A trial of combination chemotherapy followed by hormonal therapy for previously untreated metastatic carcinoma of the prostate.

We administered combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin to 25 previously untreated patients with metastatic prostate cancer in order to assess the efficacy of chemotherapy before any hormonal manipulation. Hormonal therapy was administered only after progression of disease to chemotherapy. All 25 patients were followed until time of death and all were able to receive hormonal therapy. We did not find substantially improved response rates when combination chemotherapy was applied before endocrine treatment since the 33% objective response rate to chemotherapy was only minimally higher than the response in our patients who had failed hormonal therapy and then received identical or similar chemotherapy. Furthermore, the introduction of intensive combination chemotherapy before hormonal therapy in our study did not result in any striking improvement in overall survival compared with patients who received initial hormonal therapy in many other studies. Responses to chemotherapy were not attributable to suppression of serum testosterone since all 12 patients with partial response (PR) or stable disease (SD) and four of seven patients with no response (NR) had normal testosterone levels at the time of response assessment. The initial use of chemotherapy did not adversely affect the expected high percentage of objective responses (68%) to subsequent hormonal manipulation. The frequency, duration, and quality of responses to hormonal therapy exceeded the responses to chemotherapy. The disappointing responses to chemotherapy reflect the very modest efficacy of even aggressively delivered cytotoxic agents.

Diagnosis and significance of liver metastases in small cell carcinoma of the lung.

One hundred fifty-seven consecutive patients with small cell lung cancer seen at the National Cancer Institute over a four-year period underwent a series of pretherapy liver staging procedures to determine optimal means of detection and prognostic implications of hepatic metastases. Liver evaluation included physical examination, liver function tests, and liver scan (radionuclide or computerized tomography [CT]), as well as percutaneous and/or peritoneoscopy-directed liver biopsy when possible (74%). Liver metastases were detected in 26% of patients. Peritoneoscopy was the most sensitive method of liver evaluation and increased the detection of liver metastases when done in a sequential fashion after percutaneous liver biopsy from 18 to a total of 27 patients. Of the noninvasive procedures, radionuclide and CT liver scan were the most accurate concurring with liver biopsy in 87% of patients but permitting correct discrimination of stage in excess of 96% of patients. The accuracy of this noninvasive procedure was enhanced by an algorithm combining the results of radionuclide liver scan with liver function tests to detect patients with high or low likelihood of liver involvement. The survival and response of patients with liver metastases was significantly worse than those without such metastases with no three-year disease-free survivors among patients with liver metastases.

Adrenal gland enlargement in major depression. A computed tomographic study.

To determine whether the well-documented hyperactivity of the hypothalamic-pituitary-adrenal axis in depressed patients includes adrenal gland hypertrophy, adrenal gland size was evaluated by computed tomography. Assessments consisted of (1) global ratings by two radiologists ignorant of the diagnostic identity of the subjects and (2) calculation of adrenal volume. Of the 38 patients with major depression, 12 were rated as exhibiting adrenal hypertrophy. Adrenal volumes in the depressed patients were significantly increased when compared with those of normal controls. Adrenal gland size was not correlated with dexamethasone suppression test results, patient age, duration of the depressive episode, or depression severity. These results are concordant with the hypothesis that chronic corticotropin hypersecretion in depression results in adrenocortical hypertrophy. Adrenal gland enlargement may be a measure of cumulative lifetime depression.

Radiographic Characteristics of Adrenal Masses Preceding the Diagnosis of Adrenocortical Cancer.

Incidentally discovered adrenal masses are common and the clinical evaluation and surveillance aims to diagnose hormone excess and malignancy. Adrenocortical cancer (ACC) is a very rare malignancy. This study aims to define the imaging characteristics of adrenal tumors preceding the diagnosis of ACC. Patients with prior (>5 months) adrenal tumors (<6 cm) subsequently diagnosed with ACC were identified in a large registry at a tertiary referral center. Retrospective chart and image review for patient characteristics and initial, interval, and diagnostic imaging characteristics (size, homogeneity, borders, density, growth rate, etc.) was conducted. Twenty patients with a diagnosis of ACC and a prior adrenal tumor were identified among 422 patients with ACC. Of these, 17 patients were initially imaged with CT and 3 with MR. Only 2 of the 20 patients had initial imaging characteristics suggestive of a benign lesion. Of initial tumors, 25% were <2 cm in size. Surveillance led to the diagnosis of ACC within 24 months in 50% of patients. The growth pattern was variable with some lesions showing long-term stability (up to 8 years) in size. In conclusion, antecedent lesions in patients with a diagnosis of ACC are often indeterminate by imaging criteria and can be small. Surveillance over 2 years detected only 50% of ACCs. Current practice and guidelines are insufficient in diagnosing ACCs. Given the rarity of ACC, the increased risk and health care costs of additional evaluation may not be warranted.

