Intratumoral heterogeneity after targeted therapy in murine cancer models with differing degrees of malignancy.

INTRODUCTION: Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI). MATERIALS AND METHODS: Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology. RESULTS AND DISCUSSIONS: All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.

[Pancarpal arthrodesis using a "CastLess Plate" in dogs and cats]. / Pankarpale Arthrodese unter Verwendung einer "CastLess Plate" bei Hunden und Katzen.

OBJECTIVE: Description of clinical experience with a new implant for dorsal plating in pancarpal arthrodesis. MATERIAL UND METHODS: Retrospective analysis (June 2008 - May 2009) of clinical records from a heterogenous group of dogs and cats which where treated by pancarpal arthrodesis using a PCA-plate ("CastLess-plate", Orthomed®, UK). RESULTS: In 15 dogs and three cats, a total of 20 pancarpal arthrodesis (complete fusion of carpal joints) using a PCA-plate were performed. External coaptation by cast was not used in the postoperative period. In two out of 17 arthrodesis in 15 dogs serious postoperative complications (plate deformation, wound infection) occurred which required a revision surgery. Fistula formation (8-16 weeks post surgery) was seen in six arthrodesis. They all resolved after medical therapy. In cats, all three arthrodesis showed postoperative complications (bone resorption under the plate n=1, paw swelling n=2). Long-term evaluation by telephone interview with the owners (17 owners, 6-21 months after surgery, one case lost in follow-up) revealed good or very good results for 17 of 19 arthrodesis. CLINICAL RELEVANCE: Pancarpal arthrodesis in dogs can be performed successfully using the "CastLess Plate" without additional external coaptation. Due to the size of the available implants complications have to be expected in cats.

Prostatic cavitary lesions containing urine in dogs.

OBJECTIVES: The purpose of this retrospective study was to determine the proportion of urine-containing prostatic cavitary lesions ("urinary cysts") in dogs and to describe their clinical management. METHODS: The study included dogs with clinically relevant prostatic-retention cyst/abscess (n=87) treated initially by percutaneous ultrasound-guided drainage of the prostatic cavity. Based on a prostatic fluid:serum creatinine ratio, the study population was divided into two groups: group 1 (n=16) with and group 2 (n=71) without evidence of urine within the lesion. Medical records of both the groups were reviewed. RESULTS: Cavitary lesions containing urine were observed in 16 of the 87 dogs (18·4%; group 1). In 10 (62·5%) of the group 1 dogs, abdominal surgery was recommended, because of recurrent filling during follow-up. In group 2, abdominal surgery was recommended in only 11 of 71 cases (15·5%). CLINICAL SIGNIFICANCE: In dogs, 18·4% (95% confidence interval, 10·9 to 28·1%) of the prostatic cavitary lesions contain urine. Measurement of creatinine within the prostatic cavity fluid is a helpful tool in diagnosing a presurgical intra-prostatic urethral fistulation, and these dogs tend to require a more aggressive surgical therapy than percutaneous drainage alone.

Ultrasonographic examination of injuries to the achilles tendon in dogs and cats.

The value of ultrasonography in the diagnosis of lesions of the Achilles tendon was Investigated in 42 dogs and seven cats. A standardised four-part ultrasonographic examination was established. Linear transducers with a frequency of more than 7.5 MHz were used. Ultrasonography allowed identification and differentiation of total ruptures and the differentiation of partial ruptures into deep or superficial ruptures, or those comprising muscular tears. The healing process could be monitored and imaged using this technique. Suture material was readily visible in surgically treated cases. Displacement of the superficial digital flexor tendon could be identified. In such cases, the tendon tissue was seen either medially or laterally to the calcaneus. The healing process of the Achilles tendon could also be documented using ultrasonography. However, it was not possible to determine the age of the injury and the exact end of the healing process. Ultrasonography therefore proved to be an excellent diagnostic method for imaging lesions of the Achilles tendon and associated injuries in dogs and cats. After physical examination, the technique should be the next logical step in the evaluation of a suspected injury to the Achilles tendon.

Ultrasonography for the diagnosis of diseases of the tendon and tendon sheath of the biceps brachii muscle.

