A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma

BACKGROUND: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown. METHODS: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level. RESULTS: The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients. CONCLUSIONS: The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.     

Hypoxic status in ovarian serous and mucinous tumors: relationship between histological characteristics and HIF-1α/GLUT-1 expression

Material and methods We analyzed the expression of hypoxia inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) by immunohistochemistry in ovarian serous and mucinous tumors from the point view of the histological characteristics and acquisition of malignancy. A total of 102 ovarian tumors were examined, composed of 31 adenomas (serous 17 and mucinous 14), 32 borderline tumors (serous 13 and mucinous 19), and 39 adenocarcinomas (serous 21 and mucinous 18). Results The overall positive ratios were as follows: HIF-1α, 74% of adenomas, 91% of borderline tumors, and 100% of adenocarcinomas; and GLUT-1, 68% of adenomas, 95% of borderline tumors, and 100% of adenocarcinomas. Comparing serous tumors and mucinous tumors, there was no significant difference in the positive ratios of HIF-1α and GLUT-1 of adenomas, borderline tumors, and adenocarcinomas. However, both markers were more strongly expressed in serous adenocarcinomas (HIF-1α, 3 + 100%; GLUT-1, 3 + 76%) than in mucinous adenocarcinomas (HIF-1α, 3 + 61%; GLUT-1, 3 + 28%). The results of immunoblotting and mRNA expression level analyses corresponded with those of immunohistochemical expression profiles. DNA binding assay also demonstrated that HIF-1 is more commonly activated in serous adenocarcinomas than in mucinous adenocarcinomas. Conclusion HIF-1α and GLUT-1 expressions seemed to be coordinated to adapt ovarian tumor cells into hypoxic conditions in close association with the acquisition of malignancy. We consider that the relatively strong expression of both markers in serous tumors compared with mucinous tumors is related to the difference in their histological characteristics.     

Precise anatomy of the vesico-uterine ligament for radical hysterectomy

OBJECTIVES: To clarify the anatomy of the vesico-uterine ligament (VUL), we meticulously separated the VUL under magnification (x2.5) during Okabayashi's radical hysterectomy. METHODS: Fifty-nine patients (TNM nomenclature: pTIb: 39, pT2a: 5, pT2b: 7, after trans-arterial anticancer-drug infusion treatment for the cervical cancer: 8) underwent this meticulous operation. Blood loss was recorded at two separate time points: during the separation of the VUL and after removal of the uterus. RESULTS: After complete separation of the uterine artery and superficial uterine vein from the ureter, we could identify the genuine connective tissue of the anterior leaf of the VUL in which we isolate and divide a distinct bundle of blood vessels: the cervicovesical vessels that cross over the ureter from the bladder to the cervix. The remaining tissues in the anterior leaf is only avascular connective tissue. The posterior leaf of the VUL is the tissue residing under the ureter connecting the posterior wall of the bladder and the lateral cervix/upper lateral vagina. In the connective tissues, we identified the middle and inferior vesical veins connecting with the deep uterine vein. The division of these veins could separate the urinary bladder with ureters completely from the lateral cervix and upper vagina. The mean blood loss during the separation of the VUL was 20+/-10 g (N=59) and after radical hysterectomy was 189+/-91.6 g (N=59). CONCLUSION: A precise network of blood vessels in the VUL is identified. The knowledge of this anatomy is important to perform radical hysterectomy.     

Torsion of the normal ovary and oviduct in a pre-pubertal girl

We encountered a 10-year-old prepubertal girl with a normal ovary and oviduct torsion. Hemorrhagic infarction of the ovary and oviduct occurred, and these structures were laparoscopically removed. Torsion of the normal ovary and oviduct in a prepubertal girl is discussed.     

