Evaluation of a targeted anti-αvß3 integrin near-infrared fluorescent dye for fluorescence-guided resection of naturally occurring soft tissue sarcomas in dogs.

PURPOSE: Complete resection is a key prognostic factor for survival in patients with soft tissue sarcoma (STS), in humas and companion animals alike. Fluorescence-guided surgery could improve resection accuracy. As dogs are frequently affected by STS, they serve as a model to test an anti-αvß3 integrin targeting near-infrared fluorescent (NIRF) dye (AngiostampTM800) for fluorescence-guided surgery in STS to evaluate its safety and feasibility in dogs, and if it translates into a clinically relevant benefit compared to the standard of care with regards to completeness of surgery and local recurrence. Furthermore, we aimed to correlate target expression and NIRF-signal intensity. METHODS: Twenty dogs with STS were randomly allocated to either receive Angiostamp™ (NIRF group) or physiologic saline (control group) preoperatively. The researchers were blinded for treatment, and resections were adapted based on the NIRF-signal, if needed. Margin status was histologically determined at the 1 and 3 cm margin. The tumor-to-background ratio was measured in native tissue biopsies and formalin-fixed tissue. The fluorescent area was compared to the corresponding tumor areas as confirmed by histology using the Dice coefficient. Target expression was quantified by immunohistochemistry and correlated to NIRF-signal ratios. RESULTS: A fluorescent signal was detected in all 10 tumors of the NIRF group, with a tumor-to-background ratio of 7.4 ± 5.8 in native biopsies and 13.5 ± 10.9 in formalin-fixed tissue. In the NIRF group, resection margins were adapted in 5/10 cases, leading to complete resection and preventing R1 in four of these cases. In the NIRF and control group 9/10 and 8/10 resections were R0, with one local recurrence in each group and one sarcoma-related death in the NIRF group. The NIRF-signal correlated with the histologically confirmed tumor area (Dice coefficient 0.75 ± 0.17). Target expression was higher in tumor compared to peritumoral tissue (p < 0.0003) and showed a moderate correlation with the NIRF-signal (r = 0.6516, p < 0.0001). CONCLUSION: Fluorescence-guided surgery using Angiostamp™ can pinpoint residual disease in the tumor bed and contributes to an improved resection accuracy in canine STS.

Cross-species evaluation of fibroblast activation protein alpha as potential imaging target for soft tissue sarcoma: a comparative immunohistochemical study in humans, dogs, and cats.

Introduction: Complete surgical tumor resection is paramount in the management of soft tissue sarcoma (STS) in humans, dogs, and cats alike. Near-infrared targeted tracers for fluorescence-guided surgery (FGS) could facilitate intraoperative visualization of the tumor and improve resection accuracy. Target identification is complicated in STS due to the rarity and heterogeneity of the disease. This study aims to validate the expression of fibroblast activation protein alpha (FAP) in selected human, canine, and feline STS subtypes to assess the value of FAP as a target for FGS and to validate companion animals as a translational model. Methods: Formalin-fixed and paraffin-embedded tissue samples from 53 canine STSs (perivascular wall tumor (PWT), canine fibrosarcoma (cFS), and STS not further specified (NOS)), 24 feline fibrosarcomas, and 39 human STSs (myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dermatofibrosarcoma protuberans, and malignant peripheral nerve sheath tumor) as well as six canine and seven feline healthy controls and 10 inflamed tissue samples were immunohistochemically stained for their FAP expression. FAP labeling in tumor, peritumoral, healthy skin, and inflamed tissue samples was quantified using a visually assessed semiquantitative expression score and digital image analysis. Target selection criteria (TASC) scoring was subsequently performed as previously described. Results: Eighty-five percent (85%) of human (33/39), 76% of canine (40/53), and 92% of feline (22/24) STSs showed FAP positivity in over 10% of the tumor cells. A high expression was determined in 53% canine (28/53), 67% feline (16/24), and 44% human STSs (17/39). The average FAP-labeled area of canine, feline, and human STSs was 31%, 33%, and 42%, respectively (p > 0.8990). The FAP-positive tumor area was larger in STS compared to healthy and peritumoral tissue samples (p < 0.0001). TASC scores were above 18 for all feline and human STS subtypes and canine PWTs but not for canine STS NOS and cFS. Conclusion: This study represents the first cross-species target evaluation of FAP for STS. Our results demonstrate that FAP expression is increased in various STS subtypes compared to non-cancerous tissues across species, thereby validating dogs and cats as suitable animal models. Based on a TASC score, FAP could be considered a target for FGS.

Retrospective evaluation of surgical site infection after open splenectomies with and without perioperative prophylactic antibiotic coverage.

