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Bladder Cancer Study- Final Report: What Every Scottie Owner Needs To Know
If you have never lost a Scottish Terrier to bladder cancer – or, more properly, Transitional Cell Carcinoma – consider yourself extremely lucky. Scotties have an 18 times greater likelihood of contracting the disease than their mixed-breed counterparts.
TCC is a growing concern. In North American veterinary teaching hospitals, the prevalence of dogs diagnosed with the disease has increased by more than 600% between l975 and 1995! Several breeds are at a significantly increased risk of developing TCC, including Shetland Sheepdogs, Wire Fox Terriers and Westies, but none quite as dramatic as the increase in risk associated with Scottish Terriers. This dramatic increase in TCC risk suggests a genetic predisposition to TCC in terriers and primarily in Scottish Terriers.1
In June 2001, the first scientific study of Transitional Cell Carcinoma (TCC) in Scotties was undertaken. Thanks to matching funds from the Scottish Terrier Club of America’s Health Trust Fund and the AKC Canine Health Foundation, a Purdue University research team orchestrated AKC CHF Grant No 2105: Characterization of Host and Environmental Risk Factors for Urinary Bladder Cancer in a High Risk Breed (The Scottish Terrier).
It is believed that TCC in dogs is probably multi-factorial involving both a genetic predisposition for the development of the cancer as well as environmental triggers that may “turn on” the process in susceptible individuals. Prior epidemiologic research2 conducted in a wide variety of dogs already identified certain risk factors for TCC. In this case/control study conducted in 1989, the risk of TCC was found to be unrelated to second hand cigarette smoke and household chemical exposures, but the risk was significantly increased for dogs exposed to topical insecticides, particularly the older generation flea and tick dips. If the dogs were obese or even moderately overweight, the increased risk was enhanced. Furthermore, if the dogs lived near a marsh, or any environment that could be another potential source of insecticides, the risk for TCC was enhanced.
In 1991, the National Institutes of Health (NIH) published its findings of a case/control study which reported an increased risk for malignant lymphoma in pet dogs exposed to the commonly used lawn and garden phenoxy class of herbicide, 2,4-D.3 In this study involving over 1000 dogs, there was a greater than 2 fold increased risk of lymphoma in dogs exposed to lawns, treated either by the home owner or by a commercial company, four or more times per year. Although these findings were challenged4 and later refuted5 by a Chemical Industry Task Force, a subsequent study6 demonstrated that dogs exposed to lawns treated with 2,4-D absorb enough of the chemical to excrete it in the urine for several days after the herbicide treatment.
With this earlier research as a starting point, the Purdue researchers now decided to test three specific hypotheses:
1) That exposure to lawn and garden chemicals will increase the risk for TCC in Scottish Terriers;
2) That exposure to flea and tick products will increase the risk for TCC in Scotties:
3) That certain foods, in particular certain vegetables and vitamin supplements, fed on a routine basis, will reduce the risk for TCC in Scotties.
Scottie owners were recruited via the STCA and Purdue Comparative Oncology Program websites. Many STCA members were personally contacted by veterinarian and Scottie breeder Marcia Dawson, who served on the research team, along with Lawrence Glickman, VMD, DrPH, Malathi Raghavan, DVM, PhD, Deborah Knapp, DVM, MS, DACVIM and Patty Bonney, RVT from the Purdue School of Veterinary Medicine.
Potential participants received a lengthy – 15 page – questionnaire, asking a multitude of questions on diet, supplements, medications, use of flea and tick preparations, general husbandry, and exposure to lawn and garden chemicals. None of the participants were aware of the hypotheses being tested in the study. In order to be eligible, a Scottie had to be diagnosed with TCC after January 1, 1995, and the owner had to submit proof of diagnosis. Dogs diagnosed via biopsy were considered “confirmed” and dogs diagnosed via cytology (needle aspiration, urinalysis, etc.) were considered “presumptive.” Control dogs – those who would provide comparison information so that scientific conclusions could be reached – were limited to Scotties who had never been diagnosed with TCC and were at least six years old on or after July 1995. Dogs with a recent history of urinary tract disease were eliminated from further study. Only one dog per household could participate.
Demographic information was collected on the 83 case (diagnosed with TCC) and 83 control dogs. It was found that, at the time of data collection, 63% of the diagnosed dogs had died, compared with only 12% of controls. Both groups were similar in age, with case dogs averaging 9.9 years, and controls, 9.1. Forty-one percent in both groups were males, and 59% were females. Most were neutered – not surprising, given their relatively advanced ages.
Data were subjected to rigorous statistical analysis and the conclusions drawn are troubling indeed. Scotties who had been exposed to lawn herbicides were between four and seven times more likely to develop bladder cancer than dogs that had not been exposed.
Fifty-one percent of the diagnosed dogs had been exposed to herbicides on more than an occasional basis, compared to 18% of controls. The number of case and control dogs exposed to insecticides was equal, thereby suggesting that – in this study - exposure to insecticides alone does not appear to be a significant risk factor. However, exposure to herbicides alone resulted in a nearly four times greater risk of developing bladder cancer, and exposure to both insecticides and herbicides increased the likelihood to over seven times! In other words, a Scottie exposed to herbicides on a more-than-sporadic basis is four times more likely to be diagnosed with bladder cancer, and the odds skyrocket to seven times more likely when herbicides and insecticides are combined.
The risk appeared to be greater for lawn products containing a common chemical known as 2,4-D, which is a phenoxy herbicide. Data suggest that non-phenoxy herbicides also increase the cancer risk, but results were not statistically significant. Researchers concluded that the data are consistent with a genetic-environmental interaction, meaning that Scotties with a genetic predisposition are at high risk for TCC when exposed to certain risk factors like phenoxy herbicides.
The report warns that the inert ingredients in herbicides may also be responsible. The inert ingredients – which can comprise more than half of the preparation by volume – need not be listed on the label, but often include hazardous and carcinogenic chemicals. The authors urge Scottie owners to significantly reduce access to treated lawns when either phenoxy or non-phenoxy products are used. They also recommend that Scottie owners get semi-annual microscopic examination of their pet’s urine, so that TCC can be detected in its early – and potentially treatable – stages.7
Testing the second hypothesis, the researchers looked at the relationship between use of topical flea and tick products and increased incidence of TCC. Those Scotties whose owners indicated that they had a history of exposure to such products were included in the study. Eighty-eight dogs diagnosed with TCC made up the case group, with 83 Scotties serving as controls. Owners had to have used fleas and tick products within one year prior to diagnosis in the TCC dogs, and a comparable period of time for controls. In dogs that had died prior to the study, the specified products had to have been used within one year prior to the dog’s death. Products under study included shampoos, dips, collars, powders, sprays, pills and “spot-ons” – the products that are “dribbled” down the dog’s back. Owners were asked to provide brand names, and – to ensure the validity of the data – to provide labels as well.
