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Gastric tumours in the dog and cat

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Category: Schede
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  • Disciplina: Gastroenterologia
  • Specie: Cane e Gatto

Gastric tumours account for around 1% of all neoplasms of small animals. In most cases the causes are unknown, although it has been shown that the prolonged administration of nitrosamide is involved in the development of gastric tumours in the dog, in the cat and in other animals.1 A genetic predisposition has been suggested in Belgian Shepherd dogs; however, this has never been confirmed.2,3

 

AGE 

The mean age of animals affected by gastric tumours is usually around 8 years old, with males apparently affected more frequently.4-6 Leiomyomas are the only exception; these tumours tend to occur at an older age, at around 15 years of age.7

 

TYPES OF NEOPLASMS

The gastric tumour which is most frequently encountered in dogs is adenocarcinoma (70-80% of cases).8 Other tumours which are often found are leiomyosarcoma,9 lymphoma,6 mast cell tumour,10extramedullary plasmacytoma and fibrosarcoma. In the cat, most gastrointestinal tumours are found in the bowel; the gastric tumour which is found most frequently is lymphoma.

Benign gastric tumours.  These include leiomyoma and adenomatous polyps.

Leiomyoma is a tumour of the smooth muscles of the stomach. This tumour is often associated with a paraneoplastic syndrome, with hypoglycaemic crises and convulsions in the cases that the tumour produces insulin-like growth factor (IGF), which consumes glucose.

Adenomatous polyps (Fig. 1) may be raised, sessile or pedunculated, single or multiple, and are usually found incidentally. In human medicine, these polyps are considered pre-cancerous.

 

 

Malignant gastric tumours. These include adenocarcinoma, leiomyosarcoma, lymphoma and gastrointestinal stromal tumour (GIST).

Adenocarcinoma (Fig. 2) is frequently encountered in middle-aged dogs (>8-9 years old). It is usually located on the lesser curvature of the stomach or around the pylorus, it may be localised or diffuse and very often tends to metastasise.9,12 Histologically it can be divided into diffuse or interstitial although this histological classification apparently has no impact on the clinical behaviour of the tumour.12

 

 

Leiomyosarcomas are tumours which originate from the smooth muscles of the stomach. They are more frequent in elderly dogs (>10 years old) and they more commonly affect the intestine. In various studies females were apparently affected more frequently than males.8 Just like leiomyoma, leiomyosarcoma may also produce IGF and cause hypoglycaemic crises and convulsions.

GIST constitute a relatively new category of neoplasms. These tumours originate from smooth muscles and in the past were erroneously classified as leiomyosarcomas or leiomyomas. They are often carriers of the c-Kit mutation which is important for the genesis and propagation of the tumour.13 GIST are  often located in the small bowel; the prognosis is good and survival is rather long.13The diagnosis is made through  immunohistochemical studies.

Lymphosarcoma is found in both dogs and cats, however the frequency seems to be higher in the latter (Figs. 3-7). Lymphosarcoma in the dog may be diffuse or nodular, while in the cat there is small cell type and a large cell type. Small cell lymphoma has a better prognosis, with a survival of various months.

Gastrointestinal mast cell tumours are more frequently found in cats; they are usually extremely aggressive and the prognosis is poor.

 

CLINICAL SIGNS

The clinical signs which are usually encountered  in patients with gastric tumours are vomiting, haematemesis, diarrhoea, melaena, anorexia/dysorexia, weight loss, anaemia and abdominal pain.

 

DIAGNOSIS 

The diagnosis can be made with various standard techniques, such as radiography (with or without contrast medium) (Fig. 8), abdominal ultrasonography (Figs. 9a and 9b) and endoscopy, or with more advanced techniques such as computed tomography. For a proper diagnosis a tumour biopsy is necessary (Figs. 10a-d) which, in most cases, may be obtained during an endoscopic examination, or, should this not be possible, during surgery (laparotomy/laparoscopy). Cytology of a sample of the lesion obtained by ultrasound-guided needle aspiration, if possible, may be a simple diagnostic alternative. Prior to any anaesthesia the stability of the patient should be assessed with a biochemical examination, an examination of electrolytes and a complete blood count.