OBJECTIVES: Perioperative prophylactic antibiotics (PPA) are widely used in veterinary medicine to prevent surgical site infections (SSI). Current guidelines advocate the use in clean procedures only if surgeries exceed 90 minutes, or in patients with an ASA score ≥3. Procedure specific recommendations are currently lacking. The following study aimed to analyze the protective effect of PPA in dogs undergoing open splenectomy. METHODS: The electronic database of our institution was searched for dogs that underwent splenectomy between 10/2017 and 01/2023. Data collection included age at presentation, breed, weight, reason for splenectomy, diagnosis, ASA class, PPA regime, surgery time, anesthesia time, lowest blood oxygen concentration during anesthesia, lowest body temperature, and lowest blood pressure during surgery as well as duration of hospitalization. Dogs were included if a follow-up of 30 days after surgery was available, or if death occurred within this timeframe. RESULTS: A total of 112 dogs were included. Of these, 46 dogs received PPA, and 66 did not. Most dogs were classified ASA 3 or higher (PPA 87%, non-PPA 80.3%). One SSI (1.5% SSI rate) occurred in the non-PPA group (overall SSI rate 0.9%). Due to the low SSI rate, statistical analysis of risk factors for SSI development was not possible. CONCLUSION: The described infection rate of 1.5% without PPA indicates, that splenectomy does not qualify as high-risk surgery for SSI, even in patients with ASA class 3 or higher. CLINICAL RELEVANCE: As splenectomies are frequently performed, the findings of the current study could have a major impact on the overall antimicrobial burden in routine veterinary practice.

[Neuroendocrine carcinoma of the gallbladder as a rare cause for melena and hematemesis in dogs]. / Neuroendokrines Karzinom der Gallenblase als seltene Ursache für Meläna und Hämatemesis beim Hund.

A 9-year-old male Malinois was presented for further workup of acute melena, hematemesis and chronic weight loss for a duration of one month. Clinically, the patient presented with a mildly reduced general condition. Blood tests revealed mild non-regenerative anemia as well as a mild elevation of alanine aminotransferase (ALT). Ultrasonography showed signs of an early mucocele. Treatment with gastroprotectants failed to lead to clinical improvement and the dog developed progressive anemia. Gastroduodenoscopy was unremarkable. Due to persistent clinical signs, exploratory laparotomy was performed. An ulcerated bleeding mass was detected at the gallbladder neck. Histopathological examination led to the diagnosis of a neuroendocrine carcinoma. There was no evidence of a mucocele on histopathology. Melena and hematemesis subsided postoperatively and 13 months after cholecystectomy, the dog remains without clinical signs. Neuroendocrine carcinomas of the gallbladder should be considered as a rare cause of melena and hematemesis in dogs.

Use of indocyanine green near-infrared lymphography to detect sentinel lymph nodes in a dog with a malignant insulinoma: a case report.

Malignant insulinoma is the most common type of neuroendocrine tumor found in the pancreas of dogs. Canine insulinoma displays malignant behavior with a high rate of metastasis. The most common sites of metastases are the draining lymph nodes, which are also the primary location sites for the recurrence of functional disease. However, identifying metastatic nodes can often be complicated, as the pancreas is drained by numerous lymphatic centers, and clinical enlargement or structural changes may not always be present in metastatic nodes. Additionally, unaltered nodes are frequently small (a few millimeters) and can be hard to distinguish from the surrounding tissues. Therefore, lymphadenectomy is generally recommended for affected dogs. Unlike in human medicine, there are currently no established strategies for lymph node resection in dogs with malignant insulinoma. This report presents a technique for identifying and removing sentinel nodes using indocyanine green and near-infrared lymphography (NIRFL) during surgery. A total of six sentinel nodes were detected and resected with this method. This technique could provide a more structured approach for lymph node resection in affected dogs and potentially in humans in the future. However, its therapeutic benefits must be evaluated in a larger cohort of cases.

Sentinel Lymph Node Mapping and Biopsy in Cats with Solid Malignancies: An Explorative Study.

There is increasing evidence on the utility of sentinel lymph node (SLN) biopsy (SLNB) for the staging of dogs with various malignancies; however, comparable information is missing in cats. This multi-institutional study aims at reporting the feasibility and detection rate of SLNB guided by lymphoscintigraphy and the blue dye or near-infrared fluorescent lymphography (NIRF-L) in cats with solid tumors. In total, 12 cats presented with 14 solid malignancies that underwent curative-intent surgical excision of the primary tumor and SLNB were retrospectively enrolled. The mapping technique used, location and number of SLN, correspondence with the regional lymph node (RLN), and histological status of the SLN were retrieved. The detection rate and complications of SLNB were also recorded. NIRF-L was performed in 64.3% of tumors and lymphoscintigraphy in 35.7%. The detection rate was 100% for both techniques. The SLN did not correspond (fully or partially) to the RLN in 71.4% of cases, with multiple SLN being excised in 9/14 tumors. No complications related to SLNB were recorded. At histopathology, metastases were identified in 41.7% of cats, all with mast cell tumors (MCT). SLNB guided by NIRF-L or lymphoscintigraphy is feasible and safe in cats with solid tumors and should be suggested for correct tumor staging in cats, especially with MCT.

Sentinel Lymph Node Biopsy Is Feasible in Dogs with Scars from Prior Local Excision of Solid Malignancies.

