Calcitonin levels in autoimmune atrophic gastritis-related hypergastrinemia.

PURPOSE: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels. METHODS: Three groups of patients were consecutively enrolled in this  multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females). RESULTS: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785). CONCLUSIONS: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG.

Editorial: focus on waste-heat harvesting via thermoelectric conversion: materials, devices and systems for sustainable energy technologies.

The focus collection 'Waste-heat harvestingviathermoelectric conversion: Materials, devices and systems for sustainable energy technologies' collates several research articles and a Roadmap highlighting the most recent advances in the field of thermoelectricity from the viewpoint of both basic and applied research, with a special eye on the work of the Italian community.

Thermal conductivity of silicon nanowire forests.

A large amount of parallel silicon nanowires, placed perpendicularly to a silicon substrate (silicon nanowire forests), have been contacted and assembled in order to fabricate legs of a thermoelectric generator. This paper reports the measurement of the main parameter for thermoelectric applications, which is the thermal conductivity. The reported value, which confirms the strong reduction of the thermal conductivity in nanostructures, is measured on a large amount (>107) of parallel nanowires with a diameter variable in the range 60-120 nm, and takes into account eventual non-uniformities which are unavoidable on surfaces of several mm2. As silicon nanowire forests are very thin, it has been necessary to develop a suitable measurement apparatus. The fabrication of devices based on silicon nanowire forests, the apparatus and the measurement procedure, as well as the the results, are illustrated and discussed.

Note: Improvement of the 3ω thermal conductivity measurement technique for its application at the nanoscale.

Conventional techniques for thermal conductivity measurements can lead to unreliable results when applied to nanostructures because heaters and temperature sensors needed for the measurement cannot have a negligible size and therefore perturb the result. In this paper, we focus on the 3ω technique, applied to the evaluation of the thermal conductivity of suspended silicon nanoribbons. We introduce a numerical approach based on the finite element solution of the electrical and thermal transport equations and compare its results with those of conventional methods. We show that with our approach we achieve an excellent fit of the experimental data, in particular, for nanostructured materials.

Papillary thyroid carcinoma (PTC) in Lynch syndrome: Report of two cases and discussion on Lynch syndrome behaviour and genetics.

We present here two cases of papillary thyroid carcinoma (PTC) in patients affected by Lynch syndrome (LS). The first case is a 47-year-old woman with typical hereditary non-polyposis colorectal cancer (HNPCC) syndrome, reported with endometrial and ovarian carcinoma at age 43, and colon cancer at age 45. The patient underwent total thyroidectomy and central node dissection in 2007, at 47years old, with a histological diagnosis of PTC (T1aN1a). Molecular genetics showed a germ-line mutation of the MLH1 gene, 1858 G>T(E620X), with substitution of glycine with a stop codon at position 620. This mutation has pathogenetic significance and was considered responsible for the various tumours of the HNPCC spectrum. In particular, in the same kindred, spanning 5 generations, there were 5 members with colorectal cancer, 4 with endometrial cancer, 3 with gastric and 2 with breast cancer. The second case is a 34-year-old man with typical HNPCC syndrome with colonic resection for colon cancer at age 21. The patient underwent total thyroidectomy with central and lateral node dissection in 2010, at age 34, with a histological diagnosis of PTC with nodal metastases (pT4N1b). Molecular genetic analysis showed a germ-line mutation of the MSH2 gene (thymine insertion at position 907). This mutation had pathogenetic significance and was considered responsible for HNPCC development. Two similar cases have been reported: a 39-year-old woman, and a 44-year-old woman, affected by HNPCC syndrome, with anaplastic thyroid carcinoma and undifferentiated thyroid carcinoma, respectively. We reviewed the Lynch syndrome literature on the history, genetics and expanding tumour spectrum of this condition.

Functional significance of the novel H-RAS gene mutation M72I in a patient with medullary thyroid cancer.

