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Background: The interval between the onset of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) can be termed the incubation period. However, the unrecorded onset of BO precludes its direct observation., Methods: Determining the range of intervals between BO diagnosis and OAC within the longest observational BO follow-up study. Exclusion criteria were presence of high-grade dysplasia (HGD) or OAC at baseline, death within <2 years of BO diagnosis, oesophagectomy without HGD/OAC and loss to follow-up. A total of 133 patients (M/F 73/60) were taken into account., Results: In 1967 person years of follow-up there were 13 cases of HGD/OAC, (0.66% p.a.; 95% CI 0.58-0.74), 96 patients died without HGD/OAC and 24 survived without HGD/OAC. The mean intervals between BO diagnosis and either HGD/OAC, death or end of follow-up were 10.8, 12.6 and 25.5 years, respectively, and the mean ages at endpoint were 72.5, 80.0 and 68.3 years, respectively. The survivors without HGD/OAC had a lower age at BO diagnosis (mean 42.8 vs 61.2 and 67.4 years, P<0.001). Baseline presence of low-grade dysplasia was associated with progression to HGD/OAC (log rank P<0.001)., Conclusion: The Rotterdam BO follow-up cohort revealed a long incubation period between onset of BO and development of HGD/OAC, in patients without HGD/OAC at baseline as illustrated by 24 patients diagnosed with BO at a young age and followed for a mean period of 25.5 years. Their tumour-free survival established a minimum incubation period, suggesting a true incubation period of three decades or more.

Background: Data on cancer risk in patients with long-segment Barrett's oesophagus (BO) from older studies are often difficult to interpret, since the definition of BO has evolved from an endoscopical to a histological diagnosis. In this work the diagnoses in the Rotterdam BO cohort on current standards was redefined to obtain more accurate data on cancer risk in patients who had not undergone standard endoscopic surveillance. In addition, it was determined which patient factors present at index endoscopy were associated with neoplastic progression in BO., Methods: The Rotterdam BO cohort comprises all patients with > or =3 cm BO, diagnosed at endoscopy between 1973 and 1984. In the present study, only patients with intestinal metaplasia were included (n = 105). Follow-up data were obtained by questionnaires and/or interviews with patients or treating physicians. A Kaplan-Meier analysis was used to estimate 20-year risks., Results: The mean length of the BO was 7.1 cm (range: 3-15 cm). Cancer in BO developed in 6/105 (6%) patients, and high-grade dysplasia (HGD) in 5/105 (5%) patients during 1329 patient-years of follow-up, which equals one cancer case per 221 patient-years and one HGD case per 266 patient-years. After a mean follow-up of 12.7 years, 72 (69%) patients had died; only 4 of them died of oesophageal cancer or its treatment. A longer length of BO was associated with an increased risk of progression to HGD or cancer (P < 0.02). Six of 24 patients who ever had low-grade dysplasia progressed to HGD or cancer 2-16 years after a diagnosis of BO., Conclusions: The annual risk of developing HGD or adenocarcinoma in patients with long-segment BO is 0.83%. Death due to adenocarcinoma is, however, uncommon, even in a cohort of patients with long-segment BO.

Background: Fewer complications are encountered with the use of self-expanding metal stents compared with semirigid prostheses in the palliation of patients with malignant esophagogastric obstructions. Metal stents can also be used to treat patients with complicated and/or recurrent esophagogastric carcinoma., Methods: Covered metal stents were placed in 57 patients for the following reasons: esophagorespiratory fistula (n = 16), recurrent carcinoma in a gastric tube interposition (n = 21), recurrent carcinoma after partial (n = 4) or total (n = 6) gastrectomy, or a carcinoma near the upper esophageal sphincter (n = 10)., Results: The procedure was technically successful in 55 of 57 (96%) patients. Dysphagia score improved from a mean of 3.6 to 1.6 (p < 0.001). Major complications occurred in 13 (23%) patients. In all cases, esophagorespiratory fistulas were occluded. Tumor recurred in 5 of 16 patients with a fistula, 8 of 21 patients after gastric tube interposition, 3 of 10 patients after gastrectomy, and 2 of 10 patients with a tumor immediately distal to the upper esophageal sphincter. Median survival was 61 days. Prior radiation, chemotherapy, or both increased the risk of specific stent-related complications in relation to the (neo)esophagus (6 of 16 [38%] versus 4 of 41 [10%]: odds ratio, 5.5: 95% CI [1.3, 24], p = 0.018)., Conclusions: Self-expanding metal stents are effective and relatively safe for palliation of patients with malignancy and dysphagia caused by fistula formation, postoperative recurrence, and tumors near the upper esophageal sphincter. Placement should be considered at an early stage in these conditions.

