Gastric Adenocarcinoma

Gastric adenocarcinoma is a malignant epithelial neoplasm arising from the glandular epithelium of the stomach. It is the most common primary gastric tumor in dogs, accounting for approximately 70-90% of all canine gastric malignancies, but it is rare in cats. The tumor typically presents as an infiltrative, ulcerative, or polypoid mass, most frequently located in the pyloric antrum and lesser curvature. It is characterized by aggressive local invasion, early metastasis to regional lymph nodes, liver, and lungs, and a poor overall prognosis. Histologically, it can be classified into intestinal-type (well-differentiated) and diffuse-type (signet ring cell) variants, with the latter carrying a worse prognosis. Clinical signs are often nonspecific and include chronic vomiting, weight loss, anorexia, and melena, leading to delayed diagnosis. Complete surgical resection is the treatment of choice, but due to late presentation and high metastatic rate, the prognosis remains grave.

The exact etiology of gastric adenocarcinoma in dogs and cats is largely unknown, but several risk factors have been proposed. Chronic gastritis, particularly Helicobacter pylori infection, is a well-established risk factor in humans and is suspected to play a role in canine gastric cancer, although the association is not as strong. Other potential etiologic factors include dietary carcinogens (e.g., nitrosamines, smoked or pickled foods), genetic predisposition (e.g., breeds such as Belgian Shepherd, Chow Chow, and Rough Collie), and environmental factors (e.g., exposure to certain toxins). In cats, gastric adenocarcinoma is rare, and no specific etiologic agents have been identified. Chronic inflammation, such as that seen with inflammatory bowel disease or chronic gastritis, may predispose to neoplastic transformation. Additionally, immune dysregulation and oxidative stress have been implicated in the pathogenesis of gastric cancer.

Gastric adenocarcinoma is primarily a disease of older dogs, with a median age of 8-10 years. There is no strong sex predilection, though some studies suggest a slight male predominance. Certain breeds are overrepresented, including Belgian Shepherd, Chow Chow, Rough Collie, and possibly Standard Poodles. Mixed-breed dogs are also affected. The tumor is rare in cats, with a median age of 10-12 years, and no breed predilection has been consistently identified. Geographic variation exists, with higher incidence reported in certain regions, possibly related to dietary and environmental factors. In dogs, gastric adenocarcinoma accounts for about 1% of all canine neoplasms and is the most common gastric malignancy. The incidence is lower than in humans, but the prognosis is similarly poor.

Gastric adenocarcinoma arises from the gastric mucosa, typically in the pyloric antrum. The tumor cells invade the gastric wall, causing thickening, fibrosis, and loss of normal architecture. This infiltration disrupts gastric motility and secretion, leading to delayed gastric emptying, vomiting, and maldigestion. As the tumor grows, it can ulcerate, leading to chronic blood loss and melena. Local invasion can extend into the duodenum, pancreas, liver, and adjacent lymph nodes. Metastasis occurs via lymphatic and hematogenous routes, with common sites being regional lymph nodes, liver, lungs, and occasionally the peritoneum (carcinomatosis). The diffuse-type (signet ring cell) carcinoma is particularly aggressive, with rapid dissemination. Paraneoplastic syndromes, such as cachexia and anemia of chronic disease, are common. The tumor also induces a desmoplastic response, contributing to gastric wall thickening and rigidity.

Predisposing factors for gastric adenocarcinoma include: (1) Breed: certain breeds (Belgian Shepherd, Chow Chow, Rough Collie) have a genetic predisposition. (2) Age: older dogs and cats are at higher risk. (3) Chronic gastritis: long-standing inflammation, possibly due to Helicobacter infection, may increase risk. (4) Dietary factors: high intake of nitrosamines, smoked foods, or pickled foods may be contributory. (5) Environmental toxins: exposure to certain chemicals or pollutants. (6) Immunosuppression: chronic immunosuppressive therapy or concurrent diseases may promote tumor development. (7) Genetic mutations: alterations in tumor suppressor genes (e.g., p53) and oncogenes (e.g., c-met) have been implicated. (8) Sex: some studies suggest a slight male predominance. (9) Concurrent diseases: e.g., inflammatory bowel disease may predispose to gastric neoplasia.

