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Keywords:

  • chromoendoscopy;
  • endoscopic retrograde cholangiopancreatography;
  • feline pancreatic lipase immunoreactivity;
  • healthy cats

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Cats are predisposed to diseases of the biliary tract and the exocrine pancreas and these can be challenging to diagnose. In humans and dogs > 10 kg, endoscopic retrograde cholangiopancreatography (ERCP) has been successfully used to diagnose some of these disorders. The purpose of our study was to determine whether ERCP would also be feasible in cats using a pediatric duodenoscope. Four purpose-bred, clinically healthy, castrated domestic shorthair cats participated in two studies. Study 1 compared standard white light endoscopy with chromoendoscopy for localizing the major duodenal papilla. In Study 2 ERCP was performed. Repeated clinical examinations and measurements of serum feline pancreatic lipase immunoreactivity (fPLI) were performed before and up to 18 hours after interventions on all cats. Chromoendoscopy was subjectively judged to be superior for localizing the major papilla. Insertion of the ERCP catheter was best accomplished when cats were in dorsal recumbency. Complete ERCP was successful in two cats. In the other cats, either retrograde cholangiography or pancreatography was possible. Serum fPLI concentrations increased temporarily in two cats during Study 2 when measured immediately, 2, 4, and 18 h after ERCP. Peak fPLI concentrations were detected either immediately after ERCP or 2 h later. No clinical signs of complications were observed within 18 h after the procedures. Findings indicated that ERCP is technically demanding but feasible in healthy cats. Future studies need to determine whether the temporary increases in serum fPLI concentrations are clinically important and to investigate the utility of ERCP in feline patients.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. ACKNOWLEDGMENTS
  8. REFERENCES

Cats are predisposed to diseases of the biliary duct system and the exocrine pancreas such as cholecystitis, cholangitis, and pancreatitis.[1-4] Choledocal cysts and disorders of the sphincter of Oddi (e.g., bile plug syndrome, neoplasia) have also been reported. [5-7] However, diagnostic imaging of the feline biliary tract and pancreas has been challenging and there have been many attempts to improve visualization of the normal and abnormal anatomy with varying success. Imaging techniques that have been studied so far are transabdominal ultrasound, contrast enhanced and color Doppler ultrasound, endosonography, contrast enhanced computed tomography, and magnetic resonance imaging.[8-17]

An additional technique to be considered for improving the diagnosis of disorders of the feline biliary tract and exocrine pancreas is endoscopic retrograde cholangiopancreatography (ERCP). This technique is a combination of endoscopy and fluoroscopy. Endoscopic retrograde cholangiopancreatography has been used for decades as a diagnostic and therapeutic tool in humans with suspected disorders of the biliary tract and exocrine pancreas. [18-20] Recently, ERCP has been reported to be also successfully and safely used in healthy dogs and in dogs with chronic gastrointestinal disorders.[21-23] However, it has thus far only been successful for dogs weighing > 10 kg due to the large tip diameter of the duodenoscope (11 mm) used for the examination.[21] Previous reports have suggested that ERCP might also be possible in smaller dogs and cats when using a pediatric duodenoscope (tip diameter: 7.5 mm) [21, 22], but studies documenting this were not found.

Endoscopic retrograde cholangiopancreatography offers not only possibilities as a diagnostic tool but also as a therapeutic tool. The purpose of this prospective pilot study was to determine whether ERCP is feasible in healthy cats. Our first objective was to assess the visualization of the major papilla in the duodenum of cats when using either standard white light endoscopy or chromoendoscopy, a technique which aims at facilitating the visualization and detection of small structures by staining the intestinal mucosa either with methylene blue, indigo carmine, or other stains.[24, 25] The second objective was to assess the feasibility for performing ERCP in cats using a pediatric side-viewing duodenoscope (tip diameter: 7.5 mm). The third objective was to determine whether ERCP induced short-term complications.

Material and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. ACKNOWLEDGMENTS
  8. REFERENCES

The project consisted of two separate endoscopic studies, and the same four clinically healthy cats were enrolled in both studies. All procedures were approved by the Institutional Animal Care and Use Committee at Texas A&M University. Included cats were purpose-bred, castrated domestic shorthair cats (age: 1 year, body weight: 4.0–5.5 kg). The cats had no history of clinical signs suggestive of gastrointestinal disorders, and the results of clinical examination, complete blood cell count, and standard serum biochemical profile were within reference ranges. After the study, all cats were adopted out as pets to private owners.