Medullary thyroid cancer (MTC) accounts for around 5-10% of all thyroid cancers. Though usually sporadic, 1 in 4 cases are of genetic origin, with germinal mutations in the RET proto-oncogene in familial forms and somatic mutations both in RET and in the RAS family genes in sporadic ones.This study aimed to characterize a rare H-RAS sequence variant -M72I- in a patient with sporadic MTC, focusing on its functional significance.Mutation analysis was performed for the RET, N-RAS, K-RAS and H-RAS genes by direct sequencing. Western blot analysis was done on 4 thyroid tissues from 1 patient carrying the M72I mutation in H-RAS, 1 with the Q61R mutation in H-RAS, 1 with no RET, H-RAS, K-RAS or N-RAS gene mutations, and 1 normal thyroid, using different antibodies against Erk1/2, phospho-Erk1/2 (Thr202/Tyr204), Akt and phospho-Akt (Ser473). Large-scale molecular dynamics simulations were completed for H-RAS wt and H-RAS M72I.Western blot analysis demonstrated that both MAPK and PI3K/Akt pathways were activated in the MTC patient carrying the M72I variant. In silico results showed conformational changes in H-RAS that could influence its activation by Sos and phosphate binding. Results of molecular dynamics were consistent with Western blot experiments.The M72I mutation may contribute effectively to proliferation and survival signaling throughout the MAPK and PI3K/Akt pathways. This work underscores the importance of studying genetic alterations that may lead to carcinogenesis.

Galectin-3 expression in thyroid fine needle cytology (t-FNAC) uncertain cases: validation of molecular markers and technology innovation.

Thyroid cancer is not very common, accounting for 1-2% of all cancers, with a population incidence of about 0.004%. Currently, the ability to discriminate between follicular adenoma and carcinoma represents the major challenge in preclinical diagnosis of thyroid proliferative lesions. Better discrimination between the two would help avoid unnecessary thyroidectomy and save valuable resources. Over the years, galectin-3 (Gal-3) has been proposed as a diagnostic marker with varied success. In this paper, we used Environmental Scanning Electron Microscopy Immunogold Labelling (ESEM-IGL) to investigate the expression of Gal-3 on Thin-Prep fine needle aspiration cytology (FNAC). We optimized the ESEM-IGL method on thyroid cell lines (RO-82 and FTC-133) comparing our membrane Gal-3 labeling data with Western blot. We evaluated 183 thyroid FNAC from Italian patients with a uncertain pre-surgical diagnosis. ESEM-IGL method marker sensitivity is 71.2%, while specificity is 53.3% and diagnostic efficacy is 61.2%. Our results confirmed that Gal-3 expression is associated with situations of hypertrophy and/or cellular hyperproliferation, pathophysiological situations common both to adenomas and to thyroid carcinomas. The innovation of thyroid FNAC Thin-Prep ESEM-IGL shows the levels of Gal-3 immunolabeling clearly, even through the individual cells of a thyroid nodule. However, Gal-3 alone, as a molecular marker of thyroid cancer, can still have a limited application in pre-surgery diagnosis.

Autoimmune gastritis: histology phenotype and OLGA staging.

BACKGROUND: Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. AIMS: To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. METHODS: A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. RESULTS: Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H. pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant (P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. CONCLUSIONS: In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H. pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies.

Selective doping of silicon nanowires by means of electron beam stimulated oxide etching.

Direct patterning of silicon dioxide by means of electron beam stimulated etching is shown, and a full characterization of exposure dose is presented. For its high dose, this technique is unsuitable for large areas but can be usefully employed like a precision scalpel for removing silicon dioxide by well-localized points. In this work, this technique is applied to the definition of windows through the oxide surrounding top down fabricated n-doped silicon nanowires. These windows will be employed for a selective doping of the nanowire by boron diffusion. In this way, pn junctions can be fabricated in well-localized points in the longitudinal direction of the nanowire, and an electrical contact to the different junctions can be provided. Electrical I-V characteristics of a nanowire with pn longitudinal junctions are reported and discussed.

