Intraosseous microcystic meningioma

Extradural ectopic meningioma is a rare tumor. We report on an example of microcystic meningioma arising in the skull of an elderly woman. Radiological examination revealed a localized osteolytic lesion in the left parietal bone. At surgery, it was discovered that the tumor was located within the skull without any evidence of extraosseous extension. The light microscopic, immunohistochemical and ultrastructural features were consistent with a microcystic variant of meningioma. To our knowledge, this is the first case of an intraosseous microcystic meningioma, and we believe that this type of meningioma should be considered in the differential diagnoses of myxoid bone tumors of the calvarium. Received: 10 January 2000 Revision requested: 21 February 2000 Revision received: 8 March 2000 Accepted: 13 March 2000     

Endocannabinoid system modulates relapse to methamphetamine seeking: possible mediation by the arachidonic acid cascade.

We clarified the modulating action of the endocannabinoid system, and its possible mediation by the arachidonic acid cascade, on the reinstatement of methamphetamine (METH)-seeking behavior, using the intravenous self-administration paradigm in rats. Following 12 days of self-administration of METH, the replacement of METH with saline resulted in a gradual decrease in lever press responses (extinction). Under extinction conditions, METH-priming or re-exposure to cues previously paired with METH infusion markedly increased the responses (reinstatement of drug-seeking). The cannabinoid CB1 receptor antagonist, SR141716A, blocked this behavior. Although the cannabinoid agonist, Delta8-tetrahydrocannabinol (THC), had no effects by itself, coadministration of the agonist and METH at small doses reinstated the drug-seeking behavior. THC attenuated the effects of the reinstatement-inducing dose of METH, but enhanced the effect of cues. Either given repeatedly during the extinction or singly, 24 h before the first METH-priming or cues challenge, THC suppressed the reinstatement. In another set of experiments, we found that diclofenac, a cyclooxygenase inhibitor, also attenuated the reinstatement induced by exposure to cues or drug-priming. These results suggest that the endocannabinoid system, through possible mediation by the arachidonic acid cascade, serves as a modulator of the reinstating effects of METH-priming and cues. Extending the current view on the treatment of drug dependence, these results indicate that endocannabinoid-activating substances as well as cyclooxygenase inhibitors may be promising as antirelapse agents.     

Nitroglycerin treatment may enhance chemosensitivity to docetaxel and carboplatin in patients with lung adenocarcinoma.

PURPOSE: Nitroglycerin may improve the response to chemotherapy in advanced non-small cell lung cancer. The effects and mechanisms of nitroglycerin on the enhancement of chemosensitivity to docetaxel and carboplatin regimen (DCb) in patients with lung adenocarcinoma have not been reported. EXPERIMENTAL DESIGN: Seventeen patients with operable lung adenocarcinoma and stable angina pectoris were selected to investigate the effects of nitroglycerin on immunoreactivity for hypoxia-inducible factor 1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), P-glycoprotein (P-gp), the production of which is regulated by HIF-1, and p53 proteins in their resected tumor by semiquantitative immunohistochemical analyses. Eight of 17 patients were treated with nitroglycerin patches before operation, but 9 of 17 patients were not. Furthermore, to study the relationship between changes in plasma VEGF levels by nitroglycerin treatment and response to DCb, 29 patients with advanced lung adenocarcinoma were treated with nitroglycerin for 3 days before chemotherapy using DCb. RESULTS: The rates of immunoreactive cells for HIF-1alpha, VEGF, and P-gp in tumor tissues treated with nitroglycerin were lower than those without nitroglycerin, but those for p53 were not different between those treated with and without nitroglycerin. Furthermore, the rates of immunoreactive cells for VEGF and P-gp proteins were significantly associated with those for HIF-1alpha in tumor tissue. The magnitude of decrease in plasma VEGF levels after treatment with nitroglycerin was significantly associated with response to DCb in patients with advanced lung adenocarcinoma. CONCLUSIONS: Nitroglycerin treatment may improve response to DCb in patients with lung adenocarcinoma, partly through decreasing VEGF and P-gp production via reduction of HIF-1alpha.     

Overexpression of MET is a new predictive marker for anti-EGFR therapy in metastatic colorectal cancer with wild-type KRAS

Purpose

Since the KRAS mutation is not responsible for all metastatic colorectal cancer (mCRC) patients with resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy, new predictive and prognostic factors are actively being sought.

Methods

We retrospectively evaluated the efficacy of anti-EGFR MoAb-based therapies in 91 patients with mCRC according to KRAS, BRAF, and PIK3CA mutational status as well as PTEN and MET expression.

Results

In the patient group with wild-type KRAS, the presence of BRAF mutation or PIK3CA mutations was associated with lower disease control rate (DCR), shorter progression-free survival (PFS), and shorter overall survival. Patients with MET overexpression also showed lower DCR and shorter PFS when compared with patients with normal MET expression. In a separate analysis, 44 patients harboring wild-type KRAS tumors were sorted into subgroups of 25 patients without abnormality in three molecules (BRAF, PIK3CA and MET) and 19 patients with abnormality in at least one of these three molecules. The former group showed significantly higher DCR and longer PFS following anti-EGFR therapy than the latter group.

