Radiotherapy Quality Assurance in the PORTEC-3 (TROG 08.04) Trial.

AIMS: Quality assurance in radiotherapy (QART) is essential to ensure the scientific integrity of a clinical trial. This paper reports the findings of the retrospective QART assessment for all centres that participated in PORTEC-3; a randomised controlled trial that compared pelvic radiotherapy with concurrent chemoradiotherapy to the pelvis followed by adjuvant chemotherapy. The trial showed an overall survival benefit for the addition of the chemotherapy in the management of women with high-risk endometrial cancer. MATERIALS AND METHODS: Clinicians were invited to upload a randomly selected case/s treated at each of the participating sites. Panel reviewers analysed the contours to certify that the target volumes and organ at risk structures were contoured according to guidelines. The results were categorised into acceptable, minor variation, major variation or unevaluable. The radiotherapy plans were dosimetrically evaluated using the well-established Trans-Tasman Radiation Oncology Group (TROG) protocol. RESULTS: Between August 2010 and January 2018, data from 146 patients of 686 consecutively treated patients were retrospectively reviewed. All 16 Australia and New Zealand and 71 of 77 international centres uploaded data for evaluation. In total, 3514 dosimetric and contour variables were reviewed. Of these, 3136 variables were deemed acceptable (89.2%), with 335 minor (9.6%) and 43 major variations (1.2%). Major contour variations included the clinical target volume vaginal vault, clinical target volume parametria and differential planning target volume vault expansion. CONCLUSION: The results of the QART assessment confirmed high uniformity and low rates of both minor and major deviations in contouring and dosimetry in all sites. This supports the safe introduction of the PORTEC-3 treatment protocol into routine clinical practice.

Association of tumor-infiltrating lymphocytes with distant disease-free survival in the ShortHER randomized adjuvant trial for patients with early HER2+ breast cancer.

BACKGROUND: There is the need to identify new prognostic markers to refine risk stratification for HER2-positive early breast cancer patients. The aim of this study was to evaluate the association of tumor-infiltrating lymphocytes (TILs) with distant disease-free survival (DDFS) in patients with HER2-positive early breast cancer enrolled in the ShortHER adjuvant trial which compared 9 weeks versus 1-year trastuzumab in addition to chemotherapy, and to test the interaction between TILs and treatment arm. PATIENTS AND METHODS: Stromal TILs were assessed for 866 cases on centralized hematoxylin and eosin-stained tumor slides. The association of TILs as 10% increments with DDFS was assessed with Cox models. Kaplan-Meier curves were estimated for patients with TILs ≥20% and TILs <20%. Median follow-up was 6.1 years. RESULTS: Median TILs was 5% (Q1-Q3 1%-15%). Increased TILs were independently associated with better DDFS in multivariable model [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59-0.89, P = 0.006, for each 10% TILs increment]. Five years DDFS rates were 91.1% for patients with TILs <20% and 95.7% for patients with TILs ≥20% (P = 0.025). The association between 10% TILs increments and DDFS was significant for patients randomized to 9 weeks of trastuzumab (HR 0.60, 95% CI 0.41-0.88) but not for patients treated with 1 year of trastuzumab (HR 0.89, 95% CI 0.71-1.12; test for interaction P = 0.088). For patients with TILs <20%, the HR for the comparison between the short versus the long arm was 1.75 (95% CI 1.09-2.80, P=0.021); whereas, for patients with TILs ≥20% the HR for the comparison of short versus long arm was 0.23 (95% CI 0.05-1.09, P = 0.064), resulting in a significant interaction (P = 0.015). CONCLUSIONS: TILs are an independent prognostic factor for HER2-positive early breast cancer patients treated with adjuvant chemotherapy and trastuzumab and may refine the ability to identify patients at low risk of relapse eligible for de-escalated adjuvant therapy.

Usefulness of automated breast volume scanner (ABVS) for monitoring tumor response to neoadjuvant treatment in breast cancer patients: preliminary results.

