Treatment of Wilms tumor relapsing after initial treatment with vincristine and actinomycin D: a report from the National Wilms Tumor Study Group

PURPOSE: NWTS-5 was a multi-institutional clinical trial for patients less than 16 years of age at diagnosis with specific renal neoplasms who were diagnosed between August 1, 1995 and May 31, 2002. A uniform approach to the treatment of patients with relapse was employed. PATIENTS AND METHODS: Seventy-two patients who relapsed after immediate nephrectomy (stages I and II), initial chemotherapy with vincristine (VCR) and actinomycin D and no radiation therapy were registered on stratum B of the NWTS-5 relapse protocol. Four patients were not evaluable: one due to insufficient data and three due to major protocol violations. Among the 68 remaining patients, one who was 19 years of age at initial diagnosis of Wilms tumor, five with bilateral Wilms tumor at diagnosis, three who developed a contralateral relapse, and one with persistent disease were not included in this analysis. Relapse treatment included surgical excision, when feasible, radiation therapy and alternating courses of VCR, doxorubicin and cyclophosphamide and etoposide and cyclophosphamide. RESULTS: The outcomes of 58 patients were analyzed. The lung was the only site of relapse for 31 patients. Event-free survival 4 years after relapse was 71.1% and 4-year overall survival was 81.8% for all patients and were 67.8 and 81.0% for those who relapsed only to their lungs. The most frequent toxicities were hematological. CONCLUSIONS: These results demonstrate that a significant proportion of children with Wilms tumor who relapse after initial treatment with VCR and actinomycin D can be successfully re-treated.     

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

Photocrosslinkable hyaluronic acid as an internal wetting agent in model conventional and silicone hydrogel contact lenses

Photocrosslinkable methacrylated hyaluronic acid (HA) was prepared and incorporated into model conventional and silicone hydrogel contact lenses as an internal wetting agent. The molecular weight of the HA, the degree of methacrylation as well as the amount (0.25 to 1.0 wt %) incorporated were varied. The HA-containing hydrogels were analyzed using a variety of techniques including water contact angles, equilibrium water content (EWC), and lysozyme sorption. The presence of HA could be detected in the materials using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy-attenuated total reflectance. The materials containing methacrylated HA had improved hydrophilicity and reduced lysozyme sorption. Effects of modified HA on EWC were dependent upon the materials but generally increased water uptake. Increased mobility of the HA associated with a lower molecular weight and lower degree of methacrylation was found to be more effective in improving hydrophilicity and decreasing lysozyme sorption than the less mobile HA. All results found suggest that photocrosslinkable HA has significant potential in contact lens applications.     

Class, race, ethnicity and information needs in post-treatment cancer patients

Objective

Health information-seeking behaviors (HISBs) are associated with active participation in cancer care decisions which, in turn, may positively impact health outcomes. The goal of this study was to develop a taxonomy of topics for which post-treatment cancer patients sought information, and to explore HISB patterns by sociodemographic factors and cancer type.

Methods

We examined how health information seeking is associated with social determinants in a survey of 521 post-treatment cancer patients.

Results

Four major topics of interest were found: disease/treatment, self-care management, health services, and work/finance. Assessment of the relationship between social determinants and these four topics showed associations for (1) HISBs on disease/treatment topics decreased with age and increased with education; (2) HISBs on self-care management increased with education and varied by cancer type; (3) HISBs on health services increased with education; and (4) HISBs on work/finance decreased with age and wealth, but increased with debt.

Conclusion

These results demonstrate one pathway through which social determinants may drive communication inequalities, which may result in increased disparities in health outcomes.

Practice implications

Further exploration of the relationship between social determinants and information-seeking among post-treatment cancer patients may contribute to the development of strategies to reduce health disparities.     

