| ORIGINAL PAPERS |
Usefulness of jejunal biopsy in the study of intestinal malabsorption in the elderly
B. Lobo, F. Casellas, I. de Torres1, L. Chicharro and J. R. Malagelada
Service of Digestive Diseases and 1Pathology. Hospital Universitari Vall d'Hebron. Barcelona, Spain
ABSTRACT
Background: small bowel structure and function are not different between elderly people and young people. Thus, in principle it is advisable to perform diagnostic investigation of elderly patients as well as younger patients when they present with symptoms suggestive of intestinal malabsorption. A key test for the etiologic diagnosis of intestinal malabsorption, jejunal biopsy, has not been specifically examined to assess its usefulness and risk of complications in this advanced age patients. ]]>
Aim: to establish the usefulness of jejunal biopsy with the Watson's capsule in the elderly patients with suspected intestinal malabsorption.
Patients: patients older than 65 years referred to our Unit for performance of a jejunal biopsy from 1996 to 2001 for suspicion of intestinal malabsorption.
Results: forty-seven patients were included. Appropriate biopsy sample was obtained in 45 cases, although in 3 patients a second try was required. Histologic findings: partial villous atrophy in 10 cases (22.2%), complete villous atrophy in 5 cases (11.1%), intraepithelial lymphocytosis in 5 cases (11.1%), and single cases of intestinal lymphangiectasia, amyloidosis, unspecific jejunitis, and Whipple's disease. Histology was normal in 19 cases (42%). Definitive diagnosis was celiac disease in 14 patients, bacterial overgrowth in 3, jejunitis in 3, Whipple's disease in 1, lymphangiectasia in 1, atrophic gastritis in 3, amyloidosis in 1, and ischemic colitis in 1. Jejunal biopsy achieved an etiologic diagnosis in 20 patients. There were no cases of perforations or bleeding.
Conclusion: jejunal biopsy is a useful and safe test for the etiologic diagnosis of intestinal malabsorption in elderly patients.
Key words: Intestinal malabsorption. Elderly. Jejunal biopsy. Hydrogen breath test. Xylose test. Intestinal biopsy. Biopsy complications.
Lobo B, Casellas F, de Torres I, Chicharro L, Malagelada JR. Usefulness of jejunal biopsy in the study of intestinal malabsorption in the elderly. Rev Esp Enferm Dig 2003; 96: 259-264.
Recibido: 31-03-03.
Aceptado: 02-10-03.
Correspondencia: Francesc Casellas. Servicio de Aparato Digestivo. Hopistal Universitari Vall d'Hebron. Barcelona. Pso. de la Vall d'Hebron, 119. 08035 Barcelona.
Tel/fax: 93 489 44 56.
INTRODUCTION
Various studies have revealed that the structure, architecture and function of the intestinal mucosa in the elderly do not differ from those in the child or younger adult (1,2). Moreover, D-xylose absorption does not begin to decrease until patients have more than 80 years of age (3). Thus, clinical or laboratory suspicion of malabsorption in the elderly should not be attributed to aging but instead must be adequately studied, since it may point out the presence of a small bowel disease. The causes of intestinal malabsorption in the elderly also resemble those in younger adults (4,5). Most common causes include celiac disease, bacterial overgrowth, hypochlorhydria, Crohn's disease, mesenteric ischemia, and Whipple's disease (6-8).
Reported experience on the usefulness of screening tests is scarce regarding the study of intestinal malabsorption in the elderly. A hydrogen breath test with D-xylose is successfully used in both children and adults (9). This test is based upon the fact that orally administered xylose is absorbed through passive difusion in the small bowel; however, when the intestinal mucosa integrity is disrupted, xylose is not absorbed and thus reaches the colon, where it undergoes hydrogen-releasing fermentation. Hydrogen is absorbed and then eliminated in the breath, where it can be measured. This test has a good sensitivity and specificity for the screening of patients with malabsorption syndrome caused by small bowel disease (9-11). In older age patients, H2 breath test with D-xylose has also proved to be useful with a sensitivity and specificity similar to those seen in adult patients (12).
