Prediction of pathological response following neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer: the PRE-PREVENCYS trial.

BACKGROUND: The recommended treatment for patients with non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Following NAC, 20-40% of patients experience a complete pathological response (pCR) in the RC specimen and these patients have excellent long-term overall survival. Subject to debate is, however, whether patients with a pCR to NAC benefit from RC, which is a major surgical procedure with substantial morbidity, and if these patients might be candidates for close surveillance instead. However, currently it is not possible to accurately identify patients with a pCR to NAC in whom RC might be withheld. The objective of this study is to assess whether pathological response in the RC specimen after NAC can be predicted based on clinical, radiological, and histological variables and on a wide set of molecular biomarkers assessed in tissue, blood and urine. METHODS: This is a multicentre, prospective cohort study, including patients with cT2a-T4a N0-N1 M0 urothelial cell MIBC who are scheduled to undergo cisplatin-based NAC followed by RC. Prior to start of therapy, a 2-Deoxy-2-[18F] fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is performed. Response to NAC is evaluated by CT-scan. Blood and urine, including cytology, are prospectively collected for biomarker analyses before and after NAC. Immediately before RC, participants undergo cystoscopy with bimanual examination and a re-staging transurethral resection (TUR) of all visible cancerous lesions or with biopsies from scar tissue. Subsequently, RC is performed in all patients. Tissue from the diagnostic TUR, the re-staging TUR, and the RC specimen is examined for the presence of urothelial cancer carcinoma and DNA and RNA is isolated for molecular analysis. The primary endpoint is the pathological stage (ypTN) in the RC and ePLND specimen and its association with clinical response. DISCUSSION: If the PRE-PREVENCYS trial shows that the absence of residual disease after NAC in patients with MIBC is accurately predicted, a randomized controlled trial is scheduled comparing the overall survival of NAC plus RC versus NAC followed by close surveillance for patients with a clinically complete response (PREVENCYS trial). TRIAL REGISTRATION: Netherlands Trial Register: NL8678; Registered 20 May 2020 https://www.trialregister.nl/trial/8678.

Development and External Validation of a Model Predicting Death After Surgery in Patients With a Ruptured Abdominal Aortic Aneurysm: The Dutch Aneurysm Score.

OBJECTIVE: The decision whether or not to proceed with surgical intervention of a patient with a ruptured abdominal aortic aneurysm (rAAA) is very difficult in daily practice. The primary objective of the present study was to develop and to externally validate a new prediction model: the Dutch Aneurysm Score (DAS). METHODS: With a prospective cohort of 10 hospitals (n = 508) the DAS was developed using a multivariate logistic regression model. Two retrospective cohorts with rAAA patients from two hospitals (n = 373) were used for external validation. The primary outcome was the combined 30 day and in-hospital death rate. Discrimination (AUC), calibration plots, and the ability to identify high risk patients were compared with the more commonly used Glasgow Aneurysm Score (GAS). RESULTS: After multivariate logistic regression, four pre-operative variables were identified: age, lowest in hospital systolic blood pressure, cardiopulmonary resuscitation, and haemoglobin level. The area under the receiver operating curve (AUC) for the DAS was 0.77 (95% CI 0.72-0.82) compared with the GAS with an AUC of 0.72 (95% CI 0.67-0.77). The DAS showed a death rate in patients with a predicted death rate ≥80% of 83%. CONCLUSIONS: The present study shows that the DAS has a higher discriminative performance (AUC) compared with the GAS. All clinical variables used for the DAS are easy to obtain. Identification of low risk patients with the DAS can potentially reduce turndown rates. The DAS can reliably be used by clinicians to make a more informed decision in dialogue with the patient and their family whether or not to proceed with surgical intervention.

Midterm Re-interventions and Survival After Endovascular Versus Open Repair for Ruptured Abdominal Aortic Aneurysm.

OBJECTIVE: To compare the midterm re-intervention and survival rates after EVAR and OR for ruptured abdominal aortic aneurysms (RAAA). METHODS: Observational cohort study including all consecutive RAAA patients between 2004 and 2011 in 10 hospitals in the Amsterdam ambulance region. The primary end point was re-interventions within 5 years of the primary intervention. The secondary end point was death. The outcomes were estimated by survival analyses, compared using the logrank test, and subsequently adjusted for possible confounders using Cox proportional hazard models. Re-interventions were estimated in all patients and in patients who survived their hospital stay. RESULTS: Of 467 patients with a RAAA, 73 were treated by EVAR and 394 by OR. Five years after the primary intervention, the rates of freedom from re-intervention were 55% for EVAR (26/73, 95% CI: 41-69%) and 60% for OR (130/394, 95% CI: 55-66%) (p = .96). After adjustment for age, sex, comorbidity, and pre-operative hemodynamic stability, the risk of re-intervention was similar (HR 1.01, 95% CI: 0.65-1.55). The survival rates were 36% for EVAR (45/73, 95% CI: 24-47%) and 38% for OR (235/394, 95% CI: 33-43%) (p = .83). In 297 patients who survived their hospital stay, the rates of freedom from re-intervention were 66% for EVAR (15/54, 95% CI: 52-81%) and 90% for OR (20/243, 95% CI: 86-95%) (p < .01). After adjustment for age and sex, the risk of re-intervention was higher after EVAR (HR 0.27, 95% CI: 0.14-0.52). CONCLUSIONS: Five years after the primary intervention, endovascular and open repair for ruptured abdominal aortic aneurysm resulted in similar re-intervention and survival rates. However, in patients who survived their hospital stay the re-intervention rate was higher for EVAR than for OR.