Expression of a collagenase that enables blood-brain barrier penetration for Salmonella implicated in bovine encephalopathies

Recent studies identified strains of Salmonella that induce encephalopathies in calves exposed to stressful situations. In order to cause neurologic signs (such as ataxia, head tilt, and partial blindness), the strain must be able to cross the blood-brain barrier (BBB). One possible way is through the break down of tight junctions, which regulate the permeability of the BBB and can be weakened by enzymes such as collagenases. Salmonella and other Gram-negative bacteria contain a collagenase gene (clg) that is silenced in vitro but inducibly expressed in vivo. We hypothesized that the neuropathic strains of Salmonella express clg in response to neuroendocrine factors in the host and that the expressed collagenase perturbs the BBB allowing for CNS invasion by Salmonella. Our in vitro results revealed that clg is derepressed in serum obtained from stressed cattle. Derepression is relegated to the neuropathic Salmonella strains. In vivo studies indicated that clg expression is required for neuropathogenicity and that pharmacologic maintenance of the BBB prevents both the Salmonella invasion into the brain and the resulting neurologic signs. These studies identify a host-induced Salmonella collagenase that facilitates neuropathogenicity at the level of the BBB.     

Use of alternative medicine by women with early-stage breast cancer.

BACKGROUND: We analyzed the use of alternative medicine by women who had received standard therapy for early-stage breast cancer diagnosed between September 1993 and September 1995. METHODS: A cohort of 480 patients with newly diagnosed early-stage breast cancer was recruited from a Massachusetts statewide cohort of women participating in a study of how women choose treatment for cancer. Alternative medical treatments, conventional therapies, and health-related quality of life were examined. RESULTS: New use of alternative medicine after surgery for breast cancer was common (reported by 28.1 percent of the women); such use was not associated with choices about standard medical therapies after we controlled for clinical and sociodemographic variables. A total of 10.6 percent of the women had used alternative medicine before they were given a diagnosis of breast cancer. Women who initiated the use of alternative medicine after surgery reported a worse quality of life than women who never used alternative medicine. Mental health scores were similar at base line among women who decided to use alternative medicine and those who did not, but three months after surgery the use of alternative medicine was independently associated with depression, fear of recurrence of cancer, lower scores for mental health and sexual satisfaction, and more physical symptoms as well as symptoms of greater intensity. All groups of women reported improving quality of life one year after surgery. CONCLUSIONS: Among women with newly diagnosed early-stage breast cancer who had been treated with standard therapies, new use of alternative medicine was a marker of greater psychosocial distress and worse quality of life.     

Precision-grip force changes in the anatomical and prosthetic limb during predictable load increases

This study examined precision-grip force applied to an instrumented test object held aloft while the weight of the object was predictably varied by transporting and placing loads (50, 100, or 200 g) atop the test object. Transport of the loads was performed either by the subject or the experimenter. Grip force was examined in four non-amputee control subjects and in the anatomical and prosthetic hand of a subject with a prosthetic device. As subjects transported the load, anticipatory grip-force changes occurred in the anatomical hands and prosthetic hand, which were scaled in relation to the load. When the experimenter transported the load to the anatomical hands of control subjects or the prosthetic user, anticipatory increases in grip force occurred that also were scaled in relation to load. However, when the experimenter transported the load to the prosthetic hand, anticipatory grip-force adjustments were absent. During the phase in which the load was being assumed by the postural hand, grip forces in the anatomical hands and prosthetic hand were further scaled to load demands. Ability to adapt grip force in the prosthetic hand during this phase suggested that the subject was utilizing sensory information from the residual limb to adjust grip force. Thus, while anticipatory changes precede the process of adaptation to load changes, actual sensory consequences resulting from added weight remain necessary to fully adapt grip force to load demands, even for the prosthetic user.     

