Spontaneous Chronic Corneal Epithelial Defects (SCCEDs)

 By: Rachel Mathes, DVM, MS, DACVO

 

Spontaneous chronic corneal epithelial defects or so called “SCCED” lesions are superficial corneal ulcers that occur in middle-aged, usually large breed dogs, although they may be seen in any breed (1).  SCCED lesions, also known as non-healing ulcers, “indolent” ulcers and “Boxer” ulcers, have a typical clinical presentation and appear as large superficial corneal ulcers with marked epithelial lipping (1,2).The epithelial lip may be seen using focal illumination (e.g. Finhoff transilluminator) or may be highlighted with fluorescein staining with the stain noted to migrate under the epithelial lip. Once the loose epithelium is debrided, the ulcer is often much larger than what is seen prior to debridement. These ulcers may also be associated with dramatic secondary corneal vascularization and granulation tissue.

 

Although the exact cause of SCCEDs is not known, this defect is thought to be an abnormality in the adhesive mechanism of the corneal epithelium to the stroma (1,3). Upregulation of matrix metalloproteinase (MMP) 2 and 9 is not a characteristic of these lesions (4). An acellular, hyaline membrane is found on histopathology in the ulcer bed and is thought to be contributory in preventing normal epithelial adhesion during the healing process (1).  Although uncommonly these ulcers may become secondarily infected and prophylactic antibiotic therapy is warranted, bacterial infections are not causative in these cases. Aggressive antibiotic therapy or periodic switching of topical antibiotics will have no effect on these ulcers and may potentiate resistant bacterial infection.

 

Treatment for SCCEDs is aimed at creating very superficial stromal abrasion mechanically. Occasionally, debridement of the ulcer with a sterile cotton tipped swab will effect healing. More commonly, however, a more aggressive treatment such as a diamond burr keratectomy or grid keratotomy is required to initiate healing (3.5). Grid keratotomies cause more stromal damage and resultant astigmatism than diamond burr keratectomies (5). Recent studies have shown a very high success rate after diamond burr keratectomy with 70% healed at 1 week and 92.5% healed at 2 weeks (3). Topical chondroitin sulfate may also be beneficial in promoting epithelial adhesion and may decrease surface shearing forces (5). 
 

 
 Picture A  Picture B

 

                        Image  ( A )

                       Image  ( A )

                      Image ( B )

                     Image ( B )

Typical SCCED lesions are pictured. Not the prominent irregular, raised corneal granulation tissue and epithelial margin (arrow) with fluorescein stain migrating under the epithelial lip (A). A well demarcated focally extensive superficial ulcer is present with an epithelial margin after debridement (B).  

References:

1. Bentley, et al. Spontaneous chronic corneal epithelial defects in dogs: a review. J Am Anim Hosp Assoc. 2005: 41; 158-65.

2. Ledbetter, et al. Efficacy of two chondroitin sulfate ophthalmic solutions in the therapy of spontaneous chronic corneal epithelial defects and ulcerative keratitis associated with bullous keratopathy in dogs. Vet Ophthalmol. 2006: 2; 77-87.

3. Gosling, et al. Management of spontaneous chronic corneal epithelial defects in dogs with diamond burr debridement and placement of a bandage contact lens. Vet Ophthalmol. 23 April 2012, online early view.

4. Carter, et al. Expression of matrix metalloproteinase 2 and 9 in experimentally wounded canine corneas and spontaneous chronic corneal epithelial defects. Cornea. 2007: 10; 1213-1219.

5. Da Silva, et al. Histologic evaluation of the immediate effects of diamond burr debridement in experimental superficial corneal wounds in dogs. Vet Ophthalmol. 2011: 4; 285-291.

Limbal Melanomas

By: Rachel Mathes, DVM, MS, Diplomate ACVO

Facts about Limbal Melanomas:
 

  • Benign, slow growing tumors in dogs and cats
  • Very responsive to a variety of therapies
  • Low rate of metastasis
  • Low rate of recurrence with treatment
  • Early referral recommended

Limbal melanomas are benign, slowly growing tumors of limbal melanocytic origin. These tumors typically occur along the dorsomedial to ventrolateral limbal arc of the globe at the corneal and scleral junction.1 A bimodal age distribution has been described with a peak occurrence at 3-4yrs of age and 7-10yrs of age in dogs (1,2). These tumors are thought to have an inherited basis as Golden Retrievers are four times more likely and Labradors are three times more likely to develop this compared to other breeds (1). Though benign, limbal melanomas may become globe-threatening with growth due to local invasion. Often, secondary keratitis with corneal lipid deposition will occur as a result of the tumor presence (2,3).  While these tumors are less common in cats, they may occur and have a similar clinical course as canine melanomas (3).  Feline and canine limbal melanomas are amenable to a variety of therapies including surgical debulking with a combined keratectomy and sclerectomy, cryotherapy, laser photocoagulation, radiation and surgery with homologous and autologous grafting (2,3,4). In one recent study, only 1 our of 30 tumors recurred after a combination therapy protocol (2). In addition, the incidence of side effects from surgery was low with less than 10% of complications being potentially globe threatening (2).  After laser photocoagulation, a low recurrence was reported with 1 out of 15 masses recurring at 3 months and 2 out of 15 recurring at one year. Twelve of the fifteen tumors did not recur (3). 


