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Background: Long bones are commonly affected by musculoskeletal tumors, but they also represent one of the most frequent locations for metastases. The treatment is based on pain management and the prevention or stabilization of pathological fractures by intramedullary nailing. While titanium nails are probably the most used, carbon-fiber-reinforced (CFR) nails have emerged as a new option for oncological patients. The aim of this review is to compare titanium and CFR nails according to current findings. Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards were followed: a total of 1004 articles were identified and 10 were included. Results: Traditionally, titanium implants are highly valued for their optimal biomechanical properties and ease of insertion, facilitated by their radiopacity. However, the use of titanium poses challenges in radiotherapy due to interference with radiation dosage and the creation of ferromagnetic artifacts. Conversely, CFR implants have emerged as a recommended option for intramedullary fixation, due to their biomechanical and structural properties and their benefits during radiotherapy and follow-up monitoring X-ray. Conclusions: CFR nailing represents a promising advancement in the surgical management of oncological patients with long bone metastases. However, further studies are needed to increase surgeons' confidence in their use. [ABSTRACT FROM AUTHOR]

Background: Megaprostheses were first employed in oncological orthopedic surgery, but more recently, additional applications have arisen. These implants are not without any risks and device failure is quite frequent. The most feared complication is undoubtedly the implants' infection; however, the exact incidence is still unknown. This systematic review aims to estimate in the current literature the overall incidence of megaprosthesis infections and to investigate possible risk/protective factors. Methods: We conducted a systematic search for studies published from July 1971 to December 2023 using specific keywords. To be included, studies needed to report either the megaprosthesis anatomical site, and/or whether the megaprosthesis was coated, and/or the surgical indication as oncological or non-oncological reasons. Results: The initial literature search resulted in 1281 studies. We evaluated 10,456 patients and the overall infection rate was 12%. In cancer patients, the infection rate was 22%, while in non-oncological patients, this was 16% (trauma 12%, mechanical failure 17%, prosthetic joint infections 26%). The overall infection rates comparing coated and uncoated implants were 10% and 12.5%, respectively. Conclusions: The number of megaprosthesis implants is increasing considerably. In traumatological patients, the infection rate is lower compared to all the other subgroups, while the infection rate remains higher in the cancer patient group. As these devices become more common, focused studies exploring epidemiological data, clinical outcomes, and long-term complications are needed to address the uncertainties in prevention and management. [ABSTRACT FROM AUTHOR]

Background: Post-radiation fractures are a significant complication of cancer treatment, often being challenging to manage and impacting patients' quality of life. This study systematically reviews the literature on fractures in irradiated bones, focusing on risk factors, treatment modalities, and prevention strategies. Factors increasing fracture risk include exposure to high doses of radiation of at least 50 Gy, female gender, menopausal age, and periosteal stripping. Additionally further risk factors are the size of the original tumor and osteoporosis. Methods: A search of PubMed yielded 541 articles, with 4 were ultimately included in the review. These retrospective studies focused on patients undergoing Combined Limb-Sparing Surgery and Radiation Therapy for soft tissue sarcoma. Results: Results show post-radiation fractures affect approximately 4% of patients, with the femur being the most frequently affected site. Intramedullary nailing emerges as the gold standard treatment, with prosthetic replacement or megaprostheses used in the metaepiphyseal region and as salvage procedures. Non-union and infection remain formidable complications. Conclusions: This study highlights the importance of prophylactic nailing in fracture prevention and the efficacy of free vascularized fibular flaps to achieve bone union during revision surgeries. Limited case availability and patient follow-up hinder comprehensive studies, impacting treatment outcomes. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Oncology titled "Angiogenesis and access to vasculature as a target in gastrointestinal tumors and predictive biomarkers identification: an open challenge." The editorial discusses the importance of tumor angiogenesis in gastrointestinal cancers and the need for predictive biomarkers to improve patient selection for anti-angiogenic treatments. It highlights the current lack of validated clinical/translational predictive factors and the ongoing research efforts to identify reliable markers. The editorial also provides a summary of the articles included in the research topic, which cover topics such as the role of insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) in gastric cancer, the involvement of angiogenins in tumor angiogenesis, the crosstalk between innate immunity and endothelial cells in tumor angiogenesis regulation, and the potential of anti-angiogenic treatment combined with immunotherapy in colorectal and gastric cancer patients. The authors express their gratitude to the contributing authors and emphasize the importance of further investigation in this field to identify new therapeutic targets and predictive factors for anti-angiogenic treatment response. [Extracted from the article]

