Correlation of amino-acid uptake using methionine PET and histological classifications in various gliomas

OBJECTIVE: The uptake of L-methyl-11C-methionine (MET) by gliomas is greater than that by intact tissue, making methionine very useful for evaluation of tumor extent. If the degree of malignancy of brain tumors can be evaluated by MET-PET, the usefulness of MET-PET as a means of diagnosing brain tumors will increase. METHODS: We performed this study on 67 glioma patients between 3 and 69 years of age (36 males and 31 females). Tumors included diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, ependymoma, oligodendroglioma, medulloblastoma, dysembryoplastic neuroepithelial tumor, choroid plexus papilloma, central neurocytoma, optic glioma, gliomatosis cerebri, pleomorphic xanthoastrocytoma, and ganglioglioma. Tumor activity and degree of malignancy were evaluated using Ki-67LI (LI: labeling index) and Kaplan-Meier survival curves. The correlations between methionine uptake and tumor proliferation (tumor versus contralateral gray matter ratio (T/N) and Ki-67LI) were determined for the group of all subjects. The existence of significant correlations between T/N and Ki-67LI and between SUV and Ki-67LI was determined for astrocytic tumors. Receiver operating characteristics (ROC) analysis of T/N and standardized uptake value (SUV) was performed for the group of astrocytic tumors. We also determined the ROC cut-off levels to ensure high accuracy of the analysis. RESULTS: For the 67 cases of glioma, the degree of accumulation was variable. Ki-67LI differed significantly between the high-grade group and low-grade group at T/N levels between 1.5 and 1.8 on analysis using tumor proliferative potential (p = 0.019-0.031). The prognosis differed significantly between the high-grade and low-grade groups when T/N was in the range of 1.6-1.8 (p = 0.028-0.032). The accuracy thus calculated was highest (85.7%) when T/N was 1.5 as determined by ROC analysis. CONCLUSIONS: When analysis was confined to cases of astrocytic tumor, a correlation was noted between methionine accumulation and Ki-67LI. For the astrocytic tumors, T/N ratio seemed to be more useful as a diagnostic indicator than SUV. The cut-off level of T/N ratio for distinction between high-grade and low-grade astrocytoma appears to lie between 1.5 and 1.6.     

A case of diffuse hepatic angiosarcoma diagnosed by FDG-PET

A 76-year-old woman was admitted to our hospital with a 2-month history of increasing abdominal distension, leg edema, and dyspnea. The serum transaminase level was about twice the upper limit of normal. The CT showed no tumor. Fluorine-18 2-deoxy-2-fluoro-D-glucose (FDG)-positron emission tomography (PET) showed diffuse abnormal accumulation throughout the entire liver. She was diagnosed by histopathological examination as having hepatic angiosarcoma causing veno-occlusive disease (VOD). This is the first report of hepatic angiosarcoma with FDG-PET.     

A guide to initial management of minor head injury

We reviewed the records of 1,335 minor head injury patients with initial Glasgow Coma Scale (GCS) scores of 15 treated by our neurosurgery service between January 1998 and December 2000. Skull X-ray was performed in 945 patients (71%), and Computed tomography (CT) was performed in 590 patients (44%). Skull fracture was shown radiographically in 24 patients (2.5%), and abnormalities on the initial CT were seen in 29 patients (4.9%). The most frequent intracranial lesion on CT was acute epidural hematoma with skull fracture. Significantly more intracranial lesions were found in those with a fracture than in those without by chi2 analysis. Post-traumatic vomiting was significantly associated with radiographical abnormalities, but headache and nausea did not increase the risk of skull fracture and intracranial lesions on the CT. Patients required neurosurgical intervention in 4 cases, and all of those were acute epidural hematoma with skull fracture. In this study, the first thing we should do for asymptomatic minor head injury patients with a GCS score of 15 is to investigate the presence of a skull fracture by skull X-ray. Head trauma patients with a skull fracture and post-traumatic vomiting should undergo CT to facilitate detection of intracranial lesions, even when there are no abnormal neurological signs.     

