This study was initiated to clarify the ability of magnetic resonance imaging (MRI) in defining breast carcinoma extension by comparing MRI to detailed histopathological analysis. Mastectomy (n = 14) or quadrantectomy (n = 44) specimens were sub-serially sectioned and mapped in detail in 58 breast cancer patients. Morphologically, we classified the lesions utilizing MRI into three patterns in relation to their histology. Numerically, we assessed the maximum distance of carcinoma extension using MRI, mammography, and ultrasonography (US). Linear regression was calculated for each of the three imaging measurements versus histopathological measurements. Three imaging patterns were observed by MRI, (1) localized (n = 30), (2) segmentally extended (n = 19), and (3) irregularly extended (n = 5). The localized pattern showed a distinct focal mass, but in 10 cases, microscopic ductal carcinoma in situ (DCIS), or invasive lobular carcinoma, which were not depicted by MRI, existed. The segmentally extended pattern showed diffuse enhancement along duct-lobular segments, forming a 'cone' shape. Histologically, pure (n = 4) or predominant (n = 10) DCIS was distributed segmentally. The irregularly extended pattern showed thick branches extending out from the index tumor which were histologically revealed to be stromal invasion of ductal carcinoma. From the results of linear regressions, MRI was the most accurate modality in histologically measuring the extent of the cancer. When cases were limited to patients who were classified into segmentally or irregularly extended pattern by MRI (n = 24), MRI was more accurate than mammography and US, even if they were combined (P < 0.05). MRI may provide additional information concerning carcinoma extension prior to surgery, especially in patients classified into 'extended patterns' by MRI.

Adult↗

PubMed2000

Usefulness of quantitative real-time polymerase chain reaction in following up patients with Epstein-Barr virus infection after liver transplantation.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD), which is mainly induced by Epstein-Barr virus (EBV) infection, is a cause of significant morbidity and mortality for patients undergoing liver transplantation, especially when it is detected at such an advanced stage as monoclonal malignant lymphoma. METHODS: In this series, 6 of 22 liver transplant patients suffered from EBV infection. We tested quantitative DNA (Qt-DNA) by real-time polymerase chain reaction (PCR), qualitative DNA in plasma (Q1-pDNA) by PCR, and EBV-encoded mRNA 1 (EBER 1) by in situ hybridization to clarify which of them is a better marker for the early diagnosis and prediction of EBV-associated disorders. RESULTS: Four had signs or symptoms of PTLD, but 2 did not develop individualized lymphoid lesions. In all patients, both Qt-DNA and EBER 1 exceeded the cut-off level of 10(2.5) copies/microg DNA and 0.002%, respectively, at the time of diagnosis. In 2 patients, when Qt-DNA had a poor decline, EBER 1, even if it seemed to decrease after antiviral therapy, increased again after a few months and the clinical symptoms recurred. In 2 patients, Qt-DNA and EBER 1 increased again after a few months of antiviral therapy, and Q1-pDNA remained positive, whereas, in 3 patients, no reaction of EBV could be detected once Q1-pDNA became negative, even after the cessation of therapy. CONCLUSIONS: These results suggest that real-time PCR for Qt-DNA was more sensitive to the real-time activity of EBV and that Q1-pDNA could indicate when to stop antiviral therapy.

Child, Preschool↗

PubMed2000

Rehabilitating patients with hepatopulmonary syndrome using living-related orthotopic liver transplant: a case report.

The objective of this study was to rehabilitate a patient with hepatopulmonary syndrome (HPS) who underwent living-related orthotopic liver transplantation (LT). HPS is rare; it presents severe complication in patients with liver disease. A 17-year-old woman with HPS developed portal hypertension after undergoing Kasai's surgery for congenital biliary atresia and underwent a living-related orthotopic LT. After LT, her allograft functioned well, but she continued to have hypoxemia and orthodeoxia. She was referred for rehabilitation for disuse atrophy, contracture of hip and shoulder joints, left common peroneal nerve palsy, and rehabilitation for respiratory dysfunction. By day 106 after LT, her orthodeoxia and disuse atrophy had improved because of daily exercise training and active joint range of motion exercises. Patients with HPS have orthodeoxia and poor responsiveness to oxygen therapy, and correction of hypoxemia after LT may be delayed. Therefore, rehabilitation approaches for patients with HPS should be based on the pathophysiology and characteristics of HPS.

Adolescent↗

PubMed2000

[Clinical efficacy of low-dose weekly docetaxel combined with oral 5'-deoxy-5-fluorouridine (5'-DFUR) in advanced or metastatic breast cancer: a pilot trial].