Introduction: Breast cancer is the most diagnosed tumor and a leading cause of cancer death in women worldwide. Taxanes are the most used chemotherapeutic agents and are strictly connected to neurotoxicity. Taxane-induced neuropathy (TIN) significantly impacts patients’ quality of life (QOL). Early identification and management of TIN could improve preventive strategies to preserve patients’ QOL during and after breast cancer treatment. Objective: This prospective, observational study aimed to evaluate the taxane-induced neuropathy (TIN) in early breast cancer patients treated with weekly paclitaxel at an earlier stage and identify any correlation between TIN and QOL. Methods: Data from stage I-III breast cancer patients treated with taxane-based therapy between 2018 and 2022 were collected at the Medical Oncology Unit of the University Hospital of Cagliari. Peripheral neuropathy was evaluated using the NCI-CTCAE scale (National Cancer Institute, Common Terminology Criteria for Adverse Events) at every drug administration. In contrast, QOL was assessed using EORTC QLC-CIPN20 and FACT-Taxane questionnaire at baseline (T0), after 4 weeks (T1) and 12 (T2) weeks of treatment. Statistical analysis was performed to evaluate the correlation between neurotoxicity and QOL. Results: Neurotoxicity incidence peaked at the third, fourth, and sixth week of treatment, with patients reporting grade 1 and 2 neurotoxicity. Simultaneously with increasing doses of paclitaxel, significant differences in QOL were observed in early treatment cycles relating to TIN presentation. Patients with higher neurotoxicity grades reported lower QOL scores. Conclusions: Despite the absence of effective treatments to prevent paclitaxel-induced neurotoxicity, symptoms are managed through dosage reduction, delay, or treatment interruption. Future research should focus on identifying neuroprotective measures to avoid an irreversible decline in the quality of life for breast cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Managing distal humeral fractures can be challenging for orthopedic surgeons. There are several treatment options for managing this type of fracture, and the treatment method for these fractures should be based on patient-related factors. In elderly patients with osteoporotic bone and severe comminution of the fracture, adequate fixation can be a major challenge for surgeons. The use of megaprosthesis has been recently proposed in traumatology as an alternative to osteosynthesis or conventional prosthesis for the management of comminuted articular fractures in elderly patients with poor bone stock. Methods: A consecutive case series of 5 patients who underwent reconstruction of the elbow joint with a trabecular hinged modular elbow megaprosthesis was reviewed retrospectively. All patients included had AO/OTA 13C2 and 13C3 fractures with metaphyseal extension and considerable bone loss of the distal humerus. The primary outcome was the evaluation of functional and clinical outcomes with the MEPS score in comminuted distal humerus fractures with metaphyseal extension and poor bone stock in elderly patients treated with elbow megaprosthesis. The secondary outcome was assessing the treatment-related complication rate of this technique in non-oncological fields. Results: Five patients were included in the study with a mean age of 82.66 ± 7.72 years at surgery. The mean MEPS value was 63 ± 24.2 at 1 month, 81 ± 23.53 at 3 months, 83 ± 24.2 at 6 months, and 84 ± 24.57 at 12 months. No intraoperative complications were recorded in our series. Of 5 patients, four patients had excellent clinical and functional outcomes. We did not encounter wound dehiscence, prosthetic joint infection, aseptic loosening, or periprosthetic fractures. Conclusions: The indication for this type of treatment must be selected and narrowed down, as it is a salvage procedure, and any failure would cause even more complex situations. Short operating times and early mobilization of the elbow are the advantages of this technique. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic joint infection (PJI) is a devastating complication that develops after total joint arthroplasty (TJA), whose incidence is expected to increase over the years. Traditionally, surgical treatment of PJI has been based on algorithms, where early infections are preferably treated with debridement, antibiotics, and implant retention (DAIR) and late infections with two-stage revision surgery. Two-stage revision is considered the "gold standard" for treatment of chronic prosthetic joint infection (PJI) as it enables local delivery of antibiotics, maintenance of limb-length and mobility, and easier reimplantation. Many studies have attempted to identify potential predicting factors for early diagnosis of PJI, but its management remains challenging. In this observational retrospective study, we investigated the potential role of inflammatory blood markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)) as prognostic factors in two-stage exchange arthroplasty for PJI. Methods: A single-center retrospective analysis was conducted, collecting clinical data and laboratory parameters from patients submitted to prosthetic explantation (EP) for chronic PJI. Laboratory parameters (PCR, NLR, MLR, PLR, SIRI, SII, and AISI) were evaluated at the explantation time; at 4, 6, and 8 weeks after surgery; and at reimplantation time. The correlation between laboratory parameters and surgery success was evaluated and defined as infection absence/resolution at the last follow-up. Results: A total of 57 patients with PJI were evaluated (62% males; average age 70 years, SD 12.14). Fifty-three patients with chronic PJI were included. Nine patients underwent DAIR revision surgery and chronic suppressive therapy; two patients died. Nineteen patients completed the two-stage revision process (prosthetic removal, spacer placement, and subsequent replanting). Among them, none showed signs of reinfection or persistence of infection at the last available follow-up. The other twenty-three patients did not replant due to persistent infection: among them, some (the most) underwent spacer retention; others (fewer in number) were submitted to resection arthroplasty and arthrodesis (Girdlestone technique) or chronic suppressive antibiotic therapy; the remaining were, over time, lost to follow-up. Of the patients who concluded the two-stage revision, the ones with high SIRI values (mean 3.08 SD 1.7 and p-value 0.04) and MLR values (mean 0.4 SD 0.2 and p-value 0.02) at the explantation time were associated with a higher probability of infection resolution. Moreover, higher variation in the SIRI and PCR, also defined, respectively, as delta-SIRI (mean −2.3 SD 1.8 and p-value 0.03) and delta-PCR (mean −46 SD 35.7 and p-value 0.03), were associated with favorable outcomes. Conclusions: The results of our study suggest that, in patients with PJI undergoing EP, the SIRI and MLR values and delta-SIRI and delta-PCR values could be predictive of a favorable outcome. The evaluation of these laboratory indices, especially their determination at 4 weeks after removal, could therefore help to determine which patients could be successfully replanted and to identify the best time to replant. More studies analyzing a wider cohort of patients with chronic PJI are needed to validate the promising results of this study. [ABSTRACT FROM AUTHOR]

Simple Summary: CD44 is a crucial factor in colorectal cancer, with specific isoforms demonstrating their significance in the development, progression, metastasis, and resistance to therapy. Given the clinical and pathological impact of CD44, it represents a promising molecular target for cancer therapy. In this review, we aim to highlight the predictive and prognostic significance of CD44 in various cancer types, with a particular focus on colorectal cancer. Moreover, we evaluate current therapeutic interventions that target CD44 or reduce its expression, thereby highlighting its potential as an effective therapeutic strategy. Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial–mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, we aim to analyze the molecular bases of angiogenesis in metastatic colorectal cancer (mCRC) and to provide an overview of potential predictive factors for treatment response to anti-angiogenic drugs in mCRC patients. We based our research on literature data focusing on circulating, tissue, and imaging biomarkers that can potentially be used to predict tumour response to anti-angiogenic inhibitors. In this perspective, biological factors and functional imaging seem very promising approaches and further research in these fields will provide clinicians with useful tools to improve patient selection and outcomes. Colorectal cancer (CRC) is a leading tumor worldwide. In CRC, the angiogenic pathway plays a crucial role in cancer development and the process of metastasis. Thus, anti-angiogenic drugs represent a milestone for metastatic CRC (mCRC) treatment and lead to significant improvement of clinical outcomes. Nevertheless, not all patients respond to treatment and some develop resistance. Therefore, the identification of predictive factors able to predict response to angiogenesis pathway blockade is required in order to identify the best candidates to receive these agents. Unfortunately, no predictive biomarkers have been prospectively validated to date. Over the years, research has focused on biologic factors such as genetic polymorphisms, circulating biomarkers, circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and microRNA. Moreover, research efforts have evaluated the potential correlation of molecular biomarkers with imaging techniques used for tumor assessment as well as the application of imaging tools in clinical practice. In addition to functional imaging, radiomics, a relatively newer technique, shows real promise in the setting of correlating molecular medicine to radiological phenotypes. [ABSTRACT FROM AUTHOR]

