4 research outputs found
Effect of calcitriol on bone turnover and osteocalcin in recent-onset type 1 diabetes
No full textContains fulltext :
125353.pdf (Publisher’s version ) (Open Access)BACKGROUND: Vitamin D supplementation in childhood improves the achievement of peak bone mass. We investigated the effect of supplementation with calcitriol on bone turnover in recent-onset type 1 diabetes (T1D). Moreover, the association between osteocalcin and parameters of beta-cell function and metabolic control was examined. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a post-hoc analysis of a double-blind, placebo-controlled study of calcitriol supplementation to preserve beta-cell function. 27 recent-onset T1D subjects, mean age 22 years, were randomized to 0.25 microg calcitriol per day or placebo (1:1) and followed up for one year. Changes in bone formation (osteoclacin) and resorption (beta-CrossLaps) markers, and differences between placebo and calcitriol-treated group were evaluated. At baseline, osteocalcin levels were significantly lower in female than in male patients (P<0.01) while no other metabolic parameters as HbA1c and C-peptide differed between gender. No significant correlations were found in relation to HbA1c, insulin requirement and C-peptide. At 1 year follow-up, no significant differences were observed between calcitriol and placebo groups for osteocalcin and beta-CrossLaps. In the placebo group osteocalcin levels were unrelated with parameters of metabolic control, such as C-peptide, insulin requirement or HbA1c. Changes of C-peptide, insulin requirement and HbA1c were not related to osteocalcin levels. CONCLUSIONS: Supplementation with 0.25 microg calcitriol per day to patients with new-onset T1D does not affect circulating markers of bone turnover. OC levels were unrelated to beta-cell function and other metabolic parameters suggesting that OC is ineffective to control pancreatic function in presence of aggressive autoimmune destruction
Interplay between inflammation, autoimmunity and regeneration in the NOD mouse model of type 1 diabetes and Sjogren’s Syndrome.
No full textPhDA continuous process of tissue remodelling and regeneration is a fundamental feature of the
homeostatic response of the target organ of several autoimmune diseases. In type 1 diabetes (T1D)
the β cell mass is in a constant process of death and renewal in order to regenerate the islets
damaged by the autoimmune process. The relationship linking inflammation and regeneration
during autoimmunity remains elusive. Reg genes, a multigene family discovered using cDNA
libraries derived from rat regenerating islets, have been suggested to play an important role in
epithelial regeneration not only in the pancreas but also in the salivary glands (SG) of Sjogren’s
Syndrome (SS) during autoimmune sialoadenitis.
Both in patients and animal models of T1D and SS, the chronic inflammatory/autoimmune process
is heterogeneous and display high immunological variability. In particular, in a sizeable subset of
cases, inflammatory lesions display ectopic lymphoid structures (ELS) characterised by T/B cell
segregation, follicular dendritic cells networks and differentiation of germinal center B cells.
However, there is limited evidence on the cellular and molecular mechanisms underlying ELS
formation and their contribution to autoimmunity in the pancreas during autoimmune insulitis and
in SG during autoimmune sialoadenitis. In this PhD project, I used the NOD mouse model of T1D
and SS in order to investigate i) the cellular and molecular mechanisms regulating ELS formation,
ii) the functionality of ELS in supporting in situ autoreactive B cell differentiation and iii) the
relationship between formation of ELS and the expression of REG genes.
