Ralph A. Henderson

Hyperthermia of pet animal tumours with self-regulating ferromagnetic thermoseeds

Investigations with thermally self-regulating ferromagnetic implants (thermoseeds) were done on healthy rats and pet animals with spontaneous and transmissible venereal tumours (TVT). The thermoseeds were produced from a nickel-copper alloy and electroplated with a gold-silver layer. Manufacturing conditions were varied to produce thermoseeds with various operating temperatures, the critical temperature above which heating power production sharply declines. To test for toxicity, thermoseeds were implanted into the liver of rats and left in place for up to 14 months. While atomic absorption spectroscopy showed increased nickel and copper levels in tissues near the implants, no clinical evidence of ill-effects was noted. For hyperthermia treatment, thermoseeds were implanted into tumours of pet animals, and these were placed into an induction coil which produced an 89 kHz frequency, 4000 A/m amplitude field. The highest recorded tumour temperature correlated with the nominal operating point of the thermoseeds, demonstrating their ability to regulate the temperature. Of the 15 evaluable animals with spontaneous tumours treated, 12 received concomitant 60Co radiation (two of them only after tumour recurrence following an initial treatment course of hyperthermia alone). Five of those treated with both modalities experienced complete response, five responded partially and two had no change. The treatment course of hyperthermia alone resulted in one animal achieving a complete response, and in three partial responders. Animals bearing TVT had a complete local response with hyperthermia alone. Massive tissue necrosis and seed migration caused the major treatment-related toxicity. Our findings suggest that self-regulating thermoseeds offer the possibility of predictable heat delivery to defined tissue volumes, and may be useful in the treatment of human tumours which are amenable to implantation. Until migration can be controlled, clinical trials should be limited to removable implants.

Ferromagnetic thermoseeds suitable for an afterloading interstitial implant

Previous studies have shown implantable ferromagnetic thermoseeds to be a promising hyperthermia method. However, migration from the implant site and chemical toxicity caused by corrosion of the thermoseed alloy have proven to be potential hazards. These problems could be overcome by placing the thermoseeds into removable catheters similar to those used for afterloading interstitial brachytherapy. As an additional merit, the method would allow convenient combination of heat and radiation therapy. To test the clinical performance of this method, we compared temperature distributions and biologic effects in canine muscle and transmissible venereal tumors for bare thermoseeds and thermoseeds contained within catheters. We found no significant difference in the heating patterns and similar tissue changes when all implants were removed immediately after heating. More severe tissue changes were present around bare thermoseeds that were retained. This suggests that catheters provide a safe and reliable method for thermoseed hyperthermia which would allow convenient combination with interstitial radiation.

Hemipelvectomy: Outcome in 84 dogs and 16 cats. A veterinary society of surgical oncology retrospective study

OBJECTIVE To report clinical findings, perioperative complications and long-term outcome in dogs and cats that had hemipelvectomy surgery for treatment of neoplasia. STUDY DESIGN Multi-institutional retrospective case series. ANIMALS Dogs (n = 84) and cats (16). METHODS Medical records (January 2000 to December 2009) of dogs and cats that had hemipelvectomy at participating institutions were reviewed. Postoperative progress and current status of the patient at the time of the study was determined by either medical record review, or via telephone contact with the referring veterinarian or owner. RESULTS Complications were infrequent and usually minor. Hemorrhage was the main intraoperative complication; 2 dogs required blood transfusion. One dog developed an incisional hernia. In dogs, hemangiosarcoma had the worst prognosis with a median survival time (MST) of 179 days. MST for chondrosarcoma (1232 days), osteosarcoma (533 days), and soft tissue sarcoma (373 days) were not statistically different. Median disease-free interval (DFI) for local recurrence of all tumor types was 257 days. Cats had 75% survival at 1 year, which was significantly longer than dogs. CONCLUSIONS Survival times for most tumor types can be good, but surgical margins should be carefully evaluated to ensure complete tumor removal. Adjuvant therapies may be advisable particularly for dogs to reduce rates of local recurrence or distant metastasis.

