Hair shaft miRNA‐221 levels as a new tumor marker of malignant melanoma

miRNA‐221 (miR‐221) is known to be abnormally expressed in many human cancers. The serum levels of miR‐221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR‐221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR‐221 levels could be a marker for MM. The hair shaft miR‐221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR‐221 levels above the cut‐off value were comparable to those of serum 5‐S‐CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR‐221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR‐221 and MM, and may provide a new, non‐invasive way to screen for melanoma.     

LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Preoperative concurrent chemotherapy and radiation therapy followed by surgery for esophageal cancer.

Currently, the most promising strategy to improve the prognosis of advanced esophageal cancer is preoperative chemoradiation (CRT) followed by surgery. The superiority of CRT over radiation therapy alone has been demonstrated by several randomized studies. Many phase II studies of CRT followed by surgery have shown that the pathologic complete response (CR) rate ranges from 17 to 40%, and the median survival time (MST) is 12 to 31.3 months. Five randomized trials have compared preoperative CRT followed by surgery with surgery alone for resectable esophageal cancer, and four of them did not find any significant survival benefit for the combined treatment group. There are several issues in interpreting these findings, such as the quality of the surgery, the accuracy of the preoperative staging, the statistical power and design of the trials. Until comprehensive evaluation can be done, the standard therapy for resectable esophageal cancer should be considered to be surgery alone. The histological response in the resected specimen correlates well with the prognosis. Patients with pathologic CR display significantly better survival than those with microscopic residual cancer cells in the resected specimens. These findings suggest that more potent regimens leading to higher pathologic CR rates should improve the prognosis. Chemotherapy or radiation therapy sensitivity testing needs to be established. If accurate prediction of the response is possible prior to therapy, non-responders can be excluded. Cell cycle-related genes, apoptosis-related genes, and drug metabolizing genes have been investigated in many pilot studies and need to be evaluated by large-scale clinical studies. At present, pathologic CR can not be accurately diagnosed before surgery. Endoscopic biopsy is also unreliable for the diagnosis. In the future, new diagnostic tools such as positron emission tomography scanning, a sensitivity test or molecular markers may enable accurate diagnosis of pathologic CR to guide the choice of treatment strategies for individual patients.     

Effect of non-enzymatic glycosylation and heating on browning of human stratum corneum and nail.

The purpose of the present study was to examine the effect of non-enzymatic glycosylation and subsequent heating on the browning of the plantar stratum corneum and the finger-nail, and to elucidate the pathogenesis of the yellow skin and the yellow nail seen in diabetic subjects. We incubated stratum corneum and nail from non-diabetics in 0 (control), 10 (only nail), 20 (only nail), 100 and 250 mM glucose buffer at 37 degrees C for 5 days. These glycosylated samples were dialysed against distilled water for 96 h. Distilled water was changed every 24 h. Then samples were dried for 24 h. The extent of non-enzymatic glycosylation was measured by furosine content. Each 5 mg of sample was hydrolysed by 6 N HCl and processed for measurement of furosine by high-performance liquid chromatography. The rest of each sample was stored at 37, 42 (only nail), 47 and 52 degrees C for 14 days. Browning of the stratum corneum was assessed macroscopically, and that of the nail by spectrophotometry. Based on their spectrophotometric reflectances. Munsell's scores (H = hue score, V = lightness score, C = saturation score) and (H + C)/V were calculated for objective evaluation of browning. Incubation of the stratum corneum and nail with glucose buffer increased their non-enzymatic glycosylation (furosine) dose dependently. Macroscopically, the browning of the stratum corneum was enhanced in proportion to the glucose concentration and storage temperature. However, samples incubated in 10 and 20 mM glucose and stored at 42 degrees C did not show visible browning. Munsell's score of the nail samples treated by glycosylation and heating showed increased hue and saturation but reduced lightness. (H + C)/V values of these nail samples were significantly higher than those of the control. We could not detect any fluorescence with Wood light in the browned samples. The present in vitro study demonstrated that the browning of the stratum corneum and the nail depended on the extent of both non-enzymatic glycosylation and storage temperature. We suggested a hypothesis that the non-enzymatic glycosylation and the storage temperature of the stratum corneum and the nail might be a contributory factor in the development of yellow skin and yellow nail in diabetic patients.     

A pilot study of the assessment of the quality of life, functional results, and complications in patients with an ileal neobladder for invasive bladder cancer

OBJECTIVE: To assess the functional results, health-related quality of life (QOL) outcomes, and complications in patients with an ileal neobladder in comparison to those with cutaneous diversion (ileal conduit and cutaneostomy). METHODS: Between September 1992 and February 2003, we consecutively performed an ileal neobladder (the Studer method) in 30 patients and cutaneous diversion in 38 patients. In August 2004, questionnaires were mailed to 54 patients. The questionnaire included the validated health-related quality of life (QOL) questionnaire, SF-36 General Health Survey, and a urinary incontinence questionnaire. We also evaluated the functional results in patients with an ileal neobladder and the postoperative complications in patients with both urinary diversions. RESULTS: The data from 41 patients (21 ileal neobladder procedures and 20 cutaneous diversions) were available for the analysis. No differences in the overall QOL were observed between the two groups. Complete daytime and night-time urinary continence was achieved in the 21 patients (100%) and 13 patients (61.9%), respectively. The mean value of the maximum flow rate was 15 +/- 12 mL/min in the 21 neobladder patients. There were 19 early complications in 18 patients (60.0%) and seven late complications in six patients (20.0%) with an ileal neobladder. However, there were 15 early complications in 14 patients (36.8%) and eight late complications in six patients (15.8%) with cutaneous diversions. CONCLUSION: The findings regarding the health-related QOL and the frequency of complications in the neobladder group and those in the cutaneous diversion group were similar. However, the functional results and the status of urinary continence in the neobladder patients were satisfactory.     

Histological study of effect of bone morphogenetic protein derived from bovine tooth on periosteum in rats

Summary In this study, we examined histologically the effect of a bone morphogenetic protein (BMP) derived from bovine tooth on the periosteum. Supraperiosteal injection of crude BMP into femurs of Wistar rats (28 day old) resulted in periosteal cell proliferation with subsequent bone and cartilage formation. Moreover, proliferating periosteal cells migrated into injected BMP, and formed both cartilage and bone. These observations show that exogenous BMP stimulates mesenchymal cells of the periosteum to proliferate and differentiate into osteoblasts, and therefore BMP may be one of factors which are involved in differentiation of osteoblasts in the periosteum.