Antioxidant properties and preliminary evaluation of phytochemical composition of different anatomical parts of amaranth.

Antioxidant properties of amaranth extracts isolated sequentially by acetone and methanol/water from defatted plant leaves, flowers, stems and seeds were assessed by ABTS(+•), DPPH(•), ORAC and total phenols content (TPC) assays. In addition, antioxidant properties of solid plant material were evaluated by the direct QUENCHER method using the same assays. Leaves and flowers of amaranth as well as their extracts possessed the highest antioxidant activities. Radical scavenging capacity in ABTS(+•) assay for leaves, flowers, stems and seeds evaluated by QUENCHER method were 144.24 ± 2.41, 112.33 ± 7.45, 19.05 ± 1.13 and 21.82 ± 1.06 µmol trolox equivalents in 1 g of dry weight, respectively. On-line HPLC-DPPH(•) assay was used to determine the activity of separated compounds and it was observed that rutin was the main radical scavenger in amaranth extracts. Preliminary screening of extract composition was performed by UPLC/ESI-QTOF-MS and rutin, nicotiflorin, isoquercitrin, 4-hydroxybenzoic and p-coumaric acids were identified by measuring their accurate mass and retention time.

Nutritional Components of Amaranth Seeds and Vegetables: A Review on Composition, Properties, and Uses.

A few decades ago Amaranthus was rediscovered as a most promising plant genus that may provide high-quality protein, unsaturated oil, and various other valuable constituents. Since then research has focused on various Amaranthus spp. and has been rapidly expanding, and a large number of reports have been published. Several review articles focusing on different aspects, such as botanical, agrotechnological, compositional, biological, chemical, and technological properties, as well as applications and health effects, have also been published since then. This comprehensive review is focused on amaranth composition, antioxidant properties, applications, and processing. The composition includes macrocomponets (lipids, proteins, carbohydrates, and dietary fiber) and other important constituents, such as squalene, tocopherols, phenolic compounds, phytates, and vitamins. These aspects of amaranth studies have not been comprehensively reviewed for a long time.

Floral Markers in Honey of Various Botanical and Geographic Origins: A Review.

In view of the expanding global market, authentication and characterization of botanical and geographic origins of honey has become a more important task than ever. Many studies have been performed with the aim of evaluating the possibilities to characterize honey samples of various origins by using specific chemical marker compounds. These have been identified and quantified for numerous honey samples. This article is aimed at summarizing the studies carried out during the last 2 decades. An attempt is made to find useful chemical markers for unifloral honey, based on the analysis of the compositional data of honey volatile compounds, phenolic acids, flavonoids, carbohydrates, amino acids, and some other constituents. This review demonstrates that currently it is rather difficult to find reliable chemical markers for the discrimination of honey collected from different floral sources because the chemical composition of honey also depends on several other factors, such as geographic origin, collection season, mode of storage, bee species, and even interactions between chemical compounds and enzymes in the honey. Therefore, some publications from the reviewed period have reported different floral markers for honey of the same floral origin. In addition, the results of chemical analyses of honey constituents may also depend on sample preparation and analysis techniques. Consequently, a more reliable characterization of honey requires the determination of more than a single class of compounds, preferably in combination with modern data management of the results, for example, principal component analysis or cluster analysis.

Characterization of steam volatiles in the essential oil of black currant buds and the antioxidant properties of different bud extracts.

Currently essential oil from black currant ( Ribes nigrum L.) buds is mainly used as a valuable perfumery ingredient. This study reports more comprehensive characterization of dormant buds of various black currant ( Ribes nigrum L.) cultivars which are grown in Northern European countries. Essential oils were isolated from the buds by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), GC-flame ionization detection (GC-FID), and GC--olfactometry (GC-O). The most abundant compounds in black currant bud essential oil were sabinene, delta-3-carene, and terpinolene. The most frequent descriptors of the essential oil components assessed by GC-O were "woody", "terpene", "fruity", "sweet", "citrus", "herbaceous", "pine", "green", "oily", "herbal", and "musty". The residues obtained after hydrodistillation were separated into liquid and solid fractions. The solid fraction was dried and extracted with acetone (AE), while the liquid fraction (water extract) was divided in two parts, one of which was spray-dried (SDWF extracts) and the other freeze-dried (FDWF extract). In addition, a portion of whole frozen buds was extracted with methanol (ME). The radical scavenging capacity (RSC) of black currant bud extracts varied in a wide range; in the DPPH * reaction system FDWF at the applied concentration scavenged 43-79%; SDWF, 54-80%; AE, 16-36%; ME, 42-60% of radicals; while in the ABTS *+ reaction system the RSC was 39-72, 38-53, 1-5, and 30-49%, respectively. The total amount of phenolic compounds expressed in gallic acid equivalents in FDWF varied in the range of 132-192 mg/g; in SDWF, 140-209 mg/g; in AE, 49-107 mg/g; and in ME extracts, 111-180 mg/g.