Interestingly – and sadly – the most common health problem confronting the control dogs at the time of data collection was cancer, which affected 24% of the non-TCC dogs. Also significant is the fact that only 5% of control dogs had a history of urinary tract disease prior to the study, whereas 28% of the TCC dogs had chronic problems.
Risk factors found to be significantly associated with increased risk for TCC included age, weight, having been neutered, having a close relative with a history of TCC, and, oddly enough, black coat color, although there may be some confounding factors to explain this. Exposure to the older class of flea and tick products such as powders, dips, and collars resulted in an increased risk of TCC. Using multiple products and using them more frequently also increased the risk. The relationship between use of “old-fashioned” flea/tick products and TCC was increased for overweight dogs, again suggesting that toxins stored in fat cells pose more risk due to longer exposure. The good news is that the use of “spot-ons” (Frontline ® and Advantage®) – which represent the new generation of product designed for the war on external parasites – did not result in any increased risk for bladder cancer.
Researchers advise Scottie owners to avoid the older topical flea and tick products, specifically dips, powders and collars, and to use the newer spot-on products, particularly those containing fipronil (Frontline®).8
In the third study, 93 Cases and 83 Controls were studied to assess the effects of vegetable consumption and vitamin A, C and E supplementation on the risk for TCC. Research on humans suggests that the risk of certain kinds of cancer is reduced by as much as 60% when vegetables are a significant part of the diet. However, the connection to bladder cancer is not clear, and no study before has looked at vegetable consumption and cancer risk in dogs.
Owners were asked to provide detailed information on diet, and, as any nutritionist would predict, vegetable consumption correlated negatively with bladder cancer risk in Scottish Terriers.9 Type of vegetable made a difference, with positive effects seen in dogs fed either leafy green or yellow-orange vegetables. Cruciferous vegetables such as broccoli had a protective effect, but the sample size in this study was too small to be significant. Also, no difference between Cases and Controls was found if veggies were fed only once a week or less; in order to have a positive effect, vegetables had to be fed at least three times per week. Scotties fed either leafy green or yellow-orange vegetables at least three times a week were 70% to 90% less likely to develop bladder cancer than their cohorts! Over half of the dogs studied were fed vegetables at least once a week, with carrots being the most popular choice. None of the vitamin supplements showed a significant decrease in risk.9
Over 50,000 men and women are diagnosed with bladder cancer each year. Animal studies on risk factors, to which our breed has made a significant contribution, may teach researchers more about how humans contract the disease. Furthermore, this important study will serve as a springboard for future research. For example, Dr. Glickman and his team currently have a study underway looking at the concentration of potentially dangerous chemicals in the urine of children and their pet dog(s) exposed to herbicide treated lawns. Future studies may include prospective trials using vegetables to prevent TCC in our Scotties. The Purdue study will not only make our Scotties’ lives better, but the results may also someday help make human lives better as well.
transitional cell carcinoma of the urinary bladder: A relevant model of human invasive bladder cancer. Urol Oncol, 2000; 5: 47-59.
2. Glickman LT, Schofer FS, McKee LJ, et al. Epidemiologic study of insecticide exposures, obesity, and risk of bladder cancer in household dogs. J Toxicol Environ Health, 1989; 28:407-414.
3. Hayes HM, Tarone RE, Cantor KP, et al. Case-control study of canine malignant lymphoma: positive association with dog owner’s use of 2,4-dichlorophenoxyacetic acid herbicides. J Natl Cancer Inst, 1991; 83: 1226-1231.
4. Carlo GL, Cole P, Miller AB, et al. Review of a study reporting an association between 2,4-dichlorophenoxyacetic acid and canine malignant lymphoma: report of an expert panel. Regul Toxicol Pharmacol, 1992; 16: 245-252.
5. Kaneene JB, Miller R. Re-analysis of 2,4-D use and the occurrence of canine malignant lymphoma. Vet Hum Toxicol, 1999; 41: 164-170.
6. Reynolds PM, Reif JS, Ramsdell HS, et al. Canine exposure to herbicide-treated lawns and urinary excretion of 2,4-dichlorophenoxyacetic acid. Cancer Epidemiol Biomarkers Prev, 1994; 3: 233-237.
7. Glickman LT, Raghavan M, Knapp DW, Bonney PL, Dawson MH. Herbicide exposure and the risk of transitional cell carcinoma in the urinary bladder of Scottish Terriers. J Am Vet Med Assoc, 2004; 224:1290-1297.
8. Raghavan M, Knapp DW, Dawson MH, Bonney PL, Glickman LT. Topical flea and tick pesticides and the risk of transitional cell carcinoma in the urinary bladder of Scottish Terriers. J Am Vet Med Assoc, 2004; 225:389-394.
9. Raghavan M, Knapp DW, Dawson MH, Bonney PL, Glickman LT. Evaluation of the effect of dietary vegetable consumption on reducing risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers. J Am Vet Med Assoc, 2005; Vol 227: No 1, July 1, 2005.
Original Doc: Scotties and Bladder Cancer - final copy.doc
Bladder Cancer: Remember This Treatment
Carole Fry Owen
Source: Great Scot Magazine, Jan/Feb 1999, pages 28-29, 34.
"My Scottie is having trouble urinating, and there is blood in the urine. Her veterinarian has been treating her for a urinary infection, but she's not getting better. Any ideas?
Judy and Alex Falcon, Palos Park, IL.
"Transitional cell carcinoma of the bladder is my best guess" -- "Dr." Owen, the armchair vet, told 10-year-old Tootsie's owners who called yesterday.
I wasn't making a rash, uninformed statement. My old Lucky had identical symptoms five years ago. Her diagnosis was bladder cancer, and she became something of a landmark case in making Scottie owners aware of a new cancer treatment.
