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Introduction: Immunotherapy has been established as the standard treatment option for patients with advanced hepatocellular carcinoma (aHCC). Despite the increased efficacy, disease progression occurs in a relevant proportion of patients even after an objective response. Combination concepts with locoregional therapy are currently under investigation for hepatic disease but are also in discussion for the control of distant metastasis. Radiotherapy is a highly effective treatment modality for local tumor control. It is also thought to increase the efficacy of checkpoint inhibition and sensitize distant lesions to the effects of immunotherapy, but may potentially increase adverse effects. In our center, few patients with aHCC treated with immune checkpoint inhibitors (ICIs) received concomitant radiotherapy for symptom or disease control. The aim of this study was to retrospectively analyze adverse effects and efficacy of concomitant radiotherapy in patients with aHCC treated with checkpoint inhibition., Methods: To this aim, patients who received a combination of ICI and radiotherapy in our institution were retrospectively considered for analysis. The predefined inclusion criterion was radiotherapy after initiated checkpoint inhibition and continuation of ICI therapy for at least 8 weeks. Adverse effects and efficacy measurements were performed according to local standards., Results: The database search of 2016-2021 revealed six consecutive patients fulfilling the predefined criteria for concomitant ICI and radiotherapy. Three patients received high-dose-rate brachytherapy (15 Gy) to treat progredient hepatic lesions. Two patients received stereotactic body radiotherapy (SBRT) (25-30 Gy) for symptom control, and 1 patient received brachytherapy and SBRT to treat metastases. No severe adverse events were reported in the period (<6 months) after concomitant radiotherapy. In 5 out of 6 cases, long-term tumor control could be achieved by this therapeutic combination., Conclusion: A good efficacy of concomitant radiotherapy and checkpoint inhibition has been achieved with no safety concerns. Further investigations should evaluate the safety, appropriate clinical context, and efficacy of this promising approach., (© 2023 S. Karger AG, Basel.)

Background: Pain after paediatric appendectomy and tonsillectomy is often undertreated. Benchmarking of hospitals could reveal which measures are associated with improved patient- or parent-reported pain-related outcomes., Methods: A total of 898 anonymised cases from 11 European hospitals participating in PAIN OUT infant were analysed. The children completed a questionnaire on patient-reported outcomes (PROs) 24 h after surgery. According to a composite PRO measure, including pain intensity and pain-related interference, hospitals were allocated to Group I (favourable results), II (average results), and III (unfavourable results). Benchmarking of hospital groups was performed investigating process variables (dosing of non-opioid analgesics, opioids, and dexamethasone) associated with PROs, side-effects, and children's perception of care. Variables associated with PROs were analysed using multinomial regression analysis with the PRO score-related hospital group as a dependent variable (estimated odds ratios [OR], 95% confidence interval [CI])., Results: During the first 24 h after surgery, 1.2 (1.1-1.3) full daily doses of non-opioid analgesics (non-steroidal anti-inflammatory drug [NSAID], paracetamol, metamizole) were administered in group I and 0.7 (0.6-0.8) in group III (P<0.001). Intraoperative dexamethasone was administered to 70.1 and 52.6% of the children in Group I and Group III, respectively (P<0.001). A lower number of full daily doses of non-opioid analgesics: 0.22 [0.15-0.31]), less dexamethasone (0.49 [0.33-0.71]), fewer non-opioid analgesics before the end of surgery (0.37 [0.22-0.62]) and higher opioid doses were associated with hospital allocation to group III vs group I (Nagelkerke's R 2 =0.433)., Conclusions: The results indicated substantial deficits in the concept, application, and dosing of analgesics in paediatric patients after surgery. Timely administration of adequate analgesic doses can easily be introduced into daily clinical practice., Clinical Trial Registration: clinicaltrials.gov NCT02083835., (Copyright © 2022 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Insufficiently treated pain after paediatric appendectomy and tonsillectomy is frequent. We aimed to identify variables associated with poor patient-reported outcomes., Methods: This analysis derives from the European PAIN OUT infant registry providing information on perioperative pharmacological data and patient-reported outcomes 24 h after surgery. Variables associated with the endpoint 'desire for more pain treatment' were