In this work I showed that ELS formation was preceded by local up-regulation of lymphotoxins
(LTαβ) and lymphoid chemokines CXCL13 and CCL19 and that, once formed, ELS were fully
functional in promoting autoreactive B cell activation. Importantly, inhibition of the LT-β pathway
prevented the formation of ELS and B cell autoimmunity. Finally, I showed that the expression
pattern of Reg genes was strictly related to the development of inflammatory infiltrates in NOD
7
mice and that Reg proteins were target of the autoimmune process itself, as shown by the
development of anti-Reg1 antibodies in patients with T1D. Overall, these results suggest that the
processes of destruction and regeneration occurring in chronic autoimmune/inflammatory diseases
are strongly interdependent whereby autoimmunity may be further enhanced by the attempt to
regenerate
Prognostic significance of admission levels of troponin I in patients with acute ischaemic stroke
No full textObjectives: Successful prediction of cardiac complications early in the course of acute ischaemic stroke could have an impact on the clinical management. Markers of myocardial injury on admission deserve investigation as potential predictors of poor outcome from stroke. Methods: We prospectively investigated 330 consecutive patients with acute ischaemic stroke admitted to our emergency department based stroke unit. We analysed the association of baseline levels of cardiac troponin I (cTnl) with (a) all-cause mortality over a six month follow up, and (b) inhospital death or major non-fatal cardiac event ( angina, myocardial infarction, or heart failure). Results: cTnl levels on admission were normal (lower than 0.10 ng/ml) in 277 patients (83.9%), low positive (0.10-0.39 ng/ml) in 35 (10.6%), and high positive (0.40 ng/ml or higher) in 18 (5.5%). Six month survival decreased significantly across the three groups (p<0.0001, log rank test for trend). On multivariate analysis, cTnl level was an independent predictor of mortality (low positive cTnl, hazard ratio (HR) 2.14; 95% CI 1.13 to 4.05; p = 0.01; and high positive cTnl, HR 2.47; 95% CI 1.22 to 5.02; p = 0.01), together with age and stroke severity. cTnl also predicted a higher risk of the combined endpoint "inhospital death or non-fatal cardiac event''. Neither the adjustment for other potential confounders nor the adjustment for ECG changes and levels of CK-MB and myoglobin on admission altered these results. Conclusions: cTnl positivity on admission is an independent prognostic predictor in acute ischaemic stroke. Whether further evaluation and treatment of cTnl positive patients can reduce cardiac morbidity and mortality should be the focus of future research. Univ Roma La Sapienza, Dept Neurol Sci, I-00185 Rome, Italy; Univ Roma La Sapienza, Dept Internal Med, Rome, Italy; Univ Roma La Sapienza, Dept Emergency Med, Rome, Italy; Univ Rome, Dept Cellular Biotechnol, Rome, Italy; Univ Rome, Dept Hematol, Rome, Italy Fiorelli, M (reprint author), Univ Roma La Sapienza, Dept Neurol Sci, Viale Univ 30, I-00185 Rome, Italy. [email protected] Fiorelli, Marco/F-6642-2012; Sacchetti, Maria /F-2644-2011 20 40 41 B M J PUBLISHING GROUP LONDON BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND 0022-3050 J NEUROL NEUROSUR PS J. Neurol. Neurosurg. Psychiatry JAN 2005 76 1 76 81 10.1136/jnnp.2004.041491 6 Clinical Neurology; Psychiatry; Surgery Neurosciences & Neurology; Psychiatry; Surgery 880GQ WOS:000225777400015 J Paolini, S; Ciappetta, P; Guiducci, A; Principi, M; Missori, P; Delfini, R Paolini, S; Ciappetta, P; Guiducci, A; Principi, M; Missori, P; Delfini, R Foraminal deposition of calcium pyrophosphate dihydrate crystals in the thoracic spine: possible relationship with disc herniation and implications for surgical planning - Report of two cases JOURNAL OF NEUROSURGERY-SPINE English Article calcification; calcium pyrophosphate dihydrate; disc herniation; foramen; thoracic spine OF-THE-LITERATURE; CORD COMPRESSION; CERVICAL MYELOPATHY; DISEASE; TOMOGRAPHY; EXPERIENCE; MRI The authors report two cases of nodular calcium pyrophosphate dihydrate (CPPD) crystal deposition close to the thoracic neural foramen, which caused chronic radiculopathy. Preoperatively, the lesions were interpreted as calcified disc