Intraperitoneal chemotherapy against peritoneal carcinomatosis of gastric cancer with activated carbon particles adsorbing mitomycin C for four patients

Activated carbon particles adsorbing mitomycin C (MMC-CH) was administered to four patients with peritoneal carcinomatosis of gastric cancer into their abdominal cavities. Tumor markers of CEA, CA19-9, CA125, CA72-4 and STN were measured before and after the administration. The waist of each patient was also measured. After the administration of MMC-CH, tumor markers of three out of the four patients were decreased and a large amount of ascites of all patients had disappeared. The appetite of all four patients had increased and complaints such as nausea and vomiting had decreased. The mean survival of the four patients was 291.2 days (123-542 days). Our results suggested that MMC-CH had an anti-tumor effect of peritoneal carcinomatosis and improved the QOL of patients with a large amount of ascites.     

Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2002

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 899 strains of Gram-positive bacteria, 1500 strains of Gram-negative bacteria, and 158 strains of anaerobic bacteria obtained from 28 medical institutions during 2002 was measured. The results were as follows; 1. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MIC90 of MEPM against Pseudomonas aeruginosa was the lowest of the drugs tested. MEPM showed low cross-resistant rate against both imipenem-resistant P. aeruginosa and ciprofloxacin-resistant P. aeruginosa. MEPM was active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE). 2. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli and 1.9% (2 strains) in Klebsiella pneumoniae. Carbapenems including MEPM were active against these ESBL strains. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem; at present, 7 years after available for commercial use.     

Changes in serum levels of hepatitis C virus genotype 1b monitored by real-time quantitative polymerase chain reaction as a predictor of long term response to interferon-alpha treatment

OBJECTIVE: The aim of this study was to find whether there is a relationship between the changes in the amounts of hepatitis C virus (HCV) at the start of interferon treatment and the long term response to therapy. METHODS: In 20 patients with HCV genotype 1b each given 880 MU of interferon-alpha, the changes in serum HCV RNA during the first 2 wk of therapy were monitored by real-time quantitative polymerase chain reaction (PCR). RESULTS: Real-time quantitative PCR detected HCV RNA at 10(1)-10(8) copies/ml. Serum HCV RNA decreased rapidly between 8 and 24 h after the first administration (first phase) and more slowly thereafter (second phase), with median exponential decays of 2.14 and 0.11 log10/day, respectively. Four patients had sustained virological responses, nine patients had transient responses, and seven patients had no responses. The differences in the rate of first-phase viral decline among the three groups were not significant (p = 0.34), but the differences in the rate of second-phase viral decline were significant (p = 0.0004); the median viral decline (interquartile range) in the second phase was 0.48 (0.42-0.50) log10/day in patients with sustained responses, 0.16 (0.10-0.19) log10/day in patients with transient responses, and 0.026 (0.017-0.040) log10/day in patients with no responses. CONCLUSIONS: Changes in serum levels of HCV genotype 1b in the first 2 wk of interferon-alpha treatment, monitored by real-time quantitative PCR, can be used for prediction of the long term therapeutic response.     

Therapeutic effect of camostat mesilate on Duchenne muscular dystrophy in mdx mice

Duchenne muscular dystrophy is known to be caused by a defective gene of dystrophin, a 427-kDa cytoskeletal protein, but the effective therapeutic drug is presently unavailable. We previously reported that a trypsin-like protease designated as dystrypsin is markedly activated in the muscle microsomal fraction immediately before onset of the clinical signs in mdx mice, a dystrophin-deficient hereditary animal model for human Duchenne muscular dystrophy. In order to examine the possible participation of dystrypsin in the occurrence of the disease, we investigated the therapeutic effects of dystrypsin inhibitors on the occurrence and progress of muscular dystrophy. Here, we show that camostat mesilate, a low-molecular-weight inhibitor of trypsin-like proteases, including dystrypsin, is a candidate drug for Duchenne muscular dystrophy.     

