Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma.

BACKGROUND: Given the significant activity and tolerability of gemcitabine in patients with relapsed Hodgkin's lymphoma (HL), the critical role that nuclear factor kappa B (NF-kappaB) appears to play in the pathogenesis of this tumor, the ability of bortezomib to inhibit NF-kappaB activity, and laboratory studies suggesting synergistic antitumor effects of gemcitabine and bortezomib, we hypothesized that this combination would be efficacious in patients with relapsed or refractory HL. PATIENTS AND METHODS: A total of 18 patients participated. Patients received 3-week cycles of bortezomib 1 mg/m(2) on days 1, 4, 8, and 11 plus gemcitabine 800 mg/m(2) on days 1 and 8. RESULTS: The overall response rate for all patients was 22% (95% confidence interval 3% to 42%). Three patients developed grade III transaminase elevation: one was removed from the study and two had doses of gemcitabine held. Almost all patients exhibited inhibition of proteasome activity with treatment. CONCLUSIONS: The combination of gemcitabine and bortezomib is a less active and more toxic regimen in relapsed HL than other currently available treatments. It poses a risk of severe liver toxicity and should be pursued with caution in other types of cancer.

Delayed computed tomographic characterization of renal masses: preliminary experience.

BACKGROUND: To evaluate the performance of delayed contrast enhanced computed tomography (DCT) in characterizing renal masses. METHODS: Twenty-four patients with suspected renal masses or indeterminate renal masses on previous imaging studies were prospectively evaluated with preintravenous contrast imaging, conventional contrast-enhanced computed tomography (imaging initiated 2 min after intravenous contrast injection), and DCT (imaging initiated 13 min after injection of intravenous contrast). Only lesions larger than 1.0 cm were evaluated, with scanning parameters kept constant across the three scans. RESULTS: All pathologically confirmed renal cell carcinomas (n = 6) were detected on DCT using a threshold attenuation decrease of 10 Hounsfield units (HU). A significant decrease (p = 0.031) in attenuation occurred in renal cell carcinomas (mean = 29.6 +/- 23.6 HU) compared with the attenuation change (mean decrease = 1.1 +/- 7.1 HU), which occurred in non-neoplastic renal cysts (n = 34). Non-neoplastic renal cysts were correctly classified by DCT 32 of 34 times (94%). CONCLUSIONS: In this study, DCT distinguished renal cell carcinomas from non-neoplastic cysts in a vast majority of cases and may aid in characterizing incidentally discovered renal lesions on postcontrast CT.

Doppler respiratory patterns in the femoral veins with pelvic vein obstruction.

An appropriate Doppler response to valsalva in the common femoral veins has been described previously as excluding a more proximal venous obstruction. We describe our experience in three patients in whom an appropriate response to valsalva did not exclude a more proximal pelvic venous obstruction. Dampening of the Doppler waveforms on the affected side when compared with the opposite limb led to the diagnosis of proximal venous obstruction.

Calf sonography for detecting deep venous thrombosis in symptomatic patients: experience and review of the literature.

PURPOSE: We determined the accuracy of sonography in the detection of isolated calf deep venous thrombosis (DVT) and the rate of indeterminate ultrasound examinations in patients with physical signs or symptoms suggestive of DVT. METHODS: We reviewed the medical literature (MEDLINE) to determine the accuracy of sonography and the frequency of indeterminate studies in detecting isolated calf DVT in patients with physical signs or symptoms suggestive of DVT. A meta-analysis was used to derive summary measures of sensitivity, specificity, and accuracy from studies in which 5 or more isolated calf DVT were identified. Frequencies of indeterminate examinations were recorded for studies in which these data were provided, and we pooled these results with our own data for 196 patients. RESULTS: The meta-analysis revealed that sonography correctly identified isolated calf DVT in 49 of 53 extremities (sensitivity, 92.5%; 95% confidence interval, 81.8-97.9%) and correctly identified the absence of calf DVT in 157 of 159 extremities (specificity, 98.7%; 95% confidence interval, 95.5-99. 9%), yielding an accuracy of 97.2% (95% confidence interval, 93.9-99. 0%) for ultrasound examinations considered diagnostic. However, when evaluating our patient population and the literature, we found a substantial number of indeterminate studies (overall rate of 54.6% in 463 extremities), with a wide variation in the reported frequency of indeterminate studies (9.3-82.7%). CONCLUSIONS: Sonography is highly accurate in detecting isolated calf DVT in symptomatic patients, but indeterminate studies occur frequently, with a wide range of reported rates. Each ultrasound laboratory should evaluate its own rate of indeterminate studies.

Sonography: a useful tool to detect the mechanical causes of renal transplant dysfunction.

