Chronic effect of transrectal split-focus ultrasonic ablation on canine prostatic tissue

The treatment time needed for high-intensity focused ultrasound (HIFU) ablation might be decreased substantially by using the split-focus approach, so we made a prototype 4.2-MHz split-focus therapeutic transducer combined with a small 6.5-MHz imaging ultrasonic probe for transrectally treatment of canine prostatic cancer and used it to experimentally evaluate the feasibility of using split-focus transrectal HIFU to ablate canine prostatic tissue without injuring surrounding tissues. The prostates of 5 dogs were transrectally treated with split-focus ablation at a peak intensity in the water of 1.7 kW/cm(2) for 4 s (4 shots) under the guidance of ultrasonic B-mode imaging. After ultrasonic exposure, the prostates became stiff because of thermal effect of HIFU. For the first 3-5 days after treatment, dogs were catheterized daily for urinary management and treated with oral antibiotics to prevent urinary tract infection. The dogs were able to urinate normally by a week after. Within two weeks a large centrally located cystic cavity had formed in the prostate by replacing the necrotic parenchyma around the prostatic urethra. Necropsy three months after treatment found the rectum and prostate capsule to be normal grossly and histologically. The 4 shots of split-focus HIFU destroyed the prostatic parenchyma and created a prostatic cavity 0.34-0.45 cm(3) in volume without injuring surrounding tissues. These results suggest that split-focus HIFU ablation could be used for noninvasive treatment of prostatic cancer in dogs.     

Near-infrared imaging and optical coherence tomography for intraoperative visualization of tumors

Surgical excision is the foundation of treatment for early-stage solid tumors in man and companion animals. Complete excision with appropriate margins of surrounding tumor-free tissue is crucial to survival. Intraoperative imaging allows real-time visualization of tumors, assessment of surgical margins, and, potentially, lymph nodes and satellite metastatic lesions, allowing surgeons to perform complete tumor resections while sparing surrounding vital anatomic structures. This Review will focus on the use of near-infrared imaging and optical coherence tomography for intraoperative tumor visualization.     

Implantation of VX2 carcinoma into the liver of rabbits: a comparison of three direct-injection methods

The efficacy of agarose in preventing VX2 carcinoma cell leakage was evaluated and the results were compared with two traditional methods. Forty-five rabbits were divided into 3 groups: Group 1, VX2 tumor cells were injected directly into the liver and no special procedure after removal of the needle; Group 2, the puncture site was gently compressed, using an alcoholic cotton gauze, for three minutes; Group 3, 0.2 ml of heated liquid agarose was injected to seal the aperture after injection of VX2 cells. The leakage rates were 80%, 53.3% and 6.6% for group 1, group 2 and group 3, respectively. We consider agarose is a useful material in preventing the leakage in the establishment of VX2 liver tumor models.     

The carbon dioxide laser: an alternative surgery technique for the treatment of common cutaneous tumors in dogs

Background

Tumors of the skin and subcutaneous tissue are the largest group of canine neoplasms. Total excision is still the most effective method for treatment of these skin tumors. For its universal properties the carbon dioxide (CO₂) laser appears to be an excellent surgical instrument in veterinary surgery. Laser techniques are alternatives to traditional methods for the surgical management of tumors. The aim of this study was to compare various types of laser techniques in skin oncologic surgery: excision, ablation and mixed technique and to suggest which technique of CO₂ laser procedure is the most useful in particular case of tumors in dogs.

Findings

The study was performed on 38 privately-owned dogs with total number of 40 skin tumors of different type removed by various CO₂ laser operation techniques from 2010–2013. The treatment effect was based on the surgical wound evaluation, the relative time of healing and possible local recurrence of the tumor after 3 months post surgery. Local recurrence was observed in two cases. The study showed that in 30 cases time needed for complete resection of lesions was less than 10 minutes. Time of healing was longer than 12 days in 6 cases (42.8%) with tumor excision and in 14 cases (87.5%) where excision with ablation technique was performed.

Conclusions

The advantages of the CO₂ laser surgery were better hemostasis, precision of working, non-contact dissection, less instruments at the site of operation and minimum traumatization of the surrounding tissues.     

