Impact of an ultrasound-guided radiofrequency ablation training program on the outcomes in patients with hepatocellular carcinoma.

PURPOSE: The aim of this study was to retrospectively evaluate the impact of a training program on the safety and efficacy of percutaneous ultrasound-guided radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 227 patients with 296 HCC nodules who underwent percutaneous RFA with or without transcatheter arterial chemoembolization at our institution were included. There were 163 men and 64 women with a mean age of 74.2±8.3 (SD) years (range: 41-89 years). Percutaneous ultrasound-guided RFA was performed by three trainees (205 HCC nodules in 157 patients) or a mentor (91 HCC nodules in 70 patients) after preprocedural preparation including planning ultrasonography. We compared background-related, tumor-related, and treatment-related factors, and local recurrence and complication rates between the trainee group and the mentor group. Similarly, we compared these variables among the years 2015, 2016, and 2017 for trainee group. RESULTS: The proportion of easy-to-treat tumors in the trainee group (109/205; 53.2%) was greater than that in the mentor group (33/91; 36.3%) (P=0.020). No significant differences were observed in procedure difficulty among the years 2015, 2016, and 2017 for trainee group (easy-to-treat HCC nodules: 25/47; 53.2% vs. 39/79; 49.4% vs. 45/79; 57.0%. P=0.775). The local recurrence rate in the trainee group was 8.8% (18/205 HCC nodules) which was equivalent to 7.7% in the mentor group (7/91 HCC nodules). No significant differences were observed in local recurrence rate (8.8% vs. 7.7%, respectively; P=0.621) and major complication rate (1.3% vs. 1.4%, respectively; P=0.999) between the trainee group and the mentor group. No significant differences were observed in local recurrence rates ([5/47; 10.6%] vs. [11/79; 13.9%] vs. [2/79; 2.5%]) (P=0.109) and major complication rates ([1/36; 2.8%] vs. [1/62; 1.6%] vs. [0/59; 0%]) (P=0.701) between the years 2015, 2016, and 2017 for trainee group. CONCLUSION: A well supervised training program that includes planning ultrasonography fosters the efficacy and treatment quality of RFA for HCC.

The effects of thalidomide on chemotactic migration of multiple myeloma cell lines.

We examined the effect of thalidomide and dexamethasone on the migration of multiple myeloma (MM) cell lines, U266, RPMI8226, and NCI-H929, using chemotaxis chamber plates. U266 underwent chemotactic migration in response to stromal-cell derived factor-1 alpha (SDF-1alpha), and other cell lines underwent random migration in response to SDF-1alpha or monocyte chemotactic protein-1 alpha. Following preincubation with 1 mug/ml thalidomide, the cell lines showed reduced migratory capacity in response to SDF-1alpha. Concerning the corresponding receptors, CXC chemokine receptor 4 was detected only on the surface of U266, by flow cytometry, whereas chemokine (C-C motif) receptor 2 was not detected on all three cell lines. Moreover, decreased migration by thalidomide was not accompanied by altered expression of the corresponding receptors of each cell line. This is the first report to show the effects of thalidomide on the migration of MM cell lines. The results suggest that the inhibition of chemotactic migration might be one of the mechanisms of the success of thalidomide in controlling MM.

Expression and role of MHC class I-related chain in myeloma cells.

BACKGROUND: The molecular mechanism of natural killer (NK) cell cytotoxicity to myeloma cells remains unclear. We investigated whether MHC class I-related chain (MIC), a ligand of NKG2D that is an activating NK cell receptor, is involved in the cytotoxicity of NK cells toward myeloma cells, and examined the effects of various drugs on the cytotoxicity. METHODS: Two human myeloma cell lines and fresh myeloma cells from 10 patients were used. MIC expression was examined by flow cytometry and reverse transcription (RT)-PCR. NK cell cytotoxicity was examined using a 51Cr-release assay. The effects of various drugs, including thalidomide, all-trans retinoic acid, dexamethasone, IFN-alpha and incadronate, on the MIC expression and NK cell cytotoxicity were examined. RESULTS: MIC was highly expressed on the human myeloma cell lines U266 and RPMI-8226 and in myeloma cells of one of 10 patients examined. MIC expression on these cells was not changed by various drugs except IFN-alpha, by which MIC expression was down-regulated. Although MIC and HLA class I molecules were similarly expressed at high levels on both cell lines, U266 was sensitive to NK cells whereas RPMI-8226 was not. Furthermore, cytolysis by NK cells was not inhibited by the addition of anti-MIC Ab or decreased expression of MIC caused by IFN-alpha. DISCUSSION: MIC plays a role in the cytolysis by NK cells in multiple myeloma.

