The Fife hormone service for prostate cancer patients: a cost‐effective and patient‐centric model

Injectable hormone therapy is a key element of treatment for many patients with prostate cancer. In the UK, it is typically administered in primary care. In 2003, National Health Service (NHS) Fife rolled out an innovative service for these patients, in which responsibility was moved from primary care to a specialist nurse‐led service in secondary care. The initial rationale was based on cost savings, but a significant number of other advantages have subsequently been demonstrated. These include a simpler patient journey, improved continuity of care and reduced use of consultant time. Standards of care have also improved, with fewer missed appointments, better provision of patient support and rapid access to specialist physician care when needed. An audit of 377 of 542 patients currently treated within the service has provided supportive evidence for many of these advantages. The Fife service offers a cost‐effective model for locally provided nurse‐led care that could be applied to hormone therapy services for prostate cancer elsewhere in the UK, and to services for other cancers with large numbers of patients requiring long‐term management.     

Evaluation of E-rosetting human lymphocytes with OKT11 and other monoclonal antibodies

Monoclonal antibody OKT11 was found to compete with sheep red blood cells for binding sites on human lymphocytes. Preincubation of lymphocytes with OKT11 eliminated E-rosette formation. In a study of 142 peripheral blood samples ranging from 1% to over 90% E-rosette- positive cells, comparison to the percent OKT11-positive cells yielded a correlation coefficient of 0.93. In normal donors, subsets of OKT11+ cells were identified using two-color immunofluorescent staining methods with OKT3, OKT4, and OKT8. On the average, approximately 13% of OKT11+ lymphocytes were OKT3- and 13% of OKT11+ lymphocytes were OKT4- and OKT8-. Based on our double antibody fluorescence intensity data, low antigen density OKT11+ lymphocytes were OKT3-. OKT4+ and OKT8+ lymphocytes in normal peripheral lymphocytes have similar OKT11 antigen density.     

GNAS1 T393C polymorphism and disease progression in patients with malignant melanoma

Background: Once metastasized, despite a variety of therapeutic options, the prognosis of patients with malignant melanoma (MM) is still poor. Therefore, the search for reliable markers to identify patients with high risk of disease progression is of high clinical importance. We have recently shown that TT genotypes of the single-nucleotide polymorphism (SNP) T393C in the gene GNAS1 are significantly associated with better outcome in a variety of carcinomas. - Patients: In the present study we assessed whether the T393C SNP is also related to the clinical course in MM. 328 patients with MM were retrospectively genotyped and genotypes were correlated with clinical outcome. - Results: While the allele frequency in the MM group (fC 0.52) did not significantly differ from that of healthy blood donors, the T393C SNP was associated with tumor progression of MM. Carriers of the C-allele showed a significantly more severe tumor progression as estimated from the time period to develop metastasis (HR 2.2, 95% CI 1.1-3.2, p = 0.017). Proportions of 5-year metastasis-free intervals were 87.1% for TT genotypes and 66.0% for C-allele carriers. Moreover, multivariable Cox regression analysis including tumor stage and melanoma subtype proved the T393C polymorphism to be an independent factor for metastasis (p = 0.012). - Conclusions: In summary, the GNAS1 T393C SNP represents a genetic host factor for predicting tumor progression also in patients with MM; genotyping of this SNP may contribute to better define patients who could benefit from an early individualized therapy.     

Surgical management of splenic echinococcal disease

Background

Infection of the spleen with echinococcus is a rare clinical entity. Because the diagnosis of a splenic infestation with echinococcus is sometimes delayed, large hydatid cysts or pseudotumors may develop, demanding a differential surgical approach to cure the disease.

Methods

In a retrospective study 10 patients out of 250 with abdominal echinococcosis (4%) were identified to have splenic infestation, either limited to the spleen (n = 4) or with synchronous involvement of the liver (n = 4), major omentum (n = 1), or the liver and lung (n = 1). Only one patient had alveolar echinococcosis whereas the others showed hydatid cysts of the spleen. Surgical therapy included splenectomy in 7 patients or partial cyst excision combined with omentoplasty in 3 patients. In case of liver involvement, pericystectomy was carried out simultaneously.

Results

There was no mortality. Postoperative complications were observed in 4 patients. Hospital stay and morbidity were not influenced when splenic procedures were combined with pericystectomies of the liver. Mean follow- up was 8.8 years and all of the patients are free of recurrence at this time.

Conclusions

Splenectomy should be the preferred treatment of hydatid cysts but partial cystectomy is suitable when the cysts are located at the margins of the spleen. Due to low morbidity rates, simultaneous treatment of splenic and liver hydatid cysts is recom mended.     

