Clinical and intestinal histologic features of horses treated for recurrent colic: 66 cases (2006–2015)

Holly L. Stewart Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.

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Julie B. Engiles Department of Pathobiology, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.

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Darko Stefanovski Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.

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Louise Southwood Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348.

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Abstract

OBJECTIVE To describe gastrointestinal histologic findings for horses with recurrent colic and evaluate possible associations between initial clinical signs, biopsy method, histologic diagnosis, and outcome 1 year after hospital discharge.

DESIGN Retrospective case series.

ANIMALS 66 horses with a history of recurrent colic for which gastrointestinal specimens had been submitted for histologic examination.

PROCEDURES Histologic diagnosis was categorized as inflammatory, neoplastic, ischemic, other, and undiagnosed. Relationships among initial clinical features, biopsy method, histologic diagnosis, and outcome 1 year after hospital discharge (ie, alive vs dead and persistent recurrent colic [yes vs no]) and between corticosteroid treatment and outcome were investigated. Odds ratios and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.

RESULTS Inflammatory disease (36/66 [55%]) was the most common histologic diagnosis. Horses undergoing rectal biopsy alone were significantly (OR, 14.4; 95% Cl, 2.7 to 76.1) more likely to not have a histologic diagnosis than were horses in which other biopsy methods were used. In multivariable modelling, persistence of recurrent colic (HR, 15.2; 95% Cl, 1.9 to 121.2) and a history of weight loss (HR, 4.9; 95% Cl, 1.4 to 16.5) were significantly associated with outcome (alive vs dead) 1 year after surgery. Corticosteroid treatment was not significantly associated with either outcome.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a high proportion (36/66 [55%]) of horses with recurrent colic had inflammatory gastrointestinal disease. Use of rectal biopsy alone to obtain biopsy specimens was more likely to result in no histologic diagnosis. Use of corticosteroids in horses with inflammatory gastrointestinal disease was not associated with outcome but warrants further investigation.

Abstract

OBJECTIVE To describe gastrointestinal histologic findings for horses with recurrent colic and evaluate possible associations between initial clinical signs, biopsy method, histologic diagnosis, and outcome 1 year after hospital discharge.

DESIGN Retrospective case series.

ANIMALS 66 horses with a history of recurrent colic for which gastrointestinal specimens had been submitted for histologic examination.

PROCEDURES Histologic diagnosis was categorized as inflammatory, neoplastic, ischemic, other, and undiagnosed. Relationships among initial clinical features, biopsy method, histologic diagnosis, and outcome 1 year after hospital discharge (ie, alive vs dead and persistent recurrent colic [yes vs no]) and between corticosteroid treatment and outcome were investigated. Odds ratios and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.

RESULTS Inflammatory disease (36/66 [55%]) was the most common histologic diagnosis. Horses undergoing rectal biopsy alone were significantly (OR, 14.4; 95% Cl, 2.7 to 76.1) more likely to not have a histologic diagnosis than were horses in which other biopsy methods were used. In multivariable modelling, persistence of recurrent colic (HR, 15.2; 95% Cl, 1.9 to 121.2) and a history of weight loss (HR, 4.9; 95% Cl, 1.4 to 16.5) were significantly associated with outcome (alive vs dead) 1 year after surgery. Corticosteroid treatment was not significantly associated with either outcome.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a high proportion (36/66 [55%]) of horses with recurrent colic had inflammatory gastrointestinal disease. Use of rectal biopsy alone to obtain biopsy specimens was more likely to result in no histologic diagnosis. Use of corticosteroids in horses with inflammatory gastrointestinal disease was not associated with outcome but warrants further investigation.

In a 2011 study1 of 127 horses in the United Kingdom treated for colic and followed up for 1 year, the colic recurrence rate was reported to be 50 colic events/100 horse-years at risk. Unfortunately, in most horses with recurrent colic, the underlying cause is not identified. Even in horses with recurrent colic caused by colonic displacement or impaction, the underlying reason for recurrence is usually not evident. Most published studies1–11 evaluating recurrent colic have focused on management practices that may predispose horses to recurrent colic (eg, recent dietary changes, decreased time at pasture, and stereotypic behaviors). However, there are few reports attempting to evaluate underlying histologic abnormalities in the intestinal tract of horses with recurrent colic.

