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Update on Canine and Feline Gastrointestinal Neoplasia

Stanley Marks South Africa

Although gastrointestinal (GI) neoplasms account for approximately 2% of all canine and feline neoplasms, the clinical signs associated with GI neoplasms are essentially the same as those associated with inflammatory or obstructive diseases of these organs. The most common clinical signs are related to the “mass effect” of the tumor with clinical manifestations depending on the site of the tumor within the intestinal tract. Gastric tumors are typically associated with chronic vomiting, weight loss, and inappetence. Tumors of the duodenum, jejunum, and ileum are associated with vomiting, diarrhea (melena), and weight loss, whereas tumors of the colon are associated with tenesmus and hematochezia. The clinical signs may result from metastatic lesions to the liver, spleen, mesenteric lymph nodes, and central nervous system, producing signs such as icterus, abdominal hemorrhage, and seizures. Cats may present with pale mucous membranes and have microcytic anemia secondary to chronic blood loss. It is important to remember that not all nodular lesions of the gastrointestinal tract are neoplastic. Differentials include granulomas from inflammatory bowel disease, FIP, fungal infections, or foreign body penetration.

Gastric Adenocarcinoma

The most common tumor of the stomach in dogs is gastric adenocarcinoma. Other gastric tumors diagnosed less commonly include leiomyoma/leiomyosarcoma, lymphoma, and adenoma. A male predominance has been reported and a strong breed predilection is present for Belgian Shepherds (in Italy) and Rough Collies. Gastric tumors are rare in cats and lymphoma predominates.

Behavior

Gastric adenocarcinomas often metastasize, particularly to the perigastric lymph nodes and viscera. Most tumors extend to or through the serosa from the mucosa, creating deep ulcers with hematemesis and melena.

Diagnosis

Abdominal palpation may reveal a large gastric mass (adenocarcinoma) or a diffusely thickened gastric wall (lymphoma). Plain abdominal radiographs and/or positive-contrast radiographs may reveal thickening of the gastric wall, absence of rugal folds, filling defects, or an intraluminal mass. Ultrasonographic examination of the abdominal cavity may reveal additional masses or metastases to the liver and spleen. The diagnosis is confirmed by means of a gastric biopsy procured either via endoscopy or during an exploratory laparotomy. Most carcinomas occur in the lower two thirds of the stomach, particularly the pylorus. Thoracic radiographs should always be performed prior to surgical resection of gastric tumors because up to 30% of dogs with gastric carcinoma can have visible metastatic lung lesions on initial presentation.

Treatment

The prognosis for gastric adenocarcinomas is poor because of the advanced stage at diagnosis, their diffuse nature, and their high rate of metastases. Most tumors are nonresectable because of their size or invasiveness. Most dogs die within four months of surgery from local recurrence or metastases despite wide resection (Billroth I procedure). Results of chemotherapy for adenocarcinoma have not been reported.

Gastrointestinal Lymphoma

Unlike the dog, gastric adenocarcinoma in the cat is rare, and the stomach is the least commonly affected gastrointestinal site in the cat. Lymphoma is the most common gastric tumor in the cat and may be solitary or one component of systemic involvement. Most cats with gastric lymphoma are negative for feline leukemia virus. Intestinal lymphoma has two morphologic forms; a diffuse type and a nodular type. Diffuse lymphoma is characterized by extensive infiltration of the lamina propria and submucosa with neoplastic lymphocytes that may cause malabsorption, steatorrhea, diarrhea, and weight loss. The nodular form causes a segmental thickening of the bowel, most often in the ileocolic region, with resultant luminal narrowing and partial intestinal obstruction. Metastasis to regional lymph nodes is common with both forms of the disease. Gastric lymphoma in cats is rarely confined to the stomach and is best treated with adjuvant systemic chemotherapy. The prognosis for cats with gastric lymphoma is extremely variable with treated cats having survival times ranging from less than two months to more than one year. Adjuvant chemotherapy (Table 1) is also recommended following surgical excision of a solitary lymphomatous mass

