Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer

Staging by sentinel node (SN) biopsy is the standard procedure for clinically node-negative breast cancer patients. Intra-operative analysis of the SN allows immediate axillary lymph node (ALN) dissection in SN positive patients, but a quick, reliable and reproducible method is lacking. We tested the suitability of a quantitative cytokeratin 19 (CK19) mRNA one step nucleic acid amplification (OSNA#) technique (OSNA-CK19) for intra-operative SN analysis. OSNA-CK19 involves a short manual sample preparation step and subsequent fully automated amplification of CK19 mRNA based on reverse transcription loop-mediated isothermal amplification, with results available within 30–40 min. OSNA-CK19 was compared to histological staining (Hematoxylin&Eosin and CAM5.2 and CK19 immunostaining) of 346 frozen ALNs from 32 breast cancer patients, using half of the lymph node for each method. 267 samples were negative and 61 positive by both methods. Three samples were histology positive and OSNA-CK19 negative. Fifteen samples were histology negative and OSNA-CK19 positive, 11 of which had copy numbers close to the cut-off level of OSNA-CK19. Seven of these 15 samples were RT-PCR positive for epithelial markers and/or showed CK19 protein expression by Western blot suggesting the presence of tumor deposits in the lymph node part investigated by OSNA-CK19. Concordance with histology was 94.8%, and 96.8% after exclusion of the latter 7 discordant cases. Sensitivity was 95.3% and specificity was 94.7% before and 97.1% after discordant case investigation. Our results indicate that OSNA-CK19 can potentially be useful in an intra-operative clinical setting to detect SN tumor involvement in breast cancer patients

Hospital variation and outcomes after repeat hepatic resection for colorectal liver metastases:a nationwide cohort study

Background: Approximately 70% of patients with colorectal liver metastases (CRLM) experiences intrahepatic recurrence after initial liver resection. This study assessed outcomes and hospital variation in repeat liver resections (R-LR).Methods: This population-based study included all patients who underwent liver resection for CRLM between 2014 and 2022 in the Netherlands. Overall survival (OS) was collected for patients operated on between 2014 and 2018 by linkage to the insurance database. Results: Data of 7479 liver resections (1391 (18.6%) repeat and 6088 (81.4%) primary) were analysed. Major morbidity and mortality were not different. Factors associated with major morbidity included ASA 3+, major liver resection, extrahepatic disease, and open surgery. Five-year OS after repeat versus primary liver resection was 42.3% versus 44.8%, P = 0.37. Factors associated with worse OS included largest CRLM &gt;5 cm (aHR 1.58, 95% CI: 1.07–2.34, P = 0.023), &gt;3 CRLM (aHR 1.33, 95% CI: 1.00–1.75, P = 0.046), extrahepatic disease (aHR 1.60, 95% CI: 1.25–2.04, P = 0.001), positive tumour margins (aHR 1.42, 95% CI: 1.09–1.85, P = 0.009). Significant hospital variation in performance of R-LR was observed, median 18.9% (8.2% to 33.3%).Conclusion: Significant hospital variation was observed in performance of R-LR in the Netherlands reflecting different treatment decisions upon recurrence. On a population-based level R-LR leads to satisfactory survival.</p

Septum resection in women with a septate uterus : a cohort study

© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.Peer reviewedPublisher PD

Hospital variation and outcomes after repeat hepatic resection for colorectal liver metastases:a nationwide cohort study

Background: Approximately 70% of patients with colorectal liver metastases (CRLM) experiences intrahepatic recurrence after initial liver resection. This study assessed outcomes and hospital variation in repeat liver resections (R-LR).Methods: This population-based study included all patients who underwent liver resection for CRLM between 2014 and 2022 in the Netherlands. Overall survival (OS) was collected for patients operated on between 2014 and 2018 by linkage to the insurance database. Results: Data of 7479 liver resections (1391 (18.6%) repeat and 6088 (81.4%) primary) were analysed. Major morbidity and mortality were not different. Factors associated with major morbidity included ASA 3+, major liver resection, extrahepatic disease, and open surgery. Five-year OS after repeat versus primary liver resection was 42.3% versus 44.8%, P = 0.37. Factors associated with worse OS included largest CRLM &gt;5 cm (aHR 1.58, 95% CI: 1.07–2.34, P = 0.023), &gt;3 CRLM (aHR 1.33, 95% CI: 1.00–1.75, P = 0.046), extrahepatic disease (aHR 1.60, 95% CI: 1.25–2.04, P = 0.001), positive tumour margins (aHR 1.42, 95% CI: 1.09–1.85, P = 0.009). Significant hospital variation in performance of R-LR was observed, median 18.9% (8.2% to 33.3%).Conclusion: Significant hospital variation was observed in performance of R-LR in the Netherlands reflecting different treatment decisions upon recurrence. On a population-based level R-LR leads to satisfactory survival.</p

