Gutsy Move: Solving Those Complex Gastrointestinal Cases Michael R. Lappin, DVM, PhD, DACVIM The Kenneth W. Smith Professor in Small Animal Clinical Veterinary Medicine College of Veterinary Medicine and Biomedical Sciences Colorado State University Fort Collins, Colorado Deborah S. Greco DVM, PhD, DACVIM Senior Research Scientist Nestle Purina PetCare Gastrointestinal disorders comprise a large part of veterinary practice. This article provides guidance on determining the cause and treatment of complex gastrointestinal (GI) disorders in small animals. Clinical Problem & Differentials Vomiting is forceful ejection of stomach and proximal duodenal contents through the mouth. It can be induced by vestibular, vagal, chemoreceptor trigger zone, or direct input to the emetic center. Regurgitation is passive ejection from the esophagus. Diarrhea is characterized by increased frequency, increased fluid content, or increased volume of defecation. Markedly increased frequency of defecation, small volume, tenesmus, urgency, hematochezia, and mucus are consistent with large bowel diarrhea. Slightly increased frequency, large volume, melena, steatorrhea, and polysystemic clinical signs are consistent with small bowel diarrhea. Mixed bowel diarrhea has a combination of these characteristics. Critical Updates on Canine & Feline Health 2014 NAVC/WVC Proceedings 1
Weight loss with an increased appetite has many fewer differentials (eg, diabetes mellitus in the dog, hyperthyroidism in the cat) than does weight loss with anorexia. TABLE 1 History Taking Tips for Gastrointestinal Disorders Localize the problem large bowel/small bowel diarrhea or vomiting/regurgitation. Be precise in determining the primary complaint. Ask open-ended questions. Don t ignore but don t pay too much attention to previous medical complaints or diagnoses. Pay attention to diet history and signalment! Don t lump all complaints into one diagnosis Ockhman s Razor. This mistake can result in premature exclusion of diagnoses. Do not be tricked by Common diseases occur commonly. Use electronic history forms that owners can fill out prior to the visit. Listen to the owner! Only he or she knows this animal s particular habits. Ask owners to describe the stool/vomitus in their own words; do not ask leading questions. Do not rush the owner. History An extremely important aspect of managing GI disorders is the history (Table 1). The owner should be prompted to provide a written history prior to the clinic visit or while in the reception area. Providing an online form may be helpful. Questions about the general health of the animal should make up the first part of the history, followed by specific questions directed at the presenting complaint. The presenting sign may be caused by a systemic disorder; therefore, a thorough history of all body systems may be necessary. Don t forget to ask about polydipsia (PD), polyuria (PU), coughing, sneezing, weight loss, and weight gain as well as the duration and nature of the problem. In the case of weight loss, determine whether the patient has an increased, decreased, or normal appetite. Weight loss with an increased appetite has many fewer differentials (eg, diabetes mellitus in the dog, hyperthyroidism in the cat) than does weight loss with anorexia. The dietary history is critical. Ask about the type of food that is being fed: homemade (obtain complete list of ingredients), raw, commercial cooked (primarily dry or a mixture of dry and canned), brand. How long has the food been used? When was the diet last changed? How much is the animal eating (ad libitum or restricted) and how is the food being measured (weight vs volume)? How frequently is the diet changed? How many times per day is the animal fed and by whom (obtain ages of family members)? What are other pets fed? Does the animal have access to the outdoors? It is important to remember that many clients do not perceive treats and additives such as table food as part of the animal s diet and so may forget to mention them. Also, determining who in the household is responsible for feeding the animal is important as often the primary caregiver is surprised to find that another family member has been feeding the pet. Clients may also have preconceived notions about pet foods such as excluding ingredients (corn) because of allergies. It