evaluated by elastic net regularisation (odds ratio [95% confidence interval])., Results: Data from children undergoing appendectomy (n=472) and tonsillectomy (n=466) between 2015 and 2019 were analysed. Some 24.8% (appendectomy) and 20.2% (tonsillectomy) wished they had received more pain treatment in the 24 h after surgery. They reported higher composite pain scores (5.2 [4.8-5.5] vs 3.6 [3.5-3.8]), more pain-related interference, and more adverse events than children not desiring more pain treatment, and they received more opioids after surgery (morphine equivalents (81 [60-102] vs 50 [43-56] μg kg -1 ). Regression analysis revealed that pain-related sleep disturbance (appendectomy odds ratio: 2.8 [1.7-4.6], tonsillectomy 3.7 [2.1-6.5]; P<0.001) and higher pain intensities (1.5-fold increase) increased the probability of desiring more pain treatment. There was an inverse association between the number of different classes of non-opioids administered preventively, and the desire for more analgesics postoperatively. Children not receiving any non-opioid analgesics before the end of a tonsillectomy had a 3.5-fold (2.1-6.5-fold) increase in the probability of desiring more pain treatment, compared with children receiving at least two classes of different non-opioid analgesics., Conclusions: Preventive administration of at least two classes of non-opioid analgesics is a simple strategy and may improve patient-reported outcomes., Competing Interests: Declarations of interest UMS received honoraria and reimbursement for travel costs from Syntetica and Grünenthal. WM received honoraria from Bionorica, BioQPharm, Böhringer, Grünenthal, Kyowa, Mundipharma, Northern-Swan, Sanofi, TAD, and Tilray. The other authors declare that they have no conflicts of interest., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Human telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of telomerase and is located on chromosome 5p15, a genomic region which was found to be associated with multiple cancer types. But no associations with colorectal cancer (CRC) have been reported until recently. Therefore, the purpose of this study was to investigate the influence of seven single-nucleotide polymorphisms (SNPs) of TERT on susceptibility to colorectal polyps and CRC. The study population of our ongoing colorectal cancer study of Austria (CORSA) comprised 3,842 Caucasian participants. A total of 3,264 participants was genotyped including 142 CRC cases, 492 high-risk polyps, 837 low-risk polyps, and 1,793 polyp-free controls verified by colonoscopy. Genotyping was performed by TaqMan assay using genomic DNA. The impact of each SNP was estimated by multiple logistic regression analyses performed with R Version 2.11.1. None of the investigated TERT SNPs (rs2736122, rs2853676, rs2735940, rs2736098, rs2075786, rs2736100, rs4975605) were found to be associated with risk of CRC nor colonic polyps. However, the haplotype CGTATGG was associated with a significantly increased risk of high-risk polyps (OR = 1.48, 95% CI 1.01-2.17, P = 0.043). In accordance with other studies our results suggest no major influence of the investigated TERT SNPs on CRC and colorectal polyp risk. However, relevance of telomerase in tumorigenesis of multiple malignancies demands further investigations of the 5p15 locus concerning CRC susceptibility., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: X-ray repair cross complementation group 1 (XRCC1) plays a key role in base excision repair. The purpose of this study was to examine the association of two genetic polymorphisms in XRCC1 (rs1799782 and rs25487) with risk of colorectal polyps and colorectal cancer (CRC)., Methods: In the ongoing colorectal cancer study of Austria (CORSA), a total of 3091 Caucasian participants was genotyped using 5'-nuclease TaqMan assays. Multiple logistic regression was applied to compare individuals of the control group against three different case groups namely CRC cases, high-risk and low-risk polyps., Results: The two investigated SNPs in XRCC1 were not found to be associated with neither CRC risk nor polyp risk. Comparing the CRC cases versus the controls the OR was 0.60 (95%CI 0.27-1.31) for the heterozygous polymorphic genotype of SNP rs1799782 and 1.47 (95%CI 0.81-2.65) for the homozygous polymorphic genotype of SNP rs25487. Comparing the high-risk polyp group versus the controls the OR was 2.64 (95%CI 0.61-11.42) for the homozygous polymorphic genotype of SNP rs1799782 and 0.89 (95%CI 0.60-1.33) for SNP rs25487, respectively. In an haplotype analysis also no statistically significant association was found., Conclusion: Our finding that none of the two investigated SNPs of XRCC1 were significantly associated with risk of CRC or polyps is consistent with the results of a recently published meta-analysis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)