Everyone there is so positive and professional, and, although we came there for a sad reason, we are so grateful to have met all of you.
West Orange, NJ
An approximately 9-year-old FS Beagle presented to her primary veterinarian for evaluation of a mass on her thoracic wall. The owner first noticed it a few days prior to the appointment. On physical examination, the patient was noted to have a hard lump on the right lateral ventral thorax near the axilla that measured approximately 1.5cms in diameter. Orthogonal view thoracic radiographs were performed and per the medical records the mass was soft tissue opacity and could only be identified on the ventrodorsal view. A fine needle aspirate of the mass was performed and cytology revealed a mesenchymal neoplasm with matrix and blood with the comment that findings suggest a matrix producing mesenchymal neoplasm, including chondrosarcoma or an extraskeletal osteosarcoma.
The patient was scheduled for biopsy and possible mass removal 6 days later. Preoperative chemistry and PCV were unremarkable. Surgical exploratory of the region was performed and it was noted that the mass was underneath the thoracic musculature and attached to the external aspect of the rib cage. Also, the intercostal muscles were visible adjacent to the mass. Due to concern for inadvertent entry into the thoracic cavity if removed, an incisional biopsy was performed.
Histopathology from the mass revealed a well-differentiated chondrosarcoma with a few scattered mitotic figures (1 per 10 high powered fields). Referral to an oncologist was recommended.
The owner had a phone consultation with an oncologist 8 days post biopsy and
a CT scan was recommended to help determine resectabilty and assist in surgical planning. The owner opted to pursue the CT scan, which revealed an aggressive monostotic osteolytic lesion arising from the distal aspect of the right 5th rib that was characterized by expansile lysis of the cortical, and medullary bone surrounded by a soft tissue attenuating mass measuring 1.7 x 2.8 x 3.2 cm. The mass did not come in contact with the 4th or 6th ribs and neither exhibited any periosteal reaction. The tracheobronchial and cranial mediastinal lymph nodes were normal and there was no evidence of pulmonary metastatic disease.
Based on the CT findings, mass resection with partial removal of the right 4th, 5th and 6th ribs was recommended. Approximately 3 weeks later, the owners had a surgical consultation and the recommended procedure, possible complications and postoperative care were discussed. The owner opted to admit the dog for surgery the same day. Preop bloodwork was performed which was unremarkable and the mass and previous surgery site including scar and biopsy site were resected with margins. A thoracostomy tube was placed and a latissiuus dorsal flap was used to assist in closing the thoracic wall defect. The patient recovered smoothly from anesthesia and did well postop. She was discharged from the hospital at 2 days postop and histopathology showed chondrosarcoma grade 1 with margins free of tumor (measured 8mm-1.5 cm). No further treatment was recommended and at 1 month postop the patient was doing well with no evidence of recurrence.
Primary rib tumors are uncommon but when they occur they are most often malignant sarcomas with osteosarcoma and chondrosarcoma being the most common. Other reported rib tumors include hemangiosarcoma, fibrosarcoma, soft tissue sarcoma and leiomyosarcoma.
On physical examination, rib tumors are often firm and immobile on palpation.
If concerned about a rib tumor, radiographs should be performed to not only evaluate the rib mass but also to look for possible metastatic spread to the lungs. Important to note is that the amount of bone lysis or production on radiographs has not been shown to help in distinguishing between the two most common rib tumors, osteosarcoma and chondrosarcoma.
In addition to thoracic radiographs, full blood work is recommended to evaluate the overall health of the patient. In one study ALP was not indicative of tumor type but if elevated was significantly associated with a decreased survival in dogs with rib osteosarcoma. Abdominal ultrasound can also be considered as a staging diagnostic and is more important with certain types of rib neoplasia such as hemangiosarcoma.
The next diagnostic step is ideally a CT of the thorax to help evaluation the full extent of the mass and further investigate the lungs for any evidence of metastatic disease. Thoracic lymph nodes can also be visualized, although this would not typically be the first place for spread. Surgical planning can then be based off of the CT scan.
Figure 1: CT image of aggressive monostotic osteolytic lesion arising from he distal aspect of the right 5th rib
Nuclear scintigraphy has also been reported to be used in patients with rib osteosarcoma to help determine if the rib mass is a metastatic lesion or look for metastasis of the mass. In one study of rib osteosarcoma, a 16% bone metastatic rate was noted from a primary rib osteosarcoma.