 

STAGING

Before continuing with the therapeutic plan a complete staging of the patient is necessary. This should include a biochemical examination, a complete blood count, radiography of the chest (with 3 views: right, left and dorsoventral/ventrodorsal) and ultrasonograpy of the abdomen (Fig. 11). In some cases (e.g. lymphoma) a bone marrow examination could also be useful, to check for an eventual infiltration which could influence the final choice of the therapeutic protocol to be used. Radiography of the chest and ultrasonography of the abdomen may sometimes be substituted by whole-body computed tomography, which is much more sensitive for detecting metastatic lesions.

 

TREATMENT

The treatment is varied and depends on the type of neoplasm present. With the exception of lymphoma,6,14 in which chemotherapy has a primary role, in all other types of tumours surgery is the most common modality of treatment. At times, however, the site of the tumour and the stage of the disease (often advanced at the time of diagnosis) make surgery difficult, in view of the possible complications. Adenocarcinoma is the tumour in which these difficulties are most often encountered.

In patients with adenocarcinoma, the efficacy of chemotherapy alone on survival has not yet been proven. Various agents have been used, such as carboplatin, doxorubicin, cyclophosphamide, 5-fluorouracil and COX-2 inhibitors, alone or in various combinations, but the results are still doubtful.8

Leiomyoma, leiomyosarcoma and GIST are usually well circumscribed and hence the surgical removal of these tumours is easy. Hypoglycaemia, which is the paraneoplastic sign most frequently associated with leiomyomas/leiomyosarcomas, usually disappears after the complete excision of the primary tumour (in the absence of metastatic lesions). In the case of GIST when surgery is not possible or when there is evidence of metastasis, c-kit inhibitors, such as imatinib,14-16 may be considered. The biggest limitation to the use of imatinib is the extremely high price of the drug. Other c-kit inhibitors include masitinib and toceranib phosphate.

Chemotherapy is the first-line treatment for lymphoma of the gastrointestinal tract, when it is not causing occlusions, as surgery did not prove superior compared to chemotherapy.17 In the presence of obstructions (especially of the gastrointestinal tract), surgery may be indicated as a first step, with the removal of the affected segment, followed, after healing of the wound, by chemotherapy.

In the dog, gastric lymphomas are typically treated with a CHOP protocol (prednisolone, vincristine, cyclophosphamide and doxorubicin)18,19 with the prognosis being only a few months (13-77 days), although longer remissions are possible in some animals.

In the cat, small cell gastrointestinal tract lymphoma is treated with a combination of prednisolone and chlorambucil, while CHOP-based protocols are used in the case of large cell lymphoma.

There is limited information on gastric plasmacytoma, as only a few cases have been published. Surgical excision would seem to be the best option. Various chemotherapeutic drugs have been proposed, such as the combination of melphalan and prednisolone (for the risk of systemic disease), CHOP-based protocols or doxorubicin monotherapy.1

Patients affected by gastric tumours very often have problems eating, nausea, vomiting and at times pain. These disorders, secondary to the neoplasm, may have a negative impact on the quality of life of the patient and consequently they must be treated.

Various analgesics may be used to manage pain in patients at home, such as opioids (tramadol, buprenorphine, morphine, fentanyl transdermal patch, etc.), some requiring special prescriptions (depending on the country). Other pain killers which are commonly used are non-steroidal anti-inflammatory drugs (NSAID), including meloxicam, paracetamol, carprofen, firocoxib, deracoxib, ketoprofen, piroxicam, etc., which may be used alone or in combination with opioids. Other drugs which are often prescribed are gabapentin, amitriptyline, amantadine, glucosamine with chondroitin sulphate and prednisolone. It is highly advisable not to combine NSAID with steroids, as the association can cause ulcers and gastrointestinal perforations, and to avoid using NSAID in patients with vomiting, diarrhoea, melaena or with ulcers (or with even just the suspicion of ulcers/erosions) of the mucosa.

