Improved Survival Probability Research Articles

Effect of SLCO1B3 Haplotype on Testosterone Transport and Clinical Outcome in Caucasian Patients with Androgen-Independent Prostatic Cancer

The organic anion transporter OATP1B3, encoded by SLCO1B3, is involved in the transport of steroid hormones. However, its role in testosterone uptake and clinical outcome of prostatic cancer is unknown. This study examined (a) the SLCO1B3 genotype in cancer cells as well as the uptake of testosterone by cells transfected with genetic variants of SLCO1B3; (b) the expression of OATP1B3 in normal prostate, benign prostatic hyperplasia, and prostatic cancer; and (c) the role of SLCO1B3 haplotype on clinical outcome of Caucasian patients with androgen-independent prostatic cancer. SLCO1B3 genotype was assessed in the NCI-60 panel of tumor cells by sequencing, whereas testosterone transport was analyzed in Cos-7 cells transfected with WT, 334G, and 699A SLCO1B3 variants. OATP1B3 expression in prostatic tissues was examined by fluorescence microscopy, and the relationship between SLCO1B3 haplotypes and survival was examined in patients. Cells transfected with wild-type (334T/699G) SLCO1B3, or with a vector containing either the 334G or 699A variants, actively transported testosterone, whereas its uptake was impaired in cells transfected with a gene carrying both 334G and 699A single nucleotide polymorphisms. Prostatic cancer overexpresses OATP1B3 compared with normal or benign hyperplastic tissue; patients with SLCO1B3 334GG/699AA haplotype showed longer median survival (8.5 versus 6.4 years; P = 0.020) and improved survival probability at 10 years (42% versus 23%; P < 0.023) than patients carrying TT/AA and TG/GA haplotypes. The common SLCO1B3 GG/AA haplotype is associated with impaired testosterone transport and improved survival in patients with prostatic cancer.

Genes Proximal and Distal to MYCN Are Highly Expressed in Human Neuroblastoma as Visualized by Comparative Expressed Sequence Hybridization

MYCN amplification is associated with poor prognosis in neuroblastoma disease. To improve our understanding of the influence of the MYCN amplicon and its corresponding expression, we investigated the 2p expression pattern of MYCN amplified (n = 13) and nonamplified (n = 4) cell lines and corresponding primary tumors (n = 3) using the comparative expressed sequence hybridization technique. All but one MYCN amplified cell line displayed overexpression at 2p. Expression peaks were observed frequently at 2pter and less frequently at 2p24 (MYCN locus), 2p23.3-23.2, and/or 2p23.1. Importantly, cell lines and two corresponding primary tumors displayed expression peaks at similar loci. No significant 2p24 expression level was observed for those cell lines displaying a low amplification rate (n = 3) by comparative genomic hybridization. Only the cell lines with an enhanced peak at 2p23.2-23.3 displayed coamplification of the ALK gene (2p23.2), reported to be associated with unfavorable prognosis. Finally, two of four cell lines without MYCN amplification, both derived from patients with poor outcome, also showed an expression peak at 2p23.2. These data indicate that, besides MYCN, other genes proximal and distal to MYCN are highly expressed in neuroblastoma. The prognostic significance of expression peaks at 2p23.2-23.3, independent of MYCN and ALK status, remains to be investigated.

CD44v3 levels in primary cutaneous melanoma are predictive of prognosis: Assessment by the use of tissue microarray

Despite the use of sentinel node biopsy techniques, the search continues for other strategies to improve the accuracy of estimating prognosis in melanoma patients. Various biomarkers have previously been studied for use in this role, but none has yet achieved acceptance in routine practice. We have applied the novel technology of tissue microarray for the high throughput screening of a cohort of 120 primary cutaneous melanoma specimens for expression of the transmembrane glycoprotein CD44, splice variant 3 (v3), which has previously been implicated in tumor progression. A highly significant correlation between CD44v3 expression and Breslow thickness, Clark's level and patient age was demonstrated (Spearman correlation p < 0.001). Regarding clinical outcome, CD44v3 expression was shown to be significantly associated with better outcome (chi(2) = 7.2219, p = 0.0072). Furthermore, subgroup analysis revealed a sequentially improved survival probability associated with the intensity of CD44v3 staining (chi(2) = 12.5162, p = 0.0058). Analysis in a Cox multivariate model, however, did not show CD44v3 to be independently predictive of prognosis. The implications of these findings are considered, and the use of CD44v3 as a potential prognostic marker or a target for therapeutic manipulation are discussed.