Histologic findings from horses with recurrent colic have mostly been described in single case reports or small case series.12–20 These cases may be atypical and may not necessarily reflect the larger population of horses with recurrent colic. Furthermore, we are not aware of large studies attempting to address the diagnosis and management of recurrent colic. Typically, horses with recurrent colic that do not require surgical management of an acute episode are evaluated with transabdominal ultrasonography, gastroscopy, peritoneal fluid analysis, and gastroduodenal biopsy, rectal biopsy, or both. Often, no diagnosis is made in these horses. Veterinary surgeons are often reluctant to obtain a biopsy specimen during surgical treatment of an acute colic episode because of the additional time required and the fact that doing so would convert a clean procedure to a clean-contaminated procedure. Recently at our hospital, we have developed a rapid, simple, and relatively clean method to obtain small full-thickness diagnostic intestinal biopsy specimens during exploratory celiotomy in horses with a history of recurrent colic. It is our anecdotal clinical impression that horses with recurrent colic undergoing surgery for treatment of an acute colic episode often have intraoperative evidence suggestive of inflammatory gastrointestinal disease. Some of these horses were subsequently treated with dexamethasone (0.05 to 0.2 mg/kg [0.023 to 0.09 mg/lb], IV), prednisolone (0.2 to 4.4 mg/kg [0.09 to 2 mg/lb], PO, q 24 to 48 h), or both and subjectively responded favorably, at least for some time (months to years). In light of these findings, the objectives of the study reported here were to describe histologic findings for horses with recurrent colic, compare methods used to obtain tissue samples for histologic examination, and evaluate the effect of corticosteroid treatment on outcome and recurrence of colic episodes.

We hypothesized that a high proportion of horses with a history of recurrent colic would have histologic evidence of inflammatory gastrointestinal disease; that horses undergoing gastroduodenal or rectal biopsy would be more likely to not have a histologic diagnosis, compared with horses undergoing biopsy during exploratory laparotomy or laparoscopy; and that horses with a history of recurrent colic and a histologic diagnosis of inflammatory gastrointestinal disease would respond favorably to corticosteroid treatment.

Materials and Methods

Case selection criteria and medical records review

The database of the Pennsylvania Animal Diagnostic Laboratory Service was reviewed to identify records for all intestinal histologic specimens from adult (> 1 year old) horses that were submitted between December 2006 and December 2015. The database included records for horses examined at the George D. Widener Hospital for Large Animals as well as tissue specimens from horses submitted for necropsy from other practices. Horses submitted for necropsy were included if the record contained a detailed history, including clinical features, and results of premortem diagnostic testing and treatment, and the horse had died or been euthanized because of recurrent colic. All histologic specimens had been reviewed by a board-certified veterinary pathologist at the time of original submission.

Diagnostic laboratory reports for horses considered for inclusion in the study were reviewed in conjunction with the hospital medical record to determine whether the horse had a history of recurrent colic. For purposes of the present study, recurrent colic was defined as ≥ 2 episodes of colic within a 6-month period, with at least 48 hours between colic episodes.10 Horses with a history of recurrent colic were eligible for inclusion in the study. Horses that did not have a history of recurrent colic and horses for which a detailed history was not available were excluded.

For horses included in the study, the histologic or final diagnosis was recorded, and histologic diagnoses were categorized as inflammatory, neoplastic, ischemic, other, or normal histologic appearance (ie, undiagnosed). Inflammatory lesions were further categorized as lymphocytic-plasmacytic, lymphocytic-histiocytic, eosinophilic, or neutrophilic. Data on age, breed, and short-term outcome (ie, alive vs died or euthanized prior to hospital discharge) were recorded. Horses from other practices were not included in any of the outcome analyses.

Any history of weight loss, inappetence, anorexia, or diarrhea and total plasma protein and albumin concentrations at admission were recorded. Results of additional diagnostic tests, including peritoneal fluid analysis (total protein concentration, nucleated cell count, and results of cytologic analysis), transabdominal ultrasonography, and gastroduodenoscopy, were recorded. Transabdominal ultrasonographic variables that were recorded consisted of the presence of thickened (> 3-mm wall thickness20) bowel (yes vs no), an increase in the amount of peritoneal fluid (yes vs no), or gastric distension (yes vs no); whether there was evidence of dysmotility (ie, hypomotile or distended segments of small or large intestine or an increase in intraluminal fluid; yes vs no); and whether a mass was identified (yes vs no). Gastroscopic findings were classified as unremarkable or mild, moderate, or severe gastric ulceration. Briefly, mild gastric ulceration was defined as lesions that appeared superficial with just the mucosal surface affected, moderate gastric ulceration was defined as the presence of ≥ 3 gastric ulcers that appeared to involve a greater depth of tissue, and severe gastric ulceration was defined as lesions that had signs of being active (eg, active hemorrhage) and were larger and more numerous.11

Tissue specimens submitted for histologic examination were categorized as being obtained by means of gastroduodenoscopy, rectal biopsy, laparoscopy or laparotomy, or multiple methods or obtained at necropsy. Locations from which tissue specimens were obtained were recorded and categorized as stomach, duodenum, small intestine, large intestine, rectum, a mass, other, or the whole body at necropsy. Biopsy specimens obtained by means of laparoscopy or laparotomy were usually single or multiple, small full-thickness specimens obtained with an 8-mm-diameter disposable biopsy punch. Briefly, the intestinal region of interest was exteriorized from the abdomen and held by an assistant with sterile moistened gauze. A commercially available 8-mm-diameter biopsy puncha was used to obtain a full-thickness tissue specimen. Metzenbaum scissors were used to facilitate acquisition of the mucosa in some horses. The biopsy site was closed with 2–0 synthetic absorbable suture in a cruciate pattern oversewn with a Cushing or Lembert pattern.

