Cutaneous metastasis from gastric cancer: Manifestation, diagnosis, treatment and prognosis.

INTRODUCTION: Cutaneous metastasis from gastric cancer is very rare. The understanding of this disease is incomplete. This situation delays its diagnosis and treatment, followed by poor prognosis. Here, we first report a study based on a network to improve the diagnosis, treatment and prognosis of cutaneous metastasis from gastric cancer. METHODS: A comprehensive search of PubMed was performed. All studies on cutaneous metastasis from gastric cancer were collected. The publication date was limited from 2000 to the present, and the language was limited to English. SPSS 26.0 was employed for statistical analysis. RESULTS: Seventy-two patients were included. The average patient age was 60.0 ± 16.0 years. In total, 72.2 % of the patients were male. The most common manifestation was nodular skin lesions (45.8 %). The metastases generally presented as multiple lesions (61.1 %). The most common metastasis location was the thoracoabdominal wall (56.9 %). 64.7 % of the patients simultaneously had extracutaneous metastases. Most of the tumors were poorly differentiated carcinomas (87.5 %), and 66.1 % had signet ring cells. 40.8 % of the cutaneous metastases presented as primary manifestations. Only 9.6 % had their diagnosis as soon as the cutaneous metastasis emerged. Systemic chemotherapy (65.6 %) was the most common treatment strategy, followed by radical surgery (12.5 %). The median overall survival was only 6 months. The median overall survival of 5 patients with resected tumors was 48 months. CONCLUSION: Cutaneous metastasis from gastric cancer usually manifests as an emerged nodule or erysipelas-like skin lesion. Resection of the cutaneous lesion could be helpful for patients with local metastases.

Diagnostic accuracy of swine echinococcosis cytopathological tests and challenges for a differential diagnosis: slaughterhouse data.

Echinococcosis disease shows clinical signs similar to many diseases. Hence we report cases that need to be confirmed using appropriate tests. A confirmatory study has been conducted to assess the accuracy of two cytopathological tests, with the histopathology test as the reference standard. The first cytopathological test evaluates the Ziehl Neelsen staining with an epifluorescence microscope (cytopath 1). The second cytopathological test uses the same staining followed by a transmitted light microscope examination (cytopath 2). Of a total of 2524 inspected pigs, 101 suspected cases of echinococcosis were detected, of which 67 were found positive with the two cytopathological tests and the histopathological one. The specificity of cytopath 1 (100 % [95 % CI 100 - 100]) and cytopath 2 (100 % [95 % CI 100;100]) were similar, as well as their respective positive predictive values: 100 % [95 % CI 100 - 100] vs. 100 % [95 % CI 100 - 100]. The sensitivity of cytopath 1 is 79.66 % [95 % CI 69.39 - 89.93], while cytopath 2 equals 66.10 % [95 % CI 54.02 - 78.18]. The difference in sensitivity of both tests was not significant. Negative predictive values found for cytopath 1, and cytopath 2 were 40 [95 % CI 18.53 - 61.47] and 28.57 [95 % CI 11.84 - 45.3], leading to the Generalized Estimating Equations (GEE) Model estimate for an odds ratio of 1.4 [95 % CI 0.41 - 5.2], p = 0.06. Cytopath 1 and cytopath 2 are equivalent in terms of specificity (100 % [95 % CI 100 - 100] vs. 100 % [95 % CI 100;100]) and positive predictive value (100 % [95 % CI 100 - 100]. Cytopath 1 is more sensitive than cytopath 2 but not significant (79.66 % [ 95 % CI 69.39 - 89.93] vs. 66.10 % [95 % CI 54.02 - 78.18]). However, the negative predictive value of cytopath 1 is better than that of cytopath 2: 40 % [95 % CI 18.53 - 61.47] vs. 28.57 % [95 % CI 11.84 - 45.3].

The efficiency and safety of immune checkpoint inhibitors for advanced biliary tract cancers based on gene profiles: A retrospectively controlled study.

Immune checkpoint inhibitors are potential agents to improve the survival of advanced biliary tract cancers (ABTCs). The current results are controversial because the predictors are imprecise. We present our primary experience with ABTCs based on gene landscape with exciting outcomes. ABTCs who were admitted to The First Affiliated Hospital of Henan University of Science and Technology from October 2019 to March 2021 were enrolled. They were divided into chemotherapy group or immunotherapy group according to the treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were response and toxicities. SSPS 16.0 was used for statistical analysis. A total of 33 patients were enrolled, including 25 in the chemotherapy group and 8 in the immunotherapy group. The median OS and PFS of the chemotherapy group were 2 and 4 months, respectively. The estimated median OS and PFS of immunotherapy were 10 + and 10 + months, respectively. The differences of OS and PFS between the 2 groups were significant (P = .000; P = .003). Stratified analysis showed that these differences were mainly from those patients with high expression of PD-L1 > 10%. The difference in the overall response was significant between 2 groups (χ2 = 9.275; P = .026). The difference in adverse events between the 2 groups was not significant. Immune checkpoint inhibitors were effective and safe for ABTCs with high expression of PD-L1. The threshold should be precise.

