Effects of Cyanoacrylate on the Gastric Mucosa of Dogs –Endoscopic and Histopathological Studies for Sclerotherapy of Gastric Varices–

Abstract: The effect of cyanoacrylate tissue adhesive (C. A.) on the gastric mucosa of dogs was investigated endoscopically and histopathologically. When C. A. was applied to the surface of the gastric mucosa, the endoscopic findings the next day showed local redness at the applied site (Fig. 1-a) and histopathology revealed degenerative changes in the gastric mucosa (Fig. 1-b). When C. A. was endoscopically injected into the gastric mucosa, the endoscopic findings revealed a submucosal tumor-like lesion (Fig. 2-a). One day after treatment, the endoscopic findings showed a hemorrhagic erosion on the surface of the lesion (Fig. 2-b). An histopathological examination of the resected stomach revealed C. A. in the submucosal layer (Fig. 3-a, 3-b) and the lymph duct around the muscularis mucosa with severe acute inflammation (Fig. 4-a, 4-b). One week after treatment, a deep ulcer (Ul-IV) was observed (Fig. 5, 6) and a histopathological examination of the resected specimen revealed C. A. at the site of the ulcer and inflammatory cell infiltration by fibroblasts and giant cells (Fig. 7-a, 7-b). One month after treatment, the ulcer had healed and was replaced by a scar (Fig. 8). Histopathological examination of the resected stomach revealed C. A. in both the muscularis mucosa and the submucosa and also inflammatory cell infiltration by giant cells in addition to the fibrosis (Fig. 9). When using endoscopic sclerotherapy with C. A., it should be kept in mind that there is the possibility of such a lesion occurring as demonstrated by our study.     

Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo

PURPOSE: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. MATERIALS AND METHODS: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n=6-8). RESULTS: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 micromol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 micromol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%]=growth of TAK-165 treated tumor/average growth of control tumorx100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. CONCLUSIONS: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer.     

Prognostic significance of thrombocytosis in renal cell carcinoma patients

Background: Thrombocytosis has been reported in many types of malignancies and has been studied as a prognostic factor. In the present study, we examined the incidence of thrombocytosis in patients with renal cell carcinoma (RCC) in order to evaluate the prognostic value of thrombocytosis. Methods: One hundred and ninety‐six patients treated by radical nephrectomy for RCC were enrolled in this study. We divided the patients into a normal platelet count group and a thrombocytosis group according to the presurgical platelet count. The two groups were compared pathologically and clinically, including prognosis. Results: Thrombocytosis was present in 16 patients (8.2%). Platelet counts had normalized after nephrectomy in all patients with thrombocytosis. There was no correlation between histological type or grade and thrombocytosis. However, there were correlations between thrombocytosis and tumor size and tumor stage. Patients with thrombocytosis had a worse prognosis than patients without thrombocytosis (P = 0.0028). When adjusted for stage or tumor size, the correlation was limited to low stage (stage 1 + 2: P = 0.0041, stage 3 + 4: P = 0.2983) or small tumors (tumor size: ≤4 cm, P = 0.0021; 4–7 cm, P = 0.0142; >7 cm, P = 0.8158). Conclusion: Thrombocytosis is an inexpensive and easy tool with which to evaluate the prognosis of RCC patients in daily medical practice.     

Health-related quality of life after radical prostatectomy in Japanese men with localized prostate cancer

PURPOSE: We evaluated retrospectively health-related quality of life (HRQOL) after radical prostatectomy (RP) in Japanese men with localized prostate cancer. METHODS: The study was based on self-reported HRQOL of 280 patients. Patients were divided into seven groups: time 0 (T0), baseline before operation; T1, 1-3 months after RP; T2, 4-6 months after RP; T3, 7-12 months after RP; T4, 13-24 months after RP; T5, 25-36 months after RP; and T6, more than 36 months after RP. We measured the general and disease-specific HRQOL using the RAND 36-item Health Survey 1.0 (SF-36) and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI). RESULTS: The general HRQOL of the postoperative groups was assessed by SF-36. The postoperative groups showed almost the same or higher scores than those of the baseline group. Urinary function scores decreased substantially after surgery. In contrast, there was no difference in urinary bother between the baseline and postoperative groups. Sexual function deteriorated substantially in all postoperative groups. Similarly, the sexual bother score significantly deteriorated after RP. The sexual bother score of men aged 65-years or younger was significantly worse than that of their counterparts in the T1-2 groups. CONCLUSION: Despite reports of problems with sexual activity and urinary continence, general HRQOL was mostly unaffected by RP. Although there was a substantial decrease in urinary function, recovery from urinary bother was rapid. Since the deterioration of sexual function was marked through the postoperative period, careful attention should be paid to this issue during preoperative counseling, especially for younger patients.     