Before and after each endoscopic procedure, food was withheld for 12–18 h. All cats were anesthetized twice with a minimum of 7 days between the anesthetic events. Both endoscopic procedures were performed under general anesthesia using glycopyrrolate and butorphanol for premedication, propofol for induction, and isoflurane/oxygen inhalation for maintenance. During the procedures all cats received lactated Ringer's solution intravenously at a maintenance rate plus dobutamine.

Study 1 determined how best to localize the major duodenal papilla with a forward-viewing endoscope (GIF-160, Olympus, Tokyo, Japan), followed by a side-viewing duodenoscope (PJF 160, Olympus, Tokyo, Japan). For chromoendoscopy, 1–3 drops of undiluted 1% methylene blue (Methylene blue injection 1%, American Regent Incorp, Shirley, NY) were sprayed through an ERCP catheter onto the duodenal mucosa. Visualization of the major papilla was assessed without and with the dye when using the forward-viewing endoscope. After applying the dye and visualizing the papilla, the endoscope was changed to the side-viewing duodenoscope to assess whether it is possible to find the major papilla again. Visualization of the papilla was assessed by two endoscopists (TS, MDW) who performed all procedures together. The quality of visualization was only considered reliable when the structure and the opening of the papilla were almost immediately and clearly visible.

In Study 2, ERCP was performed by two endoscopists (TS, MDW) together using chromoendoscopy. Attempts were made to insert an ERCP catheter (PR-420Q Star tip cannula, Olympus, Tokyo, Japan, tip diameter: 3 F) into the major duodenal papilla after placing the cats successively in ventral and dorsal recumbency. Once the duodenoscope was placed into the distal part of the duodenum, a standard shortening maneuver was attempted to straighten the duodenoscope. The straightening was achieved by full rightward deflection of the endoscopes lateral wheel and full upward of the large wheel with the left hand. This was followed by withdrawal and simultaneous clockwise torque applied to the duodenoscope shaft by the right hand. The maneuver has been previously described as a method for adjusting the duodenoscope to the angular fold of the stomach and keeping its tip in the proximal duodenum.[26]

After safe placement of the catheter into the major papilla, an iodine contrast medium (Omnipaque 240®, GE Healthcare Inc., Princeton, NJ, USA; Iohexol 240 mg/ml) was injected into the biliary and pancreatic duct systems using a C-arm fluoroscope (OEC 9800 Plus Super C-arm, General Medical Systems, Germantown, MD, USA) for guidance. To avoid pancreatic parenchymal filling or overdistention of the gall bladder, we limited the maximum volume of contrast to 6 ml. We injected less than 6 ml if there was sufficient opacification of the common bile duct, gallbladder, and pancreatic ducts with a lower volume.

In Studies 1 and 2, repeated clinical examinations were performed by two investigators (TS, IR) for all cats before and 18 h after both endoscopic interventions. Presence of clinical signs such as abdominal pain and fever was recorded for each examination. A final clinical examination was performed by a registered veterinary technician (CP) at the time when the cats were released from the experimental animal facility into private ownership (4 weeks after ERCP). Measurements of serum feline pancreatic lipase immunoreactivity (fPLI) were performed in all cats before and 18 h after the endoscopic procedures of Studies 1 and 2 using a previously validated in-house radioimmunoassay.[27] Preprocedure sampling was performed when the anesthetized cats were first placed on the examination table. In Study 2, one additional sample was taken from cat 1 at the time point 0.03 h after ERCP. Three additional blood samples were taken from cats 2–4 at 0.03, 2, and 4 h after ERCP.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. ACKNOWLEDGMENTS
  8. REFERENCES

In Study 1, using white light endoscopy and a forward-viewing endoscope, it was not possible to reliably visualize the major papilla in any of the cats. Chromoendoscopy consistently allowed quick visualization of the papilla and its opening in all cats. (Fig. 1). The presence of bile exiting the papilla was clearly visible with chromoendoscopy but not when using white light only. After changing to the side viewing duodenoscope, the dye was still attached to the duodenal mucosa and it was possible to find the papilla again in all cats.

image

Figure 1. Chromoendoscopic image of the feline duodenal papilla after administration of 2–3 drops of methylene blue. Note the yellow color that represents bile. The papilla (arrow) is the small slit in the mucosa. This shows how difficult it could be to find the papilla if it was not highlighted by the dye.