Análise eletromiográfica do músculo reto femoral durante a execução de movimentos do joelho na mesa extensora / Electromyographic analysis of the rectus femoris muscle during the execution of movements of the knee in leg extension machine

O músculo reto femoral foi analisado por meio da eletromiografia, utilizando eletrodos de superfície, durante os movimentos de flexão e extensão do joelho. Participaram do estudo dez sujeitos do sexo feminino, na faixa etária entre 19 e 22 anos. Inicialmente, foi realizada uma máxima contração isométrica (MCI). Posteriormente, realizou-se uma série de 12 repetições sem carga (SC); 12 séries de 12 repetições com diferentes cargas (15, 17, 19 e 21 kg). Para este trabalho selecionamos os dados referentes à MCI, movimentos sem cargas, movimento com 15 Kg, com 19 Kg e 21Kg. Os valores médios, expressos em RMS, demonstraram que na MCI o RMS foi de 139,55; no movimento realizado sem carga foi de 51,54; na carga de 15 kg foi de 134,65; na carga de 19 Kg foi de 136,54 e com 21Kg o RMS foi de 10,09. Os valores de RMS obtidos no movimento SC e com 21 kg foram inferiores aos encontrados nas condições MCI, 15 kg e 19 kg. O valor de 10,09 referente à carga de 21 Kg reflete a dificuldade em prosseguir a execução dos movimentos, podendo ser considerado o início do processo de fadiga muscular do músculo reto femoral.

The rectus femoral muscle was analyzed by electromyography, in 10 female subjects between 19 and 22 years old, during the flexing/extending movements of the knee. Surface electrodes were utilized. Initially a maximum isometric contraction (MIC) was performed. Afterwards, a series of 12 repetitions without load, and then 12 series of 12 repetitions with different loads (15, 17, 19, and 21kg) were performed. For this study, we chose data referring to the MCI, the movements without load, and those with 15kg, 19kg, and 21kg loads. The average values, expressed in RMS, were: for the Maximum Isometric Contraction (MIC), 136.55; for the movements executed without load, 51. 54; for the first series with the initial 15kg load, 134.65; for that with the 19kg load, 136.54; and for the last series with the 21kg load, 10.09. RMS values obtained from the movements without load and those with the 21kg load, reflects the difficulty in proceeding with the execution of movements and can be considered the beginning of the muscular fatigue process of the rectus femoral muscle.

Successful non-T cell-depleted HLA haplo-identical three-loci mismatched hematopoietic stem cell transplantation from mother to son based on the feto-maternal microchimerism in chronic myelogenous leukemia.

A 17-year-old male with chronic myelogenous leukemia in blast crisis received a non-T cell-depleted (TCD) HLA haplo-identical three-loci mismatched hematopoietic stem cell transplant (HSCT) from his mother. Long-term feto-maternal microchimerism was detected by nested polymerase chain reaction with sequence-specific primer typing. The post-transplantation prophylaxis against graft-versus-host disease (GVHD) was tacrolimus with minidose methotrexate. Sustained engraftment was obtained. Acute GVHD (grade 2) developed, but improved rapidly. Bone marrow aspiration on day 120 showed complete remission. Non-TCD HLA haplo-identical HSCT based on feto-maternal microchimerism might be feasible and has important implications in the selection of alternative family donors in HSCT.

Tumour necrosis factor-alpha receptors are present in the corpus luteum throughout the oestrous cycle and during the early gestation period in pigs.