Pituitary macroadenomas and macroadenocarcinomas in dogs treated with mitotane for pituitary-dependent hyperadrenocorticism: 13 cases (1981-1986)

Pituitary macroadenoma/macroadenocarcinoma (PMA; tumor size greater than or equal to 1 cm in diameter) was diagnosed in 13 dogs after 0.5 to 24 months of mitotane treatment for pituitary-dependent hyperadrenocorticism (PDH). The diagnosis of PDH was established on the basis of results of common tests of the pituitary-adrenocortical axis in conjunction with results of x-ray computed tomography or necropsy. Initial clinical findings and clinicopathologic test results were typical of PDH. Signs referable to the CNS developed in 7 of the 13 dogs. The most common neurologic sign was stupor. Pituitary macroadenoma/macroadenocarcinoma was an unexpected finding in the other 6 dogs, because none had clinical signs of disease referable to the CNS at the time that pituitary tumor was documented. In the 13 dogs, strong correlation existed between tumor volume, compression/invasion of the surrounding nervous tissue, and development of neurologic signs, ie, neurologic signs were most frequently associated with larger tumors. The size of the tumor, however, was not always an indication of whether neurologic signs would be observed. All 7 dogs with neurologic signs were euthanatized because of the deleterious effects of the PMA. Of the 6 dogs without neurologic signs, 2 died of unrelated cause. Alternative treatment (ie, hypophysectomy, 60Co-teletherapy) was used successfully in 2 other dogs. Alternative treatment would seem indicated if PMA is documented in a dog with PDH. However, identification of PMA is dependent on evaluation of x-ray computed tomographic images. Signalment, history, physical examination, and alterations in routine clinicopathologic findings in these 13 dogs of our study were similar to previously reported findings in dogs with PDH but apparently without large pituitary tumors.(ABSTRACT TRUNCATED AT 250 WORDS)     

EARLY POSTOPERATIVE MAGNETIC RESONANCE IMAGING FINDINGS IN FIVE DOGS WITH CONFIRMED AND SUSPECTED BRAIN TUMORS

Early postoperative neuroimaging has been performed in people for over 20 years to detect residual brain tumor tissue and surgical complications. The purpose of this retrospective study was to describe characteristics observed using early postoperative magnetic resonance imaging in a group of dogs undergoing craniotomy for brain tumor removal. Two independent observers came to a consensus opinion for presence/absence of the following MRI characteristics: residual tumor tissue; hemorrhage and ischemic lesions; abnormal enhancement (including the margins of the resection cavity, choroid plexus, meninges) and signal intensity changes on diffusion‐weighted imaging. Five dogs were included in the study, having had preoperative and early postoperative MRI acquired within four days after surgery. The most commonly observed characteristics were abnormal meningeal enhancement, linear enhancement at margins of the resection cavity, hemorrhage, and a thin rim of hyperintensity surrounding the resection cavity on diffusion‐weighted imaging. Residual tumor tissue was detected in one case of an enhancing tumor and in one case of a tumor containing areas of hemorrhage preoperatively. Residual tumor tissue was suspected but could not be confirmed when tumors were nonenhancing. Findings supported the use of early postoperative MRI as a method for detecting residual brain tumor tissue in dogs.     

Radiolocalization of bovine lymphosarcoma cells in athymic mice, using a monoclonal antibody against tumor-associated antigens

Mouse monoclonal antibody c 143 was purified and F(ab')2 fragments were generated by pepsin digestion and then radiolabeled with 125I. The 125I-labeled c 143 F(ab')2 fragments were injected into athymic mice bearing bovine lymphoid tumor cells. The fragments became preferentially localized in tumor tissues, but not in normal tissues, as determined by differential counting of tissue radioactivity. The fragments became localized specifically in those tumors that were reactive with c 143 in vitro, but did not become localized in unrelated tumors. Localization of labeled F(ab')2 fragments of a monoclonal antibody of the same isotype directed against Taka virus (a variant of Newcastle disease virus) was not observed in athymic mice bearing bovine lymphoid tumor cells. Tumors were detectable by radioimmunoscintigraphy, using radiolabeled c 143 F(ab')2 fragments, without background subtraction, and by use of silver-grain scattering in light microscopic autoradiography.     

溶瘤病毒在犬肿瘤治疗中的研究进展

溶瘤病毒疗法是利用病毒治疗恶性肿瘤的一种较有前景的新型生物疗法。溶瘤病毒不仅能直接特异性感染和溶解肿瘤细胞，也能刺激肿瘤部位的免疫反应来间接地溶解肿瘤组织细胞，且对正常组织细胞无杀伤或仅有较弱的杀伤作用，从而能达到理想的抗肿瘤效果。文章综述了溶瘤病毒的发展史及溶瘤病毒介导肿瘤消融术的机制，分析麻疹病毒、犬瘟热病毒、新城疫病毒、仙台病毒等8种病毒作为抗肿瘤药物在体外试验、异种移植肿瘤动物模型试验、肿瘤患犬治疗试验等不同阶段对各种犬肿瘤细胞的杀伤效果，提示溶瘤病毒疗法可能是一种安全可靠的恶性肿瘤治疗新方法，但真正将溶瘤病毒疗法应用在犬肿瘤临床治疗中时病毒肿瘤特异性、病毒使用剂量等问题仍需解决，本综述可为溶瘤病毒在犬肿瘤临床治疗中的安全使用提供新的思路和技术途径。     