Immunotherapies have revolutionized cancer treatment approaches. Because not all patients respond positively to immune therapeutic agents, it represents a challenge for scientists who strive to understand the mechanisms behind such resistance. In-depth exploration of tumor biology, using novel technologies such as omics science, can help decode the role of the tumor immune microenvironment (TIME) in producing a response to the immune blockade strategies. It can also help to identify biomarkers for patient stratification and personalized treatment. This review aims to explore these new models and highlight their possible pivotal role in changing clinical practice. [ABSTRACT FROM AUTHOR]

Background: Ankle arthroscopy is indicated for both diagnosis and treatment of a large spectrum of common ankle disorders. It has certain advantages over the open procedure; however, it is important to recognize that there are some complications associated with it. Infections after this procedure are quite uncommon, with an overall estimated incidence of 2%. Given the low incidence of infections after ankle arthroscopy, not a great deal of literature on the topic has been published. The present review aims to provide an overview of the incidence, diagnosis, and treatment of infections after ankle arthroscopy. Methods: A systematic review of the literature indexed in the PubMed, MEDLINE, and Cochrane Library databases using search term "ankle arthroscopy infections" was performed in November 2023. No restrictions were applied concerning the date of publication. The Preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. Among all surgical operations for the treatment of ankle and foot pathologies, we included articles with a described superficial or deep infection after ankle arthroscopy. Results: The search resulted in 201 studies. Only 21 studies met our inclusion criteria, and they were included in this systematic review. We evaluated 1706 patients who underwent 1720 arthroscopic tibiotalar procedures at an average age of 42 years old. Out of the 1720 procedures, 41 (2%) were complicated by infection. We divided infectious complications into superficial (68%; 28/41) and deep (32%; 13/41) infections. The most common pathogen isolated was Staphylococcus aureus. Arthroscopic arthrodesis was found to be the most affected by deep infections. Conclusions: Infection after ankle arthroscopy is an uncommon complication. Superficial infections were successfully treated with antibiotics, while surgical debridement, arthroscopic drainage, and intravenous antibiotics were necessary in cases of deep infections. Considering the amount of information on pathogens associated with knee and shoulder infections, there is still a lack of literature on pathogens associated with ankle infections, which makes their management difficulty. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of scaphoid fracture sequelae is still an unsolved problem in hand surgery. Custom-made 3D-printed titanium partial and total scaphoid prosthesis and scaphoid interosseous ligament reconstruction (SLIL) are performed in cases of non-union and isolated aseptic necrosis of the proximal scaphoid pole and when it is impossible to save the scaphoid bone, respectively. This study aims to evaluate the clinical, functional and radiographic results after these two prosthesis implantations. Methods: Between January 2019 and July 2020, nine partial and ten total scaphoid prostheses were implanted using custom-made 3D-printed titanium implants. Evaluation criteria included carpal height ratio (CHR), radioscaphoid angle, wrist extension and flexion, radial deviation and ulnar deviation of the wrist, grip strength and pinch strength, Visual Analogue Scale (VAS), the Disabilities of Arm, Shoulder, and Hand (DASH) score, and the Patient-Rated Wrist Evaluation (PRWE). Results: Clinical, functional, and radiographic improvements were found in all outcomes analyzed for both patient groups. The VAS pain scale obtained the most remarkable improvement at the one-year follow-up. The results of the DASH scores and the PRWE were good, with a great rate of patient satisfaction at the end of the follow-up. SLIL reconstruction also provided excellent stability and prevented a mid-carpal bone collapse in the short- and medium-term follow-up. Conclusions: A custom-made 3D-printed titanium partial or total scaphoid prosthesis is a viable solution for patients with scaphoid non-union and necrosis or complete scaphoid destruction in whom previous conservative or surgical treatment has failed. [ABSTRACT FROM AUTHOR]

Background and aim: Cancers are one of the most frequent causes of death and disability in humans. Skeletal involvement has a major impact on the quality of life and prognosis of cancer patients. Electrochemotherapy is a palliative and minimally invasive oncologic treatment that was first used to treat subcutaneous nodules for malignant tumors. The aim of our review is to evaluate the results of electrochemotherapy in the treatment of bone metastases. Methods: A systematic review of the literature indexed in the PubMed MEDLINE and Cochrane Library databases using the search key words "electrochemotherapy" AND ("metastasis" OR "metastases") was performed. The Preferred Reporting Items for Systematic Reviews and MetaAnalyses was followed. Inclusion criteria were proven involvement of the appendicular skeleton in metastatic carcinoma or melanoma, through at least one percutaneous electrochemotherapy session on the metastatic bone lesion. The exclusion criterion was no skeletal metastatic involvement. Results: Eight articles were finally included. We reached a population of 246 patients. The mean age and follow up were 60.1 years old and 11.4 months, respectively. The most represented primary tumor was breast cancer (18.9%). A total of 250 bone lesions were treated with electrochemotherapy. According to RECIST criteria, in our population we observed 55.5% stable diseases. The mean pre-electrochemotherapy VAS value was 6.9, which lowered to 2.7 after treatment. Adverse events occurred in 3.4% of patients. Conclusions: Electrochemotherapy as a minimally invasive and tissue-sparing treatment should be considered for patients with no other alternative to obtain tumor control and improvement in quality of life. [ABSTRACT FROM AUTHOR]

