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R C Haggitt

Publications and source records attributed to R C Haggitt.

At least 73 records · Page 4Linked to original sources
PubMed1989

Progression to cancer in Barrett's esophagus is associated with genomic instability.

Barrett's esophagus is a condition in which metaplastic columnar epithelium replaces squamous esophageal epithelium as a consequence of chronic gastroesophageal reflux. Patients with this condition are at increased risk for the development of adenocarcinoma. To better understand the progression to adenocarcinoma in this disease, we studied abnormalities in DNA content of epithelial cells in Barrett's esophagus. Using flow cytometry, we examined the spatial distribution of abnormal nuclear DNA contents (aneuploidy) in the esophagi of 14 patients with Barrett's adenocarcinoma. Multiple (2 to 14) populations of aneuploid cells were seen in 12 of the 14 cases. Some early carcinomas appeared to be associated with a single aneuploid population of cells. Surrounding dysplastic epithelium often contained multiple, different overlapping aneuploid populations. These data suggest that neoplastic progression in Barret's esophagus is associated with a process of genomic instability which leads to evolution of multiple aneuploid populations, with the ultimate development of a clone of cells capable of malignant invasion. Thus, detection of multiple aneuploid populations of cells in Barrett's esophagus may indicate a high risk of cancer. Barrett's esophagus provides a unique and readily accessible model for the study of neoplastic progression in human epithelial malignancy.

Adenocarcinoma↗
PubMed1989

Specialized metaplastic columnar epithelium in Barrett's esophagus. A comparative transmission electron microscopic study.

Barrett's esophagus develops as a complication of regurgitant esophagitis and predisposes patients to the development of dysplasia and esophageal adenocarcinoma. Prior ultrastructural studies have suggested that Barrett's epithelium is a mucous secretory epithelium that shares some morphologic features with the intestine. The origin and development of Barrett's epithelium and the cellular abnormalities accompanying its neoplastic progression are poorly understood. In an attempt to better understand the histogenesis of the mucus-producing cells that predominate in Barrett's epithelium, these cells were studied by transmission electron microscopy and compared with other upper gastrointestinal epithelia: esophageal glands, normal gastric surface, pit, and cardiac gland regions, gastric intestinal metaplasia, and normal jejunal villous tip and crypt regions. A total of 134 mucosal biopsies from the stomach and esophagus of 28 patients with Barrett's esophagus and 37 biopsies from 14 other control patients were studied. Barrett's specialized metaplastic surface cells display a spectrum of ultrastructural features among three main surface columnar epithelial cell types: mucous cells resembling those seen in the normal gastric surface epithelium or resembling mucous neck cells normally seen in the gastric pits; goblet cells similar to those seen in the jejunum; and "pseudoabsorptive" cells with features of both gastric mucous secretory cells and jejunal absorptive cells. Cytoplasmic organelles of Barrett's specialized metaplastic, normal gastric mucous neck, and normal gastric surface mucous epithelial cells, including rough endoplasmic reticulum, glycogen aggregates, Golgi apparatus, and mucous secretory granules, have common ultrastructural features associated with mucus synthesis. The morphologic heterogeneity of Barrett's specialized metaplastic cells and common ultrastructural features associated with normal mucus biosynthesis suggest that they develop from a gastrointestinal stem cell that retains the capacity for a wide range of normal and abnormal differentiation in the esophagus. The identity of this undifferentiated cell, which may reside in normal proximal gastric or esophageal mucosa, remains unknown. However, the gastric mucous neck cell has properties that suggest it could be the progenitor cell for Barrett's esophagus because it is a stem cell that has ultrastructural similarities to Barrett's specialized metaplastic epithelial cells and it is located in intact gastric mucosa adjacent to where Barrett's esophagus forms.

Adult↗
PubMed1988

Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions.