The histological examination of biopsy samples from small bowel mucosa is a key factor in the etiologic diagnosis of intestinal malabsorption. Intestinal biopsy samples may be collected by using duodenal endoscopy or a jejunal biopsy capsule. The benefits of capsule biopsy versus endoscopic biopsy include sample size in view of histological examination, jejunal instead of duodenal sampling, and lower cost. However, shortcomings include radiation exposure and relatively prolonged examination time (13). Watson's capsule is a variant of Crosby's, which is used for jejunal biopsy collection since 1957 (14). Although much experience exists regarding jejunal biopsy in children, little is known about the usefulness and risk of jejunal biopsy in the etiologic evaluation of intestinal malabsorption in the elderly (15). As a result, our goal was to analyze the cost-effectiveness of jejunal biopsy using Watson's capsule in the diagnosis of intestinal malabsorption in an advanced-age population.
MATERIAL AND METHODS
Patients
Patients older than 65 years who had been referred to our Gastrointestinal Function Testing Unit from 1996 to 2001 to undergo jejunal biopsy under clinical suspicion of intestinal malabsorption were prospectively studied. The suspicion of malabsorption was based on both clinical parameters (chronic diarrhea, asthenia, weight loss, etc.) and laboratory data (ferropenic anemia, folic acid deficiency, vitamin B12 deficiency, hypocalcemia, hypocholesterolemia, hypoalbuminemia, positive celiac serology). All patients signed their informed consent to undergo jejunal biopsy.
Methods
Clinical data were collected for all patients, and all underwent hydrogen breath test with D-xylose before performing jejunal biopsy using the Watson's capsule.
]]> For their hydrogen breath tests with D-xylose, patients were fasting and had received no antibiotics during the previous two weeks. Twenty-five grams of D-xylose in 250 mL of water were orally administered; exhaled breath samples were collected before and after D-xylose administration, and then every 30 minutes for 5 hours. Hydrogen concentration was measured as parts per million (ppm) using gas chromatography (Quintron), and results were then expressed as peak increases on H2 baseline production. Results were considered pathologic, i.e. suggestive of intestinal malabsorption, for increases above 25 ppm.Patients were fasting at the time of jejunal biopsy. A biopsy capsule is ingested, and its progression to 10 cm past Treitz's angle is helped by postural changes under fluoroscopic control, so that jejunal mucosa samples may be collected. The mean duration time for biopsy is around 30 minutes; no anesthesia is needed and radiation exposure is minimal. Biopsy samples were routinely processed using formalin fixation and hematoxilin-eosin staining. Sample validity, jejunal mucosa morphology and architecture (villi, crypts, lamina propria cells, blood and lymphatic vessels), and technique-related complications were all evaluated.
RESULTS
Patients
Forty-seven patients (24 females and 23 males) with a mean age of 72 years (range: 66 to 84 years) were included in this study. Prior to biopsy, the mean duration of symptoms consistent with malabsorption syndrome was 17 months, with a confidence interval of 11.8 months. The most common presenting symptoms included chronic diarrhea in 27 patients (58%), anemia in 19 patients (40%), weight loss in 7 patients (15%) and abdominal distension in one case (2%).
Notable laboratory data included anemia in 19/44 (43%), vitamin B12 deficiency in 10/29 (34%), hypoalbuminemia in 11/39 (28%), hypocholesterolemia in 11/44 (25%), hypocalcemia in 9/37 (24%), and folic acid deficiency in 1/26 (4%). Celiac disease serology (antiendomysium and antigliadin antibodies) was positive in 3 of 17 patients (18%).
Hydrogen breath test with D-xylose was performed in 42 patients. Mean baseline H2 excretion was 16 ppm with a confidence interval of 8.2, and average increase from baseline was 69 ppm with a confidence interval of 34.0 ppm. The test yielded abnormal results in 39 (93%) patients.
Intestinal biopsy result
A sample valid for histology was obtained in 42 patients (89%). In a second attempt, a valid sample was collected in 3 of the previously failed 5 patients (96%). Failed sample collection resulted from dysphagia, difficulty to pass through the pylorus, mouth aphthae difficulting catheter passage because of tenderness, and stomach sampling. No perforations or bleeding occurred.
