An evaluation of bone scans as screening procedures for occult metastases in primary breast cancer

Preoperative bone scans were obtained in 104 patients with operable breast cancer. Areas of increased radioactivity detected by the bone scan were correlated with appropriate radiographs. One of 64 patients (1.5%) with clinical Stage I and Stage II breast cancer had a metastatic lesion detected by the preoperative bone scan. In contrast, 10 of 41 patients (24%) with Stage III breast cancer had occult metastatic lesions detected by the preoperative bone scan. The majority of patients with abnormal bone scans and no radiographic evidence of a benign lesion to explain the cause of the increased radioactivity proved to have metastatic breast cancer on follow-examination. Even though 20% of patients with operable breast cancer will eventually develop bone metastases, our results indicate that preoperative bone scans are not an effective means of predicting which patients with Stage I and Stage II disease will develop metastatic breast cancer. Because of the considerably increased frequency of detection of occult metastases in patients with Stage III breast cancer, bone scans should be obtained routinely in the preoperative assessment of these patients.     

The use of image registration in the analysis of bone scans for the assessment of temporomandibular joint uptake

OBJECTIVE: To examine risk factors for chronic airway disease (CAD) in elderly nonsmokers, as determined by pulmonary function tests (PFTs), and to correlate reported respiratory symptoms with PFT measures. DESIGN: An observational survey. SETTING: Several communities in California. MEASUREMENTS: Exposures and respiratory history were assessed by standardized questionnaire. PFTs were performed and prediction equations derived. RESULTS: Significant risk factors for obstruction on PFTs in multiple logistic regression included reported environmental tobacco smoke (ETS) exposure (relative risk [RR]=1.44), parental CAD or hay fever (RR=1.47), history of childhood respiratory illness (RR=2.15), increasing age, and male sex. The number of years of past smoking was of borderline significance (RR=1.29 for 10 years of smoking; p=0.06). The prevalence of obstruction on PFTs was 24.9% in those with definite symptomatic CAD, compared with 7.5% in those with no symptoms of CAD. The prevalence of obstruction was 36.0% among those with asthma and 70.6% among those with emphysema. Also, symptomatic CAD correlated with reduction in lung function by analysis of covariance. The mean percent predicted FEV1 adjusted for covariates was 90.6% in persons with definite symptoms of CAD, compared with 97.8% in those without it (p < 0.001). CONCLUSIONS: Age, sex, parental history, childhood respiratory illness, and reported ETS exposures were significant risk factors for obstruction on PFTs. Self-reported respiratory symptoms also correlated significantly with PFTs.     

Increased bone marrow uptake on Tc-99m DMSA scintigraphy in a patient with renal osteodystrophy

Anxiogenic action of m-chlorophenylpiperazine (mCPP), a 5-HT1C receptor agonist, was studied in naive rats and in ethanol-tolerant rats following withdrawal from chronic ethanol administration. The purpose of this investigation was to determine whether a sensitization to mCPP develops during withdrawal from chronic ethanol. Male Long-Evans hooded rats were fed a liquid diet containing 4.5% ethanol or dextrin (as control) for four days. Twelve hours (acute withdrawal) or 4 days (protracted withdrawal) after the last dose of ethanol, rats were injected with saline or mCPP (0.08-5.0 mg/kg) and were tested in the elevated plus-maze 15 min postinjection. A reduction in percent open-arm activity, indicative of anxiogenic behavior, was observed in ethanol-treated rats injected with saline. Administration of mCPP further reduced the percent open-arm entries and time in ethanol-withdrawn rats. An eightfold reduction in maximum effective dose of mCPP was observed during acute ethanol withdrawal as compared to that in naive rats. During protracted ethanol withdrawal the maximum effective dose of mCPP was reduced by 75%. A shift of the mCPP dose-response curve to the left following withdrawal from chronic ethanol may indicate that 5-HT1C receptor sites are more sensitive to the activation by an agonist. This effect may be exploited in developing specific 5-HT1C receptor antagonists for the treatment of ethanol withdrawal symptoms.     

