Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death.

The selective cyclooxygenase-2 (COX-2) inhibitor has been reported to have antiinflammatory, neuroprotective, and antioxidant effects in ischemia models. In this study, the authors examined whether a selective COX-2 inhibitor (celecoxib) reduces cerebral inflammation and edema after intracerebral hemorrhage (ICH), and whether functional recovery is sustained with longer treatment. ICH was induced using collagenase in adult rats. Celecoxib (10 or 20 mg/kg) was administered intraperitoneally 20 minutes, 6 hours, and 24 hours after ICH and then daily thereafter. Seventy-two hours after ICH induction, the rats were killed for histologic assessment and measurement of brain edema and prostaglandin E2. Behavioral tests were performed before and 1, 7, 14, 21, and 28 days after ICH. The brain water content of celecoxib-treated rats decreased both in lesioned and nonlesioned hemispheres in a dose-dependent manner. Compared with the ICH-only group, the number of TUNEL-positive, myeloperoxidase-positive, or OX42-positive cells was decreased in the periphery of hematoma and brain prostaglandin E2 level was reduced in the celecoxib-treated group. Celecoxib-treated rats recovered better by the behavioral tests at 7 days after ICH throughout the 28-day period, and the earlier the drug was administered, the better the functional recovery. Evidence of similar effects in an autologous blood-injected model showed that direct collagenase toxicity was not the major cause of inflammation or cell death. These data suggest that celecoxib treatment after ICH reduces prostaglandin E2 production, brain edema, inflammation, and perihematomal cell death in the perihematomal zone and induces better functional recovery.     

Should all the N3 lymph nodes group metastasis be regarded as distant metastasis (M1) in curatively resected gastric cancer?

Recently, metastasis to N3 lymph nodes group was regarded as distant metastasis by the new TNM staging system due to poor overall survival. However, the 5-year overall survival rate of patients with metastasis to N3 groups was 34.5% after curative surgery. Moreover, in patients with metastasis to lymph node subgroups of #12, #13, #14, the overall 5-year survival rate increased upto 47.2% after curative resection and adjuvant chemotherapy. This was similar to that of the patients with metastasis to N1 and N2 lymph nodes groups. But in these highly tumor burden states, no survival benefit was found with the addition of immunotherapy to chemotherapy as we achieved in stage II and III. Therefore, we suggest that, at least, metastasis to #12, #13, #14 lymph nodes subgroups should not be categorized as a distant metastasis. And in these situations, active curative radical surgery with extended lymphadenectomy and adjuvant chemotherapy are recommended.     

The value of immunohistochemical detection of P-glycoprotein in breast cancer before and after induction chemotherapy.

We have studied the patterns of P-glycoprotein expression before and after 3 cycles of induction chemotherapy (5-fluorouracil, adriamycin and cyclophosphamide) using immunohistochemically stained paraffin-embedded specimen of 28 patients with locally advanced breast cancer. The frequency of P-glycoprotein expression in untreated breast cancer turned out to be very low: only one out of 28 untreated, biopsy specimen at the time of diagnosis was positive. The frequency of P-glycoprotein expression was markedly increased from 9.1% before chemotherapy to 63.6% after induction chemotherapy (p = 0.006). After 3 cycles of induction chemotherapy, 25 patients had obtained clinical response to chemotherapy (4, CR; 21, PR). Eleven out of 25 tumors (44%) showing clinical response and all three tumors (100%) with minimal response have expressed P-glycoprotein. One out of 6 patients (16.7%) with microscopic residual tumor seen in mastectomy specimen expressed P-glycoprotein, whereas 13 of 22 patients (59.1%) with gross residual tumor showed the presence of P-glycoprotein (p = 0.08). The frequency of intrinsic P-glycoprotein expression in untreated breast cancer was quite low, but approximately half of the patients do acquire P-glycoprotein expression during the cycles of induction chemotherapy. Therefore, the results suggest that the immunohistochemical detection of P-glycoprotein on residual tumor cells after induction chemotherapy can predict acquired drug resistance in breast cancer.     

Primary malignant melanoma of the cervical spinal nerve root

The authors report on a case of primary malignant melanoma of the 7th cervical spinal nerve root in a 45-year-old woman. Neuro-radiological features of this extra-dural mass were suggestive of a nerve sheath tumor. The lesion underwent total gross resection through the anterolateral approach. The patient's postoperative course was uneventful. Histopathological investigation confirmed malignant melanoma. There was no evidence of tumor recurrence or other melanotic lesions on regular follow-up examinations until the postoperative eighth month. When treating a common, benign-looking lesion of the cervical spinal nerve root, surgeons should be aware of the potential to encounter such a malignant tumor.     

Hormone replacement therapy in women with pre-existing hyperpigmented lesions

OBJECTIVES: This study was performed to determine whether skin pigmentation is darkened after hormone replacement therapy (HRT). METHODS: The color of hyperpigmentary lesions and control sites before and after 1, 2, and 3 months of HRT was measured. RESULTS: All of the three tested sites showed no significant pigment alteration in 3 months of follow up after starting HRT (P>0.05). Age, duration of menopause, and sex hormone levels did not correlate with pigmentation level. CONCLUSIONS: Pigmentation changes after HRT are not significantly associated with the treatment. This finding suggests that low-dose estrogen replacement therapy does not induce pigmentation changes alone and that differences in individual susceptibility and end organ responsiveness or other multiple factors in addition to the sex hormone may be responsible for the development and darkening of hyperpigmentary lesions.     

Amnesia syndrome following left anterior thalamic infarction; with intrahemispheric and crossed cerebro-cerebellar diaschisis on brain SPECT.

We report a 61-year-old right-handed man developing disturbance of memory after a discrete thalamic infarction. Neuropsychological assessment revealed deficits in memory with retrograde and anterograde components, especially for verbal material. Brain MRI showed a left anterior thalamic infarction with normal angiographic findings. Despite the small lesion in the thalamus, he showed prolonged memory disturbance and a Brain SPECT image revealed decreased uptake in the ipsilateral fronto-temporo-parietal cortex and contralateral cerebellum. This diaschisis, a phenomenon caused by disconnection of the neural pathway helped us to evaluate the functional state of the patient and this imaging technique was valuable for obtaining to get more information for the evaluation of the neurological state and neuronal connections. In conclusion our findings correspond well with the understanding of amnesia as a disconnection syndrome because of the evidence of diaschisis on the Brain SPECT image.     

Anin vitro invasion model for human renal cell carcinoma cell lines mimicking their metastatic abilities

We developed a modifiedin vitro invasion assay system using monolayers of vascular endothelial cells. A type I collagen gel was formed in plastic dishes, and overlaid with type IV collagen. Calf pulmonary arterial endothelial (CPAE) cells were seeded onto these plates, and incubated until they reached confluence. Five human renal cell carcinoma cell lines with various metastatic potentialsin vivo were then seeded on the monolayer CPAE cells, and their colony formation and invasion activities were examined for 9 days. At day 4, the highly metastatic cell lines increased the number of colony foci on monolayer CPAE cells several fold higher than their poorly metastatic counterpart. The horizontal spreading patterns were also different between poorly and highly metastatic cell lines. On day 9, the number of carcinoma foci that penetrated the monolayer of CPAE cells and type IV collagen sheets into type I collagen gels in highly metastatic cell lines greatly increased as compared with that of poorly metastatic cell lines. Ourin vitro invasion assay using monolayer CPAE cells would be useful to evaluate protease activities and colony formation during invasion.