Locoregional lymph nodes are routinely examined in order to define the spatial extent of neoplastic disease. As draining patterns of certain tumor types can be divergent from expected anatomical distribution, it is critical to sample the lymph nodes truly representing the draining area. The aim of this bicenter prospective pilot study was to describe the technique of computed tomographic (CT)-lymphography for primary draining lymph node mapping in tumor staging in dogs. Forty-five dogs with macro- or microscopic tumors in specified localizations were evaluated. Depending on body weight, 0.8-2 ml contrast agent (iohexol) was injected into four quadrants around the tumor, and CT-images were obtained at 1, 3, 6, 9, and 12 minutes post-injection. Attenuation of chosen regions of interest (Hounsfield units (HU)) and patterns of enhancement were assessed for 284 lymph nodes in the precontrast study with median HUs of 31.1 (Interquartile range (IQR) = 18.4) and for 275 in the intravenous postcontrast study with 104.3 HU (IQR = 31.2) (paired Wilcoxon test, P < 0.001). In the CT-lymphography study, 45 primary draining lymph nodes with a significantly higher median HU value of 348.5 (IQR = 591.4) (one-sample t-test, P < 0.001) were identified. Primary draining lymph nodes were found to be clearly visible after 1-3 minutes after local injection, often concurrent with a good visibility of the lymphatic vessel system. The herein described technique of peritumorally injected CT-contrast agent followed by subsequent CT-lymphography for primary draining lymph node mapping works well in a majority of cases in all investigated sites and warrants further validation for different tumor entities.
Contrast-enhanced ultrasound was used to study focal and multifocal lesions of the spleen in 26 dogs and two cats affected by 11 benign and 18 malignant splenic diseases. A second-generation microbubble contrast medium (Sonovue) was injected into the cephalic vein and enhancement patterns were subjectively described and time intensity curves calculated. Final diagnosis was obtained by histopathologic examination after splenectomy (n=19) or by needle aspiration and sonographic follow-up after 4 and 8 weeks (n=9). Contrast-enhanced ultrasound parameters, improving the characterization between benign and malignant lesions, were established. The most useful criterion was the hypoechogenicity of the lesion in the wash-out phase combined with the presence of tortuous feeding vessels, which was observed in association with malignancy. All malignant lesions were hypoechoic to the surrounding spleen 30s after starting the contrast medium injection. Lymphosarcoma and hemangiosarcoma had characteristic perfusion patterns. Lymphosarcoma had rapid time to peak and early wash-out phase with a honeycomb pattern during the wash-out. Hemangiosarcomas were large nonperfused masses in all phases surrounded by hypervascular splenic parenchyma. Benign lesions except one hematoma and a benign histiocytoma had the same perfusion pattern as the surrounding spleen. Ultrasonographic and contrast-enhanced ultrasound findings of an accessory spleen are reported. Contrast-enhanced ultrasound can improve the characterization of focal or multifocal lesions of the spleen.
Sixty-three dogs with newly diagnosed lymphoma underwent complete staging and received the same chemotherapy. Diffuse large B-cell lymphoma was the leading histotype (44.4%), followed by peripheral T-cell lymphoma (20.6%). Indolent lymphomas accounted for 30.2% of cases. Most dogs with aggressive B-cell lymphoma had stage IV disease. Dogs with indolent and aggressive T-cell lymphoma had more often stage V disease and were symptomatic. Liver and bone marrow were predominantly involved in B-cell and T-cell lymphoma, respectively. The clinical stage was significantly related to substage, sex and total lactic dehydrogenase (LDH) levels. Aggressive B-cell lymphomas were more likely to achieve remission. Median survival was 55 days for aggressive and indolent T-cell lymphoma, 200 and 256 days for indolent and aggressive B-cell lymphoma, respectively. The prognosis of advanced indolent lymphoma does not appear to be appreciably different from that of aggressive disease. Familiarity with the various histotypes is critical to make the correct diagnosis and drive therapy.
Purpose: Active immunotherapy is a promising antitumoral strategy; however its use in combination with chemotherapy in dogs with large B-cell lymphoma (DLBCL) remains largely untested. Heat shock proteins (HSP) bind the small peptides they chaperone (HSPPC), allowing for immunization of the host against a large repertoire of tumor-associated antigens. Hydroxylapatite vehicles HSPPCs and acts as an immunologic adjuvant. The aim of this study was to show that an autologous vaccine with hydroxylapatite and tumor-derived HSPPCs is safe and therapeutically effective in dogs with DLBCL.Experimental Design: Nineteen dogs with naturally occurring DLBCL were entered into a prospective randomized placebo-controlled double-blinded trial of HSPPCs-hydroxylapatite plus chemotherapy versus chemotherapy alone. Endpoints included time to progression (TTP), lymphoma-specific survival (LSS), and incidence of toxicoses.Results: Median first TTP after randomization to the vaccine arm was 304 days versus 41 days for the control arm (P ¼ 0.0004). There was also a statistically significant difference in duration of second remission between the two groups (P ¼ 0.02). Median LSS was 505 days for the vaccinated dogs versus 159 days for the unvaccinated dogs (P ¼ 0.0018). Six vaccinated dogs achieved molecular remission, as shown by clonal immunoglobulin H (IgH) rearrangement. Toxicoses were comparable between the two treatment arms.Conclusions: The results of this trial demonstrate that the autologous vaccine tested here is safe and efficacious in prolonging TTP and LSS in dogs with DLBCL when used in combination with dose-intense chemotherapy. On the basis of these results, additional evaluation of this novel therapeutic strategy is warranted in human DLBCL. Clin Cancer Res; 20(3); 668-77. Ó2013 AACR.
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