(1) Background: Some of the goals of orthopedic surgical oncology are saving limbs and function. The humerus is the third most frequent site in primary tumors and one of the most involved sites for metastases. Prosthetic replacement with modular megaprosthesis is one of the treatment choices, but there are several types of complications, such as problems with function and pain. The aim of our study is to assess functional outcomes and shoulder instability in the reconstruction of proximal humerus metastases. (2) Methods: This is a retrospective observational study. Twenty-eight patients, with proximal humerus metastases, admitted to the department of Orthopaedics and Traumatology of our University Hospital between 2014 and 2022 were recruited. Each patient underwent resection and prosthetic replacement surgery with modular megaprosthesis. Clinical evaluation was assessed through MSTS score, WOSI index, and DASH score. (3) Results: Twenty patients were included in the study. Fairly good results, especially regarding pain, function, and emotional acceptance, were obtained in all three tests: DASH, MSTS, and WOSI. Patients who reported shoulder instability actually have worse outcomes than those who report having stable shoulders. In addition, patients with a resection >10 cm have worse outcomes than those who had a resection of 10 cm. No significant differences were found between the deltopectoral approach group and the lateral approach group. (4) Conclusions: Reconstructive surgery with megaprosthesis of the proximal humerus in patients with metastases can be considered a treatment option, especially in patients with pathological fractures or injuries with a high risk of fracture and good life expectancy. This study shows how this type of surgery affects instability, but in terms of functionality, pain, and patient satisfaction, it gives satisfactory results. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) showed efficacy in metastatic colorectal cancer (mCRC) with mismatch-repair deficiency or high microsatellite instability (dMMR-MSI-H). Unfortunately, a patient's subgroup did not benefit from immunotherapy. Caudal-related homeobox transcription factor 2 (CDX-2) would seem to influence immunotherapy's sensitivity, promoting the chemokine (C-X-C motif) ligand 14 (CXCL14) expression. Therefore, we investigated CDX-2 role as a prognostic-predictive marker in patients with mCRC MSI-H. We retrospectively collected data from 14 MSI-H mCRC patients treated with ICIs between 2019 and 2021. The primary endpoint was the 12-month progression-free-survival (PFS) rate. The secondary endpoints were overall survival (OS), PFS, objective response rate (ORR), and disease control rate (DCR). The PFS rate at 12 months was 81% in CDX-2 positive patients vs 0% in CDX-2 negative patients (p = 0.0011). The median PFS was not reached (NR) in the CDX-2 positive group versus 2.07 months (95%CI 2.07–10.8) in CDX-2 negative patients (p = 0.0011). Median OS was NR in CDX-2-positive patients versus 2.17 months (95% Confidence Interval [CI] 2.17–18.7) in CDX2-negative patients (p = 0.026). All CDX-2-positive patients achieved a disease response, one of them a complete response. Among CDX-2-negative patients, one achieved stable disease, while the other progressed rapidly (ORR: 100% vs 0%, p = 0.0005; DCR: 100% vs 50%, p = 0.02). Twelve patients received 1st-line pembrolizumab (11 CDX-2 positive and 1 CDX-2 negative) not reaching median PFS, while two patients (1 CDX-2 positive and 1 CDX-2 negative) received 3rd-line pembrolizumab reaching a median PFS of 10.8 months (95% CI, 10.8–12.1; p = 0.036). Although our study reports results on a small population, the prognostic role of CDX-2 in CRC seems confirmed and could drive a promising predictive role in defining the population more sensitive to immunotherapy treatment. Modulating the CDX-2/CXCL14 axis in CDX-2-negative patients could help overcome primary resistance to immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC). Methods: We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona. All patients underwent neoadjuvant chemoradiotherapy. The primary objective was major TRG while secondary objectives were pathological complete response, disease-free survival (DFS) and overall survival (OS). Results: One hundred sixty patients (148 pMMR and 12 dMMR) were included in the exploratory cohort and 158 (146 pMMR and 12 dMMR) were included in the validation cohort. A major TRG has been shown in 42.6% and 43.1% patients with pMMR in exploratory and validation cohort, respectively; while no major TRG have been shown in dMMR patients in both cohorts. Exploratory and validation cohorts showed a statistically significant higher mDFS in pMMR patients compared to dMMR: NR vs. 14 months and NR vs. 17 months, respectively. Conclusion: Our results indicated an association between dMMR and poor response to preoperative chemoradiotherapy and they represent a hypothesis-generating data for new neoadjuvant strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: In our study, we analyzed the role of CD44 expression as a prognostic marker in patients with metastatic colorectal cancer. CD44 is a multi-structural and multifunctional non-kinase transmembrane glycoprotein. Its expression is recognized as a molecular marker of cancer stem cells. Due to its role in the maintenance of stemness and the function of CSCs in tumor progression, CD44 could be an important prognostic marker. In our study, elevated CD44 expression correlated with more aggressive tumor behavior and poor prognostic features, suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients. Background: The transmembrane glycoprotein CD44, the major hyaluronan (HA) receptor, has been proven to regulate cell growth, survival, differentiation, and migration. It is therefore widely considered to be involved in carcinogenesis. Its role as a new therapeutic target in solid tumors is under evaluation in clinical trials. The prognostic value remains controversial. Here, we aimed to investigate the correlation between CD44 expression and the clinicopathological features and survival in metastatic colorectal cancer (mCRC) patients. Methods: Data from 65 mCRC patients of the Medical Oncology Unit, University Hospital and University of Cagliari were retrospectively collected from 2008 to 2021. Immunohistochemical analysis was performed at the Pathology Division, University Hospital of Cagliari on 3 μm thick sections obtained from paraffin blocks. The intensity of immunohistochemical staining was subclassified into four groups: score 0 if negative or weak membrane staining in less than 10% of tumor cells; score 1+ if weak membrane staining in at least 10% of tumor cells or moderate membrane staining in less than 10% of tumor cells; score 2+ if moderate membrane staining in at least 10% of tumor cells or intensive membrane staining in less than 10% of tumor cells; score 3+ if intense membrane staining in at least 10% of tumor cells. Based on this score, we distinguished patients into low CD44 expression (score 0, 1+, 2+) and high CD44 expression (score 3+). Statistical analysis was performed with MedCalc (survival distribution: Kaplan–Meier; survival comparison: log-rank test; association between categorical variables: Fisher's exact test). Results: Patients' median age was 66 years (range 49–85). Regarding CD44 expression, score was 0 in 18 patients, 1+ in 15 patients, 2+ in 18 patients, and 3+ in 14 patients. Median overall survival (mOS) was 28.1 months (95%CI: 21.3–101). CD44 overexpression (3+) was correlated with poor prognosis (p = 0.0011; HR = 0.2), with a mOS of 14.5 months (95%CI 11.7 to 35.9) versus 30.7 months (95%CI 27.8 to 101) in lower CD44 expression. Higher CD44 expression was associated with clinically poor prognostic features: age ≥ 70 years (p = 0.0166); inoperable disease (p = 0.0008); stage IV at diagnosis (p = 0.0241); BRAF mutated (p = 0.0111), high-grade tumor (p = 0.0084). Conclusions: CD44 markedly correlated with aggressive tumor behavior and contributed to the earlier progression of disease, thus suggesting its role as a novel prognostic marker and potential therapeutic target for mCRC patients. [ABSTRACT FROM AUTHOR]