Information on whether horses received corticosteroid treatment was obtained from the discharge instructions recorded in the medical record. Long-term outcome was obtained by means of telephone conversations with the owner, trainer, or referring veterinarian. Whether the horse was alive at the time of follow-up and the number of months alive after discharge were recorded. Information on additional (ie, recurrent) episodes of colic was also recorded, if applicable.

Statistical analysis

Categorical data were initially analyzed with a Fisher exact test, and continuous data with a Kruskal-Wallis test. Categorical analyses included testing for associations between histologic diagnosis category (inflammatory, neoplastic, ischemic, other, or undiagnosed) and clinical features (weight loss, inappetence or anorexia, or diarrhea), transabdominal ultrasonographic findings, gastroscopic findings, and biopsy method. Possible associations between some of these variables and inflammatory lesion category were also evaluated. If there was a significant association between variables, then multiple pairwise comparisons between individual diagnosis categories were also performed with the Fisher exact test. No specific adjustments were made for multiple comparisons. Continuous data, including plasma total protein concentration, plasma albumin concentration, peritoneal fluid total protein concentration, and peritoneal fluid total nucleated cell count, were compared between histologic diagnosis categories. Odds ratios with 95% CIs were calculated when indicated. Categorical data are presented as percentages, and continuous data are reported as median and IQR.

Outcome variables were the number of days alive at the time of follow-up, the number of additional (ie, recurrent) colic episodes after hospital discharge, and whether the horse was alive or dead 1 year after hospital discharge. Horses with no or only 1 additional episode of colic after discharge were categorized as not having persistent recurrent colic, whereas horses with ≥ 1 additional episode of colic were categorized as having persistence of recurrent colic. Horses that were euthanized prior to hospital discharge were included in survival analyses, but were excluded from analyses of recurrent colic after hospital discharge. A Kaplan-Meier survival curve was constructed to compare survival time for each histologic diagnosis category. Horses lost to follow-up were censored. Post hoc pairwise comparisons were made between diagnosis categories following Cox regression. Cox proportional hazards analysis was performed to investigate the relationship between outcome 1 year after hospital discharge and histologic diagnosis, clinical features, and results of diagnostic tests. The predictive accuracy of the final Cox proportional hazards model was examined with the Harrell C discrimination index and the Somer D rank correlation coefficient. Whereas the Harrell C discrimination index was defined as the proportion of all usable subject pairs for which the prediction and outcome were concordant (with a C index of 0.5 indicating predictions were random and a C index of 1.0 indicating perfect discrimination), the Somer D correlation coefficient was defined as the rank correlation between the prediction and desired value. Variables with values of P ≤ 0.2 were eligible for inclusion in the multivariable model. A multivariable model was created by removing variables with values of P ≥ 0.2 from the model in a stepwise manner. The model was evaluated with area under the ROC curve. Variables associated with the occurrence of recurrent colic episodes were determined with logistic regression. Multivariable analysis was performed as described for outcome. The ORs (or coefficients) and 95% CIs were reported for each variable. All analyses were performed with commercially available statistical software.b,c For all tests, significance was defined as values of P ≤ 0.05.

Results

Clinical features and histologic diagnoses

Sixty-six horses with a history of recurrent colic from which intestinal biopsy specimens had been obtained met the criteria for inclusion in the study. Fifty-three of these horses had been admitted to the George D. Widener Hospital at New Bolton Center; the remaining 13 horses had been treated at other hospitals, which had submitted biopsy specimens to the Pennsylvania Animal Diagnostic Laboratory Service. Of the 66 horses, 56 underwent biopsy alone, 9 underwent necropsy alone, and 1 underwent both biopsy and necropsy. Antemortem biopsy specimens were not obtained from horses that underwent necropsy alone; however, all horses that underwent necropsy alone had a history of recurrent colic as described by the owners, including weight loss, lethargy, and ill-thrift, and had abnormalities identified with other diagnostic tests prior to necropsy. Two horses that underwent necropsy alone had intra-abdominal masses and 1 had abnormal peritoneal fluid (peritoneal fluid nucleated cell count, 43,000 cells/μL; peritoneal fluid total protein concentration, 2.0 mg/dL); all 3 of these horses had been euthanized because of these findings in conjunction with a prolonged (4 weeks to 12 months of intermittent signs) history of recurrent colic. Four horses that underwent necropsy alone had been given a tentative diagnosis of inflammatory gastrointestinal disease on the basis of history, clinical signs, and diagnostic test results (hematologic and serum biochemical testing and abdominal ultrasonography). An exploratory celiotomy had been performed previously in 2 of these 4 horses during an acute episode of colic, but intraoperative gastrointestinal biopsy specimens had not been obtained for histologic evaluation. One horse that underwent necropsy alone died during transportation to our hospital for treatment of colic, and 1 horse that underwent necropsy alone had been euthanized and underwent necropsy because of prior inconclusive results of diagnostic evaluation for persistent episodes of recurrent colic.

