It’s comforting to know there is "Hope".
Ilona and Bill
A 7 year old male castrated Boxer presented for evaluation of hematuria. He had a history of chronic otitis, interdigital dermatitis, a I/VI systolic murmur, and periodic episodes of gastrointestinal upset which resolve without any intervention. In 2015, pre-anesthesia CBC and chemistry prior to a sebaceous adenoma removal showed TP 7.7 (5-7.4) and Glob 3.9 (1.6-3.6). His T4 was normal. A urinalysis had a urine specific gravity (USG) of 1.020 with +1 protein, WBC 2-3, RBC 21-50, struvite 11-20, cocci <10, and squamous epithelial cells 2-3. The method of urine sampling was not listed in the medical record. During wellness lab work in November, a CBC, Superchem, T4 and UA were performed. His TP was 7.7 (5-7.4), Glob 4.1 (1.6-3.6), and ALP 149 (5-131) with +2 hemolysis. His T4 was normal. His urinalysis showed a USG of 1.023 with +2 protein, +2 bilirubin, +3 blood, WBC 2-3, and RBC >50. His Accuplex was negative x 4 and fecal O&P showed no ova or parasites and the Giardia ELISA was negative. A urine cystocentesis the following week was very muddy brown. A urine culture showed no growth of bacteria. The patient has no other urinary symptoms other than having brownish urine noticed when it snowed. He did not have any stranguria or pollakiuria. He was active and otherwise healthy at the time of presentation to Hope Veterinary Specialists.
On physical examination, interdigital dermatitis was present. There were no abnormalities noted on examination of the penis or prepuce and his rectal examination was normal. An abdominal ultrasound was normal. Two weeks of empirical enrofloxacin were prescribed in case of pyelonephritis that was not diagnosed on cystocentesis urine culture. A urinalysis was performed at the end of the two week course of therapy while still on the antibiotics. The urine specific gravity was 1.023 with +1 protein, +3 blood, WBC 2-3, RBC >50, squamous epithelial cells 0-1.
Given the history and diagnostics, idiopathic renal hematuria was the top differential but urethral disease or disease within the bladder that was unable to be seen with the ultrasound could not be ruled out. Cystoscopy was performed. The urethral and bladder were normal. Both the left and right ureterovesicular junctions were visualized. Normal urine came was seen jetting from the left. Hematuria was noted from the right. The diagnosis of idiopathic renal hematuria was confirmed.
(Click link below to view cystoscopy video)
Idiopathic renal hematuria, also called benign essential hematuria and idiopathic renal hemorrhage, is a rare condition in which a patient has gross hematuria from the kidney from unknown cause. It is a diagnosis of exclusion. The condition occurs in both dogs and cats. There are no breed, age, or sex predilections. Many patients will have hematuria as their only symptom but urinary obstruction or other lower urinary signs from blood clots or systemic signs of anemia can also occur.
If the patient’s only clinical symptom is hematuria, as was the case for this patient, no further therapy is necessary. Typically, in these patients, periodic monitoring of the PCV or hematocrit will be performed to monitor for anemia. Historically, nephrectomy was recommended if the disease was unilateral, but this therapy has fallen out of favor since about 30% of patients will eventually develop bilateral disease. For more significantly impacted patients, medical management is recommended as the first tier of therapy. Benazepril can be used to decrease intrarenal pressure. Bazelle and Foale reported on the use of benazepril at 0.22 to 0.53 mg/kg PO q 24 in 4 dogs. Resolution of macroscopic hematuria was observed in all dogs but microscopic hematuria persisted in 2 of the 4 dogs. Anecdotal reports since this 2013 suggest that the overall success rate of benazepril is not as high as was reported in this abstract. Yunnan Baiyou can also be used to decrease bleeding. Allyson Berent, one of the leading experts in this disease, sites a 10-15% success rate with Yunnan Baiyou. If significant bleeding continues despite these therapies, urethroscopy can be performed to find and cauterize the bleeding vessel.
Sclerotherapy is the most successful approach for patients with significant bleeding. In 2013, Di Cicco et al used sclerotherapy with silver nitrate to treat bilateral idiopathic renal hematuria in a dog. The symptoms resolved for 10 months prior to recurrence. Berent et al, 2013 used a povidone iodine mixture followed by a sterile silver nitrate solution administered into the renal pelvis. Complete resolution of macroscopic hematuria occurred in 4 of the 6 patients. The 2 additional patients had moderate improvement of their symptoms. In 2017, Adelman, Barges and Whittemore reported resolution of macroscopic hematuria in 2 dogs within 12 hours of povidone iodine sclerotherapy.
