Safety and Efficacy of Reproductive Organ-Sparing Radical Cystectomy in Women With Variant Histology and Advanced Stage

PurposeMuscle invasive bladder cancer surgical management has been historically a radical cystoprostatectomy in males and an anterior exenteration in females. Uterine, ovarian, and vaginal preservation are utilized, but raise concerns regarding risk to oncologic control, especially in variant histopathology or advanced stage.Materials and MethodsA retrospective single institutional analysis identified radical cystectomies performed in women, including those with variant histology, which were defined as reproductive organ sparing (uterine, vaginal, and ovary sparing) or nonorgan sparing. The Kaplan-Meier method was used for recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in patients with advanced disease.ResultsFrom 2000 to 2020, 289 women were identified, 188 underwent reproductive organ-sparing cystectomy. No statistical differences were noted for clinical parameters or presence of variant histology for organ-sparing (ROS) and nonorgan-sparing (non-ROS). Positive margin rates did not differ for ROS and non-ROS; 4.3% vs. 7.9%, P = .19, respectively. Median RFS was not statistically significantly different for ROS vs. non-ROS (26.1 vs. 15.3 months) P = .937 hazard ratio (HR) 1.024. CSS was not statistically different for ROS vs. non-ROS (36.3 vs. 28.6 months), P = .755 HR 0.9. OS was not statistically different for ROS vs. non-ROS (25.8 vs. 23.8 months), P = .5 HR = 1.178. Variant histology did not change survival (HR 1.1, P = .643).ConclusionIn this analysis, ROS in women with advanced disease did not increase positive margin rates or decrease RFS, CSS, or OS compared to non-ROS. Variant histology did not decrease survival odds. Based on preoperative assessment and intraoperative findings, ROS in patients with variant histology and advanced disease should be considered.     

Cultural eactors constraining the introduction of family planning among the Kassena-Nankana of Northern Ghana

This study presents a focus group investigation of reasons why women in a rural, Sahelian community are reluctant to adopt family planning even when convenient services are made freely available. First, women opting to practice contraception must do so at considerable risk of social ostracism or familial conflict. Implementing individual preference is something that must be done without the support of others. Second, few women view personal decisions about contraceptives as theirs to make. Women and children are the property of the corporate family-kin and community militate against reproductive control. Third, although children are highly valued for a variety of economic, social, and cultural reasons, mortality risks remain extremely high. Low fertility imposes the unacceptable risk that a woman will have no surviving children at the end of her reproductive life. Taken together, these findings attest to the inadequacy of service strategies focused on the contribution of distribution, individual agency, or personal choice. Outreach should also build a sense of community legitimacy for the program, collective health action, and traditional leadership support for family planning behavior.     

Deaths in the United States among persons with Alzheimer's disease (2010–2050)

BackgroundAlzheimer's disease (AD) profoundly affects the end-of-life experience. Yet, counts of deaths attributable to AD understate this burden of AD in the population. Therefore, we estimated the annual number of deaths in the United States among older adults with AD from 2010 to 2050.MethodsWe calculated probabilities of AD incidence and mortality from a longitudinal population-based study of 10,802 participants. From this population, 1913 previously disease-free individuals, selected via stratified random sampling, underwent 2577 detailed clinical evaluations. Over the course of follow-up, 990 participants died. We computed age-, sex-, race-, and education-specific AD incidences and education-adjusted AD mortality proportions specific to age, sex, and race group. We then combined these probabilities with US-wide census, education, and mortality data.ResultsIn 2010, approximately 600,000 deaths occurred among individuals aged 65 years or older with AD, comprising 32% of all older adult deaths. By 2050, this number is projected to be 1.6 million, 43% of all older adult deaths.ConclusionIndividuals with AD comprise a substantial number of older adult deaths in the United States, a number expected to rise considerably in coming decades.     

A five-year clinical trial of levonorgestrel silastic implants (Norplant™)

Silastic implants containing the progestin, levonorgestrel, were tested as a long-term contraceptive system in 101 women. During five full years of use, no pregnancies occurred. The 5-year continuation rate was 54%. Menstrual irregularities were the most frequent reason for termination of use but only during the first year. More than half of the terminations for this reason were in the first year. Some of the subjects elected to continue use of the implants beyond 5 years, allowing release rate data to be obtained through 6 years.From the second through the sixth year of use, the implants delivered a constant 30 micrograms per day of levonorgestrel to the subjects, and even after six years 57% of the original steroid content remained in the capsules.Return of fertility following removal was essentially immediate and not related to time of use. Medical reasons for removal were infrequent and no pattern was discernible.     

Patients’ self-assessment versus investigators’ evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15)

BackgroundToxicity, which is a key parameter in the evaluation of cancer treatments, can be underestimated by clinicians. We investigated differences between patients and physicians in reporting adverse events of androgen deprivation therapy (ADT) with or without docetaxel in a multicentre phase III trial in non-castrate metastatic prostate cancer.MethodsThe 385 patients included were invited to complete a 26-symptom questionnaire 3 and 6 months after the start of treatment, among which eighteen symptoms were also assessed by physicians, reported in medical records and graded using the Common Toxicity Criteria of the National Cancer Institute. Positive and negative agreements as well as Kappa concordance coefficients were computed.FindingsData were available for 220 and 165 patients at 3 and 6 months respectively. Physicians systematically under-reported patients’ symptoms. Positive agreement rates (at respectively 3 and 6 months) for the five most commonly reported symptoms were: 61.0% and 64.3% hot flushes, 50.0% and 43.6% fatigue, 29.4% and 31.1% sexual dysfunction, 24.4% and 14.4% weigh gain/loss, 16.7% and 19.3% for joint/muscle pain. For symptoms most frequently reported as disturbing or very disturbing by patients, the clinicians’ failure to report them ranged from 50.8% (hot flushes) to 89.5% (joint/muscle pain) at 3 months, and from 48.2% (hot flushes) to 88.4% (joint/muscle pain) at 6 months.InterpretationPhysicians often failed to report treatment-related symptoms, even the most common and disturbing ones. Patients’ self-evaluation of toxicity should be used in clinical trials to improve the process of drug assessment in oncology.FundingFrench Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, Astra-Zeneca, and Amgen.     