herniations. Both patients underwent surgery in which an extended transfacet pedicle-sparing approach was used. Incision of the posterior longitudinal ligament released soft degenerated material. In both cases, histological examination showed abundant degenerative debris along with CPPD crystals. Spinal CPPD deposition is a comparatively rare disease that almost invariably involves the posterior aspect of the spinal canal, typically the ligamentum flavum. The exceptional foraminal location of the lesions reported here, combined with the surgical findings, indicated that the CPPD crystals were deposited on a laterally herniated disc fragment. A distinctive feature in both cases was the soft consistency of the resected tissue. The consistency of the disc material and the location of the lesion in the axial plane (that is, median compared with lateral) are key factors in determining the optimal surgical approach to thoracic disc herniations. In describing consistency, terms such as "calcified" and "hard" have been used interchangeably in the literature. In the cases reported here, what appeared on computerized tomography and magnetic resonance imaging studies to be densely calcified lesions were shown intraoperatively to be soft herniations. The authors' experience underscores that not all densely calcified herniated discs are hard. Although detection of this discrepancy would have left surgical planning for the lateral disc herniations unchanged, it could have altered planning for centrally or centrolaterally located disc herniations. Osped S Maria, Serv Neuroradiol, Terni, Italy; Univ Perugia, Serv Anat Patol, Cattedra Neurochirurg, Terni, Italy; Univ Roma La Sapienza, Cattedra Neurochirurg, Rome, Italy Paolini, S (reprint author), Via Campomicciolo 8A, I-05100 Terni, Italy. [email protected] 28 2 3 AMER ASSOC NEUROLOGICAL SURGEONS CHARLOTTESVILLE UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA 0022-3085 J NEUROSURG-SPINE J. Neurosurg.-Spine JAN 2005 2 1 75 78 10.3171/spi.2005.2.1.0075 4 Clinical Neurology; Surgery Neurosciences & Neurology; Surgery 895OZ WOS:000226874100015 J Bruschi, M Bruschi, M New solvable nonlinear matrix evolution equations JOURNAL OF NONLINEAR MATHEMATICAL PHYSICS English Article QUARTIC OSCILLATORS; INTEGRABLE SYSTEMS We introduce an extension of the factorization-decomposition technique that allows us to manufacture new solvable nonlinear matrix evolution equations. Several examples of such equations are reported. Univ Roma La Sapienza, Dipartimento Fis, I-00185 Rome, Italy; Ist Nazl Fis Nucl, Sez Roma, Rome, Italy Bruschi, M (reprint author), Univ Roma La Sapienza, Dipartimento Fis, I-00185 Rome, Italy. [email protected] 6 0 0 NORBERT EULER LULEA LULEA UNIV TECHNOL, DEPT MATHEMATICS, SE-971 87 LULEA, SWEDEN 1402-9251 J NONLINEAR MATH PHY J. Nonlinear Math. Phys. JAN 2005 12 1 97 105 9 Physics, Mathematical Physics 890GZ WOS:000226501000011 J Carillo, S Carillo, S Some remarks on materials with memory: Heat conduction and viscoelasticity JOURNAL OF NONLINEAR MATHEMATICAL PHYSICS English Article MINIMUM FREE-ENERGY; LINEAR VISCOELASTICITY; MAXIMUM; STATE; WORK Materials with memory are here considered. The introduction of the dependence on time not only via the present, but also, via the past time represents a way, alternative to the introduction of possible non linearities, when the physical problem under investigation cannot be suitably described by any linear model. Specifically, the two different models of a rigid heat conductor, on one side, and of a viscoelastic body, on the other one, are analyzed. In them both, to evaluate the quantities of physical interest a key role is played by the past history of the material and, accordingly, the behaviour of such materials is characterized by suitable constitutive equations where Volterra type kernels appear. Specifically, in the heat conduction problem, the heat flux is related to the history of the temperature-gradient while, in isothermal viscoelasticity, the stress tensor is related to the strain history. Then, the notion of equivalence is considered to single out and associate together all those different thermal histories, or, in turn, strain histories, which produce the same work. The corresponding explicit expressions of the minimum