Tibial pseudotumor in a child with hemophilia

Hemophilic pseudotumor is an uncommon complication seen in approximately 1-2% of patients with severe hemophilia. Hemophilic pseudotumors are distinguished into two subdivisions based on location, proximal or distal. Plain x-rays and CT are useful in diagnosis, but MR imaging is the diagnostic test of choice because of its sensitivity to the various blood products. The choice of therapy depends on many parameters, such as the size of the tumor, the age of the patient, and the relation with underlying organs. In most cases of asymptomatic hemophilic pseudotumor, conservative treatment with administration of missing factor as well as immobilization is recommended. The authors describe a 13-year-old boy with severe hemophilia A, who presented with a tibial pseudotumor a few months after an injury. He was conservatively treated for a long period, with daily administration of recombinant factor VIII. His clinical condition improved shortly after therapy induction, but radiological improvement has been moderate. Case history, imaging findings, and therapeutic options are discussed.     

Minimizing underestimation rate of microcalcifications excised via vacuum-assisted breast biopsy: a blind study

PURPOSE: The main disadvantage of Vacuum Assisted Breast Biopsy (VABB) is the probability of underestimating atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). This study evaluates a modified way of performing VABB. METHODS: 266 women with microcalcifications graded BI-RADS 3&4 underwent VABB (11G) on the Fischer's table. 133 women were allocated to the "standard" protocol and 24 cores were obtained (1 offset-main target and one additional offset). 133 women were randomly allocated to the "extended" protocol and 96 cores were excised (one offset- main target and 7 peripheral offsets). A preoperative diagnosis was established, and the removed volume was calculated. When precursor or malignant lesions were diagnosed, open surgery was performed. A second pathologist, blind to the preoperative results and to the protocol made the postoperative diagnosis. The discrepancy between preoperative and postoperative diagnoses was evaluated. RESULTS: When the standard protocol was applied, the underestimation rate for preoperative ADH, lobular neoplasia (LN), DCIS was 16.7%, 50% and 14.3% correspondingly. In the extended protocol, no underestimation was present in LN, ADH, but the underestimation rate for DCIS was 6.3%. In the extended protocol, no precursor/malignant tissue was left after VABB in all ADH cases, in 87.5% of LN cases, in 73.3% of DCIS, and in 50% of invasive carcinomas. The volume excised was 2.33 +/- 0.60 cc and 6.14 +/- 1.30 cc for the standard and the extended protocol, respectively. The rate of hematoma formation did not differ between the two protocols. CONCLUSIONS: This recently introduced, "extended" way of performing VABB in microcalcifications safely minimizes the underestimation rate, which may lead to a modified management of ADH lesions.     

Successful treatment of patch type mycosis fungoides with tacrolimus ointment 0.1%

Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of lymphoproliferative disorders caused by clonally-derived, skin-invasive T cells. A variety of skin-directed and systemic therapies are available to treat mycosis fungoides/Sézary syndrome (MF/SS), the therapeutic choices of which are guided by the stage of disease. A 29-year-old man presented at our clinic with pruritic, erythematous macules located on the sternum and the lower back. Histological findings and immunohistochemistry studies showed patch stage MF. The patient was treated with tacrolimus ointment 0.1% twice daily for one month, achieving complete remission. Three months after the first episode a relapse was successfully treated with the same therapeutic regimen. Tacrolimus is an immunomodulatory macrolide that reduces the stimulatory capacity toward T cells and is therefore worth investigating as a treatment of CTCL. Topical tacrolimus has been related to an unknown effect with the risk for secondary malignancies including CTCL. Also, black box warnings have been proposed by the FDA for the topical calcineurin inhibitors. Nevertheless, our results in the treatment of early stage MF are in agreement with other unpublished data that have observed its efficacy. To our knowledge, there is no other case of patch type mycosis fungoides treated with tacrolimus ointment 0.1% in the medical literature.     

