Development of patient-derived orthotopic xenografts from metastatic colorectal cancer in nude mice.

Liver metastasis is the major cause of death for patients with colorectal cancer. Despite treatment with surgery and chemotherapy, patient outcomes are quite unfavourable. Thus, there is an urgent need to develop new treatment strategies with the associated establishment of good animal models. Metastatic disease can be modelled using patient-derived orthotopic xenografts, which accurately replicate intra-tumoral heterogeneity so that various chemotherapeutic agents can be tested on individual tumours to aid in clinical decision-making. The objective of this study was to develop metastatic colorectal tumours in athymic nude mice by implanting fresh tumour fragments into mouse liver parenchyma. Metastatic tumours were successfully propagated in mice following transplantation from human patients, then serially implanted in second and third-generation mice. Morphologic and immunohistochemical characteristics indicate that xenografts recreate the tumour architecture and mismatch repair gene expression for MLH1, MSH2, MSH1, and PMS2. After tumour implantation during the first passage, the time of tumour growth decreased without loss of tumour identity. Post-transplantation lymphoproliferative disease was observed in one case. This pilot study was successful in establishing the institutional PDX preclinical platform to study new therapeutic strategies, disease progression biomarkers, and treatment responsiveness.

Radical Cystectomy and Cutaneous Ureterostomy in 4 Dogs with Trigonal Transitional Cell Carcinoma: Description of Technique and Case Series.

OBJECTIVE: To describe radical cystectomy followed by cutaneous ureterostomy as a treatment of invasive bladder neoplasia in dogs. STUDY DESIGN: Retrospective study. ANIMALS: Client-owned dogs with transitional cell carcinoma of the bladder trigone (n=4). METHODS: Perioperative complications and long-term outcomes of dogs that underwent cutaneous ureterostomy following radical cystectomy and lymphadenectomy for transitional cell carcinoma of the urinary bladder trigone were reviewed. Both ureters were transected and anastomosed to the ventral abdominal skin. Polyvinyl chloride catheters were placed in the ureteral stomas and maintained for 5 days. After catheter removal, dogs were managed with an absorbent diaper over the stomas. Long-term outcome and survival were documented by follow-up visits or phone contact. RESULTS: Median age at the time of surgery was 10.3 years (range, 8-12). Average procedural time was ∼4.7 hours (range, 3.8-6.1). Minor complications occurred in all dogs, including bleeding and edema of the ureterostomy site during the first 2-3 days after surgery. One dog developed urine scald that resolved with improved stoma care and hygiene. Median survival time after surgery was 278.6 days (range, 47-498). Distant metastases were documented in 2 dogs at 47 days (bone) and 369 days (lung) after surgery. CONCLUSION: Radical cystectomy with cutaneous ureterostomy is a viable salvage procedure for urinary diversion after cystectomy in dogs with invasive bladder neoplasia. Postoperative management and quality of life were considered acceptable by most owners. Future studies are warranted to evaluate survival time in a larger number of animals.