Page 121 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

100 PART I The Biology and Pathogenesis of Cancer

An additional cause of PNS-associated gastroduodenal ulcer- less common. 16,37 PU/PD initially develops as a result of impaired
ation is gastrinoma, a gastrin-secreting pancreatic tumor, likely action of antidiuretic hormone (ADH) on the tubular cells of
the collecting duct. Dehydration is common. Renal damage can
arising from the islet D-cells. Although these tumors are rela-
VetBooks.ir tively rare, they have been reported in both dogs and cats. 10–13 then result from renal vasoconstriction; mineralization of renal
tubules, basement membranes, or interstitium; tubular degenera-
Zollinger–Ellison syndrome refers to the triad of hypergastrin-
37
emia, a non–beta cell neuroendocrine tumor in the pancreas, tion or necrosis; and/or interstitial fibrosis. Azotemia might or
and GI ulceration. Gastrinomas are covered in greater detail in might not be reversible depending on the contributing underlying
Chapter 26. etiologies.
Measurement of ionized calcium is more accurate than total
Endocrinologic Manifestations of Cancer calcium, and equations that correct total calcium are not recom-
42
mended. However, in both dogs and cats, serum total calcium
Hypercalcemia levels associated with HM tend to be higher compared with
other etiologies. 15,16 In dogs and cats with humoral HM that are
Cancer is diagnosed in 60% of dogs and 30% of cats with hyper- euhydrated and not azotemic, serum phosphate should be low
calcemia. 14–16 In dogs, hypercalcemia of malignancy (HM) is asso- to low-normal. When HM is suspected based on history, clini-
ciated most commonly with T-cell lymphoma (35%–55% of dogs cal signs, and baseline blood work, initial diagnostic evaluation
with T-cell lymphoma develop HM) and anal sac apocrine gland should include a physical examination including careful palpa-
adenocarcinoma (25% of dogs affected dogs develop HM). 15,17–22 tion of peripheral lymph nodes and digital rectal examination
Other reported cancers in dogs associated with HM include acute (dogs), CBC, chemistry profile, urinalysis, thoracic radiographs,
lymphoblastic leukemia, adrenal carcinoma, ameloblastoma, and abdominal ultrasound. If an underlying malignancy is not
chronic lymphocytic leukemia, clitoral adenocarcinoma, hepa- yet identified then cervical ultrasound; measurement of serum
tocellular carcinoma, nasal carcinoma, penile adenocarcinoma, PTH, PTHrP, and calcitriol levels; survey bone radiographs; and/
pulmonary carcinoma, thymoma, osteosarcoma, mammary carci- or bone marrow aspiration should be considered. Serum PTH
noma, melanoma, multiple myeloma, pheochromocytoma, renal should be low. Serum PTHrP usually is elevated, but it can be
angiomyxoma, renal cell carcinoma, thymoma, and thyroid car- normal (not detectable). Serum calcitriol typically is normal, but
cinoma. 17,23–32 In cats, HM is most commonly associated with it can be increased or decreased. 17,37,43
lymphoma, SCC, and multiple myeloma. 16,33,34 Other reported The most effective treatment for HM is removal of the underly-
HM-associated cancers in cats include fibrosarcoma, acute leuke- ing cause: surgically removing the tumor or inducing a remission
mia (including erythroleukemia), osteosarcoma, pulmonary carci- with chemotherapy or RT. Concurrent supportive care directed
noma, renal carcinoma, thyroid carcinoma, and undifferentiated specifically at the hypercalcemia (Box 5.2) should be considered
sarcoma. 16,35–37 Primary hyperparathyroidism, which usually is in patients that have a serum calcium concentration >16 mg/dL,
caused by a functional benign parathyroid adenoma or adenoma- patients with a calcium (mg/dL) times phosphate (mg/dL) prod-
tous hyperplasia, can also occur dogs and cats. 14–16 uct >60, patients that are clinically ill or azotemic, and patients
HM is most commonly caused by soluble mediators released with cancers that cannot be surgically removed and are unlikely
by the tumor cells into circulation that can then act on bone and to respond to chemotherapy or other therapies. 37,43 Intravenous
kidneys through endocrine and paracrine pathways, which is fluid therapy with 0.9% sodium chloride (NaCl) is recommended
referred to as humoral hypercalcemia of malignancy. Parathyroid first to correct existing dehydration and then to slightly volume
hormone-related protein (PTHrP) is involved most commonly. expand to increase glomerular filtration rate and the filtered load
PTHrP normally is released by fetal parathyroid glands and the of calcium. The high sodium content from 0.9% NaCl competes
placenta, where it is thought to play an important role in calcium with calcium for renal tubular absorption, further enhancing
transport across the placenta into the developing fetus, and by
mammary glands, where it acts in a paracrine fashion to assist

with mammary gland development and lactation. PTHrP also • BOX 5.2 Treatment for Hypercalcemia of
38
is expressed in a wide variety of normal canine tissues: skin, anal Malignancy
sac, thyroid gland, mammary gland, tongue, esophagus, stomach, Elimination of the inciting tumor is the primary goal for all categories of
kidney, bladder, and lung. Its function in many of these tissues hypercalcemia.
39
is not well understood. There is 70% sequence homology of the
first 13 N-terminal amino acids of PTHrP compared with PTH, Mild Hypercalcemia and Minimal Clinical Signs
which permits PTHrP to bind and activate PTH receptors on Fluid therapy with 0.9% NaCl—rehydrated with subcutaneous or
osteoblasts and renal tubular cells when released into circulation intravenous treatment
by tumor cells. 17,18,40,41
Various other cytokines can also contribute to the patho- Moderate to Severe Hypercalcemia and Clinical Signs
genesis of humoral HM, including IL-1, IL-6, TNF, and cal- Fluid therapy with 0.9% NaCl—correct dehydration over 4 to 6 hours, then
continue at 100 to 125 mL/kg/day (1½–2 times maintenance rate)
citriol. 17,18,40,41 HM can also be caused by osteolysis when tumors Furosemide (2–4 mg/kg every 8–12 hours IV, SC, or PO)
invade or metastasize to bone. Paracrine release of factors includ- Note: Only use after patient is fully rehydrated.
ing IL-1, IL-6, TNF, receptor activator of nuclear factor kappa-B Prednisone (1–2 mg/kg q12–24 h PO)
ligand (RANKL), TGF-α and -β, and prostaglandins (especially Note: Only use after diagnosis obtained (see text).
PGE ) can increase local osteoclast number and activity. 17,18,37 Pamidronate (1.0–2.0 mg/kg diluted in 250 mL of NaCl IV over 2 hours
2
In dogs, hypercalcemia is commonly associated with polyuria/ every 2–4 weeks)
polydipsia (PU/PD), anorexia, vomiting, and occasionally mus- Zoledronate (0.1–0.25 mg/kg diluted in 60 mL of NaCl IV over 15 minutes
cle weakness or twitching. In cats, hypercalcemia is most com- every 2–4 weeks)
monly associated with anorexia and vomiting; PU/PD is much