may also be difficult to obtain an accurate dietary history because clients are embarrassed to divulge exactly what and how much is being fed. Again, a questionnaire is often the best and most expedient way to obtain the dietary history. Physical Examination Observe the animal s posture and attitude. State of alertness may indicate metabolic problems. Animals with severe pancreatitis may assume the praying position in an effort to alleviate cranial abdominal pain. Generalized muscle weakness with GI signs is characteristic of hypoadrenocorticism. Salivation and lip smacking indicate nausea in dogs with gastric 2 Gutsy Move: Solving Those Complex Gastrointestinal Cases
or esophageal foreign bodies or hepatic encephalopathy in cats. A distended abdomen may indicate ascites, a large abdominal tumor, or gas accumulation indicative of gastric dilatation/volvulus. A thorough general physical examination is necessary to determine systemic signs that may indicate that the GI problem is secondary rather than primary. The animal s head and mouth should be carefully examined. In a vomiting cat, visualize the tongue at its root to rule out string foreign bodies. When anorexia is present, loss of senses (sight or smell), dental disease, or temporal muscle atrophy (myositis) may indicate a secondary cause (pseudoanorexia). Palpation of the neck and throat may reveal foreign bodies or pain from underlying disease in the case of dysphagia or regurgitation. The abdomen should be carefully palpated. Identify each organ within the abdominal cavity, assessing size (is the liver protruding past the ribs?), symmetry, and texture. The intestinal lymph nodes may be palpable in the mesentery if enlarged. Intussusception can be felt as a large, firm tubular section of bowel. Many foreign bodies are readily palpable depending on their location within the intestine. Lift the forelegs to palpate cranially. No physical examination is complete without a 360-degree rectal examination to detect tumors, thickening, or foreign material. Pay particular attention to the anal sacs at the 4 o clock and 8 o clock positions to rule out impaction or tumors; expression of the anal sacs will help to determine the location of a mass if detected. In addition, this step is an excellent opportunity to obtain a stool sample for fecal examination. Differential Diagnosis GI signs can result from primary or secondary diseases of the GI system (Table 2). Secondary GI diseases are generally those of the kidney, liver, pancreas (pancreatitis or exocrine pancreatic insufficiency [mainly dogs]), endocrine system (hypoadrenocorticism, diabetic ketoacidosis, hyperthyroidism [mainly cats]), or central nervous system. Differential diagnoses for primary GI diseases are often grouped into obstruction (masses, foreign body, and intussusception), dietary intolerance, drugs/toxins (garbage gut), inflammatory gastric and bowel diseases, neoplasia, infectious diseases, and parasites. The primary bacteria associated with GI disease in dogs and cats include Salmonella spp, Campylobacter spp, Clostridium perfringens, and Helicobacter spp. Conditions include bacterial overgrowth syndrome, bacterial peritonitis, and bacterial cholangiohepatitis (Table 3). The primary viral agents include parvoviruses, coronaviruses, canine distemper virus, feline leukemia virus, and feline immunodeficiency virus No physical examination is complete without a 360-degree rectal examination to detect tumors, thickening, or foreign material. this step is an excellent opportunity to obtain a stool sample for fecal examination. TABLE 2 Localizing Gastrointestinal Disease Clinical Sign Excessive salivation Oral ulceration Halitosis Borborygmus Guarded abdomen Disease Hepatic encephalopathy (cat), foreign body(dog) Chronic renal failure, immunocompromise (FIV, FeLV) Foreign body, chronic small bowel problem, periodontitis Abnormal carbohydrate/protein fermentation (colitis, inflammatory bowel disease, antibiotic responsive diarrhea) Pain from obstruction: Left cranial = hepatic problem, dorsal pain = cecum, dorsocranial = intussusception, right cranial = pancreatitis Critical Updates on Canine & Feline Health 2014 NAVC/WVC Proceedings 3
