Breast conserving therapy after neoadjuvant chemotherapy; data from the Dutch Breast Cancer Audit

Introduction: NAC has led to an increase in breast conserving surgery (BCS) worldwide. This study aims to analyse trends in the use of neoadjuvant chemotherapy (NAC) and the impact on surgical outcomes. Methods: We reviewed all records of cT1-4N0-3M0 breast cancer patients diagnosed between July 2011 and June 2016 who have been registered in the Dutch National Breast Cancer Audit (NBCA) (N = 57.177). The surgical outcomes of ‘BCS after NAC′ were compared with ‘primary BCS′ using a multivariable logistic regression model. Results: Between 2011 and 2016, the use of NAC increased from 9% to 18% and ‘BCS after NAC’ (N = 4170) increased from 43% to 57%. We observed an involved invasive margin rate (IMR) of 6,7% and a re-excision rate of 6,6%. As compared to ‘primary BCS′ the IMR of ‘BCS after NAC′ is higher for cT1 (12,3% versus 8,3%; p < 0.005), equal for cT2 (14% versus 14%; p = 0.046) and lower for cT3 breast cancer (28,3% versus 31%; p < 0.005). Prognostic factors associated with IMR for both ‘primary BCS′ as for ‘BCS after NAC′ are: lobular invasive breast cancer and a hormone receptor positive receptor status (all p < 0,005). Conclusion: The use of NAC and the incidence of ‘BCS after NAC′ increased exponentially in time for all stages of invasive breast cancer in the Netherlands. This nationwide data confirms that ‘BCS after NAC′ compared to ‘primary BCS′ leads to equal surgical outcomes for cT2 and improved surgical outcomes for cT3 breast cancer. These promising results encourage current developments towards de-escalation of surgical treatment

Breast-conserving surgery following neoadjuvant therapy-a systematic review on surgical outcomes

Purpose: Neoadjuvant chemotherapy (NACT) is increasingly used in breast cancer treatment. One of the main goals of NACT is to reduce the extent of local surgery of the breast and axilla. The aim of this study was to determine surgical outcomes for patients receiving breast-conserving therapy (BCT) after NACT, including margin status plus secondary surgeries, excision volumes, and cosmetic outcomes. Methods: A systematic review was performed in accordance with PRISMA principles. Pubmed, MEDLINE, Embase, and the Cochrane Library were searched for studies investigating the results of BCT following NACT. The main study outcomes were margin status, additional local therapies, excision volumes, and cosmetic outcomes. Non-comparative studies on NACT were also included. Exclusion criteria were studies with less than 25 patients, and studies excluding secondary mastectomy patients. Findings: Of the 1219 studies screened, 26 studies were deemed eligible for analysis, including data from 5379 patients treated with NACT and 10,110 patients treated without NACT. Included studies showed wide ranges of tumor-involved margins (2–39.8%), secondary surgeries (0–45.4%), and excision volumes (43.2–268 cm3) or specimen weight (26.4–233 g) after NACT. Most studies were retrospective, with a high heterogeneity and a high risk of bias. Cosmetic outcomes after NACT were reported in two single-center cohort studies. Both studies showed acceptable cosmetic outcomes. Interpretation: There is currently insufficient evidence to suggest that NACT improves surgical outcomes of BCT. It is imperative that clinical trials include patient outcome measures in order to allow monitoring and meaningful comparison of treatment outcomes in breast cancer

Systemic and urinary neutrophil gelatinase-associated lipocalins are poor predictors of acute kidney injury in unselected critically ill patients

Background. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine have been suggested as potential early predictive biological markers of acute kidney injury (AKI) in selected critically ill patients. Methods. We performed a secondary analysis of a multicenter prospective observational cohort study of unselected critically ill patients. Results. The analysis included 140 patients, including 57 patients who did not develop AKI, 31 patients who developed AKI, and 52 patients with AKI on admission to the ICU. Levels of sNGAL and uNGAL on non-AKI days were significantly lower compared to levels of sNGAL on RIFLE(RISK) days, RIFLE(INJURY) days, and RIFLE(FAILURE) days. The AUC of sNGAL for predicting AKI was low: 0.45 (95% confidence interval (CI) 0.27-0.63) and 0.53 (CI 0.38-0.67), 2 days and 1 day before development of AKI, respectively. The AUC of uNGAL for predicting AKI was also low: 0.48 (CI 0.33-0.62) and 0.48 (CI 0.33-0.62), 2 days and 1 day before development of AKI, respectively. AUC of sNGAL and uNGAL for the prediction of renal replacement therapy requirement was 0.47 (CI 0.37-0.58) and 0.26 (CI 0.03-0.50). Conclusions. In unselected critically ill patients, sNGAL and uNGAL are poor predictors of AKI or RR