OBJECTIVE: We investigated the accuracy of Automated Breast Volume Scanner (ABVS) compared to handheld ultrasound (HHUS) for monitoring tumor response to neoadjuvant treatment (NAT) in breast cancer (BC). PATIENTS AND METHODS: All the patients submitted to biopsy in our Institution, from January 2017 to May 2017, proven invasive BC and eligible for NAT, were enrolled in this prospective study. The participants underwent ABVS, HHUS, dynamic contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) and mammography at the beginning of NAT and ABVS, HHUS and DCE-MRI at the halfway point of therapy and before the surgery. DCE-MRI was considered the standard of reference. Two breast radiologists (R1, R2), with fifteen and five years of experience in breast imaging, independently assigned a visibility score (ordinal 5-point scale) to ABVS, HHUS, and DCE-MRI. Diagnostic performance of ABVS and HHUS as measured by sensitivity, specificity, positive and negative predictive values (PPV and NPV) was calculated. Correlations between ABVS and MRI, and between HHUS and MRI were analyzed using Pearson's correlation test. RESULTS: A total of 21 patients were enrolled. 189 examinations were performed. The comparison between ABVS and DCE-MRI was similar for the both readers: ABVS had a sensitivity of 63,16%, specificity of 83,58%, PPV of 76,60%, NPV of 72,73%, accuracy of 74,19% (R1) and a sensitivity of 54.54%, specificity of 85.51%, PPV of 75%, NPV of 70,24%, accuracy of 71.77% (R2). The comparison between HHUS and DCE-MRI showed that HHUS had a sensitivity of 63,16 %, specificity of 83,58%, PPV of 76,60%, NPV of 72,73%, accuracy of 74,19% (R1) and a sensitivity of 36.84%, specificity of 85.07%, PPV of 67.74%, NPV of 61.29%, accuracy of 62.90% (R2). The calculated Pearson's correlation coefficient r values were 7.8 for HHUS vs. DCE-MRI and 28.5 for ABVS vs. DCE-MRI (R1) and 7.8 for HHUS vs. DCE-MRI and 22.4 for ABVS vs. DCE-MRI (R2). Statistical significance of ABVS and HHUS was p < 0.0001 and 0.005 < p < 0.01, respectively (R1, R2). CONCLUSIONS: DCE-MRI is recommended for the tumor response assessment. ABVS, a product of the biotechnology development, providing reproducible images, in addition to DCE-MRI, can be a potentially useful tool for the monitoring of response to NAT.

Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety. Results: A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001). Conclusions: This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse. Trial Registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

Atypical pleomorphic neoplasms of the pineal gland: Case report and review of the literature.

BACKGROUND: Pineal region tumors are rare and diverse. Among them exist reports of pleomorphic xanthroastrocytoma (PXA) and pleomorphic granular cell astrocytoma (PGCA) of the pineal gland. These related tumors are remarkably similar sharing pleomorphic histologic features with only minor immunohistochemical and ultrastructural differences. CASE DESCRIPTION: We present a case of a 42-year old right-handed woman presented with a longstanding history of migraine headaches which had worsened over the two months leading up to her hospitalization. MRI revealed a 1.7 × 1.3 × 1.6 cm intensely enhancing lesion originating in the pineal gland. The tumor closely resembled PGCA but did not strictly fit the diagnostic requirements of either PGCA or PXA. CONCLUSION: The present case highlights the exotic nature of pineal region tumors with pleomorphic cell histology. Given the diverse range of tumors encountered in the pineal region, pathological confirmation is mandatory. Favorable clinical outcomes demonstrate that surgical resection alone can yield excellent long-term results for tumors falling within the spectrum of pleomorphic lesions of the pineal gland.

The diagnostic reliability of urinary cytology: a retrospective study.

The aim of this study was twofold. The first aim was to estimate the diagnostic reliability of urinary cytology for detection and management of urothelial neoplasms by using a specific preserving fluid for sample collection, and the liquid-based thin layer method for specimen preparation, the estimate was based on the correlation between the cytological findings of 10,000 non-hospitalized patients, and their histological diagnoses. A second aim was to compare the reliability of two instruments for thin-layer preparation, i.e., TP2000, TP3000, capable of processing the specimens at very different rates. The preservation of cell structure is ameliorated by the procedure of sample collection and treatment here described. This allows a more accurate reading of LBC slides as shown by: (a) the significant concordance between cytological and histological diagnosis (92%); (b) the significant number of low-grade urothelial carcinomas (20.5%) revealed by urinary cytology and validated by histologic diagnosis; (c) the low rate (8%) of misjudgement of cytological diagnosis reached in this study. The quality of performances of the two instruments tested for thin-layer preparation, i.e., TP2000 and TP3000, is statistically comparable. We recommend the procedure that makes use of preserving fluid for sample collection (cytolyt™) and treatment (preservcyt ™) as here described. We also recommend the use of thin-layer method for specimen preparation since it allows a more uniform distribution of the cells on the support with reduction of overlapping phenomena. Finally, economic considerations suggest the preferential use of Thin Prep 3000.

