Canine follicular cell and medullary thyroid carcinomas: Immunohistochemical characterization.

Research on modulation of iodine uptake by thyroid cells could help improve radioiodine treatment of dogs with thyroid tumors. The aim of this study was to characterize the immunohistochemical expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), vimentin, and Ki-67 in follicular cell thyroid carcinomas (FTCs) and medullary thyroid carcinomas (MTCs), and to compare protein expression between FTC causing hyperthyroidism and FTC of euthyroid dogs. Immunohistochemistry was performed in 25 FTCs (9 follicular, 8 follicular-compact, and 8 compact) and 8 MTCs. FTCs and MTCs were positive for TTF-1, and expression was higher in FTCs of euthyroid dogs compared with FTCs of hyperthyroid dogs (P= .041). Immunolabeling for thyroglobulin was higher in follicular and follicular-compact FTCs compared with compact FTCs (P = .001), while vimentin expression was higher in follicular-compact FTCs compared with follicular FTCs (P = .011). The expression of TSHR, NIS, pendrin, and TPO was not significantly different among the different subtypes of FTCs or between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. TSHR, NIS, pendrin, and TPO were also expressed in MTCs. Ki-67 labeling index was comparable between FTCs and MTCs, and between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. Proteins of iodine transport were also expressed in canine MTCs, which could have implications for diagnosis and treatment. The different expression of thyroglobulin and vimentin between FTC histological subtypes could reflect variations in tumor differentiation.

Eyelid and conjunctival mast cell tumors: A retrospective study of 26 dogs and 8 cats.

OBJECTIVE: The objective of the study was to describe clinical and histologic characteristics of eyelid (LMCT) and conjunctival (CMCT) mast cell tumors in dogs and cats presented to a referral clinic in Germany. ANIMAL STUDIED: Medical records were reviewed to identify dogs and cats diagnosed with LMCTs or CMCTs between 2006 and 2020. RESULTS: LMCT were diagnosed in 31 patients and were cutaneous (n = 28; 20 dogs and 8 cats) or subcutaneous (three dogs). Five cases involved the mucocutaneous junction (four dogs, one cat). CMCTs occurred only in dogs (n = 3). At the time of presentation two of the four canine LMCT cases involving the mucocutaneous junction had metastasized to a mandibular lymph node. When applying the Kiupel system, both these cases were categorized as high grade. 85.7% (18/21) of the canine (19 cutaneous and 2 subcutaneous) LMCT and all CMCT cases were categorized as Kiupel low grade. No local recurrences occurred in all LMCT cases in which clean surgical margins were obtained (n = 18, mean surgical margin width: dogs 9.4 mm, cats 3.8 mm). Two cats (2/4) and four dogs (4/7) with questionable or incomplete surgical margins experienced local recurrences (mean time to recurrence of 180 and 637 days in dogs and cats, respectively). CONCLUSION: Recurrence of low-grade LMCTs and CMCTs following excision with clean margins is rare. Tumors involving the mucocutaneous junction may be of higher grade and prone to lymphatic metastasis.

Outcomes and clinical features associated with surgically excised canine salivary gland carcinoma: A multi-institutional, retrospective, Veterinary Society of Surgical Oncology study.

OBJECTIVE: The objective of this study was to describe the clinical features, prognostic factors, and outcomes in dogs with surgically treated salivary gland carcinoma. STUDY DESIGN: Multi-institutional retrospective case series. ANIMALS: Seventy-two client-owned dogs from 16 institutions with surgically excised salivary gland carcinoma. METHODS: Medical records of dogs undergoing sialoadenectomy from January 1, 2000 to January 1, 2020 were reviewed for signalment, clinical signs, preoperative staging results, preoperative mass evaluation, complications, histopathologic diagnosis, local recurrence, metastatic disease, and survival times. Survival functions were estimated using the Kaplan-Meier estimator. Factors related to survival were individually tested using the log-rank test. RESULTS: The overall median survival time (MST) associated with salivary carcinoma was 1886 days. Local recurrence occurred in 29/69 (42%) dogs with an overall disease-free interval (DFI) of 191 days. Metastatic disease occurred in 22/69 (31.9%) dogs, with an overall DFI of 299 days. Lymph node metastasis was present at the time of surgery in 11/38 (28.9%) dogs in which lymphadenectomy was performed at the time of surgery; these dogs had a shorter DFI at 98 days (P = .03) and MST at 248 days (P < .001). CONCLUSION: The prognosis for dogs with salivary gland carcinoma treated surgically was more favorable than previously reported. Nodal metastasis was a negative prognostic factor for canine salivary gland carcinoma. CLINICAL SIGNIFICANCE: Surgical intervention should be considered for dogs with salivary carcinoma.

