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J L Gomez

Publications and source records attributed to J L Gomez.

34 records · Page 2Linked to original sources
PubMed1993

Response to flutamide withdrawal in advanced prostate cancer in progression under combination therapy.

The effect of flutamide withdrawal was studied in 40 patients with stage D2 prostate cancer showing progression of the disease after an initial and long (average 3.9 years) period of positive response to combination therapy with flutamide associated with medical (luteinizing hormone-releasing hormone agonist) or surgical castration. Using the criteria of response of the United States National Prostatic Cancer Project, 1 complete, 3 partial and 26 stable responses were observed, while 10 patients continued to have progression after discontinuation of flutamide. The average durations of previous treatment with combination therapy were 1,794 days for the 30 responders (complete, partial and stable responses), compared to 1,726 days for the 10 nonresponders. The average duration of response after the arrest of flutamide was 440 days. Serum prostate specific antigen, which was elevated in all patients, decreased by 90% or more in 19 of the 30 responders (63%) and returned to normal in 17 (57%). The concentration of testosterone binding globulin increased after discontinuation of flutamide, thus also suggesting the suppression of an androgenic influence, while the serum levels of testosterone and dihydrotestosterone, as well as their main metabolites, did not change after withdrawal of flutamide. Alteration of local sensitivity to androgens is a probable explanation for the paradoxical positive response to the arrest of flutamide suggested in the present preliminary study.

Adenocarcinoma↗
PubMed1993

Combination therapy with flutamide and the LHRH agonist [D-Trp6, des-Gly-NH(2)10]LHRH ethylamide in stage C prostatic carcinoma.

A series of 115 previously untreated patients displaying clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen flutamide and the LHRH agonist [D-Trp6, des-Gly-NH(2)10]LHRH ethylamide; the average follow-up was 3.9 years. Twenty-eight patients showed treatment failure with a probability of disease-free survival of 91.2% at 2 years. Twenty patients died from prostate cancer and 10 from other causes, the survival probability being 93.4% at 2 years. Local control was achieved rapidly in all patients. Urinary obstruction and hydronephrosis were corrected in all cases. When compared with data obtained after single endocrine therapy (orchiectomy or oestrogens) or radiotherapy, the treatment failure rate at 2 years was more than 3.0-fold lower after combination therapy (8.8%) than monotherapy (28.4%). The death rate 2 years after the start of combination therapy was 6.6% and was on average 22.2% (3.6-fold higher) in the studies using monotherapy (orchiectomy or oestrogens) or radiotherapy. The present data suggest that treatment of prostate cancer with combination therapy before clinical evidence of dissemination of disease permits more efficient control of local disease and a decreased rate of progression to metastatic disease.

Aged↗
PubMed1993

Optimized strategy for detection of early stage, curable prostate cancer: role of prescreening with prostate-specific antigen.

In 1,002 men aged 45-80 y, 81% of the cancers detectable by serum prostate-specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasonography (TRUS) were present in a subpopulation (19% of total) identified by serum PSA above the threshold value of 3.0 micrograms/L. This study was extended to 7,350 men using serum PSA and DRE as first approach, followed by TRUS only when 1 of these 2 tests was abnormal. Because the aim of prostate cancer detection is to find cancers at an early, potentially curable stage, it is of major interest that 71.8% of evaluable cancers were clinical stage B; 8.4% and 10.7% were stages C1 and C2, respectively; only 9.2% were stage D (metastatic) at first visit while none was at stage D at follow-up visits. This study, the first performed in an unselected, unscreened population, shows that serum PSA is the most sensitive technique to identify men at high risk of having prostate cancer and that 12% more cancers can be found at first visit by doing DRE in addition to PSA. Follow-ups can be done every second year using serum PSA alone, as 97% of the cancers detected at annual follow-up by DRE + PSA were PSA+. Cancers are discovered by the present approach at an estimated cost of $2,665 per cancer. Such cancers are potentially curable in at least 80% of cases detected at first visit and in 97% of cases at follow-up. This strategy offers the possibility to improve markedly morbidity and mortality from prostate cancer, presently the second leading cause of cancer death in North American men.

Aged↗
PubMed1993

Major advantages of "early" administration of endocrine combination therapy in advanced prostate cancer.

