Geralda Aubrey, one of our EPI FORUM members, wrote a wonderful article on EPI that was published in the Schutzhund USA (Feb 2012) magazine titled "EPI: A Tale of Poop" by Geralda Aubry. CONGRATULATIONS GERALDA!!!!!!!!!!
In the article, not only does Geralda showcase her EPI dog, "Sirius", but she also writes about some of our other EPI FORUM members EPI dogs such as Donna's "Onza", Tom's "Yo-E" and Troy's "Jade". Please check out the article: (it is in 3 pages)
Thank You Geralda and Sirius
Brief Communication - J Vet Intern Med 2010;24:450–452
Heritability of Exocrine Pancreatic Insufficiency in
German Shepherd Dogs
E. Westermarck, S.A.M. Saari, and M.E. Wiberg
Background: Several studies have revealed that exocrine pancreatic insufficiency (EPI) is an inherited disease in German
Shepherd Dogs (GSDs). Pedigree analyses have suggested an autosomal recessive inheritance model.
Objective: Test mating of 2 dogs with EPI.
Animals: A sire and dam purebred GSD both with EPI and a litter of 6 puppies.
Methods: Test mating and long-term follow-up of offspring. The pancreas was biopsied via laparotomy on 26 occasions.
Serum trypsin-like immunoreactivity was measured. Study was approved by Animal Ethics Committee.
Results: During the 12-year study period only 2 of the 6 offsprings developed pancreatic acinar atrophy (PAA). In 1 puppy,
end-stage PAA and in the other puppy partial PAA was diagnosed.
Conclusions and Clinical Importance: PAA is not a congenital disease in GSDs. This study provided evidence that PAA is
not inherited in a simple autosomal recessive fashion.
Key words: Biopsy; Pancreatic acinar atrophy; Polygenic inheritance; Test mating; Trypsin-like immunoreactivity.
EM electron microscopy
EPI exocrine pancreatic insufficiency
GSD German Shepherd Dog
PAA pancreatic acinar atrophy
TLI trypsin-like immunoreactivity
Canine exocrine pancreatic insufficiency (EPI) is a disease characterized by inadequate production of digestive enzymes by pancreatic acinar cells. Affected dogs typically show such clinical signs as polyphagia, weight loss, yellowish poorly digested loose and pulpy feces, increased fecal volume, and frequent defecation.1. EPI has been reported in many breeds, but it is most commonly seen in German Shepherd Dogs (GSDs). In GSDs, the underlying cause of EPI is pancreatic acinar
atrophy (PAA). A characteristic of PAA is selective destruction of the digestive enzyme producing acinar cells.1, PAA has features of autoimmune disease, including genetic suspectibility to disease. 1.2.
Several studies have indicated that EPI is an inherited disease in GSDs, and most research of the inheritance model by pedigree analysis suggests that EPI is inherited in an autosomal recessive fashion.3–5 The prevalence of affected dogs in most reports has, however, been lower (!15%) than expected 25% for a simple autosomal recessive trait; thus, a polygenic mode of inheritance has been proposed.4 The mutation or candidate gene has not been identified.6.
Materials and Methods
This study was performed during 1987 to 2000. Both parents were purebred GSDs (dam 4 years, sire 6 years), with different progenitors. EPI diagnosis for both parents was documented on the basis of results of the serum trypsin-like immunoreactivity (TLI) assay 7. (dam 0.9 mg/L; sire 0.8 mg/L; control 5.2–35.0 mg/L). The dogs were fed regular commercial dog food twice daily, and 50 g of raw pig pancreas was added to every meal.
At the time of mating, both dogs were clinically in good condition. The dam delivered 9 puppies, but 3 died immediately or a short time after birth. Necropsy was performed on these puppies, and histologic examination of the pancreas did not reveal abnormalities.
Of the 6 remaining puppies, 4 were females and 2 males. The puppies were weaned at 6 weeks of age and released to their owners.
The puppies were raised in private homes. The owners were informed orally about EPI and were also provided with a written information package. They were told that the dogs would likely be afflicted with EPI. The investigators and the dog owners maintained close ties throughout the study. All of the dogs lived in the Helsinki area.
Two clinically healthy Beagles were included as control dogs. The dogs were sacrificed for an unrelated research project at the age of 3
years. The experimental protocol was approved by the Ethics Committee for Animal Experiments of the College of Veterinary Medicine, Helsinki, Finland.
Tests Performed on the Puppies
Serum TLI was measured by radioimmunoassay.7. The tests were performed for the 1st time at 6 weeks of age.
The biopsies from the pancreas were taken via laparotomy under general anesthesia. The gross appearance of pancreas was evaluated. One biopsy specimen was obtained from the right duodenal limb of the pancreas at each time point by ligation of a piece of pancreatic tissue (ca. 4.0mm in diameter) through a ventral midline abdominal incision. From all puppies the 1st biopsy was taken at 6 weeks of age and subsequently at approximately 0.5, 1.2, 2.0 years of age. Besides puppy no. 2 at 5.5 and 7.0 years of age. The biopsy specimens for histologic an electron microscopy (EM) examinations were processed in a routine manner.8. The EM findings of acinar cells were classified into 4 stages.8.
Necropsy was performed on all dogs, and several samples of the pancreas were examined. The pancreas of 2 control dogs was also studied.
The dam developed a fatal mesenteric torsion 6 months after parturition. The sire was euthanized at the age of 12 years. Necropsy of both the dogs revealed a severely atrophic pancreas typical of an end-stage PAA.
The results for puppy no. 1 have been published in detail elsewhere.8 Briefly, the female puppy was clinically healthy at birth and throughout adolescence, and grew normally without signs of maldigestion. The 1st biopsy from the pancreas at the age of 6 weeks was histological normal, but EM examination revealed mild stage 1 abnormalities. The dog was clinically normal at 22 months of age, but serum TLI was decreased to 0.3 mg/L (o2.5 mg/L indicating EPI; normal reference range 5.2–
35.0 mg/L). Examination of the pancreas indicated no gross or histologic abnormalities, but EM revealed widespread degenerative changes (stages 2–4). One month
later, the dog developed typical clinical signs of EPI, and at 25 months of age the gross and histologic examination of the pancreas revealed typical features of PAA.2 Treatment with powdered pancreatic extracta and antibiotics was introduced, with good treatment response.
