Gerald D. Pond

Pulmonary Embolism Following Hemodialysis Access Thrombolysis/Thrombectomy

PURPOSE The increased use of thrombectomy with deliberate pulmonary embolization of thrombus following initial thrombolysis for occluded hemodialysis fistulas prompted the authors to measure the prevalence of pulmonary embolism (PE) due to the procedure. PATIENTS AND METHODS Thirty-one patients with 43 acutely thrombosed polytetrafluoroethylene hemodialysis fistulas were treated with thrombolysis/thrombectomy. Perfusion lung scans were obtained in 22 patients. Patients were also continuously monitored for clinical signs or symptoms of PE. RESULTS Perfusion scans were interpreted as consistent with PE in 59% of those studied, but no clinical signs or symptoms were present in 41 of the 43 cases (95%). However, two patients developed both signs and symptoms of acute PE in the postprocedural period and died. One had underlying pulmonary disease and had undergone thrombectomy before. The other had chronic heart disease. CONCLUSION Thrombolysis/thrombectomy is usually safe and effective, even though many patients develop subclinical PE. The authors urge extreme caution in patients who have underlying pulmonary or cardiac disease and/or have undergone the procedure before.

Extracellular Engagement of α6 Integrin Inhibited Urokinase-Type Plasminogen Activator–Mediated Cleavage and Delayed Human Prostate Bone Metastasis

Expression of alpha(6) integrin, a laminin receptor, on tumor cell surfaces is associated with reduced patient survival and increased metastasis in a variety of tumors. In prostate cancer, tumor extracapsular escape occurs in part via laminin-coated nerves and vascular dissemination, resulting in clinically significant bone metastases. We previously identified a novel form of alpha(6) integrin, called alpha(6)p, generated by urokinase-type plasminogen activator-dependent cleavage of the laminin-binding domain from the tumor cell surface. Cleavage increased laminin-dependent migration. Currently, we used the known conformation sensitivity of integrin function to determine if engagement of the extracellular domain inhibited integrin cleavage and the extravasation step of metastasis. We show that alpha(6) integrin was present on prostate carcinoma escaping the gland via nerves. Both endogenous and inducible levels of alpha(6)p were inhibited by engaging the extracellular domain of alpha(6) with monoclonal antibody J8H. J8H inhibited tumor cell invasion through Matrigel. A severe combined immunodeficient mouse model of extravasation and bone metastasis produced detectable, progressive osteolytic lesions within 3 weeks of intracardiac injections. Injection of tumor cells, pretreated with J8H, delayed the appearance of metastases. Validation of the alpha(6) cleavage effect on extravasation was confirmed through a genetic approach using tumor cells transfected with uncleavable alpha(6) integrin. Uncleavable alpha(6) integrin significantly delayed the onset and progression of osseous metastases out to six weeks post-injection. The results suggest that alpha(6) integrin cleavage permits extravasation of human prostate cancer cells from circulation to bone and can be manipulated to prevent metastasis.

Cutaneous ulceration due to contrast extravasation. Experimental assessment of injury and potential antidotes.

Severe cutaneous ulceration may occur as a result of contrast media extravasation. We established a definitive animal model for assessing the cutaneous toxicity of commonly employed agents and used this model to evaluate possible antidotes to the effects of contrast media extravasation. The contrast agents studied were: meglumine/sodium diatrizoate 76%, meglumine iothalamate 60% and 43%, meglumine/sodium ioxaglate 60%, iohexol 350, and iopamidol 370, in varying volumes and osmolalities. Hypertonic saline (950 and 1900 mOsm/kg) also was injected. Agents were injected intradermally into BALB/c mice. The higher osmolality agents produced dose-dependent skin ulcerations. The lower osmolality agents failed to produce any skin lesions after the same volume doses. Hypertonic saline produced skin toxicity in a dose-dependent fashion similar to hyperosmolar contrast agents. Three antidotes were tested: hyaluronidase, topical heat, and topical cold. Hyaluronidase significantly reduced skin toxicity when injected immediately following contrast injection. Cold also significantly reduced skin toxicity, while heat caused no improvement.