Similar prevalence of renovascular hypertension in selected blacks and whites.

Renovascular hypertension is a potentially curable form of high blood pressure that is thought to be extremely rare among blacks. We demonstrate, however, that in a clinically selected population, the prevalence of renovascular hypertension is similar in blacks and whites. We prospectively evaluated 167 hypertensive subjects who had one or more clinical features known to be associated with renovascular hypertension. All subjects had captopril-stimulated peripheral renin measurements and conventional renal arteriography. All significant renal artery stenoses (greater than 50% luminal narrowing) were treated with percutaneous transluminal angioplasty or surgery. Renovascular hypertension was diagnosed if there was a blood pressure response to interventional therapy, according to the criteria established by the Cooperative Study of Renovascular Hypertension. Of the total group evaluated, 24% (39 of 167) had renal artery stenosis and 14% (23 of 167) had renovascular hypertension. Renal artery stenosis or occlusion was found in 27% (26 of 97) of whites and 19% (13 of 67) of blacks (p = 0.27). Renovascular hypertension was diagnosed in 18% (17 of 97) of whites and 9% (6 of 67) of blacks evaluated (p = 0.25). Renovascular hypertension was associated with severe or refractory hypertension and with smoking, but there were no racial differences in these associations. Blacks with renovascular hypertension tended to have low captopril-stimulated peripheral renin activity. We conclude that blacks with clinical features suggestive of renovascular hypertension should be evaluated with angiography. Captopril-stimulated plasma renin may not be useful in detecting blacks with renovascular hypertension, but this and other potential screening tests require further evaluation.

Prospective analysis of strategies for diagnosing renovascular hypertension.

Renovascular hypertension is a potentially curable form of high blood pressure. However, it is unclear how best to select patients who are likely to have renovascular hypertension, what diagnostic strategy to use in these selected patients, and how to predict the hemodynamic significance of a renal artery stenosis. We determined the prevalence of renovascular hypertension in adults who exhibited suggestive clinical features. In these clinically selected patients, we then determined the test characteristics of various diagnostic and potential screening tests. Renovascular hypertension was diagnosed if correction of renal artery stenosis resulted in decreased blood pressure. Of the 66 hypertensive adults evaluated, 11 (16.7%) had renovascular hypertension. Captopril-stimulated peripheral renin activity detected renovascular hypertension with 73% sensitivity, 72% specificity, 38% positive predictive value, and 92% negative predictive value. Less optimal combinations of sensitivity and specificity were found for differential glomerular filtration rate renography, differential effective renal plasma flow renography, and selective renal vein renin ratios, each performed after a single dose of captopril. Intravenous digital subtraction renal angiography detected all patients with renovascular hypertension and was normal in 71% of patients with essential hypertension. To evaluate potential screening tests for renovascular hypertension, we calculated predictive values applied to a low prevalence population. If the observed sensitivities and specificities apply to a population with 5% prevalence of renovascular hypertension, captopril-stimulated peripheral renin would have a positive predictive value of 12% and a negative predictive value of 98%. In 16 patients with known renal artery stenosis, neither the captopril-stimulated renal vein renin ratio nor captopril-stimulated differential renography accurately predicted blood pressure response to correction of the stenosis. We conclude that clinical criteria can identify a subgroup with 16.7% prevalence of renovascular hypertension. In this high prevalence group, intravenous digital subtraction renal angiography will identify virtually all patients with renovascular hypertension, and a normal study will be sufficient to exclude renovascular hypertension. In unselected hypertensive patients, screening with captopril-stimulated peripheral renin activity may be the most useful and efficient procedure for identification of patients with renovascular hypertension. Functional tests do not accurately predict the hemodynamic significance of a renal artery stenosis.

