Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial

Objective: To present short-term outcomes of liver surgery in patients with initially unresectable colorectal liver metastases (CRLM) downsized by chemotherapy plus targeted agents. Background: The increase of complex hepatic resections of CRLM, technical innovations pushing boundaries of respectability, and use of intensified induction systemic regimens warrant for safety data in a homogeneous multicenter prospective cohort. Methods: Patients with initially unresectable CRLM, who underwent complete resection after induction systemic regimens with doublet or triplet chemotherapy, both plus targeted therapy, were selected from the ongoing phase III CAIRO5 study (NCT02162563). Short-term outcomes and risk factors for severe postoperative morbidity (Clavien Dindo grade ≥ 3) were analyzed using logistic regression analysis. Results: A total of 173 patients underwent resection of CRLM after induction systemic therapy. The median number of metastases was 9 and 161 (93%) patients had bilobar disease. Thirty-six (20.8%) 2-stage resections and 88 (51%) major resections (>3 liver segments) were performed. Severe postoperative morbidity and 90-day mortality was 15.6% and 2.9%, respectively. After multivariable analysis, blood transfusion (odds ratio [OR] 2.9 [95% confidence interval (CI) 1.1-6.4], P = 0.03), major resection (OR 2.9 [95% CI 1.1-7.5], P = 0.03), and triplet chemotherapy (OR 2.6 [95% CI 1.1-7.5], P = 0.03) were independently correlated with severe postoperative complications. No association was found between number of cycles of systemic therapy and severe complications (r = -0.038, P = 0.31). Conclusion: In patients with initially unresectable CRLM undergoing modern induction systemic therapy and extensive liver surgery, severe postoperative morbidity and 90-day mortality were 15.6% and 2.7%, respectively. Triplet chemotherapy, blood transfusion, and major resections were associated with severe postoperative morbidity

From publishers to self-publishing: disruptive effects in the book industry

This paper explores the structure of the book publishing industry post digitalisation, analysing the choices of the publishers and authors. The introduction of successful e-book readers has belatedly given digitalisation the characteristics of a disruptive technology by making self-publishing a serious option for authors. This has been supported by the entry of new types of intermediaries and the strengthening of others. These changes have reduced the general requirements for an author to get a book self-published. As a result, a larger share of the surplus from the book industry is likely to go to authors, explaining the significant increase in the supply of books. The potential oversupply of books has created a new problem by increasing competition and making consumer searches more difficult. We argue that digitalisation has shifted the potential for market failure from an inadequate supply of books to asymmetric information about quality. It remains to be seen whether the market will provide appropriate intermediaries to solve the asymmetric information problem