Effect of atorvastatin on the concentration,relative distribution,and chemical composition of lipoprotein subfractions in patients with dyslipidemias of type IIA and IIB

The authors investigated the effect of atorvastatin (40 mg qd) on low-density lipoprotein (LDL) particle distribution in patients with dyslipidemias of type IIA (n = 55) and IIB (n = 21). Atorvastatin therapy induced a significant decrease in total and LDL cholesterol in both patient groups. A significant reduction in triglyceride values, which was more profound in type IIB patients, was also observed. In type IIA patients, LDL-3 was the predominant subfraction. Atorvastatin therapy induced a significant reduction in total LDL mass in this group of patients that was mainly due to the reduction in large and intermediate subspecies (LDL-1 to LDL-3), whereas the mass of dense LDL particles (LDL-4 and LDL-5) remained unchanged. As a consequence, the percentage contribution of dense subfractions to the total LDL mass increased significantly after atorvastatin therapy. The dense LDL-4 subfraction was the predominant one in type IIB patients. In this group, atorvastatin therapy resulted in a significant reduction in the total LDL mass, which was due to the reduction in all LDL subfractions. Thus, the percentage mass distribution of LDL particles remained unaffected. These results suggest that the effect of atorvastatin on LDL subfractions is affected by the underlying genetic defect.     

Non-CpG cytosine methylation of p53 exon 5 in non-small cell lung carcinoma

Non-CpG methylation of cytosine residues, a mechanism associated with regulation of gene expression, has not been investigated in human cancer until now. Analysis of the p53 exon 5 mutation spectrum in mutation databases for lung cancer reveals frequent GC > AT transitions, several of which occur at non-CpG sequences. To investigate the involvement of cytosine methylation in this mutagenesis process, we analyzed the methylation profile of p53 exon 5, in lung carcinoma. In this report, we present evidence that extensive clustered non-CpG methylation is observed in three regions of this exon, namely the sequences spanning codons 156–159, 175–179 and the 3′ splice site, as well as in scattered CpA sequences. This methylation pattern was verified using direct methylation sequencing, and a two-stage methylation-specific PCR assay (MSP), designed for the detection of methylation in a GC rich region (oligo C sequence, of codons 175–179) of exon 5. The results from this MSP assay reveal that DNA from cancerous specimens was more heavily methylated in non-CpG cytosines, compared to that from non-cancerous lung tissue of cancer patients (14/19 cancerous and 6/19 non-cancerous, respectively). DNA isolated from human leucocytes and some non-cancerous specimens (2/19) was free of non-CpG methylation. Careful analysis of the mutations reported in p53 mutation databases also provides corroborating evidence that the high incidence of GC > AT mutations in the p53 gene, observed in lung cancer, might also be related to non-CpG methylation, as well as to the overall increase of methylation sites in this locus.     

A phase II study of non-platinum based chemotherapy with paclitaxel and vinorelbine in non-small cell lung cancer

INTRODUCTION: Paclitaxel and vinorelbine combination in previous untreated patients with stage IIIb-IV non-small cell lung cancer (NSCLC) as a phase II study. PATIENTS AND METHODS: Thirty-four patients (4 patients with stage IIIb, 30 patients in stage IV), with median age 66 and performance status 0-1, were administered paclitaxel, 175 mg/m(2) in a 3-h infusion rate on day 1 and vinorelbine, 25 mg/m(2) in a 10-min infusion rate on days 1, and 8 with G-CSF and EPO support. RESULTS: Among our 33 evaluable patients for toxicity 16 patients (48.4%) presented leukopenia and 15 patients (45.4%) presented anemia despite G-CSF and EPO administration. Two patients (6%) presented Grade III-IV peripheral neuropathy. The overall response rate was 67.7%; 5 patients (16.1%) showed complete response (2 patients stage IIIb) and 16 patients (51.6%) showed partial response (1 patient stage IIIb). The overall median survival time was 10 months (range 3-18 months) and the median disease-free survival was 9 months (range 3-15 months) with an 1-year survival time of 45.1% (14 patients). CONCLUSION: The results of the combination as 1st line treatment for patients with non-operable NSCLC are promising and should be further investigated.