Jolle Kirpensteijn

Prognostic factors in canine appendicular osteosarcoma – a meta-analysis

BackgroundAppendicular osteosarcoma is the most common malignant primary canine bone tumor. When treated by amputation or tumor removal alone, median survival times (MST) do not exceed 5 months, with the majority of dogs suffering from metastatic disease. This period can be extended with adequate local intervention and adjuvant chemotherapy, which has become common practice. Several prognostic factors have been reported in many different studies, e.g. age, breed, weight, sex, neuter status, location of tumor, serum alkaline phosphatase (SALP), bone alkaline phosphatase (BALP), infection, percentage of bone length affected, histological grade or histological subtype of tumor. Most of these factors are, however, only reported as confounding factors in larger studies. Insight in truly significant prognostic factors at time of diagnosis may contribute to tailoring adjuvant therapy for individual dogs suffering from osteosarcoma. The objective of this study was to systematically review the prognostic factors that are described for canine appendicular osteosarcoma and validate their scientific importance.ResultsA literature review was performed on selected studies and eligible data were extracted. Meta-analyses were done for two of the three selected possible prognostic factors (SALP and location), looking at both survival time (ST) and disease free interval (DFI). The third factor (age) was studied in a qualitative manner. Both elevated SALP level and the (proximal) humerus as location of the primary tumor are significant negative prognostic factors for both ST and DFI in dogs with appendicular osteosarcoma. Increasing age was associated with shorter ST and DFI, however, was not statistically significant because information of this factor was available in only a limited number of papers.ConclusionsElevated SALP and proximal humeral location are significant negative prognosticators for canine osteosarcoma.

TP53 gene mutations in canine osteosarcoma.

OBJECTIVE To investigate mutations of the TP53 gene in canine osteosarcoma (OS). STUDY DESIGN Clinical historic cohort study. ANIMALS Client-owned dogs. METHODS OS (n=59) were screened for mutations of the complete TP53 gene using polymerase chain reaction and the mutation was analyzed by single-strand conformational polymorphism. Clinical outcome of dogs with TP53-mutated OS were compared with dogs with OS without a mutation after complete surgical excision of the primary tumor. RESULTS TP53 gene mutations were observed in 24 of 59 (40.7%) OS; 3 mutated OS had 2 mutations. The alterations consisted mainly of point mutations (74%). Dogs with mutated OS had a significantly shorter survival time (ST) after surgery than dogs with normal tumor TP53 gene expression (P=.03). Other significant prognosticators for ST and disease-free interval included elevated serum alkaline phosphatase (P<.01) and tumor grade (P=.01). CONCLUSION TP53 genetic mutations are common in canine OS and may have a prognostic value. CLINICAL RELEVANCE Mutations of the TP53 gene may influence survival and should be considered when evaluating canine OS.

Comparison of Ultrasonography, Computed Tomography, and Single-Photon Emission Computed Tomography for the Detection and Localization of Canine Insulinoma

Accurate preoperative detection, localization, and staging of the primary tumor and metastases are essential for the selection of appropriate candidates for surgery. In dogs with insulinoma, preoperative assessment usually is performed with transabdominal ultrasonography (US). There are no reports on the use of computed tomography (CT) for this purpose. The preoperative use of somatostatin receptor scintigraphy (SRS) recently has been advocated for the identification of insulinoma and gastrinoma in dogs, but its accuracy remains to be established. In this report US, CT, and single-photon emission computed tomography (SPECT) with [111In-DTPA-D-Phe1]-octreotide (a specific form of SRS) were compared for their effectiveness in detecting and localizing primary and metastatic insulinoma in dogs. Findings at surgery or postmortem examination served as control. Of 14 primary insulinomas, 5, 10, and 6 were correctly identified by US, CT, and SPECT, respectively. No lymph node metastases were detected by US or SPECT. CT identified 2 of 5 lymph node metastases but also identified 28 false-positive lesions. Two of 4 livers were found to be positive for metastases by 1 of the imaging techniques. US can be used for the initial evaluation of dogs with hypoglycemia. Although CT identifies most primary tumors, intraoperative inspection and palpation of the pancreas is still superior. SPECT appears as effective as US and CT in detecting insulinomas. Future developments in preoperative imaging techniques might improve current methods of canine insulinoma detection.

Nd:YAG surgical laser effects in canine prostate tissue: temperature and damage distribution.

An in vitro model was used to predict short-term, laser-induced, thermal damage in canine prostate tissue. Canine prostate tissue samples were equipped with thermocouple probes to measure tissue temperature at 3, 6, 9 and 12 mm depths. The tissue surface was irradiated with a Nd:YAG laser in contact or non-contact mode for up to 20 s, using powers from 5 to 20 W. Prediction of thermal damage using Arrhenius theory was discussed and compared to the in vitro damage threshold, determined by histological evaluation. The threshold temperature for acute thermal tissue damage was 69 +/- 6 degrees C (means +/- SD), irrespective of exposure time. Contact mode laser application caused vaporization of tissue, leaving a crater underneath the fiber tip. The mean extent of tissue damage underneath the vaporization crater floor was 0.9 +/- 0.6 mm after 5, 10 or 20 s of contact mode laser irradiation at 10 W, whereas 20 W non-contact exposure up to 20 s causes up to 4.7 +/- 0.2 mm coagulation necrosis. It was concluded that short-term acute thermal tissue damage can be comprehensively described by a single threshold temperature.