TABLE 3 Common Pathogens Associated with Gastrointestinal Disease Organism Type Common problems/sites/syndromes Campylobacter spp Bacterium Mixed bowel diarrhea with or without vomiting Clostridium perfringens Bacterium Large bowel diarrhea, polycythemia, occasionally vomiting Histoplasma capsulatum Fungus Large bowel diarrhea, weight loss, aplastic anemia in cats, dyspnea, polysystemic infection Leptospira spp Bacterium Fever, vomiting (nephritis, hepatitis), thrombocytopenia Neorickettsia helminthoeca (dogs) Rickettsia Mixed bowel diarrhea with or without vomiting Salmonella spp Bacterium Mixed bowel diarrhea with or without vomiting While the CBC generally does not lead to a specific diagnosis, the presence of eosinophilia makes inflammatory bowel diseases and parasitism more likely. TABLE 4 Common CBC Findings with Gastrointestinal Disease High packed cell volume: Severe dehydration Low packed cell volume: Vitamin B 12 deficiency, bleeding tumor, ulcers, epilepsy Hypochromic microcytic anemia: Chronic GI bleeding Leukopenia: Parvovirus infection, panleukopenia Lymphopenia: Lymphangiectasia Inflammatory leukogram: Infectious diarrhea, pancreatitis The primary nematodes are Ancylostoma/ Uncinaria, Trichuris vulpis (dogs), Strongyloides, Dirofilaria immitis (vomiting in cats), Toxocara spp, Toxascaris leonina, Ollulanus tricuspis (cats), and Physaloptera spp. Common enteric protozoa include Giardia spp, Cystoisospora spp, Cryptosporidium spp, and Tritrichomonas foetus. The cestodes Taenia, Dipylidium, and Echinococcus generally cause subclinical infection. Diagnostic Plan Occasionally, otherwise healthy dogs or cats with acute vomiting and normal physical examination findings can be handled conservatively by withholding food for 24 hours followed by introduction of a bland food for several days. For all animals with diarrhea with no apparent cause on physical examination, perform a fecal flotation, fecal wet mount examination, complete blood cell count (CBC; Table 4), and rectal cytology if diarrhea is present. While the CBC generally does not lead to a specific diagnosis, the presence of eosinophilia makes inflammatory bowel diseases and parasitism more likely. Perform acid-fast staining of a fecal smear or immunofluorescence antibody staining (Merifluor Giardia/Cryptosporidium, meridianbioscience.com) on all animals with diarrhea to assess for the presence of Cryptosporidium spp oocysts. A wet mount examination may aid in identifying motile trophozoites of Tritrichomonas and Giardia; these agents can be seen on stained smears as well. If neutrophils or spirochetes are evident on rectal cytology, fecal culture (or polymerase chain reaction) for Salmonella spp and Campylobacter spp may be indicated. If spore-forming rods consistent with Clostridium perfringens are present in large numbers, fecal enterotoxin assay with or without polymerase chain reaction (PCR) assay for enterotoxin can be performed to 4 Gutsy Move: Solving Those Complex Gastrointestinal Cases
TABLE 5 Common Serum Chemistry Profile Changes with Gastrointestinal Disorders Increased BUN/creatinine: Hypoadrenocorticism, renal disease, whipworms Decreased Na:K ratio: Hypoadrenocorticism, whipworms, third spacing* Increased liver enzymes: Liver disease, hyperthyroidism, pancreatitis, gallbladder disease Decreased TP: Protein-losing enteropathy Decreased albumin: Protein-losing enteropathy, protein-losing nephropathy, hypoadrenocorticism Decreased cholesterol: Protein-losing enteropathy Decreased Ca and Mg: Protein-losing enteropathy *Third spacing refers to accumulation of fluid in body cavities or the intestinal tract and can lead to hyponatremia and hyperkalemia, hence a decreased Na:K ratio. centrations in the serum and effusion; if pancreatitis is occurring, the effusion lipase is usually greater than that of the serum. Fecal fat assessment with Sudan IV stain can help confirm malabsorption/maldigestion but is not specific for a single disease. If the mean cell volume is low, chronic iron deficiency should be suspected; this occurs almost exclusively with GI diseases. A serum iron panel can be used to confirm iron deficiency. Panhypoproteinemia is often associated with GI disease. Measurement of vitamin B 12, folate, and trypsin-like immunoreactivity (TLI) are also used to screen animals for small intestinal bacterial overgrowth syndrome, inflammatory bowel disease, and exocrine pancreatic insufficiency (TLI). Most commonly