Protocolo BAMP: Reporte de Caso Clínico

El presente reporte tiene como objetivo presentar de manera secuencial y visual la protracción maxilar de un paciente clase III esqueletal, utilizando el protocolo BAMP. Una vez realizado el análisis clínico del caso se decidió realiza un tratamiento ortopédico a través del uso de miniplacas de titanio con elásticos intermaxilares de clase III siguiendo el protocolo BAMP, junto a un tratamiento ortodóncico dento alveolar con aparatología fija bimaxilar prescripción Roth 0.22" Mini sprint forestadent. Se observa el éxito del enfoque interceptivo utilizando el protocolo BAMP. Este enfoque logró reducir tanto el tiempo como la complejidad del tratamiento ortodóncico, y también disminuyó la necesidad de someterse a una cirugía ortognática en la edad adulta. El tratamiento BAMP, diseñado para ciertas edades y crecimiento, se demostró exitoso en un paciente de 12 años sin potencial de crecimiento. Las miniplacas como anclaje son efectivas para protracción maxilar en varios casos, aunque se necesita seguimiento y educación postquirúrgica. Se recomienda retirar las miniplacas cuando no sean necesarias, adaptando el protocolo a cada paciente. En resumen, el tratamiento con miniplacas es eficaz para corregir anomalías Clase III esqueléticas.

The present report aims to sequentially and visually present the maxillary protraction of a Class III skeletal patient using the BAMP protocol. After conducting a clinical analysis of the case, it was decided to perform orthopedic treatment using titanium miniplates with Class III intermaxillary elastics following the BAMP protocol, in conjunction with dentoalveolar orthodontic treatment using fixed bimaxillary appliances with Roth prescription 0.022" Mini Sprint Forestadent. The success of the interceptive approach using the BAMP protocol is observed. This approach managed to reduce both the time and complexity of orthodontic treatment and also decreased the need for orthognathic surgery in adulthood. The BAMP treatment, designed for specific ages and growth stages, proved successful in a 12-year-old patient without growth potential. Miniplates as anchorage are effective for maxillary protraction in various cases, although post-surgical follow-up and education are required. It is recommended to remove the miniplates when they are no longer necessary, adapting the protocol to each patient. In summary, miniplate treatment is effective in correcting Class III skeletal anomalies.

Bendamustine-rituximab (BR) combined therapy for treatment of immuno-mediated neuropathies associated with hematologic malignancy.

In chronic polyneuropathies associated with hematologic malignancy (HM) the optimal treatment management is primarily focused on the HM, but the parallel response of the neuropathy is still unclear. Rituximab is a recognized therapeutic choice in anti-MAG antibody polyneuropathy, that might be useful also in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with HM. The efficacy of immunochemotherapy, which is the standard approach to malignant lymphoproliferative diseases, has been poorly investigated in polyneuropathies. We describe a six-months combined bendamustine-rituximab (BR) treatment in nine patients affected by CIDP or paraproteinemic IgM neuropathies with antibodies to peripheral nerve antigens in course of malignant HM. All patients had a long-lasting response with an average relapse free-survival (RFS) time of 31.5 months. Clinical improvement was evident at 6 months from the beginning of therapy, even earlier in 6/9 patients (<2 months). Two patients dramatically improved the disabling attitudinal and intentional tremor and pathogenic autoantibodies significantly declined in 4/5 patients. Neurological relapses occurred in three patients after a mean of 38 months of sustained stability, even if HM remitted. In such cases rituximab was administered but was associated with a shorter RFS time (1 year) compared to the previous BR scheme (3 years). In our case series, the combined BR regimen was a valid option in immune-mediated neuropathies associated with HM. Moreover, in some patients BR scheme allowed an earlier response and a long-lasting improvement than rituximab alone.

Recommendations for the Use of Tryptase in the Diagnosis of Anaphylaxis and Clonal Mastcell Disorders.

Summary: Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the molecular characteristics of the enzyme and its biological effects, the genetic basis of its production and the release kinetics. Recommendations for the clinical use of tryptase measurement developed by a task force of Società Italiana di Patologia Clinica e Medicina di Laboratorio and Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri are given on the best procedure for a correct definition of the reference values in relation to the inter-individual variability and to the correct determination of tryptase in blood and other biological liquids, in the diagnosis of anaphylaxis (from drugs, food, insect sting, or idiophatic), death from anaphylaxis (post mortem assessment) and cutaneous or clonal mastcell disorders.