This treatment needs even wider exposure, so I hope GSM readers will help. Two days before the Falcons phoned, I had two other calls requesting information on bladder cancer treatment, and two weeks before that still another call. Bladder cancer strikes Scotties often.
The Falcons already suspected cancer, but they had no idea that the risk might be so high for Tootsie. The fact is: the Scottish Terrier has the highest risk of bladder cancer of any purebred dog! And female Scotties have twice as much bladder cancer as male Scotties.
"This dog has been a nurse to all of our family. She has carried us through the worst of times, illnesses and such," said Judy Falcon. If the answer to Tootsie's ultrasound is bladder cancer, Judy and Al do not want to put her through surgery, radiation or conventional chemotherapy
I was delighted to be able to tell them there is a fourth option, one which Scottie owners find can improve quality of life, and, in fact, sometimes extend life-- the good life-- in Scottie bladder cancer patients. Tootsie may have a lot of "nursing" to offer her family yet.
When my Lucky was finally diagnosed, we prepared ourselves for "last rites," thinking Lucky had only weeks to live, Lucky for Lucky and us, our enterprising vet called a Texas A&M veterinary oncologist to inquire about possible treatments. Amazingly, Purdue University had tested a drug that gaveexcellent results against transitional cell carcinoma of the bladder in dogs. The drug was piroxicam, generic form of FeldeneÒ a non-steroidal anti-inflammatory medication used in humans for arthritis.
Lucky lived about a year after beginning piroxicam treatment-- with outstanding quality of life, Five months into treatment I wrote: "Lucky retains her great interest in food, She is active, can still work up a game of soccer. She delights in life and appears in no pain,"
Purdue's studies on piroxicam continued, and results of later research were even more definitive: The Scottish Terrier column in the AKC Gazette, August, 1997, reported: "In a 1994 Purdue report published in the Journal of Veterinary Internal Medicine (volume 3, number 4, pp. 273-278), 34 dogs (including eight Scotties) with inoperable transitional cell carcinoma of the bladder were treated with a daily oral dose of 0.3 mg piroxicam/kg of body weight. At 46 days, in two dogs the tumors were in complete remission, and in four they were in partial remission. The disease was stable in 18 dogs and had progressed in 10. One of the two dogs that was in full remission lived for 10 months; the other lived for two years. The median survival of all dogs was 181 days."
Heather (Ch. Windsor’s Misty Heather) owned by Margaret Plumb, Laramie, WY, was a FeldeneÒ wonderdog. Colorado State University veterinarians diagnosed Heather’s bladder cancer in March 1994, and gave her only two months to live. “Heather responded miraculously to the FeldeneÒ treatment, and we were blessed with 2 and a half more years,” says Margaret.
“Heather was still going for one-half mile to one-mile walks a week ago, without my ever pulling her lead, and she ate with a strong appetite the night of Nov. 18,” Margaret wrote CSU vets Nov. 19, 1996, the day Heather died. “I do not want you to think that I struggled for two and one-half years to keep a canine invalid alive. Heather enjoyed all of the activities of the younger, stronger dogs until practically the end. Heather always had an excellent appetite and a particular passion for cooked eggs, any style. Heather would chase off an errant squirrel, cat, or dog that might encroach upon her property, and had an endearingly pompous attitude when patrolling her territory.”
Margaret sent me a photo taken the afternoon Heather died. I agree with her. “It shows her clear eyes, her nicely fleshed body, her beautiful, healthy black coat.” In the care after the photo session, Heather gave a yelp and fell across Margaret’s knee. Her vet concluded she died of a heart attack.
Barbara Albright (Chester, NH) sings the praises of piroxicam treatment for her Mack, too. He was diagnosed with bladder cancer in late 1996 at eight years old, and still is doing well today. Mac’s ultrasound showed tumors occupying almost half of Mack’s bladder with the worst around the “neck opening.”
“After about one week of daily dosage,” wrote Barbara, “I saw more improvement, almost no repeated straining, only occasional blood, good amounts passed, and most importantly, a dog that felt better, with more energy and mingling back with the others, barking and dancing!”
A year into treatment Barbara wrote, "He looks great! He acts great!" Then last April: "He is slowing down, but still manages to dance and bark up a storm!" In June: "Mack is 18 months (into treatment) now and looks/acts pretty darn good." In August: "Mack's 10-year birthday is today, Aug. 16, 1998! Two very short years ago we thought we would not have him today. We made a big fuss this morning, and he was dancing and merrily wagging his tail although I'm sure he didn't quite know what we thought was so special!
"All his recent bloodwork showed very little kidney/liver changes: actually all indicated fine health. He sometimes doesn't make it out the door to urinate, but, heck, it is still coming out. His appetite, stools, etc., are great! He doesn't run as often as he was, and will get tired, panting when he does exert himself. He sure musters up plenty of barks all the time, and is the first one to hear a potato chip bag open."
Out of curiosity, Barbara asked for an ultrasound this fall. It showed the tumors have merged around the outside of Mack's bladder, and some lymph node involvement. But Mack is in no apparent pain, and "he can still make a big puddle." Living in New Hampshire, Barb finds snow a help in tracking blood in Mack's urine. When diagnosed, Mack had been showing tea-colored urine. Barbara suggests owners whose dogs don't eliminate on concrete or snow occasionally dab urine spots with a white paper towel to check color.
Piroxicam or FeldeneÒ can have severe gastrointestinal side effects, and should be used only under a veterinarian's direction. Both Heather and Mack received higher than the recommended doses of piroxicam, given jointly with low doses of the antibiotic amoxicillin. Heather took 10 mg FeldeneÒ every other day, and Mack receives 5 mg daily.
Barbara joins dog owners who use nutritional therapies in their cancer patients. In addition to piroxicam, Mack receives Vitamin C and supplements including Coenzyme QI0 and sometimes milk thistle. Barbara believes Vitamin C is a major factor in Mack's continued good condition: "I have run out of vitamin C several times, and have noticed more blood in the urine."
Another nutritional strategy could be garlic. Research (Cancer, vol 79: pp. 1987-1994, 1997) shows garlic as a possible new effective treatment for transitional cell carcinoma of the bladder. Mice treated with garlic orally had significant reductions in both tumor volume and mortality. Garlic is worth a try for dogs with bladder cancer. Aged garlic tablets (like KyolicÒ) do not promote offensive odor and are easy to give.
