Immunohistochemical markers for Barrett's esophagus and associations to esophageal Z-line appearance.

BACKGROUND: Data from previous studies on intestinal metaplasia at the gastroesophageal junction have been conflicting, which makes the diagnosis of Barrett's esophagus less obvious. This may partly be due to the lack of a reliable classification of the Z-line appearance. We previously proposed such a classification (the ZAP classification) that was shown to correlate with the prevalence of intestinal metaplasia. The use of different immunohistochemical techniques has increased in the study of intestinal metaplasia. In the present study our aim was to 1) evaluate the impact of different antibodies, namely cytokeratin (CK) 7, 13, and 20, CaCO3/73, and FBB2/29, in order to differentiate between Barrett's esophagus and cardia intestinal metaplasia, and 2) explore the staining patterns in different ZAP grades. METHODS: Thirty-nine specimens with intestinal metaplasia were compared--9 from Barrett's esophagus, 6 from cardia, and 24 from the Z-line. The Z-line specimens were evaluated with respect to ZAP grade. RESULTS: No differences were encountered regarding staining patterns for CK13 and CaCO3/73 in Barrett's esophagus and cardia. The staining pattern of CK7/20 was significantly different between Barrett's esophagus and cardia. CK7/20 showed a rising frequency of Barrett's esophagus staining pattern with rising ZAP grade. CONCLUSION: CK7/20 is a feasible marker for Barrett's esophagus. Intestinal metaplasia in different ZAP grades differs regarding expression of immunohistochemical markers.

A postfundoplication study on Z-line appearance and intestinal metaplasia in the gastroesophageal junction.

The purpose of this study was investigate the Z-line appearance by using a previously proposed classification, the ZAP classification, and to investigate the prevalence of intestinal metaplasia in the Z-line, among fundoplicated patients. Sixty patients, who had undergone fundoplication 2 to 17 years earlier, were included in the study. The prevalence of intestinal metaplasia was 20%. Intestinal metaplasia was found to be associated with age, more than 10 years of symptoms of gastroesophageal reflux disease preoperatively, tongues of columnar epithelium in the distal esophagus, carditis, and ZAP grade. ZAP grade, furthermore, was associated with male gender and more than 10 years of symptoms of gastroesophageal reflux disease preoperatively. Among patients with intestinal metaplasia, different ZAP grades can indicate different etiologic factors. Even among patients undergoing fundoplication (i.e., patients with an anatomically altered gastroesophageal junction), the ZAP classification is a feasible tool to characterize the Z-line appearance. The ZAP classification could prove valuable in selecting patients for follow-up treatment.

The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of chemotherapy effects in some major tumour types--summary and conclusions.

This report by The Swedish Council on Technology Assessment in Health Care (SBU) reviews, classifies, and grades the scientific literature on cancer chemotherapy in some major tumour types, describes the practice of chemotherapy in Sweden, compares practice with scientific knowledge, and analyses the costs and cost-effectiveness of chemotherapy. The report is intended primarily for decision-makers at various levels, both practitioners and administrators. It is also of interest for the medical profession. The extensive body of scientific literature was reviewed according to strict criteria that reflected the scientific weight of the literature. Sixteen experts representing different disciplines (oncology, surgery, internal medicine, health economy and quality of life research) participated in the literature review. Each section was discussed within the project group and was reviewed by at least one, but usually two international researchers. Additional input was provided by national experts representing different scientific disciplines. For the final evaluation to be as close to the objective truth as possible, a concerted effort was made to guarantee objectivity and thorough assessment of current knowledge about the effects of chemotherapy on the selected cancers. The tumour types selected for this assessment include firstly those types where three investigations had shown an increased use of chemotherapy in Sweden during the latest decade. These were non-small cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, colorectal cancer and urinary bladder cancer. Secondly, the two tumour types comprising the greatest number of patients treated with chemotherapy in Sweden, breast cancer and haematological malignancies, were included. Among the haematological malignancies, the most prevalent ones, acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), Hodgkin's disease (HD), aggressive non-Hodgkin's lymphoma (NHL) of the large B-cell type and indolent NHL of follicular type were evaluated. These constitute about 75%, of all haematological malignancies. Thirdly, ovarian cancer was included since chemotherapy has been extensively used and since, at the time of the planning of this overview, a group of very expensive drugs, the taxanes, had preliminarily shown promising results. A wealth of scientific literature has been published on cancer therapy. The review presented in this report is limited to scientific studies judged to be important for evaluating chemotherapy efficacy. Assessments of the content and quality of these studies, and a critical summary of the results in all stages of the selected tumours, have never before been attempted in this way. However, similar comprehensive overviews of certain stages of the tumours have previously been made. These overviews were also critically evaluated. Totally 1,496 studies involving 558,743 patients were reviewed. The survey of practice of chemotherapy use involved all departments of surgery, urology, gynaecology, internal medicine including haematologic units, pulmonary medicine and general and gynaecologic oncology at 16 hospitals in two health care regions in Sweden, covering 39% of the Swedish population. During the 4 weeks of the survey, all patients with the diagnoses concerned who received chemotherapy were registered. The study included 1,590 patients. The working group's general conclusions are summarised in the following points: The literature on the effects of chemotherapy is extensive. Chemotherapy has a well-documented role in the curative and palliative treatment of patients with several types of cancer. The use of chemotherapy is of utmost importance for the possibility of cure in certain tumour types. In other tumours, chemotherapy increases the possibility of cure when added to local and regional treatments, particularly surgery. In the instances of no possibility of cure, chemotherapy may to a variable extent improve both patient survival and well-being. In Sweden chemotherapy is largely used in accordance with that documented in the scientific literature. The extent of both over- and under-treatment seems to be limited but cannot be excluded at the individual patient level. The literature-based knowledge is scientifically of lower quality in the most chemotherapy sensitive tumours than in tumours showing more limited sensitivity. In the more sensitive tumours, positive effects on a symptomatic stage and survival were seen several decades ago. In those days, clinical treatment studies did not fulfil the current high quality requirements. Small life-prolonging effects of chemotherapy are sometimes very well documented in large, high quality scientific studies. Some of these s

