Molecular genetic features and risk assessment in a series of 30 patients who underwent an operation for gastrointestinal stormal tumours.

BACKGROUND: The objective of the study was to investigate the relationship between molecular genetic features and the standard criteria of risk assessment in patients affected by gastrointestinal stromal tumours (GISTs). METHOD: A review was conducted of a series of 30 patients, with a mean age of 67 years, who underwent surgery for primary GISTs. R0 resection was accomplished in 27 patients. CD117, CD34 desmin, vimentin, S-100 and smooth muscle actin were immunohistochemically tested to achieve a diagnosis of GIST. The loss of wild-type KIT or platelet-derived growth factor receptor alpha (PDGFRα) genes was investigated by sequencing the tumour DNA. RESULTS: Tumour genes mutations were reported in 23 patients (77%), and wild-type in seven. Mutations on the KIT gene occurred in 18 patients, and mutations on the PDGFRα gene in five. The average sizes of the GIST were 8.7 cm, 5.4 cm and 5.9 cm for KIT gene-mutated, PDGFRα gene-mutated and wild-type tumours, respectively. KIT gene mutations were detected in 50% of gastric and in 70% of extragastric GISTs. Moreover, 70% of tumours with a mitotic rate ≥ 5 x 50 highpower fi elds (HPFs) underwent KIT gene mutations. Conversely, PDGFRα mutations were observed only in gastric GISTs with a mitotic rate ≤ 5 x 50 HPFs. By stratifying GISTs according to classes of risk, KIT mutation was shown in most of the high-risk tumours. PDGFRα mutations occurred exclusively in lower classes of risk. CONCLUSION: Molecular analysis data might have a role as a prognostic variable in models of risk assessment for patients with GISTs.

Assessment of linear measurements of bone for implant sites in the presence of metallic artefacts using cone beam computed tomography and multislice computed tomography.

The objective was to evaluate the influence of dental metallic artefacts on implant sites using multislice and cone-beam computed tomography techniques. Ten dried human mandibles were scanned twice by each technique, with and without dental metallic artefacts. Metallic restorations were placed at the top of the alveolar ridge adjacent to the mental foramen region for the second scanning. Linear measurements (thickness and height) for each cross-section were performed by a single examiner using computer software. All mandibles were analysed at both the right and the left mental foramen regions. For the multislice technique, dental metallic artefact produced an increase of 5% in bone thickness and a reduction of 6% in bone height; no significant differences (p>0.05) were detected when comparing measurements performed with and without metallic artefacts. With respect to the cone-beam technique, dental metallic artefact produced an increase of 6% in bone thickness and a reduction of 0.68% in bone height. No significant differences (p>0.05) were observed when comparing measurements performed with and without metallic artefacts. The presence of dental metallic artefacts did not alter the linear measurements obtained with both techniques, although its presence made the location of the alveolar bone crest more difficult.

High doses of alpha-interferon are required in chronic hepatitis due to coinfection with hepatitis B virus and hepatitis C virus: long term results of a prospective randomized trial.

OBJECTIVE: Coinfection with hepatitis B (HBV) and hepatitis C (HCV) viruses is associated with a more severe liver disease, increased frequency in the development of hepatocellular carcinoma, and resistance to interferon (IFN) therapy when performed with the standard dosages used in single infections. In the attempt to verify whether the outcome of IFN therapy in patients with hepatitis B and hepatitis C coinfection can be improved, we have planned a prospective, randomized trial with medium to high dosages of interferon three times a week for 6 months. METHODS: Thirty patients with HBV-HCV coinfection, and chronic hepatitis were randomized to receive either 6 or 9 MU alpha-interferon three times a week for 6 months. Patients were HBsAg positive, anti-HBe positive, HBV DNA negative by dot blot (6/30 positive by polymerase chain reaction), and anti-HCV-positive, HCV RNA positive. Pretreatment and posttreatment liver biopsies were performed. RESULTS: Five patients treated with 9 MU IFN consistently cleared HCV RNA and HBV DNA, whereas none of those treated with 6 MU reacted in a similar fashion (p = 0.045). Responders showed significant improvement of histological activity index in comparison with nonresponders (mean Ishak score pretreatment versus posttreatment p = 0.002). Long term follow-up showed that none of the patients treated with high doses developed cirrhosis whereas 4/14 treated with low doses did develop cirrhosis. CONCLUSION: Even though the percentage was not very high, the sustained response, the striking histological improvement, and the lack of development of cirrhosis achieved in these patients, indicate that with HBV-HCV coinfection, a trial with high doses of interferon is strongly recommended.

Sources of bile pigment overproduction in Gilbert's syndrome: studies with non-radioactive bilirubin kinetics and with delta-[3,5-3H]aminolaevulinic acid and [2-14C]glycine.

1. The kinetics of non-radioactive bilirubin were investigated in 100 patients with chronic non-haemolytic unconjugated hyperbilirubinaemia and in nine normal volunteers. 2. The patients with Gilbert's syndrome were divided on the basis of a two-compartment model into two distinct groups: group 1 (74 patients) with decreased hepatic uptake and conjugation of bilirubin and a bilirubin turnover rate within the normal range, and group 2 (26 patients) having normal uptake, impaired conjugation and increased bilirubin turnover rate. 3. On the basis of these findings, studies were made of early pigment production in four patients of group 1, in six patients of group 2 and in four of the normal volunteers, with [14C]glycine and delta-[3H]aminolaevulinic acid. 4. After receiving injections of labelled haem precursors, the four patients in group 1 had a normal rate of incorporation of both tracers, whereas abnormalities in incorporation were found in group 2. Four patients showed an increase of the first component of the early peak of [14C]bilirubin as well as of the early peak of [3H]bilirubin, suggesting an increased turnover of hepatic haem. Two patients showed an increased incorporation of [14C]glycine characterized by the fusion of the two early peaks, whereas the incorporation of the delta-[3H]aminolaevulinic acid was normal, indicating the presence of a primary shunt hyperbilirubinaemia. 5. The results confirm that Gilbert's syndrome is a heterogeneous condition with respect to bilirubin turnover rate. The population of Gilbert's syndrome with increased bilirubin turnover rate comprises not only patients with an increased haem erythroid turnover, but also patients with increased metabolism of non-erythroid haem protein in the liver.