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Screening methods for colon cancer depend on detecting either precancerous changes such as certain kinds of polyps or on finding early and thus more treatable cancer. The extent to which screening procedures reduce the incidence of gastrointestinal cancer or mortality depends on the rate of precancerous and cancerous disease in that population. gFOBT (guaiac fecal occult blood test) and flexible sigmoidoscopy screening have each shown benefit in randomized clinical trials. Evidence for other colon cancer screening tools such as iFOBT (immunochemical fecal occult blood test) or colonoscopy is substantial and guidelines have been issued by several advisory groups but does not include randomized studies.
In 2009 the American College of Gastroenterology (ACG) suggest that colon cancer screening modalities that are also directly preventive by removing precursor lesions should be given precedence, and prefer a colonoscopy every 10 years in average-risk individuals, beginning at age 50. The ACG suggests that cancer detection tests such as any type of FOB are an alternative that is less preferred, and if a colonoscopy is declined, the FIT (fecal immunochemical test, or iFOBT) should be offered instead. Two other recent guidelines, from the US Multisociety Task Force (MSTF) and the US Preventive Services Task Force (USPSTF), while permitting immediate colonoscopy as an option, did not categorize it as preferred. The ACG and MSTF also included CT colonography every five years, and fecal DNA testing as considerations. All three recommendation panels recommended replacing any older low-sensitivity, guaiac-based fecal occult blood testing (gFOBT) with either newer high-sensitivity guaiac-based fecal occult blood testing (hs gFOBT) or fecal immunochemical testing (FIT). MSTF looked at six studies that compared high sensitivity gFOBT (Hemoccult SENSA) to FIT, and concluded that there was no clear difference in overall performance between these methods.
The American College of Gastroenterology has recommended the abandoning of gFOBT testing as a colorectal cancer screening tool, in favor of the fecal immunochemical test. Though the FIT test is preferred, even the guaiac FOB testing of average risk populations may have been sufficient to reduce the mortality associated with colon cancer by about 25%. With this lower efficacy, it was not always cost effective to screen a large population with gFOBT.
If colon cancer is suspected in an individual (such as in someone with an unexplained anemia) fecal occult blood tests may not be clinically helpful. If a doctor suspects colon cancer, more rigorous investigation is necessary, whether or not the test is positive.
In 2006, the Australian Government introduced the National Bowel Cancer Program which has been updated several times since; targeted screening will be done of all Australians aged over 50 to 74 by 2017–2018. Cancer Council Australia recommended that FOBT should be done every two years. Gradually government fund disbursement meant that some people are not yet eligible for the national program and should pay for a FOBT by themselves.
The Canadian Cancer Society recommends that men and women age 50 and over have a FOBT at least every 2 years.
In colon cancer screening, using only one sample of feces collected by a doctor performing a digital rectal examination is discouraged.
The use of the M2-PK Test is encouraged over gFOBT for routine screening as it may pick up tumors that are both bleeding and non bleeding. It is able to pick up 80 percent of colorectal cancer and 44 percent for adenoma > 1 centimeter, while gFOBT picks up 13 to 50 percent of colorectal cancers.
Zollinger–Ellison syndrome may be suspected when the above symptoms prove resistant to treatment, when the symptoms are especially suggestive of the syndrome, or when endoscopy is suggestive. The diagnosis is made through several laboratory tests and imaging studies:
- Secretin stimulation test, which measures evoked gastrin levels
- Fasting gastrin levels on at least three separate occasions
- Gastric acid secretion and pH (normal basal gastric acid secretion is less than 10 mEq/hour; in Zollinger–Ellison patients, it is usually more than 15 mEq/hour)
- An increased level of chromogranin A is a common marker of neuroendocrine tumors.
In addition, the source of the increased gastrin production must be determined using MRI or somatostatin receptor scintigraphy.
There are four methods in clinical use for testing for occult blood in feces. These look at different properties, such as antibodies, heme, globin, or porphyrins in blood, or at DNA from cellular material such as from lesions of the intestinal mucosa.
- Fecal immunochemical testing (FIT), and immunochemical fecal occult blood test (iFOBT). FIT products utilize specific antibodies to detect globin. FIT screening is more effective in terms of health outcomes and cost compared with guaiac FOBT. According to the guidelines of the American College of Gastroenterology, "Annual fecal immunochemical testing is the preferred colorectal cancer detection test." A FIT test detects globin levels in feces at or above 50 nanograms per mL, the established cutoff by the World Health Organization for Colorectal Cancer Screening.