Risk for cardiovascular events in an Italian population of patients with type 2 diabetes.

BACKGROUND AND AIM: This study aims to analyse the risk of cardiovascular events in a local cohort of patients with type 2 diabetes, and to evaluate the prognostic accuracy of four algorithms used to estimate cardiovascular risk: the Framingham study, United Kingdom Prospective Diabetes Study (UKPDS), Riskard study and Progetto Cuore. METHOD AND RESULTS: We analysed clinical charts of the Diabetes Clinics of Modena for the period 1991-95. Patients in the age range of 35-65 with type 2 diabetes and no previous cardiovascular disease were eligible. The incidence of new cardiovascular disease was compared with estimated rates deriving from the different functions. A stratification was obtained in subgroups at different cardiovascular risk, allowing comparison between the algorithms. A total of 1532 patients were eligible; women presented a worse cardiovascular risk profile. An absolute 10-year rate of cardiovascular events of 14.9% was observed. Comparing patients with events with event-free subjects, we found significant differences in systolic blood pressure, age at visit, smoking, high-density lipoprotein (HDL)-cholesterol, duration of diabetes, glycosylated haemoglobin (HbA1c) and co-morbidities. Comparing the estimated risk rate according to the different functions, Italian algorithms were more consistent with observed data; however, Progetto Cuore and Riskard show underestimation of events when applied to females. CONCLUSIONS: Estimation of cardiovascular risk is dependent on the algorithm adopted and on the baseline risk of the reference cohort. Functions designed for a specific population, including risk variables peculiar for diabetes, should be adopted to increase the performance of such functions which is clearly unsatisfactory at present.

Endogenous blood maximal interferon-gamma production may predict response to interferon-gamma 1beta treatment in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an untreatable lung disorder with a mean survival of 3 years after diagnosis. Treatment with interferon-gamma (IFN-gamma) 1beta has been reported to significantly improve lung function and arterial oxygen saturation in a first randomized controlled trial; unexpectedly, these findings have not been confirmed in a subsequent large placebo-controlled randomized study. Another larger placebo-controlled randomized trial has been stopped because data analyzed at interim analysis excluded the possibility that treatment with IFN-gamma 1beta would cause a significant reduction in the risk of death. METHODS: Seven Italian male patients diagnosed with IPF were treated with IFN-gamma 1beta (200 microg/die subcutaneously three times a week), accordingly to the indications of the Italian Drug Agency. Based on available studies the response to treatment was pre-defined as changes in either lung function (FVC and DLCO) or oxygen arterial saturation. All patients consented to provide a peripheral blood sample for endogenous IFN-gamma production measurement with the ELISpot assay before treatment and 6 months thereafter. RESULTS: Four of 7 patients improved or stabilized their lung function after 6 months treatment. Using the ELISpot assay to quantify the maximal production of endogenous IFN-gamma on peripheral blood samples, these 4 patients had a significantly higher endogenous IFN-gamma production before therapy, as compared to the 3 patients who deteriorated (91.3 +/- 49.6 vs. 277.8 +/- 34.2 spot forming cells, p = 0.023). No significant differences were observed after 6 months of treatment. DISCUSSION: These preliminary results suggest that some IPF patients might benefit from treatment with IFN-gamma 1beta and may help to interpret the results of large randomized trials, suggesting that individual susceptibility could determine clinical response to treatment.

A prognostic model based on nodal status and Ki-67 predicts the risk of recurrence and death in breast cancer patients with residual disease after preoperative chemotherapy.