Comparison of intravenous digital subtraction angiography and conventional arteriography in defining renal anatomy.

Intravenous digital subtraction renal angiography (IV-DSRA) is frequently used in the preoperative evaluation of living-related (LR) kidney donors. However, the true accuracy of IV-DSRA in the donor population is difficult to assess since abnormalities of the kidney and its circulation are uncommon in this group. Therefore, we evaluated IV-DSRA in a group of patients more likely to have anomalies and abnormalities that would affect LR donor selection, donor nephrectomy, and subsequent transplantation. Hypertensive adults being evaluated for renovascular hypertension had IV-DSRA and conventional renal arteriograms, which were interpreted independently. We determined the accuracy of IV-DSRA, compared with conventional arteriography, in detecting multiple renal arteries, renal artery stenosis, fibromuscular dysplasia, and abnormal renal parenchyma. Technically unsatisfactory studies were excluded from analysis. Of 59 patients evaluated, 37 had abnormalities or anomalies. IV-DSRA failed to detect 28 of 50 findings in these 37 patients. In 21 patients with multiple renal arteries, IV-DSRA underestimated the number of main renal arteries in 8. Significant renal artery stenosis, present in 16 patients, was undetected by IV-DSRA in 3 of these patients. Mild fibromuscular dysplasia was not detected by IV-DSRA in any of the 5 patients with this condition, and abnormalities of renal parenchyma were not detected in 6 of the 8 patients with scarred or cystic kidneys. When compared with conventional renal arteriography in a hypertensive population, the IV-DSRA does not accurately detect abnormalities of the kidney and its circulation. If these data are confirmed in nonhypertensive subjects, preoperative evaluation of LR kidney donors using IV-DSRA alone may fail to detect potentially important anatomic abnormalities.

Use of functional maps in renal scintigraphy to detect segmental arterial lesions.

Renography using a gamma camera, a minicomputer, [123I]orthoiodohippurate ([123I]OIH), and a canine model was employed to evaluate computer-generated maps of regional renal function. Renograms were obtained before and after ligations of the right renal arterial branch in four dogs, with subsequent angiographic and histologic confirmation of the lesions. Postoperative time-activity curves were normal. Washout and persistence index in three of four right kidneys showed regional abnormality. Functional renal mapping may provide a clinical technique for evaluating human renal vascular hypertension.

Interstitial pulmonary infiltrate following combined therapy for esophageal carcinoma.

Seven patients with squamous cell carcinoma of the esophagus received radiation therapy in twice weekly 400 rad fractions over five weeks followed by esophagectomy. Four of these patients developed severe interstitial pulmonary infiltrates and died of pulmonary insufficiency 18-50 days after surgery. In three of these patients the infiltrates were detected within 24 hours of surgery while the infiltrate was not present until the eighth postoperative day in the fourth patient. Postmortem examination revealed widespread dilatation of interstitial and subpleural lymphatics. It is postulated that the combination of large fraction radiation therapy followed by extensive surgery resulted in lymphatic obstruction.

Selective use of low-osmolar contrast media.

Two thousand thirty-four consecutive patients presented for excretory urography within a 22-month period. Of 57 observed adverse reactions (incidence 2.8%), 54 occurred in 1219 low-risk patients injected with conventional ionic contrast media (HOCM) (incidence 4.4%) while three reactions were noted in the 815 high-risk patients receiving low-osmolar contrast media (LOCM) (incidence 0.4%). Despite strict enforcement of an unchanging list of high-risk criteria by the same pool of radiologists, LOCM use was not constant, increasing in use over time from 26.5% to 55.3% of urograms. In addition, frequency of LOCM selection increased transiently (from 33% to 52%) following a single life-threatening reaction to HOCM. Our results suggest that strict guidelines for use of LOCM are subject to loose individual physician interpretation. Physicians' perceptions of safety made it increasingly difficult to withhold LOCM and progressively more patients were included in high-risk groups.

Biliary cytodiagnosis. Bile sampling for cytology.

