Protective effects of a prostaglandin E1 oligomer on taurocholate-induced rat pancreatitis

Effects of prostaglandin E (PGE) on acute pancreatitis have been controversial. This study shows the effects of PGE1 oligomer, MR-356, on trypsin-taurocholate-induced acute pancreatitis in rats. Divided intraperitoneal doses of 0.6 mg/rat were administered, which increased 24 h survival rates when the oligomer was given both at 1 h before and after (group A) and immediately and 3 h after (group B) induction of pancreatitis. In group A MR-356 significantly improved the survival rates at 18 h (94 vs 61%, P < 0.05) and 24 h (68 vs 33%, P < 0.05) when compared with controls. MR-356 improved the survival rates dose-dependently up to 0.6 mg/rat when given by the same protocol of group A. In group B MR-356 also improved the survival rate (72 vs 39%, P < 0.05) only at 24 h, while other parameters failed to improve. The present results suggest that the PGE1 oligomer may play a beneficial role in bile-induced pancreatitis, probably through its proposed effects of stabilization of lysosomal membranes, maintenance of microcirculation and inhibition of protease in the pancreas.     

Proliferative activity and genetic changes in adrenal cortical tumors examined by flow cytometry, fluorescence in situ hybridization and immunohistochemistry

BACKGROUND: To determine differences in biological features among different adrenal tumors, we investigated the DNA ploidy, numerical chromosomal aberration and proliferative activity in human adrenal cortical neoplasms. METHODS: Our study included six adrenal cortical adenomas with Cushing syndrome, 12 adenomas with hyperaldosteronism, three non-functioning adenomas and three adrenal cortical carcinomas. Isolated nuclei from frozen samples were used for fluorescence in situ hybridization (FISH) analysis, and formalin-fixed, paraffin-embedded tissues from the same materials were analyzed using flow cytometry (FCM) for DNA ploidy. Sections from paraffin blocks were stained immunohistochemically with antibodies against Ki-67 and p53. For FISH analysis, we used an alpha-centromeric enumeration probe for chromosome 17. RESULTS: The mean Ki-67 labeling index (LI) of adrenal cortical carcinomas was markedly higher than that of adrenal cortical adenomas (209.4 vs 8.7). In functional adrenal cortical adenomas, the LI was significantly lower in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004), although FCM results indicated that tetraploid patterns were more frequently observed in the former type. Tumor size was significantly smaller in adenomas with hyperaldosteronism than in those with Cushing syndrome (P = 0.004). Chromosome 17 showed disomy in all adrenal cortical adenomas, whereas chromosome 17 abnormalities were found in two of three adrenal cortical carcinomas. Only the latter two cases strongly expressed p53 protein. CONCLUSIONS: Our study characterized various biological features of benign and malignant adrenal cortical tumors. The use of a combination of markers might provide additional information to assist our understanding of the clinical behavior of an individual adrenal cortical tumor.     

Prediction of potentially insignificant prostate cancer in men undergoing radical prostatectomy for clinically organ-confined disease

BACKGROUND: The objectives of the present study were to characterize, according to tumor significance, the clinicopathological features of patients with prostate cancer who underwent radical prostatectomy, and to determine useful parameters for predicting insignificant disease before surgery. METHODS: In this series, we included 195 patients who underwent radical prostatectomy for clinically organ-confined prostate cancer at our institution between January 1999 and November 2003. Several clinicopathological factors were analyzed, focusing on whether the largest tumor volume in radical prostatectomy specimens was >/=0.5 cm(3) or <0.5 cm(3), which is the criterion defined to distinguish insignificant cancer from significant cancer. RESULTS: Potentially insignificant cancer was detected in 28 of 195 patients (14.4%). There were significant differences between patients with insignificant disease and those with significant disease in serum prostate specific antigen (PSA) as well as all biopsy parameters, with the exception of biopsy Gleason score. Furthermore, final pathological examination demonstrated that these two patient groups showed significant differences in Gleason score and the incidence of extraprostatic disease extension. Pearson's correlation analysis showed that tumor volume in the prostatectomy specimens was significantly associated with serum PSA and all biopsy parameters; however, each of the correlations was comparatively weak. There was no single parameter that could viewed as a useful predictor of tumor significance. The best model for predicting insignificant tumor was the combined use of biopsy Gleason score <7 and percent of positive biopsy core (PPBC) <15%; however, the further addition of serum PSA <10 ng/mL to these two parameters failed to enhance the predictive value of cancer significance. CONCLUSIONS: These findings indicate that clinicopathological findings suggesting favorable features are well observed in patients with potentially insignificant prostate cancer compared to those with significant prostate cancer, and the combination of a biopsy Gleason score <7 and PPBC <15% might be useful as a predictor of insignificant disease.     