Kaempferol suppresses proliferation and induces apoptosis and DNA damage in human gallbladder cancer cells through the CDK4/CDK6/cyclin D1 pathway.

OBJECTIVE: Kaempferol has been reported to play an anti-tumor role in various human cancers, while its role in gallbladder cancer (GBC) is unclear. MATERIALS AND METHODS: We found that kaempferol significantly inhibited the growth, invasion and migration, meanwhile induced apoptosis through cells arrested at G0/G1 phase of GBC cell lines, including GBC-SD and SGC996 cells in vitro. RESULTS: Kaempferol promoted the release of cytochrome C from the mitochondria to cytoplasm, the activation of c-caspase-3 and c-caspase-9 and increased the expression levels of pro-apoptotic factor Bax, meanwhile decreased the expression levels of anti-apoptotic factor Bcl-2. In addition, the expression levels of CDK4, CDK6 and cyclin D1, which are members of the CDK4/CDK6/cyclin D1 signaling pathway, were also decreased by kaempferol. Moreover, kaempferol could efficiently prevent tumor progression of GBC in the xenograft in vivo. CONCLUSIONS: Our results demonstrated that kaempferol suppressed GBC progression through activation of the CDK4/CDK6/cyclin D1 signaling pathway, suggesting that it might be a potential anti-tumor agent for clinical treatment of GBC.

Primary radiotherapy vs conservative management for localized prostate cancer--a population-based study.

BACKGROUND: Radiotherapy is the most common curative cancer therapy used for elderly patients with localized prostate cancer. However, the effectiveness of this approach has not been established. The purpose of this study is to evaluate the long-term outcomes of primary radiotherapy compared with conservative management in order to facilitate treatment decisions. METHOD: This population-based study consisted of 57,749 patients with T1-T2 prostate cancers diagnosed during 1992-2007. We utilized an instrumental variable (IV) analytical approach with competing risk models to evaluate the outcomes of primary radiotherapy vs conservative management. The IV was comprised of combined health service areas with high- and low-use areas corresponding to the top and bottom tertile in radiotherapy usage rates. RESULTS: In patients with low-/intermediate-risk prostate cancer, 10-year prostate cancer-specific and overall survival was similar in high- and low-radiotherapy use areas (96.1 vs 95.4% and 56.6 vs 56.3%, respectively). In patients with high-risk disease, however, areas with high-radiotherapy use had a higher 10-year cancer-specific survival (90.2 vs 88.1%, difference 2.1%; 95% CI 0.3-4.0%) and 10-year overall survival (53.3 vs 50.2%, difference 3.1%; 95% CI 1.3-6.3%). Results were similar irrespective of the type of radiotherapy used. To assess the robustness of our choice of IV, we repeated the IV analytical approach using different IVs (using the median utilization rate as the cutoff) and found the results to be similar. CONCLUSIONS: Among men >65 years of age, the benefit of primary radiotherapy for localized disease is largely confined to patients with high-risk prostate cancer (Gleason scores 7-10).

The complexity of obesity in U.K. adolescents: relationships with quantity and type of technology, sleep duration and quality, academic performance and aspiration.

BACKGROUND: Contemporary technology and multiple device use may link to increased body mass index (BMI). The sleep-obesity relationship is inconsistent in adolescents. Sleep duration and quality may have crucial connections to obesity development, particularly in adolescents where sleep alterations are common. Elevated BMI in adolescents may influence academic performance and aspiration, but data are limited. OBJECTIVES: The objectives of this study was to assess the linear associations between BMI z-score and (i) quantity/type of technology used; (ii) sleep quantity/quality and (iii) academic performance/aspiration. METHODS: Consenting adolescents (n = 624; 64.9% girls, aged 11-18 years) were recruited. The Schools Sleep Habits Survey and Technology Use Questionnaire were administered. Objective measures of height/weight were obtained. RESULTS: Quantity of technology was positively associated with BMI z-score ß = 0.10, P < 0.01. Those who always engaged in video gaming had significantly higher BMI z-score vs. never-users, ß = 1.00, P < 0.001. Weekday sleep duration and sleep onset latency were related to BMI z-score, ß = -0.24, P < 0.001 and ß = 0.01, P < 0.001, respectively. An inverse linear association was observed between BMI z-score and academic performance, ß = -0.68, P < 0.001. CONCLUSIONS: If confirmed prospectively, reducing bedtime use of technology and improving sleep hygiene in adolescents could be an achievable intervention for attenuating obesity with potentially positive effects on academic performance.

