Precise timing of audiovisual stimulation conquers chemobrain.

In a recent study, Kim et al. utilized gamma entrainment using sensory stimuli (GENUS) to rescue cognitive impairment and glial dysregulation associated with cisplatin and methotrexate chemotherapy, specifically when applied both throughout and after chemotherapy administration. GENUS provides a time-dependent, non-invasive method for treating chemobrain, with broader implications for resolving neurodegenerative neuroinflammation.

Canine Prostate Cancer: Current Treatments and the Role of Interventional Oncology.

Prostate carcinoma is one of the most common cancers worldwide in men, with over 3 million men currently living with prostate carcinoma. In men, routine screening and successful treatment schemes, including radiation, prostatectomy, or hormone therapy, have allowed for high survivability. Dogs are recognized as one of the only mammals to spontaneously develop prostate neoplasia and are an important translational model. Within veterinary medicine, treatment options have historically been limited in efficacy or paired with high morbidity. Recently, less invasive treatment modalities have been investigated in dogs and people and demonstrated promise. Below, current treatment options available in dogs and people are reviewed, as well as a discussion of current and future trends within interventional treatment for canine PC.

Next Directions in the Neuroscience of Cancers Arising outside the CNS.

SUMMARY: The field of cancer neuroscience has begun to define the contributions of nerves to cancer initiation and progression; here, we highlight the future directions of basic and translational cancer neuroscience for malignancies arising outside of the central nervous system.

Evaluation of mediastinoscopy for cranial mediastinal and tracheobronchial lymphadenectomy in canine cadavers.

OBJECTIVE: To report technical feasibility and describe procedural details of a novel single incision minimally invasive approach to the mediastinum in cadaver dogs. STUDY DESIGN: Cadaveric study. ANIMALS: Large breed (25-40 kg) cadaver dogs (n = 10). METHODS: Three of 10 cadavers were used for preliminary technique development without data recording. Cadaver specimens underwent pre- and postoperative thoracic computed tomographic scans. Seven dogs were placed in dorsal recumbency and mediastinoscopy was performed via a SILS port placed cranial to the thoracic inlet with CO2 insufflation of the mediastinum at 2-4 mmHg. Retrieval of all CT and visually identified mediastinal lymph nodes (LN) was attempted; endoscopic compartmental and individual LN dissection times and subjective operative challenges were recorded. Procedural success scores for visualization and dissection as well as NASA-task force index scores were recorded per lymph node, per cadaver. RESULTS: Median time required for initial approach including SILS placement was 5 min (range 5-10 min). Individual LN retrieval times ranged from 2 to 32 min. Mediastinoscopic retrieval of LNs was most commonly successful for the left tracheobronchial LN (7/7), followed by the right tracheobronchial LN (4/7), the left and right sternal LNs (3/7 each), and the cranial mediastinal LNs (1/7). Post-procedure pleural gas was identified on CT in 4/7 cadavers. CONCLUSIONS: Mediastinoscopy as reported was feasible in large breed canine cadavers and retrieval or cup biopsy of a variety of lymph nodes is possible from the described approach. Application in living animals and its associated challenges should be further investigated. CLINICAL SIGNIFICANCE: Mediastinoscopy may provide a novel minimally invasive approach to the evaluation and oncologic staging of the cranial mediastinum in dogs.

Augmenting Veterinary Minimally Invasive Surgery: Evidence-based Review of Foundational and Novel Devices and Technology.

Veterinary minimally invasive surgery continues to grow as a specialty. With increasing experience in this field, comes improved accessibility as well as progressive complexity of procedures performed. Advancement in technology has been both a response to the growth and a necessary driver of continued refinement of this field. Innovative research leading to advancements in surgical equipment has led to the development of novel image acquisition platforms, cannulas, smoke evacuation systems, antifog devices, instrumentation, and ligating/hemostatic devices. These innovations will be reviewed and potential clinical applications are discussed.