Puppy no. 2 (female) was clinically healthy during the 1st 5 years. Laparotomy was performed 4 times (at 1.5, 5,14, and 24 months of age). Gross and histologic examination was normal every time, and EM studies revealed stage 1 changes. Serum TLI was measured 12 times, and on 2 occasions the TLI value was subnormal (3.4 and 4.1 mg/L).
At the age of 5.5 years, the dog was still clinically healthy and of normal weight, but serum TLI was abnormally low (2.1 mg/L) and at laparotomy, the gross
examination showed partial atrophy of the pancreas. There were scattered areas of pancreas that had lost their glandular appearance and changes typical for partial
PAA resulting from atrophic lymphocytic pancreatitis.1,2 Lymphocytic inflammation was most extensive in the border zone areas of normal and partially affected tissue.
EM showed evidence of atrophy, mainly type 3 and 4 degenerative changes. The islet cells were normal.
The dog was treated with immunosuppressives (prednisolon and azathioprined).9 Prednisolon treatment was discontinued after 1 year and azathioprine treatment
after 1.5 years.
The dog lived another 6 years after diagnosis of partial AA. No signs of EPI were present. Serum TLI was measured 11 times; the values were always o5.2 mg/L, 5
times being abnormally low, o2.5 mg/L (range 0.2–2.4 mg/L).
The dog died of internal hemorrhage at the age of 12 years. At necropsy the pancreas was severely diminished in size and histologic examination showed mild lymphocytic pancreatitis, especially in the border zone regions. In areas of more advanced tissue destruction, the findings were similar to those found in end-stage PAA.
Puppy nos. 3 to 6 showed no clinical signs typical of EPI during their lifetime. A laparotomy was performed 4 times on each dog (between 6 weeks and 24 months of age), and the pancreas on every occasion was grossly normal, and a biopsy was taken. Histologic examinations revealed a normal pancreas. EM of the biopsies often
showed type 1 changes in acinar cells. After each laparotomy, recovery was uncomplicated and postoperative assays of serum amylase and lipase activities provided
no indication of pancreatitis or pancreatic tissue damage. Serum TLI was measured 7 to 15 times, and in each dog the value was at least once subnormal. The lowest values in dog nos. 3 to 6 were 2.7, 3.4, 3.4, and 4.9 mg/L, respectively. The dogs died due to different causes at ages 8 to 13 years. At necropsy, the pancreas was grossly and histologically normal in each dog.
The TLI value of the 2 control dogs (7.5 and 8.4 mg/L) was within the normal range, and necropsy of the dogs revealed a normal pancreas both grossly and histologically. EM study of the control samples revealed evidence of type 1 changes.
Several previous studies have suggested that EPI is inherited in an autosomal recessive fashion. Here, when 2 affected EPI dogs were mated, only 2 of the 6 offspring
revealed atrophic changes in the exocrine part of the pancreas. This is much less than expected if a disease is inherited by Mendelian genetics. A polygenic mode of
inheritance is therefore the only explanation for this outcome. This is, however, a logical result as PAA in GSDs has been shown to be an autoimmune disease.2
Performing test mating in dogs is laborious, particularly in late-onset diseases such as EPI. Test matings have been used more often in early-onset diseases, but also in these cases the keeping of affected animals purely for test purposes is ethically problematic. Fortunately, EPI is a treatable disease, and with medication an affected dog can live a more or less normal life. In our study, all dogs, including the two with degenerative changes in the pancreas, lived a normal life.
Our previous report on puppy no. 1 described the rapid progression from EM findings to the gross appearance of a completely atrophied pancreas. We noted also
that mild stage 1 changes were found in acinar cells at the age of 6 weeks.8 To check whether the stage 1 changes were fixation artifacts instead of real degenerative changes, the pancreas of 2 healthy control dogs was examined. These dogs revealed similar changes. In conclusion, the changes earlier reported to be stage 1 changes are artifacts, thereby confirming that previous evidence indicating that PAA is a congenital disease in GSDs is not reliable.
To halt the degenerative process on puppy no. 2, immunosuppressive medication was initiated. Whether the treatment was responsible for arresting the destruction process remains, however, unknown. Some dogs have been reported to stay in the subclinical phase of EPI for Exocrine Pancreatic Insufficiency 451
years, or sometimes for life, without treatment.9 Currently, no treatment is recommended when dogs with partial PAA have no clinical signs.9
The other 4 siblings showed neither clinical signs typical of EPI nor degenerative or inflammatory changes in the pancreas. During their lifetime a pancreatic biopsy
was taken by laparotomy 4 times, and the pancreas was also examined at necropsy.
To take serial biopsies from pancreas was the only reliable way to gain information about the pathological processes involved with the early stages of PAA before
the clinical signs of EPI appear. The 1st biopsies were taken after the weaning of the puppies to find out if EPI is a congenital disease. In an earlier study it was shown
that in about every 2nd EPI dog the clinical signs appear before 2 years of age.1 This is why we took almost all the biopsies during the 1st 2 years. During the study, the recovery from biopsy samplings was uneventful and no complications were detected.
Measurement of serum TLI is the most commonly used test of pancreatic function, being both a sensitive and practical method for detecting severe EPI. We have reported that repeatedly low serum TLI values (o5.2 mg/L) in clinically healthy dogs can be a valuable marker of subclinical EPI and suggestive of partial PAA in GSDs.10 The results of puppy no. 2 are in agreement with this conclusion. During the last 6 years of its life the serum (TLI value was constantly low, fluctuating between subnormal (2.5–5.2 mg/L) and abnormally low (o2.5 mg/L). However, we have also concluded that diagnosing partial PAA may be problematic with an indirect pancreatic function test because of overlapping results in normal and partially affected dogs.10 This was also seen in these puppies, as each of the 4 healthy puppies had on at least some occasion subnormal serum TLI values.
Our findings revealed that PAA is not a congenital disease in GSDs, and in this canine family PAA was not inherited by a simple autosomal recessive fashion of a
single gene. The study also showed that the atrophic process can destroy the entire exocrine part of the pancreas in a very short time, but the process can be halted, remaining in this position for the rest of the dog’s life. The function test helped to detect the stage of the exocrine pancreas, but it was not completely reliable.
