Expanded 99mTc-methylene diphosphonate (MDP) bone scan

Patients with prostatic cancer frequently require evaluation of bony metastases as well as renal function. 99mTc-methylene diphosphonate, a commonly used bone-imaging agent, is about 60 per cent localized in the bony skeleton and about 40 per cent excreted by the kidneys. Immediate imaging after intravenous injection of the isotope may yield high-quality radionuclide nephrourograms, which provide excellent visual and graphic displays of renal anatomy and excretory function. Our preliminary studies suggest that the immediate 99mTc-methylene diphosphonate scan may usefully expand the value of a routine bone scan to screen for ureteral obstruction. Patients with underlying malignancy who require simultaneous evaluation and follow-up of bony metastases and renal function might be conveniently served by the dual functions of the expanded bone scan to include immediate imaging of the kidneys.     

Expanded Tc-methylene diphosphonate (MDP) bone scan

Patients with prostatic cancer frequently require evaluation of bony metastases as well as renal function. ^99mTc-methylene diphosphonate, a commonly used bone-imaging agent, is about 60 per cent localized in the bony skeleton and about 40 per cent excreted by the kidneys. Immediate imaging after intravenous injection of the isotope may yield high-quality radionuclide nephrourograms, which provide excellent visual and graphic displays of renal anatomy and excretory function. Our preliminary studies suggest that the immediate ^99mTc-methylene diphosphonate scan may usefully expand the value of a routine bone scan to screen for ureteral obstruction. Patients with underlying malignancy who require simultaneous evaluation and follow-up of bony metastases and renal function might be conveniently served by the dual functions of the expanded bone scan to include immediate imaging of the kidneys.     

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium

Of 92 patients who received methotrexate, vinblastine, doxorubicin and cisplatin complete and partial remissions were observed in 69 +/- 10 per cent of 83 adequately treated measurable and evaluable patients with advanced stages (N+M0 and N0M+) transitional cell urothelial cancer. Complete remission was achieved in 37 +/- 10 per cent of the patients clinically, pathologically and after surgical resection of residual disease. With 17 of 31 complete responders (55 per cent) surviving for 26+ to 49+ months, the estimated probability of survival at 2 and 3 years was 71 and 55 per cent, respectively. Partial remission occurred in 31 +/- 10 per cent of the patients, while 8 per cent had a minor response and 23 per cent had progression with median survivals of 11, 11 and 7 months, respectively. Whereas all metastatic sites responded, including the bone and liver, complete tumor regression was observed more frequently with nodal, pulmonary and local-regional lesions. Brain metastases occurred within 6 to 42 months in 18 per cent of the responders, half of whom never had systemic relapse. Of the remaining 9 patients 2 with nontransitional cell histological tumors did not respond, 5 (5 per cent) were inadequately treated and 2 were excluded from response data because of inevaluable disease parameters but they were free of disease at 16+ and 31+ months. Toxicity was significant, with 20 per cent of the patients experiencing nadir sepsis, 4 per cent a drug-related death, 31 per cent +1 renal toxicity and 41 per cent +1 mucositis. The applications and advantages of the newly proposed international response criteria for bladder cancer are discussed in reference to 25 patients who underwent surgical re-staging, indicating that the disease was understaged clinically in 24 per cent (T less than P), as well as in reference to attainment of true (pathological) complete remission and to other urothelial tract trials. While this therapy seems to have limited antitumor activity against nontransitional cell histological cancer, stage Tis disease and later development of de novo lesions, the regimen is efficacious in selected patients with advanced urothelial tract transitional cell carcinoma.     

