AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Cronkhite-Canada syndrome (CCS) is a rare nonfamilial syndrome characterized by marked epithelial disturbances in the GI tract and epidermis. The GI changes are generalized hamartomatous polyposis with abnormal intervening mucosa. The mucosal proliferation leads to fluid and electrolyte abnormalities, malabsorption, malnutrition, GI bleeding, and surgical complications. The prevalence of GI malignancy in CCS patients is about 10%. Epidermal manifestations include alopecia, onychodystrophy, and hyperpigmentation. Approximately two thirds of all cases occur in individuals of Japanese descent. A few case reports have described an infantile form of this syndrome associated with a poor prognosis.¹

Cronkhite and Canada described the first 2 cases in 1955. Many case reports and several accumulated series bring the total cases reported in the medical literature to more than 400. Current understanding of the disease is based on small series and anecdotal reports. The etiology, the factors leading to progression or spontaneous remission, and the optimal treatment have not been established. In particular, the coordination of profound disturbances in 2 discrete epithelia, either concurrently or sequentially, is a provocative but unexplained phenomenon.

Pathophysiology

The characteristic features are GI polyposis and ectodermal changes. The polyps are part of a generalized GI mucosal disturbance that results in malabsorption and protein-losing enteropathy. These changes lead to the clinical symptoms, including diarrhea, abdominal pain, and profound malnutrition.

Dermatologic signs accompany the GI symptoms. The vast majority of affected individuals have alopecia and alterations in the nail beds and skin pigmentation. Although data from most cases support the belief that ectodermal features are the result of profound malnutrition, many symptoms and signs appear or remit in a manner inconsistent with this theory.

Diarrhea is multifactorial. Dilated glands in the GI mucosa release protein-enriched secretions into the lumen of the gut. The disrupted mucosa cannot digest disaccharides or absorb carbohydrates and lipids. The beneficial affects of antibiotics are attributed to small-bowel overgrowth. Steroids are most likely effective as anti-inflammatory agents. Polyps are believed to contribute to diarrhea. However, some therapeutic modalities and spontaneous remissions have improved diarrhea without affecting the number of polyps.

The disease usually evolves rapidly over several months. Mild GI and nutritional symptoms progress to substantial weight loss and edema. Ectodermal changes are usually observed several weeks or months after GI symptoms begin. Aside from the consequences of malnutrition, which can become life-threatening, most of the complications encountered are manifestations of the polyposis. Some patients with CCS have been diagnosed after presenting initially with other gastrointestinal conditions including Helicobacter pylori gastritis, eosinophilic gastroenteritis, and intestinal candidiasis.  

Juvenile GI polyposis is a syndrome described in infants who present with hamartomatous polyposis, macrocephaly, alopecia, nail dystrophy, clubbing of fingers and toes, hypotonia, hepatosplenomegaly, anemia, and hypoproteinemia due to protein-losing enteropathy. Although some authors consider this syndrome a form of CCS, others think it is a different entity. The prognosis is usually very poor. 

With the increasing observation of gastric and colorectal cancer in patients with CCS, various authors have attempted to hypothesize about this association. A group from Japan found a 40% prevalence of serrated adenomatous polyps in patients with CCS compared with a 1% incidence of this histology in all GI polyps.² Furthermore, this same group described a patient with microsatellite instability and overexpression of the p53 protein in the cancer and serrated adenoma. They proposed the possibility of a serrated adenoma-carcinoma sequence underlying some CCS GI malignancy.

Frequency

United States

As of 1995, only 15 authenticated cases were reported in American literature. As the number of cases reported has increased over the last decade, this has increased.

International

Two thirds of the 400 or so reported cases come from Japan.³ An old estimate is an incidence of 1 case in 1 million population.

Mortality/Morbidity

About one half of reported cases have resulted in long-term survival; however, many patients die from unrelated causes because of their advanced age. The grave prognosis has been modified with the identification of long-term survivors.