Some dog owners also opt for cancer diets which, in general, are low carbohydrate, high fat, and high quality protein. To customize a diet for your dog with cancer, contact a holistic veterinarian, or read "Eating Right to Fight Cancer" in The Whole Dog Journal, December, 1998.
Epidemiologist Dr. Howard Hayes wrote a comprehensive article on cancer in Scotties for the 1986 Scottish Terrier Club of America Handbook. He states that tobacco usage and occupational chemical exposures are known risk factors for human bladder cancer. Dogs Dr. Hayes studied which lived in geographical areas with greater industrial activity also showed an increased frequency of bladder cancer compared with other cancers. He suggests that the pet dog (yes, our Scottish Terrier) is a sentinel model for this type of environmentally related cancer.
Since Scotties have the greatest risk for bladder cancer of any purebred dog, Dr. Hayes speculates they may be especially sensitive to environmental bladder carcinogens. The fact that female dogs have twice as much bladder cancer as males may be because males’ “scent marking” sends urine-borne carcinogens through their bladders quicker.
A strategy to reduce risk of bladder cancer in Scotties should include reduced exposure to possible urine-borne carcinogens. Pre-emergent week killers, herbicides, fertilizers and pesticides you use in the backyard; carpet cleaners inside your house; residue from pest extermination; frequent use of anti-flea products; second-hand tobacco smoke; and even drinking water and preservatives in dog food may pose dangers. Lower your Scotties’ toxic burden, and you may reduce the risk of bladder cancer, and other cancers! Remember: our Scotties live on the ground and on the floor—ground zero for many possible carcinogens.
Chronic inflammatory conditions and chronic allergies may increase risk of various cancers. With Scotties’ high incidence of bladder cancer, it is important to diagnose, treat and cure urinary tract infections in a timely manner.
Bonnie Lamphear, Clearwater, FL., whose Scottie Sonny has just started FeldeneÒ treatment, cautions owners to check their prescriptions carefully. Her vet phoned a prescription for FeldeneÒ. The pharmacy misunderstood and filled it with SeldaneÒ which is an antihistamine. Bonnie discovered quite by accident she was giving Sonny the wrong medicine.
Bonnie also emphasizes the importance of expert ultrasound/ sonography evaluation. If your Scottie is having strained urination, bloody urine and chronic urinary infections, and if conventional treatment is going nowhere, insist on ultrasound. It is the non-invasive diagnostic tool of choice.
You're wondering about Tootsie? Yes, she does have bladder cancer. The specialist who did Tootsie’s ultrasound was quite insistent he would not find bladder cancer. He admitted, "I was wrong." The Falcons have started her on piroxicam.
Knowledge that Scotties are the #1 breed affected by transitional cell carcinoma of the bladder, and that bladder cancer is the #2 cancer affecting Scotties, gives you, the Scottie owner, more information than 95% of veterinarians have. You are the person with breed specific information, and a wise veterinarian will use your knowledge when looking for an illusive diagnosis.
The good news: I predict Tootsie has months, maybe years, to "nurse" her family. Check this column for future updates on Tootsie!
Ó1998 Carol Owen
Howard M, Hayes, Jr., D.V.M, "Hospital Prevalence of Cancer in the Scottish Terrier; STCA Handbook, 1986, pp. 158- 167.
Original Doc: Remember This Treatment.doc
Canine Bladder Cancer
Carolyn J. Henry, DVM, MS University of Missouri-Columbia Columbia, MO, USA
Source: Canine Bladder Cancer (VET-259) Western Veterinary Conference 2004
The objective of this presentation is to discuss the pros and cons of current diagnostic methods and treatment options for canine bladder cancer.
Early detection of canine bladder cancer may be facilitated by knowledge of relevant clinical signs and breed predispositions, as well as appropriate use of screening and confirmatory tests.
Because canine bladder cancer often exhibits metastatic behavior, treatment plans should address both local disease and metastasis.
Of the malignancies reported to occur in the canine urinary bladder, transitional cell carcinoma (TCC) is the most common and will be the focus of this discussion. Because initial signs of bladder cancer may be subtle, TCC is often quite invasive by the time it is clinically detectable and diagnosed. The estimated metastatic rate at the time of diagnosis is <20%, but may exceed 50% later in the disease course. Therefore, early diagnosis is essential and should be followed by therapy that is aimed at addressing both local disease and the potential for development of metastatic lesions.
Clinical features and history
Most reports suggest that canine TCC is more commonly diagnosed in older female dogs, with Scotties, Shelties, West Highland white terriers, Airedale terriers, collies, and beagles considered to be at high risk. Typical presenting complaints include pollakiuria, stranguria, hematuria, or tenesmus. Occasionally, lameness due to bone metastasis may be the reason for initial clinical presentation. Oftentimes, the history of a dog with TCC will include an apparent improvement in clinical signs after administration of antibiotics prescribed for presumed cystitis.
Diagnostic testing for bladder cancer generally begins with a urinalysis. Unfortunately, findings may be confusingly similar to those noted with cystitis, including pyuria, hematuria, and bacteruria. Urine sediment exam can reveal tumor cells in >30% of cases. However, reactive transitional cells may look very similar to TCC cells, thus cytology should be interpreted carefully. Care should also be taken when obtaining urine for analysis because tumor cell transplantation may occur with manipulation of TCC. For this reason, the author cautions against cystocentesis in dogs for which TCC is suspected.
A urine dipstick test that detects a veterinary bladder tumor antigen (VBTA) is now available to screen for canine urinary tract TCC. In evaluating this test clinically, we have found that it functions best when run on spun urine samples and should be performed within 48 hours of urine sample collection. An initial published report showed that the test had 90% specificity and 78% sensitivity for the diagnosis of TCC. Subsequent reports, including one study by the author and others have yielded similar results. False positive test results may occur when samples contain blood, protein, or glucose. However, false negative test results are uncommon. Thus the VBTA test is a reasonable screening, but not confirmatory, test. The results of the VBTA test should be interpreted in light of other clinical findings, with further diagnostic testing pursued when positive results are obtained.
Tumor imaging and staging
Bladder imaging or direct tumor visualization, along with cytological or histopathological demonstration of neoplastic cells is needed to confirm the diagnosis of TCC. Contrast cystography is a reliable method to identify bladder masses in greater than 95% of all cases. Tumor staging procedures should include sublumbar lymph node imaging and 3-view chest radiographs (right lateral, left lateral, and ventrodorsal views) to assess for metastatic disease. Ultrasonography is a valuable tool for bladder imaging and for detection of metastatic lesions in abdominal organs and lymph nodes. It is also an ideal means to aid in procurement of biopsy samples via urinary catheterization. Alternatively, biopsies may be obtained via cystoscopy or laparotomy.
