Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus.

OBJECTIVE: Endoscopic therapy is increasingly being used in the treatment of high-grade intraepithelial neoplasia (HGIN) and mucosal adenocarcinoma (BC) in patients with Barrett's oesophagus. This report provides 5 year follow-up data from a large prospective study investigating the efficacy and safety of endoscopic treatment in these patients and analysing risk factors for recurrence. DESIGN: Prospective case series. SETTING: Academic tertiary care centre. PATIENTS: Between October 1996 and September 2002, 61 patients with HGIN and 288 with BC were included (173 with short-segment and 176 with long-segment Barrett's oesophagus) from a total of 486 patients presenting with Barrett's neoplasia. Patients with submucosal or more advanced cancer were excluded. INTERVENTIONS: Endoscopic therapy. MAIN OUTCOME MEASURES: Rate of complete remission and recurrence rate, tumour-associated death. RESULTS: Endoscopic resection was performed in 279 patients, photodynamic therapy in 55, and both procedures in 13; two patients received argon plasma coagulation. The mean follow-up period was 63.6 (SD 23.1) months. Complete response (CR) was achieved in 337 patients (96.6%); surgery was necessary in 13 (3.7%) after endoscopic therapy failed. Metachronous lesions developed during the follow-up in 74 patients (21.5%); 56 died of concomitant disease, but none died of BC. The calculated 5 year survival rate was 84%. The risk factors most frequently associated with recurrence were piecemeal resection, long-segment Barrett's oesophagus, no ablative therapy of Barrett's oesophagus after CR, time until CR achieved >10 months and multifocal neoplasia. CONCLUSIONS: This study showed that endoscopic therapy was highly effective and safe, with an excellent long-term survival rate. The risk factors identified may help stratify patients who are at risk for recurrence and those requiring more intensified follow-up.

Development of an MHC-class I peptide selection assay combining nanoparticle technology and matrix-assisted laser desorption/ionisation mass spectrometry.

Human leukocyte antigen (HLA)-bound peptides are central for recognition of infected/transformed cells by T cells, and have formed the basis for many immunotherapy strategies. Epitopes from a given protein sequence (e.g. from viral proteins or oncoproteins) can be predicted by algorithms, as individual HLA receptors bind peptides through defined binding motifs. Peptides with the highest predicted binding score are then normally tested for their binding ability in binding assays. However, with the assays already established, only one peptide can be tested for binding per assay. This is certainly not a reflection of the in vivo situation, where several peptides generated via the major histocompatability complex (MHC)-class I processing pathway compete for HLA-receptor binding. Here, we describe the development of a method that can mimic the competition between multiple peptides for binding to a single HLA receptor molecule. We used silica nanoparticles with immobilised HLA-A2 complexes to screen HLA-A2 binder-peptides out of a known peptide mixture. The washed beads were analysed for selectively bound peptides by matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry. The advantage of the system is that the bound peptides can be unambiguously identified without any prior modification (e.g. radioactive or fluorescence labelling), even from complex peptide mixtures.

Secondary sclerosing cholangitis after long-term treatment in an intensive care unit: clinical presentation, endoscopic findings, treatment, and follow-up.

BACKGROUND AND STUDY AIMS: We present ten patients who developed secondary sclerosing cholangitis following long-term treatment in an intensive care unit (ICU) between 1999 and 2004. PATIENTS AND METHODS: Ten consecutive patients who had no evidence suggestive of pre-existing hepatobiliary disease were admitted to an ICU because of trauma (n = 5), intracerebral hemorrhage (n = 3), or nonabdominal postsurgical complications (n = 2). All the patients had required treatment with long-term ventilation, catecholamines, total parenteral nutrition, and several antimicrobial agents. RESULTS: Cholestasis was first noted within 11 days after the initial insult. Endoscopic retrograde cholangiopancreatography (ERCP), performed after a median follow-up of 69 days, revealed multifocal stricturing and beading of the intrahepatic bile ducts, and attenuation of the peripheral branches. In all the patients, the bile ducts were partially filled by black-pigmented thrombotic material. All the patients underwent endotherapy, which comprised sphincterotomy and removal of the occluding material, in an attempt to improve biliary drainage; the treatment had to be repeated in seven of the ten patients. After a median follow-up period of 21 months, despite transient clinical improvement following endotherapy, complete recovery has not been achieved in any of the patients and so far one patient has had to undergo orthotopic liver transplantation as a result of end-stage liver disease. CONCLUSIONS: The development of secondary sclerosing cholangitis in patients who have received long-term treatment in an ICU is a rare event of unknown pathophysiology, but patients demonstrate characteristic findings on ERCP. It is not known whether endotherapy can delay the progress of the condition in the long term.