A case of primary intrapulmonary thymoma: its entity and the problem of lymph node dissection

Primary intrapulmonary thymomas are defined as primary thymomas arising in an intrapulmonary location without an associated mediastinal component, and they are very rare. A total of 20 cases have been reported only sporadically in the English literature since 1951. We reported the case of 41-year-old woman who had a 3.5 x 3.0 x 3.0 cm lower right lobe mass with nodal metastasis that extended over the left atrium. We also summarized the clinicopathological features of a total of 21 cases and discussed the problems involved with diagnosis, pathogenesis and treatment. Knowledge of the biological behavior of primary intrapulmonary thymomas is limited because of their rarity. In particular, the issue of the need for lymph node dissection has not been adequately discussed. In this case, pathohistological examination revealed that the routes of lymphatic spread and the sites of noda metastases from primary intrapulmonary thymoma resemble those of primary lung cancer. Therefore, systematic mediastinal lymph node dissection according to the lymph node map for primary lung cancer should be recommended for malignant cases.     

Human plasma concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and physiologically based pharmacokinetic modeling

To predict concentrations in humans of the herbicidal carbamate molinate, used exclusively in rice cultivation, a forward dosimetry approach was carried out using data from lowest-observed-adverse-effect-level doses orally administered to rats, wild type mice, and chimeric mice with humanized liver and from in vitro human and rodent experiments. Human liver microsomes preferentially mediated hydroxylation of molinate, but rat livers additionally produced molinate sulfoxide and an unidentified metabolite. Adjusted animal biomonitoring equivalents for molinate and its primary sulfoxide from animal studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and human metabolic data with a simple physiologically based pharmacokinetic (PBPK) model. The slower disposition of molinate and accumulation of molinate sulfoxide in humans were estimated by modeling after single and multiple doses compared with elimination in rodents. The results from simplified PBPK modeling in combination with chimeric mice with humanized liver suggest that ratios of estimated parameters of molinate sulfoxide exposure in humans to those in rats were three times as many as general safety factor of 10 for species difference in toxicokinetics. Thus, careful regulatory decision is needed when evaluating the human risk resulting from exposure to low doses of molinate and related carbamates based on data obtained from rats.     

The current status of perioperative chemotherapy for invasive bladder cancer: a multiinstitutional retrospective study in Japan

Background We conducted a multiinstitutional analysis to clarify the clinical significance of perioperative chemotherapy, in invasive bladder cancers in Japan, and to identify the patient subpopulations who could benefit from perioperative chemotherapy.Methods A total of 913 consecutive patients aged less than 80 years who underwent radical cystectomy for invasive bladder cancer from 1990 to 2000 at 32 Japanese hospitals were retrospectively analyzed. Median follow-up was 3.8 years (range, 0.1 to 11.8 years).Results In total, 341 patients (37.3%) were treated with perioperative chemotherapy, including neoadjuvant chemotherapy (n = 174), adjuvant chemotherapy (n = 114), or a combination of both chemotherapies (n = 53). With cisplatin-based combination chemotherapy, the MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was the one most frequently used for perioperative chemotherapy, but the average number of cycles was distinctly less than that in reported randomized trials. MEC (methotrexate, epirubicin, and cisplatin) chemotherapy had efficacy similar to that of the MVAC regimen. On analysis of patients stratified by stage, the overall survival of patients with adjuvant chemotherapy was significantly better than that of those without adjuvant chemotherapy, in patients with pT2b, pN0 or pT3, pN0 (P = 0.016 or 0.020, respectively), but adjuvant chemotherapy had no, or the opposite, effect on patients with pT2a, pN0, pT4, pN0, or pTany, pN+. On the other hand, neoadjuvant chemotherapy provided a statistically significant survival benefit only for patients with clinical T3N0 (P = 0.015). Of note, in the high-risk subgroup, the overall survival rate for patients with complete response (CR) after neoadjuvant chemotherapy was significantly better than that of patients with partial response (PR) or no change (NC)/progressive disease (PD) (P = 0.043).Conclusion In Japan, cisplatin-based combination chemotherapy has been the main modality adopted perioperatively for high-risk patients with radical cystectomy. This studys clinical results indicated that perioperative chemotherapy may improve survival in patients with T3N0 or pT2b/pT3, pN0 bladder cancer.     

