Diagnostic usefulness of FDG-PET/CT in advanced malignant lymphoma of the uterus: report of two cases.

Summary Malignant lymphoma of the uterus is difficult to diagnose because of its rarity and nonspecific symptoms. However, recently, 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become an important non-invasive diagnostic tool for the management of lymphoma patients. The authors report two cases of malignant lymphoma of the uterus, in which FDG-PET/CT was useful for diagnosis. Examination using ultrasonography or magnetic resonance imaging (MRI) demonstrated a normal-sized uterus and normal endometrium, but FDG-PET/CT showed FDG accumulation in the uterine body in both cases. Endometrial biopsy revealed diffuse large B-cell lymphoma, and chemotherapy with rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) was initiated immediately. Primary malignant lymphoma of the female genitalia is reported to be rare. The present authors' experience with FDG-PET/CT suggests that malignant lymphoma of the female genitalia (including metastasis) may not be as rare as previously reported. Uterine malignant lymphoma may be overlooked by the examination of ultrasound, CT, or MRI.

Diagnostic laparoscopy identifies a peritoneal adenomatoid-like mesothelioma masquerading as ovarian cancer: a case report.

The authors report a rare case of peritoneal adenomatoid mesothelioma in a woman with no history of asbestos exposure. A 61-year-old woman was originally suspected of having a bilateral ovarian tumor based on chest radiography and magnetic resonance imaging (MRI). Upon referral to our hospital, the presence of two solid masses was confirmed by enhanced MRI and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG-PET/CT). Physical examination was normal, as were serum concentrations of the tumor markers CA 19-9, CA 125, and CEA. Laparoscopic surgery showed a right ovarian tumor and laparoscopic right salpingo-oophorectomy and adhesiotomy were performed. Two months later, the patient underwent laparoscopic segmental resection of the sigmoid colon, with histological analysis identifying an adenomatoid-like tumor. The final diagnosis was peritoneal adenomatoid-like mesothelioma with invasion of the right ovary. This case report demonstrates that imaging techniques must be coupled with laparoscopic surgery for an accurate diagnosis of peritoneal mesothelioma.

Polyphenols and fatty acids responsible for anti-cyanobacterial allelopathic effects of submerged macrophyte Myriophyllum spicatum.

Myriophyllum spicatum is known to inhibit the growth of cyanobacteria such as Microcystis aeruginosa by releasing anti-cyanobacterial allelochemicals. The allelochemicals possibly responsible for the inhibition include five polyphenols and three fatty acids, but the extent to which these are indeed responsible for the anti-cyanobacterial effects is unclear. The goal of this research was to determine the contribution of these compounds to the allelopathic effect of M. spicatum on M. aeruginosa. We first collected information on the release rates of these compounds and then added the compounds to a cyanobacterial medium on the basis of their release rates so as to simulate their excretion by M. spicatum. Addition of the polyphenols and fatty acids inhibited the growth of M. aeruginosa, and the interaction of the polyphenols and fatty acids was additive. The EC50 of a polyphenol and fatty acid mixture was compared with that of M. spicatum itself as previously determined in a mixed culture system in which M. spicatum and M. aeruginosa were incubated. The former was about 1.9 times higher than that of the latter, the implication being that the inhibitory effect of the polyphenols and fatty acids contributed about 53% of the allelopathic effect of M. spicatum. This paper is the first to describe allelochemicals that account for a half of the anti-cyanobacterial allelopathic effect of a macrophyte.

Quantitative blood flow measurements in gliomas using arterial spin-labeling at 3T: intermodality agreement and inter- and intraobserver reproducibility study.

