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Additional file 1: Comparison between American and European Academies of Neurology eligible studies.

In the last decades, many contributions have examined the Mass Transport Deposits (MTDs) in both modern and ancient examples for the comprehension of the sedimentary dynamics along the carbonate escarpments. Such sedimentary bodies have a great economic significance, since they are widely considered prone to the development of petroleum systems. In particular, MTDs from Cretaceous escarpments are well known from many regions of the world, since they are typically rich in rudists aragonite fragments determining high percentages of porosity. In these respect the deep knowledge on the facies architecture of these depositional systems is of broad interest as can offer examples for the prediction of the geometry and distribution of the facies types. Subsurface studies based on seismic data require comparisons with analogues from outcrops that allow the observation of structure and sedimentary characters of the MTDs. On this topic, we carried out a sedimentological study in northwestern Sicily on a well-exposed Cretaceous escarpment, (Custonaci Cretaceous Escarpment, CCE). At present the original escarpment is dismembered in several tectonic units in the Maghrebian Chain. The biostratigraphic data allow to constrain the beginning of the slope sedimentation at the lowermost Cretaceous. Along the succession, the MTDs formed by huge bodies of megabreccias, alternate to finer grained skeletal rudstone and floatstone emplaced by turbidity currents and grain flows. The presence of pillow basalt intercalations suggests a major role of the tectonics as trigger for the MTDs emplacement. Furthermore, synsedimentary listric faults, slump scars and channel filling megabreccias allow to reconstruct the present day polarity of the slope. The emplacement of coarse megabreccia beds at Custonaci can be documented until the Santonian. However, upward alternances of Scaglia-type pelagic calcilutites and skeletal turbidites and debrite beds lasted up to the Maastrichtian. Nevertheless the Tertiary deformations have obscured the relationships of the CCE with the original source areas, there is a tight correlation between the evolution of the Cretaceous Panormide Platform and the studied slope.

Objective: To verify whether immunohistochemistry might be useful in the distinction between a true laterocervical metastasis of an undetected thyroid carcinoma and a primary tumor outside the gland. Design: Galectin-3, cytokeratin 19, and HBME-1 were assessed in six cases (group A) of laterocervical masses harboring papillary thyroid carcinoma (PTC) but without a thyroid tumor, and in eight cases (group B) showing PTC both in the thyroid and in the laterocervical masses. In both groups, normal-looking follicles adjacent to the laterocervical neoplasia were present. Main outcome: We found that the apparently normal follicles in group A were negative for all the antibodies, while group B showed strong and diffuse positive immunostaining. The neoplastic areas were always positive for all the antibodies in both groups. Conclusion: Even if immunohistochemical patterns of residual follicles of group B are very well differentiated that they resemble normal thyroid parenchyma, they may well be metastatic carcinomas. On the contrary, the presence of morphologically and immunohistochemically normal-looking follicles in group A, with no intrathyroid tumor, suggests that the primary PTC might possibly develop in the ectopic thyroid tissue. In cases showing morphologically and immunohistochemically normal-looking follicles in laterocervical masses, these findings might lead to a reduction of the overdiagnosis of metastatic disease of an undetected carcinoma. © Mary Ann Liebert, Inc.

BACKGROUND: The role of Barrett esophagus in carcinogenesis is widely accepted, but the significance of esophageal columnar mucosa without histological intestinal metaplasia, known as columnar-lined esophagus, is debated. MATERIAL/METHODS: We studied 128 patients free of Helicobacter pylori with reflux-related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients with Barrett esophagus (referred to as the Barrett group) and 22 patients without intestinal metaplasia (columnar group). Samples from 20 subjects free of H. pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20 (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming (MUC2), and tumor protein p53 (TP53) was assessed. RESULTS: Samples taken 1 cm above the gastroesophageal junction showed KRT7 staining in all cases in the Barrett and columnar groups and none in the control group. Immunostaining for TP53 was absent in the control group, and more frequent in the columnar group (7, 31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a total of 11 specimens (50.0%). CONCLUSIONS: The expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression. Expression of KRT7 may occur in basal glandular cells as a result of their multipotentiality and susceptibility to immunophenotype changes induced by reflux.

Introduction and Objective: The clinical value of early intravesical adjuvant chemotherapy after TUR of intermediate risk non-muscle-invasive bladder cancer (NMI TCCB) is well established. On the other hand, the optimal schedule regimen and the role of maintenance are still debated. The aim of the present study was to evaluate the effectiveness of one-year maintenance schedule in patients submitted to TUR plus adjuvant early intravesical chemotherapy. Methods: Between May 2002 and August 2003, 577 patients, were recruited. All patients underwent TUR and early (within 6 hours) intravesical chemotherapy with epirubicin at the dose of 80 mg diluted in 60 ml of saline solution. When histology was available, 95 patients were excluded from the study since they were harbouring T1G3, Tis or single and primary Ta G1-G2 tumors. Four hundred eighty-two patients with intermediate risk NMI TCCB were randomized according 2 different intravesical instillation schedules: Arm A, 5 more weekly instillations; arm B, 5 more weekly instillations followed by monthly instillations for a total of 16 instillations. All patients were submitted 3-monthly for the first 2-years and then 6-monthly to cytology, cystoscopy and biopsy of every suspicious bladder lesion. Results: Out of 482 randomized patients, 396 are evaluable for toxicity and 392 for efficacy. The tumours were multiple in 318 patients (66.0%) and recurrent in 192 (39.8%). No difference emerged between the 2 arms in relation to tumors’ characteristics. The median follow-up time was 22 months (range: 3-56). Eighty-two (20.9%) patients recurred at a median time of 9 months from TUR. Four patients progressed (1%). The recurrence rate was 24.5% (47/192) in arm A and 17.5% (35/200) in arm B (p=0.05). No difference was evident between the two arms for recurrence rate at 3 months (p=0.06). However, an advantage in favour of maintenance emerged in terms of recurrence rate at 6 (p=0.01), 9 (p=0.04) and 12 months (p=0.03) and in terms of recurrence-free interval (p=0.03). No difference for toxicity was evident according to treatment schedule. Conclusions: A preliminary analysis at 2-year mean follow-up, in patients with intermediate risk NMI TCCB treated with early epirubicin intravesical chemotherapy followed by 5 weekly instillation, the risk of tumour recurrence is significantly reduced without enhanced toxicity by one-year maintenance.