From the Department of Equine and Small Animal Medicine (Westermarck, Wiberg) and the Department of Basic Veterinary Sciences (Saari), Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. Data for one of the dogs have previously been published in Am J Vet Res 1993;54:1088-1094. Corresponding author: Elias Westermarck, Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014 Helsinki, Finland; e-mail: firstname.lastname@example.org.
Submitted June 2, 2009; Revised September 3, 2009; Accepted
November 18, 2009.
Copyright r 2010 by the American College of Veterinary Internal
a Viokase V, Fort Dodge Laboratories, Fort Dodge, IA
b Tylan, Elanco, Geneva, Switzerland
c Prednisolon, Leiras, Tammisaari, Finland
d Azamun, Leiras
1. Westermarck E, Wiberg M. Exocrine pancreatic insufficiency
in dogs. Vet Clin Small Anim 2003;33:1165–1179.
2. Wiberg ME, Saari SAM, Westermarck E. Exocrine pancreatic
atrophy in German Shepherd Dogs and rough-coated Collies: An
end result of lymphocytic pancreatitis. Vet Pathol 1999;36:530–541.
3. Weber W, Freudiger U. Erbanalytische Untersuchungen uber
die chronisce exocrine Pankreasinsuffizienz beim Deutshen Scha¨ ferhund.
Schweiz Arch Tierheilkd 1977;119:257–263.
4. Westermarck E. Hereditary nature of canine pancreatic degenerative
atrophy in the German Shepherd Dog. Acta Vet Scand
5. Moeller ME, Steiner JM, Clark LA, et al. Inheritance of pancreatic
acinar atrophy in German Shepherd Dogs. Am J Vet Res
6. Clark LA, Wahl JM, Steiner JM, et al. Linkage analysis and
gene expression profile of pancreatic acinar atrophy in the German
Shepherd Dog. Mammalian Genome 2005;16:955–962.
7. Williams DA, Batt RM. Sensitivity and specificity of radioimmunoassay
of serum trypsin-like immunoreactivity for the
diagnosis of canine exocrine pancreatic insufficiency. J Am Vet
Med Assoc 1988;192:195–200.
8. Westermarck E, Batt RM, Vaillant C, Wiberg M. Sequential
study of pancreatic structure and function during development of
panreatic acinar atrophy in German Shepherd Dog. Am J Vet Res
9. Wiberg ME, Westermarck E. Subclinical exocrine pancreatic
insufficiency in dogs. J Am Vet Med Assoc 2002;220:1183–1187.
10. Wiberg ME, Nurmi AK, Westermarck E. Serum trypsin like
immunoreactivity measurement for the diagnosis of subclinical exocrine
pancreatic insufficiency. J Vet Intern Med 1999;13:426–432.
452 Westermarck et al
EDMONTON - Bad dog, or sick dog? It’s not always easy to tell.
Katherine and Alan Hrynyk of Vegreville own three large shepherd breed dogs. One of them, Arvo — isn’t he a beautiful dog? — was diagnosed with exocrine pancreatic insufficiency, or EPI, a couple of years ago. Not before he lost a tremendous amount of weight, though, and not before presenting symptoms which the couple found puzzling, and initially wondered if were more behavioural than physical.
And therein lies part of the problem. Unfortunately, the disease often goes either undiagnosed or misdiagnosed, and dogs can end up as strays or in dog shelters. Some die a painful death from malnourishment, starvation or organ failure.
Dogs with EPI have a voracious appetite, yet gradually waste away because their pancreas does not produce the enzymes they need to digest food. A lack of nutrients often results in temperament changes, which can manifest in fear and/or aggression.
When food isn’t available, EPI dogs will eat whatever is. Bizarrely, Arvo ate everything from lawn mower pull cords, extension cords, door mats, fences, even the stuffing from his dog bed. Because he ate so much, he pooped constantly, both where he should and where he shouldn’t, and often ate his own feces.
The disease, while not curable, is manageable with treatment, and with a special diet. It’s not uncommon but often goes unrecognized and untreated, even by some breeders and veterinarians.
Katherine and her husband are longtime dog owners and always thought they were pretty knowledgeable about canine diseases — until this one came along.
“It hit us with a big jolt,” she says. “Educating ourselves has been one long learning curve.”
I asked Louis Kwantes, a veterinarian at Park Veterinary Centre in Sherwood Park, about EPI. He says that while it’s a relatively well-known syndrome, it is more difficult to diagnose in the early stages, or if there are other medical issues going on.
“When the condition presents in a classic or severe form, though, you can get a pretty good idea that a dog has EPI from history and physical exam alone,” says Kwantes, “although confirmatory testing is available and not cost-prohibitive.”
He says EPI is most commonly seen in German shepherds and collies but can be seen in other breeds of dogs, and less commonly in cats. He has never diagnosed EPI in a cat, in fact, but has treated a number of dogs at the clinic, and with good success.
Arvo, meanwhile, is thriving, according to Katherine. The couple has recently discovered that three of Arvo’s half siblings — same sire, different dam — also have EPI. She says the couple now belongs to some EPI groups online and one of them — www.epi4dogs.com — has started an international project called EPI Awareness, its goal to educate owners and thereby save dogs’ lives. There’s also a Yahoo forum — K9-epiglobal — which is open to pet owners whose dogs suffer from the disease. Sadly, says Katherine, membership is growing by the week, but it’s a very friendly and helpful site, especially for owners whose pets have just been diagnosed.
EPI Article in Purina Pro Club Newsletter - published May 2010
"Used with permission from the Purina Pro Club Update newsletter, Nestle Purina PetCare"
Exocrine Pancreatic Insufficiency May Have Complex Inheritance Pattern
“Izzy” had lost one-third of her body weight. Despite a voracious appetite, the 1-year-old Spanish Water Dog dropped to 27 pounds in four months. Owner Olesia Kennedy went from feeding two cups of food daily to eight cups.
“She was still losing weight,” says Kennedy, of
A fecal test for bacterial infection came back negative, yet Izzy continued to decline, going from having a few loose stools to constant diarrhea. “I frantically called the veterinarian and said something is seriously wrong with my dog,” Kennedy recalls.
Kennedy’s veterinarian suggested testing for exocrine pancreatic insufficiency (EPI). Within a week, the results of the blood test came back positive for the disease.
EPI is a disorder in which the pancreas fails to produce an adequate amount of digestive enzymes. Without those enzymes, food is not properly digested and absorbed. No matter how much food is ingested, a dog with EPI can literally starve to death.