Background: Endoscopic cancer surveillance has been advocated for patients with Barrett's oesophagus. However, only a small minority of patients dies from adenocarcinoma in Barrett's oesophagus. It has been calculated that endoscopic cancer surveillance will only add to the quality of life of individuals in whom the incidence of adenocarcinoma in Barrett's oesophagus is greater than 1/200 patient-years., Objective: To determine the proportion of a consecutive cohort of patients, in whom Barrett's oesophagus was diagnosed over a 5-year period, likely to benefit from endoscopic cancer surveillance., Methods: All patients who had died during the observation period or were over 75 years old and those with diseases likely to impair survival were excluded. Next, all patients in whom the risk of developing adenocarcinoma in Barrett's oesophagus fell below 1/200 patient-years were excluded (including all women, all men under the age of 60 and all men with Barrett's oesophagus of < 3 cm in length). Patients with dysplasia of any degree and/or presence of an ulcer or stricture in Barrett's oesophagus were reinstated., Results: Of 335 adult patients diagnosed with Barrett's oesophagus but without adenocarcinoma or high-grade dysplasia, 75 had died from unrelated causes, 47 had other diseases limiting survival and 59 were over 75 years old. After exclusion of all women, all men with Barrett's oesophagus of < 3 cm in length and all men under 60 years old, 15 patients were left. However, 32 were reinstated because of risk factors and another five because of insufficient data, resulting in 52 of the original 335 patients (15.5%) being eligible for endoscopic cancer surveillance., Conclusion: This study suggests that less than 20% of patients identified with Barrett's oesophagus at routine endoscopy would benefit from endoscopic cancer surveillance. Prospective surveillance programmes should be limited to patients with an increased cancer risk and a good health profile.

Background: Metal stents are not superior to conventional endoprostheses with respect to the incidence of recurrent dysphagia because of tumor ingrowth with uncovered stents and migration with their covered counterparts. To overcome these limitations, a partially covered (inside-out covering) metal stent with a conical shape and a varying braiding angle of the mesh along its length, the Flamingo stent, has been developed., Methods: From March 1997 to October 1997, 40 consecutive patients with dysphagia due to malignant tumors had either a small diameter (proximal/distal diameter 24/16 mm; n = 21) or a large diameter Flamingo stent (proximal/distal diameter 30/20 mm; n = 19) placed., Results: There was statistically significant improvement in dysphagia, but improvement was not greater with large diameter stents compared to small diameter stents (p = 0.21). Major complications (bleeding [4], perforation [1], fever [1] and fistula [1]) occurred in 7 (18%) patients. Large diameter stents tended to be associated with more major complications than small diameter stents (5 vs. 2; p = 0.07). Pain following stent placement was observed in 9 (22%) patients and occurred more frequently in those who had prior radiation and/or chemotherapy (p = 0.02). Recurrent dysphagia (mainly due to tumor overgrowth) occurred in 10 (25%) patients., Conclusions: Flamingo stents are effective for palliation of malignant dysphagia, but the large diameter stent seems to be associated with more complications involving the esophagus than the small diameter stent. Because recurrent dysphagia is mainly due to tumor progression, further technical developments in stent design are needed.

Background: Self-expanding metal stents seem to be safer than conventional prostheses for palliation of malignant esophagogastric obstruction. However, recurrent dysphagia caused by tumor ingrowth in uncoated types remains a problem. In addition, prior radiation and/or chemotherapy may entail an increased risk of complications., Methods: Seventy-five patients with an esophagogastric carcinoma were randomly assigned to placement of a latex prosthesis under general anesthesia or a coated, self-expanding metal stent under sedation. At entry, patients were stratified for location of the tumor in the esophagus or cardia and for prior radiation and/or chemotherapy., Results: Technical success and improvement in dysphagia score were similar in both groups. Major complications were more frequent with latex prostheses (47%) than with metal stents (16%) (odds ratio 4.07: 95% CI [1.35, 12.50], p = 0.014). Recurrent dysphagia was not different between latex prostheses (26%) and metal stents (24%). Hospital stay was longer, on average, after placement of latex prostheses than metal stents (6.3 +/- 5.2 versus 4.3 +/- 2.3 days; p = 0.043). Only prior radiation and/or chemotherapy increased the risk of specific device-related complications with respect to the esophagus (12 of 28 [43%] versus 8 of 47 [17%]; odds ratio 3.66: 95% CI [1.24, 10.82], p = 0.029)., Conclusions: Coated, self-expanding metal stents are associated with fewer complications and shorter hospital stay as compared with latex prostheses, and prior radiation and/or chemotherapy increases the risk of device-related complications with respect to the esophagus.