Long term control and vision are attainable and reasonable goals with appropriate therapy. Early referral is recommended to preserve vision and globe integrity.

A dorsomedial limbal melanoma in the left eye is pictured. The mass is heavily pigmented, raised, irregular and well-demarcated with an arc of white corneal lipid at the leading edge.

Glaucoma

Dr. Rachel Mathes, DVM, MS, Diplomate ACVO

 Facts about Glaucoma

• Secondary glaucoma more common than primary glaucoma

• Females overrepresented 2:1 for primary glaucoma

• Primary glaucoma typically associated with iridocorneal angle closure and increased intraocular pressure during middle age (6-8 years old)

• Canine glaucoma tends to be aggressive

• Feline glaucoma is almost exclusively secondary

• Concurrent institution of prophylactic therapy for the contralateral eye should be instituted if an eye is enucleated for primary glaucoma

• Imperative to address IOP spikes immediately as they may quickly cause complete blindness

Glaucoma is a term used to describe a group of diseases that cause elevated, often severely, intraocular pressure. This condition is very painful and treatment is aimed not only at preservation of vision, but also for pain management. The pain of glaucoma may be referred pain (migrane headache) and patients may exhibit discomfort by decreased activity, increased sleeping or subtle changes in behavior.1 The signs of pain may not even be noted by the owner until the discomfort is treated, at which time the patient may be noted to return to normal activity or “act like themselves again.” Primary, or breed related, glaucoma in dogs is most commonly due to closure of the aqueous drainage angle or Primary Angle Closure Glaucoma (PACG).1 Females are approximately twice as likely to develop PACG compared to males.2 PACG has different features for different canine breeds, however, the end result is failure of normal aqueous outflow, causing significant intraocular pressure elevation. Acute primary glaucoma may often be treated medically or surgically if addressed immediately, even if there is vision loss at the time of increased intraocular pressure.1,3,4 Chronic primary glaucoma causes extensive intraocular damage and blindness. Therapy is aimed at preventing intraocular pressure spikes, decreasing intraocular pressure and maintaining functional vision.4-7 This therapeutic goal is rarely achieved long term with medication alone and surgical intervention is almost always necessary.5 To preserve functional vision, glaucoma surgery is usually recommended early in the disease course due to the aggressive nature of this disease. Typical surgeries performed include laser cyclophotocoagulation (ciliary body destruction) and anterior chamber valve placement.5 The combination of these surgeries resulted in good control of the intraocular pressure in 76% of cases.5 In cases of irreversibly blind globes, more permanent salvage procedures are recommended as glaucoma is painful (enucleation or an intrascleral prosthesis).

Secondary glaucoma results from other underlying ocular pathology. The most common causes are lens luxations (most often seen in Terrier breeds), uveitis and cataracts. Treatment is aimed at reducing the intraocular pressure and addressing the underlying cause of pressure elevation. Topical glaucoma therapy should be limited, in cases of secondary glaucoma, to medications that do not exacerbate pre-existing ocular disease. Topical carbonic anhydrase inhibitors (e.g. dorzolamide, brinzolamide) or topical beta blockers (e.g. timolol) are recommended for primary or secondary glaucoma. Prostaglandin analogs (e.g. latanoprost, travaprost), while often the first line of therapy for primary glaucoma, should be avoided for secondary glaucoma therapy as they may exacerbate pre-existing ocular disease.


 

          Image ( A )

         Image ( A )

                   Image ( B )

                   Image ( B )

  

A patient with acute glaucoma is depicted (A). Note the severe scleral injection and corneal edema. Acute glaucoma must be addressed immediately in order to preserve vision and treat patient discomfort. A patient with chronic glaucoma is depicted (B) Note the significant buphthalmos (globe enlargement), scleral injection and corneal edema. This eye is irreversibly blind, but is quite painful. Therapy is aimed at providing long term patient comfort. Prophylactic therapy should always be instituted in the contralateral eye if an eye is removed for intractable, primary glaucoma.

References

1. Reinstein S, et al. Canine glaucoma: pathophysiology and diagnosis. Compend Contin Educ Vet. 2009:10;450-2.

2. Tsai S, et al. Gender differences in iridocorneal angle morphology: a potential explanation for the female predisposition to primary angle closure glaucoma in dogs. Vet Ophthalmol. 2012:15S1;60-3.

3. Scott E, et al. Early histopathologic changes in the retina and optic nerve in canine primary angle-closure glaucoma. Vet Ophthalmol. 2013:16S1;79-86.

4. Dees D, et al. Efficacy of prophylactic antiglaucoma and anti-inflammatory medications in canine primary angle-closure glaucoma: a multicenter retrospective study (2004-2012). Vet Ophthalmol. 2013:5.

5. Sapienza J, et al. Combined transscleral diode laser cyclophotocoagulation and Ahmed gonioimplantation in dogs with primary glaucoma: 51 cases (1996-2004). Vet Ophthalmol. 2005:8:121-7.

6. Miller P, et al. The efficacy of topical prophylactic antiglaucoma therapy in primary closed angle glaucoma in dogs: a multicenter clinical trial. J Am Anim Hosp Assoc. 2000:36:431-8.