Minimally invasive splenectomy is associated with a low perioperative complication rate and short operative time in cats.

OBJECTIVE: To report the perioperative outcome and complications in cats undergoing minimally invasive splenectomy. ANIMALS: 17 client-owned cats. METHODS: Perioperative data were collected from cats undergoing minimally invasive splenectomy from September 2010 to June 2023. Data included history, signalment, preoperative examination and diagnostic testing results, operative technique and time, perioperative outcomes, complications, hospitalization duration, histopathological diagnosis, and outcome. RESULTS: 13 spayed females and 4 neutered males were included, with a median age of 144 months (48 to 196 months). Seven cats underwent total laparoscopic splenectomy (TLS), with 1 cat requiring conversion from TLS to laparoscopic-assisted splenectomy (LAS) due to splenomegaly and an additional cat requiring conversion from TLS to open splenectomy due to uncontrollable splenic capsular hemorrhage. Ten cats underwent LAS, with 1 cat requiring conversion to open splenectomy due to splenomegaly. Additional procedures were performed in 13 cats, with the most common being liver biopsy in 10 cats. Median operative times were 50 minutes (45 to 90 minutes) for TLS and 35 minutes (25 to 80 minutes) for LAS. An intraoperative complication occurred in 1 cat. All but 1 cat survived to discharge. Median follow-up time was 234 days (18 to 1,761 days), with 15 of 16 cats confirmed alive at 30 days and 9 of 16 cats alive at 180 days postoperatively. CLINICAL RELEVANCE: Minimally invasive splenectomy in this cohort of cats was associated with short operative times and a low perioperative complication rate. Veterinary surgeons may consider minimally invasive splenectomy as an efficient and feasible technique in the treatment of splenomegaly or modestly sized splenic masses for diagnostic and therapeutic purposes in cats.

Adrenal tumors treated by adrenalectomy following spontaneous rupture carry an overall favorable prognosis: retrospective evaluation of outcomes in 59 dogs and 3 cats (2000-2021).

OBJECTIVE: To conduct a retrospective multi-institutional study reporting short- and long-term outcomes of adrenalectomy in patients presenting with acute hemorrhage secondary to spontaneous adrenal rupture. ANIMALS: 59 dogs and 3 cats. METHODS: Medical records of dogs and cats undergoing adrenalectomy between 2000 and 2021 for ruptured adrenal masses were reviewed. Data collected included clinical presentation, preoperative diagnostics, surgical report, anesthesia and hospitalization findings, histopathology, adjuvant treatments, and long-term outcome (recurrence, metastasis, and survival). RESULTS: Median time from hospital admission to surgery was 3 days, with 34% of surgeries being performed emergently (within 1 day of presentation). Need for intraoperative blood transfusion was significantly associated with emergent surgery and presence of active intraoperative hemorrhage. The short-term (≤ 14 days) complication and mortality rates were 42% and 21%, respectively. Negative prognostic factors for short-term survival included emergent surgery, intraoperative hypotension, and performing additional surgical procedures. Diagnoses included adrenocortical neoplasia (malignant [41%], benign [12%], and undetermined [5%]), pheochromocytoma (38%), a single case of adrenal fibrosis and hemorrhage (2%), and a single case of hemangiosarcoma (2%). Local recurrence and metastasis of adrenocortical carcinoma were confirmed in 1 and 3 cases, respectively. Overall median survival time was 574 days and 900 days when short-term mortality was censored. No significant relationship was found between histopathological diagnosis and survival. CLINICAL RELEVANCE: Adrenalectomy for ruptured adrenal gland masses was associated with similar short- and long-term outcomes as compared with previously reported nonruptured cases. If hemodynamic stability can be achieved, delaying surgery and limiting additional procedures appear indicated to optimize short-term survival.

Laparoscopic adrenalectomy for resection of unilateral noninvasive adrenal masses in dogs is associated with excellent outcomes in experienced centers.

