibition may be an option for chemoprevention or curative treatment for nearly all prostate cancers.

Selective activation of the fatty acid synthesis pathway in human prostate cancer

A substantial subset of breast, colorectal, ovarian, endometrial and prostatic cancers displays markedly elevated expression of immunohistochemically detectable fatty acid synthase, a feature that has been associated with poor prognosis and that may be exploited in anti‐neoplastic therapy. Here, using an RNA array hybridisation technique complemented by in situ hybridisation, we report that in prostate cancer fatty acid synthase expression is up‐regulated at the mRNA level together with other enzymes of the same metabolic pathway. Contrary to the observations that in many cell systems (including androgen‐stimulated LNCaP prostate cancer cells) fatty acid and cholesterol metabolism are co‐ordinately regulated so as to supply balanced amounts of lipids for membrane biosynthesis, storage or secretion, no changes in the expression of genes involved in cholesterol synthesis were found. These findings point to selective activation of the fatty acid synthesis pathway and suggest a shift in the balance of lipogenic gene expression in a subgroup of prostate cancers. Int. J. Cancer 88:176–179, 2000.

Is the diverticulum of the distal and collecting tubules a preliminary stage of the simple cyst in the adult

Whereas the outlines of nephrons and collecting ducts in kidneys from subjects less than 20 years old age regular, the number of diverticula on the distal tubule in kidneys from adults increase with age. An embryogenic progression from diverticula to microscopic and macroscopic cysts to radiologically detectable cysts can be established from morphological anomalies found in kidneys from adults. Therefore, a diverticulum on distal and collecting tubules and collecting tubules is postulated as the precursor of a simple cyst.

Initial evaluation of the bladder tumor antigen test in superficial bladder cancer

PURPOSE We analyzed the value of the Bard bladder tumor antigen (BTA*) test for the diagnosis of stage Ta superficial bladder cancer and carcinoma in situ, and compared it to the highly sensitive bladder washing cytology. MATERIALS AND METHODS The BTA test is a latex agglutination test that qualitatively detects the presence of basement membrane complexes in the urine. A total of 60 patients with superficial bladder cancer underwent voided urine BTA analysis and bladder washing cytologies. RESULTS Of the patients 65% were correctly diagnosed with the BTA test compared to 32% with bladder washings, which is statistically significant (p < 0.001). CONCLUSIONS The BTA test is a noninvasive diagnostic tool that is superior to bladder washing cytology for diagnosing superficial bladder cancer.

Clinical fluorescence diagnosis of human bladder carcinoma following low-dose Photofrin injection.

A point-monitoring fluorescence diagnostic system based on a low-energy pulsed laser, fiber transmission optics, and an optical multichannel analyzer was used for diagnosis of patients with bladder malignancies. Twenty-four patients with bladder carcinoma, carcinoma in situ, and/or dysplasia were injected with hematoporphyrin derivative, Photofrin, 0.35 or 0.5 mg/kg body weight, forty-eight hours prior to the investigation. The ratio between the red sensitizer emission and the bluish tissue autofluorescence provided excellent demarcation between papillary tumors and normal bladder wall. Certain cases of dysplasia also could be differentiated from normal mucosa. Benign exophytic lesions such as malakoplakia appeared different from malignant tumors in fluorescence. Flat suspicious bladder mucosa such as seen in infectious diseases or after radiation therapy appeared normal on fluorescence.

Whole Bladder Wall Photodynamic Therapy with in Situ Light Dosimetry for Carcinoma in Situ of the Bladder

We report on the preliminary results of 12 patients with multifocal carcinoma in situ of the bladder treated with whole bladder wall photodynamic therapy. The total light dose (scattered plus nonscattered light) measured in situ was 100 joules per cm.2 in the first 6 patients (group 1) and 75 joules per cm.2 in the remaining 6 (group 2). These light doses correspond on the average to 27 joules per cm.2 and 15.5 joules per cm.2 nonscattered light as reported by other investigators. Followup ranged from 6 to 22 months (average 11.5). In group 1, 2 tumors recurred after 6 and 9 months, respectively, and 2 other patients had a permanently shrunken bladder without evidence of disease. In group 2, 1 tumor recurred 5 months after photodynamic therapy. In this group the bladder capacity increased on the average to 135% of the pretreatment value 3 months after photodynamic therapy. All recurrences were in patients with a history of invasive bladder cancer (stages T1 and T2). These preliminary results demonstrate the importance of in situ scattered light dosimetry for minimizing local side effects of whole bladder photodynamic therapy.