Wound,pressure ulcer and burn guidelines – 1: Guidelines for wounds in general,second edition

The Japanese Dermatological Association prepared the clinical guidelines for the “Wound, pressure ulcer and burn guidelines”, second edition, focusing on treatments. Among them, “Guidelines for wounds in general” is intended to provide the knowledge necessary to heal wounds, without focusing on particular disorders. It informs the basic principles of wound treatment, before explanations are provided in individual chapters of the guidelines. We updated all sections by collecting references published since the publication of the first edition. In particular, we included new wound dressings and topical medications. Additionally, we added “Question 6: How should wound-related pain be considered, and what should be done to control it?” as a new section addressing wound pain, which was not included in the first edition.     

Endovascular Treatment for Ruptured Vertebral Artery Dissecting Aneurysms: Results from Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2

In treating ruptured vertebral artery dissecting aneurysms (VADAs), neuroendovascular therapy (NET) represented by coil obliteration is considered to be a reliable intervention. However, there has been no multi-center based study in this setting so far. In this article, results of NET for ruptured VADA obtained from Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2 were assessed to elucidate the factors associated with favorable outcome. A total of 213 in JR-NET1 and 381 patients in JR-NET2 with ruptured VADA were included, and they were separately analyzed because several important datasets such as vasospasm and site of dissecting aneurysms in relation to the posterior inferior cerebellar artery (PICA) were collected only in JR-NET1. The ratio of poor World Federation of Neurosurgical Societies (WFNS) grade (4 and 5) was 48.8% and 53.9%, and the ratio of favorable outcome (modified Rankin scale, mRS 0 to 2) at 30 days after onset was 61.1 % and 49.1% in JR-NET1 and 2, respectively. In both studies, poor WFNS grade and procedural complication were independently correlated as negative factors for favorable outcome. In JR-NET1, PICA-involved lesion was also designated as a negative factor while elderly age and absence of postprocedural antithrombotic therapy was detected as other negative factors in JR-NET2. The ratios of favorable outcome in poor grade patients were 25.4% in JR-NET1 and 31.3% in JR-NET2, which seemed compatible with the previous studies. These results may provide a baseline data for the NET in this disease and could be useful for validating the benefits of novel devices.     

Possible Application of Microwave Coagulation Therapy for Recanalising Tumor-occluded Self-expandable Metallic Stents

Abstract: There is no consensus regarding optimal management of tumor ingrowth through self-expandable metallic stents in the biliary system. We investigated the possibility that microwave therapy could be used to treat stent occlusion. We evaluated the thermal properties of a muscle equivalent phantom subjected to microwave energy. The temperature of the phantom was continuously monitored using the probe sensor of a fiberoptic thermometer embedded into the phantom model at different distances from a microwave electrode with and without a stent in place. The temperature of the phantom increased incrementally as the power increased from 30 to 50 watts at distances 2 and 5 mm from the electrode (p<0.01). With the goal of achieving adequate local heating without excessive distant heating, the most effective power was 40 watts. There was a significantly lower rise in temperature with stent in place than that without stent at 2 and 5 mm from the electrode at 40 watts. The temperature increase when the tip of the electrode was kept in contact with the stent was significantly smaller than when the conductor tip was kept apart from the stent (p<0.05). Using this method, the microwave energy did not induce destruction of the stent filament. In a muscle equivalent phantom model, the temperature changes induced by microwave energy were consistent with possible safe and effective application of this modality to recanalization of occluded metallic stents. (Dig Endosc 1999; 11: 158–164)     

E1AF expression is associated with extra‐prostatic growth and matrix metalloproteinase‐7 expression in prostate cancer