Skin and lung toxicity in synchronous bilateral breast cancer treated with volumetric-modulated arc radiotherapy: a mono-institutional experience.

PURPOSE: To evaluate acute and late skin/subcutaneous toxicities and radiation-induced lung fibrosis (RILF) in patients treated with adjuvant radiotherapy (RT) for synchronous bilateral breast cancers (SBBC), after conservative surgery. METHODS/PATIENTS: Twenty-five patients were treated with volumetric-modulated arc therapy (VMAT/RapidArc®) on both breasts, and checked clinically for detecting RT toxicities during and after treatment. A high-resolution computed tomography (HRCT) was performed, for detecting RILF during follow-up. RESULTS: We registered acute Grade-1 skin toxicity in 18 patients (72%), while six patients (24%) experienced Grade-2 toxicity. No breath symptoms were reported during and after RT. Late Grade-1 subcutaneous toxicity and late Grade-2 skin toxicity were registered in four patients (16%) and one patient (4%), respectively, at a mean follow-up of 36 months. Grade-1 RILF was detected in six patients (30%). The median volume of fibrosis area was 6.5 cc (range 1.3-21.5 cc). The partial volumes receiving a specified dose (V20, V30, V40, and V50) in patients who developed lung fibrosis were significantly bigger than who did not (p < 0.01). We showed that the mean volume of the tumour boost of patients who developed fibrosis (77.7 cc) was not significantly different from the other patients (90.8 cc) (p = 0.5). CONCLUSION: The clinical impact of this technique is favourable, and this is the first clinical study showing RILF by HRCT in a setting of SBBC. Further study with larger accrual is mandatory.

Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor (PLA2R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases.

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.

Extra central nervous system metastases from glioblastoma: a new possible trigger event?

Extra-cranial metastases of glioblastoma (GBM) represent a rare event, and the biological-genetic mechanisms involved in the pathogenesis have not yet been determined. We report the case of a young patient with multiple visceral and osseous metastases occurred after 4 years after first diagnosis of GBM. The strangeness as well as the rarity of this event does not allow to identify an effective treatment for GBM metastases, making the management of this ominous tumor an even greater challenge.

Relationship between circulating anti-thyroglobulin antibodies (TgAb) and tumor metabolism in patients with differentiated thyroid cancer (DTC): prognostic implications.

PURPOSE: TgAb have been proposed as tumor markers in DTC. Recent evidence links TgAb levels with DTC aggressiveness. We aimed to evaluate the relationship between TgAb and tumor glucose metabolism in DTC patients. METHODS: Seventy-one DTC patients who underwent 18F-FDG PET/CT were included. According to TgAb value and trends, patients were divided into TgAb positive (TgAb+) or negative (TgAb-) as well as in patients with increasing (Inc-TgAb) or decreasing (Dec-TgAb) trend. On the basis of the results of FDG-PET, post-therapy 131I and Tg levels, patients were divided into two groups according to the evidence (ED) or absence (NED) of disease. ED patients were further divided into three subgroups: 1. radioiodine avid with positive 18F-FDG PET/CT (PET+/131I+), 2. radioiodine refractory with positive 18F-FDG PET/CT (PET+/131I-) and 3. radioiodine avid with negative 18F-FDG PET/CT (PET-/131I+). MeanSUV of FDG-avid lesions was assessed and averaged for each patient (SUVmean-pt). T test was performed to assess the difference between SUVmean in TgAb-, TgAb+ and in Inc-TgAb and Dec-TgAb subgroups. Difference in TgAb between ED and NED patients as well as between ED patients and PET+/131I+, PET+/131I- and PET-/131I+ subgroups was compared. RESULTS: SUVmean was significantly higher in Inc-TgAb with respect to Dec-TgAb subgroup (5.2 ± 1.5 vs. 2.9 ± 1.1, p < 0.05). TgAb were higher only in the ED PET+/131I+ subgroup with respect to NED patients (p < 0.01). CONCLUSIONS: The relationship between higher tumor metabolism and trend of TgAb supports a prognostic relevance of TgAb in DTC patients. Significantly higher TgAb in radioiodine avid tumors with positive 18F-FDG PET/CT further testify the role of TgAb as surrogate tumor marker in DTC.

Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes.

Despite moderate improvements in outcome of glioblastoma after first-line treatment with chemoradiation recent clinical trials failed to improve the prognosis of recurrent glioblastoma. In the absence of a standard of care we aimed to investigate institutional treatment strategies to identify similarities and differences in the pattern of care for recurrent glioblastoma. We investigated re-treatment criteria and therapeutic pathways for recurrent glioblastoma of eight neuro-oncology centres in Switzerland having an established multidisciplinary tumour-board conference. Decision algorithms, differences and consensus were analysed using the objective consensus methodology. A total of 16 different treatment recommendations were identified based on combinations of eight different decision criteria. The set of criteria implemented as well as the set of treatments offered was different in each centre. For specific situations, up to 6 different treatment recommendations were provided by the eight centres. The only wide-range consensus identified was to offer best supportive care to unfit patients. A majority recommendation was identified for non-operable large early recurrence with unmethylated MGMT promoter status in the fit patients: here bevacizumab was offered. In fit patients with late recurrent non-operable MGMT promoter methylated glioblastoma temozolomide was recommended by most. No other majority recommendations were present. In the absence of strong evidence we identified few consensus recommendations in the treatment of recurrent glioblastoma. This contrasts the limited availability of single drugs and treatment modalities. Clinical situations of greatest heterogeneity may be suitable to be addressed in clinical trials and second opinion referrals are likely to yield diverging recommendations.

Vertebral augmentation for neoplastic lesions with posterior wall erosion and epidural mass.

BACKGROUND AND PURPOSE: The presence of a cortical erosion of the posterior wall or an epidural mass is commonly considered a contraindication to performing a vertebral augmentation, considering the perceived increased risk of an epidural cement leak. Our aim was to assess technical and clinical complications of vertebral augmentation procedures performed for pain palliation and/or stabilization of neoplastic lytic vertebral body lesions, with cortical erosion of the posterior wall, often associated with a soft-tissue epidural mass. MATERIALS AND METHODS: In 48 patients, we performed retrospective vertebral augmentation assessment on 70 consecutive levels with cortical erosion of the posterior wall, as demonstrated by preprocedural CT/MR imaging. An epidural mass was present in 31/70 (44.3%) levels. Cavity creation was performed with Coblation Wands before cement injection in 59/70 levels. Injection of high-viscosity polymethylmethacrylate was performed under real-time continuous fluoroscopic control. Postprocedural CT of the treated levels was performed in all cases. Clinical follow-up was performed at 1 and 4 weeks postprocedurally. RESULTS: In 65/70 (92.8%) levels, the vertebral augmentation resulted in satisfactory polymethylmethacrylate filling of the lytic cavity and adjacent trabecular spaces in the anterior half of the vertebral body. An epidural leak of polymethylmethacrylate occurred in 10/70 (14.2%) levels, causing radicular pain in 3 patients, which spontaneously resolved within 1 week in 2 patients, while 1 patient with a T1-T2 foraminal leak developed severe weakness of the intrinsic hand muscles and a permanent motor deficit. CONCLUSIONS: In our series of vertebral augmentation of neoplastic lytic vertebral lesions performed for palliation of pain and/or stabilization, we observed a polymethylmethacrylate epidural leak in only 14.2% of levels, despite the presence of cortical erosion of the posterior wall and an epidural mass, with an extremely low rate of clinical complications. Our data seem to justify use of vertebral augmentation in patients with intractable pain or those at risk for vertebral collapse.

Rhinitis is associated with a greater risk of intermittent claudication in adults.

