Helen M. Shields

Detection by scanning electron microscopy of a distinctive esophageal surface cell at the junction of squamous and Barrett's epithelium

Metaplastic columnar epithelium replaces the normal squamous epithelium in Barretts esophagus. We characterized the surface epithelial cells of the junction between squamous and Barretts epithelium using scanning electron microscopy and light microscopy. In four biopsy specimens from the squamous-Barretts junction in three patients, we found a distinctive cell type having features intermediate between those of squamous and columnar epithelium. Its distinguishing characteristic is the presence on its surface of two disparate structures not normally present on the same cell in the gastrointestinal tract: microvilli (a scanning electron microscopy feature of glandular epithelium) and intercellular ridges (a scanning electron microscopy feature of squamous mucosa). The surface characteristics of this newly recognized cell were strikingly similar to those of cells found in the transformation zone of the uterine cervix, an area in which squamous epithelium physiologically replaces columnar epithelium. We also examined 28 biopsies of the gastroesophageal junction area from 14 patients with and without a history of heartburn but with no evidence of Barretts esophagus. None of these biosies showed the distinctive cell. We hypothesize that this distinctive cell represents an intermediate step in either the development or the healing of Barretts epithelium, during which surface characteristics of two different cell types, columnar and squamous, coexist on the same cell.

Prospective evaluation of multilayered epithelium in Barrett's esophagus

OBJECTIVE:We recently identified a distinctive type of multilayered epithelium in two patients with Barretts esophagus, which shows morphological characteristics of both squamous and columnar epithelium. This study was performed to prospectively evaluate the prevalence of multilayered epithelium in patients with Barretts esophagus.METHODS:Mucosal biopsies were obtained from the squamocolumnar junction (Z-line) of 58 patients with endoscopic evidence of esophageal columnar epithelium and from the gastroesophageal junction in 21 patients without endoscopic evidence of esophageal columnar epithelium. Specimens were evaluated for the presence of multilayered epithelium and goblet cells.RESULTS:Twenty-four of 58 (41%) of the patients with endoscopic evidence of esophageal columnar epithelium had multilayered epithelium compared with only one of 21 patients (5%) in the control group (p = 0.005). Of the 58 patients in the study group, 43 had goblet cell metaplasia and 15 did not (p < 0.001). Only patients with goblet cell metaplasia had multilayered epithelium. Shorter lengths of columnar epithelium were noted in the 24 patients with goblet cells and multilayered epithelium compared with the 19 patients with goblet cells and no multilayered epithelium (p < 0.05).CONCLUSIONS:Multilayered epithelium is strongly associated with goblet cell metaplasia in patients with endoscopic evidence of esophageal columnar epithelium. These data support the hypothesis that multilayered epithelium may represent a transitional stage in the development of Barretts esophagus.

Scanning electron microscopy of Barrett's epithelium and its correlation with light microscopy and mucin stains

The surface epithelial cells of Barretts esophagus were characterized using quantitative scanning electron microscopy and light microscopy with mucin histochemical stains. Fifty-one biopsy specimens of Barretts esophagus from 15 patients and 31 control specimens of the stomach and intestines from 9 patients were examined. Three distinct surface cell types, in addition to the goblet cell, were recognized in Barretts epithelium: the gastric-like cell in 31% of specimens, which was similar to the normal gastric surface cell by quantitative scanning electron microscopy; the intestinal-like cell in 41%, which was most similar to the normal small intestinal surface cell; and the variant cell in 80%, which had a range of surface features. By light microscopy, all specimens with variant and intestinal-like cells were classified as specialized columnar epithelium. The surface mucous cells in Barretts epithelium displayed a variety of mucin staining patterns with acid nonsulfated (small intestinal-like) mucin present in 90% of specimens and acid sulfated (colonic-like) mucin in 43% of specimens. Quantitative scanning electron microscopy and mucin histochemical stains reveal a striking cellular heterogeneity not apparent by routine light microscopy.