Clinical outcome of low-risk differentiated thyroid cancer patients after radioiodine remnant ablation and recombinant human thyroid-stimulating hormone preparation.

AIM: Recombinant human thyroid-stimulating hormone (rhTSH) has been approved in Europe as a preparation tool for radioiodine ablation of post-surgical thyroid remnants in patients with low-risk differentiated thyroid cancer (DTC). Published studies report that, both thyroid hormone withdrawal and rhTSH preparation result in similar rates of successful remnant ablation, but few studies have determined the effectiveness of rhTSH preparation on disease recurrence. We sought to determine the clinical outcome, considering both ablation success and disease recurrence, of low-risk DTC patients who underwent (131)I ablation. MATERIALS AND METHODS: This retrospective study describes the clinical outcome of 100 patients treated with (131)I remnant ablation after preparation with rhTSH. After ablation, patients were classified as in complete remission, as having no evidence of persistent disease, or as having clinical recurrence on the basis of a subsequent diagnostic whole body scan with (131)I, stimulated thyroglobulin and cross-sectional imaging studies. RESULTS: Overall assessment of ablation success was verified and obtained in 75% of patients (75/100). Considering only patients who underwent a diagnostic whole body scan and stimulated thyroglobulin without interfering anti-thyroglobulin antibody, complete ablation was obtained in 96% of patients (75/78). After a follow-up of about 4 years, 78 patients are in complete remission: 75 with initial ablation success and three who achieved a complete remission during subsequent follow-up. Among the remaining 22 patients, 21 have no clinical evidence of disease (NCED), indicating the inability to verify the complete remission or to detect residual disease, as in patients with positive thyroglobulin antibody, whereas one has persistent disease demonstrated only by stimulated thyroglobulin. No recurrences were observed. Of four patients initially classified as having persistent disease, one obtained a complete remission and two are now considered NCED. CONCLUSION: Our data confirm the favourable outcome, with low rates of recurrence and persistent disease, of patients with low-risk DTC who underwent (131)I ablation after rhTSH. Moreover, our results compare favourably with those reported in the literature in patients prepared with rhTSH, but also in patients prepared with hormone withdrawal.

Report on a case of Rothmund-Thomson syndrome associated with esophageal stenosis.

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis. While its incidence is unknown, approximately 300 cases have been reported in the literature. The syndrome typically presents with a characteristic facial rash (poikiloderma), its diagnostic hallmark, and heterogeneous clinical features including congenital skeletal abnormalities, sparse hair distribution, juvenile cataracts, and a predisposition to osteosarcoma. Gastrointestinal symptoms, such as pyloric stenosis, anal atresia, annular pancreas, and rectovaginal fistula, have also been reported sporadically. This is a report describing a patient diagnosed with RTS referred to us because of dysphagia caused by esophageal stenosis. Long-term results of endoscopic dilation are also presented.

Gastritis OLGA-staging and gastric cancer risk: a twelve-year clinico-pathological follow-up study.

BACKGROUND: Intestinal-type gastric cancer (GC) still ranks among the high-incidence, highly lethal malignancies. Atrophic gastritis is the cancerization field in which GC develops. The current histological reporting formats for gastritis do not include any (atrophy-based) ranking of GC risk. AIM: To test the gastritis OLGA-staging (Operative Link for Gastritis Assessment) in prognosticating neoplastic progression. METHODS: Ninety-three Italian patients were followed up for more than 12 years (range: 144-204 months). Clinical examinations, pepsinogen serology, endoscopy and histology (also assessing Helicobacter pylori status) were performed both at enrolment (T1) and at the end of the follow-up (T2). RESULTS: All invasive or intra-epithelial gastric neoplasia were consistently associated with high-risk (III/IV) OLGA stages. There was a significant inverse correlation between the mean pepsinogen ratio and the OLGA stage (test for trend; P < 0.001). OLGA-staging at T1 predicted both the OLGA stage (Kaplan-Maier log-rank test, P = 0.001) and the neoplasia at T2 (Kaplan-Maier log-rank test, P = 0.001). CONCLUSIONS: This long-term follow-up study provides the first evidence that gastritis OLGA-staging conveys relevant information on the clinico-pathological outcome of gastritis and therefore for patient management. According to OLGA-staging and H. pylori-status, gastritis patients could be confidently stratified and managed according to their different cancer risks.