BACKGROUND AND PURPOSE: QUASAR is a particular application of the ASL method and facilitates the user-independent quantification of brain perfusion. The purpose of this study was to assess the intermodality agreement of TBF measurements obtained with ASL and DSC MR imaging and the inter- and intraobserver reproducibility of glioma TBF measurements acquired by ASL at 3T. MATERIALS AND METHODS: Two observers independently measured TBF in 24 patients with histologically proved glioma. ASL MR imaging with QUASAR and DSC MR imaging were performed on 3T scanners. The observers placed 5 regions of interest in the solid tumor on rCBF maps derived from ASL and DSC MR images and 1 region of interest in the contralateral brain and recorded the measured values. Maximum and average sTBF values were calculated. Intermodality and intra- and interobsever agreement were determined by using 95% Bland-Altman limits of agreement and ICCs. RESULTS: The intermodality agreement for maximum sTBF was good to excellent on DSC and ASL images; ICCs ranged from 0.718 to 0.884. The 95% limits of agreement ranged from 59.2% to 65.4% of the mean. ICCs for intra- and interobserver agreement for maximum sTBF ranged from 0.843 to 0.850 and from 0.626 to 0.665, respectively. The reproducibility of maximum sTBF measurements obtained by methods was similar. CONCLUSIONS: In the evaluation of sTBF in gliomas, ASL with QUASAR at 3T yielded measurements and reproducibility similar to those of DSC perfusion MR imaging.

Comparison of the added value of contrast-enhanced 3D fluid-attenuated inversion recovery and magnetization-prepared rapid acquisition of gradient echo sequences in relation to conventional postcontrast T1-weighted images for the evaluation of leptomeningeal diseases at 3T.

BACKGROUND AND PURPOSE: The usefulness of contrast-enhanced 3D T2-FLAIR MR imaging for the evaluation of leptomeningeal diseases has not been systematically investigated. The purpose of this study was to assess the value added by contrast-enhanced 3D T2-FLAIR and MPRAGE sequences to conventional postcontrast T1-weighted images in the evaluation of leptomeningeal diseases. We also undertook in vitro studies in attempts to understand the consequences of our patient study. MATERIALS AND METHODS: Twelve patients with confirmed leptomeningeal diseases underwent postcontrast T1-weighted, MPRAGE, and 3D T2-FLAIR imaging at 3T. Two radiologists independently assessed the presence of additional information on postcontrast 3D MR images compared with postcontrast T1-weighted images. The effect of different Gd concentrations and flow velocities on the signal intensity on 3D T2-FLAIR images was investigated in vitro. RESULTS: According to both reviewers, 3D T2-FLAIR images yielded significantly more information than did MPRAGE images (P < .05 and P < .01, respectively). In the in vitro study, 3D T2-FLAIR was more highly sensitive to low Gd concentrations and less sensitive to high Gd concentrations than were T1-weighted or MPRAGE sequences. On 3D T2-FLAIR sequences, at a flow velocity exceeding 1.0 cm/s, the signal intensity of blood-mimicking fluids at concentrations of 0 and 0.1 mmol/L was as low as at 1.3 mmol/L. CONCLUSIONS: For the depiction of leptomeningeal diseases, postcontrast 3D T2-FLAIR provides more additional information than postcontrast MPRAGE imaging. The superiority of the 3D T2-FLAIR sequence is associated with its high sensitivity to flow.

Assessment of vascular supply of hypervascular extra-axial brain tumors with 3T MR regional perfusion imaging.

BACKGROUND AND PURPOSE: The vascular supply of extra-axial brain tumors provided by the external carotid artery has not been studied with RPI. The purpose of this work was to determine whether RPI assessment is feasible and provides information on the vascular supply of hypervascular extra-axial brain tumors. MATERIALS AND METHODS: Conventional ASL and RPI studies were performed at 3T in 8 consecutive patients with meningioma. On the basis of MRA results, we performed RPI by placing a selective labeling slab over the external carotid artery. Five patients underwent DSA before surgery. Two neuroradiologists independently evaluated the overall image quality, the degree of tumor perfusion, and the extent of the tumor vascular territory on conventional ASL and RPI. RESULTS: In overall quality of conventional ASL and RPI, no images interfered with interpretation. In comparisons of the vascular tumor territory identified by the conventional ASL and RPI techniques, the territories coincided in 3 cases, were partially different in 4, and completely different in 1. The interobserver agreement was very good (kappa = 0.82). In 5 patients who underwent DSA, the 4 patients in whom the dominant supply was the external carotid artery were scored as coincided or partially different. The 1 patient in whom the vascular supply was from the internal carotid artery was scored as completely different. CONCLUSIONS: RPI with selective labeling of the external carotid artery is feasible and may provide information about the vascular supply of hypervascular extra-axial brain tumors.

