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produced in large amounts by H. pylori. Though the sensitiv- ities and specificities are fairly high with all modalities, some of them possess certain drawbacks. Considered by some as the gold standard, culture of the organism is a tedious, lengthy method, taking as long as 3 to 6 days for a definitive result that may be negative even with the histologic presence of the organism (J Clin Pathol 1985;38:1127-31). Histologic tech- niques with stains such as the Warthin-Starry silver, Giemsa, and hematoxylin and eosin are fairly accurate; however, they too may require from several hours to 2 to 3 days before results are available (Mayo Clin Proc 1987;62:265-8). Serologic evi- dence for H. pylori has its inherent disadvantages of the inability to determine the stage of infection and histologic presence of H. pylori, potential cross-reactivity, and current lack of knowledge concerning the natural history of H. pylori infection. Urea breath tests with l3C and 14C have been shown to be highly accurate methods for diagnosing H. pylori (Lancet 1987;1:1174-7; J Nucl Med 1988;29:1-16). However, both tests take in excess of 20 min to perform and the l3C breath test requires the use of a mass spectrometer, whereas l4C is itself a radioactive substance not currently licensed for use in humans. These drawbacks explain why the urea breath tests are not more readily available. RUTs, in contrast, are highly accurate, simple, and inexpensive, which makes them very practical for clinical use. The results obtained by Thilliainayagam et al. are very impressive in this regard. Furthermore, one could perhaps predict that the sensitivity of the test would have been even higher had results been assessed a few minutes past their 1- min guideline. Minor criticisms of the study include the use of culture as the gold standard and gram stain, which has been shown to be inferior to the Warthin-Starry silver and Giemsa stains, as the histologic technique. In addition, it would have been more useful to have compared the ultra- rapid urease test with the commercially available CLO test'" rather than with Christensen's urea broth. Nonetheless, the accuracy of the authors' test is comparable to existing RUTs with the added benefit of speed. Virtually all of the RUTs demonstrate greater than 90% accuracy, sensitivity, specificity, and predictive values. However, turnaround time for results varies with a majority, and results are not always available by the time the patient leaves the physician's office. For example, Marshall et al. (Am J Gas- troenteroI1987;82:210) showed that although 75% of biopsy specimens containing H. pylori gave a positive CLO test after 20 min, it may take up to 24 hours before all H. pylori- containing specimens become positive. Similar incubation times are seen with other RUTs. One may wonder whether the availability of a test result within 1 min as opposed to 24 hours is clinically meaningful. One obvious advantage is efficiency. Treatment can be initi- ated earlier, making phone calls and follow-up visits unnec- essary. The immediacy of the result also minimizes the ad- mittedly small, but potential, possibility of the mishandling or loss of specimens and inadvertent failure to follow-up on test results. Finally, patient satisfaction is increased as many patients who present for endoscopy expect decisions on diag- nosis and therapy to be made after the procedure. RUTs appear to be emerging as the primary diagnostic method for H. pylori infection. The accuracy, simplicity, avail- ability, and cost make it ideal for widespread clinical use. Thilliainayagam et al. have now introduced a modified RUT VOLUME 38, NO.1, 1992 possessing those same features, but in addition, providing more rapid results, thereby allowing earlier treatment inter- vention. JOSEPH KIM JAMES S. BARTHEL Columbia, Missouri Biliary patency imaging after endoscopic retrograde sphincterotomy with gallbladder in situ HOLBROOK RF, JACOBSON FL, ET AL. Arch Surg 1991;126:738-42 The authors performed HIDA scans in 62 patients who had previously undergone ERCP and sphincter- otomy for pancreato-biliary disease with their gall- bladders in situ. All of the patients had patent cystic ducts as evidenced by balloon cholangiography. Twenty-nine percent of the patients had a non-visu- alizing HIDA scan, and 71 % were normal or delayed. Five ofthe patients (39%) without HIDA visualization and gallstones subsequently required surgery, whereas only 1 of 21 patients with gallstones and cystic duct visualization on HIDA scan required surgery. Follow- up was more than 6 months in all patients. This is a small, but important, prospective study that used a combination of balloon cholangiography and HIDA scanning as a means of addressing the problem of predicting which patients with cholelithiasis are