The choice of surgery as a treatment option for dogs with TCC should be based upon tumor location and invasiveness, as well as client goals. Numerous surgical options exist, including partial cystectomy, total cystectomy with ureterocolonic or ureterourethral anastomosis, or permanent cystostomy tube placement. Often, the least invasive techniques are chosen based on issues of quality of life and convenience. In one report of partial cystectomy in 11 dogs, the procedure provided survival times ranging from 2 to > 48 months and a 54.5% one-year survival rate. Importantly, visual assessment at the time of surgery was noted to be an inaccurate method for determining tumor-free margins. Accordingly, if intraoperative evaluation of surgical margins (via cytology or frozen section) is not possible, margins should be taken as generously as is reasonable. Partial cystectomy is a viable option for treatment of localized TCC. One must bear in mind, however, that it does not address metastasis and is a poor treatment option for advanced TCC. As the entire bladder mucosa is likely to have been exposed to the inciting carcinogen that led to tumor development, multifocal lesions or diffuse disease may limit the ability to achieve complete surgical excision. In one published report, only two of 67 dogs undergoing surgery for TCC had complete surgical excision of their disease and both later had tumor recurrence/progression.
A multitude of medical therapies and combination chemotherapy protocols have been evaluated for the treatment of canine TCC. The systemic therapies that have been reported in the literature or evaluated by the author are reviewed below:
The nonsteroidal anti-inflammatory drug (NSAID), piroxicam, has shown efficacy, both as a single agent and in combination therapy, against canine TCC. Although the complete mechanism of action of piroxicam is unclear, it may relate to inhibition of cyclooxygenase 2 (COX-2) expressed on TCC cells and to inhibitory effects on tumor angiogenesis. In the first prospective evaluation of piroxicam for treatment of canine bladder TCC, responses were noted in 6/34 dogs for a median of 7 months. Side effects may include gastrointestinal (GI) irritation and nephrotoxicity. Regular evaluation of PCV, BUN, creatinine, and urine specific gravity are advised in order to monitor for renal toxicity and GI bleeding.
Doxorubicin and Cyclophosphamide
Although not evaluated prospectively, the combination of doxorubicin and cyclophosphamide provided a median survival time of 259 days for dogs with TCC, compared to 57 days with intravesicular thiotepa and 86 days with surgery alone in one retrospective study. Because these results compare favorably to those obtained using other protocols and the drugs are relatively inexpensive, it may be worthwhile to prospectively evaluate this combination therapy for canine TCC.
Cisplatin is used to treat human invasive bladder cancer, but has been disappointing as a single agent for the treatment for canine TCC. Response rates have been < 25%, with median survival times of 6 months or less. When single-agent cisplatin was compared to the combination of cisplatin and piroxicam, none of the dogs receiving cisplatin alone experienced remission, while ten of 14 dogs receiving the combination protocol responded. Unfortunately, renal toxicity was frequent (12/14 dogs; 87%) and dose limiting in the combination protocol group. Until dosage modifications or substitution of other NSAIDs are found to result in a safe and effective combination protocol, the author does not recommend routine use of cisplatin and NSAIDs together in clinical practice for treatment of TCC.
In a prospective clinical trial, the combination of carboplatin and piroxicam provided five partial remissions in 13 dogs and did not cause nephrotoxicity.While this 38% remission rate compared favorably to that of dogs treated with carboplatin alone, the median survival time of dogs treated with the combination (93 days) was not better than what has been achieved with either single-agent carboplatin (132 days) or piroxicam (180 days).
The synthetic anthracycline, mitoxantrone, in combination with piroxicam is currently the protocol the author utilizes for first-line therapy of canine TCC. Mitoxantrone (5 mg/m2 IV) is administered every 3 weeks for four treatments and piroxicam (0.3 mg/kg PO) is given daily. In a prospective multi-institutional study, our initial response rate was 35%, with subjective improvement in ¾ of all patients and a median survival time of 350 days. When considering this protocol, one must ensure that patients have normal renal function prior to treatment. Monitoring for GI and renal side effects is necessary, although our rate of toxicity was less than 15%.
Radiation therapy is a reasonable treatment option in the palliative or adjuvant setting for select TCC cases. While intraoperative radiation therapy has provided promising results, it is a technically challenging alternative that requires facilities and personnel adept at coordinating the surgical and radiation treatments during one anesthetic event. Initial results of experience with external beam radiation therapy and chemotherapy for canine TCC suggest that relief of symptoms may be superior to that achieved with chemotherapy alone, although overall survival times have been similar.
Canine bladder cancer presents veterinarians with treatment challenges due to its invasive nature and likelihood of metastasis. An understanding and appropriate utilization of available diagnostic tools is necessary for early detection of canine TCC. In the setting of early detection, many options are available to provide relief of symptoms and prolongation of good quality of life for dogs with bladder cancer.
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2. Chun R, Knapp DW, Widmer WR, et al. Phase II clinical trial of carboplatin in canine transitional cell carcinoma of the urinary bladder. J Vet Intern Med 1997;11(5):279-283.
3. Chun R, Knapp DW, Widmer WR, et al. Cisplatin treatment of transitional cell carcinoma of the urinary bladder in dogs: 18 cases (1983-1993). J Am Vet Med Assoc 1996;209(9):1588-1591.
4. Helfand SC, Hamilton TA, Hungerford LL, et al. Comparison of three treatments for transitional cell carcinoma of the bladder in the dog. J Am Anim Hosp Assoc 1994;30:270-275.
5. Henry CJ. Management of transitional cell carcinoma. Vet Clinics of North America Small Anim Prac 2003;33:597-613.
6. Henry CJ, Tyler JW, McEntee MC, et al. Evaluation of a bladder tumor antigen test as a screening test for transitional cell carcinoma of the lower urinary tract in dogs. Am J Vet Research 2003;64(8):1017-20.
7. Henry CJ, McCaw DL, Turnquist SE, et al. Clinical evaluation of mitoxantrone and piroxicam in a canine model of human invasive urinary bladder carcinoma. Clinical Cancer Research 2003;9:906-911.