used imaging techniques include radiographs, contrast radiographs, and ultrasound. Abdominal radiographs, sometimes with contrast agent, can be used in dogs or cats to support palpation findings. Perform endoscopy or exploratory laparotomy based on physical examination and abdominal radiographic findings. Ultrasonography of the intestinal tract can be hard to interpret and is operator dependent. Diagnosis of gastric foreign bodies and diffuse inflammatory diseases can be made by endoscopy. Endoscopically obtained biopsies are small; take at least 8 to 10 biopsies from stomach, duodenum, colon, and ileum if possible. Even if a lesion is present, endoscopically obtained biopsies can be falsely negative, requiring full thickness biopsies. Gastric biopsies should be placed on urea slants to assess for urease, which is found in the cell wall of Helicobacter spp. Full thickness biopsies can be made using laparoscopy to pull appropriate loops of bowel to the abhelp confirm the diagnosis. However, these tests can be positive in healthy animals as well, so they have less than 100% predictive value. In one study of cats with diarrhea, amplification of the C perfringens enterotoxin gene by PCR was statistically associated with diarrhea. 1 A biochemical profile, urinalysis, FeLV antigen assay (cats), and FIV antibody assay (cats) are indicated if secondary GI diseases are on the differential list or if dehydration is present (Table 5). Perform a total T 4 on all cats with vomiting or small bowel diarrhea that are older than 5 years. While amylase and lipase are poor predictors of pancreatitis in cats, a pancreatic lipase immunoreactivity assay has now been validated. It can be used to diagnose pancreatitis (increased) in dogs and cats. The positive predictive value is better for acute pancreatitis than chronic pancreatitis. The negative predictive value (negative test correlates well with a lack of pancreatitis) appears to be high. If an animal with suspected pancreatitis has abdominal effusion, assay lipase con- If an animal with suspected pancreatitis has abdominal effusion, assay lipase concentrations in the serum and effusion; if pancreatitis is occurring, the effusion lipase is usually greater than that of the serum. Critical Updates on Canine & Feline Health 2014 NAVC/WVC Proceedings 5
TABLE 6 Common Drugs for Management of Idiopathic Inflammatory Bowel Disease Generic drug name Common dosage Comments Amoxicillin 22 mg/kg q24h 5 d PO C perfringens, bacterial overgrowth, Salmonella A metronidazole challenge is often tried because of efficacy against Giardia, some GI bacteria (anaerobes, Clostridium perfringens, Helicobacter spp), and a potential antiinflammatory effect. However, do not use metronidazole long term because it is a potential cumulative neurotoxin. Azathioprine 1-2 mg/kg q24h 5 d PO; then q48h Inflammatory bowel disease Dogs only Azithromycin 7-15 mg/kg q12h 5-7 d PO C parvum, T gondii Budesonide 0.5-3 mg/animal q12-24h PO Inflammatory bowel disease Clarithromycin 5-10 mg/kg q12h 7 d PO T gondii, Helicobacter spp Chlorambucil 2 mg/cat q48-72h PO Cats only Cyclosporine 5 mg/kg q12-24h PO Dogs or cats Fenbendazole 50 mg/kg q24h 3-7 d PO Nematodes, Giardia, Taenia spp Metronidazole 10-25 mg/kg q12h 7 d PO Giardia, Entamoeba histolytica, bacterial overgrowth, C perfringens Methylprednisolone acetate 7.5-20 mg/cat q3-4wk SC Cats only Ponazuril 20 mg/kg q24h 2 d PO Dogs or cats Prednisone 0.5-4 mg/kg (divided) q12h PO Dogs Prednisolone 0.5-4 mg/kg (divided) q12h PO Dogs or cats Pyrantel pamoate 5-20 mg/kg q14-21d PO Nematodes Sulfadimethoxine 50-60 mg/kg q24h 5-20 d PO Cystoisospora spp Trimethoprim-sulfa 15 mg/kg q12h 5 d PO Cystoisospora spp, T gondii Tylosin 10-40 mg/kg q8-12h 21 d PO Bacterial overgrowth, C perfringens, Cryptosporidium spp dominal wall to perform a key hole incision for sample procurement. Therapy To exclude nematodes, a therapeutic trial with pyrantel or fenbendazole should be tried. Pyrantel may be more effective for the stomach worms, Ollulanus and Physaloptera. Fenbendazole has the advantage of being effective for Trichuris and Giardia. A metronidazole challenge is often tried because of efficacy against Giardia, some GI bacteria (anaerobes, Clostridium perfringens, Helicobacter spp), and a potential antiinflammatory effect. However, do not use metronidazole long term because it is a potential cumulative neurotoxin. A tylosin challenge should be considered, especially if bacterial overgrowth or infection with Campylobacter spp or Cryptosporidium spp is possible. Some animals have dietary intolerance and simply changing food may resolve vomiting and diarrhea. In fact, recent studies have shown that as many as 60% of animals with food intolerance will respond to dietary change. 2 Some causes of diarrhea will respond to the administration of a probiotic. Enterococcus 6 Gutsy Move: Solving Those Complex Gastrointestinal Cases