free energy are compared. Univ Roma La Sapienza, Dipartimento Metodi & Modelli Matemat Sci Applica, I-00161 Rome, Italy Carillo, S (reprint author), Univ Roma La Sapienza, Dipartimento Metodi & Modelli Matemat Sci Applica, Via A Scarpa 16, I-00161 Rome, Italy. [email protected] Carillo, Sandra/C-8949-2011 Carillo, Sandra/0000-0001-9260-1839 23 7 7 NORBERT EULER LULEA LULEA UNIV TECHNOL, DEPT MATHEMATICS, SE-971 87 LULEA, SWEDEN 1402-9251 J NONLINEAR MATH PHY J. Nonlinear Math. Phys. JAN 2005 12 1 163 178 10.2991/jnmp.2005.12.s1.14 16 Physics, Mathematical Physics 890GZ WOS:000226501000016 J Degasperis, A; Manakov, SV; Santini, PM Degasperis, A; Manakov, SV; Santini, PM Integrable and nonintegrable initial boundary value problems for soliton equations JOURNAL OF NONLINEAR MATHEMATICAL PHYSICS English Article NONLINEAR SCHRODINGER-EQUATION; EVOLUTION-EQUATIONS; BURGERS-EQUATION; HALF-LINE; SCATTERING; TRANSFORM; INTERVAL; SEMILINE; GENERATION; PDES It is well-known that the basic difficulty in studying the initial boundary value problems for linear and nonlinear PDEs is the presence, in any method of solution, of unknown boundary values. In the first part of this paper we review two spectral methods in which the above difficulty is faced in different ways. In the first method one uses the analyticity properties of the x-scattering matrix S(k, t) to replace the unknown boundary values by elements of the scattering matrix itself, thus obtaining a closed integro-differential evolution equation for S(k, t). In the second method one uses the analyticity properties of S(k, t) to eliminate the unknown boundary values by a suitable projection, obtaining a nonlinear Riemann Hilbert problem for S(k, t). The second approach allows also to identify in a natural way a known subclass of boundary conditions which gives rise to a spectral formalism based on linear operations (and therefore called "integrable boundary conditions"). In the last part of the paper we present a new method to identify a whole hierarchy of integrable boundary conditions. Univ Roma La Sapienza, Dipartimento Fis, I-00185 Rome, Italy; Ist Nazl Fis Nucl, Sez Roma, I-00185 Rome, Italy; Acad Sci, LD Landau Theoret Phys Inst, Moscow, Russia Degasperis, A (reprint author), Univ Roma La Sapienza, Dipartimento Fis, Piazzale Aldo Moro 2, I-00185 Rome, Italy. [email protected]; [email protected] 35 4 4 WORLD SCIENTIFIC PUBL CO PTE LTD SINGAPORE 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE 1402-9251 J NONLINEAR MATH PHY J. Nonlinear Math. Phys. JAN 2005 12 1 228 243 16 Physics, Mathematical Physics 890GZ WOS:000226501000021 J Donini, LM; De Felice, MR; Tagliaccica, A; De Bernardini, L; Cannella, C Donini, LM; De Felice, MR; Tagliaccica, A; De Bernardini, L; Cannella, C Nutritional status and evolution of pressure sores in geriatric patients JOURNAL OF NUTRITION HEALTH & AGING English Article nutritional status; pressure sores; elderly; long term care; geriatrics NURSING-HOME RESIDENTS; TERM-CARE RESIDENTS; RISK-FACTORS; ELDERLY PATIENTS; ULCERS; MALNUTRITION; POPULATION; PREVENTION; MANAGEMENT The prevalence of pressure sores (PS) ranges from 1 to 18% of in-patients and from 3 to 28% of those admitted to long-term settings. The aim of our study was to verify, a posteriori, how nutritional status influenced the evolution of PS in a population of elderly subjects hospitalised in a long-term care setting. Materials and Methods: The charts of 125 patients with ulcerative or necrotic pressure ulcers were evaluated retrospectively. For each subject we took note of: PS characteristics (stage, ulcer surface, evolution), clinical characteristics (comorbidity, adverse clinical events, cognitive, functional and nutritional status). Results: In 58 patients (46.4%) there was overall healing of the lesions while in 39 patients (31.2%) we had however an "improvement" of PS. The course of PS was not significantly influenced by the patient's physiological characteristics, by cognitive status or by initial characteristics of PS. Instead, we noticed a significant difference in the course of PS as a function of the level of autonomy and clinical status. The course of PS, and in particular the Healing Index, were influenced by the Nutritional Status and, above all, by its