Incisional biopsy can be performed either via Tru-cut biopsy or surgical wedge biopsy prior to surgical removal. The advantage of the surgical biopsy over the incisional biopsy is that a larger sample can be obtained and it has been shown that the larger the biopsy sample the increased chance of a correct diagnosis. A biopsy is beneficial in helping determine prognosis with different treatments not the best treatment option, because in general, surgery is the initial recommended treatment regardless of diagnosis if no metastatic lesions are noted.
With surgical resection of rib tumors, the tumor is removed en bloc with margins that include one rib cranial and one rib caudal to the lesion as well as 3 cms dorsal and ventral to the mass. Advanced imaging results help determine if the overlying skin and which overlying muscle(s) needs resected. If the mass was biopsied prior to surgery, it is important to make sure the entire biopsy tract is included in removal. The reported maximum number of ribs that can be removed is 6 but up to 7 has been reported to be performed successfully. Removing more than 6 though increases the risk of severe respiratory compromise and dysfunction postop.
For closure, the use of an autogenous (such as a latissimus dorsi flap) or prosthetic technique (mesh) can be used. The latissimus dorsi flap is the most commonly used local tissue flap and it can be used as a muscle flap or myocutaneous flap. In one study, use of mesh alone was associated with an increased risk of postop complications compared to local tissue flap closure and therefore closure with a local tissue flap or a composite closure using a combination of a autogenous and prosthetic technique is preferred. Diaphragmatic advancement can be used with caudal thoracic wall defects and the use of omentum tunneled into the defect from the subcutaneous tissue or through the diaphragm has been reported.
Use of spinal plates to help with chest wall stability has been reported and it is recommended to suture the muscle flap or mesh taut to help maintain rigidity however absolute rigid reconstuction of the thoracic wall has not been shown to be necessary.
Tumor type is important in determining prognosis. Rib osteosarcoma has similar biological behavior of appendicular osteosarcoma. In one study, rib osteosarcoma treated with surgery alone had a mean survival time of 90 days. Postop chemotherapy can prolong survival and treatment with surgery and postoperative chemotherapy had a mean survival time of 240 days.
Chondrosarcoma, the second most common primary rib tumor has a better prognosis than osteosarcoma with reported median survival times of even greater than 3820 days in one study. If clean margins without metastatic disease are found, adjuvant chemotherapy is not commonly recommended for chondrosarcoma.
Submitted by: Lauren May, DVM
Hunt GB. Thoracic wall. In Tobias KM, Johnston SA, eds. Veterinary Surgery Small Animal. St. Louis, MO: Elsevier, 2012; 1769-1786.
Fossom TW. Surgery of the lower respiratory system. In: Fossom TW, Hedlund CS, Johnson AL, eds. Small Animal Surgery. St. Louis, MO: Mosby Elsevier, 2007; 867-895.
Liptak JM, Kamstock DA, Dernell WS, Monteith GJ, Rizzo SA, Withrow SJ. Oncologic outcome after curative-intent treatment in 39 dogs with primary chest wall tumors (1992-2005). Vet Surg. 2008 Jul;37(5):488-96. http://onlinelibrary.wiley.com/doi/10.1111/j.1532-950X.2008.00415.x/full
Liptak JM, Dernell WS, Rizzo SA, Monteith GJ, Kamstock DA, Withrow SJ.
Reconstruction of chest wall defects after rib tumor resection: a comparison of autogenous, prosthetic, and composite techniques in 44 dogs. Vet Surg. 2008 Jul;37(5):479-87. http://onlinelibrary.wiley.com/doi/10.1111/j.1532-950X.2008.00413.x/full
Liptak, JM. Tumors of the Thoracic Wall. In Monnet E, ed. Small Animal Soft Tissue Surgery. Chidester, UK: John Wiley & Sons, Ltd, 2012; 709-719.
Marina M, Boton, S, Morello E, Withrow ST. Respiratory tract and thorax. In: Kudnig ST, Sequin B, eds. Veterinary Surgical Oncology. UK: Wiley-Blackwell, 2012; 273-328.