A systematic overview of chemotherapy effects in gastric cancer.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This overview of the literature on chemotherapy in the treatment of gastric cancer is based on 153 scientific papers including one meta-analysis, 18 reviews, 60 randomised studies and 57 prospective studies. The trials consist of 12,367 patients. The conclusions reached can be summarized into the following points: A meta-analysis of 21 randomised adjuvant studies revealed a statistically significant survival benefit. The Odds Ratio (OR) is 0.84 (95% confidence interval, 95% CI, 0.74-0.96). However, by analysing Western world and Asian studies separately, a statistically significant difference can be noticed; the Western world studies showed an OR of 0.96 (95% CI 0.83-1.12) and the Asian an OR of 0.58 (95% CI 0.44-0.76). The cause of this difference is not apparent. There is not sufficient evidence to recommend adjuvant chemotherapy as routine treatment in the Western world. Preoperative chemotherapy given to patients with non-resectable tumours or locally advanced potentially resectable tumours has achieved resectability rates of 40-100% and potentially curative resections in 37-80%. One out of two randomised studies showed a significant survival benefit, but reported data are not convincing. Experimental data in favour of preoperative therapy has not yet been confirmed in randomised clinical studies. Therapy is only justified in controlled clinical trials. Published studies on the use of intraperitoneal chemotherapy are few and not conclusive regarding the efficiency and safety. This method of drug administration is, accordingly, justified only in controlled clinical trials. In advanced gastric cancer, phase II studies have indicated better response rates using drug combinations than using single drug regimens, differences that have not, however, been convincingly demonstrated in randomised studies. No firm conclusions can be drawn regarding the superiority for any of the studied drug combinations with respect to response or survival gain. A statistically significant survival benefit has been shown in trials comparing drug combinations with a best supportive care arm in the treatment of advanced gastric cancer. However, the number of included patients is small. The median survival benefit in advanced disease is in the range of three to nine months. The use of chemotherapy in advanced gastric cancer is justified in selected patients, e.g. in younger patients in good performance status, low tumour burden and no other serious medical condition after adequate information of potential gains and risks. The influence of chemotherapy on quality of life in advanced gastric cancer has been reported in only a few studies. It appears that about 50% of the patients have a clinically relevant relief of tumour-related symptoms and thereby improved quality of life. In one study, quality-adjusted survival was estimated to a median of six months in the treated patients compared with two months in the controls. The quality of the literature addressing chemotherapy for gastric cancer is frequently poor with few properly designed randomised trials. In a number of randomised multi-centre adjuvant studies the inclusions rates are remarkably low, which reduces the scientific value of the studies.

The Z-line appearance and prevalence of intestinal metaplasia among patients without symptoms or endoscopical signs indicating gastroesophageal reflux.

BACKGROUND: A four-graded classification of the Z-line appearance (ZAP) has been proposed, which was shown to correlate with the prevalence of intestinal metaplasia (IM) among patients with gastroesophageal reflux disease (GERD). The aim of this study was to determine the ZAP grade and the prevalence of IM among patients without GERD. METHODS: In this study, 53 consecutive patients without signs or symptoms of GERD were included. RESULTS: A normal Z-line (ZAP grade 0) was found in 26 patients (51%), and this group had a lower prevalence of Helicobacter pylori infection and atrophy in the cardia than ZAP grade patients. The non-GERD patients in this study had less ZAP pathology than the GERD patients in our previous study. Intestinal metaplasia at the Z-line, observed in 17% of the patients, was found to associate with peptic ulcer and carditis. CONCLUSION: The normal Z-line is feasibly defined as ZAP grade 0.