Epidermo?d carcinoma of uterine cervix with bone metastases in lower limbs (author's transl)

Bone lesions are infrequent in the evolution of epidermo?d carcinoma of the uterine cervix. Direct bone invasion from the primary tumor, extension from lymph node metastases and distant metastases can be seen. The frequency of these lesions is about 3 to 4%. Hematogen bone metastases are very uncommon. They are often located in the lower limb. We report a case of a patient with a cervical carcinoma who developed isolated bone metastases in all the bones of a lower limb.     

Bisphosphonates in the treatment and prevention of bone metastases

Bone metastases occur frequently in cancer and are commonly associated with bone degradation due to the tumoral production of factors which stimulate the development and activation of osteoclasts. During osteolysis growth factors are released which stimulate tumour growth. Bisphosphonates inhibit osteoclastic bone resorption. Recently, in several large randomised studies of patients with multiple myeloma or bone metastases of breast cancer, long-term treatment with clodronate or pamidronate gave significant bone protection.     

Renogram deconvolution in the management of diabetic nephropathy: utility of the measurement of initial tracer uptake

Our objective was to assess mean transit time (MTT) and initial uptake, both parameters derived from the renal retention function (RRF), in the study of renal function in patients with diabetic nephropathy. We studied 25 patients, 7 with type I diabetes mellitus and 18 with type II diabetes mellitus, all of whom fulfilled the criteria for diabetic nephropathy with proteinuria and/or retinopathy. We found a statistically significant correlation between initial uptake and the other biochemical and renographic parameters studied except proteinuria: serum creatinine (r = 0.66, P < 0.002), creatinine clearance (r = 0.61, P < 0.003), glomerular filtration rate (r = 0.74, P < 0.003) and effective renal plasma flow (r = 0.66, P < 0.003). The other renographic parameters studied (maximal activity of the conventional renogram and MTT of the deconvoluted renogram) did not show any correlation. Initial uptake is a semi-quantitative renographic parameter that can provide complementary information to biochemical data and it may be useful in the management of diabetic nephropathy, especially in patients with high serum creatinine or creatinine clearance.     

False-negative rates of tumor metastases in the histologic examination of bone marrow

The phenomenon of enantioselectivity in the metabolism of mexiletine (MEX) conjugation was investigated in eight female patients with the arrhythmic form of chronic Chagas' heart disease treated with racemic mexiletine hydrochloride (two 100 mg capsules every 8 hr). Blood samples were collected up to 24 hr after the administration of the morning dose, with discontinuation of the subsequent doses during the study period. Plasma concentrations of N-hydroxymexiletine glucuronide were calculated as the difference between the concentrations of unchanged and total (unchanged + conjugated) MEX enantiomers. Total plasma MEX concentrations were analyzed by HPLC after enzymatic hydrolysis with beta-glucuronidase, the formation of diastereomeric derivatives with the chiral reagent N-acetyl-L-cysteine/o-phthalaldehyde, and fluorescence detection. The differences in the pharmacokinetic parameters of the enantiomers were evaluated by the paired t-test. The plasma concentrations of the (+)-(S)-MEX did not differ before and after enzymatic hydrolysis. The pharmacokinetic parameters calculated for (-)-(R)-N-hydroxymexiletine glucuronide are presented as means (95% confidence interval): maximum plasma concentration Cmax = 194.0 ng.ml-1 (154.3-233.7), time to maximum plasma concentration tmax = 1.4 hr (0.3-2.5), area under the plasma concentration versus time curve AUC0-24 = 2099.2 ng.h.ml-1 (1585.6-2612.6), elimination half-life t1/2 beta = 12.8 hr (9.9-15.6) and extent of conjugation of 31.6% (24.3-38.9%). The present data indicate stereospecific conjugation of (-)-(R)-N-hydroxymexiletine in the female patients with the arrhythmic form of Chagas' heart disease.     