The benefits of combining early radionuclide renal scintigraphy with routine bone scans in patients with prostate cancer

Based upon the rapid early renal excretion of bone imaging radiopharmaceuticals, we performed a prospective study to determine the use of combining renal evaluation with routine bone scans in 79 consecutive patients with prostate cancer. The radionuclide renal scintigraphy consisted of a 1-minute sequence of 2.5-second frames with a bolus injection of 99mtechnetium-methylene diphosphonate followed by a series of 2-minute images for 24 minutes. Whole body bone scans were performed after a 3-hour delay. All patients had at least 1 confirmatory study with excretory urography (62), ultrasonography (49) or computerized tomography (30). Results were interpreted independently and compared. Ten studies were normal. Radionuclide renal scintigraphy was able to identify 45 of 49 cortical abnormalities (90 per cent) with a false positive rate of 4 per cent. Accuracy of renal cyst detection was only 47 per cent (15 of 32 cases). All acutely obstructed kidneys were identified correctly by radionuclide renal scintigraphy (5 of 5 cases). Of 12 chronically obstructed kidneys 8 (67 per cent) were identified correctly. The 4 missed kidneys were small and nonfunctioning, and they were diagnosed correctly as such but obstruction as the etiology of nonfunction was unidentifiable by radionuclide renal scintigraphy. The false positive rate of obstructive diagnosis by radionuclide renal scintigraphy was 24 per cent (4 of 17 cases). These findings demonstrate that renal evaluation combined with routine bone scanning is an effective screening procedure for renal complications of prostate cancer; no significant abnormalities were missed. The procedure is entirely free of morbidity and does not add to the radiation dose from the bone scan. Furthermore, it is cost-effective, since it avoids the routine need for 2 separate procedures at followup of patients with prostate cancer.     

Distribution of skeletal metastases in prostatic and lung cancer. Mechanisms of skeletal metastases

The distribution of skeletal metastases in prostatic and lung cancer was examined to test the hypothesis that prostatic carcinoma spreads by a unique hematogenous route. Abnormal technetium-99m methylene diphosphonate bone scans were retrospectively reviewed in 71 patients with prostatic carcinoma and 41 patients with lung cancer comparing patterns of osseous involvement. Differences in the distribution of lesions were not significant. It is concluded that prostatic carcinoma does not metastasize to specific skeletal sites by a singular hematogenous pathway.     

Positive random iliac bone biopsy in advanced prostatic cancer

Forty-one patients with biopsy proved prostatic cancer and with biopsy proved bone metastases were retrospectively evaluated. In 16 per cent of the patients, bone biopsy was positive in spite of negative skeletal survey. Positive skeletal survey and increased serum acid phosphatase levels were found in 78 per cent of the patients, although bone marrow acid phosphatase was elevated in all patients. The determination of bone marrow acid phosphatase was found to be the most sensitive parameter in detection of bone metastases in patients with advanced prostatic cancer.     

Multimodal treatment of advanced testicular tumor with radical reductive surgery and multisequential chemotherapy with cis platinum, bleomycin, vinblastine, vincristine and actinomycin D.

Advanced testicular tumors in 34 patients were treated by combination chemotherapy with bleomycin, vinblastine, vincristine, cis platinum and actinomycin D. The therapy was divided into 3 phases: 1) induction, 2) consolidation and 3) maintenance. Induction lasted 4 weeks and consisted of 420 mg. bleomycin, 0.2 mg./kg. vinblastine, 4 mg./kg. cis platinum, and 20 mg. prednisone daily. Consolidation lasted 6 weeks and consisted of 5 mg. actinomycin D, 6 mg. vincristine and 6 mg./kg. cis platinum. Maintenance therapy was achieved with 2.5 mg. actinomycin D every 6 weeks and 1 mg./kg. cis platinum every 3 weeks. A tumor reductive operation was done before induction of chemotherapy in 13 patients and after induction of chemotherapy in 12 patients. Nine patients were treated with chemotherapy alone. Three patients with brain metastases received concomitant radiotherapy to the brain (3,000 rads). A previous operation and chemotherapy had failed in 11 patients and previous radiotherapy had failed in 1 patient. All patients treated had at least 1 objective response (34 of 34 or 100 per cent). Partial clinical remission was achieved in 7 of 34 patients (21 per cent). A complete clinical remission was observed in 27 of 34 patients (79 per cent) and of this group 6 had a relapse. At present, 22 of 34 patients are free of disease from 4 to 24 months, with an average of 13 months (65 per cent). The toxicity consisted of nausea, vomiting, mucositis, alopecia, mild leukopenia and tinnitus. This approach seems to be effective in producing long clinical remissions in the majority of patients with advanced disease.     

