High-Risk Merkel Cell Carcinoma of the Skin Treated With Synchronous Carboplatin/Etoposide and Radiation: A Trans-Tasman Radiation Oncology Group Study-TROG 96:07

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy was prospectively assessed in a group of patients with high-risk Merkel cell carcinoma (MCC) of the skin. Patients and Methods: Patients were eligible if they had disease localized to the primary site and nodes, and were required to have at least one of the following high risk features: recurrence after initial therapy, involved nodes, primary tumor size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks and synchronous carboplatin (area under the curve, 4.5) and intravenous etoposide 80 mg/m(2) days 1 to 3 was given in weeks 1, 4, 7, and 10. The median age of the group was 67 (range, 43-86) years, and there were 39 males and 14 females. Involved nodes (stage II) were present in 33 cases (62%). The sites involved were head and neck (22 patients), occult primary (13 patients), upper limb (eight patients), lower limb (eight patients), and trunk (two patients). Results: Fifty-three patients were entered between 1996 and 2001. The median potential follow-up was 48 months. There were no treatment related deaths. The 3-year overall survival, locoregional control, and distant control were 76%, 75%, and 76%, respectively. Tumor site and the presence of nodes were factors that were predictive for local control and survival. Multivariate analysis indicated that the major factor influencing survival was the presence of nodes; however, this was not a significant factor in locoregional control. Conclusion: High levels of locoregional control and survival have been achieved with the addition of chemotherapy to radiation treatment for high-risk MCC of the skin. The role of chemoradiotherapy for high-risk MCC warrants further investigation. (C) 2003 by American Society of Clinical Oncology.

Midline rectovaginal fascial plication for repair of rectocele and obstructed defecation

OBJECTIVE: To estimate the efficacy of midline fascial plication of the posterior vaginal wall in women with rectoceles and obstructed defecation. METHODS: Prospective evaluation of 38 consecutive women with symptomatic rectoceles (stage II or greater) and obstructed defecation included pre- and postoperative standardized pelvic floor questions, pelvic organ prolapse quantification measurements, validated bowel function questionnaires, defecating proctogram, and patient satisfaction. Reviews were conducted by nonsurgical coauthors. RESULTS: The median follow-up was 12.5 months (range 2.5-26 months). The subjective success rates were 97% (95% confidence interval [CI] 0.83-1.00%) at 12 months and 89% (95% CI 0.55-0.98%) at 24 months. The objective success rates were 87% (95% CI 0.64-0.96%) at 12 months and 79% (95% CI 0.51-0.92%) at 24 months. The average points, Ap and Bp, were significantly reduced from -0.1 (range -2 to 3) and 1.1 (range -1 to 8), preoperatively, to -2.6 (range -3 to -1) and -2.5 (range -3 to 0), postoperatively, respectively (P

Perinatal outcomes with laser surgery for twin-twin transfusion syndrome

The aim of this tertiary hospital-based cohort study was to determine and compare perinatal outcome and neonatal morbidities of pregnancies with twin-twin transfusion syndrome (TTTS) before and after the introduction of a treatment program with laser ablation of placental communicating vessels. Twenty-seven pregnancies with Stage II-IV TTTS treated with amnioreduction were identified (amnioreduction group). The data were compared with that obtained from the first 31 pregnancies with Stage II-IV TTTS managed with laser ablation of placental communicating vessels (laser group). Comparisons were made for perinatal survival and neonatal morbidities including abnormalities on brain imaging. The median gestation at therapy was similar between the two groups (20 vs. 21 weeks, p = .24), while the median gestation at delivery was significantly greater in the laser treated group (34 vs. 28 weeks, p = .002). The perinatal survival rate was higher in the laser group (77.4% vs. 59.3%, p = .03). Neonatal morbidities including acute respiratory distress, chronic lung disease, requirement for ventilatory assistance, patent ductus arteriosus, hypotension, and oliguric renal failure had a lower incidence in the laser group. On brain imaging, ischemic brain injury was seen in 12% of the amnioreduction group and none of the laser group of infants (p = .01). In conclusion, these findings indicate that perinatal outcomes are improved with less neonatal morbidity for monochorionic pregnancies with severe TTTS treated by laser ablation of communicating placental vessels when compared to treatment by amnioreduction.