Ocular metastasis of a vaccine-associated fibrosarcoma in a cat

A 6-year-old, neutered male domestic shorthair cat was evaluated for a recurrent vaccine-associated fibrosarcoma. The cat had three excisions of the tumour prior to presentation and was referred for radiation therapy. Ten months following treatment with radiation therapy, the cat was presented again for a cloudy appearance to the eye. An exenteration was performed, and biopsy revealed fibrosarcoma. At the same time, two discrete pulmonary nodules were identified on thoracic radiographs. Two doses of doxorubicin (20 mg/m(2)) and cyclophosphamide (100 mg/m(2)) were administered intravenously 3 weeks apart. Despite treatment, the pulmonary nodule doubled in size. This case represents the first antemortem report of ocular metastasis of a vaccine-associated sarcoma and supports the highly aggressive nature of these tumours.

A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs

BackgroundSplenic masses are common in older dogs; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are short, non-coding RNAs that play a role in post-transcriptional regulation, and differential expression of miRNAs between normal and tumor tissue has been used to diagnose neoplastic diseases. The objective of this study was to determine differential expression of miRNAs by use of RNA-sequencing in canine spleens that were histologically confirmed as hemangiosarcoma, nodular hyperplasia, or normal.ResultsTwenty-two miRNAs were found to be differentially expressed in hemangiosarcoma samples (4 between hemangiosarcoma and both nodular hyperplasia and normal spleen and 18 between hemangiosarcoma and normal spleen only). In particular, mir-26a, mir-126, mir-139, mir-140, mir-150, mir-203, mir-424, mir-503, mir-505, mir-542, mir-30e, mir-33b, mir-365, mir-758, mir-22, and mir-452 are of interest in the pathogenesis of hemangiosarcoma.ConclusionsFindings of this study confirm the hypothesis that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. A large portion of the differentially expressed miRNAs have roles in angiogenesis, with an additional group of miRNAs being dysregulated in vascular disease processes. Two other miRNAs have been implicated in cancer pathways such as PTEN and cell cycle checkpoints. The finding of multiple miRNAs with roles in angiogenesis and vascular disease is important, as hemangiosarcoma is a tumor of endothelial cells, which are driven by angiogenic stimuli. This study shows that miRNA dysregulation is a potential player in the pathogenesis of canine splenic hemangiosarcoma.

Total prostatectomy as a treatment for prostatic carcinoma in 25 dogs

OBJECTIVE To describe the complications and outcome after total prostatectomy in dogs with histologically confirmed prostatic carcinoma. STUDY DESIGN Multi-institutional retrospective case series. ANIMALS 25 client-owned dogs. METHODS Medical records of dogs undergoing total prostatectomy were reviewed from 2004 to 2016. Data retrieved included signalment, presenting signs, preoperative clinical findings, laboratory data, diagnostic imaging, surgical technique, histologic diagnosis, postoperative complications, occurrence of postoperative metastasis, and survival. RESULTS Twenty-five dogs underwent total prostatectomy for prostatic carcinoma. Urinary anastomotic techniques included urethrourethral anastomosis in 14 dogs, cystourethral anastomosis in 9 dogs, ureterocolonic anastomosis in 1 dog, and anastomosis between the bladder neck and penile urethra in 1 dog. All dogs survived to discharge. Fifteen dogs were diagnosed with transitional cell carcinoma, 8 dogs with prostatic adenocarcinoma, 1 with prostatic cystadenocarcinoma, and 1 with an undifferentiated carcinoma. Permanent postoperative urinary incontinence was present in 8 of 23 dogs. The median survival time was shorter in dogs with extracapsular tumor extension compared with those with intracapsular tumors. The overall median survival time was 231 days (range, 24-1255), with 1- and 2-year survival rates equal to 32% and 12%, respectively. CONCLUSION AND CLINICAL SIGNIFICANCE Total prostatectomy, combined with adjunct therapies, prolongs survival and lowers complication rates compared to previous reports of dogs with prostatic carcinoma. It should be noted, however, that case selection likely played a significant role in postoperative outcome.