In a recent report of 39 cats with well-differentiated gastrointestinal lymphoma, the most common clinical signs were vomiting (87%), weight loss (79%), anorexia (53%), diarrhea (53%), and lethargy (47%). Nine percent had neither vomiting nor diarrhea. An abdominal mass was palpated in 26% of cats, while 32% had thickened gastrointestinal loops. Twenty-six cats were treated of which 23 received prednisone (5 mg q12h) and chlorambucil (2 mg per cat every four to five days). Fourteen (61%) achieved complete remission (CR). The disease free interval of those who achieved CR ranged from 5.75 to 24 months (median 15.5 months). The overall survival ranged from 0.33 to 25 months (median 12 months). There was no significant difference in disease-free interval or survival due to age, sex, breed, palpability of the abdominal mass, retroviral status, localization of the tumor, or presence of hypoalbuminemia. Endoscopic biopsy was quite useful for obtaining a definitive diagnosis. The survival times in this study are better than those seen in cats with poorly differentiated gastrointestinal lymphoma treated with more complex and expensive protocols. Lymphoma is rarely confined to the stomach and is best treated with systemic chemotherapy. Responses of cats with gastrointestinal lymphoma to vincristine, cyclophosphamide, and prednisone are poor, with treated cats having a median survival time of less than two months.

A recent retrospective study of 21 cats with alimentary lymphoma treated with a more expensive multidrug protocol of prednisone, L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and methotrexate revealed an overall median duration of first remission of 20 weeks, and an overall median survival time of 40 weeks. The only factor significantly associated with duration of first remission was whether cats had a complete response following induction chemotherapy; duration of first remission was significantly associated with survival time. Cats tolerated treatment well; only one cat had a delay in the treatment schedule because of neutropenia. All cats were negative for FeLV and 3/19 cats were positive for FIV. Thirteen tumors were stage III, seven were stage IV, and one was stage V. Immunophenotyping was performed on 13 tumors; 10 were T-cell and three were B-cell lymphomas. This refutes the previous literature that states that almost all intestinal lymphomas are of B-cell origin.

Other Intestinal Neoplasms

Intestinal tumors occur most commonly in the rectum and colon of dogs and the small intestine of cats. Lymphoma is the most common intestinal tumors of cats, and adenocarcinomas and mast cell tumors follow lymphoma in frequency. Other tumors affecting the intestinal tract include fibrosarcoma, undifferentiated sarcoma, carcinoids, leiomyomas/leiomyosarcomas, and plasmacytoma. Intestinal carcinomas typically occur in older animals. Any region of the gut can be affected, but in the cat, adenocarcinomas most commonly occur in the jejunum and ileum, whereas adenocarcinoma in the dog occurs most frequently in the large intestine and duodenum. Siamese cats are reported to have a higher frequency of small intestinal adenocarcinoma than other breeds. Mucosal ulceration is frequent and can result in melena and chronic blood loss anemia.

Leiomyosarcomas of the intestine are the most common sarcoma and occur most often in the cecum and jejunum. These tumors are locally invasive malignant smooth muscle neoplasms that are slow to metastasize. Intestinal lymphoma represents approximately 7% of all canine lymphoma cases and occurs most commonly in middle-aged dogs. In cats, intestinal lymphoma is often part of a multicentric disease. The jejunum and ileum are most commonly affected with lymphoma in cats. The majority of cats with intestinal lymphoma are also feline leukemia virus (FeLV) negative.

Behavior

The majority of intestinal neoplasms are malignant. Intestinal adenocarcinoma is usually in an advanced stage when diagnosed. Extension of the neoplasm beyond the bowel wall was found in 85% of dogs and 71% of cats at necropsy. The most common sites of metastases in the dog include the regional lymph nodes, liver, and lungs. In cats, the most common sites of metastases are abdominal serosa, lymph nodes, lung, and liver. Adenocarcinoma has been described as annular or intraluminal. Canine adenocarcinomas have been histologically classified into four groups that may overlap: acinar, solid, mucinous, and papillary. Papillary carcinomas tend to spread horizontally with few distant metastases. In contrast, acinar, solid, and mucinous adenocarcinoma tends to show more vertical growth and extend into bowel wall, serosa, and other organs. The clinical, gross, and morphologic types of feline intestinal adenocarcinoma are similar to that in dogs.