Combination therapy with the antiandrogen flutamide and the luteinizing hormone-releasing hormone (LHRH) agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide or orchiectomy was administered to 268 patients with previously untreated metastatic stage D2 prostate cancer for an average of 1,191 d (3.26 y). Only 17 of the 268 evaluable patients (6.5%) showed no objective positive response to the combination therapy assessed according to the National Prostatic Cancer Project objective criteria of response. The median duration of the disease-free response was 2.23 y and median overall survival was 3.58 y. The median survival for patients with only 1-5 bone metastases was not yet reached at 8 y, but for patients with 6-10 bone lesions, 11-40 bone lesions, and multiple bone metastases (superscan), median survival was markedly reduced to 3.56, 2.36, and 1.76 y, respectively. Analysis of patients according to general symptomatology, pain, and performance status showed median survivals of 5.47, 2.71, and 2.1 y for minimal, moderate, and severe symptoms, respectively. The present data demonstrate that administration of combination therapy to stage D2 prostate cancer patients having 1-5 bone metastases adds a minimum of 4.4 y of good quality life compared with patients whose disease is slightly more advanced. Our findings clearly demonstrate the major importance of starting combination therapy as soon as possible after diagnosis of metastatic prostatic cancer.

Androgen Antagonists↗
PubMed1992

Incidence of liver toxicity associated with the use of flutamide in prostate cancer patients.

PURPOSE: The incidence of flutamide-related liver toxicity was studied in 1,091 consecutive patients treated for stage C or D prostate cancer with the antiandrogen flutamide and the luteinizing hormone-releasing factor (LHRH) agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide. PATIENTS AND METHODS: Liver function tests, namely measurement of serum aspartate amino-transferase (AST) and alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase (gamma-GT), and prothrombin and thromboplastin times, were performed at 4, 8, and 12 weeks and every 3 months thereafter. Clinical signs and symptoms of liver dysfunction were also sought. The causal link between the antiandrogen used and liver injury was assessed on the basis of the temporal relationship with the use of the drug in the absence of other possible causes and, in two patients, through rechallenge of the putative causative drug after a period of normalization of liver function. RESULTS: An increase in AST and ALT at fourfold or more above upper normal limits was observed in only four patients (0.36%). Total serum bilirubin and alkaline phosphatase were elevated in only one patient at 126 mmol/L and 640 IU/L, respectively. Among the four patients, only two developed clinical manifestations of liver disease (0.18%). Biopsy was performed in one patient, and the histopathologic findings showed a mixed pattern of cytotoxic and cholestatic changes. All clinical and biologic manifestations of liver toxicity rapidly disappeared upon discontinuation of flutamide alone. No sequelae were observed in the long-term follow-up at 18, 22, 31, and 62 months. The 1,087 remaining patients experienced no or mild (less than fourfold upper normal limit) and transient elevation in aminotransferase serum levels during the first 6 months of treatment, with normalization at later time intervals. CONCLUSION: Despite the fact that the cases reported so far, along with our large series, indicate that the incidence of flutamide-induced liver toxicity is very low, we recommend serial blood aminotransferase measurements at 2 and 4 weeks of treatment in order to detect early signs of possible flutamide-induced hepatic injury, thus avoiding the low potential risk of clinically significant liver toxicity.

Adenocarcinoma↗
PubMed1992

Simultaneous liver and lung toxicity related to the nonsteroidal antiandrogen nilutamide (Anandron): a case report.

We report the case of a 69-year-old patient treated for stage C adenocarcinoma of the prostate with the combination of the luteinizing hormone-releasing hormone agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide and the antiandrogen nilutamide (Anandron) who developed simultaneous liver and lung toxicity. Investigation revealed an abnormal chest radiograph accompanied by altered respiratory function tests, suggesting the diagnosis of interstitial lung disease. This diagnosis was confirmed by an open chest biopsy. At the same time, liver function tests yielded abnormal results. All toxic manifestations disappeared after cessation of treatment with Anandron.

Adenocarcinoma↗
PubMed1992

Serum prostate specific antigen as pre-screening test for prostate cancer.