7. Willis A, et al. Advances in topical glaucoma therapy. Vet Ophthalmol. 2002:5;9-17.

Salivary Mucocele

By: April Guille, DVM, Diplomate ACVS

A salivary mucocele, or a sialocele, is a collection of saliva in the subcutaneous tissues near the site of a leaking salivary duct or gland. The most common gland affected is the sublingual salivary gland, but any of the four major salivary glands can cause a sialocele. The location of the swelling often determines the presenting signs and indicates the involved salivary gland. The two most common locations of saliva collection are the ventral cervical area and under the tongue, although swelling can occur in the pharyngeal area, causing dyspnea, or under the ventral orbit, leading to exophthalmos. Animals with labored breathing due to a pharyngeal sialocele are in danger of airway obstruction and the swelling should be opened up for immediate drainage. Sialoceles can be caused by trauma, sialoliths, neoplasia, foreign bodies, or recent oral surgery, but often the cause is unknown. No sex predisposition has been found; dachshunds, poodles, Australian silky terriers, and German shepherds are predisposed.

On aspirate, the fluid is often viscous and clear or blood-tinged with small to moderate numbers of nondegenerate nucleated cells in a proteinanceous background. Conservative treatment by drainage alone is not recommended due to the high rate of recurrence. Definitive treatment involves removing the affected glands along with drainage; ranulas and pharyngeal sialoceles are treated with marsupialization. Although the sublingual gland and duct system are the most commonly affected, removal of the sublingual gland requires removal of the mandibular gland as well due to their common capsule and close association. The prognosis is excellent with complete removal of the gland, with a recurrence rate of less than 5 percent.

Facts about Sialoceles

Four main presentations include exophthalmos, labored breathing, dysphagia, or ventral cervical swelling

Sublingual salivary gland is the most commonly affected gland

Surgical removal of the affected gland is recommended to prevent recurrence

Excellent prognosis with surgery

 

Transitional Cell Sarcomas in Dogs

Dr. Gail Mason, DVM, MA, DACVIM
Kathi Smith, RVT, Internal Medicine & Oncology Technician

Primary cancer of the bladder in dogs is relatively uncommon. Of those occurring in that location, transitional cell carcinoma (TCC) accounts for 50-80% of all reported cases.


Diagnosis of Transitional Cell Carcinomas
The clinical signs of bladder cancer in dogs are generally similar to those of urinary tract infections (cystitis) and urinary stones (cystic calculi). For this reason diagnosis by cytology of biopsy is required. Tests used in diagnosing TCC include:

• Urinalysis
• Cytology (urine or tissue aspirate)
• ultrasonography (+/- guided needle biopsy)
• abdominal radiographs (x-rays)
• routine bloodwork
• cystoscopy (fiberoptic exam of bladder/urethra)

Treatment for TCC
The overall metastatic rate for TCC is approximately 50%, and unfortunately, at this time there is no know cure of this disease. Control of local disease and its clinical signs are the main goal of therapy.

Surgery for TCC
Surgery can be a viable option for TCC patients but often the extent and tumor location provide multiple challenges. Surgery is generally considered palliative (vs. curative) for this tumor and may include:
• partial bladder removal (cystectomy)
• urinary tract diversion (catheter placement)
• bladder reconstruction

The risks and benefits expected with surgical treatment of TCC are worthy of a detailed discussion with a veterinary surgical specialist to determine if it is a reasonable option for a particular patient.

Chemotherapy for TCC
Systemic chemotherapy for bladder or urethral TCC has produced varying results. Drugs that have been employed include:
• Doxorubicin
• Mitoxantrone
• Cisplatin
• Cyclophosphamide

Though these drugs are relatively well tolerated in animals, most all reported survival times of less than one year. A recent retrospect study of 25 dogs with inoperable urinary bladder carcinoma suggested a survival advantage might exist when dogs receive doxorubicin (or mitoxantrone) in addition to a platinum-based compound (cisplatin or carboplatin). Similar combinations warrant further investigation. The drugs do, however, frequently abate the patientÕs symptoms.

Piroxicam
Interestingly, though not anticancer drugs per se, piroxicam and other non-steroidal anti-inflammatory drugs (deracoxib, metacam) have shown activity against TCC in dogs. They can be used alone or in combination with chemotherapeutic agents.

Anti-inflammatory drugs can exert antitumor activity by several mechanisms. They appear to include reduction of swelling, pain, formation of new blood vessels in tumor tissue, and perhaps direct antitumor effects on malignant cells.

Piroxicam can be extremely useful in the management of TCC in dogs. It works rapidly to reduce tumor swelling and obstruction to urine outflow. As a single agent, it is known to control TCC for at least as long as multiple-drug protocols.

These drugs can be used safely in many dogs and cats. However, adverse reactions in the gastrointestinal tract (gastritis, vomiting, bleeding ulcers) and in renal (kidney) function have been reported. If your pet is taking such a drug, monitor him/her for signs of decreased appetite, vomiting, or dark black stools, which may necessitate drug withdrawal.

Prognosis
Early diagnosis and intervention in patients with TCC are likely to produce the most favorable prognosis. Currently, recommended combination therapy with surgery, anti-inflammatory agents, and chemotherapeutics offer the best chance of tumor control. The long-term prognosis still remains guarded to poor as remission times uncommonly exceed 1 year. However, remission time can be good quality time for both pet and owner.