2例犬肝胆管细胞癌的病理学诊断

肝胆管细胞癌是来源于肝胆管上皮细胞的恶性肿瘤,在多物种中都有发生。笔者运用组织病理学和免疫组织化学的方法,对2例犬肝肿瘤进行了诊断。结果显示：肝肿瘤眼观均为圆球形白色肿块,组织病理学检查肿瘤组织由呈腺管状排列的瘤细胞构成,有的腺管中央有坏死脱落的细胞,有的有黏液样物质,腺管间以薄的纤维结缔组织分隔,瘤组织有大片的坏死。瘤细胞多呈卵圆形,细胞核大、卵圆形,核分裂象多见,瘤细胞的CK19阳性表达,而CK18和AFP呈阴性表达。根据组织病理学和免疫组织化学检查结果判断,2例犬肝肿瘤为肝胆管细胞癌,本研究为犬肝肿瘤诊断积累了病理学资料。     

Heterotransplantation of canine sarcoma cells (BLU284) in athymic (nude) mice

Undifferentiated canine sarcoma cells from a primary lesion were implanted subcutaneously in athymic (nude) mice. Tumors were implanted at 2 sites in each of 4 mice, and 6 of the 8 inoculation sites developed into tumors. Tumors grew and invaded surrounding tissues, as shown by histologic examination. Karyotype analysis verified that tumors were of canine origin. Cells from this tumor were serially heterotransplanted 26 times without consistent change in growth rate. Once established in nude mice, samples from 2 generations of this canine sarcoma cell line were stored cryogenically and were implanted into nude mice. Over 26 generations, 93.7% of fresh implants developed into tumors. Preliminary screening of antineoplastic drugs indicated that this tumor line was sensitive to cyclophosphamide and vincristine. The difference in sensitivity of this heterotransplanted tumor in nude mice toward the various antineoplastic agents provides a useful model for the elucidation of biochemical bases of antineoplastic drug resistance in tumors.     

H-ras consensus sequence and mutations in primary hepatocellular carcinomas of lemurs and lorises

The authors have determined a consensus sequence for exons 1 and 2 of H-ras from captive lemurs and lorises and evaluated samples of nonneoplastic liver and hepatocellular carcinomas (HCC) from affected animals for mutations in these exons. Frozen liver samples were collected from 20 animals representing 9 different species with a sex distribution of 10 males and 10 females. A total of 26 liver samples, including 11 normal livers, 9 HCC, and 6 samples from nonneoplastic regions of liver from animals with HCC, were evaluated. This is the first report of the consensus sequence for exons 1 and 2 of H-ras in prosimians, and the authors have determined that it is identical to that of human H-ras and differs only slightly from the chimpanzee sequence. Point mutations were identified in 6 of the 9 HCC samples examined with codons 7, 22, 32, 56, 61, 84, and 96 affected. Two carcinomas had double mutations, and one tumor had triple mutations. One HCC had a mutation in codon 61, which is identical to a recognized affected codon for an H-ras "hot spot" in rodent neoplasia that has also been reported in human tumors. Although not statistically different, metastasis occurred in 5 of 6 HCC with H-ras mutation and only 1 of 3 HCC without mutations. There were 4 silent mutations that did not contain changes in the encoded amino acids, 2 of which were found in nonneoplastic regions of tumor-bearing liver.     

PROSPECTIVE COMPARISON OF TUMOR STAGING USING COMPUTED TOMOGRAPHY VERSUS MAGNETIC RESONANCE IMAGING FINDINGS IN DOGS WITH NASAL NEOPLASIA: A PILOT STUDY