A case of advanced gastric cancer attaining histological CR of paraaortic lymph node after TS-1/CDDP neoadjuvant chemotherapy

A 60-year-old male complaining of anemic symptoms went through examinations and was diagnosed with gastric cancer (cardia, type 3', cT2, cN3, cH0, cP0, cM0, cStage IV). Further inspection showed multiple lymph node metastases, including, No. 1, 3, 7, 11, and 16 (paraaortic LNs). Poor prognosis was predicted, yet we tried neoadjuvant chemotherapy (NAC) expecting down staging of the tumor. With the efficacy and safety previously proven, we chose TS-1 + CDDP as NAC regimen. TS-1 (tegafur gimestat otastat potassium, = 80 mg/m2) was administered orally for 21 days, followed by CDDP (cisplatin, = 60 mg/m2) i.v. on day 9. One course was completed without any significant adverse effects. The tumor itself showed PR-MR to the chemotherapy, but all the lymph nodes were expected to attain PR from CT findings. Total gastrectomy, lymph node dissection (D3) with Roux-en-Y reconstruction was performed, and histological re-evaluation was made. Macroscopically, the stomach seemed to be penetrated into serosa by the tumor, i.e., se invasion was suggested, yet histologically no cancerous cells were detected within mp and ss layer. Many of the lymph nodes were replaced with fibrosis, some with normal lymph node structure remained. Definitely no malignant cells were detected throughout all the lymph node specimens (Grade 3). Because pathological CR of paraaortic lymph nodes has never been reported previously, this case shows TS-1 + CDDP as a promising NAC regimen for advanced gastric cancer, in a sense that tumors once diagnosed as inoperable would still have the possibility of CR.     

Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma

Unlike other types of cancer, hepatocellular carcinoma (HCC) is usually preceded by chronic inflammation caused by viral infection. The mutation of mitochondrial DNA (mtDNA) in hepatocarcinogenesis associated with viral infection was investigated. Compared with control liver tissue, the frequency of mtDNA mutations was markedly increased in both noncancerous and cancerous liver specimens from individuals with HCC. The accumulation of mtDNA mutations in HCC tissue reflected the degree of malignancy. The frequency of mtDNA mutations in HCC tissue was also greater than that described previously for other types of tumors. These observations suggest that the repeated destruction and regeneration of liver tissue associated with chronic viral hepatitis lead to the accumulation of mtDNA mutations. The genetic instability that results in the high rate of mtDNA mutation in cancerous liver tissue is also consistent with the multicentric hepatocarcinogenesis detected clinically.     

Two cases of histopathologically advanced (stage IV) early gastric cancers

We report two cases of early gastric cancer with distant metastases (stage IV). At our institute 1428 cases of primary gastric cancer were resected between 1980 and 1997; 536 were diagnosed as early gastric cancer based on the resected specimens (304 cases of mucosal cancer, Tis--TNM classification--and 232 of submucosal cancer, T1). 528 of these 536 cases were classified as histological stage I, six as stage II, none as stage III and two as stage IV. The incidence of stage IV early gastric cancer was 0.14% of all gastric cancers and 0.37% of the early gastric cancers. The two patients with stage IV early gastric cancer were women. Both tumors were defined as early cancer because they were confined to the submucosa. One was a type 0 IIc + III early cancer, histologically classifiable as a small, moderately differentiated adenocarcinoma (tub2 according to the Japanese Classification of Gastric Carcinoma, G2; TNM classification: ICD-O C16), size 10 x 8 mm; the other was a surface spreading type 0 IIc, classifiable as a signet-ring cell carcinoma (sig, G3), size 50 x 35 mm. Stage IV factors were N3 in the first and ovarian metastasis (Krukenberg tumor) in the second case.