Time sequential chemotherapy for primary refractory or relapsed adult acute myeloid leukemia: results of the phase II Gemia protocol

BACKGROUND AND OBJECTIVE: High-dose cytarabine (HDAra-C), mitoxantrone and etoposide are the mainstay of several active regimens against relapsed or refractory acute myelogenous leukemia (AML). We designed a phase II study to assess the efficacy and side effects of a time sequential application of mitoxantrone plus intermediate-dose Ara-C followed by HDAra-C plus etoposide (GEMIA) in adult patients with refractory or relapsed AML. DESIGN AND METHODS: Patients with refractory or relapsed AML were eligible for GEMIA salvage therapy, which comprised mitoxantrone 12 mg/m2/day on days 1-3, Ara-C 500 mg/m2/day as a 24-hour continuous infusion on days 1-3, followed by HDAra-C 2 g/m2/12-hourly on days 6-8 and etoposide 100 mg/m2/12-hourly on days 6-8. Granulocyte colony-stimulating factor was started on day 14. In patients above the age of 55 the dose of Ara-C in the first sequence (days 1-3) was reduced to 250 mg/m2. RESULTS: Twenty patients were included, of whom 12 achieved complete remission after GEMIA (60%, 95% CI 40-80%), one was refractory and five died early from infection. Two additional patients achieved partial remission after GEMIA and complete remission after consolidation chemotherapy, for a final CR rate of 70% (95% CI 48-88%). Neutrophils recovered at a median of 27 days (range, 22-43) and platelets 46 days (range, 25-59) after the start of treatment. The median duration of remission was 133 days (range, 36-417+) whereas overall survival time lasted for a median of 153 days (range, 13-554+). Treatment-associated toxicity was comprised predominantly of infection, mucositis and diarrhea that reached World Health Organization grades III-V in 40%, 40% and 30% of patients, respectively. Despite the intention to rapidly proceed to a hematopoietic stem cell transplant in patients in remission, only five patients reached the transplant. INTERPRETATION AND CONCLUSIONS: The GEMIA time sequential chemotherapy regimen appears effective in obtaining remissions in refractory and relapsed adult AML. The high toxicity seen, however, suggests that its design is amenable to further improvements, especially in more elderly patients. Since remissions are short-lived, more innovative post-remission strategies are needed.     

A comparison of the use of cone-beam computed tomography and panoramic radiography in the assessment of pre-eruptive intracoronal resorption

Objective: This study aimed to investigate the prevalence of pre-eruptive intracoronal resorption (PIR) using cone beam computed tomography (CBCT) and panoramic radiography and to compare the findings of these imaging techniques.

Methods: This retrospective study consisted of 733 patients who had at least one unerupted tooth and had undergoneimaging with both three-dimensional (3D) CBCT and two-dimensional (2D) panoramic radiography. In all the images, the number of teeth with intracoronal resorption, affected tooth type and number, and size and location of the PIR defects were recorded. The McNemar test was used to compare the prevalence of PIR in the CBCT and panoramic images.

Results: Fewer PIR defects were detected in the panoramic images (3.1% of the patients) than in the CBCT images (9.5% of the patients) (pConclusions: CBCT detected more cases of PIR than panoramic radiography. The mandibular third permanent molar was the most commonly affected tooth.     

Bone and Skin-Supported Stereolithographic Surgical Guides for Cranio-Facial Implant Placement

Purpose

Osseointegrated skin-penetrating implants enhance the retention and stability of the craniofacial prostheses and provide the long-term comfort. However, to determine the implant locations is a great challenge facing the surgeon. Implants may either be located in conventional manner or by STL generated surgical guides.

Materials and Methods

Present study reports the CT based 3D virtual modeling, preoperative virtual planning and the implant placement by using a STL surgical guide, in an anotia case.

Results

Employed materials and the methods facilitated the implant surgery while improving the operational security.

Conclusions

CT based 3D virtual modeling of the surgical site, determining the implant locations virtually and the STL guided placement of the craniofacial implants, were found useful applications in order to facilitating the surgical intervention and providing prevention from complications.

     

A Giant Plunging Sublingual Dermoid Cyst Excised by Intraoral Approach

Objective

Dermoid and epidermoid cysts are rare cysts of the head and neck region, which should be considered in differential diagnosis of sublingual mass, constituting 0.01 % of all oral cavity cysts. There are suspected theories regarding the basis of the pathology.

Case Report

30-year-old male referred to our clinic with a chief complaint of sublingual mass which had been present for many years but the lesion enlarged over the past 3 years. MRI examination revealed a giant cystic mass which was 3.6 × 3.9 mm in diameter and medially located at sublingual region.

Treatment and Prognosis

Intraoral approach was preferred for surgery and no recurrence or complaints were detected during follow-up period.

Conclusion

When a cystic mass is detected on the floor of oral cavity, we must consider dermoid cysts for differential diagnosis. Surgery is the only treatment. If possible, intraoral approach should be preferred because of its perfect cosmetic results.

     

Coronary stent symmetry and vascular injury determine experimental restenosis

OBJECTIVE—To assess the impact of stent symmetry on restenosis using the coronary overstretch sheep model.
METHODS—Neointimal thickness, injury index, and percentage diameter and area stenosis were calculated by digital morphometry. The standard deviation of the angular burden was used to assess stent symmetry for each section.
MATERIALS—15 healthy Merino sheep (63-75 kg) underwent implantation of 30 slotted tube stents (7 mm). Restenosis was induced by calculated overstretch of the coronary artery. Twenty eight days after implantation, stents were excised and underwent histological examination using quantitative digital morphometry.
RESULTS—The severity of vessel injury was positively correlated with neointimal thickness and with percentage diameter and area stenosis (p < 0.001). Mean neointimal thickness and mean vascular injury per cross section were strongly related to the standard deviation of angular burden, with correlation coefficients of 0.6 and 0.8, respectively (p < 0.001).
CONCLUSIONS—The well known relation between vascular injury and restenosis was confirmed, and a new relation was discovered between stent asymmetry and restenosis. If these results apply to human coronary arteries, restenosis may also be dependent on the degree of asymmetric stent expansion. These results should influence the development of new stent designs to reduce asymmetric stent expansion, leading to a more homogeneous strain distribution in stented coronary segments.


Keywords: stent symmetry; vascular injury; restenosis; interventional cardiology     

Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice

The recombination-activating gene (RAG)1 and RAG2 proteins comprise the lymphocyte-specific components of the V(D)J recombinase and are required for the assembly of antigen-receptor variable-region genes. A mutant truncated RAG2 protein ("core" RAG2) lacking the C-terminal 144 amino acids, together with core RAG1, is able to mediate the basic biochemical steps required for V(D)J recombination in vitro and in transfected cell lines. Here we examine the effect of replacing the endogenous RAG2 locus in mice with core RAG2. These mice generate substantial numbers of B and T cells, demonstrating that the core RAG2 protein retains significant in vivo function. However, core RAG2 mice display a reduction in the total number of B and T cells, reflecting impaired lymphocyte development at the progenitor stage associated with reduced chromosomal V(D)J recombination. We discuss potential roles of the RAG2 C terminus in mediating rearrangement of endogenous antigen-receptor loci.