Advances in Myocardial Perfusion MR Imaging: Physiological Implications,the Importance of Quantitative Analysis,and Impact on Patient Care in Coronary Artery Disease

Stress myocardial perfusion imaging (MPI) is the preferred test in patients with intermediate-to-high clinical likelihood of coronary artery disease (CAD) and can be used as a gatekeeper to avoid unnecessary revascularization. Cardiac magnetic resonance (CMR) has a number of favorable characteristics, including: (1) high spatial resolution that can delineate subendocardial ischemia; (2) comprehensive assessment of morphology, global and regional cardiac functions, tissue characterization, and coronary artery stenosis; and (3) no radiation exposure to patients. According to meta-analysis studies, the diagnostic accuracy of perfusion CMR is comparable to positron emission tomography (PET) and perfusion CT, and is better than single-photon emission CT (SPECT) when fractional flow reserve (FFR) is used as a reference standard. In addition, stress CMR has an excellent prognostic value. One meta-analysis study demonstrated the annual event rate of cardiovascular death or non-fatal myocardial infarction was 4.9% and 0.8%, respectively, in patients with positive and negative stress CMR. Quantitative assessment of perfusion CMR not only allows the objective evaluation of regional ischemia but also provides insights into the pathophysiology of microvascular disease and diffuse subclinical atherosclerosis. For accurate quantification of myocardial perfusion, saturation correction of arterial input function is important. There are two major approaches for saturation correction, one is a dual-bolus method and the other is a dual-sequence method. Absolute quantitative mapping with myocardial perfusion CMR has good accuracy in detecting coronary microvascular dysfunction. Flow measurement in the coronary sinus (CS) with phase contrast cine CMR is an alternative approach to quantify global coronary flow reserve (CFR). The measurement of global CFR by quantitative analysis of perfusion CMR or flow measurement in the CS permits assessment of microvascular disease and diffuse subclinical atherosclerosis, which may provide improved prediction of future event risk in patients with suspected or known CAD. Multi-institutional studies to validate the diagnostic and prognostic values of quantitative perfusion CMR approaches are required.     

A large negative magnetoresistance effect in semiconducting crystals composed of an octahedrally ligated phthalocyanine complex with high-spin manganese(iii)

A design for an octahedrally ligated phthalocyanine complex with high-spin manganese(iii) (S = 2) and Mn^III(Pc)Cl₂ (Pc = phthalocyanine) is presented. The presence of high-spin state Mn^III in the fabricated Ph₄P[Mn^III(Pc)Cl₂]₂ (Ph₄P = tetraphenylphosphonium) semiconducting molecular crystal is indicated by the Mn–Cl distance, which suggests an electronic configuration of (d_yz, d_zx)²(d_xy)¹(d_z²)¹. This was confirmed by the Curie constant (C = 5.69 emu K mol⁻¹), which was found to be significantly larger than that of the isostructural Ph₄P[Mn^III(Pc)(CN)₂]₂, where Mn^III adopts a low-spin state (S = 1). The magnetoresistance (MR) effects of Ph₄P[Mn^III(Pc)Cl₂]₂ at 26.5 K under 9 T static magnetic fields perpendicular and parallel to the c-axis were determined to be −30% and −20%, respectively, which are significantly larger values than those of Ph₄P[Mn^III(Pc)(CN)₂]₂. Furthermore, the negative MR effect is comparable to that of Ph₄P[Fe^III(Pc)(CN)₂]₂ (S = 1/2), which exhibits the largest negative MR effect reported for [M^III(Mc)L₂]-based systems (Mc = macrocyclic ligand, L = axial ligand). This suggests that the spin state of the metal ion is the key to tuning the MR effect.

A Ph4P[Mn^III(Pc)Cl2]2 molecular crystal where Mn^III adopts a high-spin state (S = 2) was designed. The large magnetoresistance effect of fabricated Ph4P[Mn^III(Pc)Cl2]2 suggests that the spin state of the metal ion is the key to tuning the MR effect.     

IgG4-Related Lung Disease Exhibiting the Invasion into the Diaphragm: A Case Report

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition which involves various organs. This is a very rare case of IgG4-related lung disease (IgG4-RLD) with the invasion into diaphragm. The patient was a 71-year-old man with a long-term exposure to asbestos who had a mass shadow in the left lower lung lobe, which was suspected to invade the left diaphragm on computed tomography (CT). Positron emission tomography (PET)/CT also presented an avid intake of fluorodeoxyglucose in the mass, which suspected lung cancer. Although bronchoscopic biopsy could not lead to the definite diagnosis, we performed left lower lobectomy combined with the resection of left diaphragm. The specimen showed the features of IgG4-RLD on pathology: the vein stenosis and fibrosis around the vein, the infiltration of IgG4-positive cells, and IgG cells to IgG4 cells ratio of 40%. Furthermore, there were inflammatory cells infiltrating to the diaphragm.