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The Cochrane Database of Systematic... Jul 2021Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable.
OBJECTIVES
To assess the effectiveness and safety of SCT in adults with non-ischaemic DCM.
SEARCH METHODS
We searched CENTRAL in the Cochrane Library, MEDLINE, and Embase for relevant trials in November 2020. We also searched two clinical trials registers in May 2020.
SELECTION CRITERIA
Eligible studies were randomized controlled trials (RCT) comparing stem/progenitor cells with no cells in adults with non-ischaemic DCM. We included co-interventions such as the administration of stem cell mobilizing agents. Studies were classified and analysed into three categories according to the comparison intervention, which consisted of no intervention/placebo, cell mobilization with cytokines, or a different mode of SCT. The first two comparisons (no cells in the control group) served to assess the efficacy of SCT while the third (different mode of SCT) served to complement the review with information about safety and other information of potential utility for a better understanding of the effects of SCT.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened all references for eligibility, assessed trial quality, and extracted data. We undertook a quantitative evaluation of data using random-effects meta-analyses. We evaluated heterogeneity using the I² statistic. We could not explore potential effect modifiers through subgroup analyses as they were deemed uninformative due to the scarce number of trials available. We assessed the certainty of the evidence using the GRADE approach. We created summary of findings tables using GRADEpro GDT. We focused our summary of findings on all-cause mortality, safety, health-related quality of life (HRQoL), performance status, and major adverse cardiovascular events.
MAIN RESULTS
We included 13 RCTs involving 762 participants (452 cell therapy and 310 controls). Only one study was at low risk of bias in all domains. There were many shortcomings in the publications that did not allow a precise assessment of the risk of bias in many domains. Due to the nature of the intervention, the main source of potential bias was lack of blinding of participants (performance bias). Frequently, the format of the continuous data available was not ideal for use in the meta-analysis and forced us to seek strategies for transforming data in a usable format. We are uncertain whether SCT reduces all-cause mortality in people with DCM compared to no intervention/placebo (mean follow-up 12 months) (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.54 to 1.31; I² = 0%; studies = 7, participants = 361; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection in people with DCM (data could not be pooled; studies = 7; participants = 361; very low-certainty evidence). We are uncertain whether SCT improves HRQoL (standardized mean difference (SMD) 0.62, 95% CI 0.01 to 1.23; I² = 72%; studies = 5, participants = 272; very low-certainty evidence) and functional capacity (6-minute walk test) (mean difference (MD) 70.12 m, 95% CI -5.28 to 145.51; I² = 87%; studies = 5, participants = 230; very low-certainty evidence). SCT may result in a slight functional class (New York Heart Association) improvement (data could not be pooled; studies = 6, participants = 398; low-certainty evidence). None of the included studies reported major adverse cardiovascular events as defined in our protocol. SCT may not increase the risk of ventricular arrhythmia (data could not be pooled; studies = 8, participants = 504; low-certainty evidence). When comparing SCT to cell mobilization with granulocyte-colony stimulating factor (G-CSF), we are uncertain whether SCT reduces all-cause mortality (RR 0.46, 95% CI 0.16 to 1.31; I² = 39%; studies = 3, participants = 195; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection (studies = 1, participants = 60; very low-certainty evidence). SCT may not improve HRQoL (MD 4.61 points, 95% CI -5.62 to 14.83; studies = 1, participants = 22; low-certainty evidence). SCT may improve functional capacity (6-minute walk test) (MD 140.14 m, 95% CI 119.51 to 160.77; I² = 0%; studies = 2, participants = 155; low-certainty evidence). None of the included studies reported MACE as defined in our protocol or ventricular arrhythmia. The most commonly reported outcomes across studies were based on physiological measures of cardiac function where there were some beneficial effects suggesting potential benefits of SCT in people with non-ischaemic DCM. However, it is unclear if this intermediate effects translates into clinical benefits for these patients. With regard to specific aspects related to the modality of cell therapy and its delivery, uncertainties remain as subgroup analyses could not be performed as planned, making it necessary to wait for the publication of several studies that are currently in progress before any firm conclusion can be reached.