Bone can be affected by different neoplastic conditions. Limb salvage surgery has become the preferred treatment strategy for most malignant tumors of the extremities. Advanced 3D printing technology has transformed the conventional view of oncological surgery. These types of implants are produced by electron beam melting (EBM) technology by sintering titanium powder in a scaffold shape designed following a project designed from HRCT and MRI. The aim of our study was to evaluate the outcomes and the mid-term follow-up of a population treated with 3D-printed custom-made prosthesis implantation in major oncological bone resection or after failure of primary implants. The primary outcome was the general patient satisfaction one year after surgery. The secondary outcomes were: mortality rate, treatment related complication rate, functional and clinical outcomes (KPS, ADL and IADL). Eight patients were included, five females and two males, with a mean age of 50.3 (±23.72) years at the surgery. The enrolled patients reported a mean satisfaction rate after surgery of 7.38 (±2) where 10 was the maximum value. There were no changes between pre- and postoperative mean KPS (81.43 +/−10.69). Mean preoperative ADL and IADL score was in both cases 4.86 (±1.07), while postoperative was 5 (±0.82), with a delta of 0.13 (p > 0.05). Custom-made prosthesis permits reconstructing bone defects caused by large tumor resection, especially in anatomically complex areas, restoring articular function. [ABSTRACT FROM AUTHOR]

Articular distal femur fractures represent 4% to 6% of femur fractures. Locking compression plates (LCPs) are the main treatment option. Nevertheless, a reoperation rate of 12.9% has been reported; nonunion is reported at 4.8%, delayed union at 1.6%, and malunion at 0.6%. Treatment of nonunions can be challenging as no unanimous consensus regarding the best surgical technique has been reached. The aim of this study was to evaluate and compare two types of revision surgery as treatment of LCP-treated articular distal femoral fracture nonunion: retrograde nail or replating. A retrospective cohort study of patients admitted from January 2015 to February 2017 for nonunion of AO/OTA 33C2 fractures previously treated with a lateral LCP was conducted. Patients were treated either with intramedullary nailing (Group A) or with replating (Group B). One independent observer performed clinically and radiographically followed up at 1, 3, 6, 9, 12, 24, and 36 months after surgery. The nonunion scoring system (NUSS) was used. Nine patients were included in our study. The mean follow-up was 2 years. Five patients were treated with intramedullary nailing and four with replating. The NUSS score was 24.2 ± 6.8 in the nailing group and 37.3 ± 3 in the replating group (P = 0.03). In the nailing group, radiographic consolidation was obtained in all cases. In the replating group, nonunion was found in 3 patients and failure of osteosynthesis in one patient. Therefore, four patients (Group B) underwent implant removal and retrograde femoral nailing, obtaining radiological healing. The union time was 7.6 months in the nailing group. Retrograde intramedullary nailing can be used as an effective treatment of aseptic AO-33C distal femoral nonunion following primary locking plating. [ABSTRACT FROM AUTHOR]

Background: Rechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently, the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population. Methods: CRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status. Results: A total of 26 patients were included in our analysis. In the global population, RR was 25.0%, median overall survival (mOS) was 5.0 months, and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months, HR: 0.26, p = 0.048); anti-EGFR free interval > 14 months and anti-EGFR free interval > 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months, HR: 0.27, p = 0.013 and not reached vs. 3.0 months, HR: 0.20, p = 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months, HR: 0.27, p = 0.013 and 13.0 vs. 5.0 months, HR: 0.20, p = 0.002). Previous lines >2 were correlated with improved mPFS (4.0 vs. 1.0 month, HR: 0.05, p = 0.041) and with improved mOS (7.0 vs. 1.0 month, HR: 0.045, p = 0.034). In a multiple logistic regression model, only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS. Conclusions: Liquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS, the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option. [ABSTRACT FROM AUTHOR]

DNA methylation alterations are early events during tumourigenesis, affecting genes involved in the crosstalk between cells and surroundings in colorectal cancer (CRC). Among these genes, GRIA4, Glutamate Ionotropic Receptor AMPA Type Subunit 4, displays hypermethylation in the promoter region, and is an early diagnostic biomarker. It is well known that methylation can also affect alternative transcription. The purpose of this study is to evaluate the expression, at transcript and protein level, of GRIA4 main isoforms (the canonical one and a short variant) in 23 CRC and matched normal samples, of which we previously verified the methylation status. We further predicted miRNA/transcript target interactions as a possible post-transcriptional regulation using bioinformatics tools. As expected, downregulation of both variants has been observed in tumours. Interestingly, in contrast to what observed at transcriptional level, the GluR4 protein short isoform displayed higher expression than the canonical one either in normal or tumoural tissues. This may be explained by miRNA specifically targeting the canonical isoform. Our study is the first one that shows the expression of both isoforms in colon tissues. To note, the evident expression of the short isoform suggests a functional role in intestinal cell biology. [ABSTRACT FROM AUTHOR]

Background: Deep periprosthetic infection after total hip arthroplasty (THA) is a serious and challenging complication for the orthopedic surgeon. Muscular flaps may represent a valid management option for the treatment of this condition. We present a systematic literature review about the use of muscular flaps for the treatment of hip prosthetic joint infection.Methods: The review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventy-seven articles, out of 279 titles, were considered eligible for the full-text analysis. Finally 15 studies that met inclusion criteria were included in this review.Results: Overall, 210 patients (49% males, 48.6% females and 2.4% not reported) suffering from THA infection treated with muscular flaps were collected. The mean age was 69.6 years. Mean follow-up, reported in all studies, was 3.3 years. The results presented by the different authors, highlight the effectiveness of muscular flaps for the treatment of periprosthetic infection, in terms of function, limb salvage, prevention of the recurrences, cost-effectiveness, and quality of life postoperatively.Conclusions: Muscle flaps provide an excellent management option for patients with persistent infection after total hip arthroplasty. [ABSTRACT FROM AUTHOR]

Introduction: In the past, targeted therapies have not shown positive results as they have been used without adequate molecular selection of patients with biliary tract cancer (BTC). This has led to an expansion of research on characteristics and molecular selection to identify new effective strategies in this setting. Improved knowledge of the molecular biology of these neoplasms has highlighted their extraordinary heterogeneity and has made it possible to identify targetable gene alterations, including fibroblast growth factor receptor (FGFR) 2 gene fusions, and isocitrate dehydrogenase (IDH) mutations. The FDA recently approved ivosidenib and pemigatinib for the treatment of BTCs.Areas Covered: We review data in the literature regarding targeted therapies for the treatment of BTCs, as well as on the prospects deriving from the extraordinary molecular heterogeneity of these neoplasms.Expert Opinion: At present, it is essential to evaluate the expression of the genetic alterations expressed by these neoplasms to offer patients an increasingly personalized therapeutic approach. Studies are needed to better define the limits and potentials of targeted therapies and their role in the therapeutic algorithm to improve the poor prognosis of these patients. [ABSTRACT FROM AUTHOR]