Validation of Immunohistochemistry for Canine Proteins Involved in Thyroid Iodine Uptake and Their Expression in Canine Follicular Cell Thyroid Carcinomas (FTCs) and FTC-Derived Organoids.

Thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, and thyroid peroxidase (TPO) are essential for the uptake of iodine by follicular thyroid cells. The aim of this study was to establish immunohistochemistry (IHC) protocols for TSHR, NIS, pendrin, and TPO in canine tissues and characterize their expression in organoids derived from canine follicular cell thyroid carcinoma (FTC) and in the respective primary tumors. This constitutes a fundamental step to establish organoids as a model to study the uptake of iodine in canine FTC. Commercially available antibodies directed against human proteins were selected. Antibody specificity was confirmed by western blot using lysates of the HTori-3 human thyroid cell line and healthy canine thyroid gland. IHC was validated using HTori-3 cells and a set of canine normal tissues including healthy thyroid gland. The expression of TSHR, NIS, pendrin, and TPO was evaluated in 3 organoid lines derived from FTC and respective primary tumors. All 4 antibodies produced specific bands by western blot and cytoplasmic labeling in follicular cells by IHC in both human HTori-3 cells and canine thyroid gland. NIS also showed basolateral membrane immunolabeling in follicular cells. All 4 proteins were highly expressed in organoids derived from FTC. The expression was similar or higher compared to the primary tumors. The results of this study characterize organoids derived from canine FTC as a suitable in vitro model to investigate iodine uptake, opening new research possibilities in the field of canine thyroid cancer therapy.

Colonic or ileocecocolic volvulus in 13 dogs (2005-2016).

OBJECTIVE: To describe the clinical and clinicopathological features of colonic or ileocecocolic volvulus (CV/ICV) in dogs. STUDY DESIGN: Retrospective case series. ANIMALS: Thirteen dogs with surgically confirmed CV/ICV. METHODS: Medical records were reviewed for signalment, medical history, clinical signs, laboratory data, radiographic findings, treatment, and outcome. RESULTS: All cases consisted of large-breed dogs (median weight 37.1 kg, range, 22.7-58.5 kg), 8 of these male (6 intact). The most common clinical signs included vomiting, depression, inappetence, and diarrhea with or without tenesmus. All cases presented in shock with abdominal distension, abdominal pain, or both. Dogs were treated for shock and operated immediately after a presumptive diagnosis was based on clinical and radiographic examinations. Three dogs were euthanatized during surgery, 10 dogs were discharged live from the hospital, 9 of these were alive at follow-up 6 to 70 months (median 24 months) after surgery. CONCLUSION: CV and ICV are rare disorders that seem to carry a better prognosis than mesenteric volvulus. Immediate laparotomy is recommended in suspected cases and the prognosis is fair.

Melanoma of the dog and cat: consensus and guidelines.