Soft Tissue Sarcomas

Soft Tissue Sarcomas (STS) in Cats and Dogs

Soft tissue sarcomas

Soft tissue sarcoma is a general term that refers to a group of tumors that form in tissues of mesenchymal origin such as the connective tissue (e.g. fat, smooth-muscle, blood vessels, lymph vessels, skeletal muscle, etc.) They tend to have similar histologic appearance and biological behavior, and can be either benign (noncancerous) or malignant (cancerous). Soft tissue sarcomas can arise in any part of the body although skin and subcutaneous (the layer of tissue directly underlying the skin) tumors are the most commonly observed.

Soft tissue sarcomas (STS) behave in a locally invasive manner. The incidence of metastasis (spread to different sites) varies from about 8% to 20%. This rate is generally lower than other types of tumors in animals; therefore, aggressive local control of the disease is the key goal.

Diagnosis

The individual STS tumor types can be challenging to distinguish between. Fine-needle aspirates or tissue biopsies are required to confirm a diagnosis. Not infrequently, additional pathology tests are required to more precisely determine the tissue of origin. Also, additional tests are performed in order to evaluate how advanced the disease is. The tests will depend on the type of soft tissue sarcoma but generally involve blood and serum biochemical tests, chest X-rays and imaging.

Disease Staging

Imaging studies of the local tumor may be recommended prior to planning the surgical removal of the tumor and/or radiation therapy, especially in animals with suspected intra-abdominal soft-tissue sarcomas. Advanced imaging techniques such as CT (computed tomography) and MRI (magnetic resonance imaging) are especially useful due to their high level of resolution and detail.

Diagnostic tests that evaluate whether the tumors have spread to other organs include chest X-rays (to check for metastasis to the lungs), abdominal ultrasound (to check for metastasis in the spleen, liver, etc.) and fine-needle aspirates/biopsy of regional lymph nodes (to check for lymph node metastasis). At the very minimum, chest X-rays should be performed prior to initiating treatment since soft tissue sarcomas commonly spread to the lungs. Lymph node metastasis is not common for typical soft tissue sarcoma but their biopsy/cytology should be assessed in animals whose lymph nodes appear abnormal and/or whose specific tumor type is suspected to have a high metastatic potential.

Treatment Options

Surgery

Invasive STS can be challenging to treat as they expend into surrounding structures and require extensive surgery to achieve complete removal. The first surgery is the key opportunity to achieve complete excision. A general principle for removing such tumors is that the tumor should be removed with a significant margin of normal tissue around it (in all directions) to ensure complete removal of all malignant cells. An experienced, board-certified veterinary surgeon is recommended for STS resections.

Some STS appear in locations in which complete resection is difficult without disturbing normal tissue. Depending upon the tumor location, such surgeries as limb amputation, rib resection, and nasal/jaw reconstructions may be required. It is important to note that veterinary patients recover quickly and cosmetically even from these more extensive surgeries.

Radiation Therapy

Radiation therapy can be combined with surgery in either a pre or post-surgical manner. If given prior to surgery, the tumor may decrease in size and be subsequently easier to remove. If radiation therapy is given after surgery, it is intended to eradicate tumor cells which may have left behind during an incomplete excision.





Veterinary patients are quite tolerant of this form of cancer treatment and it can increase the changes for successful long term disease management. This is a highly specialized form of cancer treatment and is provided by veterinary radiation oncologists at:

  • New England Veterinary Oncology Group (NEVOG), Waltham, MA. 781-684-8688

  • Angell Memorial Animal Hospital, Boston, MA. 781-522-7282

  • Tufts University School of Veterinary Medicine, N. Grafton, MA. 508-839-5395

Chemotherapy

The benefit of chemotherapy in the treatment of soft tissue sarcomas has not been quantified. However, recent research has shown that chemotherapy can delay regrowth or spread of aggressive soft tissue sarcomas. Chemotherapeutic agents used include doxorubicin, carboplatin, and certain alkylating agents. Low-dose daily metronomic chemotherapy is also showing promise as treatment for STS. In general, chemotherapy is recommended in patients deemed to have an aggressive tumor (high grade), metastatic disease, and/or intra-abdominal tumors.

Prognosis

The prognosis for soft tissue sarcoma is variable, though long term control or cure is possible. Local control of the tumor is very challenging and local tumor recurrence rates after surgery (with or without radiation) range from 7% to 32%. Poor prognostic factors for local tumor recurrence include large tumor size, incomplete surgical removal and high histologic tumor grade (high grade corresponds with aggressive tumor behavior). Management of recurrent soft tissue sarcomas is usually more difficult than the original tumor, emphasizing the need for aggressive treatment of the initial tumor. Because the median time for tumor recurrence is 368 days, the pets should undergo long term follow-up and frequent check-ups. The metastatic rate for soft tissue sarcomas varies from 8% to 17% with a median time to metastasis of 1 year, depending on the tumor’s properties. The median survival time for dogs with soft tissue sarcomas is 1416 days with surgical treatment and 2270 days with surgical and radiation treatment. Overall, up to 33% of dogs eventually die of tumor related causes.