• Malnutrition: Acute fluid and electrolyte disturbances can follow long-term nutrient depletion and can be exacerbated by enteral losses of serum proteins. These disturbances result in anasarca, congestive heart failure, and immunologic deficiencies.
• Anemia: Acute and chronic GI blood losses secondary to gastroduodenal ulceration and erosions of colorectal polyp epithelium compound nutritional deficiencies of iron, folate, and, possibly, vitamin B-12 and reticulocytopenia found in chronic disease. Packed RBC transfusions may be required. Patients may die from severe GI hemorrhage.
• Surgery: In the early literature, bowel resection was performed to make a diagnosis. It is now mainly reserved for emergency complications. A compromised preoperative state contributes to the high surgical mortality rate.

Race

• The cause of the frequent case reports from Japan is unclear. The author of the largest series postulates that mental and physical stresses are contributory factors.³ Evidence does not suggest a genetic or specific infectious basis.
• After Japanese patients, most patients are Caucasians from North America and western Europe.

Sex

In Japan, the male-to-female ratio is 2:1. Outside Japan, the small number of cases has no sexual predilection.

Age

The age distribution of published cases ranges from 31-85 years, with onset of disease occurring most commonly in patients aged 50-60 years. Similar to the experience of one author presented in abstract form, an Italian group has described a case of a 17-year-old with clinical features consistent with CCS.⁴ 

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• At the time of presentation and throughout the course of Cronkhite-Canada syndrome (CCS), the symptoms are manifestations of the degree of GI mucosal disease. The duration from onset of symptoms to diagnosis is less than 3 months in about 50% of patients.
• Several recognized patterns of disease evolution include either diarrhea or hypogeusia (taste disturbances) as the initial symptom. Diarrhea usually occurs, followed by a variable sequence of the triad that includes nail dystrophy, alopecia, and hyperpigmentation (see Staging).
• The etiology of hypogeusia is uncertain; it may result from disturbances of zinc absorption, possibly secondary to diarrhea or mucosal changes. In some individuals, xerostomia (unusual oropharyngeal sensation) precedes diarrhea or ectodermal changes. Another pattern in which ectodermal changes precede diarrhea is less common but well described.
• Diarrhea is multifactorial and is observed in 90% of patients. Patients typically have 5-7 loose, watery bowel movements each day, with stool volumes as much as 4-6 L. Hematochezia and steatorrhea both occur. Abdominal pain, anorexia, emesis, weakness, and weight loss often greater than 10 kg accompany the diarrhea. Weakness can be related to caloric deprivation, muscle wasting, dehydration, and fecal electrolyte losses, including calcium, magnesium, potassium, and zinc.
• A few patients have neurologic symptoms. These include numbness and tingling in the extremities, dysphagia, and seizures. Convulsions are often secondary to electrolyte imbalance. Whether recent reports of CCS in patients with psychiatric illness has any significance besides coincidence is unclear.

Physical

Physical examination reveals characteristic ectodermal changes starting several weeks or months after the initial GI symptoms in almost all patients. Most patients have 2 or more of the cutaneous triad that consists of alopecia, nail changes, and hyperpigmentation.

• Alopecia
• • The alopecia is initially patchy; however, it rapidly progresses and leads to complete hair loss.
  • Hair loss typically involves the scalp, eyebrows, face, axillae, pubic areas, and extremities; however, loss of only scalp hair has also been described.
  • Regrowth is noted after treatment, during spontaneous remissions, and despite ongoing active disease.
• Onychodystrophy (nail changes)
• • Nail changes involve thinning, splitting, and color changes in all fingernails and toenails.
  • Onycholysis (partial separation of the nail from its bed) leads to a unique pattern of an inverted triangle of normal nail bordered by a dystrophic nail.
  • Onychomadesis (the loss of all finger and toenails) occurs over several weeks.
  • Partial or total regeneration of nails occurs spontaneously in spite of active disease or remission.
• Hyperpigmentation
• • Hyperpigmented light-to-dark brownish macules and plaques are diffusely distributed. Although they are most commonly found on the hands and arms, they are also found on the legs, face, palms, soles, neck, trunk, and elsewhere.
  • They may coalesce and range from a few millimeters to 10 cm in diameter.
  • Patchy vitiligo is relatively common.
  • Similar to the other ectodermal changes, pigmentation can persist or resolve after medical therapy, surgical treatment, or no therapy.
• Other signs
• • Other signs are often secondary to long-standing protein, vitamin, and mineral depletion.
  • Findings include Chvostek and Trousseau signs, glossitis, edema that can range from mild peripheral findings to anasarca, and vestibular disturbances.