The most common histologic diagnosis category was inflammatory (36/66 [55%]), followed by neoplastic (9/66 [14%]), other (8/66 [12%]), and ischemic (2/66 [3%]). No diagnosis was made in 11 of the 66 (17%) horses. Of the 36 horses with inflammatory lesions, 20 (56%) had lymphocytic-plasmacytic infiltrates, 6 (17%) had eosinophilic infiltrates, 5 (14%) had neutrophilic infiltrates, and 5 (14%) had mixed-cell infiltrates (eosinophilic-lymphocytic-plasmacytic, n = 2; histiocytic-lymphocytic, 1; neutrophilic-eosinophilic, 1; and lymphocytic-eosinophilic, 1). Of the 9 horses with neoplastic lesions, 4 had lymphoma, 3 had gastrointestinal stromal tumors, 1 had adenocarcinoma, and 1 had mesothelioma. Abnormalities in the 8 horses with other lesions included small intestinal muscularis hyperplasia or hypertrophy (n = 4), ileal stenosis (1), ileal diverticula with serosal fibrosis (1), colonic bacterial overgrowth (1), and mucosal fibrosis (1). Ischemic lesions were small colon strangulating pedunculated lipoma (n = 1) and post-foaling jejunal necrosis (1).

Median age of the horses was 10 years (IQR, 6 to 15 years). Most were Thoroughbreds or Thoroughbred crosses (29/66 [44%]); 14 (21%) horses represented American breeds (including Quarter Horse, Paint, and Morgan), 13 (20%) were warmbloods, 4 (6%) were Arabians, 3 (5%) were Standardbreds, 1 (2%) was a draft horse, and 1 (2%) was a miniature horse (information on breed was unavailable for 1 horse).

Transabdominal ultrasonography was performed on 47 of the 66 horses (Table 1). The proportion of horses with ultrasonographic evidence of thickened bowel was significantly lower for horses with neoplastic disease than for horses with inflammatory disease (P = 0.029), horses with other histologic diagnoses (P = 0.015), and horses without a diagnosis (P = 0.041). A mass, located intramurally or intimately associated with a focal area of the gastrointestinal tract, was identified in a significantly (P = 0.015) higher proportion of horses with neoplasia than horses with inflammatory disease. There were no significant associations between clinical features and histologic diagnosis category (Supplementary Table S1, avmajournals.avma.org/doi/suppl/10.2460/javma.252.10.1279).

Table 1—

Transabdominal ultrasonographic findings in 47 horses with recurrent colic.

 Histologic diagnosis category
Transabdominal ultrasonographic findingInflammatory (n = 26)Neoplastic (n = 6)Other (n = 5)Ischemic (n = 1)Undiagnosed (n = 9)
Thickened bowel (P = 0.030)
 Yes18a1b5a1a,b7a
 No85002
Increased peritoneal fluid (P = 0.742)
 Yes31002
 No235517
Mass (P = 0.041)
 Yes1a3b0a,b0a,b1a,b
 No253518
Abnormal motility/distention (P = 0.403)
 Yes60100
 No206419

Data represent number of horses in each category; P values were estimated with the Fisher exact test.

In each row, proportions for values with different superscript letters were significantly (P ≤ 0.05) different from each other.

Gastroduodenoscopy was performed in 32 horses, and gastric ulceration was observed in 13 of the 32. Nine of 20 horses with inflammatory disease had gastric ulceration, which was classified as mild in 3 horses, moderate in 4, and severe in 2. One of 4 horses with neoplasia had moderate gastric ulceration, 1 of 2 horses with other histologic lesions had severe gastric ulceration, and 2 of 6 horses without a diagnosis had gastric ulceration, which was classified as mild in 1 horse and moderate in the other. Histologic diagnosis category was not significantly (P = 0.834) associated with whether gastric ulceration was identified during gastroscopy.

Horses were cross classified on the basis of biopsy method and histologic diagnosis category (Table 2). The proportion of horses in which tissue specimens were obtained by rectal biopsy alone was significantly higher for horses without a histologic diagnosis than for horses with inflammatory disease (P = 0.012), horses with neoplastic disease (P = 0.038), and horses with other histologic lesions (P = 0.045). Horses that underwent rectal biopsy alone were significantly (OR, 14.4; 95% CI, 2.7 to 76.1; P = 0.001) more likely to not have a histologic diagnosis than were horses in which tissue specimens were obtained by any other biopsy method (gastroduodenal biopsy alone, gastroduodenal and rectal biopsy, laparotomy or laparoscopy, or necropsy). Horses that underwent gastroduodenal and rectal biopsy were significantly (OR, 5.7; 95% CI, 1.2 to 26.5; P = 0.031) more likely to not have a histologic diagnosis than were horses in which tissue specimens were obtained by any other biopsy method. Horses that underwent laparotomy or laparoscopy were significantly (OR, 0.15; 95% CI, 0.03 to 0.75; P = 0.009) less likely to not have a histologic diagnosis than were horses in which tissue specimens were obtained by any other biopsy method. There was a significant (P ≤ 0.001) association between histologic diagnosis category and lesion location, with all specimens from the stomach, duodenum, or rectum classified as having inflammatory disease, whereas specimens from the small intestine or large intestine were classified as having inflammatory disease, neoplastic disease, ischemia, or other lesions (Table 3).