Expression and methylation pattern of TSLC1 cascade genes in lung carcinomas

TSLC1 (tumor suppressor in lung cancer-1, IGSF4) encodes a member of the immunoglobulin superfamily molecules, which is involved in cell-cell adhesion. TSLC1 is connected to the actin cytoskeleton by DAL-1 (differentially expressed in adenocarcinoma of the lung-1, EPB41L3) and it directly associates with MPP3, one of the human homologues of a Drosophila tumor suppressor gene, Discs large. Recent data suggest that aberrant promoter methylation is important for TSLC1 inactivation in lung carcinomas. However, little is known about the other two genes in this cascade, DAL-1 and MPP3. Thus, we investigated the expression and methylation patterns of these genes in lung cancer cell lines, primary lung carcinomas and nonmalignant lung tissue samples. By reverse transcription-polymerase chain reaction, loss of TSLC1 expression was observed in seven of 16 (44%) non-small-cell lung cancer (NSCLC) cell lines and in one of 11 (9%) small-cell lung cancer (SCLC) cell lines, while loss of DAL- 1 expression was seen in 14 of 16 (87%) NSCLC cell lines and in four of 11 (36%) SCLC cell lines. By contrast, MPP3 expression was found in all tumor cell lines analysed. Similar results were obtained by microarray analysis. TSLC1 methylation was seen in 13 of 39 (33%) NSC LC cell lines, in one of 11 (9%) SCLC cell lines and in 100 of 268 (37%) primary NSCLCs. DAL-1 methylation was observed in 17 of 39 (44%) NSCLC cell lines, in three of 11 (27%) SCLC cell lines and in 147 of 268 (55%) primary NSCLCs. In tumors of NSCLC patients with stage II-III disease, DAL-1 methylation was seen at a statistically significant higher frequency compared to tumors of patients with stage I disease. A significant correlation between loss of expression and methylation of the genes in lung cancer cell lines was found. Overall, 65% of primary NSCLCs had either TSLC1 or DAL-1 methylated. Methylation of one of these genes was detected in 59% of NSCLC cell lines; however, in SCLC cell lines, methylation was much less frequently observed. The majority of nonmalignant lung tissue samples was not TSLC1 and DAL-1 methylated. Re-expression of TSLC1 and DAL-1 was seen after treatment of lung cancer cell lines with 5-aza-2$-deoxy-cytidine. Our results suggest that methylation of TSLC1 and/or DAL-1, leading to loss of their expression, is an important event in the pathogenesis of NSCLC.

Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine

Advanced metastatic melanoma is incurable by standard treatments, but occasionally responds to immunotherapy. Recent trials using dendritic cells (DC) as a cellular adjuvant have concentrated on defined peptides as the source of antigens, and rely on foreign proteins as a source of help to generate a cell-mediated immune response. This approach limits patient accrual, because currently defined, non-mutated epitopes are restricted by a small number of human leucocyte antigens. It also fails to take advantage of mutated epitopes peculiar to the patient's own tumour, and of CD4(+) T lymphocytes as potential effectors of anti-tumour immunity. We therefore sought to determine whether a fully autologous DC vaccine is feasible, and of therapeutic benefit. Patients with American Joint Cancer Committee stage IV melanoma were treated with a fully autologous immunotherapy consisting of monocyte-derived DC, matured after culture with irradiated tumour cells. Of 19 patients enrolled into the trial, sufficient tumour was available to make treatments for 17. Of these, 12 received a complete priming phase of six cycles of either 0.9X10(6) or 5X10(6) DC/intradermal injection, at 2-weekly intervals. Where possible, treatment continued with the lower dose at 6-weekly intervals. The remaining five patients could not complete priming, due to progressive disease. Three of the 12 patients who completed priming have durable complete responses (average duration 3 5 months +), three had partial responses, and the remaining six had progressive disease (WHO criteria). Disease regression was not correlated with dose or with the development of delayed type hypersensitivity responses to intradermal challenge with irradiated, autologous tumour. However, plasma S-100B levels prior to the commencement of treatment correlated with objective clinical response (P = 0.05) and survival (log rank P < 0.001). The treatment had minimal side-effects and was well tolerated by all patients. Mature, monocyte-derived DC preparations exposed to appropriate tumour antigen sources can be reliably produced for patients with advanced metastatic melanoma, and in a subset of those patients with lower volume disease their repeated administration results in durable complete responses.

Does chemotherapy improve survival in high-risk Stage I and II Merkel cell carcinoma of the skin?

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m(2) i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For disease-specific survival, recurrent disease was the only significant factor. Primary site on the lower limb had an adverse effect on locoregional control. For distant control, the only significant factor was residual disease. Conclusions: The multivariate analysis suggests chemotherapy has no effect on survival, but because of the wide confidence limits, a chemotherapy effect cannot be excluded. A study of this size is inadequately powered to detect small improvements in survival, and a larger randomized study remains the only way to truly confirm whether chemotherapy improves the results in high-risk MCC. (c) 2006 Elsevier Inc.