OBJECTIVE: To report the short- and long-term outcomes of laparoscopic adrenalectomy (LA) for resection of unilateral adrenal masses and to document risk factors for conversion and peri- and postoperative morbidity. ANIMALS: 255 client-owned dogs. METHODS: Dogs were included if LA was attempted for resection of a unilateral adrenal mass. Medical records were evaluated and relevant data were reported, including complications, conversion, perioperative death, and long-term outcomes. Signalment, clinicopathological data, and surgical experience were factors statistically evaluated for possible associations with capsular penetration during surgery, conversion, surgical time, duration of hospital stay, death prior to discharge, mass recurrence, and survival time. RESULTS: 155 dogs had left-sided tumors, and 100 had right-sided tumors. Conversion to an open approach was performed in 9.4% of cases. Capsular penetration (19.2%) and major hemorrhage (5.4%) were the most prevalent intraoperative complications. Of the dogs operated on, 94.9% were discharged from the hospital. Lesion side, portion of the gland affected, and surgeon experience influenced surgical time. Conversion rate increased with increasing body condition score and lesion size. Risk of death prior to discharge increased with increasing lesion size. Risk of conversion and death prior to discharge were lower when performed by more experienced surgeons. Capsular penetration during LA increased the risk of tumor recurrence. CLINICAL RELEVANCE: LA for resection of unilateral adrenal masses is associated with excellent outcomes in experienced centers. Surgeons with greater experience with LA have lower surgical times, conversion rates, and risk of death prior to discharge.

Review: therapeutic approaches for circadian modulation of the glioma microenvironment.

High-grade gliomas are malignant brain tumors that are characteristically hard to treat because of their nature; they grow quickly and invasively through the brain tissue and develop chemoradiation resistance in adults. There is also a distinct lack of targeted treatment options in the pediatric population for this tumor type to date. Several approaches to overcome therapeutic resistance have been explored, including targeted therapy to growth pathways (ie. EGFR and VEGF inhibitors), epigenetic modulators, and immunotherapies such as Chimeric Antigen Receptor T-cell and vaccine therapies. One new promising approach relies on the timing of chemotherapy administration based on intrinsic circadian rhythms. Recent work in glioblastoma has demonstrated temporal variations in chemosensitivity and, thus, improved survival based on treatment time of day. This may be due to intrinsic rhythms of the glioma cells, permeability of the blood brain barrier to chemotherapy agents, the tumor immune microenvironment, or another unknown mechanism. We review the literature to discuss chronotherapeutic approaches to high-grade glioma treatment, circadian regulation of the immune system and tumor microenvironment in gliomas. We further discuss how these two areas may be combined to temporally regulate and/or improve the effectiveness of immunotherapies.

Comparative Oncology: Management of Hepatic Neoplasia in Humans and Dogs.

Primary hepatic neoplasia is uncommonly reported in dogs. Hepatocellular carcinoma (HCC) is the most frequent neoplasia identified in dogs and considerable effort has been committed towards identifying definitive and palliative treatment options. HCC is well recognized in humans as a sequelae of liver disease such as hepatitis or cirrhosis, while in dogs a similar link has failed to be fully elucidated. Management of HCC in people may be curative or palliative dependent on staging and transplant eligibility. Despite differences in etiology, there is substantial similarity between treatment options for liver neoplasia in human and veterinary medicine. The below summary provides a comparative discussion regarding hepatic neoplasia in dogs and people with a specific focus on HCC. Diagnosis as well as descriptions of the myriad treatment options will be reviewed.

Perioperative characteristics, histologic diagnosis, complications, and outcomes of dogs undergoing percutaneous drainage, sclerotherapy or surgical management of intrarenal cystic lesions: 18 dogs (2004-2021).