Drugs used to manage nausea and vomiting (ranitidine, cimetidine, famotidine, maropitant, metoclopramide, ondansetron, omeprazole, sucralfate, etc.) are indicated to reduce signs and symptoms and to stimulate appetite.

Should the patient not be able to feed appropriately by itself, a feeding tube (naso-oesophageal or gastric) is indicated,  in order to ensure adequate calorie intake and to avoid excessive weight loss and cachexia (Figs. 12 and 13).

In the cat, drugs such as cyproheptadine (1/4 of a 4 mg tablet two/three times a day per os) or mirtazapine (3 mg/cat every 3 days or 1 mg/cat/day  per os) may stimulate appetite. Mirtazapine is a serotonin agonist, which may produce the “serotonin syndrome”, with tremors, hyperexcitability and hypersensitivity, caused by the release of serotonin a few hours after taking the drug. In such cases cyproheptadine may be used as an antidote (being a serotonin antagonist) and the dose of mirtazapine should be reduced further. In cats, it is better to avoid drugs such as diazepam in view of possible idiosyncratic reactions which could trigger fulminant hepatitis and sometimes even cause the death of the patient.

In the dog, cyproheptadine does not give good results and mirtazapine seems to be the only option for oral use. The dose varies depending on the weight: 0.75-30 mg/dog once a day.

Vitamin B12 is indicated for cats with gastric lymphoma. The dose is 0.5 ml/cat once a week for 4 weeks and then once a month. It seems that there is a marked deficiency of this vitamin in the presence of gastrointestinal,20 as well as in other,21 diseases, The dose is arbitrary and currently there are no studies indicating the optimal dose.

 

PROGNOSIS 

For most gastric tumours the prognosis is poor.  The prognosis of adenocarcinoma is particuarly poor, even after surgical excision, with most patients not surviving beyond 6 months.8 In rare cases, the patient can live for longer periods.2 In the case of leiomyosarcoma the prognosis is better and the mean survival is around 1 year.9 The survival of animals with gastric lymphomas is short (13-77 days),18,19with the exception of small cell gastrointestinal lymphoma in the cat, in which survival may exceed 2 years.22 Gastrointestinal mast cell tumours usually metastasise to regional lymph nodes and the survival of affected animals is short.10,11 Gastric plamacytomas have a very favourable prognosis following surgery and chemotherapy.11 In patients with benign tumours cure may be achieved with complete surgical excision.5

 