AUTHORS' CONCLUSIONS
We are uncertain whether SCT in people with DCM reduces the risk of all-cause mortality and procedural complications, improves HRQoL, and performance status (exercise capacity). SCT may improve functional class (NYHA), compared to usual care (no cells). Similarly, when compared to G-CSF, we are also uncertain whether SCT in people with DCM reduces the risk of all-cause mortality although some studies within this comparison observed a favourable effect that should be interpreted with caution. SCT may not improve HRQoL but may improve to some extent performance status (exercise capacity). Very low-quality evidence reflects uncertainty regarding procedural complications. These suggested beneficial effects of SCT, although uncertain due to the very low certainty of the evidence, are accompanied by favourable effects on some physiological measures of cardiac function. Presently, the most effective mode of administration of SCT and the population that could benefit the most is unclear. Therefore, it seems reasonable that use of SCT in people with DCM is limited to clinical research settings. Results of ongoing studies are likely to modify these conclusions.
Topics: Arrhythmias, Cardiac; Bias; Cardiomyopathy, Dilated; Cause of Death; Granulocyte Colony-Stimulating Factor; Humans; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Severity of Illness Index; Stem Cell Transplantation; Walk Test; Watchful Waiting
PubMed: 34286511
DOI: 10.1002/14651858.CD013433.pub2 -
The Journal of Urology Jul 2023Men on active surveillance with Grade Group 1 prostate cancer who reclassify to Grade Group 2 on surveillance biopsy often leave active surveillance. We aimed to...
PURPOSE
Men on active surveillance with Grade Group 1 prostate cancer who reclassify to Grade Group 2 on surveillance biopsy often leave active surveillance. We aimed to identify subgroups of men who can safely remain on active surveillance despite preoperative reclassification to Grade Group 2.
MATERIALS AND METHODS
We studied 249 active surveillance patients with surveillance biopsies classified as Grade Group 1 or Grade Group 2 who underwent radical prostatectomy. Perineural invasion, cancer volume, linear length and maximum percentage of Gleason pattern 4, and prostate-specific antigen density were evaluated. Radical prostatectomy adverse pathology was defined by any of: pN1; ≥pT3; ≥Grade Group 2 with ≥20% Gleason pattern 4; intraductal carcinoma; large cribriform glands.
RESULTS
A multivariable logistic regression model incorporating prostate-specific antigen density and perineural invasion stratified radical prostatectomy adverse pathology risk among Grade Group 1 and Grade Group 2 active surveillance patients. 57% (39/68) of Grade Group 1 men reclassified to Grade Group 2 while on active surveillance had favorable radical prostatectomy pathology. Those without biopsy perineural invasion and with low prostate-specific antigen density were more likely to have favorable radical prostatectomy pathology.
CONCLUSIONS
Most Grade Group 1 men who enter active surveillance and subsequently reclassify to Grade Group 2 have favorable findings at radical prostatectomy and can remain on active surveillance. Among patients reclassified to Grade Group 2, those with low prostate-specific antigen density and without perineural invasion had the lowest risk of radical prostatectomy adverse pathology, comparable to (or below) that of Grade Group 1 patients who were not reclassified to Grade Group 2 preoperatively. Prostate-specific antigen density and perineural invasion stratify risk in active surveillance patients reclassified to Grade Group 2 and, if concordant with other clinicopathological and radiographic findings, can enable more patients to remain on active surveillance. Reclassification to Grade Group 2 alone should not disqualify men from remaining on active surveillance.