HPLC determination of the composition and stability of blackcurrant anthocyanins.

High-performance liquid chromatography with UV and mass spectrometry detectors are used to monitor the composition and stability of anthocyanins in blackcurrants harvested from different Ribes nigrum breeds at various ripeness phases. The highest amounts of pigments are found in overripe berries. The concentration of anthocyanins is higher in the berries of late blackcurrant breeds (Vakariai and Ben Alder). Delphinidin- 3-rutinoside is the dominant component in the reddish color berries (onset of ripening), and cyanidin-3-rutinoside is a major pigment in the black ones (ripe berries). Studies of the effect of temperature and light on the stability of the main pigments in blackcurrants show that aqueous solution prepared from a dry colorant is more stable when compared with the liquid water and ethanol extracts of coloring substances. Cyanidin-3-rutinoside is found to be the most thermally stable anthocyanin.

Determination of rosmarinic acid in sage and borage leaves by high-performance liquid chromatography with different detection methods.

Rosmarinic acid is separated and identified on the basis of high-performance liquid chromatography (HPLC)-UV-mass spectrometry data in 80% methanol in water extracts from the leaves of Salvia species (S. officinalis, S. glutinosa, S. aethiopis, S. sclarea, and Borago officinalis) as a dominant radical scavenger towards the 2,2'-diphenyl-1-picrylhydrazyl (DPPH*) stable radical in HPLC-DPPH* system. The content of rosmarinic acid in the plants is calibrated and quantitated from chromatograms obtained by UV detection at 280 nm. The concentration ranges from 13.3 to 47.3 mg of the phenolic acid per gram dried leaves of all plants is tested. S. glutinosa and S. sclarea have the highest concentration of rosmarinic acid. The amount of rosmarinic acid in borage leaves is similar compared with Salvia officinalis (15 mg/g). The HPLC-DPPH* system is calibrated for quantitative DPPH* scavenging assessment of rosmarinic acid. The results reveal excellent correlation (r2 = 0.98) between the rosmarinic acid concentration and antiradical activity.

Observer variation in the diagnosis of superficial oesophageal adenocarcinoma.

BACKGROUND AND AIMS: When to perform oesophagectomy for neoplastic progression in Barrett's oesophagus is controversial. Some resect for high grade dysplasia whereas others defer treatment until intramucosal adenocarcinoma is diagnosed. Interobserver agreement for a diagnosis of high grade dysplasia or intramucosal adenocarcinoma remains unknown and may have therapeutic implications. METHODS: Histological slides from 75 oesophagectomy specimens with high grade dysplasia or T(1) adenocarcinoma were blindly reviewed by two gastrointestinal pathologists and one general surgical pathologist, and classified as high grade dysplasia, intramucosal adenocarcinoma, or submucosal adenocarcinoma. A subsequent re-review of all 75 cases by the same observers following establishment of uniform histological criteria was undertaken. Interobserver agreement was determined by kappa statistics. Coefficients <0.21, 0.21-0.40, 0.41-0.60, 0.61-0.80, and >0.80 were considered poor, fair, moderate, good, and very good agreement, respectively. RESULTS: Interobserver agreement among all pathologists and between gastrointestinal pathologists when comparing high grade dysplasia with intramucosal adenocarcinoma was only fair (k=0.42; 0.56, respectively) and did not substantially improve on subsequent re-evaluation following establishment of uniform histological criteria (K=0.50; 0.61, respectively). CONCLUSIONS: When evaluating resection specimens and after implementation of uniform histological criteria, even experienced gastrointestinal pathologists frequently disagree on a diagnosis of high grade dysplasia versus intramucosal adenocarcinoma. Treatment strategies based on the histological distinction of high grade dysplasia from intramucosal adenocarcinoma using limited biopsy specimens should be re-evaluated.