To determine the physiological significance of tumour necrosis factor-alpha (TNFalpha) in the regulation of luteal functions in pig, this study was conducted to identify the presence of functional TNFalpha receptors in porcine corpora lutea (CL) throughout the oestrous cycle and the early gestation. The CL were isolated from pigs on days 4, 6, 8, 12 or 15 of the oestrous cycle (n=3; day 0 = oestrus) and days 15, 20 or 25 of gestation (n=3; day 0 = mating). A Scatchard analysis revealed the presence of a high-affinity binding site for TNFalpha in all samples (dissociation constant; 2.7 +/- 0.51 to 5.8 +/- 0.50 nM). The concentration of TNFalpha receptors was higher on day 15 of the oestrous cycle than on days 4 and 8 of the oestrous cycle (p < 0.05). Furthermore, TNFalpha receptor concentrations in the CL on days 15, 20 and 25 of gestation were significantly lower than on day 15 of the oestrous cycle (p < 0.05). On day 9 of the oestrous cycle, exposure of cultured luteal cells to 0.06-60 nM TNFalpha stimulated prostaglandin (PG) F2alpha and PGE2 secretion in a dose-dependent manner (p < 0.05). These results indicate that functional TNFalpha receptors are present in the porcine CL throughout the oestrous cycle and early gestation, and suggest that TNFalpha plays one or more physiological roles in regulating CL function throughout the oestrous cycle and the early gestation period. In addition, TNFalpha receptor concentration in the CL of the late luteal stage (day 15) of the oestrous cycle was higher than on the respective day in the early pregnant pig, suggesting that TNFalpha plays a role in accomplishing luteolysis in the porcine CL.

Promoting effect of beta-mercaptoethanol on in vitro development under oxidative stress and cystine uptake of bovine embryos.

The effects of beta-mercaptoethanol (beta-ME) on in vitro development under oxidative stress and cystine uptake of bovine embryos were investigated. Bovine 1-cell embryos obtained by in vitro fertilization were cultured in TCM-199 or synthetic oviductal fluid (SOF) in 20% O(2) supplemented with beta-ME. Addition of beta-ME significantly (P < 0.01) promoted embryo development when cultured in both TCM-199 and SOF under high levels of O(2), to almost the same rates when they were cultured in 5% O(2). To investigate whether the growth-promoting effect of beta-ME was related to cystine uptake, which is an important amino acid for intracellular glutathione (GSH) synthesis, 1-cell, 8-cell, morula, and blastocyst stage embryos were incubated in cystine, cysteine-free TCM-199 containing radioisotope-labeled cystine supplemented with or without beta-ME. It was found that cystine uptake was consistently low in each embryo stage incubated without beta-ME. In contrast, addition of beta-ME significantly (P < 0.05 to 0.0001) promoted cystine uptake in each stage of embryo development. This increase of cystine uptake by beta-ME was significantly inhibited by supplementation of buthionine sulfoximine, a specific inhibitor of GSH biosynthesis (P < 0.0001). High-performance liquid chromatography (HPLC) analysis clearly revealed a decrease of cystine in culture medium after supplementation by beta-ME, thereby forming another peak. HPLC analysis also showed the incorporated cystine by supplementation of beta-ME was possibly metabolized for GSH synthesis in the embryos. These results indicate that beta-ME has a protective effect in embryo development against oxidative stress and that the effect of beta-ME is associated with the promotion of cystine uptake of low availability in embryos.

Subcutaneous infection with Mycobacterium fortuitum after allogeneic bone marrow transplantation.

Reports of cases of mycobacterial infections after SCT are rare. We report a 30-year-old female with a cutaneous infection of Mycobacterium fortuitum 30 months after allogeneic bone marrow transplantation for acute lymphoblastic leukemia. The patient was successfully treated with surgical debridement followed by oral minocycline and clarithromycin. Mycobacterial infections should be considered in SCT patients with undiagnosed refractory chronic cutaneous infection, and surgical debridement is useful for the diagnosis and treatment of such infections.

Early relapse after high-dose chemotherapy rescued by tumor-free autologous peripheral blood stem cells in acute lymphoblastic leukemia: importance of monitoring for WT1-mRNA quantitatively.

