Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.     

Ultraflex expandable stents for the management of air leaks.

Postoperative empyema and aspergillosis were diagnosed in a 66-year-old man. Since non-operative therapy was not effective, we performed surgery. On the 8th postoperative day, a covered Ultraflex expandable stent (Boston Scientific, Galway, Ireland) was implanted to make a one-way airway for blocking a major air leak from a bronchopleural fistula causing respiratory distress. His general condition improved gradually, and he was discharged 30 days after stenting. In conclusion, we used a covered Ultraflex expandable stent to make an airway to block an air leak. This may be a new application for this stent.     

Hepatic Disposition Characteristics of Electrically Charged Macromolecules in Rat in Vivo and in the Perfused Liver

The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C–dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4–3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (E _ss) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The E _ss for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested.     

Intravenous fate of poly(2-(dimethylamino)ethyl methacrylate)-based polyplexes

The objective of this study was to assess the in vivo fate of poly(2-(dimethylamino)ethyl methacrylate) (pDMAEMA)-based polyplexes after intravenous administration into mice. Circulation kinetics and tissue distribution in terms of plasmid localization and transfection efficiency were assessed. To gain more insight into the observed biodistribution and gene expression profile, the interaction of pDMAEMA-based polyplexes with blood components (erythrocytes and albumin) was investigated in vitro. In the case of i.v. injection of positively charged polyplexes at a dose of 30 microg DNA most of the radioactivity was found in the lungs and the liver 60 min after injection. In the case of pDMAEMA/DNA polyplexes with a negative charge, uptake occurred mainly by the liver. Administration of positively charged complexes at a 30 microg DNA dose resulted in reporter gene expression primarily in the lungs. Injection of negatively charged complexes and naked plasmid did not result in luciferase expression in any of the organs examined. In vitro turbidity experiments showed the induction of a charge dependent aggregation process upon addition of albumin to the polyplexes pointing out to the involvement of aggregate formation in the dominant lung uptake of the positively charged polyplexes. Also, incubations of polyplexes after pre-incubation with a physiological concentration of albumin with washed erythrocytes confirmed that polyplexes induce the formation of extremely large structures. This paper underlines the need for the design of systems with reduced interaction with blood components to promote the delivery of DNA to target tissues outside the lungs.     

Pancreatic metastasis of malignant melanoma diagnosed by EUS-guided fine needle aspiration (EUS-FNA)]

Pancreatic metastasis of malignant melanoma is rarely diagnosed while the patient is alive. We report a case of metastatic melanoma of the pancreas in a 35-year-old woman presenting with a solid mass of the pancreas. Her past medical history included a radical hysterectomy 2 years previously for malignant melanoma of the vagina. Twelve months later, lung metastasis was also resected. EUS-guided fine needle aspiration (EUS-FNA) identified that the pancreatic tumor was histologically and immunohistochemically identical to the surgical specimen of her lung neoplasm. Imaging studies including US, CT, and MRI have limited value to distinguish the tumors from primary ductal adenocarcinoma. EUS-FNA can provide tissue diagnosis from pancreatic masses, specifically when other modalities have failed.     

Scintigraphic detection of recurrence of medullary thyroid cancer

A case of recurrent medullary thyroid cancer (MTC) was evaluated with¹²³I-MIBG,^99mTc(V)-dimercaptosuccinic acid (DMSA), and²⁰¹Tl scintigraphy. This patient had been operated on for MTC in the right thyroid. Recently a left neck mass was noticed, and was suspected of being a. recurrence of MTC based on increased plasma calcitonin (CT) and carcinoembryonic antigen (CEA). He was operated on for the neck mass which revealed MTC, and papillary thyroid cancer was incidentally found in the left thyroid, but the CT and CEA levels remained high, and remaining MTC tumor was suspected. But the location of the tumor was unknown. Although^99mTc(V)-DMSA scintigraphy is generally believed to be superior in sensitivity to¹²³I-MIBG scintigraphy, it did not demonstrate the tumor site but²⁰¹Tl and¹²³I-MIBG did. Furthermore,¹²³I-MEBG scintigraphy has greater specificity for tumors which arise in the neural crest. Judging from the results of this case and cases reported in the literatures, both¹²³I-MIBG and^99mTc(V)-DMSA should be performed in the detection of recurrent MTC.     

Molecular oncogene markers and their significance in cutaneous malignant melanoma

Background: Oncogenes and other molecular tumor markers that predict tumor aggressiveness may allow individualization and optimization of surgical therapy of intermediate-thickness malignant melanoma. We examined the expression of selected markers, including the HLA-DR antigen, the heat shock protein-70 (HSP-70), and the c-myc oncogene in primary melanoma and regional nodes and related these findings to metastatic potential and survival. Methods: Forty patients with primary melanoma (1.5–4.0 mm) were studied, all of whom had prophylactic lymph node dissection and were followed for 18 months to 7 years. The primary tissue and nodes were examined using immunohistochemical techniques for the presence of HLA-DR antigen and HSP-70 protein and the expression of the c-myc oncogene. Results: Of 40 patients, there were 23 with lesions 1 to 2.9 mm thick and 17 with lesions 3 to 4 mm thick. Nodal metastases were present in 25 of the 40 patients who had elective node dissection. HLA-DR antibody stained the primary tumor in 10 patients (25%), but there was no correlation with survival in this group. HLA-DR antibody stained the stroma and cellular infiltrates surrounding the primary tumor in 28 of 40 patients; in this group there was a correlation of HLA-DR staining of the peritumoral stroma with improved survival overall. HLA-DR staining of the peritumoral stroma also influenced survival when patients were stratified by tumor thickness groups 1 to 2.9 mm and 3 to 4 mm and presence of nodal metastases. HSP-70 was demonstrated in the primary tumor in 25% of patients, who were also shown to have significantly improved survival when compared with those whose primary tumor did not stain with HSP-70. C-myc was expressed in the primary tumor in 25%, but showed no correlation with survival. None of these proteins correlated with or predicted the presence of nodal metastases. Conclusion: We conclude that the use of specific molecular-oncogene markers in intermediate-thickness primary melanoma may identify patients at high risk for conventional treatment failure and reduced survival who may profit from more aggressive surgery, adjuvant therapy, or both.Presented at the 48th Annual Cancer Symposium of The Society of Surgical Oncology, Boston, Massachusetts, March 23–26, 1995.