Trends in incidence,initial treatment and survival of myelodysplastic syndromes: A population-based study of 5144 patients diagnosed in the Netherlands from 2001 to 2010

BackgroundStudies with long-term follow-up of patients with myelodysplastic syndromes (MDS) based on data from nationwide population-based cancer registries are lacking. We conducted a nationwide population-based study to assess trends in incidence, initial treatment and survival in MDS patients diagnosed in the Netherlands from 2001 to 2010.MethodsWe identified 5144 MDS patients (median age, 74 years) from the Netherlands Cancer Registry (NCR). The NCR only includes MDS cases that were confirmed by bone marrow examinations. Information regarding initial treatment decisions was available in the NCR.ResultsThe age-standardised incidence rate of MDS was 2.3/100,000 in 2001–2005 and 2.8/100,000 in 2006–2010. The incidence increased with older age, with the highest incidence among those aged ⩾80 years (32.1/100,000 in 2006–2010). Forty-nine percent of all MDS cases were unspecified. Of all patients, 89% receive no treatment or only supportive care and 8% were started on intensive therapy as initial treatment. Survival did not improve over time. The 5-year relative survival was 53%, 58%, 48%, 38% and 18% in patients with refractory anaemia (RA), RA with ringed sideroblasts, 5q-syndrome, refractory cytopenia with multilineage dysplasia, and RA with excess blasts, respectively.ConclusionThe incidence of MDS increased over time due to improved notification and better disease awareness, and has stabilised since 2007. The classification of MDS seems challenging as almost half of the pathologically confirmed cases were unspecified. The lack of improvement in survival might be explained by the limited availability of therapeutic agents. Therefore, ameliorated management and new treatment options are warranted.     

Effect of intrauterine copper wire on resorption of fetuses in rats

A copper ring was transfixed through the uterine lumen after implantation (Day 6 of pregnancy) in the rat. The copper ring was either left $\text{in situ}$ or removed during pregnancy. The incidence of resorption of embryo in relation to the duration of the copper present in the uterus was examined.In the first experiment, the percentage of the fetuses which were resorbed increased from 16.7 on Day 12 to 59.6 on Day 18 when the wire remained $\text{in situ}$. In the second experiment, only 15.4% of the fetuses were resorbed by Day 18 and Day 21, when the wire was removed on Day 12. However, 25.9% of the fetuses were resorbed on Day 18 and 48.1% on Day 21, when the wire was removed on Day 18.The results indicate that an intrauterine copper wire did affect the incidence of resorption of fetuses and that this effect upon the fetuses became apparent only after Day 12 of pregnancy.It can be concluded from this study that the longer the copper remains in the uterus during the late stages of pregnancy, the greater effect it has upon the rate of resorption of the fetuses.     

New antifertility agents active in the rabbit vaginal contraception (RVC) method

Zinc salts in aqueous K-Y Jelly are effective vaginal contraceptives in the rabbit. The minimum effective dose is 54 to 60 mg Zn/ rabbit as acetate, gluconate or lactate. Zinc salts added to suboptimal doses of Ortho-Gynol Jelly or Delfen Cream improves the vaginal contraceptive efficacy of these products. Twenty-seven mg zinc/rabbit as lactate or acetate and 28 mg zinc/rabbit as sulfate or chloride in 0.1 to 0.5 ml of cream or jelly are effective. Gossypol is effective at a dose of 2 mg/rabbit. Although there is some rationale for their use, manganese has no antifertility effect and Valium appears to promote fertility. The rabbit vaginal contraception (RVC) method shows undesirable variation but use of sufficient animals yields logical and reliable results. Artificial insemination instead of breeding appears to decrease variation.     

Subdermal norethindrone pellets — A method for contraception?

The mode of action of compressed pellets containing 85 per cent norethindrone (NET) and 15 per cent cholesterol was studied. Four pellets were inserted subcutaneously, in each of five healthy volunteers and left in place for 200–229 days. The NET content of the pellets varied between 23.9 mg and 25.6 mg; and the cholesterol content between 4.2 mg and 4.5 mg. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. Plasma levels of NET varied mostly between 1–2 ng/ml the first month after insertion. After two months plasma levels of NET ranged between 0.5 ng/ml and 1 ng/ml in all volunteers and there was a gradual decrease of the plasma NET levels throughout treatment. Pronounced day-to-day variations in plasma NET levels were recorded. The release rates of NET was calculated to be between 187 μg/day and 243 μg/day among the five volunteers. Ovulations occurred in four out of five subjects during treatment. This study indicates that the release of gestagen from four NET pellets was only initially high enough to completely inhibit ovulation, and that to accomplish full contraceptive efficacy, a higher dose, i.e. more pellets, would have to be inserted.