Dextran sulfate sodium-induced acute colonic inflammation in angiotensin II type 1a receptor deficient mice.

OBJECTIVE: Angiotensin II (Ang II) receptor blockers have been reported to contribute to cytoprotective effects in various organs. However, the role of renin-angiotensin system (RAS) in modulation of the inflammatory bowel disease (IBD) remains unclear. In this study we assessed the role of angiotensin II type 1a (AT1a) receptor on the outcome of dextran sulfate sodium (DSS)-induced acute colitis by employing AT1a receptor deficient mice. MATERIALS AND METHODS: The acute colitis was induced in wild type (WT) and AT1a receptor deficient mice by giving orally 3% DSS in drinking water for 7 days. RESULTS: Induction of DSS colitis resulted in up-regulation of Ang II and AT1a receptor in the colonic mucosa of WT mice. In parallel, loss of body weight, an increase in disease activity index (DAI), and the shortening of colon were found in DSS-challenged WT mice. In addition, an increase in thiobarbituric acid (TBA)-reactive substances and myeloperoxidase (MPO) activity, along with the up-regulation of tumor necrosis factor (TNF)-alpha were detected in the colonic mucosa of DSS-challenged WT mice. The endpoints mentioned above were significantly ameliorated in DSS-challenged AT1a receptor deficient mice. CONCLUSIONS: RAS is involved in the pathophysiology of DSS-induced colitis and AT1a receptor may be a novel therapeutic target for the treatment of IBD.

Identification of the novel AML1 fusion partner gene, LAF4, a fusion partner of MLL, in childhood T-cell acute lymphoblastic leukemia with t(2;21)(q11;q22) by bubble PCR method for cDNA.

The AML1 gene is frequently rearranged by chromosomal translocations in acute leukemia. We identified that the LAF4 gene on 2q11.2-12 was fused to the AML1 gene on 21q22 in a pediatric patient having T-cell acute lymphoblastic leukemia (T-ALL) with t(2;21)(q11;q22) using the bubble PCR method for cDNA. The genomic break points were within intron 7 of AML1 and of LAF4, resulting in the in-frame fusion of exon 7 of AML1 and exon 8 of LAF4. The LAF4 gene is a member of the AF4/FMR2 family and was previously identified as a fusion partner of MLL in B-precursor ALL with t(2;11)(q11;q23), although AML1-LAF4 was in T-ALL. LAF4 is the first gene fused with both AML1 and MLL in acute leukemia. Almost all AML1 translocations except for TEL-AML1 are associated with myeloid leukemia; however, AML1-LAF4 was associated with T-ALL as well as AML1-FGA7 in t(4;21)(q28;q22). These findings provide new insight into the common mechanism of AML1 and MLL fusion proteins in the pathogenesis of ALL. Furthermore, we successfully applied bubble PCR to clone the novel AML1-LAF4 fusion transcript. Bubble PCR is a powerful tool for detecting unknown fusion transcripts as well as genomic fusion points.

Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney development and injury.

Once developed, end-stage renal disease cannot be reversed by any current therapy. Bone morphogenetic protein-7 (BMP-7), however, is a possible treatment for reversing end-stage renal disease. Previously, we showed that the BMP antagonist uterine sensitization-associated gene-1 (USAG-1, also known as ectodin and sclerostin domain-containing 1) negatively regulates the renoprotective action of BMP-7. Here, we show that the ratio between USAG-1 and BMP-7 expression increased dramatically in the later stage of kidney development, with USAG-1 expression overlapping BMP-7 only in differentiated distal tubules. Examination of USAG-1 expression in developing kidney indicated that a mosaic of proximal and distal tubule marker-positive cells reside side by side in the immature nephron. This suggests that each cell controls its own fate for becoming a proximal or distal tubule cell. In kidney injury models, the ratio of USAG-1 to BMP-7 expression decreased with kidney damage but increased after subsequent kidney regeneration. Our study suggests that USAG-1 expression in a kidney biopsy could be useful in predicting outcome.