The effects of clodronate on increased bone turnover and bone loss due to ovariectomy in rats

The present study was carried out to investigate the ability of clodronate to inhibit ovariectomy-induced bone loss and increased bone turnover in rats. Estradiol was administered as a reference compound. Seventy Sprague-Dawley rats were ovariectomized (OVX) or sham-operated (Sham) at the age of 90 days and divided into seven groups. Two Sham and two OVX groups received subcutaneously either the vehicle of clodronate or the vehicle of estradiol. Other OVX groups were given s.c. either disodium clodronate at two dose levels (5 mg/kg or 12.5 mg/kg twice a week) or 17 beta-estradiol (10 micrograms/kg five times a week) for 8 weeks. Femur length, volume, dry weight, and ash weight were determined, and proximal ends of tibiae were used for bone histomorphometry. Markers of bone metabolism were measured from urine and serum. A significant loss of 54% of trabecular bone area of proximal tibial metaphysis was found at 8 weeks after ovariectomy. Clodronate and estradiol inhibited (p < 0.001) this osteopenia. Both drugs prevented the decrease in ash weight/volume of the femur. The inhibitory effect of clodronate and estradiol on bone resorption in OVX rats could be detected also in decreased urinary excretion of hydroxyproline and lysylpyridinoline (p < 0.001). Clodronate and estradiol decreased (p < 0.001) the ovariectomy-induced enhanced tibial endocortical mineral apposition rate (Ec.MAR) on the lateral cortex to the level of the Sham group. In contrast, periosteal MAR analyzed on the medial side of tibial cortical bone did not change significantly in the OVX/Veh group. Estradiol decreased periosteal MAR to below the level in the Sham group (p < 0.01). These results suggest that ovariectomy of growing rats resulted in tibial and femoral osteopenia two months later. Clodronate as well as estradiol can suppress bone resorption and turnover in ovariectomized rats, inhibiting the development of osteopenia. Both clodronate doses (5 and 12.5 mg/kg) had beneficial effects in ovariectomized animals.     

Percent 131I uptake and post-therapy 131I scans: their role in the management of thyroid cancer

Renal disease in patients infected with human immunodeficiency virus (HIV) often presents with significant proteinuria and progressive renal failure; focal glomerulosclerosis is the most common renal pathology identified. To our knowledge, we report the first case of nephrotic-range proteinuria and preserved renal function in an HIV-infected patient in association with disseminated histoplasmosis. The initial level of proteinuria was 12.5 g/24 h. The patient developed a concomitant lesion on his neck, which was biopsied and identified as Histoplasma capsulatum by fungal stains and culture. The serum CF titer of antibody against yeast antigens of H. capsulatum was 1:8. The level of serum albumin decreased to 2.0 g/dL, and the level of serum cholesterol increased to 284 mg/dL. Immunohistochemical staining of renal biopsy tissue demonstrated immune complexes within the mesangium; H. capsulatum antigen was also demonstrated in the mesangium. Therapy with oral itraconazole resulted in marked clinical improvement. The findings in this case emphasize the need to rule out treatable causes of the nephrotic syndrome in AIDS, especially in cases of immune-complex glomerulonephritis.     

Dosimetric basis of mean fractionation in the irradiation of bone metastases in breast cancer

Proceeding from the drawing of maps with biologically isoeffective percentage doses the authors provide a dosimetric substantiation of gamma-beam irradiation of different parts of the bony skeleton using the following irradiation scheme: a single dose of 4 Gy, 5-6 fractions daily. It has been shown that to choose a therapeutic plan in the utilization of a nonstandard scheme of fractionation, the calculation of the TDF factor by Orton's tables is safe and illustrative. By way of example are given maps of isoeffective doses used in the irradiation of bone metastases in breast cancer patients with metastases to different parts of the skeleton.     