Pirkey-Ehrhart, Nicole, et al. “Primary rib tumors in 54 dogs.” Journal of the American Animal Hospital Association 31.1 (1994): 65-69. http://europepmc.org/abstract/med/7820767
Signalment: 9-year-old male neutered domestic shorthair cat
History: Presented to the Emergency Service as a transfer from his primary veterinarian for further evaluation of abdominal distention. The patient’s abdomen had become distended over the past several days. He was still acting normally with no vomiting, diarrhea, or change in appetite or labored breathing. He is indoors only. He was adopted as a kitten, only animal in the household, no travel history, and up to date on vaccinations.
Physical Exam Findings: Markedly distended, tense, abdomen with palpable fluid wave. Remainder of exam within normal limits.
Initial treatments: Abdominocentesis was preformed and 1325mls of milky white fluid was removed without complication.
Diagnostic Evaluation: A CBC performed at RDVM prior to referral showed neutropenia (0.07 k/ul, RR: 2.5-15 k/ul) and thrombocytopenia (clumping?), chemistry was normal with a low normal albumin (2.6, RR: 2.3-3.9 g/dl). Thoracic radiographs were normal. He was Felv/FIV neg. Abdominal Ultrasound showed a moderate volume of echogenic effusion. The mesentery and omentum were thickened and hyperechoic. Echocardiogram showed no cardiac disease. Abdominal Fluid analysis was consistent with chylous effusion, nucleated cells were predominantly small mature lymphocytes, with triglycerides >3200 and TP 6.1.
Assessment: Possible causes for chyloabdomen included neoplasia such as lymphosarcoma or other cancer, lymphangiectasia, FIP, or cardiac disease, but the later had been excluded based on normal echocardiogram and FIP was considered less likely given age and lack of exposure.
Plan: He was started on Rutin (250 mg PO q8 hours) with a plan to follow up with internal medicine.
Follow-up exam with Internal Medicine: Since discharge from the ER, the patient’s appetite had been slightly decreased since starting the Rutin and it was decreased to twice daily. Otherwise doing well.
On recheck exam, the patient had a palpable abdominal fluid wave and had muscle wasting along his spine. He had gained weight (0.4 kg since discharge). A brief ultrasound showed a moderate amount of echogenic effusion, no pleural effusion was noted. There was not enough peritoneal effusion to do an abdominocentesis. An FIP PCR on the abdominal effusion was discussed. An abdominal exploratory was recommended for a more definitive diagnosis.
Abdominal Exploratory Findings: The omentum was very friable. The mesentery was diffusely friable and dark in color. A dark red mass was noted at the ileocolic junction. There were numerous small nodules on the surface of the intestines, the majority on the jejunum but also present on the deudenum, ileum, and large intestines. There was peritoneal effusion in the abdominal cavity. The right lobes of the liver contained a large amount of what appeared to be fibrin and the lobes were rounded.
The surgical findings were discussed with the owners. They opted for humane euthanasia due to concern for quality of life, and amount and severity of widespread disease on exploratory.
Histopathology findings: The ileocecocolic mass, jejunal and liver biopsy were submitted for histopathology.
Moderately differentiated serosal hemangiosarcoma, intestines; Mild lymphoplasmocytic portal hepatitis.
Chylous effusion are predominantly composed of chyle, the lymphatic fluid that flows thru the lacteals of the small intestines and the thoracic duct. The effusion has a characteristic milky white appearance. Underlying causes for chylous effusion include cardiac disease, mediastinal masses, heartworm disease, trauma, granulomas, congenital thorax duct abnormality, biliary cirrhosis, Vitamin E deficiency and diffuse lymphatic disease such as lymphangiectasia or lymphosarcoma (Borku et. Al 2005). Unlike chylothorax, chyloabdomen is uncommon in cats. There are various causes of chylous abdominal effusion in cats such as trauma, lymphoma, chronic pancreatitis, feline infectious peritonitis (FIP), cancer. In one study, seven out of nine cats with chyloabdominal had intra-abdominal neoplasia. Hemangiosarcoma (3 cats), paraganglioma (1 cat) lymphoma (2 cats, small intestinal), lymphangiosarcoma (1 cat, abdominal wall). Unfortunately, four of the cats had unresectable tumors. Survival times varied depending on location and type of neoplasia ranging from euthanasia at the time of surgery, 5 cats were euthanized within 3 months of surgery, one cat with lymphoma lived for 14 months after surgery and also received chemotherapy. Of the two cats with non-neoplastic disease, one had severe biliary cirrhosis and the other had vitamin E deficiency (Gores BR et al 1994). There have also been several case reports of cats with chylous abdominal effusion with FIP, one cat had chylous effusion in the thorax and abdomen (Boreu et al 2005).
