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The aim of this work was to evaluate the possible beneficial effects of a nutraceutical diet on a careless dermal melanoma in an elderly dog. Hemato-biochemical and metabolic parameters as well as clinical symptoms evaluations were performed to monitor the possible improvements of the clinical picture of the dog following a nutraceutical diet supplementation. Hemato-biochemical analyzes and clinical symptoms before nutraceutical diet and after specific diet suspension showed an overall improvement. Moreover, no strong evidence of metastasis after radiographic investigations was observed. This study suggests that clinical status and quality of life (QoL) of an elderly dog affected by dermal melanoma can be positively influenced by a nutraceutical diet supplementation.
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Intern J Appl Res Vet Med • Vol. 16, No. 2, 2018. 117
KEY WORDS: dermal melanoma,
nutraceutical diet, median survival time,
QoL, elderly dog
ABSTRACT
The aim of this work was to evaluate the
possible benecial effects of a nutraceuti-
cal diet on a careless dermal melanoma in
an elderly dog. Hemato-biochemical and
metabolic parameters as well as clinical
symptoms evaluations were performed
to monitor the possible improvements of
the clinical picture of the dog following a
nutraceutical diet supplementation. Hemato-
biochemical analyzes and clinical symptoms
before nutraceutical diet and after specic
diet suspension showed an overall improve-
ment. Moreover, no strong evidence of
metastasis after radiographic investigations
was observed.
This study suggests that clinical sta-
tus and quality of life (QoL) of an elderly
dog affected by dermal melanoma can be
positively inuenced by a nutraceutical diet
supplementation.
INTRODUCTION
Among canine skin tumors, cutaneous mela-
nomas represent 0.8–2%.1 Multiple factors
affect biological behavior and prognosis of
the melanomas such as:
• tumor site,2
• the mitotic index (three or more mitotic
gures per 10 high-powered elds indi-
cate malignancy),3
• degree of pigmentation,
• necrosis,
• ulceration,
• inammation presence2
Most of cutaneous melanomas in dogs
are benign, with a low mortality rate com-
pared with those occurring in other districts
such as eye, feet/digit and mucosa.4,5 Digit
melanomas have an intermediate progno-
sis and are generally benign. However, an
A Case of Canine Dermal Melanoma: A
Nutraceutical Approach
Sergio Canello1
Gianandrea Guidetti2
Alessandro Di Cerbo3*
Raffaella Cocco4
1Forza10 USA Corp., Research and Development Department, Orlando,
6450 Kingspointe Pkwy Orlando Fl 32819, USA; E-mail.sergio@forza10usa.com,
2Research and Development Department, SANYpet S.p.a., 35023 Bagnoli di Sopra,
Padua, Italy; E-mail. Gianandrea@forza10.com
3Department of Medical, Oral and Biotechnological Sciences, Dental School,
University G. d`Annunzio of Chieti-Pescara, Chieti, Italy; E-mail Alessandro811@hotmail.it
4Department of Veterinary Medicine, Pathology and Veterinary Clinic Section,
University of Sassari, 07100 Sassari, Italy; E-mail. Rafco@uniss.it
(*) Corresponding author: Alessandro Di Cerbo,
Department of Medical, Oral and Biotechnological Sciences, Dental School,
University G. D`Annunzio of Chieti-Pescara, Chieti, Italy;
E-mail. alessandro811@hotmail.it; Ph. +393923731318
Vol. 16, No.2, 2018 • Intern J Appl Res Vet Med.
118
epidemiologic survey from Spangler et al
(2006) revealed that feet melanomas have
a diagnosis of malignancy in 74% of the
cases, a recurrence or possibility to metas-
tasize of 38% and a median survival time of
158 days.
Elective treatments for melanomas are
surgical excision or systemic chemotherapy.6
However, molecular targeted therapies, e.g,
receptor tyrosine kinase (RTK) inhibitors,7
IFN-α 8, and cancer vaccines 9,10 have gained
great attention.
To the best of our knowledge, this is the
rst case of an elderly dog treated with a
commercially available nutraceutical diet for
a right hind paw malignant melanoma. The
nutraceutical diet consisted in a commercial
mixed formula based on sh proteins, rice
carbohydrates, Cucumis melo, Ascophyllum
nodosum, Hematococcus pluvialis, Aloe
vera, Carica papaya, Punica granatum,
Camellia sinensis, Polygonum cuspida-
tum, Curcuma longa, Piper nigrum, zinc,
and a Omega3/6 ratio of 1:0.8, which was
already proven to signicantly decrease
type 1 helper T lymphocyte (Th1) cells and
increase T regulatory (Treg) cells in dogs
affected by Leishmania infantum11, signi-
cantly improve clinical signs and symptoms
of canine keratoconjunctivitis sicca 12 and
exert a signicant anti-inammatory activity
in vitro.13
CASE PRESENTATION
On September 2014, a 13-years-old male
mixed breed dog presented to the veterinary
Hospital of the University of Sassari for
treatment of asthenia, increased weight, and
appetite loss.