Two dimensional echocardiography and intravenous digital video subtraction angiography for diagnosis and evaluation of double aortic arch

Two infants and one 7 year old child with double aortic arch are described in whom subcostal two dimensional echocardiography identified the bifurcation of the aorta high within the thorax and imaged the proximal portions of the right and left aortic arches. In one of the infants and in the 7 year old child, the diagnosis was confirmed using intravenous digital video subtraction angiography, thus avoiding aortography and permitting accurate evaluation of the anatomic features. All cases were confirmed surgically. If X-ray examination after barium swallow and clinical history are suggestive of double aortic arch, two dimensional echocardiography is useful in verifying this possibility. Intravenous digital video subtraction angiography provides the capability for precise documentation of the anatomic features.

STENT VERSUS ENDOVASCULAR GRAFT HEALING CHARACTERISTICS IN THE PORCINE ILIAC ARTERY

PURPOSE To evaluate the healing characteristics of stents versus endovascular grafts in the porcine iliac artery. MATERIALS AND METHODS A total of 20 iliac arteries in 10 domestic swine were used to evaluate the healing characteristics of stents versus endovascular grafts. Each animal received one stent and one endovascular graft in opposite iliac arteries. The endovascular grafts were constructed with use of 6 cm of expanded polytetrafluoroethylene (ePTFE) (3 mm inner diameter, 30 microm internodal distance) and Palmaz stents (P204 or P188) secured at each end of the graft. A solitary Palmaz stent (P308 or P294) was used on the opposite side. The devices were explanted at 1, 5, and 12 weeks. RESULTS One of three endovascular grafts and two of three stents were patent at 1 week. Two of three endovascular grafts and all three stents were patent at 5 weeks. All three endovascular grafts and stents were patent at 12 weeks. Gross examination, histologic, and scanning electron microscopy demonstrated differences in the healing response of the two devices. A marked abluminal inflammatory response to the graft material was observed. This resulted in neovascularization of the tissue along the abluminal surface of the graft. In addition, marked neointimal thickening at the unsupported section of the endovascular graft resulted in significant luminal narrowing. CONCLUSION The porcine model may be used for evaluating the healing characteristics of endovascular grafts. Intravascular placement of ePTFE prosthetic graft material dramatically alters the healing of this type of graft material. The graft material did not prevent the formation of a progressively thickening neointima.

CT findings after hepatic chemoembolization

Hepatic arterial chemoembolization (CE) with a mixture of particulate collagen and chemotherapeutic agents was evaluated as therapy for hepatic metastases from colorectal carcinoma. This article describes the characteristic sequential pattern of change seen on liver CT scans following CE. Thirty CT scans were performed on seven patients who had undergone a total of 11 CE procedures. All patients had baseline, immediate postprocedural, and follow-up CT exams at 1 to 2 month intervals following CE. Immediate postprocedural CT scans mapped the area of embolization owing to the density of the contrast mixed with the CE agents. Some lesions seen easily on baseline were more difficult to see as they became isodense with normal liver. Reflux of embolic material into the cystic artery and gallbladder wall was also observed on postprocedural scans in three patients. In all patients, early follow-up scans (1 month after CE) demonstrated changes in lesions seen on baseline scans consistent with tumor necrosis. This was corroborated by a decrease in carcinoembryonic antigen (CEA) levels. In three patients, however, low attenuation regions developed in areas in which there had been no lesion before. The significance of these is uncertain, but the low CEA values and the subsequent evolution in appearance of these sites on CT suggest that they were regions of hepatic ischemia/infarction as opposed to heretofore unidentifiable metastases, now “unmasked.” Intermediate follow-up scans (2–3 months) revealed maximal effect on tumor volume, with a decrease of ≥25% in five of seven patients (71%). Late follow-up scans (≥3 months after the last CE) confirmed recurrent disease and new lesions in all cases.