Melanoma of the dog and cat poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current melanoma challenges and controversies. Melanocytic tumors are common in dogs but rare in cats. The history and clinical signs relate to the anatomic site of the melanoma. Oral and subungual malignant melanomas are the most common malignant types in dogs. While many melanocytic tumors are heavily pigmented, making diagnosis relatively straightforward, melanin pigmentation is variable. A validated clinical stage scheme has been defined for canine oral melanoma. For all other locations and for feline melanoma, TNM-based staging applies. Certain histological characteristics have been shown to bear prognostic significance and can thus prove instructive in clinical decision making. Surgical resection using wide margins is currently the mainstay of therapy for the local control of melanomas, regardless of primary location. Radiotherapy forms an integral part of the management of canine oral melanomas, both as a primary and an adjuvant therapy. Adjuvant immunotherapy or chemotherapy is offered to patients at high risk of developing distant metastasis. Location is the major prognostic factor, although it is not completely predictive of local invasiveness and metastatic potential. There are no specific guidelines regarding referral considerations for dogs with melanoma, as this is likely based on a multitude of factors. The ultimate goal is to provide the best options for patients to extend quality of life and survival, either within the primary care or referral hospital setting.

[Adjuvant treatment of canine splenic hemangiosarcoma with autologous dendritic cell therapy - a prospective, randomized double-blind study]. / Adjuvante Behandlung des caninen Hämangiosarkoms der Milz mit der autologen dendritischen Zelltherapie ­ eine prospektive, placebokontrollierte, randomisierte Doppelblindstudie.

OBJECTIVE: Canine splenic hemangiosarcomas (HSA) are malignant mesenchymal tumors with a high tendency for metastasis. Median survival times after splenectomy followed by adjuvant chemotherapy usually range between 5 and 8 months. The aim of this prospective randomized double-blinded study was to examine the efficacy of a commercially available dendritic cell therapy (PetBioCell) following splenectomy. In addition, possible side effects of this therapy were evaluated. MATERIAL AND METHODS: Twenty-one dogs with histologically confirmed splenic HSA without metastasis (stages I or II) were included in the study. Ten dogs received the dendritic cell therapy, and 11 dogs received a placebo. Injections were administered according to the manufacturer's instructions monthly for the first 3 months and then every 3 months until death. Survival times and toxicoses of both groups were compared. RESULTS: Follow-up data were available for all 21 patients; the observation period ranging until euthanasia or metastasis-related death. One patient that had received the dendritic cell therapy was euthanized due to prostatitis and experienced the longest survival time (668 days). One dog in the placebo-group lived for 448 days after splenectomy. The median survival times in the dendritic cell therapy and the placebo group amounted to 74 and 126 days, respectively. There was no significant difference in tumor-free interval (t(18) = 1.4, p = 0.911) and survival times (t(19) = -0.094, p = 0.463) between the 2 groups. Toxicoses reported in both groups were mild and self-limiting. CONCLUSION: Immunotherapy using autologous, immature and unprimed dendritic cells according to the PetBioCell method failed to show efficacy on tumor-free interval and survival time in the presented dog population with splenic hemangiosarcoma.

Frontal sinus carcinoma in forty-one dogs (2001-2022).

Reports on canine frontal sinus carcinomas (FSCs) are scarce. This retrospective review of 41 dogs with FSC (2001-2022) describes demographic and clinical characteristics of canine FSC and reports the clinical experience and overall survival following treatment with toceranib phosphate (TOC) and meloxicam in 10 cases. Median age at diagnosis was 10.6 years (range: 6.5-15.4 years). There was a male-to-female-ratio of 2.4:1. The most common breeds were Jack Russell Terriers (JRT) (n = 7; 17.1%) and Rottweilers (n = 3, 7.3%). Mesocephalic breeds (70.6%) were most commonly affected, brachycephalics accounted for 8.8%. The most frequent clinical signs included skull deformation dorsomedial to the eye (87.5%), pain/head-shyness (40.0%), ocular (22.5%)/nasal (17.5%) discharge, and exophthalmos (17.5%). Duration of symptoms prior to diagnosis varied from a few days to 9 months. There were no neurological signs at initial presentation despite imaging evidence of osteolysis of the lamina interna of the frontal bone in most dogs (69.4%). In 11.5%, pulmonary changes suggestive of metastasis or concurrent primary pulmonary neoplasia were present. Tumour types included squamous cell carcinoma (58.5%), unspecified carcinoma (29.3%), and adenocarcinoma (9.8%). Ten dogs were treated with TOC (median 2.8 mg/kg EOD or three times per week) and meloxicam (0.1 mg/kg, EOD) (TOC-M), resulting in subjective regression of skull deformity in 8/10 (80.0%) patients. Overall median survival time with TOC-M was 183.5 days (range: 120-434 days). FSCs typically present with skull deformation, but no overt neurological signs. Male dogs and JRT may be overrepresented. The use of TOC-M in FSC appears promising and warrants further prospective evaluation.