The combination of cyproterone acetate and low dose diethylstilbestrol in the treatment of advanced prostatic carcinoma

Cyproterone acetate is a steroidal antiandrogen with weak progestational activity that results in the partial suppression of pituitary gonadotropin. We demonstrate that the associated decrease in serum testosterone is more complete and prolonged if cyproterone acetate (200 mg. daily) is combined with a low dose of diethylstilbestrol (0.1 mg. daily). The effectiveness of the combination in the treatment of prostatic carcinoma was investigated in 51 patients with stage D2 malignancy. From an initial concentration of 360 +/- 23 ng. per dl. (mean +/- standard error), serum testosterone decreased to 56 +/- 5 ng. per dl. after 1 week and reached a plateau of approximately 30 ng. per dl. after 2 months. This was accompanied by a decrease in serum prostatic acid phosphatase from a mean starting concentration of 43 +/- 11 ng. per ml. to a low of 3 +/- 1 ng. per ml. at 12 months; the proportion of normal values increased from 10 to 80 per cent. A complete response was observed in 7 patients (13 per cent), partial response in 35 (69 per cent) and stable disease in 8 (16 per cent), yielding an over-all objective response rate of 98 per cent (1980 National Prostatic Cancer Project criteria). The actuarial median time to progression was 17 months and the median survival time was 23.5 months. In 26 patients who subsequently had signs of progressive carcinoma the relapse rate in bone (85 per cent) far exceeded that in nonskeletal sites (23 per cent). The incidence of cardiovascular toxicity was 12 per cent. These results indicate that cyproterone acetate and low dose diethylstilbestrol may be co-administered to achieve a synergistic and potent androgen withdrawal effect in the treatment of advanced prostatic carcinoma.     

Evaluation of a comprehensive algorithm for blunt and penetrating thoracic and abdominal trauma.

The objective was to develop a single branched-chain decision tree for both blunt and penetrating thoracic and abdominal trauma and to test its feasibility to track clinical decisions. The algorithm consisted of 14 specific patient management loops and 31 decision nodes. During a 4-month period, the management decisions and clinical course of 434 trauma patients were prospectively observed. Thirty-four patients had no signs of life on arrival to the emergency department (ED) and were excluded from the statistical evaluation; the remaining 400 patients constituted the study group. The mean Injury Severity Score (ISS), Penetrating Abdominal Trauma Index (PATI), and Trauma Score (TS) scores in the series were 21 +/- 10, 34 +/- 12, and 13 +/- 3. The overall patient mortality of the study group was 17 per cent; it was 61 per cent in those patients with major deviations from the algorithm and 6 per cent in patients who complied with the algorithm. The ISS, PATI, and TS scores were 29 +/- 9, 32 +/- 12, and 13 +/- 2 in patients with deviations and 20 +/- 10, 37 +/- 12, and 14 +/- 2 in patients who complied with the algorithm. Of the 37 patients who died with major deviations from the algorithm, the deviation was directly contributory to death in 21 cases (57%) and probably contributory in another 14 cases (38%). There were 108 patients with ISS scores between 20 and 50. In this group, mortality was 55 per cent when a major deviation occurred and 5 per cent without major deviations from the algorithm. The authors conclude that the survival of trauma patients may be improved by following the specific management criteria outlined by the algorithm.     

Incidental carcinoma of the prostate: significance of staging transurethral resection

We compared the results of staging by a second circumferential transurethral resection and/or transperineal needle biopsy in 42 patients with stage A prostatic adenocarcinoma on initial transurethral resection (defined as tumor of low grade, Gleason sum 2 to 4, and low volume, less than 5 per cent of the specimen or less than 3 foci). Transurethral resection only was done in 16 patients, transperineal needle biopsy only in 2 and both procedures in 24. In the 24 patients who underwent both procedures residual carcinoma was identified by transurethral resection in 6 and confirmed by transperineal needle biopsy in only 1. Thirty-two patients (76 per cent) had no residual carcinoma. Of the 10 patients (24 per cent) with residual carcinoma 5 underwent radical prostatectomy with pelvic lymphadenectomy, 1 had interstitial irradiation with pelvic lymphadenectomy and 1 had pelvic lymphadenectomy only. No lymphatic metastases were detected; persistent carcinoma confined to the prostate was noted in all 5 patients who had undergone radical prostatectomy and 3 of these tumors were upstaged because of higher grade and/or volume. We conclude that residual carcinoma cannot be assessed accurately with transperineal needle biopsy, whereas transurethral resection staging enabled us to define a substantial number of our patients (24 per cent) with persistent disease. Importantly, upstaging by either low volume/high grade or high volume carcinoma was identified in 3 patients at the time of radical prostatectomy. However, the true stage and prognosis of those patients with persistent low volume and low grade prostatic carcinoma remain to be determined.     