Docetaxel (TXT) has been shown to be an up-regulator of human pyrimidine nucleoside phosphorylase (PyNPase) in tumors. We have tried to use the combination of low-dose weekly TXT with 5'-DFUR (LD + D) in patients with advanced or metastatic breast cancer. In this study, we compared the clinical efficacy of LD + D with that of conventional full-dose TXT (FD) and that of low-dose weekly TXT (LD). Twenty-one patients received 3 or 4 cycles of FD 60 mg/m2 every 3 or 4 weeks (group I), 14 patients received 8 cycles of LD 20-30 mg/m2 every week (group II) and 25 patients received 8 cycles of LD 20-30 mg/m2 weekly with oral 5'-DFUR 600-1,200 mg per day (group III). The overall response rates of groups I, II and III were 29%, 29% and 52% (p = 0.24), respectively. Grade 3-4 neutropenia was observed in 91% of group I, 6% of group II and 3% of group III. Nausea was present in 27% of group I, 28% of group II and 40% of group III. Higher incidence of gastrointestinal symptoms was found in LD + D, but the symptoms abated when the doses of 5'-DFUR were reduced. Low-dose weekly TXT with oral 5'-DFUR produced a higher response rate, but less hematologic toxicity than full-dose TXT, suggesting that this combination therapy is clinically useful and may be effective for patients with advanced or metastatic breast cancer.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Frequent loss of copy number on the long arm of chromosome 21 in human esophageal squamous cell carcinoma.

To understand the molecular pathogenesis of human esophageal cancer, we performed a comparative genomic hybridization (CGH) analysis using 10 esophageal squamous cell carcinomas. Frequent gains of 1q, 3q, 7p, 7q, 8q, 11q, and 20q and losses of 3p, 4p, 4q, 5q, 9p, 11p, 11q, 13q, 18q, 21q, and Y were observed. Among these regions, 21q has not yet been investigated in detail. We performed an allelotype study using 55 squamous cell carcinomas of the esophagus and 20 microsatellite markers on 21q and found LOH in 36 cases (65%): 22 (61%) of 36 cases with LOH indicated allelic loss in all informative loci, suggesting loss of the whole chromosome arm 21q, and five smallest regions of overlap were found. Our present results suggest the existence of a tumor suppressor gene(s) that plays a role in the genesis of squamous cell carcinoma of the esophagus.

Chromosome Aberrations↗

PubMed2000

Comparison of intratumoral distribution of 99mTc-MIBI and deoxyglucose in mouse breast cancer models.

UNLABELLED: The aims of this study were to evaluate the distribution of 99mTc-methoxyisobutylisonitrile (MIBI) in 3 animal models of breast cancer, the effect of radiotherapy on 99mTc-MIBI uptake, and the relationship between uptake and microvessel density. METHODS: We used syngeneic, subcutaneously transplanted FM3A, MM48, and Ehrlich mouse breast cancer. 99mTc-MIBI and FDG were injected intravenously, and tumor uptake was measured 30 min later. Double-tracer macroautoradiography (ARG) images were prepared with 99mTc-MIBI and 2-deoxy-D-[1-14C]-glucose (14C-DG), analyzed quantitatively, and compared with histology. The radiotherapeutic effects of 20 Gy x-ray irradiation were monitored by measuring tumor volume, tumor uptake, and ARG findings using 99mTc-MIBI and FDG in FM3A tumors. Microvessel density was quantified by immunohistochemical staining for CD34 and compared with ARG using 99mTc-MIBI in FM3A tumors. RESULTS: FM3A, MM48, and Ehrlich tumors showed different growth rates and radiosensitivities. Uptake of FDG, but not of 99mTc-MIBI, correlated significantly with growth rates. Compared with 14C-DG, 99mTc-MIBI accumulated more in cancer cells and less in infiltrating fibroblasts and macrophages in all tumor models. Irradiation significantly decreased 99mTc-MIBI uptake, but a rapid increase was noted at recurrence on day 7. Changes in FDG uptake were not significant at recurrence. Microvessel density in tumor tissue correlated significantly with 99mTc-MIBI uptake on ARG. CONCLUSION: Accumulation of 99mTC-MIBI in cancer cells is preferential and can be used as a sensitive marker to examine the response to radiotherapy. Angiogenesis seems to enhance accumulation of 99mTc-MIBI in tumors. These characteristics may be favorable for tumor imaging using 99mTC-MIBI.

Animals↗

PubMed1999

Elimination of Kupffer cells and nafamostat mesilate rinse prevent reperfusion injury in liver grafts from agonal non-heart-beating donors.