Factors that influence the decision to do an adequate evaluation of a patient with a positive stool for occult blood

OBJECTIVE:The factors that influence the decision to do an adequate evaluation for a positive test for fecal occult blood in a middle-aged or elderly patient are largely unknown. Our study was undertaken to determine whether factors such as the number of positive Hemoccult II card windows, age, gender, family history of colon cancer, the patients concern that he or she might have colon cancer, or history of rectal bleeding influence the evaluation performed.METHOD:A mass screening program for colon cancer was performed using unrehydrated Hemoccult II cards in the Boston area.RESULTS:Among the 23,593 Hemoccult II cards returned to Beth Israel Deaconess Medical Center, cards from 1112 patients (4.7%) were found to be positive for one or more of the six possible card windows. Ninety percent, or 940 patients, over 40 yr of age had follow-up information available. As the number of positive windows increased from one to four, there was a significant trend (p < 0.001) for the adequacy of the evaluation to increase. Family history (p = 0.044) and a patients worry that he or she might have colon cancer (p = 0.003) significantly improved a patients chance for an adequate evaluation.CONCLUSIONS:Hemoccult testing is not followed by an adequate evaluation in a significant proportion of patients. Our study points out for the first time that the number of positive Hemoccult windows significantly influences the decision-making.

Morphological characterization of the squamocolumnar junction of the esophagus in patients with and without Barrett's epithelium

Barretts esophagus is a metaplastic condition in which the normal stratified squamous epithelium of the distal esophagus is replaced by columnar epithelium. Our group has previously characterized a unique surface cell (the “distinctive cell”) at the junction of squamous and Barretts epithelium. This cell is notable for the simultaneous presence on its surface of both squamous and columnar cell features. The aims of our present study were, first, to evaluate prospectively the frequency with which Barretts patients have the distinctive cell at the squamo-Barretts junction; second, to further elucidate the characteristics of the distinctive cell; and third, to perform a combined morphological study of the squamo-Barretts junction using scanning electron microscopy followed by transmission and light microscopy. We divided study patients into two groups: Group I consisted of Barretts patients and group II of non-Barretts control patients. Of eight group I Barretts patients with junctional biopsies, three were noted to have the distinctive cell (37.5%). In contrast, this cell was not observed in any of the group II control patients. Biopsies in control patients as well as Barretts patients without the distinctive cell revealed abrupt squamogastric or squamo-Barretts junctions by scanning electron microscopy and light microscopy. In contrast, biopsies from the Barretts patients with the distinctive cell revealed junctions that were not abrupt and had the distinctive cells overlying normal squamous epithelium. By scanning electron microscopy, the distinctive cells were flattened, polygonal cells with surface microvilli (a columnar cell feature) and were demarcated from one another by shallow depressions, or by intercellular ridges (a squamous cell feature). By transmission electron microscopy, the distinctive cells were cuboidal in shape with abundant apical microvilli and secretory vesicles. We have confirmed that distinctive cells are present in some Barretts patients. This cell is a morphologic hybrid, sharing features of both squamous and columnar cells, and may be analogous to hybrid cells identified in other locations that undergo metaplasia (eg, the human cervix). Its origin may be the result of transformation of multipotential basal cells of squamous epithelial origin. We hypothesize that the distinctive cells may represent an intermediate stage in the development of Barretts epithelium.

A Faculty Development Program to Train Tutors to Be Discussion Leaders Rather Than Facilitators