Types of Soft Tissue Sarcomas

Tissue of origin

Benign tumor

Malignant tumor

Primary sties

Risk of malignant tumor metastasis

Organ of metastasis

Adipose (fat) tissue

Lipoma

Liposarcoma

Limbs, abdominal or chest cavity

Low to moderate

Lungs, liver, spleen, bone

Fibrous tissue

Fibroma

Fibrosarcoma

Limbs, oral cavity

Low to moderate

Lungs

Histiocytic cells

Histiocytoma

Histiocytic sarcoma

Limbs

Moderate to high

Lymph nodes, lungs, spleen, liver, kidneys

Lymph vessels

Lymphangioma

Lymphangiosarcoma

Limbs

Moderate

Lymph nodes

Blood vessels

Hemangioma

Hemangiosarcoma

Spleen, heart, liver, muscle, bone, kidneys

High

Lungs, liver, lymph nodes, distant dermal sites

Nervous tissue

-

Peripheral nerve sheath tumor

Limbs

Low to moderate

Lugns

Skeletal muscle

Rhabdomyoma

Rhabdomyosarcoma

Tongue, larynx, heart, bladder

Low to moderate

Lungs, liver, spleen, kidneys

Synovial tissue

Synovioma

Synovial cell sarcoma

Joints

Moderate to high

Lymph nodes, lungs

Myxoma tissue

Myxoma

Myxosarcoma

Limbs, joints

Low to moderate

Lungs

Source: Withrow Stephen J, and David M. Vail. Small Animal Clinical Oncology, St. Louis: Saunders Elsevier, 2007.

Canine Melanoma Vaccine

Portland Veterinary Specialists

The oncologist recommended Canine Melanoma Vaccine for my dog.  What will it do?  How does it work?

Canine Melanoma Vaccine alerts the immune system to the presence of melanoma proteins, which results in the immune system fighting the cancer cells.  In conjunction with surgery and/or radiation to treat the initial tumor, this immune response may help extend the survival time for most dogs.  The melanoma vaccine is not meant to replace surgery and/or radiation therapy but is intended to be used along with these therapies


Since this is a vaccine, does that mean my dog can get it as a preventative?  Should my dog receive it every year with other vaccinations?

Currently, this vaccine has only been tested as a therapeutic vaccine, for use with dogs that have oral melanoma.  Most experts believe that the incidence of canine melanoma is too low to justify preventive melanoma vaccines for all dogs.


How and where is the vaccine administered?  Why are four doses of the vaccine necessary?

The vaccine is administered into the inner thigh muscle of the dog with by a needle-free injection.  Initial treatment requires administration of four doses of vaccine, one every two weeks.  After this initial series, dogs receive one booster dose every six months.  Each time dogs receive a dose, their immune response becomes stronger in the fight against melanoma.


Is injection of the therapeutic vaccine with the device painful for my dog?

Based on observations made during administrations, dogs do not react to the vaccine in a way that would suggest the vaccine is any more painful than a traditional injection.


What are the risks and side effects associated with my dog receiving Canine Melanoma Vaccine?

A temporary, low-grade fever or redness and swelling at the injection site may be observed in some dogs.  These side effects do not require any treatment and resolve quickly.  No other clinically significant safety issues were observed in safety studies used to support product licensure.


Will this therapeutic vaccine extend my dog’s life?  By how long?

Dogs with advanced melanoma (stages II, III and IV) have a reported survival time of less than five months when treated with standard therapies.  While the effect of therapeutic vaccines varies from one animal to another, most dogs with Stage II (tumors between 2-5 cm) and III (tumor with metastasis to local lymph nodes and/or greater than 5 cm) disease, that have participated in vaccine studies, have recorded improved survival times of one year or more.

Mast Cell Tumors in Dogs

Dr. Gail Mason, DVM, MA, DACVIM
Kathi L. Smith, RVT
 

Mast cell tumors (MCTs) are fairly common tumors in dogs. They are most frequently found in the superficial layers of the skin, on any part of the body. Frequently, there will be ulceration over the area of the tumor, and the dog may scratch or bite at the affected area. The appearance of the tumor does not reveal its potential for spread or recurrence with any certainty. The tumors are usually singular, but dogs may present with multiple nodules, or recurrent ones. Some nodules occasionally enlarge and then regress in size on their own, due to swelling within the tumor itself. This should always raise the suspicion of the presence of an MCT.

Diagnosis of Mast Cell Tumors

Mast cell tumors do not have a specific appearance. However, they are fairly easily detected by a "needle aspirate and cytology." Insertion of a small needle into the tumor (virtually painless) area is followed by examination of the cells under a microscope. Mast cells are large, round cells that usually have dark granules in them. The granules contain substances which, when released, cause swelling, itching, and redness. Infrequently, when a large number of granules spontaneously discharge their chemical contents into the bloodstream, vomiting, stomach ulcers, shock and even death may result.

Mast Cell Tumor Staging

Mast cell tumors can be somewhat unpredictable in their behavior, relative to other types of tumors in dogs. Because of this, care is taken to "grade" the tumors that are discovered. The grade reflects the degree to which the malignant mast cells differ from normal, non-malignant mast cells. The stage can generally be correlated with tumor behavior, tumor recurrence, and survival of the patient. Mast cell tumors affecting the limbs, head, or neck tend to correlate with a more favorable prognosis than those found on the trunk or groin. Multiple mast cell tumors or those exhibiting rapid growth tend to have a more guarded prognosis. A pathologist determines the tissue grade of the tumor after the tumor is biopsied or removed.

