Introduction

Exocrine pancreatic carcinoma arises from ductular or acinar cells, and it is reported to account for <0.5% of all reported tumors in dogs and cats.¹ Pancreatic carcinoma in cats is locally invasive with a high propensity for metastasis to the draining lymph nodes, peritoneum, liver, small intestine, and lungs.^2,3 Differential diagnoses for a pancreatic mass include nodular hyperplasia, benign pseudocyst, primary or metastatic neoplasia, or pancreatitis. There have been few reports of long-term response to surgical excision of pancreatic exocrine carcinoma in cats, because the majority of patients present in a debilitated state with tumors that are unresectable or that have already metastasized. In one retrospective study of eight cats with exocrine pancreatic carcinoma, seven were euthanized within 8 days of diagnosis. Four of those eight cats had metastatic disease at the time of diagnosis. Furthermore, none of the cats in Seaman’s study received any therapy specifically aimed at treating the pancreatic carcinoma (chemotherapy or surgery).³ In another retrospective study of 34 cats with pancreatic exocrine carcinoma, the overall median survival time was 97 days following diagnosis. Eleven cats in that same study had confirmed metastatic disease, and the median survival time for those eleven cats was 33 days. Five cats had diabetes mellitus, which raised the question of whether cats with diabetes mellitus are predisposed to pancreatic carcinoma, as humans are.² The purpose of this retrospective study was to describe the clinical outcome of cats with exocrine pancreatic carcinoma, with no evidence of metastatic disease on presentation, following surgical excision.

Materials and Methods

Medical records from Colorado State University Veterinary Teaching Hospital, Fort Collins, Colorado; University of Wisconsin-Madison Veterinary Medical Teaching Hospital, Madison, Wisconsin; Red Bank Veterinary Hospital, Tinton Falls, New Jersey; Centre Veterinaire Rive-Sud, Brossard, Quebec, Canada; Southern California Veterinary Specialty Hospital, Irvine, California; Oregon State University Lois Bates Acheson Teaching Hospital, Corvallis, Oregon; and Metropolitan Veterinary Associates and Emergency Services, Valley Forge, Pennsylvania, were searched for cases of feline patients diagnosed with pancreatic carcinoma from 2007 to 2016. Cats were included in the study if a diagnosis of pancreatic carcinoma was confirmed via histopathology, if no metastatic disease was found on presentation, and if they were rendered macroscopically disease-free by marginal excision of a pancreatic mass. Data collected included breed, age, sex, clinical presentation, physical examination and diagnostic abnormalities, adjunctive medical treatment, surgical findings, histopathologic diagnosis, outcome (date of disease progression), and survival time. Survival time was defined as the time elapsed from surgery to the date of death or last follow-up. Kaplan-Meier analysis was used to illustrate median survival time (MST).

Results

Nine cats were eligible for inclusion in the study. Four of these were neutered males and five were spayed females. The mean ± standard deviation age was 11.9 ± 1.4 yr (range, 10–14 yr). There were five domestic shorthairs, two domestic longhairs, one Persian, and one Sphinx cat represented in the study. History and clinical signs included hyporexia in five cats, vomiting in three cats, lethargy in three cats, and one cat with a several-month history of polyuria and polydipsia. One cat had a single occurrence of hematochezia prior to presentation, and one cat had a 2 mo history of inappropriate urination and defecation prior to presentation. Physical examination findings included a palpable abdominal mass in four cats, a heart murmur in two cats, abdominal distension in one cat, and mild icterus in one cat.

Abdominal ultrasound was performed in all nine cats. One cat had an ultrasonographically normal pancreas, but had a 5 × 3 cm cystic hepatic mass noted. One cat had an abdominal ultrasound conducted before being referred for surgery; the results of the abdominal ultrasound were not reported. In the remaining seven cats, abnormalities of the pancreas were noted on abdominal ultrasound. One cat was reported to have an enlarged and coarse pancreas, and other ultrasonographic changes suggestive of pancreatitis. Fine needle aspiration of the pancreas in this cat revealed cytological findings consistent with neuroendocrine pancreatic carcinoma. One cat had two nodules <0.5 cm in diameter found on the right and left lobes of the pancreas. One cat had a solid, round, 2.5 cm hypoechoic mass of the right pancreas, an enlarged hypoechoic left pancreatic lobe, and a left lateral cystic liver mass measuring 4.3 × 5.2 cm. One cat had a 1.5 cm left pancreatic nodule, a 2 cm anechoic cyst in the body of the pancreas, and signs of pancreatitis in the right portion of the pancreas. One cat had a 2.7 × 4.7 cm fluid-filled structure in the right lobe of the pancreas. In two cats, pancreatic masses were noted on abdominal ultrasound, but measurements were not provided (Table 1).