Angiogenic polypoid proliferation adjacent to ileal carcinoid tumors: a nonspecific finding related to mucosal prolapse.

Case reports have highlighted angiogenic polypoid proliferation in the mucosa adjacent to ileal carcinoid tumors, describing them as granulation tissue polyposis and florid angiogenesis. Some authors have proposed that the ileal carcinoid tumors themselves produce growth factors that cause the change. The purpose of this study was to determine the frequency of angiogenic polypoid proliferation in a large cohort of resected ileal carcinoid tumors compared with control groups. Search of the Cleveland Clinic and Summa Health System pathology files (1985 to 1999) yielded 65 resected ileal carcinoid tumors. Mucosal abnormalities adjacent to the ileal carcinoid tumors were graded 0 to 4+. Twenty ileal resection margins from colonic carcinoma cases served as normal controls. Ileal mucosa adjacent to 22 noncarcinoid neoplasms were also examined. The mucosa adjacent to 54/65 ileal carcinoid tumors (83%) showed mucosal abnormalities (vs. 3/20 normal controls), including mucosal edema, capillary ectasia, muscularis mucosae hypertrophy, fibrosis/smooth muscle proliferation within the lamina propria, club-shaped villi, and intramucosal capillary proliferation. Forty ileal carcinoid tumor cases (61%) showed some degree of angiogenic polypoid proliferation characterized by club-shaped villi and prominent intramucosal capillaries, with 17 (26%) graded as 3+ or 4+. Angiogenic polypoid proliferation was associated with hypertrophy of the muscularis mucosae, lamina proprial fibrosis/smooth muscle proliferation, and capillary ectasia similar to that described with gastrointestinal mucosal trauma/prolapse. This trauma/prolapse change was identified in 45 cases (69%) and was graded 3+ or 4+ in 23 (35%). Seventeen (77%) of the noncarcinoid neoplasms showed trauma/prolapse changes, with 7 (32%) graded as 3+ or 4+. Angiogenic polypoid proliferation also correlated with trauma/prolapse change in the noncarcinoid neoplasm controls. Neither APP (P =.24) nor the prolapse changes (P =.33) were found to be statistically different between the two tumor groups. Angiogenic polypoid proliferation of the adjacent ileal mucosa is common in patients with ileal carcinoid tumors and with noncarcinoid neoplasms. Angiogenic polypoid proliferation almost invariably coexists with fibromuscular change and capillary ectasia within the lamina propria, suggesting that mucosal trauma/prolapse plays a role in the histogenesis. The association of angiogenic polypoid proliferation with a variety of different neoplasms makes it unlikely that the tumors themselves secrete growth factors.

Endoscopic and histologic evaluation together with symptom assessment are required to diagnose pouchitis.

BACKGROUND & AIMS: Pouchitis often is diagnosed based on symptoms alone. In this study, we evaluate whether symptoms correlate with endoscopic and histologic findings in patients with ulcerative colitis and an ileal pouch-anal anastomosis. METHODS: Symptoms, endoscopy, and histology were assessed in 46 patients using Pouchitis Disease Activity Index (PDAI). Patients were classified as either having pouchitis (PDAI score > or =7; N = 22) or as not having pouchitis (PDAI score <7; N = 24). RESULTS: Patients with pouchitis had significantly higher mean total PDAI scores, symptom scores, endoscopy scores, and histology scores. There was a similar magnitude of contribution of each component score to the total PDAI for the pouchitis group. Of note, 25% of patients with symptoms suggestive of pouchitis did not meet the PDAI diagnostic criteria for pouchitis. In both groups, the correlation coefficients between symptom, endoscopy, and histology scores were near zero (range, -0.26 to 0.20; P > 0.05). CONCLUSIONS: The symptom, endoscopy, and histology scores each contribute to the PDAI and appear to be independent of each other. Symptoms alone do not reliably diagnose pouchitis.

Methylene blue staining of dysplastic and nondysplastic Barrett's esophagus: an in vivo and ex vivo study.