likely to require surgery. Com- mon duct and cystic duct visualization was achieved after clearing the biliary tree. Visualization was aided by the use of balloon cholangiography. Those who had no evidence for gallstones (25 patients) did not require surgery. Five of these did not visualize on HIDA scanning. The failure to visualize the cystic duct after sphincterotomy is fraught with interpretative difficulties. The authors argue that those who do visualize their gallbladders have a low resistance to filling with HIDA agent. Those who do not, have a gradient between the gallbladder and the common bile duct. This predisposes to cholecystitis. It is of note that three of the six patients in this category developed either gangrene or empyemas of the gallbladder. All of the patients in the study were regarded as unsuitable for elective surgery on the basis of age. Thus, the strategy of following ERCP, sphincterotomy, and cholangiography with a HIDA scan provides an approach that may have useful predictive value in a population that is a poor surgical risk. Those with gallstones and non-filling of the gallbladder have a 39% chance of needing surgery within 16 months. DAVID R. CAVE Boston, Massachusetts Carcinoma and DNA aneuploidy in Crohn's colitis-a histological and flow cytometric study LOFBERG R, BROSTROM 0, KARLEN P, ET AL. Gut 1991;32:900-4 The authors studied 24 patients with long-standing Crohn's colitis (more than 7 years), examining them 107
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produced in large amounts by H. pylori. Though the sensitivities and specificities are fairly high with all modalities, someof them possess certain drawbacks. Considered by some as thegold standard, culture of the organism is a tedious, lengthymethod, taking as long as 3 to 6 days for a definitive resultthat may be negative even with the histologic presence of theorganism (J Clin Pathol 1985;38:1127-31). Histologic techniques with stains such as the Warthin-Starry silver, Giemsa,and hematoxylin and eosin are fairly accurate; however, theytoo may require from several hours to 2 to 3 days before resultsare available (Mayo Clin Proc 1987;62:265-8). Serologic evidence for H. pylori has its inherent disadvantages of theinability to determine the stage of infection and histologicpresence of H. pylori, potential cross-reactivity, and currentlack of knowledge concerning the natural history of H. pyloriinfection. Urea breath tests with l3C and 14C have been shownto be highly accurate methods for diagnosing H. pylori (Lancet1987;1:1174-7; J Nucl Med 1988;29:1-16). However, bothtests take in excess of 20 min to perform and the l3C breathtest requires the use of a mass spectrometer, whereas l4C isitself a radioactive substance not currently licensed for use inhumans. These drawbacks explain why the urea breath testsare not more readily available. RUTs, in contrast, are highlyaccurate, simple, and inexpensive, which makes them verypractical for clinical use.
The results obtained by Thilliainayagam et al. are veryimpressive in this regard. Furthermore, one could perhapspredict that the sensitivity of the test would have been evenhigher had results been assessed a few minutes past their 1min guideline. Minor criticisms of the study include the useof culture as the gold standard and gram stain, which hasbeen shown to be inferior to the Warthin-Starry silver andGiemsa stains, as the histologic technique. In addition, itwould have been more useful to have compared the ultrarapid urease test with the commercially available CLO test'"rather than with Christensen's urea broth.
Nonetheless, the accuracy of the authors' test is comparableto existing RUTs with the added benefit of speed. Virtuallyall of the RUTs demonstrate greater than 90% accuracy,sensitivity, specificity, and predictive values. However,turnaround time for results varies with a majority, and resultsare not always available by the time the patient leaves thephysician's office. For example, Marshall et al. (Am J GastroenteroI1987;82:210) showed that although 75% of biopsyspecimens containing H. pylori gave a positive CLO test after20 min, it may take up to 24 hours before all H. pyloricontaining specimens become positive. Similar incubationtimes are seen with other RUTs.
One may wonder whether the availability of a test resultwithin 1 min as opposed to 24 hours is clinically meaningful.One obvious advantage is efficiency. Treatment can be initiated earlier, making phone calls and follow-up visits unnecessary. The immediacy of the result also minimizes the admittedly small, but potential, possibility of the mishandling orloss of specimens and inadvertent failure to follow-up on testresults. Finally, patient satisfaction is increased as manypatients who present for endoscopy expect decisions on diagnosis and therapy to be made after the procedure.