Conclusions

Our data point to the usefulness of MET overexpression, in addition to BRAF and PIK3CA mutations, as a new predictive marker for responsiveness to anti-EGFR MoAbs in mCRC patients with wild-type KRAS. This study also suggests that application of multiple biomarkers is more effective than the use of a single marker in selecting patients who might benefit from anti-EGFR therapy.     

Phase II study of sequential high-dose methotrexate and fluorouracil combined with doxorubicin as a neoadjuvant chemotherapy for scirrhous gastric cancer

Background. The prognosis of scirrhous gastric cancer remains poor when it is treated with surgical resection alone or chemotherapy alone. A phase II study of sequential high-dose methotrexate and fluorouracil, combined with doxorubicin, as a neoadjuvant chemotherapy was conducted in an attempt to evaluate the efficacy of this regimen in improving the survival of patients with scirrhous gastric cancer. Methods. Patients were eligible if they had potentially resectable scirrhous gastric cancer with adequate organ functions and no prior treatment. The treatment schedule consisted of methotrexate (1 g/m², day 1) fluorouracil (1.5 g/m², day 1), leucovorin (15 mg/m², days 2–4), and doxorubicin (30 mg/m², day 15), repeated at a 28-day interval, and followed by radical surgery. Results. A total of 20 eligible patients were registered. Objective responses in the neoadjuvant chemotherapy segment were observed in 3 of the 20 (15%) patients. No complete remission was observed. The neoadjuvant chemotherapy was associated with grade 3 or 4 neutropenia in 14 of the 20 (70%) patients. The median time from the initial therapy to the operative day was 82 days. Thirteen of the 20 (65%) patients underwent curative resection. No treatment-related deaths occurred. However, the 2-year survival rate in this treatment program (25%) did not show any superiority over that in historical controls. Conclusions. Sequential high-dose methotrexate and fluorouracil, combined, with doxorubicin, as a neoadjuvant chemotherapy for scirrhous gastric cancer did not improve the survival rate in spite of improving the curative resection rate. Received: August 2, 2001 / Accepted: September 27, 2001     

Primary Gastric Carcinoma Cells Frequently Lose Heterozygosity at the APC and MCC Genetic Loci

Loss of heterozygosity (LOH) at APC and MCC gene loci (both mapped to 5q21) was investigated in 24 surgical specimens of primary gastric carcinomas using the polymerase chain reaction after tumor cell enrichment by cell sorting based on differences in DNA content. LOH at APC and/or MCC was detected in 87% (13/15) of the cases; at the APC in 86% (12/14) and at the MCC locus in 100% (7/7). LOH at the APC locus was always accompanied by LOH at the MCC locus. LOH at the APC and/or MCC was found in both differentiated and undifferentiated types in both early and advanced stages of gastric carcinoma. Thus, LOH at APC and/or MCC is considered to be one of the most prevalent genetic alterations in human gastric carcinoma and occurs at an early stage of the carcinogenesis.     

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.     

Abdominal aortic calcification is associated with Fibrosis‐4 index and low body mass index in type 2 diabetes patients: A retrospective cross‐sectional study

Aims/IntroductionThis study aimed to clarify the nature of the relationship between the abdominal aortic calcification (AAC) grade and the presence of cardiovascular diseases, and determine factors related to AAC grade in people with type 2 diabetes mellitus.Materials and MethodsThis retrospective cross‐sectional study enrolled 264 inpatients with type 2 diabetes mellitus. The AAC score and length were measured using the lateral abdominal radiographs. Logistic regression models were used to assess the associations between AAC scores/lengths and the presence of coronary artery disease (CAD), cerebral infarction (CI) and peripheral artery disease (PAD). The correlation between AAC scores/lengths and other clinical factors were evaluated using linear regression models.ResultsThe AAC score was significantly correlated with prevalent CAD and CI independent of age and smoking, but not with the prevalence of PAD. AAC length was not significantly correlated with the presence of CAD, CI or PAD; however, the sample size was insufficient to conclude, probably due to low prevalence. Both the AAC score and length were correlated inversely with body mass index (BMI) and, with the Fibrosis‐4 (Fib‐4) index >2.67; these correlations were significant after adjusting for cardiovascular risk factors and BMI, although AAC was not associated with ultrasonography‐diagnosed fatty liver. There was a significant interaction between BMI and Fib‐4 index; lower BMI and Fib‐4 index >2.67 showed a synergistic association with high AAC grade.ConclusionsAAC score is associated with CAD and CI morbidity in participants with type 2 diabetes mellitus. Low BMI and Fib‐4 index >2.67 can be valuable indicators of AAC in people with type 2 diabetes mellitus.