The patient evaluated at Hope was not having significant enough clinical signs to warrant therapy at this time. We will closely monitor him for signs of anemia or lower urinary symptoms secondary to cystic blood clot formation. We plan to recheck his PCV/TS several times a year to monitor him for anemia.
Submitted by: Laurie Prober, VMD, DACVIM
Bazelle J, Foale R. The Successful Treatment of Idiopathic Renal Haemorrhage with Benazepril in Four Dogs. British Small Animal Veterinary Congress 2011. http://www.vin.com/doc/?id=4823393
Berent AC et al. Endoscopic-guided sclerotherapy for renal-sparing treatment of idiopathic renal hematuria in dogs: 6 cases (2010-2012). J Am Vet Med Assoc. 2013;242(11):1556-63. http://avmajournals.avma.org/doi/abs/10.2460/javma.242.11.1556
Adelman LB, Bartges J, Whittemore JC. Povidone iodine sclerotherapy for treatment of idiopathic renal hematuria in two dogs. J Am Vet Med Assoc. 2017;250(2):205-210. http://avmajournals.avma.org/doi/abs/10.2460/javma.250.2.205
Di Cicco MF et al. Management of bilateral idiopathic renal hematuria in a dog with silver nitrate. Can Vet J. 2013;54(8):761-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711164/
HELPFUL HINT 1: KNOW TUMOR BIOLOGY
Mast cell tumors are the most common cutaneous tumor in dogs (1). They do not have a specific look or feel (1) – we have diagnosed mast cell tumors that have a similar appearance to that of small pimples, skin tags, large ulcerated lesions, and soft fatty masses. Increased risk is associated with the following breeds: Boxer, Boston Terrier, English Bulldogs, Pugs, Labrador Retriever, Golden Retriever, Cocker Spaniel, Schnauzer, Staffordshire Terrier, Beagle, Rhodesian Ridgeback, Weimaraner, Shar-Pei (1). These tumors occur more often in middle-older aged dogs (1).
Mast cells contain biologically active compounds within the basophilic granules that are seen in the cytoplasm on microscopic evaluation (1). Histamine is the best-known compound; however these granules also contain heparin, proteases, and growth factors (1). These compounds play a role in the localized clinical symptoms and post-operative delay in wound healing seen in some patients with these tumors; specifically, histamine induced inflammation, heparin induced decrease in clot production and prolongation of bleeding, and protease induced protein and tissue breakdown. These granules may also play a role in systemic side effects from mast cell cancer including gastric ulceration induced vomiting, melena, hematochezia, weight loss and diminished appetite.
Mast cell tumors are locally aggressive and often extend beyond what is palpable on the surface (1). Metastasis depends on tumor grade with Grade 1, 2 and 3 tumors (Patnaik Grading Scale) metastasizing less than 10%, less than 20%, and approximately 90% of the time, respectively (2). More recently, a 2-tier grading scale (Kiupel Scale) has been established, with low grade vs high grade (3). The 2-tier scale was established to provide a more objective set of grading criteria for pathologists as the previously used scales may be prone to subjectivity and result in discordant grading results among pathologists (3). Metastatic disease is most often found in regional lymph nodes, liver, spleen, and less commonly the bone marrow (1). Low grade (Grade 1 or Grade 2) tumors typically grow slowly and are relatively quiescent while high grade (Grade 3) tumors have more aggressive behavior with rapid growth and may be associated with ulceration (1-3).
Approximately 20% of dogs will develop multiple cutaneous mast cell tumors (1). Therefore, a dog with prior history of mast cell tumor presenting for a new skin or subcutaneous mass should have that mass aspirated and cytology performed. Several studies have found that dogs with multiple mast cell tumors do not have a poorer prognosis than dogs with just one mast cell tumor (4, 5), although this is somewhat controversial.
EXAMPLES OF WHY IT IS IMPORTANT TO KNOW TUMOR BIOLOGY
- Patient presents for a mass with recent rapid growth. The mass was present for months to years with minimal change but in the past 2 weeks it has doubled in size, growing from a pea to a tennis ball size. The mass is removed and histopathology indicated Grade 1, complete margins. Given the histopathology you may consider this cured with the complete margins and Grade 1 designation; however, the ‘recent rapid growth’ history is concerning and indicates more aggressive tumor behavior. For this reason, a discussion with the pathologist, second opinion pathology review, and/or additional testing on the tumor, such as mast cell tumor proliferation panel, should be considered.
- Tumor biology helps us in our diagnostic plan. The most common staging tests recommended for dogs with mast cell cancer are routine baseline bloodwork (CBC/Chemistry), abdominal ultrasound, needle aspirate of the mass, either needle aspirate and cytology (or more preferred, removal and histopathology) of the regional/draining lymph node, and histopathology with margin assessment of the tumor (1).
