Clinical study on the metastasis to the eyes from breast cancer

In our hospital, 24 patients who underwent surgery for breast cancer during 1980 to 2001 were diagnosed with metastasis to the eye. Metastasis to the choroid was found most frequently, making the choroid the most common site of metastasis. A few patients had metastasis in the orbit. Decreased visual acuity and tunnel vision were frequently found in patients who had metastasis to the choroid, and ocular floaters and blurred vision were also found in a few patients. Patients with metastasis to the orbit showed diplopia caused by ocular dyskinesia and eyelid swelling. The mean postoperative period until the diagnosis with metastasis to the eye was 3 years and 2 months, with most cases diagnosed between 20 and 40 months postoperatively, a relatively long period. We performed radiotherapy in 21 of the 24 patients, and more than half of the patients showed improvement. The mean survival period after diagnosis with metastasis to the eye was 10 months, and most of them already had recurrence to other organs such as the bones or lungs. Examination with consideration of metastasis to the eyes is required to improve the quality of life of cancer patients.     

Promoter methylation profiling of 30 genes in human malignant melanoma

Aberrant methylation and demethylation of promoter CpG islands lead to silencing of tumor-suppressor genes and abnormal expression of normally methylated genes, respectively. Here, we analyzed human melanomas for their methylation and demethylation profiles. Methylation status of core regions in promoter CpG islands was examined for 20 (candidate) tumor-suppressor genes, 4 genes that are not considered as tumor-suppressors, but are frequently silenced in human cancers, and 6 normally methylated melanoma antigen genes (MAGEs). Analysis of 13 melanoma cell lines and 2 cultured normal human epidermal melanocytes (HEMs) showed that 9 tumor-suppressor genes and all 4 non-tumor-suppressor genes were methylated in at least 1 cell line, but never in HEMs, and that all 6 MAGE genes were demethylated in 3 to 13 cell lines. Interestingly, we detected no methylation of MGMT, PTEN, MTAP and p27, which were previously reported as silenced in melanomas. Furthermore, 3 genes that were frequently methylated in the cell lines and 6 MAGE genes were analyzed in 25 surgical melanoma samples. RARB, RASSF1A and 3-OST-2 were methylated in 5 (20%), 9 (36%) and 14 (56%) samples, respectively. MAGE-A1, A2, A3, B2, C1 and C2 were demethylated in 9 (36%), 22 (88%), 20 (80%), 7 (28%), 21 (84%) and 16 (64%) samples, respectively. At least 1 gene was methylated in 18 (72%) samples and at least 1 was demethylated in 24 (96%) samples. No correlation between frequent methylation and frequent demethylation was observed. These profiles showed that both aberrant methylation and demethylation occur widely in human melanomas.     

Meta-analysis of five studies on tegafur plus uracil (UFT) as post-operative adjuvant chemotherapy for breast cancer

Meta-analysis of 5 studies on postoperative breast cancer cases (2 studies on surgery alone vs. tegafur plus uracil (UFT) and 3 studies on tamoxifen (TAM) alone vs. TAM + UFT) were carried out to evaluate the anticancer drug UFT in oral postoperative adjuvant chemotherapy. Of the 1973 patients enrolled, 1898 were eligible and 75 were excluded (exclusion rate 3.8%). There was no bias in major background factors in either the UFT-treated (965) or non-UFT-treated (933) groups. The reduction in the odds of death and the odds of recurrence were 17 +/- 17% (p = 0.33) and 21 +/- 11% (p = 0.060), respectively. Multivariate analysis using Cox's proportional hazards model emphasized the effectiveness of UFT treatment for suppression of recurrence compared with non-treatment with UFT (p = 0.038). Suppression of recurrence was remarkable in the group treated with UFT for 2 years. (the reduction in the odds of recurrence: 23 +/- 11%, p = 0.048) Stratified analysis was applied concerning recurrence, and improved results were obtained in premenopausal cases (the reduction in the odds of recurrence: 33 +/- 11%, p = 0.019). These results suggested that UFT treatment for 2 years was effective as postoperative adjuvant chemotherapy for stage I - IIIA breast cancer for the prolongation of the recurrence-free survival period.     

