Project description:Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.).
Project description:Background:Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers. Materials and methods:Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18?years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival. Results:A total of 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared with 75 (86%) patients in region B. Overall survival was 5.8?years (95% CI 4.5-7.2) in region A compared with 14.4?years (95% CI 10.4-18.5) in region B (P?<?0.01). The effect of surgical strategy remained after adjustment for molecular markers (P?=?0.001). Conclusion:In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.
Project description:A "watch and wait" strategy in rectal cancer is increasingly considered in patients who achieve an excellent response to radiotherapy. While a growing number of studies have shown the feasibility of this strategy in selected patients, the optimal therapeutic regimen to maximize response rates still needs to be established. Furthermore, accurate response prediction and the management of minor residual findings after radiotherapy remain a matter of debate. Finally, concerns regarding the long-term oncological safety of the "watch and wait" approach have been expressed. Therefore, the present review aims to address the open questions in the context of a "watch and wait" strategy and focuses on the diagnosis of a clinical complete response and the ideal management thereafter.
Project description:To determine the short term efficacy and safety of tonsillectomy for recurrent streptococcal pharyngitis in adults. Design Randomised controlled trial.Academic referral centre in Finland.70 adults with documented recurrent episodes of streptococcal group A pharyngitis.Instant tonsillectomy (n=36) or remaining on waiting list as control (n=34).Percentage change in the risk of an episode of streptococcal pharyngitis at 90 days. Rates of all episodes of pharyngitis and days with symptoms and adverse effects.The mean (SD) follow-up was 164 (63) days in the control group and 170 (12) days in the tonsillectomy group. At 90 days, streptococcal pharyngitis had recurred in 24% (8/34) in the control group and 3% (1/36) in the tonsillectomy group (difference 21%; 95% confidence interval 6% to 36%). The number needed to undergo tonsillectomy to prevent one recurrence was 5 (3 to 16). During the whole follow-up, the rates of other episodes of pharyngitis and days with throat pain and fever were significantly lower in the tonsillectomy group than in the control group. The most common morbidity related to tonsillectomy was postoperative throat pain (mean length 13 days, SD 4).Adults with a history of documented recurrent episodes of streptococcal pharyngitis were less likely to have further streptococcal or other throat infections or days with throat pain if they had their tonsils removed.Clinical Trials NCT00136877.
Project description:BackgroundFibrous dysplasia (FD) is a benign bone tumor which most commonly involves the craniofacial skeleton. The most devastating consequence of craniofacial FD (CFD) is loss of vision due to optic nerve compression (ONC). Radiological evidence of ONC is common, however the management of this condition is not well established. Our objective was to compare the long-term outcome of patients with optic nerve compression (ONC) due to craniofacial fibrous dysplasia (CFD) who either underwent surgery or were managed expectantly.Methodology/principal findingsWe performed a meta-analysis of 27 studies along with analysis of the records of a cohort of patients enrolled in National Institutes of Health (NIH) protocol 98-D-0145, entitled Screening and Natural History of Fibrous Dysplasia, with a diagnosis of CFD. The study group consisted of 241 patients; 122 were enrolled in the NIH study and 119 were extracted from cases published in the literature. The median follow-up period was 54 months (range, 6-228 months). A total of 368 optic nerves were investigated. All clinically impaired optic nerves (n?=?86, 23.3%) underwent therapeutic decompression. Of the 282 clinically intact nerves, 41 (15%) were surgically decompressed and 241 (85%) were followed expectantly. Improvement in visual function was reported in fifty-eight (67.4%) of the clinically impaired nerves after surgery. In the intact nerves group, long-term stable vision was achieved in 31/45 (75.6%) of the operated nerves, compared to 229/241 (95.1%) of the non-operated ones (p?=?0.0003). Surgery in asymptomatic patients was associated with visual deterioration (RR 4.89; 95% CI 2.26-10.59).ConclusionsMost patients with CFD will remain asymptomatic during long-term follow-up. Expectant management is recommended in asymptomatic patients even in the presence of radiological evidence of ONC.