Effects of potent VEGF blockade on experimental Wilms tumor and its persisting vasculature

We characterized the effect of potent vascular endothelial growth factor (VEGF) blockade on early-stage Wilms tumor xenograft growth, vasculature and metastasis. VEGF is a key mediator of both physiologic and tumor angiogenesis. We recently described that potent VEGF blockade induces regression of established Wilms tumor xenografts and vessels, also reducing the size but not the incidence of pre-existing metastases. In these studies, we examined the effects of potent VEGF blockade on earlier stages of experimental Wilms tumors, focusing on tumor growth, vasculature and metastasis. Athymic mice received intrarenal human Wilms tumor cell implants. Biweekly treatment with vehicle or the VEGF-Trap, a high-affinity soluble decoy receptor incorporating regions of VEGFR1 and VEGFR2, was begun 1 week later (100 or 500 micrograms/dose, n=20 in each group). Mice were euthanized at week 6 to examine tumor weight, incidence of lung metastases, vascularity and expression of angiogenic factors. A cohort of mice was examined 2 weeks after cessation of treatment. Compared to controls, VEGF-Trap treated tumors were significantly smaller (100 micrograms/dose: 92.7% smaller, p=0.0017; 500 micro g/dose: 99.0% smaller, p=0.0009). The incidence of lung metastasis also decreased significantly (p<0.0055). VEGF-Trap nearly eradicated tumor vasculature. Rare persisting vessels were characterized by large caliber, quiescence (lacking proliferation/apoptosis) and arterialization (both phenotypic and molecular). Potent VEGF blockade caused near-arrest of experimental Wilms tumor growth, resulted in nearly avascular tumors, and also decreased the incidence and size of metastases. Persistent vessels in tumors treated with VEGF-Trap displayed specific morphologic and molecular features, suggestive of arterialization. Future strategies that target these persisting vessels may enhance the efficacy of VEGF blockade therapy.     

静脉内平滑肌瘤病伴细胞不典型

患者，女性，54岁，中国籍，因急性左下肢水肿就诊。既往有子宫肌瘤史2年。腹部及盆腔凹显示左髂总静脉血栓及子宫左下部肌瘤(直径6cm)。考虑静脉血栓系肌瘤压迫髂静脉所致，予抗凝治疗，为缩小子宫体积以减轻其对髂静脉的压力，皮下注射促性腺激素释放激素类似物(GnRHa)3个月。患者对GnRHa冶疗无不良反应，治疗后闭经。4月后复查腹部及盆腔CT显示子宫明显缩小，     

p53 accumulation in favorable-histology Wilms tumor is associated with angiogenesis and clinically aggressive disease

Background/Purpose: Unfavorable histology (UH) in Wilms tumor has been linked to malfunction of the p53 tumor suppressor gene, which regulates (1) the endogenous angiogenesis suppressor thrombospondin-1 (TSP-1) and (2) vascular endothelial growth factor (VEGF). The authors hypothesized that clinically aggressive favorable histology Wilms tumor (FH), like UH, but distinct from standard-risk FH disease, would display altered p53/TSP-1 function and upregulated angiogenesis. Methods: Three Wilms tumor specimens manifesting different histology and clinical behavior were obtained: clinically aggressive UH, clinically aggressive FH, and standard-risk FH disease. Xenografts were induced intrarenally in athymic mice. P53, TSP-1, and VEGF status and neovascularity were assessed in tumor tissues. Lungs were evaluated for metastasis. Results: Clinically aggressive FH Wilms tumor displayed progressive alteration in p53/TSP-1 status and upregulation of VEGF. Such alteration was observed in the UH tumor, but was absent from the standard-risk FH tumor. Xenografts from clinically aggressive tumors displayed brisk neoangiogenesis and yielded lung metastases. Conclusions: This is the first report of altered p53/TSP-1 function in association with clinically aggressive behavior in FH Wilms tumor. These characteristics were not observed in parallel studies of a nonaggressive FH tumor. Loss of wild-type p53 function may contribute to disease progression in FH Wilms tumor, in part by upregulation of VEGF.     

Tissue distribution and macromolecular binding of extremely low doses of [14C]-benzene in B6C3F1 mice

The tissue distribution and macromolecular binding of benzene was studied over a dose range spanning nine-orders of magnitude to determine the nature of the dose-response and to establish benzene's internal dosimetry at doses encompassing human environmental exposures. [14C]-Benzene was administered to B6C3F1 male mice at doses ranging between 700 pg/kg and 500 mg/kg body wt. Tissues, DNA and protein were analyzed for [14C]-benzene content between 0 and 48 h post-exposure (625 Ng/kg and 5 microg/kg dose) by accelerator mass spectrometry (AMS). [14C]-Benzene levels were highest in the liver and peaked within 0.5 h of exposure. Liver DNA adduct levels peaked at 0.5 h, in contrast to bone marrow DNA adduct levels, which peaked at 12-24 h. Dose- response assessments at 1 h showed that adducts and tissue available doses increased linearly with administered dose up to doses of 16 mg/kg body wt. Tissue available doses and liver protein adducts plateau above the 16 mg/kg dose. Furthermore, a larger percentage of the available dose in bone marrow bound to DNA relative to liver. Protein adduct levels were 9- to 43-fold greater than DNA adduct levels. These data show that benzene is bioavailable at human-relevant doses and that DNA and protein adduct formation is linear with dose over a dose range spanning eight orders of magnitude. Finally, these data show that the dose of bioactive metabolites is greater to the bone marrow than the liver and suggests that protein adducts may contribute to benzene's hematoxicity.