No Evidence for Correlation of DDX1 Gene Amplification With Improved Survival Probability in Patients With MYCN-Amplified Neuroblastomas

No Evidence for Correlation of <i>DDX1</i> Gene Amplification With Improved Survival Probability in Patients With <i>MYCN</i>-Amplified Neuroblastomas

Paediatric trauma teams in Australia

Trauma teams have been associated with improved survival probability of paediatric trauma patients. The present study seeks to estimate the use of trauma teams in Australian paediatric tertiary referral centres and describe their medical composition, leadership and criteria for activation. Australian paediatric tertiary referral centres were identified. A structured questionnaire assessing the presence, composition and means of activation of a trauma team was mailed to the 'Director, Emergency Department' of all identified hospitals. Three months later, all hospitals were contacted by telephone to complete and verify data collection. Questionnaires were distributed to eight hospitals. Seventy-five per cent had an established trauma team. Hospitals without a trauma team claimed to have insufficient doctors to form a team and insufficient trauma caseload to justify a team. All trauma teams were potentially activated by prehospital paramedic data (field triage) and required a combination of anatomical, physiological and mechanistic criteria for activation. The two methods of mobilizing a trauma team were by dispatching a common call onto individual pagers (66%) or a specific trauma pager (33%) carried by trauma team members. Fifty per cent of hospitals had a two-tier, stratified trauma team response. All teams consisted of emergency, surgical and intensive care unit registrars. Trauma team leaders were emergency medicine specialists/registrars (33%), surgical registrars (33%) and non-defined (33%). Consultant surgeons were not members of any trauma team. Eighty-three per cent of trauma teams consisted of more junior members after hours. Fifty per cent of hospitals did not have a surgical registrar on site outside of business hours. Eighty-eight per cent of hospitals engaged in some form of trauma audit. Trauma teams are utilized by most Australian paediatric tertiary referral centres, with fairly uniform medical composition and criteria for activation. Paediatric surgeons presently have limited leadership roles and membership of Australian paediatric trauma teams.

Prophylactic cranial irradiation in limited disease small-cell lung cancer in complete remission: a retrospective analysis

Recently a meta-analysis showed an improved survival probability of prophylactic cranial irradiation (PCI) in limited disease small-cell lung cancer (LD SCLC) in complete remission after chemotherapy.We evaluated treatment results of PCI+and PCI−in these patients. Whether PCI (n=65) or no PCI (n=37) was administered did not depend either on patients or on tumour characteristics.After 2 years the incidence of brain metastases was 11% in PCI+patients and 51% in PCI−patients. Both disease-free survival and overall survival were significantly longer after PCI.PCI reduces the incidence of brain metastases, prolongs brain metastases-free period, and overall survival in LD SCLC patients in complete remission after chemotherapy.

Squamous cell carcinoma of skin with perineural invasion.

Perineural invasion of squamous cell carcinoma of the skin causes increased mortality. We compared survival rates for treatment with Mohs surgery with previous studies of conventional surgery and postoperative radiotherapy. With a computerized tumor registry we identified 44 cases of squamous cell carcinoma with perineural invasion recurrence, and hazard rates were calculated. Of 44 patients treated with Mohs surgery, three had recurrences. On this basis a survival probability of 88.7% was calculated. Calculation of hazard rate showed highest probability of recurrence 3 to 6 years after Mohs surgery. The clinical characteristics associated with perineural tumor invasion were male sex, size of tumor (> 2 cm), forehead location, and previous therapy. When compared with conventional surgical excision and postoperative radiotherapy, early detection and treatment by Mohs surgery of squamous cell carcinoma with perineural invasion result in a much improved survival probability.

Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer.

