Biomedical subjects
Publications and source records attributed to P Rigatti.
We present the case of a 44-year old man, presenting with acute left flank pain and gross haematuria, affected by bilateral renal mass and massive para-aortic and mediastinic lymphadenopathy, highly suspicious for metastatic renal cancer.
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Androgen ablation or blockade of androgen action through the androgen receptor (AR) has been the cornerstone of treatment of advanced prostate cancer. The relative merits of monotherapy or combined androgen blockade (CAB) are still the subject of debate. Each treatment strategy/hormonal agent has favourable and unfavourable effects. Patients with advanced prostate cancer will clearly benefit androgen deprivation-based treatment for palliating their symptoms and for improving their quality of life (QOL). However, whether these therapies prolong survival when administered before there are symptoms caused by disease progression remains controversial. Data from multiple recent studies indicate that an earlier treatment in patient's disease course likely leads to better outcome, but it is not easy to predict the best timing of hormonal therapy for asymptomatic advanced disease. For the purpose of delaying the onset of androgen-independent growth of prostate cancer, different regimen of intermittent androgen blockade (IAB) have been applied to patients. The use of IAB is increasing but, despite theoretical advantages in terms of patient QOL, clinical studies have yet to prove superiority over continuous therapy. The role of androgen deprivation in combination with surgery or radiotherapy has been also evaluated. While neoadjuvant hormonal therapy (NHT) can significantly decrease the incidence of positive margins at the time of radical prostatectomy (RP), 3 months of treatment is not long enough to have any significant effect on biochemical recurrence rates. The results of studies investigating longer courses (8 months) of NHT are awaited. High-risk patients should be considered for early adjuvant hormonal therapy (AHT) after surgery, as they may be most likely to benefit. The rationale for the use of NHT in combination with radiotherapy is that it reduces tumour volume and therefore the amount of radiation therapy that is needed to treat the tumour. It has been found that 3-4 months of hormonal treatment reduces prostate volume by 25-50%. Intermediate-risk patients treated with NHT and concomitant hormonal therapy have been found to have a 94% freedom for biochemical failure after 4 years, suggesting that this group is the ideal patient population to receive short-term hormonal therapy in combination with brachytherapy. Several studies suggested the current consensus that patients with clinically localized or locally advanced high-grade tumours benefit from definitive radiation therapy and long-term AHT. The current treatment for advanced prostate cancer remains essentially palliative. However, an increased understanding of the heterogeneous nature of the disease, the mechanisms that lead to hormone-refractory prostate cancer (HRPC) has identified novel therapeutic targets and led to the development of selective new therapies, that may help to prolong survival and maintain QOL for patients with HRPC.
In the long-term there is biochemical evidence of recurrent prostate carcinoma in approximately 40% of patients after radical prostatectomy (RP). Detecting the site of recurrence (local vs distant) is critical for defining the optimum treatment. Pathological and clinical variables, e.g. Gleason score, involvement of seminal vesicles or lymph nodes, margin status at surgery, and especially the timing and pattern of prostate-specific antigen (PSA) recurrence, may help to predict the site of relapse. Transrectal ultrasonography (TRUS) of the prostatic fossa in association with TRUS-guided needle biopsy is considered more sensitive than a digital rectal examination for detecting local recurrence, especially if PSA levels are low. Although it cannot detect minimal tumour mass at very low PSA levels (< 1 ng/mL) TRUS biopsy is presently the most sensitive method for detecting local recurrence. Nevertheless, the conclusive role of biopsy of the vesico-urethral anastomosis remains unclear. However, 111In-capromab pendetide scintigraphy and [11C]-choline tomography (which are better than conventional imaging for detecting metastatic tumour), have low detection rates for local disease and are considered complementary to TRUS in this setting. Patients with a high PSA after RP may be managed with external beam salvage radiotherapy. An initial PSA of < 1 ng/mL, Gleason score < 8 and radiation dose of 66-70 Gy seem to be key factors in determining success. Although a positive TRUS anastomotic biopsy may predict a better outcome after radiation therapy, the need to take a biopsy in the event of PSA failure remains under investigation. The value of salvage radiation to the prostatic bed for PSA-only progression after RP remains in question.