BACKGROUND: Preoperative chemotherapy (PCT) allows for in vivo testing of treatment effects on tumor and its microenvironment. Aim of this analysis was to evaluate the effect of PCT on tumor biomarker expression and to evaluate the prognostic role of treatment-induced variation of these biomarkers (molecular response). METHODS: Two hundred and twenty-one stage II-III breast cancer patients were included. The following parameters were evaluated at baseline and on surgical specimens after PCT: estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, human epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and apoptosis. RESULTS: A pathological complete response was observed in 8.8% of the patients. PCT induced a significant reduction in the expression of ER, PgR, Ki-67, and apoptosis. As by multivariable model, Ki-67 > or = 15% and nodal positivity after preoperative chemotherapy (PCT) were significant predictors of worse disease-free survival [hazard ratio (HR) 3.79, P < 0.0001 and HR 2.31, P = 0.037, respectively]. Ki-67 > or = 15% after PCT was also a significant predictor of overall survival (HR 3.75, P = 0.013). On the basis of these two parameters, patients were classified into three groups: (i) low risk (negative nodes and Ki-67 <15%), (ii) intermediate risk (nodal positivity or Ki-67 > or = 15%), and (iii) high risk (nodal positivity and Ki-67 > or = 15%). As compared with the low-risk group, the HRs for recurrence were 3.1 and 9.3 for the intermediate- and high-risk group, respectively (P = 0.0001); the HRs for death were 2.4 and 6.5 for the intermediate- and high-risk group, respectively (P = 0.042). CONCLUSIONS: Ki-67 and nodal status have been used to generate a simple and easily reproducible prognostic model, able to discriminate patients with worse prognosis among the heterogeneous group of women with residual disease after PCT.

Migraine is a risk factor for hypertensive disorders in pregnancy: a prospective cohort study.

The aim was to assess whether women suffering from migraine are at higher risk of developing hypertensive disorders in pregnancy. In a prospective cohort study, performed at antenatal clinics in three maternity units in Northern Italy, 702 normotensive women with singleton pregnancy at 11-16 weeks' gestation were enrolled. Women with a history of hypertensive disorders in pregnancy or presenting chronic hypertension were excluded. The presence of migraine was investigated according to International Headache Society criteria. The main outcome measure was the onset of hypertension in pregnancy, defined as the occurrence of either gestational hypertension or preeclampsia. Two hundred and seventy women (38.5%) were diagnosed with migraine. The majority (68.1%) suffered from migraine without aura. The risk of developing hypertensive disorders in pregnancy was higher in migraineurs (9.1%) compared with non-migraineurs (3.1%) [odds ratio (OR) adjusted for age, family history of hypertension and smoking 2.85, 95% confidence interval (CI) 1.40, 5.81]. Women with migraine also showed a trend to increased risk for low birth weight infants with respect to women without migraine (OR 1.97, 95% CI 0.98, 3.98). Women with migraine are to be considered at increased risk of developing hypertensive disorders in pregnancy. The diagnosis of primary headaches should be taken into account at antenatal examination.

Epidermal growth factor receptor gene copy number, K-ras mutation and pathological response to preoperative cetuximab, 5-FU and radiation therapy in locally advanced rectal cancer.

BACKGROUND: Cetuximab improves activity of chemotherapy in metastatic colorectal cancer (mCRC). Gene copy number (GCN) of epidermal growth factor receptor (EGFR) has been suggested to be a predictive factor of response to cetuximab in patients (pts) with mCRC; on the contrary, K-ras mutation has been associated with cetuximab resistance. PATIENTS AND METHODS: We have conducted a phase II study with cetuximab administered weekly for 3 weeks as single agent and then with 5-fluorouracil and radiation therapy as neo-adjuvant treatment for locally advanced rectal cancer (LARC). EGFR immunohistochemistry expression, EGFR GCN and K-ras mutation were evaluated on diagnostic tumor biopsy. Dworak's tumor regression grade (TRG) was evaluated on surgical specimens. RESULTS: Forty pts have been treated; 39 pts are assessable. TRG 3 and 4 were achieved in nine (23.1%) and three pts (7.7%) respectively; TRG 3-4 rate was 55% and 5.3% in case of high and low GCN, respectively (P 0.0016). Pts with K-ras mutated tumors had lower rate of high TRG: 11% versus 36.7% (P 0.12). In pts with wild-type K-ras, TRG 3-4 rate was 58.8% versus 7.7% in case of high or low GCN, respectively (P 0.0012). CONCLUSIONS: In pts with LARC, EGFR GCN is predictive of high TRG to cetuximab plus 5-FU radiotherapy. Moreover, our data suggest that a wild-type K-ras associated with a high EGFR GCN can predict sensitivity to cetuximab-based treatment.

Impact of preoperative testing on ophthalmologic and systemic outcomes in cataract surgery.