Signs of EPI include weight loss, ravenous appetite, diarrhea, eating feces, vomiting, gas, changes in temperament, and loose, foul-smelling stool. In many cases, signs of the condition — which can strike at any age — do not appear until as much as 90 percent of the pancreas is destroyed.
Signs of Exocrine Pancreatic Insufficiency
• Weight loss
• Malnourished, thin or emaciated appearance
• Voracious appetite
• Chronic or intermittent diarrhea
• Eating feces or nonfood items
• Voluminous and frequent foul-smelling, yellowish, greasy stools with a watery to cow-pie consistency
• Gas (burping or flatulence)
• Rumbling digestive sounds
• Abdominal discomfort
• Dry, dull or brittle coat
There is no cure for EPI, but the disease can be successfully managed. Treatment, however, is lifelong.
About 8,000 dogs worldwide are diagnosed with EPI every year, says Jörg M. Steiner, Dr.med.vet., Ph.D., director of the Gastrointestinal Laboratory at
The list of affected breeds is long, says David A. Williams, Vet.M.B., Ph.D., chairman of the Department of Veterinary Clinical Medicine at the University of Illinois College of Veterinary Medicine. “I stopped counting in the late 1980s when the breed count diagnosed through my laboratory went well past 100,” he says. “While certain breeds have an above-average occurrence, essentially all breeds are at risk. The disease is known to be prevalent in German Shepherd Dogs, Rough-Coated Collies and Chow Chows.”
Shortage of Digestive Enzymes
The pancreas is a glandular organ located under the stomach that produces and secretes digestive enzymes. Acinar cells in the pancreatic tissue produce amylase to digest carbohydrates, lipase to digest fats, and trypsin and other proteases to digest proteins. These enzymes are secreted into the small intestine to help break down food into smaller parts so nutrients can be absorbed through the intestinal wall. An insufficiency of these enzymes causes nutrients to remain in the gastrointestinal tract undigested and pass in the feces.
The most common cause of EPI in dogs is pancreatic acinar atrophy (PAA) in which the acinar cells decrease in number and function. Though little is known about the cause of PAA, researchers believe the condition is genetically inherited. PAA usually develops between 6 months and 6 years of age. German Shepherd Dogs represent the majority of the cases identified in several studies.
EPI also can develop due to chronic pancreatitis, or inflammation of the pancreas. The pancreas synthesizes all the major digestive enzymes, but repeated bouts of pancreatitis can destroy acinar cells that synthesize these enzymes. Risk factors for chronic pancreatitis include high-fat diets and some anti-seizure and cancer drugs, Steiner says. In some cases, chronic pancreatitis may be an inherited condition.
In rare cases, EPI results from pancreatic cancer or pancreatic hypoplasia. Pancreatic hypoplasia is a congenital condition in which the exocrine pancreas does not fully develop.
Amy Vose has bred and owned German Shepherd Dogs for 33 years, but she had never heard of EPI until after her obedience champion “Dulcimer” (OTCH LuJon’s Dulcimer of Ashmead, UDX) had her second litter in 1992. Vose kept a female puppy she named “Sassafras” and sold the other nine puppies.
“When the puppies were about 1 year old, I received a phone call from one of the buyers,” says Vose, of Paw Paw,
Contacting everyone who bought a puppy, Vose encouraged them to have their dogs tested. Though Dulcimer did not have EPI, six of her puppies did, including Sassafras.
Vose was able to turn that tragedy into hope. When she learned that researchers at
Though a genetic marker for EPI has not been identified, several studies previously indicated that PAA is an autosomal recessive disease. This means that affected dogs inherit a copy of the gene mutation from both their sire and dam.
Results from a study published in the Journal of Veterinary Internal Medicine in the March/April 2010 issue and performed at the
“That study clearly shows that it’s not autosomal recessive,” Steiner says.
EPI now is believed to have a more complex mode of inheritance, says Leigh Anne Clark, Ph.D., assistant professor of genetics and biochemistry at
Until then, Clark, Steiner and Williams advise against breeding dogs with EPI or repeating matings that produced affected dogs. “The only way to decrease prevalence of the disease is by not breeding affected dogs,” Steiner says.
Complicated Disease to Diagnose
Veterinarians sometimes have difficulty diagnosing EPI because signs of the disease mirror those of other health issues. “The clinical signs are much more variable than most veterinarians realize, especially in the early stages of the disease before there is extreme weight loss,” Williams says. “The disease was formerly underdiagnosed in dogs with the disease and overdiagnosed in dogs without the disease.”
That situation improved considerably when a blood test for EPI was developed in
The cTLI test measures the amount of trypsinogen, an enzyme produced by the pancreas and converted into trypsin, in the blood. Dogs with EPI have low levels of trypsinogen. The test costs less than $100, and results are available in less than a week.
“With the advent of the serum cTLI test, there is simply no excuse for not testing suspect cases early, long before the classical signs of extreme weight loss and ravenous appetite become apparent,” Williams says.
Along with the cTLI test, Steiner suggests testing cobalamin (vitamin B12) and folate levels since dogs with EPI often have low levels of cobalamin and high levels of folate. Performing the cTLI and cobalamin and folate blood tests together can save time and money.
This combination indicates small intestinal bacterial overgrowth (SIBO), a condition in which bad bacteria thrive on undigested food in the small intestine. SIBO can be treated with antibiotics. Cobalamin deficiency should be treated with injections of B12, a vitamin that is necessary for almost all cell functions, from normal neurological function to digestion and absorption of food.
EPI cannot be cured, but it can be managed and the prognosis is good. “Dogs having EPI can be treated with enzyme supplements that allow them to properly digest their food and live normal lives,”
Pancreatic enzyme supplements are available in tablet, capsule or powder form. Given before a meal or mixed with food, the supplements contain amylase, lipase, proteases and other pancreatic enzymes that replace the naturally occurring digestive enzymes depleted by EPI. The monthly cost of supplements is estimated at $60 to $100.
Most EPI dogs also require diet modification, including reducing fiber or grain. Many veterinarians recommend feeding several small meals a day and increasing the normal recommended amount until a dog reaches his or her target weight.
After their condition stabilizes, dogs still should be tested periodically, Williams says. “Cobalamin deficiency and other complications can occur years after the initial diagnosis of EPI even though classical signs of weight loss and diarrhea are well controlled by enzyme replacement,” he says.
