A 13-year old boy with acute lymphoblastic leukemia had bilateral paresis of the upper extremities and aphasia 1 week after high dose methotrexate and triple intrathecal therapy (methotrexate, cytarabin, hydrocortisone). The stroke-like neurological symptoms disappeared on the third day. T2-weighted magnetic resonance imaging showed hyperintensities of white matter on the second day. Despite resolution of the neurological symptoms, magnetic resonance images were still abnormal 3 years after the attack. Methotrexate has been considered to be responsible for ischemic damage to oligodendroglial cells, resulting in demyelination. The changes are occasionally prolonged without persistent neurologic symptoms.

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Fabry disease is an inherited lysosomal storage disorder characterized by a pathological intracellular glycosphingolipid deposition. The disease is caused by a deficit in the lysosomal enzyme α-galatosidase A, the gene for which is located in the X chrosomal region Xq 22. Globotriaosylceramide (Gb3) accumulate progressively in multi-organ vulnerable cells throughout the body, including cardiovascular, renal, and cerebrovascular systems. The present manuscript is to review cardiovascular and renal manifestations of Fabry disease and the new diagnostic procedures for earlier detection and the therapeutic assessments of this disease. We are applying noninvasive cardiovascular and microcirculation analysis methods and novel cardiac biomarkers. Novel therapeutic strategies for this disease have been developing in recent years, which include the clinically introduced enzyme infusion replacement therapy and experimentally developing gene-transfer therapy. We have reported that AAV-mediated muscule-directed gene transfer is very effective for long-term systemic delivery of α-gal A (25% of normal mice enzyme activity), resulting in complete clearance of multi-organs Gb3 accumulation. Echocardiographic and immunohistochemical examination demonstrated structural improvement of cardiac hypertrophy. When and to whom the novel therapeutic strategies should be applied to obtain the maximum efficacy and safety remain to be established.

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Purpose: To determine the efficacy of power Doppler ultrasound (PDU)in the diagnosis of prostate cancer, the rate of detection of cancer with PDU-guided target biopsy and sextant biopsy, the clinicopathological features of cancer positive specimens, and the relation between these two findings were studied. Methods: From January 1998 through March 2000, 302 men suspected to have prostate cancer underwent sextant biopsy in association with additional PDU-guided target biopsy. Cases with positive biopsy results were divided into 9 groups as follows: T0: sextant biopsy was positive, but target biopsy was negative; S0: all sextant biopsies were negative, but target biopsy was positive; S1∼S6: both sextant biopsy and target biopsy were positive (number indicates number of positive sextant biopsy); Tx: sextant biopsy was positive, but no target biopsy was performed owing to a lack of echogenic abnormalities. The Gleason score (GS) and percent organ confined disease (%OCD) were compared between these 9 groups. Results: Cancer was pathologically detected in 143 of 302 patients (47.4%). PDU detected 39 of 49 digital rectal examination-negative cancers (79.6%) and 5 of 13 transrectal ultrasound-negative isoechoic cancers (38.5%). Of 143 biopsy-positive cases, 6 were in the T0 group (4.2%), 10 in S0 (7.0%), 119 in S1∼S6 (83.2%), and 8 in Tx (5.6%). Target biopsy missed 14 (sum of T0 and Tx) cancers, and sextant biopsy missed 10 (S0). The average GS in the Tx group was significantly lower than that in the other groups; consequently, the %OCD was significantly higher. Retrospective analysis revealed that the failure to obtain cancer tissue in 4 of the 6 cases in the T0 group is most likely due to technical failure in obtaining specimens. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PDU were 90.2%, 77.4%, 78.2%, 89.8% and 83.4%, respectively. Conclusion: PDU in association with sextant biopsy is a useful tool for increasing the rate of detection of prostate cancer. Further advances in ultrasound technology may enable the detection of prostate cancer by target biopsy alone and consequently may reduce the number of unnecessary biopsies. However, PDU-guided target biopsy alone is insufficient for cancer detection at the present time because of possible technical failure in obtaining specimens and the existence of PDU-negative cancer. Although more evidence is required, PDU-negative cancer is suggested to be less aggressive clinically, possibly justifying a watch and wait policy.