Palliative therapies for advanced oesophageal cancer include surgery, radiation therapy, chemotherapy, endoscopic procedures and combinations of these. Of the non-endoscopic modalities is external beam radiation therapy (EBRT) effective and non-invasive. A disadvantage is that relief of dysphagia only occurs over a period of 4-6 weeks. Brachytherapy is more rapid in locally controlling tumour growth and in relieving dysphagia. One of the more commonly used endoscopic procedures is laser therapy, which provides symptomatic relief with low complication rates. Recurrent dysphagia is a problem necessitating repeated treatment sessions. Self-expanding metal stents offer a high degree of palliation and are associated with fewer complications compared with prosthetic tubes. Longer palliation and perhaps even longer survival might be achieved by the combination of different therapies. Most promising are the combination of EBRT plus brachytherapy or chemoradiation. Now is the time to determine which treatment (combination) is best for individual patients.

Giant pedunculated esophageal polyps are very rare. They may stay asymptomatic for a long time, and first come to the attention of the patient and the clinician after regurgitation into the mouth. Regurgitation, however, can be dangerous and has been known to lead to asphyxia and death due to closure of the larynx by the polyp mass. For this reason resection of the giant polyp is essential when it is discovered. We have seen four cases of giant esophageal polyps (GEP) at our institution. All four patients have undergone removal of the giant polyps. The histological diagnoses were fibrovascular polyp, liposarcoma, hamartoma and multiple lipomas. The mode of clinical presentation, radiological appearances, variable histological diagnoses, and therapy options in these four patients are presented along with a review of the literature.

In the search for effective chemotherapy regimens which can be used in multimodality treatment programmes for patients with cancer of the oesophagus, we conducted a phase II trial to determine the activity and toxicity of the combination of cisplatin and etoposide in patients with advanced squamous cell carcinoma of the oesophagus. Seventy-three consecutive patients with unresectable or metastatic squamous cell carcinoma of the thoracic oesophagus were treated with cisplatin 80 mg m-2 by 4 h infusion on day 1, etoposide 100 mg (fixed dose) by 2 h infusion on day 1 and 2, and etoposide 200 mg m-2 orally on day 3 and 5. Courses were repeated every 4 weeks, for a maximum of six courses. The oral dosages of etoposide were modified individually until a significant degree of myelosuppression was reached. Of 65 evaluable patients, five complete responses (CRs) and 26 partial responses (PRs) were seen, for an overall response rate of 48% (95% confidence interval 35-60%). Median time to progression was 7 months (range 3-72 + months). There were two toxic deaths (neutropenic sepsis). The response rate equals that of other cisplatin-based regimens. Its toxicity profile allows addition of a third active drug such as 5-fluorouracil.

Background: Barrett's oesophagus carries a 30-fold to 40-fold increased risk of oesophageal cancer. It is unknown whether endoscopic surveillance programmes reduce mortality from oesophageal cancer., Methods: A cohort study was undertaken of all 166 patients in whom the diagnosis Barrett's oesophagus had been established between 1973 and 1986., Results: One hundred and fifty five of 166 patients could be traced (93%). During a mean follow up of 9.3 years (amounting to 1440 patient years) eight patients had developed oesophageal cancer at random intervals (one case in 180 patient years). All but one of the tumours were diagnosed at endoscopy for symptoms, three in the stage of carcinoma in situ. Risk factors for the development of oesophageal cancer were extensive Barrett's oesophagus exceeding 10 cm (p = 0.02) and Barrett's ulcer at the time of intake (p = 0.009). Seventy six patients were alive; three had undergone surgery for oesophageal cancer and were without recurrence respectively, 12.8 years, 12.1 years, and 7 months postoperatively. Seventy nine patients had died; five of them had developed oesophageal cancer, but in only two cases this had been the cause of death (2.5%)., Conclusions: Oesophageal cancer is an uncommon cause of death in patients with Barrett's oesophagus. The patients of this cohort would not have benefited from an endoscopic surveillance programme.