Diffuse intrahepatic bile duct dilation caused by a very small hepatic cyst

A 72-year-old woman presented to our hospital with diffuse dilation of the intrahepatic bile ducts. Imaging studies revealed a solitary hepatic cyst, 3 cm in diameter, in segment 4 of Couinaud's category of the liver, riding on the hilar hepatic duct. Deroofing of the hepatic cyst was performed, and the dilation of the intrahepatic bile ducts was attenuated. We concluded that even a very small solitary hepatic cyst might cause stenosis of the common hepatic duct, if it is located just above the hepatic hilum. Received: March 1, 2002 / Accepted: October 17, 2002 RID="*" ID="*" Offprint requests to: T. Inaba     

MuSC is involved in regulating axonal fasciculation of mouse primary vestibular afferents

Regulation of axonal fasciculation plays an important role in the precise patterning of neural circuits. Selective fasciculation contributes to the sorting of different types of axons and prevents the misrouting of axons. However, axons must defasciculate once they reach the target area. To study the regulation of fasciculation, we focused on the primary vestibulo-cerebellar afferents (PVAs), which show a dramatic change from fasciculated axon bundles to defasciculated individual axons at their target region, the cerebellar primordium. To understand how fasciculation and defasciculation are regulated in this system, we investigated the roles of murine SC1-related protein (MuSC), a molecule belonging to the immunoglobulin superfamily. We show: (i) by comparing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil) labelling and anti-MuSC immunohistochemistry, that downregulation of MuSC in PVAs during development is concomitant with the defasciculation of PVA axons; (ii) in a binding assay with cells expressing MuSC, that MuSC has cell-adhesive activity via a homophilic binding mechanism, and this activity is increased by multimerization; and (iii) that MuSC also displays neurite outgrowth-promoting activity in vestibular ganglion cultures. These findings suggest that MuSC is involved in axonal fasciculation and its downregulation may help to initiate the defasciculation of PVAs.     

A long surviving case of resected gastric cancer presenting with a synchronous adrenal metastasis

Received for publication on Jan. 28, 1999; accepted on May 29, 1999     

Rapid deflation of the bronchial cuff of the double-lumen tube after decreasing the concentration of inspired nitrous oxide

Deflationary phenomena of the endotracheal tube cuff may occur after inspired nitrous oxide (N(2)O) concentrations are reduced, but deflationary phenomena of the double-lumen tube (DLT) cuff have not been investigated. In this study, tracheal and bronchial cuffs of left-sided Mallinckrodt (Athlone, Ireland) DLTs were inflated with air, 40% N(2)O, or 67% N(2)O (Air, N40, or N67 groups, respectively) in 24 patients undergoing thoracic surgery; 40 min later, O(2) was substituted for N(2)O in some of the patients in the N40 group (N40-c group). Intracuff gas volumes, N(2)O concentrations, and cuff compliance were also measured. Both tracheal and bronchial cuff pressures significantly increased in the Air group but decreased in the N67 group. Neither pressure significantly changed in the N40 group, but both decreased in the N40-c group after terminating N(2)O anesthesia; the time required for bronchial cuff pressures to decrease by half (12.0 +/- 5.5 min) was less than that for tracheal cuff pressures (31.2 +/- 11.0 min, P < 0.01). The volume change in the N40-c group was not significantly different between the tracheal and bronchial cuffs, but tracheal cuff compliance was significantly higher than bronchial compliance. Therefore, filling DLT cuffs with 40% N(2)O stabilizes cuff pressure during anesthesia with 67% N(2)O, but bronchial cuffs deflate more quickly than tracheal cuffs after cessation of N(2)O administration through smaller compliance. IMPLICATIONS: We demonstrated that after cessation of nitrous oxide (N(2)O) administration, bronchial N(2)O-filled cuffs of the double-lumen tube deflate more rapidly than tracheal cuffs. To avoid insufficient separation of the lungs by the bronchial cuff, a frequent check of the cuff pressure is recommended after the inspired N(2)O concentration is decreased.