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ABSTRACT: Different ablation techniques have been utilized in the treatment of Barrett’s esophagus (BE) to reduce the risk of degeneration.
Treatment complications, risk of recurrence, and buried intestinal metaplasia (IM) are all major concerns. The effect of diode
laser treatment on BE, studied in a group of patients over a long-term period, is presented here. All patients with histology
of IM or low-grade dysplasia (LGD) treated with diode laser therapy for BE and followed for at least 24months were included
in the study. Treatment sessions were carried out every 3months and bioptic follow-up examinations were done yearly. Patients
without antireflux surgery received proton pump inhibitors. A total of 20 patients with IM, four of them with LGD, were treated
with 161 laser sessions (in mean eight per patient) without complications. Complete, sustained endoscopic and histologic remission
was obtained in 13 patients (11/12 with BE ≤ 3cm and 2/8 with BE >3cm, p < 0.01) and a mean of 83 ± 27% of the metaplasic tissue was removed in all the patients. All four cases of LGD healed to
squamous tissue. No buried metaplasia, recurrences, or disease progressions were reported after a mean follow-up of 6years
and 2months. Diode laser ablation is a safe and effective method in most cases of short BE, while it is less effective in
the long form, requiring a large number of sessions. Long-term results show that the risk of recurrence and of buried intestinal
metaplasia underneath neosquamous epithelium is negligible.
KeywordsAblation–Barrett’s esophagus–Diode laser–Endoscopy–Intestinal metaplasia
Lasers in Medical Science 04/2012; 26(2):223-228. · 2.00 Impact Factor
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Giovanni Zaninotto, Paola Parente,
Renato Salvador,
Fabio Farinati,
Chiara Tieppo,
Nicola Passuello,
Lisa Zanatta,
Matteo Fassan,
Francesco Cavallin,
Mario Costantini,
Claudia Mescoli,
Giorgio Battaglia,
Alberto Ruol,
Ermanno Ancona,
Massimo Rugge
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ABSTRACT: Barrett's esophagus (BE) is the most serious complication of GERD. In BE patients, this observational study compares the effects of antireflux surgery versus antisecretory medical therapy.
Overall, 89 BE patients (long BE = 45; short BE = 44) were considered: 45 patients underwent antireflux surgery and 44 underwent medical therapy. At both initial and follow-up endoscopy, symptoms were assessed using a detailed questionnaire; BE phenotypic changes [intestinal metaplasia (IM) presence/type, Cdx2 expression] were assessed by histology (H&E), histochemistry (HID), and immunohistochemistry. Surgical failures were defined as follows: (1) abnormal 24-h pH monitoring results after surgery, (2) endoscopically evident recurrent esophagitis, and (3) recurrent hiatal hernia or slipped fundoplication on endoscopy or barium swallow.
Reversion of IM was observed in 12/44 SSBE and 0/45 LSBE patients (p < 0.01). Reversion was more frequently observed after effective antireflux surgery than after medical treatment (p = 0.04). In patients with no further evidence of IM after therapy, Cdx2 expression was also absent (p = 0.02). The extent of IM was reduced, and the IM phenotype improved in SSBE patients after surgery.
Patients with short BE (but not those with long BE) may benefit from surgically reducing the esophagus' exposure to GE reflux; among these patients, successful surgery carries a higher IM reversion rate than medical treatment.
Journal of Gastrointestinal Surgery 11/2011; 16(1):7-14; discussion 14-5. · 2.83 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Different ablation techniques have been utilized in the treatment of Barrett's esophagus (BE) to reduce the risk of degeneration. Treatment complications, risk of recurrence, and buried intestinal metaplasia (IM) are all major concerns. The effect of diode laser treatment on BE, studied in a group of patients over a long-term period, is presented here. All patients with histology of IM or low-grade dysplasia (LGD) treated with diode laser therapy for BE and followed for at least 24 months were included in the study. Treatment sessions were carried out every 3 months and bioptic follow-up examinations were done yearly. Patients without antireflux surgery received proton pump inhibitors. A total of 20 patients with IM, four of them with LGD, were treated with 161 laser sessions (in mean eight per patient) without complications. Complete, sustained endoscopic and histologic remission was obtained in 13 patients (11/12 with BE ≤ 3 cm and 2/8 with BE >3 cm, p < 0.01) and a mean of 83 ± 27% of the metaplasic tissue was removed in all the patients. All four cases of LGD healed to squamous tissue. No buried metaplasia, recurrences, or disease progressions were reported after a mean follow-up of 6 years and 2 months. Diode laser ablation is a safe and effective method in most cases of short BE, while it is less effective in the long form, requiring a large number of sessions. Long-term results show that the risk of recurrence and of buried intestinal metaplasia underneath neosquamous epithelium is negligible.