Primary intestinal mast cell neoplasia of the intestinal tract is the third most common feline intestinal tumor after lymphoma and adenocarcinoma. Intestinal mast cell tumors are less differentiated than cutaneous mast cell tumors. The small intestine is usually affected and lesions can be solitary or multiple, 1 to 7 cm diameter, firm segmental thickenings of the intestine. Most cats have a detectable intra-abdominal mass identified by either palpation or radiographic examination. Peritoneal effusion, fever, and mild anemia may be noted. Cats frequently have concurrent hepatic and splenic involvement and peritoneal effusion can occur. Intestinal MCT is associated with widespread dissemination and carries a poor prognosis. Unlike splenic MCT’s, intestinal MCT’s are not associated with a peripheral mastocytosis. Metastases are common to mesenteric lymph nodes and the liver, followed by the spleen, lung, and bone marrow. Biopsy of a regional lymph node is recommended to document the presence or absence of metastatic disease. Because circulating mast cells may be observed in gastrointestinal disease, the significance of a positive buffy coat smear in this particular disease must be interpreted with caution. Most animals either die or are euthanized soon after diagnosis. If surgery is feasible, wide surgical margins, including 5 to 10 cm of normal bowel proximal and distal to the tumors are recommended. Ranitidine (1 to 2 mg/kg orally q12h) should be administered following confirmation of the diagnosis of intestinal MCT. Corticosteroids should be withheld until 14 days post-surgery to ensure adequate healing of the enterotomy site.

Diagnosis

Physical examination may reveal an abdominal mass, thickened bowel loops, or mesenteric lymphadenopathy. The majority of dogs with colorectal adenocarcinoma have rectal masses that can be palpated via digital rectal examination. Pulmonary metastases are rarely detected on thoracic radiographs. Proctoscopy or colonoscopy should always be performed following digital rectal examination to identify additional tumors proximal to the rectum. Contrast radiographic studies, particularly enteroclysis, may reveal mucosal abnormalities or obstructive lesions. Ultrasonography is a valuable diagnostic tool and may reveal bowel thickening, localized ileus, or enlarged mesenteric lymph nodes. The most common abnormalities on the hemogram and serum biochemical profile are anemia and hypoproteinemia, and elevated serum hepatic enzyme concentrations.

Definitive diagnosis is usually made by intestinal biopsy via celiotomy or endoscopy. Caution must be exercised when diagnosing intestinal lymphoma via endoscopy. In some cats, the initial biopsy is interpreted as inflammatory bowel disease (lymphocytic-plasmacytic enteritis), and patients frequently show a favorable response to dietary modification and glucocorticoid therapy. These patients ultimately become refractory to therapy and necropsy reveals intestinal lymphoma. It is uncertain whether the initial lesion represented prelymphomatous change or whether it was erroneous because of sampling error.

Treatment

The most common treatment for solitary intestinal tumors is surgical resection with margins of at least 4 cm being the goal. Adjuvant chemotherapy for intestinal adenocarcinoma and leiomyosarcoma has been recommended although the efficacy of such treatment has not been reported in the dog and cat. Intestinal lymphoma should be managed surgically if the tumor is associated with intestinal obstruction or perforation. Biopsies and impression smears for cytological evaluation should be performed on adjacent intestine, lymph nodes, spleen, and liver to clinically stage the disease. Diffuse intestinal lymphoma should be managed with systemic chemotherapy once the diagnosis has been confirmed.

Adenomatous polyps are benign pedunculated masses that arise from the mucosa and protrude into the lumen. Rectal polyps occur most commonly in the rectum and descending colon in dogs, whereas they occur most commonly in the small intestine of cats. Fifty percent of the canine rectal tumors showed transition from benign polypoid lesions to adenocarcinoma in one study. Fifty percent of the reported feline cases of rectal polyps have been in cats of Asian ancestry. Rectal adenomatous polyps may be pedunculated or have a sessile base. Most polyps are within 2 cm of the anus and may be treated by surgical excision, electrosurgery, or cryosurgery. Rectal polyps on a stalk can be transfixed with a ligature and the base frozen with a cryoprobe. There are several surgical techniques for resecting rectal tumors. Various techniques such as end-to-end anastomosis (usually requiring a pelvic osteotomy for access), rectal pull through, or the dorsal rectal approach have been described. The morbidity and mortality associated with surgical resection of rectal tumors underscores the difficulty in deciding how to manage these tumors. Local excision and cryosurgery for adenocarcinoma of the colon have significantly extended the life of dogs compared with other methods of surgical treatment, however 82% (9/11 dogs) treated with cryosurgery suffered complications (rectal prolapse, stricture, perineal hernia, and recurrence). Electrosurgery may be a viable treatment alternative when the tumor is not annular and is located distally facilitating prolapse of the rectum. The prognosis for completely excised rectal polyps is excellent, although large or sessile polyps can reoccur.

