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Biomedical subjects

E Mukamel

Publications and source records attributed to E Mukamel.

At least 37 records · Page 2Linked to original sources
PubMed1993

[Value of determining prostate specific antigen in follow-up of prostatic cancer].

The value of measuring serum prostate specific antigen (PSA) in monitoring cases of prostatic cancer was studied in 239 patients. 30 patients with benign prostatic hyperplasia served as controls. The patients were treated by radical prostatectomy, radiotherapy or chemotherapy. In the controls PSA levels were elevated in 60%, indicating that PSA measurement is not specific for prostatic cancer. Among 35 patients before and after radical prostatectomy, in those without disease progression, PSA levels were repeatedly low, but were elevated in all with progression. Among 25 patients after radiation and in 28 before and after radiation, low PSA levels were found in all those, without disease progression. High PSA levels, or a rise in levels after irradiation, preceded local growth or metastatic spread. In the 95 patients with metastatic spread who received hormone-and/or chemo-therapy, low PSA levels following initiation of treatment, were a favorable prognostic indicator, with a sensitivity of 100%. High levels, or a rise of levels after initiation of treatment indicated disease progression. The rise in PSA levels preceded clinical evidence of progression by 0 to 30 months. We conclude that serum PSA is a valuable marker for following patients with prostatic cancer.

Biomarkers, Tumor↗
PubMed1992

[Immunotherapy for metastatic renal cell carcinoma: treatment with PLAK cells and low-dose interleukin-2].

During the past 5 years publications from the NIH (Rosenberg et al.) and other centers have reported encouraging results in the treatment of metastatic renal cell carcinoma. Adoptive immunotherapy was applied, using lymphocytes activated by interleukin-2 (LAK cells) plus high doses of interleukin (IL-2) systemically. The mean clinical response rate was 20-35%. Severe lifethreatening adverse reactions to high doses of IL-2 were noted, although they were all of short duration. Laboratory findings of Novogrodsky et al. from Beilinson Medical Center, Israel showed that oxidizing mitogens can induce lymphocyte activation (PLAK cells). Further studies suggested that a combination of such activated cells with low doses of IL-2 could produce effective toxicity to tumor cells without the need for high doses of IL-2 which could be very toxic for the patient. In the past year we treated 7 patients with PLAK cells and IL-2. 4 completed the treatment, of whom 1 responded partially (regression of more than 50% of lung metastases), 1 is stable and in 1 liver metastases regressed but metastases in lumbar vertebrae and in the pelvis progressed. 1 patient died a month after discharge from hospital, probably due to rapid progression of the disease. Our protocol follows that of the Phase II clinical study of 40 patients treated at the Rogosin Institute, New York Hospital--Cornell Medical Center. The mean clinical response rate was 23.6%. Toxicity of IL-2 is dose-dependent. In this protocol, the low doses of IL-2 gave significantly fewer adverse reactions.

Adult↗
PubMed1992

Fifteen years' experience of combined hormone/chemotherapy in metastatic prostate cancer.

Fifteen years ago we embarked on a treatment protocol for prostatic cancer patients with widespread disease (Stage D2) which included both hormonotherapy (i.e., orchiectomy and diethylstilbestrol [DES] 5 mg/day--later substituted with cyproterone acetate [CPA] 0.2 g/day) and chemotherapy (cyclophosphamide and 5-fluorouracil 10 mg/kg/week). The rationale for such an approach was the universally poor results obtained from the conventional approach which advocated consecutive single-treatment schedules once the previous therapy had ceased to be effective. As such a conventional approach probably allowed the selection of new resistant cell clones, we assumed that perhaps an aggressive combined systemic therapeutic approach from the start, would give such a group of patients--already with generalized disease--a better long-term result. In retrospect, after fifteen years, the chemotherapy on a series of 50 patients so treated has been well tolerated with only minimal, temporary side effects. This regimen was continued up to five years with a reduced maintenance dose. The hormonotherapy was also well tolerated, and was fully maintained. Only 28 percent died of their disease (16% within the first 2 years); 28 percent died of other causes; 40 percent are still alive (14% with clinical disease). In only 9 cases was the chemotherapy discontinued for various reasons. No control arm was originally designed in this protocol, but the long-term results suggest that our original concept was probably valid. Further studies, with the possible use also of newer chemotherapeutic agents, may well justify considering this combined therapeutic approach when dealing with this disease in its widespread form.

Aged↗
PubMed1991

The effect of intravesical bacillus Calmette-Guerin therapy on the upper urinary tract.

