Prospective long-term endoscopic and histological follow-up of short segment Barrett's esophagus: comparison with traditional long segment Barrett's esophagus

OBJECTIVES: Barrett's esophagus is associated with adenocarcinoma of the cardia and esophagus, regardless of its extent. The aim of this study was to compare the prevalence and incidence of dysplasia and adenocarcinoma in short segment and traditional long segment Barrett's esophagus. METHODS: Seventy-four patients with short segment Barrett's and 78 with traditional Barrett's entered the study. RESULTS: There were no significant differences in age or gender between the two groups of patients with Barrett's esophagus. A greater percentage of patients with short segment barrett's were black (p = 0.04). The prevalence of dysplasia at diagnosis in patients with short segment Barrett's was 8.1% versus 24.4% in patients with traditional Barrett's (p < 0.007). Adenocarcinoma was noted at diagnosis only in patients with traditional Barrett's (p < 0.0005). Twenty-six patients with short segment Barrett's and 29 with traditional Barrett's were followed prospectively for 12-40 months. Dysplasia developed during follow-up in two patients with short segment Barrett's and in six patients with traditional Barrett's (p < 0.05). Neither high grade dysplasia nor cancer developed in any patients with short segment Barrett's. High grade dysplasia did develop in two patients with traditional Barrett's esophagus, and mucosal adenocarcinoma developed in one. The frequency of dysplasia on the latest surveillance examination continued to be significantly higher for patients with traditional Barrett's (p = 0.03). Follow-up surveillance biopsy specimens of Barrett's mucosa frequently demonstrated an absence of goblet cells in patients with short segment Barrett's compared with patients with traditional Barrett's (p < 0.0001). CONCLUSIONS: The prevalence of dysplasia or adenocarcinoma and the incidence of dysplasia in patients with traditional Barrett's esophagus are significantly higher than in patients with short segment Barrett's esophagus. Further prospective surveillance is required to determine whether the incidence of adenocarcinoma in patients with short segment Barrett's esophagus is significantly lower.     

Dysplasia in Barrett's esophagus: diagnosis, surveillance and treatment

Barrett's esophagus is a premalignant metaplastic change in the lining of the distal esophagus. It represents a peculiar form of healing which occurs in response to chronic gastroesophageal reflux disease. The condition should be considered in all patients undergoing endoscopy for symptoms of reflux disease and is confirmed when any biopsy shows the presence of specialized intestinal metaplasia irrespective of the macroscopic appearance of the distal esophagus. Endoscopic surveillance with multiple biopsy sampling of the esophageal mucosa is indicated for all medically fit patients with Barrett's esophagus. The diagnosis of dysplastic change within this abnormal mucosa requires histological examination of the biopsies by 2 independent but experienced pathologists. Identification of high-grade dysplasia heralds the development of invasive cancer and offers the physician an opportunity to intervene. Despite extensive endoscopic sampling of the esophageal mucosa the differentiation between high-grade dysplasia and invasive adenocarcinoma is unreliable. Esophagectomy remains the treatment of choice for patients with high-grade dysplasia since adenocarcinoma of the esophagus carries such a poor prognosis.     

Barrett's esophagus: a review

Complications of Barrett's esophagus include ulceration, stricture, hemorrhage, perforation, and the development of malignancy. Barrett's esophagus and adenocarcinoma may be diagnosed simultaneously and that gastroesophageal reflux symptoms may be absent in many cases. Although endoscopic surveillance is justified, no agreement on the frequency can be made. Survival of patients with adenocarcinoma in Barrett's esophagus depends on the stage at diagnosis.     

Performing a cost-effectiveness analysis: surveillance of patients with ulcerative colitis

OBJECTIVE: To illustrate the principles of cost-effectiveness analysis, this third article in the "Primer on Economic Analysis for the Gastroenterologist" applies published criteria for appraising an economic analysis to a study of the cost-effectiveness of surveillance of patients with ulcerative colitis. METHODS: We review and apply the 10 standard criteria for critical appraisal and evaluation of cost-effectiveness analyses. SUMMARY: We outlined the development and critique of a decision analytic model that examines the cost-effectiveness of surveillance of patients with ulcerative colitis, and we compared the cost-effectiveness of surveillance of patients with ulcerative colitis to other well-accepted medical practices.     