The role of insulin-like growth factor II and its receptor in mouse preimplantation development

Insulin-like growth factor II (IGF-II) and its receptor, the IGF-II/mannose-6-phosphate (IGF-II/M6P) receptor, are first expressed from the zygotic genome at the two-cell stage of mouse development. However, their role is not clearly defined. Insulin-like growth factor II is believed to mediate growth through the heterologous type 1 IGF and insulin receptors, whereas the IGF-II/M6P receptor is believed to act as a negative regulator of somatic growth by limiting the availability of excess levels of IGF-II. These studies demonstrate that IGF-II does have a role in growth regulation in the early embryo through the IGF-II/M6P receptor. Insulin-like growth factor II stimulated cleavage rate in two-cell embryos in vitro. Moreover, this receptor is required for the glycaemic response of two-cell embryos to IGF-II and for normal progression of early embryos to the blastocyst stage. Improved development of embryos in crowded culture supports the concept of an endogenous embryonic paracrine activity that enhances cell proliferation. These responses indicate that the IGF-II/M6P receptor is functional and likely to participate in such a regulatory circuit. The functional role of IGF-II and its receptor is discussed with reference to regulation of early development.

Phototoxicity of photosystem II (PSII) herbicides to coral

Recent reports of contamination of the Great Barrier Reef Marine Park by herbicides used in antifouling paints and in agriculture have caused concern over the possible effects on corals in nearshore areas. Pulse-Amplitude Modulated (PAM) chlorophyll fluorescence techniques were used to examine changes in the maximum effective quantum yield (ΔF/Fm′) of symbiotic dinoflagellates within the host tissues (in hospite) of the coral Seriatopora hystrix exposed to a number of Photosystem II (PSII) inhibiting herbicides in short-term toxicity tests. The concentration of herbicide required to reduce ΔF/Fm′ by 50% (median effective concentration [EC50]) differed by over 2 orders of magnitude: Irgarol 1051 (0.7 μg l-1) > ametryn (1.7 μg l-1) > diuron (2.3 μg l-1) > hexazinone (8.8 μg l -1) > atrazine (45 μg l-1) > simazine (150 μg l-1) > tebuthiuron (175 μg l-1) > ionynil (> 1 mg l-1). Similar absolute and relative toxicities were observed with colonies of the coral Acropora formosa (Irgarol 1051 EC50: 1.3 μg l-1, diuron EC50: 2.8 μg l-1), Time-course experiments indicated that ΔF/Fm′ was rapidly reduced (i.e. within minutes) in S. hystrix exposed to Irgarol 1051 and diuron. On return to fresh running seawater, ΔF/Fm′ recovered quickly in diuron-exposed corals (i.e. in minutes to hours), but slowly in corals exposed to Irgarol 1051 (i.e. hours to days). Time-course experiments indicated that the effects of diuron (3 μg l-1) on S. hystrix were inversely related to temperature over the range 20 to 30 °C, although initially the effects were less at the lower temperatures. Repeated exposure to pulses of Irgarol 1051 (daily 2 h exposure to 30 μg l -1 over 4 d) resulted in a 30% decrease in the density of symbiotic dinoflagellates in the tissues of S. hystrix.

Randomized controlled trial of an educational intervention for managing fatigue in women receiving adjuvant chemotherapy for early-stage breast cancer

Purpose To evaluate the efficacy of a psychoeducational intervention in improving cancer-related fatigue. Patients and Methods This randomized controlled trial involved 109 women commencing adjuvant chemotherapy for stage I or II breast cancer in five chemotherapy treatment centers. Intervention group patients received an individualized fatigue education and support program delivered in the clinic and by phone over three 10- to 20-minute sessions 1 week apart. Instruments included a numeric rating scale assessing confidence with managing fatigue; 11-point numeric rating scales measuring fatigue at worst, average, and best; the Functional Assessment of Cancer Therapy-Fatigue and Piper Fatigue Scales; the Cancer Self-Efficacy Scale; the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; and the Hospital Anxiety and Depression Scale. For each outcome, separate analyses of covariance of change scores between baseline (T1) and the three follow-up time points (T2, T3, and T4) were conducted, controlling for the variable's corresponding baseline value. Results Compared with the intervention group, mean difference scores between the baseline (T1) and immediate after the test (T2) assessments increased significantly more for the control group for worst and average fatigue, Functional Assessment of Cancer Therapy-Fatigue, and Piper fatigue severity and interference measures. These differences were not observed between baseline and T3 and T4 assessments. No significant differences were identified for any pre- or post-test change scores for confidence with managing fatigue, cancer self-efficacy, anxiety, depression, or quality of life. Conclusion Preparatory education and support has the potential to assist women to cope with cancer-related fatigue in the short term. However, further research is needed to identify ways to improve the potency and sustainability of psychoeducational interventions for managing cancer-related fatigue.