Sentinel lymph node (SLN) biopsy is a well-established staging tool in canine oncology. This study aims to explore the feasibility of SLN biopsy in dogs with scars from prior excised solid malignancies that were referred for further tumor staging and/or adjuvant treatment options. Mapping was either performed using radiopharmaceutical, methylene blue, and/or near-infrared fluorescent (NIRF) imaging. Thirty-three dogs with 34 scars from prior excision of the mast cell tumor (MCT) (n = 29), soft tissue sarcoma (n = 2), oral melanoma (n = 1), subungual melanoma (n = 1), and mammary adenocarcinoma (n = 1) were retrospectively enrolled. Primary treatment consisted of curative intent/wide tumor excisions in 50.0% of dogs and marginal excision in the remaining 50.0%. The median time between tumor excision and SLN biopsy was 50 days (range 17-110 days). The procedure was successful in 31/34 scars, translating to a detection rate of 91.2%. The SLN did not correspond to the regional lymph node in 19/31 scars (61.3%). SLN metastases were histologically identified in 13/31 (41.9%) dogs, all of them affected by MCT. Based on our results, SLN biopsy using lymphoscintigraphy/methylene blue and/or NIRF is feasible in dogs presenting with scars from the prior surgical excision of solid tumors, and should be suggested for accurate nodal staging.

Case Report: Indocyanine Green-Based Angiography for Real-Time Assessment of Superficial Brachialis Axial Pattern Flap Vascularization in Two Dogs.

This case report describes the method and feasibility of near-infrared angiography (NIRA) to improve the surgical procedure of two superficial brachial axial pattern flaps intraoperatively using two camera systems. Two client-owned dogs were treated for tumors on their antebrachia with wide surgical excision. The defects were closed with a superficial brachial flap in both cases. A different NIRA camera system was used for each case to identify the perforator vessel and flap margins accordingly. Case 1 developed a seroma and healed without further complications. Case 2 developed partial flap necrosis, underwent revision surgery, and healed by secondary intent. NIRA proved useful intraoperatively in identifying the perforator vessel and determining flap margins. As these are only two cases, caution should be used in extrapolating the results.

[Comparison of the antibacterial efficacy of polyhexanide, cold atmospheric argon plasma and saline in the treatment of canine bite wounds]. / Vergleich der Effizienz von Polyhexanid-Biguanid, Argon-Kaltplasma und Kochsalzlavage zur Dekontamination von Bisswunden beim Hund.

OBJECTIVE: To evaluate the bacterial contamination rate and to compare the efficacy of polyhexanide, cold argon plasma and saline at reducing bacterial bio-burden in dog bite wounds. MATERIAL AND METHODS: Dogs with bite-wound injuries were included when surgical debridement was pursued with subsequent treatment using either polyhexanide-biguanide lavage (A), cold argon plasma treatment (B) or saline lavage (C). Culture swabs were taken after debridement as well as after lavageor argon treatment. Statistical analysis was performed using the chi-square test. RESULTS: A total of 40 dogs were enrolled in the study (A: n = 12; B: n = 10; C: n = 18). The majority of injuries were minor and 87.5% of patients had positive bacterial culture results pre-lavage, with 19.8% of isolates classified as multidrug resistant. A reduction in wound bioburden was achieved in 8/12 patients in group A, 5/10 patients in group B and 14/18 patients in group C. Complete decontamination was achieved in 5/12 patients in group A, 2/10 in group B and 9/18 in group C. None of these differences were statistically significant nor associated with the development of complications. CONCLUSION: No statistically significant differences were detected between the treatment groups; however, the cold argon plasma treatment provided the least effective decontamination. CLINICAL RELEVANCE: Bite wounds yield a high rate of bacterial contamination, with increasing multidrug-resistance rates. Based on these preliminary results, no superior effect was detected for lavage using polyhexanidebiguanide or cold argon plasma.

Retrospective comparison of negative pressure wound therapy and silver-coated foam dressings in open-wound treatment in cats.

Objectives The objective of this study was to evaluate negative pressure wound therapy (NPWT) for the treatment of complicated wounds in cats. Methods Twenty cats undergoing open-wound treatment in two clinics were classed according to treatment method: NPWT (group A, n = 10) and polyurethane foam dressing (group B, n = 10). Pairs of patients from each group were matched based on wound conformation, localisation and underlying cause. Cats from both groups were compared in terms of duration of previous treatment, time to closure and complications. Results Signalment, duration of previous treatment, antibiotic and antiseptic treatment, and bacterial status were comparable between groups. Total time to wound closure was significantly shorter ( P = 0.046, strong effect size; Cohen d = 0.8) in group A (25.8 days, range 11.0-57.0 days) compared with group B (39.5 days, range 28.0-75.0 days). NPWT-treated wounds suffered fewer complications and became septic less frequently during treatment compared with wounds treated with a foam dressing. The progression of fat tissue necrosis was particularly well controlled under NPWT, resulting in fewer deaths due to this condition in this group. However, although a strong effect of NPWT on the progression of infection, fever and sepsis was detected (Cramer-V 0.5), this difference was not significant. Conclusions and relevance This study demonstrated that time to healing was considerably shorter, and complication rate lower, in NPWT-treated animals compared with foam dressing-treated cats. In particular, the effective management of infection by NPWT emphasises the value of NPWT in the treatment of cats suffering from infected wounds.