Radiation therapy as definitive treatment for localized carcinoma of prostate

A progress report on the treatment of 116 patients with adenocarcinoma of the prostate treated by external irradiation is presented. Fifteen, 60, and 41 patients presented initially with Stages A, B, and C, respectively. The majority of the patients received 7,000–7,500 rads during a period of seven to eight weeks, locally to the prostate gland. The five-year actuarial survival were 90, 70, and 40 per cent for Stages A, B, and C, respectively. The five-year survival rates for patients with well and moderately differentiated tumors were significantly better (45 per cent) than for those with poorly differentiated tumors (24 per cent). The five-year survival rate in the patients who received prior or concomitant hormone manipulation was lower (33 per cent) as compared with those receiving radiation therapy alone (43 per cent). All of the above differences were statistically significant (0.01 level). Of the patients failing, distant metastases have developed in 88 per cent suggesting that subclinical distant metastases might have been present prior to initiation of radiotherapy. The local control rate was 82 per cent. The morbidity of this mode of therapy was found to be acceptable. Radical radiation therapy is an effective method for control of carcinoma of the prostate and is potentially curative.     

Hemiresection of the prostate: short-term randomized comparison with standard transurethral resection

BACKGROUND AND PURPOSE: During transurethral resection of the prostate (TURP) for a very large and vascular gland in a medically compromised patient, there may arise the need for quick termination of the procedure because of medical problems that develop as a result of fluid absorption or bleeding if the surgery is prolonged. In such a situation, an alternative solution proposed by us is termination of the procedure after complete resection of one lateral lobe (and the median lobe, if present) of the prostate (hemiresection). PATIENTS AND METHODS: From January 1998 to December 2001, 161 consecutive symptomatic men with prostates >50 cc and an indication for prostatectomy were randomized to receive either a standard TURP (group 1; 80 patients) or prostatic hemiresection; i.e., complete resection of one lateral lobe and the median lobe, if present (group 2; 81 patients). The two groups were comparable in terms of age and prostate size. Preoperative and postoperative parameters were compared in the two groups using Student's t-test. RESULTS: Resected tissue weight was significantly greater in group 1, while the resection time and operative blood loss were significantly lower in group 2. The two groups had comparable improvement in symptom score and flow rate. CONCLUSIONS: Hemiresection of the prostate produces short-term functional results comparable to those of standard TURP in patients with prostates >50 cc, with shorter operative duration and significantly less bleeding. It is an acceptable surgical option in medically compromised patients with significant cardiac, pulmonary, or renal comorbidity.     

Infliximab and semen quality in men with inflammatory bowel disease

BACKGROUND: Infliximab is effective for induction and maintenance of remission in reproductive age men with Crohn's disease. There is no available data on the effects of infliximab on semen quality. The aim of this study was to determine whether changes in semen quality occurred in men receiving infliximab. METHODS: In this prospective study, each patient served as his own control. Patients completed general health and fertility questionnaires and were assessed for disease activity. Two semen analyses were completed before infusion with infliximab and 1 semen analysis was completed 1 week after infusion. Mean semen parameters before infusion were compared with postinfusion parameters by paired t tests. RESULTS: Ten men completed the study. Seven were on maintenance infliximab (group 1) and 3 were receiving a first dose (group 2). Seven had Crohn's disease, 2 had indeterminate colitis, and 1 had ulcerative colitis. All group 1 patients were in remission. Group 2 patients had moderate or severe disease. In comparing pre- and postinfusion semen parameters in all 10 patients, there was a significant increase in semen volume (P = 0.013) after infusion with infliximab and a trend toward decreased sperm motility (P = 0.061). Group 1 had a significant increase in semen volume after infusion (P = 0.039) and a significant decrease in normal oval forms after infusion (P = 0.038). In comparing group 1 and group 2, there was a significant difference in sperm progression. CONCLUSIONS: Infliximab therapy in men may decrease sperm motility and the number of normal oval forms. Whether these findings translate into impaired fertility is an area for further study.     

Hydroxyurea or placebo combined with radiation to treat stages IIIB and IV cervical cancer confined to the pelvis.