FIT testing has replaced most gFOBT tests as the colon cancer screening test of choice. This methodology can be adapted for automated test reading and to report quantitative results, which are potential factors in design of a widescale screening strategy. The number of fecal samples submitted for FIT may affect the clinical sensitivity and specificity of the methodology.[8] High sensitivity gFOBT tests such as Hemoccult SENSA remains an accepted option;[8] and may retain a role in monitoring gastrointestinal conditions such as ulcerative colitis; however the FIT test is preferred in recent guidelines.
- Stool guaiac test for fecal occult blood (gFOBT): – The stool guaiac test involves smearing some feces onto some absorbent paper that has been treated with a chemical. Hydrogen peroxide is then dropped onto the paper; if trace amounts of blood are present, the paper will change color in one or two seconds. This method works as the heme component in hemoglobin has a peroxidase-like effect, rapidly breaking down hydrogen peroxide. In some settings such as gastric or proximal upper intestinal bleeding the guaiac method may be more sensitive than tests detecting globin because globin is broken down in the upper intestine to a greater extent than is heme. There are various commercially available gFOBT tests which have been categorized as being of low or high sensitivity, and only high sensitivity tests remain an acceptable alternative to FIT testing, which is now the best-practices recommendation in colon cancer screening. Optimal clinical performance of the stool guaiac test depends on preparatory dietary adjustment.
- Stool DNA screening tests look for DNA alterations that have been associated with cancer.
Additional methods of looking for occult blood are being explored, including transferrin dipstick and stool cytology.
Besides the clinical picture, fasting VIP plasma level may confirm the diagnosis, and CT scan and somatostatin receptor scintigraphy are used to localise the tumor, which is usually metastatic at presentation.
Tests include:
- Blood chemistry tests (basic or comprehensive metabolic panel)
- CT scan of the abdomen
- MRI of the abdomen
- Stool examination for cause of diarrhea and electrolyte levels
- Vasoactive intestinal peptide (VIP) level in the blood
Bile acid malabsorption is common in Crohn's disease but not always recognised. Most patients with previous ileal resection and chronic diarrhea will have abnormal SeHCAT tests and can benefit from bile acid sequestrants.
Patients with primary bile acid diarrhea are frequently misdiagnosed as having the irritable bowel syndrome as clinicians fail to recognize the condition. When SeHCAT testing is performed, the diagnosis of primary bile acid diarrhea is commonly made. In a review of 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable bowel syndrome patients, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant.
Estimates of the population prevalence taken from this review suggest that 1% of the adult population could have primary bile acid diarrhea (Type 2 bile acid malabsorption).
Proton pump inhibitors (such as omeprazole and lansoprazole) and histamine H2-receptor antagonists (such as famotidine and ranitidine) are used to slow acid secretion. Once gastric acid is suppressed, symptoms normally improve.
There is no cure for short bowel syndrome except transplant. In newborn infants, the 4-year survival rate on parenteral nutrition is approximately 70%. In newborn infants with less than 10% of expected intestinal length, 5 year survival is approximately 20%. Some studies suggest that much of the mortality is due to a complication of the total parenteral nutrition (TPN), especially chronic liver disease. Much hope is vested in Omegaven, a type of lipid TPN feed, in which recent case reports suggest the risk of liver disease is much lower.
Although promising, small intestine transplant has a mixed success rate, with postoperative mortality rate of up to 30%. One-year and 4-year survival rate are 90% and 60%, respectively.
For practical purposes, gastric pH an endoscopy should be done in someone with suspected achlorhydria. Older testing methods using fluid aspiration through a nasogastric tube can be done, but these procedures can cause significant discomfort and are less efficient ways to obtain a diagnosis.
A complete 24-hour profile of gastric acid secretion is best obtained during an esophageal pH monitoring study.
Achlorhydria may also be documented by measurements of extremely low levels of pepsinogen A (PgA) () in blood serum. The diagnosis may be supported by high serum gastrin levels ().
The "Heidelberg test" is an alternative way to measure stomach acid and diagnose hypochlorhydria/achlorhydria.
A check can exclude deficiencies in iron, calcium, prothrombin time, vitamin B-12, vitamin D, and thiamine. Complete blood count with indices and peripheral smears can be examined to exclude anemia. Elevation of serum folate is suggestive of small bowel bacterial overgrowth. Bacterial folate can be absorbed into the circulation.
Once achlorhydria is confirmed, a hydrogen breath test can check for bacterial overgrowth.
