The minimal incubation period from the onset of Barrett's oesophagus to symptomatic adenocarcinoma.

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.

Trends in the incidence of adenocarcinoma of the oesophagus and cardia in the Netherlands 1989-2003.

Over the 15-year period 1989-2003, the incidence of oesophagus-cardia adenocarcinoma in the Netherlands rose annually by 2.6% for males and 1.2% for females. This was the net outcome of annual increases in the incidence of adenocarcinoma of the oesophagus (ACO) of 7.2% for males and 3.5% for females and annual declines in the incidence of adenocarcinoma of the gastric cardia (AGC) of more than 1% for both genders. Nonlinear cohort patterns were found in females with ACO and for both genders in AGC; a nonlinear period pattern was observed only in males with AGC. These differing epidemiological patterns for ACO and AGC do not support a common aetiology. Proposed underlying factors for the rise in ACO incidence appear to have little effect on AGC incidence. This and the secular decline in smoking among males may have led to the decline in AGC incidence.

Causes and treatment of recurrent dysphagia after self-expanding metal stent placement for palliation of esophageal carcinoma.

BACKGROUND AND STUDY AIMS: Recurrent dysphagia frequently complicates the palliative treatment of esophageal cancer with self-expanding metal stents. Strategies for repeat interventions and subsequent outcomes have not been adequately reported to date. PATIENTS AND METHODS: A total of 216 patients underwent placement of a self-expanding metal stent (Ultraflex, n = 75; Flamingo Wallstent, n = 71; Z-stent, n = 70) for malignant dysphagia, and were followed up prospectively. The causes of stent-related recurrent dysphagia, the intervals after first stent placement, and the procedures used for repeat intervention and their outcomes were evaluated. RESULTS: Seventy-four episodes of stent-related recurrent dysphagia occurred in 63 patients (29 %), mainly due to tumor overgrowth (n = 30; median 129 days), stent migration (n = 26; median 92 days) and food bolus obstruction (n = 16; median 80 days). Stent migration occurred more frequently ( P = 0.05), whereas tumor overgrowth occurred less frequently ( P = 0.05) with Ultraflex stents in comparison with Flamingo Wallstents and Z-stents. Tumor overgrowth was treated in 25 patients mainly by a second stent (n = 19) and was effective in 23 of the 25 patients (92 %). Five patients received no further treatment. Stent migration was treated by placing a second stent (n = 14), repositioning the migrated stent (n = 7), other treatments (n = 3), or no further treatment (n = 2), and treatment was effective in 20 of 24 (83 %) patients. Food bolus obstruction was treated by endoscopic stent clearance in all patients. Repeat intervention for stent-related recurrent dysphagia improved the dysphagia score from a median of 3 to 1 ( P < 0.001). The median survival period after repeat treatment was 68 days. CONCLUSIONS: Recurrent dysphagia occurs in almost one-third of patients after stent placement. Repeat interventions for stent-related recurrent dysphagia are effective in over 90 % of patients. New innovations in stent design are needed to reduce the risk of stent-related recurrent dysphagia.

Self-expanding metal stents for complicated and recurrent esophagogastric cancer.

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.

A comparison of 3 types of covered metal stents for the palliation of patients with dysphagia caused by esophagogastric carcinoma: a prospective, randomized study.

BACKGROUND: There are currently 3 types of covered metal stents available in Europe for palliation of patients with malignant dysphagia. Their relative merits have not been compared in a prospective, randomized study. METHODS: One hundred consecutive patients with esophagogastric carcinoma were randomized to placement of an Ultraflex stent, a Flamingo Wallstent, or a Gianturco-Z stent. Malignant strictures of the esophagus were treated by insertion of a small-diameter stent (n = 71), whereas those involving the gastric cardia were treated with a large-diameter stent (n = 29). RESULTS: At 4 weeks, dysphagia had improved in all patient groups (p < 0.001), but the degree of improvement did not differ among the 3 groups (p = 0.14). There were differences among the 3 stent types with respect to major complications (Ultraflex stent: 8/34 [24%], Flamingo Wallstent: 6/33 [18%], and Gianturco-Z stent: 12/33 [36%]), but these were not statistically significant (p = 0.23). Nine patients (26%) with an Ultraflex stent, 11 (33%) with a Flamingo Wallstent, and 8 (24%) with a Gianturco-Z stent had recurrent dysphagia (p = 0.73), mainly because of tumor overgrowth or stent migration; 12 of 13 episodes of migration involved small-diameter stents in the esophagus. CONCLUSIONS: All 3 covered metal stents evaluated offer the same degree of palliation of patients with malignant dysphagia. Placement of Gianturco-Z stents was associated with more complications as compared with Ultraflex stents and Flamingo Wallstents. Although stent migration is reduced by increasing stent diameter, tumor overgrowth remains an intractable problem that requires a new approach.

A majority of patients with Barrett's oesophagus are unlikely to benefit from endoscopic cancer surveillance.

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.

Cholecystogastric fistula presenting with haematemesis: diagnosed by endoscopic retrograde cholangiography.