Histological changes were seen in 55% of intestinal mucosa biopsy samples. Partial atrophy was the most commonly found alteration (22%). Other findings included total atrophy and lymphocytic infiltration, each in 11% of samples, as well as jejunitis in 7% of patients and isolated cases of amyloidosis, Whipple's disease or intestinal lymphangiectasia.
]]> A probable etiologic diagnosis of malabsorption was obtained for 57% of patients. In more than one half of cases the diagnosis was based on intestinal biopsy findings. The most commonly found condition was celiac disease, which amounted for 52% of cases, followed by bacterial overgrowth (15%), atrophic gastritis (11%), jejunitis (11%), and amyloidosis, Whipple's disease, intestinal ischemia, and intestinal lymphangiectasia making up the remaining 15%. In 10 patients diagnosed histologically of celiac disease, the presence of antigliadin and antiendomysium antibodies had been previously investigated, but these were positive in just only 3 patients. However, such results are scarcely assessable since these tests had been performed, in some cases, following the introduction of a gluten-free diet.No histologic pattern is pathognomonic for celiac disease, which is characterized by various nonspecific findings (partial or total villous atrophy, lymphocyte infiltrates, etc.). Therefore, the criterion to confirm the diagnosis of celiac disease was a good -particularly clinical- response (weight gain and decreased diarrhea) to a gluten-free diet, with improved laboratory and/or histologic parameters.
DISCUSSION
To establish the usefulness and risks of the capsule intestinal biopsy in the elderly, we analyzed the results obtained in a group of 47 patients older than 65 years, who had been referred for a study of intestinal malabsorption syndrome suspected from clinical and laboratory data, and confirmed using hydrogen breath test with D-xylose. The usefulness of such intestinal malabsorption screening test was recently assessed in an older-age group of patients (12). This test has the advantage of not being influenced by age or renal function. Results obtained in this study reveal that jejunal histology is pathological in more than one half of patients of older age with suspected malabsorption, and that biopsy demonstrates the more likely etiology of intestinal malabsorption in 74% of cases. These results are in contrast with those reported, in 1978, by Linaker and Calam (15), who showed that the efficacy of jejunal biopsy was only 12% in the elderly. This discrepancy may be probably ascribed to differences in the selection of patients for biopsy, as a result of the long time lapse separating both studies.
In patients who had no histologic changes in jejunal biopsy samples, we attributed malabsorption to bacterial overgrowth (one case confirmed using the hydrogen breath test with glucose) (17), ischemic ileitis (one case demonstrated by colonoscopy and confirmed by histology), atrophic gastritis (3 cases revealed by histology), collagenous colitis (one case confirmed by colonoscopic biopsy), diarrhea secondary to drugs (one case in which diarrhea regressed following flutamide withdrawal and recurred following flutamide reintroduction), and infectious diarrhea in one patient in whom coproculture was positive for Blastocystis hominis; in the remaining patients, diarrhea was considered a chronic, nonspecific syndrome with a good response to loperamide.
As regards intestinal malabsorption causes, celiac dis-ease is seen as the most common origin of malabsorption in this age group. The diagnosis of celiac disease was established on the presence of jejunal histologic lesions consistent with this diagnosis, together with good response to a gluten-free diet. The finding of an isolated positive serology was not considered diagnostic of celiac disease (18). This diagnosis is usually long delayed in the elderly, up to 28 years on average according to a published study (19). In this population subgroup, such diagnostic delay occurs even in the presence of a classical celiac disease manifestations (20). In other instances, however, this delay may be attributed to an atypical presentation -occasionally silent- or to a monosymptomatic presentation, such as anemia, iron deficiency, folic acid deficiency or hypocalcemia. However, early diagnosis is vital for these patients, since the incidence of serious complications, including intestinal lymphoma, may be prevented by the timely onset of an adequate dietary therapy (21). This is why screening tests such as the hydrogen breath test with D-xylose, and confirmation tests such as jejunal biopsy are so much advisable for elderly patients with clinically suspected malabsorption, since they are useful in the diagnosis of disease and have a low risk of iatrogenic complications.