The impact of PSA testing frequency on prostate cancer incidence and treatment in older men.

To quantify the downstream impact of PSA testing on cancer characteristics and utilization of cancer therapies among men aged 70 or older, we utilized patients diagnosed with prostate cancer in 2004-2005 in the Surveillance, Epidemiology and End Results (SEER)-Medicare and their Medicare claims before their cancer diagnosis during 2000-2005. Among men in the highest testing group (4-6 PSA tests), 75% were diagnosed with low- or intermediate-risk of disease, but 77% received treatments within 180 days of cancer diagnosis. More than 45% of newly diagnosed patients in 2004-2005 had 4-6 PSA tests before their cancer diagnosis during 2000-2005. Men in the high testing group were 3.57 times more likely to receive cancer treatments (either surgery, radiation or hormonal therapy) when compared with men who had no previous PSA testing during the same time period. Among men aged 75+ diagnosed with low-risk cancer, men in the high testing group were 78% more likely to receive treatment than those who had no previous PSA testing. In conclusion, given the lack of evidence of effective treatment for elderly patients diagnosed with low- and intermediate-risk prostate cancer and our inability to distinguish indolent from aggressive cancer, more frequent PSA testing among elderly population may exacerbate the risk of overdiagnosis and overtreatment.

Treatment profile and complications associated with cryotherapy for localized prostate cancer: a population-based study.

The aim of this study was to assess the treatment patterns and 3-12-month complication rates associated with receiving prostate cryotherapy in a population-based study. Men >65 years diagnosed with incident localized prostate cancer in Surveillance Epidemiology End Results (SEER)-Medicare-linked database from 2004 to 2005 were identified. A total of 21,344 men were included in the study, of which 380 were treated initially with cryotherapy. Recipients of cryotherapy versus aggressive forms of prostate therapy (ie, radical prostatectomy or radiation therapy) were more likely to be older, have one co-morbidity, low income, live in the South and be diagnosed with indolent cancer. Complication rates increased from 3 to 12 months following cryotherapy. By the twelfth month, the rates for urinary incontinence, lower urinary tract obstruction, erectile dysfunction and bowel bleeding reached 9.8, 28.7, 20.1 and 3.3%, respectively. Diagnoses of hydronephrosis, urinary fistula or bowel fistula were not evident. The rates of corrective invasive procedures for lower urinary tract obstruction and erectile dysfunction were both <2.9% by the twelfth month. Overall, complications post-cryotherapy were modest; however, diagnoses for lower urinary tract obstruction and erectile dysfunction were common.