Some dogs stabilize quickly, while others require trying different combinations of supplements and food in varying amounts until the correct balance is achieved. Williams advises owners to keep a treatment log of each combination, and work closely with a veterinarian.
“EPI is generally a manageable disease, but some cases require a little extra effort to get the best results,” Williams says. “With the right balance, most EPI dogs can live a full and wonderful life.”
Izzy and Sassafras are two examples. Once her condition was managed, Sassafras went on to become an unofficial therapy dog for children with emotional and behavioral troubles at the junior high school where Vose works. She lived for 11 years after her diagnosis.
Izzy’s condition stabilized in about three months, allowing her to return to pet therapy work at a local residence for senior citizens. She eventually gained back the weight she’d lost and then some, tipping the scale at 48 pounds and leading Kennedy to put her on a diet last summer.
Izzy, now 5 years old, “can do anything any dog can do,” Kennedy says. “Most days, I forget that there is even anything wrong with her.”
A Web Site With a
Olesia Kennedy bought her Spanish Water Dog “Izzy” to start a breeding program. Those plans changed when Izzy developed exocrine pancreatic insufficiency (EPI) at age 1.
Two years ago, Kennedy started the Web site www.epi4dogs.com to raise awareness of EPI. The site offers comprehensive information about the disease and includes before- and after-treatment photographs, the latest research findings and a list of affected breeds. Fundraising items also are featured.
Visitors can share their experiences with EPI, ask questions and find emotional support through the site’s discussion forum. “It is very helpful to talk with others also dealing with EPI,” Kennedy says. “This is why I created the EPI forum.”
Researchers and EPI dog owners frequently contribute information on the popular Web site. “The site now averages approximately 10,000 hits a month, which indicates to me that EPI is much more widespread than anyone ever thought,” Kennedy says. “More and more breeds are being diagnosed with EPI. About half our visitors own German Shepherd Dogs with EPI, and half own other breeds. Hopefully, the Web site provides information that helps people realize there are many choices when dealing with EPI.”
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An article on two very different EPI dogs, "Hondo" by Karen Gilmer and "Nichole" by Amy Greenhut, was published in the May 2009 edition of the GSD Reveiw. http://www.gsdca.org/Noframes/review.html . A very moving story of how differently EPI can effect different dogs.
Also, an article on EPI was published in the March 2009 edition of The Whole Dog Journal at: http://www.whole-dog-journal.com/.
*** Please note that since this article was printed..... EPI Genetic Research being conducted by Drs. Leigh Anne Clark and Keith E. Murphy has moved from Texas A&M University to now being performed at Clemson University ***
Exocrine Pancreatic Insufficiency (EPI) prevents absorption of food.
Janis Fitzhugh, a member of the Almost Home Organization, knew she had to rescue Pandy, an extremely thin and seeminly vicious four-year-old Dachshund. Pandy had been relinquished to a shelter in Orange County (California), who turned her over to Southern California Dachshund Rescue. Deemed people- and animal-aggressive, Pandy appeared to have been starved, and weighed just 13 pounds. Fitzhugh thought the dog deserved a break, and brought Pandy home in May 2007.
During the first couple of weeks in her new home, Pandy managed to pull a chicken down from the counter and proceeded to eat the entire bird, including bones, plastic tray and grocery bag, in less than the 10 minutes that Fitzhugh was out of the room. Pandy was rushed to the vet and emergency surgery was performed, as the bones had ruptured her stomach lining in three places. Luckily she survived.
Pandy’s voracious appetite, large voluminous stools, and aggressive disposition were all caused by a medical condition called exocrine pancreatic insufficiency (EPI). With Fitzhugh’s loving care, including enzyme supplements and a change of diet, Pandy stabilized. Within a year, Pandy had transformed into a beautiful, funny, 26-pound Dachshund who gets along great with all the human and animal members in the Fitzhugh household.
What is EPI?Exocrine Pancreatic Insufficiency, or EPI, also referred to as Pancreatic Hypoplasia or Pancreatic Acinar Atrophy (PAA), is a disease of maldigestion and malabsorption, which when left untreated eventually leads to starvation. One of the major difficulties with this disease is in the prompt and accurate diagnosis. Astonishingly, visible symptoms may not appear until 80 to 95 percent of the pancreas has atrophied.
There are two primary functions of the pancreas:
Incomplete digestion causes the continual presence of copious amounts of fermenting food in the small intestine. This can lead to a secondary condition that is common in many EPI dogs, called SIBO (small intestinal bacterial overgrowth). If an EPI dog has a lot of belly grumbling/noises, gas, diarrhea, and sometimes vomiting, she most likely has SIBO.
The condition occurs when the "bad" bacteria that is feeding on the fermenting food overpopulates the tissue lining of the small intestine, further impairing the proper absorption of vital nutrients and depleting the body's store of vitamin B12. Treatment of SIBO includes a course of antibiotics to eliminate the bad bacteria. Treatment may also include supplemental cobalamin (B12) injections that help reestablish friendly bacteria colonies, which in turn helps inhibit the malabsorption.
Severity of the disease may vary, making it even more difficult to diagnose. EPI can be subclinical (no recognizable symptoms) for many months, sometimes even years, before it worsens and becomes noticeable. The symptoms can be exacerbated by physical or emotional stress, change of food or routine, and/or environmental factors. The most common symptoms include:
With hunger as an overwhelming force, many dogs act almost feral. Desperately seeking vital nutrition, many ingest inappropriate items, but nothing gets absorbed. As the disease progresses, the deterioration becomes quite rapid. Some dogs lose interest in any activities, preferring to just lie down or hide somewhere. Many owners of EPD dogs become increasingly frustrated, as they feed more than normal amounts and yet the dog continues to waste away before their eyes.
Since chronic loose stools are usually the first visible symptom in an EPI dog, most vets will prescribe an antibiotic to destroy what they suspect to be harmful intestinal bacteria. Owners are happy, because the problem appears to go away, at least for a while. No one has any reason to investigate further, until the loose stools return or the dog starts losing weight, and then the merry-go-round cycle begins. Vet visits become numerous and costly, and one possible diagnosis after another is suggested. Expenses may include testing (and retesting) for giardia, coccidiosis, and other parasitic diseases; x-rays; ultrasound; MRI; antibiotics; and even surgery.
