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:Watchful waiting (WW) is one of the standard approaches for newly diagnosed follicular lymphoma (FL) patients with low-tumor burden. However, the impact of WW in FL patients at the first progression, remains unclear. We reviewed 206 FL patients who experienced the first progression after responding to the initial treatment at our institution between 1998 and 2017. Patients were classified into either the WW cohort (132 patients) or the immediate treatment cohort (74 patients). Overall, the median follow-up from the first progression was 79.8 months (range, 2.1-227.0 months). In the WW cohort, the estimated median time to next treatment (TNT) was 19.7 months (95% confidence interval [CI], 13.4-30.2), and 76.5% (95% CI, 68.0-84.1) of the patients subsequently underwent the second-line treatment at 5 years. There was a significant difference in the median time to treatment failure in the WW cohort (72.8 months; 95% CI, 64.6-94.0) compared to the immediate treatment cohort (23.3 months; 95% CI, 13.4-38.8) (HR, 2.13; 95% CI, 1.48-3.06), whereas overall survival and the cumulative incidence of histological transformation were not significantly different between two cohorts. In a multivariate analysis, rituximab refractory status, progression of disease within 24 months from the induction of first-line therapy, and a high Follicular Lymphoma International Prognostic Index score at diagnosis were significantly associated with shorter TNT. Interestingly, 15 patients (11%) of the WW cohort experienced spontaneous tumor regression during WW, and their TNT (median, 82.1 months, 95% CI, 11.7-NA) was longer than that of the remaining patients in the WW cohort (median, 16.5 months, 95% CI, 13.0-25.4), with a significant difference (p = 0.01). The results of the present study suggested that WW could be a safe and reasonable option even at the first progression for the selected FL patients, without a negative impact on clinical outcomes.
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:IntroductionGiven that reports on severe diazoxide (DZX) toxicity are increasing, we aimed to understand if the short-term clinical outcomes of small-for-gestational-age (SGA) infants with hyperinsulinemic hypoglycemia (HH) managed primarily by supportive care, termed watchful waiting (WW), are different from those treated with DZX.MethodA real-life observational cohort study was conducted from 1 September 2014 to 30 September 2020. The WW or DZX management decision was based on clinical and biochemical criteria. We compared central line duration (CLD), postnatal length of stay (LOS), and total intervention days (TIDs) among SGA-HH infants treated with DZX versus those on a WW approach. Fasting studies determined the resolution of HH.ResultAmong 71,836 live births, 11,493 were SGA, and 51 SGA infants had HH. There were 26 and 25 SGA-HH infants in the DZX and WW groups, respectively. Clinical and biochemical parameters were similar between groups. The median day of DZX initiation was day 10 of life (range 4-32), at a median dose of 4 mg/kg/day (range 3-10). All infants underwent fasting studies. Median CLD [DZX, 15 days (6-27) vs. WW, 14 days (5-31), P = 0.582] and postnatal LOS [DZX, 23 days (11-49) vs. WW, 22 days (8-61), P = 0.915] were comparable. Median TID was >3-fold longer in the DZX than the WW group [62.5 days (9-198) vs. 16 days (6-27), P < 0.001].ConclusionCLD and LOS are comparable between WW and DZX groups. Since fasting studies determine the resolution of HH, physicians should be aware that clinical intervention of DZX-treated SGA-HH patients extends beyond the initial LOS.