Table 2—

Cross classification of biopsy method versus histologic diagnosis category for 66 horses with a history of recurrent colic.

 Histologic diagnosis category
Biopsy methodInflammatory (n = 36)Neoplastic (n = 9)Other (n = 8)Ischemic (n = 2)Undiagnos (n = 11)
Gastroduodenal biopsy alone* (P = 0.715)
 Yes40000
 No3298211
Rectal biopsy alone (P = 0.022)
 Yes3a0a0a0a,b5b
 No339826
Gastroduodenal and rectal biopsy (P = 0.137)
 Yes50004
 No319827
Laparotomy or laparoscopy (P = 0.081)
 Yes206522
 No163309
Necropsy (P = 0.076)
 Yes43300
 No3265211

One gastric and 3 duodenal biopsies.

Two horses underwent laparoscopy alone.

See Table 1 for remainder of key.

Table 3—

Location from which diagnostic biopsy specimens were obtained for 55 horses with a history of recurrent colic categorized on the basis of histologic diagnosis.

 Histologic diagnosis category
Biopsy siteInflammatory (n = 36)Neoplastic (n = 9)Other (n = 8)Ischemic (n = 2)
Stomach1000
Duodenum3000
Duodenum and rectum2000
Rectum6000
Small intestine7751
Large intestine12021
Small intestine and large intestine5210

Outcome

Survival rate—Forty-five of the 53 (85%) horses admitted to the George D. Widener Hospital were alive at hospital discharge, including 29 of 33 (88%) horses with inflammatory disease, 3 of 6 horses with neoplastic disease, 2 of 2 horses with ischemic disease, 2 of 3 horses with other histologic lesions, and all 9 horses without a diagnosis. Four of the 45 horses discharged from the hospital were lost to follow-up, and 2 of the 45 horses that were alive at the time of follow-up were not alive 1 year after hospital discharge. The proportion of horses alive 1 year after discharge was significantly (P = 0.037) higher for horses with inflammatory disease than for horses in the “other” diagnosis category (Figure 1; Table 4); however, proportions of horses alive 1 year after discharge did not differ significantly among lesion categories for horses with inflammatory disease (Table 5). In pairwise comparisons after Cox regression analysis, there were no significant differences in survival rates between histologic diagnosis categories.

Figure 1—
Figure 1—

Kaplan-Meier survival curves for 45 horses with recurrent colic categorized on the basis of histologic diagnosis (inflammatory disease, n = 28; neoplasia, 6; ischemia, 2; other, 3; and undiagnosed, 6). Horses that were lost to follow-up, died, or were euthanized for reasons unrelated to colic or gastrointestinal disease were censored.

Citation: Journal of the American Veterinary Medical Association 252, 10; 10.2460/javma.252.10.1279

Table 4—

Cross classification of outcome 1 year after hospital discharge versus histologic diagnosis category for 45 horses with recurrent colic.

 Histologic diagnosis category
OutcomeInflammatoryNeoplasticOtherIschemicUndiagnosed
Alive 1 year after discharge (P = 0.041)
 Yes20a2a,b0b2a,b4a,b
 No84302
Persistent recurrent colic (P = 0.494)*
 Yes132204
 No121025

Horses lost to follow-up (n = 4) were not included.

See Table 1 for remainder of key.

Table 5—

Cross classification of outcome 1 year after hospital discharge versus histologic lesion for 28 horses with recurrent colic that were found to have inflammatory gastrointestinal disease.

 Inflammatory cell type
OutcomeLymphocytic-plasmacyticEosinophilicNeutrophilicMultiple
Alive 1 year after discharge (P = 0.304)
 Yes9641
 No6101
Persistent recurrent colic (P = 0.223)*
 Yes9310
 No4431

Horses lost to follow-up (n = 3) were not included.

Results of univariable analyses of factors potentially associated with outcome 1 year after hospital discharge were summarized (Supplementary Table S2, available at avmajournals.avma.org/doi/suppl/10.2460/javma.252.10.1279). In multivariable analysis, persistence of recurrent colic after discharge (HR, 15.2; 95% CI, 1.9 to 121.2; P = 0.010) and a history of weight loss (HR, 4.9; 95% CI, 1.4 to 16.5; P = 0.011) were significantly associated with outcome 1 year after hospital discharge. The Harrell C discrimination index for the multivariable model was 0.882, indicating that the model had good predictive accuracy. The Somer D rank correlation coefficient was 0.764, implying that the model predicted that a horse that survived at least 1 year after hospital discharge was 76.4% more likely to have a lower HR than a horse that did not survive. Administration of corticosteroids was not significantly associated with outcome 1 year after hospital discharge (P = 0.562; Supplementary Table S3, available at avmajournals.avma.org/doi/suppl/10.2460/javma.252.10.1279).

