Mariana Afonso

A European case series of endoscopic submucosal dissection for gastric superficial lesions

BACKGROUND EMR is an accepted method for resection of superficial lesions in the GI tract. However, because it leads, not unusually, to piecemeal resection, histopathologic interpretation problems and an increased risk of recurrence are noticeable. Endoscopic submucosal dissection (ESD) allows a higher rate of en bloc resection, with low recurrence. Nevertheless, this technique, namely in the upper-GI tract, has rarely been described in Western countries, probably because of the rarity of gastric cancer in most countries. OBJECTIVE To describe the efficacy and safety of ESD for gastric superficial lesions in a European country. DESIGN Consecutive case-series report. SETTING A tertiary specialized center. PATIENTS Nineteen patients with gastric superficial lesions (15-30 mm), with high-grade (n = 15) or low-grade (n = 4) noninvasive epithelial neoplasias, in the antrum (n = 12), incisura angularis (n = 2), body (n = 3), and cardia (n = 2). INTERVENTION ESD with the patient under general anesthesia in the endoscopic room (40-300 minutes) by using an insulated-tip-knife. MAIN OUTCOME MEASUREMENTS Complete (R0) and en bloc resection, and complications. RESULTS ESD was achieved in all cases, with 89% R0 resection and 79% en bloc resection rates observed. Major bleeding was reported in 1 case (5%); there were no cases of perforation. With a median follow-up of 10 months, a single recurrence (5%) was observed. LIMITATIONS A small series at a single center, with a short median follow-up time. CONCLUSION We report the feasibility and effectiveness of gastric ESD in Europe. A further description of a Western series is expected, and guidelines for its dissemination are desirable to define the role of this technique in Western countries.

Purification of metallurgical grade silicon by acid leaching

Abstract The purification of metallurgical grade silicon (≈98% Si) from Companhia Portuguesa de Fornos Electricos by acid leaching is studied as a function of the particle size, time, temperature and concentration of leaching agents (HNO3, H2SO4, HCl and HF). It was found that using only hydrochloric acid (16%, 5 h, 80°C) and a relatively coarse fraction (116 μm) it is possible to remove ∼85% of the impurities and to obtain 99.9% pure Si after further leaching with hydrofluoric acid (2.5%, 2 h, 80°C). All the other acids and their mixtures, including aqua regia, gave results poorer than those for hydrochloric acid. The finer fractions were more difficult to purify. These results differ from other previously reported on purification studies of silicon by acid leaching and are ascribed to the unusual composition of the MG-Si used in this study.

Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes

Several ETS transcription factors are involved in the pathogenesis of human cancers by different mechanisms. As gene copy number gain/amplification is an alternative mechanism of oncogenic activation and 1q gain is the most common copy number change in breast carcinoma, we investigated how that genomic change impacts in the expression of the three 1q ETS family members ETV3, ELK4, and ELF3. We have first evaluated 141 breast carcinomas for genome-wide copy number changes by chromosomal CGH and showed that 1q21 and 1q32 were the two chromosome bands with most frequent genomic copy number gains. Second, we confirmed by FISH with locus-specific BAC clones that cases showing 1q gain/amplification by CGH showed copy number increase of the ETS genes ETV3 (located in 1q21~23), ELF3, and ELK4 (both in 1q32). Third, gene expression levels of the three 1q ETS genes, as well as their potential targets MYC and CRISP3, were evaluated by quantitative real-time PCR. We here show for the first time that the most common genomic copy number gains in breast cancer, 1q21 and 1q32, are associated with overexpression of the ETS transcription factors ETV3 and ELF3 (but not ELK4) at these loci irrespective of molecular subtypes. Among the three 1q ETS genes, ELF3 has a relevant role in breast carcinogenesis and is also the most likely target of the 1q copy number increase. The basal-like molecular subtype presented the worst prognosis regarding disease-specific survival, but no additional prognostic value was found for 1q copy number status or ELF3 expression. In addition, we show that there is a correlation between the expression of the oncogene MYC, irrespectively of copy number gain at its loci in 8q24, and the expression of both the transcriptional repressor ETV3 and the androgen respondent ELK4.

Chromosome copy number changes carry prognostic information independent of KIT/PDGFRA point mutations in gastrointestinal stromal tumors

BackgroundOncogenic point mutations in KIT or PDGFRA are recognized as the primary events responsible for the pathogenesis of most gastrointestinal stromal tumors (GIST), but additional genomic alterations are frequent and presumably required for tumor progression. The relative contribution of such alterations for the biology and clinical behavior of GIST, however, remains elusive.MethodsIn the present study, somatic mutations in KIT and PDGFRA were evaluated by direct sequencing analysis in a consecutive series of 80 GIST patients. For a subset of 29 tumors, comparative genomic hybridization was additionally used to screen for chromosome copy number aberrations. Genotype and genomic findings were cross-tabulated and compared with available clinical and follow-up data.ResultsWe report an overall mutation frequency of 87.5%, with 76.25% of the tumors showing alterations in KIT and 11.25% in PDGFRA. Secondary KIT mutations were additionally found in two of four samples obtained after imatinib treatment. Chromosomal imbalances were detected in 25 out of 29 tumors (86%), namely losses at 14q (88% of abnormal cases), 22q (44%), 1p (44%), and 15q (36%), and gains at 1q (16%) and 12q (20%). In addition to clinico-pathological high-risk groups, patients with KIT mutations, genomic complexity, genomic gains and deletions at either 1p or 22q showed a significantly shorter disease-free survival. Furthermore, genomic complexity was the best predictor of disease progression in multivariate analysis.ConclusionsIn addition to KIT/PDGFRA mutational status, our findings indicate that secondary chromosomal changes contribute significantly to tumor development and progression of GIST and that genomic complexity carries independent prognostic value that complements clinico-pathological and genotype information.

