Chemoradiation followed by esophagectomy is a standard treatment option for patients with locally advanced esophageal cancer (LAEC). Esophagectomy is a high-risk procedure, and recent evidence ...suggests select patients may benefit from omitting or delaying surgery. This study aims to compare surgery versus active surveillance for LAEC patients with complete clinical response (cCR) after neoadjuvant chemoradiotherapy (nCRT).
Decision analysis with Markov modeling was used. The base case was a 60-year-old man with T3N0M0 esophageal cancer with cCR after nCRT. The decision was modeled for a 5-year time horizon. Primary outcomes were life-years and quality-adjusted life-years (QALY). Probabilities and utilities were derived through the literature. Deterministic sensitivity analyses were performed using ranges from the literature with consideration for clinical plausibility.
Surgery was favored for survival with an expected life-years of 2.89 versus 2.64. After incorporating quality of life, active surveillance was favored, with an expected QALY of 1.70 versus 1.56. The model was sensitive to probability of recurrence on active surveillance (threshold value 0.598), probability of recurrence being resectable (0.318), and disutility of previous esophagectomy (−0.091). The model was not sensitive to perioperative morbidity and mortality.
Our study finds that surgery increases life expectancy but decreases QALY. Although the incremental change in QALY for either modality is insufficient to make broad clinical recommendations, our study demonstrates that either approach is acceptable. As probabilities of key factors are further defined in the literature, treatment decisions for patients with LAEC and a cCR after nCRT should consider histology, patient values, and quality of life.
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Randomized clinical trials have recently examined the benefit of adding docetaxel or abiraterone to androgen deprivation therapy (ADT) in hormone-naïve advanced prostate cancer (PCa).
To perform a ...systematic review and network meta-analysis of randomized clinical trials, indirectly evaluating overall survival (OS) for men treated with abiraterone acetate plus prednisone/prednisolone with ADT (Abi-ADT) versus docetaxel with ADT (Doce-ADT) in hormone-naïve high-risk and metastatic PCa.
Medline, Embase, Web of Science, Scopus, and Clinicaltrials.gov databases were searched in August 2017. We pooled results using the inverse variance technique and random-effects models. The Bucher technique for indirect treatment comparison was used to compare Abi-ADT with Doce-ADT. A priori subgroup and sensitivity analyses were performed.
Overall, 6067 patients from five trials were included: 1181 (19.5%) patients who received Doce-ADT, 1557 (25.7%) patients who received Abi-ADT, and 3329 (54.9%) patients who received ADT-alone. There was a total of 1921 deaths: 391 in the Doce-ADT group, 353 in the Abi-ADT group, and 1177 in the ADT-only group. The pooled hazard ratio (HR) for OS was 0.75 (95% confidence interval CI: 0.63–0.91, I2=51%, 3 trials, 2951 patients) for Doce-ADT versus ADT-alone and 0.63 (95% CI: 0.55–0.72, I2=0%, 2 trials, 3116 patients) for Abi-ADT versus ADT-alone. The indirect comparison of Abi-ADT to Doce-ADT demonstrated no statistically significant difference in OS between these approaches (HR: 0.84, 95% CI: 0.67–1.06). Findings were similar in various a priori subset analyses, including patients with metastatic disease. Bayesian analyses demonstrated comparable results (HR: 0.83, 95% CI: 0.63–1.16). Despite the lack of statistical significance, Surface Under the Cumulative Ranking Analysis demonstrated an 89% probability that Abi-ADT was preferred.
We did not identify a significant difference in OS between Abi-ADT and Doce-ADT for men with hormone-naïve high-risk or metastatic PCa, although Bayesian analysis demonstrates a high likelihood that Abi-ADT was preferred.
We synthesized the evidence available from studies examining the administration of docetaxel or abiraterone in combination with hormonal therapy for patients with newly diagnosed, advanced prostate cancer. While these studies did not directly compare these agents, we used methodological techniques to indirectly compare them and found no significant difference in overall survival.
A number of recent randomized controlled trials have demonstrated the benefit of adding abiraterone and prednisone or docetaxel to androgen deprivation therapy in men with hormone-naïve metastatic prostate cancer. However, which treatment to choose remains unclear. In this network meta-analysis, we found no significant difference in survival between men treated with abiraterone and prednisone and those treated with docetaxel in addition to androgen deprivation therapy.