RADICAL PROSTATECTOMY AND POSTOPERATIVE IRRADIATION IN PATIENTS WITH PATHOLOGICAL STAGE C (T3) CARCINOMA OF THE PROSTATE

PURPOSE Adenocarcinoma of the prostate is the most common human cancer of internal organs. Radical surgery is regarded by many to be the treatment of choice for capsule confined disease. Since accurate preoperative assessment of tumor stage is difficult to define, many patients are subsequently found to have pathological stage C (T3) disease. These patients should be considered for adjuvant radiotherapy. METHODS AND MATERIALS A group of 201 PS C (T3) unselected patients, treated with radical prostatectomy and limited pelvic lymphadenectomy, received postoperative irradiation to the prostate bed. This radiotherapy was given between 42-90 days after surgery and consisted of a median dose of 48 Gy. Patient survival, disease free survival, time to clinical and chemical relapse and the incidence of local and systemic relapse were analyzed. The influence of multiple parameters on the treatment outcome including patient age, treatment period, clinical stage, pathological stage, Gleasons score, prostate specific antigen (PSA), radiotherapy techniques and radiation dose were examined using univariate and multivariate analysis. Follow-up ranged from 3 to 15 years, with a median of 5 years. RESULTS The overall 5- and 10-year actuarial survival was 92% and 83% (median > 10 years), respectively and the 5- and 10-year disease-free survival (clinical and PSA) was 67% and 53% (median > 10 years), respectively. A total of 61 (30%) patients had a recurrence, including 23 (11%) patients who had clinical and 38 (19%) who had PSA recurrence. Of the 23 patients with clinical recurrence, 10 (5%) had local recurrence, including two patients who had local and systemic recurrence. Pathological stage and Gleasons score were independently predictive of recurrence (each with p < 0.001 after controlling for the other). Patients in the worst prognostic category with pathological stage C3 and Gleasons score 8-10 were predicted to be at 7.2 times the risk of recurrence, compared to stage C1 or C2 and Gleasons score 2-7 patients. Preoperative PSA level (> 25 ng/ml) was also an important independent factor predicting tumor recurrence, p = 0.05. All other investigated parameters were not significant in predicting tumor recurrence. This treatment program was very well tolerated by the study patients, with seven (3.5%) recorded with major and 18 (9%) with minor surgical complications, while 65% of patients had minor and clinically insignificant radiation complications. CONCLUSION Surgery followed by moderate dose radiotherapy in patients with PS C (T3) prostatic carcinoma was well tolerated and resulted in excellent overall and disease free survival, with a low incidence of local recurrence. New treatment strategies need to be developed for patients with C3 tumors and those with high (8-10) Gleasons score and those with high (> 25 ng/ml) PSA level at diagnosis.

Electromagnetic extracorporeal shock wave lithotripsy in children

Extracorporeal shock wave lithotripsy (ESWL) was performed for the treatment of urinary tract calculi in 28 children. All treatments were done with the standard Siemens Lithostar device in situ: no special adaptations for adequate positioning of children are required to target the stone precisely. A total of 42 calculi in 30 renal units was treated, requiring 50 ESWL sessions. The mean energy used was 16.4 kv. and the number of shock waves averaged 3,188. Mean fluoroscopy time per session was 1.5 minutes. In 26 of 50 sessions (52%) general anesthesia was needed for the child to remain perfectly still. A complete stone-free rate was achieved in 38 of 42 calculi (90.5%): after 1 session in 30 (71.4%), after 2 sessions in 6 (13.7%) and after 3 sessions in 2 (4.8%). Five staghorn calculi were treated with ESWL monotherapy. A complete stone-free result was obtained after 3 treatments in 2 patients, while 2 had residual fragments in the lower pole (5 mm. after 6 sessions and 11 months of followup in 1, and 7 mm. after 3 sessions and 3 months of followup in 1). A cystine staghorn stone necessitated open nephrolithotomy after 3 sessions without any fragmentation. One impacted sacroiliac ureteral stone required endoscopic laser lithotripsy. Except for these 2 failures no adjuvant procedures were needed. There were no intraoperative or postoperative complications and minor skin bruising at the coupling site after 3 treatments did not require any therapy. We conclude that electromagnetic ESWL with the standard Lithostar unit is a safe and effective method to treat calculi throughout the urinary tract in children.

Long-term results of whole bladder wall photodynamic therapy for carcinoma in situ of the bladder

OBJECTIVES This article evaluates the results of whole bladder wall photodynamic therapy (PDT) for multifocal carcinoma in situ after a mean follow-up time of 3 years. METHODS Photofrin II was used as a photosensitizer (2 mg/kg) and in situ dosimetry to obtain the best possible central positioning of the light diffuser as well as to know exact dosimetry data (scattered plus nonscattered light). RESULTS Major classical drawbacks of PDT, such as severe bladder irritative symptoms and bladder shrinking, can be minimized with the help of in situ dosimetry. The success rate after 3-year follow-up is 60%. Fifty percent of the recurrences occurred in the prostatic urethra without evidence of disease of the bladder. CONCLUSIONS A success rate of 60% is comparable to the results obtained after bacille Calmette-Guérin (BCG). Side effects such as loss of bladder capacity can be minimized with adequate light dosimetry but they are still higher than with BCG (9% versus 1% cystectomy).

Transcutaneous Nitroglycerin Therapy in the Treatment of Impotence

In order to avoid the side effects and drawbacks of intravenous injection of vasoactive drugs, we evaluated the use of transcutaneous nitroglycerin, a powerful smooth muscle relaxant, in enhancing the quality of erection. In this study, 26 impotent patients were treated with (nitroglycerin or placebo) patches applied to the skin of the penile shaft. A positive response was reported by 21 patients and 17 men out of the 21 were able to distinguish a marked difference between the nitroglycerin and placebo patches. These results indicate that nitroglycerin patches have to be tried, especially in patients with moderate erection disturbances.