Leeuwenburgh, I.

Efficacy and safety of a partially covered stent in malignant gastric outlet obstruction: A prospective Western series (Article)

2013-04-01T00:00:00Z

Achalasia, Studies on Long-Term Outcome (Doctoral Thesis)

2012-04-18T00:00:00Z

Achalasia is a rare motility disorder of the esophagus with evidence for an auto-immune etiology as auto-immune thyroid diseases appear more common in patients with achalasia. However this observation has not led to causative treatment. Treatment is still purely symptomatic at lowering the lower esophageal sphincter pressure. Pneumatic dilatation is an effective LES pressure lowering treatment module, however young age, classic achalasia, high LES-pressure 3 months after PD and incomplete obliteration of the balloon's waist are important predictors for the need of repeated treatment and alternative treatment as surgery should in these cases be considered. Patients with achalasia have a considerable risk to develop esophageal carcinoma (HR 28), which is often detected in a late incurable state. Efforts should be made to define those patients with the highest risk, who could benefit from a more intense surveillacne protocol. Long lasting disease, p53 overexpression and inflammation in esophageal surveillance biopsy samples, food stasis at endoscopy and development of Barrett's metaplasia appeared to be independent risk factors. Future research should focus on the best surveillance interval and strategy. The patients with risk factors should be offered a, probably annual, surveillance endoscopy starting 10 years after onset of symptoms. To improve the yield of surveillance endoscopy the esophagus should be properly cleaned by prescribing the patients with food stasis a liquid diet 2-3 days before endoscopy. In case of severe food stasis at endoscopy or severe inflammation in the surveillance biopsy samples retreatment should be considered even in the absece of deterioration of symptoms as these are important risk factors. To prove this strategy, a prospective randomized study is needen but will be hard to perform. Therefore it is important to cluster and follow achalasia patients by a strict protocol, to study the cancer risk as follow-up lengthens and to study the outcome of a more intensive surveillance and treatment protocol.

Practice patterns for achalasia - Room for improvement? (Letter To Editor)

2011-07-01T00:00:00Z

Predictors for outcome of failure of balloon dilatation in patients with achalasia (Article)

2011-01-01T00:00:00Z

Background: Pneumatic balloon dilatation (PD) is a regular treatment modality for achalasia. The reported success rates of PD vary. Recurrent symptoms often require repeated PD or surgery. Objective: To identify predicting factors for symptom recurrence requiring repeated treatment. Methods: Between 1974 and 2006, 336 patients were treated with PD and included in this longitudinal cohort study. The median follow-up was 129 months (range 1-378). Recurrence of achalasia was defined as symptom recurrence in combination with increased lower oesophageal sphincter (LOS) pressure on manometry, requiring repeated treatment. Patient characteristics, results of timed barium oesophagram and manometry as well as baseline PD characteristics were evaluated as predictors of disease recurrence with Kaplan-Meier curves and Cox regression analysis. Results: 111 patients had symptom recurrence requiring repeated treatment. Symptoms recurred after a mean follow-up of 51 months (range 1-348). High recurrence percentages were found in patients younger than 21 years in whom the 5 and 10-year risks of recurrence were 64% and 72%, respectively. These risks were respectively 28% and 36% in patients with classic achalasia, respectively 48% and 60% in patients without complete obliteration of the balloon's waist during PD and respectively 25% and 33% in patients with a LOS pressure greater than 10 mm Hg at 3 months post-dilatation. These four predictors remained statistically significant in a multivariable Cox analysis. Conclusion: Although PD is an effective primary treatment in patients with primary achalasia, patients are at risk of recurrent disease, with this risk increasing during long-term follow-up. Young age at presentation, classic achalasia, high LOS pressure 3 months after PD and incomplete obliteration of the balloon's waist during PD are the most important predicting factors for the need for repeated treatment during follow-up. Patients who meet one or more of these characteristics may be considered earlier for alternative treatment, such as surgery.

Long-Term Esophageal Cancer Risk in Patients With Primary Achalasia: A Prospective Study (Article)

2010-10-01T00:00:00Z

OBJECTIVES:Achalasia patients are considered at increased risk for esophageal cancer, but the reported relative risks vary. Identification of this risk is relevant for patient management. We performed a prospective evaluation of the esophageal cancer risk in a large cohort of achalasia patients with long-term follow-up.METHODS:Between 1975 and 2006, all patients diagnosed with primary achalasia in our hospital were treated and followed by the same protocol. After graded pneumatic dilatation, all patients were offered a fixed surveillance protocol including gastrointestinal endoscopy with esophageal biopsy sampling.RESULTS:We surveyed a cohort of 448 achalasia patients (218 men, mean age 51 years at diagnosis, range 4-92 years) for a mean follow-up of 9.6 years (range 0.1-32). Overall, 15 (3.3%) patients (10 men) developed esophageal cancer (annual incidence 0.34 (95% confidence interval 0.20-0.56)). The mean age at cancer diagnosis was 71 years (range 36-90) after a mean of 11 years (range 2-23) following initial presentation, and a mean of 24 years (range 10-43) after symptom onset. The relative hazard rate of esophageal cancer was 28 (confidence interval 17-46) compared with an age- and sex-identical population in the same timeframe. Five patients received a potential curative treatment.CONCLUSIONS:Although the gastro-esophageal cancer risk in patients with longstanding achalasia is much higher than in the general population, the absolute risk is rather low. Despite structured endoscopical surveillance, most neoplastic lesions remain undetected until an advanced stage. Efforts should be made to identify high-risk groups and develop adequate surveillance strategies.Am J Gastroenterol advance online publication, 29 June 2010; doi:10.1038/ajg.2010.263.