Abstract Background A biologic rationale exists for the association between metabolic syndrome (MetS) and prostate cancer (PCa). However, epidemiologic studies have been conflicting. Objective To ...evaluate the association between MetS and the odds of PCa diagnosis in men referred for biopsy. Design, setting, and participants Patients without prior PCa diagnosis undergoing prostate biopsy were identified from a large prostate biopsy cohort (in Toronto, Canada). The definition of MetS was based on the most recent interim joint consensus definition, requiring any three of five components (obesity, elevated blood pressure, diabetes or impaired fasting glucose, low high-density lipoprotein-cholesterol, and hypertriglyceridemia). Both the individual components of MetS and the cumulative number of MetS components were evaluated. Outcome measurements and statistical analysis The outcomes were PCa detection overall, clinically significant PCa (CSPC; defined as any Gleason pattern ≥4, >50% involvement of a single biopsy core, or more than one of three total number of cores involved), and intermediate- or high-grade PCa (I-HGPC; Gleason 7–10). Tests for trend and multivariable logistic regression analyses were performed. Results and limitations Of 2235 patients, 494 (22.1%) had MetS. No individual MetS component was independently associated with PCa. However, increasing number of MetS components was associated with higher PCa grade ( p < 0.001), as well as progressively higher odds of PCa outcomes (three or more; ie, MetS) compared with no MetS components: Odds ratios were 1.54 for PCa overall (95% confidence interval CI, 1.17–2.04; p = 0.002), 1.56 for CSPC (95% CI, 1.17–2.08; p = 0.002), and 1.56 for I-HGPC (95% CI, 1.16–2.10; p = 0.003) in multivariable analyses. The main limitation is the retrospective design. Conclusions Although the individual MetS components are not independently associated with PCa outcomes, MetS is significantly associated with higher odds of PCa diagnosis, CSPC, and I-HGPC. There is a biologic gradient between the number of MetS components and the risk of PCa, as well as cancer grade. Patient summary Metabolic syndrome is a collection of metabolic abnormalities that increases one's risk for heart disease. Our study shows that an increasing degree of metabolic abnormality is also associated with an increased risk of diagnosis of overall and aggressive prostate cancer.
Nearly all existing direct current (DC) chemical vapor sensing methodologies are based on charge transfer between sensor and adsorbed molecules. However, the high binding energy at the charge-trapped ...sites, which is critical for high sensitivity, significantly slows sensors’ responses and makes the detection of nonpolar molecules difficult. Herein, by exploiting the incomplete screening effect of graphene, we demonstrate a DC graphene electronic sensor for rapid (subsecond) and sensitive (ppb) detection of a broad range of vapor analytes, including polar, nonpolar, organic, and inorganic molecules. Molecular adsorption induced capacitance change in the graphene transistor is revealed to be the main sensing mechanism. A novel sensor design, which integrates a centimeter-scale graphene transistor and a microfabricated flow column, is pioneered to enhance the fringing capacitive gating effect. Our work provides an avenue for a broad spectrum real-time gas sensing technology and serves as an ideal testbed for probing molecular physisorption on graphene.
Abstract Context High-grade T1 (formerly T1G3) bladder cancer (BCa) has a high propensity to recur and progress. As a result, decisions pertaining to its treatment are difficult. Treatment with ...bacillus Calmette-Guérin (BCG) risks progression and metastases but may preserve the bladder. Cystectomy may offer the best opportunity for cure but is associated with morbidity and a risk of mortality, and it may constitute potential overtreatment for many cases of T1G3 tumours. For purposes of this review, we continue to refer to high-grade T1 lesions as “T1G3.” Objective To review the current literature on the management of T1G3 BCa and to provide recommendations for its treatment. Evidence acquisition A National Center for Biotechnology Information (NCBI) PubMed search for relevant articles published between 1996 and 9 January 2009 was performed using the Medical Subject Headings “T1G3” or “T1” and “Bladder cancer.” Articles relevant to the treatment of T1G3 BCa were retained. Evidence synthesis The diagnosis of T1G3 disease is difficult because pathologic staging is often unreliable and because of the risk of significant understaging at initial transurethral resection (TUR) of bladder tumour. A secondary restaging TUR is recommended for all cases of T1G3. A single dose of immediate post-TUR chemotherapy is recommended. For a bladder-sparing approach, intravesical BCG should be given as induction with maintenance dosing. Immediate or early radical cystectomy (RC) should be offered to all patients with recurrent or multifocal T1G3 disease, those who are at high risk of progression, and those failing BCG treatment. Conclusions Both bladder preservation and RC are appropriate options for T1G3 BCa. Risk stratification of patients based on pathologic features at initial TUR or at recurrence can select those most appropriate for bladder preservation compared to those for whom cystectomy should be strongly considered.
Background
A reduction in surgical site infections (SSIs) has been reported in several discrete patient populations during the COVID-19 pandemic. Herein, this study evaluates the impact of the ...COVID-19 pandemic on SSI in a large patient cohort incorporating multiple surgical disciplines. We hypothesize that enhanced infection control and heightened awareness of such measures is analogous to an SSI care bundle, the hypothetical “COVID bundle”, and may impact SSI rates.
