What Does This Mean?

The small intestinal tract is a remarkable organ. It has to neutralize acid from the stomach, apply digestive enzymes, absorb and conduct away the microscopic nutrients, and move its contents from one end of our body to the other. There is also immunological reactivity, hormonal activity and response, and the matter of housing a variety of bacteria without allowing them to access the interior of our bodies.

Its layers act as both a barrier and gateway, plus it must have muscle strength for tone and motion. Proper function depends in part on the normal thickness of all the delicate layers.

Diseases of Infiltration

Disease can lead to an invasion of inappropriate cells into the layers of the intestine. This infiltration by abnormal cells creates thickening and puffiness, which hampers function. The thick intestine does not move its contents properly, which leads to food pooling and sludging. Pooling and sludging lead to the sensation of nausea and malaise. The thick intestine also cannot absorb nutrients properly, which leads to weight loss and diarrhea. Frequently, ulceration and bleeding occur as the membranes become unhealthy.

Dysbiosis

Bacterial populations become altered when the nutrients available to them changes in composition. In other words, what sort of bacteria live in the bowel depends on what nutrients are in abundance around them. Different nutrients promote different bacterial populations for better or worse. Abnormal nutrient absorption can lead to an overgrowth of bacteria or at least an alteration in the proportions of different populations of bacteria, creating a bad neighborhood in the bowel. Toxic bacterial products can be produced. Bacteria can over-power natural barriers, allowing them to crawl up the pancreatic duct or bile duct, creating inflammation in organs that are normally sterile (pancreas and liver).

Obviously, none of this is a good thing.

Fixing it Depends on Knowing the Nature of the Infiltration

There are two common diseases that involve infiltration: intestinal lymphoma and inflammatory bowel disease (IBD). Both diseases involve lymphocytes infiltrating the delicate bowel. In lymphoma, these are malignant cancerous lymphocytes. In the case of IBD, they are immunologically stimulated lymphocytes reacting inappropriately to an immunological trigger (such as a food or bacterial waste product).  A biopsy is necessary to distinguish these two diseases, and distinguishing the two conditions allows for the most effective treatment.

Treating Lymphoma
There are two forms of lymphoma: small cell and large cell. The small cell form is associated with a rapid and sustained response to therapy with remissions of one year or longer being common. The large cell form is nearly untreatable, with remissions being unreliable or short in duration. A biopsy will determine which type a cat has. Confirmation of lymphoma also allows for a more tailored protocol so as to maximize the quality of remission.

Treating Inflammatory Bowel Disease
IBD is an immune-mediated disease and treatment centers on suppressing the inappropriate immunological response so that the bowel can recover. Specific diets may be employed to minimize inappropriate reactions to food in long-term management. It is theoretically possible, eventually, to recover from this disease completely, though most patients need long-term medications to control the inflammation.

The potentially good news here is that because both conditions involve lymphocyte infiltration, there is a great deal of overlap in therapy, so it is possible to create a treatment plan that will cover both possibilities with a reasonable chance of success. This is not optimal but provides a route to inexpensive therapy.

Ultrasound of a Kidney with Lymphoma

Photo Courtsey Dr. Ginny Kunch

Beginning with Tests

A cat with a long-standing GI problem will need some foundational lab work in the form of a blood panel and urinalysis but there are some special tests that should be done early to be sure we are on the right track.

• testing for pancreatitis (usually added to the basic panel)
• testing for cobalamin (vitamin B12) because deficiency is common in most long-standing GI diseases (blood test requiring a 12 hour fast)
• testing for digestive enzyme deficiency (blood test requiring a 12 hour fast so special scheduling might be needed)

Concurrent pancreatitis adds a dimension of inflammation and pain beyond disease and should be identified. Similarly, a vitamin B12 deficiency complicates recovery for many intestinal diseases so that should either be identified or covered with injectable or oral supplements. A digestive enzyme deficiency (called exocrine pancreatic insufficiency) can occur at any age and has a specific treatment so we don't want to miss it. 

Diet Trials

Many patients with inflammatory GI disease will respond to diet and luckily, diet trials are short. Response is obvious within 2 weeks so, unless the situation is drastic, it is worth taking the time to test for diet response. Typical diets are hypoallergenic (hydrolyzed or novel protein), low residue/easily digested, or high fiber. 

Ultrasound of the Belly

• Severe bowel layer distortion implies (but does not confirm) malignancy.
• Milder bowel layer changes could be from either IBD or lymphoma.
• If any lymph nodes are enlarged, they may be aspirated with ultrasound guidance. If lymphoma is found, the diagnosis is made. If the node is immunologically reactive only, this does not rule out lymphoma but implies benign disease.
• If no lymph nodes are enlarged, the liver may be aspirated. If lymphoma is found, the diagnosis is made. If lymphoma is not found in the liver, it is not ruled out in the intestine.
• Growths or masses may be discovered that are best managed with surgical removal.
• Disease in other organs may be discovered.

Decision to Biopsy: Endoscopy or Surgery

If ultrasound findings are not specific and the diagnosis remains ambiguous, in a perfect world, referral for endoscopy or even surgery follows. Biopsy samples are taken, and a tailored therapy can initiate or at least informed decisions can be made.

Not every patient is stable for anesthesia, however, and not every owner is financially able to pursue a specialized procedure. There is controversy about whether full-thickness biopsy samples (which can only be obtained through surgery) are worth the invasiveness of surgical exploration. Endoscopy allows the surface of the bowel to be viewed from the inside of the intestine so that a biopsy sample can be taken from a specific site. Endoscopy is vastly less invasive, and the American College of Veterinary Internal Medicine has indicated that endoscopy is the preferred method of sampling. 

As with ultrasound, there is a great deal of overlap in findings between lymphoma and inflammatory bowel disease, as both conditions involve lymphocyte infiltration. Sorting it all out often requires more than a pathologist looking at the cells and how they are nested in the intestinal lining. Immunohistochemistry involves special stains for special proteins, antigens and mutations and can help with classification. PARR testing which looks for antigen arrangements to determine if the infiltrating lymphocytes are from one tumorous parent cell or multiple stimulated parent lymphocytes. Cancer cells by definition stem from one cell gone cancerous and thus the entire group of lymphocytes involved in the disease will share genetic markers while inflammatory infiltrates come from a group of cells and will show much more genetic variability. 

Having a confirmed diagnosis allows for accuracy in prognosis and precision in treatment and may be well worth the expense of this extra step. 

Treatment in Cases Lacking a Definitive Diagnosis

If one follows all the diagnostic steps described above, there is a very good chance that a diagnosis can be reached but sometimes it is not possible to perform the medical work up you want. Expense is involved and not every patient is stable for anesthesia and biopsy. In this situation, therapy can be designed to exploit the overlap of these two conditions. Corticosteroids kill lymphocytes whether they are benign or malignant. Vitamin B12 supplements can be healing in many GI diseases as can diet. If complete testing is not going to happen for whatever reason, your veterinarian may be able to devise a plan that provides coverage for both diseases so that the patient has a fair chance at improvement. Your veterinarian will guide you in this regard.

If your clinic does not have endoscopy equipment, your veterinarian can refer you.