Introduction: Tumors of salivary glands constitute 3% of neoplasms of the body. Clinical signs and symptoms usually occur in tumors at advance stages. Dynamic-contrast-enhanced and diffusion-weighted MR sequences have been described as useful diagnostic tools in other locations. Our goal is to evaluate the utility of these techniques for parotid tumors.
Material and methods:We retrospectively reviewed the Parotid tumors operated by our department whit Dynamic-contrast-enhanced and diffusion-weighted MR sequences between 2012 and 2015. We correlate the results with the final histopathological diagnosis.Results: From 44 parotid tumors studied, Warthin tumors were the most common (43%). They showed high enhancement and high washout in perfusion series, so as low ADC values. Pleomorphic adenomas (41%) are hyperintense tumors in T2, with moderate constant enhancement in perfusion and high Apparent Diffusion Coefficient values. It is not possible to establish consistent results for malignant tumors given their underrepresentation in this sample.
Conclusion:Advanced MRI techniques contribute to the differential diagnosis of parotid tumors. Perfusion is useful in diagnosis of Warthin tumors and Pleomorphic adenomas. There is greater overlap in other tumors, for which diffusion-weighted MR sequences can help in discriminating malignancies. Both malignancies and Warthins show low Apparent Diffusion Coefficient values.
Ruxolitinib is the front-line non-palliative treatment for myelofibrosis (MF). However, a significant number of patients lose or present suboptimal response, are resistant or have unacceptable toxicity. In an attempt to improve response and avoid the adverse effects of this drug, we evaluated the combination of 17 drugs with ruxolitinib in
ex vivo
models of peripheral blood mononuclear cells from MF patients and cell lines. We found that the combination ruxolitinib and nilotinib had a synergistic effect against MF cells (ΔEC
50
nilotinib, −21.6%). Moreover, the addition of prednisone to combined ruxolitinib/nilotinib improved the synergistic effect in all MF samples studied. We evaluated the molecular mechanisms of combined ruxolitinib/nilotinib/prednisone and observed inhibition of JAK/STAT (STAT5, 69.2+11.8% inhibition) and MAPK (ERK, 29.4+4.5% inhibition) signaling pathways. Furthermore, we found that the triple therapy combination inhibited collagen protein and
COL1A1
gene expression in human bone marrow mesenchymal cells. Taken together, we provide evidence that combined ruxolitinib/nilotinib/prednisone is a potential therapy for MF, possibly through the anti-fibrotic effect of nilotinib, the immunomodulatory effect of ruxolitinib and prednisone, and the anti-proliferative effect of ruxolitinib. This combination will be further investigated in a phase Ib/II clinical trial in MF.
Eosinophilic fasciitis (EF) is a rare entity characterized by symmetrical and painful thickness and induration of the skin, especially localized on forearms and thorax and generally accompanied by eosinophilia. Although several reports indicate the relationship between EF and hematological disorders such as aplastic anemia, polycythemia vera, or myelomonocytic leukemia, the association with lymphomas is extremely rare. Only a few cases of EF have been previously described preceding or concomitant to the Hodgkin disease, peripheral T-cell lymphoma, B-cell lymphoma, and mycosis fungoides. We report for the first time a 76-year-old man with an EF associated with a peripheral T-cell lymphoma not otherwise specified. We review the relationship between both conditions. In conclusion, we present a unique case of EF as a manifestation of a T-cell lymphoma not otherwise specified. The present case demonstrates the importance of clinical and radiological studies in those cases of EF to rule out a visceral, lymph node, or cutaneous lymphoma.
Precision medicine can significantly improve outcomes for cancer patients, but implementation requires comprehensive characterization of tumor cells to identify therapeutically exploitable vulnerabilities. Here we describe somatic biallelic TET2 mutations in an elderly patient with acute myeloid leukemia (AML) that was chemoresistant to anthracycline and cytarabine (Ara-C), but acutely sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy resulting in longterm morphological remission. Given the role of TET2 as a regulator of genomic methylation, we hypothesized that mutant TET2 allele dosage affects response to 5'-Aza. Using an isogenic cell model system and an orthotopic mouse xenograft, we demonstrate that biallelic TET2 mutations confer sensitivity to 5'-Aza compared to cells with monoallelic mutation. Our data argue in favor of using hypomethylating agents for chemoresistant disease or as first line therapy in patients with biallelic TET2-mutated AML and demonstrate the importance of considering mutant allele dosage in the implementation of precision medicine for cancer patients.
Purpose:
In the present study, the performance of four VMAT beam arrangements used for hippocampal-sparing whole-brain radiation therapy is addressed.
Material and Methods:
Data corresponding to 20 patients were utilized so as to generate plans for every beam configuration. A preliminary study was conducted to assess the optimal distance between optimization structures (PTVx) and hippocampi. V
25
, V
30
, D
50%
, D
2%
, D
98%
, homogeneity index (HI) and Paddick conformity factor (CF) were evaluated for PTV. D
100%
and D
max
were considered for hippocampi. All plans were required to perform at least as recommended in RTOG 0933 trial regarding organs at risk (OAR) sparing and PTV objectives.
Results:
Considerable hippocampi sparing alongside with a reasonably low decrease in PTV coverage was achieved using a 7 mm distance between hippocampi and PTV optimization structure. Beam setup 3 (comprised of two full arcs with 0° couch angle and two half arcs with 90° couch angle) achieved the best PTV coverage, HI and CF, while it performed the second-best sparing in hippocampi and lenses. Moreover, beam setup 3 was the second-fastest treatment, although it resulted in the highest number of delivered MU among all beam setups. Beam setup 1 (comprised of two full arcs with no couch angles) was the fastest and it delivered a significantly less amount of monitor units compared with the other beam setups evaluated. Furthermore, a higher robustness was obtained by using no couch angles. Although beam setup 1 was the least optimal considering OAR sparing, it still performed better than required in the RTOG 0933 trial.
Conclusions:
Overall, beam setup 3 was considered to be the best. It is worth mentioning that, apart from our results, the election of one of these beam arrangements might be dependent on the amount of patient workload at a specific institution.
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