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In Study 2, insertion of the ERCP catheter into the duodenal papilla was impossible in all four cats when positioned in ventral recumbency but successful when the cats were placed in dorsal recumbency. In one cat (cat 3), it was possible to perform a standard shortening maneuver.[26] Using this technique, the post-contrast radiographic image showed a common bile duct, gall bladder, and pancreatic ducts filled with contrast and in their normal anatomical position (Fig. 2). In the other three cats, it was impossible to straighten the endoscope and only the “long approach” could be used for visualization and cannulation of the duodenal papilla.[26] Using this technique, cholangiography occurred in cat 1 and pancreatography occurred in cat 2. Complete ERCP was possible in cat 4. However, the gallbladder of cat 4 seemed displaced toward the central axis of the abdomen, and the pancreatic duct system was located more to the right relative to cat 3 (Fig. 3). None of the three cats with contrast filling of the common bile duct and the gallbladder had imaging characteristics consistent with biliary tract diseases such as dilations, strictures, obstructions, wall irregularities, or contrast leakage into the abdominal cavity.[31] Also, in the three cats with retrograde pancreatography, the duodenal and gastric branches of the main pancreatic ducts were clearly visible without any signs of duct abnormalities suggestive for pathologic processes.

image

Figure 2. Radiographic image acquired following endoscopic retrograde cholangiopancreatography in cat 3. Notice that the endoscope has been subjected to a shortening maneuver, i.e. the duodenoscope has been straightened and adjusted to the angular fold with its tip in the proximal duodenum. (E = endoscope, PD = pancreatic ducts, C = catheter, GB = gallbladder).

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image

Figure 3. Radiographic image acquired following endoscopic retrograde cholangiopancreatography in cat 4. Notice that the endoscope is used in the “long approach,” which means that it runs along the wall of the entire gastric body with its tip in the proximal duodenum. This technique causes an extension of the stomach by the endoscope and could possibly lead to a distortion of the intra-abdominal anatomy. (E = endoscope, PD = pancreatic ducts, C = catheter, GB = gallbladder).

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Two technical problems occurred during ERCP: contrast filling the pancreatic parenchyma in cat 3 and injection of air into the pancreatic duct system of cat 4. After ERCP, all cats had an uneventful recovery from anesthesia and the endoscopic procedure. In study 1 and 2, no clinical signs of short-term complications such as acute pancreatitis and cholangitis (i.e., anorexia, abdominal pain, vomiting, or fever) were detected during the postoperative observation period of 18 h. All cats remained healthy during a minimum resting phase of 7 days between the two studies and until their release from the experimental facility into private ownership 4 weeks after ERCP.

Determination of serum fPLI revealed that cats 1–3 had fPLI concentrations within the reference range before and 18 h after the endoscopic procedure in Study 1 and the ERCP in Study 2 (4.1–12.9 ug/l).[27] Cat 4 showed increased serum fPLI concentrations before the endoscopic procedures of Studies 1 and 2. In this cat, serum fPLI concentration measured in Study 1 decreased from an initial 22.1μg/l to 8.8μg/l at 18 h post endoscopy. In Study 2, the serum fPLI concentration of this cat increased from 22.4 μg/l before to 72.7μg/l at 18 h after ERCP.

In Study 2 and cat 1, serum fPLI concentrations determined before and at 0.03 and 18 h after ERCP remained within or slightly below the reference range (7.3, 3.4, and 5.1μg/l respectively). For cats 2–4, additional samples taken at 0.03, 2, and 4 h after ERCP revealed a temporary increase in post-ERCP serum fPLI concentrations in two of three cats (cats 3 and 4, Fig. 4). Peak serum fPLI concentrations were detected directly after ERCP (cat 4: fPLI = 455.7 μg/l) and 2 h later (cat 3, fPLI = 67.8 μg/l), respectively. At 18 h after ERCP, the serum fPLI concentration of cat 3 but not of cat 4 returned to the reference range (Fig. 4). In cat 2, serum fPLI concentrations remained within the reference range after the ERCP procedure throughout the observation period (Fig. 4).

image

Figure 4. Serum feline pancreatic lipase immunoreactivity (fPLI) concentrations before and after endoscopic retrograde cholangiopancreatography in three healthy cats. The dotted line represents the upper reference range for serum fPLI (12.9 μg/l).[30]