Background: KRAS mutations in metastatic colorectal cancer (mCRC) define a subset of tumors that have primary resistance to anti-EGFR-based therapy. Data concerning whether different KRAS mutations may also have a prognostic value are lacking. Furthermore, novel KRAS G12C inhibitors are currently in development. The aim of our analysis was to compare response rates in patients treated with first-line chemotherapy doublet + Bevacizumab among different KRAS variants. Secondary end-points were progression free survival (PFS) and overall survival (OS). Methods: Patients with KRAS mutated mCRC treated with either FOLFIRI/FOLFOX/XELOX + Bevacizumab were eligible for enrollment. Patients whose tumor harbored NRAS mutations or that coexpressed also BRAF mutations were excluded from this retrospective analysis. Patients' individual data were collected from patients' records. Propensity score matching (nearest method, 1:2 ratio) was used to define the two different groups of patients for comparison (KRAS G12C mutated vs other KRAS variants). Eastern Cooperative Oncology Group Performance Status (ECOG PS), sex, metastatic site of involvement, synchronous vs metachronous metastatic disease, tumor sidedness, mucinous histology, primary tumor surgery, more than two lines of treatment for metastatic disease, and radical surgery of metastases were used as matching factors. Response rate (RR) was calculated by RECIST 1.1 criteria. Both progression free-survival and overall survival were calculated by Kaplan–Meier method. Categorical variables were compared by Fisher exact test for binomial variables and by chi-square test for all other instances. The level of statistical significance p was set at 0.05 for all tests. Results: A total of 120 patients were assessed in the final analysis. Out of the 120 patients, 15 (12%) were KRAS G12C mutated. In the whole cohort of patients, 59/120 (49%) had partial response (PR), 42/120 (35%) had stable disease (SD), and 19/120 (16%) had progressive disease (PD) as the best response. In KRAS G12C patients, 4/15 (27%) had PR, 6/15 (40%) had SD, and the remaining 5/15 (33%) had PD as the best response. In patients with other KRAS mutations, 55/105 (52%) had PR, 37/105 (35%) had SD, and the remaining 13/105 (12%) had PD as the best response. The difference in RR between the two groups of patients was statistically significant (p=0.017). On the other hand, no difference in PFS (p=0.76) and OS (p=0.56) was observed. After matching procedures, the difference in response rates between KRAS G12C mutated patients vs the matched cohort of patients with other KRAS mutations remained statistically significant (p=0.016). KRAS G12C mutations were not associated with differences in sites of metastatic involvement, sex, and ECOG PS. On the other hand, synchronous vs metachronous metastatic disease (p=0.039), age > 75 years (p=0.043), and mucinous histology (p=0.008) were more frequent in G12C mutated tumors. Conclusions: In our cohort of patients, it was observed that KRAS G12C mutations are associated with worse response rates compared to other KRAS variants when treated with standard chemotherapy doublet + Bevacizumab. On the other hand, both PFS and OS were not significantly different. Based on these findings, we believe that new treatment options focused on KRAS G12C inhibition should be tested mainly in first-line setting and in addition to standard chemotherapy doublet + Bevacizumab for mCRC patients, as they might "fill the gap" in response rates that was seen in our study. [ABSTRACT FROM AUTHOR]

Background: Preclinical and clinical data indicate that p53 expression might modulate the activity of the epidermal growth factor receptor (EGFR), influencing response/resistance to anti-EGFR monoclonal antibodies. However, the association between p53 status and clinical outcome has not been clarified yet. Objective: In our study, we evaluated the role of p53 expression in patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) receiving irinotecan/cetuximab in an exploratory and a validation cohort. Patients and Methods: p53 expression was analysed in patients with RAS/BRAF wild-type mCRC receiving second-line or third-line irinotecan/cetuximab. Survival distribution was assessed by the Kaplan–Meier method, while the log-rank test was used for survival comparison. Results: Among 120 patients with RAS/BRAF wild-type mCRC included in our analysis, 52 (59%) and 19 (59%) patients showed p53 overexpression in the exploratory and validation cohort, respectively. In the exploratory cohort, low p53 expression was correlated with better median progression-free survival (hazard ratio 0.39; p < 0.0001), median overall survival (hazard ratio: 0.23; p < 0.0001) and response rate (p < 0.0001). These results were confirmed by data of the validation cohort where we observed better median progression-free survival (hazard ratio: 0.48; p = 0.0399), median overall survival (hazard ratio: 0.26; p = 0.0027) and response rate (p =0.0007) in patients with p53 normal expression mCRC. Conclusions: In our study, p53 overexpression was associated with anti-EGFR treatment resistance in patients with RAS/BRAF WT mCRC, as confirmed in a validation cohort. Larger studies are needed to validate the role of p53 and investigate EGFR cross-talk in these patients. [ABSTRACT FROM AUTHOR]

Background: Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations. Methods: Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR. Results: We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples. Conclusions: We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices. [ABSTRACT FROM AUTHOR]