Identification of nasal neoplasia extension and tumor staging in dogs is most commonly performed using computed tomography (CT), however magnetic resonance imaging (MRI) is routinely used in human medicine. A prospective pilot study enrolling six dogs with nasal neoplasia was performed with CT and MRI studies acquired under the same anesthetic episode. Interobserver comparison and comparison between the two imaging modalities with regard to bidimensional measurements of the nasal tumors, tumor staging using historical schemes, and assignment of an ordinal scale of tumor margin clarity at the tumor‐soft tissue interface were performed. The hypotheses included that MRI would have greater tumor measurements, result in higher tumor staging, and more clearly define the tumor soft tissue interface when compared to CT. Evaluation of bone involvement of the nasal cavity and head showed a high level of agreement between CT and MRI. Estimation of tumor volume using bidimensional measurements was higher on MRI imaging in 5/6 dogs, and resulted in a median tumor volume which was 18.4% higher than CT imaging. Disagreement between CT and MRI was noted with meningeal enhancement, in which two dogs were positive for meningeal enhancement on MRI and negative on CT. One of six dogs had a higher tumor stage on MRI compared to CT, while the remaining five agreed. Magnetic resonance imaging resulted in larger bidimensional measurements and tumor volume estimates, along with a higher likelihood of identifying meningeal enhancement when compared to CT imaging. Magnetic resonance imaging may provide integral information for tumor staging, prognosis, and treatment planning.     

Evaluation of Liposomal Radiochemotherapy for Treatment of Cancer

Introduction: Pegylated liposomes target solid tumors by exploiting the capillary leakage properties of tumor neovasculature. The goal of the study was to investigate distribution and tumor targeting properties of the alpha‐particle emitter ²²³Ra, encapsulated in doxorubicin‐containing‐liposomes (Caelyx^®/Doxil^®). Methods: Caelyx^® was given before the injection of liposomal ²²³Ra to reduce the reticulo‐endothelial‐system uptake. A pilot study was conducted to determine the optimal time interval between the pre‐treatment/treatment. Subsequently a more extensive distribution study was performed in normal BalbC mice. In addition, distribution and tumor uptake was evaluated in a human osteosarcoma xenograft mice model and in a dog with spontaneous osteosarcoma. Results: Optimal blood‐to‐liver and blood‐to‐spleen ratios of liposomal radium was achieved in animals that received pre‐treatment with Caelyx^® 4 days in advance. Blood clearance was relatively slow, in mice t_1/2 was ～28 h (BalbC mice) and in the dog t_1/2 was ～ 39 h. In mice the liver uptake appeared to be relatively low in contrast to the spleen, where there was a significant uptake. In the dog the uptake in both liver and spleen was moderate. In the xenograft model there was generally a higher retention of activity in the tumor vs. soft tissue. In the dog the 24 h uptake was considerably higher in both calcified and non‐calcified tumor metastases of different organs, than in normal tissue. Conclusions: Liposomal ²²³Ra has a relevant biodistribution and blood clearance for tumor targeting. More extensive future studies are supported by the favourable tumor/normal‐tissue ratio in a dog with spontaneous osteosarcoma.     

Spinal meningiomas in dogs: Description of 8 cases including a novel radiological and histopathological presentation

Clinical, imaging, and histological features of 8 canine spinal meningiomas, including a cervical cystic meningioma with imaging and intraoperative features of an arachnoid cyst, are described. All meningiomas were histologically classified and graded following the international World Health Organization human classification for tumors. Six meningiomas were located in the cervical spinal cord. Myelography showed intradural/ extramedullary lesions in 3/4 cases. Magnetic resonance imaging revealed hyperintense intradural/extramedullary masses on pre-contrast T1-weighted and T2-weighted images with homogeneous contrast enhancement in 7/8 cases. One dog had a cerebrospinal fluid-filled subarachnoid cavity dorsal to the cervical spinal cord. A spinal arachnoid cyst was diagnosed on imaging, but the histopathological study of the resected tissue revealed a grade I meningothelial cystic meningioma. There were no differences in outcome associated with tumor grade and surgical treatment (6/8). Cystic meningioma should be considered in the differential diagnosis of intraspinal cystic lesions, and biopsy is necessary for definitive diagnosis.     

INVITED REVIEW—NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

The evaluation of therapeutic response using cross‐sectional imaging techniques, particularly gadolinium‐enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the response evaluation criteria in solid tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging‐based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and response assessment in neuro‐oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment‐induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy‐induced changes. Finally, although objective endpoints such as MR imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria.     

