Cure of Barrett's carcinoma by ifosfamide chemotherapy.
Explore the source record for details and available documents.
Antineoplastic Agents, Alkylating↗
Biomedical subjects
Peter D Siersema
Publications and source records attributed to Peter D Siersema.
Allelic imbalance of 7q32.3-q36.1 during tumorigenesis in Barrett's esophagus.
Malignant transformation of Barrett's esophagus is characterized by three distinct premalignant stages: intestinal metaplasia (MET), low- (LGD), and high-grade dysplasia (HGD). We reported recently an increase in the frequency of loss of 7q33-q35 between LGD and HGD as determined by comparative genomic hybridization (P. H. J. Riegman et al., Cancer Res., 61: 3164-3170, 2001). Now the 7q32.3-q36.1 region was additionally characterized by allelotype analysis with 11 polymorphic markers in 15 METs, 20 LGDs, 20 HGDs, and 20 Barrett's adenocarcinomas from different patients. Low percentages of imbalance were determined in METs and LGDs, 7% and 10%, respectively, whereas HGDs and Barrett's adenocarcinomas revealed high percentages of loss, 75% and 65%, respectively. This difference in frequency between LGDs and HGDs appeared highly significant: P = 0.00007. The majority of imbalances were found at D7S2439 and D7S483, located on 7q36.1. These data suggest that markers from this area can be used as a diagnostic tool in Barrett's esophagus, i.e., to distinguish between watchful waiting and active treatment.
Allelic Imbalance↗
In situ light dosimetry during photodynamic therapy of Barrett's esophagus with 5-aminolevulinic acid.
BACKGROUND AND OBJECTIVES: Previous studies with PhotoDynamic Therapy (PDT) in bladder and bronchi have shown that due to scattering and reflection, the actually delivered fluence rate on the surface in a hollow organ can be significantly higher than expected. In this pilot study, we investigated the differences between the primary calculated and the actual measured fluence rate during PDT of Barrett's Esophagus (BE) using 23 independent clinical measurements in 15 patients. STUDY DESIGN/MATERIALS AND METHODS: A KTP-dye module laser at 630 nm was used as light source. Light delivery was performed using a cylindrical light diffuser inserted in the center of an inflatable transparent balloon with a length corresponding to the length of the Barrett's epithelium. The total light output power of the cylindrical diffuser was calibrated using an integrating sphere to deliver a primary fluence rate of 100 mW cm(-2). Two fiber-optic pseudo sphere isotropic detectors were placed on the balloon and were used to measure fluence rate at the surface of the esophageal wall during PDT. RESULTS AND CONCLUSIONS: The actual fluence rate measured was 1.5-3.9 times higher than the primary fluence rate for 630 nm. In general, the fluence rate amplification factor decreased with increasing redness of the tissue and was less for shorter diffusers. Fluence rate variations in time were observed which coincided with patients coughing, movement, and esophageal spasms. These factors combined with inter patient variability of the fluence rate measured appears to justify the routine application of this technique in PDT of BE.
Aminolevulinic Acid↗
Timing of 5-aminolaevulinic acid-induced photodynamic therapy for the treatment of patients with Barrett's oesophagus.
5-Aminolaevulinic acid-induced photodynamic therapy (ALA-PDT) is being used as an experimental treatment of Barrett's oesophagus (BE), a pre-malignant disorder in the distal oesophagus. The present study aims to acquire detailed knowledge on the pharmacokinetics of ALA and the photosensitizer protoporphyin IX (PPIX) in tissues and plasma of patients with BE to provide a rationale for the conditions used in ALA-PDT. A total of 26 patients with BE were randomized to varying time intervals between ingesting 60 mg/kg ALA and undergoing an endoscopy with biopsies of BE, normal oesophageal and gastric mucosa. At 1, 2, 7, 8 and 24 h, two patients at each time, and at 3, 4, 5 and 6 h, four patients at each time after ALA ingestion were included. ALA, porphyrin intermediates and PPIX were determined in all biopsy and plasma samples. The maximum concentration of PPIX was found earlier in BE (4.6+/-0.5 h) than in squamous epithelium (SQ) (6.6+/-2.2 h) (P<0.05). PPIX concentrations were higher in SQ than in BE especially at longer time intervals. In addition, tissue ALA concentrations were found to be 20-fold higher than the plasma concentrations at 1 h after ALA ingestion, suggesting uptake from the oesophageal lumen. Skin photosensitivity was short-lasting but often debilitating. Our results provide a rationale for the use of ALA-PDT for the treatment of BE at 4-5 h after ALA ingestion and for local application of ALA in the oesophagus. Patients undergoing ALA-PDT must be strongly advised to avoid sunlight for at least 24-36 h.
Administration, Oral↗
Cure of Barrett's carcinoma by ifosfamide chemotherapy.