Hemangiosarcoma (HSA) in cats is also uncommon and accounts for less than 2% (visceral and non-visceral HSA) of feline malignancy. The frequency of feline visceral HSA was estimated to be 0.04%. HSA typically has a poor to guarded prognosis since it is highly metastatic. One study, reports 77% of cats had multifocal disease at the time of diagnosis (Culp et al. 2008). Chemotherapy with doxorubicin and vincristine have been used in select cases.
Submitted by: Sarah Muhrer, DVM
1. Borku MK, Ural K, Karakurum MC, et al: Chylous pleural and peritoneal effusion in a cat with feline immunodeficiency virus; diagnosis by lipoprotein electrophoresis. Revue Med.Vet 12: 612-614, 2005.http://www.revmedvet.com/2005/RMV156_612_614.pdf2.x/full
2. Culp WN, Drobatz KJ, Glassman, MM et al: Feline visceral hemangiosarcom: Journal of Veterinary Internal Medicine 22: 148-152, 2008 http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2008.002
3. Gores BR, Berg J, Carpenter JL et al:Chylous ascites in cats: nine cases (1978-1993): Journal of the American Veterinary Medical Association 8: 1161-1164, 1994. https://www.researchgate.net/publication/15307805_Chylous_ascites_in_cats_Nine_cases_1978-1993
4. Savary KC, Sellon RK, and Law JM: Chylous abdominal effusion in a cat with feline infectious peritonitis. Journal of the American Animal Hospital Association 37: 35-40, 2001. www.jaaha.org/doi/pdf/10.5326/15473317-37-1-35
Alfaxalone is a neurosteroid anesthetic agent used clinically to induce general anesthesia in a variety of species including dogs and cats. Although alfaxalone is classified as a steroid, it has not been shown to have glucocorticoid or mineralocorticoid activity. Like many other intravenous hypnotic agents, including propofol, etomidate, and thiopental, alfaxalone produces it’s sedative effect through interaction with the GABAA receptor. Older formulations of the drug (e.g. Saffan®) caused histamine release and other adverse reactions due to the use of a castor oil surfactant (Cremophor EL) to solubilize the alfaxalone. New formulations solubilized in 2-hydroxypropyl beta-cyclodextrin (Alfaxan®) do not have that effect and have been approved in the US for intravenous use in dogs and cats. Alfaxan® comes as a clear, preservative- free 1% solution (10 mg/ml) and is currently scheduled as a class IV controlled substance.
Alfaxalone produces smooth, rapid induction of anesthesia, excellent muscle relaxation, and a short duration of anesthesia (6 – 10 min after 2 mg/kg in unpremedicated dogs), clinically similar to propofol. In dogs, cardiovascular function is generally well maintained after an induction dose of 2 mg/kg given over 1 minute. A dose-dependent decrease in arterial blood pressure and transient increase in heart rate have been noted in dogs and tachycardia may be pronounced in some dogs. The most common side effect is dose–related respiratory depression, although this seems to be less pronounced than that seen with propofol (mean duration of apnea being 30 seconds after a dose of 2 mg/kg alfaxalone). However, decreases in PaO2 can also occur, possibly due to changes in ventilation/perfusion matching, and supplemental oxygen should be provided.
Alfaxalone has minimal cumulative effect due to it’s rapid metabolism and may be given by continuous rate infusion (4-6 mg/kg/hr), Recovery is generally uneventful. In contrast to propofol, alfaxalone is metabolized by the liver and this should be taken into account when using the drug in patient’s with severely impaired liver function.
In cats, clinically relevant doses of 2 – 5 mg/kg IV given over 1 minute in unpremedicated cats also cause dose-dependent cardiopulmonary depression. The decrease in arterial blood pressure is related to a decrease in systemic vascular resistance, with minimal changes in heart rate or cardiac output. A dose-dependent decrease in respiratory rate is the most common side effect. A decrease in PaO2 unrelated to changes in ventilation has been noted and supplemental oxygen should be provided. Occasional excitement in the recovery period has been reported in cats.