8. Knapp DW: Tumors of the urinary system. In Withrow SJ, MacEwen EG (eds): Small Animal Clinical Oncology, ed 3. Philadelphia, WB Saunders, 2001:490-499.
9. Knapp DW, Glickman NW, DeNicola DB, et al. Naturally-occurring canine transitional cell carcinoma of the urinary bladder. A relevant model of human invasive bladder cancer. Urol Oncol 2000;5:47-59.
10. Knapp DW, Glickman NW, Widmer WR, et al. Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. Cancer Chemother Pharmacol 2000;46(3):221-226.
11. Knapp DW, Richardson RC, Chan TCK, et al. Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder. J Vet Intern Med 1994;8(4):273-278.
12. Moore AS, Cardona A, Shapiro W, et al. Cisplatin (cisdiaminedichloroplatinum) for treatment of transitional cell carcinoma of the urinary bladder or urethra. A retrospective study of 15 dogs. J Vet Intern Med 1990;4(3):148-152.
13. Norris AM, Laing EJ, Valli VEO, et al. Canine bladder and urethral tumors: a retrospective study of 115 cases (1980-1985) J Vet Intern Med 1992;6(3):145-153.
14. Nyland TG, Wallack ST, Wisner ER. Needle-tract implantation following US-guided fine-needle aspiration biopsy of transitional cell carcinoma of the bladder, urethra, and prostate. Vet Radiol & Ultrasound 2002;43(1):50-53.
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16. Stone EA, George TF, Gilson SE, et al. Partial cystectomy for urinary bladder neoplasia: surgical technique and outcome in 11 dogs. J Sm Anim Pract 1996;37(10):480-485.
17. Stone EA, Withrow SJ, Page RL, et al. Ureterocolonic anastamosis in ten dogs with transitional cell carcinoma. Vet Surgery 1988;17(3):147-153.
18. Walker M, Breider M: Intraoperative radiotherapy of canine bladder cancer. Vet Radiol 1987;28:200-204.
19. Withrow SJ, Gillette EL, Hoopes PJ, et al. Intraoperative irradiation of 16 spontaneously occurring canine neoplasms. Vet Surgery 1989;18(1):7-11.
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Original Doc: Canine Bladder Cancer C Henry (copy).doc
Bladder Stones - Where Do They Come From? What Can You Do?
By Joanne M. Orth, Ph.D.
Bladder stones (uroliths) occur in dogs when crystals form in the urine and these crystals "grow" within the bladder to a size where they irritate the bladder lining or, even worse, cause partial or complete obstruction of the urethra, the channel that leads from the bladder to the outside world. While no dog owner would consider by-passing the vet in dealing with a problem like bladder stones, it can be important for the owner to have a general understanding of the dog's condition since this can directly affect the success of the treatment In this article, I'll describe what types of symptoms can occur when bladder stones are present, I'll provide some background on what can cause stones to form, and, in general terms, what treatments are available.
The symptoms of bladder stones are really not different from those associated with a bladder infection, or cystitis, and this condition can in fact be a cause of stones, as described below. Your dog may begin to urinate frequently, or have accidents in the house, and you may see some evidence of straining during urination and possibly see blood in the urine. In an extreme case, where some obstruction has taken place, you will see the dog strain for some time and only a little urine will appear. In all of these cases, a trip to the vet is warranted; if you can obtain a urine specimen to take along, all the better. With females, this can be done pretty easily by slipping something flat like a clean saucer under the bitch while she is urinating. With males, it is easier to let the vet obtain the sample by slipping a canula directly into the bladder, which can also be done with females; any skilled vet should be able to do this with either sex. A bonus of this approach is that the sample will be "sterile", that is, taken directly from the bladder without contamination by the outside environment. This sample is the first step in diagnosis, because urinanalysis can provide information about any bacteria that are present, whether blood or crystals are being excreted, the pH of the urine, etc. The ultimate diagnosis of stones can be made with an X-ray, since stones are radio-opaque and will therefore be visible on the film. The vet can also get information from the level of bacteria and the amount of blood in the urine because stones can be a constant source of irritation to the bladder lining and result in significant bleeding within the bladder. However, a bladder infection can be the cause of stones or can result from the presence of stones that formed for another reason and caused chronic bladder irritation. As a result, identifying the presence and cause of bladder stones can be tricky and it can help if one has some understanding of what factors lead to their formation.
First, it's important to realize that the pH of urine is generally low, somewhere around 5-6; this means that the urine is normally quite acid. The most common problem that leads to bladder stones is any condition that results in a rise in urinary pH, that is, makes urine more alkaline than normal. A bladder infection, or cystitis, is a common cause of alkaline urine, because enzymes released by the bacteria cause the urinary pH to go up. Moreover, since our pets can't tell us about the early symptoms, we usually don't know that such a condition exists until it's been there for awhile. In normally acidic urine, salts that are being excreted by the kidney like phosphates and urates are soluble and pass harmlessly out; however, in alkaline urine these become insoluble and crystallize out. When concentrations of these salts are high enough in the urine, stones will begin to form. The most common type of stone is called a "struvite" stone; these stones are made up of a complex form of magnesium, ammonium and phosphate, and possibly calcium, and are sometimes called "super phosphate" or "triple phosphate" crystals. Other types that form in alkaline urine are either urate-based or composed of the amino acid cystine. These types of stones can be dissolved, over time, if the underlying cause of the alkaline urine is treated and the urine becomes acid again. For these stones, the problem can be a urinary tract infection, as already described, or something more unusual and harder to diagnose, like a genetic defect in kidney function (cystine stones) or liver function (urate stones) or a dietary problem where the intake of calcium is too high (lots of milk products, or eating lots of bones, or feeding "puppy" chow in an adult). However, there are also rarer types of stones which can occur even in urine that is acid. An example of these is oxalate stones, consisting of calcium, magnesium, or ammonium oxalate. The cause of this type of stone is less well understood but many green vegetables, like spinach or broccoli, are very high in oxalates, and ingestion of lots of veggies, or maybe grass, could be a cause of oxalate stones. Also, certain molds that exist in water excrete high levels of oxalate, so a water bowl that isn't cleaned frequently enough to discourage molds from growing might contribute to this problem. As you can see from this very general description, there can be many underlying problems that cause bladder stones, so it's important to know, whenever possible, the makeup of the stone. Sometimes, the owner can actually retrieve a stone when it is passed in urine, if it's big enough and the timing is "just right". Or, if surgery is necessary (see below) the vet will save a stone for analysis. Finally, even if stones are removed or dissolved, it's important to follow-up by checking the dog sometime later for normal urine, to be sure that the underlying cause has been identified and dealt with in treatment.