Although other laboratories can run the TLI test, most blood samples are analyzed at Texas A&M University. The lab recently revised its reference ranges: values below 2.5 are now considered diagnostic for EPI. Results between 3.5 and 5.7 may reflect subclinical pancreatic disease that may ultimately lead to EPI. When values are between 2.5 and 3.5 µg/L, Texas A&M recommends repeating the TLI test after one month, paying particular attention to the fast before the blood sample is collected.
Even when a dog tests positive for EPI, it is important to retest TLI after the dog stablizes following treatment. For example, chronic inflammation can put such a strain on the pancreas that the production of digestive enzymes ceases or is greatly reduced. Consequently, when the TLI blood test is analyzed, it accurately depicts lack of enzyme production, even though the dog may not actually have EPI. In this case, it is important for the dog to be treated with pancreatic enzymes until his condition is stable. Enzyme treatment breaks down the food, allowing the stressed albeit non-EPI pancreas to recuperate and, in time, start producing the enzymes needed to digest foods.
Dorsie Kovacs, DVM, of Monson Small Animal Clinic in Monson, Massachusetts, has seen some young dogs with false-positive EPI readings. Even when they display the lighter-colored “cow patty” stools, something other than EPI may be the cause. Sometimes a food allergy or an overabundance of bad bacteria has irritated or inflamed the pancreas, temporarily inhibiting enzyme production. In these situations, says Dr. Kovacs, it's important to put the dog on a pancreatic enzyme supplement for two months, allowing the stressed pancreas to heal. The dog should then be retested to confirm or rule out EPI.
In addition, Dr. Kovacs says, “It is also important to introduce good gut flora (bacteria) by adding yogurt, green tripe, or supplements such as Digest-All Plus (a blend of plant enzymes and probiotics). Good gut flora should continue to be maintained with supplements even after the inflamed or irritated pancreas has healed.” Dr. Kovacs has also noticed that some dogs with food allergies (especially dogs fed dry kibble) show rapid improvement when their diets are switched to raw or canned food. Raw meats contain natural enzymes, and fresh vegetables support the growth of good bacteria in the dog's gut..
Enzyme supplementation is the first step in managing EPI. The dog will need pancreatic enzymes incubated on every piece of food ingested for the remainder of his or her life. The best results are usually obtained with freeze-dried, powdered porcine enzymes rather than plant enzymes or enzyme pills. Plant enzymes and enzymes in pill form do work for some, though with enzyme supplements, as with diet, much is dependent on the individual EPI dog. Some of the most widely used prescription enzyme supplements are Viokase, Epizyme, Panakare Plus, Pancrease-V, and Pancrezyme. Bio Case V is a non-prescription generic equivalent.
Enzyme potency is measured in USP units. Prescription enzyme powders range from 56,800 to 71,400 units of lipase, 280,000 to 434,000 units of protease, and 280,000 to 495,000 units of amylase per teaspoon.
Pancreatic enzymes are also available as generic pancreatin. Strengths of 6x, 8x, etc. indicate that the dosage is concentrated. A level teaspoon of powdered porcine pancreatin 6x might contain 33,600 units lipase and 420,000 units protease and amylase, comparable to prescription enzyme products.
Some EPI dogs have allergies and cannot tolerate the ingredients in the most common enzyme supplements. Those owners learn to develop alternative methods such as using plant enzymes, or a different source of pancreatic enzymes such as beef-based (rather than porcine-based). Raw beef, pork or lamb pancreas can also be used. One to three ounces of raw chopped pancreas can replace one teaspoon of pancreatic extract.
The starting dosage of prescription enzymes is usually one level teaspoon of powdered enzymes per cup of food. As time goes on and a dog stablizes, many owners find that they can reduce the amount of enzymes administered with each meal, sometimes to just ½ teaspoon, although some EPI dogs require an increased dosage of enzymes in their senior years.
Enzymes need to be incubated, meaning that you add them to moistened food prior to feeding, letting them sit on the food at room temperature for at least 20 minutes. Some find incubation up to one or two hours works even better. Too often, EPI owners are instructed that enzyme incubation is not necessary; however, some dogs will develop blisters or sores in their mouth from the enzymes when they are not first incubated on the food.
How do you judge what works best for your dog? When dealing with EPI, everything is gauged by the dog's stool quality. EPI dog owners are always on “poop-patrol”. The goal is to obtain normal looking, chocolate brown, well-formed stools. When your dog produces something other than normal poop, it indicates she is not properly digesting her food. Sometimes longer enzyme incubation helps. Other times using more or less enzymes (since too little or too much enzymes can both cause diarrhea), changing the diet, treating a flare-up of SIBO, or starting a regimen of B12 shots solves the problem. Make only one change at a time. It is advisable to keep a daily journal as it may help you to identify the cause of a flare up or setback.
Prescription enzyme supplements can be very expensive. A $5,000 per year price tag for enzymes is not uncommon for a large dog -- but don't panic! There are several ways to reduce this cost. My 40-pound Spanish Water Dog has the dubious honor of being the first of her breed ever to be positively diagnosed with EPI. When the TLI results came in, I felt like my world came crashing down. Izzy is my once-in-a-lifetime best companion, and was very sick. Using information my vet gave me, I estimated that the enzymes alone were going to cost me $1,200 a year. She was only a year and a half old at the time, with an expected life span of 13 to 15 years. Eeek!
Today those enzymes cost me a mere $200 a year. How? I joined an EPI support group and learned what others do to better manage the ongoing care of their EPI dogs. I buy enzymes from an EPI enzyme co-op that purchase enzymes in bulk and passes the savings on to owners who have a veteriniarian-confirmed EPI dog. The savings from these bulk purchases can be quite substantial. (For both groups, see Resources for Products mentioned in the Article below). Today, Izzy is a plump, active, happy dog who gives me more joy than any other dog I have had in my 55 years. I would have paid whatever it cost to help her, but not everyone has this option.
Another solution that can dramatically save money is to obtain raw beef, pork or lamb pancreas. Ask your butcher if he can get fresh pancreas, or check with meat inspectors in your state to find out if and where you can obtain fresh pancreas. A letter from your vet explaining why you need fresh pancreas may allow you to purchase it from a slaughterhouse. Fresh beef pancreas can also be ordered from suppliers such as Hare Today and Greentripe.com.