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Alterations and defective expression of three putative tumor-suppressor genes, the deleted in colorectal cancer (DCC), p51, and O⁶-methylguanine-DNA methyltransferase (MGMT), have been demonstrated in many cancers. However, it is not known whether the defective expression of each of these genes is independent or whether it reflects a specific methylation abnormality. Here, we investigated the expression of the DCC, p51 and MGMT genes and the methylation status of the 5'flanking CpG region in 17 cell lines established from hematological malignancies. The reverse transcriptase-polymerase chain reaction method showed DCC expression to be absent in 13 of the 17 cell lines and showed expression of both p51 and MGMT to be absent in 5 of the 17 cell lines. The methylation patterns were analyzed with methylation-specific polymerase chain reaction (MSP) of the 5'flanking region of the DCC and p51 genes and the promoter region of the MGMT gene. Although unmethylated patterns of the CpG region in the DCC, p51, and MGMT genes were observed in all 11 normal controls, abnormal methylation patterns of these genes were found even in many cell lines expressing these genes. A hypermethylation pattern was detected for the CpG region of MGMT and p51 in cells that did not express these genes. In contrast, a hypermethylation pattern was not always detected for the CpG region of DCC in cells with reduced DCC expression. The results of this study indicate that in many hematological cell lines, the DCC, p51, and MGMT genes have been abnormally methylated in the CpG region. Hypermethylation of these three genes may be independent events in each cell line.

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Purpose: The management of rectal tumors is complex, because of the balance between preserving rectoanal function and curing the patient. Transanal endoscopic microsurgery (TEM) is both an effective treatment for benign rectal tumors and early cancers, and a diagnostic tool for determining tumor depth, or for residual tumors of post endoscopic mucosal resection. In the present study, we evaluated the role of TEM in the management of rectal tumors. Methods: Twenty-six patients with rectal tumors underwent TEM from December 2000 through March 2005 in our department. The operations were performed by a single surgeon, and the indications were mainly limited to a) benign tumors for which endoscopic resection was difficult, b) early cancers that had invaded the submucosa within 500 μm of the muscularis mucosae, c) submucosal tumors, i.e., gastrointestinal stromal tumor, carcinoid tumors, d) local excision for diagnosis, and e) palliative resection for high-risk cases. Anesthesia, operation time, sizes of the tumor and of resected specimens, postoperative complications, length of hospitalization, pathological results, and postoperative recurrence rate were reviewed. Results: The mean age of patients was 61.9 years, and the cases included 14 rectal cancers, 7 adenomas, 1 gastrointestinal stromal tumor, and 3 rectal carcinoid tumors. The mean operation time was 96 min (range, 40∼235 min.). The average postoperative hospital stay was 4.8 days. All tumors were resected with horizontal and vertical safety margin. The mean size of the resected specimens was 9.0 cm². In one case, the tumor had infiltrated the proper muscle layer, as shown by intraoperative frozen sectioning, which necessitated abdominoperineal resection. In 3 cases, pathological examination revealed massive infiltration into the submucosal layer. 2 patients underwent low anterior resection, and the remaining patient refused additional surgery despite our recommendation. No deaths occurred. No major postoperative complications were noted. The mean follow-up period was 27.2 months. Only one case of lymph node metastasis was observed, in the left iliac lymph node 3 years after TEM. Conclusions: TEM is a minimally invasive surgical procedure for rectal tumors, which allows the whole depth of the rectal wall to be resected with a safety surgical margin. Although TEM requires technical skill and accurate preoperative diagnosis, the procedure is safe, facilitates accurate diagnosis of tumor depth, and limits the need for additional surgery.

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We report a patient with cardiac involvement associated with primary amyloidosis presenting marked left ventricular (LV) wall thickening, severely decreased systolic and diastolic function, and complete atrioventricular block (CAVB), who died suddenly of cardiac arrest caused by electro-mechanical uncoupling occurring immediately after permanent pacemaker implantation. Post mortem examination showed no procedural complications such as cardiac or venous perforation. The heart was densely infiltrated with amyloid fibrils, especially in the extracellular tissues surrounding the papillary vessels.

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Although rheumatoid involvement of the lumbar spine is relatively rare, we report a patient with rapidly progressing cauda equina symptoms due to rheumatoid diskitis. A 72-year-old woman was admitted to our hospital because of motor weakness below the iliopsoas muscle and sensory disturbance beneath the level of L2. Plain X-ray films, computed tomography, and magnetic resonance imaging demonstrated destruction of the L2/3 intervertebral disc and endplates with subluxation of the facet joints. The dural sac was compressed. Based on a diagnosis of spinal canal stenosis due to rheumatoid diskitis, we performed partial laminectomy and posterolateral fusion with pedicle screws. The neurological deficits improved immediately. The mechanism of intervertebral disc destruction in this case is thought to be rheumatoid nodes or enthesitis. Destruction of the facet joints and the intervertebral disc might have led to severe instability and spinal canal stenosis.