Project description:BACKGROUND:An increasing proportion of prostate cancer is being managed conservatively. However, there are no randomized trials or consensus regarding the optimal follow-up strategy. OBJECTIVE:To compare life expectancy and quality of life between watchful waiting (WW) versus different strategies of active surveillance (AS). DESIGN, SETTING, AND PARTICIPANTS:A Markov model was created for US men starting at age 50, diagnosed with localized prostate cancer who chose conservative management by WW or AS using different testing protocols (prostate-specific antigen every 3-6 mo, biopsy every 1-5 yr, or magnetic resonance imaging based). Transition probabilities and utilities were obtained from the literature. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Primary outcomes were life years and quality-adjusted life years (QALYs). Secondary outcomes include radical treatment, metastasis, and prostate cancer death. RESULTS AND LIMITATIONS:All AS strategies yielded more life years compared with WW. Lifetime risks of prostate cancer death and metastasis were, respectively, 5.42% and 6.40% with AS versus 8.72% and 10.30% with WW. AS yielded more QALYs than WW except in cohorts age >65 yr at diagnosis, or when treatment-related complications were long term. The preferred follow-up strategy was also sensitive to whether people value short-term over long-term benefits (time preference). Depending on the AS protocol, 30-41% underwent radical treatment within 10 yr. Extending the surveillance biopsy interval from 1 to 5 yr reduced life years slightly, with a 0.26 difference in QALYs. CONCLUSIONS:AS extends life more than WW, particularly for men with higher-risk features, but this is partly offset by the decrement in quality of life since many men eventually receive treatment. PATIENT SUMMARY:More intensive active surveillance protocols extend life more than watchful waiting, but this is partly offset by decrements in quality of life from subsequent treatment.
Project description:BACKGROUND:Gel-forming mucins (GFMs) play important roles in otitis media (OM) pathogenesis. Increased mucin expression is activated by pathogens and proinflammatory cytokines. Bacterial biofilms influence inflammation and resolution of OM and may contribute to prolonged mucin production. The influence of specific pathogens on mucin expression and development of chronic OM with effusion (OME) remains an area of significant knowledge deficit. OBJECTIVES:To assess the relationship between GFM expression, specific pathogens, middle ear mucosal (MEM) changes, biofilm formation, and antibiotic utilization. METHODS:Mixed gender chinchillas were inoculated with nontypeable Haemophilus influenzae (NTHi) strain 86028NP or Streptococcus pneumoniae (SP) strain TIGR4 via transbulla injection. Antibiotic was administered on day 3-5 post inoculation. GFM expression was measured by quantitative PCR. Biofilm formation was identified and middle ear histologic changes were measured. RESULTS:SP infection resulted in higher incidence of biofilm and ME effusion compared with NTHi infection. However, NTHi persisted in the ME longer than SP with no substantive bacterial clearance detected on day 10 compared with complete bacterial clearance on day 10 for 50-60% of the SP-infected chinchillas. Both infections increased MEM inflammatory cell infiltration and thickening. NTHi upregulated the Muc5AC, Muc5B and Muc19 expression on day 10 (p?=?0.0004, 0.003, and 0.002 respectively). SP-induced GFM upregulations were trended toward significant. In both NTHi and SP infections, the degree of GFM upregulation had a direct relationship to increased MEM hypertrophy, inflammatory cell infiltration and biofilm formation. Antibiotic treatment reduced the incidence of ME effusion and biofilm, limited the MEM changes and reversed the GFM upregulation. In NTHi infection, the rate of returning to baseline level of GFMs in treated chinchillas was quicker than those without treatment. CONCLUSIONS:In an animal model of OM, GFM genes are upregulated in conjunction with MEM hypertrophy and biofilm formation. This upregulation is less robust and more quickly ameliorated to a significant degree in the NTHi infection with appropriate antibiotic therapy. These findings contribute to the understanding of pathogen specific influences on mucin expression during OM pathogenesis and provide new data which may have implications in clinical approach for OM treatment.