A systematic review and economic evaluation of epoetin alpha, epoetin beta and darbepoetin alpha in anaemia associated with cancer, especially that attributable to cancer treatment.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of epoetin alpha, epoetin beta and darbepoetin alpha (referred to collectively in this report as epo) in anaemia associated with cancer, especially that attributable to cancer treatment. DATA SOURCES: Electronic databases were searched from 2000 (1996 in the case of darbepoetin alpha) to September 2004. REVIEW METHODS: Using a recently published Cochrane review as the starting point, a systematic review of recent randomised controlled trials (RCTs) comparing epo with best standard was conducted. Inclusion, quality assessment and data abstraction were undertaken in duplicate. Where possible, meta-analysis was employed. The economic assessment consisted of a systematic review of past economic evaluations, an assessment of economic models submitted by the manufacturers of the three epo agents and development of a new individual sampling model (the Birmingham epo model). RESULTS: In total 46 RCTs were included within this systematic review, 27 of which had been included in the Cochrane systematic review. All 46 trials compared epo plus supportive care for anaemia (including transfusions), with supportive care for anaemia (including transfusions), alone. Haematological response (defined as an improvement by 2 g/dl(-1)) had a relative risk of 3.4 [95% confidence interval (CI) 3.0 to 3.8, 22 RCTs] with a response rate for epo of 53%. The trial duration was most commonly 16-20 weeks. There was little statistical heterogeneity in the estimate of haematological response, and there were no important differences between the subgroups examined. Haemoglobin (Hb) change showed a weighted mean difference of 1.63 g/dl(-1) (95% CI 1.46 to 1.80) in favour of epo. Treatment with erythropoietin in patients with cancer-induced anaemia reduces the number of patients who receive a red blood cell transfusion (RBCT) by an estimated 18%. Health-related quality of life (HRQoL) data were analysed using vote counting and qualitative assessment and a positive effect was observed in favour of an improved HRQoL for patients on epo. Published information on side-effects was of poor quality. New trials provided further evidence of side-effects with epo, particularly thrombic events, but it is still unclear whether these could be accounted for by chance alone. The results of the previous Cochrane review had suggested a survival advantage for epo (HR 0.84, 95% CI 0.69 to 1.02), based on 19 RCTs. The update, based on 28 RCTs, suggests no difference (HR 1.03, 95% CI 0.88 to 1.21). Subgroup analysis suggested some explanations for this heterogeneity, but it is difficult to draw firm conclusions without access to the substantial amounts of missing or unpublished data, or more detailed results from some of the trials with heterogeneous patient populations. The conclusions are, however, broadly in line with those of a Food and Drug Administration (FDA) safety briefing, which recommended that patients with a haemoglobin above 12 g/dl(-1) should not be treated; the target rate of rise in Hb should not be too great, and further carefully conducted trials are required to determine which subgroups of patients may be harmed by the use of these products, in particular through the stimulation of tumour activity. Five published economic evaluations identified from the literature had inconsistent results, with estimates ranging from a cost per quality-adjusted life-year (QALY) under pound 10,000 through to epo being less effective and more costly than standard care. The more favourable evaluations assumed a survival advantage for epo. The three company models submitted each relied on assumed survival gains to achieve relatively low cost per QALY, from pound 13,000 to pound 28,000, but generated estimates from pound 84,000 to pound 159,000 per QALY when no survival gain was assumed. Each of these models relied on Hb levels alone driving utility, and each assumed gradual normalisation of Hb in the standard treatment arm after the end of treatment. The Birmingham epo model followed the company models in regard to the relationship between Hb levels and utility, and also assumed normalisation in the base case. With no survival gain, the incremental cost per QALY was pound 150,000, falling to pound 40,000 when the lower, more favourable, confidence interval for survival was used. CONCLUSIONS: Epo is effective in improving haematological response and reducing RBCT requirements, and appears to have a positive effect on HRQoL. The incidence of side-effects and effects on survival remains highly uncertain. However, if there is no impact on survival, it seems highly unlikely that epo would be considered a cost-effective use of healthcare resources. The main target for further research should be improving estimates of impact on survival, initially through more detailed secondary research, such as the individual patient data meta-analysis started by the Cochrane group. Further trials may be required, and have been recommended by the FDA, although many trials are in progress, completed but unreported or awaiting mature follow-up. The Birmingham epo model developed as part of this project contains new features that improve its flexibility in exploring different scenarios; further refinement and validation would therefore be of assistance. Finally, further research to resolve uncertainty about other parameters, particularly quality of life, adverse events, and the rate of normalisation, would also be beneficial.

A brief pain management program compared with physical therapy for low back pain: results from an economic analysis alongside a randomized clinical trial.

OBJECTIVE: Guidelines for the management of acute low back pain in primary care recommend early intervention to address psychosocial risk factors associated with long-term disability. We assessed the cost utility and cost effectiveness of a brief pain management program (BPM) targeting psychosocial factors compared with physical therapy (PT) for primary care patients with low back pain of <12 weeks' duration. METHODS: A total of 402 patients were randomly assigned to BPM or PT. We adopted a health care perspective, examining the direct health care costs of low back pain. Outcome measures were quality-adjusted life years (QALYs) and 12-month change scores on the Roland and Morris disability questionnaire. Resource use data related to back pain were collected at 12-month followup. Cost effectiveness was expressed as incremental ratios, with uncertainty assessed using cost-effectiveness planes and acceptability curves. RESULTS: There were no statistically significant differences in mean health care costs or outcomes between treatments. PT had marginally greater effectiveness at 12 months, albeit with greater health care costs (BPM 142 pounds, PT 195 pounds). The incremental cost-per-QALY ratio was 2,362 pounds. If the UK National Health Service were willing to pay 10,000 pound per additional QALY, there is only a 17% chance that BPM provides the best value for money. CONCLUSION: PT is a cost-effective primary care management strategy for low back pain. However, the absence of a clinically superior treatment program raises the possibility that BPM could provide an additional primary care approach, administered in fewer sessions, allowing patient and doctor preferences to be considered.