BACKGROUND: Chronic inflammatory airway disorders have been reported to be associated with vascular diseases of the heart and central nervous system, but their association with peripheral arterial disease (PAD), a high-prevalence vascular illness, has not been investigated. OBJECTIVE: To evaluate the association of asthma and rhinitis with intermittent claudication, which is a typical symptom of PAD. METHODS: The data were collected in the gene-environment interaction in respiratory disease survey, a population-based, multicase-control study. Participants underwent a standardized interview, skin prick tests and pulmonary function tests. The associations between respiratory diseases and intermittent claudication (i.e. pain in the leg during walking that disappears within 10 min when standing still) were estimated through relative risk ratios (RRR) by multinomial logistic regression models. RESULTS: 1174 subjects (aged 20-64 years, of which 52% were females) underwent clinical examinations and were classified into four groups: asthma only (n = 81), asthma-rhinitis overlap (n = 292), rhinitis only (n = 299) and controls (n = 345). The prevalence of intermittent claudication in these groups was, respectively, 2.5%, 3.4%, 6.4% and 2.3%. After adjusting for smoking habits and a wide range of established and potential vascular risk factors, rhinitis without asthma was associated with intermittent claudication (RRR:4.63, 95% CI:1.72-12.5), whereas no significant association was found with asthma alone (RRR:1.45, 95% CI:0.27-7.76) or asthma-rhinitis overlap (RRR:2.89, 95% CI:0.91-9.18). Atopy did not modify the observed association between intermittent claudication and rhinitis. CONCLUSIONS: Our findings suggest that rhinitis is associated with PAD, a predictor of future cerebrovascular and cardiovascular events, independently of the presence of atopy.

Radioiodine therapy of hyperfunctioning thyroid nodules: usefulness of an implemented dose calculation algorithm allowing reduction of radioiodine amount.

AIM: Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. METHODS: Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. RESULTS: Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. CONCLUSION: The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.

A study of the efficacy of radioiodine therapy with individualized dosimetry in Graves' disease: need to retarget the radiation committed dose to the thyroid.

Although Iodine-131 (131I) therapy is fully validated for Graves' disease (GD), there is debate about radioiodine amount to be administered (prescribed activity), as well as the use of individualized dosimetry vs fixed 131I activity. The clinical outcome of 119 GD patients treated with 131I from 2003 to 2008 has been evaluated. The prescribed activity was calculated according to a dosimetric protocol taking into account several variables, including thyroid volume reduction during treatment. In addition, we performed a simulation according to other dosimetric protocols, by calculating the corresponding prescribed activities. The patients were followed up for at least 12 months after treatment. In the first period of observation (2003), a 120-200 Gray (Gy) radiation dose to the thyroid was prescribed, according to the guidelines published by the Italian Societies of Endocrinology, Nuclear Medicine and Medical Physics: hyperthyroidism cure with a single radioiodine administration was obtained in 53% of patients. This outcome raised up to 89% when a higher radiation dose to the target (200- 250 Gy) was prescribed, although the administered activities were still lower, as a rule, than the most commonly employed fixed activities (400-600 Mega-Becquerel--MBq). Our method showed a high level of individual dose optimisation, particularly when compared to simplified methods. In conclusion, the protocol adopted in this study ensures a satisfactory rate of hyperthyroidism cure, while administering quite low 131I activities, provided that an adequate committed radiation dose to the thyroid is prescribed. In this context, the dose indication given by the aforementioned guidelines should probably be revised.

Thyrotropin receptor autoantibody measurement following radiometabolic treatment of hyperthyroidism: comparison between different methods.

BACKGROUND: TSH receptor antibodies (TRAb) play a crucial role in the pathogenesis of Graves' disease (GD). The use of human recombinant TSH-receptor far improved the analytical performance of TRAb assays (2nd-generation assays). The 3rd-generation assay is based on the inhibition of binding of a human biotin-labeled monoclonal thyroid- stimulating antibody (M22) to TSH-receptor by the autoantibodies present in the serum. AIM: We aimed to assess the ability of the 2nd- and 3rd-generation assays to detect serum TRAb following radioiodine therapy for hyperthyroidism. METHODS: Sera from 47 hyperthyroid (25 autoimmune, 22 non-autoimmune) patients were tested using the two different assays before and at different time intervals after radioiodine therapy. The modifications of TRAb were evaluated, as well as the correlation between the two methods. RESULTS: The results obtained by the two methods proved to be closely correlated. A rise in TRAb was invariably observed in GD patients following radioiodine, with a median peak at 6 months, irrespective of their initial clinical status, presence of ophthalmopathy, smoking habits or other variables. Such a rise was nearly superimposable using both methods. No TRAb appearance was observed in patients with non-autoimmune hyperthyroidism. CONCLUSIONS: The use of methods of higher sensitivity with respect to that formerly used indicate that nearly all GD patients develop TRAb following radioiodine, and that this phenomenon is transient and not related to baseline conditions and clinical outcome/efficacy of treatment.