Topics: Male; Humans; Prostate-Specific Antigen; Watchful Waiting; Prostatic Neoplasms; Prostate; Prostatectomy; Biopsy; Neoplasm Grading
PubMed: 37042826
DOI: 10.1097/JU.0000000000003461 -
Interactive Cardiovascular and Thoracic... Jan 2015A best evidence topic in vascular surgery was written according to a structured protocol. The question addressed was whether, in patients with persistent type 2 endoleak... (Review)
Review
A best evidence topic in vascular surgery was written according to a structured protocol. The question addressed was whether, in patients with persistent type 2 endoleak (T2EL) post-endovascular abdominal aortic aneurysm repair (EVAR), intervention is associated with better outcomes than observation. Four hundred and eighty-three papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. In a recently published systematic review including 21 744 patients who underwent EVAR, 35.4% of T2ELs resolved spontaneously, 28.5% of secondary interventions were unsuccessful and rupture occurred in only 0.9% of patients with isolated T2EL. Spontaneous sealing in 62-75% of T2ELs were reported by two included studies. A failure rate of 80% associated with transarterial embolization in aggressive treatment of any T2EL was reported by one study. Conversely, another study reported a clinical success rate of 80% associated with the transarterial approach. One study reported that of patients who underwent embolization of a persistent T2EL, 37.9% continued to experience sac growth and 20% had recurrent endoleak at 5 years. One study demonstrated that the transealing procedure for T2EL had a technical success rate of 94.1%. We conclude that the available evidence with regard to management of persistent T2EL is mainly based on retrospective case series. Conflicting results from heterogeneous studies, however, failed to support an optimal threshold for intervention. Considering the reported relatively benign natural course of most T2ELs and the fact that most T2ELs seal spontaneously, conservative management of persistent T2EL in the absence of sac expansion might be appropriate. Where intervention is indicated, imaging should exclude occult type I and III leaks as ∼25% are not simple T2EL. Translumbar embolization of T2EL is associated with higher success rates than transarterial. Following a successful intervention, continued long-term surveillance is necessary due to the high risk (25-80%) of recurrence. The current evidence indicates that aneurysmal rupture due to an isolated T2EL is rare. Long-term prospective studies may provide better evidence to define the optimal threshold for intervention.
Topics: Aged; Aortic Aneurysm, Abdominal; Benchmarking; Blood Vessel Prosthesis Implantation; Embolization, Therapeutic; Endoleak; Endovascular Procedures; Evidence-Based Medicine; Female; Humans; Male; Predictive Value of Tests; Recurrence; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Watchful Waiting
PubMed: 25301297
DOI: 10.1093/icvts/ivu335 -
Prevention Science : the Official... Apr 2017Although parenting is one of the most commonly studied predictors of child problem behavior, few studies have examined parenting as a multidimensional and dynamic...
Although parenting is one of the most commonly studied predictors of child problem behavior, few studies have examined parenting as a multidimensional and dynamic construct. This study investigated different patterns of developmental trajectories of two parenting dimensions (harsh discipline [HD] and parental warmth [PW]) with a person-oriented approach and examined the associations between different parenting patterns and child externalizing problems and callous-unemotional traits. Data were drawn from the combined high-risk control and normative sample (n = 753) of the Fast Track Project. Parent-reported HD and observer-reported PW from kindergarten to grade 2 were fit to growth mixture models. Two subgroups were identified for HD (low decreasing, 83.0 %; high stable, 17.0 %) and PW (high increasing, 78.7 %; low increasing, 21.3 %). The majority of parents (67.0 %) demonstrated the low decreasing HD and high increasing PW pattern, while the prevalence of the high stable HD and low increasing PW pattern was the lowest (6.8 %). Parenting satisfaction, parental depression, family socioeconomic status, and neighborhood safety predicted group memberships jointly defined by the two dimensions. Children from the high stable HD and low increasing PW pattern showed the highest levels of externalizing problems in grades 4 and 5. Children from the low decreasing HD and low increasing PW pattern showed the highest levels of callous-unemotional traits in grade 7. These findings demonstrate the utility and significance of a person-oriented approach to measuring parenting as a multidimensional and dynamic construct and reveal the interplay between HD and PW in terms of their influences on child developmental outcomes.
Topics: Child; Child, Preschool; Conduct Disorder; Female; Humans; Logistic Models; Male; Observation; Parent-Child Relations; Parenting; Surveys and Questionnaires; United States
PubMed: 27179538
DOI: 10.1007/s11121-016-0665-0 -
Annals of Surgery Apr 2023To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in...
Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer: Findings From a Prospective Phase 2 Trial (PKUCH-R01 Trial, NCT02860234).
OBJECTIVE
To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer.
BACKGROUND
Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested.
METHODS
This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate.
RESULTS
Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%-24.7%] in cCR and 42.9% (95% CI: 6.2%-79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%-78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%-100%), 92.2% (95% CI: 85.5%-98.9%), and 82.7% (95% CI: 73.5%-91.9%), respectively.