Background: Biliary tract cancers (BTC) are rare but highly aggressive tumours with poor prognosis, usually detected at advanced stages. Herein, we aimed at identifying BTC-specific DNA methylation alterations.Methods: Study design included statistical power and sample size estimation. A genome-wide methylation study of an explorative cohort (50 BTC and ten matched non-tumoral tissue samples) has been performed. BTC-specific altered CpG islands were validated in over 180 samples (174 BTCs and 13 non-tumoral controls). The final biomarkers, selected by a machine-learning approach, were validated in independent tissue (18 BTCs, 14 matched non-tumoral samples) and bile (24 BTCs, five non-tumoral samples) replication series, using droplet digital PCR.Results: We identified and successfully validated BTC-specific DNA methylation alterations in over 200 BTC samples. The two-biomarker panel, selected by an in-house algorithm, showed an AUC > 0.97. The best-performing biomarker (chr2:176993479-176995557), associated with HOXD8, a pivotal gene in cancer-related pathways, achieved 100% sensitivity and specificity in a new series of tissue and bile samples.Conclusions: We identified a novel fully efficient BTC biomarker, associated with HOXD8 gene, detectable both in tissue and bile by a standardised assay ready-to-use in clinical trials also including samples from non-invasive matrices. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the typical inflammation-induced neoplasia. It often prospers where a chronic liver disease persists, thus leading a strong rationale for immune therapy. Several immune-based treatments, including immune checkpoint inhibitors (ICI), cytokines, adoptive cell transfer, and vaccines, have been tested in the treatment of HCC. In this review, we summarize the role of the ICI in HCC patients in various sets of treatment. As for advanced HCC, the anti-Programmed cell Death protein 1 (PD1) antibodies and the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibodies have been examined in patients with enthusiastic results in phase I-II-III studies. Overall, this led the Food and Drug Administration (FDA) to approve pembrolizumab, nivolumab, and nivolumab + ipilimumab in the second-line setting. The anti- Programmed Death-Ligand 1 (PDL-1) antibodies have also been evaluated. Thanks to the results obtained from phase III IMbrave study, atezolizumab + bevacizumab is now the standard of care in the first-line advanced setting of HCC. As for localized HCC, the putative immunological effect of locoregional therapies led to evaluate the combination strategy with ICI. This way, chemoembolization, ablation with radiofrequency, and radioembolization combined with ICI are currently under study. Likewise, the study of adjuvant immunotherapy following surgical resection is underway. In addition, the different ICI has been studied in combination with other ICI as well as with multikinase inhibitors and anti-angiogenesis monoclonal antibody. The evidence available suggests that combining systemic therapies and locoregional treatments with ICI may represent an effective strategy in this context. [ABSTRACT FROM AUTHOR]

Background: SARS-CoV-2 pandemic left a deep mark in the health systems around the globe, leading to an important change in the way we intend the access to the healthcare and its fruition. Hospitals faced something unexpected, and they underwent a deep change and so did orthopaedic activity. Materials and methods: In "A. Gemelli" University hospital new protocols were adopted for the safe management of patients affected by SARS-CoV-2. Among these patients, six had to be treated also for orthopaedic problems. The management of these patients, from the admission in the Emergency Room (E.R). to the operating room (O.R.), followed the protocols we developed for the coronavirus crisis. Results: Four among the six patients underwent surgical treatments. Two of them showed a change of their clinical status, due to a worsening of COVID-19 symptoms, so the surgical option was postponed. All of them were admitted to the Infectious Diseases Unit, rather than the Orthopaedic and Traumatology Unit, in order to provide the best measures to prevent the spread of the contagion and to ensure the best treatment for COVID-19. No O.R. staff was infected by SARS-CoV-2. Conclusions: More studies are needed to provide a higher statistical significance to the safety measures taken in order to contrast the spread of SARS-CoV-2 in the Surgical Room. Orthopaedic surgeons are more exposed to the contagion due to the particular tools set they use. A more sensible and specific quick test for novel Coronavirus is particularly needed, due to the lack of sensitivity of the serological rapid test. [ABSTRACT FROM AUTHOR]

Background: Sorafenib represents one of the therapeutic strongholds for advanced hepatocellular carcinoma (HCC), but unfortunately, predictive factors are lacking. We previously reported that the VEGF single nucleotide polymorphisms (SNPs) rs2010963 and rs4604006 might correlate with clinical outcomes in sorafenib-treated HCC patients.Objective: The objective of the ALICE-2 study is to define a prognostic angiogenesis profile to better identify HCC patients who are more likely to benefit from sorafenib treatment.Patients and Methods: From 2008 to 2015, all consecutive HCC patients receiving sorafenib according to the Italian label were tested for specific HIF-1α, VEGF, and VEGFR SNPs. Results from angiogenesis genotyping were then correlated with clinical outcome parameters.Results: Globally, a total of 210 patients were enrolled. At multivariate analysis rs12434438 of HIF1α, rs2010963 of VEGF-A, and rs4604006 of VEGF-C were confirmed as independent predictive factors. At the combined analysis of significant SNPs, the presence of two favourable alleles of rs2010963 and rs4604006 of VEGF compared to only one or to none favourable alleles, was able to identify three separate patients populations with different time-to-progression (TTP) (10.8 vs. 5.6 vs. 3.7 months, respectively; p < 0.0001) and overall survival (OS) (19.0 vs. 13.5 vs. 7.5 months, respectively; p < 0.0001). Furthermore, the presence of the GG genotype of rs12434438 (HIF-1α) seemed able to select a population with a particularly poor outcome, independently from the clinical effect of the two VEGF SNPs (TTP: 2.6 months, HR: 0.54, p = 0.0374; OS: 6.6 months, p = 0.0061, HR: 0.43).Conclusions: Our findings show that polymorphism analysis of HIF-1α, VEGF, and VEGFR genes may represent a prognostic panel to better identify HCC patients who are more likely to benefit from sorafenib treatment. [ABSTRACT FROM AUTHOR]

Despite continued research, pancreatic ductal adenocarcinoma (PDAC) remains one of the main causes of cancer death. Interest is growing in the role of the tumour suppressors breast cancer 1 (BRCA1) and BRCA2-typically associated with breast and ovarian cancer-in the pathogenesis of PDAC. Indeed, both germline and sporadic mutations in BRCA1/2 have been found to play a role in the development of PDAC. However, data regarding BRCA1/2-mutant PDAC are lacking. In this review, we aim to outline the specific landscape of BRCA-mutant PDAC, focusing on heritability, clinical features, differences between BRCA1 and 2 mutations and between germline and sporadic alterations, as well as established therapeutic strategies and those that are still under evaluation. [ABSTRACT FROM AUTHOR]

Introduction: BRAF mutant colorectal cancer (BRAF MT CRC) is a unique category of colorectal tumour with peculiar molecular, pathological and clinical features and poor prognosis; despite recent research, BRAF mutation predictive value and standard treatment of BRAF MT CRC still have to be defined. In this review, we focused on this challenging topic. Areas covered: The potential use of BRAF mutational status among recent additional prognostic and predictive indicators and current treatment strategy in use in these patients is discussed. Moreover, implications and characteristics of new BRAF mutations other than BRAFV600E are analyzed. An in-deep outlook on the immediate future for clinical and translational research in this subgroup of patients is also presented, such as combination therapy with agents targeting the RAS/RAF/MEK/ERK pathway and standard chemotherapy in order to overcome resistance. We performed a research on Pubmed typing ‘BRAF mutation’, ‘colorectal cancer’, ‘predictive and prognostic value’, ‘targeted therapy’, ‘BRAF inhibition’. Expert commentary: BRAFV600E mutation represents a strong, independent negative prognostic factor in II-III stage MSS CRC and mCRC. The best treatment still has to be identified; currently, in good performance status patients, an intensive-chemotherapy-combination remains the standard of care. Further investigations are warranted to explore new horizons to change BRAF MT mCRC outcomes. [ABSTRACT FROM AUTHOR]