Performance and endocrine responses of group housed weaner pigs exposed to the air quality of a commercial environment

The growth performance and endocrine responses of male weaner pigs (3 to 8 weeks of age) was evaluated in two different environments (clean and dirty) and housing (single or groups of 10 pigs/pen) conditions. The dirty environment contained significantly elevated ammonia, carbon dioxide and dust levels compared with the clean environment. Pigs grew faster and consumed more feed in the clean environment and this was associated with reduced plasma cortisol concentrations compared with pigs in the dirty environment. Pigs housed in groups in the dirty environment had increased β-endorphin and decreased IGF-I concentrations compared to group housed pigs in the clean environment. Feed conversion efficiency did not differ due to environment or group housing. Plasma concentration of cortisol, p-endorphin, IGF-I and IGF-II did not differ between single and group housed pigs. Activity of the hypothalamic-pituitary-adrenal (HPA) axis was greater in response to environmental conditions than group housing, and this was associated with reduced growth in weaner pigs. © 2004 Elsevier B.V. All rights reserved.

Effects of Photosystem II inhibiting herbicides on mangroves - preliminary toxicology trials

Mangroves are sensitive to the root application of Photosystem II inhibiting herbicides and Avicennia marina is more sensitive than other mangroves tested. Seedlings of four mangrove species, including two salt-excreting species (A. marina and Aegiceras corniculatum) and two salt-excluding species (Rhizophora stylosa and Ceriops australis) were treated with a range of concentrations of the herbicides diuron, ametryn and atrazine. Assessment of responses required the separation of seedlings into two groups: those that had only their roots exposed to the herbicides through the water (A. marina and R. stylosa) and those that had both roots and leaves exposed to herbicides through the water (A. corniculatum and C australis). Salt-excreting species in each group were more susceptible to all herbicide treatments than salt-excluding species, indicating that root physiology was a major factor in the uptake of toxic pollutants in mangroves. Submergence of leaves appeared to facilitate herbicide uptake, having serious implications for seedling recruitment in the field. Each herbicide was ranked by its toxicity to mangrove seedlings from most damaging to least effective, with diuron > ametryn > atrazine. The relative sensitivity of A. marina found in these pot trials was consistent with the observed sensitivity of this species in the field, notably where severe dieback had specifically affected A. marina in the Mackay region, north eastern Australia. (c) 2004 Elsevier Ltd. All rights reserved.

Low level microsatellite instability may be associated with reduced cancer specific survival in sporadic stage C colorectal carcinoma

Background: Colorectal cancers (CRCs) may be categorised according to the degree of microsatellite instability (MSI) exhibited, as MSI-high (MSI-H), MSI-low (MSI-L), or microsatellite stable (MSS). MSI-H status confers a survival advantage to patients with sporadic CRC. Aims: To determine if low levels of MSI are related to the clinicopathological features and prognosis of sporadic stage C CRC. Patients: A total of 255 patients who underwent resection for sporadic stage C CRC were studied. No patient received chemotherapy. Minimum follow up was five years. Methods: DNA extracted from archival malignant and non-malignant tissue was amplified by polymerase chain reaction using a panel of 11 microsatellites. MSI-H was defined as instability at greater than or equal to40% of markers, MSS as no instability, and MSI-L as instability at >0% but,40% of markers. Patients with MSI-H CRC were excluded from analysis as they have previously been shown to have better survival. Results: Thirty three MSI-L and 176 MSS CRCs were identified. There was no difference in biological characteristics or overall survival of MSI-L compared with MSS CRC but MSI-L was associated with poorer cancer specific survival (hazard ratio 2.0 (95% confidence interval 1.1-3.6)). Conclusions: Sporadic MSI-L and MSS CRCs have comparable clinicopathological features. Further studies are required to assess the impact of MSI-L on prognosis.