Several methods have been developed to identify the disorder but there are difficulties with all of them. Fecal bile acid quantification is unpleasant for both the patient and laboratory. Diagnosis of bile acid malabsorption is easily and reliably made by the SeHCAT test. This nuclear medicine test involves two scans a week apart and so measures multiple cycles of bile acid excretion and reabsorption. There is limited radiation exposure (0.3 mSv). Retention of SeHCAT at 7 days is normally above 15%; values less than 15%, 10% and 5% predict respectively mild, moderate and severe abnormal retention and an increasing likelihood of response to bile acid sequestrants. This test is not licensed in the USA, and is underutilized even where it is available.
Older methods such as the C-glycocholic breath test are no longer in routine clinical use.
Measurement of 7α-Hydroxy-4-cholesten-3-one, a bile acid precursor, in serum, shows the increased bile acid synthesis found in bile acid malabsorption. This test is an alternative diagnostic means when available. Fasting blood FGF19 values may have value in the recognition of the disease and prediction of response.
Currently, there are two tests for evaluating BAM in the U.S. One test, currently available only for research purposes, measures serum levels of the marker 7α-hydroxy-4-cholesten-3-one (C4), a downstream product of CYP7A1. Plasma C4 levels increase when bile acid synthesis increases, and C4 levels are substantially elevated in BAM patients with a sensitivity and specificity of 90 percent and 79 percent, respectively. C4 levels have also been shown to correlate well with SeHCAT retention. This makes fasting serum C4 attractive as a screening test for BAM, although it can produce false-positives and false-negatives in patients who have liver disease or are taking statins.
The second test, which can now be clinically ordered, is the fecal bile acid excretion test. It quantifies individual and total bile acids in a 48-hour stool collection. Increased total fecal bile acids are seen in patients with chronic functional diarrhea and higher levels of CA and CDCA are associated with IBS-D.
A clinical validation involving 94 healthy volunteers, 60 patients with IBS-D and 28 patients with IBS with constipation (IBS-C) found that the sum of CA and CDCA concentrations above 3.7 percent were indicative of IBS-D with 72 percent sensitivity and 90 percent specificity. In addition, the upper limit of normal total fecal bile acid excretion over the 48 hours has been defined.
With a certain degree of clinical suspicion, the most useful initial test is the 24-hour urine levels of 5-HIAA (5-hydroxyindoleacetic acid), the end product of serotonin metabolism. Patients with carcinoid syndrome usually excrete more than 25 mg of 5-HIAA per day.
For localization of both primary lesions and metastasis, the initial imaging method is Octreoscan, where indium-111 labelled somatostatin analogues (octreotide) are used in scintigraphy for detecting tumors expressing somatostatin receptors. Median detection rates with octreoscan are about 89%, in contrast to other imaging techniques such as CT scan and MRI with detection rates of about 80%. Gallium-68 labelled somatostatin analogues such as Ga-DOTA-Octreotate (DOTATATE), performed on a PET/CT scanner is superior to conventional Octreoscan.
Usually, on a CT scan, a spider-like/crab-like change is visible in the mesentery due to the fibrosis from the release of serotonin. F-FDG PET/CT, which evaluate for increased metabolism of glucose, may also aid in localizing the carcinoid lesion or evaluating for metastases. Chromogranin A and platelets serotonin are increased.
Symptoms of short bowel syndrome are usually addressed with medication. These include:
- Anti-diarrheal medicine (e.g. loperamide, codeine)
- Vitamin, mineral supplements and L-glutamine powder mixed with water
- H2 blocker and proton pump inhibitors to reduce stomach acid
- Lactase supplement (to improve the bloating and diarrhoea associated with lactose intolerance)
In 2004, the USFDA approved a therapy that reduces the frequency and volume of total parenteral nutrition (TPN), comprising: NutreStore (oral solution of glutamine) and Zorbtive (growth hormone, of recombinant DNA origin, for injection) together with a specialized oral diet. In 2012, an advisory panel to the USFDA voted unanimously to approve for treatment of SBS the agent teduglutide, a glucagon-like peptide-2 analog developed by NPS Pharmaceuticals, who intend to market the agent in the United States under the brandname Gattex. Teduglutide had been previously approved for use in Europe and is marketed under the brand Revestive by Nycomed.
Surgical procedures to lengthen dilated bowel include the Bianchi procedure, where the bowel is cut in half and one end is sewn to the other, and a newer procedure called serial transverse enteroplasty (STEP), where the bowel is cut and stapled in a zigzag pattern. Heung Bae Kim, MD, and Tom Jaksic, MD, both of Children's Hospital Boston, devised the STEP procedure in the early 2000s. The procedure lengthens the bowel of children with SBS and may allow children to avoid the need for intestinal transplantation. As of June 2009, Kim and Jaksic have performed 18 STEP procedures. The Bianchi and STEP procedures are usually performed by pediatric surgeons at quaternary hospitals who specialize in small bowel surgery.