faecium SF68 (FortiFlora, purinaveterinarydiets.com/veterinarian/product/fortiflora CanineProbioticNutritionalSupplements.aspx) has been shown to have immune-enhancing properties. 3,4 A recent study showed that administration of Enterococcus faecium SF68 lessened acute diarrhea in shelter cats. 5 Another probiotic was successful in the management of chronic, nonspecific diarrhea in clientowned cats. 6 In another study, it was shown that Enterococcus faecium SF68 could be administered concurrently with metronidazole and that the combination was superior to empirical use of metronidazole alone. 7 Patients that have true dietary hypersensitivity may respond to a novel antigen or hydrolyzed diet. The choice of diet (novel protein vs hydrolyzed) depends on the age of the animal (some hydrolyzed diets are inappropriate for puppies), the owner s preference, and palatability. The optimal diet is the one that the animal will eat and that works. Dietary effects may take several weeks to maximize, so concurrent antiinflammatory agents can be used to achieve early remission. Some veterinarians recommend budesonide as the firstchoice glucocorticoid as it may have reduced systemic side effects compared with other glucocorticoids. However, as budesonide is absorbed, it can have systemic side effects and the adrenal pituitary axis can still be suppressed. In cases resistant to budesonide or if the owner cannot afford the drug, prednisone in dogs and prednisolone in cats are options. Most cats and dogs can tolerate prednisolone or prednisone at 0.5 mg/kg q48h, so this is the ultimate target dose. In the case of idiopathic inflammatory bowel disease, treatment can include antibiotics, glucocorticoids, and other antiinflammatory agents (Table 6). Treatment is long term as the disease is chronic. While oral drugs can be used in dogs, some cats require methylprednisolone acetate because it is impossible for the owners to treat orally. Also in cats, different glucocorticoids (dexamethasone or triamcinolone) are sometimes more effective due to resistance to prednisolone. Other than the risk of developing diabetes mellitus, cats are fairly resistant to the development of glucocorticoid-induced side effects. Try a second glucocorticoid in resistant feline cases before cytotoxic drugs. Cats are often also more resistant to glucocorticoid therapy than dogs and so may require higher doses for maintenance. In such cases, chlorambucil or cyclosporine can be used as an additive drug. Chlorambucil should be used if small cell lymphoma is on the differential list. Cyclosporine can be effective at lower than published doses in some cats; start with 2.5 mg/kg daily PO and treat to effect. Maximum response is usually recognized in 4 to 6 weeks. In dogs resistant to glucocorticoid therapy, use azathioprine followed by cyclosporine (if azathioprine is ineffective). Weekly administration of vitamin B 12 injections is indicated for several weeks until malabsorption resolves. Use of omega 3/omega 6 fatty acid supplements may allow for lower doses of glucocorticoids. After 4 to 8 weeks of antiinflammatory therapy and a novel antigen diet, some animals can be maintained on the diet alone. References 1. Prevalence of common enteric pathogens in cats before and after placement in an animal shelter. (Poster). Gingrich EN, Scorza AV, Leutenegger CM, et al. ACVIM Annual Forum, 2010. 2. Pitfalls and progress in the diagnosis and management of canine inflammatory bowel disease. Simpson K, Jergens A. Vet Clin North Am Small Anim Pract 41:381-398, 2011. 3. Supplementation of food with Enterococcus faecium (SF68) stimulates immune functions in young dogs. Benyacoub J, Czarnecki-Maulden GL, Cavadini C, et al. J Nutrition 133:1158, 2003. 