Method
Data collected for the American College of Surgeons National Surgical Quality Improvement Program between January 1, 2015, and April 1, 2021, were retrospectively analyzed. SSI rates were compared among time-dependent patient cohorts: Cohort A (pre-pandemic,
N
= 24,060, 87%) and Cohort B (pandemic,
N
= 3698, 13%). Time series and multivariable analyses predicted pre-pandemic and pandemic SSI trends and tested for association with timing of surgery.
Results
The overall SSI incidence was reduced in Cohort B versus Cohort A (2.8% vs. 4.5%,
p
< 0.001). Multivariable analysis indicated a downward SSI trend before pandemic onset (IRR 0.997, 95% CI 0.994, 1). At pandemic onset, the trend reduced by a relative factor of 39% (IRR 0.601, 95% CI 0.338, 1.069). SSI then trended upward during the pandemic (IRR 1.035, 95% CI 0.965, 1.111). SSI rates significantly trended downward in general surgical patients at pandemic onset (IRR 0.572, 95% CI 0.353, 0.928).
Conclusion
Although overall SSI incidence was reduced during the pandemic, a statistically significant decrease in the predicted SSI rate only occurred in general surgical patients at pandemic onset. This trend may suggest a positive impact of the “COVID bundle” on SSI rates in these patients.
Previous randomised controlled trials comparing bladder preservation with radical cystectomy for muscle-invasive bladder cancer closed due to insufficient accrual. Given that no further trials are ...foreseen, we aimed to use propensity scores to compare trimodality therapy (maximal transurethral resection of bladder tumour followed by concurrent chemoradiation) with radical cystectomy.
This retrospective analysis included 722 patients with clinical stage T2–T4N0M0 muscle-invasive urothelial carcinoma of the bladder (440 underwent radical cystectomy, 282 received trimodality therapy) who would have been eligible for both approaches, treated at three university centres in the USA and Canada between Jan 1, 2005, and Dec 31, 2017. All patients had solitary tumours less than 7 cm, no or unilateral hydronephrosis, and no extensive or multifocal carcinoma in situ. The 440 cases of radical cystectomy represent 29% of all radical cystectomies performed during the study period at the contributing institutions. The primary endpoint was metastasis-free survival. Secondary endpoints included overall survival, cancer-specific survival, and disease-free survival. Differences in survival outcomes by treatment were analysed using propensity scores incorporated in propensity score matching (PSM) using logistic regression and 3:1 matching with replacement and inverse probability treatment weighting (IPTW).
In the PSM analysis, the 3:1 matched cohort comprised 1119 patients (837 radical cystectomy, 282 trimodality therapy). After matching, age (71·4 years IQR 66·0–77·1 for radical cystectomy vs 71·6 years 64·0–78·9 for trimodality therapy), sex (213 25% vs 68 24% female; 624 75% vs 214 76% male), cT2 stage (755 90% vs 255 90%), presence of hydronephrosis (97 12% vs 27 10%), and receipt of neoadjuvant or adjuvant chemotherapy (492 59% vs 159 56%) were similar between groups. Median follow-up was 4·38 years (IQR 1·6–6·7) versus 4·88 years (2·8–7·7), respectively. 5-year metastasis-free survival was 74% (95% CI 70–78) for radical cystectomy and 75% (70–80) for trimodality therapy with IPTW and 74% (70–77) and 74% (68–79) with PSM. There was no difference in metastasis-free survival either with IPTW (subdistribution hazard ratio SHR 0·89 95% CI 0·67–1·20; p=0·40) or PSM (SHR 0·93 0·71–1·24; p=0·64). 5-year cancer-specific survival for radical cystectomy versus trimodality therapy was 81% (95% CI 77–85) versus 84% (79–89) with IPTW and 83% (80–86) versus 85% (80–89) with PSM. 5-year disease-free survival was 73% (95% CI 69–77) versus 74% (69–79) with IPTW and 76% (72–80) versus 76% (71–81) with PSM. There were no differences in cancer-specific survival (IPTW: SHR 0·72 95% CI 0·50–1·04; p=0·071; PSM: SHR 0·73 0·52–1·02; p=0·057) and disease-free survival (IPTW: SHR 0·87 0·65–1·16; p=0·35; PSM: SHR 0·88 0·67–1·16; p=0·37) between radical cystectomy and trimodality therapy. Overall survival favoured trimodality therapy (IPTW: 66% 95% CI 61–71 vs 73% 68–78; hazard ratio HR 0·70 95% CI 0·53–0·92; p=0·010; PSM: 72% 69–75 vs 77% 72–81; HR 0·75 0·58–0·97; p=0·0078). Outcomes for radical cystectomy and trimodality therapy were not statistically different among centres for cancer-specific survival and metastasis-free survival (p=0·22–0·90). Salvage cystectomy was done in 38 (13%) trimodality therapy patients. Pathological stage in the 440 radical cystectomy patients was pT2 in 124 (28%), pT3–4 in 194 (44%), and 114 (26%) node positive. The median number of nodes removed was 39, the soft tissue positive margin rate was 1% (n=5), and the perioperative mortality rate was 2·5% (n=11).