The case is reported of a 72-year-old woman suffering from morbid obesity, who presented with haematemesis while on anti-coagulant therapy. The source of the bleeding proved to be the gastric exit of a cholecystogastric fistula. Subsequent cholangitis was successfully treated by endoscopic retrograde cholangiography (ERC) and endoscopic sphincterotomy (ES) while simultaneously the extent of the fistula was established. Cholecystectomy and closure of the fistula was contraindicated because of her morbid obesity. She remained well for 6 months but then presented with a gallstone ileus while another stone was found to be escaping from the gastric fistula. Her morbid obesity resulted in surgical procrastination, which eventually proved fatal. This patient experienced both of the most common types of complication in cholecysto-enteral fistulation, cholangitis and gallstone ileus. Although cholecysto-enteral fistulas (CEF) are probably less common than several decades ago, they are now most likely to be diagnosed during ERC. Gastroenterologists therefore need to be aware of their potential to contribute to the diagnosis and treatment of this surgical condition.

A new design metal stent (Flamingo stent) for palliation of malignant dysphagia: a prospective study. The Rotterdam Esophageal Tumor Study Group.

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.

Randomized comparison of prevertebral and retrosternal gastric tube reconstruction after resection of oesophageal carcinoma.

BACKGROUND: After potentially curative resection of oesophageal cancer and prevertebral gastric tube reconstruction, approximately one-quarter of patients develop secondary dysphagia due to locoregional recurrence. In half of them dysphagia can be prevented by using an extra-anatomical reconstruction route. The present randomized study was conducted to compare the technical and functional results after prevertebral and retrosternal gastric tube reconstruction. METHODS: Sixty patients underwent resection of a carcinoma of the oesophagus or gastro-oesophageal junction with curative intent. Subsequently, these patients were randomly allocated to either prevertebral (n = 30) or retrosternal (n = 30) gastric tube reconstruction. Early and late complications and functional results were carefully monitored. RESULTS: Creation of the retrosternal tunnel was not accompanied by any perioperative complications. Postoperative recovery, anastomotic leakage and benign stricture formation were not significantly different between the two groups. Functional results, as measured by scintigraphic gastric emptying, quantitative and qualitative oral food intake, and changes in body-weight were similar in the two groups. CONCLUSION: After subtotal oesophagectomy retrosternal gastric tube reconstruction can be performed easily and safely, and gives functional results similar to those obtained with prevertebral reconstruction. In patients at high risk for developing secondary malignant dysphagia the extra-anatomical route is the reconstruction of first choice.

Palliation of malignant dysphagia from oesophageal cancer. Rotterdam Oesophageal Tumor Study Group.

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.

Coated self-expanding metal stents versus latex prostheses for esophagogastric cancer with special reference to prior radiation and chemotherapy: a controlled, prospective study.

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.

Reduced expression of the cadherin-catenin complex in oesophageal adenocarcinoma correlates with poor prognosis.

The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. Oesophageal adenocarcinomas causes early metastases, progress rapidly, and consequently have a poor prognosis. By means of immunohistochemistry, the expression of E-cadherin and alpha- and beta-catenin was studied in 65 oesophageal adenocarcinomas and 15 lymph node metastases. Expression of these proteins was evaluated with respect to clinico-pathological parameters and patient survival. Expression of the proteins was strongly correlated. In carcinomas, reduced expression of E-cadherin, alpha-catenin, and beta-catenin was found in 74, 60, and 72 per cent, respectively. Expression of E-cadherin and alpha-catenin correlated significantly with stage and grade of the carcinomas, whereas expression of beta-catenin correlated only with grade. Reduced expression of all three proteins correlated with shorter patient survival. In contrast to grade, E-cadherin and beta-catenin were significant prognosticators for survival, independent of disease stage. We conclude that in oesophageal adenocarcinomas, decreased expression of E-cadherin, alpha-catenin and beta-catenin are related events. Furthermore, expression of at least E-cadherin and beta-catenin is significantly correlated with poor prognosis.

Massive hemorrhage caused by a perforating Gianturco-Z stent resulting in an aortoesophageal fistula.

Endoscopic placement of self-expanding metal stents is regarded as a safe and effective method of palliating obstructive esophageal malignancies. We report here the case of a 49-year-old woman with an inoperable squamous-cell carcinoma located in the mid-esophagus. After two courses of chemotherapy, a silicone-covered Gianturco-Z stent was placed because of progressive tumor growth. Eighteen days after the stent placement, the patient presented with hematemesis, and died 24 hours after admission. At autopsy, the proximal end of the stent was found to have perforated through the normal esophageal mucosa into the aorta, resulting in an aortoesophageal fistula. This complication should be considered in patients who present with massive hemorrhage after undergoing radiotherapy or chemotherapy, or both, before stent placement in the mid-esophagus.

Choledochocele presenting with anaemia.

A 31-year-old man presented with abdominal pain and iron deficiency anaemia due to gastrointestinal blood loss. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a choledochocele, located between the ampullary sphincter and the sphincters of the common bile duct and pancreatic duct. The choledochocele was removed surgically and appeared to be covered with duodenal mucosa. Gastrointestinal blood loss is explained by the extensive erosions found in the duodenal mucosa of the choledochocele. Choledochoceles should be treated by radical resection.