The localization of human breast carcinomas by radiolabelled monoclonal antibodies

Immune-deprived mice bearing HX99 human breast carcinoma xenografts were injected with a radiolabelled monoclonal antibody, LICR-LON-M8 (M8), to investigate the dependence of tumour localization on (i) tumour site and (ii) antibody radiolabel. No significant difference was found in the degree of localization of radio-iodinated M8 in subcutaneous, renal or intracranial xenografts, but a highly significant improvement in HX99 localization by M8 was recorded using an 111indium-DTPA conjugate of the antibody (111In-DTPA-M8), related to its rapid tumour uptake and blood pool clearance. Radio-iodinated or 111In-labelled M8 was given to 29 patients with breast cancer, 7 with primary tumours and 22 with metastases. Tumour localization was assessed by (i) examination of surgical specimens and (ii) antibody scans, which were compared with conventional X-rays and 99mTc-methylene diphosphonate (MDP) bone scans. Radiolabelled M8 localized preferentially in all primary tumours (radioactivity tumour: normal breast = 6.2 +/- 1.4 [mean +/- s.e.]). All ten patients with skeletal metastases had positive 111In-DTPA-M8 scans, but the correlation with X-rays and MDP scans showed a regional variation. Radio-iodinated M8 failed to identify metastases in any site. The favourable biodistribution of 111In-DTPA-M8 has led to the clear localization of breast carcinomas in patients and mice. In future such reagents may rationalize the clinical management of breast cancer.     

Effect of local tumor control on distant metastasis and survival in prostatic adenocarcinoma

Of 495 patients definitively irradiated for prostatic carcinoma, 286 with a minimum follow-up of thirty-six months were studied. While tumor histology appeared to predict prognosis, the poorly differentiated tumors showing the highest incidence of distant metastasis and the lowest survival, local tumor control was an important factor within the poorly differentiated group. Of those with local recurrence, distant metastases developed in 68 per cent compared with 37 per cent of those with no local disease (p = 0.025). Survival was similarly affected with 86 per cent of those with locally controlled tumor who were alive at five years (not significantly different from the more well-differentiated tumors) versus a 56 per cent actuarial survival in those with locally recurrent disease (p less than 0.05).     

Role in acute urinary retention

The relationship between prostatic infarction and acute urinary retention was studied. Serial sections of two groups of 100 prostates each were studied for evidence of infarction. One group consisted of patients with acute urinary retention while the other group consisted of patients with benign prostatic hypertrophy. Eighty-five per cent of the retention group had prostatic infarcts while only 3 per cent of the patients with benign prostatic hypertrophy had infarcts. Despite the close association of acute urinary retention with infarction of the prostate, the exact mechanism in the production of acute retention is as yet undetermined.     

Response of patients with advanced prostatic cancer to administration of somatostatin analog RC-160 (vapreotide) at the time of relapse