This multi-institutional study provides the best evidence to date showing similar oncological outcomes between radical cystectomy and trimodality therapy for select patients with muscle-invasive bladder cancer. These results support that trimodality therapy, in the setting of multidisciplinary shared decision making, should be offered to all suitable candidates with muscle-invasive bladder cancer and not only to patients with significant comorbidities for whom surgery is not an option.
Sinai Health Foundation, Princess Margaret Cancer Foundation, Massachusetts General Hospital.
IMPORTANCE: Antithrombotic medications are among the most commonly prescribed medications. OBJECTIVE: To characterize rates of hematuria-related complications among patients taking antithrombotic ...medications. DESIGN, SETTING, AND PARTICIPANTS: Population-based, retrospective cohort study including all citizens in Ontario, Canada, aged 66 years and older between 2002 and 2014. The final follow-up date was December 31, 2014. EXPOSURES: Receipt of an oral anticoagulant or antiplatelet medication. MAIN OUTCOMES AND MEASURES: Hematuria-related complications, defined as emergency department visit, hospitalization, or a urologic procedure to investigate or manage gross hematuria. RESULTS: Among 2 518 064 patients, 808 897 (mean SD age, 72.1 6.8 years; 428 531 53% women) received at least 1 prescription for an antithrombotic agent over the study period. Over a median follow-up of 7.3 years, the rates of hematuria-related complications were 123.95 events per 1000 person-years among patients actively exposed to antithrombotic agents vs 80.17 events per 1000 person-years among patients not exposed to these drugs (difference, 43.8; 95% CI, 43.0-44.6; P < .001, and incidence rate ratio IRR, 1.44; 95% CI, 1.42-1.46). The rates of complications among exposed vs unexposed patients (80.17 events/1000 person-years) were 105.78 for urologic procedures (difference, 33.5; 95% CI, 32.8-34.3; P < .001, and IRR, 1.37; 95% CI, 1.36-1.39), 11.12 for hospitalizations (difference, 5.7; 95% CI, 5.5-5.9; P < .001, and IRR, 2.03; 95% CI, 2.00-2.06), and 7.05 for emergency department visits (difference, 4.5; 95% CI, 4.3-4.7; P < .001, and IRR, 2.80; 95% CI, 2.74-2.86). Compared with patients who were unexposed to thrombotic agents, the rates of hematuria-related complications were 191.61 events per 1000 person-years (difference, 117.3; 95% CI, 112.8-121.8) for those exposed to both an anticoagulant and antiplatelet agent (IRR, 10.48; 95% CI, 8.16-13.45), 140.92 (difference, 57.7; 95% CI, 56.9-58.4) for those exposed to anticoagulants (IRR, 1.55; 95% CI, 1.52-1.59), and 110.72 (difference, 26.5; 95% CI, 25.9-27.0) for those exposed to antiplatelet agents (IRR, 1.31; 95% CI, 1.29-1.33). Patients exposed to antithrombotic agents, compared with patients not exposed to these drugs, were more likely to be diagnosed as having bladder cancer within 6 months (0.70% vs 0.38%; odds ratio, 1.85; 95% CI, 1.79-1.92). CONCLUSIONS AND RELEVANCE: Among older adults in Ontario, Canada, use of antithrombotic medications, compared with nonuse of these medications, was significantly associated with higher rates of hematuria-related complications (including emergency department visits, hospitalizations, and urologic procedures to manage gross hematuria).
The ability to tune the molecular interaction electronically can have profound impact on wide-ranging scientific frontiers in catalysis, chemical and biological sensor development, and the ...understanding of key biological processes. Despite that electrochemistry is routinely used to probe redox reactions involving loss or gain of electrons, electrical probing and tuning of the weaker noncovalent interactions, such as molecular physisorption, have been challenging, primarily due to the inability to change the work function of conventional metal electrodes. To this end, we report electrical probing and tuning of the noncovalent physisorption of polar molecules on graphene surface by using graphene nanoelectronic heterodyne sensors. Temperature-dependent molecular desorptions for six different polar molecules were measured in real-time to study the desorption kinetics and extract the binding affinities. More importantly, we demonstrate electrical tuning of molecule–graphene binding kinetics through electrostatic gating of graphene; the molecular desorption can be slowed down nearly three times within a gate voltage range of 15 V. Our results provide insight into small molecule–nanomaterial interaction dynamics and signify the ability to electrically tailor interactions, which can lead to rational designs of complex chemical processes for catalysis and drug discovery.
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