Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone.

BACKGROUND: Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). METHODS: Patients receiving G 900 mg/m(2) d 1, 8; D 75 mg/m(2) d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. RESULTS: Fifty-one patients were included, with a median age of 17 years (8-71), 26 (51%) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49%) patients had metastases limited to lungs, 26 (51%) multiple sites. HISTOLOGY: 40 (78%) osteosarcoma, 11 (22%) HGS. Eight (16%) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46%, and significantly better for patients with ECOG 0 (ECOG 0: 54% vs ECOG 1: 43% vs ECOG 2: 0%; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75% vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56% vs HGS 18%; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13%) patients had a partial response (PR), 20 (43%) had stable disease (SD) and 20 (43%) had progressive disease (PD). The 1-year OS was 30%: 67% for PR, 54% for SD and 20% for PD (p = 0.005). CONCLUSIONS: GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma.

Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls.

Children born small for gestational age (SGA) may present advanced bone maturation in childhood and reduced final height. The objectives of the study were to evaluate adrenarche, pubertal development, age at menarche and final height in full-term born-SGA girls. Twenty-four girls (12 born-SGA and 12 matched controls) were evaluated at 6-7.5 years of age for clinical signs of puberty and dehydroepiandrosterone sulfate (DHEAS) levels, as a marker of adrenarche. Thirty-eight girls (19 born-SGA and 19 matched controls) were evaluated at 17.5-18.5 years of age to assess final height, sexual maturation and age at menarche. SGA girls had a mean final height (160.1 cm vs 165.8 cm, p < 0.01) and mean weight (52.1 kg vs 56.5 kg, p < 0.05) significantly lower than controls. Controls had a mean final height significantly higher than their mean target height. Sexual maturation was at stage 5 of Tanner's staging in SGA girls and control subjects. SGA girls had a slightly anticipated puberty (9.9 vs 10.4 years for initial breast development) and a lower age at menarche (11.9 vs 12.3 years). At 6-7.5 years of age, SGA females and controls did not show any difference for clinical signs of puberty; however, DHEAS levels (0.75 + 0.18 microgram/ml vs 0.57 + 0.22 microgram/ml, p < 0.05) were significantly higher in SGA girls than in control subjects. We concluded that full-term born-SGA females have impaired final height and weight in adolescence but substantially normal sexual maturation and age at menarche. Increased DHEAS levels before puberty in born-SGA girls may predispose to increased bone maturation in childhood with a reduced final height. In our population a progressive increment in final stature is evident.

Symptomatic hypercalcemia in the first months of life: calcium-regulating hormones and treatment.

Neonatal hypercalcemia is a rare condition often of unclear pathogenesis. If unrecognized and untreated it may result in central nervous system and renal damage. We studied three infants with symptomatic neonatal hypercalcemia pointing out pathogenetic and therapeutic aspects. One infant was found to have transient hyperparathyroidism with high intact parathyroid hormone (iPTH) levels. One infant had an incomplete form of Williams syndrome with hypercalcemia and an elfin facies. The pathogenesis is unclear in this case. A reduced secretion of calcitonin or an hypersensitivity to vitamin D might be the underlying defect. The third case was found to have subcutaneous fat necrosis and hypercalcemia associated with high 1,25(OH)2D levels and suppressed iPTH levels. These findings suggest an unregulated extrarenal 1,25(OH)2D production. These infants were treated with hydratation, furosemide, corticosteroids and low calcium diet. Symptomatic neonatal hypercalcemia should be treated promptly. However blood has to be taken before starting treatment to study calcium-regulating hormones and clarify pathogenesis.

Serum iodothyronines in the human fetus and the newborn: evidence for an important role of placenta in fetal thyroid hormone homeostasis.

UNLABELLED: The pattern of circulating iodothyronines in the fetus differs from that in the adult, being characterized by low levels of serum T3. In this study, concentrations of various iodothyronines were measured in sera from neonates of various postconceptional age (PA). Results obtained in cord sera at birth (PA, 24-40 weeks), reflecting the fetal pattern, were compared with those found during extrauterine life in newborns of 5 days or more of postnatal life (PA, 27-46 weeks). The main findings are: Starting at 30 weeks of PA, serum levels increase linearly during extrauterine life; and at 40 weeks, they are more than 200% of those measured in cord sera from newborns of equivalent PA. Serum reverse T3 (rT3) levels during fetal life are higher than those measured during extrauterine life; but they significantly decrease, starting at 30 weeks of PA. Serum T3 sulfate (T3S) does not significantly differ between the two groups, showing the highest values at 28-30 weeks of PA, and significantly decreasing at 30-40 weeks. T3S levels are directly correlated with rT3, both in fetal and extrauterine life, whereas a significant negative correlation between T3S and T3 is found only during extrauterine life. IN CONCLUSION: 1) changes in serum concentrations of iodothyronines in umbilical cord and during postnatal life indicate that maturation of extrathyroidal type I-iodothyronine monodeiodinase (MD) accelerates, starting at 30 weeks of PA; 2) high levels of type III-MD activity in fetal tissues prevent the rise of serum T3, whereas they maintain high levels of rT3 during intrauterine life; 3) an important mechanism leading to the transition from the fetal to the postnatal thyroid hormone balance is a sudden decrease in type III-MD activity; iv) because placenta contains a high amount of type III-MD, it is conceivable that placenta contributes to maintain low T3 and high rT3 serum concentrations during fetal life and that its removal at birth is responsible for most changes in iodothyronine metabolism occurring afterwards.

Final height in girls with slowly progressive untreated central precocious puberty.

A group of six girls with slowly progressive idiopathic precocious puberty (IPP) and a good initial height prognosis was followed without treatment. At first observation the girls had a bone age advance over chronological age of no more than 18 months, a delta height age (delta HA): delta bone age (delta BA) ratio higher than 0.9 and height prognosis was unimpaired after 6 months. During the first two years of follow-up the girls maintained an acceptable height potential. The delta HA:delta BA ratio remained constant at greater than 0.9. Predicted height showed a slight increase or decrease (+/- 4 cm). The girls were reevaluated after the age of 14 years and followed-up until they reached their final height (FH). The mean FH (155.4 +/- 2.8 cm) was below the mean target height (159.3 +/- 4.2 cm) by 3.9 cm (range -2.1 to -6.7 cm); this difference was not statistically significant. The FH was more than 5 cm below the target height in only one case; this girl had the most precocious onset of puberty, at 6 years of age. In three cases FH was between the 3rd and 10th centiles. These three girls had a target height below 158 cm (< 25th centile). Girls with slowly progressive IPP and a good initial height prognosis preserved height potential with an acceptable final height without therapy.