Surgery can usually cure VIPomas. However, in one-third to one-half of patients, the tumor has spread by the time of diagnosis and cannot be cured.
Diagnosis may be simple in cases where the patient's signs and symptoms are idiopathic to a specific cause. However this is generally not the case, considering that many pathogens which cause enteritis may exhibit the similar symptoms, especially early in the disease. In particular, "campylobacter, shigella, salmonella" and many other bacteria induce acute self-limited colitis, an inflammation of the lining of the colon which appears similar under the microscope.
A medical history, physical examination and tests such as blood counts, stool cultures, CT scans, MRIs, PCRs, colonoscopies and upper endoscopies may be used in order to perform a differential diagnosis. A biopsy may be required to obtain a sample for histopathology.
Often, a diagnosis can be made based on the patient's description of their symptoms, but other methods which may be used to verify gastritis include:
- Blood tests:
- Blood cell count
- Presence of "H. pylori"
- Liver, kidney, gallbladder, or pancreas functions
- Urinalysis
- Stool sample, to look for blood in the stool
- X-rays
- ECGs
- Endoscopy, to check for stomach lining inflammation and mucous erosion
- Stomach biopsy, to test for gastritis and other conditions
It is important to differentiate DPI from small intestinal obstruction, since obstruction may require surgical intervention, but this can at times be difficult. Horses suffering from DPI usually have a higher protein concentration in their peritoneal fluid compared to horses with small intestinal obstruction, often without a concurrent increase in nucleated cell count. They usually have some relief and decrease in pain after gastric decompression, while horses with an obstruction often still act colicky after nasogastric intubation. Distention of the small intestine may be less than what is felt on rectal examination of horses with obstruction, especially after gastric decompression. Horses with DPJ usually produce larger volumes of reflux (usually greater than 48 liters in the first 24 hours) than those with obstruction, and are often pyretic (temperatures of 101.5–102.5) and have alterations in white blood cell levels, while those with obstructions usually have a normal or lower than normal temperature and normal leukocyte levels.
Ultrasound can also be helpful to distinguish DPJ from obstruction. Horses with small intestinal obstruction will usually have an intestinal diameter of −10 cm with a wall thickness of 3–5mm. Horses with proximal enteritis usually have an intestinal diameter that is narrower, but wall thickness is often greater than 6mm, containing a hyperechoic or anechoic fluid, with normal, increased, or decreased peristalsis. However, obstructions that have been present for some time may present with thickened walls and distention of the intestine.
DPJ can only be definitively diagnosed during surgery or at necropsy, when its gross appearance of the small intestine may be evaluated.
Little is known on the prognosis of achlorhydria, although there have been reports of an increased risk of gastric cancer.
A 2007 review article noted that non-"Helicobacter" bacterial species can be cultured from achlorhydric (pH > 4.0) stomachs, whereas normal stomach pH only permits the growth of "Helicobacter" species. Bacterial overgrowth may cause false positive H. Pylori test results due to the change in pH from urease activity.
Small bowel bacterial overgrowth is a chronic condition. Retreatment may be necessary once every 1–6 months. Prudent use of antibacterials now calls for an antibacterial stewardship policy to manage antibiotic resistance.
There is no single, specific test for malabsorption. As for most medical conditions, investigation is guided by symptoms and signs. A range of different conditions can produce malabsorption and it is necessary to look for each of these specifically. Many tests have been advocated, and some, such as tests for pancreatic function are complex, vary between centers and have not been widely adopted. However, better tests have become available with greater ease of use, better sensitivity and specificity for the causative conditions. Tests are also needed to detect the systemic effects of deficiency of the malabsorbed nutrients (such as anaemia with vitamin B12 malabsorption).
Proximal enteritis usually is managed medically. This includes nasogastric intubation every 1–2 hours to relieve gastric pressure secondary to reflux, which often produces to 2–10 L, as well as aggressive fluid support to maintain hydration and correct electrolyte imbalances. Maintaining hydration in these patients can be very challenging. In some cases, fluid support may actually increase reflux production, due to the decreased intravascular oncotic pressure from low total protein and albumin levels, leading to loss of much of these IV fluids into the intestinal lumen. These horses will often display dependent edema (edema that collects in locations based on gravity). Colloids such as plasma or Hetastarch may be needed to improve intravascular oncotic pressure, although they can be cost prohibitive for many owners. Reflux levels are monitored closely to help evaluate fluid losses, and horses recovering from DPJ show improved hydration with decreased reflux production and improved attitude.