Neo-adjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase II study.

BACKGROUND: Preoperative chemoradiation is now standard treatment for stages II-III rectal cancer. Capecitabine (CAP) and oxaliplatin (OX) are synergistic with radiotherapy (RT) and active in colorectal neoplasms. PATIENTS AND METHODS: Two cycles of CAP 825 mg/m(2) b.i.d. (days 1-14) and OX 50 mg/m(2) (days 1 and 8) every 3 weeks were given concomitantly with pelvic conformal RT (45 Gy). Patients with a > or =T3 and/or node-positive rectal tumour were eligible. The pathologic tumour response was defined according to the tumour regression grade (TRG) scale. RESULTS: Forty-six patients were enrolled. Gastrointestinal adverse events were mostly G1-G2; only two patients experienced G3 vomiting and diarrhoea and six patients had G1 peripheral neuropathy. Haematological toxicity was rare. G2 proctitis and anal pain occurred in two patients. Pathological complete response (TRG1) was observed in nine patients (20.9%; 95% CI 8.7%-33.1%); TRG2 in 19 patients (44.2%); TRG3 in 12 patients (27.9%); and TRG4 in three patients (7%). Overall, nine patients recurred: five with distant metastases, one with local recurrence, and three with both local recurrence and distant metastases. CONCLUSIONS: CAP-OX-RT as preoperative treatment for rectal cancer induces a remarkable rate of complete or near-complete pathologically documented response and is well tolerated.

Tumour-specific induction of immune complexes: DCP-IgM in hepatocellular carcinoma.

BACKGROUND: In the sera of liver, colorectal and prostate cancer patients, several biomarkers may be detected as IgM immune complexes. To determine whether the presence of immune complexes was correlated to an increase of IgMs, we measured the IgM content in the sera of patients with hepatocellular carcinoma (HCC) and cirrhosis, and evaluated the occurrence of des-gamma-carboxy prothrombin (DCP) as immune complexes (DCP-IgM) compared to the levels of DCP and alpha-fetoprotein (AFP). PATIENTS AND METHODS: Serum samples from 31 patients with cirrhosis, 33 untreated HCC patients diagnosed by ultrasound, computed tomography and/or magnetic resonance and confirmed by histopathology, when indicated, and 30 healthy controls were analysed. Concentrations of IgM and DCP-IgM were determined by ELISAs. RESULTS: Circulating IgM in patients with HCC (median level = 1.79 mg mL(-1)) and cirrhosis (1.09 mg mL(-1)) were not significantly different (P = 0.1376) while DCP-IgM were significantly higher in HCC patients (median level = 2171.2 AU mL(-1)) than in those with cirrhosis (1152 AU mL(-1), P = 0.0047). No correlation was found between DCP-IgM and IgM in HCC (r = 0.227) and cirrhosis patients (r = 0.475). DPC-IgM was positive in 55% (18/33) of HCC patients and in 26% (8/31) of cirrhosis patients compared to 39% and 26% for DCP and 48% and 13% for AFP. DCP-IgM, DCP and AFP tests had 100% specificity in healthy controls. CONCLUSIONS: DCP-IgM in HCC patients was not associated with an increase in IgM concentration. DCP-IgM was more frequently detected in HCC patients than DCP and AFP, strengthening the diagnostic role of IgM immune complexes for liver cancer.

Occurrence of overt celiac disease in the elderly following total thyroidectomy.

We report the case of a female patient in whom gluten-induced entheropathy was revealed at the age of 71 yr by resistance to treatment with levothyroxine (L-T4), calcium carbonate and alfacalcidol. Hypothyroidism and hypoparathyroidism were the consequence of a total thyroidectomy performed at the age of 65 yr for a large multinodular goiter. Six months after thyroid ablation the patient started to complain of abdominal pain, diarrhea and weight loss. Following, anemia and osteopenia were documented. A progressive increase of replacement therapy for hypothyroidism and hypoparathyroidism was necessary. The clinical presentation suggested a malabsorption syndrome: celiac disease (CD) was diagnosed by serological markers and duodenal biopsy. Following gluten-free diet a normalization of clinical and serological findings was observed, bone mass density improved and a reduction of L-T4, calcium and vitamin D requirements was observed.