Project description:We examined patient reported outcomes among patients with prostate cancer treated with watchful waiting in a nationwide cohort.We collected treatment information and patient reported outcomes from 1,230 patients with prostate cancer diagnosed with T1-T2 prostate cancer in the Physicians' Health Study, of whom 125 were initially treated with watchful waiting. Cox proportional hazards regression was used to identify predictors of treatment initiation among patients on watchful waiting. Logistic regression was used to calculate the OR and 95% CI to assess disease targeted quality of life by initial treatment or watchful waiting.At a mean 7.3-year followup 41% of patients on watchful waiting remained free of treatment while 34% had received radiotherapy or brachytherapy, 16% had received primary hormonal therapy and 10% had undergone prostatectomy. Younger age, higher clinical stage, higher Gleason score and higher prostate specific antigen at diagnosis predicted progression to treatment. Watchful waiting compared to immediate treatment was associated with less urinary incontinence (3.5% vs 10%) and impotence (68% vs 78%) but more common obstructive urinary symptoms (22% vs 13%) on univariate analysis (each p <0.05). Incontinence and impotence differences remained significant after adjusting for age, comorbidity and time after cancer diagnosis. Quality of life outcomes in men who underwent delayed treatment after initially waiting were not worse than in men who underwent immediate treatment.Findings suggest quality of life benefits after watchful waiting in select patients with early stage prostate cancer compared to men treated immediately after diagnosis. Younger age and greater cancer severity at diagnosis predicted progression to treatment.
Project description:BACKGROUND AND OBJECTIVES:Severe aortic stenosis (AS) with left ventricular systolic dysfunction (LVSD) is a class I indication for aortic valve replacement (AVR) but this recommendation is not well established in those at the stage of moderate AS. We investigate the clinical impact of AVR among patients with moderate AS and LVSD. METHODS:From 2001 to 2017, we consecutively identified patients with moderate AS and LVSD, defined as aortic valve area 1.0-1.5 cm² and left ventricular ejection fraction <50%. The primary outcome was all-cause death. The outcomes were compared between those who underwent early surgical AVR (within 2 years of index echocardiography) at the stage of moderate AS versus those who were followed medically without AVR at the outpatient clinic. RESULTS:Among 255 patients (70.1±11.3 years, male 62%), 37 patients received early AVR. The early AVR group was younger than the medical observation group (63.1±7.9 vs. 71.3±11.4) with a lower prevalence of hypertension and chronic kidney disease. During a median 1.8-year follow up, 121 patients (47.5%) died, and the early AVR group showed a significantly lower all-cause death rate than the medical observation group (5.03PY vs. 18.80PY, p<0.001). After multivariable Cox-proportional hazard regression adjusting for age, sex, comorbidities, and laboratory data, early AVR at the stage of moderate AS significantly reduced the risk of death (hazard ratio, 0.43; 95% confidence interval 0.20-0.91; p=0.028). CONCLUSIONS:In patients with moderate AS and LVSD, AVR reduces the risk of all-cause death. A prospective randomized trial is warranted to confirm our findings.
Project description:ObjectiveTo compare long-term clinical and economic outcomes associated with 3 management strategies for reducible ventral hernia: repair at diagnosis (open or laparoscopic) and watchful waiting.BackgroundThere is variability in ventral hernia management. Recent data suggest watchful waiting is safe; however, long-term clinical and economic outcomes for different management strategies remain unknown.MethodsWe built a state-transition microsimulation model to forecast outcomes for individuals with reducible ventral hernia, simulating a cohort of 1 million individuals for each strategy. We derived cohort characteristics (mean age 58 years, 63% female), hospital costs, and perioperative mortality from the Nationwide Inpatient Sample (2003-2011), and additional probabilities, costs, and utilities from the literature. Outcomes included prevalence of any repair, emergent repair, and recurrence; lifetime costs; quality-adjusted life years (QALYs); and incremental cost-effectiveness ratios. We performed stochastic and probabilistic sensitivity analyses to identify parameter thresholds that affect optimal management, using a willingness-to-pay threshold of $50,000/QALY.ResultsWith watchful waiting, 39% ultimately required repair (14% emergent) and 24% recurred. Seventy per cent recurred with repair at diagnosis. Laparoscopic repair at diagnosis was cost-effective compared with open repair at diagnosis (incremental cost-effectiveness ratio $27,700/QALY). The choice of operative strategy (open vs laparoscopic) was sensitive to cost and postoperative quality of life. When perioperative mortality exceeded 5.2% or yearly recurrence exceeded 19.2%, watchful waiting became preferred.ConclusionsVentral hernia repair at diagnosis is very cost-effective. The choice between open and laparoscopic repair depends on surgical costs and postoperative quality of life. In patients with high risk of perioperative mortality or recurrence, watchful waiting is preferred.