Alfaxalone is commonly used for short-term sedation or induction of anesthesia. As with most anesthetic drugs, alfaxalone may be given in combination with other sedative or anesthetic agents including opioids (butorphanol, methadone, hydromorphone, oxymorphone), benzodiazepines (midazolam, diazepam), and/ or alpha-2 agonists and the dose should be adjusted accordingly (1-2mg/kg (dogs); 2-4 mg/kg (cats) with the alfaxalone titrated to effect). In smaller patients, the alfaxalone may be diluted 1:1with sterile saline to allow more accurate dosing.
Although not approved for intramuscular use in the US, alfaxalone is clinically effective when given by this route and may be especially helpful in handling fractious or stressed cats (1-2 mg/kg when given in combination with an opioid and benzodiazepine) to allow physical examination and i.v. catheter placement. The volumes of drug required in larger dogs somewhat limits its usefulness in those patients. Alfaxalone does not provide analgesia when given alone, but may act synergistically with other analgesic agents, such as opioids. Recent reports comparing Apgar scores after Caesarian section in dogs, show improvement in scores in puppies after alfaxalone induction relative to propofol induction. In addition, alfaxalone has proved an effective anesthetic in other species including iguanas, turtles, rabbits and marmosets.
Submitted by: Sandra Z Perkowski, VMD, PhD, Dipl ACVAA
Bertelsen MF, Sauer CD. Alfaxalone anaesthesia in the green iguana (Iguana iguana). Vet Anaesth Analg 2011;38(5):461-466
Grint NJ, Smith HE, Senior JM. Clinical evaluation of alfaxalone in cyclodextrin for the induction of anesthesia in rabbits. Vet Rec 2008;163(13):395-396.
Grubb TL, Greene SA, Perez TE. Cardiovascular and respiratory effects, and quality of anesthesia produced by alfaxalone administered intramuscularly to cats sedated with dexmedetomidine and hydromorphone. J Feline Med Surg 2013;15(10):858-865.
Muir W, Lerche P, Wiese A, Nelson L, Pasloske K, Whittem T. Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs. Vet Anaesth Analg 2008;35(6):451-462.
Muir W, Lerche P, Wiese A, Nelson L, Pasloske K, Whittem T. The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats. Vet Anesth Analg 2009: 36,42-54.
Doebeli A, Michel E, Bettschart R, Harnack S, Reichter IM. Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol. Theriogenology 2013: 80(8): 850-854.
Tamura J, Ishizuka T, Fukui S, et al. The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs. J Vet Med Sci. 2015;77(3):289-296.
Whittem T, Pasloske KS, Heit MC, Ranasinghe MG. The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan at clinical and supraclinical doses. J Vet Pharmacol Ther 2008;31(6):571-579.
The use of intralipid therapy has been gaining traction as a treatment option for an ever expanding range of toxicities. While it has not quite become the standard of care, it has been viable for patients in the veterinary field and has been reported as case studies in the human field.
Veterinary literature has reviewed intravenous lipid emulsion therapy (ILE) [1,2] and published case reports or studies are available noting efficacy in toxicities including macrocyclic lactones [3,4], baclofen , beta-blockers, calcium channel blockers , NSAID [7,8], bromethalin , lidocaine , permethrin toxicity [11,12], tricyclic antidepressants (13). Intravenous lipid emulsion (ILE) in human literature has been reported as a therapy for local anesthetic [14,15] calcium channel blocker [16,17], psychotropic medication  , glyphosatesurfactant herbicide toxicities and even cocaine overdosage . Original work performed by Weinberg noted a response in rats with bupivicaine induced systole with lipid emulsion . How exactly ILE works is not certain but two theories are considered. The “lipid sink” theory is most commonly considered the primary mode of action. In this theory, the formation of a lipid compartment within the intravascular space can serve as a “sink” into which the lipophilic drug will be drawn into. The drug is then excreted/metabolized. Determination of a drug’s lipophilicity may be noted by its log P value. A value >1 indicates lipophilic compound which may move into the temporary lipid phase and be less distributed throughout the body. The formulation of ILE utilized may play a role and supports the “lipid-sink” theory based on one study . This theory has been supported in two case reports that followed plasma ropivacaine  and serum verapamil concentrations . An alternate theory is that the lipid provides an energy source for the cardiac myocytes by increasing the availability of FFA. The increase of FFA may also aid in increasing the activation of voltage-gated calcium channels in the myocardium, increasing cytosolic calcium channels This mechanism may be most important in cases of calcium-channel blockade [23,24].
