Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.     

Sequential morphological change of Chiari malformation type II following surgical repair of myelomeningocele

Purpose

To document long-term morphological changes of Chiari type II malformation (CM-II) following closure of spina bifida manifesta (SBM).

Methods

We retrospectively evaluated postnatal magnetic resonance images of the CM-II and posterior fossa (PF) in 28 consecutive cases. We measured changes in vertebral level and length of the cerebellar peg (CP), cerebrospinal fluid (CSF) spaces anterior and posterior to the cerebrospinal junction, PF area, and the anteroposterior diameters of the foramen magnum (FM) and C1 vertebra. We examined the morphological differences between the cases with and without ventriculoperitoneal (VP) shunting and derived predicted means by nonlinear mixed-effect modeling.

Results

At birth, there were significant differences in CP length, PF area, and FM and C1 diameters between those who underwent VP shunting and those who did not. In cases with a CP below C1, VP shunting was required in every case but one. In those with visible CSF space at birth, VP shunts were not required. In 17 of 18 cases with a CP below C1, the vertebral level ascended by mean two vertebral levels (range 0–5 levels) within 4–6 months of delivery. In the remaining case, slowly progressive hydrocephalus and delayed CP descent required VP shunting at 8 months. Predicted mean CP length and FM and C1 diameters were greater in those who underwent VP shunting, but there was no difference in predicted mean PF area.

Conclusion

The morphology of CM-II and the presence of hydrocephalus influence each other in children who have undergone postnatal SBM repair.

     

Acupuncture needle-associated prosthetic knee infection after total knee arthroplasty

The case of a patient who previously had permanent acupuncture needles placed in the knee joint and had been doing well, with no evidence of infection, but who eventually underwent a revision total knee arthroplasty due to acupuncture needle-associated prosthetic infection is presented. The microorganism responsible for the infection was Enterococcus faecalis, a bacterium which rarely causes infection following arthroplasty. This case should be highlighted to increase the awareness of healthcare providers to acupuncture-associated subclinical infection that may be exacerbated by surgical manipulation.     

The significance of strong histone deacetylase 1 expression in the progression of prostate cancer

Song Y H, Shiota M, Tamiya S, Kuroiwa K, Naito S & Tsuneyoshi M
(2011) Histopathology 58 , 773–780 The significance of strong histone deacetylase 1 expression in the progression of prostate cancer Aims: Histone deacetylases (HDACs) play important roles in many types of cancer. Recently, it has been reported that HDAC1 expression in prostate cancer is significantly higher than in benign prostate cell lines and tissues. The expression of HDAC1 in association with the clinicopathological data was investigated to define its functional and pathological roles in prostate cancer. Methods and results: HDAC1 expression was examined immunohistochemically in 148 patients with prostate cancer. Strong expression of HDAC1 in benign prostate glands, high‐grade prostatic intraepithelial neoplasia (PIN) and prostate cancer was observed in 17/148 (11%), 19/71 (27%) and 69/148 (47%) patients. Strong HDAC1 expression was correlated with high Gleason score (P = 0.025) and high pT stage (P = 0.012). Patients with strong HDAC1 expression had higher biochemical recurrence rates (P = 0.0010). Furthermore, strong HDAC1 expression had a significant impact on patient biochemical recurrence rates in multivariate analysis (P = 0.004). Conclusions: These results indicate that overexpression of HDAC1 contributes to progression and poor prognosis in prostate cancer. The findings may play an important role in the emergence of effective new approaches for therapy and prognostic markers of prostate cancer.     