Prostate cancer has become the most common cancer and the second cause of death due to cancer in men in North America. Since curative therapies are limited to early stages of the disease, the availability of an efficient, easy to perform, widely acceptable and cost-effective method of early detection of prostate cancer is particularly important. Thus, digital rectal examination, transrectal ultrasonography of the prostate as well as measurements of serum prostate specific antigen (PSA) were performed independently in a series of 1,002 men between 45 and 80 years old randomly selected from the electoral rolls of Quebec City and its vicinity as part of a screening program for prostate cancer. Using this population of randomly chosen men, various cutoff serum PSA values were selected in an attempt to find the optimal decision threshold that would indicate a much greater risk of having prostatic cancer. At a threshold value of 3.0 micrograms./l. the sensitivity and specificity of the test are 80.7 and 89.6%, respectively, while the area under the receiver operating characteristic curve reflecting the accuracy of the test is 87.8 +/- 3.3% (plus or minus standard deviation). Moreover, the negative predictive value was estimated at 98.6%, thus leaving only a 1.4% chance of missing cancer when the serum PSA value was 3.0 micrograms./l. or less. Most importantly, such a threshold level of serum PSA retains only 19% of the whole cohort as candidates for transrectal ultrasonography and expensive diagnostic procedures, thus leading to the finding of 1 prostate cancer of 4 such examinations. The present data indicate that simple measurement of serum PSA can be used efficiently as a pre-screening test for prostate cancer in the general population to identify, at a low cost, the subpopulation of men at a much greater risk of having prostate cancer, and who should then be submitted to the more elaborate and expensive diagnostic procedures.

Age Factors↗
PubMed1991

Prostate specific antigen and prostatic acid phosphatase for monitoring therapy of carcinoma of the prostate.

Serial serum prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) measurements were performed in 871 patients treated with hormonal combination therapy for stage C (95 patients) or stage D2 (776) prostate cancer for an average followup of 26 months. The relative efficacy of serum PAP and PSA for predicting recurrence of the disease was evaluated by 2 statistical methods at the time of progression as well as 6 and 12 months before clinical relapse of disease using optimized cut-off values of 2.0 and 4.0 micrograms/l. for serum PAP and PSA, respectively. At the time of progression the sensitivity (plus or minus standard deviation) of the 2 tests was estimated at 61.1 +/- 3.2% and 86.7 +/- 3.1% for PAP and PSA, respectively, while the specificity (plus or minus standard deviation) was calculated at respective values of 79.6 +/- 1.3% and 92.4 +/- 4.1%. Receiver operating characteristic analysis disclosed a greater accuracy for PSA at 89.2 +/- 1.7% versus 78.7 +/- 1.6% (plus or minus standard deviation) for PAP. The somewhat lower positive predictive value of the PSA test (81.4% versus 89.6%) is more than compensated by its superior negative predictive value (92.4% versus 79.6%). The present data also show that serum PSA measurements are superior to those of serum PAP for predicting disease recurrence in stages C and D prostate cancer patients treated by combination endocrine therapy and they indicate that measurement of serum PAP does not add significantly to single measurement of serum PSA alone.

Acid Phosphatase↗
PubMed1984

Tumor-activated NK cells trigger monocyte oxidative metabolism.

We have examined the hypothesis that tumor cells can stimulate a respiratory burst by human natural killer (NK) cells in vitro as measured by luminol-dependent chemiluminescence (CL). Percoll-purified NK cells, containing 40% HNK-1+ cells and less than 1 to 4% esterase-positive contaminating monocytes, can generate a strong CL response after stimulation with the NK-susceptible K562 tumor but not with the NK-resistant P815 tumor cells. Although the response was NK dependent, as shown by depletion with NK-directed monoclonal antibodies (HNK-1, OKT-11, and OKM-1), the cell generating the CL response was not the NK cell. On the basis of several independent experimental approaches the CL response always required the presence of monocytes in the NK preparation. a) Treatment with a monocyte-specific monoclonal antibody (MO2) and complement completely abolished CL. b) The cells producing the CL response were strongly adherent to nylon wool columns (NWC), and large granular lymphocyte preparations containing less than 0.1% esterase-positive cells were inactive. c) NK cells cultured in IL 2-containing medium and tested over several days did not generate CL. d) Optimal numbers of monocytes (less than 1 to 2%) added to a non-CL NWC-purified NK population restored CL, whereas larger or smaller amounts were ineffective. Neither these procedures nor the addition of superoxide dismutase (which completely blocked CL) had any effect on NK lytic activity. We subsequently demonstrated that a factor present in supernatants obtained from NK/K562 incubations, but not from NK or tumor cells alone, could stimulate monocyte CL. We therefore propose that the CL response measured in NK-enriched Percoll fractions originated from contaminating monocytes that were triggered by factor(s) released from tumor-activated NK cells, and that superoxide anion was not required for NK lysis.

