Docetaxel in the treatment of metastatic castration-resistant prostate cancer (mCRPC): an observational study in a single institution.

BACKGROUND: Treatment with docetaxel in combination with prednisone is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). For patients failing first-line docetaxel no standard has emerged. OBJECTIVES: The outcome in routine daily clinical practice of a cohort of unselected chemotherapy-naïve mCRPC patients treated with docetaxel plus methylprednisolone as first- and further-line treatment in a single institution was investigated. PATIENTS AND METHODS: Data from the medical records of patients treated with docetaxel plus methylprednisolone either in a three-weekly (75 mg/m(2)) (D3) or a three-of-four-weekly (35 mg/m(2))(D1) schedule as first- or further-line treatment were analysed with respect to clinical and prostate-specific antigen (PSA) response, time-on-treatment (TOT), treatment-free interval (TFI), overall survival time (OS) and toxicity and were compared to the results of the registration study TAX 327. RESULTS: Out of 41 patients, 28 and 13 received first-line docetaxel according to the D3 and the D1 schedules respectively. An overall PSA response ≥50% was achieved in thirty patients (73%). In ten patients (24%) the PSA level was normalised. The median OS of the total population was 18.7 months. No significant differences were observed between the D3 and the D1 regimens with respect to PSA response, duration of PSA response, TOT, TFI and OS. Patients obtaining a normalisation of PSA level achieved a significantly superior OS, TOT and TFI compared to those without normalisation of PSA. Second-line treatment with docetaxel in nine patients induced a normalisation in PSA level in two (22%). The TOT and TFI from the start of second-line treatment, was significantly superior in docetaxel compared to non-docetaxel treated patients. Treatment with docetaxel was well-tolerated and only two patients were withdrawn for non-haematological toxicity during first- and further-line treatment. There were no differences in either subjective or objective side-effects between both treatment schedules. CONCLUSION: The results of the retrospective analysis of non-selected patients with mCRPC treated with docetaxel chemotherapy are in line with the data from TAX 327. Normalisation of PSA during first-line treatment with docetaxel is associated with a better survival irrespective of second- or further-line treatment used. Retreatment with docetaxel in second- or further-line remains a treatment option in docetaxel-sensitive patients.

To the core of porcine matter: evaluating arguments against producing transgenic pigs.

BACKGROUND: The production of transgenic pigs for xenotransplantation is based on an urgent human need for transplantable organs. Although the particular genetic modifications are small and do not alter the organism phenotypically, several authors consider it to be morally problematic. In this paper we attempt to establish if there are genuine reasons to refrain from producing 'humanized' pigs. METHODS: We distinguish between two types of ethical arguments against transgenesis often confused in debating the matter: consequentialist and inherent arguments. Whereas the first type of argument pertains to the potentially negative effects of the procedure, the second type claims that genetic engineering of animals is 'inherently' wrong; that the action itself regardless of the effects - is to be considered immoral. If this is the case, then the discussion need not be taken further. If not, then these arguments do not stand in evaluating the procedure. RESULTS: We demonstrate that none of the claims asserting inherent wrongness of transgenesis is valid as such. CONCLUSION: Sound resistance to producing transgenic pigs is restricted to concerns regarding the concrete effects of the applications.

Proceeding with clinical trials of animal to human organ transplantation: a way out of the dilemma.

The transplantation of porcine organs to humans could in the future be a solution to the worldwide organ shortage, but is to date still highly experimental. Further research on the potential effects of crossing the species barrier is essential before clinical application is acceptable. However, many crucial questions on efficacy and safety will ultimately only be answered by well designed and controlled solid organ xenotransplantation trials on humans. This paper is concerned with the question under which conditions, given the risks involved and the ethical issues raised, such clinical trials should be resumed. An alternative means of overcoming the safety and ethical issues is suggested: willed body donation for scientific research in the case of permanent vegetative status. This paper argues that conducting trials on such bodies with prior consent is preferable to the use of human subjects without lack of brain function.

Transrectal ultrasound in the diagnosis of prostate cancer: state of the art and perspectives.

OBJECTIVES: Transrectal ultrasound (TRUS) is an important tool in diagnosing prostate cancer. However, specificity and sensitivity of conventional grey-scale TRUS for the detection of prostate cancer are disappointingly low. New ultrasound modalities are designed to overcome the disappointing results and improve the use of ultrasound in the diagnosis of prostate cancer. This work is a review of the recent literature, combined with own experiences. METHODS: The papers were collected using a Medline search, combined with some papers by author selection. The terms used for the Medline search included among other things: transrectal ultrasound, prostate, prostate cancer, prostate biopsies, colour Doppler ultrasound, power Doppler ultrasound, contrast ultrasound. The authors used their own experiences for illustrations of various techniques. RESULTS AND CONCLUSIONS: Although several modalities show a significant improvement in sensitivity and specificity for the detection of prostate cancer, none of the TRUS modalities discussed can replace prostate biopsies as a definitive diagnostic. Several techniques, especially contrast ultrasound, show definitive promise. However, two valid conclusions can be made from the data presented. First: with today's technology, none of the TRUS modalities discussed can replace systemic biopsies in the early detection of prostate cancer. Second: none of the discussed TRUS modalities has found a definitive place in routine clinical practice.

