Riccardo Finotello

Prognostic factors for dogs with mammary inflammatory carcinoma: 43 cases (2003–2008)

OBJECTIVE To describe clinical characteristics, treatment, and outcome of dogs with inflammatory carcinoma (IC) and identify patient-, tumor-, and treatment-related factors associated with overall survival time. DESIGN Retrospective case series. ANIMALS 43 client-owned dogs. PROCEDURES Records of dogs with a clinical diagnosis of IC that had histologic evidence of dermal lymphatic invasion were reviewed. Data on clinical staging, treatment, toxicoses, response, and survival time were retrieved. Results-26 (60%) dogs had primary IC and 17 (40%) had secondary IC. Thirty-five (81%) dogs had distant metastases and 2 (5%) had local metastases at the time of initial examination. Six of 29 (21%) dogs had a coagulopathy. Sixteen (37%) dogs did not receive specific treatment for IC, 24 (56%) received medical treatment only, 2 (5%) underwent surgical excision and received medical treatment, and 1 (2%) underwent surgical excision only. Forty-one (95%) dogs had progressive disease, and 2 (5%) had stable disease. Mean survival time for all dogs was 60 days (range, 1 to 300 days). Dogs with a coagulopathy survived a significantly shorter time than did dogs without a coagulopathy (odds ratio, 0.28), and dogs that received medical treatment survived significantly longer than dogs that did not (odds ratio, 2.54). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that mammary IC is a biologically aggressive condition in dogs associated with a guarded prognosis. In addition, results suggested that medical treatment may improve outcome, thereby supporting its use in dogs with IC.

Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous mast cell tumors: 386 cases (2009–2014)

OBJECTIVE To compare the Kiupel (2 categories) and Patnaik (3 categories) histologic grading systems for predicting the presence of metastasis at the time of initial examination in dogs with cutaneous mast cell tumors (MCTs). DESIGN Retrospective case series. ANIMALS 386 client-owned dogs with cutaneous MCTs. PROCEDURES Medical records of dogs with newly diagnosed, histologically confirmed cutaneous MCTs that had undergone complete clinical staging were reviewed for clinical and histopathologic data. RESULTS All Patnaik grade 1 MCTs (n = 52) were classified as Kiupel low-grade MCTs, and all Patnaik grade 3 MCTs (43) were classified as Kiupel high-grade MCTs. Of the 291 Patnaik grade 2 MCTs, 243 (83.5%) were classified as Kiupel low-grade tumors, and 48 (16.5%) were classified as Kiupel high-grade MCTs. Dogs with Patnaik grade 3 MCTs were significantly more likely to have metastases at the time of initial examination than were dogs with grade 1 or 2 MCTs (OR, 5.46), and dogs with Kiupel high-grade MCTs were significantly more likely to have metastases than were dogs with Kiupel low-grade MCTs (OR, 2.54). However, 3 of 52 (5.8%) dogs with Patnaik grade 1 tumors, 48 of 291 (16.5%) dogs with Patnaik grade 2 tumors, and 44 of 295 (14.9%) dogs with Kiupel low-grade tumors had metastatic disease. CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that in dogs with cutaneous MCTs, prognostication should not rely on histologic grade alone, regardless of grading system used, but should take into account results of clinical staging.

First-line metronomic chemotherapy in a metastatic model of spontaneous canine tumours: a pilot study

Metronomic chemotherapy—the low-dose, long term and frequently administered chemotherapy—has revealed in these years an important impact on the stabilization of cancer disease for its known antiangiogenic effects, prolonged clinical benefits and the improved quality of life of several cancer patients, without any high grade toxicity [1–3]. Both the low cost and the oral administration of the drugs are key characteristics of this schedule and may offer important social advantages [4]. Anecdotical case reports [5–7] and experiences in small subsets of patients enrolled in retrospective clinical studies [8–10] on metastatic cancers have been recently published about the use of metronomic therapy as a first-line treatment. These point out the possible importance of metronomic chemotherapy as an alternative approach to first-line therapy in frail patients requiring palliation or patients refusing the standard chemotherapy for its impact on the quality of life. However, no data of prospective clinical trials on first line metronomic chemotherapy are currently available in metastatic cancer human patients. The veterinary medical oncology has advanced dramatically over the past few decades, because of the successful application of a number of conventional chemotherapeutic drugs to the cancer conditions diagnosed in veterinary patients [11]. Veterinary oncology cases often present a unique opportunity to investigate novel drugs and treatment schedules providing many in vivo information to the larger medical community and giving new effective options for dogs themselves [12]. As well recently pointed out by Paoloni and Khanna [13], these studies may also have a great translational relevance, predicting new therapies and related surrogate markers in human beings because pet dogs with cancers might assist the transition between mouse models and human patients. Moreover, in the clinical practice, veterinarians and their clients are generally less willing to accept a high degree of side effects, which most often results in lower drug doses than the ones that are used in human oncology. The aim of the present pilot study was to test a first-line metronomic oral combination of cyclophosphamide (CTX) and celecoxib (CXB) in canine metastatic spontaneous tumours, characterizing possible biomarkers to translate in human clinical research.