Radiation therapy enhances the therapeutic effect of immunotherapy on pulmonary metastases in a murine renal adenocarcinoma model

In order to improve the efficacy of immunotherapy, we have evaluated the effects of radiation therapy combined with interleukin 2 (IL-2) treatment in a murine metastatic renal adenocarcinoma model (Renca). Pulmonary metastases were induced in Balb/c mice by intravenous injection of Renca and five days later a sublethal dose of radiation (300 rads) was administered either to the whole body or to the left lung only. One day following radiation, immunotherapy was given for 5 consecutive days of IL-2 at 5,000 Cetus units intraperitoneally, twice daily. The animals were either sacrificed on day 23 or 33 to assess tumor burden, or were followed for long term survival. We found that pretreatment with irradiation greatly enhanced the therapeutic efficacy of immunotherapy and was manifested by a significant reduction in pulmonary metastases and an increase in survival. When combined with immunotherapy, local tumor irradiation was not only as effective as whole body irradiation, but irradiation of one lung reduced the number of metastases similarly in both lungs. This suggests that local tumor irradiation may act through a systemic mechanism to increase the anti-tumor response mediated by IL-2 therapy.     

Segmented areas of increased attenuation in the liver caused by right adrenal tumors: CT features

OBJECTIVE: Our goal was to describe attenuation differences bordered by a straight line in the right hepatic lobe on enhanced CT in patients with right adrenal tumors and to discuss the cause of this appearance. MATERIALS AND METHODS: Three patients showing attenuation differences bordered by a straight line were discovered in the CT files of 26 cases of right adrenal tumor over 3 cm in diameter. All CT scans were examined by incremental dynamic study. RESULTS: Two patients had large zone of hyperattenuation in the right lobe bordered with a straight line intersecting both anterior branches of the right portal vein and the inferior vena cava (IVC). A third patient and one of the two patients mentioned already had zones of relative hyper- and hypoattenuation in the medial portion of the posterior hepatic segment, respectively. All three patients had large right adrenal tumors, which severely compressed the right hepatic vein near its confluence with the IVC and/or the IVC in or below its intrahepatic portion. The distribution of attenuation differences was similar to the hyperattenuation at CT arteriography or perfusion defect at CT arterial portography under temporary balloon occlusion of the right hepatic vein and inferior right hepatic vein, respectively. CONCLUSION: Straight-bordered attenuation differences within the right hepatic lobe at dynamic CT can be caused by compression of the right hepatic vein by large right adrenal tumors.     

The utility of video-assisted thoracic surgery in the diagnosis of pulmonary metastases from renal cell carcinoma

To assess the clinical usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for small cell lung carcinoma (SCLC), we measured serum levels of Pro-GRP with a newly developed ELISA and measured serum levels of neuron-specific enolase (NSE) in 44 patients with untreated SCLC and 77 patients with untreated non-SCLC. We prospectively measured serum levels of Pro-GRP and NSE in SCLC patients after initial treatment until relapse. The sensitivity (70%) and specificity (91%) of Pro-GRP were similar to those of NSE (70 and 86%). Thirty-nine % of patients who had a partial response still had elevated serum levels of Pro-GRP at the time of restaging after initial treatment. In follow-up study, 94% of patients had elevated serum levels of Pro-GRP again at the time of relapse, whereas 37% of patients showed elevated levels of NSE. Levels of Pro-GRP increased a median of 35 (-95 to 151) days before clinical evidence of relapse was detected with successive physical examinations and imaging studies, whereas levels of NSE increased 20 (-85 to 124) days after relapse was detected (P < 0.05). Pro-GRP was helpful as a diagnostic aid and a marker for therapeutic effect and relapse in patients with SCLC, supplemented to serum NSE.     

Significance of radioisotope bone marrow uptake on 99m technetium sulphocolloid scan in portal hypertension