Minimally invasive enucleation of esophageal leiomyoma.

BACKGROUND: Leiomyoma accounts for 70% of all benign tumors of the esophagus. Open enucleation via thoracotomy has long been the standard procedure, but thoracoscopic and laparoscopic approaches have recently emerged as interesting alternatives. To date, only case reports or very small series of such techniques have been reported. The authors report their experience over the past decade. METHODS: Between January 1999 and August 2005, 11 patients (6 men and 5 women; median age, 44 years) underwent surgery after presenting with dysphagia, chest pain, or heartburn. The surgical approaches included right video-assisted thoracoscopy (n = 7) for tumors of the middle lower third of the esophagus and laparoscopy (n = 4) for tumors within 4 to 5 cm of the lower esophageal sphincter or located at the gastroesophageal junction (GEJ). Intraoperative endoscopy with air insufflation during enucleation was used to confirm mucosal integrity and safeguard against esophageal perforation. Reapproximation of the muscle layers was performed after tumor enucleation to prevent the development of a pseudodiverticulum. A Nissen or Toupet fundoplication was added for patients undergoing laparoscopic enucleation of the leiomyoma. RESULTS: The median operative time was 150 min. All tumors were benign leiomyomas (median size, 4.5 cm). One leiomyoma located at the gastroesophageal junction required intraoperative mucosal repair with three stitches for an esophageal perforation (preoperative biopsies had been taken). There were no major morbidities, including deaths or postoperative leaks. The median postoperative hospital stay was 6 days. All the patients were free of dysphagia during a median followup period of 27 months. One patient had a small (< 2 cm) asymptomatic pseudodiverticulum at the 6-month follow-up endoscopy. CONCLUSIONS: Video-assisted enucleation of esophageal leiomyoma can be performed effectively and safely with no mortality and low morbidity. Thoracoscopic and laparoscopic techniques for the removal of esophageal leiomyomas may be recommended as the treatment of choice in centers experienced with minimally invasive surgery.

High prevalence of isolated tumour cells in regional lymph nodes from pN0 colorectal cancer.

BACKGROUND: The prevalence of isolated tumour cells (ITCs) in regional lymph nodes from colorectal cancer (CRC) is controversial and has never been prospectively assessed in large groups of consecutive patients. pN0 early-relapsing CRC can be explained by lymph node-ITC. AIM: To assess the prevalence of ITCs in regional lymph nodes from 309 consecutive patients with pN0M0 (pathological (p)-tumour-node-metastasis (TNM) staging system) CRCs. PATIENTS AND METHODS: ITCs were assessed by immunohistochemistry (MNF116 monoclonal antibody (1:100); Dako, Glostrup, Denmark) in two serial histological sections obtained from 5016 mesenteric lymph nodes from 309 patients with pN0 CRCs (mean number of lymph nodes per patient = 16.2; p-TNM stage 0, n = 25; p-TNM stage I, n = 123; and p-TNM stage II (A+B), n = 161). Tumour histology, vascular cancer invasion and pathological stage were also recorded. RESULTS: ITCs were detected in the regional lymph nodes of 156 of 309 (50.5%) patients with CRC, mostly in nodes located within 3 cm from the neoplasia. ITC status correlated with (a) tumour p-TNM stage (Pearson's chi(2): p<0; ordered logistic regression: odds ratio (OR) = 4.6; 95% confidence interval (CI) = 2.88 to 7.33; p<0) and (b) pT value (Pearson's chi(2): p = 0; ordered logistic regression: OR = 4.9; 95% CI = 3.1 to 7.7; p<0). By multivariate analysis, including p-TNM stage, vascular invasion and ITC status, both stage (OR = 5.1; 95% CI = 2.9 to 8.9; p<0) and vascular invasion (OR = 4.2; 95% CI = 1.94 to 8.98; p<0) were found to be independent variables associated with ITC+ lymph nodes. CONCLUSION: More than 50% of pN0-CRC patients have ITCs in the mesenteric lymph nodes. ITC status is significantly correlated with cancer stage and vascular cancer invasion. The clinicopathological effect of ITC remains to be prospectively evaluated.