The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor, predominantly due to metastatic spread of the tumor. Depending on the type of tumor histology, the pathway of metastases is mainly peritoneal or hepatic dissemination. Interruption of this mechanism may be possible by intraperitoneal chemotherapy (IPT). In a prospective randomized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer, 33 patients underwent adjuvant postoperative IPT with cisplatin, while 34 control subjects remained untreated. Patients in the treatment group received a median of four IPT perfusions. Apart from frequent nausea, no adverse reactions or complications were noted. The median disease-free survival durations were 12.7 months and 9.7 months in treated patients and controls, respectively (P = .8). After a median follow-up duration of 72 months, 54 patients (80%) had died of primary disease or related complications. The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls (P = .6). Autopsies were performed on 12 (18%) of 54 patients who died, and showed tumor spread to the peritoneal cavity and/or to the liver, irrespective of the application of IPT. IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer. The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent, an inefficient modus of application, or a lack of sufficient drug penetration into the serosa or peritoneal metastasis.

Immune stimulation with interleukin-2 after autologous stem cell transplantation in children and adolescents with solid tumors

Children with solid tumors of poor prognosis have benefitted from autologous bone marrow transplantation as a treatment modality. Adjuvant interleukin-2 (IL2) therapy has previously been shown to improve prognosis in adults with some solid tumors. In this setting improved survival probability has been attributed to IL2-mediated augmentation of antineoplastic activity of the immune system. In this study 8 pediatric patients in complete remission after autologous stem cell transplantation were treated with recombinant IL2 administered in 3 cycles of 5 days continuous intravenous infusions and a two week rest in between. We demonstrated that IL2 therapy increased transplantation-related activation of the immune system both on cellular and humoral levels. Peripheral blood T and NK cell number increased by the factors 1.7 and 6.0 respectively. NK and T cell activation were further enhanced as indicated by elevated levels of soluble IL2 receptor. The production of tumor cytotoxic cytokines like alpha TNF and gamma INF was stimulated. The elevated aTNF and gamma INF cytokine synthesis seemed to be mainly related to the activation and proliferation of NK cells, as T cells obtained from patients after IL2 therapy showed a definite cytokine production deficiency after T cell specific stimulation.

Evaluation of a new classification of cerebrovascular disease: CHAT

A new scheme that classifies cerebrovascular disease on the basis of current and prior clinical symptoms, arteriographic findings, and target organ abnormalities has been evaluated. The scheme proved to be easy to learn and to use. Its utility was demonstrated by the previously unreported distinctions that became apparent when various patient subsets were analyzed according to the CHAT classification. These included an improved probability of stroke-free survival in patients operated on for brief strokes (transient ischemic attack) as opposed to temporary strokes (reversible ischemic neurologic deficit), and similarly improved survival probability in patients operated on for amaurosis fugax in comparison to those with carotid territory hemispheric transient ischemic attacks. The impact of multiple arterial lesions and positive computerized tomography scan findings appeared to be minimal with respect to both late stroke and survival in our preliminary observations. The simplicity and utility of the CHAT scheme make it a useful method to evaluate and report clinical experience with cerebrovascular disease.

POST-IRRADIATION CASTRATION OF THE MALE AND ENHANCED SURVIVAL.

Summary and conclusions1. Male mice of the ICR and CF1 strains were X-irradiated to the LD/50/30 range and some were castrated in order to determine whether the loss of testosterone might alter survival. 2. In both strains, post-irradiation castration (within 30 minutes) did indeed increase statistically the survival of the mice. 3. A delay in castration of 24 hours after irradiation (of the CF1 males) increased survival chances, and estradiol (at that time) further improved survival probability. However, estradiol benzoate given immediately after X-irradiation and castration had an unfavorable effect. 4. It is suggested that the mechanism of effect of castration may be in the encouragement of lymphocyte recovery, thus reducing the usual effects of lymphopenia attendant upon X-irradiation. 5. Since the survival improvement by post-irradiation castration is statistically significant, but amounts to only about 30%, its efficacy lies near the LD/100/30 range, and not higher. Possibly in combination with bone...