There has not been an absolute protocol established for administration of intralipid therapy. A commonly utilized protocol includes an IV bolus of 20% ILE (1.5 mL/kg) followed by a continuous rate infusion of 0.25 mL/kg/min for 30–60 minutes. IntraLipid 20% (Baxter) is the most commonly referred to solution. It is composed 20% Soybean Oil, 1.2% Egg Yolk Phospholipids, 2.25% Glycerin, and Water for Injection. It may be infused through a peripheral intravenous catheter (350 mOsmol/kg water) without the use of a filter. The solution must be handled aseptically. Complications of ILE therapy may include fever, hyperlipemia, thrombocytopenia, hemolysis, prolonged coagulation times, seizures or anaphylactoid reactions to the soybean component. In one cat corneal lipidosis was suspected following treatment for ivermectin toxicity . The ph of Intralipid may vary from 6-9 pending where it is is in its shelflife which should be taken into account in the individual patient. While the log P value predicts the lipophilicity of a drug, other factors such as distribution, patient pH, intravascular volume and oxygenation status affect response to ILE. Restoration of intravascular volume and oxygenation should be corrected prior to initiating ILE treatment.
Submitted by: William Pullin, DVM, DACVIM
1. Fernandez, AL, Lee JA, Rahilly L, et al. Use of intravenous lipid emulsion as an antidote in veterinary toxicology. J Vet Emerg Crit Care 2011 Aug;21(4):309-20. doi: 10.1111/j. 1476-4431.2011.00657.x
2. Gwaltney-Brant S, Meadows I. Use of intravenous lipid emulsions for treating certain poisoning cases in small animals. Vet Clie North Am Small Animal Pract. 2012 Mar;42(2): 251-62, vi. doi:10.1016/j.cvsm.2011.12.001
3. Clarke DL, Lee JA, Murphy LA, Reineke EL. Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie. J Am Vet Med Assoc. 2011 Nov 15;239(10):1328-33. doi: 10.2460/javma.239.10.1328
6. Maton BL, Simonds EE, Lee JA, et al. Use of high-dose insulin therapy and intravenous lipid emulsion to treat severe, refractory diltiazem overdose in a dog. J Vet Emerg Care. 2013 May/June ;23(3):321-7. don 10.1111/vec.12053
7. Herring JM, McMichael MA, Corsi R, Wurlod V. Intravenous lipid emulsion therapy in three cases of canine naproxen overdose. J Vet Emerg Crit Care (San Antonio). 2015 Sep-Oct; 25(5):672-8. doi: 10.1111/vec.12307
11. Peacock R, Hosgood G, Swindells KL, Smart L. Randomized, controlled clinical trial of intravenous lipid emulsion as an adjunctive treatment for permethrin toxicosis in cats. J Vet Emerg Crit Care. 2015 Sep-Oct;25(5):597-605. doi: 10.1111/vec.12322
12. Seitz MA, Burkitt-Creedon JM. Persistent gross lipemia and suspected corneal lipidosis following intravenous lipid therapy in a cat with permethrin toxicosis.J Vet Emerg Crit Care 2016 Nov-Dec;26(6):804-8
13. Cave G, Harvey M, Shaw T, et al. Comparison of intravenous lipid emulsion, bicarbonate, and tailored liposomes in rabbit clomipramine toxicity. Acad Emerg Med. 2013 Oct;20(10): 1076-9. doi 10.111/acem.12224
14. Litz RJ, Roessel T, Heller AR, Stehr SN. Reversal of central nervous system and cardiac toxicity after local anesthetic intoxication by lipid emulsion injection. Anesth Analg. 2008;106:1575–1577. doi: 10.1213/ane.0b013e3181683dd7
15. Mizutani K, Oda Y, Sato H. Successful treatment of ropivacaine-induced central nervous system toxicity by use of lipid emulsion: effect on total and unbound plasma fractions. J Anesth. 2011 Jun;25(3):442-5
16. Young AC, Velez LI, Kleinschmidt KC. Intravenous fat emulsion therapy for intentional sustained-release verapamil overdose. Resuscitation. 2009;80:591–593. doi: 10.1016/ j.resuscitation.2009.01.023
17. French D Armenian P, Ryan W, et al. Serum verapamil concentrations before and after Intralipid therapy during treatment of overdose. Clin Toxicol (Phila). 2011 Apr;49(4):340-4. doi 10.3109/15563650.2011.572556
18. Nair F, Paul FK, Protopapas M. Management of near fatal mixed tricyclic antidepressant and selective serotonin reuptake inhibitor overdose with Intralipid 20% emulsion. Aneasth Intensive Care. 2013 Mar;41(2):264-5
19. Han SK, Jeong J, Yeom S, Ryu J, Park S. Use of a lipid emulsion in a patient with refractory hypotension caused by glyphosate-surfactant herbicide. Clin Toxicol (Phila) 2010;48(6):566– 568. doi: 10.3109/15563650.2010.496730
21. (Weinberg GL, VadeBoncouer T, Ramaraju GA, et al. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivicaine-induced asystole in rats. Anesthesiology 1998; 88(4): 1071-1075.)