BACKGROUND AND STUDY AIMS: Methylene blue selectively stains specialized columnar epithelium in Barrett's esophagus with high accuracy. We prospectively evaluated the methylene blue staining properties of dysplastic and nondysplastic Barrett's esophagus and the association of these properties with the risk for dysplasia and cancer. PATIENTS AND METHODS: In a ex vivo study, we mapped, photographed, and sampled esophagectomy specimens with high grade dysplasia and/or early adenocarcinoma before and after methylene blue staining. In a concurrent in vivo study, we performed methylene blue staining and characterized methylene blue stain characteristics. Pathologists estimated the proportion of specialized columnar epithelium in each specimen and graded dysplasia. RESULTS: We examined 551 biopsies from 47 patients with biopsy-proven Barrett's esophagus and 48 sections from five surgical specimens with Barrett's esophagus and dysplasia and early adenocarcinoma. The accuracy of ex vivo and in vivo methylene blue staining for specialized columnar epithelium was 87% and 90%, respectively. It was influenced by the length of Barrett's esophagus, biopsy location, and the presence of esophagitis and/or dysplasia. Light to absent staining (p = 0.01) and moderate to marked heterogeneity (p = 0.01) were significantly associated with high grade dysplasia or cancer in the univariate analysis and in a multivariate model that adjusted for the length of Barrett's esophagus and the presence of a lesion. These staining characteristics were present in all patients with severe dysplasia and/or adenocarcinoma. CONCLUSIONS: Highly dysplastic or malignant Barrett's esophagus stains differently with methylene blue. Increased heterogeneity and decreased methylene blue stain intensity are significant independent predictors of high grade dysplasia and/or cancer. These features may help to direct biopsies in patients without a lesion.

Association of susceptibility locus for inflammatory bowel disease on chromosome 16 with both ulcerative colitis and Crohn's disease.

A susceptibility locus for inflammatory bowel disease (IBD) on chromosome 16 (IBD1) has been linked to Crohn's disease in genome-wide linkage studies. We performed a case-control study with two markers for this locus using leukocyte DNA from 127 Crohn's patients, 83 ulcerative colitis patients, and 74 control patients. Allele, genotype, and haplotype frequencies of the polymerase chain reaction products were determined using autoradiography. Haplotype frequencies differed for ulcerative colitis and Crohn's disease, particularly for haplotype CC (22% ulcerative colitis vs 10% Crohn's disease, P = 0.002 Chi2 = 10.0) and haplotype CD (18% Crohn's disease vs 9% ulcerative colitis, P = 0.025 Chi2 = 5.02). These data demonstrate the association of the IBD1 locus with both ulcerative colitis and Crohn's disease in a group of unrelated IBD patients. The use of such microsatellite markers when combined with others, might help distinguish ulcerative colitis from Crohn's disease in patients with ambiguous clinical and histological features.

The importance of diagnostic accuracy in colonic inflammatory bowel disease.

OBJECTIVE: Crohn's disease (CD) and ulcerative colitis (UC) may both affect the colon. However, in approximately 10-20% of these cases, it is impossible to distinguish between these two entities either clinically or histologically, and a diagnosis of indeterminate colitis (IC) is made. Correct diagnosis is important because surgical treatment and long-term prognosis differ for UC and CD. The purpose of this study was to determine the extent of interobserver agreement among board-certified pathologists and a specialist gastrointestinal (GI) pathologist regarding the histological diagnosis of colonic inflammatory bowel disease (IBD). METHODS: A total of 24 university medical center pathologists from eight institutions evaluated 84 colectomy specimens and 35 sets of biopsy specimens from 119 consecutive patients with colonic IBD. A specialist GI pathologist subsequently reviewed all cases without knowledge of clinical data and prior diagnosis. RESULTS: The GI pathologist's diagnoses differed from the initial diagnoses in 45% of surgical specimens and 54% of biopsy specimens. Of 70 cases initially diagnosed as UC, 30 (43%) were changed to CD or IC, whereas 4 of 23 cases (17%) initially diagnosed as CD were changed to UC or IC. The kappa coefficient for the overall agreement of initial diagnoses with the specialist GI pathologist's diagnoses was -0.01 (p = 0.98). CONCLUSIONS: There is significant interobserver variation in the histological diagnosis of colonic IBD. This may have a profound effect on clinical patient care and, especially, on the choice of operation. More accurate diagnostic criteria are needed to facilitate patient care and to optimize treatment outcome.

Immunohistochemistry in the differential diagnosis of acinar and endocrine pancreatic neoplasms.