The quickest and most direct method of treating bladder stones is surgical removal. However, this involves general anesthesia and abdominal surgery so, although this surgery is not an uncommon procedure and well within the skills of a good vet, it is a major trauma to the dog. For this reason, if the symptoms are not too severe and if the urine is alkaline, many vets will recommend "medical" treatment, that is, taking steps to acidify the urine and attempting in this way to dissolve the stones. If an infection if present, one would obviously begin antibiotic therapy, with a broad spectrum antibiotic if a culture has not been performed to identify the bacteria. If there isn't a quick response (3-5 days), a culture might be advisable so a more appropriate antibiotic can be started. Drinking lots of water can also help since this will increase urinary volume and help to "flush" out the stones. Adding just a little salt to a dog's diet can increase the intake of water and accomplish this. The dog will usually be placed on a special calculolytic diet like Hill's S/D which, if effective, usually takes about 2 months to dissolve the stones. Once these are no longer present, it is important to insure that the urine has also returned to normal, that is, that it is acidic. Again, whether this will occur depends largely on what caused the stones in the first place. In some cases, a "metabolic" problem may exist and the vet may recommend a special diet like Hill's C/D, which has a mineral composition that helps keep the urine acidic. However, even on this diet it is important to check the urine to be sure the pH is acid since, from my own personal experience, this is not effective for all dogs. In such a case, a direct additive to food such as "Uroeze" or "Methigel" twice a day may solve the problem. In the rare case where stones formed in acid urine or were of a type indicating another organ is involved, the vet will recommend another treatment to deal with the cause, like a diet change, etc. With the right treatment and some owner-delivered tender loving care, there's every reason to expect a life of normal health and length for a dog afflicted with bladder stones.
Original Doc: bstones.doc
Gallbladder Disease and Scotties
by Ilene Stewart (and Pete) - San Francisco Bay STC
Source:San Francisco Bay STCA Newsletter, The Medicine Cabinet column. Date/Issue unknown.
Pete [Am/Can SKC Ch Substantial Reward] was very ill 5 years ago. Symptoms: High fever (105), vomiting, and lethargy. When a Vet sees a very ill dog, first the symptoms are alleviated to help the dog, then look for the cause when the dog is stabilized. Pete was placed on IV both for dehydration and to administer antibiotics. His blood test revealed slightly elevated alkaline phosphatase and SGPT. This seemed to indicate a liver infection. Pete does not have vWD or Cushings. When Pete felt better, he came home with a supply of antibiotics. He seemed to recover with no further problem. He did well until 1996.
May '96: Same symptoms, same treatment, liver values slightly more abnormal than the first episode. He recovered, did well but got sick again in July '96! We were very concerned, liver values were even higher but not alarmingly so. Our Vet got him through the crisis, put him on a low fat diet and said that if it happened again we should consider a liver biopsy. She suspected low grade hepatitis. We'd taken him to emergency_rooms (dogs always fall ill in the middle of the night), the Vet there suspected prostatitis but this diagnosis was completely wrong. We learned that Scottie boys have large prostate glands! I'd seen a post about two Scots with gallbladder disease on the intemet, so mentioned this to my Vet. She didn't think Pete had that problem as it is rare in dogs to begin with, plus according to the laboratory, his cholesterol level was normal.
Pete was very ill again in September '96. Off to the Vet at the first sign of illness, his fever so high that his eyes were unfocused and rolling. I was terrified we might lose him. While he was at the Vet's on IV, I asked for help on the internet, and a wonderful lady named Heather Franklyn, from British Columbia, sent me a post describing gallbladder disorder in Scotties. As a gallbladder victim myself, (mine has been gone since '89 and good riddance!) I had my Vet read it. She wasn't convinced, but referred Pete to a specialist for an ultrasound.
This is what Heather wrote:
"In May 1995 Simon [her Scottie] was suddenly very sick and spent 3 days on IV. His alkaline phosphatase and SGPT levels were off the scale. Test for Cushing's negative. An ultrasound revealed the gallbladder filled with gunk. Treatment: Amoxicillin for several weeks followed by another ultrasound. This ultrasound showed less gunk but the gallbladder was still far from normal.
Our breeder had an identical problem with one of her older bitches; her Vet had consulted a specialist in Illinois and received a most interesting letter from which I quote: '...We have found a consistent problem of primary gallbladder disease in the Scottish Terrier with ultrasound disclosure of a dilated gallbladder sac distended with sludge, inspissated bile, and/or oven stone formation. Majority of the Scottie patients presented to our facility for episodic weakness, fever of unknown origin, lethargy, regurgitation and/or vomitation, and partial anorexia, coupled with laboratory parameters of cholestasis and mild hypercholesterolemia, have been found to have the aforementioned gallbladder disorder...'''
When 'Would He' [another Scottie] became sick I asked Jane [his owner] what her Vet had prescribed for him and this is what she replied: 'First, tell your Vet to call Dr. James McConnell at Southpaws Veterinary Referral Center at 703/569-0300. He saved Would He's life last month. They did an ultrasound and needle liver biopsy to determine the type of liver/bile duct/gallbladder infection Would He had. He is [now] on Baytril (20 mg twice a day) and Acugall (75 mg once a day) and doing great!"
I'm sorry not to know the name of this Illinois specialist, but note the letter mentions "a consistent problem of primary gallbladder disease in the Scottish Terrier..." "Majority of Scottie patients..." This means more than just an occasional Scottie has suffered from this condition. This is something we need to be aware of. Pete's symptoms were identical with what the Illinois Vet described. He had the elevated alk. Phos. and SGPT, fever of unknown origin, lethargy, uncontrollable vomiting, and anorexia. Early blood work didn't reveal high cholesterol but later blood work did. Still ill, Pete got his ultrasound from Dr. Stewart at Berkeley Dog & Cat Hospital. Some of the best veterinary specialists in the Bay Area work there. This ultrasound seemed to reveal a contracted g.b. with sludge in it. I was not concerned about the contracture at the time because my own ultrasound revealed the same when I had my g.b. disease! It contracts after passing a stone. At the time I didn't realize just what that contracted-looking appearance meant for Pete. More blood work revealed the liver values were higher, and now extremely high cholesterol. A debate followed: surgery or medication? I was terrified of surgery, as Pete was 8 years old. But if the medication failed, he'd have another attack. Those were so nasty I was afraid he'd die. The specialists and my own vet recommended surgery, so we agreed.