PURPOSE: To evaluate the incidence of ophthalmologic and systemic complications in patients who undergo cataract surgery without preoperative tests compared to subjects undergoing cataract surgery preceded by preoperative tests. METHODS: The randomized controlled study included 1276 consecutive patients admitted to the Institute of Ophthalmology of the University of Modena and Reggio Emilia for cataract surgery. The patients were randomly divided into two groups: 638 were assigned not to undergo preoperative evaluation based on routine medical tests and electrocardiograms; the other 638 underwent preoperative evaluation based on said tests. Ophthalmologic and systemic complications were assessed intraoperatively and 1 month after surgery. RESULTS: Eleven intraoperative complications occurred in the group without preoperative tests and eight in the group with preoperative tests; at 1 month six complications were recorded in the group without tests and five in the group with tests. Systemic adverse events occurred intraoperatively in four patients, whereas no systemic adverse event was recorded at 1 month in either group. No statistically significant differences were observed between the two groups. CONCLUSIONS: The findings of this study have broad applicability, because the sample is representative of the population existing in numerous social and healthcare settings; they are of value for administrative purposes, because they may be taken as reference in resource allocation plans; and they have medicolegal implications, as the resulting conduct of healthcare providers is supported by a rigorous scientific study.

Evaluation of the impact of highly active antiretroviral therapy on immune recovery in antiretroviral naive patients.

OBJECTIVES: To examine the extent of immune reconstitution in treatment-naive patients with CD4 T-cell counts <500 cells/microL following 48 weeks of highly active antiretroviral therapy (HAART). METHODS: Thirteen antiretroviral naive patients were evaluated longitudinally for 48 weeks on HAART utilizing immune functional and lymphocyte phenotyping assays, including lymphocyte proliferation assay, flow cytometric evaluation of cell surface markers, and delayed type hypersensitivity skin tests. Virologic responses were monitored using commercially available viral load assays and gag/pol mRNA quantification using simultaneous immunophenotyping/UltraSensitive fluorescence in situ hybridization (ViroTect In Cell HIV-1 Detection Kit; Invirion, Frankfort, MI). Thymic function was evaluated for a subset of four patients using real-time polymerase chain reaction (PCR) for T-cell receptor excision circle (TREC) quantification and thymic scans using computerized axial tomography (CT) of the thymus. RESULTS: HAART initiation resulted in a significant decline in plasma viremia and percentage of infected peripheral blood cells, and a rise in CD4 T cells from a baseline median of 207 cells/microL to a week-48 median of 617 cells/microL. The rise was predominately in CD4 memory cells. Naive T cells also increased in number, but at a slower rate. Activated (HLA-DR CD38) CD4 and CD8 T cells were elevated at baseline (24 and 62%, respectively) and declined by week 48 (17 and 36%, respectively) but did not reach normal levels. The number of Fas CD4 T cells increased from a baseline median of 169 to 381 cells/microL at week 48. Both soluble interleukin (IL)-2 and tumour necrosis factor (TNF) II receptors declined by week 48. HIV p24 lymphocyte proliferation assay responses were transiently detected in three patients. TREC values increased from a median 6400 copies/microg at baseline to a week-48 median value of 26 697 copies/microg. CONCLUSION: Immune functional reconstitution was not achieved in these HAART naive patients.

Multiple paragangliomas of the head and neck.

Multiple paragangliomas of the head and neck are rare conditions. The incidence of multiple paragangliomas is reported to the approximately 10% of the total patients, but in familial cases it increases up to 35-50%. In the head and neck region, the most common association is represented by bilateral carotid body tumors or by carotid body tumor associated with tympanic-jugular glomus. The presence of three synchronous glomus tumors is really rare, as well as association with vagal glomus and carotid body. In this paper the authors present a patient affected ipsilaterally by a carotid body tumor and vagal paraganglioma, focusing on the diagnostic options offered by imaging techniques (CT and MRI).

Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral and single internal mammary arteries.