To conclude, the results of the present study suggest that jejunal biopsy using Watson's capsule in the elderly is a useful, safe diagnostic procedure when it comes to establishing the causes of intestinal malabsorption.
REFERENCES
1. Corazza GR, Frazzoni M, Gatto MRA, et al. Ageing and small bowel mucosa: A morphometric study. Gerontology 1986; 32: 60-5. [ Links ]
2. Lipski PS, Bennett MK, Kelly PJ, James OF. Ageing and small-bowell morphometry. Journal of Clinical Pathology 1992; 45: 450-2. [ Links ]
3. Webster SGP, Leeming JT. Assessment of small bowel function in the elderly using a modified xylose tolerance test. Gut 1975; 16: 109. [ Links ]
4. Peter R, Holt MD. Diarrhea and malabsorption in the elderly. Gastroenterology Clinics of North America 2001; 30: 427-44. [ Links ]
5. Hoffmann JC, Zeitz M. Best Practice and Research Clinical Gastroenterology 2002; 16: 17-36. [ Links ]
6. Montgomery RD, Haboubi NY, Mike NH, et al. Causes of malabsorption in the elderly. Age Ageing 1986; 15: 235-40. [ Links ]
7. Montgomery RD, Haeney MR, Ross IN, et al. The ageing gut: A study of intestinal absorption in relation to nutrition in the elderly. Q J Med 1978; 47: 197-211. [ Links ]
8. Price HL, Gazzard BG, Dawson AM. Steatorrhoea in the elderly. BMJ 1977; 1: 1582. [ Links ]
9. Casellas F, Chicharro L, Malagelada JR. Potential usefulness of hydrogen breath test with D-xylose in clinical management of intestinal malabsorption. Dig Dis Sci 1993; 38: 321-7. [ Links ]
10. Carlson S, Craig RM. D- Xylose hydrogen breath tests compared to absorption kinetics in human patients with and without malabsorption. Dig Dis Sci 1995; 40: 2259-67. [ Links ]
11. Craig RM, Atkinson AJ. D-xylose testing: a review. Gastroenterology 1988; 95: 223-31. [ Links ]
12. Casellas F, Sardi J, de Torres I, Malagelada JR. Hydrogen breath test with D-xylose for celiac disease screening is as useful in the elderly as in other age groups. Dig Dis Sci 2001; 46: 2201-5. [ Links ]
13. Mee AS, Burke M, Vallon AG, Newman J, Cotton PB. Small bowel biopsy for malabsorption: comparison of the diagnostic adequacy of endoscopic forceps and capsule biopsy specimens. Br Med J 1985; 291: 769. [ Links ]
14. Linaker BD, Calam J. Jejunal biopsy with the Watson capsule and perforation in the elderly. Gastroenterology 1978; 75: 723-5. [ Links ]
15. Linaker BD, Calam J. Is jejunal biopsy valuable in the elderly? Age Ageing 1978; 7: 244. [ Links ]
16. Casellas F, de Torres I, Malagelada JR. Follow-up of celiac disease with the D-xylose breath test. Dig Dis Sci 1996; 41: 2106-11. [ Links ]
17. Casellas F, Guarner L, Vaquero E, Antolín M, de Gracia X, Malagelada JR. Hydrogen breath test with glucose in exocrine pancreatic insufficiency. Pancreas 1998; 16: 481-6. [ Links ]
18. Clinical Practice and Practice Economics Committee. American Gastroenterological Association Medical Position Statement: Celiac Sprue. Gastroenterology 2001; 120: 1522-5. [ Links ]
19. Hankey GL, Holmes GKT. Coeliac disease in the elderly. Gut 1994; 35: 65-7 [ Links ]
20. Gasbarrini G, Ciccocioppo R, de Vitis I, Corazza GR. Coeliac disease in the elderly. Gerontology 2001; 47: 306-10. [ Links ]
21. Tai V, Crowe M, O'Keeffe S. Celiac disease in older people. J Am Geriatrics Soc 2000; 48: 1690-6. [ Links ] ]]>