Dr. Stewart (no relation) was the internist, Dr. Alexander was the surgeon. Dr. A. said she couldn't promise this would help Pete, but it was her best opinion. No abnormalities of pancreas, liver or ducts were observed on ultrasound. But Dr. A. also said that once she was doing the surgery, she would observe, then do a liver biopsy to be sure his troubles were in fact gallbladder-caused and not some nasty surprise waiting in his liver. By then, he was over the attack and making up to the Vets at Berkeley Dog & Cat, eating a little, and charming the whole staff there. Yes, they kept him there in order to observe him. I felt he was in the safest of hands.
Dr. Stewart planned to put him on Actigall following; the surgery. Pete wouldn't have a gallbladder but Dr. S. felt Actigall would keep his bile ducts open and avoid bile backing up to his liver, causing inflammation. Dr. Alexander said that Actigall works to keep the ducts clear, not allowing bile to thicken and back up. It turned out we didn't need to do this. Neither Vet actually said this, but I got the impression that bile secreted by the liver, which is stored by the gallbladder backs up to the liver in cases of g.b. disease. It blocks the ducts, which in turn causes the elevated liver values that are.seen. The bile turns to sludge and sits there harboring bacteria and a chronic infection. This in turn causes pain, fever, and illness. Dr. A. explained that dogs with this disease don't usually get stones as people do, but develop sludge in the gallbladder blocking up everything and causing attacks.
Gary and I spent surgery day at the hospital. It was delayed a while due to emergencies, but finally it was done, and Dr. Alexander told us how it went. To her surprise-, she opened Pete's abdomen to discover dried bile sticking to his insides and a g,.b. that had ruptured long ago, probably in May when he was first sick! The contracted g.b. shown on the ultrasound was only what was left of the organ. She removed his remaining g.b., closed the duct leading to it, cultured the infection to know the correct antibiotic, removed the dried up bile and and checked to see if his common bile duct was working properly. It was was working as it should. A ruptured g.b. is normally a killer, human or canine..., bile spills into the abdomen, causing peritonitis and death. How did Pete manage to survive? Why was he fine between attacks? When we were told his g.b. had ruptured, we were absolutely horrifyed by what our little guy had been through. He never complained or showed any indication of trouble except when the infection flared up!
They sent us home, and we returned to see Pete the next day. Two technicians brought him in on a wheeled cart, holding his IV pole. They put a blanket on a table and placed him on it. He'd had demerol and was out of it but he knew us...the tip of his tail wagged and when each of us leaned over to talk to him, we each got a little kiss. All I could think was that it was a miracle he was alive, and that he is most certainly the world's toughest dog. His eyes were blank, he was well sedated to ease his pain: When I had my own surgery they gave me demerol and it certainly works...no pain, no anxiety. I hope it was the same for Pete! He received superb care. All Weekend, Pete was monitored every hour, around the clock. He was given demerol for pain, and kept on IV. I was given a copy of the notes taken by the Vet techs on their rounds. They covered everything from how much fluid went in, how much came out, if he was awake, asleep, temperature taken, pulse, coloring of his gums, and his attitude. If he seemed uncomfortable, they gave him demerol. As the weekend progressed, notes like, "resting comfortably, friendly," began to appear, but the note that brought tears to my eyes had just 2 words: "SWEET DOG."
When Pete's glb. ruptured, it had been full of sludge which had gummed up the duct leading in from his liver. The duct had nearly closed up by itself. Meanwhile, the rupture leaked bile inside poor Pete, causing peritonitis (infection of the peritoneum, the lining of the inside of the body, which if uncontrolled causes death). The peritonitis made Pete sick; I'd rush him to my Vet who immediately put him on strong antibiotics. This kept the infection in check for about a 2 month period, then it would return. We'd blamed his then-undiagnosed illness on everything from eating plum leaves to food allergy! Pete's symptoms made my local Vet think of liver-infection rather than g.b. disease. She x-rayed his abdomen but no abnormalities showed. If I hadn't seen Heather's post, we might never have caught it in time. You can't x-ray a gallbladder you have to see it on ultrasound. I am still amazed that our tough little diehard made it through a ruptured gallbladder and extensive surgery.
Pete was at Berkeley for 4 days. When we brought him home, he had stitches running from his private parts to his rib cage. We were told to keep him quiet, not to stress him, no stairs, no jumping. Naturally the first thing he did was attempt to jump on the bed to sleep in his usual spot. I made him understand that I would pick him up and lift him to get down, and he was very cooperative. He weighed 17 3/4 lb. upon release from the hospital. In just two weeks he'd gained 3 lb., and after 3 months he was a new dog! When we brought him back to have his stitches removed we were treated to the sight of our quiet,- dignified dog acting like a silly butt-scooting puppy at the sight of his friend Dr. Alexander. He raced around her, tail wagging a mile a minute, butt in the air ...obviously delighted to see her. I swear he understood what she had done for him! He is now nearly 25 lb., active, playful, happy and healthy! Every Vet I've spoken to is amazed at his story. and most have never seen a dog with gall-bladder disease. 18 months later, he remains in good health, age 9 1/2, looking and behaving like a much younger dog. My local Vet calls him 'Mr. Indestructible'.
Many who knew about all this sent good wishes Pete's way. Without their prayers, I'm not sure where Pete would be. Special thanks to the internet community- who helped keep our spirits up. I'm grateful to them all! Everyone's Vet should see this article...it may save a Scottie s life. Gary and I credit Heather Franklyn with giving us the information that saved Pete'e life and the knowledge and skills of the Vets in Berkeley who knew what to do for Pete, sending home to us a healthy, happy dog. If your Scottie exhibits symptoms like Pete's, have a gallbladder disease check and ultrasound, too. Few survive what Pete lived through, so don't take chances with your Scottie's life and health. There is nothing we did 'wrong' that may have brought on Pete's illness, but because it can and docs occur in Scotties, be aware of it and watch for it if your Scot becomes ill. I'd like to be like Heather and know I've helped even one Scottie by making their people aware of this problem!