Since it was initially described in 1992 laparoscopic adrenalectomy (LA) has been gaining popularity amongst urologists and its range of applications has progressively widened. Ten years after the first report of LA this type of operation is presently considered to be the 'standard of care' for most adrenal diseases requiring surgery. We define the current role of laparoscopy in the management of surgical adrenal diseases, using a Medline search (1997-2002) to assess reports of LA, focusing on indications, approaches (transperitoneal and retroperitoneoscopic) and comparative analyses, taking particular care to evaluate operative duration, rate of conversion and transfusion, complications and hospital stay. With both approaches LA is safe and effective and, when compared with open surgery, offers the same functional results with all the advantages of minimally invasive surgery. We conclude that LA based on either approach should be considered the treatment of choice for benign adrenal lesions. Although very promising, conservative surgery and LA should still be evaluated in cases of malignancy.
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The widespread acceptance of prostate-specific antigen (PSA) measurement as an early detection method for prostate cancer (Pca), coupled with the recent heightened public awareness of Pca as a common disease, has led to an increase in the detection of Pca. It has been established that digital rectal examination (DRE) and PSA are the most useful front-line methods for assessing an individual's risk of Pca. In addition to an elevated PSA above 4 ng/mL and an abnormal DRE, the decision to proceed with TRUS-guided biopsy may also be supported by other factors. Determining the presence of a significant rise in PSA between tests, whether the degree of PSA is concordant with the size of the prostate, and age appropriate PSA may aid in the interpretation of this risk. Grayscale transrectal ultrasound (TRUS) has been established as the first choice imaging technique making it possible to take biopsies, measure the volume and obtain a general overview of the prostate. To improve, however, the TRUS detection rate of Pca, many ultrasonographic technique improvements have been introduced and continuously evaluated. As for prostate biopsy, in the prostate with visible lesions, lesion-guided biopsies only play a role in combination with systematic biopsies, while the systematic prostate biopsy scheme should at the present time include 10 or 12 cores according to prostatic weight. The other imaging techniques actually play a marginal role in Pca detection, but may be useful for staging newly diagnosed Pca or in patient re-staging in case of biochemical failure after radical treatment.
The prevalence of superficial transitional cell carcinoma of the bladder (STCCB) is still increasing in spite of improved adjuvant chemotherapeutic and/or immunoprophylaxis approaches. Thus, there is certainly an urgent need to improve our ability to control this disease. Local hyperthermia has a therapeutical potential for the treatment of many solid tumors, especially when used in combination with other treatments, such as radiation and chemotherapy. In particular, a synergistic or, at least, supra-additive anti-tumor cell killing effect was documented when local hyperthermia was administered in combination with selected cytostatic drugs. Recently, advances in miniaturized technology have allowed the development of a system specifically designed for delivering an endovesical thermo-chemotherapy regimen in humans. In preliminary clinical experiences, insofar mainly carried out as mono-institutional investigations, the combined treatment using this system was demonstrated to be feasible, minimally invasive and safe when performed on out-patient basis. Moreover, the anti-tumoral efficacy seemed to be significantly enhanced when compared with that obtained using intravesical chemotherapy alone for both adjuvant (prophylaxis) and neo-adjuvant (ablative) approaches to superficial bladder cancer.
It is well recognized that sexual stimulation leading to penile erection is controlled by different areas in the brain. Animal erection studies have shown that apomorphine (a D2>D1 dopamine receptors nonselective agonist) seems to act on neurons located within the paraventricular nucleus and the medial preoptic area of the hypothalamus. Yet, only recently, was a centrally acting agent, apomorphine sublingual, approved for the treatment of erectile dysfunction. The present functional magnetic resonance imaging placebo-controlled study presents the first in vivo demonstration of the apomorphine-induced modulation of cortical and subcortical brain structures in patients with psychogenic erectile dysfunction. Noteworthy, patients in comparison with potent controls, showed an increased activity in frontal limbic areas that was downregulated by apomorphine. This suggests that psychogenic impotence may be associated with previously unrecognized underlying functional abnormalities of the brain.
In this multicentre, double-blind study, patients with LUTS/BPH were randomised to 26 weeks with finasteride 5 mg once daily (n=204) or tamsulosin 0.4 mg once daily (n=199). Double-blind treatment was continued for another 26 weeks (total treatment duration: 1 y). The primary efficacy parameter was the difference in mean change in total Symptom Problem Index (SPI) from baseline to end point at week-26 in the intention-to-treat (ITT) and per protocol (PP) populations. Tamsulosin induced a greater improvement in total SPI (-5.2 points or -37%) compared to finasteride (-4.5 points or -31%) at week-26 (P=0.055 in ITT and P=0.032 in PP). Tamsulosin improved urinary symptoms (particularly the more bothersome storage symptoms) and flow more quickly than finasteride. The difference was statistically significant for the SPI from week-1 (reduction, respectively, -2.5 vs -1.8 points, P=0.043) to week-18 and for Qmax from week-1 (increase, respectively, 2.3 vs 0.7 ml/s, P=0.0007) to week-12. Both treatments were well tolerated with a comparable incidence of adverse events, including urinary retention.