Early oesophageal and gastric cancer are unique forms of oesophageal and gastric carcinoma with an excellent prognosis. Remarkable changes have taken place in the epidemiology of upper gastrointestinal malignancies. In particular, the incidence of adenocarcinoma of the distal oesophagus and the gastric cardia has risen over the past two decades. In the United States and Europe, early detection is dependent on a low threshold for upper gastrointestinal endoscopy with biopsy, because specific symptoms and physical findings are rarely present in patients with early oesophageal and gastric cancer. In addition to histology, the detection of possible markers of malignancy, such as aneuploidy (detected by flow cytometry) and the presence of oncogenes and tumour-suppressor genes, in biopsy material may be of value in the diagnosis of early cancers. For patients with early oesophageal or gastric cancer, surgery offers the best hope of cure. If patients are at high risk for surgery, an endoscopic resection may be an alternative option. This review discusses the definitions, the changes in epidemiology, the current options for diagnosis and treatment, and the value of screening programs for patients with early oesophageal or gastric cancer.

Giant oesophageal polyp (GOP) is a very rare intraluminal tumour. It is usually a benign, fibrovascular polyp arising from the proximal third of the oesophagus. We describe a patient with such a polyp but with a histological diagnosis of hamartoma. Regurgitation of the polyp into the mouth, which can lead to asphyxia, is a feared complication. A barium swallow and oesophagoscopy are the common diagnostic procedures. The site of the polyp and its volume often define the method of resection.

Background: To evaluate the importance of the length of columnar-lined esophagus, sex, age, smoking, and drinking habits as risk factors for malignant degeneration, the authors performed a retrospective case-control study comparing patients with and without adenocarcinoma in Barrett esophagus., Methods: The records of 96 patients (53 male and 43 female; mean age, 61 years) with a benign columnar-lined esophagus and 62 patients (47 male and 15 female; mean age, 62 years) with an adenocarcinoma in columnar-lined esophagus referred to the Rotterdam Esophageal Tumor Study Group, diagnosed over the same period (1978-1985), were reviewed. A frequency distribution of the length of columnar-lined esophagus in both groups was made. Statistical analysis was performed with multivariate methods., Results: The length of columnar-lined esophagus was related significantly to carcinoma: a doubling of the length resulted in a 1.7 times increased risk. Smokers had a 2.3-fold increased risk as compared with nonsmokers. Male sex as a risk factor approached statistical significance (P = 0.06). Adjusted for these risk factors, no relation between carcinoma and age or alcohol consumption was found., Conclusions: The risk of development of an adenocarcinoma in Barrett esophagus increased with the length of Barrett epithelium. Smoking and possibly male sex were also risk factors. The identification of these risk factors may help in developing more efficient screening programs for patients with Barrett esophagus.

Barrett's oesophagus is a risk factor for the development of oesophageal cancer and for this reason annual endoscopic surveillance has been proposed. In this retrospective study of all patients with Barrett's oesophagus diagnosed in a 12 year period carcinoma had developed in only four patients. The incidence of oesophageal cancer in this series was one in 170 patient years, which means a 30-fold increase compared with the general population. The survival of patients with Barrett's oesophagus was not different, however, from an age and sex matched control population. It is concluded that systematic endoscopic surveillance of patients with Barrett's oesophagus is not indicated.

The treatment results of the Rotterdam working group on esophageal cancer during the period January 1970-January 1978 were assessed. A total number of 328 patients were treated: 230 males and 98 females. Of the 133 patients eligible for a combined treatment modality i.e. preoperative radiotherapy and surgery, 52 showed irresectable or metastatic disease during operation. The five year actuarial survival rate of the 81 patients, in whom curative surgical resection of the tumor was performed, amounted to 21%. Females fared better than males, the five year survivals being 42% and 12% respectively. This female preponderance in survival is partly explained by the considerable postoperative mortality of the male patients: 28% vs 7.4% in females. Patients who received only radiation therapy, whether curative or palliative, had a very bad prognosis. It is concluded that preoperative irradiation followed by surgical removal of the tumor should be performed in all operable-curable patients.

During the period 1978-1981 172 patients were referred to the Rotterdam Joint Group on Esophageal Carcinoma. Ninety-one patients were considered for combined therapy, comprising radiation therapy and surgery, and 10 patients refused surgery. The figures given in this material are actuarial survival values corrected for intercurrent death (the actuarial overall survival in parentheses). The 4-year survival in 69 patients who completed this treatment was 39 per cent (26%) (significantly better for women compared with men; significantly better for tumors less than 2 vertebrae compared with tumors greater than or equal to 2 vertebrae). The resectability rate was 85 per cent and the operation mortality rate 20 per cent. Thirty-eight patients had curative radiation therapy with a 4-year corrected survival of 5 per cent (3%). For palliative treatment, radiation therapy and endoscopic introduction of a Celestin tube were mostly used. The results of curative as well as of palliative treatment of esophageal carcinoma have shown improvement during the past decade compared with an earlier period.