Neuroendoscopic management of a solitary pineal region tumor. Case report of an adenocarcinoma metastasis.

The present case describes a two-step endoscopic management of hydrocephalus and diagnosis of a single pineal region metastasis arising from a gastric adenocarcinoma. A 62-year-old man presenting with signs of subacute obstructive hydrocephalus from a pineal region mass had at first been treated with an endoscopic third ventriculostomy. As cerebrospinal fluid tumor markers (alpha-fetoprotein, beta-human chorionic gonadotropin) were negative, an endoscopic biopsy of the pineal region tumor was performed through a more anterior frontal burr hole. Pathology showed an adenocarcinoma and primary tumor work-up revealed an unsuspected gastric tumor, the pathology of which matched with the intracranial metastasis. The present report emphasizes the role of neuroendoscopy in pineal region tumors and reports a rare case of a solitary gastric adenocarcinoma metastasis in this location.

Neoadjuvant phase II multicentre study of new agents in patients with malignant glioma after minimal surgery. Report of a cohort of 187 patients treated with temozolomide.

BACKGROUND: The aim of this study was to assess the efficacy of new agents in patients with malignant glioma in a neoadjuvant setting not confounded by surgery. The first study of neoadjuvant temozolomide aimed to provide a benchmark for future evaluation of new treatments. PATIENTS AND METHODS: This was a multicentre phase II study of chemotherapy in patients with histologically verified glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) who had undergone biopsy alone. Patients were planned to receive two cycles of temozolomide at 200 mg/m(2) orally daily for 5 days at a 28-day interval prior to radiotherapy. Response was assessed by two central observers on pre- and post-chemotherapy enhanced scans using bi-dimensional criteria and as progression-free survival (PFS) at the time of second assessment prior to radiotherapy. Withdrawal from the study due to worsening clinical condition was, in the absence of second imaging, assessed as progressive disease. Survival and quality of life (QOL) were secondary endpoints. RESULTS: Between August 1999 and June 2002, 188 patients from 15 UK and two Italian centres were entered into the study and 187 were analysed. Overall, 162 patients were assessable for response; seven had partial and 25 had minimal response. The objective response rate was 20% [95% confidence interval (CI) 14-26%] and PFS prior to commencing radiotherapy was 64% (95% CI 57-72%). The median survival was 10 months, and 1-year survival 41%. The median survival of responders was 16 months compared to 3 months in patients with progressive disease (P <0.001 on multivariate analysis). CONCLUSION: The phase II study design of primary chemotherapy in patients with malignant glioma following biopsy alone is feasible and provides as objective a method of assessment of efficacy as is currently available. The baseline data on temozolomide provide a benchmark for assessment of efficacy of other agents and combinations.

Analytical and diagnostic accuracy of "second generation" assays for thyrotrophin receptor antibodies with radioactive and chemiluminescent tracers.

AIMS: To investigate the analytical and diagnostic accuracy of thyrotrophin (TSH) receptor antibody assays using recombinant human TSH receptors. METHODS: Sera from 68 patients with Graves' disease, 23 patients with autoimmune thyroiditis, and 119 healthy controls were evaluated in four different laboratories using both radioactive and chemiluminescent tracers. Functional sensitivity, interlaboratory precision, optimal cutoff values for Graves' disease, and the correlation between the two methods were evaluated. RESULTS: Functional sensitivity was 0.98 IU/litre for both assays. Interlaboratory precision, expressed as per cent coefficient of variation over a wide range of antibody concentrations, varied from 5.7% to 15.1% for the radioligand, and from 6.6% to 19.9% for the chemiluminescence assay. The two methods (radioactive and chemiluminescent) were closely correlated. All the sera from untreated or relapsing patients with Graves' disease gave TSH receptor antibody values above 2.1 IU/litre, whereas in none of the healthy controls did values exceed 2.5 IU/litre. Receiver operating curve analysis allowed an optimal cutoff point to be defined at 1.99 IU/litre, according to a sensitivity of 100% and specificity of 99.1%. CONCLUSIONS: These data show the high analytical and diagnostic accuracy of the human TSH receptor assays, both with radioactive and chemiluminescent tracers, when both functional sensitivity and interlaboratory reproducibility are considered. These two methods could be proposed as first line diagnostic markers for Graves' disease.