There is uncertainty regarding the value of endoscopic biopsy surveillance in Barrett's esophagus because, in retrospective studies, some patients with high-grade dysplasia in endoscopic biopsy specimens have had unexpected advanced adenocarcinoma discovered at the time of esophageal resection. We compared the accuracy of preoperative endoscopic biopsy diagnoses with the final pathologic diagnoses in esophagectomy specimens in 4 patients who had both high-grade dysplasia and intramucosal carcinoma and 4 other patients who had only high-grade dysplasia preoperatively. The histologic lesions in all 8 patients were documented in intact mucosa with no gross evidence of neoplasia by endoscopy. The preoperative diagnoses were defined with an endoscopic biopsy protocol in which specimens were taken with large-channel biopsy forceps at least every 2 cm throughout the length of Barrett's epithelium. Final pathologic diagnoses derived from detailed analysis of the resected specimens confirmed high-grade dysplasia without carcinoma in 4 patients and intramucosal carcinoma in 2 patients. The remaining 2 patients with a preoperative diagnosis of intramucosal carcinoma had focal submucosal invasion by carcinoma in the resected specimens, but no involvement of the muscularis propria or adventitial lymph nodes. Because the natural history of high-grade dysplasia is not known, the decision to operate on patients with this lesion must be carefully weighed and individualized for each patient. Two of our patients who underwent esophageal resection for high-grade dysplasia without cancer died, one immediately postoperatively and the other 9 mo later after a postoperative stroke. Once intramucosal carcinoma is documented, surgery should be considered if the patient is an acceptable operative risk. We conclude that systematic preoperative endoscopic biopsy of intact mucosa in Barrett's esophagus can correctly detect high-grade dysplasia, either alone or in combination with early, treatable adenocarcinoma.

Adenocarcinoma↗
PubMed1988

Observer variation in the diagnosis of dysplasia in Barrett's esophagus.

The potential value of biopsy surveillance of patients with Barrett's esophagus for dysplasia is diminished by a lack of agreement on the diagnostic criteria for dysplasia. In a preliminary consensus conference, experienced gastrointestinal pathologists from four medical centers agreed on criteria for a five-tiered histologic classification of dysplasia in Barrett's esophagus--negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and intramucosal carcinoma. Eight morphologists in the four centers tested the criteria for interobserver agreement by examining a set of coded slides that had been chosen to include some especially difficult interpretative problems in all five histologic classifications. Interobserver agreement of 85 and 87% was achieved in successive reviews when the combined group of high-grade dysplasia and intramucosal carcinoma was compared with the combined group of low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia. Comparison of other groups yielded less agreement. For example, negative for dysplasia could be distinguished from all other diagnoses with an interobserver agreement of 72%. We conclude that experienced gastrointestinal morphologists can diagnose high-grade dysplasia and intramucosal carcinoma with a high degree of agreement and thus can detect those patients who may need immediate rebiopsy or esophageal resection. Either further refinement of histologic criteria or alternate diagnostic methods will be needed to achieve the reproducible diagnosis of indefinite changes and low-grade dysplasia. This is important because patients with such changes theoretically merit closer endoscopic surveillance.

Barrett Esophagus↗
PubMed1988

Barrett's esophagus. Correlation between mucin histochemistry, flow cytometry, and histologic diagnosis for predicting increased cancer risk.

A predominance of sulfated mucin in the nongoblet columnar cells of Barrett's specialized metaplastic epithelium has been postulated to be a form of mild dysplasia and to indicate an increased risk of adenocarcinoma. Flow cytometry for the analysis of nuclear DNA content and cell cycle parameters has also been postulated to be an objective aid in the diagnosis of dysplasia and carcinoma in Barrett's esophagus. The authors investigated the relationship among sulfated mucin, flow cytometric data, and histologic diagnosis in each of 152 biopsies from 42 patients who had Barrett's specialized metaplastic epithelium. Sulfated mucin, as detected by the high iron diamine-Alcian blue stain, was present in biopsies from 8 of 11 (73%) patients with the histologic diagnosis of dysplasia or carcinoma, in 7 of 9 (78%) patients whose biopsies were indefinite for dysplasia, and in 12 of 22 (55%) patients whose biopsies were negative for dysplasia (P = 0.37). Sulfated mucins predominated in 9%, 22%, and 9% of the patients, respectively (P = 0.56). Abnormal flow cytometry (aneuploidy or increased G2/tetraploid fraction) was found in all patients with the histologic diagnosis of dysplasia or carcinoma, in 3 of 9 (33%) indefinite for dysplasia, and in 1 of 22 (5%) negative for dysplasia (P = less than 0.0001). Neither the presence nor the predominance of sulfated mucin in the specialized metaplastic epithelium of Barrett's esophagus has sufficiently high sensitivity or specificity for dysplasia or carcinoma to be of value in managing patients. Abnormal flow cytometry shows excellent correlation with the histologic diagnosis of dysplasia and carcinoma; it detects a subset of patients whose biopsies are histologically indefinite or negative for dysplasia, but who have flow cytometric abnormalities similar to those otherwise seen only in dysplasia and carcinoma.