RUTs appear to be emerging as the primary diagnosticmethod for H. pylori infection. The accuracy, simplicity, availability, and cost make it ideal for widespread clinical use.Thilliainayagam et al. have now introduced a modified RUT
VOLUME 38, NO.1, 1992
possessing those same features, but in addition, providingmore rapid results, thereby allowing earlier treatment intervention.
JOSEPH KIM
JAMES S. BARTHEL
Columbia, Missouri
Biliary patency imaging after endoscopicretrograde sphincterotomy with gallbladder insitu
HOLBROOK RF, JACOBSON FL, ET AL.Arch Surg 1991;126:738-42
The authors performed HIDA scans in 62 patientswho had previously undergone ERCP and sphincterotomy for pancreato-biliary disease with their gallbladders in situ. All of the patients had patent cysticducts as evidenced by balloon cholangiography.Twenty-nine percent of the patients had a non-visualizing HIDA scan, and 71% were normal or delayed.Five of the patients (39%) without HIDA visualizationand gallstones subsequently required surgery, whereasonly 1 of 21 patients with gallstones and cystic ductvisualization on HIDA scan required surgery. Followup was more than 6 months in all patients.
This is a small, but important, prospective study that used acombination of balloon cholangiography and HIDA scanningas a means of addressing the problem of predicting whichpatients with cholelithiasis are likely to require surgery. Common duct and cystic duct visualization was achieved afterclearing the biliary tree. Visualization was aided by the use ofballoon cholangiography. Those who had no evidence forgallstones (25 patients) did not require surgery. Five of thesedid not visualize on HIDA scanning.
The failure to visualize the cystic duct after sphincterotomyis fraught with interpretative difficulties. The authors arguethat those who do visualize their gallbladders have a lowresistance to filling with HIDA agent. Those who do not, havea gradient between the gallbladder and the common bile duct.This predisposes to cholecystitis. It is of note that three of thesix patients in this category developed either gangrene orempyemas of the gallbladder. All of the patients in the studywere regarded as unsuitable for elective surgery on the basisof age. Thus, the strategy of following ERCP, sphincterotomy,and cholangiography with a HIDA scan provides an approachthat may have useful predictive value in a population that isa poor surgical risk. Those with gallstones and non-filling ofthe gallbladder have a 39% chance of needing surgery within16 months.
DAVID R. CAVE
Boston, Massachusetts
Carcinoma and DNA aneuploidy in Crohn'scolitis-a histological and flow cytometricstudy
LOFBERG R, BROSTROM 0, KARLEN P, ET AL.
Gut 1991;32:900-4
The authors studied 24 patients with long-standingCrohn's colitis (more than 7 years), examining them
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prospectively by means of colonoscopy and biopsy in10 pre-determined locations of the entire colon. Thebiopsy specimens were examined both histopathologically and by DNA flow cytometry.
Dysplasia was not detected in any patient, whereasDNA aneuploidy was found in three (incidence of12.5%). One of these subsequently developed a carcinoma in the ascending colon. The authors concludethat dysplasia is rare in patients with Crohn's colitis,but findings of DNA aneuploidy warrant vigilance infollow-up and careful consideration of colectomy.
Flow cytometry has been used for some years for the study ofthe DNA content of biopsy samples taken during endoscopicexaminations. Cells containing a normal quantity of DNA areknown as "diploid," whereas those with an abnormal quantityare "aneuploid." First used for blood disease, this techniquewas then applied to the study of solid tumors and, in particular, of digestive tract tumors. Attempts were made to findprognostic indicators for colorectal tumors, but the overallresults were disappointing. The same can be said for adenomatous polyps.
Flow cytometry has also been used, with interesting results,in pre-cancerous disease of the digestive tract. As far asBarrett's esophagus is concerned, the repeated demonstrationof aneuploidy in follow-up endoscopies seems to be associatedwith high-grade dysplasia. Patients with these characteristicsrequire closer endoscopic surveillance.