Hyperthermia ameliorates 2,4,6-trinitrobenzene sulphonic acid-induced colitis in rats: the role of heat shock proteins.

PURPOSE: Hyperthermia is known to protect against cellular injury through the expression of heat shock proteins. In this study, the therapeutic effects of hyperthermia on experimental colitis in the rat were evaluated. MATERIALS AND METHODS: Male Wistar rats were given a single intracolonic injection of 2,4,6-trinitrobenzene sulphonic acid (TNBS). Hyperthermia was induced in anesthetized rats by placing them in a temperature-controlled water bath. We started the hyperthermic treatment on the day after the enema. The severity of colitis was evaluated pathologically, and the activities of tissue myeloperoxidase were measured 6 days after the induction of colitis. Furthermore, cytokines, and hyperthermia-induced heat shock proteins in colonic mucosa were detected by enzyme-linked immunosorbent assay and Western blotting. We also investigated the effects of geranylgeranylacetone and zinc protoporphyrin IX on the therapeutic effect of hyperthermia. RESULTS: Hyperthermia significantly improved the macroscopic scores of colitis. The TNBS-induced increases in the activities of myeloperoxidase in the colonic tissue were blunted significantly in hyperthermia-treated animals. Furthermore, hyperthermia attenuated increases in cytokine-induced neutrophil chemoattractants-1 and tumor necrosis factor-alpha in the colon. Furthermore, hyperthermia induced the production of heat shock proteins in rat colonic mucosa, and the combination of geranylgeranylacetone with hyperthermia further induced the heat shock protein HSP70, which resulted in further improvement of TNBS-induced colitis. On the other hand, the combination of zinc protoporphyrin IX with hyperthermia attenuated the therapeutic effect of hyperthermia. CONCLUSIONS: Hyperthermia ameliorates TNBS-induced colitis in rats through the expression of HSP70 and HO-1. It is postulated that hyperthermia may be useful for the treatment of inflammatory bowel diseases.

Metastatic brain tumor surgery using fluorescein sodium: technical note.

As for the surgical treatment of glioma, the recent employment of fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) or high-dose fluorescein sodium has increased the rate of radical tumor resection. On the other hand, there is no specific technique for metastatic brain tumor surgery. We have used a fluorescence-guided tumor resection procedure with the aid of high-dose fluorescein sodium in surgery for metastatic brain tumor. Fluorescein sodium has been used in 13 cases, and achieved effective stainability in all cases. Fluorescein sodium is inexpensive, highly safe, and comparatively easy to use, and does not require any special equipment. We believe that the use of fluorescein sodium is beneficial for resection of the metastatic brain tumor.

Heme oxygenase-1 (Hsp32) is involved in the protection of small intestine by whole body mild hyperthermia from ischemia/reperfusion injury in rat.

AIM: The aim of the present study was to explore whether heme oxygenase-1 (HO-1) is involved in the hyperthermia-provided protection of the small intestine from ischemia/reperfusion injury in rats. METHODS: Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion. Whole-body hyperthermia was induced in anesthetized rats by placement in a temperature-controlled water bath. Whole-body hyperthermia to a core temperature of 42-43 degrees C for 15 min was followed by passive cooling. We started the hyperthermic treatment 6 h before the vascular clamping. The severity of the mucosal injury was evaluated by several biochemical markers and histological findings. Hyperthermia-induced heat-shock proteins were detected by Western blotting. We also investigated the effect of zinc protoporphyrin IX (an HO-1 inhibitor) on the protective effect of hyperthermia. RESULTS: The rats, which were killed after ischemia/reperfusion, had severe intestinal inflammation. Hyperthermia significantly induced the production of Hsp70 and HO-1 in intestinal mucosa and significantly reduced ischemia/reperfusion-induced mucosal injury. The combination of zinc protoporphyrin IX with hyperthermia extinguished the protective effects of hyperthermia on ischemia/reperfusion injury. CONCLUSION: Hyperthermia protects against ischemia/reperfusion injury in rat small intestine through the expression of heat-shock proteins, especially HO-1.