Histologic differential diagnosis of acinar cell carcinoma (ACC), mixed acinar-endocrine cell carcinoma (MAEC), and pancreatic endocrine tumors (PET) can be difficult but is important because of differences in their clinical behavior. This study investigates the utility of immunohistochemistry (IHC) in this differential diagnosis using immunohistochemical stains that are available in most laboratories. IHC was performed on paraffin-embedded tissue in ACC (n = 6), MAEC (n = 2), and PET (n = 13), using synaptophysin (SYN), chromogranin (CHR), chymotrypsin (CHY), and alpha-1-antitrypsin (AAT). Electron microscopy (EM) was performed in all cases to confirm the diagnosis. Long-term follow-up and death of disease (DOD) was known in all patients. The ACCs stained as follows: CHY (4/6), AAT (3/6), SYN (4/6); CHR was negative in all cases. Both cases of MAEC stained with CHY, AAT, and SYN (2/2); CHR was negative. PET stained as follows: SYN (13/13), CHR (8/13), CHY (4/13), AAT (5/13). In the ACC/ MAEC group, six of eight patients were DOD at mean follow-up of 11 months. Among the PET, two of 16 patients were DOD at mean follow-up of 37 months. Considerable immunophenotypic overlap exists between ACC, MAEC, and PET. Consequently, one can neither confirm nor rule out a diagnosis of ACC or MAEC using generally available immunohistochemical stains alone. These findings support a role for EM in the evaluation of exocrine and endocrine pancreatic neoplasms.

Short- and long-term follow-up of treatment for lymphocytic and collagenous colitis.

Collagenous colitis and lymphocytic colitis cause chronic watery diarrhea. Multiple therapies have been found to improve symptoms but there have been few long-term follow-up studies. Our goal was to obtain long-term clinical follow-up on a cohort of patients with independently confirmed typical histopathologic changes. Pathology slides from 32 cases of collagenous or lymphocytic colitis patients from 1988-1992 were independently reviewed. Twenty-five cases were confirmed by both groups of pathologist as collagenous or lymphocytic colitis. For these 25 patients, charts were reviewed and telephone follow-up interviews were performed in 1992 and 1995. Seven of 32 (22%) of the original cases were not confirmed on independent pathologic interpretation. A 15.8% discordance rate was found between the different groups of pathologists. Patient demographics were similar to previously published reports except one-half of our patients had diarrhea of only 6 months or less. Eighty-one percent of patients receiving 5-ASA agents reported improvement as well as 100% of those receiving prednisone. At 23 month follow-up 86% of patients reported improvement in diarrhea and only 32% required routine medications. At 47 month follow-up all patients reported improved diarrhea and only 29% required routine medications. Collagenous and lymphocytic colitis can sometimes be identified in patients with relatively brief duration diarrhea. Clinical parameters and response to therapy are similar for collagenous or lymphocytic colitis. Most patients with lymphocytic and collagenous colitis improve with therapy such as 5-ASA preparations or steroids. Over a follow-up period of several years, most patients have improvement in diarrhea and generally do not require maintenance medications. Independent pathologic confirmation of the diagnosis should be obtained in patients not responding to therapy.

Use of a microsatellite marker in predicting dysplasia in ulcerative colitis.

BACKGROUND: Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer. The current screening protocol involves an annual colonoscopy and biopsy after the patient has had the disease for 8 years. This, however, does not prevent the development of colorectal cancer. HYPOTHESIS: A microsatellite marker for IBD1 may identify individuals who are at greater risk of developing dysplasia and therefore colorectal cancer. DESIGN: Case-control study. SETTING: Single surgical practice. PATIENTS AND METHODS: DNA was extracted from peripheral leukocytes of 152 patients: 22 with UC and dysplasia; 48 with UC and no dysplasia; 24 with colorectal cancer; and 58 with noninflammatory bowel disease, nonmalignant gastrointestinal tract disease who were used as control patients. A microsatellite marker for IBD1 (D16S541) was amplified by polymerase chain reaction. Genotypes were identified using autoradiography. RESULTS: Six alleles and 15 genotypes were identified for marker D 16S541. Genotype CC was found in 33% (8/24) of cancer patients but only 12% (7/58) of controls (chi2 = 5.5; P = .02). Thirty-two percent (7/22) of patients with dysplastic UC also had this genotype, whereas only 8% (4/ 48) of patients with nondysplastic UC had the genotype (chi2 = 4.6; P = .03; vs controls: chi2 = 3.1; P = .08). CONCLUSIONS: This microsatellite marker for IBD1, when combined with other markers, has the potential to be used as a screening tool for colorectal cancer and dysplasia in patients with UC. Such a marker would be of particular use in improving the sensitivity and specificity of the current screening protocol for dysplasia and colorectal cancer for patients with UC.

