A prospective pilot study on the effects of endoscopic sinus surgery on upper and lower airway performance.

OBJECTIVE: The relationship between chronic rhinosinusitis, asthma and allergic rhinitis is well known, but only recently has the scientific community started to evaluate these as different manifestations of a common pathogenic phenomenon, considering them as a unified airway disease. METHODS: Twenty-two patients with chronic rhinosinusitis treated with endoscopic sinus surgery (ESS) were included in the study. Sino-nasal assessment questionnaire (SNAQ) investigating subjective evaluation of sino-nasal state was administered to patients, while objective evaluations included nasal endoscopy, sinonasal CT, skin prick tests, nasal cytology, spirometry, bronchodilator responsiveness testing and sputum eosinophil count. All tests were performed before surgery. Two months after surgery, SNAQ questionnaire, nasal endoscopy, spirometry and bronchodilator responsiveness testing were repeated. RESULTS: All patients had significant improvement of subjective status: mean SNAQ score decreased in all from 99.31 to 16.04. Mean Forced Expiratory Volume in the 1st second (FEV1) significantly improved after surgery from 3.23 to 3.45 L/s. CONCLUSIONS: ESS achieved a beneficial effect on upper and lower airway status in patients with chronic rhinosinusitis with or without lower airway diseases.

Flexible Fiber CO2 Laser in Microsurgical Treatment of Intraventricular Tumors: Usefulness and Limitations.

OBJECTIVE: To assess usefulness and limitations of flexible fiber carbon dioxide (CO2) laser in the microsurgical treatment of intraventricular tumors. METHODS: We reviewed a series of 9 patients treated with microsurgical resection of intraventricular tumors using a flexible fiber CO2 laser. The lesions involved the third ventricle (8) and the frontal horn of the right lateral ventricle (1). Histology revealed 6 craniopharyngiomas, 1 pituitary macroadenoma, 1 subependymoma, and 1 neurocytoma. In all cases, an interhemispheric transcallosal approach was performed. The laser was used during callosotomy, fornix column sectioning, tumor debulking, and to facilitate tumor dissection. We used a 5-tiered score system to assess laser's efficacy in each surgical step (approach, dissection, debulking): grade 1: laser was not at all helpful, grade 5: laser was extremely helpful. Limits of the instrument also are discussed. RESULTS: Gross total resection was achieved in 6 cases and subtotal resection in the remaining 3. Three patients had pulmonary complications treated without clinical sequelae. No laser-related complication was described. Mean utility score observed was 4.2 (range 3-5) during approach, 2.8 (range 2-4) during tumor dissection; and 3.3 (range 2-5) during tumor debulking. Main limits were low hemostatic effect and inefficiency versus calcified and highly vascularized tumors. CONCLUSIONS: The CO2 laser proved to be a useful and safe tool that could be used for intraventricular pathology; its design is suitable for narrow surgical corridors like interhemispheric fissure and foramen of Monro; its main utility is the ability to create precise and relatively bloodless cut (callosotomy, tumor debulking); low hemostatic effect is its main limit.

Identification of a novel candidate gene, CASC2, in a region of common allelic loss at chromosome 10q26 in human endometrial cancer.

Allelic deletions, which are suggestive for the presence of tumor suppressor genes, represent a common event in endometrial cancer (EC). Previous loss-of-heterozygosity studies for human chromosome 10q identified a candidate deletion interval at 10q25-q26, which we further narrowed to a 160-kb region at 10q26, bounded by markers D10S1236 and WIAF3299. Using a positional candidate approach, we identified three alternative transcripts of a novel human gene, CASC2 (cancer susceptibility candidate 2; formely C10orf5). One of such transcripts, CASC2a, encodes a short protein of 102 amino acids with no similarity to any other known gene product. Three (7%) CASC2a mutations were identified in tumor DNA from 44 EC patients. While c.-156G>T and c.22C>T (p.Pro8Ser) are sequence variants with unknown functional significance, c.84delA is a mutation with a truncation effect on the predicted protein (p. Asn28fsX50). Expression studies by real-time RT-PCR on several normal and tumor cells revealed that CASC2a mRNA is downregulated in cancer, suggesting that it may act as a potential tumor suppressor gene. The very low mutation rate seems to also indicate that inactivation of CASC2a might probably be due to mechanisms different from genetic alterations.

Microsatellite instability and mutation analysis of candidate genes in unselected sardinian patients with endometrial carcinoma.

BACKGROUND: Microsatellite instability (MSI) is due mostly to a defective DNA mismatch repair (MMR). Inactivation of the two principal MMR genes, hMLH1 and hMSH2, and the PTEN tumor suppressor gene seems to be involved in endometrial tumorigenesis. In this study, Sardinian patients with endometrial carcinoma (EC) were analyzed to assess the prevalence of both the mutator phenotype (as defined by the presence of MSI and abnormal MMR gene expression at the somatic level) and the hMLH1, hMSH2, and PTEN germline mutations among patients with MSI positive EC. METHODS: Paraffin embedded tissue samples from 116 consecutive patients with EC were screened for MSI by polymerase chain reaction-based microsatellite analysis. Immunohistochemistry (IHC) with anti-hMLH1 and anti-hMSH2 antibodies was performed on MSI positive tumor tissue sections. Germline DNA was used for mutational screening by denaturing high-performance liquid chromatography analysis and automated sequencing. RESULTS: Thirty-nine patients with EC (34%) exhibited MSI; among them, 25 tumor samples (64%) showed negative immunostaining for hMLH1/hMSH2 proteins (referred to as IHC negative). No disease-causing mutation within the coding sequences of the hMLH1/hMSH2 and PTEN genes was found in patients with EC who had the mutator phenotype (MSI positive and IHC negative), except for a newly described hMLH1 missense mutation, Ile655Val, that was observed in 1 of 27 patients (4%). Although MSI was more common among patients with advanced-stage EC and increased as the tumor grade increased, no significant correlation with disease free survival or overall survival was observed among the two groups (MSI positive or MSI negative) of patients with EC. CONCLUSIONS: In patients with MSI positive EC, epigenetic inactivations rather than genetic mutations of the MMR genes seem to be involved in endometrial tumorigenesis. No prognostic value was demonstrated for MSI in patients with EC.