Animals↗
PubMed1978

Congenital dilatation of the intrahepatic bile ducts (Caroli's disease).

Caroli's disease (congenital dilatation of the intrahepatic bile ducts) was diagnosed in an 11-year-old girl with the aid of intravenous cholangiography. Recurrent abdominal pain, fever, and intermittent obstructive jaundice are the most common symptoms and usually develop during childhood or young adulthood. Operative cholangiography has been the most valuable method of diagnosing the condition and determining the location and extent of the disease process.

Bile Ducts, Intrahepatic↗
PubMedDate not supplied

Liposarcoma of the stomach.

We present a case of gastric liposarcoma, a very uncommon pathology; only nine cases have been reported in the literature. We describe the radiologic findings of this neoplasm and emphasize the correlation between computed tomography (CT) and the macroscopic morphology of the tumor, which is conditioned by its histology. In our case, CT demonstration of fatty areas within the gastric mass facilitated the diagnosis. This finding has not been described for liposarcomas of the stomach.

Adipose Tissue↗
PubMedDate not supplied

DHEA and the intracrine formation of androgens and estrogens in peripheral target tissues: its role during aging.

Human and some other primates are unique since their adrenals secrete large amounts of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), which are converted into androstenedione (4-dione) and then into potent androgens and estrogens in peripheral tissues, therefore providing autonomous intracrine control to target tissues that can adjust the formation and metabolism of active sex steroids according to local requirements. Knowledge in this area has recently made rapid progress with the elucidation of the structure of most of the tissue-specific cDNAs and genes that encode the steroidogenic enzymes responsible for the transformation of these inactive precursor steroids into androgens and/or estrogens. It is estimated that 30 to 50% of total androgens in men are synthesized in peripheral intracrine tissues from inactive adrenal precursors while, in women, peripheral estrogen formation is even more important, the best estimate being 75% before menopause and 100% after menopause. The marked reduction in the formation of DHEA-S by the adrenals during aging, especially before the age of 50 years, results in a dramatic fall in the formation of active sex steroids in peripheral target tissues, a situation which is thought to be associated with a long series of age-related decreases such as insulin resistance, obesity, osteoporosis, cardiovascular diseases, loss of muscle mass, cancer and other diseases. We have demonstrated for the first time a series of medically important beneficial effects of DHEA administered for 12 months to post-menopausal women. Most interestingly, the bone mineral density significantly increased. This relatively rapid change was associated with an increase in plasma osteocalcin, a marker of bone formation, while a decrease in bone resorption reflected by a decrease in urinary hydroxyproline excretion was observed in parallel. In addition, the estrogenic stimulation of vaginal cytology in the absence of any sign of stimulatory effect on the endometrium is also of potentially major interest for the prevention and management of menopause. Furthermore, the inhibitory effect of DHEA on the growth of human breast cancer xenografts in vivo in nude mice supports the beneficial use of DHEA as hormone replacement therapy in women.

Aging↗
PubMedDate not supplied

Use of abnormalities in the Friedman curve as a predictor of operative delivery in macrosomic babies.

OBJECTIVE: To assess the use of the Friedman labor curve as a predictor of operative delivery in macrosomic pregnancies. STUDY DESIGN: Medical records of 1141 patients who had delivered babies > or =4000 gm (group 1) were reviewed and were compared with the results of the next mother who delivered a neonate with birth weight <4000 gm (group 2). The variables studied were progress of labor as denoted on the Friedman curve, oxytocin use, and need for operative delivery. RESULTS: In the 1141 patients with neonatal birth weights > or =4000 gm, there was a trend toward a longer second stage, arrest disorder, and operative delivery but this did not reach statistical significance. CONCLUSION: Abnormalities in the Friedman curve were not useful as a predictor for operative delivery in pregnancies complicated by fetal macrosomia. There were no statistically significant differences between the two groups in terms of the variables studied.

Birth Weight↗