BACKGROUND: Canine intrarenal cystic lesions (ICLs) are infrequently reported in the veterinary literature. Several treatment options have been described including cyst fenestration (partial nephrectomy/deroofing) +/- omentalization, sclerotherapy using alcohol as a sclerosing agent, percutaneous cyst drainage (PCD), and ureteronephrectomy. Information regarding presenting clinical signs, physical examination findings, histologic diagnosis and outcomes of dogs with ICLs treated by different methods is limited. Medical records of 11 institutions were retrospectively reviewed to identify dogs that underwent PCD, sclerotherapy, surgical deroofing +/- omentalization, or ureteronephrectomy for management of ICLs from 2004 to 2021. Six weeks postoperative/post-procedural follow-up was required. Cases suspected to represent malignancy on preoperative imaging were excluded. The study objective was to provide information regarding perioperative characteristics, complications, and outcomes of dogs undergoing treatment of ICLs. RESULTS: Eighteen dogs were included, with 24 ICLs treated. Ten had bilateral. There were 15 males and 3 females, with crossbreeds predominating. PCD, sclerotherapy, deroofing and ureteronephrectomy were performed in 5 (5 ICLs treated), 7 (11 ICLs), 6 (6), and 7 (7) dogs, respectively, with 5 dogs undergoing > 1 treatment. Seven dogs experienced 8 complications, with requirement for additional intervention commonest. PCD, sclerotherapy and deroofing resulted in ICL resolution in 0/5, 3/11 and 3/6 treated ICLs, respectively. Histopathology identified renal cysts (RCs) in 7/13 dogs with histopathology available and neoplasia in 6/13 (4 malignant, 2 benign). Of 5 dogs diagnosed histopathologically with neoplasia, cytology of cystic fluid failed to identify neoplastic cells. Among 7 dogs with histologically confirmed RCs, 4 had concurrent ICLs in ipsilateral/contralateral kidney, compared with 2/6 dogs with histologically confirmed neoplasia. CONCLUSIONS: Benign and neoplastic ICLs were approximately equally common and cystic fluid cytology failed to differentiate the 2. Among renal-sparing treatments, deroofing most commonly resulted in ICL resolution. Presence of concurrent ICLs in ipsilateral/contralateral kidney does not appear reliable in differentiating benign from malignant ICLs.

Ethylene vinyl alcohol copolymer to treat an intracranial arteriovenous malformation in a dog.

A 6-year-old neutered male German shepherd dog was evaluated for obtundation, blindness, and bilateral exophthalmos. A magnetic resonance imaging scan of the brain was performed and identified an arteriovenous malformation (AVM) with several feeding arterial branches, and venous drainage through the cavernous sinus. Venous vessels rostral to the AVM were severely distended and extended into the retrobulbar spaces. Liquid embolization by injection of ethylene vinyl alcohol copolymer was performed from access points in the maxillary arteries and internal carotid arteries. No intraprocedural complications were encountered, and the dog was discharged the next day. Bilateral enucleation eventually was performed because of exposure keratopathy. At 31 months post-embolization, owners reported that the dog was doing very well clinically with high activity level and normal appetite, and the dog also appeared to be pain free. Although intracranial AVMs are very rare in companion animals, successful treatment using liquid embolization is possible and should be considered.

NF1 mutation drives neuronal activity-dependent initiation of optic glioma.

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood3,4, raising  the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1)5 to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.

Removal and repositioning of urinary tract implants by use of an endovascular snare system in dogs and cats (2013-2019).