A total of 66 patients with low grade, low stage transitional cell carcinoma of the bladder who were treated with intravesical bacillus Calmette-Guerin (BCG) underwent cystourethrography to detect vesicoureteral reflux. BCG was instilled weekly for 6 weeks and monthly thereafter for up to 24 months. Whenever vesicoureteral reflux was found or morphological abnormalities were detected on excretory urography (IVP) an isotope renal scan was performed to evaluate the relative renal function. Vesicoureteral reflux was found in 13 patients (19.7%): 10 had grades 1 and 2A, and 3 had grade 2B reflux. The number of BCG instillations ranged from 8 to 22. IVPs were normal in 11 patients. In 2 patients mild unilateral dilatation was present before BCG instillations, and this remained unchanged during and after therapy. None of the 13 patients with vesicoureteral reflux had IVP features suggestive of urinary tuberculosis. In 11 patients the refluxing renal systems had normal relative renal function (50 to 55%). Two patients had a decrease to 40% of the relative renal function with normal IVPs, suggesting a nonBCG related cause. We conclude that BCG therapy is safe in patients with minimal reflux.

Aged↗
PubMed1990

Clinical and pathological findings in prostates following intravesical bacillus Calmette-Guerin instillations.

The prostates of 36 patients who were treated with intravesical bacillus Calmette-Guerin were evaluated by digital rectal examination and transrectal ultrasonography. When abnormal palpatory and/or ultrasonographic findings were detected, core needle biopsies from the suspicious areas were performed. Of the 36 patients 20 underwent biopsies of the prostate. Pathological findings revealed typical granulomas in 8 patients (3 caseating and 5 noncaseating multifocal granulomas). Nonspecific chronic prostatitis was noted in 4 patients and benign prostatic hyperplasia was noted in 8. The number of bacillus Calmette-Guerin instillations ranged from 6 to 19. The interval from initiation of therapy to biopsy ranged from 1.5 to 14.5 months. Caseating granulomas were found during the early course of bacillus Calmette-Guerin instillations (1.5 to 3.0 months), whereas noncaseating granulomas were detected at later stages (4 to 14.5 months). These findings present a high incidence of granuloma formation in patients treated with intravesical bacillus Calmette-Guerin. The duration of therapy is a determinant factor in the induction of granuloma type.

Administration, Intravesical↗
PubMed1990

Significance of histological prognostic indicators in patients with carcinoma of the prostate.

The relationship between histological prognostic indicators and their relative significance in prognosis were studied in 139 patients who underwent radical prostatectomy. The estimated progression rates at 5 and 8 years were 14 and 52% respectively for patients with high grade tumours, 25 and 50% for those with capsular penetration, 31 and 58% for patients with seminal vesicle invasion and 23 and 55% for those with lymph node metastases. Each of the 4 parameters yielded an approximately equal increased risk of disease progression at 5 and 8 years. The occurrence of 2 or more risk factors in the same patient did not result in a statistically increased risk of progression at 5 and 8 years. The effect of capsular involvement on progression was directly related to the extent of invasion. The progression rate at 8 years was 3% for patients with mild involvement, 19% for those with extensive invasion and 50% for those with capsular penetration.

Adult↗
PubMed1989

Prognostic significance of the DNA content of renal carcinoma.

DNA analysis was performed on fresh frozen samples of the primary tumor in 32 patients with renal carcinoma (13 with apparently localized disease and 19 with metastases at presentation). A comparison of ploidy with staging and standard histologic variables was performed. None of the patients who presented without metastases died of disease during the follow-up period. Eleven of 13 patients of this group had a diploid/near diploid pattern, and metastases developed in only one patient. Patients with metastatic disease and a diploid/near diploid DNA content had a significantly better survival rate than those with aneuploid primary tumors. Statistical analysis showed that grade and ploidy contributed significant but independent prognostic information. We concluded that DNA content is a useful prognostic factor in renal carcinoma.

Adult↗
PubMed1989

Conservative treatment of diffuse carcinoma in situ of the bladder with repeated courses of intravesical therapy.

We present a series of 13 patients with diffuse carcinoma in situ (CIS) of the bladder who failed an initial induction course of intravesical therapy with Mitomycin C, thiotepa, doxorubicin or Bacillus Calmette Guérin (BCG). Cystectomy, although indicated, was, for various reasons, not performed after the first failure of intravesical therapy and all patients were subsequently treated topically with the same or different agents. Of the 7 patients treated with 2 induction courses, 6 showed a complete response during a follow-up period of 24 to 42 months. Although 1 patient initially responded completely, he developed invasive transitional cell carcinoma (TCC) Grade IV 30 months later. Among the 3 patients who underwent 3 induction courses, 2 had a complete response at 42 and 60 months of follow-up and 1 developed TCC Grade IV with muscle invasion 18 months later. Two of the 3 patients treated with 4 induction courses are free of disease at 48 and 57 months; the third developed low grade, low stage TCC. This experience suggests that the majority of patients with CIS who fail initial treatment usually respond to further treatment with the same or a different drug. The question as to whether a second course of intravesical therapy, subsequent to failure of the first course, should be given before cystectomy requires further investigation.