A prospective study of 101 consecutive patients of portal hypertension was carried out to study the possible relationships between bone marrow activity on 99m technetium labelled sulphocolloid scan and severity of liver disease, etiology of portal hypertension and cirrhosis, as well as presence and extent of collateral circulation, including esophageal varices. The patients were divided into 4 etiological groups: alcoholic cirrhosis (ALD), (38) non-alcoholic cirrhosis (NALD) (35) non-cirrhotic portal fibrosis (NCPF) (14) and extrahepatic portal vein obstruction (EHPVO) (14). Patients of cirrhosis were categorised according to modified Child-Pugh's classification. Esophageal varices were graded endoscopically as (1) no varix (2) small varices (< 5mm) (3) large varices (> 5mm). All patients underwent radionuclide imaging using 99m Technetium labelled sulphocolloid and bone marrow activity was studied. Evaluation of portasystemic collaterals was done ultrasonically. We found that 16.6%, 44.6% and 72.72% patients with Child A, B and C cirrhosis respectively, had increased marrow activity (p < 0.05). There was no significant difference between marrow activity of patients with ALD (52.6%) and NALD (40%). None of the non-cirrhotic patients demonstrated bone marrow uptake of radioisotope. There was no significant difference between bone marrow uptake presence of lienorenal collaterals and presence or size of esophageal varices. We thus conclude the bone marrow activity on radioisotope scanning depends only on the severity of liver disease and does not vary a according to the etiology of cirrhosis, or presence and extent of portasystemic collaterals, including esophageal varices.     

Endothelial cell morphology in areas of in vivo Evans blue uptake in the aorta of young pigs. II. Ultrastructure of the intima in areas of differing permeability to proteins

The fine structure of the intima of the pig aortic arch is described for areas of spontaneously differing in vivo endothelial permeability, as demarcated by uptake of the protein-binding azo dye Evans blue. Areas of enhanced permeability (blue areas) consistently show a variety of features not observed in areas devoid of dye accumulation (white areas). The subendothelial space of blue areas is markedly thickened and edematous, containing collagen, elastic tissue elements, and undifferentiated cells dispersed in an amorphous floccular matrix of low electron density. Endothelial cells in blue areas are generally cuboidal, with relatively short, frequently vacuolated junctions. In contrast, endothelial cells from white areas are flat and elongate, with long intercellular junctions exhibiting many interdigitations. Cytoplasmic differences include a well-developed rough endoplasmic reticulum and more frequent lysosomal bodies in blue areas and a prominent Golgi apparatus in the endothelium of white areas. Additionally, endothelial cell injury or death with and without denudation occurs with a significantly greater frequency in blue relative to white areas. An endothelial glycocalyx is some threefold thicker over the surface of white relative to blue areas. It is concluded that neither endothelial structure nor function are homogeneous within the aortic arch of the young pig and that areas of spontaneously differing permeability to proteins are associated with a spectrum of alterations in endothelial and intimal morphology.     

The relationship between the serum level of prostate specific antigen and bone and CT scans in the staging of the primary carcinoma of the prostate

OBJECTIVE: To determine the relationship between the serum level of prostate-specific antigen (PSA) and the presence of abnormalities in a skeletal or CT scan in patients with primary carcinoma of the prostate. DESIGN: Retrospective. SETTING: Academic Medical Centre, Amsterdam. PATIENTS AND METHODS: The serum PSA levels were compared with the findings in the skeletal and CT scans of 440 patients with carcinoma of the prostate without clinical signs of metastases, seen in the period from January 1990 to December 1994 in the outpatient clinics for Urology of the Academic Medical Centre (AMC) in Amsterdam, Hospital Gooi-Noord in Blaricum and Hospital De Heel in Zaandam. CT scan data were analysed only from the AMC and Hospital Gooi-Noord. RESULTS: There were 76 patients with a positive bone scan (17.3%) and 31 (out of 337; 9.2%) with a positive CT scan. Higher PSA serum levels went together with increasing risk of abnormalities in bone or CT scan. Of 85 patients with PSA values < 10 micrograms/l, none had a positive bone scan and one (out of 73; 1%) a positive CT scan; of the 180 patients with PSA levels < 20 micrograms/l, 4 (2.2%) had a positive bone scan and 2 (out of 154; 1.3%) a positive CT scan. The T stage, the histological grading and the serum alkaline phosphatase activity appeared not to have any supplementary value. CONCLUSION: In view of the low frequency of abnormalities in a bone or CT scan in patients with low PSA levels, it appears justified no longer to recommend bone or CT scanning for staging of patients for a clinically non-metastasized carcinoma of the prostate and serum PSA levels < 20 micrograms/l.