Recurrent colic—Twenty-one of the 41 (51%) horses that survived to hospital discharge and for which follow-up information was available had persistent recurrent colic (> 1 additional episode of colic after hospital discharge). Results of univariable analysis of clinical variables potentially associated with having persistent recurrent colic after hospital discharge were summarized (Supplemental Table S2). When identification of thickened bowel ultrasonographically was normalized as a confounder in the model (HR, 4.09; 95% CI, 0.57 to 29.1; P = 0.160), admission plasma total protein concentration was significantly (HR, 0.37; 95°% CI, 0.16 to 0.82; P = 0.014) associated with having persistent recurrent colic after hospital discharge. Therefore, both variables were retained in the final multivariable model for prediction of persistent recurrent colic after discharge (P = 0.023; area under the ROC = 0.746). Corticosteroid administration was not significantly associated with the likelihood of having persistent recurrent colic after hospital discharge (P = 0.658; Supplementary Table S3).

Discussion

Results of the present study indicated that a high proportion (36/66 [55%]) of horses with a history of recurrent colic also had evidence of inflammatory disease on the basis of histologic evaluation of gastrointestinal biopsy specimens. The fact that most (20/36 [56%]) horses with inflammatory disease had lymphocytic-plasmacytic infiltrates suggested that these cellular infiltrates may be an important component of the disease process in some horses with recurrent colic.

In the present study, it was interesting that 6 of the 8 horses in the “other” histologic diagnosis category had intestinal fibrosis or muscular hypertrophy or hyperplasia, which are conditions that can be associated with chronic inflammation, particularly lymphocytic-plasmacytic inflammation.21 The presence of lymphocytic-plasmacytic cellular infiltrate in the lamina propria has been considered an essential diagnostic feature of chronic inflammatory bowel disease in human patients.22 Therefore, it is plausible that these horses may have had distinct cellular infiltrates associated with intestinal inflammation during previous acute episodes of colic. Continued understanding of the relationship between histologic findings, especially inflammation, fibrosis, and hyperplasia-hypertrophy, and recurrent colic would require prospective studies to evaluate the temporal relationship between colic episodes and histologic findings.

There is always a concern that when obtaining biopsy specimens during laparotomy, intestinal distension, displacement, and manipulation may create an inflammatory response resulting in overdiagnosis of inflammatory disease. In view of the retrospective nature of the present study, there was no means to control for timing of intestinal biopsy or individual variation in surgical technique in handling the intestines. An assessment of tissue quality of the intestines or surgical judgment when electing to obtain biopsy specimens was not always reported in the medical record. Recently, in a study of horses undergoing laparotomy, Hopster-Iversen et al23 reported that intestinal manipulation resulted in an increase in neutrophilic inflammation as well as in the migration of eosinophils toward the intestinal lumen. Importantly, the predominant inflammatory cell type in the present study was lymphocytic-plasmacytic (20/36 horses with inflammatory disease), which was not associated with intestinal manipulation in the study by Hopster-Iversen et al.23 Further, in the present study, there was no significant association between biopsy method and predominant inflammatory cell type (data not shown), suggesting there was no influence of biopsy method on histologic diagnosis. Future investigation of the potential association between mild to moderate intestinal inflammation and clinical signs of recurrent colic in horses is indicated, with a focus on defining the extent of inflammation that may be considered within normal limits as well as other morphological changes associated with recurrent colic.

On the basis of results of the present study, we suggest that gastrointestinal biopsy specimens be obtained from any horse examined because of recurrent colic and undergoing exploratory laparotomy. Samples can be obtained from an enterotomy or enterectomy site; however, evaluation of additional samples from distant sites obtained with an 8-mm-diameter biopsy punch would likely provide a more representative assessment of widespread infiltrative disease. Aside from the single case involving a strangulating lipoma in the present case series, masses identified in the present study represented either intramural thickening (eg, lymphoma) within the gastrointestinal tract wall or tumors associated with the intestine (eg, gastrointestinal stromal tumor). Histologic evaluation of biopsy specimens of these types of masses as well as of the adjacent bowel should always be performed for a complete diagnosis. Some risk is involved when obtaining biopsy samples of the intestine; however, we suggest that these risks are low when performed by experienced surgeons, and biopsy with an 8-mm-diameter biopsy punch should strongly be considered as a routine adjunctive diagnostic test in all horses with recurrent colic.