Organoids of patient-derived medullary thyroid carcinoma: The first milestone towards a new in vitro model in dogs.

Organoid cultures could constitute a valuable in vitro model to explore new treatments for canine (c) medullary thyroid carcinoma (MTC). The study's objectives were to establish and characterize 3D organoid cultures of cMTC using histology and immunohistochemistry (IHC) and to evaluate the effect of antitumor drugs on organoids' viability. Five cMTC tissue samples were used to develop organoid cultures of which one organoid line, named cMTC N°2, could be passaged for an extended period. This cMTC N°2 organoid line was further compared to the primary tumour regarding morphology and IHC expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, calcitonin, synaptophysin, vimentin, Ki-67, cyclooxygenase-2 (COX-2), P-glycoprotein and vascular endothelial growth factor (VEGF). Quality control of the cMTC N°2 organoid line was achieved by a single nucleotide polymorphism (SNP) array of the organoids, primary tumour and healthy blood cells of the same dog. The effect of carboplatin, meloxicam and toceranib phosphate (TOC) on cMTC N°2 organoids' viability was evaluated. The cMTC N°2 organoid line was cultured for 94 days and showed similar histological features with the primary tumour. Immunolabelling for TTF-1, thyroglobulin, calcitonin and VEGF was similar between the primary tumour and cMTC N°2 organoids. Compared to the primary tumour, organoids showed higher immunolabelling for vimentin and Ki-67, and lower immunolabelling for synaptophysin, COX-2 and P-glycoprotein. The SNP genotype was similar for each chromosome between healthy blood cells, primary tumour and cMTC N°2 organoids. Carboplatin, meloxicam and TOC had no effect on cMTC N°2 organoid cell viability within achievable in vivo concentration range. In conclusion, the cMTC N°2 organoid line is a promising first milestone towards an established in vitro organoid model to explore pathophysiology and new treatment modalities in cMTC.

Ovariectomy reduces the risk of tumour development and influences the histologic continuum in canine mammary tumours.

Influence of neutering on canine mammary tumorigenesis has been a source of vivid discussion over the last decades. The purpose of this retrospective study was to describe the association between neuter status, tumour size and degree of malignancy in a large population of 625 female dogs with altogether 1459 removed mammary tumours (MTs). MT-bearing dogs were predominantly intact (80.3%) and intact dogs were overrepresented in the tumour population compared to the control group of >19 000 females (p < .0001). Multiple MT occurred in 340 patients (54.4%) and were significantly more common in intact dogs (57.8% vs. 40.7% spayed). Neutered dogs were not only significantly more likely to have a malignant MT (p < .0001) but were significantly more often affected by more aggressive tumour subtypes (p < .0001). Positive correlation between increasing tumour size and increasingly malignant phenotype was slightly stronger in spayed (rs  = .217; p = .021) compared to intact (rs  = .179; p = .0003) patients. After ovariectomy, progression from benign to malignant occurs in smaller size tumours, as MT ≥2 cm in diameter were malignant in 86.9% of the spayed patients, compared to 62.0% in intact patients (p = .0002). Intact bitches have a higher risk for MTs and tumour multiplicity. MTs in neutered females are more often malignant and belong to more aggressive subtypes compared to MTs in intact dogs. In neutered bitches, histologic progression from benign to malignant and further along the cancer progression continuum occurs at smaller tumour sizes.