Effects of oxygen tension on tumor colony formations assessed by human tumor clonogenic assay

To clarify the effects of oxygen tension on colony formation of fresh human tumor cells, we examined 25 fresh human tumor samples (sixteen gastric cancers, three colon cancers, three breast cancers, one esophageal cancer, one leiomyosarcoma and one malignant lymphoma), using the human tumor clonogenic assay (HTCA) technique. Three different oxygen tensions (2 per cent, 5 per cent, 20 per cent) were tested. At 5 per cent O2, which is considered to be physiological oxygen tension, 19 out of 26 tumors (13/16 in gastric cancer, 2/3 in colon cancer, 1/3 in breast cancer, 1/1 in esophageal cancer, and 1/1 in leiomyosarcoma) showed significant increases of plating efficiencies as compared to those at 20 per cent O2. On the other hand, decreases in plating efficiencies were observed at 2 per cent O2 in seven out of 12 tumors as compared to 20 per cent O2 and eight out of 12 tumors, as compared to 5 per cent O2.     

Liver function after sevoflurane or isoflurane anaesthesia in neurosurgical patients

Purpose

Although both sevoflurane and isoflurane are thought to be less hepatotoxic than halothane or enflurane, recent case reports have described liver injury after sevoflurane or isoflurane anaesthesia. There are no studies comparing liver function after sevoflurane or isoflurane anaesthesia. The purpose of this study was to compare serum liver enzyme concentrations in patients receiving either sevoflurane or isoflurane anaesthesia prospectively.

Methods

Ninety patients scheduled for elective neurosurgery were studied. Serum concentrations of aspartame aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBil), alkaline phosphatase (ALP), γ- glutamyl transpeptidase (GTP), and lactate dehydrogenase (LDH) were measured before and, 1, 2, 3, 7, and 14 days after either sevoflurane (45 patients) or isoflurane (45 patients) anaesthesia.

Results

AST ALT and GTP increased peaking seven days after anaesthesia, especially in the isoflurane group. The numbers of patients with abnormal values in AST and ALT were not different in the isoflurane from that in the sevoflurane group. The increase in TBil peaked one day after anaesthesia in both groups.

Conclusion

Even in a small number of patients, isoflurane induced an elevation of serum levels of liver enzymes more frequently than did sevoflurane three to 14 days after anaesthesia.     

Inferior vena caval resection for renal cell carcinoma: usefulness of renal venous pressure measurement]

Renal cell carcinoma with extended tumor thrombi densely adherent to the vena caval wall sometimes requires vena caval resection. If the tumor is on the right side and the collateral veins of the left renal vein are abundant, vena caval reconstruction may not be required. We recently performed radical nephrectomy and vena caval resection on 2 right renal cell carcinoma patients. To decide the necessity of vena caval reconstruction, left renal vein pressure was measured before and after clamping of the vena cava. In case 1, because the pressure was elevated from 21 cmH2O, to 61 cmH2O, total replacement with Gore-Tex graft was performed. In case 2, because the pressure change was from 22 cmH2O to 23 cmH2O, reconstruction was not performed. The most important test to decide the necessity of vena caval reconstruction is thought to be the change of renal venous pressure before and after clamping of the vena cava.     

Genotoxicity studies of glycidol fatty acid ester (glycidol linoleate) and glycidol

Glycidol fatty acid esters (GEs) are found in refined edible oils. Safety concerns have been alleged due to the possible release of glycidol (G), an animal carcinogen.     

Effect of sarpogrelate on cardiovascular disorders

The present article, dedicated to Dr NS Dhalla on the occasion of the jubilee of his life’s work, is a brief review of articles based on the authors’ studies of sarpogrelate conducted in collaboration with Dr NS Dhalla. These studies on the effects of sarpogrelate on cardiovascular disorders have been ongoing for more than 10 years, and 10 articles have been published to date.     

Enhanced Percolation and Gene Expression in Tumor Hypoxia by PEGylated Polyplex Micelles

In regard to gene vectors for cancer gene therapy, their percolation into the tumor tissue should be essential for successful outcome. Here, we studied the tumor penetrability of nonviral vectors (polyplexes) after incubation with the multicellular tumor spheroid (MCTS) models and intratumoral (i.t.) injection into subcutaneous tumors. As a result, polyethylene glycolated (PEGylated), core–shell type polyplexes (polyplex micelles) showed facilitated percolation and improved transfection inside the tumor tissue, whereas conventional polyplexes from cationic polymers exhibited limited percolation and localized transfection. Furthermore, the transfection of hypoxia-responsive plasmid demonstrated that polyplex micelles allowed the transfection to the hypoxic region of the tumor tissue in both in vitro and in vivo experiments. To the best of our knowledge, our results demonstrated for the first time that polyplex micelles might show improved tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the tumor tissue.