In the present study, horses that underwent rectal biopsy either alone (OR, 14.4; 95% CI, 2.7 to 76.1) or in conjunction with gastroduodenal biopsy (OR, 5.7; 95% CI, 1.2 to 26.5) had the highest odds of remaining without a histologic diagnosis. We suggest that histologic examination of rectal biopsy samples is likely not a sensitive diagnostic test for detection of cellular infiltrates in tissue layers other than the mucosa, and may be nondiagnostic if the cellular infiltrates do not correspond to the location of the biopsy (ie, if the biopsy is performed distant from the site of lesions). The exact location of rectal biopsies was not reported in the present study. In a previous study24 evaluating histologic diagnoses based on the results of rectal biopsy specimens, half (53/105) of the horses evaluated did not have a diagnosis. There were fewer horses without a histologic diagnosis in the present study (11/66); however, only 3 of the 66 horses had a definitive diagnosis on the basis of rectal biopsy alone. Thirteen horses had gastroduodenal biopsy performed, either alone or in combination with rectal biopsy, and evaluation of these gastroduodenal biopsy specimens appeared to have been somewhat more useful in obtaining a definitive diagnosis, possibly because specimens were obtained from sites closer to the site of disease. Alternatively, the high proportion of horses with a definitive diagnosis on the basis of gastroduodenal biopsy alone (4/4) may have represented more focused sampling in horses with a specific abnormality observed at the time of gastroduodenoscopy. Unfortunately, this possibility could not be evaluated given the retrospective nature of this study. Furthermore, in the present study, histologic evaluation of gastroduodenal or rectal biopsy specimens enabled diagnosis of inflammatory lesions; however, this method may be ineffective for the diagnosis of ischemic, neoplastic, and some other lesion types because these biopsy specimens are partial-thickness, and some lesions may involve distinct layers other than the mucosa. For example, inflammatory lesions typically involve the mucosa, but muscular hypertrophy lesions involve the muscular layers of the intestinal wall. In the present study, inflammatory disease was diagnosed in all 4 horses that underwent gastroduodenal biopsy alone; nonetheless, we suggest that these horses may have had a more severe disease that was undiagnosed and that could have increased the risk of persistent recurrent colic.

Minimally invasive diagnostic procedures (eg, peritoneal fluid analysis, transabdominal ultrasonography, and gastroscopy) and intestinal biopsy (gastroduodenal or rectal) are often preferred by owners and veterinarians but may not provide a diagnosis in horses with recurrent colic. Peritoneal fluid analysis can be useful as part of the diagnostic evaluation in horses with acute signs of colic (eg, for identification of a strangulating lesion); however, unless abnormal cells are found on cytologic analysis, peritoneal fluid analysis is less useful for horses with recurrent colic. In the present study, results suggested that transabdominal ultrasonography may be worthwhile. Identification of a mass during transabdominal ultrasonography was associated with a high likelihood of a definitive diagnosis of neoplasia (3/5). Thickened bowel was a frequent finding in horses with inflammatory disease or ischemic disease, horses in the “other” diagnosis category, and horses that remained without a diagnosis. Additionally, although thickened bowel identified ultrasonographically was not a significant variable alone (HR, 4.09; 95% CI, 0.57 to 29.1; P = 0.160), it was retained in the final multivariable model evaluating the risk of persistent recurrent colic. Results of a recent study by Norsworthy et al25 suggest that a high percentage (83%) of cats with chronic small bowel disease had segmental or diffuse evidence of thickened bowel when examined with transabdominal ultrasonography, with a final diagnosis of enteritis in 50% of cats. As such, horses with recurrent colic and ultrasonographic evidence of thickened bowel may warrant thorough investigation for an underlying disease process.

Slightly less than half (13/32) of the horses in the present study had signs of gastric ulceration. Dukti et al26 similarly found that 49% of 100 horses with colic had gastric ulceration. In that study,26 horses with duodenitis-proximal jejunitis tended to have a higher rate of gastric ulceration, compared with horses with other gastrointestinal lesions, suggesting that the disease process may involve a more generalized gastroenteritis. Gastric ulceration has also been associated with crib-biting or windsucking,27 which also may be associated with recurrent colic.10 The role of gastric ulceration and crib-biting or windsucking in horses with recurrent colic and inflammatory disease warrants further investigation. A prospective study to determine whether these are a cause or an effect of the recurrent colic is indicated.

In the present study, we were unable to demonstrate a clear benefit of corticosteroid administration. Kaikkonen et al20 reported that 15 of 20 (75%) horses with a diagnosis of inflammatory bowel disease initially responded to corticosteroid and anthelmintic treatment and those that responded favorably to the initial treatment had a better long-term (3-year) prognosis, compared with horses that did not respond. A specific regimen for corticosteroid treatment has not been established. In the present study, both dexamethasone and prednisolone were administered, often in combination, for a 4- to 8-week period after the initial colic episode that prompted referral. It is possible that longer-term administration of corticosteroids may be beneficial in some of these cases. In dogs with inflammatory bowel disease, treatment may last for 8 weeks, and corticosteroids are typically given in combination with other immunosuppressive treatments and allergen restriction.28–30 In the present study, the lack of a clear benefit of corticosteroid administration may have partly been a result of the relatively low number of horses, particularly those with inflammatory gastrointestinal disease, treated with corticosteroids. Nonetheless, for the horses in the inflammatory histologic diagnosis category with medical records that contained information regarding use of corticosteroids (n = 26), the proportion that appeared to benefit from corticosteroid administration was not significantly different from the proportion that did not (10/12 [83%] vs 10/14 [71%]), indicating that, regardless of the lack of significant results, the benefit of corticosteroids was not clear or definitive. More specific evaluation of the relationship between corticosteroid administration (dosage, route of administration, duration of treatment, and type of corticosteroid), recurrent colic episodes, and type of inflammatory disease is necessary before firm recommendations can be made regarding corticosteroid use in horses with recurrent colic or inflammatory gastrointestinal disease.