Radiofrequency ablation: effect of surrounding tissue composition on coagulation necrosis in a canine tumor model

PURPOSE: To determine the effect of surrounding tissue type on coagulation necrosis from radiofrequency (RF) ablation in a homogeneous animal tumor model. MATERIALS AND METHODS: Thirty canine venereal sarcomas were implanted in three tissue sites (subcutaneous, kidney, and lung) in 13 mildly immunosuppressed dogs. Five of 25 tumors, which were 19 mm +/- 3 (mean +/- SD) in diameter, were allocated to each of five groups: (a) subcutaneous tumors, (b) kidney tumors, (c) lung tumors with blood flow, and (d) subcutaneous and (e) renal tumors without blood flow, which was achieved by sacrificing the animal to eliminate tumor perfusion. A sixth group comprised larger subcutaneous tumors (mean diameter, 46 mm +/- 4) that were also treated. RF ablation was performed with a 1-cm tip and 5 minutes of ablation at 90 degrees C +/- 1. Impedance, temperature, and resultant coagulation diameter were recorded and compared. Data were analyzed statistically, including one-way analysis of variance to determine the effect of tissue conductivity (ie, systemic impedance) on necrosis size and tissue temperatures. Linear regression analysis was used to compare changes in impedance between the control and experimental groups. RESULTS: Increasing linear correlation was observed between tumor coagulation diameter and overall baseline system impedance (R(2) = 0.65). RF ablation of lung tumors resulted in the greatest coagulation diameter (13.0 mm +/- 3.5) compared with that in the other groups (P <.01). The smallest coagulation diameter was observed in kidney tumors in the presence of blood flow (7.3 mm +/- 0.6) compared with that in the other groups (P <.01). Elimination of blood flow in kidney tumors increased coagulation diameter to 10.3 mm +/- 0.6 (P <.01). After RF ablation, coagulation diameter in the subcutaneous tumor groups was the same (mean, 9.8 mm +/- 1.0) (difference not significant), regardless of tumor size or presence of blood flow. CONCLUSION: The characteristics of tissue that surrounds tumor, including vascularity and electric conductivity, affect ablation outcome. Predominance of tissue-specific characteristics will likely result in site-specific differences in RF-induced coagulation necrosis.     

A Comparison of Bone-Targeted Exercise With and Without Antiresorptive Bone Medication to Reduce Indices of Fracture Risk in Postmenopausal Women With Low Bone Mass: The MEDEX-OP Randomized Controlled Trial

The goal of the MEDEX-OP trial was to compare the efficacy of a known effective high-intensity resistance and impact training (HiRIT) with a low-intensity exercise control (Buff Bones® [BB]), alone or in combination with antiresorptive bone medication, on indices of fracture risk (bone mass, body composition, muscle strength, functional performance), compliance, and safety. Primary study outcomes were 8-month change in lumbar spine (LS) and total hip (TH) bone mineral density (BMD). Healthy postmenopausal women with low bone mass (T-score ≤ −1.0) on or off stable doses (≥12 months) of antiresorptive medication were recruited. A total of 115 women (aged 63.6 ± 0.7 years; body mass index [BMI] 25.5 kg/m²; femoral neck [FN] T-score −1.8 ± 0.1) were randomly allocated to 8-month, twice-weekly, 40-minute HiRIT (5 sets of 5 repetitions, >80% to 85% 1 repetition maximum) or BB (low-intensity, Pilates-based training), stratified by medication intake, resulting in four groups: HiRIT (n = 42), BB (n = 44), HiRIT-med (n = 15), BB-med (n = 14). HiRIT improved LS BMD (1.9 ± 0.3% versus 0.1 ± 0.4%, p < 0.001) and stature (0.2 ± 0.1 cm versus −0.0 ± 0.1 cm, p = 0.004) more than BB. Both programs improved functional performance, but HiRIT effects were larger for leg and back muscle strength and the five times sit-to-stand test (p < 0.05). There was a positive relationship between maximum weight lifted and changes in LS BMD and muscle strength in the HiRIT groups. Exploratory analyses suggest antiresorptive medication may enhance exercise efficacy at the proximal femur and lumbar spine. Exercise compliance was good (82.4 ± 1.3%) and both programs were well tolerated (7 adverse events: HiRIT 4; BB 3). HiRIT improved indices of fracture risk significantly more than Buff Bones®. More trials combining bone medication and bone-targeted exercise are needed. © 2021 American Society for Bone and Mineral Research (ASBMR).