Clinical signs of gastric adenocarcinoma are often insidious and nonspecific, leading to delayed diagnosis. Common signs include: (1) Chronic vomiting, which may be intermittent or progressive, often occurring hours after eating. (2) Weight loss and cachexia. (3) Anorexia or decreased appetite. (4) Melena or hematemesis due to tumor ulceration. (5) Abdominal pain or distension. (6) Lethargy and weakness. (7) Polydipsia/polyuria may occur if there is concurrent renal or metabolic derangement. In advanced stages, signs of metastasis may include respiratory distress (pulmonary metastasis), icterus (hepatic metastasis), or ascites (peritoneal carcinomatosis). Physical examination may reveal a palpable abdominal mass in some cases, but often the tumor is not palpable. Signs are typically chronic, lasting weeks to months before diagnosis.

Differential diagnoses for gastric adenocarcinoma include: (1) Gastric lymphoma: distinguished by cytology/histopathology (lymphocytic infiltrate), often more diffuse, and may respond to chemotherapy. (2) Gastric leiomyoma/leiomyosarcoma: arise from smooth muscle, often well-circumscribed, diagnosed via histopathology. (3) Gastric polyps: benign, but can be adenomatous and potentially malignant; biopsy is needed. (4) Chronic gastritis (e.g., Helicobacter-associated, lymphocytic-plasmacytic): inflammatory disease, may mimic signs, but imaging and biopsy differentiate. (5) Gastric ulceration (e.g., due to NSAIDs, stress, mast cell tumor): may cause similar signs, but endoscopy and biopsy are definitive. (6) Gastric foreign body: acute onset, imaging (radiography/ultrasound) may show foreign material. (7) Pancreatitis: causes vomiting and abdominal pain, but laboratory findings (lipase, cPLI) and imaging (ultrasound) help differentiate. (8) Inflammatory bowel disease (IBD): chronic vomiting, but biopsy shows inflammation, not neoplasia. (9) Gastric dilatation-volvulus (GDV): acute, severe, with characteristic radiographic findings. (10) Metastatic disease to the stomach (e.g., from mammary or lung carcinoma): rare, but possible.

The diagnostic approach to gastric adenocarcinoma should be systematic: (1) Complete history and physical examination, with attention to chronic vomiting, weight loss, and melena. (2) Baseline laboratory tests: CBC, serum biochemistry, urinalysis, and possibly fecal occult blood. (3) Abdominal radiographs: may show a mass effect, gastric wall thickening, or loss of serosal detail; however, sensitivity is low. (4) Abdominal ultrasound: is more sensitive, revealing gastric wall thickening, loss of layering, or a mass; also allows assessment of regional lymph nodes and metastasis. (5) Thoracic radiographs: to evaluate for pulmonary metastasis. (6) Endoscopy: is the gold standard for visualization and biopsy; multiple deep biopsies are essential, as the tumor may be submucosal. (7) Histopathology: confirms the diagnosis and differentiates from other tumors. (8) Advanced imaging (CT or MRI): may be used for surgical planning and staging. (9) Fine-needle aspiration of enlarged lymph nodes or liver for cytology. (10) If surgery is planned, abdominal exploration and biopsy of any suspicious lesions.

Laboratory findings in gastric adenocarcinoma are often nonspecific. CBC may reveal anemia (due to chronic blood loss or anemia of chronic disease), neutrophilia, or thrombocytosis. Serum biochemistry may show hypoalbuminemia (due to protein-losing enteropathy or malnutrition), elevated liver enzymes (if hepatic metastasis), and electrolyte imbalances (e.g., hypokalemia, hypochloremia, metabolic alkalosis) secondary to vomiting. Urinalysis is usually unremarkable. Fecal occult blood may be positive. Specific biomarkers such as C-reactive protein (CRP) may be elevated. In cats, feline pancreatic lipase immunoreactivity (fPLI) may be normal. There are no specific tumor markers for gastric adenocarcinoma in veterinary medicine. Histopathology is required for definitive diagnosis.