Administration, Intravesical↗
PubMed1988

Incidental small renal tumors accompanying clinically overt renal cell carcinoma.

We searched 66 kidneys with renal cell carcinoma for subcapsular or intraparenchymal small nodules in the apparently normal-appearing portion of the kidney. Differentiation between adenoma and carcinoma was done according to histological characteristics. Of the 66 kidneys 20 (30 per cent) contained a total of 58 small nodules ranging from 1 to 15 mm. in diameter. In 9 kidneys the lesions were consistent histologically with carcinoma, in 7 with adenoma and in 4 with carcinoma plus adenoma. Thus, 13 of the 66 kidneys (19.7 per cent) contained small carcinoma. In view of the high incidence of small carcinoma accompanying clinically overt renal cell carcinoma, we suggest that the indications for partial nephrectomy in the management of renal cell carcinoma should be reevaluated.

Adenoma↗
PubMed1988

The effect of bacillus Calmette-Guerin on the urinary system of pigs.

An experimental study was conducted to determine the changes in structure and function of the pig kidney and renal pelvis following intrarenal infusion of bacillus Calmette-Guerin (BCG). Bilateral nephrostomy tubes were inserted in six pigs through a subcostal (flank) retroperitoneal approach. One week later, antegrade pyelograms and renal scans with hippuran I-131 were obtained. The left kidney was then infused weekly for six weeks with two ampules of BCG (Tice strain) dissolved in 75 cc of saline. The right kidney, serving as a control, was infused concomitantly with 75 cc of saline. On week 7, bilateral antegrade pyelograms and renal scans were repeated. Two pigs were sacrificed at four, eight and 12 weeks after completion of BCG therapy. In all pigs, antegrade pyelograms of the left kidney before BCG instillation were identical to those obtained after completion of treatment and to those of the saline infused kidneys. The isotope renal scan in five pigs showed no significant change in image appearance or relative renal plasma flow in the pre-treatment and post-treatment images. In one pig, there was a decrease in the relative clearance of hippuran in the saline infused kidney. In this kidney, an upper pole abscess was found. Microscopic examination of the renal cortex, medulla, pelvis and ureter of the BCG infused kidneys was normal and identical to the saline infused kidneys. The urothelium was intact and no inflammatory changes were noted in the renal cortex or medulla. These results show that direct infusion of BCG into the renal collecting system has no adverse effect on the structure and function of pig kidneys when followed one to three months after treatment.

Animals↗
PubMed1988

Recombinant interferon alfa-2a in metastatic renal cell carcinoma: assessment of antitumor activity and anti-interferon antibody formation.

Twenty-one patients with advanced, measurable, renal cell carcinoma (RCC) were administered recombinant interferon alfa-2a (rIFN-alpha 2a) (Roferon-A; Roche Laboratories, Nutley, NJ) intramuscularly beginning at 3 x 10(6) units and escalating to 36 x 10(6) units, 5 d/wk for a total induction period of 14 weeks. rIFN-alpha 2a antibody production was measured using an enzyme immunoassay (EIA). Those sera found to be positive for presence of antibody by the EIA were tested for the presence of neutralizing antibodies (NA) by an antiviral neutralization bioassay (ANB). All patients were evaluable for toxicity, and 19 were evaluable for response and for incidence of antibody formation. Five patients (26%; 95% confidence interval, 6% to 46%) had complete responses (CR) or partial responses (PR) with a median duration of 283 days. An additional ten patients (53%) had minor tumor regressions with a median duration of 86 days. Fifty-one percent of evaluable patients are alive at 18.6 months. Antibodies to rIFN-alpha 2a as measured by the EIA, were detected in 12 (63%) patients. NA were measured in the serum of six (50%) of those EIA-positive patients. Overall, six of 19 patients (32%) developed NA. Median time to the development of antibody as measured by EIA or NA was 8 and 14 weeks, respectively. Median NA titer was 1,200 IFN neutralizing U/mL. NA-positive and -negative patients had a median duration of response of 13.7 v 9.9 months, and survival of greater than 21.3 v 18.3 months, respectively. Clinical toxicity was mild and not therapeutically limiting. Autoantibody production (ANA, rheumatoid factor [RF], Coombs' direct/indirect) occurred in both NA-positive and -negative patients. The clinical significance of the antibodies to rIFN-alpha 2a and the associated autoantibody formation remain unclear; however, presence of antibody was not associated with adverse clinical sequelae.

Adult↗
PubMed1988

Staging of localized prostate cancer: a clinical-pathologic correlation.