Methylene blue-directed biopsies improve detection of intestinal metaplasia and dysplasia in Barrett's esophagus.

BACKGROUND: Endoscopically applied methylene blue selectively stains specialized columnar epithelium in Barrett's esophagus. METHODS: The diagnostic yield and cost of cancer surveillance in patients with Barrett's esophagus using methylene blue-directed biopsies (MBDB) were compared with surveillance using a "jumbo" random biopsy technique in a prospective, sequential, controlled trial. Esophagogastroduodenoscopy was performed with either MBDB or random biopsy in a randomized sequence. The proportions of various types of epithelia in each biopsy were estimated and dysplasia was graded in a blinded fashion. RESULTS: Forty-three patients with short- (n = 8), limited- (n = 10), and long-segment (n = 25) Barrett's esophagus were studied. Using MBDB technique, the average number of biopsies obtained per patient was significantly lower and the proportion of specialized columnar epithelium in each specimen was significantly higher compared with random biopsy. Dysplasia or cancer was diagnosed in significantly more MBDB specimens (12% vs. 6%, p = 0.004). Despite fewer biopsies per patient using MBDB, dysplasia or cancer was diagnosed in significantly more patients (44% vs. 28%, p = 0.03) than by random biopsy technique. MBDB cost less and detected more cancers than random biopsy. CONCLUSIONS: MBDB is a more accurate and cost-effective technique than random biopsy for diagnosing specialized columnar epithelium and dysplasia/cancer, particularly in long-segment Barrett's esophagus.

The diagnosis of low-grade dysplasia in Barrett's esophagus and its implications for disease progression.

OBJECTIVE: The reported risk of progression from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or carcinoma (CA) in Barrett's esophagus varies. However, the validity of a diagnosis of LGD may be questioned because of interobserver variability. METHODS: A search of the Cleveland Clinic Foundation surgical pathology files between 1986 and 1997 yielded biopsy specimens from 43 patients with Barrett's esophagus diagnosed and coded as LGD. Patients with concurrent or prior diagnoses of HGD or carcinoma were excluded. The LGD cases were randomized and blindly reviewed by three gastrointestinal (GI) pathologists along with cases originally diagnosed as Barrett's esophagus without dysplasia (ND; n = 28), indefinite for dysplasia (IND; n = 14), or HGD (n = 15). Each pathologist classified every biopsy specimen as ND, IND, LGD, or HGD, and interobserver agreements were determined by kappa statistics (K). Follow-up data were available on 25 patients originally diagnosed with LGD. Progression was defined as a subsequent diagnosis of HGD or CA on esophageal biopsy or resection specimens. RESULTS: Agreement between two GI pathologists for a diagnosis of LGD was fair (K = 0.28) and poor (K = 0.21 and -0.04). Individual GI pathologists agreed with the original diagnosis of LGD in 70%, 56%, and 16% of cases. The 25 patients with follow-up included 21 men and four women (mean age, 67 yr) with a mean follow-up of 26 months (range: 2-84 months). Seven patients (28%) with follow-up developed HGD (five patients) or CA (two patients), 2-43 months (median: 11 months) after a diagnosis of LGD. The individual GI pathologists' diagnosis did not correlate with progression. However, when at least two GI pathologists agreed on LGD, there was a significant association with progression (seven of 17 patients, 41%, p = 0.04). When all three GI pathologists agreed on a diagnosis of LGD, four of five patients progressed (p = 0.012). In contrast, of the eight patients with follow-up and no agreement among GI pathologists for a diagnosis of LGD, none progressed. CONCLUSIONS: A high degree of interobserver variability is seen in the histological diagnosis of Barrett's esophagus-related LGD. Although the number of observations is low, a consensus diagnosis of LGD among GI pathologists suggests an increased risk of progression from LGD to HGD or carcinoma.

Incidence and natural history of dysplasia of the anal transitional zone after ileal pouch-anal anastomosis: results of a five-year to ten-year follow-up.

