TL;DR: C242-DM1 represents a new generation of immunoconjugates that may yet fulfill the promise of effective cancer therapy through antibody targeting of cytotoxic agents.
Abstract: The maytansinoid drug DM1 is 100- to 1000-fold more cytotoxic than anticancer drugs that are currently in clinical use. The immunoconjugate C242-DM1 was prepared by conjugating DM1 to the monoclonal antibody C242, which recognizes a mucin-type glycoprotein expressed to various extents by human colorectal cancers. C242-DM1 was found to be highly cytotoxic toward cultured colon cancer cells in an antigen-specific manner and showed remarkable antitumor efficacy in vivo. C242-DM1 cured mice bearing subcutaneous COLO 205 human colon tumor xenografts (tumor size at time of treatment 65-130 mm3), at doses that showed very little toxicity and were well below the maximum tolerated dose. C242-DM1 could even effect complete regressions or cures in animals with large (260- to 500-mm3) COLO 205 tumor xenografts. Further, C242-DM1 induced complete regressions of subcutaneous LoVo and HT-29 colon tumor xenografts that express the target antigen in a heterogeneous manner. C242-DM1 represents a new generation of immunoconjugates that may yet fulfill the promise of effective cancer therapy through antibody targeting of cytotoxic agents.
TL;DR: The medical records of equine gastrointestinal colic cases presented to the Western College of Veterinary Medicine between 1992 and 2002 are reviewed and the recovery rates were comparable with those of other studies.
Abstract: The medical records of equine gastrointestinal colic cases presented to the Western College of Veterinary Medicine between 1992 and 2002 are reviewed. There was no breed predisposition to colic. Geldings were more prone to colic than females and stallions. Overall, the 3 most common causes of colic were large colon impaction (20.8%), large colon displacement (16.5%), and spasmodic colic (11.7%), after excluding the 13% of cases in which the diagnosis was undetermined. Of the medical cases, large colon impaction (38.4%) and spasmodic colic (22.5%) were the most common. Of the surgical cases, large colon displacement (24.5%), large colon torsion (14.3%), and strangulating lipoma (13.5%) were the most common. Recovery rate for the medical cases was 93.6%. Recovery rate for surgical cases was 73.5%. In conclusion, most of the equine colic cases were medical, and the recovery rates for both surgical and medical cases were comparable with those of other studies.
TL;DR: Adult equine jejunum sustains more serosal damage than the ascending colon after similar periods of ischemia-reperfusion injury and the small intestine is more susceptible to seromuscular layer damage thanThe ascending colon.
Abstract: Objective— To document morphologic changes that occur in equine intestinal serosa after experimentally induced ischemia and subsequent reperfusion (jejunum, ascending colon) or after intraluminal distention and decompression (jejunum).
Study Design— Morphologic effects of ischemia-reperfusion or intraluminal distention-decompression determined on the serosal layer of the equine jejunum. The large colon serosa was evaluated after ischemia-reperfusion injury.
Animals or Sample Population— Seven adult horses.
Methods— After induction of general anesthesia and ventral median celiotomy, ischemia was created by arteriovenous (AVO) and lumen occlusion of a 20-cm segment of jejunum and ascending colon for 70 minutes, followed by a 60-minute reperfusion period. Intraluminal distention (25 cm H2O) was created in a second 20-cm jejunal segment and maintained within the abdomen for 120 minutes, followed by a 120-minute decompression period. Seromuscular biopsies were obtained upon entering the abdomen and after the ischemic and reperfusion periods, and after the distention and decompression periods along with corresponding control seromuscular biopsies. Samples were processed and examined by light microscopy, transmission electron, and scanning electron microscopy.
Results— Ischemia and reperfusion, and intraluminal distention and decompression, resulted in severe morphologic changes in the seromuscular layer of equine jejunum. A similar period of ischemia-reperfusion caused minimal changes in the ascending colon serosa.
Conclusion— Adult equine jejunum sustains more serosal damage than the ascending colon after similar periods of ischemia-reperfusion injury. Intraluminal distention and subsequent decompression causes serosal damage in the equine jejunum.
Clinical Relevance— The small intestine is more susceptible to seromuscular layer damage than the ascending colon.
TL;DR: Interpretation of changes in colonic morphology can be used to accurately predict postoperative survival in horses with large colon torsion.
Abstract: Objective— To determine if morphologic evaluation of intraoperative biopsies of the large colon could be used to accurately predict outcome in horses with large colon torsion.
Study Design— Clinical study.
Animals— Fifty-four horses with large colon torsion.
Methods— A full-thickness biopsy was collected from the pelvic flexure of the ascending colon after correction of naturally occurring colonic torsion. Morphologic changes were evaluated and graded for interstitial tissue to crypt ratio (I:C ratio), percentage loss of superficial and glandular epithelium, and the degree of hemorrhage and edema. These variables were then used to predict survival.
Results— Morphologic variables could be used to correctly predict survival or death in 51 horses (P < .0001). This corresponded to a sensitivity of 95.1% (82.2%-99.2%; 95% CI) and a specificity of 92.3% (62.0%-99.6%; 95% CI). Of 6 horses that had colonic resection, 5 survived; an accurate prediction of outcome based on morphologic criteria was made for each horse.
Conclusions— Interpretation of changes in colonic morphology can be used to accurately predict postoperative survival in horses with large colon torsion.
Clinical Relevance— Use of frozen colonic tissue sections is a rapid, reliable, and relatively inexpensive method for assessing morphologic damage associated with large colon torsion during surgery. Intraoperative evaluation of pelvic flexure biopsies can aid in the prediction of survival and guide surgical judgment as to the need for colonic resection.
TL;DR: Horses that survive the early postoperative period and are discharged after large colon resection and anastomosis have a good chance for long-term survival with minimal negative impact on quality of life and use.
Abstract: Objective— To report complications and survival after large colon resection and end-to-end anastomosis in horses with strangulating large colon volvulus.
Study Design— Retrospective case series.
Animals— Horses (n=73) with strangulating large colon volvulus.
Methods— Records (January 1995 to December 2005) of horses that had large colon resection and anastomosis for strangulating large colon volvulus were reviewed for complications. Follow-up data were obtained by telephone questionnaire at least 1 year postoperatively. Cox proportional hazards model was used for multivariate association with survival time. Variables included admission date, age, temperature, heart rate, packed cell volume, total plasma protein concentration, white blood cell count, breed, and sex. Significance was set at P<.05.
Results— The most common postoperative complication was diarrhea. None of the 9 variables of interest were significant for survival. Short-term survival rate (to discharge) was 74%. Overall survival rates at 1, 2, and 3 years postoperatively were 67.8%, 66.0%, and 63.5%, respectively. Four horses died of colic in the first year after surgery. All horses surviving long-term (>1 year) returned to their intended use (37 brood mares, 2 racehorses, and 1 show horse) with no chronic problems related to the surgical procedure.
Conclusion— None of the variables examined were associated with survival. Outcomes were similar to other large studies of surgical colic in the horse. Self-limiting diarrhea is common after large colon resection and the prognosis for survival after hospital discharge is favorable.
Clinical Relevance— Horses that survive the early postoperative period and are discharged after large colon resection and anastomosis have a good chance for long-term survival with minimal negative impact on quality of life and use.