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. ACKNOWLEDGMENTS
  8. REFERENCES

As the result of Study 1, chromoendoscopy was subjectively judged to be superior for endoscopic localization of the major papilla in cats when compared to standard white light endoscopy. In Study 2, the insertion of the ERCP catheter was best accomplished when cats were in dorsal recumbency. Complete ERCP was successful in two cats. In the other two cats, either retrograde cholangiography or pancreatography was achieved. Therefore, it was possible to assess either the images of the common bile duct and the gallbladder or of the pancreatic ducts of three cats. In, between, and up to 4 weeks after both studies, none of the cats developed clinical signs of ERCP complications. However, cats 3 and 4 had marked but temporary increases in serum fPLI concentrations during Study 2.

An easy visualization of the major papilla in the proximal duodenum of cats is an important basis for performing a successful ERCP. As known from humans, the application of dyes such as methylene blue or indigo carmine onto the intestinal mucosa for chromoendoscopy facilitates the visualization of small changes being not visible when using white light endoscopy only.[24, 25] When performing standard white light endoscopy, the very small size of the feline major papilla made it nearly impossible to localize it in any of the cats of this study. Using chromoendoscopy improved the visibility of the papilla in such a degree that it was decided to use this technique when performing Study 2.

In humans, the standard positioning for ERCP is the ventral recumbency. [26] This approach was also tried in the four cats of this study. However, the cannulation of the major papilla with an ERCP catheter succeeded only when the cats were turned into dorsal recumbency. This observation is similar to the previously reported dorsal positioning of healthy dogs and dogs with chronic enteropathies when performing an ERCP. [21, 22] The main problem in performing an ERCP in dogs and cats is the current need to use the so called “long approach” when visualizing the papilla. [26] The term refers to the situation where the endoscope is coiled up in the stomach when following the major curvature from the lower esophageal sphincter to the pylorus before being placed in the duodenum. In contrast to the “short approach” where the endoscope lays along the gastric angle fold, the “long approach” makes it difficult to guide the tip of the side-viewing duodenoscope into a place that allows easy cannulation of the papilla. When using the “long approach,” it seems currently more successful to place the cat in dorsal rather than in ventral recumbency. Further developments in performing ERCPs in cats should aim at training to perform the standard shortening maneuver as it is applied in humans.[26] This should improve the cannulation of the papilla with an ERCP catheter.

In the majority of cats, the pancreatic ducts join up and terminate with the common bile duct in the hepatopancreatic ampulla of the major papilla. [28] This gives an anatomical situation similar to the majority in humans but different from the majority of dogs, in which the common bile duct terminates with the major papilla and the pancreatic ducts drain mostly via the minor papilla. [26, 28] The close proximity between the openings of the biliary and pancreatic duct systems in the human major papilla requires their selective cannulation, depending on which duct system shall be visualized with contrast. [26] Due to the small size of the feline major papilla, it was only possible to achieve an unselected contrast filling of both duct systems in half of the cats. This probably happened because of the placement of the ERCP catheter into the common junction of both duct systems. The selected contrast filling of the biliary or pancreatic duct system of the two other cats was probably achieved by inserting the catheter only into the opening of the corresponding duct. Due to the risk of inducing pancreatitis or a retrograde overfilling of the gallbladder, we did not repeat the ERCP procedure with the attempt to inject contrast medium also into the unfilled duct system and the contrast injection was stopped with a maximum of 6 ml contrast medium. To our knowledge, only the sonographically assessed volume of the feline gallbladder has been reported so far to be 2.42 ml (range 0.84–4.50 ml).[29] The volume of the common bile duct, and the extrahepatic and pancreatic ducts is unknown. This could cause an increased risk of overfilling the feline gall bladder or performing a pancreatic parenchyma filling when using too large volumes of contrast medium. Overfilling has been used to experimentally induce acute pancreatitis in dogs by ERCP guided injection of 20–30 ml contrast medium into the canine pancreatic duct system.[30] In a previous study in Beagle dogs weighing 14.1 ± 3.0 kg, the maximum volume of contrast medium injected into common bile duct and gallbladder was 10–20 ml, and into the pancreatic ducts 2 ml.[21, 23] In the cited study, none of the dogs developed clinical signs of acute pancreatitis despite a transient increase in serum activities of pancreatic enzymes.[23]