*Grade I: well-differentiated-25% recurrence rate post-surgery

*Grade II: moderately differentiated-44% recurrence rate post-surgery

*Grade III: poorly differentiated-76% recurrence rate post-surgery

 

Treatment for Mast Cell Tumors

Treatment for mast cell tumors may involve surgery (the mainstay), chemotherapy, and/or radiation therapy. Recommendations for treatment are based on the type and grade of the tumor, surgical feasibility, and the presence or absence of spread (dissemination) of malignant mast cells throughout the body. Your veterinarian will usually submit blood tests and request abdominal ultrasound or radiographs (x-rays) to determine the likelihood of malignant mast cells elsewhere in the dog's body. Bone marrow biopsies are no longer routinely done, as they have not shown to have high predictive value for tumor staging.

 

Surgery
For single mast cell tumors, a surgical procedure known as a "wide resection" by an experienced surgeon is performed. This means aggressively excavating the tumor and surrounding tissues so that at least 2-3 cm of normal tissue in all directions is removed. This must include a "deep margin" which involves removing tissue below the tumor. The margins of the removed tissue are marked and examined by a pathologist to determine the presence of any lingering malignant cells. If negative, we refer to it as "clean margins". If the pathologist suspects the presence of mast cells in the remaining tissues of the surgery site, we refer to it as "dirty margins". If the remaining, malignant cells are less than 2 cm from the edge of the biopsy specimen, it is referred to as "close margins".

An aggressive surgery early in the course of mast cell tumor disease is associated with the best overall prognosis. A grade I or II tumor that has been completely removed usually requires no other immediate therapy. A grade III tumor, multiple tumors, recurrent tumors, or tumors with dirty margins (those which for anatomical reasons could not be subjected to further surgery) often require follow-up or "adjunct" therapy.

Radiation Therapy
Radiation therapy is an option for dogs whose mast cells tumors are localized, but too large for a clean resection or in an area difficult to resect such as tissues of the facial region, or as follow-up therapy for tumors with dirty margins. Dogs tolerate radiation therapy well, and it can offer long-term control for these tumors. Radiation therapy would not be appropriate for dogs with multiple tumors or those with evidence of disease throughout the body since the radiation beam treats only a single focus of disease. Radiation treatment can be accessed at New England Veterinary Oncology Group (NEVOG) in Waltham MA., Angell Memorial Animal Hospital in Boston, MA. and Tufts University School of Veterinary Medicine in Grafton, MA. This is a highly specialized form of therapy and we are pleased to refer your pet to these centers if need arises.

Chemotherapy
Chemotherapy denotes the administration of certain anti-cancer drugs in order to delay/prevent tumor growth or spread. It may be used before or after surgery, or alone.

Prednisone (a cortisone) is the most commonly used drug for therapy of mast cell tumors. It is well tolerated by dogs and is usually employed for a minimum of six months. If no new tumors appear within that time, your doctor may wean your dog off the prednisone completely. The side effects of prednisone include weight gain, increased appetite and thirst, bladder or skin infections, and panting. Occasionally, stomach irritation or ulcers can occur, or inflammation of the pancreas. Most of the time, the drug dose can be titrated to the patient to minimize any overt symptoms. If the tumor type is determined to be aggressive, additional drugs such as stomach protectants may be prescribed to guard against untoward tumor effects. By itself, prednisone is considered to have only mild anti-cancer effects on MCTS.

Chlorambucil Protocol
If your pet is deemed to have an increased risk of tumor recurrence, we may recommend combination oral therapy with prednisone and chlorambucil (Leukeran¨). Chlorambucil is a chemotherapy drug that is extremely well tolerated in most patients and yet offers more tumor protection than prednisone alone. This drug is usually administered twice weekly and requires that your pet be monitored at least every 6-8 weeks. The minimum treatment period is 6 months.

Vinblastine Protocol
For recurrent or multiple tumors, and for those tumors that cannot be surgically removed, combination chemotherapy can be effective in controlling tumor growth and spread for weeks to months or more. A cure per se is generally not realistic, but many dogs tolerate therapy extremely well. The six-month protocol involves:

Prednisone: high dose at first, then taper over 4 months
Vinblastine: an outpatient injection, given once every 21 days
Cyclophosphamide (Cytoxan¨): an oral chemotherapy drug, given by the owners on days 8,9,10, and 11 of a 21-day cycle.

This protocol has produced a 1 and 2 year survival rate for grade 2 tumors of 91%. For patients with grade 3 tumors, the 1-year survival rate is 66%.

Side Effects
The side effects of prednisone are discussed above. Vinblastine and Cytoxan have the ability to cause nausea and or vomiting, though this is not usual. The most important possible side effects are lowering the body's defenses so that infections occurs, or (rarely) causing many mast cells to release their contents at once. Both situations can be life threatening. However, these are NOT common, and the risk of these is significantly lower than the risk of untreated mast cell disease. You will be given instructions on what to do if any side effects occur, so do not hesitate to contact us.

Lomustine (CeeNu¨) 
CeeNu is a potent oral chemotherapy drug that can be used once every three weeks in patients who MCTs have become resistant to other treatments. It is very well tolerated in general. However, because it can increase the risk of infection (especially seven days after it is given), any noted fever, depression, weakness, or refusal to eat should be reported to us or your veterinarian, or an emergency hospital immediately. Infection is almost always completely reversible. This drug is more potent than Cytoxan¨ and maybe substituted for it if indicated. Occasionally, this drug may decrease patient blood cell counts, which requires a dose reduction or discontinuance.