The prognosis of patients with oesophageal cancer is poor, with an overall 5-year survival rate below 15%. The best chance for cure of patients with oesophageal cancer is surgical resection. However, more than 50% of patients have inoperable disease and can only be palliated for dysphagia. Some of these patients participate in studies investigating the activity of single-agent or combination chemotherapy. We report a patient who was cured of metastatic adenocarcinoma in Barrett's oesophagus by six courses of ifosfamide, a chemotherapeutic agent with little or no activity in other patients with adenocarcinoma of the oesophagus or gastro-oesophageal junction. After a follow-up of 13 years and 7 months, no evidence of tumour recurrence was found, while biopsies from the Barrett's oesophagus revealed only low-grade dysplasia. This case obviously raises the question as to how patients with inoperable oesophageal carcinoma can sometimes be cured by chemotherapy alone.
Adenocarcinoma↗
Predictors of outcome of single-dose brachytherapy for the palliation of dysphagia from esophageal cancer.
BACKGROUND: Single-dose brachytherapy is a commonly used palliative treatment modality for esophageal carcinoma, however, a considerable number of patients need additional treatment for persistent or recurrent dysphagia. Our aim was to establish predictors of an unfavorable outcome after single-dose brachytherapy. METHODS AND MATERIALS: Between December 1999 and July 2002, 95 patients with dysphagia from inoperable esophageal carcinoma were treated with single-dose (12 Gy) brachytherapy. Patients were followed-up prospectively by monthly home visits by a specialized research nurse. We investigated the patient and tumor characteristics that influence the risk of persistent dysphagia (continuing dysphagia within 4 weeks after treatment necessitating a second treatment) or recurrent dysphagia (occurring more than 4 weeks after treatment) after single-dose brachytherapy, using logistic and Cox regressions. RESULTS: At 4 weeks after brachytherapy, the dysphagia score was improved in 62/84 (74%) patients. Major complications occurred in 11/95 (12%) patients. In total, 42/95 (44%) patients were treated for persistent (n = 18) and/or recurrent dysphagia (n = 28). Persistent dysphagia (n = 18) was caused by persisting obstructing tumor confirmed at endoscopy, and these patients were treated with stent placement. Patients needing dilation before treatment had a higher risk of persistent dysphagia (odds ratio = 4.1; 95% CI 1.3-12). There was a trend toward a higher risk of persistent dysphagia for patients previously treated with chemotherapy (odds ratio = 3.2; 95% CI 0.81-12). In total, 34 events of recurrent dysphagia occurred in 28 patients, caused by obstructing tumor regrowth (n = 26), food bolus obstruction (n = 5), or other reasons (n = 3). None of the investigated patient and tumor characteristics had a significant association with the risk of developing recurrent dysphagia. Of all patients needing additional treatment (42/95), those who needed dilation before treatment had a higher risk of persistent and/or recurrent dysphagia (hazard ratio = 2.1; 95% CI 1.1-4.1). CONCLUSIONS: Patients with stenotic esophageal tumors that cannot be bypassed or who previously underwent chemotherapy are poor candidates for single-dose brachytherapy. For these patients, a higher and/or fractionated dose of brachytherapy or alternative palliative treatment modalities should be considered.
Aged↗
Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial.
BACKGROUND: Both single-dose brachytherapy and self-expanding metal stent placement are commonly used for palliation of oesophageal obstruction due to inoperable cancer, but their relative merits are unknown. We undertook a randomised trial to compare the outcomes of brachytherapy and stent placement in patients with oesophageal cancer. METHODS: Nine hospitals in the Netherlands participated in our study. Between December, 1999, and June, 2002, 209 patients with dysphagia from inoperable carcinoma of the oesophagus or oesophagogastric junction were randomly assigned to stent placement (n=108) or single-dose (12 Gy) brachytherapy (n=101), and were followed up after treatment. Primary outcome was relief of dysphagia during follow-up, and secondary outcomes were complications, treatment for persistent or recurrent dysphagia, health-related quality of life, and costs. Analysis was by intention to treat. FINDINGS: Nine patients (six [brachytherapy] vs three [stent placement]) did not receive their allocated treatments. None was lost to follow-up. Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. Stent placement had more complications than brachytherapy (36 [33%] of 108 vs 21 [21%] of 101; p=0.02), which was mainly due to an increased incidence of late haemorrhage (14 [13%] of 108 vs five [5%] of 101; p=0.05). Groups did not differ for persistent or recurrent dysphagia (p=0.81), or for median survival (p=0.23). Quality-of-life scores were in favour of brachytherapy compared with stent placement. Total medical costs were also much the same for stent placement (8215) and brachytherapy (8135). INTERPRETATION: Despite slow improvement, single-dose brachytherapy gave better long-term relief of dysphagia than metal stent placement. Since brachytherapy was also associated with fewer complications than stent placement, we recommend it as the primary treatment for palliation of dysphagia from oesophageal cancer.
Aged↗