There are different metabolic imaging methods, various tracers, and emerging anatomic modalities to stage neuroendocrine tumor (NET). We aimed to compare NET lesion detectability among 99m Tchydrazinonicotinamide (HYNIC)-octreotide (somatostatin receptor scintigraphy [SSRS]) SPECT/CT, 68 Ga-DOTATATE PET/CT, and whole-body diffusion-weighted MR imaging (WB DWI). Methods: Nineteen consecutive patients (34-77 y old; mean, 54.3 ± 10.4 y old; 10 men and 9 women) underwent SSRS SPECT/CT, 68 Ga-DOTATATE PET/CT, and WB DWI. Images were acquired with a maximum interval of 3 mo between them and were analyzed with masking by separate teams. Planar whole-body imaging and SPECT/CT were performed from thorax to pelvis using a double-head 16-slice SPECT/CT scanner 4 h after injection of 111-185 MBq of 99m Tc-HYNIC-octreotide. 68 Ga-DOTATATE PET/CT was performed from head to feet using a 16-slice PET/CT scanner 45 min after injection of 185 MBq of tracer. WB DWI was performed in the coronal plane using a 1.5-T scanner and a body coil. The standard method of reference for evaluation of image performance was undertaken: consensus among investigators at the end of the study, clinical and imaging follow-up, and biopsy of suggestive lesions. Results: McNemar testing was applied to evaluate the detectability of lesions using 68 Ga-DOTATATE PET/CT in comparison to SSRS SPECT/CT and WB DWI: a significant difference in detectability was noted for pancreas (P 5 0.0455 and P 5 0.0455, respectively), gastrointestinal tract (P 5 0.0455 and P 5 0.0455), and bones (P 5 0.0082 and P 5 0.0082). Two unknown primary lesions were identified solely by 68 Ga-DOTATATE PET/CT. 68 Ga-DOTATATE PET/CT, SSRS SPECT/CT, and WB DWI demonstrated, respectively, sensitivities of 0.96, 0.60, and 0.72; specificities of 0.97, 0.99, and 1.00; positive predictive values of 0.94, 0.96, and 1.00; negative predictive values of 0.98, 0.83, and 0.88; and accuracies of 0.97, 0.86, and 0.91. Conclusion: 68 Ga PET/CT seems to be more sensitive for detection of well-differentiated NET lesions, especially for bone and unknown primary lesions. NET can be staged with 68 Ga-DOTATATE PET/CT. WB DWI is an efficient new method with high accuracy and without ionizing radiation exposure. SSRS SPECT/CT should be used only when 68 Ga-DOTATATE PET/CT and WB DWI are not available.

The recommended phase II dose of CPT-11 in a 3-week schedule is 600 mg/m2 in less heavily, and heavily pretreated children with solid tumors.

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Topoisomerase I inhibitors, such as CPT-11, are potent anticancer drugs against neuroblastoma (NB). Differentiating agents, such as retinoids, improve the survival of children with metastatic NB. To characterize the biological effects associated with exposure to CPT-11 in vivo, athymic mice bearing a human NB xenograft, named IGR-NB8 and characterized as an immature NB with poor prognostic markers, were treated with CPT-11. Prolonged stable disease was observed, resulting in an overall tumor growth delay of 115 days. During treatment, tumors differentiated into ganglioneuroblastomas (GGNB), which reverted into an immature phenotype when treatment was discontinued. In contrast, 13-cis retinoic acid failed to induce differentiation of IGR-NB8 in vivo. Tumor differentiation was associated with decreased N-myc expression, induction of p73 expression in the perinuclear area and cytoplasm, and a dramatic 35-fold decrease in topoisomerase I (topo I) catalytic activity. The full-length M r 100,000 topo I protein was present in both pre and post-treatment immature NB xenografts. In contrast, differentiated GGNBs did not contain the M r 100,000 protein but an intense M r 48,000 topo I fragment. Furthermore, redistribution of the M r 48,000 and 68,000 forms to the cytoplasm was observed in differentiated tumors. The same pattern of topo I expression and catalytic activity was observed in NBs and GGNBs obtained from pediatric patients. Our data suggest that prolonged in vivo exposure to CPT-11 induces differentiation of NB xenografts, which is associated with truncation of the topo I enzyme, relocation of the degraded forms to the cytoplasm, and decreased catalytic activity.

This study identified significant differences among sickle cell/β-thalassemia patients according to the beta mutation involvement, pointing to an important predictor of disease severity.

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-Fibrodysplasia ossificans progressiva is a rare genetic disease characterized by widespread soft tissue ossification and congenital stigmata of the extremities. We report on a male child followed for ten years since the age of 3 years and 9 months, when the diagnosis was made. He was born with bilateral hypoplasic hallux valgus and ventricular septal defect, corrected by transsternal approach when 32 months old. Restriction of neck mobility followed and foci of ectopic ossification appeared. Four crises of disease exacerbation were treated with oral prednisone and/or other antiinflammatory drugs. Sodium etidronate 5 to 10 mg/kg/day was prescribed intermittently during about six years but was discontinued due to osteopenia. The disease course has been relentless, with severe movement restriction including the chest wall. A review showed few similar case reports in the Brazilian literature. We revisit the criteria for diagnosis and the essentials of management and treatment.KEY WORDS: fibrodysplasia ossificans progressiva, myositis ossificans, muscle biopsy, rigid spine, Tc-MDP scan, etidronate treatment. Fibrodisplasia ossificante progressiva: relato de casoRESUMO -Fibrodisplasia ossificante progressiva é uma doença genética rara, caracterizada por ossificação disseminada em tecidos moles e estigmas congênitos nas extremidades. Relatamos sobre uma criança do sexo masculino, branca, que vem sendo acompanhada desde seus 3 anos e 9 meses quando diagnosticamos a doença. Nascida com halux valgo hipoplásico bilateral e defeito do septo interventricular, submeteu-se a correção cirúrgica através de esternotomia, aos 32 meses de vida. Seguiram-se progressiva restrição de movimentos cervicais e aparecimento de nódulos duros e dolorosos em regiões paravertebrais cérvico-torácicas. Em dez anos, assistimos a quatro episódios bem definidos de exacerbação da doença, com acréscimos de ossificação ectópica. Nessas ocasiões, prescrevíamos prednisona oral e/ou antiinflamatórios não hormonais. Etidronato de sódio, 5 a 10 mg/ kg/dia, foi utilizado em períodos de dois ou três meses, com intervalos de dois meses, durante seis anos. Osteopenia obrigou-nos a interromper o uso do quelante. A evolução tem sido inexorável, com limitação intensa de movimentos torácicos e corpóreos. A revisão da literatura brasileira revelou poucos casos semelhantes. Enfatizamos os critérios para diagnóstico e princípios básicos de tratamento. PALAVRAS-CHAVE: fibrodisplasia ossificante progressiva, miosite ossificante, biópsia muscular, espinha rígida, cintilografia com MDP99m