PURPOSE: The purpose of this study was to evaluate the utility of sonography in distinguishing between mechanical and nonmechanical causes for renal transplant dysfunction. METHODS: We reviewed all ultrasound examination reports (n = 286) for 63 consecutive patients who received 64 renal transplants. We assessed the sensitivity and specificity of different degrees of hydronephrosis (mild, moderate, or severe) in detecting urinary tract obstruction; different volumes of new or increasing peritransplant fluid in detecting urine leaks; different total volumes of peritransplant fluid in predicting significant compression of the transplant; and Doppler vascular criteria for predicting arterial and venous occlusion. RESULTS: All mechanical complications were detected (100% sensitivity) with specificities of 91.9% for ureteral obstruction (criterion, moderate hydronephrosis), 83.4% for urine leaks (criterion, any new fluid or any increase), 91.4% for fluid collections that compressed the transplant (criterion, > 100 ml), and 100% for vascular occlusion (criteria, no flow for arterial occlusion; no venous flow and reversal of arterial flow during diastole for venous occlusion). CONCLUSIONS: Sonography is very useful in distinguishing between mechanical and nonmechanical causes for renal transplant dysfunction. It has high sensitivity and acceptable specificity in this setting.

Effect of angiotensin converting enzyme inhibition on the Doppler waveform in dogs with renal artery stenosis.

Our objective was to investigate whether the angiotensin converting enzyme inhibitor enalaprilat improves detection of hemodynamically significant renal artery stenoses in dogs. Renal artery stenoses of 50 to 99% were surgically created unilaterally in five dogs. Doppler ultrasonographic evaluation was performed at baseline (no stenosis), after creation of the stenosis, and after the administration of enalaprilat. The resistive index increased in the nonstenotic kidney (P < 0.01) but not in the stenotic kidney after administration of enalaprilat. The difference in resistive indices between nonstenotic and stenotic kidneys increased significantly (P < 0.05) after administration of enalaprilat. Measurement of the resistive index after administration of an angiotensin converting enzyme inhibitor in humans may improve the performance of Doppler ultrasonography in detecting hemodynamically significant renal artery stenoses.

Urine leaks in renal transplant patients. Diagnostic usefulness of sonography and renography.

We evaluated the utility of sonography and nuclear medicine renography in the detection of urine leaks in 57 renal transplant patients. Sonography and renography were equally sensitive in detecting leaks. But renography was more specific and therefore accurate (p < 0.0001) in detecting leaks. Urine leaks should be considered on sonography, which is often the first imaging study ordered in evaluating renal transplants, with new or increasing peritransplant fluid collections. Leaks should be confirmed by renography before performing additional invasive radiologic or surgical procedures.

Nontraumatic rupture of the thoracic aorta: chest radiographic features of an often unrecognized condition.

OBJECTIVE: The purpose of our study was to evaluate chest radiographic features of nontraumatic mediastinal hemorrhage occurring after extrapericardial thoracic aorta rupture. MATERIALS AND METHODS: Twenty-seven consecutive chest radiographs obtained at admission of patients with hemorrhage from ruptured thoracic aorta aneurysms, aortic dissections, or penetrating aortic ulcers were randomized with radiographs of 23 subjects with nonruptured thoracic aorta aneurysms, 20 subjects with nonruptured dissections, and 20 control subjects. Diagnoses were established by interpreting CT scans, MR images, and findings at surgery or autopsy or both. A retrospective review was performed by three independent radiologists who were unaware of patients' diagnoses. Observers assessed 20 parameters on each of these 90 radiographs and summarized their findings with final diagnoses. The 20 parameters were analyzed with logistic regression and rank correlation to determine the best predictors of hemorrhage. RESULTS: Logistic regression analysis showed a combination of obscuration or convexity of the aorticopulmonary window and a displaced left paraspinal interface to be the most useful predictor of hemorrhage (p < .05). Rank correlation analysis indicated obscuration or convexity of the aorticopulmonary window; a displaced left paraspinal interface; enlarged aortic knob width; enlarged thoracic aorta size; an enlarged, obscured, or irregular aortic margin; and left pleural or extrapleural space fluid were potential individual predictors of hemorrhage (p < .05). Observer sensitivities for recognizing hemorrhage were 30-59% and specificities were 83-91%. Sensitivities for distinguishing an abnormal (n = 70) from a normal (n = 20) mediastinum were 79-90% and specificities were 65-90%. CONCLUSION: Obscuration or convexity of the aorticopulmonary window and a displaced left paraspinal interface on radiographs may indicate mediastinal hemorrhage. Further imaging is required to establish a definitive diagnosis.