Page 606 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

584 PART IV Specific Malignancies in the Small Animal Patient

with a vessel sealing device. 428 If evidence of metastatic disease decreased significantly after administration of octreotide in dogs
is seen, especially to the liver, then as much metastatic disease with insulinoma, but GH, ACTH, cortisol, and glucagon levels
436
These findings
did not change, and glucose levels increased.
as possible should be removed. Potential postoperative com-
VetBooks.ir plications include persistent hypoglycemia, pancreatitis, and suggest that the use of octreotide warrants further investigation in
In general, hyperglycemia will be tran-
375,429
hyperglycemia.
canine patients with insulinoma, although the cost of the medica-
sient if it occurs, but a small percentage of cases require insulin tion may be a significant impediment.
therapy. 375,429 Postoperatively patients should be managed with The prognosis for dogs with insulinomas is good in the short
intravenous fluid therapy, multimodal analgesia, and antinausea term but guarded to poor in the long term. Patients that undergo
medications, and with careful monitoring of the blood glucose surgery and then medical management are more likely to become
level and for signs of pancreatitis. Any tissue removed or biop- euglycemic, remain euglycemic for longer periods, and have
sied at surgery should be submitted for histopathologic exami- longer STs compared to patients that receive only medical ther-
nation to confirm the diagnosis. 401 Limited reports exist on the apy. 387,392 MSTs after partial pancreatectomy range from 12 to
use of cytology, typically performed during preoperative patient 14 months. 435 The prognosis after surgery depends on the clini-
evaluation, to support the diagnosis of insulinoma. 401,430,431 cal stage of the disease. 375 Dogs with stage I disease have a lon-
Medical treatment of insulinoma is used to stabilize patients ger DFI compared to dogs with stages II and III disease; 50%
preoperatively, as an alternate therapy if surgery is not possible, of dogs with stage I disease are free of hypoglycemia 14 months
and in conjunction with surgical management. Medical therapies after surgery, whereas less than 20% of dogs in stage II and III
primarily are used to control hypoglycemia, but cytotoxic agents disease are free of hypoglycemia at this time. 384 Dogs with stage
also have been used to destroy pancreatic beta cells. Streptozocin III disease have a significantly shorter ST than dogs with stage I
(streptozotocin) is the chemotherapeutic drug that has been used and II disease – approximately 50% of dogs with metastasis are
most often, albeit infrequently, in dogs. Its use in dogs histori- dead by 6 months. 384 A more recent retrospective study showed an
cally was limited by its nephrotoxicity, 375 but more recent reports improved ST in dogs with insulinoma compared to earlier reports
suggest that the risk of nephrotoxicity is reduced significantly if with a median DFI and MST of 496 days and 785 days, respec-
streptozocin is administered in combination with intensive saline tively, for 19 dogs undergoing partial pancreatectomy. 392 A subset
diuresis. 432–434 Other side effects include vomiting during admin- of nine dogs treated with partial pancreatectomy and postopera-
istration, diabetes mellitus, hypoglycemia, increased liver enzyme tive prednisolone had an MST of 1316 days. For eight dogs that
activity, and mild hematologic changes. 432–434 The administration received medical therapy alone, the MST was 196 days. When
of streptozocin does not significantly increase the duration of nor- all the dogs that received medical therapy were considered as a
moglycemia in dogs with insulinoma compared with control dogs group, the MST after institution of the medical treatment was
treated medically or surgically. 432 Although individual dogs have 452 days. 392 These results lend strong support to the use of medi-
demonstrated reductions in tumor size or resolution of paraneo- cal therapy in canine patients with insulinoma, particularly when
plastic neuropathy with streptozocin, it still is unclear whether the clinical signs recur after surgery.
risks of therapy outweigh the benefits of this treatment for dogs
with insulinoma. 375,434 Beta-Cell Tumors in Cats
Strategies used to control hypoglycemia consist of dietary
modification and medical therapy with prednisone, diazoxide, or Compared to dogs, significantly fewer reports of insulinomas
octreotide. Excitement should be avoided in these patients and exist for cats. 373,437–441 History, clinical signs, and biologic
exercise limited. Diets high in fat, protein, and complex carbohy- behavior in this species appear to be similar to those in the dog,
drates should be fed in small, frequent meals, and simple sugars and concurrent measurements of blood glucose and serum insu-
should be avoided. 375 Prednisone is used for its insulin-antagoniz- lin concentrations are used to confirm the diagnosis; however,
ing, gluconeogenic, and glycogenolytic effects. 375 A starting dose it is important to use an insulin assay that has been validated
of 0.25 mg/kg by mouth (PO) twice daily is recommended, with in cats. 375 Surgical management has been reported in cats, with
gradual dose increases as needed to control hypoglycemia. 375,401 STs ranging from 1 to 32 months. Conservative therapy with
Typical glucocorticoid side effects should be anticipated. Diazox- dietary management and prednisolone also has been used in cats.
ide is a nondiuretic benzothiadiazine that suppresses insulin Octreotide may be considered, although little evidence supports
release from beta cells. It also stimulates hepatic gluconeogenesis its use, and no evidence supports the use of diazoxide or strepto-
and glycogenolysis and inhibits cellular uptake of glucose. Diazox- zotocin in this species. 375
ide is not cytotoxic and does not inhibit insulin synthesis. A start-
ing dose of 5 mg/kg PO twice daily is recommended, and the dose
can be increased gradually to 30 mg/kg daily dose ose can be ates Gastrointestinal Endocrine Tumors
hepatic glucon. 375,401 Approximately 70% of canine insulinoma Gastrinoma
patients respond to diazoxide therapy. 375,383 Adverse effects are
uncommon but may include ptyalism, vomiting, anorexia, and Gastrinomas are neuroendocrine tumors that secrete excessive
diarrhea. 375,401,435 The use of diazoxide is limited by its cost and amounts of gastrin. Zollinger-Ellison syndrome refers to the triad
inconsistent availability. 401 Octreotide is a somatostatin receptor of a non–beta-cell neuroendocrine tumor in the pancreas, hypergas-
ligand that inhibits synthesis and secretion of insulin by pancre- trinemia, and GI ulceration. Gastrinomas are rare in dogs and very
atic beta cells. It has been reported to alleviate hypoglycemia in rare in cats. 442,443 Almost all reported gastrinomas in these species
up to 50% of dogs with insulinoma, although some may become were identified in the pancreas, although one report exists of a duo-
refractory to treatment. 375,388 The suggested dose is 10 to 50 μg denal gastrinoma in a dog. 444 Gastrinomas are highly metastatic,
SQ 2 or 3 times daily, and side effects appear to be rare. In a with involvement of the liver, regional lymph nodes, spleen, perito-
more recent study a single 50 μg dose of octreotide was adminis- neum, small intestine, omentum, or mesentery identified in 85% of
tered to 12 dogs with insulinoma. Plasma insulin concentrations dogs and cats at the time of initial diagnosis. 442,443,445–447