Sixty consecutive patients were staged clinically by digital rectal examination, acid phosphatase and bone scan prior to radical retropubic prostatectomy and pelvic lymphadenectomy. Twenty-one patients also had magnetic resonance imaging (MRI) and computerized tomography (CT) of the pelvic. The surgical specimens were step-sectioned for pathologic staging. Understaging was documented in 0% of A2 patients, 27% of B1 patients and 67% of B2 patients. Capsular invasion was found in 12% of B1 and 52% of B2 patients, while seminal vesicle extension was documented in 18% of B1 and 52% of B2 patients. Lymph node metastases occurred in 3% of B1 and 29% of B2 patients. Clinical staging error was related to tumor size, tumor grade and history of prior TURP or radiotherapy. Neither CT scan nor MRI improved the accuracy of the digital rectal examination.

Carcinoma↗
PubMed1987

Selection of initial therapy for renal cell carcinoma.

Complete surgical excision is the only effective method of treatment for renal cell carcinoma (RCC) and patients with extensive regional or distant metastases are incurable by any means. Accurate preoperative staging is therefore of critical importance, and computerized tomography and magnetic resonance imaging are the most accurate staging modalities. The traditional operative procedure for RCC has been the radical nephrectomy with excision of Gerota's fascia and its contents, resulting in a 60% to 70% 5-year survival of patients with localized tumors (T1-2 and N0 and M0). Extensive lymphadenectomy has not appreciably improved the cure rate. Indeed, less aggressive surgery has been recently proposed by some authors, based on the excellent results achieved after partial nephrectomy or for tumors in solitary kidneys, with survival after partial nephrectomy or enucleation similar to that after radical nephrectomy. Preoperative adjuvants such as angioinfarction or radiotherapy have not increased survival or local tumor control, and no regional or systemic postoperative adjuvant has proven to be of value. Until further data is accumulated, radical nephrectomy remains the treatment of choice for localized RCC.

Adenoma↗
PubMed1987

The incidence and significance of seminal vesicle invasion in patients with adenocarcinoma of the prostate.

The incidence and significance of seminal vesicle invasion in patients with adenocarcinoma of the prostate were determined in 139 patients who underwent radical prostatectomy. Of the 36 patients who had seminal vesicle invasion, 27 (75%) also had capsular invasion and 13 (43%) had lymph node metastases. Disease progression rates were 31% and 58% at 5 and 8 years, respectively. Survival rate at 5 years was 90.6% and at 8 years it was 83.7%. Of the 103 patients without seminal vesicle invasion, 21 (20.4%) also had capsular invasion and 11 (12%) had lymph node metastases. Disease progression rates were 2.5% and 15.7% at 5 and 8 years, respectively. Survival rate at both 5 and 8 years was 98.4%. These data suggest that the majority of patients with seminal invasion do not have lymph node metastases on presentation and thus they cannot be detected by lymph node dissection before radical prostatectomy. Improved techniques for preoperative detection of seminal vesicle invasion can assist in patient selection for surgery and improve the results of radical prostatectomy.

Adenocarcinoma↗
PubMed1987

Pitfalls in preoperative staging in prostate cancer.

Clinical staging in 60 patients with adenocarcinoma of the prostate was compared with pathologic staging to identify factors which may contribute to staging errors. Understaging was directly related to tumor stage and was documented in 0 per cent of A2, 26.5 per cent of B1, and 66.7 per cent of B2 patients. Capsular invasion was found in 11.8 per cent of B1 and 52.4 per cent of B2 patients, seminal vesicle extension in 17.7 per cent of B1 and 52.4 per cent of B2 patients, and lymph node metastases in 2.9 per cent of B1 and 28.6 per cent of B2 patients. The majority of patients who had unnoticed gross extension of the tumor beyond the prostate underwent transurethral resection of the prostate or failed irradiation therapy prior to radical prostatectomy. The results suggest that intraprostatic or periprostatic changes caused by previous treatment to the prostate may interfere with the preoperative staging.

Adenocarcinoma↗
PubMed1987

Combined hormone-chemotherapy for metastatic prostatic carcinoma. Eleven-year follow-up.

Thirty-six patients with histology-proved Stage D2 carcinoma of the prostate were treated with a combination of bilateral orchiectomy, diethylstilbestrol 3 mg/day, and chemotherapy (5-fluorouracil and cyclophosphamide) soon after diagnosis was established. The combined therapy was well tolerated by the patients, and complications were not severe and of a transient nature. The majority of patients showed a subjective and objective improvement: 75 per cent of patients had relief of bone pain, and 80 per cent reported relief in urinary symptoms. There was regression or stabilization of the primary tumor in 82.2 per cent. Disappearance or stabilization of osteoclastic lesions on bone scans was noted in 55.5 per cent of patients. The cumulative survival rate at eleven years is 55.5 per cent.

Aged↗