Causes

• At this time, speculation on the etiology is limited to anecdotal associations. The author of the largest series described mental stress, such as mental suffering or family problems, and physical fatigue as the most frequent precipitating factors for Japanese patients.³ Unlike many other GI polyposis syndromes, familial patterns of inheritance have not been identified. In particular, mutations in PTEN, which are responsible for Cowden disease, have not been found in patients with CCS.
• The unique involvement of 2 epithelial tissues in CCS suggests that potentially reversible derangements in epithelial cell-to-cell signaling or maturation may play a pivotal role in initiating the syndrome. Although no experimental evidence has validated this hypothesis, the observation that sulindac administration led to regression of CCS polyps may be interpreted as consistent with this mechanism.⁵ Nonsteroidal anti-inflammatory drugs (NSAIDs) are felt to inhibit cellular proliferation through various methods, including influencing cell-cycle regulatory proteins.
• Although the efficacy of corticosteroids provides the strongest evidence to suggest an inflammatory cause for CCS, additional reports could support this theory. Patients with CCS have been described with coexisting autoimmune conditions such as type 1 diabetes mellitus, hypothyroidism, membranous glomerulopathy, and high titers of antinuclear antibody.
• A recent provocative report described the infiltration of immunoglobulin G4 (IgG4)–producing plasma cells in half of the CCS polyps studied in 7 affected individuals.⁶ This histochemical finding is the criteria for IgG4–related autoimmune disease (IRAD), which includes autoimmune pancreatitis, sclerosing cholangitis, and retroperitoneal fibrosis. The authors of this report speculate that CCS is an intestinal manifestation of IRAD.
• As detailed above, many signs and symptoms are secondary to the changes in the GI mucosa and the consequential malabsorption of nutrients.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Polyposis syndromes

• Generalized juvenile polyposis
• Hyperplastic polyposis
• Lipomatous polyposis
• Nodular lymphoid hyperplasia
• Inflammatory polyposis
• Lymphomatous polyposis
• Peutz-Jeghers polyposis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

Because the diagnosis is clinical, relatively little effort is made to comprehensively categorize laboratory data in affected patients. Testing is necessary to identify and monitor complications of the disease.

• Baseline blood testing: Important baseline blood results include serum electrolyte (eg, calcium, magnesium, potassium, zinc), BUN, creatinine, albumin, and total protein levels, as well as the prothrombin time (PT) and/or the activated partial thromboplastin time (aPTT) and CBC count.
• Erythrocyte sedimentation rate (ESR) testing: In the early stages of the syndrome, blood obtained for ESR testing and stools obtained for cultures and evaluation for ova, parasites, and leukocytes are helpful in ruling out other causes of diarrhea.
• Serial evaluations
• • Results of serial evaluations may guide therapy and minimize morbidity.
  • Evaluations help in identifying treatable causes of anemia (eg, iron, folate, and vitamin B-12 deficiency); the Schilling test is occasionally used.
  • Evaluations are performed to characterize malabsorption by using the serum xylose, carotene, hydrogen breath, fecal alpha-1-antitrypsin, and fat excretion tests.
  • Evaluations elucidate secondary immunologic deficiencies by measuring serum globulins.
  • Nuclear medicine studies based on technetium-labeled human serum albumin can be used to localize the site of protein-losing enteropathy and to direct surgical resection.
• Other tests
• • Previous investigators determined that Cronkhite-Canada syndrome (CCS) is not primarily associated with pituitary, adrenal, pancreatic, renal, or liver abnormalities.
  • A small number of patients have hypothyroidism. The nature of this association is unknown.

Imaging Studies

• Upper GI series: This, along with small-bowel follow-through, is used to evaluate polyps in the stomach and small bowel, especially those beyond the ligament of Treitz.
• Colonoscopy: When colonoscopy is unavailable, barium enema with reflux into the terminal ileum is used to investigate colonic and distal small-bowel polyps.
• Plain radiography and contrast-enhanced studies: Complications that require surgical intervention, such as ulcer perforation and intussusception, are diagnosed with plain radiography of the abdomen and contrast studies.
• Imaging and endoscopic studies
• • Although the esophagus is rarely involved, the stomach and colon almost always contain polyps. Polyps are noted in the small bowel in approximately one half of all patients, most often in the duodenum and terminal ileum.⁷ Although most polyps are sessile, pedunculated lesions are frequently encountered.
  • Gastric folds can enlarge⁸ and create the appearance of Menetrier syndrome.
• Wireless capsule endoscopy: This has recently been used to visualize the abnormal mucosal appearance that was found throughout most of the small bowel.⁹ This noninvasive technique may enhance our understanding of the temporal relationships between mucosal changes and the development of malabsorption and clinical symptoms. It may also have a role in evaluating the early response of patients with CCS to various treatment modalities.