Targeting integrin α6 stimulates curative-type bone metastasis lesions in a xenograft model.

Laminin-binding integrin receptors are key mediators of epithelial cell migration and tumor metastasis. Recent studies have demonstrated a role for the α6 integrin (ITGA6/CD49f) in maintaining stem cell compartments within normal bone marrow and in residency of tumors metastatic to bone. In this study, we tested a function-blocking antibody specific for ITGA6, called J8H, to determine if preexisting cancer lesions in bone could be slowed and/or animal survival improved. Human prostate tumors were established by intracardiac injection into male SCID mice and treatment with J8H antibody was initiated after 1 week. Tumor progression was monitored by micro-computed tomography (CT) imaging of skeletal lesions. Animals that received weekly injections of the anti-ITGA6 antibody showed radiographic progression in only 40% of osseous tumors (femur or tibia), compared with control animals, where 80% of the lesions (femur or tibia) showed progression at 5 weeks. Kaplan–Meier survival analysis demonstrated a significant survival advantage for J8H-treated animals. Unexpectedly, CT image analysis revealed an increased proportion of bone lesions displaying a sclerotic rim of new bone formation, encapsulating the arrested lytic lesions in animals that received the anti-ITGA6 antibody treatment. Histopathology of the sclerotic lesions demonstrated well-circumscribed tumor within bone, surrounded by fibrosis. These data suggest that systemic targeting of the ITGA6-dependent function of established tumors in bone may offer a noncytotoxic approach to arrest the osteolytic progression of metastatic prostate cancer, thereby providing a new therapeutic strategy for advanced disease. Mol Cancer Ther; 13(6); 1558–66. ©2014 AACR.

Prospective Comparison of Plain Abdominal Radiography with Conventional and Digital Renal Tomography in Assessing Renal Extracorporeal Shock Wave Lithotripsy Patients

Most publications citing the effectiveness of renal extracorporeal shock wave lithotripsy have used plain abdominal radiography to assess residual calculi after treatment. We compared radiologist sensitivity and specificity in the detection of calculi on plain abdominal radiographs versus conventional film-screen and digital renal tomograms in extracorporeal shock wave lithotripsy patients. Of the patients 50 were imaged before and within 24 hours after lithotripsy. Six radiologists evaluated the resultant 300 studies for the presence and location of calculi. The mean sensitivity for digital tomograms was 83% for pre-lithotripsy and post-lithotripsy studies, which was significantly higher than for plain abdominal radiography and conventional tomography after lithotripsy. However, there were significantly more false positive stone diagnoses associated with digital tomogram interpretation. Signal detection analysis verified the over-all superiority of digital tomography for post-extracorporeal shock wave lithotripsy imaging. Calculus detection by conventional and digital tomography is superior to detection by plain abdominal radiography. However, because we did not perform delayed imaging, it is not possible to say what impact digital tomography might have on the management of extracorporeal shock wave lithotripsy patients.

Computed radiographic evaluation of simulated pulmonary nodules. Preliminary results.

We evaluated the capabilities of a computed radiography system (CRS) and a standard radiography system (SRS) in the detection of simulated solitary pulmonary lung nodules of various sizes and contrast. A phantom simulated the pulmonary anatomy, and specially shaped plexiglass disks were externally mounted to simulate solitary pulmonary nodules of different diameters and thicknesses. ROC curves were generated based on the performance of each of the radiologists observing each film set. In this preliminary study, the overall performance for both the CRS and the SRS were comparable in detecting simulated pulmonary nodules.

Dependence of substance CT number on scanning technique and position within scanner

A body tissue will vary in its CT value from one study to another not only because of changes in its physiology, but also because of technical factors related to the scanning procedure itself. Changing the mAs of a scan and/or position of a substance within the CT scanner was shown by the use of a phantom study to give a small relative but readily measurable change in the CT value of the substance. Thus, small relative changes in CT numbers should be regarded with caution when comparing one substance or area with another or one study with another.