Childhood Malignant Thymoma: Clinical, Therapeutic, and Immunohistochemical Considerations

Malignant thymomas are among the least common mediastinal tumors in the pediatric age group. Thymomas are considered malignant on the basis of macroscopic and microscopic invasiveness. As only 20 well-documented cases involving children have been reported in the literature, the pattern of responsiveness to therapy and the value of prognostic signs is obscure. Two cases of malignant pediatric thymomas are reported with pathognomonic histoimmunological features of aggressive thymoma. One was cured, with a follow-up of 70 months, and one died while on therapy. Analysis of the histological features and the immunoperoxidase staining displays the complexity of pediatric thymomas and the inability to prognosticate the outcome, respectively.     

Ocular changes in mucopolysaccharidosis IV A (Morquio A syndrome) and long-term results of perforating keratoplasty

BACKGROUND: The mucopolysaccharidoses (MPS) are an inhomogeneous group of disorders of errors in the carbohydrate metabolism with severe ocular involvement (corneal opacification, retinal degeneration, optic atrophy). PATIENT PRESENTATION: We report on a boy aged 12 years, with Morquio A (MPS IV A) syndrome. Ocular findings: progressive pseudoexophthalmus due to shallow orbits, increasing corneal stromal clouding, intermittent dissociated manifest nystagmus of the left eye, nyctalopia. Visual acuity OD cc = 0.16, OS cc = 0.05. Electrophysiology: changes suggesting a symptomatic tapetoretinal degeneration and optic atrophy. TREATMENT AND COURSE OF DISEASE: OS: perforating keratoplasty. Postoperative improvement of visual acuity to 0.25 for nearly a year, followed by progressive reopacification of the corneal graft. Both eyes: progressive signs of tapetoretinal degeneration and optic atrophy. Visual acuity now reduced to OD 0.05, OS 0.1. CONCLUSIONS: Success of a keratoplasty is limited by (1) reopacification of the cornea, (2) visual impairment due to (a) retinal degeneration and (b) optic atrophy. The indication for perforating keratoplasty has to be thought about very carefully in these multimorbid patients. In our patient, beside progressive visual impairment there is a progressive deafness which dominates his social and school life. Attending school is severely complicated by the double handicap. Perforating keratoplasty enabled the boy to attend a school for physically handicapped without a special low-vision care for another year. Progressive visual loss without further treatment options now renders optical and electronic low-vision aids necessary. Although the time of improved visual acuity lasted less than a year, we think patients with a life expectancy of less than 20 years should have every possible improvement of their situation - even if it does not last permanently. We therefore propose perforating keratoplasty in spite of insufficient long-term results.     

Iatrogenic hyperthyroidism does not promote weight loss or prevent ageing-related increases in body mass in thyroid cancer survivors

Context Thyroid cancer survivors represent a unique population in which the potential long‐term effects of brief periods of intentional thyroid hormone withdrawal and/or prolonged periods of iatrogenic hyperthyroidism on body weight and body mass were evaluated. Objectives The objectives of this study were to characterize body mass changes over several years in a cohort of thyroid cancer patients with iatrogenic hyperthyroidism and to compare these changes with the expected weight gain in age‐matched healthy control populations. We also evaluated the possibility that the method of preparation [thyroid hormone withdrawal (THW) vs recombinant human TSH (rhTSH)] for radioactive iodine remnant ablation may be associated with differences in body mass at the time of the final follow‐up. Design/Setting/Patients/Interventions A retrospective review identified 153 patients with thyroid cancer who underwent total thyroidectomy at one major medical centre. Of the 153 patients, 143 also had radioactive iodine remnant ablation: 70 after THW and 73 after rhTSH. Main Outcome Measures Change in weight and BMI at 1–2 and 3–5 years of follow‐up points were examined. Annualized weight variation within the cohort was compared with age‐matched population controls expressed in kilogram/year. Results Significant weight gain was noted for the full cohort after 3–5 years of follow‐up as compared to baseline (76 ± 21 kg at baseline vs 79 ± 23 kg at 3–5 years of follow‐up, P < 0·01), which represented a 3·2% increase. Female and male patients with thyroid cancer experienced 0·46 and 0·94 kg/year gain in weight, respectively, which is similar or somewhat higher than previously published age‐matched population controls (ranging from 0·23 to 0·34 kg/year). When expressed as per cent change and comparing the final weight to the pre‐operative baseline, the rhTSH group experienced approximately a 1·7% increase in weight compared with the 3·9% increase seen with THW patients (P = 0·02). When expressed as kg/year change, the rhTSH cohort had 0·34 kg/year change compared with the 0·64 kg/year change seen in the thyroid hormone withdrawal patients (P = 0·02). Conclusion In otherwise, healthy patients with differentiated thyroid cancer, significant weight gain occurred during the 3–5 years of follow‐up despite ongoing thyrotropin suppression. The data suggest that mild iatrogenic hyperthyroidism does not promote weight loss or prevent ageing‐related weight gain. Greater weight gain was seen in patients prepared for radioactive remnant ablation with THW than with rhTSH.     

Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients

Metformin may affect the risk of atherothrombotic disease. However, metformin increases levels of homocysteine (Hcy), considered an independent risk factor for atherosclerosis. We evaluate whether homocysteine-lowering has a beneficial effect on arterial elasticity and metabolic parameters in metformin-treated diabetic patients. In double-blind, placebo-controlled study, 60 diabetic patients treated with high dose of metformin were randomly assigned to receive daily oral supplementation with folate (1000 mcg), vitamins B12 (400 mcg) and B6 (10 mg) (group 1) or placebo (group 2). Lipid profile, HbA1C, insulin, C-peptide, hs-CRP, vitamin B12, folic acid, homocysteine, endothelin, homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, MN). The two groups were similar at baseline in terms of hemodynamic and arterial elasticity parameters. After a 4-month small artery elasticity index (SAEI) was significantly greater in patients who received Hcy-lowering agents than in the placebo group: 4.3 ± 2.04 ml/mm Hg × 100 versus 3.2 ± 1.1 ml/mm Hg × 100, p = 0.01. Post-treatment vitamin B12 and folic acid levels were greater in group 1 versus group 2: 738.1 ± 279.9 pg/ml versus 566.1 ± 167.4 pg/ml, p = 0.007 and 14.9 ± 4.8 ng/ml versus 8.3 ± 2.9 ng/ml, p < 0.0001, respectively. Hcy level decreased significantly in the treatment group from 10.0 ± 4.4 to 7.6 ± 2.5 μmol/l, p = 0.002 and did not change in placebo group (p = 0.9). Hcy-lowering therapy improved small arterial elasticity in diabetic patients treated with high dose of metformin. The improvement was associated with a decrease in Hcy as well as an increase in folic acid and vitamin B12. These findings suggest that Hcy-lowering may have beneficial vascular effect in metformin-treated diabetic patients.     

Toxin positivity and <Emphasis Type="Italic">tcdB</Emphasis> gene load in broad-spectrum <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection

Purpose

This study aimed to evaluate the clinical significance of toxin positivity and toxin gene load, and the relation between them in the broad spectrum of Clostridium difficile infection (CDI) including colonization, significant diarrhea, and severe disease.

Methods

We included 2671 fecal samples submitted for CDI diagnosis and 180 samples from healthy individuals. The clinical spectrum was categorized as category I (toxigenic C. difficile positive without clinical CDI criteria), category II (mild CDI), and category III (severe CDI). Clinical parameters were compared based on toxin EIA and tcdB C _t values. C _t values of tcdB PCR for predicting toxin EIA positivity were assessed using receiver-operating characteristic (ROC) curves.

Results

The median C _t values of tcdB PCR and toxin positivity were not significantly correlated with clinical spectrum of CDI (27.5, 28.2, and 26.1 for tcdB C _t and 55.0, 56.6, and 60.9% for toxin EIA positivity in category I, II, and III, respectively, P > 0.05). There were significant differences in the tcdB C _t values between toxin EIA-positive and -negative groups (P < 0.001). Optimal cutoff for the tcdB C _t value for estimating toxin EIA positivity was 26.3 with 79.3% sensitivity and 83.6% specificity with good area under the curves (AUC, 0.848).

Conclusions

The C _t values successfully predicted toxin EIA positivity and could be used as a surrogate for toxin EIA positivity in the diagnostic algorithm and routine analysis. Further studies are needed to validate the clinical significance of tcdB PCR C _t value in toxigenic C. difficile colonization and infection.

     

Acute myeloid leukemia with a RUNX1-RUNX1T1 t(1;21;8)(q21;q22;q22) novel variant: a case report and review of the literature

Variants of t(8;21)(q22;q22) account for approximately 3% of all t(8;21) in acute myeloid leukemia (AML). We report a 63-year-old female patient with AML, who showed a 3-way novel variant of t(8;21), t(1;21;8)(q21;q22;q22). She presented with gastric discomfort and splenomegaly, and her complete blood count was: white blood cell count 7.96 × 10(9)/l, with 7% blasts; hemoglobin 8.3 g/dl, and platelets 66 × 10(9)/l. Her bone marrow showed increased blasts (32.5%) with a basophilic cytoplasm, salmon-pink granules and Auer rods. Cytogenetic analysis revealed a karyotype of 46,XX,t(1;21;8)(q21;q22;q22), and fluorescence in situ hybridization confirmed a RUNX1-RUNX1T1 fusion signal on the derivative chromosome 8. After induction chemotherapy, the patient achieved complete remission and has been stable for 6 months. To the best of our knowledge, this is the first report on the novel variant of t(8;21) involving the breakpoint 1q21 and the third case with a translocation among chromosomes 1, 21 and 8. Although the clinical relevance of variant t(8;21) is still unclear, a review of 24 such cases in the literature does not imply a poorer prognosis of variant t(8;21) than of the classic t(8;21).