Microsatellite instability and gastric non-invasive neoplasia in a high risk population in Cesena, Italy.

BACKGROUND/AIMS: In the natural history of gastric cancer, non-invasive neoplasia (NiN) precedes invasive carcinoma. A histological classification of gastric NiN has recently been proposed by a World Health Organisation international panel of experts. Genetic instability is known to be among the molecular pathways involved in gastric oncogenesis. In this retrospective cross sectional study, microsatellite instability (MSI) was analysed in a consecutive series of NiN and NiN related histological alterations from a northern Italian region at high risk for gastric cancer. PATIENTS/METHODS: Fifty five consecutive cases (indefinite for NiN, 29 cases; low grade NiN, 17 cases; high grade NiN, nine cases) were analysed by radioactive polymerase chain reaction and electrophoresis for microsatellite alterations at six loci (BAT25, BAT26, D2S123, D5S346, D17S250, and D3S1317). MSI was defined according to the Bethesda criteria distinguishing: (1) no instability in the analysed loci; (2) low frequency MSI (MSI-L); and (3) high frequency MSI (MSI-H). Immunohistochemical expression of MLH1 and MSH2 proteins was also analysed in all cases. RESULTS: Overall, MSI was found in 11 of 55 cases (indefinite for NiN, five of 29 (MSI-L, four; MSI-H, one); low grade NiN, three of 17 (MSI-L, one; MSI-H, two); high grade NiN, three of nine (MSI-L, one; MSI-H, two). CONCLUSIONS: In an Italian high risk area for gastric cancer, MSI is part of the spectrum of genetic alterations in gastric non-invasive neoplasia. In European populations at high risk of gastric cancer, DNA repair system alterations are thought to be among the early molecular events in gastric carcinogenesis.

The long term outcome of gastric non-invasive neoplasia.

BACKGROUND: The cancer risk associated with gastric non-invasive neoplasia (formerly dysplasia) is debated. This prospective long term follow up study investigates the clinicopathological behaviour of non-invasive gastric neoplasia (and related lesions), focusing on the cancer risk associated with each different histological phenotype. PATIENTS AND METHODS: A total of 118 consecutive cases (nine indefinite for non- invasive neoplasia; 90 low grade non-invasive neoplasia; 16 high grade non- invasive neoplasia; and three suspicious for invasive adenocarcinoma) with a histological follow up of more than 12 months (average 52 months; range 12-206) were prospectively followed up with a standardised protocol. Patients in whom gastric cancer was detected within 12 months from the initial diagnosis of non-invasive neoplasia were excluded, assuming that invasive carcinoma had been missed at the initial endoscopy procedure. RESULTS: Non-invasive neoplasia was no longer detectable in 57/118 cases (48%), was unchanged in 32 (30%), and evolved into gastric cancer in 20 patients (17%). Evolution to invasive adenocarcinoma was documented in both low and high grade non-invasive neoplastic lesions (8/90 low grade; 11/16 high grade) and correlated with histological severity (low versus high grade) at baseline (p<0.001). Seventy five per cent of cancers occurring during the long term follow up were stage I. CONCLUSIONS: The risk of invasive gastric cancer increases with the histological grade of the non-invasive neoplasia. Following up non-invasive gastric neoplasia increases the likelihood of gastric cancer being detected in its early stages.