Antibodies to hepatitis C virus and elevated transaminase levels in a town of hyperendemicity in Iwate, Japan

In an annual survey for liver function tests in persons aged > xs35 years in Iwate Prefecture, Japan, a town was identified where high levels of alanine aminotransferase abounded. Of 5152 inhabitants aged > 35 years in this town, antibodies to hepatitis C virus (HCV) determined by enzyme-linked immunosorbent assay with HCV core peptides were detected in 798 (15.5%) people, hepatitis B surface antigen was detected in 47 (0.9%) people and antibodies to hepatitis B surface antigen and/or hepatitis B core antigen unaccompanied by surface antigenaemia were detected in 1748 (33.9%) people. Antibodies to HCV core peptides correlated closely with the antibodies detected by passive haem-agglutination with recombinant HCV proteins of the second generation. Antibodies to HCV core peptides were particularly common in one of the nine districts of the town (district 8), where 276 (45.3%) of 609 inhabitants tested positive; there were no differences in the frequency of serological markers of hepatitis B virus (HEV) infection among residents in the nine districts. Of the 798 individuals with antibodies to HCV core peptides, 257 (32.2%) were found to have elevated transaminase levels. A history of transfusion was associated with a high frequency of antibodies to HCV core peptides, except in district 8 where such antibodies were equally frequent in residents irrespective of transfusions. These results indicate an epidemiology of HCV distinct from that of HBV in this town and a very local spread of HCV, as well as a high frequency of hepatic injuries in individuals with antibodies to HCV.     

Histochemical localisation of versican, aggrecan and hyaluronan in the developing condylar cartilage of the fetal rat mandible

We investigated the histochemical localisation of versican, aggrecan and hyaluronan in the developing condylar cartilage of the fetal rat mandible at d 15–17 of gestation. At d 15 of gestation, immunostaining for versican was detected in the anlage of the future condylar process (condylar anlage), although the staining intensity showed a considerable regional variation. At d 16 of gestation, a metachromatically stained matrix firstly appeared in the condylar anlage. Aggrecan, hyaluronan and versican were simultaneously detected in this newly formed condylar cartilage. At d 17 of gestation, immunostaining for versican became restricted to the perichondrium and was barely detected in the cartilage. Colocalisation of versican and aggrecan was also seen in the cranial base cartilage at d 14 of gestation. These results indicate that although versican is replaced by aggrecan during the transition from prechondrogenic tissue to cartilage, both molecules were temporally colocalised in the newly formed cartilage. A hyaluronan-rich, low-versican area was identified in the posterior end of the condylar anlage during d 15–17 of gestation. The existence of this area is a unique structural feature of the developing condylar cartilage.     

Plasma abnormal prothrombin (PIVKA-π): A new and reliable marker for the detection of hepatocellular carcinoma

We evaluated the clinical usefulness of a protein induced by vitamin K absence, antagonist-prothrombin (PIVKA-II), in detecting hepatocellular carcinoma (HCC) specifically in patients with liver cirrhosis, and the possible correlation between levels of PIVKA-II and pathological features of HCC. Plasma levels of PIVKA-II and alpha-fetoprotein (AFP) were measured in 628 patients with various diseases, including 253 with liver cirrhosis and 116 with HCC. PIVKA-II was detected (greater than or equal to 0.1 arbitrary unit/mL) in 54.3% of HCC and the concentration showed a positive correlation with the tumour size. As a screening test for the detection of HCC, PIVKA-II produced values comparable with those of AFP with a sensitivity, specificity and validity of 52.8, 98.8 and 51.6% respectively. Sixteen of 45 patients (37%) with HCC who had low AFP (less than 100 ng/mL) levels were positive for PIVKA-II. No apparent relationship, however, could be found between the levels of PIVKA-II and the aetiology or pathological findings of HCC. These results suggest that PIVKA-II can be a reliable marker for detecting HCC in patients with liver cirrhosis.     

Growth and growth hormone secretion in children after bone marrow transplantation

Long-term sequelae of bone marrow transplantation (BMT) are a major concern among long-term survivors since the procedure has been considerably developed over the past decade. In this study, linear growth and growth hormone (GH) secretion were evaluated in 25 children (14 males and 11 females) with various neoplastic or non-neoplastic hematological disorders who had survived for more than 3 years after BMT. Impaired linear growth after BMT, as defined by a change in height standard deviation score (SDS) by more than ? 1.0 SD, was observed in 14 patients (56%). Four children showed severe growth suppression with a decrease in SD score by more than 2.0, and 10 exhibited a moderate reduction by between 1.0 and 2.0 SD. A recovery of normal height velocity was observed in those who had received BMT at a younger age. The type of disease, a difference in preconditioning regimen, the presence of chronic graft-versus-host disease or a GH secretory capacity 1 year after BMT were not contributing factors for impaired growth. A serial examination of GH secretion with insulin-induced hypoglycemia demonstrated that poor GH secretion was not necessarily a prerequisite for impaired growth. These results indicate that the secretory status of GH does not predict the future growth pattern of children who received BMT.