Barrett Esophagus↗
PubMed1987

Cross-sectional imaging method. A system to compare ultrasound, computed tomography, and magnetic resonance with histologic findings.

Studies comparing imaging modalities require a precise knowledge of the type and location of tissue structures. When comparing cross-sectional techniques such as ultrasound, computed tomography, and magnetic resonance imaging, the images must be obtained through the same tissue section that is examined histologically. An experimental system that permits comparison of these modalities with histologic sections of precisely corresponding tissue is described. Application in 30 gastrointestinal tissue specimens shows a high degree of correspondence between cross-sectional images and histologic sections. This method should be useful in tissue imaging research for anatomic correlation and for comparisons between imaging modalities.

Digestive System↗
PubMed1987

Colorectal neoplasms: accuracy of US in demonstrating the depth of invasion.

Six normal and 16 neoplastic colorectal specimens were examined with 8.5-MHz ultrasound (US). An articulated system facilitated precise spatial correlation between US and histologic sections. Images were blindly interpreted and then compared with histologic results. All six normal specimen showed five distinct echo layers and were distinguished from neoplastic specimens by all the observers. The central echogenic layer, corresponding to the submucosa, is useful in determining the depth of origin of a neoplasm and the presence of submucosal invasion. US had an accuracy of 92.5% in demonstrating invasion of the submucosa and 77% for invasion of the muscularis externa. For mucosal neoplasms with invasion through the muscularis externa and extension into the subserosal tissues, nearly 90% of US interpretations were correct. High-frequency US may be useful in determining the depth of invasion of mucosal tumors with respect to the submucosa and in differentiating mucosal from extramural masses.

Biopsy↗
PubMed1987

Barrett's esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma.

The value of endoscopic surveillance biopsy for dysplasia and carcinoma in patients with Barrett's esophagus is controversial. One reason is that the available histologic criteria are not adequate to separate patients with lesser degrees of dysplasia or predysplastic changes who are at increased risk for carcinoma and therefore require more frequent surveillance from those patients who are not at increased risk. We used flow cytometry and histology to evaluate 317 biopsy specimens from 64 consecutive patients who were in a cancer surveillance program for Barrett's esophagus and 3 additional patients with adenocarcinoma in Barrett's esophagus. Specimens from 10 patients had aneuploid cells; 9 of these had dysplasia or carcinoma, or both, but 1 patient had only specialized metaplastic epithelium. Twenty specimens ahd G2/tetraploid fractions greater than 6%; all 20 came from patients who had cancer or dysplasia, or were indefinite for dysplasia. All patients with dysplasia or adenocarcinoma had evidence of genomic instability (aneuploidy) or abnormalities of mucosal proliferation by flow cytometry, even when the dysplasia was focal or difficult to recognize histologically. In a small subset of patients with specialized metaplastic epithelium whose specimens were histologically negative or indefinite for dysplasia, the mucosa had aneuploid cell populations or proliferative abnormalities that were otherwise found only in dysplasia or carcinoma. Additional study may prove that this subset of patients merits more frequent endoscopic biopsy surveillance because of an increased risk for developing carcinoma. Because the abnormalities we have detected by flow cytometry correlate well with the conventional histologic diagnoses of dysplasia and carcinoma, they may prove to be a valuable objective adjunct in the diagnosis of dysplasia and carcinoma in Barrett's esophagus.

Adenocarcinoma↗
PubMed1986

Hereditary gastrointestinal polyposis syndromes.

Hereditary gastrointestinal polyposis syndromes can be divided into adenomatous and hamartomatous types. Familial adenomatous polyposis coli (FAPC) is the prototype adenomatous polyposis syndrome and is defined by the autosomal dominant transmission of multiple (more than 100) colorectal adenomas. Virtually all affected patients develop colorectal carcinoma if untreated. Adenomas may develop also in the stomach and small bowel in FAPC patients, but the incidence of carcinoma in these sites is low. A variety of extracolonic manifestations has been reported in FAPC, with the name Gardner's syndrome applied to kindreds with osteomas of the skull and mandible, multiple epidermal cysts, and other skin and soft-tissue lesions. In Turcot's syndrome, brain tumors are present. The distinction between Gardner's and Turcot's syndromes and classical FAPC has become blurred because of marked overlap between them; some authorities consider them to be varying manifestations of a single genetic defect. The hamartomatous polyposes include Peutz-Jeghers syndrome, familial juvenile polyposis, Cowden's disease, intestinal ganglioneuromatosis, and the Ruvalcaba-Myrhe-Smith syndrome. The incidence of gastrointestinal cancer in patients with Peutz-Jeghers syndrome and familial juvenile polyposis exceeds that in the normal population, but is relatively low. In Cowden's disease, the gastrointestinal tract may be the site of multiple hamartomas, but there is no associated increase in the incidence of gastrointestinal cancers; instead, there is an increased incidence of carcinoma of the breast and thyroid. Intestinal ganglioneuromatosis occurs in von Recklinghausen's disease, in association with multiple endocrine neoplasia, type 2b, or as an isolated abnormality. Patients with ganglioneuromatosis do not appear to have an increased risk of developing gastrointestinal cancer. Ruvalcaba-Myrhe-Smith syndrome comprises macrocephaly, mental deficiency, an unusual craniofacial appearance, hamartomatous intestinal polyposis, and pigmented macules on the penis. No increased risk of developing cancer has been identified in the few reported cases.