Editor's Choice--External Validation of Models Predicting Survival After Ruptured Abdominal Aortic Aneurysm Repair.

OBJECTIVE: Prediction of survival after intervention for ruptured abdominal aortic aneurysms (RAAA) may support case mix comparison and tailor the prognosis for patients and relatives. The objective of this study was to assess the performance of four prediction models: the updated Glasgow Aneurysm Score (GAS), the Vancouver scoring system, the Edinburgh Ruptured Aneurysm Score (ERAS), and the Hardman index. DESIGN, MATERIALS, AND METHODS: This was a retrospective cohort study in 449 patients in ten hospitals with a RAAA (intervention between 2004 and 2011). The primary endpoint was combined 30 day or in hospital death.The accuracy of the prediction models was assessed for discrimination (area under the curve [AUC]). An AUC>0.70 was considered sufficiently accurate. In studies with sufficiently accurate discrimination, correspondence between the predicted and observed outcomes (i.e. calibration) was recalculated. RESULTS: The AUC of the updated GAS was 0.71 (95% confidence interval [CI] 0.66-0.76), of the Vancouver score was 0.72 (95% CI 0.67-0.77), and of the ERAS was 0.58 (95% CI 0.52-0.65). After recalibration, predictions by the updated GAS slightly overestimated the death rate, with a predicted death rate 60% versus observed death rate 54% (95% CI 44-64%). After recalibration, predictions by the Vancouver score considerably overestimated the death rate, with a predicted death rate 82% versus observed death rate 62% (95% CI 52-71%). Performance of the Hardman index could not be assessed on discrimination and calibration, because in 57% of patients electrocardiograms were missing. CONCLUSIONS: Concerning discrimination and calibration, the updated GAS most accurately predicted death after intervention for a RAAA. However, the updated GAS did not identify patients with a ≥95% predicted death rate, and therefore cannot reliably support the decision to withhold intervention.

Fate of patients unwilling or unsuitable to undergo surgical intervention for a ruptured abdominal aortic aneurysm.

INTRODUCTION: The primary objective of this study was to assess the duration of in-hospital survival in 57 patients with ruptured abdominal aortic aneurysms (RAAA) who did not undergo surgical intervention. REPORT: Two hours after registration in the emergency room, 58% (95% CI 45-71) of patients were still alive. The median survival was 2.2 hours (interquartile range 1-18). In a subgroup including 26 haemodynamically stable patients, survival after 2 hours was 96% (95% CI 89-100). CONCLUSION: In patients with an RAAA without surgical intervention, the duration of in-hospital survival is limited. However, a group of haemodynamically stable patients can be identified in whom survival is much longer.

Effect of regional cooperation on outcomes from ruptured abdominal aortic aneurysm.

BACKGROUND: Care for patients with a ruptured abdominal aortic aneurysm (rAAA) in the Amsterdam ambulance region (The Netherlands) was concentrated into vascular centres with a 24-h full emergency vascular service in cooperation with seven referring regional hospitals. Previous population-based survival after rAAA in the Netherlands was 46 (95 per cent confidence interval (c.i.) 43 to 49) per cent. It was hypothesized that regional cooperation would improve survival. METHODS: This was a prospective observational cohort study carried out simultaneously with the Amsterdam Acute Aneurysm Trial. Consecutive patients with an rAAA between 2004 and 2011 in all ten hospitals in the Amsterdam region were included. The primary outcome was 30-day survival after admission. Multivariable logistic regression, including age, sex, co-morbidity, intervention (endovascular or open repair), preoperative systolic blood pressure, cardiopulmonary resuscitation and year of intervention, was used to assess the influence of hospital setting on survival. RESULTS: Of 453 patients with rAAA from the Amsterdam ambulance region, 61 did not undergo intervention; 352 patients were treated surgically at a vascular centre and 40 at a referring hospital. The regional survival rate was 58.5 (95 per cent c.i. 53.9 to 62.9) per cent (265 of 453). After multivariable adjustment, patients treated at a vascular centre had a higher survival rate than patients treated surgically at a referring hospital (adjusted odds ratio 3.18, 95 per cent c.i. 1.43 to 7.04). CONCLUSION: After regional cooperation, overall survival of patients with an rAAA improved. Most patients were treated in a vascular centre and in these patients survival rates were optimal.