A 24-year-old woman who suffered from ALL with MLL gene rearrangement received high-dose chemotherapy followed by autologous PBSC transplantation during complete remission (CR). Reverse transcriptase-polymerase chain reaction (RT-PCR) used to detect MLL/LTG4 chimeric mRNA showed no minimal residual disease (MRD) in the graft or bone marrow at the transplantation. However, the leukemia relapsed four months after transplantation. Retrospective analysis of quantitative measurement of Wilms tumor gene (WT-1) mRNA showed an increased level in the bone marrow although it was within the normal range. These observations suggest that careful monitoring of MRD by quantitative measurement of WT-1 mRNA in addition to disease-specific chimeric mRNA is required to predict relapse.

Clinical characteristics of B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS): comparison of CD5+ with CD5- B-LAHS.

OBJECTIVE: B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) has been increasingly reported in Asia and is regarded as a variant of intravascular lymphomatosis (IVL). Recently CD5 was reported to be expressed in some cases of diffuse large cell lymphoma and IVL. We therefore examined the expression of CD5 on lymphoma cells in B-LAHS and compared the clinical and laboratory data between CD5+ and CD5- B-LAHS. METHODS: The expression of CD5 on lymphoma cells was examined using flow cytometry and immunohistochemical analysis of paraffin sections. The clinical records were reviewed to characterize clinical features. PATIENTS: Twelve patients with B-LAHS; ten men and two women, age ranging from 41 to 82 years (median, 63.5 years) were included in this study. RESULTS: B-LAHS is characterized by fever and hepatosplenomegaly without lymphadenopathy at the initial presentation. Histological examination showed hemophagocytosis and infiltration of lymphoma cells in the bone marrow, and in some cases intravascular proliferation of lymphoid cells characteristic of IVL. All patients showed increased levels of lactate dehydrogenase, C-reactive protein, ferritin and soluble interleukin-2 receptor. In eight of the twelve patients, lymphoma cells were positive for CD5. But no differences were observed in the clinical or laboratory findings between CD5+ B-LAHS and CD5- B-LAHS. CONCLUSION: No clinical differences were observed between CD5+ B-LAHS and CD5- B-LAHS. Further studies are required to elucidate the differences in pathogenesis between these two subgroups of B-LAHS.

[Philadelphia chromosome-positive acute lymphoblastic leukemia with monosomy 7 successfully treated with intermediate- and high-dose ara-C].

A 52-year-old man was admitted for treatment of acute lymphoblastic leukemia (ALL). The bone marrow was hypercellular with 67.2% blasts, which were negative for peroxidase, and expressed CD13, CD33, CD34, CD10 and CD7. Cytogenetic and molecular studies revealed t(9;22) and -7(Ph/-7) with major BCR/ABL rearrangement. The patient was treated with the L-AdVP regimen, but failed to achieve complete remission (CR). He then received two courses of chemotherapy consisting of intermediate- and high-dose cytarabine (ara-C), resulting in CR. This case suggests that Ph/-7 ALL with major BCR/ABL gene rearrangement showing coexpression of myeloid antigens may be sensitive to intermediate- and high-dose ara-C.

[Therapy-related myeloid leukemia following platinum-based chemotherapy for ovarian cancer].

A 40-year-old woman, who had suffered from AML (M1) in 1983, developed ovarian cancer (stage IIIc) in December 1996 after long-term remission. She underwent surgical resection of the cancer, 10 courses of standard chemotherapy and tandem PBSCT (total dose: CBDCA 6,750 mg, CDDP 200 mg, CPA 16,000 mg, THP-ADR 450 mg). After receiving the last course of chemotherapy in June 1998, she was referred to our hospital in September 1998 because of pancytopenia. Laboratory findings showed pancytopenia with 34% leukemic cells, which were positive for alpha NBE and negative for POX and CAE. Surface-marker analysis of the leukemic cells showed positivity for CD11c, CD33, CD56, and DR, and chromosome analysis revealed 47, XX, +8. The patient was diagnosed as having AML (M5a), and received induction therapy consisting of IDR and Ara-C, which led to complete remission. As she had not received etoposide, this case was thought to have been therapy-related leukemia due to the platinum agents used for treating the ovarian cancer.