Validating the MSKCC nomogram and a clinical decision rule in the prediction of non-sentinel node metastases in a Portuguese population of breast cancer patients

BACKGROUND In order to assess the risk of non-sentinel node involvement in breast cancer patients, some prediction tools have been developed and tested. However, a wide range of results are observed. We tested a simplified clinical decision rule, against the complex nomogram created from the MSKCC sentinel node database. METHODS Two single institutional consecutive series of patients with a positive SN, submitted to SN biopsy plus axillary dissection from June 1999 to October 2007, were evaluated. A receiver operating curve was drawn and the area under the curve was calculated as well as the negative predictive value for both tests, assuming discriminative values of 10 and 15%. RESULTS Considering the derivation series, our results showed an area under the curve of 0.69 for both our clinical decision rule and the MSKCC nomogram. The analysis of the validation series showed an area under the curve of 0.65 for our clinical decision rule and of 0.67 for the MSKCC nomogram. The nomogram results are inferior to those found in the original population and are similar to our clinical decision rule results. CONCLUSIONS Individual centres should develop and prospectively test their own clinical decision rules, based on their institutional Sentinel Node data.

Genetic diagnosis of alveolar rhabdomyosarcoma in the bone marrow of a patient without evidence of primary tumor

Alveolar rhabdomyosarcoma (ARMS) is characterized by two pathognomonic translocations, both involving the FOXO1 gene. We describe a case of a 10‐year‐old child with multiple lytic lesions involving all the vertebral bodies, sternum and femur and a bone marrow biopsy compatible with a small round cell neoplasia, but no evidence of a primary tumor. Interphase FISH analysis with specific probes evidenced a rearrangement involving the FOXO1 gene and RT‐PCR identified the PAX7‐FOXO1 fusion transcript. These data show a case of ARMS with no evidence of primary tumor presenting the PAX7‐FOXO1 fusion gene. Pediatr Blood Cancer 2008;51:554–557.

Identification of previously unrecognized FAP in children with Gardner fibroma

Fibromatous soft tissue lesions, namely desmoid-type fibromatosis and Gardner fibroma, may occur sporadically or as a result of inherited predisposition (as part of familial adenomatous polyposis, FAP). Whereas desmoid-type fibromatosis often present β-catenin overexpression (by activating CTNNB1 somatic variants or APC biallelic inactivation), the pathogenetic mechanisms in Gardner fibroma are unknown. We characterized in detail Gardner fibromas diagnosed in two infants to evaluate their role as sentinel lesions of previously unrecognized FAP. In the first infant we found a 5q deletion including APC in the tumor and the novel APC variant c.4687dup in constitutional DNA. In the second infant we found the c.5826_5829del and c.1678A>T APC variants in constitutional and tumor DNA, respectively. None of the constitutional APC variants occurred de novo and both tumors showed nuclear staining for β-catenin and no CTNNB1 variants. We present the first comprehensive characterization of the pathogenetic mechanisms of Gardner fibroma, which may be a sentinel lesion of previously unrecognized FAP families.

Superficial Thrombophlebitis of the Breast in a Patient with an Arteriovenous Fistula for Hemodialysis

12 (6%) had various focal nodular patterns and the remaining 16 patients had other mammographic signs of malignancy including asymmetry, dilated retroareolar ducts, ill-defined rounded tumor, focal architectural distortion, sub-areolar mass, and developing density. The DCIS in our patient manifests as linearly distributed microcalcifications overlying noncalcified band-like density. The band-like density represents noncalcified portions of the affected lactiferous duct surrounding the calcifications, and is better identified in digital breast tomosynthesis than in conventional mammography. We propose to call this new tomosynthesis finding the Milky Way sign because the linearly distributed fine pleomorphic calcifications over the band-like density resembled bright stars overlying the dimly glowing stripe of the Milky Way galaxy arching across the night sky. The Milky Way sign can be one of potential diagnostic tools to aid in the detection of DCIS in the context of tomosynthesis.

Much more than anxiety

Pheochromocytoma and paraganglioma are rare neuroendocrine tumours in paediatric ages. We report a case of a 14-year-old girl referred to our oncology centre due to an abdominal mass. She had an 11-month history of paroxysmal episodes of headache, nausea, dizziness, palpitations and visual disturbances. Imaging studies showed a left paravertebral mass measuring 5.8×4.6×3.5 cm. Metaiodobenzylguanidine scintigraphy revealed an abnormal hyperfixation on the left upper quadrant. Chromogranin A was elevated, as well as normetanephrine. The patient was submitted to surgery during which a connection between this mass and the adrenal gland was found. A diagnosis of pheochromocytoma was performed.