Multifocal metanephric adenoma in childhood

Metanephric adenoma is the most commonly occurring member of the metanephric tumor family, which also includes metanephric adenofibroma and metanephric stromal tumor. According to the World Health Organization classification, however, it is not commonly multifocal. Reported herein is the case of a 9-year-old boy with multifocal metanephric adenoma. Histologically, surgical sections showed multifocal proliferation of small rounded and uniform cells with smooth nuclear contours, scant pale-staining cytoplasm, dark-staining nuclei, and inconspicuous nucleoli: the cells were arranged in sheets and acinal, ductal, glomeruloid, and papillary structures. On immunohistochemistry the tumor cells were positive for vimentin, cytokeratins (CAM5.2, AE1/AE3, and CK18), and WT1, but negative for cytokeratin 7 (CK7) and epithelial membrane antigen (EMA). The Ki-67 labeling index was <1%. In addition, cytogenetic analysis indicated a normal karyotype (46XY). Other histologically similar tumors are papillary renal cell carcinoma and nephroblastoma, and it is necessary to distinguish metanephric adenoma from those tumors because of malignancy. In contrast to those tumors, metanephric adenoma has inconspicuous nucleoli, loss of CK7 and EMA expression, and no mitotic figures. Thus, the histological and immunohistochemical features of the present case were compatible with metanephric adenoma.     

Both Fibrous Capsule Formation and Extracapsular Penetration Are Powerful Predictors of Poor Survival in Human Hepatocellular Carcinoma: A Histological Assessment of 365 Patients in Japan

Background  A new definition of infiltration to the capsule (fc-inf) has been proposed as a novel marker for predicting the prognosis of 88 patients with hepatocellular carcinoma (HCC). The current aim was to present evidence to develop the fibrous capsule and fc-inf, from the Japanese histological findings for HCC, and to validate their biological significances and predictive power of survival in a large series. Methods  A total of 365 HCCs were divided into HCCs without the fibrous capsule (NC type; n = 135) and HCCs with the fibrous capsule (FC type; n = 230). Then, FC type was subclassified into two types: extracapsular infiltrating (EC) type (n = 125), in which cancer cells penetrated outside the fibrous capsule, and intracapsular (IC) type (n = 105), in which the infiltrating cancer cells stayed inside the fibrous capsule. Results  The proportion of less histological differentiation and portal venous invasion was higher in FC type than in NC type. The fibrous capsule came to be observed according to the increase of tumor size (P < 0.0001). FC type had significantly poorer outcome for overall survival than NC type (P = 0.0022). EC type showed more intrahepatic metastasis than IC type. The macroscopic subclassifications were significantly affected the presence of fc-inf. EC type had significantly poorer outcome for disease-free survival than IC type (P = 0.0132) and was an independent prognostic factor for disease-free survival (P = 0.0482). Conclusions  Fc-inf defined as extracapsular penetration was verified to be a novel marker for predicting prognosis, and presence of fc-inf might be predicted by tumor gross features.     

Sex hormone and gender difference--role of testosterone on male predominance in Brugada syndrome

Introduction: The clinical phenotype is 8 to 10 times more prevalent in males than in females in patients with Brugada syndrome. Brugada syndrome has been reported to be thinner than asymptomatic normal controls. We tested the hypothesis that higher testosterone level associated with lower visceral fat may relate to Brugada phenotype and male predominance.
Methods and Results: We measured body-mass index (BMI), body fat percentage (BF%), and several hormonal levels, including testosterone, in 48 Brugada males and compared with those in 96 age-matched control males. Brugada males had significantly higher testosterone (631 ± 176 vs 537 ± 158 ng/dL; P = 0.002), serum sodium, potassium, and chloride levels than those in control males by univariate analysis, and even after adjusting for age, exercise, stress, smoking, and medication of hypertension, diabetes, and hyperlipidemia, whereas there were no significant differences in other sex and thyroid hormonal levels. Brugada males had significantly lower BMI (22.1 ± 2.9 vs 24.6 ± 2.6 kg/m²; P < 0.001) and BF% (19.6 ± 4.9 vs 23.1 ± 4.7%; P < 0.001) than control males. Testosterone level was inversely correlated with BMI and BF% in both groups, even after adjusting for the confounding variables. Conditional logistic regression models analysis showed significant positive and inverse association between Brugada syndrome and hypertestosteronemia (OR:3.11, 95%CI:1.22–7.93, P = 0.017) and BMI (OR:0.72, 95%CI:0.61–0.85, P < 0.001), respectively.
Conclusions: Higher testosterone level associated with lower visceral fat may have a significant role in the Brugada phenotype and male predominance in Brugada syndrome.