OBJECTIVE: To report the fluoroscopic removal or repositioning of urinary tract implants in dogs and cats by use of an endovascular snare system (ESS) and to report procedural usefulness and complications in dogs and cats. ANIMALS: 3 cats and 14 dogs. PROCEDURES: A medical records review was performed to identify dogs and cats that underwent removal or repositioning of urinary tract foreign bodies or implants by use of an ESS with fluoroscopic guidance at a veterinary teaching hospital from 2013 to 2019. RESULTS: Dogs had a median weight of 25 kg (55 lb) with a range of 3.5 to 60.6 kg (7.7 to 133.3 lb), and cats had a median weight of 5 kg (11 lb) with a range of 4.2 to 5.4 kg (9.2 to 11.9 lb). By use of an ESS, 12 patients (2 cats and 10 dogs) underwent transurethral retrieval of retained vesicourethral implants or ureteral stents, 2 dogs underwent transurethral ureteral stent repositioning, 1 cat and 2 dogs underwent transnephric retrieval of ureteral stents, and 1 dog underwent cystoscopic-assisted transureteral ureteral stent retrieval. All procedures were successfully performed, and there were no associated procedural complications. CONCLUSIONS AND CLINICAL RELEVANCE: Retained vesicourethral implants or ureteral stents were successfully retrieved by use of an ESS in dogs and cats transurethrally or with an open or percutaneous transnephric approach and fluoroscopic guidance. These techniques should be considered as an alternative or adjunct to more invasive methods for implant retrieval or manipulation.

Microglia in Cancer Therapy-Related Cognitive Impairment.

Millions of cancer survivors experience a persistent neurological syndrome that includes deficits in memory, attention, information processing, and mental health. Cancer therapy-related cognitive impairment can cause mild to severe disruptions to quality of life for these cancer survivors. Understanding the cellular and molecular underpinnings of this disorder will facilitate new therapeutic strategies aimed at ameliorating these long-lasting impairments. Accumulating evidence suggests that a range of cancer therapies induce persistent activation of the brain's resident immune cells, microglia. Cancer therapy-induced microglial activation disrupts numerous mechanisms of neuroplasticity, and emerging findings suggest that this impairment in plasticity is central to cancer therapy-related cognitive impairment. This review explores reactive microglial dysregulation of neural circuit structure and function following cancer therapy.

Pediatric Primary Care Provider Perspectives on a Computer-Facilitated Screening and Brief Intervention System for Adolescent Substance Use.

PURPOSE: This study aimed to elicit pediatric primary care providers' (PCPs) feedback on the acceptability and feasibility of implementing a tablet computer-facilitated Screening and Brief Intervention (cSBI) system for adolescent substance use in their practices. METHODS: We trained PCPs at five Boston area practices and enrolled their 12- to 18-year-old patients in a pilot randomized trial of cSBI versus usual care. PCPs completed an 18-item poststudy questionnaire. We computed frequencies and thematically coded open-ended responses. RESULTS: The analysis sample included 49 of 54 participating PCPs (90.7%). Overall, 89.8% of participants agreed the cSBI system was useful, and 81.6% reported increased confidence in providing brief counseling. Most useful were the immediate availability of screen results, talking points on substance use risks, and counseling prompts. Challenges included time and unfamiliarity with tablet computers. Many suggested electronic health record integration of cSBI to improve efficiency. CONCLUSIONS: cSBI showed high acceptability and increased confidence among pediatric PCPs. Feasibility could be enhanced by electronic health record integration.

Evaluation of transanal minimally invasive surgery for submucosal rectal resection in cadaveric canine specimens.

OBJECTIVE: To evaluate the feasibility of transanal minimally invasive surgery (TAMIS) for submucosal rectal resection in large breed dogs. STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Canine cadavers (n = 6) weighing between 37.5 and 60 kg. METHODS: Dogs were positioned in sternal recumbency. After rectal cleansing, a transanal access platform was placed in the rectum, and a pneumorectum was established. An area of ventral rectal wall approximately 2 × 2 cm was resected in a submucosal plane by using laparoscopic instruments and submitted for histopathological evaluation. The rectal wall defect was closed with a single-layer continuous suture pattern with barbed suture. Postoperatively, the rectum was removed en bloc and evaluated for suture or surgical penetration of the serosal surface. RESULTS: Submucosal rectal resection was successfully completed by using TAMIS in all dogs. The median length of resected specimens after fixation was 24.5 mm (range 9.8-26.5). In two of six dogs, suture was macroscopically visible on the serosal surface, but no dogs had evidence of iatrogenic full-thickness surgical penetration of the rectum. The median distance from the aborad extent of the suture closure line to the anocutaneous junction was 35 mm (range, 35-105). CONCLUSION: Submucosal resection of the canine rectal wall was feasible in large breed dogs by using TAMIS. No evidence of full-thickness penetration of the rectal wall was seen in these cadaveric specimens. CLINICAL SIGNIFICANCE: Transanal minimally invasive surgery may provide an alternative minimally invasive approach for resection for benign adenomatous rectal polyps in large breed dogs that might otherwise require a rectal pull-through.

