Bone Cement as a Local Chemotherapeutic Drug Delivery Carrier in Orthopedic Oncology: A Review

Metastatic bone lesions are common among patients with advanced cancers. While chemotherapy and radiotherapy may be prescribed immediately after diagnosis, the majority of severe metastatic bone lesions are treated by reconstructive surgery, which, in some cases, is followed by postoperative radiotherapy or chemotherapy. However, despite recent advancements in orthopedic surgery, patients undergoing reconstruction still have the risk of developing severe complications such as tumor recurrence and reconstruction failure. This has led to the introduction and evaluation of poly (methyl methacrylate) and inorganic bone cements as local carriers for chemotherapeutic drugs (usually, antineoplastic drugs (ANPDs)). The present work is a critical review of the literature on the potential use of these cements in orthopedic oncology. While several studies have demonstrated the benefits of providing high local drug concentrations while minimizing systemic side effects, only six studies have been conducted to assess the local toxic effect of these drug-loaded cements and they all reported negative effects on healthy bone structure. These findings do not close the door on chemotherapeutic bone cements; rather, they should assist in materials selection when designing future materials for the treatment of metastatic bone disease

Injectable Glass Polyalkenoate Cements: Evaluation of their Rheological and Mechanical Properties with and Without the Incorporation of Lidocaine Hydrochloride

Lidocaine hydrochloride is used as an anesthetic in many clinical applications. This short communication investigates the effect of complete substitution of lidocaine hydrochloride for deionized (DI) water on the physico-chemical properties of two novel glass polyalkenoate cements. Substituting DI water with lidocaine hydrochloride resulted in cements with shorter working times but comparable setting times and mechanical properties. Fourier transform infrared spectroscopy confirmed that the setting reaction in cements containing DI water and lidocaine hydrochloride was completed within 24 h, post cement preparation and maturation. Further, it was explained that lidocaine hydrochloride binds to poly(acrylic) acid (PAA) due to electrostatic forces between the positively charged amino group of lidocaine hydrochloride and the carboxylic group of the PAA, resulting in a compact poly-complex precipitate

Effect of skin tone on the accuracy of the estimation of arterial oxygen saturation by pulse oximetry: a systematic review

BACKGROUND: Pulse oximetry-derived oxygen saturation (SpO2) is an estimate of true arterial oxygen saturation (SaO2). The aim of this review was to evaluate available evidence determining the effect of skin tone on the ability of pulse oximeters to accurately estimate SaO2. METHODS: Published literature was screened to identify clinical and non-clinical studies enrolling adults and children when SpO2 was compared with a paired co-oximetry SaO2 value. We searched literature databases from their inception to March 20, 2023. Risk of bias (RoB) was assessed using the QUADAS-2 tool. Certainty of assessment was evaluated using the GRADE tool. RESULTS: Forty-four studies were selected reporting on at least 222 644 participants (6121 of whom were children) and 733 722 paired SpO2-SaO2 measurements. Methodologies included laboratory studies, prospective clinical, and retrospective clinical studies. A high RoB was detected in 64% of studies and there was considerable heterogeneity in study design, data analysis, and reporting metrics. Only 11 (25%) studies measured skin tone in 2353 (1.1%) participants; the remainder reported participant ethnicity: 68 930 (31.0%) participants were of non-White ethnicity or had non-light skin tones. The majority of studies reported overestimation of SaO2 by pulse oximetry in participants with darker skin tones or from ethnicities assumed to have darker skin tones. Several studies reported no inaccuracy related to skin tone. Meta-analysis of the data was not possible. CONCLUSIONS: Pulse oximetry can overestimate true SaO2 in people with darker skin tones. The clinical relevance of this bias remains unclear, but its magnitude is likely to be greater when SaO2 is lower. SYSTEMATIC REVIEW PROTOCOL: International Prospective Register of Systematic Reviews (PROSPERO): CRD42023390723

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013–2022: Data from the European Registry on H. pylori Management (Hp-EuReg)

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the “most important” variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013–2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin–clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth–quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin–amoxicillin–metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year

The role of statins on helicobacter pylori eradication: Results from the european registry on the management of h. pylori (hp-eureg)

Statins could increase the effectiveness of Helicobacter pylori eradication therapies due to their anti-inflammatory effect. The aim of this study was to analyze the impact of this therapeutic association in real life. This is a multicenter, prospective, non-interventional study aimed at evaluating the management of H. pylori by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap from 2013 to 2020. The association between statin use and H. pylori eradication effectiveness was evaluated through multivariate analysis. Overall, 9988 and 705 patients received empirical and culture-guided treatment, respectively. Overall, statin use was associated with higher effectiveness in the empirical group (OR = 1.3; 95%CI = 1.1-1.5), but no association was found with first-line treatment effectiveness (N = 7738); as an exception, statin use was specifically associated with lower effectiveness of standard triple therapy (OR = 0.76; 95%CI = 0.59-0.99). In the rescue therapy empirical group (N = 2228), statins were associated with higher overall effectiveness (OR = 1.9; 95%CI = 1.4-2.6). However, sub-analyses by treatment schemes only confirmed this association for the single-capsule bismuth quadruple therapy (OR = 2.8; 95%CI = 1.3-5.7). No consistent association was found between statin use and H. pylori therapy effectiveness. Therefore, the addition of statins to the usual H. pylori treatment cannot be currently recommended to improve cure rates. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas

Background: Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy. Methods: Tumour biopsies from patients (n=14) with TNM stage IB–IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations. Results: We identified 520 genes with differential expression (Mann–Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin. Conclusions: In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma

Erratum: Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas

Correction to: Corrigendum: British Journal of Cancer (2015) 113, 1641–1641. doi:10.1038/bjc.2015.391; published online 1 December 2015 Upon publication of the above corrigendum in the British Journal of Cancer, the authors noted that author KM Matula had been placed in the incorrect position on the author listing. The publishers would like to apologise for this mistake. The full and correct author listing is reproduced above