E1AF is associated with malignant aggressiveness via regulation of matrix metalloproteinases (MMPs), which play pivotal roles in invasion through the degradation of extracellular matrix of tissues surrounding tumors. However, the clinical significance of E1AF and MMPs in patients with prostate cancer is not fully understood. We reviewed 50 tissue samples from patients with T2‐3N0M0 prostate cancer who had undergone radical operation. Expression levels of E1AF, MMP‐1, ‐3, ‐7, ‐9 and ‐14 were determined semiquantitatively by immunohistochemistry. The mean ± SD percentage of E1AF‐stained cancer cells was 8.56 ± 5.22, and it was significantly higher (p < 0.001) than the E1AF‐immunostaining index of normal cells (1.17 ± 0.61). E1AF immunostaining index in pT3 (12.74 ± 4.80) was significantly higher (p < 0.001) than that in pT2 (5.78 ± 3.31). Although E1AF expression correlated with that of MMP‐7 and MMP‐9 (r = 0.47, p < 0.001 and r = 0.41, p = 0.004, respectively), multivariate analysis showed that E1AF correlated with only MMP‐7 expression (OR = 5.81, 95% CI = 1.27–26.59, p = 0.023). Our results demonstrated that increased expression of E1AF is involved in tumor aggression of prostate cancer. This finding may be influenced by regulation of MMP‐7. We speculate that E1AF is a possible target in treatment and prevention of tumor growth in prostate cancer.     

The Effectiveness of the Stereotactic Burr Hole Technique for Deep Brain Stimulation

Deep brain stimulation (DBS) is performed by burr hole surgery. In microelectrode recording by multi-channel parallel probe, because all microelectrodes do not always fit in the burr hole, additional drilling to enlarge the hole is occasionally required, which is time consuming and more invasive. We report a stereotactic burr hole technique to avoid additional drilling, and the efficacy of this novel technique compared with the conventional procedure. Ten patients (20 burr holes) that received DBS were retrospectively analyzed (5 in the conventional burr hole group and 5 in the stereotactic burr hole group). In the stereotactic burr hole technique, the combination of the instrument stop slide of a Leksell frame and the Midas Rex perforator with a 14-mm perforator bit was attached to the instrument carrier slide of the arc in order to trephine under stereoguidance. The efficacy of this technique was assessed by the number of additional drillings. Factors associated with additional drilling were investigated including the angle and skull thickness around the entry points. Four of the 10 burr holes required additional drilling in the conventional burr hole group, whereas no additional drilling was required in the stereotactic burr hole group (p = 0.043). The thicknesses in the additional drilling group were 10.9 ± 0.9 mm compared to 9.1 ± 1.2 mm (p = 0.029) in the non-additional drilling group. There were no differences in the angles between the two groups. The stereotactic burr hole technique contributes to safe and exact DBS, particularly in patients with thick skulls.     

Early decline of the HCV core antigen can predict SVR in patients with HCV treated by Pegylated interferon plus ribavirin combination therapy

OBJECTIVE: Pegylated interferon (PEG‐IFN) plus ribavirin (RBV) combination therapy is now a popular treatment for patients with chronic hepatitis C; however, the reported sustained virologic response (SVR) rate remains at nearly 50% in genotype 1b infected patients. Therefore, it is of clinical benefit to be able to predict the effect of combination therapy on individual patients earlier in the treatment. We estimated the predictive serum HCV core antigen levels for SVR in the early therapeutic stage of combination therapy. METHODS: The HCV core antigen in patients with high‐level HCV viremia, in whom standard PEG‐IFNα2b plus RBV combination therapy had been completed, was measured at baseline and at 3, 7, 14, 28 and 84 days of treatment, and their SVR was determined at 24 weeks after treatment. Sixty genotype 1b‐ and 30 genotype 2‐infected patients were included. RESULTS: Thirty (50%) genotype 1b and 27 (90%) genotype 2 patients achieved a SVR. In genotype 1b patients the decline of HCV core antigen levels was statistically different between the SVR and non‐SVR groups. When we defined a separation level at 500 fmol/L, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for SVR at day 7 was 79.4%, 88.5%, 90%, 76.7%, and 83.3%, respectively. In genotype 2 patients, there was no significant difference in the HCV core antigen values between the SVR and non‐SVR groups. CONCLUSION: In genotype 1b patients, 500 fmol/L of HCV core antigen level at day 7 was the best predictor for therapeutic response in the early stage of treatment.