Prognosis
The factors that are known to influence patient outcome are grade of tumor (I is best, III is most dangerous), completeness of surgical removal (clean margins), and tumor location. Dogs with high-grade tumors, multiple or recurrent tumors, or evidence of spread to the bloodstream or other organs have a much more guarded prognosis for a lengthy survival.

Patient Monitoring
Close patient monitoring is essential in dogs with a history of mast cell tumors. As with many tumors, early detection and treatment increases the chances of successful treatment. You may be asked to have your dog examined and monitored every 6-8 weeks following surgery, or every 21 days during chemotherapy. Blood tests and/or needle aspirates are often requested to assess tumor control. Any time you suspect a new or recurrent tumor, or that your dog is physically ill, contact us immediately. We welcome the opportunity to help you and your dog in any manner we can.

 

Reference: Mast cell tumors in dogs; In: Managing The Veterinary Cancer Patient; Ogilvie, OK and Moore, As. © 1995 Veterinary Learning Systems. Trenton, NJ. *Based on protocol published by Elmslie, Robin; published in the Veterinary Cancer Newsletter.

 

Care and Feeding of the Canine Cancer Patient

Dr. Gail Mason, DVM, MA, DACVIM
Kathi Smith, RVT, Internal Medicine & Oncology Technician

 

Cancer treatment will no doubt have effects on both the normal and malignant cells of your dogs body. However, there are several ways in which we can minimize side effects of therapy and promote a fairly normal lifestyle for your dog.

Diet

The burden of malignancy alone can cause a negative nutritional status in both humans and animals. This, coupled by potential side effects of certain chemotherapeutics can accelerate loss of body condition. Providing adequate caloric intake is important in preventing ongoing energy losses. Calories alone do not tell the whole story. It has been convincingly shown in human and animal cancer patients that cancer survival is enhanced if the diet is:

• Low fat
• Low carbohydrate
• High protein (at least 21%)
• Has adequate fiber levels
• N-3 omega fatty acid enhanced

The suggested daily caloric intake is [1.1 x {30(patient weight in kilograms)} + 70]. Some commercial foods that we have found to provide close to the above profile include:

• MaxCal by IAMS
• Duck & Potato by Innovative Vet. Diets
• Canine Nutral Select by Innovative Vet. Diets

Additions
Based on recent and current research, we are also recommending: 
• Fish oil or marine oil supplementation 500-1000mg daily (in pharmacies or grocery stores) 
• Antioxidant therapy - a human combination product such as Protegra (adult label dose) or CAS options - a veterinary compounded formula that is available from us

Antioxidants and fish oils are generally used after week 4 of chemotherapy is completed. Theoretically, this reduces the chances of rescuing the malignant cells during the initial drug-induced damage.

 

Anal Sac Tumors in Cats and Dogs

Anal Sac (Apocrine Gland) Tumors in Dogs and Cats


KEY TAKEAWAYS
*    Anal sac (apocrine gland) tumors can be found by rectal examination.
*    Common symptoms include difficult or painful bowel movements, scooting, swelling around the anus, ribbon-like stool and bleeding as a result of local irritation.
*    Anal sac tumors can result in high calcium levels, which will cause increased thirst increased urination, decreased appetite, weight loss, vomiting, muscle weakness, and low heart rate.                                        
*    Surgical removal of anal sac tumors is the treatment of choice whenever possible.
*    It is estimated that the cancer has spread in 50-80% of cases at the time of diagnosis.
*    Dogs whose cancer spread to other organs have a median survival of 6 months after surgery compared to 15.5 months for dogs without metastases (spread of the cancer).
*    The tumors typicall occur in older dogs and some studies suggest that females may be at higher risk of anal sac cancer.  


Anal sac tumors
     Anal sacs are paired structures, one sac on each side of the anus, which are lined by many glands. These glands produce liquid that is expelled with each bowel movement as a form of territorial marking. Anal sac tumors arise from the glands of the anal sac, and may be either benign (known as anal sac adenomas) or malignant (known as anal sac adenocarcinomas). Anal sac adenocarcinoma is very rare in cats, but has been reported. The tumor itself usually affects only one of the two anal sacs; however, some pets may have tumors in both. The tumor can be very small or quite large, sometimes producing a hormone which causes blood calcium levels to rise above normal levels. The high level of calcium is called hypercalcemia, and can cause problems by damaging the kidneys. Unfortunately, by the time the diagnosis of anal sac adenocarcinoma is made, the tumor may have already metastasized (spread) to other sites such regional lymph nodes, lumbar spine or the liver, spleen, or lungs.