Physical examination revealed bright-
ness, poor responsiveness and altered vital
parameters (T = 37.6 °C, P = 65 bpm, RR =
18 brpm). A 17 cm, haired mass raised over
the dog’s right hind paw was noted (Figure
1).
A biopsy revealed malignant mela-
noma with approximately 3 mitoses per
10 high-powered elds (HPF). Generally,
mucocutaneous junctions and glabrous skin
lesions refer to malignant forms, while the
others are considered as benign. In this case
the presence of atypical pleomorphic nuclei
(multiple nucleoli) lay for a malignant form
despite the low proliferative activity (Figure
2). The work-up for the dog also included
hemato-biochemical and metabolic analysis,
three-view thoracic radiographs, and ab-
dominal ultrasound in order to obtain a base-
line health status on the dog. Initial blood
exam and serum proteins electrophoresis
evidenced a slight lymphopenia (19.4%, ref.
val. 25-50%) and an alfa2 and beta2 frac-
Figure 1. Clinical pictures of right hind paw melanoma. (a) A 17 cm haired, stiff and homoge-
neous mass before and (B) after (13 cm) 2 months of nutraceutical treatment.
Intern J Appl Res Vet Med • Vol. 16, No. 2, 2018. 119
tions increase (16.4%, ref. val. 7.9-13.0%;
36.3%, ref. val. 11.5 - 23.2%; respectively).
None of the metabolic prole parameters
resulted altered.
In spite of the need for surgical excision
of the mass to reduce the risk of metastasis,
the advanced age, the low survival rate after
a surgical intervention, and the previous un-
successful pharmacological treatments come
out in favor of a nutraceutical approach.
After 1 month of nutraceutical diet
administration, a normalization of lympho-
cytes was observed, while the alfa2 and
beta2 fractions increase still persisted.
The same trend was observed after 3
months of nutraceutical diet supplementa-
tion. After 5 months, the metabolic prole
showed a total bilirubin and CPK increase
(1.18 mg/dl, ref. val. 0.11- 0.31 mg/dl; 279
U/l, ref. val. 42-155 U/l; respectively),
while a decrease of alfa1 (2.2%, ref. val.
2.6 - 4.5%) and an increase in alfa2, beta,
and gamma were observed (14.0, ref. val.
7.9 - 13.0; 33.0%, ref. val. 11.5 - 23.2% and
14.6%, ref. val. 6.5 - 14.0%; respectively).
Due to the reduced metabolic require-
ments of the dog, the nutraceutical diet was
suspended and a specic diet for elderly
dogs was administered. A further increase
of CPK, creatinine, P, GOT, and Mg was
observed (540 U/l, ref. val. 42-155 U/l; 1.69
mg/dl ref. val. 0.8- 1.42 mg/dl; 11.3 mg/dl,
ref. val. 2- 3.5 mg/dl; 82 U/l ref. val. 21-44
U/l; 2.35 mg/dl ref. val. 0.67-0.94 mg/dl;
respectively). Hence, the diet was suspended
and the nutraceutical diet reintroduced. After
3 months CPK, creatinine, P, GOT, and Mg
resulted decreased within normal range.
The three-view radiographs were clini-
cally normal and negative for metastasis.
The abdominal ultrasound revealed a dif-
fusely, mildly enlarged spleen with normal
echogenicity. Based on these ndings,
there was no strong evidence of metastasis
and overall the dog appeared to be in good
health.
Figure 2. Photomicrograph of right hind paw melanoma. Presence of atypical pleomorphic
nuclei (multiple nucleoli) at different magnications (a-b) 4x, (c) 10x, (d) 20x.
Vol. 16, No.2, 2018 • Intern J Appl Res Vet Med.
120
Physical exams and diagnostic tests were
also repeated 6, 12 and 24 months since
nutraceutical diet supplementation begin.
Unfortunately, after 26 months since
nutraceutical diet supplementation, the dog
died due to a rapid worsening of clinical
picture.
DISCUSSION
The initial lymphopenia might be ascribed to
the right hind paw lesion. In fact, it is typical
of an acute inammatory status or infec-
tions, mostly viral. The metabolic prole did
not evidence any alteration. Therefore, the
appetite loss, the consequent slimming and
asthenia, as well as the breath frequency in-
crease might be the consequence of the pain/
complaint derived by the lesion. Physical
exam did not show any alteration of the car-
diocirculatory and respiratory system. Also,
the increase of alfa2 globulins might be
referred to the presence of the lesion, while
the increase of beta globulins was linked to
the overall inammatory status.
The signicant reduction of the lesion
dimensions (~24%) was a clear evidence of
the anti-inammatory activity exerted by the
nutraceutical diet 14,15, as well as the normal-
ization of the blood exam and appetite. After
5 months, the reduction of blood cells count
and hemoglobin and the increase of bilirubin
addressed toward the diagnosis of hemolytic
anemia.