Clinical and cost-effectiveness of newer immunosuppressive regimens in renal transplantation: a systematic review and modelling study.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of the newer immunosuppressive drugs for renal transplantation: basiliximab, daclizumab, tacrolimus, mycophenolate (mofetil and sodium) and sirolimus. DATA SOURCES: Electronic databases. Industry submissions. Current Clinical Trials register. Cochrane Collaboration Renal Disease Group. REVIEW METHODS: The review followed the InterTASC standards. Each of the five company submissions to the National Institute for Clinical Excellence (NICE) contained cost-effectiveness models, which were evaluated by using a critique covering (1) model checking, (2) a detailed model description and (3) model rerunning. RESULTS: For induction therapy, three randomised controlled trials (RCTs) found that daclizumab significantly reduced the incidence of biopsy-confirmed acute rejection and patient survival at 6 months/1 year compared with placebo, but not compared with the monoclonal antibody OKT3. There was no significant gain in patient survival or graft loss at 3 years. The incidence of side-effects with daclizumab reduced compared to OKT3. Eight RCTs found that basiliximab significantly improved 6-month/1-year biopsy-confirmed acute rejection compared to placebo, but not compared to either ATG or OKT3. There was no significant gain in either 1-year patient survival or graft loss. The incidence of side-effects with basiliximab was not significantly different compared to OKT3/ATG. For initial/maintenance therapy, 13 RCTs found that tacrolimus reduced the 6-month/1-year incidence of biopsy-proven acute rejection compared to ciclosporin. There was no significant improvement in either 1-year or long-term (up to 5 years) graft loss or patient survival. The acute rejection benefit of tacrolimus over ciclosporin appeared to be equivalent for Sandimmun and Neoral. There were important differences in the side-effect profile of tacrolimus and ciclosporin. Seven RCTs found that mycophenolate mofetil (MMF) reduced the incidence of acute rejection. There was no significant difference in patient survival or graft loss at 1-year or 3-year follow-up. There appeared to be differences in the side-effect profiles of MMF and azathioprine (AZA). No RCTs comparing MMF with AZA were identified. One RCT compared mycophenolate sodium (MPS) to MMF and reported no difference between the two drugs in 1-year acute rejection rate, graft survival, patient survival or side-effect profile. Two RCTs suggest that addition of sirolimus to a ciclosporin-based initial/maintenance therapy reduces 1-year acute rejections in comparison to a ciclosporin (Neoral) dual therapy alone and substituting azathioprine with sirolimus in initial/maintenance therapy reduces the incidence of acute rejection. Graft and patient survival were not significantly different with either sirolimus regimen. Adding sirolimus increases the incidence of side-effects. The side-effect profiles of azathioprine and sirolimus appear to be different. For the treatment of acute rejection, three RCTs suggested that both tacrolimus and MMF reduce the incidence of subsequent acute rejection and the need for additional drug therapy. Only one RCT and one subgroup analysis in children (<18 years) were identified comparing ciclosporin to tacrolimus and sirolimus, respectively. CONCLUSIONS: The newer immunosuppressant drugs (basiliximab, daclizumab, tacrolimus and MMF) consistently reduced the incidence of short-term (1-year) acute rejection compared with conventional immunosuppressive therapy. The independent use of basiliximab, daclizumab, tacrolimus and MMF was associated with a similar absolute reduction in 1-year acute rejection rate (approximately 15%). However, the effects of these drugs did not appear to be additive (e.g. benefit of tacrolimus with adjuvant MMF was 5% reduction in acute rejection rate compared with 15% reduction with adjuvant AZA). Thus, the addition of one of these drugs to a baseline immunosuppressant regimen was likely to affect adversely the incremental cost-effectiveness of the addition of another. The trials did not assess how the improvement in short-term outcomes (e.g. acute rejection rate or measures of graft function), together with the side-effect profile associated with each drug, translated into changes in patient-related quality of life. Moreover, given the relatively short duration of trials, the impact of the newer immunosuppressants on long-term graft loss and patient survival remains uncertain. The absence of both long-term outcome and quality of life from trial data makes assessment of the clinical and cost-effectiveness on the newer immunosuppressants contingent on modelling based on extrapolations from short-term trial outcomes. The choice of the most appropriate short-term outcome (e.g. acute rejection rate or measures of graft function) for such modelling remains a matter of clinical and scientific debate. The decision to use acute rejection in the meta-model in this report was based on the findings of a systematic review of the literature of predictors of long-term graft outcome. Only a very small proportion of the RCTs identified in this review assessed patient-focused outcomes such as quality of life. Since immunosuppressive drugs have both clinical benefits and specific side-effects, the balance of these harms and benefits could best be quantified through future trials using quality of life measures. The design of future trials should be considered with a view to the impact of drugs on particular renal transplant groups, particularly higher risk individuals and children. Finally, there is a need for improved reporting of methodological details of future trials, such as the method of randomisation and allocation concealment. A number of issues exist around registry data, for example the use of multiple drug regimens and the need to assess the long-term outcomes. An option is the use of observational registry data including, if possible, prospective data on all consecutive UK renal transplant patients. Data capture for each patient should include immunosuppressant regimens, clinical and patient-related outcomes and patient demographics.

Screening for fragile X syndrome: a literature review and modelling study.