Procedures

• Diagnostic endoscopy: This test, which is superior to radiographic imaging, allows direct visualization and biopsy of the GI mucosa. Abnormal intervening mucosa distinguishes CCS from the generalized polyposis syndromes prior to the ectodermal changes.
• Therapeutic endoscopy: This is used to identify and treat sources of GI bleeding and to remove polyps with suspected dysplasia and carcinoma.

Histologic Findings

The universal finding is hamartomatous polyps of the juvenile (retention) type throughout the GI tract without typically involving the esophagus. Mucosal changes are characterized by intact surface epithelium, edematous chronically inflamed lamina propria, and proliferated tortuous glands, some of which are cystically dilated and filled with proteinaceous fluid or inspissated mucus. The mucosa often contains engorged vascular channels, surface erosions, and prominent eosinophilic infiltration. Compared with the hamartomas seen in patients with juvenile colonic polyposis, colonic CCS polyps generally have a broader sessile base.

In CCS, but not in generalized juvenile polyposis coli, the mucosa between polyps is also abnormal, with edema, congestion, and inflammation of the lamina propria and focal glandular ectasia. Adenomatous changes and carcinoma occur in, or in close proximity to, hamartomatous polyps in almost 15% of affected patients. As indicated above, future work may corroborate the importance of serrated adenoma as a premalignant lesion.

Staging

No staging system is available for this rare entity. However, Goto et al have divided the clinical presentation into 5 categories; this may assist clinicians considering this diagnosis.¹⁰ The categories, based on presenting symptoms and subsequent clinical course, are as follows:

• Diarrhea (35%)
• • Skin hyperpigmentation and nail dystrophy (56%)
  • Hypogeusia, alopecia, skin hyperpigmentation, and nail dystrophy (28.2%)
  • Nail dystrophy, alopecia, skin hyperpigmentation, and hypogeusia (15.4%)
• Hypogeusia (40.9%)
• • Diarrhea, alopecia, hyperpigmentation of skin, and nail dystrophy (71.1%)
  • Nail dystrophy, alopecia, skin hyperpigmentation, and diarrhea (22.2%)
  • Nail dystrophy and alopecia (13.3%)
• Xerostomia (6.4%) - Diarrhea, alopecia, skin hyperpigmentation, and nail dystrophy
• Abdominal discomfort (9.1%) - Alopecia, hyperpigmentation of skin, nail dystrophy, and diarrhea  
• Alopecia (8.2%)
• • Diarrhea, nail dystrophy, skin hyperpigmentation, and hypogeusia (55.6%)
  • Skin hyperpigmentation, diarrhea, and hypogeusia (44.4%)

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Neither evidence-based medicine nor systematic investigations of medical or surgical interventions are available.¹¹ Reported therapies include supportive care, hyperalimentation, antibiotics, corticosteroids, acid suppression, cromolyn, anabolic steroids, surgery, administration of zinc, and eradication of H pylori with standard therapy as well as combinations of these therapies. Each approach is successful in some cases. A short communication has described the successful use of NSAIDs to regress Cronkhite-Canada syndrome (CCS) polyps, as has been described in patients with hereditary polyposis adenoma-to-carcinoma syndromes.⁵
• A published expert opinion described successful management recommendations that included treating GI symptoms, aggressive nutritional support, and vigilant monitoring for complications requiring emergent surgery. Many anecdotal reports support the use of corticosteroid and, less commonly, anabolic steroids if deterioration continues. Antibiotics are indicated for sepsis, peritonitis, and possible small-bowel overgrowth.
• Abdominal pain, anorexia, and Hemoccult-positive stools may be related to gastroduodenal mucosal erosions that respond to acid suppression and sucralfate. Flatulence of abdominal pain secondary to distension is addressed by restricting disaccharides, especially lactose, and decreasing small-bowel flora. Dramatic increases in abdominal pain are secondary to perforation or intussusception.
• The degree of malabsorption present dictates the form of nutritional therapy. Elimination diets or antiperistaltic agents attenuate diarrhea. Mild malnutrition is reversed with replacement of nutrients, the above measures, and treatment of small bowel overgrowth. Specific antibiotic regimens are not suggested. Elemental diets and parenteral hyperalimentation are required with progressive compromise.