None of the three cats with contrast filling of the common bile duct and the gallbladder had imaging characteristics consistent with biliary tract diseases such as dilations, strictures, obstructions, wall irregularities, or contrast leakage into the abdominal cavity.[31] Also in the three cats with retrograde pancreatography, the duodenal and gastric branches of the main pancreatic ducts were clearly visible without any signs of duct abnormalities suggestive for pathologic processes. In humans, abnormal contrast pancreatograms are used to grade the stage of chronic pancreatitis by the Cambridge classification system from mild to severe.[32, 33] Due to the healthy clinical status and the age of the cats, the ERCP findings in the current study were considered to represent normal findings. However, due to the “long approach” technique for performing an ERCP in cats there is the possibility of distorting the intra-abdominal anatomy due to the extension of the stomach by the endoscope as was seen in cat 3 (Fig. 2). This might lead to an over or underinterpretation of ERCP findings.

Short-term complications after ERCP are the most feared problem in humans since they can lead to longer hospitalization times, increased morbidity, or even mortality. In human medicine, consensus definitions exist for the major short-term complications of ERCP such as pancreatitis, bleeding, perforation, and infection (cholangitis). Short-term complications are graded as mild, moderate, or severe based on clinical signs, laboratory findings, necessary lengths of hospitalization, and the necessity for intensive care unit admission.[34] Infection (cholangitis) is suspected when there is fever for more than 24–48 h.[34] Since the cats of our study appeared clinically normal throughout the investigation time, we considered this complication was very unlikely. In humans, post-ERCP pancreatitis is considered mild when there are typical clinical signs and an increase in serum amylase activity at least three times normal at more than 24 h after the procedure, requiring admission or prolongation of planned admission to 2–3 days.[34] Cat 4 may fit into this category although it did not show any clinical signs suggestive for pancreatitis, despite a fivefold increase in serum fPLI concentration 18 h after ERCP. Whether this cat had an underlying intestinal or pancreatic pathology or reacted to the injection of air with a high rise in serum fPLI remains speculative. Since we did not want to sacrifice the cats for the study and did not have a permission to collect pancreatic biopsies after completing the ERCP examinations, we were unable to investigate the reasons for the very high serum fPLI concentrations in this particular cat. It cannot be excluded that ERCP could have caused subclinical pancreatitis in cat 4. A recent study in eight healthy dogs in which ERCP was performed to induce pancreatitis demonstrated biochemical and histologic changes consistent with pancreatitis. Despite these changes, seven of the eight dogs remained free of classic clinical signs of pancreatitis.[30] In contrast to our study in cats, the dogs received very high amounts of contrast medium (20–30 ml) to induce a contrast filling of the pancreatic parenchyma. Some of the dogs also underwent balloon occlusion and endoscopic pancreatic sphincterotomy of the papillary orifice with and without intraductal infusion of ursodeoxycholic acid.[30] The maximum amount given to the cats in the presented study was 6 ml for both, the biliary and the pancreatic duct system together. The risk of inducing short term complications when performing ERCP procedures in feline patients suffering from diseases of the biliary tract or the pancreas remains unknown. Therefore studies that include post-ERCP monitoring for short-term complications are needed in clinically affected cats.

Since we considered it unethical to test feasibility for performing ERCPs using client-owned cats, we performed this experimental pilot study using a relatively low number of four, healthy, purpose-bred cats. The amount of cats was considered sufficient for such a study by our animal care review committee and complied with the principles of replacement, reduction, and refinement of animal experiments.[35]

In summary, findings from this pilot study indicated that ERCP is feasible in healthy cats when using a pediatric side-viewing duodenoscope in combination with chromoendoscopy. No clinical signs of short-term complications were observed, however some temporary increases in fPLI occurred. Further studies are needed to determine whether temporary increases in serum fPLI concentrations should be considered to be a sign of minor complications. Clinical studies are needed to assess the utility and safety of ERCP in feline patients with spontaneous biliary and pancreatic disease.

ACKNOWLEDGMENTS

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. ACKNOWLEDGMENTS
  8. REFERENCES

This project was funded by the Finnish Veterinary Foundation and the Helvi-Knuuttila Foundation, Finland. The authors thank Dr. Satu Sankari for logistical support, David Caldwell for project animal care, Carin Ponder for help with anesthetic procedures and animal care, and Carol Ann Pelli for English language editing.

REFERENCES

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. ACKNOWLEDGMENTS
  8. REFERENCES