BACKGROUND: The aim of this study was to evaluate the effects of administration of the somatostatin analog RC-160 (vapreotide) at the time of relapse in patients with androgen independent prostate cancer. METHODS: Our study included 13 patients with biopsy-proven prostate cancer, stage D3. Eight patients had been treated with a depot formulation of the agonist D-Trp-6-LH-RH, with a median remission time of 68 (range 48-102 months). Five patients were initially treated by surgical orchiectomy, but relapsed after a median time of 33 months (range 17-91 months). A new remission period with a median duration of 10 months (range 2-29 months) was induced with Ketoconazole in the orchiectomy group. At the relapse time, all the patients received 1 mg of vapreotide t.i.d., by subcutaneous route, in addition to D-Trp-6-LH-RH, or Ketoconazole in the orchiectomy group. RESULTS: Eight of 13 patients demonstrated clinical improvement after 3 months of therapy with vapreotide, six showing a decrease in serum prostate specific antigen (PSA) from 234.5 +/- 308.5 to 68.2 +/- 60.5 ng/ml (mean decline 71 +/- 8%; P < 0.05). Two additional patients presented a fall in serum prostatic acid phosphatase (PAP). Responding patients showed a decrease in the bone pain score from 2.62 +/- 0.48 to 0.37 +/- 0.69 and an increase in the Karnofsky performance status from 72.3 +/- 4.21 to 83.6 +/- 23.2 (P < 0.05). In accord with the ECOG criteria, two patients had a complete response; four had partial response, and two had a stable response. Four patients did not respond and one was not evaluable. Two patients died in remission, one at 16 months due to myocardial infarction and the other at 24 months due to pneumonia. Three patients relapsed at 5, 17, and 19 months respectively. Three patients who have been followed-up for more than 3 years continued in remission (79, 45, and 45 months) respectively. Vapreotide was well tolerated, only three patients having transitory mild diarrhea. CONCLUSIONS: Our results indicate that therapy with the somatostatin analog vapreotide at the time of relapse can induce objective clinical responses in some patients with prostate cancer who are refractory to androgen ablation induced by LH-RH analogs or orchiectomy.     

The diagnostic and prognostic value of tumor markers in nonseminomatous stage-III to -IV testicular tumors

The effect of combined treatment was studied in 97 patients with nonseminomatous testicular tumors with regional and distant metastases with regard to the blood serum levels of alpha-fetoprotein and chorionic gonadotropin. The disease stage was found closely correlating with the efficacy of the treatment and the level of tumor markers. Complete remission was observed in 84.2 per cent (16 out of 19) patients with normal marker levels and in 26.8 per cent (11 out of 41) of those in whom both markers levels were raised (p less than 0.05). A continuous follow-up revealed that increased marker levels were the evidence of tumor relapse or metastases in clinically silent patients.     

Bone metastases in osteosarcoma patients treated with neoadjuvant or adjuvant chemotherapy: the Rizzoli experience in 52 patients

INTRODUCTION: There have been no large-scale studies reporting the outcome of patients with osteosarcoma who first relapse with bone metastases, but there have been several case reports describing a much poorer prognosis for these patients than for those who relapse with lung metastases. METHODS: We compared 52 patients with skeletal metastases as first relapse after neoadjuvant or adjuvant treatment for osteosarcoma of the extremity given at our institution between 1972 and 1999 with 371 contemporary patients treated with the same chemotherapy protocols, who first relapsed with lung metastases. RESULTS: We found that the 52 patients with bone metastases had a higher rate of local recurrences (36% vs. 6%), a lower rate of remission (35% vs. 77%), and lower rates of 5-year event-free survival (11% vs. 27%) and overall survival (13% vs. 31%) (p < 0.01 for all comparisons). INTERPRETATION: The prognosis of patients who relapse with bone metastases--unless they have a single late-appearing metastasis--is worse than the prognosis of patients who first relapse with lung metastases. There was no difference in outcome between patients with single, resectable and late-appearing skeletal metastases and patients relapsing in the lung.     

Relapsing membranous nephropathy. Response to therapy of relapses compared to that of the original disease.