TABLE 1 Clinical Data in Nine Cats with Pancreatic Carcinoma

View Fullscreen

Ultrasound-guided fine needle aspiration and cytology of a pancreatic mass was performed in five of the nine cats. This led to a cytological diagnosis of carcinoma in two of the five cats. In one cat, a cytological diagnosis of sterile pancreatic abscess was made. In two cats, both suppurative inflammation and epithelial cells were noted, and a differential diagnosis of inflammation or carcinoma was provided.

Seven cats underwent surgery for excision of a pancreatic mass that was found on an abdominal ultrasound. One cat underwent surgery after abdominal ultrasound revealed a cystic hepatic mass. A 1 cm-wide pancreatic mass was found and excised in surgery. One other cat had an enlarged and coarse pancreas on abdominal ultrasound; this cat was taken to surgery after a cytological diagnosis of pancreatic carcinoma was made based on fine needle aspirates of the pancreas. A well-defined 1.5 × 2.5 cm mass present at the right tail of the pancreas was found at the time of surgery, and the mass was removed with 4.5–5.5 mm margins. Marginal excision of a pancreatic mass was performed in all nine cats, and all of them were rendered macroscopically disease-free at the time of surgery. Margin measurements were not reported for eight cats in this study.

Histopathological diagnosis of pancreatic adenocarcinoma was confirmed in all nine cases. Other histopathological and surgical findings include a biliary cystadenoma in one cat and severe diffuse necrotizing and hemorrhagic splenitis with intralesional gram-positive bacterial cocci in another. In these two cats, no metastatic disease was identified in the liver parenchyma associated with the cystadenoma, or in the spleen for the cat with splenitis. A splenectomy was performed in the cat with splenitis at the time of surgery for the pancreatic mass. Eight of the nine cats recovered from surgery without complication. One cat had a naso-esophageal feeding tube placed due to persistent anorexia postoperatively.

Six of the nine cats received varying protocols of adjunctive chemotherapy after surgery. Two cats received alternating carboplatin and gemcitabine, two cats received carboplatin alone, one cat received alternating carboplatin and mitoxantrone, and one cat received gemcitabine alone. One cat was treated with prednisolone alone. Serial abdominal ultrasound examinations of one cat who received one dose of carboplatin (160 mg/m²) revealed cystic structures and nodular changes of the right limb and body of the pancreas, and mesenteric lymphadenopathy 37 days postoperatively. This cat was subsequently started on mitoxantrone (5–5.5 mg/m² IV) and was administered seven total doses. Serial abdominal ultrasound revealed stable pancreatic disease after starting mitoxantrone; this cat survived 209 days following surgery.

At the time of the last follow-up, six cats had died and three were still alive with no evidence of disease. One cat died 591 days after surgery due to progression of the disease. This cat was treated with prednisolone after surgery. Of the three cats who were still alive, one received carboplatin and gemcitabine (alive 258 days after surgery) and two received carboplatin alone (alive 309 days and 702 days after surgery). Two cats died of unrelated causes on day 25 (cardiopulmonary arrest) and day 964 (multiple myeloma) after surgery. Four cats died due to progression of disease from 42 to 755 days after surgery. The overall median postsurgical survival time of the nine cats, defined as the time elapsed from surgery to the date of death or last follow-up, was 316.5 days (range, 25–964 days), with four cats living more than 1 yr (Figure 1). The MST for the seven cats receiving chemotherapy after surgery was 309 days (range, 42–964 days). A necropsy was not performed on any of the cats in this study.