The suggested dosage of raw pancreas is 3 to 4 ounces per 44 lbs of the dog’s weight daily. The pancreas can be blended or finely chopped, then frozen into either cubes in an ice tray or “calculated by the dog’s weight” single meal amounts in Ziploc bags. Raw pancreas can be frozen for several months without losing potency. When ready to use, thaw naturally and serve the raw pancreas with the dog’s food.
A very important factor about enzymes -- whether using raw pancreas, powdered pancreatic enzymes, or pills -- is that all digestive enzymes work best at body temperature. Cold inhibits the enzymatic action while heat destroys it. Never cook, mix with very hot water, or microwave either raw pancreas or supplemental enzymes.
Antibiotics are the next line of defense, in order to combat SIBO (bad bacteria growth overtaking growth of good bacteria), the secondary condition that frequently accompanies EPI. Tylosin (Tylan) or metronidazole (Flagyl) are the commonly prescribed antibiotics, usually given for a 30 days. Some dogs have trouble with metronidazole due to possible side effects; in that case, Tylan is given. Be warned: Tylan is bitter- tasting, and many dogs refuse to eat their meals when it's added. There are tricks to deal with this. Some put the Tylan powder in gelatin capsules; I camouflage it for my dog by inserting the required dose in a small chunk of cream cheese. Not all EPI dogs can tolerate dairy, so the camouflage method should depend on the individual dog’s tolerance.
B12 (cobalamin) injections are needed if the dog has very low serum cobalamin. A blood test is required to determine this, costs about $31, and is best done simultaneously with the TLI test. Many EPI dogs cannot replenish B12 levels on their own, so B12 injections are used. B12-complex formulas are not recommended since they contain much lower concentrations of cobalamin and appear to cause pain at the injection sites. Generic formulations of cobalamin (B12) are acceptable.
The recommended cobalamin dosage is calculated according to the dog’s weight and may be found on Texas A&M University website (see Resources below). Your vet can show you how to give your dog subcutandous (beneath the skin) B12 injection. What seems to work best are weekly injections for the first six weeks, then biweekly (every other week) injections for the next six weeks, and finally monthly B12 injections .
Sometimes it is much more complicated! Some dogs can tolerate much more fat. My dog, Izzy, for example, does extremely well on grain-free kibble with 22 percent fat content, well above the 12 percent range. Other dogs cannot tolerate even as little as 12 percent fat. The same applies to the fiber content. Some EPI dogs have unrelated food allergies, further limiting their diet.
Many dogs with EPI thrive on raw diets and some owners find a raw diet is the only one that works for their dogs. Conversely, other EPI dogs cannot tolerate raw diets. Some owners successfully feed grain-free kibble, some make home-cooked meals for their dog, while others feed a combination of commercial and homemade.
When adding to ar adjust a diet, feed the dog tiny chunks of raw carrot with the diet. These carrot pieces will present themselves in the stools (for better or worse) of that meal's elimination. This helps you to understand which foods/vitamins, etc., work well together and which don't.
Recommendations keep evolving and changing with new research, as well as the feedback from networks of owners of EPI dogs. A recent change in feeding recommendations concerns dietary fat. Multiple studies from the past decade indicated that a fat-restricted diet is of no benefit whatsoever to the EPI dog. A 2003 EPI paper by Edward J. Hall, of the University of Bristol in England, states that there is experimental evidence to show that the percentage fat absorption increases with the percentage of fat that is fed. This may explain why some EPI dogs can tolerate higher concentrations of fat. For those dogs who cannot tolerate more than 12 percent fat, this may mean that the fat content needs to be increased very gradually, or perhaps that certain types of fat may be tolerated better than others. Much more research is needed to answer these questions.
Veterinarians usually recommend an initial diet of a prescription or veterinary food, such as Hill's Prescription Diet w/d, i/d, or z/d Ultra Allergen-Free; Royal Canin's Veterinary Diet Canine Hypoallergenic Diet or Digestive Low Fat Diet; or Purina's EN. Prescription diets that are made with hydrolyzed ingredients (carbohydrates and proteins that have been chemically broken down into minute particles for better absorption in the small intestine, leading to more complete digestion, better/faster weight gain, and firmer stools) appear to work for many EPI dogs. However, these diets are usually starch-based (often almost 60 percent carbohydrates on a dry matter basis); the digestive system of a dog is designed more for fats and protein than for starches, which may be why many EPI dog owners achieve better results by reserving prescription diets for short-term use and feeding other diets over the long haul.
The best results for managing EPI requires combining veterinarian advice with the experience of actual EPI dog owners. Too many times, managing EPI can be a real roller coaster ride! For example, initial research studies showed that supplemental enzyme powders needed to incubate on the food. Additional research studies then suggested that food incubation with enzymes was no longer necessary. Consequently, some EPI dogs developed mouth sores, so owners are again being advised to let the enzymes incubate to prevent this side effect. Until the causes and effects of this disease are better understood, it will continue to be managed via trial and error.
Once an EPI dog is stable, some owners find that they can ”cheat” and give their dog a smidgeon of a treat without any enzymes on it. Others find the least little crumb ingested without enzymes will cause a flare-up.
If possible, feed two to four meals a day, taking into consideration whether the dog’s condition has stabilized and whether the family’s schedule can accommodate multiple feedings. Feeding smaller, more frequent meals puts less stress on the EPI dog’s digestive system.
At first calculation, many owners of EPI dogs wonder if they can sustain the added expense of all these “special foods” in addition to the enzymes. It may take many attempts to find just the right diet for a dog with EPI that is also affordable by the owner, but it can be done. Following are some suggestions and techniques that owners of dogs with EPI have successfully used.
* Kibble or Canned: Many EPI owners who feed commercial kibble or canned dog food have found more success when feeding a grain-free product. Much depends on the individual dog.
When feeding kibble, many owners let the food and enzymes incubate until the food has an oatmeal-like consistency. Some even grind the kibble to allow for more surface contact with the enzymes. Some also add a teaspoon of pumpkin or sweet potato, which may help firm stools and reduce coprophagia; plus, both ingredients are packed with vitamins C and D. Sweet potato is also an excellent source of vitamin B6.
* Combination Kibble and Homemade: Many owners feed a combination of commercial food and raw or home-cooked. EPI owners mix foods at a ratio of 20 to 80 percent. An example would be 20 percent raw meat mixed with 80 percent dry food, or 20 percent kibble with 80 percent raw meat. As always with an EPI dog, enzyme supplements should be mixed in with the wet portion of the food at room temperature and allowed to incubate.