Erectile dysfunction (ED) is a common medical condition that affects the sexual life of millions of men worldwide. Many drugs are now available for treating ED; oral pharmacotherapy represents the first-line option for most patients with ED. Sildenafil, an inhibitor of the enzyme phosphodiesterase type 5, is currently the most widely prescribed oral agent and has a very satisfactory efficacy-safety profile in all patient categories. Apomorphine SL is a dopamine D1- and D2-receptor agonist which has recently been approved for marketing in Europe. It is best selected for treating patients with mild to moderate ED. Vardenafil and tadalafil are new phosphodiesterase type 5 inhibitors which are expected to be approved this year. Both of them have significant positive efficacy-safety profiles. Patients who do not respond to oral pharmacotherapy or who cannot use it are good candidates for intracavernosal and intraurethral therapy. Alprostadil is the most widely used drug, both for injection therapy and for the intraurethral route. The efficacy of second-line treatment is high but the attrition rate remains significant.
Erectile dysfunction is common in the ageing man and reliable therapies are needed. The pathophysiology of erectile dysfunction in this group mainly includes chronic ischaemia, which triggers the deterioration of cavernosal smooth muscle and the development of corporeal fibrosis. Assessing the ageing man with erectile dysfunction who seeks medical treatment should comprise a thorough medical and sexual history, a systemic and focused physical examination and selected blood tests. Oral drug therapy represents a safe and effective option for most ageing men.
PURPOSE: We compared [11C]choline-positron emission tomography (PET) with [18F]fluorodeoxyglucose-PET for re-staging prostate cancer in a group of 100 patients. MATERIALS AND METHODS: A total of 100 consecutive patients referred for whole body [18F]fluorodeoxyglucose-PET for clinical prostate re-staging after radical treatment for prostate cancer were retrospectively included in the study. Mean prostate specific antigen (PSA) was 6.57 ng./ml. In all cases [11C]choline-PET was also performed. PET studies were done with a multiring device 5 minutes after intravenous injection of approximately 370 MBq. [11C]choline and 60 minutes after injection of approximately 370 MBq. [18F]fluorodeoxyglucose. PET findings were compared with those obtained with different conventional imaging and with PSA assessed at the time of PET and 1 year later. RESULTS: Areas of abnormal focal increases were noted in 47% of patients on [11C]choline-PET and in 27% on [18F]fluorodeoxyglucose-PET. Of the 100 patients 49 had positive conventional imaging findings. All except 14 [11C]choline-PET findings were concordant with conventional imaging, including 6 negative and 8 positive conventional imaging results. All except 1 [11C]choline-PET negative cases also had negative conventional imaging after 1 year. PSA at 1 year remained stable or decreased in 80% and 62% of [11C]choline-PET negative and positive cases, respectively. CONCLUSIONS: [11C]choline-PET seems to be useful for re-staging prostatectomy cases with increasing serum PSA levels. It is superior to [18F]fluorodeoxyglucose-PET and complementary to conventional imaging but with the advantage of staging disease at a single step.
Seed embolisation to the lung is a possible risk following permanent prostate brachytherapy. The purpose of this work is to analyse a seed migration case and to suggest methods to reduce such occurrences. With this aim, the clinical history of the patient who experienced seed migration, the implant technique and the pre- and post-plan procedures have been investigated. The massive seed migration has been detected in the patient by means of a pelvic X-ray and a CT-scan of the thorax. The use of loose seeds, the implant technique and the presence of unfavourable anatomical characteristics, have been recognised as possible causes of this event. The use of linked seeds embedded in vicryl sutures for the peripheral portions of prostate, and the development of an implant technique based on both transverse and longitudinal ultrasound guidance are proposed in order to reduce seed migration.
Guidelines for management of patients with erectile dysfunction indicate that intraurethral and intracavernosal injection therapies represent the second-line treatment available. Efficacy of intracavernosal injections seems superior to that of the intraurethral delivery of drugs, and this may explain the current larger diffusion of the former modality. Safety of these two therapeutic options is well established; however, the attrition rate with these approaches is significant and most patients eventually drop out of treatment. Newer agents with better efficacy-safety profiles and using user-friendly devices for drug administration may potentially increase the long-term satisfaction rate achieved with these therapies. Topical therapy has the potential to become a first-line treatment for erectile dysfunction because it acts locally and is easy to use. At this time, however, the crossing of the barrier caused by the penile skin and tunica albuginea has limited the efficacy of the drugs used.