- Tumor biology helps us in our treatment plan. With wide roots, 2-3cm margins are generally recommended although for low grade (Grade 1 and Grade 2) tumors, less aggressive margins may be adequate (further discussion below). With incomplete excision (roots left behind), high grade tumors have higher risk for recurrence than low grade, as such adjuvant therapy such as additional surgery or radiation is often recommended (1, 3). Furthermore, high grade tumors have highest risk for metastasis as such adjuvant chemotherapy is recommended in these cases (1, 3, 6). With incomplete excision of low grade (Grade 1 and Grade 2) tumors, additional surgery or radiation is recommended to help reduce risk of recurrence (1).
HELPFUL HINT 2: REVIEW THE MICROSCOPIC DESCRIPTION ON THE HISTOPATHOLOGY REPORT
The microscopic description provides key information in helping predict the behavior of the tumor, aiding in prognostication and treatment planning. Key elements of this description include: mitotic index, presence and number of multinucleated cells, presence and number of bizarre nuclei, presence of karyomegaly, degree of granulation, margins (1-3).
High grade (Grade 3) tumors generally have some of the following characteristics: a mitotic index greater than 5-7 mitotic figures/10 high power field, 3 or more multinucleated cells, 3 or more bizarre nuclei per 10 high powder field, karyomegaly (enlarged cellular nucleus), poorly granulated cells (1-3).
Low grade (Grade 1 and Grade 2) tumors generally have some of the following characteristics: infrequent-rare mitosis (less than 2 mitotic figures/10 high power field), abundant cytoplasmic granules, rare-no multinucleated cells and/or bizarre nuclei (1-3).
In the past, 3cm margins were the standard recommendation. More recent studies are finding 1cm lateral margins and 0.4cm deep margins are sufficient at controlling the tumor in many dogs with low grade (Grade 1 and Grade 2) tumors (7, 8). Wider margins are generally recommended for dogs with high grade tumors due to higher risk for recurrence with this phenotype.
It is important to request and read the microscopic description to get a clear view of the histologic appearance of the tumor and compare this to the historic behavior of the tumor (what your physical exam shows you and what the clients described). For example – if the tumor has been present for months to years with minimal growth and microscopic descriptors are that of low-intermediate grade tumor than this corroborates. If there is discordant data between the history/exam and microscopic description then this warrants further investigation (conversation with pathologist, second opinion pathology review, and/or mast cell tumor proliferation panel).
WHEN TO RECOMMEND THE MAST CELL TUMOR PROLIFERATION PANEL
This panel tests for markers of cellular proliferation, c-kit, AgNOR, KI67, and PCNA, through immunohistochemistry (special stains) and tests for the c-kit mutation through PCR (polymerase chain reaction) (9). This panel is not automatically run on every mast cell tumor and requires additional fee. This panel may be performed on every mast cell tumor if the clinician/client chose; however, this can be cost prohibitive. There are many labs that offer this testing a la carte, so you can pick and choose which tests within this profile you would like performed.
Instances on when to recommend the panel may include:
- Incompletely excised low-intermediate grade tumor, to help further elucidate risk for recurrence (recommend performing the entire panel)
- High grade tumors or tumors with high grade biology, i.e. already metastasized, to help determine chemotherapy protocol (recommend performing the c-kit PCR alone). A recent study demonstrated that tumors with c-kit mutation respond to the small molecule inhibitor Toceranib more often than tumors without the c-kit mutation, as such, Toceranib may be considered as part of the chemotherapy plan in this subset of patients.
HELPFUL HINT 3: TREATMENT RECOMMENDED
The standard of care treatment, first and foremost is surgery (1). If bulky mast cell disease is present, antihistamine (H1 and H2) blockers are recommended including: diphenhydramine or chlorpheniramine (H1 blockers), cimetidine, famotidine, ranitidine (H2 blockers) or proton pump inhibitor omeprazole (instead of H2 blockers). In some cases, surgical pre-treatment with steroid such as prednisone for 1-2 weeks may be recommended to reduce inflammation caused by the tumor and facilitate improved surgical margins (10).
Here are some helpful hints on when to recommend adjuvant therapy or alternative therapy if surgery is not an option.