Adenomatous Polyposis Coli↗
PubMed1985

Prognostic factors in colorectal carcinomas arising in adenomas: implications for lesions removed by endoscopic polypectomy.

Endoscopic polypectomy has become the preferred technique for the removal of most colorectal adenomas. Whether polypectomy alone or segmental colectomy is the appropriate management of the patient whose adenoma contains carcinoma is a controversial issue. We studied 129 colorectal carcinomas that arose in adenomas and in which invasion was no deeper than the submucosa of the underlying colonic wall. The following factors were evaluated: location; gross appearance (sessile versus pedunculated); histologic type of adenoma (tubular, villous, mixed); grade of carcinoma; level of invasion (0--carcinoma confined to the mucosa, 1--head, 2--neck, 3--stalk, 4--submucosa of underlying colonic wall); vascular invasion; and adequacy of excisional margins. Patients were divided into two groups with respect to outcome: adverse (dead from colorectal carcinoma, alive with colorectal carcinoma or positive nodes on colectomy), and favorable (absence of above). Sixty-three patients were treated by polypectomy alone and 66 by colectomy (21 preceded by polypectomy); there were no operative deaths. Mean follow-up was 81 mo. None of 65 patients with carcinoma confined to the mucosa had an adverse outcome, but 8 of 64 patients with invasive carcinoma did. Level 4 invasion (p less than 0.001) and rectal location (p = 0.025) were the only statistically significant adverse prognostic factors. Seven of 28 level 4 lesions and six of 42 rectal lesions had an adverse outcome; level 4 lesions were overrepresented in the rectum (14 of 42; p = 0.032). We conclude that the level of invasion should be the major factor in determining prognosis for the management of carcinoma arising in an adenoma.

Adenocarcinoma↗
PubMed1985

Malignant epithelioid hemangioendothelioma of the liver in young women. Relationship to oral contraceptive use.

Epithelioid hemangioendothelioma (EH) is a vascular neoplasm that occurs predominantly in soft tissue and is not infrequently misdiagnosed as an epithelial neoplasm or angiosarcoma. Only a few cases of hepatic EH have been described, and a relationship to oral contraceptive (OC) use in patients with the hepatic lesions has not generally been recognized. We present a series of five patients with malignant epithelioid hemangioendothelioma of the liver. Confirmation of the endothelial origin of these tumors was provided by positive immunoperoxidase staining for Factor-VIII-related antigen in the four cases studied by that technique, and by the demonstration of Weibel-Palade bodies in two tumors examined by electron microscopy. All five patients were young women (mean age 33 years) and all five gave a history of OC use of 4-7 years' duration. The clinical course varied from indolent but progressive to rapid death. One patient who underwent resection of the primary tumor has survived 3 years without evidence of disease, and one patient with metastatic disease who was treated with radiation and chemotherapy has survived for 8 years with disease. Three patients with extrahepatic spread have died of the tumor. Early diagnosis of this distinctive tumor might offer the hope of salvage by resection or liver transplantation.

Adult↗
PubMed1985

Biopsy-directed immunosuppression following hepatic transplantation in man.

Patients undergoing orthotopic hepatic transplantation were studied with routinely available liver function studies and serial hepatic biopsies. Rejection was diagnosed only if confirmed histologically. Cyclosporine and a rapidly decreasing dose of corticosteroids were used for immunosuppression. Hepatic dysfunction suggesting rejection was seen in 22 instances, but acute rejection was diagnosed histologically in only 6 patients. The liver function studies used in these patients did not accurately distinguish rejection from other causes of hepatic dysfunction. We conclude that liver biopsy as performed in these patients is an accurate and safe means of assessing the adequacy of immunosuppression and minimizing the use of high dose corticosteroids.