OBJECTIVE: To describe the ultrasonographic appearance of the normal and diseased biceps brachii tendon and its tendon sheath in dogs. STUDY DESIGN: A prospective clinical study. ANIMALS: One hundred twenty client-owned dogs. METHODS: In the first part of the study, the ultrasonographic appearance of the normal biceps brachii muscle and the surrounding soft tissue was determined in 27 healthy dogs. Standard views were described and established. In the second part, 120 dogs with suspected pathology of the biceps brachii muscle were examined ultrasonographically. Fifty-five of these dogs had no sonographic changes, and 65 dogs had sonographically detectable pathologic changes of the tendon or the tendon sheath or both. The mean age of the affected dogs was 3.7 years. The ratio of males to females was 1.95:1. Sedation or anesthesia of the dogs was required because of the extreme movements of the leg necessary for the examination. To achieve a perpendicular view of the tendon and the tendon sheath, the area of the shoulder joint was rotated outward and abducted as far as possible. Examination of the muscle-tendon apparatus of the biceps brachii muscle was divided into 4 main sections. RESULTS: Linear transducers (7.5-10 MHz) allowed the soft tissue structures to be easily visualized with ultrasonography. Pathologic changes of the tendon and tendon sheath were visualized sonographically by using high-frequency linear probes. Partial or complete tendon rupture, medial luxation of the tendon, corpora libera in the tendon sheath, and tenosynovitis were clearly shown. CONCLUSIONS: High-frequency ultrasonography using linear transducers allows the examiner to accurately define the pathologic changes in the region of the biceps brachii tendon in dogs. CLINICAL RELEVANCE: The use of sonography for diagnosis of disease processes of the tendon and tendon sheath of the biceps brachii muscle complements clinical and radiographic examination findings.

Sonography of the canine stifle.

When diagnosing disease of the stifle in dogs ultrasonography is a good addition to clinical and radiological examination. Radiology can evaluate the bony aspects of the joint and their relationship to each other. In contrast, sonography allows visualization of the soft tissue. For most evaluations the 7.5 MHz linear scanner is suited best. Normal stifles of 58 dogs of different breeds were evaluated using a standardized examination procedure. This procedure had been derived from that used in humans. The stifle is divided into several regions which are examined and evaluated. These are the suprapatellar, infrapatellar, lateral, caudal and medial region. One hundred twenty seven patients which had problems associated with the stifle joint were examined sonographically after a clinical and radiographic exam. Osteochondrosis dissecans, ruptured cranial cruciate ligament, meniscal damage, arthritis, tumor, post surgical conditions, injuries of the patella, patellar ligament or tibial tuberosity and luxating patella were examined sonographically and the findings recorded.

[Diseases of the Achilles tendon in dogs and cats]. / Achillessehnenerkrankungen bei Hund und Katze.

Dogs and cats rarely have problems with the Achilles tendon and if so, it usually results from a direct trauma. Prime area for injuries is the insertion on the tuber calcanei or directly proximal. One defers between complete and partial ruptures, acute and chronic injuries as well as displacement of the tendon of the superficial digital flexor muscle. In 38 cases (33 dogs and five cats) the clinical examination, radiology, ultrasonography and therapy are shown. Usually the clinical examination is sufficient for a diagnosis (hyperflexion of the hock and weight-bearing on the plantar surface of the metatarsus). The radiology primarily shows up abnormalities on the calcaneus, mineralisations of the tendon and allows the assessment of implants. Ultrasonography is the diagnostic imaging of choice for judgement of tendon diseases as well as the progress of their healing. Tendon suture is advisable if the rupture is open, fresh and/or complete and in cases of luxation of the superficial digital flexor muscle. Immobilisation of the tarsus in hyperextension seems to be of utmost importance no matter if an operative or conservative therapy is chosen.

[Excision arthroplasty of the hip joint in dogs and cats. Long-term results of the veterinary surgery clinic at the Justus Liebig University of Giessen]. / Resektionsarthroplastik des Hüftgelenkes bei Hunden und Katzen. Ergebnisse einer Langzeitstudie an der Chirurgischen Veterinärklinik der Justus-Liebig-Universität Giessen.

Since the introduction of excision arthoplasty in veterinary medicine the question of indication is often asked. The maximum of the patient's body weight up to which surgery should be performed is another discussed problem. A long-term study from January 1985 to July 1995 at the Veterinary Surgery Department at the Justus-Liebig-University was carried out to answer these questions (222 patients, 155 dogs and 67 cats). Trauma and Legg-Calvé-Perthes disease came first in the list of indications. In case of postoperative problems trouble with lameness after high activity, long rest or at the time of change in weather could be seen. No owner of an animal thought that the life quality of his animal was restricted by this occasional problems. At a body weight over 30 kg the occasional problems were more often seen but every patient had less clinical problems after surgery than before. In this group no deterioration was seen.

Sonography of the musculoskeletal system in dogs and cats.

Sonography of the musculoskeletal system in dogs and cats was undertaken to evaluate the application of this imaging procedure in orthopedics. In most of the patients a 7.5 MHz linear transducer was used because of its flat application surface and its resolving power. The evaluation of bone by sonography is limited, but sonography can provide addition information regarding the bone surface and surrounding soft tissue. Ultrasound is valuable for assessing joint disease. Joint effusion, thickening of the joint capsule and cartilage defects can be identified sonographically. It is also possible to detect bone destruction. Instabilities are often identified with the help of a dynamic examination. Soft tissue abnormalities of the musculoskeletal system lend themselves to sonographic evaluation. Partial or complete muscles or tendon tears are able to be differentiated and the healing process can be monitored. Most of the diseases that are in the area of the biceps or the achilles tendon, such as dislocation of the tendon, old injuries with scarification, free dissecates in the tendonsheath, tendinitis and/or tendosynovitis can be differentiated by sonography. In addition, with clinical and laboratory findings, it is often possible to make a correct diagnosis with ultrasound in patients with abscesses, foreign bodies, hematomas, soft tissue tumors and lipomas.