View Figure

• Download as Powerpoint
• Download Figure

Discussion

Feline exocrine pancreatic carcinoma is an uncommon, aggressive tumor with a high metastatic rate.² In a previous case study of 34 cats, 9 underwent marginal excision of a pancreatic mass and 3 had an incisional biopsy performed due to extensive local invasion of the tumor. The MST for the 12 cats who underwent surgery for a pancreatic mass in that study was 165 days, compared with 30 days for cats who did not have surgery.² In this study, the median postsurgical survival time was 316.5 days, with three cats alive at a median follow-up time of 309 days.

Two of the nine cats in this study died at days 25 and 42 after surgery. The cat who died 25 days postoperatively did not receive chemotherapy, and the cat who died on day 42 received three doses of gemcitabine and did not return for further treatment. The remaining seven cats lived from 209 to 964 days postoperatively, and three are still alive at the time of this report. One of those seven cats received prednisolone only, and one was administered no postoperative chemotherapy. The remaining five cats received some combination of gemcitabine and carboplatin (with one receiving carboplatin and mitoxantrone). One publication reported that cats with pancreatic carcinoma treated with chemotherapy had an MST of 165 days compared with 7 days for cats who did not receive chemotherapy.² These results may have been skewed if cats deemed too debilitated to receive chemotherapy were included in the latter population. Although a controlled prospective study assessing the efficacy of postoperative chemotherapy for pancreatic carcinoma would be ideal, the rarity of the disease would make case accrual difficult.

The standard of care for chemotherapy in humans with pancreatic carcinoma over the past decade has been the purine analogue gemcitabine. No benefit has been found when using gemcitabine in combination with other cytotoxic chemotherapeutic drugs in phase 3 clinical trials. Modest improvement in survival time was found when gemcitabine was used in combination with the tyrosine kinase inhibitor erlotinib. The benefit of tyrosine kinase inhibitors in cats with pancreatic carcinoma is currently unknown.⁸

Pancreatic carcinoma in humans is an aggressive disease that carries a poor prognosis, with an overall median survival time around 8 mo and a 5 yr survival of 5%.⁸ Humans who undergo surgical excision of pancreatic carcinoma with margins containing no evidence of microscopic disease have a 3 yr survival of 15%; however, up to 85% of human patients present with metastatic or advanced-stage disease, making complete surgical excision impossible in most cases.⁹ Survival time in humans is improved in patients who present with localized disease that is amenable to complete surgical excision. This study supports the idea that cats with localized pancreatic carcinoma have improved survival times after complete surgical excision when compared with previous reports.

Although a histologic diagnosis of pancreatic carcinoma was confirmed in all nine cases in this study, the slides were not reviewed by a single pathologist. Furthermore, differentiating between a diagnosis of chronic pancreatitis and pancreatic carcinoma can be particularly difficult, as the two diseases share several histopathological abnormalities.¹⁰ It is possible that survival times in this study were skewed based on a misdiagnosis of pancreatic carcinoma.

Conclusion

The selection criteria for cats without evidence of metastatic disease at the time of presentation in this study were likely the most significant factors contributing toward an increased survival time when compared with previous studies of feline pancreatic carcinoma. Twenty cats with pancreatic carcinoma were excluded from the present study due to metastatic disease at the time of presentation, extensive local disease, or owner’s unwillingness to proceed with surgical excision. The nonspecific clinical signs, lack of quality screening diagnostic tests, and similarities between pancreatitis make early diagnosis of pancreatic carcinoma challenging. Subsequently, most feline patients have evidence of metastatic disease at the time of presentation. Similarly, in newly diagnosed human patients with pancreatic carcinoma, as few as 15% are good candidates for surgical excision.¹¹ These findings highlight the importance of early diagnosis followed by marginal surgical excision of pancreatic carcinoma. Other limitations to this study include the relatively small study population, having animals lost to follow-up, and varying adjuvant chemotherapy protocols. The retrospective, multi-institution nature of this study also makes it possible that data regarding progression of disease is inaccurate. Regardless, this study supports prior findings in that early diagnosis followed by surgical removal of the tumor appears to prolong survival time in cats with pancreatic carcinoma.