Imaging findings in gastric adenocarcinoma: (1) Abdominal radiographs: may show a soft tissue mass in the cranial abdomen, gastric wall thickening, or loss of serosal detail; however, these findings are nonspecific and often absent. (2) Abdominal ultrasound: is more sensitive, showing focal or diffuse gastric wall thickening, loss of normal wall layering, and a hypoechoic mass. The tumor may appear as an infiltrative lesion, often in the pyloric region. Regional lymphadenopathy may be detected. Ultrasound also allows guided fine-needle aspiration or biopsy. (3) Computed tomography (CT): provides detailed assessment of gastric wall thickness, local invasion, and metastasis; useful for surgical planning. (4) Endoscopy: allows direct visualization of the gastric mucosa, revealing ulceration, mass, or thickened rugae; multiple biopsies should be taken. (5) Fluoroscopy: may be used to assess gastric emptying, but is less commonly employed. (6) Thoracic radiographs: essential to rule out pulmonary metastasis.

Cytology from fine-needle aspiration of gastric masses or enlarged lymph nodes may reveal malignant epithelial cells, but the yield is often low due to the desmoplastic nature of the tumor. Histopathology is the gold standard. On biopsy, gastric adenocarcinoma shows infiltrative glands or cords of neoplastic epithelial cells, often with signet ring cells in the diffuse type. There is marked desmoplasia (fibrous tissue proliferation), and the tumor invades through the muscularis mucosae into the submucosa and muscularis externa. Special stains, such as mucicarmine, may highlight mucin production. Immunohistochemistry can be used to differentiate from lymphoma (e.g., cytokeratin positive, CD3 negative). The tumor is often poorly differentiated, and the mitotic index is variable.

Treatment of gastric adenocarcinoma is primarily surgical. Complete surgical excision (e.g., partial gastrectomy or pylorectomy) offers the best chance for long-term survival, but is often not feasible due to extensive local invasion or metastasis. In cases where surgery is not possible, palliative treatment may include: (1) Medical management of vomiting with antiemetics (e.g., maropitant 1 mg/kg IV/SC q24h, or metoclopramide 1-2 mg/kg/day CRI). (2) Gastroprotectants: proton pump inhibitors (e.g., omeprazole 0.7-1 mg/kg PO q12h) or H2 blockers (e.g., famotidine 0.5-1 mg/kg PO/IV q12h). (3) Nutritional support: feeding tubes (e.g., esophagostomy or gastrostomy) may be necessary if anorexia is severe. (4) Chemotherapy: may be attempted, but gastric adenocarcinoma is generally chemoresistant. Protocols using doxorubicin (30 mg/m² IV q3weeks) or carboplatin (300 mg/m² IV q3weeks) have been tried, but response rates are low. (5) Palliative radiation therapy: may provide temporary relief of pain or obstruction. (6) Analgesia: for pain, using opioids (e.g., buprenorphine 0.01-0.02 mg/kg IV/IM q8-12h) or NSAIDs (with caution due to GI ulceration). (7) Supportive care: fluid therapy, antiemetics, and appetite stimulants (e.g., mirtazapine 3.75 mg/cat PO q48h).

The prognosis for gastric adenocarcinoma is grave. Median survival time in dogs after surgical resection is approximately 3-6 months, with 1-year survival rates of less than 10%. Factors associated with a poorer prognosis include: presence of metastasis at diagnosis, diffuse-type histology, incomplete surgical margins, and advanced clinical stage. Cats have a similarly poor prognosis, with median survival times of 1-3 months. Palliative therapy may improve quality of life but does not significantly extend survival. Early detection and complete surgical excision offer the best chance, but this is rare due to the insidious onset of clinical signs.