course during the treatment period. Conclusions: The development of PS is multifactorial. Whereas, it is clear that factors other than nutrition influence the risk of developing PS, an important role for nutrition in the development and resolution of PS is suggested. Our data certainly confirm the "Quality indicators for prevention and management of pressure ulcers in vulnerable elders", especially were they say "if a vulnerable elder is identified as at risk for pressure ulcer development and has malnutrition, then nutritional intervention or dietary consultation should be instituted because poor diet, particularly low dietary protein intake, is an independent predictor of pressure ulcer development". Univ Roma La Sapienza, Ist Sci Alimentaz, I-00185 Rome, Italy Donini, LM (reprint author), Univ Roma La Sapienza, Ist Sci Alimentaz, Piazzale Aldo Moro 5, I-00185 Rome, Italy. [email protected] 40 7 9 SERDI EDITION PARIS 320 RUE SAINT-HONORE, PARIS, 75001, FRANCE 1279-7707 J NUTR HEALTH AGING J. Nutr. Health Aging 2005 9 6 446 454 9 Geriatrics & Gerontology; Nutrition & Dietetics Geriatrics & Gerontology; Nutrition & Dietetics 993RX WOS:000233973700009 J Scarpino, S; Di Napoli, A; Taraboletti, G; Cancrini, A; Ruco, LP Scarpino, S; Di Napoli, A; Taraboletti, G; Cancrini, A; Ruco, LP Hepatocyte growth factor (HGF) downregulates thrombospondin I (TSP-I) expression in thyroid papillary carcinoma cells JOURNAL OF PATHOLOGY English Article thyroid papillary carcinoma; thyroid tumours; thyroid cancer; thrombospondin-1; hepatocyte growth factor; HGF; HGF receptor; Met protein TUMOR ANGIOGENESIS; EPITHELIAL-CELLS; MET PROTEIN; FIBROBLASTS; OVEREXPRESSION; PROGRESSION; MOTILITY; CANCER; VEGF This study investigates the expression of thrombospondin-1 in papillary carcinoma of the thyroid and the role of Met-HGF interaction in TSP-1 regulation. In tissue sections, immunostaining for TSP-1 was associated with the fibrous tumour stroma, and showed areas of marked intensity adjacent to the basal membrane of tumour cells. Investigation of TSPI RNA expression showed that, in 10 of 14 cases, TSP-1 mRNA levels were significantly lower in tumour tissue (20-100% reduction; mean = 55% +/- 20; p = 0.001) than in the corresponding normal thyroid. Since it has been reported that HGF can downregulate the expression of TSP-1 mRNA, TSP-1 mRNA levels were measured in 7 primary cultures, established from thyroid papillary carcinomas (TPC), and in I TPC cell line prior to, or after, stimulation with HGF. A marked decrease in TSP-1 mRNA levels was observed after HGF stimulation in 6/7 primary cultures (60-100% decrease (mean = 79 +/- 15%;p = 0.006) and in the TPC cell line; moreover, the decrease in TSP-1 mRNA in cell extracts was associated with a decrease in TSP-1 protein in culture supernatants. The HGF activity was dose dependent and the downregulation lasted for at least 48 h after stimulation. The high-level expression of Met protein, the high-affinity receptor for HGF, in most cases of papillary carcinoma of the thyroid is consistent with the possibility that HGF-Met interaction plays a crucial role in regulating the expression of TSP-1 in this tumour type. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd. Univ Roma La Sapienza, Fac Med & Chirurg 2, Dipartimento Diagnost Med & Pathol,Osped St Andre, Lab Istopatol, I-00189 Rome, Italy; Ist Ric Farmacol Mario Negri, Bergamo, Italy; Univ Roma La Sapienza, Fac Med & Chirurg 2, Osped St Andrea, Dipartimento Chirurg C, I-00189 Rome, Italy Scarpino, S (reprint author), Univ Roma La Sapienza, Fac Med & Chirurg 2, Dipartimento Diagnost Lab,Osped St Andrea, Lab Istopatol, Via Di Grottarossa 1035-1039, I-00189 Rome, Italy. [email protected] 26 9 10 JOHN WILEY & SONS LTD CHICHESTER THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND 0022-3417 J PATHOL J. Pathol. JAN 2005 205 1 50 56 10.1002/path.1675 7 Oncology; Pathology Oncology; Pathology 882DT WOS:000225919600006 J Crino, A; Schiaffini, R; Ciampalini, P; Suraci, MC; Manfrini, S; Visalli, N; Matteoli, MC; Patera, P; Buzzetti, R; Guglielmi, C; Spera, S; Costanza, F; Fioriti, E; Pitocco, D; Pozzilli, P Crino, A; Schiaffini, R; Ciampalini, P; Suraci, MC; Manfrini, S; Visalli, N; Matteoli, MC; Patera, P; Buzzetti, R; Guglielmi, C; Spera, S; Costanza, F; Fioriti, E; Pitocco, D; Pozzilli, P