Purpose During 2003, 2004, and 2005, the role of 70 tutors was changed from that of facilitator to discussion leader, in a preclinical PBL learning course, Gastrointestinal Pathophysiology, by use of three key business school teaching strategies: questions, summaries, and schematics. The purpose of this study was to learn what difference this new approach made. Method During each of the three study years, 171 (2003), 167 (2004), and 170 (2005) students were given Likert-scale attitudinal questionnaires to rate whether their tutors encouraged student direction of the tutorials and whether the summaries and closure schematics benefited their learning. Students’ overall course evaluations and mean USMLE scores were quantitatively analyzed, pre- and postintervention. A variety of statistical tests were used to assess the statistical significance of means at the confidence level of .05. Results In the third year of the program, student ratings indicated that their tutors were significantly better at encouraging student direction of the tutorials than in the first year (P < .05). The students reported that the tutorial made a more important contribution to their learning (P < .05), and the course objectives were better stated (P = .038) and better met (P = .007). Overall satisfaction with the course also improved significantly (P = .006). Part I gastrointestinal system mean scores of the USMLE showed a statistically significant increase in 2005 compared with 2001 or 2002. Conclusions The tutor as a discussion leader who questions, summarizes, and uses schematics to illustrate concepts had a significant and positive impact on learning in tutorials, achieving course objectives, improving overall course satisfaction, and increasing a standardized national exam’s mean score.

Juvenile and adenomatous gastrointestinal polyposis

SummaryThis is the fourth report of a case showing an association between juvenile and adenomatous polyposis. Starting at age 14, this patient underwent multiple polypectomies and gastrointestinal resections over a 15-year period. Although initial biopsies were diagnosed as juvenile polyps, later biopsies showed both adenomatous polyps and large polypoid masses with a mixture of juvenile and adenomatous features. Several typical small hyperplastic polyps were also found in the stomach. This case contrasts with the previous three cases in that the gastrointestinal tract is more widely involved and in that there is an unusual marked hyperplasia of argentaffin-and argyrophil-positive cells. The case reported here strengthens the relation between adenomatous polyposis and juvenile polyposis.

Scanning electron microscopic appearance of chronic ulcerative colitis with and without dysplasia

This study was conducted to determine whether scanning electron microscopy of colonic mucosal biopsy specimens can help to detect dysplasia in patients with chronic ulcerative colitis. In the first phase of the study, using light microscopy as the standard for the diagnosis, the scanning electron microscopic appearance of specimens from patients with chronic ulcerative colitis and control patients was examined. Descriptive criteria were established to identify normal, atrophic, and dysplastic colonic mucosa. In the second phase, quantitative techniques were used to develop more objective criteria for the diagnosis of dysplasia in ulcerative colitis. Twenty-one coded colonic specimens from 11 patients were sequentially examined by scanning electron microscopy and by light microscopy. The three morphometric analyses performed on the surface epithelial cells were number of cells per unit area, number of microvilli per unit area, and percentage of microvilli with a normal width. The cell count and percentage of microvilli with a normal width were significantly reduced in the seven specimens with colonic dysplasia as compared with non-dysplastic tissues. Scanning electron microscopy may serve as an adjunct to light microscopy in the diagnosis of colonic dysplasia.

Occurrence of an Adenocarcinoma at the Choledochoenteric Anastomosis 14 Years After Pancreatoduodenectomy for Benign Disease

A 35-year-old man underwent a pancreatoduodenectomy for what proved to be chronic pancreatitis. He did well until 14 years later, when he presented with right upper quadrant pain and jaundice. At laparotomy, an adenocarcinoma was found in fibrous tissue obstructing the choledochoenteric anastomosis. The exact origin of the tumor, from pancreas or biliary tract, could not be ascertained. This case points out the difficulties in attempting to diagnose the etiology of jaundice in a patient who has had a pancreatoduodenectomy without doing a laparotomy. The importance of this diagnosis lies in the known occurrence of benign strictures at the choledochojejunostomy site after a pancreatoduodenectomy.

Barrett's esophagus: natural history

The following on the natural history of Barretts esophagus (BE) includes commentary on histological sequences of the development of Barrett mucosa; the transformation of esophageal cells from squamous to columnar phenotype; the stages of natural history of dysplasia; the difficulties of predicting progression of dysplasia to adenocarcinoma; the preferable biopsy protocols; the role of Helicobacter pylori infection and gastric atrophy in the risk of BE; the value of decrease of proton pump inhibitor efficacy following eradication of H. pylori; the place of antireflux surgery in the natural history of BE; the newest procedures for the endoscopic detection of early neoplasia; and the essential importance of a good understanding of the natural history for the best management of high‐grade dysplasia.