Outcomes of liver surgery:A decade of mandatory nationwide auditing in the Netherlands

Background: In 2013, the nationwide Dutch Hepato Biliary Audit (DHBA) was initiated. The aim of this study was to evaluate changes in indications for and outcomes of liver surgery in the last decade. Methods: This nationwide study included all patients who underwent liver surgery for four indications, including colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), and intrahepatic– and perihilar cholangiocarcinoma (iCCA – pCCA) between 2014 and 2022. Trends in postoperative outcomes were evaluated separately for each indication using multilevel multivariable logistic regression analyses. Results: This study included 8057 procedures for CRLM, 838 for HCC, 290 for iCCA, and 300 for pCCA. Over time, these patients had higher risk profiles (more ASA-III patients and more comorbidities). Adjusted mortality decreased over time for CRLM, HCC and iCCA, respectively aOR 0.83, 95%CI 0.75–0.92, P &lt; 0.001; aOR 0.86, 95%CI 0.75–0.99, P = 0.045; aOR 0.40, 95%CI 0.20–0.73, P &lt; 0.001. Failure to rescue (FTR) also decreased for these groups, respectively aOR 0.84, 95%CI 0.76–0.93, P = 0.001; aOR 0.81, 95%CI 0.68–0.97, P = 0.024; aOR 0.29, 95%CI 0.08–0.84, P = 0.021). For iCCA severe complications (aOR 0.65 95%CI 0.43–0.99, P = 0.043) also decreased. No significant outcome differences were observed in pCCA. The number of centres performing liver resections decreased from 26 to 22 between 2014 and 2022, while median annual volumes did not change (40–49, P = 0.66). Conclusion: Over time, postoperative mortality and FTR decreased after liver surgery, despite treating higher-risk patients. The DHBA continues its focus on providing feedback and benchmark results to further enhance outcomes.</p

Corrigendum: Septum resection in women with a septate uterus:a cohort study

The authors of the above article would like to apologise for an error in one of the authors' names. W. Kuchenbecker should be W.K.H. Kuchenbecker, as above. The electronic version of this article has been updated at https:// doi.org/10.1093/humrep/dez284. The print version is correct. The Authors would like to assure readers that this does not affect any other content of the article.</p

Practice variation and outcomes of minimally invasive minor liver resections in patients with colorectal liver metastases:a population-based study

Introduction: In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM). Methods: This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan–Meier analysis on patients operated until 2018. Results: Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50–0.75, p &lt; 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50–0.67, p &lt; 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99–0.99, p &lt; 0.01), cardiac complications (aOR 0.29, CI:0.10–0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50–0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94–0.99, p &lt; 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21. Conclusion: Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery. Graphical abstract: [Figure not available: see fulltext.].</p

Case-mix adjustment to compare nationwide hospital performances after resection of colorectal liver metastases

Background: Differences in patient demographics and disease burden can influence comparison of hospital performances. This study aimed to provide a case-mix model to compare short-term postoperative outcomes for patients undergoing liver resection for colorectal liver metastases (CRLM). Methods: This retrospective, population-based study included all patients who underwent liver resection for CRLM between 2014 and 2018 in the Netherlands. Variation in case-mix variables between hospitals and influence on postoperative outcomes was assessed using multivariable logistic regression. Primary outcomes were 30-day major morbidity and 30-day mortality. Validation of results was performed on the data from 2019. Results: In total, 4639 patients were included in 28 hospitals. Major morbidity was 6.2% and mortality was 1.4%. Uncorrected major morbidity ranged from 3.3% to 13.7% and mortality ranged from 0.0% to 5.0%. between hospitals. Significant differences between hospitals were observed for age higher than 80 (0.0%-17.1%, p <0.001), ASA 3 or higher (3.3%-36.3%, p <0.001), histopathological parenchymal liver disease (0.0%-47.1%, p <0.001), history of liver resection (8.1%-36.3%, p <0.001), major liver resection (6.7%-38.0%, p <0.001) and synchronous metastases (35.5%-62.1%, p <0.001). Expected 30-day major morbidity between hospitals ranged from 6.4% to 11.9% and expected 30-day mortality ranged from 0.6% to 2.9%. After case-mix correction no significant outliers concerning major morbidity and mortality remained. Validation on patients who underwent liver resection for CRLM in 2019 affirmed these outcomes. Conclusion: Case-mix adjustment is a prerequisite to allow for institutional comparison of short-term postoperative outcomes after liver resection for CRLM. (C) 2020 University Medical Center Groningen. Published by Elsevier Ltd