Dogs with colonic or rectal adenocarcinoma are usually euthanatized because of local failure manifested by failure to control dyschezia and hematochezia. Clinical signs associated with metastases were not observed in 78 dogs with confirmed colorectal adenocarcinoma. In another study, dogs with surgically managed intestinal carcinomas had a mean survival of 6.9 months with local recurrence being the reason for euthanazia. Dogs with single, pedunculated, polypoid adenocarcinoma lesions had a mean survival of 32 months, those with nodular or cobblestone-like lesions had a mean survival time of 12 months, and dogs with annular masses causing strictures had a mean survival time of 1.6 months. High-dose radiotherapy appears effective for palliating adenocarcinomas of the distal half of the rectum and anus. The rectum is prolapsed with stay sutures and the beam is restricted by a cone onto an area approximately 1 cm greater than the diameter of the grossly visible tumor. The prognosis for small intestinal adenocarcinoma is poor because of advanced disease by the time of diagnosis. The mean survival following surgery is approximately seven months, although survivals of two or more years have been reported.

TABLE 1: Chemotherapy Protocols for Cats and Dogs with Gastrointestinal Lymphoma

Chlorambucil and Prednisone Protocol for Cats

Chlorambucil

2 mg (1 tablet per cat) PO every 4-5 days

Prednisone

5 mg q12h for the rest of the cats life

COAP Protocol

Cyclophosphamide

50 mg/m2 PO 4 days a week or every other day for 8 weeks

Vincristine

0.7 mg/m2 IV once a week for 8 weeks

Cytosine arabinoside

100 mg/m2 IV or SC q12h for 4 days

Prednisone

40-50 mg/m2 PO q24h for seven days; then 20-25 mg/m2 PO every other day for seven weeks; in cats use 5 mg q12h for rest of cats life

COP Protocol

Cyclophosphamide

50 mg/m2 PO 4 days a week or every other day for 8 weeks

Vincristine

0.7 mg/m2 IV once a week for 8 weeks

Prednisone

40-50 mg/m2 q24h PO for seven days; then 20-25 mg/m2 PO every other day for seven weeks; in cats use 5 mg q12h for rest of cats life

Adriamycin Protocol

Adriamycin (doxorubicin)

30 mg/m2 IV every 3 weeks for dogs or 20 mg/m2 for cats (do not exceed 240 mg/m2 total); OR 1 mg/kg IV every 3 weeks for small dogs and cats

L-Asp-VCAP Protocol

L-asparaginase

10,000 IU/kg IP on day one of therapy

Vincristine

0.7 mg/m2 IV every week for 4 weeks, then every 3 weeks

Cyclophosphamide

250 mg/m2 PO on week 7, 13, 16, and 22 of therapy

Adriamycin

30 mg/m2 on week 10 and 19

Prednisone

40-50 mg/m2 q24h PO for seven days; then 20-25 mg/m2 PO every other day for seven weeks; in cats use 5 mg q12h for rest of cats life

References

1.  Fondacaro JV, Richter KP, Carpenter JL, et al. Feline gastrointestinal well differentiated lymphocytic lymphoma: 39 cases. Abstract. Proceedings of the 17th annual ACVIM. Page 722, 1999.

2.  Zwahlen CH, Lucroy MD, Kraegel SA, Madewell BR. Results of chemotherapy for cats with alimentary malignant lymphoma: 21 cases (1993-1997). J Am Vet Med Assoc 15;213(8):1144-9, 1998.

3.  Birchard SJ, Couto CG, Johnson S. Nonlymphoid intestinal neoplasis in 32 dogs and 14 cats. J Am Anim Hosp Assoc 22:533-537, 1986.

4.  Brodey RS. Alimentary tract neoplasms in the cat: A clinicopathologic survey of 46 cases. Am J Vet Res 27:74-80, 1966.

5.  Turk MAM, Gallina AM, Russel TS. Nonhematopoeitic gastrointestinal neoplasia in cats. A retrospective study of 44 cases. Vet Pathol 18:614-620, 1981.


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