Biopsy, Needle↗
PubMed1985

Liver transplantation with cyclosporine and low-dose corticosteroids.

Twenty consecutive patients receiving 21 hepatic transplants were treated with cyclosporine and low-dose corticosteroids. Survival was 80 per cent at 30 days, 75 per cent at 6 months, and 65% in the 6-17 months follow-up period. Compared with earlier series, this improved survival using cyclosporine results from fewer infectious and sound healing complications. Reliance on hepatic biopsy to confirm the diagnosis of rejection may also reduce the corticosteroid exposure and help diminish the complications of excessive immunosuppression.

Biopsy↗
PubMed1984

The prevalence and prognostic significance of argyrophil cells in colorectal carcinomas.

The presence of argyrophil cells in the proliferative compartment of noncarcinoid carcinomas of the GI tract is well-documented; however, their prevalence and prognostic significance in colorectal carcinomas have never been systematically investigated and reported in the English literature. We applied the Churukian-Schenk argyrophil stain, a histochemical technique previously shown to be the most effective for demonstrating argyrophil cells, to 94 carcinomas of the colon and rectum from patients in whom a minimum 5-year follow-up was available. The 94 cases included 25 nonmucinous colonic and 25 nonmucinous rectal adenocarcinomas; 25 mucinous adenocarcinomas from all sites; and 19 undifferentiated carcinomas from all sites. Twenty control colorectal carcinoids all gave a positive argyrophil stain. Nineteen (20%) of the 94 carcinomas contained argyrophil cells as follows: adenocarcinoma of the colon, 52%; adenocarcinoma of the rectum, 16%; mucinous adenocarcinoma, 4%; and undifferentiated carcinoma, 5%. Crude 5-year survival rates were: carcinoids 80%; all carcinomas containing argyrophil cells, 37%; all without argyrophil cells, 27%. Chi-square between the later two groups was 0.723 (p less than 0.5). Because of the intrinsically poorer prognosis of mucinous and undifferentiated carcinomas, a comparison of survival rates was made excluding these tumors; chi-square was 0.095 (p less than 0.8). We conclude that argyrophil cells are commonly present in nonmucinous adenocarcinoma of the colon, but are less common in nonmucinous adenocarcinomas of the rectum and rare in mucinous and undifferentiated carcinomas. The presence of argyrophil cells did not influence prognosis in this series of cases.

Adenocarcinoma↗
PubMed1984

Portal vein obstruction in patients requiring hepatic resection or transplantation.

Four patients with chronic portal vein occlusion (or near occlusion) who required major hepatic resection or transplantation are described. In each case, portal vein patency was restored, and objective evidence of long-term patency is presented in three patients. These patients demonstrate the feasibility of restoring and indefinitely maintaining portal venous flow coincident to major hepatic surgery.

Adult↗
PubMed1983

Dysplasia in inflammatory bowel disease: standardized classification with provisional clinical applications.

Assessment of epithelial dysplasia in ulcerative colitis has been hindered by inconsistencies in and disagreements about nomenclature and interpretation. To resolve these issues, pathologists from ten institutions participated in three exchanges of multiple slides and, following each exchange, in discussions of the results. A classification system for the epithelial changes that occur in ulcerative colitis was developed, which should be applicable to other forms of inflammatory bowel disease as well. The classification makes use of standardized terminology, addresses specific problem areas, and offers practical solutions. The reproducibility of the system was studied by means of examinations of both inter- and intra-observer variations. The clinical implications of the findings were incorporated into suggestions for patient management. The basis of the classification is that the term "dysplasia" is reserved for epithelial changes that are unequivocally neoplastic and may therefore give rise directly to invasive carcinoma. Specimens are categorized as negative, indefinite, or positive for dysplasia. The negative category includes all inflammatory and regenerative lesions and indicates that only continued regular surveillance is required. The indefinite category is applied to epithelial changes that appear to exceed the limits of ordinary regeneration but are insufficient for an unequivocal diagnosis of dysplasia or are associated with other features that prevent such unequivocal diagnosis. Clinically, it indicates that early repeat biopsy is often required to assess the changes more accurately. The positive category is divided into two subcategories: 1) high-grade dysplasia, for which colectomy should be strongly considered after confirmation of the diagnosis, and 2) low-grade dysplasia, which also requires confirmation and early repeat biopsy or colectomy, depending on other findings.

Biopsy↗