The esophageal Z-line appearance correlates to the prevalence of intestinal metaplasia.

BACKGROUND: Intestinal metaplasia at the gastroesophageal junction is associated with Barrett esophagus, gastric cardiac cancer, and gastritis. The aim of this study was to determine the prevalence of intestinal metaplasia among patients with symptoms suggestive of gastroesophageal reflux disease (GERD) and to study clinical, endoscopic, and histologic associations with intestinal metaplasia at the squamocolumnar junction. METHODS: One hundred and eighty-six patients with symptoms indicating gastroesophageal reflux were included in the study. A new classification of the Z-line appearance was used. RESULTS: The Z-line appearance was found to correlate with the prevalence of intestinal metaplasia at the squamocolumnar junction (P = 0.0001). Intestinal metaplasia at the squamocolumnar junction was found in 15.0% of the patients. There was a statistically significant association between intestinal metaplasia at the squamocolumnar junction and tongues of columnar epithelium at the Z-line (P = 0.020), intestinal metaplasia in the cardia (P = 0.020), positive CLO test (P = 0.026), smoking (P = 0.041), and age (P = 0.050). There was no association with endoscopic or histologic signs of esophagitis or with the severity or duration of GERD symptoms. CONCLUSION: Intestinal metaplasia at the squamocolumnar junction correlates with the Z-line appearance, which would justify a new classification.

Normal plasminogen activator inhibitor levels at long-term follow-up after jejuno-ileal bypass surgery in morbidly obese individuals.

Forty-five patients who had been subjected to jejuno-ileal bypass (JIB) surgery for morbid obesity and 10 obese nonsurgery subjects were studied. The former group was examined 14 to 20 years after surgery, and was found to have lower mean plasminogen activator inhibitor type 1 (PAI-1) activity (8.4 v 32 U/mL, P < .001), tissue plasminogen activator (tPA) antigen concentrations (7.2 v 12 micrograms/L, P < .01), body mass index (BMI), and fasting plasma insulin, triglyceride, and cholesterol levels. The PAI-1 levels were correlated with BMI, waist to hip ratio, and insulin, triglyceride, and cholesterol levels. Thus, previously obese subjects have normal PAI levels 14 to 20 years after treatment with JIB surgery, in contrast to the high PAI-1 levels in nonsurgery obese subjects.

Colorectal cancer risk after jejunoileal bypass: dysplasia and DNA content in longtime follow-up of patients operated on for morbid obesity.

Jejunoileal bypass (JIB) has been a widespread operation for treatment of morbid obesity. Bile acids are regarded as cofactors in the carcinogenesis of the colon, and, since intestinal bypass involves increased exposure of bile acids to the large intestinal mucosa, JIB has been postulated to increase the risk for colorectal carcinoma. In experimental studies on animals, the results have indicated an increased frequency of induced carcinomas, but in clinical series only one patient with colon carcinoma has been reported. Thirty women, operated on with JIB 11 to 17 years earlier, were examined by colonoscopy with multiple biopsies, systematically taken for histologic evaluation and flow cytometric DNA analysis. In only one patient, low-grade dysplasia was detected in an initial adenomatous lesion but was not visible macroscopically. No DNA aneuploidy was found. In a control group of 11 patients examined for non-neoplastic disease, neither dysplasia nor aneuploidy was diagnosed. Within 17 years postoperatively, we have, by these methods, not been able to verify any colorectal malignant transformation in patients operated on with JIB. However, since carcinogenesis is a long process, further surveillance will be demanded before an increased risk for colorectal carcinoma can be excluded.

Abdominal aortic aneurysma with postoperative delayed paraparesis. Case report.

A 54-year-old man with an expanding abdominal aortic aneurysm was operated on with a straight aortic graft. A paraparesis ensued three days postoperatively. Possible causative mechanisms, including influence on spinal venous pressure and direct effects of extradurally injected local anesthetic, are discussed.

Ulcerative colitis. Colorectal cancer risk in an unselected population.

One hundred twenty-seven patients were studied, representing the unselected population of patients with ulcerative colitis from a defined catchment area of about 70,000 inhabitants during 1961-1983. Seventy-seven patients had total colitis, and 50 patients had left-sided colitis. No prophylactic colectomy was performed. Despite this and a comprehensive follow-up of patients with long-standing, extensive colitis, primary colorectal carcinomas were diagnosed in only three patients, all of whom had total colitis. This was significantly (p less than 0.001) more than the expected number of patients with colorectal cancer in this subgroup, namely, 0.13. There were no deaths in colorectal carcinoma. Factors determining completeness of inclusion are discussed, and it is concluded that, in an unselected series of patients with ulcerative colitis, close cancer surveillance is indicated, although prophylactic surgery does not seem to be generally warranted.