AIMS: To assess the effect of local hyperthermia on the systemic absorption of mitomycin C (MMC) during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma of the bladder, and to establish the likely safety of this procedure. METHODS: Group 1 (n = 12) received 20 mg intravesical MMC plus local hyperthermia, group 2 (n = 13) 20 mg MMC alone, group 3 (n = 16) 40 mg MMC plus local hyperthermia and group 4 (n = 10) 40 mg MMC alone. Patients in groups 1, 2, and 4 underwent post-tumour resection adjuvant treatment, whereas those in group 3 still had tumour present and were treated to eradicate it. Intravesical instillation lasted 60 min, with the solution (50 ml) being replaced after the first 30 min. Blood samples were taken before, and every 15 min during instillation. MMC concentrations in plasma and in urine were determined by h.p.l.c. RESULTS: The highest MMC plasma concentration (67.9 ng ml(-1)) occurred in a patient in group 3. This value was well below the threshold concentration (400 ng ml-1) for myelosuppression. Local hyperthermia associated with the intravesical chemotherapy enhanced plasma MMC concentrations at 30, 45 and 60 min compared with chemotherapy alone (Group 1 vs 2, P < or = 0.008). Systemic exposure to MMC was not significantly increased by doubling the intravesical dose when intravesical chemotherapy alone was administered. Patients in group 3 displayed the highest degree of MMC absorption and the greatest variability in pharmacokinetics between patients. CONCLUSIONS: Local hyperthermia enhances the systemic absorption of MMC during intravesical chemotherapy for bladder cancer. In the doses used, plasma MMC concentrations were always more than six times lower than those shown to cause toxicity.
PURPOSE: Radical cystectomy is advocated for high risk patients with superficial bladder cancer. To preserve complete urinary continence, normal sexual function and fertility in young patients, we developed an innovative technique based on nerve and seminal sparing radical cystectomy. MATERIALS AND METHODS: Radical cystectomy was recommended for 8 patients with superficial bladder cancer that was not conservatively manageable. Average patient age was 44 years (range 36 to 48), and all patients were extremely anxious to maintain potency and fertility. The surgical procedure consisted of transurethral resection of the prostate, pelvic iliac lymph node dissection and extraperitoneal radical cystectomy performed while preserving the vas deferens seminal vesicles and neurovascular bundles. Urinary diversion was accomplished with a W-shaped ileal reservoir anastomosed to the prostatic capsule. RESULTS: Patients were generally discharged from the hospital 15 days after surgery, and postoperative morbidity was limited. Daytime and nighttime continence was immediate and complete after catheter removal. Normal erectile function was clinically documented in all patients while fertility potential with semen retrieval via urine was recorded in 7. The quality of life, as reported by the patients, was highly satisfactory at 18-month followup. CONCLUSIONS: The surgical approach we describe should be considered in young men with clinical, superficial bladder tumors refractory to conservative treatment who wish to maintain potency and fertility, and to guarantee as good a quality of life as possible. To ensure oncological success scrupulous patient selection is a primary step of this procedure.
At present, a significant proportion of patients with prostate cancer are diagnosed at an early stage and may receive treatments able to bring about the long-term control of the disease. Thus, the impact of available treatments on the patient's quality of life has been gaining increasing importance; for patients with prostate cancer, counselling on the treatment-related effects on sexual function has become mandatory. Radical prostatectomy is very frequently performed in patients with clinically localized prostate cancer. Postoperative erectile function has been reported as being satisfactory in the majority of the patients operated on in centers of excellence for this procedure. However, overall, the results for postoperative potency are disappointing in view of the large amounts of data available from community practices. Attempts to improve postoperative potency include the intraoperative use of cavernous nerve stimulation and grafting of peripheral nerves to restore the innervation of the corpora cavernosa. Erectile dysfunction has also been associated with prostate radiotherapy. It has been shown that both ultrasound-guided brachytherapy and three-dimensional conformal radiation therapy cause an impairment of erectile function that is usually seen some time after the completion of therapy. Treatment with sildenafil citrate remains a viable option both for patients treated with radical prostatectomy (in whom the cavernous nerve function is at least partially present) and in patients treated with radiotherapy.