Mortality factors, environmental contaminants, and parasites of white-tailed sea eagles from Greenland

Twelve white-tailed sea eagles (Haliaeetus albicilla groenlandicus) found dead between 1997 and 2000 in Greenland were examined to investigate the health status, including the causes of death and the burden of organochlorine contaminants and potentially toxic heavy metals. The determined causes of death were unspecific trauma (n = 6), lead poisoning (n = 2) with 36 and 26 ppm lead in the liver tissue, infectious diseases (n = 1), injuries sustained during intraspecific conflict (n = 1), and gunshot (n = 1). One lead poisoned eagle had a single lead shot pellet in its gizzard. No diagnosis could be made in one case because of decomposition of the carcass. Four of the investigated eagles were injured with lead shot or bullet fragments; one of the birds was killed with about 69 lead shots. Levels of organochlorine pesticides, polychlorinated biphenyls, mercury, and cadmium in organs were moderate. The parasite fauna consisted of one coccidian and three helminth species. The acanthocephalas Profiliocollis botulus and Corynosoma suduche as well as the nematode Stegophorus stellaepolaris are all new records for the white-tailed sea eagle.     

Disseminated mast cell tumor infiltrating the sphenoid bone and causing blindness in a dog

Mast cell tumors are found in most organs and tissues with variable biologic behavior in dogs. This case illustrates the clinical and magnetic resonance imaging (MRI) findings in a dog with disseminated mast cell tumor infiltrating the sphenoid bones. A 6‐year‐old male neutered Greyhound presented with a 3‐day history of acute onset of blindness. General physical examination was normal. Neurological examination revealed mildly disorientated mental status, absent menace response in both eyes, bilaterally decreased vestibulo–oculocephalic reflexes and absent direct and consensual pupillary light reflex in both eyes. An electroretinogram indicated normal retinal function in both eyes. A lesion involving the middle and rostral cranial fossa was suspected. Hematology and serum biochemistry were normal except decreased urea (1.2 mmol/L). MRI of the head revealed heterogeneous signal intensity of the sphenoid bones on T2‐weighted images and loss of their normal internal architecture. Cerebrospinal fluid analysis was normal. Abdominal ultrasound revealed hepatosplenomegaly and mesenteric lymphadenopathy. Fine needle aspirates were taken from the jejunal lymph nodes and the spleen. Results were consistent with disseminated mast cell tumor. The owner declined any treatment and the dog was euthanatized. Postmortem examination confirmed disseminated mast cell tumor affecting multiple organs, including the sphenoid bones. To our knowledge, this is the first case describing MRI features of disseminated mast cell tumor affecting the sphenoid bones and causing acute onset of blindness in a dog.     

CONTRAST-ENHANCED ULTRASONOGRAPHY FOR CHARACTERIZATION OF CANINE FOCAL LIVER LESIONS

In six normal beagles and 27 dogs with spontaneous focal or multifocal liver lesions, contrast-enhanced ultrasonography using Sonazoid^® was performed. Sonazoid^® is a newly developed second-generation contrast agent with the ability to be used for real-time contrast imaging along with parenchymal imaging. An appropriate protocol for the evaluation of all three phases (arterial, portal, and parenchymal) was established based on the results for normal beagles. By evaluation of the echogenicity of hepatic nodules during the arterial and parenchymal phases it was possible to differentiate malignant tumors from benign nodules with very high accuracy. In 15 of 16 dogs diagnosed as malignant tumors, nodules were clearly hypoechoic to the surrounding normal liver during the parenchymal phase. Additionally, malignant tumors had different echogenicity compared with the surrounding normal liver during the arterial phase in 14 of 15 dogs. In the portal phase, there were no characteristic findings. Contrast-enhanced ultrasonography with Sonazoid^® appears to improve the characterization of canine focal and multifocal hepatic lesions.     

MR imaging of hepatic injury in the LEC rat under a high magnetic field (7.05 T).

Visualization of copper-induced hepatitis (CuH) in LEC rats was performed by using an MRI apparatus equipped with a magnet producing a high magnetic field of 7.05 T. When three groups of LEC rats (6-16 [pre-hepatitis], 15-26 [acute hepatitis] and 40-77 [chronic hepatitis] weeks old) were examined by MRI under T2-weighted imaging conditions which are suitable for the diagnosis of human hepatitis, hypointense MR images of the livers were, as a whole, obtained in all groups, suggesting that these conditions were not adequate for imaging of CuH of LEC rats. The shortening of the T1 and T2 relaxation times of livers due to an excess amount of paramagnetic irons under the high magnetic field was responsible for the lowering of MR signal intensities of the livers, especially those of 15 to 26-week old rats showing acute hepatitis. However, theoretical calculation of the MR signal intensities using the T1 and T2 relaxation times of the livers indicated that their imaging might be possible under proton density-weighted conditions even with a high magnetic field. Experimental results showed that hepatic injury was visualized as hyperintense regions in the MR image of the liver in the acute-phase rat.