Treatment of a well-differentiated hepatocellular carcinoma with CyberKnife stereotactic radiation therapy
The patient, an 11-year-old FS Golden Retriever, presented to a referral hospital where she was diagnosed with a low grade hepatocellular carcinoma (HCC). The only clinical sign present was an increase in ALT of 137 (reference range ALP 0-120) and ALP of 427 (reference range 0-140) which was found on routine bloodwork. An ultrasound revealed a 13 x 8 cm isoechoic mass occupying the right medial and portions of the right lateral liver lobes. The mass was mostly solid but with an approximately 5 x 6 cm hypoechoic region which appeared cavitated. Tru-cut biopsies were obtained of the mass and histopathology confirmed low grade HCC. Thoracic radiographs were free of metastatic disease. Due to the location and size of the mass within the liver, surgical resection was not deemed a reasonable treatment option. Other pertinent medical history included complete resection of a low grade mammary carcinoma nine months prior to diagnosis with HCC.
The patient was referred to a second specialty hospital for stereotactic radiation therapy in the form of CyberKnife. This type of radiation therapy is the delivery of a highly conformal dose of radiation therapy to a target with steep dose gradients resulting in a very low dose of radiation being delivered to surrounding normal tissue. This form of therapy relies on highly accurate target localization and precise delivery of radiation. The accuracy associated with this type of RT results in the ability to deliver a higher dose of radiation more rapidly with less normal tissue toxicity.
Prior to treatment with radiation, the patient underwent ultrasound-guided fiducial marker placement in the solid portions of the tumor to allow accurate localization of the tumor during the radiation treatments and a planning CT scan in order to define the tumor and surrounding healthy tissue such as the GI tract, lungs, spinal cord and kidneys. The patient received 3 treatments of CyberKnife stereotactic radiation therapy for a total dose of 30 Gy within a one week time period. Due to motion of the tumor with each phase of respiration, tracking was used in the form of Synchrony cameras which can track the motion of the tumor in “real time” and continuously deliver radiation as the tumor moves. The patient did well for each of her treatments and was discharged from the hospital successfully.
Three months after treatment, the patient had a repeat abdominal ultrasound performed which revealed that the tumor had decreased in size to 5 x 5 cm. Bloodwork at that time revealed an ALT of 242 (reference range 18-121 U/L) with all other values being within normal limits. Another repeat ultrasound was performed in 6 months after treatment which revealed that the tumor had further decreased in size to 3.7 x 4.1 x 4.1 cm. Bloodwork at this point showed that ALT had decreased to 180 (reference range 18-121 U/L). All other values were within normal limits.
In human medicine, stereotactic radiation therapy is becoming more routinely used for non-resectable HCC. Doses of 30-60 Gy are typically used over 3-6 treatments. 1-4 In these cases, other options for treatment include arterial chemoembolization or conformal fractionated external beam radiation therapy. The latter treatment modality has been limited in the past due to the risk of radiation-induced liver disease (RILD). RILD is a sub-acute form of liver injury due to radiation damage to normal, healthy liver tissue surrounding the tumor. It typically occurs 4-8 weeks after completion of RT but has been described in humans as late as 7 months after radiation. Clinical signs of classical RILD include fatigue, abdominal pain, hepatomegaly, ascites and elevation of alkaline phosphatase out of proportion to other liver enzymes. A second form of RILD (non-classical) include jaundice and markedly elevated serum transaminase. 5 In the patient being currently described, the decision to use a radiation dose at the low end of typical human doses was due to the proximity of the mass to the stomach and our attempt to avoid normal tissue toxicity. A moderate elevation in ALT was noted after therapy, which may have correlated with a low grade RILD, however, other abnormal clinical signs associated with typical RILD were not observed.