PURPOSE: Preservation of the anal transitional zone during ileal pouch-anal anastomosis is still controversial because of the risk of dysplasia and the theoretical risk of associated cancer. Without long-term follow-up data, the natural history and optimal treatment of anal transitional zone dysplasia are unknown. The aim of this study was to determine the long-term risk of dysplasia in the anal transitional zone and to evaluate the outcome of a conservative management policy for anal transitional zone dysplasia. METHODS: Two hundred ten patients undergoing anal transitional zone-sparing ileal pouch-anal anastomosis for ulcerative or indeterminate colitis between 1987 and 1992 and who were studied with serial anal transitional zone biopsies for at least five years postoperatively were included. Median follow up was 77 (range, 60-124) months. RESULTS: Anal transitional zone dysplasia developed in seven patients 4 to 51 (median, 11) months postoperatively. There was no association with gender, age, preoperative disease duration or extent of colitis, but the risk of anal transitional zone dysplasia was significantly increased in patients with prior cancer or dysplasia in the colon or rectum. Dysplasia was high grade in one and low grade in six. Two patients each with low-grade dysplasia detected on three separate occasions underwent mucosectomy 29 and 38 months after detection of low-grade dysplasia, but no cancer was found. The five other patients with dysplasia on one or two occasions were treated expectantly and were apparently dysplasia-free for a median of 72 (range, 48-100) months. CONCLUSIONS: Anal transitional zone dysplasia after ileal pouch-anal anastomosis is infrequent, is most common in the first two to three years postoperatively and may apparently disappear on repeated biopsy. Anal transitional zone preservation did not lead to the development of cancer in the anal transitional zone after five to ten years of follow-up. Long-term surveillance is recommended to monitor dysplasia. If repeat biopsy confirms persistent dysplasia, anal transitional zone excision with neoileal pouch-anal anastomosis is recommended.

Colonic epithelial lymphocytosis without a thickened subepithelial collagen table: a clinicopathologic study of 40 cases supporting a heterogeneous entity.

Lymphocytic colitis (LC) is classically described as a triad of chronic nonbloody, watery diarrhea, normal or nearly normal endoscopy findings, and colonic epithelial lymphocytosis without a thickened subepithelial collagen table (SECT). It is unknown how often patients with colonic epithelial lymphocytosis without a thickened SECT actually present with this classic triad. Cases diagnosed histologically as lymphocytic or microscopic colitis were reviewed. Criteria for inclusion were the presence of at least 15 surface lymphocytes per 100 epithelial cells and the absence of a thickened SECT (<12 microm). Clinical features and course were recorded by chart review and telephone follow-up. Forty patients met the inclusion criteria, including 25 women and 15 men with a mean age of 63.2 years (range, 25-83 years). Twenty-eight patients had the classic triad and were designated as having classic LC. The other 12 patients fulfilled the histologic criteria but not the clinical or endoscopic criteria for classic LC and were classified as having atypical LC (constipation, five patients; macroscopic colitis at endoscopy, five patients; hematochezia, one patient; and incidental finding, one patient). Clinically, patients with classic LC were predominantly women and had a higher incidence of autoimmune disease (p = 0.03) than did those with atypical LC. Histologically, surface eosinophilia was significantly greater in patients with classic LC (p = 0.04). Twenty patients were using nonsteroidal antiinflammatory drugs at the time of their colonic biopsy. Surface epithelial lymphocyte counts were higher in these patients, particularly in the distal sigmoid colon (p = 0.02). Fourteen patients had associated autoimmune disease, including three patients with sprue diagnosed by small bowel biopsy, all of whom responded to gluten withdrawal. Diarrhea present in 25 patients, without documented evidence of celiac sprue, was self-limited in five, resolved with treatment in three, required intermittent treatment in eight, daily treatment in five, and was refractory to treatment in four. All eight patients who experienced spontaneous or treatment-related symptom resolution had classic LC. No histologic feature correlated with clinical course. In conclusion, our study shows that colonic epithelial lymphocytosis without a thickened SECT is a histologic finding seen in a heterogeneous group of patients. Within this heterogeneous group is a distinct subset of patients who have the classic clinicopathologic triad of LC. This subset of patients has striking similarities to patients with collagenous colitis, lending further support to a close relationship between these two entities. Atypical LC comprises a heterogeneous group and includes patients with idiopathic constipation, coexisting LC and inflammatory bowel disease, and possibly infectious colitides. Because of the clinical heterogeneity among our study population, the descriptive term colonic epithelial lymphocytosis may be a more prudent diagnosis than lymphocytic colitis in the absence of adequate clinical information.