Diagnosis
     Anal sac adenocarcinomas are usually identified during physical examination of the anus, although some tumors are not always easily felt. Some tumors are found during routine rectal examination for impacted anal glands or when taking the animal's rectal temperature. If a mass is detected veterinarians will typically perform several follow-up tests. Complete blood count (CBC), serum chemistry profile, and urinalysis will identify possible hypercalcemia, evaluate the pet’s overall health, and help identify any other abnormalities. To confirm whether the mass is benign or malignant, a fine needle aspirate or tissue biopsy is performed. Incisional biopsy (when a small piece of the tumor is taken) is usually performed on large tumors under sedation and local anesthesia whereas excisional biopsy (when the entire tumor is removed) is usually performed on small tumors under general anesthesia. Additionally, cells can also be isolated from the sublumbar lymph nodes (lymph nodes that are close to the anal sac and the first site to which the tumor will spread) to determine if the tumor has already spread to this region. To test whether the cancer has spread to other organs, abdominal X-rays, chest X-rays and abdominal ultrasound are performed. Advanced imaging techniques such as CT scans can be used to get a more precise and more complete assessment. 


Treatment options
Surgery 
    The initial treatment for anal sac tumors is complete surgical excision. Whenever possible, the surgery will remove the anal sac tumor as well as a wide margin of normal tissue around and under it in order to maximize the likelihood that no tumor cells are left behind. Depending on the tumor’s size, its surgical removal may very infrequently result in fecal incontinence and you should discuss this with your veterinary surgeon to get a clearer idea of its severity given your pet’s condition. If recovering well without complications, most pets are discharged 1-2 days after surgery. Pets may need to take stool softeners until tissue swelling is resolved, and pain medications should be prescribed to make the pet more comfortable given the invasive nature of surgery.

     Metastasis (spread of the cancer) to the nearby sublumbar lymph nodes occurs in more than 50% of cases, therefore, their surgical removal may be required if the lymph nodes are enlarged. If the pets showed increased levels of calcium (hypercalcemia), it will usually resolve on its own 24-96 hours after the surgery, however, it is recommended to periodically measure the pet’s calcium levels to monitor possible cancer recurrence or metastasis. Pets with persistently high calcium levels may be given medication in order to prevent damage to the kidneys. 

Chemotherapy
     In addition to surgery, chemotherapy may be used to kill any remaining cancer cells left behind after the surgery. Even if there is no evidence of metastasis at the time of diagnosis, it is possible that some tumor cells are already circulating throughout the pet’s body, getting ready to establish new tumors in distant organs. Chemotherapy can also be used in pets if the tumor could not be removed with surgery, has already metastasized at the time of diagnosis, or if the surgery was not able to remove all of the tumor. While unlikely to cure the cancer, it can offer the pet more quality time.  Many patients experience successful management of their disease for months to up to two years.  

Radiation therapy
     Radiation therapy is typically used to treat anal sac tumors that could not be removed by surgery or if the surgery was not able to remove the entire tumor.


Treatment associated risks
     Any surgical procedure has the rare risk of anesthetic death but use of modern anesthetic protocols and careful monitoring have largely minimized the risk. Because the surgery is performed near the anus, there is an increased likelihood of developing an infection but the administration of antibiotics after the procedure should control this potential complication. If the sublumbar lymph nodes are also being removed, there is a risk of bleeding during the surgery because the tumor-invaded lymph nodes are often closely associated with blood vessels. These lymph nodes are also very close to nerves, especially those connecting with the bladder, and their removal may cause nerve damage leading to temporary or in some cases permanent post-operative urinary incontinence (inability to control urination). Fecal incontinence (inability to control bowel movement) can occur in a small percentage of animals after the surgery. For pets having difficulty defecating, high-fiber diet and/or stool softeners are usually prescribed to alleviate this problem. Pets undergoing radiation treatment may experience radiation complications such as mild to severe moist desquamation (shedding of skin cells that were exposed to radiation), colitis, difficulty to empty the bowel, and discomfort.


Prognosis
     The prognosis will largely depend on the extent of the disease at the time of diagnosis. Pets with local disease (has not spread to other organs) whose tumor was completely removed by surgery have a much better prognosis than pets whose cancer has already spread, or whose tumor could not be completely removed. 

     There is only limited number of published studies regarding outcomes of anal sac tumors in pets. One study of 32 dogs showed that female dogs had a worse prognosis compared to male dogs, and had a 50% chance of cancer recurrence (cancer coming back) after surgery. It is estimated that by the time diagnosis of anal sac tumors is made, the cancer has spread in 50-80% cases. Dogs whose cancer metastasized had a median survival after surgery of 6 months (range from 1.5 to 39 months) whereas dogs without metastasis had median survival after surgery of 15.5 months (range from 3to 35 months).

     The largest published study involved 113 dogs with varying stages of anal sac cancer treated with different therapies. Of these 113 dogs, 104 underwent treatment consisting of surgery, radiation therapy, chemotherapy or combination. The results showed that median survival for the treated dogs was 544 days (meaning that at 544 days, 50% of the dogs were alive). The study also showed that dogs treated with chemotherapy alone had shorter survival (median of 212 days) compared to those who received other treatments (median of 584 days). Dogs who did NOT receive surgery experienced shorter survival (median of 402 days) compared to those who did undergo surgery (median of 548 days). For dogs with large tumors (>10cm2), the median survival was 292 days compared to 584 days for those with smaller tumors (<10cm2). Dogs whose blood tests show increased calcium levels faced shorter survival (median of 256 days) compared to those with normal calcium levels (median of 584 days). Dogs with metastases to the lungs had significantly shorter median survival (219 days) compared to those without metastases (548 days) (Williams, J Am Vet Med Assoc, 2003)