WHEN TO RECOMMEND RADIATION
There are several common scenarios in which radiation is recommended (not exhaustive list):
- Incompletely excised mast cell tumor if second surgery not feasible (any grade)
- Bulky mast cell tumor that is not amenable to surgery (palliative purposes in this setting)
WHEN TO RECOMMEND CHEMOTHERAPY
There are several common scenarios in which chemotherapy is recommended (not exhaustive list):
- High grade (Grade 3) designation
- Known metastasis to regional lymph node, liver, spleen, etc
- Incompletely excised mast cell tumor (any grade)
- Bulky mast cell tumor that is not amenable to surgery
HELPFUL HINT 4: PROGNOSIS
As with any cancer, outcomes vary depending on stage, grade, treatment chosen, and interpatient variability.
Dogs with low grade (Grade 1 or Grade 2) mast cell tumors, with no evidence of metastasis, receiving surgery with wide and clean margins OR adequate local tumor control (surgery then treat roots with radiation or scar revision surgery) then there is good chance for long term control of this tumor (1). Inform the client that approximately 20% will develop another mast cell tumor in another location so diligent monitoring is recommended.
Dogs with high grade (Grade 3) mast cell tumors, or biologically aggressive tumors (i.e. those tumors with Grade 1 or Grade 2 designation but have known lymph node metastasis), receiving surgery with complete margins, removal of metastatic lymph node, followed by chemotherapy have an average survival time of over 3 years in one study (11).
Dogs with distant metastasis (liver/spleen/bone marrow) may receive radiation and chemotherapy for palliative purposes. Prognosis is generally poor but these treatments may help slow growth and progression as well as palliate clinical symptoms of illness for an estimated 3-4 months, depending on tumor response with therapy.
Dogs with large tumors not amenable to surgery may receive palliative radiation and chemotherapy to help slow growth and metastasis for a median progression free interval of approximately 300 days (12).
Submitted by: Dr. Kate Vickery, VMD, MS, Diplomate ACVIM, CVA
1- Withrow and McEwen. Small Animal Clinical Oncology. 5th ed. Eds Withrow, Vail, Page. Mast Cell Tumors. 335-355.
2 -Patnaik, AK, et al. Canine cutaneous mast cell tumor: morphologic grading and survival time in 83 dogs. Veterinary Pathology. 1984. 21(5): 469—74. https://www.ncbi.nlm.nih.gov/pubmed/6435301
3- Kiupel, M, et al. Proposal of a 2-tier histologic grading systemi for canine cutanoes mast cell tumors to more accurately predict biological behavior. Veterinary Pathology. 2011. Jan; 48(1): 147-55. https://www.ncbi.nlm.nih.gov/pubmed/21062911
4- Mullins, M, et al. Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004). JAVMA. 2006. 228(1): 91-95. https://www.ncbi.nlm.nih.gov/pubmed/16426175
5- Thamm, D, et al. Prednisone and vinblastine for canine mast cell tumor – 41 cases. JVIM 1999. 13: 491-97. https://www.ncbi.nlm.nih.gov/pubmed/10499735
6- Stefanello D, et al. Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous mast cell tumors: 386 cases (2009-2014). JAVMA 2015. 246(7): 765-69. https://www.ncbi.nlm.nih.gov/pubmed/25794126
7- Schultheiss, PC, et al. Association of histologic tumor characteristics and size of surgical margins with clinical outcome after surgical removal of cutaneous mast cell tumors in dogs. JAVAM. 2011. 238(11): 1464-69. https://www.ncbi.nlm.nih.gov/pubmed/21627510
8- Pratschke, KM, et al. Evaluation of a modified proportional margins approach for surgical resection of mast cell tumor sin dogs: 40 cases (2008-2012). JAVMA. 2013. 243(10): 1436-41. https://www.ncbi.nlm.nih.gov/pubmed/24171373
9- Bergman, P, et al. Correlation of histologic grading of canine mast cell tumors with KI67/PCNA/AgNOR/c-kit scores: 38 cases. VCO. 2004. 2: 98. http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5810.2004.0045a.x/abstract
10- Stanclift, RM, et al. Evaluation of neoadjuvant prednisone administration and surgical excision in treatment of cutaneous mast cell tumors in dogs. JAVMA. 2008. 232: 53-62. https://www.ncbi.nlm.nih.gov/pubmed/18167109
11- Thamm, D, et al. Outcome and prognostic factors following adjuvant prednisone/vinblastine chemotherapy for high-risk canine mast cell tumor: 61 cases. J Vet Med Sci. 2006. 68: 581-87. https://www.ncbi.nlm.nih.gov/pubmed/16820715
12- Carlsten, KS, et al. Multicenter Prospective Trial of Hypofractionated Radiation Treatment, Toceranib, and Prednisone for Measurable Canine Mast Cell Tumors. JVIM. 2012. 26: 135–141. https://www.ncbi.nlm.nih.gov/pubmed/22176473
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.