Specificity and accuracy of TRUS-measured PSA-density and transition zone-PSA in the diagnosis of prostate cancer.

Between 4 and 15 ng/ml serum prostate-specific antigen (PSA) has a low specificity for prostate cancer (PCa). One accepted method to enhance this specificity is transrectal ultrasonography (TRUS)-measured PSA-density (PSA-D). We compared this method with a new alternative, transition zone PSA (PSA-TZ). We measured total and transition zone prostatic volumes by TRUS and calculated PSA-D and PSA-TZ in 59 patients with suspicion of PCa and PSA between 4 and 15 ng/ml. All patients then had sextant biopsies of the prostate, 30 were positive for PCa and 29 showed benign tissue. With a cut-off value of 0.35, PSA-TZ had a positive predicted value of 77% for PCa, whereas PSA-D, with a cut-off value of 0.12, had a positive predicted value of 55%. Our data suggest PSA-TZ to be more reliable for avoiding unnecessary biopsies in patients with PCa suspicion and serum PSA below 15 ng/ml. PSA-TZ, calculated by TRUS, enhances the specificity of PSA for needle biopsy diagnosis of PCa.

Review of recent placebo-controlled trials utilizing phytotherapeutic agents for treatment of BPH.

BACKGROUND: In order to assess the efficacy of phytotherapeutic agents for the treatment of benign prostatic hyperplasia (BPH), a review of recently published double-blind placebo-controlled trials was undertaken. METHODS: Only those studies reviewed by the Other Medical Therapies Committee of the Fourth International Consultation on BPH were included. RESULTS: These studies suggest a possible benefit for the use of phytotherapeutic preparations in the treatment of BPH. CONCLUSIONS: These studies need to be confirmed in larger long-term placebo-controlled studies in order to ascertain the true efficacy of these agents.

A patient with Peyronie's disease: ultrasonographic features.

Clinical, radiographic, and ultrasonographic findings in a 45-year-old patient with Peyronie's disease are reported. Ultrasonography precisely identified calcified as well as fibrous plaques characteristic of this disorder.

Long-term survival in an adult metastatic renal peripheral primitive neuroectodermal tumor (PPNET) with multimodality treatment including high-dose chemotherapy.

We describe a 42-year-old male patient with a primitive peripheral neuroectodermal tumor (PPNET) arising from the kidney. The patient was treated sequentially with surgery, radiotherapy, experimental cytokine treatment (rhIL-6), combination chemotherapy and consolidated in complete remission with high-dose chemotherapy, supported by autologous stem cells (AST) and hematopoietic growth factors. The patient remains in complete remission at 34+ months after AST and is surviving disease-free for five years after initial presentation. The case presented here is unusual because of the renal origin and the long remission duration and survival when compared with the usual outcome of adult metastatic PPNET. High-dose chemotherapy may have favorably influenced the outcome in this patient. The case is discussed in the context of the general treatment of metastatic PPNET.

Prothipendylhydrochloride-induced priapism: case report.

We present the first case of a patient with priapism after oral intake of the phenothiazine prothipendylhydrochloride.

Laparoscopy: any indication in the work-up and treatment of undescended testis?

About 10% of undescended testis are non palpable. Surgical exploration of the inguinal region was the standard treatment, mainly because reliable "localisation tests" were not available. Today, laparoscopy is becoming the first step for optimal management of this problem. This technique combines relevant diagnostic information with therapeutic facilitations.

Endoscopic submucosal Teflon injection (STING): an alternative treatment of vesicoureteric reflux in children.

The authors present their results in treating vesicoureteric reflux with an endoscopic submucosal teflon injection (STING) of the refluxing ureter. One hundred refluxing units in 68 children were treated with a maximum follow-up of five years. Indications were high grade reflux (III-V), persistence or progression of reflux despite conservative therapy, breakthrough urinary infections despite antibiotic prophylaxis and finally bad antibiotic compliance. Treatment was performed on an outpatient basis and appeared to be free of complications. Reflux was cured with a success rate of 75% after a single injection and 96% after two injections. With respect to the grade of reflux, best results were obtained in low grade reflux (Grade I-II). A 60-70% success rate was obtained in high grade reflux (III-V). The main advantage over open reimplantations lies in its non invasiveness, simplicity and possibility of being repeated in case of failure.

Endocrine profiles during administration of the new non-steroidal anti-androgen Casodex in prostate cancer.