Gastrointestinal obstruction secondary to activated charcoal granule impaction in a dog.

OBJECTIVE: To describe a serious adverse event of gastrointestinal obstruction requiring surgery following routine administration of multiple doses of activated charcoal (AC) granules, which were prescribed for carprofen toxicosis. CASE SUMMARY: A 2-year-old female neutered Airedale Terrier presented for ingestion of 207 mg/kg of carprofen. Decontamination was initiated with apomorphine to induce emesis. Along with additional supportive care, the dog received an initial dose of 75 mL of AC suspension containing sorbitol by mouth (15.6 g of AC, or 0.6 g/kg), followed by 50 g of AC granules every 8 hours for 4 additional doses. While hospitalized, the dog experienced clinical signs, including vomiting and black diarrhea, as well as bloodwork changes including mild to moderate elevations in kidney and liver enzymes. Given clinical improvement after 72 hours of hospitalization, the patient was discharged for monitoring and ongoing care at home. Two days later, the patient presented again for nausea, dark diarrhea with frank blood, and panting. Abdominal ultrasound showed findings suspicious for partially obstructive foreign material or atypical impacted fecal material partially occluding the distal ileum. Despite medical management overnight, recheck ultrasound the following day demonstrated persistent obstruction with ileal foreign material. Exploratory laparotomy and enterotomy revealed moderate distension and obstruction of the distal ileum with black granular foreign material consistent with charcoal granules. The patient remained in hospital for supportive care for 4 days following the procedure, and all clinical signs were resolved at the time of discharge. NEW OR UNIQUE INFORMATION PROVIDED: This report documents a serious adverse event of gastrointestinal obstruction associated with routine multidose AC administration, which has been occasionally reported in people but not in dogs. The potential for this complication should be taken into account when prescribing multiple doses of AC granules.

Severe intermittent lameness secondary to a migrating metallic foreign body in a dog.

CASE DESCRIPTION: An 11-month-old mixed-breed dog was evaluated because of a 2-day history of acute-onset, intermittent vocalization and collapse several days after ingesting metallic wire foreign material. CLINICAL FINDINGS: Physical examination findings were initially unremarkable. After a brief period of hospitalization, the patient acutely developed non-weight-bearing lameness with signs of severe pain localized to the left thoracic limb and inability or refusal to rise. Results of cervical, thoracic, and abdominal radiography revealed a linear metallic foreign body at the thoracic inlet and a single metallic foreign body in the cranial aspect of the abdomen. Neuropathic pain at the level of the left brachial plexus was suspected. Results of a subsequent CT scan were consistent with a metallic foreign body in the left axilla with associated abscess formation and neuritis and an additional metallic foreign body within the omental fat near the pyloroduodenal junction. TREATMENT AND OUTCOME: Intraoperative fluoroscopy was used to facilitate localization and surgical removal of the axillary foreign body. The intra-abdominal foreign body was removed laparoscopically. Complete resolution of clinical signs was observed before discharge from the hospital the following day. On telephone follow-up 8 months after surgery, the owners reported the patient had no signs of lameness or complications. CLINICAL RELEVANCE: Migrating metallic foreign bodies may be identified as incidental findings with the potential to cause harm in the future or may be a cause for severe clinical signs. Migrating foreign bodies should be considered as a differential diagnosis for patients reported to have acute collapse or lameness and consistent clinical history.