4. Effect of supplementation with Enterococcus faecium (SF68) on immune functions in cats. Veir JV, Knorr R, Cavadini C, et al. Vet Ther 8:229, 2007. 5. Effect of the probiotic Enterococcus faecium SF68 on presence of diarrhea in cats and dogs housed in an animal shelter. Bybee SN, Scorza AV, Lappin MR. J Vet Intern Med 25:856-860, 2011. 6. Open-label trial of a multi-strain synbiotic in cats with chronic diarrhea. Hart ML, Suchodolski JS, Steiner JM, Webb CB. J Feline Med Surg 14:240-245, 2012. 7. Evaluation of Enterococcus faecium SF68 supplementation with metronidazole for the treatment of Dietary effects may take several weeks to maximize, so concurrent antiinflammatory agents can be used to achieve early remission. Critical Updates on Canine & Feline Health 2014 NAVC/WVC Proceedings 7
non-specific diarrhea in dogs housed in animal shelters (poster). Fenimore A, Groshong L, Scorza V, et al. ACVIM Annual Forum, 2012. Suggested Reading Adherent and invasive Escherichia coli is associated with granulomatous colitis in boxer dogs. Simpson KW, Dogan B, Rishniw M, et al. Infect Immun 74:4778-4792, 2006. Bacterial enteritis in dogs and cats: Diagnosis, therapy, and zoonotic potential. Weese JS. Vet Clin North Am Small Anim Pract 41:287-309, 2011. Canine parvovirus type 2 vaccine protects against virulent challenge with type 2c virus. Spibey N, Greenwood NM, Sutton D, et al. Vet Microbiol 128:48-55, 2008. Characterisation of canine parvovirus strains isolated from cats with feline panleukopenia. Decaro N, Buonavoglia D, Desario C, et al. Res Vet Sci 89:275-278, 2010. Chronic enteropathies in dogs: Evaluation of risk factors for negative outcome. Allenspach K, Wieland B, Grone A, et al. Vet Intern Med 21:700-708, 2007. Common virus infections in cats, before and after being placed in shelters, with emphasis on feline enteric coronavirus. Pedersen NC, Sato R, Foley JE, et al. J Feline Med Surg 6:83-88, 2004. Companion animals symposium: Microbes and gastrointestinal health of dogs and cats. Suchodolski JS. J Anim Sci 89:1520-1530, 2011. Comparison of direct immunofluorescence, immunoassays, and fecal flotation for detection of Cryptosporidium spp. and Giardia spp. in naturally exposed cats in 4 northern California animal shelters. Mekaru SR, Marks SL, Felley AJ, et al. J Vet Intern Med 21:959-965, 2007. Comparison of direct immunofluorescence, modified acid fast staining, and enzyme immunoassay techniques for detection of Cryptosporidium spp. in naturally exposed kittens. Marks SL, Hanson TE, Melli AC. JAVMA 225:1549-1553, 2004. Cryptosporidiosis and giardiasis in dogs and cats: Veterinary and public health importance. Bowman DD, Lucio Forster A. Exp Parasitol 124:121-127, 2010. Diarrhea associated with Tritrichomonas in cats. Gookin JL, Breitschwerdt EB, et al. JAVMA 215:1450-1454, 1999. Effect of vaccination on parvovirus antigen testing in kittens. Patterson EV, Reese MJ, Tucker S, et al. JAVMA 230:359-363, 2007. Enteropathogenic bacteria in dogs and cats: Diagnosis, epidemiology, treatment, and control. Marks SL, Rankin SC, Byrne BA, Weese JS. J Vet Intern Med 25:1195-1208, 2011. Feline idiopathic inflammatory bowel disease: What we know and what remains to be unraveled. Jergens AE. J Feline Med Surg 14:445-458, 2012. Feline zoonoses guidelines from the American Association of Feline Practitioners. Brown RR, Elston TH, Evans L, et al. Compend Contin Educ Pract Vet 25:936-965, 2003. Idiopathic inflammatory bowel disease in cats. Rational treatment selection. Trepanier L. J Feline Med Surg 11:32-38, 2009. Idiopathic inflammatory bowel disease in dogs and cats: 84 cases (1987-1990). Jergens AE, Moore FM, Haynes JS, et al. JAVMA 201:1603-1608, 1992. Nutritional management of feline gastrointestinal diseases. Zoran DL. Topics Companion Anim Med 23:200-206, 2008. Outbreak of Salmonella typhimurium in cats and humans associated with infection in wild birds. Tauni MA, Osterlund A. J Small Anim Pract 41:339-341, 2000. Perceptions, practices, and consequences associated with foodborne pathogens and the feeding of raw meat to dogs. Lenz J, Joffe D, Kauffman M, et al. Can Vet J 50:637-643, 2009. The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease. Suchodolski JS, Markel ME, Garcia-Mazcorro JF, et al. Plos ONE 2012; 7:e51907. 8 Gutsy Move: Solving Those Complex Gastrointestinal Cases