Surgical Care

Reports describe patients whose conditions were diagnosed only after surgical resection and others who achieved symptomatic remission after the polypoid tissue was removed. Because of the generalized nature of CCS and the possibility of operative complications in an elderly and compromised patient population, surgery is usually reserved to treat complications (eg, bleeding ulcers, perforation, intussusception, malignancy).

Consultations

The team that successfully cares for a CCS patient includes a nutritional support group, a surgeon, and a gastroenterologist able to perform diagnostic and therapeutic endoscopy.

Diet

As outlined above, dietary requirements evolve as the mucosal involvement varies. Preservation of an adequate nutritional status is essential to minimize morbidity.

Activity

The overall clinical condition of the patient determines the level of physical activity. Prophylactic dietary or activity modifications are not recommended as prevention for CCS.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

A generalized algorithm for treating Cronkhite-Canada syndrome (CCS), such as one that addresses the use of any specific pharmacologic agent or nonstandard dosages, has not been established. Therapy is always supportive and includes vigorous fluid and electrolyte replacement and maintenance of macronutrient and micronutrient requirements. Antibiotics are given orally to treat small-bowel overgrowth or parenterally to treat systemic infections. Broad-spectrum coverage should be provided to patients with immunocompromise. Corticosteroids are frequently used for advanced stages. Anabolic steroids are used as a last resort, presumably for their regenerative properties. However, data supporting their use are questionable and insufficient to warrant specific recommendations.

Drug Category: Corticosteroids

These drugs are presumably used for their anti-inflammatory effect. They elicit anti-inflammatory and immunosuppressive properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Hyperalimentation, including electrolytes, minerals, protein, vitamins, dextrose, and lipids, are given because of the clinically significant losses of nutrients and fluid from the GI tract.
• Monitor the patient for impending surgical complications.

Further Outpatient Care

• Although remissions may persist for longer than 10 years, patients must be monitored for nutritional deficiencies.
• Patients should regularly undergo upper endoscopy and colonoscopy because more than 10% of patients with Cronkhite-Canada syndrome (CCS) develop GI (stomach, colon) cancer.

In/Out Patient Meds

• The literature does not support prophylactic therapy.
• All therapy should be individualized for the patient's specific symptoms and complications.

Transfer

• Consider transferring the patient to an intensive care unit for surgical intervention, diagnostic and therapeutic GI endoscopy, and parenteral hyperalimentation.

Deterrence/Prevention

• Specific recommendations are not available.
• Epidemiologic data do not suggest specific infectious etiology.

Complications

• Dehydration, electrolyte abnormalities, and shock
• Kwashiorkor and various nutritional deficiencies
• Small bowel overgrowth, systemic infections, and sepsis
• Anemia related to GI blood losses and deficiencies
• Edema, anasarca, and congestive heart failure
• Thromboembolic phenomena
• Reportedly high rates of surgical complications
• Secondary immune deficiencies

Prognosis

• Early reports indicated a grave prognosis. Large series have shown that more than one half of affected patients have a remission; long-term survivors are reported.
• Survival largely depends on adequate and sometimes prolonged intensive care.
• Although the diagnosis depends on alopecia, nail dystrophy, or pigmentation changes, the prognosis is related to only the GI mucosal pathology.

Patient Education

• Patients who go into remission should promptly report any change in GI symptoms or weight loss to their physicians.
• Regular surveillance endoscopy is important for long-term survivors.
• Patients should be reassured that CCS is neither contagious nor familial.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize ectodermal signs delays diagnosis and obscures the severity of the GI mucosal condition.
• Failure to initiate prompt supportive therapy compromises the elderly patient's ability to survive the profuse diarrhea.
• Failure to detect surgical complications at an early stage results in emergent surgery with a higher complication and mortality rate.
• Failure to provide prompt appropriate nutritional intervention results in cachexia, multiple deficiencies, and secondary complications.
• Failure to provide ongoing surveillance endoscopy results in lack of early recognition of malignant transformation.