[Clinicopathologic characteristics, postoperative outcome, and prognostic factors in dogs with primary pulmonary carcinomas - A retrospective study of 61 dogs]. / Klinisch-pathologische Befunde, postoperative Überlebenszeiten und prognostische Faktoren bei Hunden mit primären Lungenkarzinomen.

INTRODUCTION: Canine primary pulmonary carcinomas (PLC) are treated surgically. The goal of this study was to increase the veterinary database concerning clinical and pathological findings, postsurgical median survival times (mST), and prognostic factors in this tumor type. MATERIALS AND METHODS: Retrospective analysis of 61 dogs with 62 PLC treated surgically between 2007 and 2017. Survival analyses were performed using the Kaplan-Meier and Logrank methods. RESULTS: Of the 62 tumors, 35 (56 %) were located peripherally in the lung, 21 (34 %) close to the hilus and 6 (10 %) affected the entire lobe. In 49 cases, differentiated (papillary or bronchoalveolar) adenocarcinomas were diagnosed; undifferentiated carcinomas or anaplastic carcinomas (n = 10) and squamous cell carcinomas (n = 2) were rare. There was no predisposition for specific lung lobes. Thirteen (21 %) of the patients exhibited no clinical signs, and 10 (16 %) displayed unspecific signs, unrelated to the respiratory tract. In total, forty-eight (79 %) dogs showed clinical signs such as coughing, dyspnea, lethargy, weight loss, exercise intolerance, vomiting and/or fever. Histologic examination of the tracheobronchial lymph nodes (TBLN), was positive for metastasis (N1) in 9 cases, negative (N0) in 42 patients, no TBLN histology was performed in 10 cases. Long-term follow-up information was available for 50 dogs. Variables with prognostic impact were presence of TBLN metastasis (mST: N1 41 days, N0 570 days; p < 0.01), lung metastases (mST: M1 125 days, M0 630 days; p < 0.01), histologic subtype (mST: tracheobronchial or papillary carcinoma 620 days; other carcinomas 135 days; p < 0.01); tumor diameter larger than 3 cm (mST < 3 cm 1155 days, ≥ 3 cm 330 days p = 0.02), and location of the tumor (mST: hilar 330 days, peripheral 650 days; p = 0.04). CONCLUSION: In PLK, TBLN status, M1, tumor location, histological subtype and tumor size are important, prognostically relevant factors; dogs without prognostically negative factors may have a good prognosis. More than one third of the dogs present asymptomatically (21 %) or without respiratory signs (16 %).

Utility of Serum Ki-67 as a Marker for Malignancy in Dogs.

Tumour markers are scarcely used in veterinary medicine, although they are non-invasive, contribute to a faster diagnosis and new therapeutic options. The nuclear protein Ki-67 is absent in G0-phase but is detectable throughout all active phases of the cell cycle. Consequently, it is used as a marker for the proliferating cell fraction of a cell population and thus could indicate neoplastic tissue present. Our study is designed to show whether Ki-67 can be considered as a potential canine serum tumour marker for veterinary medicine. We measured serum concentrations of Ki-67 in dogs with various malignant tumours (carcinomas (n = 35); sarcomas (n = 26); lymphomas (n = 21)) using a commercially available quantitative sandwich ELISA from mybiosource. Dogs with malignant tumours showed significantly higher serum Ki-67 concentrations compared to healthy dogs (n = 19) and non-neoplastic diseased dogs (n = 26). No significant difference in serum Ki-67 concentration was detected between carcinoma, sarcoma, and lymphoma, nor between mammary adenocarcinoma and adenoma. In our investigations we also included some inflammatory parameters measured in blood, such as neutrophils, lymphocytes, and monocytes, and gained mixed results. The results of our study suggest that Ki-67 may be useful as a potential serum tumour marker, providing information about the presence of malignancies in a dog.

Kinetic Energy Dose as a Unified Metric for Comparing Ball Mills in the Mechanocatalytic Depolymerization of Lignocellulose.