The records of 121 patients who presented for PTC and biliary drainage within a five-year period were reviewed. Fifty-eight bile samples had been obtained from 38 of these patients for cytologic analysis. Malignancy was detected in 14 of 32 patients with carcinoma (sensitivity 44%). Repeat sampling was positive in four of nine patients whose initial specimen contained no tumor cells. Bile duct carcinoma, pancreatic carcinoma, and metastatic disease were all detected. An approach to biliary cytodiagnosis is offered that, it is hoped, will further minimize future false negative results.

Interventional uroradiology.

Major interventional uroradiologic techniques including percutaneous nephrostomy, vascular augmentation and reduction procedures, percutaneous cyst aspiration, chronic peritoneal dialysis catheter manipulation and urethroplasty are reviewed. A brief history of the development and techniques for performing these procedures are included. The results of clinical series are assessed and their role in patient management is addressed. The development of these procedures has had a significant impact on patient care by providing effective nonoperative therapy.

Extravascular toxicity of two magnetic resonance contrast agents. Preliminary experience in the rat.

We compared the relative toxicities of standard concentrations of two magnetic resonance imaging (MRI) contrast agents, ionic gadolinium diethylenetriaminepentacetic acid (DTPA) and low-osmolar gadolinium-1, 4, 7 tris (carboxymethyl)-10-(2'-hydroxypropyl)-1, 4, 7, 10 tetra-azacyclododecane (HP-DO3A) with that of the conventional radiographic contrast medium meglumine diatrizoate, when extravasated into the deep dermal tissues of laboratory rats. Gadolinium-DTPA caused moderate necrosis, hemorrhage, and edema which was not statistically different than meglumine diatrizoate. In contrast, gadolinium HP-DO3A was significantly less toxic than meglumine diatrizoate. Additional experience will be needed in order to determine whether these laboratory results will be clinically relevant in humans.

Infectious complications of percutaneous biliary drainage.

The infectious complications of percutaneous biliary drainage were reviewed in 132 patients with obstructive jaundice. Cholangitic or septic episodes occurred more frequently in patients with malignant (54%) than in those with benign (22%) disease, and frequently were not related to catheter insertions or manipulations. The frequency and mechanisms of bacterial colonization of bile and blood in patients with obstructive jaundice before and after biliary drainage are reviewed. The significant morbidity and mortality related to postdrainage infectious episodes is stressed, and the efficacy of antibiotic prophylaxis is discussed. The significant risks and complications of percutaneous biliary drainage must be considered prior to catheter placement, particularly in the most debilitated patients.

Computed tomographic evaluation of an experimental model for pyogenic liver abscesses.

Computed tomography (CT) was used to evaluate 15 rabbits with experimentally induced liver abscesses. The animals were examined both before and after intravenous contrast injection. After sacrificing the animals, postfreeze CT scans were made to mark the abdomen for 1-cm thick whole body sections for correlating the gross pathology with the results of the CT scans. CT detected 15 abscesses in 13 of the 14 rabbits with true positive lesions. Ten abscesses less than 1.4 cm in diameter were not detected by CT. Contrast agent enhancement was helpful in 70% of the studies. These abscesses have characteristics similar to human liver abscesses, but there was more gas and calcium in the experimentally induced abscesses than is encountered in humans with hepatic abscesses. The model and its CT characteristics appear well suited for future studies in the diagnosis and treatment of liver abscesses.

Percutaneous drainage of pelvic lymphatic fluid collections in the renal transplant patient.

Seventeen renal transplant patients with pelvic lymphatic fluid collections were treated with percutaneous drainage. Eleven of 16 patients with lymphoceles (69%) were successfully managed without surgery, although seven of these patients required repeat catheter insertions, and three patients developed local infections. The patient with an ovarian cystadenoma was treated with surgery. The mean duration of catheter insertion was ten days for initial drainage and 16 days for repeat drainage. Elevated serum creatinines decreased in 14 of the patients with lymphoceles (88%), including all five patients without pelvocaliectasis, but never returned to baseline in six instances. This observation may reflect the inadequate therapy of frequently encountered concurrent renal parenchymal abnormalities (rejection, cyclosporine toxicity, acute tubular necrosis). While percutaneous management of lymphoceles is technically easy and usually ultimately effective, the interventional radiologist should be prepared for long duration of catheter insertions, repeat interventions, and variable clinical courses. Differentiation of lymphoceles from other fluid collections, such as cystic ovarian neoplasms, may be difficult.

