Introduction

Colorectal carcinoma accounts for approximately 15% of all cancers in human beings and it is the second leading cause of cancer-related death in the United States. In the nonhuman primate, intestinal cancer appears to be the most common malignant neoplasm, and it is a significant cause of morbidity and mortality in the geriatric population.

A retrospective review of intestinal carcinoma in macaques between (1982–1999) at the California Regional Primate Research Center was undertaken to identify the incidence, clinicopathologic features and survival rate.

Materials and Methods

The medical records of 34 macaques with intestinal adenocarcinomas were reviewed retrospectively. Thirty-two monkeys were selected for inclusion in the study based on the following criteria: histopathologic diagnosis, follow-up period of >6 mo, and complete necropsy performed at time of death.

Clinical evaluation

In addition of physical examination, a complete blood count, serum biochemistry and urinalysis. Clinical evaluation involved a variety of diagnostic tests including upper gastrointestinal contrast series, ultrasonography, jejunoscopy, colonoscopy, and exploratory celiotomy.

Results

Of the 32 cases reviewed; 30 were rhesus macaques (Macaca mulatta) and 2 were crab-eating macaques (Macaca fascicularis). The median age of macaques diagnosed with intestinal adenocarcinoma was 23.3 yr (range, 4–29 yr). There were 15 males and 17 females.

Clinical presentation included severe weight loss, inappetence, or anorexia. A palpable cranial epigastric abdominal mass was present in the majority of the cases. Other signs noted included emesis, hematochezia, diarrhea, partial intestinal obstruction with scant or no stool, and episodes of bloating.

Marked microcytic, hypochromic anemia, fecal occult blood positive, hypoproteinemia, hypoalbuminemia, hypocalcemia and decreased albumin/globulin ratio were the predominant clinical laboratory findings. Pre- and postoperative human carcinoembryogenic antigen (CEA) serology proved to be of no significant clinical value.

The most common sites of occurrence of adenocarcinoma were the colon (25%; n=8), ileo-cecal (ICC) junction (21.8%; n=7), ICC-cecum-colon (18.75%; n=6), jejunum (9%; n=3), ICC–cecum (3%; n=1), ICC-ileum-cecum (3%; n=1), and jejunum-ileum (3%; n=1).

Pathology

Grossly, the mass appeared as a circumferential to nodular focal thickening of the intestinal wall. Lesions typically grew as bulky, fungating, ulcerated masses causing a luminal stricture and partial obstruction. Multiple synchronous neoplasias in the intestinal tract were found in 12.5% (n=4) of the cases and included one of each renal adenocarcinoma, hepatic cholangiocarcinoma, and gastric adenocarcinoma.

Metachronous lesions, a second primary neoplasia, was noted in a case that had hepatic hemangioma and squamous cell carcinoma of the cheek pouch (3%; n=1).

Local recurrence was noted in a single animal 50 mo post-surgical excision (3%). Metastases were evident in 25% (n=8) of the cases and involved regional nodes (n=4), liver (n=4), lungs (n=3), pancreas (n=1) and adrenal (n=1) in order of occurrence.

DNA Analysis

In 10 of 13 cases DNA was successfully extracted from archived paraffin blocks. PCR-SSCP (single-strand conformational polymorphism) analysis of these 10 cases were analyzed to determine the presence of K-ras mutations. However, it showed no evidence of K-ras mutations in Exon 1 or 2.

Surgical Excision

Exploratory celiotomy was performed in 56% (n=18) of the animals; 27% (n=5) of the animals were euthanatized on the surgical table due to a perceived poor prognosis or the presence of gross metastasis. The remaining cases (40%) had surgical excision with intestinal resection and anastomosis. One animal was lost to follow-up, two animals died during the immediate postoperative, five animals died as a resulted of dissemination of the adenocarcinoma (median survival rate [MST] 18 mo; x=22.2 ± 16 mo; and five animals are currently alive [MST] 25 mo postoperatively).

Survival Analysis

Disease-free interval was defined to be the interval from date of surgical excision to date of death due to recurrence. There was an 11% mortality rate during the postoperative period (3–17 days). Adenocarcinoma dissemination lead to death or euthanasia of 15.5% (n=5) of the surgical excision cases. Median survival time was 18 mo (range 11–50 mo).

Currently, five animals are still alive. Median survival time is 25 mo postoperatively (range 8–30 mo).

The results of intestinal resection and anastomosis in 12 macaques indicated an overall survival of 83% at 6 mo, 58% at 1 yr (in addition 16%; 2 cases are currently alive at 8 mo postoperatively), 50% at 1.5 yr, 33% at 2 yr and 8% at 4 yr.

Discussion

Intestinal adenocarcinomas are typically slow growing and result in gradual and progressive weight loss, microcytic anemia and partial intestinal obstruction.

Most macaques with intestinal adenocarcinomas responded well to surgical excision alone. Immediate postoperative mortality was 11% and was associated with dehiscence of anastomosis and consequently peritonitis. The preliminary results suggest surgical excision of intestinal adenocarcinomas in geriatric macaques is associated with low perioperative mortality and greater than 50% survival 1 yr postoperatively. Survivability could be potentially improved by the use of adjuvant therapies.