Lasers in Medical Science 03/2011; 26(2):223-8. · 2.00 Impact Factor
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Matteo Fassan,
Stefano Volinia,
Jeff Palatini,
Marco Pizzi,
Raffaele Baffa,
Marina De Bernard,
Giorgio Battaglia, Paola Parente,
Carlo M Croce,
Giovanni Zaninotto,
Ermanno Ancona,
Massimo Rugge
[show abstract]
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ABSTRACT: Barrett's esophagus (BE) is characterized by the native stratified squamous epithelium (N) lining the esophagus being replaced by a columnar epithelium with intestinal differentiation (Barrett's mucosa; BM). BM is considered as the main risk factor for esophageal adenocarcinoma (Barrett's adenocarcinoma; BAc). MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting messenger RNAs and they are reportedly dysregulated in BM. To test the hypothesis that a specific miRNA expression signature characterizes BM development and progression, we performed miRNA microarray analysis comparing native esophageal mucosa with all the phenotypic lesions seen in the Barrett's carcinogenic process. Specimens were collected from 14 BE patients who had undergone esophagectomy, including: 14 with N, 14 with BM, 7 with low-grade intraepithelial neoplasia, 5 with high-grade intra-epithelial neoplasia and 11 with BAc. Microarray findings were further validated by quantitive real-time polymerase chain reaction and in situ hybridization analyses using a different series of consecutive cases (162 biopsy samples and 5 esophagectomies) of histologically proven, long-segment BE. We identified a miRNA signature of Barrett's carcinogenesis consisting of an increased expression of 6 miRNAs and a reduced expression of 7 miRNAs. To further support these results, we investigated target gene expression using the Oncomine database and/or immunohistochemical analysis. We found that target gene expression correlated significantly with miRNA dysregulation. Specific miRNAs are directly involved in BE progression to cancer. miRNA profiling significantly expands current knowledge on the molecular history of Barrett's carcinogenesis, also identifying molecular markers of cancer progression.
International Journal of Cancer 12/2010; 129(7):1661-70. · 5.44 Impact Factor
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ABSTRACT: In Barrett's mucosa, both aneuploidy and TP53 mutations are consistently recognized as markers of an increased risk of Barrett's adenocarcinoma. Overexpression of the mitotic kinase encoding gene (AURKA) results in chromosome instability (assessed from the micronuclei count) and ultimately in aneuploidy. Eighty-seven esophageal biopsy samples representative of all the phenotypic lesions occurring in the multistep process of Barrett's carcinogenesis (gastric metaplasia in 25, intestinal metaplasia in 25, low-grade intraepithelial neoplasia in 16, high-grade intraepithelial neoplasia in 11, and Barrett's adenocarcinoma in 10) were obtained from long segments of Barrett's mucosa. Twenty-five additional biopsy samples of native esophageal mucosa were used for control purposes. In all tissue samples, the immunohistochemical expression of both AURKA and TP53 gene products was scored; and the micronuclei index was calculated. AURKA immunostaining increased progressively and significantly along with dedifferentiation of the histologic phenotype (P < .001). Nine of 10 Barrett's adenocarcinomas showed AURKA immunostaining. AURKA expression correlated significantly with p53 expression and the micronuclei index (both Ps < .001). AURKA overexpression is significantly associated with Barrett's mucosa progressing to Barrett's adenocarcinoma and contributes to esophageal carcinogenesis via chromosome instability. The identification of AURKA as a novel molecular target of cancer progression in Barrett's mucosa provides a lead for the development of new therapeutic approaches in Barrett's mucosa patients.
Human pathology 10/2010; 41(10):1380-6. · 3.03 Impact Factor
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ABSTRACT: To test the contribution of programmed cell death 4 (PDCD4) tumour suppressor gene in Barrett's carcinogenesis.
PDCD4 immunohistochemical expression was assessed in 88 biopsy samples obtained from histologically proven long-segment Barrett's mucosa (BM; 25 non-intestinal columnar metaplasia, 25 intestinal metaplasia (IM), 16 low-grade intraepithelial neoplasia (LG-IEN), 12 high-grade IEN (HG-IEN) and 10 Barrett's adenocarcinoma (BAc)). As controls, 25 additional samples of native oesophageal mucosa (N) were obtained from patients with dyspepsia. To further support the data, the expression levels of miR-21, an important PDCD4 expression regulator, in 14 N, 5 HG-IEN and 11 BAc samples were determined by quantitative real-time PCR analysis. Results PDCD4 immunostaining decreased progressively and significantly with the progression of the phenotypic changes occurring during Barrett's carcinogenesis (p<0.001). Normal basal squamous epithelial layers featured strong PDCD4 nuclear immunoreaction (mostly coexisting with weak-moderate cytoplasmic staining). Non-intestinal columnar metaplasia and intestinal metaplasia preserved a strong nuclear immunostaining; conversely, a significant decrease in PDCD4 nuclear expression was seen in dysplastic (LG-IEN and HG-IEN) and neoplastic lesions. Weak-moderate cytoplasmic immunostaining was evident in cases of LG-IEN, while HG-IEN and BAc samples showed weak cytoplasmic or no protein expression. As expected, miR-21 expression was significantly upregulated in HG-IEN and BAc samples, consistently with PDCD4 dysregulation.
These data support a significant role for PDCD4 downregulation in the progression of BM to BAc, and confirm miR-21 as a negative regulator of PDCD4 in vivo. Further efforts are needed to validate PDCD4 as a potential prognostic marker in patients with Barrett's oesophagus.
Journal of clinical pathology 08/2010; 63(8):692-6. · 2.43 Impact Factor
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Human pathology 09/2009; 40(8):1206-7; author reply 1207-8. · 3.03 Impact Factor
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Cancer Prevention Research 02/2009; 2(1):94. · 4.91 Impact Factor
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The American Journal of Gastroenterology 12/2008; 103(11):2944-6; author reply 2946-7. · 7.28 Impact Factor