Editor's Choice - Endovascular aneurysm repair versus open repair for patients with a ruptured abdominal aortic aneurysm: a systematic review and meta-analysis of short-term survival.

BACKGROUND: There is clinical equipoise between open (OR) and endovascular aneurysm repair (EVAR) for the best treatment of ruptured abdominal aortic aneurysm (RAAA). OBJECTIVE: The aim of the study was to perform a systematic review and meta-analysis to estimate the short-term (combined 30-day or in-hospital) survival after EVAR and OR for patients with RAAA. Data sources included Medline, Embase, and the World Health Organization International Clinical Trials Registry until 13 January 2014. All randomised controlled trials (RCTs), observational cohort studies, and administrative registries comparing OR and EVAR of at least 50 patients were included. Articles were full-length and in English. METHODS: Standard PRISMA guidelines were followed. The methodological quality of RCTs was assessed with the Cochrane Collaboration's tool for assessing risk of bias. The quality of observational studies was assessed with a modified Cochrane Collaboration's tool for assessing risk of bias, the Newcastle-Ottawa Scale, and the Methodological Index for Non-Randomized Studies. The results of the RCTs, of the obersvational studies, and of the administrative registries were pooled separately and analysed with the use of a random effects model. RESULTS: From a total of 3,769 articles, three RCTs, 21 observational studies, and eight administrative registries met the inclusion criteria. In the RCTs, the risk of bias was lowest and the pooled odds ratio for death after EVAR versus OR was 0.90 (95% CI 0.65-1.24). The majority of the observational studies had a high risk of bias and the pooled odds ratio for death was 0.44 (95% CI 0.37-0.53). The majority of the administrative registries had a high risk of bias and the pooled odds ratio for death was 0.54 (95% CI 0.47-0.62). CONCLUSION: Endovascular aneurysm repair is not inferior to open repair in patients with a ruptured abdominal aortic aneurysm. This supports the use of EVAR in suitable patients and OR as a reasonable alternative.

Outcomes after open repair for ruptured abdominal aortic aneurysms in patients with friendly versus hostile aortoiliac anatomy.

OBJECTIVES: In patients with a ruptured abdominal aortic aneurysm (RAAA), anatomic suitability for endovascular aneurysm repair (EVAR) depends on aortic neck and iliac artery characteristics. If the aortoiliac anatomy is unsuitable for EVAR ("hostile anatomy"), open repair (OR) is the next option. We hypothesized that the death rate for OR is higher in patients with hostile anatomy than in patients with friendly anatomy. METHODS: We conducted an observational cohort study in 279 consecutive patients with an RAAA treated with OR between 2004 and 2011. The primary endpoint was 30-day or in-hospital death. Aortoiliac anatomy (friendly vs. hostile) was determined prospectively by the vascular surgeon and the interventional radiologist treating the patient. A multivariable logistic regression analysis was done to assess the risk of dying in patients with hostile anatomy after adjustment for age, sex, comorbidity, and hemodynamic stability. RESULTS: Aortoiliac anatomy was friendly in 71 patients and hostile in 208 patients. Death rate was 38% (95% confidence interval (CI): 28 to 50%) in patients with friendly anatomy and 30% (95% CI: 24 to 37%) in patients with hostile anatomy (p = .23). After multivariable adjustment, the risk of dying was not higher in patients with hostile anatomy (adjusted odds ratio 0.744, 95% CI 0.394 to 1.404). CONCLUSION: The death rate after open repair for an RAAA is comparable in patients with friendly and hostile aortoiliac anatomy.

Measurement of exhaled nitric oxide as a potential screening tool for pulmonary tuberculosis.

BACKGROUND: There is a need for low-technology, inexpensive screening tools for active tuberculosis (TB) case finding. OBJECTIVE: to assess the potential usefulness of measuring exhaled nitric oxide (eNO). DESIGN: Cross-sectional comparison in Hanoi, Viet Nam, comparing 90 consecutive smear-positive, culture-confirmed TB patients presenting at a referral hospital with office workers (no X-ray confirming TB) at this hospital (n = 52) and at a construction firm (n = 84). eNO levels were analysed using a validated handheld analyser. RESULTS: eNO levels among TB patients (median 15 parts per billion [ppb], interquartile range [IQR] 10-20) were equal to those among construction firm workers (15 ppb, IQR 12-19, P = 0.517) but higher than those among hospital workers (8.5 ppb, IQR 5-12.5, P < 0.001). Taking the hospital workers as the comparison group, best performance as a diagnostic tool was at a cut-off of 10 ppb, with sensitivity 78% (95%CI 68-86) and specificity 62% (95%CI 47-75). Test characteristics could be optimised to 84% vs. 67% by excluding individuals who had recently smoked or consumed alcohol. CONCLUSION: While eNO measurement has limited value in the direct diagnosis of pulmonary TB, it may be worth developing and evaluating as a cost-effective replacement of chest X-ray in screening algorithms of pulmonary TB where X-ray is not available.