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We report a case of cervical spondylitis that developed during treatment with a series of stellate ganglion blocks. A 65-year-old man was scheduled for 10 sessions of stellate ganglion block for treatment of right-sided deafness of sudden onset due to Ramsay Hunt syndrome. Administration of betamethasone was started 5 days before the first block and was continued for 6 weeks. After disinfection of the skin by povidone iodine, each stellate ganglion block was performed via the paratracheal approach. The first four block sessions were uneventful. However, during the fifth session, the patient complained of neck pain. After 10 sessions, the deafness improved and the patient was discharged from the hospital. Three weeks after discharge, he was readmitted for sustained neck and bilateral shoulder pain and numbness of the right hand. Cervical roentgenography and magnetic resonance imaging revealed spondylitis of C5 and C6. Antibiotics were administered for 2 weeks. The inflammatory variables on blood examination improved, but cervical roentgenography performed 8 weeks after the last block showed that the vertebral body of C6 was nearly completely destroyed. Four months after the last block, the vertebral bodies of C5 and C6 had fused. This case indicates that when stellate ganglion block is performed in patients who are taking a corticosteroid, the disinfection procedure must be strictly followed and that if the patient complains of neck or shoulder pain, cervical roentgenography or magnetic resonance imaging or both should be immediately performed to assess the presence of spondylitis.

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We measured the blood concentration of propofol in a patient with delayed emergence from propofol-nitrous oxide anesthesia. A 78-year-old man underwent subtotal gastrectomy under both epidural and propofol-nitrous oxide anesthesia and did not regain consciousness soon after termination of propofol infusion. Preoperative laboratory examination revealed anemia and a low blood total protein concentration, but there was no evidence of impaired liver function. While the anesthesiologists were waiting for the patient to regain consciousness, a surgeon mentioned that the common hepatic artery might have been occluded during surgical manipulation. Arterial blood samples were obtained 50 and 80 minutes after termination of propofol infusion, and the blood concentration of propofol was measured. We considered that clearance of propofol through the hepatic route may have been impaired; however, the actual blood concentrations of propofol were not significantly increased compared with the respective blood concentrations obtained in the simulation. Therefore, the acute liver damage did not significantly impair elimination of propofol. Because most propofol molecules in the blood bind to proteins and erythrocytes, it is suspected that the anemia and low blood total protein concentration led to an increase in the free fraction of propofol in the blood, thereby delaying emergence from anesthesia.

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Calcifications within primary gastrointestinal tumors are rare. Gastrointestinal stromal tumor (GIST) is an unusual nonepithelial tumor that develops in the gastrointestinal tract. In this paper we describe a case of spurt bleeding from a calcificated GIST in the stomach successfully treated by partial gastric resection. A 77-year-old man was admitted for chest discomfort and loss of consciousness. Endoscopic examination revealed spurt bleeding from the top of the submucosal tumor. No other lesions or points of bleeding were found in the stomach. Emergency partial gastrectomy was performed, and the stomach was closed. The cut surface of the tumor had a firm, solid, whitish-gray parenchyma with patchy calcification. Microscopic observation revealed a profusion of spindle-shaped tumor cells with calcification growing from the gastric muscular propria to the submucosa. The cells exhibited low mitotic activity and no prominent signs of nuclear atypia. Immunohistochemical staining of the tumor demonstrated positive reactivity for CD34, KIT, and vimentin, but negative reactivity for α-smooth muscle actin, desmin, and S-100 protein. Tumor cells positive for Mib-1 were rare. The diagnosis of the tumor was established as GIST.

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Nocardial brain abscesses are uncommon and are not preceded by clear infectious symptoms in most cases. Delayed identification of the bacteria is responsible for a high mortality rate. A 58-year-old afebrile woman was admitted to our hospital because of progressive right hemiparesis and aphasia. Magnetic resonance imaging (MRI) showed a single ring-enhanced lesion in the left frontal lobe. It was extremely difficult to establish the diagnosis of brain abscess, because the laboratory data provided little evidence of bacterial infection, ²⁰¹TlCl-scintigraphy revealed definite accumulation of thallium in the lesion, and follow-up MRI demonstrated rapid enlargement of the lesion. Total resection was performed because of the possibility of a malignant brain tumor, but brain abscess was finally diagnosed with histological examination. A nocardial species was detected through microscopic examination of the pus obtained at surgery, and this precise diagnosis of nocardial brain abscess in the early stage enabled the administration of appropriate antibiotics and the patient's quick recovery. Nocardial brain abscesses are often misdiagnosed as malignant brain tumors, and a definitive diagnosis may not be possible without detecting bacteria from the lesion. Total excision of the abscess can produce good results when the abscess is large and located superficially, but incomplete aspiration and drainage of a lesion is associated with a high chance of relapse.

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