Identification of molecular markers for metastasis-related genes in primary breast cancer cells

Comparing differential gene expression profiles established by cDNA microarray between normal cells (N), primary carcinoma cells (T), and metastatic carcinoma cells (M) may determine those critical genes directly associated with progression and metastasis of breast cancer. Total RNA was extracted by laser microdissection (LMD) from 20 slices of T, N and M from 6 cases. After amplification by a T7-based system, differentially expressed genes between T, N and M were identified by cDNA microarray. In addition, to clarify the mechanism for altered gene expression, we determined the methylation status by sequencing after bisulfite treatment for intriguing genes. As a result, the expression of motility related protein-1 (MRP-1/CD9), peripheral myelin protein-22 (PMP-22), and caspase 3 (CASP-3) were down-regulated in M compared to T. We focused especially on MRP-1 and found that the expression status of MRP-1 was significantly inversely associated with stage of disease in 56 cases of breast cancer (P<0.05), and the relapse free survival in 5 years was significantly higher in MRP-1 positive cases than those negative cases (P<0.05). Conversely, overexpression, by 11-fold, of signal transduction and translation factors were observed in T compared to N. The cancer specific methylation was observed only in CASP-3 in a case. In conclusion, the establishment of the present assay allows us to detect genes directly associated with each cell population within tumor tissue and gives us clues to identify metastasis-related genes comprehensively in clinical breast cancer cases.     

Extraskeletal osteosarcoma: Extensive tumor thrombus on fused PET-CT images

A 30-year-old woman developed extraskeletal osteosarcoma in the right buttock and thigh. Radiographs and unenhanced computed tomography (CT) showed a large, multilobulated mass accompanied by mineralized matrix. Contrast-enhanced CT and magnetic resonance (MR) images showed extensive tumor thrombus in the right internal- and external iliac veins. Co-registered positron emission tomography (PET) and CT images showed abnormal F-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in the tumor thrombus. PET study in our patient provided information concerning disease extent and viability of tumor thrombus.     

A case of prostate cancer with cyst formation

We treated a case of prostate cancer with cyst formation in an 80-year-old Japanese man presenting with constipation. Fist-sized elastic soft mass was palpable by digital rectal examination. Computed tomography and magnetic resonance imaging demonstrated a retrovesical cystic mass arisen from the prostate. Serum prostate-specific antigen (PSA) was elevated to 15.7 ng/ml. Transrectal prostate needle biopsy revealed moderately differentiated adenocarcinoma and puncture of the cyst yielded aseptic bloody fluid. With a clinical diagnosis of prostate cancer (T2b N0 M1b) with cystic formation, hormonal therapy with a luteinizing hormone releasing hormone analogue and bicalutamide significantly lowered the serum PSA level. One year later, the cyst was reduced in volume and constipation had resolved. A total of 57 cases of prostate cancer with cyst formation are reviewed.     

Clinical utility of sequential imaging of hepatocellular carcinoma by contrast-enhanced power Doppler ultrasonograpy

The aim of this study was to investigate the clinical utility of sequential imaging of hepatocellular carcinoma (HCC) by contrast-enhanced power Doppler ultrasonograpy (CE-PDUS) to differentiate hepatocellular carcinoma from adenomatous hyperplasia (AH) and regenerated nodule (RN) and to predict the degree of differentiation of HCC. Fifty-one patients with 62 hepatic lesions including 33 moderately and poorly differentiated HCCs, 19 well-differentiated HCCs, seven AHs and three large RNs were examined by CE-PDUS. The imaging patterns during early arterial phase (tumor vessel image), late vascular phase (tumor perfusion image) and post-vascular phase (liver perfusion image) were classified as diffuse, basket, peripheral, central and no enhancement; as whole tumor, partial tumor and no enhancement; as whole tumor, partial tumor and no defect, respectively. The diffuse pattern in the tumor vessel image, the whole enhancement pattern in the tumor perfusion image and the whole defect pattern in the liver perfusion image were observed in moderately and poorly differentiated HCCs only. The basket pattern in the tumor vessel image and the partial defect pattern in the tumor perfusion image were observed in HCCs only. All AH/RNs showed no defect pattern in the liver perfusion image. The sequential imaging of HCC during early arterial, late vascular and post-vascular phases by CE-PDUS is clinically useful to differentiate HCC from AH/RN and to predict the degree of differentiation of HCC.     

Anesthetic management of a patient with suspected pseudothrombocytopenia

A 74-year-old male was operated for sigmoid colon cancer. Because of an agglutination of the patient's platelet, it was difficult to measure his platelet count under ethylene diamine tetra acetate (EDTA), heparin or citrate as anticoagulants with an automated cell counter. Even though there was a strong possibility of pseudothrombocytopenia, anesthetic management for the patient was safely conducted. His condition was stable throughout the perioperative course and no bleeding tendency was observed. Nitrous oxide, oxygen, sevoflurane, propofol and pancuronium were useful in this case.     