[The ultrasonic diagnosis of foreign bodies in the dog and cat]. / Die sonographische Diagnostik von Fremdkörpern bei Hund und Katze.

For the search of foreign bodies by means of ultrasound the 5 resp. 7.5 Mhz transducers are best used depending on the position. The appearance of different materials in the echotomogram such as plant parts, wood, metal or plastic is described. While in the abdominal organs, excluding the intestinal tract, a foreign body can be well detected, it can however only be visible in the abdominal cavity, when the surrounding tissue is inflamed (such as granuloma, abscess, free fluid). The ultrasound was only able to detect foreign bodies in the intestinal tract in approximately half of the cases. In those cases secondary sonographic signs of an ileus are often decisive. Penetrating foreign bodies in the area of the soft tissue of the musculoskeletal system are evaluated in the ultrasound according to their position, size and form. They are best seen when the inflamed reaction-line is well developed. Probes and catheters are definitively detected in the sonographic examination. Their position can be checked.

[Sonographic possibilities in emergency medicine]. / Sonographische Möglichkeiten in der Notfallmedizin.

Sonography can help to find quickly the correct diagnosis of emergency cases. More than a few ml's of fluid can easily be detected in the thoracic and abdominal cavity. Cells in this fluid are visible as fine dots. In this paper, diseases of the diaphragm, the spleen and the urogenital system, that can be diagnosed or excluded echotomographically with high security, are discussed. For the examination of the stomach, the intestines and the pancreas, sonography is an important time-saving supplementation to radiology. Therefore contrast media can often be avoided. Necessary punctures and biopsies can be performed sonographically aimed with a minimum of risk.

[Ultrasonic studies in reptiles]. / Ultraschalluntersuchung bei Reptilien.

Ultrasonography in reptiles is a safe, noninvasive repeatable diagnostic imagine method. Size, volume and inner structure of organs can easily be determined. Based on 460 ultrasonographic examinations in 8 species of terrapins, 12 species of snakes and 22 species of lizard normal appearance of heart, gonads, fat bodies, kidneys, bladder and gastrointestinal tract are described. Pathological findings are explained in details using examples.

[The importance of sonography in orthopedics for dogs]. / Die Bedeutung der Sonographie in der Orthopädie beim Hund.

For the ultrasonographic examination of the musculoskeletal system in dogs a 7,5 MHz linear scanner is used best, in some cases with a standoff pad. Radiography is the technique of choice to detect bone abnormalities. For certain circumstances the sonography can be used to give additional information (e.g. surrounding tissue with osteomyelitis or bone tumors). For the diagnostic of joint diseases ultrasonography is an excellent completion for the radiographic examination. Joint effusion and thickened capsule can be detected. Defects of articular cartilage like osteochondrosis dissecans in the knee or shoulder joint can be well seen. Instabilities of the joint can be identified with a dynamic examination. For evaluating the soft tissue areas ultrasonography is the optimal imaging procedure. Tears of muscles or tendons (e.g. achilles or biceps tendon), partial or complete ones, are seen in the sonographic examination. The process of healing with consolidation of the tendon can be controlled and documented. The tendon of the biceps brachii muscle is often affected in the soft tissue area of the shoulder. Luxation of the tendon, old injuries with scar formation, free dissections in the biceps tendon sheath and a tendovaginitis can be seen. Abscesses, foreign bodies, hematomas and soft tissue tumors in the musculoskeletal system can be well presented in the echotomogram. A tumor in the region of the brachial plexus can be detected directly with ultrasound.

[Ulna growth retardation syndrome in the dog]. / Das Syndrom der Wachstumshemmung der Ulna beim Hund. Diagnostik und Therapiemöglichkeiten.

Premature closure of the distal ulnar physis leads to medial bowing of the radius, later to lateral deviation of the carpus, and ventral subluxation of the elbow. Diagnosis of this growth disturbance depends on accurate radiographical examination. There are different surgical treatments to allow the radius to grow without impediment. The prognosis depends on early treatment.

[Diagnosis of prostatic diseases in the dog using ultrasonics]. / Die Diagnose von Prostataerkrankungen beim Hund mittels Ultraschall.

The use of sonography in diagnosing prostate gland diseases has proven very helpful. In contrast to x-raying, it allows the exact determination of the size and position of the prostate, without invasive methods or the danger of side-effects. It also allows the evaluation of its inner construction. For the veterinarian, this is important when weighing the different therapeutic possibilities. Through sonographic findings the kind, extent and localisation of necessary surgery can be decided before hand. The prognosis is facilitated and a continuous control of the intraprostatic process can be carried out, (for example; regression after castration, marsupialisation or antibiotic therapy). One must point out that, when judging prostate gland diseases, the diagnosis should never be made solely on sonographic results, but only in combination with clinical and laboratory examinations.