Delayed complications after placement of self-expanding stents in malignant esophageal obstruction: treatment strategies and survival rate.

PURPOSE: Placement of self-expanding metal stents is regarded as a safe and effective treatment in patients with incurable malignant esophagogastric obstruction. However, proceeding and possible benefit of re-interventions in patients with recurrent dysphagia due to delayed complications (>4 weeks after stent insertion) is unclear. PATIENTS AND METHODS: In 133 patients with malignant stricture of the esophagus or the esophagogastric junction 164 expandable metal stents were placed. About 89 patients were followed up until death. All tumor- or stent-related complications and consequent re-interventions were recorded. RESULTS: The overall incidence of delayed complications was 53.4% (71 of 133 pts.), with 34 patients (25.6%) experiencing more than one complication. Recurrent dysphagia due to tumor ingrowth (22%) or overgrowth (15%), bolus obstruction (21%), stent migration (9%), and development of esophagorespiratory fistula (9%) was successfully treated by dilatation (24%), placement of a second/third stent (27%), laser therapy (16%), and/or placement of a feeding tube (PEG, 19%). The median survival of patients with endoscopic therapy was significantly longer (222 +/- 26 days) compared to patients without re-intervention (86 +/- 14 days, P < 0.0001). CONCLUSIONS: Delayed complications after metal stent placement for malignant esophageal stricture are common, but can be treated successfully by endoscopic re-intervention in most cases. Regular interventional therapy may also improve survival.

Germline NF1 mutational spectra and loss-of-heterozygosity analyses in patients with pheochromocytoma and neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a pheochromocytoma-associated syndrome. Because of the low prevalence of pheochromocytoma in NF1, we ascertained subjects by pheochromocytoma that also had NF1 in the hope of describing the germline NF1 mutational spectra of NF1-related pheochromocytoma. MATERIALS AND METHODS: An international registry for NF1-pheochromocytomas was established. Mutation scanning was performed using denaturing HPLC for intragenic variation and quantitative PCR for large deletions. Loss-of-heterozygosity analysis using markers in and around NF1 was performed. RESULTS: There were 37 eligible subjects (ages 14-70 yr). Of 21 patients with corresponding tumor available, 67% showed somatic loss of the nonmutated allele at the NF1 locus vs. 0 of 12 sporadic tumors (P = 0.0002). Overall, 86% of the 37 patients had exonic or splice site mutations, 14% large deletions or duplications; 79% of the mutations are novel. The cysteine-serine rich domain (CSR) was affected in 35% but the RAS GTPase activating protein domain (RGD) in only 13%. There did not appear to be an association between any clinical features, particularly pheochromocytoma presentation and severity, and NF1 mutation genotype. CONCLUSIONS: The germline NF1 mutational spectra comprise intragenic mutations and deletions in individuals with pheochromocytoma and NF1. NF1 mutations tended to cluster in the CSR over the RAS-GAP domain, suggesting that CSR plays a more prominent role in individuals with NF1-pheochromocytoma than in NF1 individuals without this tumor. Loss-of-heterozygosity of NF1 markers in NF1-related pheochromocytoma was significantly more frequent than in sporadic pheochromocytoma, providing further molecular evidence that pheochromocytoma is a true component of NF1.