BACKGROUND: Coronary artery bypass grafting (CABG) is the commonest major operation in most developed countries. A single internal mammary artery (IMA) graft has proven survival benefits, but the additional survival advantage of a second graft is unknown. We systematically reviewed published studies of bilateral versus single IMA grafts in CABG to assess any differences in survival. METHODS: We identified from Medline all studies in which single and bilateral IMA grafts were compared. We included studies in which at least 100 patients in each group had been followed up for at least 4 years. We assessed study quality on the basis of patient selection, comparability of intervention groups (especially for age, sex, ventricular function, and diabetes status), outcome assessment, and completeness of follow-up. Our primary outcome was survival. Estimates of treatment effect (single versus bilateral) expressed as hazard ratios were pooled across studies. FINDINGS: None of the studies was a randomised trial, but nine cohort studies met our inclusion criteria. Seven studies yielded survival data for meta-analysis, and included 15962 patients: 11269 single and 4693 bilateral IMA grafts. The bilateral group had significantly better survival than the single group (hazard ratio for death 0.81; 95% CI 0.70-0.94). Exclusion of methodologically weak studies improved survival rates with bilateral IMA grafts. INTERPRETATION: Because no study was a randomised trial, our results are more uncertain than is indicated by the 95% CI. Nevertheless, bilateral IMA grafts seem to give better survival rates than single grafts.

Results and complications of facial reanimation following cerebellopontine angle surgery.

The present study was undertaken to evaluate the results of a group of patients following treatment for cerebellopontine angle lesions who developed postoperative facial palsy and underwent facial nerve repair in order to reanimate the muscles of facial expression. A retrospective study was performed on 23 patients treated between 1988 and 1997 at the 2nd and 4th ENT chairs of University "La Sapienza" of Rome for facial palsy following cerebellopontine angle surgery. Tumors included acoustic neuromas (n = 3). Seventeen patients underwent hypoglossal-facial anastomoses [10 with end-to-end anastomoses, 4 with May's interposition "jump-nerve" grafts and 3 with partial (30%) use of the hypoglossal nerve plus a facial cross-over]. The remaining patients were operated on using a cable graft with the sural nerve (n = 2) and the great auricular nerve (n = 4). Postoperative facial function was determined by the House-Brackmann 6-scale classification The hypoglossal-facial anastomoses resulted in long-term grade III or IV findings. Cable grafts improved facial function from grade VI to grade III. None of the patients operated on with the modfied VII-XII anastomosis developed swallowing disturbances. The ten patients having traditional hypoglossal-facial anastomoses showed different degrees of tongue disability and retention of residue in the oral cavity. Surgical recovery of postoperative facial palsy can be obtained with various techniques according to the availability of the proximal facial nerve stump at the brain stem. Since a traditional hypoglossal-facial anastomosis procedure can be a source of a separate disability for the patient, techniques are preferred that leave the hypoglossal nerve mostly intact and uncompromised.

Reconstruction of the posterior auditory canal with hydroxyapatite-coated titanium.

There are a variety of techniques for treating chronically discharging radical mastoid cavities. The purpose of this article is to report the preliminary results of an original technique for reconstruction of the posterior auditory canal using a titanium net combined with porous hydroxyapatite coating. Titanium is fixed with two screws to the mastoid tip and zygomatic root to prevent the risk of implant dislocation. Eight patients with chronically discharging radical mastoid cavities that failed medical management underwent reconstruction of the mastoid cavity using this technique. After surgery, all cases had rapid healing and good aeration of the middle ear and mastoid. One tympanic membrane reperforated, and no extrusion of the prostheses were detected clinically or on computed tomography scanning. The minimum postoperative follow-up period has been 12 months (range 12-48 months). To date, there has been no evidence of cholesteatoma recurrence. The preliminary results remain encouraging. Larger series and longer follow-up, however, are advisable to prove real validity.

Meta-analysis of clinical trials with copolymer 1 in multiple sclerosis.

Glatiramer acetate (copolymer 1) was licensed in the USA in 1996 for the treatment of relapsing-remitting multiple sclerosis. In order to assess its efficacy, a meta-analysis of all randomized controlled trials was performed. Two double-blind studies, accounting for a total number of 299 patients, contribute to this analysis. Patients undergoing the treatment have decreased probability of relapse at 12 months (OR 0.17, 95% CI 0.05-0.51, p = 0.002) and of unsustained progression of disability at 24 and 35 months (OR 0.57, 95% CI 0. 34-0.95, p = 0.031, and OR 0.50, 95% CI 0.28-0.90, p = 0.019). These data suggest that glatiramer acetate represents an alternative to interferon treatment in relapsing-remitting multiple sclerosis. However, further evidence of efficacy is required to justify its use in clinical practice.