CONCLUSIONS
Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.
Topics: Humans; Neoadjuvant Therapy; Organ Preservation; Prospective Studies; Rectal Neoplasms; Chemoradiotherapy; Magnetic Resonance Imaging; Watchful Waiting; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 35766394
DOI: 10.1097/SLA.0000000000005507 -
The Cochrane Database of Systematic... May 2015Melanoma is the leading cause of skin cancer-associated mortality. The vast majority of newly diagnosed melanomas are confined to the primary cutaneous site. Surgery... (Review)
Review
BACKGROUND
Melanoma is the leading cause of skin cancer-associated mortality. The vast majority of newly diagnosed melanomas are confined to the primary cutaneous site. Surgery represents the mainstay of melanoma treatment. Treatment strategies include wide excision of the primary tumour and sentinel lymph node biopsy (SLNB) to assess the status of the regional nodal basin(s). SLNB has become an important component of initial melanoma management providing accurate disease staging.
OBJECTIVES
To assess the effects and safety of SLNB followed by completion lymph node dissection (CLND) for the treatment of localised primary cutaneous melanoma.
SEARCH METHODS
We searched the following databases up to February 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2015, Issue 1), MEDLINE (from 1946), EMBASE (from 1974), and LILACS ((Latin American and Caribbean Health Science Information database, from 1982). We also searched the following from inception: African Index Medicus, IndMED of India, Index Medicus for the South-East Asia Region, and six trials registers. We checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We searched ISI Web of Science Conference Proceedings from inception to February 2015, and we scanned the abstracts of major dermatology and oncology conference proceedings up to 2015.
SELECTION CRITERIA
Two review authors independently assessed all RCTs comparing SLNB followed by CLND for the treatment of primary localised cutaneous melanoma for inclusion. Primary outcome measures were overall survival and rate of treatment complications and side effects.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted and analysed data on survival and recurrence, assessed risk of bias, and collected adverse effect information from included trials.
MAIN RESULTS
We identified and included a single eligible trial comparing SLNB with observation and published in eight different reports (from 2005 to 2014) with 2001 participants. This did not report on our first primary outcome of overall survival. The study did report on the rate of treatment complications. Our secondary outcomes of disease-specific and disease-free survival, local recurrence and distant metastases were reported. There were 1347 participants in the intermediate-thickness melanoma group and 314 in the thick melanoma group.With regard to treatment complications, short-term surgical morbidity (30 days) in 1735 participants showed no difference between SLNB and observation (risk ratio [RR] 1.11; 95% confidence interval [CI] 0.9 to 1.37) for wide excision of the tumour site but favoured observation for complications related to the regional nodal basin (RR 14.36; 95% CI 6.74 to 30.59).The study did not report the actual 10-year melanoma-specific survival rate for all included participants. Instead, melanoma-specific survival rates for each group of participants: intermediate-thickness melanoma (defined as 1.2 to 3.5 mm) and thick melanomas (defined as 3.50 mm or more) was reported.In the intermediate-thickness melanoma group there was no statistically significant difference in disease-specific survival between study groups at 10 years (81.4 ± 1.5% versus 78.3 ± 2.0%, hazard ratio [HR] 0.84; 95% CI 0.65 to 1.09). In the thick melanoma group, again there was no statistically significant difference in disease-specific survival between study groups at 10 years (58.9.3 ± 4.1% versus 64.4 ± 4.6%, HR 1.12; 95% CI 0.77 to 1.64). Combining these groups there was some heterogeneity (I² = 34%) but the total HR was not statistically significant (HR 0.92; 95% CI 0.74 to 1.14). This study failed to show any difference for its stated primary outcome.The summary estimate for disease-free survival at 10 years favoured SLNB over observation in participants with intermediate-thickness and thick melanomas (HR 0.75; 95% CI 0.63 to 0.89).With regard to the rate of local and regional recurrence as the site of first recurrence, a benefit of SLNB uniformly existed in both groups of participants with intermediate-thickness and thick melanomas (RR 0.56; 95% CI 0.45 to 0.69). This is in contrast with a uniformly unfavourable effect of SLNB with regard to the rate of distant metastases as site of first recurrence, in both groups of participants with intermediate-thickness and thick melanomas (HR 1.33; 95% CI 1.03 to 1.72).