Expression of p53 as predictor for the development of esophageal cancer in achalasia patients (Article)

2010-08-01T00:00:00Z

Patients with longstanding achalasia have an increased risk of developing esophageal cancer. Surveillance is hampered by chronic stasis. We investigated whether aberrant expressions of tumor suppressor gene p53 and proliferation marker ki67 are early predictors for progression to malignancy. In 399 achalasia patients, 4% died of esophageal cancer despite surveillance. We performed a cohort study, using surveillance biopsies from 18 patients (11 carcinoma, one high-grade dysplasia [HGD], and six low-grade dysplasia [LGD]) and 10 controls (achalasia patients without cancer or dysplasia development). One hundred sixty-four biopsies were re-evaluated and studied for p53 and ki67 expression using immunohistochemistry. Eighty-two percent of patients with cancer/HGD showed p53 overexpression in surveillance biopsies at a mean of 6 (1-11) years prior to cancer development. In 67% of patients with LGD and only in 10% of the controls p53 overexpression was present. The proportion of samples with p53 overexpression increased with increasing grades of dysplasia. We found no difference for ki67 overexpression. p53 overexpression may identify achalasia patients at increased risk of developing esophageal carcinoma. Further study is needed to determine if patients with p53 overexpression would benefit from intensive surveillance to detect esophageal neoplasia at a potential curable stage.

Proton pump inhibitor therapy in gastro-oesophageal reflux disease decreases the oesophageal immune response but does not reduce the formation of DNA adducts (Article)

2008-07-01T00:00:00Z

Background: Chronic oesophageal inflammation and related oxidative stress are important in the pathogenesis of erosive oesophagitis (EO) and its malignant progression. Aim: To study the effect of proton pump inhibitors (PPIs) on oesophageal cellular immune response and oxidative damage in EO patients. Methods: Forty gastro-oesophageal reflux disease (GERD) patients [non-erosive reflux disease (NERD): 15, EO: 25] were included, after 7 days off antisuppressive drugs. EO patients were randomized to 20-mg rabeprazole once daily for either 4 or 8 weeks with baseline and follow-up endoscopy with distal oesophageal biopsies. T lymphocytes, macrophages and mast cells were quantified by immunohistochemistry. DNA adducts were measured by analysis of 8-oxo-deoxyguanosine levels. Results: Erosive oesophagitis patients had more T lymphocytes and CD8+T lymphocytes in squamous epithelium than NERD patients (P = 0.001, P = 0.002, respectively). Levels of DNA adducts between both groups were, however, not different (P = 0.99). Four- and eight-week rabeprazole treatment in EO patients resulted in a significant decrease in number of T lymphocytes and CD8+T lymphocytes (all P < 0.05). PPIs did not, however, affect levels of DNA adducts. Conclusions: Short-term PPI therapy in EO patients reduces the oesophageal cellular immune response, but does not change oxidative damage. PPI therapy may therefore not be effective in reducing the risk of oesophageal cancer in GERD patients.

Severe jaundice, due to vanishing bile duct syndrome, as presenting symptom of Hodgkin's lymphoma, fully reversible after chemotherapy (Article)

2008-02-01T00:00:00Z

Liver involvement in Hodgkin's lymphoma is common and is caused by hepatic infiltration, biliary obstruction by lymphoma, hepatitis, sepsis or complications of chemotherapeutic treatment. Jaundice caused by the vanishing bile duct syndrome related to Hodgkin's lymphoma is very rare. The mechanism is poorly understood but a paraneoplastic effect seems most likely as liver biopsy samples show cholestasis in the absence of lymphoma cells. Despite adequate treatment almost all reported patients died of liver failure or disease progression. Disease progression is explained partly by the difficulties encountered in the administration of potential hepatotoxic chemotherapy in severely cholestatic patients. We describe a 17-year-old man with vanishing bile duct syndrome and Hodgkin's lymphoma who was treated successfully with chemotherapy. The markedly elevated serum bilirubin levels completely normalized. Our case demonstrates that although dosing of chemotherapy in this situation can be very difficult, a good clinical outcome is possible, which makes the attempt at curative treatment worthwhile.