Minimising cold damage during reproductive development among temperate rice genotypes. II. Genotypic variation and flowering traits related to cold tolerance screening

Low temperature during microspore development increases spikelet sterility and reduces grain yield in rice (Oryza sativa L.). The objectives of this study were to determine genotypic variation in spikelet sterility in the field in response to low-temperature and then to examine the use of physio-morphological traits at flowering to screen for cold tolerance. Multiple-sown field experiments were conducted over 4 consecutive years in the rice-growing region of Australia to increase the likelihood of encountering low-temperature during microspore development. More than 50 cultivars of various origins were evaluated, with 7 cultivars common to all 4 years. The average minimum temperature for 9 days during microspore development was used as a covariate in the analysis to compare cultivars at a similar temperature. The low-temperature conditions in Year 4 identified cold-tolerant cultivars such as Hayayuki and HSC55 and susceptible cultivars such as Sasanishiki and Doongara. After low temperature conditions, spikelet sterility was negatively correlated with the number of engorged pollen grains, anther length, anther area, anther width, and stigma area. The number of engorged pollen grains and anther length were found to be facultative traits as their relationships with spikelet sterility were identified only after cold water exposure and did not exist under non-stressed conditions.

Production of triploid Kuruma shrimp, Marsupenaeus (Penaeus) japonicus (Bate) nauplii through inhibition of polar body I, or polar body I and II extrusion using 6-dimethylaminopurine

This study investigated the chromosome ploidy level of Marsupenaeus (Penaeus) japonicus (Bate) non-viable (unhatched) embryos and nauplii after exposure to 6-dimethylaminopurine (6-DMAP), timed to stop either polar body (PB) I, or PBI and II extrusion. Embryos from eight separate families or spawnings were exposed to 150 or 200 mu M 6-DMAP from 1- to 3-min post-spawning detection (psd) for a 4- to 5-min duration (timed to stop PBI extrusion). Separate aliquots of embryos from five of the same spawnings were also exposed to 200 mu M of 6-DMAP from 1- to 3-min psd for a 16-min duration (timed to stop both PBI and II extrusion). For one spawning, a third aliquot of embryos was exposed to 400 p M of 6-DMAP from 1- to 3-min psd for a 16-min duration (timed to stop both PBI and II extrusion). At 18-h psd, non-viable embryo and nauplii samples were taken separately for fluorescent activated cell sorting (FACS). FACS revealed that there were diploids and triploids among all treated non-viable embryos and nauplii. All control non-viable embryos and nauplii were diploid. Percentages of triploid induction for the 4- to 5-min and 16-min durations were not significantly different (P > 0.05). Additionally, no difference was found in the triploidy level of nonviable embryos compared to nauplii in these treatments. The percentage of triploid embryos and nauplii when exposed to 6-DMAP for a 4- to 5-min duration ranged from 29.57% to 99.23% (average 55.28 +/- 5.45%) and from 5.60% to 98.85% (average 46.70 +/- 7.20%), respectively. The percentage of triploid embryos and nauplii when exposed to 6-DMAP for a 16-min duration ranged from 11.71% to 98.96% (average 52.49 +/- 11.00%) and from 47.5% to 99.24% (average 79.38 +/- 5.24%), respectively. To our knowledge, this is the first documentation of successful PBI or PBI and II inhibition in shrimp. This study conclusively shows that treatment of M. japonicus embryos with 6-DMAP at 1- to 3-min pscl for either a 4- to 5-min duration (timed to stop PBl extrusion) or 16-min duration (timed to stop both PBI and II extrusion) results in viable triploid nauplii. (c) 2006 Elsevier B.V. All rights reserved.

Evaluating the properties of a stage-specific self-efficacy scale for physical activity using classical test theory, confirmatory factor analysis and item response modeling

The purpose of this paper was to evaluate the psychometric properties of a stage-specific selfefficacy scale for physical activity with classical test theory (CTT), confirmatory factor analysis (CFA) and item response modeling (IRM). Women who enrolled in the Women On The Move study completed a 20-item stage-specific self-efficacy scale developed for this study [n = 226, 51.1% African-American and 48.9% Hispanic women, mean age = 49.2 (67.0) years, mean body mass index = 29.7 (66.4)]. Three analyses were conducted: (i) a CTT item analysis, (ii) a CFA to validate the factor structure and (iii) an IRM analysis. The CTT item analysis and the CFA results showed that the scale had high internal consistency (ranging from 0.76 to 0.93) and a strong factor structure. Results also showed that the scale could be improved by modifying or eliminating some of the existing items without significantly altering the content of the scale. The IRM results also showed that the scale had few items that targeted high self-efficacy and the stage-specific assumption underlying the scale was rejected. In addition, the IRM analyses found that the five-point response format functioned more like a four-point response format. Overall, employing multiple methods to assess the psychometric properties of the stage-specific self-efficacy scale demonstrated the complimentary nature of these methods and it highlighted the strengths and weaknesses of this scale.