The metabolic parameters variations led
to a suspension of the nutraceutical diet due
to its metabolizable energy content, which
was higher with respect to that recommend-
ed for an elderly dog. The new hemato-
biochemical analyzes revealed the onset of a
kidney insufciency, preannounced by clini-
cal symptoms such as appetite loss, polyuria,
and polydipsia. Therefore, the nutraceutical
diet was reintroduced. After 3 months, all
hematological parameters resulted improved
along with clinical symptoms, thus demon-
strating the good tolerability of the diet de-
spite the high metabolizable energy content.
In conclusion, the introduction of a
nutraceutical diet resulted particularly effec-
tive in extending the median survival time
of an elderly dog right hind paw melanoma,
improving the hematological parameters and
related clinical symptoms and consequently
the QoL.
STATEMENT OF AUTHORSHIP
The authors hereby certify that all work con-
tained in this article is original. The authors
claim full responsibility for the contents of
the article.
CONFLICT-OF-INTEREST STATEMENT
The authors certify that there is no conict
of interest with any nancial organization
regarding the material discussed in the
manuscript. This research was performed
in collaboration with some scientists from
the Division of Research and Development,
Sanypet SpA, Padua, Italy (as indicated in
the Author’s afliation) according to scien-
tic and ethical principles of the scientic
community.
REFERENCES
1. Conroy JD. Canine skin tumours. J Am Anim Hosp
Assoc. 1983;19:91–114.
2. Liu W, Bennett M, Helm T. Canine melanoma: a
comparison with human pigmented epithelioid
melanocytoma. Int J Dermatol. 2011;50(12):1542-
1545.
3. Goldschmidt MH. Histological Classication of
Epithelial and Melanocytic Tumors of the Skin
of Domestic Animals. Armed Forces Institute of
Pathology; 1998.
4. Bosenberg M, Arnheiter H, Kelsh R. Melanoma in
mankind’s best friend. Pigment Cell Melanoma
Res. 2014;27(1):1.
5. Spangler WL, Kass PH. The histologic and epi-
demiologic bases for prognostic considerations
in canine melanocytic neoplasia. Vet Pathol.
2006;43(2):136-149.
6. Bongiovanni L, D’Andrea A, Porcellato I, et al. Ca-
nine cutaneous melanocytic tumours: signicance
of beta-catenin and survivin immunohistochemical
expression. Vet Dermatol. 2015;26(4):270-e259.
7. Martin PD, Argyle DJ. Advances in the management
of skin cancer. Vet Dermatol. 2013;24(1):173-180
e138.
8. Kruth SA. Biological response modiers: interfer-
ons, interleukins, recombinant products, liposomal
products. Vet Clin North Am Small Anim Pract.
1998;28(2):269-295.
9. Milner RJ, Salute M, Crawford C, Abbot JR, Farese
J. The immune response to disialoganglioside GD3
vaccination in normal dogs: a melanoma surface
antigen vaccine. Vet Immunol Immunopathol.
2006;114(3-4):273-284.
Intern J Appl Res Vet Med • Vol. 16, No. 2, 2018. 121
10. Chapman PB, Wu D, Ragupathi G, et al. Sequential
immunization of melanoma patients with GD3
ganglioside vaccine and anti-idiotypic monoclo-
nal antibody that mimics GD3 ganglioside. Clin
Cancer Res. 2004;10(14):4717-4723.
11. Cortese L, Annunziatella M, Palatucci AT, et al. An
immune-modulating diet increases the regulatory T
cells and reduces T helper 1 inammatory response
in Leishmaniosis affected dogs treated with stan-
dard therapy. BMC Vet Res. 2015;11(1):295.
12. Destefanis S, Giretto D, Muscolo MC, et al. Clini-
cal evaluation of a nutraceutical diet as an adjuvant
to pharmacological treatment in dogs affected
by Keratoconjunctivitis sicca. BMC Vet Res.
2016;12(1):214.
13. Guidetti G, Di Cerbo A, Giovazzino A, et al. In
Vitro Effects of Some Botanicals with Anti-In-
ammatory and Antitoxic Activity. J Immunol Res.
2016;2016:5457010.
14. Di Cerbo A, Centenaro S, Beribe F, et al. Clinical
evaluation of an antiinammatory and antioxidant
diet effect in 30 dogs affected by chronic otitis
externa: preliminary results. Vet Res Commun.
2016;40(1):29-38.
15. Di Cerbo A, Morales-Medina JC, Palmieri B, et al.
Functional foods in pet nutrition: Focus on dogs
and cats. Res Vet Sci. 2017;112:161-166.
... Blood fatty acid composition could be used as a biomarker of dietary intake and could be an important parameter to understand the relationship between diet, metabolism, and some diseases. Some fatty acids (FA), such as polyunsaturated fatty acids (PUFA), have a potential role in the prevention of several diseases, such as atherosclerosis, cancer, and inflammation [1][2][3][4][5][6][7][8]. A positive correlation between the total content of dietary PUFA in the diet and the relative amount of PUFA in the blood lipid fraction has been documented in humans [9,10] and animals [11]. ...
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