Recurrence rate and transplantability after liver resection in patients with hepatocellular carcinoma who initially met transplantation criteria.

To understand the recurrence rate and transplantability after liver resection (LR), which are essential factors to predict the prognosis of initial resection and salvage transplantation for hepatocellular carcinoma (HCC), we reviewed the clinical records of 279 consecutive HCC patients who met the Milan criteria and underwent LR between 1990 and 2000. Recurrence-free survival rates after 1, 2, 3, 5, and 10 years following LR were 84%, 62%, 49%, 29%, and 17%, respectively. Multivariate analysis using clinical factors such as age, sex, histological differentiation, serum levels of alpha-fetoprotein and 7S domain of type IV collagen (7S collagen), platelet counts, indocyanin green retention test after 15 minutes, and type of LR (resection of one or more segments, or less than one segment) revealed 7S collagen to be a independent factor that significantly affects recurrence-free survival. Yearly recurrence rates up to 5 years after resection ranged from 14% to 27%, averaging 20%. Concerning 169 patients who underwent tests for 7S collagen, the average yearly recurrence rate (27%) in patients with 7S collagen levels 8.0 ng/mL or higher was remarkably greater than that in the patients with levels less than 8.0 ng/mL (16%). The transplantability rate at the time of recurrence meeting the Milan criteria was roughly 60%. There were no pre-LR factors that significantly predicted transplantability. This result indicates that patients with lower 7S collagen levels are more eligible for initial LR and then salvage LT rather than primary LT.

Detection of p53 mutations in the plasma DNA of patients with ovarian cancer.

Mutation of p53 is one of the most common genetic abnormalities detected in up to 81% of cases of ovarian cancer. To evaluate the use of plasma DNA analysis as a method for somatic mutation screening, we measured the presence of p53 mutations in DNA isolated from plasma and cancer tissue from patients with ovarian cancer. We analyzed the plasma DNA for the presence of p53 mutations (exons 5-8). Of 27 cases of ovarian cancer, 12 cases (44%) had mutations of p53 in cancer tissue. In two of the 12 cases (16.7%), identical mutations were detected in DNA of their preoperative plasma. In our follow-up of the two patients with p53 mutations in their plasma, mutant DNA was undetectable in their plasma after surgery. In one case, the p53 mutation re-surfaced in their plasma 16 months after surgery, and the patient died 2 months later. We have shown that tumor-derived DNA can be detected in the plasma of some patients with ovarian cancer, particularly in those with more advanced stage.

Splenic marginal zone lymphoma presenting as myelofibrosis associated with bone marrow involvement of lymphoma cells which secrete a large amount of TGF-beta.

We report here on a patient with splenic marginal zone lymphoma presenting diffuse fibrosis of bone marrow and spleen. After splenectomy and chemotherapy, bone marrow biopsy demonstrated an improvement of fibrosis. Plasma concentration of transforming growth factor (TGF)-beta was much higher in this patient than in those of age-matched non-Hodgkin's lymphoma patients ( n=5) at diagnosis, decreasing after resolution of myelofibrosis. Immunostaining with the TGF-beta antibody revealed that the lymphoma cells in bone marrow and spleen were positive for TGF-beta. TGF-beta secreted by tumor cells was thought to stimulate the growth of fibroblasts and synthesize collagen in bone marrow and splenic fibroblasts, and play an important role in the development of marrow and splenic fibrosis in this patient. This is the first report of a patient with splenic marginal zone lymphoma presenting as myelofibrosis associated with bone marrow involvement of lymphoma cells which secrete a large amount of TGF-beta.