Extravascular extravasation of radiographic contrast media. Effects of conventional and low-osmolar agents in the rat thigh.

We compared the damage resulting from intradermal injection of four commonly used radiographic contrast media in laboratory rats. Sixty percent meglumine diatrizoate (Reno M 60) and ioxaglate (Hexabrix) produced significantly more ulceration and crusting on gross inspection and more necrosis, edema, and hemorrhage on histologic evaluation than iopamidol 300 (Isovue) or 0.9% (normal) saline. Thirty percent meglumine diatrizoate (Reno M Dip) had an intermediate toxicity, resulting in significantly more visible swelling and more microscopically detected hemorrhage than iopamidol or saline, but less ulceration/crusting and necrosis than Reno M 60 and ioxaglate. Since the three contrast agents of similar osmolality produced different degrees of tissue damage, our results suggest that factors other than high osmolality are partially responsible for determining the severity of injuries from extravasated contrast media.

Renovascular hypertension in blacks.

To define the clinical characteristics of renovascular hypertension (RVH) and determine the clinical usefulness of captopril stimulated peripheral renin and postcaptopril renography in blacks at risk for RVH, 79 clinically selected hypertensive blacks were evaluated. Unstimulated (U-PRA), captopril stimulated (S-PRA) peripheral renin, and postcaptopril renography (PC-RENO) were obtained. All subjects underwent conventional renal arteriography. Renal artery stenosis (RAS) was present in 14 of 79 (18%) patients. Renovascular hypertension (RVH) was found in 7 of 79 (9%) patients. S-PRA had a sensitivity and specificity of 38% and 86% respectively to detect RAS; and a sensitivity and a specificity of 17% and 85% respectively to detect RVH. PC-RENO had a sensitivity and a specificity of 64% and 58% respectively to detect RAS; and a sensitivity and a specificity of 67% and 58% respectively to detect RVH. This study suggests that RAS occurs in 18% of clinically selected hypertensive blacks. RVH was present in 9% of this population. Captopril stimulated peripheral renin and postcaptopril renography are not useful as screening tools for the diagnosis of renovascular disease in blacks. Blacks at high risk should be evaluated with angiography.

Captopril renography in the diagnosis of renovascular disease.

Several investigators have reported methods for the use of renal scintigraphy in the diagnosis of renal artery stenosis. We report the experience of Duke University Medical Center, and offer some suggestions for standardizing and optimizing the use of this potential screening tool. We evaluated 140 clinically selected hypertensive adults with postcaptopril renal scintigraphy (renography), pre- and postcaptopril peripheral renin activity, and conventional renal arteriography. Postcaptopril renography (using 99mTc-diethylenetriaminepentaacetic acid (DTPA) to measure glomerular filtration and [131I]iodohippurate to measure renal plasma flow) was considered abnormal if one kidney contributed 47% or less of total activity. Postcaptopril renin was considered elevated if it was at least 4 ng/mL/h. Renovascular disease was defined as 50% or greater main renal artery stenosis. Of 140 subjects, 31 (22%) had significant renovascular disease. Captopril-stimulated DTPA renography suggested asymmetric function in 24 (74%) of these, but was also abnormal in 61 of 109 (56%) with normal renal arteries. Captopril-stimulated hippuran renography performed in a similar manner. Captopril-stimulated renin activity was elevated in only 58% of subjects with renal artery stenosis, and had a false positive rate of 24%. These data differ from reports from other centers, perhaps due to differences in renography methods, criteria for interpretation of renography, and/or patient selection criteria.

Results and morbidity of percutaneous nephrolithotripsy.

The medical records of the first 210 patients treated with percutaneous nephrolithotripsy at Duke University Medical Center were reviewed. Eleven patients were treated for bilateral stones for a total of 221 renal units. The procedure failed in 6 patients (2.7%). Stone fragments were retained in 55 patients (24.9%), with unplanned fragments in 41 cases (18.6%). Open surgery was subsequently performed in 4 patients (1.8%). There were no nephrectomies or deaths in our patients. Percutaneous nephrolithotripsy is a highly successful method for removal of upper tract stones and has a complication rate no higher than that of open surgical procedures.