In a prospective study by the Gynecologic Oncology Group (GOG), 104 evaluable patients with cervical squamous cell carcinoma Stages IIIB and IVA were randomly assigned to treatment with hydroxyurea or placebo in combination with radiation. There were no deaths resulting from the treatment. Hematologic toxicity was more common and more severe in patients who received hydroxyurea. Response was evaluated in terms of complete tumor regression, duration of progression-free interval and survival probability. By all those parameters the response was significantly better in the groups of patients receiving hydroxyurea.     

Radical cystectomy in septuagenarian patients with bladder cancer

Introduction: Clinical results of radical cystectomy performed on elderly bladder cancer patients over 70 years old were assessed to determine whether age is one of the critical points for the application of this type of surgery. Materials: From January 1992 to December 2002, 41 radical cystectomy performed in septuagenarian population were compared with 197 performed in patients less than 70 years of age. Results: The early and late complication rate for septuagenarians was 29.7% and 12%, compared with 26.9% and 9.6% for patients younger than 70 years respectively. The overall mortality rate for septuagenarians was 4.9%, compared with 8.6% for patients younger than 70 years. There was no significant difference between the two groups with regard to pathologic stage or length of hospital stay. The 5-year overall survival rate for septuagenarians was 53% compared with 59% for patients younger than 70 years. Conclusions: When indicated after adequate preoperative assessment and optimization of the patient, radical cystectomy is a safe procedure in the septuagenarians and patient should not be denied surgery dependent on chronologic age.     

Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity

Fatty acid amide hydrolase (FAAH) is the primary catabolic regulator of several bioactive lipid amides in vivo, including the endogenous cannabinoid anandamide and the sleep-inducing substance oleamide. Inhibitors of FAAH are considered a potential therapeutic approach for the treatment of several nervous system disorders, including pain, anxiety, and insomnia. However, for FAAH inhibitors to achieve clinical utility, they must not only display efficacy in vivo but also selectivity for this enzyme relative to the numerous other serine hydrolases present in mammalian proteomes. Here, we report a general strategy for evaluating the pharmacological activity and target specificity of FAAH inhibitors and its implementation to develop the first class of selective reversible inhibitors of this enzyme that are highly efficacious in vivo. Using a series of functional proteomics, analytical chemistry, and behavioral pharmacology assays, we have identified a class of alpha-keto-heterocycles that show unprecedented selectivity for FAAH relative to other mammalian hydrolases, and, when administered to rodents, raise central nervous system levels of anandamide and promote cannabinoid receptor 1-dependent analgesia in several assays of pain sensation. These studies provide further evidence that FAAH may represent an attractive therapeutic target and describe a general route by which inhibitors of this enzyme can be optimized to achieve exceptional potency, selectivity, and efficacy in vivo.     

Enhancement of purinergic neurotransmission by galantamine and other acetylcholinesterase inhibitors in the rat vas deferens

Galantamine, a mild acetylcholinesterase inhibitor and an allosteric ligand of nicotinic receptors, enhanced in a concentration-dependent manner the amplitude of purinergic twitch contractions of the electrically stimulated rat vas deferens (0.2 Hz, 1 ms, 60 V). Other acetylcholinesterase inhibitors also increased the twitches, showing a hierarchy of potencies of galantamine>physostigmine>tacrine>rivastigmine=donepezil. The potentiations seem to be unrelated to the ability to inhibit acetylcholinesterase, since the hierarchy of potencies to block the enzyme in vas deferens was tacrine>physostigmine>rivastigmine>donepezil>galantamine. Acetylcholine also increased the twitches; such effect was produced by a low range of concentrations of acetylcholine (10(-10)-10(-7) M). This facilitatory effect of acetylcholine on twitches was significantly potentiated by galantamine (10(-7)-10(-6) M), but not by rivastigmine or donepezil. A striking enhancement of twitches was also caused by charybdotoxin, a blocker of high-conductance Ca2+-activated K+ channels, and by 4-aminopyridine, a non-specific blocker of K+ channels; in addition, apamin, a blocker of small-conductance Ca2+-activated K+ channels, induced a lower potentiation. The antagonist mecamylamine (10(-7)-10(-6) M) reduced by 80% the potentiation by galantamine, indicating the involvement of nicotinic receptors. Therefore, it is suggested that, besides an inhibition of acetylcholinesterase, some additional mechanisms, such as blockade of Ca2+-dependent K+ channels, or activation of nicotinic receptors of nerve terminals, might be involved in twitch potentiation. These results are relevant in the context of the clinical use of galantamine to improve cognition and behaviour in patients with Alzheimer's disease.