Laparoscopic ovariectomy in cats: Comparison of laser and bipolar electrocoagulation

Fourteen mixed-breed domestic cats underwent laparoscopic ovariectomy (lapOVE) using paediatric equipment, an Nd:YAG laser and a bipolar electrocoagulation forceps. Cats were placed in 10° Trendelenburg position (head down) and insufflation pressure was kept at 4 mmHg, while surgery was performed through three midline portals. Randomly-assigned unilateral laser resection of one ovary (laserOVE) and bipolar electrocoagulation (BECOVE) of the contralateral ovary were performed. Duration of predetermined surgery intervals was recorded, as well as occurrence of intra- and postoperative complications. Both methods were successful and without complications. Duration of laserOVE was significantly increased compared to BECOVE. The right ovary was more difficult to access; however, both ovaries were easy to manipulate because of the relatively long suspensory ligament. The ovarian ligaments contained minimal amounts of fat and obesity did not influence surgery duration. Convalescence period was short (0.9±0.4 days) and owner satisfaction high.

Comparison of surgical variables and short-term postoperative complications in healthy dogs undergoing ovariohysterectomy or ovariectomy

OBJECTIVE To determine whether ovariohysterectomy (OVH) required more time to complete and was associated with more short-term postoperative complications than ovariectomy (OVE) in dogs. DESIGN Randomized prospective clinical trial. ANIMALS 40 healthy, sexually intact female dogs. PROCEDURES OVH (in 20 dogs) or OVE (20 dogs) was performed by use of standardized anesthetic and surgical protocols. Physical characteristics of the dogs, surgical variables, pain scores derived from behavior-based composite pain scales, and surgical wound characteristics were analyzed. RESULTS Body weight, age, body condition score, and distance between the sternal manubrium and the pubic rim were comparable among dogs that underwent either surgical procedure. Body weight was positively correlated with the total duration of the procedure and with time required for closure of the surgical wound. No effect of body condition score was determined for any variable. Skin and fascia incision lengths relative to the distance from the sternal manubrium to pubic rim were significantly greater in dogs that underwent OVH, compared with those of dogs that underwent OVE, but total surgical time was not different for the 2 procedures. No other significant differences were detected between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Significant differences in total surgical time, pain scores, and wound scores were not observed between dogs that underwent OVH and dogs that underwent OVE via standardized protocols.

Innovative approach to laparoscopic adrenalectomy for treatment of unilateral adrenal gland tumors in dogs

Objective To report a technique for, and short-term outcome of unilateral laparoscopic adrenalectomy in dogs positioned in sternal recumbency without abdominal support. Study Design Experimental and prospective clinical study. Animals Healthy dogs (n = 5) and dogs with unilateral adrenal gland tumor (n = 9). Methods Anesthetized dogs were positioned in sternal recumbency with 2 cushions placed under the dog to elevate the chest and pelvic area so that the abdomen was not in contact with the surgical table allowing gravitational displacement of the abdominal viscera. Three 5-mm portals were located in the paralumbar fossa. Adrenal glands were carefully dissected and surrounding tissues sealed and cut using a vessel-sealing device. A retrieval bag or part of a surgical glove finger was used to remove the adrenal gland from the abdomen. Surgical time and complications were recorded, and short-term outcome assessed. Results Adrenal glands in normal dogs and unilateral adrenal tumors (8 left, 1 right) not involving the caudal vena cava in affected dogs were successfully removed laparoscopically. There were no major intraoperative complications. Of the dogs with adrenal tumors, 1 dog died within 24 hours of surgery from unrelated causes. Eight dogs recovered within 1 day and were discharged within 72 hours. Surgical times ranged from 42 to 117 minutes and were significantly shorter than those reported previously. Conclusions Positioning anesthetized dogs in sternal recumbency with the abdomen suspended to facilitate gravitational displacement of the abdominal viscera improves access to, and visibility of, the adrenal gland for laparoscopic removal.OBJECTIVE To report a technique for, and short-term outcome of unilateral laparoscopic adrenalectomy in dogs positioned in sternal recumbency without abdominal support. STUDY DESIGN Experimental and prospective clinical study. ANIMALS Healthy dogs (n = 5) and dogs with unilateral adrenal gland tumor (n = 9). METHODS Anesthetized dogs were positioned in sternal recumbency with 2 cushions placed under the dog to elevate the chest and pelvic area so that the abdomen was not in contact with the surgical table allowing gravitational displacement of the abdominal viscera. Three 5-mm portals were located in the paralumbar fossa. Adrenal glands were carefully dissected and surrounding tissues sealed and cut using a vessel-sealing device. A retrieval bag or part of a surgical glove finger was used to remove the adrenal gland from the abdomen. Surgical time and complications were recorded, and short-term outcome assessed. RESULTS Adrenal glands in normal dogs and unilateral adrenal tumors (8 left, 1 right) not involving the caudal vena cava in affected dogs were successfully removed laparoscopically. There were no major intraoperative complications. Of the dogs with adrenal tumors, 1 dog died within 24 hours of surgery from unrelated causes. Eight dogs recovered within 1 day and were discharged within 72 hours. Surgical times ranged from 42 to 117 minutes and were significantly shorter than those reported previously. CONCLUSIONS Positioning anesthetized dogs in sternal recumbency with the abdomen suspended to facilitate gravitational displacement of the abdominal viscera improves access to, and visibility of, the adrenal gland for laparoscopic removal.