OBJECTIVES: To compare the effectiveness, estimate the associated costs, and summarise available evidence about the feasibility and acceptability of different screening strategies in England and Wales. Also to establish a model for estimating effectiveness and costs of these different strategies. DATA SOURCES: Literature searches were restricted to MEDLINE and EMBASE, as well as citations in included papers. A broad search strategy was used involving all aspects of fragile X syndrome (FXS) and covered all relevant literature published between 1991 and 2001. REVIEW METHODS: An assessment was conducted of published literature and efforts focused on the development of a model that could be used to synthesise data from various sources, estimate cost-effectiveness of different strategies, and conduct sensitivity analyses according to different assumptions. RESULTS: The identified screening programmes were effective in detecting carriers, but a comparison of different strategies was not possible. Simulation results by the FXS Model showed that, over the first 10 years, 4% of premutation (PM) females and 70% of full mutation (FM) females could be detected by active cascade screening; it is 10% and 58%, respectively, by prenatal screening. The maximal detection rate for FM carriers by active cascade screening is higher than that by prenatal screening (91% versus 71%). However, the maximal rate of detection of female PM carriers by active cascade screening (6%) is much lower than that by prenatal screening (60%). During the first 10 years of simulation, the estimated direct cost per year to the NHS in England and Wales is 0.7-0.2 million pounds sterling by active cascade screening and 14.5-9.1 million pounds sterling by a programme of prenatal screening. The incremental cost per extra carrier detected (using current practice as the reference standard) is on average only 165 pounds sterling by active cascade screening and 7543 pounds sterling by prenatal screening. The incremental cost per FXS birth avoided is on average 8494 pounds sterling by active cascade screening and 284,779 pounds sterling by prenatal screening. CONCLUSIONS: The empirical evidence suggests that both prenatal screening and cascade screening are feasible and acceptable. Population-based prenatal screening is more efficacious, but it will cost more than active cascade screening. The active cascade screening of affected families is more efficient, cheaper, but less effective than a population-based prenatal screening. It is suggested that both strategies be evaluated in large-scale trials, which might also help to determine whether and how the different strategies could be simultaneously or sequentially combined.

Transurethral resection of the prostate among medicare beneficiaries: 1984 to 1997. For the Patient Outcomes Research Team for Prostatic Diseases.

PURPOSE: We examine the epidemiology and associated risks of transurethral resection of the prostate among Medicare beneficiaries for the period 1984 to 1997. MATERIALS AND METHODS: We used hospital claims for transurethral resection of the prostate from a 20% national sample of Medicare beneficiaries for the period 1991 to 1997. Risk of mortality and reoperation were evaluated using life table methods and compared to those for the period 1984 to 1990. We also examined the association between surgical volume and adverse outcomes following resection using unique urologist identifier codes from the 1997 part B Medicare claims. RESULTS: Compared to 1984 to 1990, age adjusted rates of transurethral resection for benign prostatic hyperplasia (BPH) during 1991 to 1997 declined by approximately 50% for white (14.6 to 6.72/1,000) and 40% for black (11.8 to 6.58/1,000) men. Of the men who underwent resection for BPH during the recent period 53% were 75 years old or older but 30-day mortality in men 70 years old or older was significantly lower than that in 1984 to 1990. Since 1987 the 5-year risk for reoperation following transurethral resection for BPH has remained 5%. For resection performed in 1997 we observed no statistically significant association between urologist surgical volume and risks of reoperation or 30-day mortality. CONCLUSIONS: Compared to the peak period of its use in the 1980s, older men are now undergoing transurethral resection of the prostate. Nevertheless, outcomes for men 65 years old or older continue to be good.

Effect of age and surgical approach on complications and short-term mortality after radical prostatectomy--a population-based study.

OBJECTIVES: To use population-based data to accurately delineate the types and incidence of complications, risk of readmission, and influence of age and surgical approach on short-term mortality after radical prostatectomy. METHODS: Medicare claims from 1991 to 1994 were used to identify and quantify the types and risks of complications, rehospitalization within 90 days, and mortality at 30 and 90 days after perineal or retropubic prostatectomy. Logistic regression was used to determine the relationships between age, surgical approach, and short-term outcomes while adjusting for potential confounders. RESULTS: On the basis of data from 101,604 men, complications affected 25.0% to 28.8% of patients treated with the perineal or retropubic approach. The retropubic approach had a higher risk of respiratory complications (relative risk [RR] = 1.53, 95% confidence interval [CI] 1.37 to 1.71) and miscellaneous medical complications (RR = 1.77, 95% CI 1.60 to 1.97) and a lower risk of miscellaneous surgical complications (RR = 0.86, 95% CI 0.78 to 0.94). Differences in medically related gastrointestinal complications partially accounted for the differences in miscellaneous medical complications. Rectal injury with the perineal approach was only approximately 1% to 2%. Readmission within 90 days was necessary for 8.5% to 8.7% of patients who underwent the retropubic or perineal approach. The 30-day mortality was less than 0.5% for men aged 65 to 69; it approached 1% for men aged 75 and older. CONCLUSIONS: Complications and readmission after prostatectomy are substantially more common than previously recognized. Notable differences exist in the incidence of respiratory and nonsurgical gastrointestinal complications, although many short-term outcomes are comparable for the two approaches. Older age is associated with elevated surgical mortality and complications.