AUTHORS' CONCLUSIONS
We contacted the trial authors querying the lack of data on overall survival which was the primary outcome of their important study. They stated "there are numerous additional analyses that have yet to be reported for the trial". We expect that overall survival data will be available in a future update of this review.Disease-free survival and rate of local and regional recurrence favoured SLNB in both groups of participants with intermediate-thickness and thick melanomas but short-term surgical morbidity was higher in the SLNB group, especially with regard to complications in the nodal basin.The evidence for the outcomes of interest in this review is of low quality due to the risk of bias and imprecision of the estimated effects. Further research may have an important impact on our estimate of the effectiveness of SLNB in managing primary localised cutaneous melanoma. Currently this evidence is not sufficient to document a benefit of SLNB when compared to observation in individuals with primary localised cutaneous melanoma.
Topics: Disease-Free Survival; Humans; Lymph Node Excision; Melanoma; Randomized Controlled Trials as Topic; Sentinel Lymph Node Biopsy; Skin Neoplasms; Survival Rate; Watchful Waiting; Melanoma, Cutaneous Malignant
PubMed: 25978975
DOI: 10.1002/14651858.CD010307.pub2 -
Vascular and Endovascular Surgery Jul 2023The gold standard for patients with carotid body tumors (CBT) is surgical resection; nevertheless, some patients are unfit for surgery or, for other reasons, could not...
BACKGROUND
The gold standard for patients with carotid body tumors (CBT) is surgical resection; nevertheless, some patients are unfit for surgery or, for other reasons, could not be operated on. Active surveillance has been known to be a reasonable strategy for these cases. This study aimed to evaluate tumor growth in unoperated patients with CBTs.
METHODS
A retrospective review of all unoperated patients with CBT from a single academic hospital diagnosed between 2014 and 2021 was performed. Results of nonparametric testing were presented using the median and ranges for Mann-Whitney-U or Kruskal-Wallis. Significance was defined as a 2-tailed P < .05.
RESULTS
The cohort included a total of 31 patients, with a median age of 60 years (range: 37-80 years), of which 27 (87.1%) were females. The patients live at a median altitude of 2800 meters (range: 2756-2980 meters) above sea level. Twenty (64.5%) patients had Shamblin I tumors, eight (25.8%) patients had Shamblin II tumors, and three (9.7%) patients had Shamblin III tumors. Median CBT volume at diagnosis was 14.1 cm3 (range: .9 - 213.3 cm). Median volume at diagnosis of symptomatic tumors was substantially larger than asymptomatic tumors, 49.2 cm vs 7.9 cm, respectively (P = .03). Median growth of the tumors during a median 15-month follow-up (range: 3-43 months) was 3.3 cm (range: 0-199.9 cm). Overall, 77% (n = 24) of the CBTs grew at least 1 cm.
CONCLUSION
Most patients in the present study had tumor growth by at least 1 cm, with a median tumor growth of 3.3 cm. In the present study tumor growth was shown to be greater than other low altitude CBT active surveillance studies; therefore, surgical resection should be recommended in patients with CBT living at high altitudes.
Topics: Female; Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Male; Carotid Body Tumor; Altitude; Vascular Surgical Procedures; Watchful Waiting; Treatment Outcome; Retrospective Studies
PubMed: 36683142
DOI: 10.1177/15385744231154089 -
The Lancet. Oncology Feb 2022Endoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective...
BACKGROUND
Endoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus.
METHODS
We first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance.
FINDINGS
The prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia.
INTERPRETATION
Cytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways.
FUNDING
Medical Research Council, Cancer Research UK, Innovate UK.