Prognostic factors of early metastasis and mortality in dogs with appendicular osteosarcoma after receiving surgery: an individual patient data meta-analysis

Recently an aggregated data meta-analysis showed that serum alkaline phosphatase (SALP) and proximal humerus location are predictors for shorter survival in canine osteosarcoma. To identify additional prognostic factors of mortality and metastasis an individual patient data meta-analysis (IPDMA) was conducted. Individual patient data from 20 studies, identified via the VSSO society, were pooled. Univariable and multivariable hazard ratios (HR) for metastasis and mortality were assessed, using stratified Cox models. The study included 1405 dogs who received surgical treatment, of which the metastasis status was measured in 1155 dogs and mortality status in 1336 dogs; median survival was 256 days. High versus normal SALP and weight (kg) were associated with an increase in hazard of metastasis [HR 1.34 (95%CI 1.07; 1.68) and HR 1.02 (per kg increase) (95%CI 1.01; 1.03)] and for mortality [HR 1.43 (95%CI 1.16; 1.77) and HR 1.02 (95%CI 1.01; 1.02)]. Distal radius tumor was associated with a lower hazard of metastasis compared to other locations: HR 0.75 (95%CI 0.58; 0.96). Proximal humerus and distal femur or proximal tibia location were related with an increased mortality: HR 1.53 (95%CI 1.26; 1.84) and HR 1.23 (95%CI 1.01; 1.49) compared to other locations. Older age (years) was associated with a higher hazard for mortality [HR 1.06 per year (95%CI 1.03; 1.09)] but not for metastasis: HR 1.03 (95%CI 0.99; 1.06). These results confirm findings from a recent aggregated data meta-analysis and (in addition) showed that tumor location, SALP, weight were prognostic factors for both mortality and metastasis. Age was a prognostic factor for mortality but not for metastasis.

A Clinicopathological Study of 52 Feline Epulides

A retrospective study was performed to characterize 52 new cases of feline epulides between 1995 and 2001, with clinical and pathological results classified according to Heads histopathologic criteria for canine epulides. The incidence of the fibromatous, acanthomatous, ossifying, and giant cell epulis were respectively 57.7% (30/52), 7.7% (4/52), 5.8% (3/52), and 28.8% (15/52). Giant cell epulides presented significant differences in clinical behavior compared with the fibromatous type, including rapid growth (P < .0001), presence of ulcerative changes (P < .01), and rapid recurrence after surgery (P < .01) from which euthanasia was judged necessary in 4 cases. Fifteen giant cell epulides were additionally examined in order to characterize the lesion both histochemically and immunohistochemically and to investigate the origin of the multinucleated giant cells (MGCs). Van Gieson staining showed osteoid and woven bone formation in 11 cases. Both the MGCs and a fraction of the mononuclear cells were positive for vimentin, tartrate-resistant acid phosphatase (TRAP), a commonly accepted marker for osteoclasts, and the polyclonal antibody receptor activator of nuclear factor κβ (RANK), a cytokine leading to the differentiation of osteoclast progenitors into mature osteoclasts in presence of its ligand. MGCs were negative for smooth muscle actin, MIB-1, and factor VIII. The giant cell epulis may be a variant of the fibromatous and ossifying epulis in which extensive ulceration and inflammation results in increased osteoclastic activity. The osteoclast-like giant cells are most likely formed from a monocyte/ macrophage-like osteoclast precursor that differentiates into osteoclasts under the influence of mononuclear osteoblast-like stromal cells.

Evaluation of clinico-pathological criteria and the Ki67 index as prognostic indicators in canine insulinoma

The establishment of reliable prognostic biomarkers for canine insulinoma are warranted to facilitate optimal patient management. Using univariate and multivariate analyses, the present study evaluated the prognostic power of several clinical and histopathological criteria, as well as the Ki67 index, in 26 dogs with insulinoma. On univariate analysis, stromal fibrosis within these tumours was found to be significantly predictive for survival, while tumour size, the Ki67 index, and TNM (Tumour, Node, Metastasis) stage were significant in the prognosis of both disease-free interval and survival time. On multivariate analysis, tumour size retained predictive power for disease-free intervals, while the Ki67 index proved prognostically significant for both the disease-free interval and overall survival time. This study demonstrates that, in addition to known factors such as tumour size and stage, Ki67 can act as a biomarker of insulinoma that can be used to predict clinical outcome.