Tacrolimus (FK506) increases neuronal expression of GAP-43 and improves functional recovery after spinal cord injury in rats.

Tacrolimus (FK506), a widely used immunosuppressant drug, has neurite-promoting activity in cultured PC12 cells and peripheral neurons. The present study investigated whether tacrolimus affects the expression of the neuronal growth-associated protein, GAP-43, as well as functional recovery after photothrombotic spinal cord injury in the rat. In injured animals receiving tacrolimus, the number of neurons expressing GAP-43 mRNA and protein approximately doubled compared to that in injured animals receiving vehicle alone. This increase in GAP-43-positive cells was paralleled by a significant improvement in neurological function evaluated by open-field and inclined plane tests. Another FKBP-12 ligand (V-10,367) had similar effects on GAP-43 expression and functional outcome, indicating that the observed effects of tacrolimus do not involve inhibition of the phosphatase calcineurin. Thus, tacrolimus, a drug which is already approved for use in humans, as well as other FKBP-12 ligands which do not inhibit calcineurin, could potentially enhance functional outcome after CNS injury in humans.

Use of radical prostatectomy among Medicare beneficiaries before and after the introduction of prostate specific antigen testing.

PURPOSE: We monitored the use of radical prostatectomy in medicare beneficiaries before and after the introduction of prostate specific antigen (PSA) testing. MATERIALS AND METHODS: Radical prostatectomies performed on medicare beneficiaries between 1984 and 1995 were identified through the medicare claims data base. Medicare enrollment files were used to define the population at risk and age-adjusted rates were standardized to the 1990 United States medicare population. RESULTS: Rates of radical prostatectomy have steadily increased since 1984. A sharp increase in radical prostatectomy rates followed the institution of PSA testing after which a prominent decrease, particularly among older age groups, was evident. During the peak year of 1992 the age-adjusted rates of radical prostatectomy for white and black men 65 to 79 years old in the United States were 461.2 and 294.5/100,000 men. Between 1992 and 1995 the rates of radical prostatectomy among white men decreased by 22, 47 and 69% for patients 65 to 69, 70 to 74 and 75 to 79 years old, respectively. The corresponding changes among black men were +6, -18 and -47%, respectively. Differences in the age-adjusted rates between white and black men have narrowed in recent years, ranging from 166.7 (1992) to 29.7 (1995)/100,000 men. CONCLUSIONS: Recent years have been marked by a rapid increase in the use of radical prostatectomy, which peaked in 1992. Subsequent to 1992 a sharp decrease occurred, which was particularly evident in older and white men. Racial differences in the use of radical prostatectomy have narrowed in recent years.

Selective upregulation of cytokine receptor subchain and their intracellular signalling molecules after peripheral nerve injury.

Numerous studies have suggested that growth factors and cytokines play an important role in the survival of injured neurons and in neurite elongation. Therefore, intracellular signalling pathways activated by growth factors and cytokine receptors play an important role in neuronal survival or for the re-establishment of connection. Since the JAK (janus kinase)-STAT (signal transducers and activators of transcription) signal transduction pathway is known to play a major role in cytokine receptor signalling, we first examined regulation of JAK gene expression following peripheral nerve injury by in situ hybridization histochemistry. The rat hypoglossal nerve was axotomized unilaterally and the mRNA levels for JAK1, JAK2. JAK3 and TYK2 were examined in the hypoglossal nucleus at postoperative times ranging from 1 to 35 days. Among the JAK family members, JAK2 and JAK3 were substantially increased in injured hypoglossal motoneurons, whereas no significant increases were observed for JAK1 and TYK2. These changes were further confirmed by immunohistochemistry using antibodies specific to JAK2 and JAK3. In addition, we examined the JAK2 and JAK3 associated cytokine receptor components, IL-2R gamma and gp130, which are common to various cytokine receptors. Among these, gp130 immunostaining was upregulated after nerve injury. This was also confirmed by in situ hybridization. These results suggest that the injured neuron prepares the molecular machinery involved in certain cytokine receptor signalling pathways at an early phase of the regenerative process, accelerating for the neuron to respond to cytokines that may regulate survival and/or neurite elongation.

Population-based study of long-term survival in patients with clinically localised prostate cancer.