Special Concerns

• Pediatric patients have not been definitively described. Patients with generalized juvenile polyposis can present with some of the nutritional and GI sequelae observed in Cronkhite-Canada syndrome (CCS).
• Because the mean age for patients is 50-60 years, geriatric physicians must suspect this diagnosis for anyone with hair loss, nail changes, or hyperpigmentation that accompanies GI or nutritional deterioration.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Ruymann FB. Juvenile polyps with cachexia. Report of an infant and comparison with Cronkhite-Canada syndrome in adults. Gastroenterology. Oct 1969;57(4):431-8. [Medline].
2. Yashiro M, Kobayashi H, Kubo N, et al. Cronkhite-Canada syndrome containing colon cancer and serrated adenoma lesions. Digestion. 2004;69(1):57-62. [Medline].
3. Goto A. Cronkhite-Canada syndrome: epidemiological study of 110 cases reported in Japan. Nippon Geka Hokan. Jan 1 1995;64(1):3-14. [Medline].
4. Vernia P, Marcheggiano A, Marinaro V, et al. Is Cronkhite-Canada Syndrome necessarily a late-onset disease?. Eur J Gastroenterol Hepatol. Oct 2005;17(10):1139-41. [Medline].
5. Hizawa K, Nakamori M, Yao T, Matsumoto T, Iida, M. A Case of Cronkhite-Canada Syndrome with Colorectal Adenomas: Effect of the Nonsteroidal Anti-Inflammatory Drug Sulindac. Am J Gastroenterol. August 2007;102 (8):1831-2. [Medline].
6. Riegert-Johnson DL, Osborn N, Smyrk T, Boardman LA. Cronkhite-Canada Syndrome Hamartomatous Polyps are Infiltrated with IgG4 Plasma Cells. Digestion. 2007/05;75 (2-3):96-97. [Medline].
7. Dachman AH, Buck JL, Burke AP, Sobin LH. Cronkhite-Canada syndrome: radiologic features. Gastrointest Radiol. 1989;14(4):285-90. [Medline].
8. Kilcheski T, Kressel HY, Laufer I, Rogers D. The radiographic appearance of the stomach in Cronkhite-Canada syndrome. Radiology. Oct 1981;141(1):57-60. [Medline].
9. Cao XC, Wang BM, Han ZC. Wireless capsule endoscopic findings in Cronkhite-Canada syndrome. Gut. 2006;55 (6):899-900. [Medline].
10. Goto A, Mimoto H, Shibuya C, Matsunami E. Cronkhite-Canada syndrome: an analysis of clinical features and follow-up studies of 80 cases reported in Japan. Nippon Geka Hokan. Nov 1 1988;57(6):506-26. [Medline].
11. Freeman K, Anthony PP, Miller DS, Warin AP. Cronkhite Canada syndrome: a new hypothesis. Gut. May 1985;26(5):531-6. [Medline].
12. Daniel ES, Ludwig SL, Lewin KJ, et al. The Cronkhite-Canada Syndrome. An analysis of clinical and pathologic features and therapy in 55 patients. Medicine (Baltimore). Sep 1982;61(5):293-309. [Medline].
13. Nonomura A, Ohta G, Ibata T, et al. Cronkhite-Canada syndrome associated with sigmoid cancer case report and review of 54 cases with the syndrome. Acta Pathol Jpn. Sep 1980;30(5):825-45. [Medline].
14. Russell DM, Bhathal PS, St John DJ. Complete remission in Cronkhite-Canada syndrome. Gastroenterology. Jul 1983;85(1):180-5. [Medline].
15. Samoha S, Arber N. Cronkhite-Canada syndrome. Digestion. 2005;71(4):199-200. [Medline].
16. Ward EM, Wolfsen HC. Pharmacological management of Cronkhite-Canada syndrome. Expert Opin Pharmacother. Mar 2003;4(3):385-9. [Medline].

Article Last Updated: Apr 1, 2008