Mechanochemistry utilizes mechanical forces to activate chemical bonds. It offers environmentally benign routes for both (bio) organic and inorganic syntheses. However, direct comparison of mechanochemistry results is often very challenging. In mechanochemical synthetic protocols, ball mill setup (mechanical design and grinding vessel geometry) in addition to experimental parameters (milling frequency, duration, ball count and size) vary broadly. This fact poses a severe issue to further progress in this exciting research area because ball mill setup and experimental parameters govern how much kinetic energy is transferred to a chemical reaction. In this work, we address the challenge of comparing mechanochemical reaction results by taking the energy dose provided by ball mills as a unified metric into account. In this quest, we applied kinematic modeling to two ball mills functioning under distinct working principles to express the energy dose as a mathematical function of the experimental parameters. By examining the effect of energy dose on the extent of the mechanocatalytic depolymerization (MCD) of lignocellulosic biomass (beechwood), we found linear correlations between yield of water-soluble products (WSP) and energy dose for both ball mills. Interestingly, when a substrate layer is formed on the grinding jar wall and/or grinding medium, a weak non-linear correlation between water-soluble products yield and energy dose is identified. We demonstrate that the chemical reaction's best utilization of kinetic energy is achieved in the linear regime, which presents improved WSP yields for given energy doses. In the broader context, the current analysis outlines the usefulness of the energy dose as a unified metric in mechanochemistry to further the understanding of reaction results obtained from different ball mills operating under varied experimental conditions.

Canine mammary tumours: Size matters-a progression from low to highly malignant subtypes.

The purpose of this study was to evaluate a possible association between mammary tumour size and increasing degree of malignancy. Data of 625 dogs with a total of 1459 mammary tumours were analysed retrospectively. 80.3% dogs were intact, mean age at diagnosis was 9.7 ± 2.5 years, 75.8% were pure breed dogs. Median body weight was 20.0 kg. Malignant tumours (n = 580) were significantly larger than their benign counterparts (1.94 cm vs 0.90 cm in mean, respectively; P ≤ .0001), resulting in a positive correlation between increasing tumour size and a change from benign to malignant (P ≤ .0001; rs  = 0.214). When malignant tumours were grouped into four degrees of increasing malignancy (complex/simple/solid/anaplastic carcinomas) a significant positive correlation between increasing tumour size and more malignant tumour degree (P ≤ .0001; rs  = 0.195) could be demonstrated. In a number of cases, highly malignant tumours were found to arise within less malignant lesions, supporting the concept of a further progression within the malignant tumour subtypes. In patients with multiple tumours, mean tumour sizes for malignant tumours were significantly smaller compared to patients with only one tumour (1.67 vs 2.71 cm in mean, respectively; P < .0001). These findings suggest that mammary tumours progress not only from benign to malignant but also from low to highly malignant. An increase in diameter of only a few millimetres may therefore have a big impact on the patient's outcome.

Investigation of serum survivin in dogs suffering from cancer: a multicenter study.

BACKGROUND: In contrast to human medicine, only a small number of serum tumor markers are established in veterinary medicine even though they are a non-invasive diagnostic tool. OBJECTIVES: This study examined whether survivin could be suitable as a potential canine serum tumor marker. METHODS: This study measured the serum survivin concentrations of dogs with mammary tumors (n = 33), squamous cell carcinoma (n = 9), soft-tissue sarcoma (n = 18) and multicentric lymphoma (n = 22), using a commercially available, competitive immunoassay kit (BlueGene). The serum survivin concentrations were compared with those of a healthy control group (n = 20) and a control group of dogs with non-neoplastic diseases (n = 17). RESULTS: Dogs with malignant tumors had serum survivin concentrations between 15 and 5,906 pg/mL (median, 72 pg/mL), those in the healthy group ranged from 7 to 99 pg/mL (median, 21 pg/mL) and those in the group of dogs suffering from non-neoplastic diseases from 15 to 93 pg/mL (median, 42 pg/mL). The differences in the survivin concentrations between the healthy dogs and dogs with malignant tumors and between the dogs with non-neoplastic diseases and those with malignant tumors were significant (p < 0.001 and p = 0.006, respectively). CONCLUSIONS: The serum survivin concentrations in dogs with malignant tumors, with some exceptions, are higher than in dogs with benign tumors and dogs that do not suffer from a malignancy. Therefore, survivin can provide information on the presence of malignant tumors and be used as a tumor marker in dogs.