In the present study, the proportion of horses in the “other” diagnosis category still alive 1 year after hospital discharge was quite low (0/3), most likely because these horses tended to have advanced disease. Horses with neoplasia that was amenable to surgical treatment (eg, complete resection) had a good prognosis, whereas horses with lymphoma (or mesothelioma) were euthanized. It was interesting that horses with inflammatory gastrointestinal disease and those without a histologic diagnosis had similar median survival times, suggesting that a similar disease process may have been present. It is possible that horses that were not given a diagnosis had inflammatory disease that was not detected by means of histologic examination of either rectal or gastroduodenal biopsy samples. Alternatively, this similarity in survival time may have been coincidental.

It was not surprising that persistence of recurrent colic and a history of weight loss (likely representing more severe intestinal injury) significantly increased the risk of death (20/51) in the present study. Furthermore, horses with a higher plasma total protein concentration had lower odds (OR, 0.55; 95% CI, 0.23 to 1.32) of persistent recurrent colic, possibly reflecting the absence of protein-losing enteropathy.

The present study was intended as an initial attempt to further our understanding of the possible relationship between recurrent colic and inflammatory disease in horses. Limitations of this study included the relatively small number of horses, particularly in certain subgroups. Furthermore, adjustments for multiple comparisons between individual diagnosis categories were not made; however, such multiple comparisons were only performed when the overall relationship between the main variables was significant. Because of the retrospective nature of the present study, there was no standardization of the location or technique for obtaining biopsy specimens (especially for those samples obtained per rectum), and biopsy specimens obtained from the large intestine were likely overrepresented as the site for infiltrative disease because this site is the easiest to access for biopsy. In addition, a thorough dietary and management history could not always be obtained, and it was difficult to ascertain which horses were treated with anthelmintics. Because this was a retrospective study, it was not possible to have a control population (eg, horses without gastrointestinal disease or horses having had only a single acute colic episode). Therefore, we can only conclude that in this population of horses undergoing intestinal histologic evaluation, inflammatory disease was diagnosed in a large proportion. We cannot make conclusions regarding the overall role of inflammation in recurrent colic. Whereas the present study was intended as an investigation of horses with a history of recurrent colic, 2 study horses had ischemic lesions. Although these types of lesions are not necessarily thought of as being related to recurrent colic, these cases could not be excluded on the basis of our inclusion criteria, and doing so would have resulted in selection bias. Horses with a history of recurrent colic submitted for necropsy alone were included, as we believed that this represented an important population of horses affected by recurrent colic. These cases all had definitive abnormalities on other diagnostic tests, and necropsy was used to obtain a final and complete diagnosis of the underlying cause of recurrent colic. Although all biopsy specimens were evaluated by a board-certified veterinary pathologist at the time of sample collection, in reviewing the pathology reports, it was our impression that there was considerable disparity in the criteria used to diagnose inflammatory disease, suggesting the need for further study. Because the present study was performed at 1 hospital with horses from 1 geographic region, our results and statistical models warrant validation at other hospitals and locations.

Recognizing these limitations, the high prevalence of inflammatory disease (55%) and histologic features (fibrosis and hyperplasia-hypertrophy) noted in the present study that might be a result of chronic inflammation should prompt future studies investigating the role of intestinal inflammation in horses with recurrent colic. Potential relationships between histologic findings, dietary and management factors, stereotypic behaviors, and the gut microbiome should be investigated. Our results indicated that biopsy samples obtained via laparotomy or laparoscopy were more likely to result in a diagnosis than samples obtained per rectum. We were unable to demonstrate a benefit of corticosteroid treatment in horses with inflammatory gastrointestinal disease.

Acknowledgments

Presented in part at the 11th Equine Colic Research Symposium, Dublin, July 2014.

ABBREVIATIONS

AUC

Area under the curve

CI

Confidence interval

HR

Hazard ratio

IQR

Interquartile (25th to 75th percentile) range

ROC

Receiver operating characteristic

Footnotes

a.

Miltex, Integra LifeSciences Corp, York, Pa.

b.

JMP Pro11 Statistical Discovery, SAS Institute, Cary, NC.

c.

STATA, version 14, StataCorp, College Station, Tex.

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