In veterinary medicine, to the author’s knowledge, there are no studies evaluating the use of stereotactic radiation therapy to treat HCC, however, one study exists which evaluates a more traditional form of radiation therapy in the form of 3D conformal external beam radiation therapy. This modality is capable of delivering equivalent doses of radiation, however, the precision and accuracy of stereotactic radiotherapy is lacking, resulting in a greater possibility of RILD due to the inclusion of larger amounts of normal tissue in the radiation field. However, in the aforementioned study, only 1 of 6 dogs included in the study developed RILD. Individual fraction sizes ranged from 6-10 Gy with the total dose administered being 18-42 Gy over several weeks. Five of 6 dogs had an objective response and median follow-up time was 534 days.6
The tumor tracking capability of CyberKnife Synchrony cameras has been shown in human medicine to significantly reduce the volume of normal liver tissue included in the radiation field, while maintaining high precision in tumor localization, conformity and tumor coverage. This may be especially useful in patients with preexisting liver disease or poor liver function in which they are at a higher risk for developing RILD. 1
This case report demonstrates the successful treatment of a dog with non-resectable low grade HCC with stereotactic radiation therapy. Consideration can be given in the future to dose escalation in which a higher dose of radiation can be given over 3 doses, or more doses can be added to the treatment protocol for a higher cumulative dose.
1. Gated Volumetric-Modulated Arc Therapy vs. Tumor-Tracking CyberKnife Radiotherapy as Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Dosimetric Comparison Study Focused on the Impact of Respiratory Motion Managements. Yoon K, Kwak J, Cho B, Park JH, Yoon SM, Lee SW, Kim JH. PLoS One. 2016 Nov 22;11(11):e0166927. doi: 10.1371/journal.pone.0166927https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119818/
2.Stereotactic body radiotherapy for primary hepatic malignancies – Report of a phase I/II institutional study. Weiner AA, Olsen J, Ma D, Dyk P, DeWees T, Myerson RJ, Parikh P. Radiother Oncol. 2016 Oct;121(1):79-85. doi: 10.1016/j.radonc.2016.07.020. http://www.thegreenjournal.com/article/S0167-8140(16)31236-1/abstract
3. Stereotactic Body Radiotherapy for Hepatocellular Carcinoma. McPartlin AJ, Dawson LA. Cancer J. 2016 Jul-Aug;22(4):296-301. doi: 10.1097/PPO.0000000000000201. http://journals.lww.com/journalppo/Abstract/2016/07000/Stereotactic_Body_Radiotherapy_for_Hepatocellula r.10.aspx
4.Stereotactic Body Radiotherapy for Hepatocellular Carcinoma Resulting in a Durable Relapse-Free Survival: A Case Report Monitoring Editor: Alexander Muacevic and John R Adler Samual Francis,1 Ned Williams,1 Christopher J Anker,2 Akram Shaaban,3Robin Kim,4 Dennis Shrieve,1 and Jonathan Tward1Cureus. 2016 Oct; 8(10): e841. Published online 2016 Oct 24. doi: 10.7759/cureus.841 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120964/
5. Radiation induced liver disease: A clinical update R. Bensona, R. Madana, , , R. Kilambib, S. Chandera Journal of the Egytial National Cancer Institute. 2016 March 28 (1) 7-11 http://www.sciencedirect.com/science/article/pii/S1110036215000849
6.Three-dimensional conformal radiation therapy for inoperable massive hepatocellular carcinoma in six dogs. J Small Anim Pract. July 2015;56(7):441-5. T Mori 1, Y Ito 1, M Kawabe 1, R Iwasaki 1, H Sakai 2, M Murakami 1, K Maruo 1http://onlinelibrary.wiley.com/doi/10.1111/jsap.12352/abstract