BACKGROUND: We hypothesized that microcirculatory disturbance was an obstacle to liver transplantation (LTx) from non-heart-beating donors (NHBDs) and that it was attributed mainly to a deterioration of sinusoidal endothelial cells (SECs) and sinusoidal narrowing. This study was designed to examine porcine orthotopic LTx using livers obtained from pretreated agonal NHBDs, and to determine whether the maintenance of the liver microcirculation would result in successful LTx from agonal NHBDs. METHODS: Pigs were allocated to five groups: (i) control group; (ii) NM group, in which grafts were rinsed with nafamostat mesilate (NM) rinse; (iii) LD group, in which Kupffer cells in grafts were eliminated by liposome-encapsulated dichloromethylene diphosphonate (L-DMDP); (iv) LDNM group, in which grafts pretreated with L-DMDP were rinsed with NM rinse; (v) heart-beating donor (HBD) group. In all groups, but the HBD group, the livers were pretreated with FK506 and prostaglandin I2 analogue, and were preserved in University of Wisconsin solution after cardiac arrest. Thereafter orthotopic LTx was performed. RESULTS: After reperfusion, it was histologically demonstrated that elimination of Kupffer cells prevented SECs deterioration and NM rinse prevented sinusoidal narrowing. The hepatic energy charge recovered in all groups except the control group. In the LDNM group, three of four recipients survived more than 7 days. CONCLUSIONS: For a successful LTx from agonal NHBDs, it is important to prevent microcirculatory disturbance caused by SEC deterioration and sinusoidal narrowing after reperfusion. Combination therapy consisting in the elimination of Kupffer cells and NM rinse prevented primary graft non-function in liver grafts from agonal NHBDs.

Adenosine Triphosphate↗

PubMed1999

Fragility of the electron transport chain and superoxide generation in mitochondria of the liver graft after cold ischemia.

BACKGROUND: After cold ischemia, electrons transferred in the electron transport chain may leak out of the mitochondria in proportion to the deterioration of mitochondrial oxidative phosphorylation. This seems to be one major cause of the lipid peroxidation that occurs mainly in the hepatocytes at reperfusion in liver transplantation. To examine this hypothesis, we investigated superoxide generation and the amount of oxidative phosphorylation in the mitochondria isolated from rat livers after cold preservation. METHODS: Rat liver was preserved in University of Wisconsin solution at 4 degrees C for 24 hr. The mitochondrial fraction was prepared, and the amount of ATP synthesis and superoxide generation was investigated. Superoxide generation in the electron transport chain of submitochondrial particles was also measured by a chemiluminescence recorder. RESULTS: The amount of ATP synthesis was significantly decreased after 12 hr of cold preservation. In the whole mitochondria, superoxide production in the presence of succinate was approximately 1/2000 to 1/3000 less than that observed in the submitochondrial particles at any determination point, and superoxide production was not affected by cold preservation. In the presence of antimycin A, superoxide production in the mitochondria after 18 hr of preservation increased significantly. CONCLUSION: These results indicate that the electron transfer in the complex III of the mitochondrial membrane becomes leaky after long periods of cold ischemia, but that leakage of superoxide anion did not increase, although the mitochondrial respiratory phosphorylation was deteriorated. We conclude that superoxide through the mitochondrial membrane cannot cause lipid peroxidation in hepatocytes at reperfusion even after a long period of cold ischemia.

Adenosine Triphosphate↗

PubMed1999

The mechanism of injury in a steatotic liver graft during cold preservation.

BACKGROUND: Fatty livers are more prone to primary nonfunction after transplantation. It is known that cell injury is strongly associated with alterations in the content and composition of membrane lipids. We assumed that plasma membrane (PM) fluidity, which is the most important property of the membrane, differed between fatty and normal livers. METHODS: The livers from obese and lean Zucker rats were flushed with cold Ringer's lactate and University of Wisconsin (UW) solution via the portal vein and preserved in cold UW solution for 24 hr. Histological examinations of electron microscopy were performed to investigate of sinusoidal lining cells (SLCs). PMs were isolated using a discontinuous density gradient of Percoll, and the lipid compositions were determined by chromatography. RESULTS: SLCs of fatty livers were markedly injured compared with control livers even after short preservation time. Moreover, many blebs were observed in the obese rats even after short preservation time. As for PM lipid composition, the cholesterol/phospholipid (PL) ratio of total PM was 0.14+/-0.03 in the obese rats and 0.21+/-0.03 in the lean rats (P<0.05). The relative proportions of polyunsaturated fatty acids among PLs in PM were 35.7+/-1.2% vs. 45.9+/-1.5% (P<0.0001). These results indicated that the fluidity of the PM in the obese rats is decreased after exposure to low temperatures. CONCLUSIONS: Our results suggest that steatotic livers from obese donors are more susceptible to cold preservation injury than livers without steatosis because of the severe deterioration of SLCs, and it is associated with PM fluidity even after short-term cold preservation.

Adenosine↗