Development of silicone rubber hollow fiber membrane oxygenator for ECMO

Silicone rubber hollow fiber membrane produces an ideal gas exchange for long-term ECMO due to nonporous characteristics. The extracapillary type silicone rubber ECMO oxygenator having an ultrathin hollow fiber membrane was developed for pediatric application. The test modules were compared to conventional silicone coil-type ECMO modules. In vitro experiments demonstrated a higher O2 and CO2 transfer rate, lower blood flow resistance, and less hemolysis than the conventional silicone coil-type modules. This oxygenator was combined with the Gyro C1E3 centrifugal pump, and three ex vivo experiments were conducted to simulate pediatric V-A ECMO condition. Four day and 6 day experiments were conducted in cases 1 and 2, respectively. Case 3 was a long-term experiment up to 2 weeks. No plasma leakage and stable gas performances were achieved. The plasma free hemoglobin was maintained within a normal range. This compact pump-oxygenator system in conjunction with the Gyro C1E3 centrifugal pump has potential for a hybrid total ECMO system.     

Intracerebral pneumocephalus following a head injury: case report

We report a case of intracerebral pneumocephalus following a head injury. This condition is relatively rare, and only 14 cases, including the present case, have been reported to data. A 40-year-old man fell from a 3rd floor window on June 29, 1999. The patient was admitted to the hospital. Plain skull X-ray films revealed a left basal skull fracture, and CT scan revealed a small contusion at the left frontobasal lobe. The patient was treated conservatively. On July 16, he underwent an MRI, and a small contusion was revealed at the left frontobasal lobe. In addition, the brain appeared to have herniated into the ethmoidal sinus. On July 22, the patient underwent a CT scan, and a intracerebral pneumocephalus was revealed in the left frontal lobe. On August 2, an MRI was performed, and intracerebral pneumocephalus in the left frontal lobe and herniation of the brain into the ethmoidal sinus were noted. In addition, intracerebral pneumocephalus had increased. The patient was admitted to our hospital. Clinotherapy was performed, but intracerebral pneumocephalus increased. On August 9, the patient underwent surgery to repair the skull base. During surgery, it was noted that the left frontal contusion had adhered to the edge of the lacerated dura around the bone defect of the ethmoidal sinus. Following surgery, no recurrence of pneumocephalus was noted. We conclude that once intracerebral air volume increases, early surgical repair should be carried out for intracerebral pneumocephalus. Meticulous MRI investigations of the lesion causing the intracerebral pneumocephalus should be conducted to select an appropriate operative procedure.     

In vivo studies of phenylalanine hydroxylase by phenylalanine breath test: diagnosis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency

Tetrahydrobiopterin (BH4)-responsive phenylalanine hydroxylase (PAH) deficiency is characterized by reduction of blood phenylalanine level after a BH4-loading test. Most cases of BH4-responsive PAH deficiency include mild phenylketonuria (PKU) or mild hyperphenylalaninemia (HPA), but not all patients with mild PKU respond to BH4. We performed the phenylalanine breath test as reliable method to determine the BH4 responsiveness. Phenylalanine breath test quantitatively measures the conversion of L-[1-13C] phenylalanine to 13CO2 and is a noninvasive and rapid test. Twenty Japanese patients with HPA were examined with a dose of 10 mg/kg of 13C-phenylalanine with or without a dose of 10 mg . kg(-1) . d(-1) of BH4 for 3 d. The phenylalanine breath test [cumulative recovery rate (CRR)] could distinguish control subjects (15.4 +/- 1.5%); heterozygotes (10.3 +/- 1.0%); and mild HPA (2.74%), mild PKU (1.13 +/- 0.14%), and classical PKU patients (0.29 +/- 0.14%). The genotypes in mild PKU cases were compound heterozygotes with mild (L52S, R241C, R408Q) and severe mutations, whereas a mild HPA case was homozygote of R241C. CRR correlated inversely with pretreatment phenylalanine levels, indicating the gene dosage effects on PKU. BH4 loading increased CRR from 1.13 +/- 0.14 to 2.95 +/- 1.14% (2.6-fold) in mild PKU and from 2.74 to 7.22% (2.6-fold) in mild HPA. A CRR of 5 to 6% reflected maintenance of appropriate serum phenylalanine level. The phenylalanine breath test is useful for the diagnosis of BH4-responsive PAH deficiency and determination of the optimal dosage of BH4 without increasing blood phenylalanine level.