Curative-intent radical en bloc resection using a minimum of a 3 cm margin in feline injection-site sarcomas: a retrospective analysis of 131 cases.

Objectives Owing to its highly infiltrative growth, feline injection-site sarcoma (FISS) carries a significant risk of local tumour recurrence. Parameters of possible prognostic significance (eg, tumour size and location, resection of de novo vs recurrent tumours, and achievement of tumour-free surgical margins) were examined with regard to their influence on recurrence rate (RR), disease-free interval (DFI) and survival time (ST). Methods This was a retrospective analysis of cats with FISSs located on the chest or abdominal wall or the interscapular region treated in a single institution using a standardised radical resection technique with 3 cm lateral margins and full-thickness body wall resection (tumours over chest/abdominal wall) or a minimum of two fascial planes (interscapular tumours). Results Median postoperative DFI and ST of 131 cats with FISSs was 21 and 24 months, respectively. Patients operated on for recurrent tumours were significantly more likely to die from tumour-related reasons compared with patients with de novo tumours ( P <0.001). RR and DFI in the different tumour locations were comparable ( P = 0.544 and P = 0.17, respectively). Local tumour recurrence occurred in 38.1% of the cats. Cats operated on for tumour recurrences had a significantly higher chance of another recurrence (RR 55.5% vs 33.3%; P = 0.005). Completeness of excision was determined by taking tumour bed biopsies. Tumour bed biopsies that did not contain tumour cells were associated with a significantly lower RR compared with those with tumour cells (30.5% vs 76.2%). Conclusions and relevance Depending on prognostic factors such as surgery for primary vs recurrent tumour, tumour-free resection margins and tumour location, the RR in FISS ranges from 33-55%, despite curative intent radical surgery. This study may help in identifying patients at risk for recurrence.

Kinematic Modeling of Mechanocatalytic Depolymerization of α-Cellulose and Beechwood.

Mechanocatalytic depolymerization of lignocellulose presents a promising method for the solid-state transformation of acidified raw biomass into water-soluble products (WSPs). However, the mechanisms underlining the utilization of mechanical forces in the depolymerization are poorly understood. A kinematic model of the milling process is applied to assess the energy dose transferred to cellulose during its mechanocatalytic depolymerization under varied conditions (rotational speed, milling time, ball size, and substrate loading). The data set is compared to the apparent energy dose calculated from the kinematic model and reveals key features of the mechanocatalytic process. At low energy doses, a rapid rise in the WSP yield associated with the apparent energy dose is observed. However, at a higher energy dose obtained by extended milling duration or high milling speeds, the formation of a substrate cake layer on the mill vials appear to buffer the mechanical forces, preventing full cellulose conversion into WSPs. By contrast, for beechwood, there exists a good linear dependence between the WSP yield and the energy dose provided to the substrate over the entire range of WSP yields. As the formation of a substrate cake in depolymerization of beechwood is less severe than that for the cellulose experiments, the current results verify the hypothesis regarding the negative effect of a substrate layer formed on the mill vials upon the depolymerization process. Overall, the current findings provide valuable insight into relationships between the energy dose and the extent of cellulose depolymerization effected by the mechanocatalytic process.

Detection of novel polymorphisms in the ckit gene of canine patients with lymphoma, melanoma, haemangiosarcoma, and osteosarcoma.

