Endoscopic versus histological characterisation of polyps during screening colonoscopy.

BACKGROUND: As screening colonoscopy becomes more widespread, the costs for histopathological assessment of resected polyps are rising correspondingly. Reference centres have published highly accurate results for endoscopic polyp classification. Therefore, it has been proposed that, for smaller polyps, the differential diagnosis that guides follow-up recommendations could be based on endoscopy alone. OBJECTIVE: The aim was to prospectively assess whether the high accuracy for endoscopic polyp diagnosis as reported by reference centres can be reproduced in routine screening colonoscopy. DESIGN: Ten experienced private practice endoscopists had initial training in pit patterns. Then they assessed all polyps detected during 1069 screening colonoscopies. Patients (46% men; mean age 63 years) were randomly assigned to colonoscopy with conventional or latest generation HDTV instruments. The main outcome measure was diagnostic accuracy of in vivo polyp assessment (adenomatous vs hyperplastic). Secondary outcome measures were differences between endoscopes and reliability of image-based follow-up recommendations; a blinded post hoc analysis of polyp photographs was also performed. RESULTS: 675 polyps were assessed (461 adenomatous, 214 hyperplastic). Accuracy, sensitivity and specificity of in vivo diagnoses were 76.6%, 78.1% and 73.4%; size of adenomas and endoscope withdrawal time significantly influenced accuracy. Image-based recommendations for post-polypectomy surveillance were correct in only 69.5% of cases. Post hoc analysis of polyp photographs did not improve accuracy. CONCLUSIONS: In everyday practice, endoscopic classification of polyp type is not accurate enough to abandon histopathological assessment and use of latest generation colonoscopes does not improve this. Image-based surveillance recommendations after polypectomy would consequently not meet guideline requirements. TRIALREGNO: NCT01297712.

Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection.

BACKGROUND: Current endoscopic therapy for neoplastic Barrett's oesophagus (BO) consists of complete resection/ablation of all Barrett's tissue including neoplastic lesions. Recurrence seems to be frequent after thermal therapy, such as radiofrequency ablation. OBJECTIVE: To analyse long-term recurrence of neoplasia and BO after successful widespread endoscopic mucosal resection (EMR). DESIGN: In a retrospective analysis, all patients undergoing widespread EMR of neoplastic BO between 2002 and 2007 at two referral centres were followed for at least 3 years after completion of endotherapy. Recurrence was diagnosed if neoplasia and/or BO were detected following previous successful complete removal, defined as at least two negative endoscopies and biopsies. RESULTS: Ninety patients undergoing widespread EMR were included (mean age 63 years; 82 male), 58% of whom underwent additional thermal ablation for minor residual disease. Complete eradication of neoplasia and Barrett's tissue was achieved in 90% of patients. On further follow-up (mean 64.8 months), recurrence of neoplastic and non-neoplastic BO was found in 6.2% and 39.5%, respectively. Recurring neoplasia (3 adenocarcinomas, 1 low-grade and 1 high-grade dysplasia) were found after a median of 44 months (range 38-85) and could be retreated endoscopically. In a multivariate analysis, Barrett's length was the only factor significantly associated with recurrence (OR 2.73). CONCLUSIONS: Even after seemingly complete endoscopic resection, recurrence of BO is frequent and independent of additional thermal therapy. Due to the possibility of neoplasia recurrence even after long disease-free intervals, follow-up should be extended beyond 5 years.

Subsquamous extension of intestinal metaplasia is detected in 98% of cases of neoplastic Barrett's esophagus.

BACKGROUND & AIMS: Subsquamous intestinal metaplasia (SSIM) has been observed after endotherapy in patients with neoplastic Barrett's esophagus (BE). However, it is not clear whether SSIM occurs in untreated patients. Incompletely eradicated SSIM could provide a source of recurrent disease. We assessed its prevalence in a large cohort of patients who had not received endoscopic therapy. METHODS: Two experienced pathologists analyzed 138 samples of 506 resection specimens found to contain squamous epithelium from 110 patients with neoplastic BE treated by widespread endoscopic mucosal resection (92 men; mean age, 66 years). The maximum extent of SSIM was measured. RESULTS: Of the 138 samples analyzed, 124 (89.9%) were found to contain SSIM from 108 of the 110 patients (98.2%). The mean length of SSIM was 3.3 mm (range, 0.2-9.6 mm; 25% ≥ 5 mm); SSIM length correlated with BE length (P < .05). In 83 of 138 samples (60.1%), the SSIM consisted partially or entirely of neoplasias of different grades, with a mean subsquamous extension of 3.3 mm; the extension correlated with grade of neoplasia (P = .0001). CONCLUSIONS: Most patients with BE with neoplasia (of all grades) have subsquamous extension of intestinal metaplasia, including subsquamous extension of lesions at the squamocolumnar junction. Therefore, biopsy and resection of neoplastic BE should extend at least 1 cm into the squamous epithelium.

Systematic mutagenesis of potential glycosylation sites of lysosomal acid lipase.

Lysosomal acid lipase (LAL; EC 3.1.1.13) is a key enzyme in the intracellular lipid metabolism. It hydrolyzes exogenous triglycerides and cholesterol esters taken up by various cell types. LAL has six potential N-glycosylation sites and one potential O-glycosylation site. Elimination of each of the six Asn-(X)-Ser/Thr sites by site-directed mutagenesis and expression in baculovirus-infected Spodoptera frugiperda cells resulted in two single-mutant enzymes without lipolytic activities (N134Q and N246Q) and four mutants with preserved activities. The two inactive mutants were not detectable on immunoblot analysis, indicating that they were not secreted. Six double mutants in all possible combinations except for the two inactive single mutants were produced and expressed. Double mutants in combination with the N9 glycosylation site showed reduced activities as compared to the other mutants or the wild-type enzyme. Kinetic data of LAL glycosylation mutants indicate that substrate affinity of N9Q was not changed, but k (cat) of N9 mutants was reduced distinctly compared to the wild-type enzyme. Peanut agglutinin lectin did not recognize LAL, demonstrating that the protein has no core1 structure (Galbeta 1-3 GalNAc) of O-glycosylation. These data indicate that at least two of the six N-glycosylation sites are used in native lipase. N134 and N246 were found to be essential for LAL activity. We conclude that glycosylation plays an important role in the formation of functional LAL.