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain relief, reduction of inflammation, and for their anti-endotoxin effects, but care must be taken since they may produce gastrointestinal ulceration and damage the kidneys. Due to a suspected link to "Clostridial" infection, anti-microbials are often administered, usually penicillin or metronidazole. Aminoglycosides should be used with extreme caution due to the risk of nephrotoxicosis (damage to the kidney). The mucosa of the intestines is damaged with DPJ, often resulting in absorption of endotoxin and risking laminitis, so therapy to combat and treat endotoxemia is often employed. This includes treatment with drugs that counteract endotoxin such as Polymyxin B and Bio-Sponge, fluid support, and laminitis prevention such as icing of the feet. Prokinetic drugs such as lidocaine, erythromycin, metoclopramide, and bethanechol are often used to treat the ileus associated with the disease.
Horses are withheld food until reflux returns to less than 1–2 L of production every 4 hours, and gut sounds return, often requiring 3–7 days of therapy. Parenteral nutrition is often provided to horses that are withheld feed for greater than 3–4 days. It is suspected to improve healing and shorten the duration of the illness, since horses often become cachexic due to the protein losing enteropathy associated with this disease.
Surgery may need to be performed to rule out colic with similar presenting signs such as obstruction or strangulation, and in cases that are long-standing (> 7 days) to perform a resection and anastomosis of the diseased bowel. However, some horses have recovered with long-term medical support (up to 20 days).
Hemosuccus pancreaticus, also known as pseudohematobilia or Wirsungorrhage, is a rare cause of hemorrhage in the gastrointestinal tract. It is caused by a bleeding source in the pancreas, pancreatic duct, or structures adjacent to the pancreas, such as the splenic artery, that bleed into the pancreatic duct. Patients with hemosuccus may develop symptoms of gastrointestinal hemorrhage, such as blood in the stools, maroon stools, or melena. They may also develop abdominal pain. Hemosuccus pancreaticus is associated with pancreatitis, pancreatic cancer and aneurysms of the splenic artery. Angiography may be used to diagnose hemosuccus pancreaticus, where the celiac axis is injected to determine the blood vessel that is bleeding. Concomitant embolization of the end vessel may terminate the hemorrhage. Alternatively, a distal pancreatectomy may be required to stop the hemorrhage.
A blood serum glucagon concentration of 1000 pg/mL or greater is indicative of glucagonoma (the normal range is 50–200 pg/mL).
However, recent studies have shown that forty percent of patients have plasma glucagon levels ranging from 500 to 1000 pg/mL. Increased levels have been reported in cases of decreased kidney function, acute pancreatitis, hypercorticism, liver diseases, severe stress, extended fasting, and familial hyperglucagonemia. Rarely do these cases result in levels over 500 pg/mL, except in the case of patients with liver diseases.
Blood tests may also reveal abnormally low concentrations of amino acids, zinc, and essential fatty acids, which are thought to play a role in the development of NME. Skin biopsies may also be taken to confirm the presence of NME.
A CBC can uncover anemia, which is an abnormally low level of hemoglobin.
The tumor itself may be localized by any number of radiographic modalities, including angiography, CT, MRI, PET, and endoscopic ultrasound. Laparotomy is useful for obtaining histologic samples for analysis and confirmation of the glucagonoma.
A prospective study in 1994 noted that body mass index remains the strongest predictor of symptomatic gallstones among young women. Other risk factors are having over four pregnancies, weight gain, and cigarette smoking. Alcohol was shown to have an inverse relationship between use and gallbladder disease.
Gastroscopy, or endoscopic evaluation of the stomach, is useful in chronic cases of colic suspected to be caused by gastric ulcers, gastric impactions, and gastric masses. A 3-meter scope is required to visualize the stomach of most horses, and the horse must be fasted prior to scoping.
X-ray computed tomography (CT scan) findings of cysts in the pancreas are common, and often are benign. In a study of 2,832 patients without pancreatic disease, 73 patients (2.6%) had cysts in the pancreas. About 85% of these patients had a single cyst. Cysts ranged in size from 2 to 38 mm (mean, 8.9 mm). There was a strong correlation between the presence of cysts and age. No cysts were identified among patients less than 40 years of age, while 8.7 percent of the patients aged 80 to 89 years had a pancreatic cyst.
Cysts also may be present due to intraductal papillary mucinous neoplasm.
Radiographs (x-rays) are sometimes used to look for sand and enteroliths. Due to the size of the adult horse's abdomen, it requires a powerful machine that is not available to all practitioners. Additionally, the quality of these images is sometimes poor.