Platinum levels in various tissues of a patient who died 181 days after cisplatin overdosing determined by electrospray ionization mass spectrometry

Platinum (Pt) levels were determined in various tissues and body fluids obtained from a patient who died 181 days after cisplatin overdosing. The symptoms of cisplatin overdose, however, might have almost disappeared by day 40, and the patient’s death was ascribed to the recurrence of malignant lymphoma. Determination of Pt derived from cisplatin was performed by electrospray ionization mass spectrometry (ESI-MS) using silver (Ag) as internal standard. Pt and Ag complexed with diethyldithiocarbamate (DDC) in wetashed blood, and tissue solutions were extracted into isoamyl alcohol, and then acidified with oxalic acid. By injecting an aliquot of the isoamyl alcohol layer into a mass spectrometer in the direct flow injection mode, the quantitation was performed using the signals of Pt(DDC)₃ ⁺ and Ag(DDC)₂ ⁺ at m/z 639 and 403, respectively. The Pt levels ranged from 25ng/ml in blood to 2050ng/g wet weight in the liver of the patient, indicating that Pt remained at high levels in tissues, even after a period as long as 181 days after cisplatin overdosing.     

Integrating PET and CT information to improve diagnostic accuracy for lung nodules: A semiautomatic computer-aided method.

Our objective was to develop and evaluate 3 semiautomatic computer-aided diagnostic (CAD) schemes for distinguishing between benign and malignant pulmonary nodules by use of features extracted from CT, 18F-FDG PET, and both CT and 18F-FDG PET. METHODS: We retrospectively collected 92 consecutive cases of pulmonary nodules (<3 cm) in patients who underwent both thoracic CT and whole-body PET/CT. Forty-two of the nodules were malignant and 50 benign, as confirmed by pathologic examination and clinical follow-up. The interval between CT and PET was less than 1 mo. Four clinical parameters, including patient age, sex, smoking status, and history of previous malignancy, were used for the CAD schemes. Sixteen CT features based on size, shape, margin, and internal structure of nodules were independently rated subjectively by 2 chest radiologists. Four PET features were viewed on a PET/CT workstation. CAD schemes based on clinical parameters together with CT features, PET features, and both CT and PET features were then used to differentiate benign from malignant nodules. Finally, the output from the CAD schemes was evaluated by use of receiver-operating-characteristic analysis. RESULTS: When we used clinical parameters and CT features as input units (CAD scheme 1), the area under the receiver-operating-characteristic curve (A(z) value) of the CAD scheme was 0.83. When we used clinical parameters and PET features as input units (CAD scheme 2), the A(z) value for the computer output was 0.91. However, when we used all data as input units (CAD scheme 3), the A(z) value for the computer output was 0.95. The performance of CAD scheme 3 was better than that of CAD scheme 1 or 2. A statistically significant difference existed between the A(z) values of CAD schemes 3 and 2 (P = 0.037) and between those of CAD schemes 3 and 1 (P = 0.015). CONCLUSION: Our CAD scheme based on both PET and CT was better able to differentiate benign from malignant pulmonary nodules than were the CAD schemes based on PET alone and CT alone.     

Myocardial 11C-diacylglycerol accumulation and left ventricular remodeling in patients after myocardial infarction.