Flow cytometry has been evaluated in inflammatory boweldisease. In patients with long-standing ulcerative colitis,aneuploidy was found in 9% of patients (Lofberg et al. Gut1987;28:1101-6). A significant correlation was found betweenthe grading of dysplasia and the incidence ofDNA aneuploidy;dysplasia and aneuploidy were also shown to be positivelyassociated with malignant change (Melville et al. Gastroenterology 1988;95:668-75).
In the most recent study of Lofberg et al., the method wasapplied to Crohn's colitis. The study seems to demonstratethe possibility that, like ulcerative colitis, long-standing colonic Crohn's disease may also be complicated by the development of carcinomas of the colon and the rectum and thatthis risk is greater ifaneuploidy is found in the mucosal biopsyspecimens. Unlike ulcerative colitis, dysplasia is rare in patients with Crohn's colitis. If colonoscopic surveillance isconsidered necessary in Crohn's colitis, a flow cytometricstudy of colonic biopsies might identify patients with a highrisk of developing a carcinoma better than a histological studyfor dysplasia. Other prospective studies are, however, necessary before this diagnostic strategy can be recommended.
1I0NELLO GANDOLFIBologna, Italy
Incidence of heterotopic gastric mucosa in theupper esophagus
BORHAN-MANESH F, FARNUM JB
Gut 1991;32:968-72This prospective study evaluated the incidence andsignificance of heterotopic gastric mucosa in the upper
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esophagus. The study was composed of 634 patientsreferred for upper endoscopy, of whom 64 (10%) werefound to have heterotopic gastric mucosal patches.These lesions ranged in size from 0.2 to 0.3 cm up to3.0 to 5.0 cm (28% were less than 1 cm in diameter).The patches were found just below the upper esophageal sphincter with occasional proximal extensionabove the sphincter. Endoscopy results showed thatthe patches were single in 29 patients (45.3%), multiple on opposite sides ("kissing patches") in 26 patients(40.6%), and multiple but one-sided in 9 patients(14.0%). Twenty-two patients (34.4%) had endoscopicevidence for gastroesophageal reflux disease in thedistal esophagus, and five (7.8%) of these demonstrated Barrett's intestinal metaplasia on biopsy (fromthe distal esophagus). Of those 570 patients withoutheterotopic gastric mucosal patches, evidence for reflux esophagitis was found in 217 (38.1%) and Barrett's epithelium was found in 40 (7.0%).
All of the 61 patients whose proximal heterotopicgastric mucosal patches were biopsied showed a basicfundic-type or antral-type gastric mucosa with fewvariations. Twenty-eight patients showed a near-normal body or fundic-type mucosa with deep glandsshowing uppermost parietal cells intermixed withmore basilar chief cells. Eleven patients demonstratedbiopsy findings more suggestive of antral mucosa (absence of chief cells, less than 5% parietal cells),whereas 15 patients showed a "transitional"-type mucosa with features of antral mucosa superimposed onthe fundic glands. Biopsies of the heterotopic gastricmucosa also varied by the amount of interveningfibrous tissue between the glands. Although, in general' inflammation was not prominent in these lesions,it was found more often associated with the antraltype mucosa. No intestinal metaplasia was found onany of the heterotopic gastric mucosal biopsies. Thefive patients who demonstrated Barrett's columnarepithelium in the distal esophagus all showed cardiactype columnar mucosa with variable intestinal metaplasia in the lower esophagus. Of interest was thehistologic finding of chronic peptic esophagitis on allof the 55 biopsies taken from the squamous epitheliumadjacent to the heterotopic gastric mucosal patches.The degree of esophagitis varied (67.3%had moderateto-severe), with greater severity being inversely related to distance from the patches.
The authors conclude that this lesion is more common than was suggested by previous endoscopic studies and may be easily missed by less-than-diligenttechnique at the time of upper endoscopy. Pathogenesis seems most consistent with a congenital origin,as supported by its location in the proximal esophagus,lack of correlation with reflux esophagitis, and theknown pattern of fetal re-epithelialization of the
GASTROINTESTINAL ENDOSCOPY