BACKGROUND: Although controversial, treatment of membranous nephropathy appears to yield a reduction in the degree of proteinuria and conservation of renal function. METHODS: We report herein our experience with the treatment with steroids alone (group II, n = 13), or in combination with immunosuppressants (group III, n = 19) of patients with membranous nephropathy and the nephrotic syndrome, with a mean follow-up of 8.37 years. RESULTS: All patients underwent a first remission, with 24-hour urine protein excretion falling to 0.63 +/- 0.25 g in group II and 0.62 +/- 0.26 g in group III (p = NS) after 12.69 +/- 10.94 months of treatment in group II and 18.95 +/- 13.17 months in group III (p = NS). Three patients from group II (23%) and seven patients from group III (36.8%) experienced four and eight relapses, respectively (proteinuria in 24 h 4.0 +/- 0.80 g in group II relapsers and 4.4 +/- 0.87 in group III relapsers; p = NS). On treatment, all relapses remitted (second remission) after 7 +/- 6.93 months of therapy for group II and 8.6 +/- 6.70 months of treatment for group III (p = NS). Thereafter, no patients from group II, but 3 patients from group III (33.3%) had a second relapse. After treatment, all relapses remitted (third remission) in 3.3 +/- 1.53 months of therapy. CONCLUSIONS: These studies show that relapses, which occur in one-third of patients, respond favorably to treatment albeit remitting in approximately half the time, and that the duration of remission gets progressively longer in the later compared to the earlier remission.     

Hepatic resections: an eight year experience at a community hospital

Between April 1979 and March 1987 24 patients underwent 26 hepatic resections. Colorectal liver metastases constituted the largest group (n = 18), followed by hepatocellular carcinoma (n = 2), Echinococcal liver cyst (n = 1), cholangiocarcinoma (n = 1), and leiomyosarcoma (n = 1). The mean age was 41.8 +/- 14.6 years (range: 23-69 years). Fifteen women and nine men comprised the group. The operative morbidity was 21 per cent, the 30-day operative mortality was 8 per cent (two deaths). Both operative deaths occurred in patients with colorectal liver metastases. The 18 patients with colorectal liver metastases included ten women and eight men. The mean age was 59.1 +/- 6.5 years (range: 46-69 years). There were seven synchronous and 11 metachronous liver metastases. Carcinoembryonic antigen (CEA) was found elevated in 14 of the original primary colonic carcinomas, and in all but one patient with metachronous liver metastases. The mean time from colorectal carcinoma resection to occurrence of metachronous metastases was 17.1 +/- 5.8 months. To date, 10 patients have had recurrences of liver metastases after hepatic resection for colorectal liver metastases. The mean time of recurrence was 12.6 +/- 11.9 months. The size of the metastases was 3.8 +/- 3.2 cm (range: 0.2-17 cm). The mean number of lesions present was 1.5 +/- 1.0. The 1 year and 2 year actuarial survival rates were 87.5 and 43.8 per cent respectively. The longest survivor is alive 54 months after his hepatic resection for colorectal liver metastases and remains to this date disease free.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of bilateral adrenalectomy (and oophorectomy) in the management of patients with metastatic breast cancer.

One hundred consecutive patients who underwent bilateral adrenalectomy for metastatic breast cancer with at least a 2 year "tumor-free" interval and with symptomatic bony, local-regional, pleural, or discrete pulmonary or mediastinal metastases had objective remission rates of 65 per cent at 6 months, 48 per cent at 12 months, 28 per cent at 18 months, and 16 per cent at 24 months.     

The natural course of prostatic carcinoma in relation to initial cytological grade

We investigated retrospectively 91 patients with prostatic carcinoma diagnosed cytologically between 1978 and 1979. Of the patients 57 had no metastases (M0) at presentation. The majority of the patients without metastases had well or moderately well differentiated carcinoma. Of 18 patients with poorly differentiated carcinoma 17 had metastases at presentation. The patients without metastases were left untreated, while those with metastases received active antitumor treatment. Local progression and/or development of metastases during surveillance occurred in 24 patients (42 per cent) and antitumor treatment was initiated. Mean observation time in the group untreated throughout observation was 47 months. Mean interval to progression in the patients treated subsequently was 31 months. In the surveillance group no difference in mean interval to progression, frequency of local progression, development of metastases or death rate of prostatic carcinoma was found when the patients with initially well and moderately well differentiated carcinoma were compared. Therefore, in our study initial cytological grade failed to predict a difference in progression in patients with well and moderately well differentiated prostatic carcinoma. Since almost all patients with poorly differentiated carcinoma had metastases at presentation a poor differentiation seems to predict a worse prognosis compared to well and moderately well differentiated tumors.