Dopamine stabilizes milrinone-induced changes in heart rate and arterial pressure during anaesthesia with isoflurane.

BACKGROUND AND OBJECTIVE: Phosphodiesterase-III inhibitors and dobutamine effectively improve cardiac function in patients with cardiac failure, but they are limited by possible hypotensive effects. We tested the hypothesis that dopamine contributes to stabilizing milrinone-induced haemodynamic changes. METHODS: Nine patients undergoing major surgery were anaesthetized using nitrous oxide and oxygen supplemented with isoflurane 1-2%. After baseline haemodynamics were recorded, milrinone (25 or 50 microg kg(-1)) was administered over 10min, followed by a continuous infusion (0.5 microg kg(-1) min(-1). The second set of haemodynamic values was measured 50 min after beginning the continuous infusion of milrinone. Dopamine (4 microg kg(-1) min(-1)) was then administered with milrinone. RESULTS: Milrinone significantly increased the heart rate from 81 +/- 8 to 102 +/- 16beats min(-1), but it decreased the mean arterial pressure from 83 +/- 10 to 66 +/- 10 mmHg and systemic vascular resistance (P < 0.05 for each). The pulmonary capillary wedge pressure, cardiac index and pulmonary vascular resistance did not change significantly. The addition of dopamine to the milrinone infusion significantly decreased the heart rate (94 +/- 12 beats min(-1)) and increased the mean arterial pressure (82 +/- 11 mmHg). Dopamine and milrinone, but not milrinone alone, significantly increased the cardiac index and the rate-pressure product. CONCLUSIONS: The combination regimen of milrinone and dopamine improved cardiac function, and changes in heart rate and mean arterial pressure induced by milrinone were attenuated by dopamine. The results suggest that a combination regimen of milrinone and dopamine rather than milrinone alone should be used to maintain arterial pressure.

Mechanism allowing an insect to survive complete dehydration and extreme temperatures.

Cryptobiosis describes the state of an organism whose body water is completely dehydrated and metabolic activity has become undetectable. Our study aimed to elucidate the physiological mechanism of cryptobiosis in the highest cryptobiotic invertebrate, Polypedilum vanderplanki. Larvae of this insect rapidly accumulated a large amount of the carbohydrate, trehalose, (18% of dry body mass) during desiccation for 2 days, suggesting that a high level of trehalose accumulation contributed to the successful induction of cryptobiosis in P. vanderplanki as well as in other lower cryptobiotic organisms. When larvae deprived of the brain, suboesophageal ganglion (SG) and thoracic ganglia (TG) were completely dehydrated and then rehydrated, they were able to recover and move actively. During desiccation, such larvae also accumulated trehalose, although only about half as much as the intact larvae. It is concluded that the brain, SG and TG do not affect the induction and termination of cryptobiosis, and hence in this higher multicellular animal cryptobiosis is independent of brain, SG and TG regulation, just as in plants or in unicellular organisms.

MRI of intracranial germ-cell tumours.

Our aim was to review the MRI appearances of primary intracranial germ-cell tumours (GCT). We reviewed the MRI studies of 32 patients: 19 with germinomas, five with teratomas, one with an embryonal carcinoma, five with mixed and two with malignant nongerminomatous GCT. Eleven were in the pineal region, 12 suprasellar, five in the both sites, two in the basal ganglia and two in the corpus callosum. Contrast-enhanced images were available for 27 patients. The solid parts of GCT were nearly isointense with grey matter on both T1- and T2-weighted images. In seven patients with nongerminomatous GCT high-signal components were found on T1-weighted images, representing haemorrhage, high-protein fluid or fat. Cystic components were detected in 17 of 27 patients; eight germinomas and all nine nongerminomatous GCT had cysts. The solid components of germinomas enhanced homogeneously in eight cases and heterogeneously in 10, while all nongerminomatous GCT showed heterogeneous enhancement. MRI features tumours can facilitate correct diagnosis of GCT, including histological subtypes.