Helicobacter pylori colonization of Barrett's esophagus and its progression to cancer

Helicobacter pylori (HP) plays a crucial role in gastric carcinogenesis. Few studies have looked at the relationship between HP and Barrett's esophagus/cancer. To further investigate this, a study comparing the prevalence of HP and increasing grades of dysplasia was undertaken. Biopsies from 19 malignant and 94 benign cases of Barrett's esophagus were analysed histologically for the presence of HP. 34% of non-dysplastic Barrett's epithelium was colonized with HP compared with only 17% of dysplastic/malignant cases (P = 0.04). No relationship was found between HP status and: (i) length of Barrett's esophagus; (ii) the presence of ulcers or strictures; and (iii) previous anti-reflux surgery. HP colonization of Barrett's esophagus is not uncommon. We found that HP has a negative correlation with increasing dysplasia which is analogous to gastric carcinogenesis. This finding should be investigated in prospective studies to elucidate its role in Barrett's adenocarcinoma.     

Effectiveness and patient satisfaction with nurse-directed treatment of Barrett's esophagus

OBJECTIVE: Using clinical practice guidelines, a registered nurse adjusted antireflux medications, evaluated esophageal biopsy reports, determined the interval between surveillance endoscopies, and provided education for patients with Barrett's esophagus. No previous reports have assessed the effectiveness or patient satisfaction associated with registered nurse-provided primary care. Because estimates of the incidence of dysplasia and adenocarcinoma vary widely, we also prospectively followed a cohort of patients with Barrett's esophagus. METHODS: Charts were reviewed to determine the frequency of variation from guidelines, the annual incidence of dysplasia and adenocarcinoma, and frequency of reflux symptoms. Patients were mailed a questionnaire to assess satisfaction with their medical care and with the nurse. RESULTS: Variation by the nurse from the guidelines on surveillance endoscopy (1.9%) and the treatment of reflux (1.3%) was rare. Most patients were very satisfied (score of 6 on 0-6-point Likert scale) with overall medical care (88%), and patient education (76%), and most patients did not think that increased physician involvement would improve their care (93%). Ninety-seven percent of patients had control of reflux symptoms. Two patients with long segment Barrett's esophagus (n = 67) developed high grade dysplasia over 323 patient-yr of follow-up (1 of 162 patient-yr for an annual incidence of 0.6%). No patients with short segment Barrett's esophagus (n = 56) developed high grade dysplasia or adenocarcinoma over 172 patient-years of follow-up. CONCLUSION: The registered nurse in our clinical setting effectively administered clinical practice guidelines for the management of Barrett's esophagus without clinically significant morbidity or patient dissatisfaction. Before these results can be generalized to other settings, further studies will need to be performed.     

Analysis of mammographic density and breast cancer risk from digitized mammograms

To evaluate the association between mammographic density and breast cancer risk, a simple, observer-assisted technique called interactive thresholding was developed that allows reliable quantitative assessment of mammographic density with use of a computer workstation. Use of this technique helps confirm that mammographic density is one of the strongest risk factors for breast cancer and is present in a large proportion of breast cancer cases. The strong relationship between mammographic density and breast cancer risk suggests that the causes of breast cancer may be better understood by identifying the factors associated with mammographically dense tissue and determining how such tissue changes as these factors vary. Furthermore, because it can be modified, mammographic density may also be a good vehicle for the development and monitoring of potential preventive strategies. Areas of ongoing investigation include evaluating a potential genetic component of mammographic density by comparing density measurements in twins and understanding changes in density relative to age, menopausal status, exogenous hormone use, and exposure to environmental carcinogens. In addition, work is ongoing to establish measurements from imaging modalities other than mammography and to relate these measurements directly to breast cancer risk.     

Metaplastic carcinoma of the breast: mammographic appearance with pathologic correlation

OBJECTIVE: The objective of this study was to describe the mammographic appearance with pathologic correlation of metaplastic carcinoma of the breast. CONCLUSION: Metaplastic carcinomas of the breast are masses with mammographic characteristics of low suspicion because of their histologic appearance. Metaplastic carcinoma should be included in the differential assessment of predominately circumscribed, noncalcified masses revealed on mammography. One salient feature that may distinguish metaplastic carcinomas is the occurrence of a circumscribed portion with a spiculated portion, which is seen in carcinomas that have a significant mixture of metaplastic and invasive carcinoma growth patterns.     

Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study

OBJECTIVES: In Barrett's esophagus, early adenocarcinomas are often missed on endoscopic biopsy. We therefore examined the distribution and extent of dysplasia and carcinoma in the resected esophagus for comparison with the preoperative biopsy findings. METHODS: Patients whose endoscopy showed Barrett's esophagus but no visible cancer had four-quadrant esophageal biopsies taken every 2 cm. After resection for high-grade dysplasia or early adenocarcinoma, the esophagus was mapped histologically. RESULTS: Nineteen patients had surgery for high-grade dysplasia; two of them (10.5%) had adenocarcinoma in the resected esophagus. Eleven patients had resection after a biopsy diagnosis of adenocarcinoma or suspicion of adenocarcinoma. Esophagectomy mapping confirmed carcinoma in only five of them. Median surface areas were: total Barrett's esophagus 32 sq cm, low-grade dysplasia 13 sq cm, high-grade dysplasia 1.3 sq cm, adenocarcinoma (seven cases) 1.1 sq cm. CONCLUSIONS: Areas of high-grade dysplasia and microscopic carcinoma in Barrett's esophagus are often small. Biopsy differentiation between these lesions is difficult. A systematic endoscopic biopsy protocol will reduce the chance of missing early malignancy in Barrett's esophagus.     

I-131 uptake in the breast for thyroid cancer surveillance with biopsy-proven benign tissue

A 37-year-old woman was seen for recurrent papillary carcinoma of the thyroid after thyroidectomy. After repeated surgery and I-131 therapy, follow-up I-131 scanning and thyroglobulin levels were negative. Subsequent I-131 surveillance, however, demonstrated bilateral breast uptake. A biopsy taken of this area in the right breast proved that the increased uptake was secondary to benign disease.     

Limitations in upper-body strength associated with breast cancer: a comparison of black and white women

We examined differences in reported upper-body limitations between black and white breast cancer cases and controls aged 40 to 84 years at 3 and 12 months after diagnosis in the Detroit metropolitan area (n = 954 cases and 1000 controls at 3 months; n = 879 cases and 909 controls at 12 months). At 3 months black cases were more likely than white cases to report limitations in upper-body strength (30.4 versus 19.8%). No difference was found between black and white controls (8.0 versus 9.4%). At 12 months, the proportion of white patients with upper-body limitation returned to the same level as white controls. Black patients with limitations, however, did not return to the same level as black controls. Stage of disease was strongly associated with upper-body limitations, especially for black women. Race and stage differences in upper-body limitation could not be explained by differences in breast cancer treatment, financial adequacy, education, marital status, or comorbidity. Recommendations are made for more comprehensive studies of rehabilitation.     

Squamous cell carcinoma of the thoracic esophagus following radiation therapy for breast cancer

Between 1981 and 1995, 4 patients (3 females, 1 male; aged 48-80) were diagnosed with squamous cell carcinoma of the esophagus, following mediastinal irradiation for breast cancer. The interval between irradiation and the presentation of esophageal cancer was 10.75 years on average (7-19). The treatment consisted of: radiotherapy only; a partial esophagectomy with proximal gastrectomy without post-operative radiotherapy; laser photocoagulation for a superficial tumor; and, palliative treatment including gastrostomy, tracheal photocoagulation and chemotherapy for 1 patient suffering from advanced stage cancer with tracheal invasion, respectively. Radiotherapy of the esophageal cancer (exclusive or adjuvant) should take into account previous esophageal radiation therapy. The indications of curative excision surgery are the same as for other types of esophageal cancer, but the anastomoses should be performed in a non-irradiated area. Excision by esophageal stripping without thoracotomy is contraindicated because of the presence of peri-esophageal sclerosis. Preventive measures in radiation therapy for breast cancer are suggested.     