The Dutch Breast Implant Registry: Registration of Breast Implant-Associated Anaplastic Large Cell Lymphoma-A Proof of Concept

BACKGROUND: The Dutch Breast Implant Registry (DBIR) was established in April of 2015 and currently contains information on 38,000 implants in 18,000 women. As a clinical registry, it evaluates the quality of breast implant surgery, including adverse events such as breast implant-associated (BIA) anaplastic large cell lymphoma (ALCL). To examine the efficacy of the DBIR, the capture rate of BIA-ALCL was compared to the registration of BIA-ALCL in the Dutch Nationwide Network and Registry of Histo- and Cytopathology (PALGA) as a gold standard, in combination with matching these databases to obtain complementary information. METHODS: All BIA-ALCL patients diagnosed and registered in The Netherlands in 2016 and 2017 were identified separately in the PALGA and DBIR databases. In addition, both databases were matched using indirect key identifiers. Pathologic information from the PALGA and clinical and device characteristics from the DBIR were obtained for all patients. RESULTS: Matching of both databases gave a capture rate of BIA-ALCL in the DBIR of 100 percent (n = 6) in 2016 and 70 percent (n = 7) in 2017. In total, 17 patients were identified in the PALGA, of which 14 patients were also identified in the DBIR; three patients were not registered; and 10 patients were registered false-positive. Of all confirmed patients, symptoms, staging results, treatment, and implant information were registered. CONCLUSIONS: Currently, the DBIR contains 2 full registration years and captures most of the BIA-ALCL patients despite overestimation. Therefore, pathology confirmation remains essential. By matching these databases, complementary clinical and implant information could be retrieved, establishing the DBIR as an essential postmarketing surveillance system for health risk assessments

Effect of a lower vs higher positive end-expiratory pressure strategy on ventilator-free days in ICU patients without ARDS: A randomized clinical trial

IMPORTANCE It is uncertain whether invasive ventilation can use lower positive end-expiratory pressure (PEEP) in critically ill patients without acute respiratory distress syndrome (ARDS). OBJECTIVE To determine whether a lower PEEP strategy is noninferior to a higher PEEP strategy regarding duration of mechanical ventilation at 28 days. DESIGN, SETTING, AND PARTICIPANTS Noninferiority randomized clinical trial conducted from October 26, 2017, through December 17, 2019, in 8 intensive care units (ICUs) in the Netherlands among 980 patients without ARDS expected not to be extubated within 24 hours after start of ventilation. Final follow-up was conducted in March 2020. INTERVENTIONS Participants were randomized to receive invasive ventilation using either lower PEEP, consisting of the lowest PEEP level between 0 and 5 cm H2O (n = 476), or higher PEEP, consisting of a PEEP level of 8 cm H2O (n = 493). MAIN OUTCOMES AND MEASURES The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for the difference in ventilator-free days at day 2 of −10%. Secondary outcomes included ICU and hospital lengths of stay; ICU, hospital, and 28- and 90-day mortality; development of ARDS, pneumonia, pneumothorax, severe atelectasis, severe hypoxemia, or need for rescue therapies for hypoxemia; and days with use of vasopressors or sedation. RESULTS Among 980 patients who were randomized, 969 (99%) completed the trial (median age, 66 [interquartile range {IQR}, 56-74] years; 246 [36%] women). At day 28, 476 patients in the lower PEEP group had a median of 18 ventilator-free days (IQR, 0-27 days) an 493 patients in the higher PEEP group had a median of 17 ventilator-free days (IQR, 0-27 days) (mean ratio, 1.04; 95% CI, 0.95-∞; P = .007 for noninferiority), and the lower boundary of the 95% CI was within the noninferiority margin. Occurrence of severe hypoxemia was 20.6% vs 17.6% (risk ratio, 1.17; 95% CI, 0.90-1.51; P = .99) and need for rescue strategy was 19.7% vs 14.6% (risk ratio, 1.35; 95% CI, 1.02-1.79; adjusted P = .54) in patients in the lower and higher PEEP groups, respectively. Mortality at 28 days was 38.4% vs 42.0% (hazard ratio 0.89; 95% CI, 0.73-1.09; P = .99) in patients in the lower and higher PEEP groups, respectively. There were no statistically significant differences in other secondary outcomes. CONCLUSIONS AND RELEVANCE Among patients in the ICU without ARDS who were expected not to be extubated within 24 hours, a lower PEEP strategy was noninferior to a higher PEEP strategy with regard to the number of ventilator-free days at day 28. These findings support the use of lower PEEP in patients without ARDS