BACKGROUND: Choice of treatment in localised prostate cancer has been hampered by a lack of unbiased, representative data on outcome. Most existing data have come from small cohorts at specialised academic centres; precise overall and cancer-grade-specific data are not available, and the data are subject to differential staging bias. Randomised clinical trials have been undertaken, but the results will not be available for another decade. We have carried out a large population-based study to ascertain overall and prostate-cancer-specific survival in men treated by prostatectomy, radiotherapy, or conservative management. METHODS: Data for 59,876 cancer-registry patients aged 50-79 were analysed. We examined the effect of differential staging of prostate cancer by analysing the data both by intention to treat and by treatment received. Estimated survival was calculated by the Kaplan-Meier method. FINDINGS: By the intention-to-treat approach, 10-year prostate-cancer-specific survival for grade 1 cancer was 94% (95% CI 91-95) after prostatectomy, 90% (87-92) after radiotherapy, and 93% (91-94) after conservative management. The corresponding survival figures in grade 2 cancers were 87% (85-89), 76% (72-79), and 77% (74-80); those in grade 3 cancer were 67% (62-71), 53% (47-58), and 45% (40-51). Although the intention-to-treat and treatment-received analyses yielded similar results for radiotherapy and conservative management, the 10-year disease-specific survival after prostatectomy differed substantially (83% [81-84] by intention to treat vs 89% [87-91] by treatment received). INTERPRETATION: The overall and cancer-grade-specific survival found in this study differ substantially from those in previous studies. Previous studies that used a treatment-received approach have generally overestimated the benefits of radical prostatectomy. We found that grade 3 tumours are highly aggressive irrespective of stage.

Heterogeneity of hip fracture: age, race, sex, and geographic patterns of femoral neck and trochanteric fractures among the US elderly.

To explore potential etiologic differences in the two major types of hip fracture, the authors computed the incidence rates of fractures of the femoral neck and trochanteric region of the proximal femur using a 5 percent sample of the US Medicare population aged 65-99 years. For the period they examined, July 1, 1986, through June 30, 1990, the rates of both hip fracture types increased with age in all race and sex categories. The proportion of hip fractures that occurred in the trochanteric region rose steeply with age among white women, but not among black women, white men, or black men. Within the United States, a north-to-south gradient in rates of both fracture types was observed among women, while no clear pattern was found for men. These findings raise the possibility of etiologic differences in the two fracture types, and the results provide further evidence of sex and racial differences in the risk of osteoporotic fractures.

Follow-up prostate cancer treatments after radical prostatectomy: a population-based study.

BACKGROUND: Radical prostatectomy is one of the most commonly used curative procedures for the treatment of localized prostate cancer. The probability that a patient will undergo additional cancer therapy after this procedure is largely unknown. PURPOSE: The objective was to determine the likelihood of additional cancer therapy after radical prostatectomy. METHODS: Data for this study were derived from a linked dataset that combined information from the Surveillance, Epidemiology, and End Results Program and Medicare hospital and physician claims. Records were included in this study if patient histories met the following criteria: (a) residing in Connecticut, Washington (Seattle-Puget Sound), or Georgia (Metropolitan Atlanta); (b) having been diagnosed with prostate cancer during the period from January 1, 1985, through December 31, 1991; (c) undergoing radical prostatectomy by December 31, 1992; and (d) having no evidence of other types of cancer. Patients were considered to have had additional cancer therapy if they had had radiation therapy, orchiectomy, and/or androgen-deprivation therapy by injection after radical prostatectomy. The interval between the initial treatment and any follow-up treatment was calculated from the date of radical prostatectomy to the 1st day of the follow-up cancer therapy. All presented probabilities are based on Kaplan-Meier estimates. RESULTS: The study population consisted of 3494 Medicare patients, 3173 of whom underwent radical prostatectomy within 3 months of prostate cancer diagnosis. Although radical prostatectomy is often reserved for localized cancer, less than 60% (1934) of patients whose records were included in this study had organ-confined disease, according to final surgical pathology. Overall, the 5-year cumulative incidence of having any additional cancer treatment after radical prostatectomy reached 34.9% (95% confidence interval [CI] = 31.5%-38.5%). For patients with pathologically organ-confined cancer, the 5-year cumulative incidence was 24.3% (95% CI = 20.0%-29.3%) overall and ranged from 15.6% (95% CI = 9.7%-24.5%) for well-differentiated cancer (Gleason scores 2-4) to 41.5% (95% CI = 27.9%-58.4%) for poorly differentiated cancer (Gleason scores 8-10). The corresponding figures for pathologically regional cancer were 22.7% (95% CI = 12.0%-40.5%) and 68.1% (95% CI = 58.7%-77.1%). CONCLUSION: Further treatment of prostate cancer was done in about one third of patients who had had a radical prostatectomy with curative intent and in about one quarter of patients who were found to have organ-confined disease. IMPLICATIONS: Given the common requirement for follow-up cancer treatments after radical prostatectomy and the uncertainties about the effectiveness of the various follow-up treatment strategies, further investigation of these treatments is warranted.