Gastrointestinal Parasites in Mammals of Two Italian Zoological Gardens

Abstract The prevalence of gastrointestinal parasites was investigated in mammals housed in two of the main Italian zoological gardens: the Zoo Safari of Fasano (province of Bindisi, Apulia, Italy) and the Giardino Zoologico of Pistoia (Tuscany, Italy). In November 2007, fecal samples were collected at the Zoo Safari of Fasano (n  =  96) and at the Giardino Zoologico of Pistoia (n  =  60), from primates, carnivores, perissodactyls, artiodactyls and proboscideans. In most of the cases, the same animal species or genera were considered in both the zoos. One or more intestinal parasites were detected in 61.5% of the examined samples. However, very different percentages of protozoa- and helminth-positive samples were obtained in the animals from the two zoos, with an overall gastrointestinal parasitic infection of 77.1% in the Zoo Safari of Fasano and 36.7% in the Giardino Zoologico of Pistoia. Overall, 10% (Cryptosporidium sp.) and 43.3% (Toxocara cati, Strongyloides stercoralis, Toxascaris leonina, and hookworms) of carnivores, 66.7% (Cryptosporidium spp.) and 100% (Trichuris spp. and Strongyloides fülleborni) of primates, 25.0% (Eimeria spp., Cryptosporidium spp.), and 57.1% (Trichuris sp., Toxocara [Neoascaris] vitulorum, gastrointestinal strongyles, and Paramphistomidae) of artiodactyls were infected with protozoa and helminthes parasites, respectively. Only gastrointestinal strongyles were diagnosed in 16.7% of proboscideans and in 50.0% of perissodactyls examined. The results of this study suggest that zoonotic protozoans and gastrointestinal helminths are common in zoo mammals and that these animals may serve as a potential reservoir and transmit these parasites to humans. The different animal management in the two zoos indicates that the regular monitoring of parasitic diseases and the use of selective treatments can represent effective measures for the control of several gastrointestinal infections in zoological gardens.

Clinical relevance of serial determinations of lactate dehydrogenase activity used to predict recurrence in dogs with lymphoma

OBJECTIVE To evaluate whether serial determinations of serum lactate dehydrogenase (LDH) activity in dogs with lymphoma could be used to predict outcome and assist in early recognition of disease progression. DESIGN Prospective cohort study. ANIMALS 50 dogs with lymphoma. PROCEDURES LDH activity was determined in dogs with newly diagnosed lymphoma or that had not received treatment. The LDH activity was measured at time of initial diagnosis, at completion of chemotherapy, and at 1, 3, and 6 months after chemotherapy. Treatment response and recurrence were recorded. At the end of chemotherapy and at each time point thereafter, the proportion of dogs in complete remission with elevated LDH activity was compared between dogs that did or did not have recurrence within the successive 45 or 90 days. Use of the LDH activity at admission to predict disease-free and survival intervals was evaluated. RESULTS The proportion of dogs in complete remission with increased LDH activity at completion of chemotherapy and at 1 month after chemotherapy with recurrence during the successive 45 days was significantly higher (3/9 and 7/9 dogs, respectively) than the proportion of dogs without recurrence (0/32 and 1/26 dogs, respectively). At 3 or 6 months, only 1 dog without recurrence within 45 days had increased LDH activity. Increased LDH activity at time of diagnosis was not associated with disease-free and survival intervals. CONCLUSIONS AND CLINICAL RELEVANCE Determination of LDH activity may help with identifying episodes of recurrence in dogs with lymphoma. Anticipation of recurrence is an appropriate reason to begin rescue treatment.

Serum lactate dehydrogenase activity in canine malignancies

Lactate dehydrogenase (LDH) is commonly used in human cancer patients for prognostic purposes. Aim of this study was to determine the magnitude of serum LDH elevation in dogs with cancer compared with healthy dogs and dogs with non-neoplastic disease, and to verify whether it may support the diagnosis of specific malignancies. About 128 healthy dogs, 211 diseased dogs and 188 cancer dogs were enrolled. Dogs with cancer had significantly higher LDH than diseased (P < 0.001) and healthy dogs (P < 0.001), but large overlap was found. Dogs with lymphoma showed significantly higher LDH compared with dogs with carcinoma (P < 0.001) or mast cell tumour (MCT; P < 0.05) but not compared with other malignancies. When considering lymphoma and MCT, LDH levels were not different between early and advanced clinical stages. Measuring LDH levels may not be useful as a screening tool for cancer detection. More studies are needed to define its role in specific tumours.