Depending on each individual dog’s tolerance, any variety of meats and fish may be used. Sources of proteins can include beef, chicken, turkey, pork, venison, rabbit, lamb, canned or cooked salmon, and jack mackerel, as well as eggs, yogurt and cottage cheese. Organ meats, such as liver, kidney, and heart should also be included in the diet. Green tripe is another good option. Variety is key! Again, incubate the food with the enzymes and feed 2 to 4 times daily, depending on your individual dog’s needs and your own schedule.
* Raw and home-cooked: Over the last few years, many owners have been able to stabilize their EPI dogs by feeding a raw diet. Raw food has the innate advantage of maintaining natural food enzyme activity that aids digestion. Many vets disapprove of feeding a raw food diet, especially to compromised dogs (possibly exposing them to further complications), while other vets suggest that raw is best for an EPI dog. There have been many anecdotal cases of dramatic improvement when the owners feed their EPI dog a raw diet, especially when all else fails.
Most EPI dogs cannot handle the 20 to 25 percent bone content in the diet that is commonly fed to normal dogs. With EPI dogs, it's smart to start with only 10 to 12 percent of bone. Some dogs still have difficulty digesting this amount of the bone and the ratio will need to be reduced even further, to 3 to 5 percent bone. Note we are talking about the amount of actual bone, not the amount of raw meaty bones, which are usually at least half meat.
Vegetables may be a large or small portion of the diet, or not included at all, depending on the individual dog’s tolerance. If included, they should always be mashed. Organ meats are usually recommended at 10 to 15 percent of the EPI diet, but once again, not all can tolerate this.
Most EPI dog owners add coconut oil and/or wild salmon oil to their dog’s diet. Many EPI dogs cannot digest other fats and develop dry, itchy skin or dry, brittle coats. Coconut oil contains medium-chain triglycerides (MCTs). Most vegetable oils have longer chain triglycerides, called LCTs. MCTs are utilized faster and burned more quickly for energy, raising the body’s metabolism, while LCTs are utilized more slowly. Also, coconut oil is one of the richest sources of lauric acid. Its benefits have recently been touted to aid in destroying various bacteria and viruses such as listeria, giardia, herpes simplex virus-1, and maybe even yeast infections such as candida.
Wild Alaskan salmon oil is an excellent source of omega-3 fatty acids, which help reduce inflammation.
Probiotics are another important addition to the EPI diet, especially since most EPI dogs are or have been treated with antibiotics because of SIBO. Antibiotics wipe out not only bad bacteria, but also good bacteria. Probiotics help maintain good gut flora. One popular brand of probiotics that has been successfully used by EPI owners is Primal Defense, but there are many quality probiotics available.
Zinc deficiency is another consideration with EPI dogs. It is difficult to accurately measure zinc absorption, Human EPI patients often develop a zinc deficiency, and though no studies have confirmed this to be true of dogs with EPI, many vets sugest a zinc supplement for EPI dogs.
Vitamin E (tocopherol) levels may also be low in an EPI dog due to malabsorption. Vitamin E is a fat-soluble vitamin that is an antioxidant and helps in the formation of cell membranes, cell respiration, and with the metabolism of fats. Vitamin E deficiency may cause cell damage in the skeletal muscle, heart, testes, liver and nerves; supplementation with vitamin E can help prevent these problems.
Other natural nutrient sources that are often included in an EPI diet are kelp, green tripe, slippery elm, and alfalfa.
If you own a purebred GSD, with or without EPI, and would like to contribute a blood sample, please contact Dr. Leigh Anne Clark at Clemson University (see Resources below).
It is important that this research continues. EPI is rapidly spreading across all breeds. It is no longer just a GSD disease, or a working dog disease. Dogs of all breeds, including crossbreeds, are being diagnosed with EPI. It is happening in family lines too often to be coincidence without a genetic component. Yet, not every family member or generation in affected lines has EPI. For now, until we can actually test for the genetic markers, the best possible control is to remove positively-confirmed EPI dogs from breeding programs. Once genetic markers are identified in GSDs, the markers in other breeds will be more easily detechted.
Although there are many success stories, there are also heart-wrenching tales of dogs who cannot thrive, families who cannot afford the treatment, and throughout it all, the painful suffering the dog endures unless successfully treated. EPI can no longer be a “hush-hush” disease. My hope is that this article will make a difference by helping raise awareness of EPI to the level of other major canine diseases.
Olesia Kennedy, a retired research analyst, and previously involved in Canine Search & Rescue, currently devotes her skills and time to EPI research. She resides with her husband and three Spanish Water Dogs in Georgetown, Indiana.
Many EPI dogs flourish
Kara was lucky; she was diagnosed with EPI. While in foster care for four months, Audrey Blake met Kara twice during training classes and the frail little dog with the outgoing personality captured her heart. Although she understood that Kara would need pancreatic enzymes for every meal and a special diet, Blake took Kara home. Today, Kara is known as "U-CD Twenty-Four Karat Gold, UD, TDI, CGC (Kara), Rescue Sheltie," and happily resides with Blake in Long Island, New York!
Sadly, Some Dogs Perish
Wayde was in the kennel for many months. Finally, a couple who was familiar with EPI, Pamela and Peter Burghardt from Wilmot, New Hampshire, decided to foster Wayde. In their home, his whole demeanor changed; he became happy and gained more than 2 pounds the first week. Wayde soon settled in with his foster family and became a sweet “Velcro” dog. He became best friends with his foster sister, another white GSD.
Sadly, Wayde was diagnosed with cancer a few weeks after going into foster care and passed away four months later. Despite the cancer, he had gained 14 pounds and was active and happy to the end.
Please Support Research for EPI
Texas A&M University website for recommended cobalamin dosage: http://www.cvm.tamu.edu/gilab/research/cobalamin.shtml
To participate in the EPI genetic research studies at please contact Dr. Leigh Anne Clark at Clemson University, SC, USA
To contact Dr. Clark, her office telephone number is: 1-864-656-4696; her email address is: email@example.com
Leigh Anne Clark, PhD.
To support EPI research, send donations to: Keith E. Murphy, PhD., Professor and Chair, Department of Genetics and Biochemistry, 100 Jordan Hall, Clemson University, Clemson, SC 29634-0318
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