OBJECTIVE: Casodex (Zeneca) is a new potent, long-acting non-steroidal anti-androgen, which produces androgen deprivation by blocking the androgen receptor. We evaluated the endocrine effects of Casodex 150 mg daily given in monotherapy as primary treatment for patients with prostate cancer. DESIGN: As part of a large, multicentre study comparing the therapeutic effects of surgical castration with 150 mg/day Casodex in monotherapy for patients with prostate cancer, a subgroup of 23 patients on Casodex were studied in detail for changes in endocrine parameters. Serum levels of LH, FSH, testosterone, DHT, oestradiol, prolactin, sex hormone binding globulin and free testosterone were measured at the start of therapy and after 1, 4, 8, 12 and 24 weeks. Effects on libido, sexual activity and the appearance of hot flushes, breast pain and gynaecomastia were recorded. RESULTS: Administration of Casodex resulted in a rise in LH levels in all patients with a mean increase after 24 weeks of 102% (P < 0.001). Mean FSH levels showed a limited increase (7%) after 24 weeks, which was significant only after 1 week (P < 0.001). As a result of the high LH levels, total testosterone levels increased after 24 weeks by 66% (P < 0.001), free testosterone by 57% (P < 0.001) and dihydrotestosterone by 24% (P = 0.0112). Parallel to testosterone, oestradiol levels rose by a mean of 66% (P < 0.001). Mean sex hormone binding globulin and prolactin levels rose by respectively 8% (P = NS) and 65% (P < 0.01). Despite an increase in testosterone levels, excellent androgen blockade was obtained, as shown by a decrease in prostate specific antigen levels in 22/23 patients. Libido was maintained in 8/11 patients, and sexual activity in 5/6. No patient complained of hot flushes. However, mild gynaecomastia and/or breast tenderness were seen in 48 and 30% of cases respectively. CONCLUSION: Casodex 150 mg/day monotherapy resembles surgical castration in achieving androgen deprivation, despite an increase in LH and testosterone levels. In contrast to castration, libido and sexual activity are usually maintained and hot flushes are rare. However, mild gynaecomastia and/or breast tenderness were noted in 48 and 30% of patients.

[Technetium 99m labeled dimercaptosuccinic acid (99m Tc-DMSA) scintigraphy in the diagnosis and follow-up of urinary infections in children]. / Apport de la scintigraphie à l'acide dimercaptosuccinique marqué au technétium 99m (99mTc-DMSA) dans le diagnostic et le suivi des infections urinaires de l'enfant.

BACKGROUND: The site of a urinary tract infection (UTI) is located by clinical findings plus imaging techniques. Renal imaging with technetium 99mTc-dimercaptosuccinic acid (99mTc-DMSA) has shown promise but its efficacy for detecting acute pyelonephritis is still debated as is its ability to differentiate between acute, potentially curable disease and scarring, definitive changes. PATIENTS AND METHODS: The files of all the 166 patients that underwent one or two (32 patients) 99mTc-DMSA imaging sessions for UTI in 1989 and 1990 in our department were analysed. The results of this technique were compared with the clinical and laboratory data and with those of other imaging techniques (ultrasonography and retrograde voiding cystourethrogram). The patients (92 girls and 74 boys, mean age: 5 years, range 15 days-17 years) were assigned to one of 3 categories: 1) acute pyelonephritis (27 patients), 2) low UTI (60 patients) and 3) uncertain UTI (79 patients), on the basis of the clinical and laboratory data. RESULTS: The first 99mTc-DMSA imaging was normal in 110 children; changes were unilateral in 45 and bilateral in 11 children. Images suggesting either acute or chronic changes were observed respectively in 19 and 48 children. 4 of the 7 acute changes were normalized on the second radioisotope scanning while 2 became worse; 19 of the 23 chronic changes were unchanged at the second scanning. Radioisotope scanning changes were seen in 81% of the patients classified as acute pyelonephritis and in only 27% of those with lower UTI. Reflux was detected in 56% of abnormal kidneys and in 36% of normal kidneys. The results of radioisotope scanning and ultrasound scan findings were not correlated in 24 patients (19 only abnormal radioisotope imaging, 5 only abnormal ultrasound scan). CONCLUSIONS: DMSA scans are useful for investigating and following UTI. They help to distinguish acute pyelonephritis and lower UTI. It is a reliable method of detecting structural abnormalities and identifying children at risk of progressive renal damage.

[The population explosion in sociobiological perspective]. / De bevolkingsexplosie in sociobiologisch perspectief.

The author uses the assertions of Anne and Paul Erlich regarding population growth as a basis for his analysis of whether the field of sociobiology offers hope that humans can control reproduction effectively. He notes that "sociobiology is rather pessimistic about this since it is the essence of human nature to reproduce and multiply. In spite of this there are reasons to believe that humankind is able to achieve...a declining birth rate, and this thesis...takes account of the genetic or natural and the cultural make-up of human beings." (SUMMARY IN ENG)