Redox status evaluation in dogs affected by mast cell tumour.

Oxidative stress status has been evaluated in depth in human medicine and its role in carcinogenesis has been clearly established. The purpose of this prospective study was to evaluate antioxidant concentrations and oxidative stress in dogs with mast cell tumours (MCTs) that had received no previous treatments, and to compare them to healthy controls. In 23 dogs with mast cell tumour and 10 healthy controls, oxidative status was assessed using the Reactive Oxygen Metabolites-derived compounds (d-ROMs) test, antioxidant activity was measured by the Biological Antioxidant Potential (BAP) test, and α-tocopherol levels were evaluated using high-performance liquid chromatography and ultraviolet analysis. At baseline, dogs with MCT had significantly higher d-ROMs (P < 0.00001) and lower BAP (P < 0.0002) compared with healthy controls. However, no significant difference was observed for α-tocopherol (P = 0.95). Results suggest that oxidative stress pattern and oxidative defence barrier are altered in dogs with newly diagnosed MCT compared with control dogs. Future studies are needed in order to assess the prognostic role of oxidative stress and to evaluate the impact of different therapeutic approaches.

A retrospective analysis of chemotherapy switch suggests improved outcome in surgically removed, biologically aggressive canine haemangiosarcoma†

Haemangiosarcoma (HSA) has an aggressive biological behaviour and carries a poor prognosis, with less than 10% of treated dogs surviving longer than 1 year. In this retrospective study a varied metronomic chemotherapy (MC) regimen preceded by adjuvant doxorubicin-based maximum-tolerated dose chemotherapy (MTDC) was compared with MTDC, in terms of efficacy [time to metastasis, (TTM) and survival time (ST)] and safety in dogs with biologically aggressive HSA. Dogs were eligible if they had no metastasis after MTDC and received either no further chemotherapy or MC maintenance. Twelve dogs received MTDC, and 10 received MC thereafter. Median TTM and ST were significantly longer for dogs receiving MTDC-MC (not reached versus 150 days, P = 0.028; and not reached versus 168 days, P = 0.030, respectively). Treatment was well tolerated. MTDC followed by MC is safe and suggests improved TTM and ST in dogs with surgically removed, biologically aggressive HSA that are treated in the microscopic setting.

Preliminary report on the expression of leptin and leptin receptor (ObR) in normal, hyperplastic and neoplastic canine mammary tissues.

Leptin and its receptor (ObR) expression were investigated by immunohistochemistry in normal, hyperplastic and neoplastic canine mammary tissues and related to clinical-pathological features. Leptin expression was detected in healthy mammary tissues, adenosis and in benign mammary tumours and was lower in ductal hyperplasias and malignant tumours. A high percentage of ObR-positive cells were present in adenosis, benign tumours and in complex carcinomas, while ObR expression was lower in healthy mammary tissues, in ductal hyperplasias and in a large part of invasive mammary carcinomas. Our data demonstrated that cancer cells expressed at low level leptin and ObR in canine mammary tumours with a more aggressive behaviour, as well as in lymph node metastases. Consequently, leptin and ObR expressions in this species resulted to be not associated with a reduced overall survival.

Comparison of doxorubicin–cyclophosphamide with doxorubicin–dacarbazine for the adjuvant treatment of canine hemangiosarcoma

Canine hemangiosarcoma (HSA) is a neoplasm of vascular endothelial origin that has an aggressive biological behaviour, with less than 10% of dogs alive at 12-months postdiagnosis. Treatment of choice consists of surgery followed by adjuvant doxorubicin-based chemotherapy. We prospectively compared adjuvant doxorubicin and dacarbazine (ADTIC) to a traditional doxorubicin and cyclophosphamide (AC) treatment, aiming at determining safety and assessing whether this regimen prolongs survival and time to metastasis (TTM). Twenty-seven dogs were enrolled; following staging work-up, 18 were treated with AC and 9 with ADTIC. Median TTM and survival time were longer for dogs treated with ADTIC compared with those receiving AC (>550 versus 112 days, P = 0.021 and >550 versus 142 days, P = 0.011, respectively). Both protocols were well tolerated, without need for dose reduction or increased interval between treatments. A protocol consisting of combined doxorubicin and dacarbazine is safe in dogs with HSA and prolongs TTM and survival time.