IMDIAB Grp A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM English Article nicotinamide; type 1 diabetes mellitus; C-peptide; intensive insulin therapy RANDOMIZED-TRIAL; IDDM; INTERVENTION Background and Aims: A number of trials have evaluated residual beta-cell function in patients with recent onset type I diabetes mellitus (DMI) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and HT for up to 2 years after diagnosis. Patients and Methods: We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (<4 weeks) to HT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom HT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA(1c) levels were evaluated at 12 and 24 months after diagnosis. Results: In the course of the follow-up, patients on nicotinamide + HT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA(1c) was significantly lower 2 years after diagnosis in patients treated with nicotinamide + HT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p <0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. Conclusion: Implementation of HT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as,assessed by HbA(1c). In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + HT at diagnosis of DMI prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period. Univ Campus Biomed, Dept Endocrinol & Diabet, I-00155 Rome, Italy; Univ Cattolica Sacro Cuore, Med Clin, Rome, Italy; Osped Pediat Bambino Gesu, Rome, Italy Pozzilli, P (reprint author), Univ Campus Biomed, Dept Endocrinol & Diabet, Via E Longoni 83, I-00155 Rome, Italy. [email protected] Pozzilli, Paolo/A-5235-2010 12 17 17 FREUND PUBLISHING HOUSE LTD LONDON STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND 0334-018X J PEDIATR ENDOCR MET J. Pediatr. Endocrinol. Metab. 2005 18 8 749 754 6 Endocrinology & Metabolism; Pediatrics Endocrinology & Metabolism; Pediatrics 967ZG WOS:000232129500004 J Schiavetti, A; Hadjistilianou, T; Clerico, A; Bonci, E; Ragni, G; Castello, MA Schiavetti, A; Hadjistilianou, T; Clerico, A; Bonci, E; Ragni, G; Castello, MA Conservative therapy in intraocular retinoblastoma - Response/recurrence rate JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY English Article intraocular retinoblastoma; chemoreduction; focal ophthalmic therapy LOCAL TREATMENT; SECONDARY LEUKEMIA; CHEMOTHERAPY; CHEMOREDUCTION; EPIPODOPHYLLOTOXINS; RISK; MANAGEMENT; TUMORS Purpose: To evaluate the response/recurrence rate and the outcome in intraocular retinoblastoma treated with chemoreduction and focal therapy, the authors performed a retrospective review of their patients. Methods: The series included 46 newly diagnosed patients with unilateral or bilateral intraocular retinoblastoma (58 eyes) receiving carboplatin/etoposide chemotherapy associated with focal therapy (laser or cryotherapy). The mean follow-up was 53 months (range 11-125). Results: Fifty-one eyes (88%) presented with complete response after four to eight courses of chemotherapy combined with focal treatment. The response rate was 100% in group 1, 94% in group 2, 100% in group 3, 83% in group 4, and 70% in group 5 (5 vs. 1-4, P < 0.03; 5-4 vs. 1-3, P < 0.025). Twenty-nine eyes (57%) relapsed after a mean of 7 months (range 2-36). The relapse rate was 30% in group 1, 27.% in group 2, 67% in group 3, 80% in group 4, and 100% in group 5 (5 vs. 1-4, P < 0.001 ; 4-5 vs. 1-3, P < 0.001). Seven of 18 cases achieved a second complete response with further conservative treatment (total courses 8-14). Twenty-nine eyes (50%) were treated without external-beam radiotherapy or enucleation: 90% in group 1, 69% in group 2, 67% in group 3, 33% in group 4, and 6% in group 5 (5 vs. 1-4, P < 0.01; 5-4 vs. 1-3, P < 0.001). Ten eyes (17%) required external-beam radiotherapy and 21 eyes (36%) enucleation. The ocular salvage rate was 67%. Conclusions: Although all groups of patients with intraocular retinoblastoma responded to carboplatin/etoposide chemotherapy associated with focal therapy, all the cases in group 5 relapsed. This approach is questionable in group 5, in which could be justified to delay aggressive treatment in a very young child. Univ Roma La Sapienza, Dept Pediat, Rome, Italy; Univ Siena, Dept Ophthalmol, I-53100 Siena, Italy