References

  1. Sasajima K, Kawachi T, Sano T, Sugimura T, Hirota T.: “Esophageal and gastric cancers with metastasis induced in dogs by N-ethyl-N’-nitro-N nitrosoguanide” Journal of  National Cancer Institute 58: 1789-1794, 1977
  2. Fonda D, Gualtieri M, Scanziani E,: “Gastric carcinoma  in the dog: a clinicopathological study of 11 cases” Journal of Small Animal Practice, 30, 353-360, 1989
  3. Scanziani E, Giusti Am, Gualtreri M,  Fonda D. “Gastric carcinoma in the Belgian shepherd dog”, Journal of Small Animal Practice 32, 465-469, 1991
  4. Sautter JH, Hanlon JF: “Gastric neoplasm in the dog: a report of 20 cases”, Journal of American Veterinary Medical Association, 166: 691-696, 1975
  5. PatnaikAk, Hurvitz AJ, Johnson GE: “Canine gastric adenocarcinoma” Veterinary Pathology 15, 600-607, 1978
  6. Couto CG, Rutgers HC, Sherding RG, Rojko J: “Gastrointestinal lymphoma in 20 dogs” Journal of veterinary internal medicine, 3, 73-78, 1989
  7. PatnaikAk, Hurvitz AI, Johnson GF: “Canine gastrointestinal neoplasms” Veterinary Pathology 14, 547-555, 1994
  8. Swann HM, Holt DE: ”Canine gastric adenocarcinoma and leiomyosarcoma: a retrospective study of 21 cases (1986-1999) and literature review” Journal of American animal hospital association, 38, 157-164, 2002
  9. Kapatkin  AS, Mullen HS, Matthiesen DT, Patnaik  AK: ” Leiomyosarcoma in dogs:44 cases (1983-1988)”, Journal of American Veterinary Medical Association,, 201, 1077-1079, 1992
  10. Ozaki K, Yamagami T, Nomura K, Narama I.:  ”Mast Cell tumors of the gastrointestinal tract in 39 dogs” Veterinary Pathology 39, 557-564, 2002
  11. Brunnert SR, Dee LA, Herrin AJ, Altman NH: “Gastric extramedullary plasmacytoma in  a dog” Journal of American Veterinary Medical Association, 200, 1501-1502, 1992
  12. Murray M, Robinson  PB, McKeating FJ: “Primary gastric neoplasia in the dog: a clinicopathological study” Veterinary Record, 91, 474-479,1972
  13. Maas CP, Ter Haar G, Van der Gaag I, Kirpernsteijin J:  ”Reclassification of small intestinal and cecal smooth muscle tumors in 72 dogs: clinical, histologic and immunohistochemical evaluation” Veterinary Surgery, 34, 4, 302-313, 2007
  14. MacEwen EG, Mooney S, Brown NO.: Management of feline neoplasms . In Holzworth J: Diseases of the cat, vol. 1. Philadelphia 1987, WB, Saunders
  15. Ishizuka M, Nagai S, Sakamoto KQ, Fujita S. Plasma pharmacokinetics and CYP3A12-dependent metabolism of c-Kit inhibitor imatinib in dogs. Xenobiotica , 37, 5, 503-13, 2007
  16. Lachowicz JL, Post GS, Brodsky E. A Phase I Clinical Trial Evaluating Imatinib Mesylate (Gleevec) in Tumor-Bearing Cats. Journal of veterinary internal medicine 19, 6, 860-864, 2005
  17. Gualtieri M, Monzeglio MG, Scanziani E. Gastric neoplasia. Veterinary Clinics of North American  Small Animal Practice 29, 2, 415-440, 1999
  18. Frank JD, Reimer SB, Kass PH, Kiupel M. Clinical outcomes of 30 cases (1997-2004) of canine gastrointestinal lymphoma. Journal of American animal hospital association, 43, 6, 313-321, 2007
  19. Rassnick KM, Moore AS, Collister KE, Northrup NC, Kristal O, Chretin JD, Bailey DB Efficacy of combination chemotherapy for treatment of gastrointestinal lymphoma in dogs Journal of veterinary internal medicine, 23, 2, 317-322, 2009
  20. Reed N, Gunn-Moore D, Simpson K. Cobalamin, folate and inorganic phosphate abnormalities in ill cats. J Feline Medicine e  Surgery 2007, 9(4):278-88
  21. Barron PM, Mackie JT, Evans NA, Langer N Serum cobalamin concentrations in healthy cats and cats with non-alimentary tract illness in Australia Australian  Veterinary  J.ournal  2009l;87(7):280-3
  22. Stein TJ, Pellin M, Steinberg H, Chun R Treatment of feline gastrointestinal small-cell lymphoma with chlorambucil and glucocorticoids. Journal of  American  Animal  Hospital Association 2010; 6 :413-7
  23. Kerpsack SJ, Birchard SJ. Removal of leiomyomas and other non invasive masses from the cardiac region of the canine stomach. JAAHA, 30, 500-504, 1994
  24. Rolfe DS, Twedt DC, Seim HB Chronic regurgitation or vomiting caused by oesophageal leiomyoma in three dogs. JAAHA, 30, 425-430, 1994
  25. Beck JA, Simpson DS, Surgical treatment of gastric leiomyoma in a dog. Aus Vet J, 161-162, 1999.