Risk factors for breast cancer in women with a breast cancer family history

For the study of the relationship of the pelviureteric system of one kidney to that of the contralateral one, bilateral cutaneous ureterostomy was performed in 14 dogs. The renal pelvis (RP) and ureter (U) of one side were distended separately with a balloon filled with saline in increments of 1 and 0.25 ml, respectively, and the pressure response of the contralateral RP and U was recorded. The test was repeated after anesthetization of the RP and U. RP distension with 1 ml of saline effected a pressure rise (P < 0.05) in the ipsilateral RP but no pressure response in the ipsilateral U or the contralateral RP or U (P > 0.05). RP distension with 2, 3, and 4 ml of saline induced a significant pressure rise in the ipsi- and contralateral RP but not in the ureters. Ureteric distension produced a pressure elevation (P < 0.05) on the ipsilateral U but had no effect on the contralateral U (P > 0.05) or on either of the renal pelves (P > 0.05). Distension of the anesthetized RP or U effected no pressure response in any of the ipsi- or contralateral RPs or Us. In conclusion, distension of the RP with large volumes led to an increase in pressure in the contralateral RP but not in the U. A reflex relationship is postulated to exist between the two renal pelves and to be mediated through a reflex we call the reno-renal pelvic reflex. It seems that this reflex acts to allow either of the kidneys to share an extra load of the other one by increasing the contractile activity of the RP, thus assumedly assisting the regulation of urine flow.     

Modeling the cost-effectiveness of granulocyte colony-stimulating factor use in early-stage breast cancer

PURPOSE: To model the cost-effectiveness (CE) of granulocyte colony-stimulating factor (G-CSF) in early-stage breast cancer when its use is directed to those most in need of the medication. METHODS: A conditional CE model was developed for the use of G-CSF based on a ranking of patient need as determined by patient blood counts during the first cycle of chemotherapy. In the base case, no G-CSF was used. In the alternative case, G-CSF was used in the following manner. If the risk of a neutropenic event (as defined by a predictive model based on nadir absolute neutrophil count [ANC] and hemoglobin decrease in cycle 1) was equal to or exceeded a predetermined critical value "T," then patients would receive G-CSF in cycles 2 through 6 of chemotherapy. If the risk of an event was less than T, patients would not use G-CSF unless an event occurred, at which time G-CSF would be administered with every subsequent cycle. RESULTS: A decision rule (T) that would allow the most needy 50% of early-stage breast cancer patients to receive G-CSF after the first cycle of chemotherapy resulted in a CE ratio of $34,297 dollars per life-year saved (LYS). If only the most needy 10% of patients received G-CSF, then the associated CE ratio was $23,748/LYS; if 90% of patients could receive the medication, the CE ratio would be $76,487/LYS. These estimates were relatively insensitive to inpatient hospital cost estimates (inpatient costs for fever and neutropenia of $3,090 to $7,726 per admission produced dollar per LYS figures of $34,297 to $32,415, respectively). However, the model was sensitive to assumptions about the shape of the relationship between dose reduction and disease-free survival (DFS) at 3 years. CONCLUSION: Providing G-CSF to the neediest 50% of early-stage breast cancer patients (as defined by first-cycle blood counts) starting after the first cycle of chemotherapy is associated with a CE ratio of $34,297/LYS, which is well in the range of CE ratios for treatment of other common medical conditions. Furthermore, conditional CE studies, based on predictive models that incorporate individual patient risk, allow one to define populations for which therapy is, or is not, cost-effective. Limitations of our present understanding of the shape of the chemotherapy dose-response curve, especially at low levels of dose reductions, affect these results. Further work is required to define the shape of the dose-response curve in early-stage breast cancer.     

Are increases in mammographic screening still a valid explanation for trends in breast cancer incidence in the United States?

A number of studies have attributed much of the sharp increase in breast cancer incidence in the United States during the 1980s to the increased detection through mammography. The most recent breast cancer data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program show that the incidence trend has slowed, while results from the National Health Interview Survey (NHIS) of 1987 and 1990 indicate that the percentage of women receiving mammograms continues to increase. This phenomenon suggested the need to reassess the relationship between increasingly early detection of breast cancer and overall incidence trends. A polynomial age-cohort model was used to establish the secular trend in incidence rates excluding the impact of recent increases in detection due to the rising use of mammography. Based on the model, the incidence trend in the youngest age group (40 to 49 years) would peak and then begin to decline in the early 1980s. This pattern would manifest itself later in successively older age groups as these younger cohorts age. Breast cancer trends are seen to be generally consistent with the impact of the increased use of mammography when its effect is superimposed upon the background of declining or slowing secular trends. These results support previous reports linking incidence rates with the increase in screening-mammography.