Page 119 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

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Paraneoplastic Syndromes

DENNIS B. BAILEY

Paraneoplastic syndromes (PNSs) are cancer-associated alterations The exact diagnostic criteria for cancer cachexia continue to
in bodily structure and/or function that are not directly related be debated, but moderate to severe weight loss is reported in
4,5
to the physical effects of the primary or metastatic tumor. PNSs 30% to 70% of people with various cancers. Having said this,
are most commonly caused by tumor production of small mol- 40% to 60% of people are overweight or obese at the time of
ecules (e.g., hormones, cytokines, or peptides) that are released cancer diagnosis, and fewer than 10% have obvious malnutri-
4
into circulation, tumor depletion of normal small molecules, or tion. Therefore evidence of cachexia and sarcopenia was preva-
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host responses to the tumor (often immune mediated). 1 lent across all body mass index (BMI) categories. Similarly,
Many PNSs parallel the underlying malignancy, and success- when body condition score (BCS) and weight loss were evaluated
ful treatment of the tumor leads to disappearance of the PNS. in dogs with various malignancies, 29% were classified as mark-
Conversely, recurrence of the PNS after successful treatment can edly overweight (BCS ≥7), and only 4% were classified as emaci-
signal tumor recurrence and might even precede clinically detect- ated (BCS ≤3). However, muscle wasting was identified in 35%
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able tumor. Some PNSs do not consistently resolve with treatment of these dogs, and over the 12 months before cancer diagnosis,
of the underlying malignancy, especially cancer cachexia and those 14% of these dogs had lost 5% to 10% of body weight and 23%
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of an immune or neurologic etiology. 1 had lost >10% of body weight. When BCS and muscle wasting
A PNS might be the first sign of malignancy, and a specific PNS were evaluated in cats presenting with various cancers, 44% had
often is associated with a relatively small group of tumor types. a BCS <5, although it is worth noting that a high percentage of
Therefore an understanding of PNSs is paramount for early cancer these cats were diagnosed with gastrointestinal lymphoma or oral
detection and appropriate therapy. In addition, a PNS may result squamous cell carcinoma (SCC), tumor types in which difficulty
in greater morbidity than that associated with the actual tumor. with food intake or absorption may have been the primary causes
Therapy directed at the PNS might be warranted, especially when for weight loss. Muscle wasting was identified in 93% of cats,
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there is substantial morbidity and/or the underlying cancer can- including 72% of cats with a BCS ≥5. Across tumor types, low
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not be effectively treated. Box 5.1 summarizes the most common body weight and low BCS were negative prognostic factors for
PNSs of dogs and cats and the tumors associated with them. survival. 7
For a detailed discussion regarding the metabolic alterations
Gastrointestinal Manifestations of Cancer associated with cancer and nutritional support for veterinary can-
cer patients, the reader is directed to Chapter 16, Section B.
Cancer Anorexia and Cachexia
Gastrointestinal Ulceration
Several mechanisms contribute to weight loss in cancer patients.
Hyporexia or anorexia is common in veterinary patients with Mast cell tumors (MCTs) are the most common cause of PNS-
advanced cancers, often a result of an enhanced inflammatory state associated gastrointestinal (GI) ulceration. Hyperhistaminemia
and cytokines such as interleukin-1 (IL-1) and IL-6 interfering is regarded as a main factor contributing to GI ulceration and
2
with the normal balance of anorexigenic and orexigenic signals. perforation. Histamine binds to gastric parietal cell H recep-
8,9
2
Cancer cachexia is a profound destructive process characterized by tors, stimulating gastric acid secretion. In addition, histamine
skeletal muscle wasting, with or without loss of fat mass, and harm- exerts direct effects on the gastric mucosa, causing increased vas-
ful abnormalities in fat and carbohydrate metabolism in spite of cular permeability, localized protein exudation, and increased
adequate nutrient intake. Tumor necrosis factor-alpha (TNF-α), mucosal blood flow. Histamine release can be spontaneous, or it
8
2,3
IL-1, and IL-6 play primary roles in cancer cachexia by induc- can be triggered by tumor manipulation, chemotherapy, or radia-
ing anorexia, increasing energy metabolism, and accelerating tion therapy (RT). Plasma histamine concentrations are elevated
2
loss of lean body mass. This results in large part from activation in dogs with macroscopic MCTs, although concentrations are
8,9
of nuclear factor kappa-B (NF-κB), which in turn activates the not predictive of clinical signs of GI ulceration. Symptomatic
ubiquitin proteasome pathway. TNF-α, via NF-κB signaling, therapies such as histamine H blockers, proton-pump inhibitors,
2
also upregulates myostatin, a member of the transforming growth misoprostol, sucralfate, and rehydration are warranted in dogs
factor-beta (TGF-β) superfamily that negatively regulates muscle and cats with clinical signs of GI ulceration or prophylactically in
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mass. TNF-α also interferes with the anabolic effects of growth patients with advanced-stage tumors. MCTs are covered in greater
hormone (GH) and insulin-like growth factor-1 (IGF-1). 2 detail in Chapter 21.
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