Follow-up for gastric adenocarcinoma should be structured: (1) Post-operative: monitor for complications such as dehiscence, infection, or delayed gastric emptying. (2) Recheck examinations every 1-3 months for the first year, including physical examination, body weight, and owner assessment of vomiting, appetite, and energy level. (3) Serial abdominal ultrasound every 2-3 months to assess for local recurrence or metastasis. (4) Thoracic radiographs every 3-4 months to monitor for pulmonary metastasis. (5) Laboratory monitoring: CBC and serum biochemistry every 1-2 months, especially if chemotherapy is administered. (6) If chemotherapy is used, monitor for myelosuppression and gastrointestinal toxicity. (7) Adjust supportive medications as needed. (8) Consider referral to a veterinary oncologist for ongoing management.

Pearls: (1) Gastric adenocarcinoma should be suspected in older dogs with chronic vomiting and weight loss, especially in high-risk breeds. (2) Endoscopic biopsies should be deep and multiple, as the tumor may be submucosal. (3) Abdominal ultrasound is a valuable screening tool, but a normal ultrasound does not rule out gastric cancer. (4) Surgical resection, if feasible, is the only potentially curative treatment. (5) Palliative care can significantly improve quality of life. Pitfalls: (1) Delaying endoscopy due to nonspecific signs. (2) Relying on cytology alone, which may be falsely negative. (3) Underestimating the extent of disease without staging (thoracic radiographs, abdominal ultrasound). (4) Using NSAIDs in patients with gastric ulceration, which can worsen bleeding. (5) Assuming that a gastric mass is lymphoma and treating with chemotherapy without a biopsy.

Current drug protocols for gastric adenocarcinoma are primarily palliative. Antiemetics: Maropitant (Cerenia) 1 mg/kg IV/SC q24h or 2 mg/kg PO q24h; Metoclopramide 1-2 mg/kg/day as a CRI or 0.2-0.4 mg/kg PO q8h. Gastroprotectants: Omeprazole 0.7-1 mg/kg PO q12h; Famotidine 0.5-1 mg/kg PO/IV q12h; Sucralfate 0.5-1 g/dog PO q8h (administer 30 min before meals). Appetite stimulants: Mirtazapine 3.75 mg/cat PO q48h or 15-30 mg/dog PO q24h; Capromorelin (Entyce) 3 mg/kg PO q24h. Analgesics: Buprenorphine 0.01-0.02 mg/kg IV/IM q8-12h; Tramadol 2-5 mg/kg PO q8-12h (dogs). Chemotherapy: Doxorubicin 30 mg/m² IV q3weeks (dogs) or 1 mg/kg IV q3weeks (cats); Carboplatin 300 mg/m² IV q3weeks (dogs) or 200 mg/m² IV q3weeks (cats). Note: These protocols are based on Plumb's Veterinary Drug Handbook and may require dose adjustments for renal or hepatic impairment. Always monitor for adverse effects.

Evidence-based literature on gastric adenocarcinoma in dogs and cats is limited to retrospective studies and case series. A landmark study by Swann et al. (2002) reported a median survival time of 3 months in dogs with gastric adenocarcinoma treated with surgery alone. Another study by Gualtieri et al. (1999) found that complete surgical excision resulted in a median survival of 6 months, while incomplete excision or non-surgical management had a median survival of 1 month. Chemotherapy has not been shown to significantly improve survival. A recent retrospective study by Selting et al. (2019) evaluated the use of doxorubicin and carboplatin in dogs with gastric adenocarcinoma and found no significant survival benefit. Consensus guidelines from the World Small Animal Veterinary Association (WSAVA) and the Veterinary Cancer Society recommend surgical resection as the primary treatment, with palliative therapy for advanced cases. There is a need for prospective studies to evaluate novel therapeutic approaches, such as targeted therapies and immunotherapy.