Silver coating has demonstrated good antimicrobial activity and low toxicity. Silver-coated megaprostheses have been introduced in oncological musculoskeletal surgery considering the high rate of infection. We conducted a retrospective analysis on 68 cases of primary or metastatic bone tumors, affecting the proximal femur, treated between 2005 and 2016 with wide margins resection and tumor implants reconstruction. All patients were treated by the same surgeon, with antibiotic prophylaxis according to a standard protocol. In 55.9% of patients silver-coated hip hemiarthroplasty was implanted; in the remaining 44.1% uncoated megaprostheses were implanted. Patients were reevaluated recording the complications and focusing the analysis on infective complications. The average follow-up was 46.5 months. No patient has shown any sign of local or general silver toxicity. A SEM analysis was conducted on the 3-silver-coated hip hemiarthroplasty explanted confirming a severe degradation with a small amount of residual silver on the coating surface. Silver-coated hip prostheses have a lower rate of early infection than traditional implants but showed a reduction of antimicrobial activity for silver coating wear. We recommend using silver-coated prosthesis as primary implants for limb salvage surgery, in primary or metastatic bone tumors affecting the proximal femur, considering the absence of signs of toxicity and the lower rate of early infection. [ABSTRACT FROM AUTHOR]

A case of acinic cell carcinoma of the right parotid gland metastasizing to the right iliac crest is presented. Generally, for this rare low-grade malignant salivary gland neoplasm, 20% of cases may have local recurrences whereas about 10% of cases have distant metastases. They may arise many years after the initial presentation of the original tumor. The most frequent locations are the cervical lymph nodes, liver, lungs, contralateral orbit and bones. Occurrence in the appendicular skeleton is very rare and in our knowledge this is the first report of metastases to the pelvis. [ABSTRACT FROM AUTHOR]

Background: The data from randomised trials suggested that primary tumour sidedness could represent a prognostic and predictive factor in colorectal cancer (CRC) patients, particularly during treatment with anti-epidermal growth factor receptor (EGFR) therapy. However, an in-deep molecular selection might overcome the predictive role of primary tumour location in this setting.Methods: We conducted a retrospective analysis in which tumour samples from RAS/BRAF wild-type (WT) metastatic CRC patients treated with second-third-line irinotecan/cetuximab were analysed for EGFR gene copy number (GCN) and promoter methylation. Study objective was to evaluate the correlation of tumour sidedness, EGFR promoter methylation and EGFR GCN with clinical outcome. Median follow-up duration was 14.3 months.Results: Eighty-eight patients were included in the study, 27.3% had right-sided CRC, 72.7% had left-sided CRC; 36.4% had EGFR GCN<2.12 tumour, 63.6% had EGFR GCN⩾2.12 tumour; 50% had EGFR promoter-methylated tumour. Right-sided colorectal cancer (RSCRC) were associated with reduced overall response rate (ORR) (4.2% for RSCRC vs 35.9% for left sided colorectal cancer (LSCRC), P=0.0030), shorter progression-free survival (PFS) (3.0 vs 6.75 months, P<0.0001) and shorter overall survival (OS) (8 vs 13.6 months, P<0.0001). EGFR GCN<2.12 tumours were associated with reduced ORR (6.2% for EGFR GCN<2.12 vs 39.3% for EGFR GCN⩾2.12 tumours, P=0.0009), shorter PFS (3.5 vs 6.5 months, P=0.0006) and shorter OS (8.5 vs 14.0 months, P<0.0001). Epidermal growth factor receptor-methylated tumours were associated with reduced ORR (9.1% for methylated vs 45.5% for unmethylated, P=0.0001), shorter PFS (3 vs 7.67 months, P<0.0001) and shorter OS (8 vs 17 months, P<0.0001). At multivariate analysis, EGFR GCN and EGFR promoter methylation maintained their independent role for ORR (respectively P=0.0082 and 0.0025), PFS (respectively P=0.0048 and<0.0001) and OS (respectively P=0.0001 and<0.0001).Conclusions: In our study, an accurate molecular selection based on an all RAS and BRAF analysis along with EGFR GCN and EGFR promoter methylation status seems to be more relevant than primary tumour sidedness in the prediction of clinical outcome during cetuximab/irinotecan therapy. However, these data need to be validated with future prospective and translational studies. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the structural properties of femur-patellar tendon graft complex in anterior cruciate ligament (ACL) reconstruction using different femoral fixation devices. Type of study is biomechanical testing. An ACL reconstruction was performed on 40 cadaver porcine knees, using patellar tendon (PT) graft. Specimens were divided into four groups according to the femoral fixation: interference absorbable screw (Group A), metallic setscrew (Group B), absorbable pins (Group C), and a combination of metallic setscrew and pin (Group D). Other ten knees were used as controls. On each sample, a cyclic loading test, then a load-to-failure test were performed. Elongation after 1,000 loading cycles, ultimate failure load, yield load, stiffness, deformation at the yield point, and mode of failure were recorded. Kruskal-Wallis test and Tukey test were used to compare the differences between groups. The lowest mean elongation after 1,000 load cycles was observed for Group B (1.7 +/- 1.4 mm) and D (1.2 +/- 0.3 mm). Ultimate failure load of Group D (1,021.8 +/- 199.4 N) was comparable with that of normal ACL (1,091.2 +/- 193.3 N) and PT graft (1,140.6 +/- 285.7 N). All other groups were lower than the controls. For mean stiffness, all the groups, excepting for Group D (172.8 +/- 40.4 N/mm), were significantly lower than PT control group (216 +/- 78.4 N/mm). Mode of failure was graft pullout for Groups A and B, distal pin breakage for Group C, and midsubstance graft rupture in 80% of the cases for Group D. Only combined compression and suspension fixation did not show significantly different structural properties in comparison with normal ACL and PT graft. Furthermore, it showed no risk of graft pullout or hardware breakdown in comparison with other fixation devices. [ABSTRACT FROM AUTHOR]