Topics: Adenocarcinoma; Aged; Barrett Esophagus; Biomarkers; COVID-19; Clinical Decision-Making; Clinical Trials as Topic; Cross-Sectional Studies; Decision Trees; Disease Progression; Esophageal Neoplasms; Esophagoscopy; Feasibility Studies; Female; Humans; Male; Middle Aged; Patient Selection; Pilot Projects; Prospective Studies; Retrospective Studies; Risk Assessment; Risk Factors; SARS-CoV-2; Trefoil Factor-3; Tumor Suppressor Protein p53; Watchful Waiting
PubMed: 35030332
DOI: 10.1016/S1470-2045(21)00667-7 -
Current Opinion in Urology Sep 2016Approximately one in three patients with nonmetastatic renal cell carcinoma (RCC) at the time of surgery will subsequently develop local or metastatic recurrence. The... (Review)
Review
PURPOSE OF REVEIW
Approximately one in three patients with nonmetastatic renal cell carcinoma (RCC) at the time of surgery will subsequently develop local or metastatic recurrence. The purpose of this review is to examine the current rationale for surveillance, describe sites of RCC metastasis, evaluate the existing guidelines for postsurgical follow-up studies, and analyze the risk stratification systems following RCC surgery.
RECENT FINDINGS
Although 75% of recurrences will be identified during the first 5 years following surgery, late recurrences are not uncommon. The risk of recurrence can be predicted from the tumor stage, grade, and other pathologic features. Advanced risk stratification will likely be possible in the future with increased use of molecular classification and serum biomarkers. Patient comorbidities, age, and individual recurrence risk should also be considered when designing individualized surveillance protocols.
SUMMARY
Follow-up after surgery for RCC should focus on imaging of the chest and abdomen to detect common sites of recurrence. Patients should be stratified for risk, and surveillance imaging should be more frequent and intensive in healthy patients with higher risk. Future research is needed to define an optimal individualized surveillance strategy that balances the potential benefits of early cancer detection with the risks and cost of surveillance.
Topics: Carcinoma, Renal Cell; Follow-Up Studies; Humans; Kidney Neoplasms; Neoplasm Recurrence, Local; Nephrectomy; Postoperative Period; Risk Factors; Watchful Waiting
PubMed: 27467135
DOI: 10.1097/MOU.0000000000000308 -
Prostate Cancer and Prostatic Diseases Mar 2022Expectant management (EM) has been widely recommended for men with low-risk prostate cancers (PCa). We evaluated trends in EM and the sociodemographic and clinical...
BACKGROUND
Expectant management (EM) has been widely recommended for men with low-risk prostate cancers (PCa). We evaluated trends in EM and the sociodemographic and clinical factors associated with EM, initiating a National Comprehensive Cancer Network guideline-concordant active surveillance (AS) monitoring protocol, and switching from EM to active treatment (AT).
METHODS
We used the SEER-Medicare database to identify men ages 66+ diagnosed with a low-risk PCa (PSA < 10 ng/mL, Gleason ≤ 6, stage ≤ T2a) in 2010-2013 with ≥1 year of follow-up. We used claims data to capture (1) PCa treatments, including surgical procedures, radiotherapy, and hormone therapy, and (2) AS monitoring procedures, including PSA tests and prostate biopsy. We defined EM as receiving no AT within 1 year of diagnosis. We used multivariable regression techniques to identify factors associated with EM, initiating AS monitoring, and switching to AT.
RESULTS
During the study period, EM increased from 29.4% to 49.0%, p < 0.01. Age < 77, being married/partnered, non-Hispanic ethnicity, higher median ZIP code income, lower PSA levels, stage T1c, and more recent year of diagnosis were associated with EM. Nearly 39% of the EM cohort initiated AS monitoring; age <77, White race, being married/partnered, higher median ZIP code income, and lower PSA levels were associated with initiating AS. By three years after diagnosis, 21.3% of the EM cohort had switched to AT, usually after undergoing AS monitoring procedures.
DISCUSSION
We found increasing uptake of EM over time, though over 50% still received AT. About 60% of EM patients did not initiate AS monitoring, even among those with life expectancy >10 years, implying that a substantial proportion was being managed by watchful waiting. AS monitoring was associated with switching to AT, suggesting that treatment decisions likely were based on cancer progression.
Topics: Aged; Humans; Male; Medicare; Prostate-Specific Antigen; Prostatic Neoplasms; Risk; United States; Watchful Waiting; White People
PubMed: 34108645
DOI: 10.1038/s41391-021-00393-6