Tyrosine kinase inhibitors (TKIs) that specifically target cKIT represent a therapeutic approach for non-resectable canine mast cell tumours (MCTs) grade II/III. The therapeutic benefit of TKIs has been investigated in other tumours based on clinical response rates and identification of gain-of-function mutations. In the present study, cKIT expression in 14 dogs with osteosarcoma, melanoma, haemangiosarcoma, lymphoma, and fibrosarcoma was analysed. Tissue samples were used for cKIT sequencing to (I) detect the cKIT transcript and to (II) identify gain-of-function mutations. The cKIT transcript was detected in ten patients. Four novel amino acid substitutions and five silent polymorphisms were identified. Furthermore, an insertion mutation (GNSK) was discovered in the tissue, but not in the blood sample of one dog. CKIT expression was identified in a variety of canine tumours and, therefore, TKIs might have a broader therapeutic indication apart from treatment of MCTs. Further investigations will be necessary to localize the cKIT protein in the respective tumours and to evaluate the functional consequence of the cKIT variants identified in the present study.

[Multicentric lymphoma in 411 dogs - an epidemiological study]. / Das multizentrische Lymphom bei 411 Hunden - eine epidemiologische Studie.

OBJECTIVE: To provide an overview of the epidemiology of canine multicentric lymphoma in Germany. MATERIAL AND METHODS: A total of 411 dogs with multicentric malignant lymphoma were retrospectively analysed regarding breed, age, sex, weight and the number of animals dogs with hypercalcaemic lymphoma and B-/T-immunophenotype, and compared to two reference populations (total own clinic population, n   =   52  142; dogs with health insurance in Germany, n   =   123  423). RESULTS: In total, 298 (72.5%) of the 411 dogs belonged to 86 different breeds, while 113 (27.5%) dogs were mixed breed. In comparison to both reference populations, a breed predisposition for the American Pitbull Terrier (odds ratio [OR] 5.2 and 18.5), American Staffordshire Terrier (OR 3.3 and 4.6), Briard (OR 5.6 and 9.5), Bullmastiff (OR 7.8 and 5.0), Irish Setter (OR 3.3 and 4.1) and Rottweiler (OR 2.8 and 3.6) was found. Golden Retrievers (n = 22, OR 1.3 and 0.9) and Bernese Mountain Dogs (n = 22, OR 2.4 and 2.0) were frequently affected in absolute numbers, but when compared to the reference populations an OR < 3 was detected. Mean body weight was 30.2 ± 13.7 kg; only 75 (18%) dogs weighed < 15 kg. Amongst the small dogs (< 15 kg), there was a large number of West Highland White Terriers (n = 12). Mean age of the dogs with lymphoma was 7.9 ± 2.7 years. Dogs weighing ≥ 15 kg were significantly (p < 0.001) younger (7.6 ± 2.4 years) compared to dogs weighing < 15 kg (9.3 ± 3.2 years). Dogs with a B-cell immunophenotype (8.5 ± 2.6 years) were significantly older compared to dogs with a T-cell immunophenotype (6.4 ± 1.8 years) (p < 0.001). There was no gender predisposition (54% male, 46% female). Hypercalcaemia as an indicator of T-cell lymphoma was present in 44 (11.4%) of the dogs. A T-cell and B-cell immunophenotype was found in 20.6% and 79.4% of the dogs, respectively. CLINICAL RELEVANCE: This study confirms previous data about breed predispositions for canine malignant multicentric lymphoma and demonstrates that further breeds are predisposed (Briard, West Highland White Terrier, Irish Setter). Small-breed dogs (< 15 kg BM) appear to be affected with lymphoma at a greater age.

Sequentially photocleavable protecting groups in solid-phase synthesis.

[reaction: see text] A sequential solid-phase peptide synthesis was developed using both photolabile linker and protecting groups. The chromatic sequential lability between a tert-butyl ketone-derived linker (sensitive to irradiation at 305 nm) and a nitroveratryloxycarbonyl (NVOC) group (sensitive at 360 nm) was exploited to prepare Leu-Enkephalin in a 55% overall yield. This new strategy allows the preparation of peptides in essentially neutral medium, by avoiding the use of common deprotection reagents such as trifluoroacetic acid or piperidine.