Left ventricular (LV) remodeling after myocardial infarction (MI) is a maladaptive process that increases the risk of heart failure and death. The myocardial phosphoinositide cycle, which is located downstream from several neurohumoral factors, plays a crucial role in LV remodeling. Our animal studies demonstrated that 1-[1-11C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) can be used to visualize regions with an activated phosphoinositide cycle. Therefore, we examined whether myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement and systolic dysfunction in post-MI patients. METHODS: We performed PET with 11C-DAG in 13 post-anteroseptal MI patients and 4 healthy volunteers. We placed regions of interest on the noninfarcted myocardium and calculated the myocardium-to-left atrial (LA) chamber ratio of 11C-DAG accumulation. RESULTS: The myocardium-to-LA chamber ratio of 11C-DAG was significantly higher in the post-MI patients (mean +/- SD, 1.73 +/- 0.35) compared with that of the healthy volunteers (mean +/- SD, 1.25 +/- 0.13; P < 0.05). In the post-MI patients, the myocardium-to-LA chamber ratio of (11)C-DAG was significantly correlated with the LV end-diastolic volume index (r = 0.79, P < 0.01) and the plasma concentration of brain natriuretic peptide (r = 0.85, P < 0.001) and negatively correlated with the LV ejection fraction (r = -0.69, P < 0.01). CONCLUSION: These findings suggest that the myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement, LV systolic dysfunction, and humoral activation in post-MI patients. This new imaging strategy based on intracellular signaling may contribute to the assessment and treatment of post-MI patients.     

Surgical outcomes of partial nephrectomy for renal cell carcinoma: A joint study by the Japanese Society of Renal Cancer

OBJECTIVE: A joint study was undertaken by the Japanese Society of Renal Cancer to investigate the present status of partial nephrectomy in Japan and to speculate about what may be the indications for partial nephrectomy in patients with renal cell carcinoma. METHODS: Data were tabulated for 469 patients from participating medical institutions and various clinical factors were investigated with regard to disease progression (local recurrence and distant metastasis). RESULTS: Disease progression was observed in 21 patients (4.5%). No significant relation to disease progression was observed for sex, laterality, tumor histology, grade and tumor size. Although patients with solitary tumors displayed excellent prognosis irrespective of tumor diameter, patients with multiple tumors displayed a high likelihood of disease progression. Patients older than 77 years old and patients with imperative indication were found to have a poorer prognosis. CONCLUSION: In patients with solitary tumors, partial nephrectomy can be actively performed, even if the patient displays elective indications and the tumor is >4 cm in diameter. In patients displaying multiple tumors with imperative indications, the decision whether to perform partial nephrectomy should be made by the patients and their physicians after considering the impact on curability and the quality of life.     

Significance of the hepatic mitochondrial redox state in the development of posttraumatic jaundice

The effect of the hepatic energy status on the development of posttraumatic jaundice (PTJ) was studied to clarify the mechanism of PTJ. Fifty-four patients with severe torso injury who were expected to develop PTJ on admission with an average Injury Severity Score of 27 were selected for this study. They were retrospectively divided into three groups according to their maximum bilirubin concentration by day 10: group H, 12 patients with marked elevation of serum bilirubin (>8 g/dl); group L, 23 with mild bilirubinemia (2–8 g/dl); and group N, 19 with no bilirubinemia (<2 g/dl). Group H patients, in whom trauma-related shock was severe and prolonged, developed severe hyperbilirubinemia, and their arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state and is closely correlated to its energy production, was significantly lower throughout the first week. In contrast, the AKBR increased to an above normal level, indicating enhanced energy production in groups N and L. The serum direct/total bilirubin was also higher in group H. The abnormal hepatic energy metabolism is considered to have reduced the excretion of conjugated bilirubin from the hepatocytes into the bile canaliculi, which is a process that has to proceed against the bilirubin concentration gradient. The subsequent diffusion of the accumulated water-soluble conjugated bilirubin in hepatocytes into the blood is thus considered to be one of the causes of PTJ.     

Gliomatosis cerebri with good prognosis

A 52-year-old man was admitted to our clinic with severe headache and bilateral papilledema. Magnetic resonance (MR) images on admission demonstrated diffuse swelling of the cerebral cortex without formation of a tumor mass. Biopsy revealed diffuse infiltration with neoplastic glial cells. After radiation and chemotherapy, the MR images returned to normal. The morphological and neurological features of the present case met the criteria for gliomatosis cerebri. However, this patient showed an unusually good response to radiation and chemotherapy.