Ulcerative colitis. Cancer surveillance in an unselected population.

An unselected series of patients with chronic ulcerative colitis from a defined catchment area underwent endoscopic and histologic cancer surveillance from 1977 to 1985. At the end point of the study, which included a total of 93 patients, there were 38 patients with total colitis of more than 10 years' duration. There was one case of colonic carcinoma, two cases of high-grade dysplasia, and no death due to colorectal cancer. We conclude that in an unselected group of patients with ulcerative colitis, the risk for colorectal dysplasia and cancer is low and that a surveillance program is reliable and can be performed at a community hospital.

Ulcerative colitis. Mortality and surgery in an unselected population.

125 patients with ulcerative colitis, considered to represent the unselected population of patients with this disease from a defined catchment area during the years from 1961 to 1983, were studied. The mortality from colitis was 5%, with no peroperative death after 1978. No prophylactic proctocolectomy was performed and there were no deaths in colorectal cancer. The cumulative operation frequency was 26%, and 37% in the subgroup of patients with total colitis. During the first 5 years of disease the operation frequency was 14%. It is concluded that, in a unselected population of patients with ulcerative colitis, satisfying results can be obtained at a community hospital, providing the surgical attitude to severe acute and disabling chronic disease is aggressive.

Carcinoembryonic antigen (CEA) in the gastric mucosa after partial gastrectomy.

Carcinoembryonic antigen (CEA) was studied by the three-layer bridge immunoperoxidase technique in gastric biopsy specimens taken from 49 patients, 13--20 years after partial gastrectomy. Routine histological examination revealed various degrees of chronic atrophic gastritis in all patients. A positive CEA reaction was found in 6 out of 9 with malignant or premalignant mucosal changes and in 4 out of 40 without these changes. In two cases of carcinoma the biopsies revealed a positive CEA reaction. In 4 patients with carcinoma diagnosed 1--2 years after the first examination the initial nonmalignant biopsies were CEA-positive in one case. All biopsies from mucosa with severe dysplasia and adenomatous polyps were CEA-positive. Four patients without malignant or premalignant changes in the gastric mucosa had CEA-positive biopsies. No carcinoma has been found in these patients at re-examinations after 1 year. The results indicate that the occurrence of immunohistochemically detectable CEA may be associated with malignant transformation of the gastric mucosa. The value of this method in screening patients at increased risk of gastric carcinoma will be further explored.

Gastric polyps and precancerous mucosal changes after partial gastrectomy.

Gastric polyps are considered to be rare. However, at endoscopy the prevalence of gastric polyps after partial gastrectomy was found to be 8.9% (30/336 patients) compared with 4.9% (20/407) in a clinical control material with a comparable age and sex distribution. Four patients with precancerous mucosal alterations were found in the operated group. Repeated endoscopic check-ups have at present been performed in 57.4% of these patients. In our experience the diagnostic accuracy with regard to malignancy is not entirely satisfactory. Histological examination of the surgical specimen from one of the 4 patients with precancerous changes showed a macroscopically invisible early carcinoma. Follow-up examinations (within 4 years) have in 5 out of 26 cases with sessile polyps disclosed carcinoma in 3 cases and precancerous changes or adenoma in another 2 cases. Careful re-examination of all patients with precancerous changes and gastric polyps is recommended.

The development of mucosal changes after gastric surgery for ulcer disease.

The development of morphological changes in the body mucosa after partial gastrectomy for ulcer disease according to Billroth I and II was studied early (within 3 years) and late (10-24 years) postoperatively with gastroscopy and forceps biopsies. The morphological findings in the body mucosa of the operation specimens and biopsies from the stomas were compared. The effect of time, ulcer disease, operation procedure, sex, and age was studied. In duodenal ulcer patients, with significantly less pronounced inflammatory mucosal changes in the operation specimen, partial gastrectomy caused acute and chronic gastritis to the same degree as seen in gastric ulcer patients within 3 years postoperatively. Duodenal ulcer patients also developed mucosal atrophy, cystic dilatation of the gastric glands, and intestinal metaplasia by time to an extent not significantly different from what was found in gastric ulcer patients. No correlation could be found between the mucosal changes and factors like age, sex, or operation procedure. Mucosal atrophy, chronic gastritis, and intestinal metaplasia are regarded as possible features of malignant transformation. If this concept is true, our findings may explain why stump carcinoma is frequently reported with the same incidence independent of preoperative ulcer disease or anastomotic procedure.