Inflammation and infiltration: can the radiologist draw a line? MRI versus CT to accurately assess medullary involvement in parosteal osteosarcoma

Cancer causes inflammation as it progresses through healthy tissue. The differentiation of tumoral growth from the surrounding inflammatory change is paramount in planning surgeries seeking to preserve function. This retrospective study aims at illustrating how a careful use of imaging (computed tomography (CT)/magnetic resonance imaging (MRI)) can help to draw the line between infiltration and inflammation. Out of 72 cases of parosteal osteosarcoma in our institution we selected 22 which had pretreatment imaging, and out of those, 14 that had both MRI and CT. Using Fisher’s exact test, we evaluated the performance of each technique on accurately diagnosing medullary tumor infiltration, using histological analysis as a gold standard. All cases (14/14) demonstrated medullary abnormality on MRI, but only 6/14 (42.9%) demonstrated abnormality on CT. The 8/14 cases with MRI abnormality but no CT abnormality (57.1%) showed inflammation with no tumoral cells present on histological analysis. In the cases where the two examinations showed medullary abnormality (6/14) histology demonstrated tumoral infiltration. MRI demonstrated high sensitivity and negative predictive value, but low specificity and low positive predictive value and accuracy (P=1). CT demonstrated high sensitivity, specificity, high positive and negative predictive values and accuracy (P = 0.000333). MRI is highly sensitive for the detection of medullary abnormality but lacks specificity for tumor invasion. Correlation with CT is recommended in all cases of positive MR to add specificity for tumors. The adequate use of the two imaging methods allows to differentiate between inflammatory change and tumoral infiltration in POS, relevant for surgical planning

Secondary peripheral chondrosarcoma arising in solitary osteochondroma: variables influencing prognosis and survival

Background: Secondary peripheral chondrosarcomas arising in solitary osteochondromas is an unusual complication, reported in small series. In this study, we aimed to present our experience with this rare variant of chondrosarcoma and compare results with already published data in order to determine prognostic factors for overall and disease-free survival. Methods: The case study includes retrospective data from patients diagnosed at a single institution from 1943 to 2019. Clinical data were collected reviewing all available medical records from first to last follow-up visits. To exclude the presence of the Multiple Osteochondroma Hereditary Syndrome, few patients, with a suspect of a familial form of the disease, were evaluated for the presence of germline heterozygous variants in EXT1 and EXT2 genes. Results were summarized using descriptive statistics and statistical analysis were performed to reveal associations between variables. Results: Two hundred and fourteen secondary peripheral chondrosarcomas that arose exclusively from solitary osteochondromas diagnosed in a multidisciplinary setting at the IRCCS Istituto Ortopedico Rizzoli were retrospectively identified, 66.4% males and 33.6% females with a median age at diagnosis of 38 years. The local recurrence rate was 17.3%, while the metastases one was 5.1%. Besides age, a high histologic grade is the only factor associated with worse 5-year and 10-year overall survival (log-rank p = 0.0005, HR = 3.74; 95% CI 1.69–8.26). Moreover, high histological grade (HR = 3.75; 95% CI = 1.69–8.34; p = 0.001) and surgical debulking (HR = 3.71; 95% CI = 1.57–8.79; p = 0.003) were associated with a significantly worse disease-free survival. Conclusions: Our study confirm the low-grade behavior of secondary peripheral chondrosarcomas and demonstrate that the best choice of treatment for those arising in solitary osteochondromas is the wide surgical excision, when possible. Location per se is not a factor that affects prognosis, while the accurate histological grade assessment is correlated with the tumor aggressiveness and a long term follow up is necessary for this rare variant of chondrosarcoma

Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed.

BACKGROUND: Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H\u2009+-rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma. METHOD: MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin. RESULTS: Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients. CONCLUSION: This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy

Comparison of Branched and Linear Perfluoropolyether Chains Functionalization on Hydrophobic, Morphological and Conductive Properties of Multi-Walled Carbon Nanotubes

The functionalization of multi-walled carbon nanotubes (MW-CNTs) was obtained by generating reactive perfluoropolyether (PFPE) radicals that can covalently bond to MW-CNTs\u2019 surface. Branched and linear PFPE peroxides with equivalent molecular weights of 1275 and 1200 amu, respectively, have been thermally decomposed for the production of PFPE radicals. The functionalization with PFPE chains has changed the wettability of MW-CNTs, which switched their behavior from hydrophilic to super-hydrophobic. The low surface energy properties of PFPEs have been transferred to MW-CNTs surface and branched units with trifluoromethyl groups, CF3, have conferred higher hydrophobicity than linear units. Porosimetry discriminated the effects of PFPE functionalization on meso-porosity and macro-porosity. It has been observed that reactive sites located in MW-CNTs mesopores have been intensively functionalized by branched PFPE peroxide due to its low average molecular weight. Conductivity measurements at different applied pressures have showed that the covalent linkage of PFPE chains, branched as well as linear, weakly modified the electrical conductivity of MW-CNTs. The decomposed portions of PFPE residues, the PFPE chains bonded on carbon nanotubes, and the PFPE fluids obtained by homo-coupling side-reactions were evaluated by mass balances. PFPE-modified MW-CNTs have been characterized by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), static contact angle (SCA), surface area, and porosity measurements

Indications and Limits of Surgery for Spinal Metastases Derived from Lung Cancer: A Single-Center Experience

Lung cancer is the second most frequently diagnosed cancer in the world, and surgery is an integral part of the treatment for spinal metastases. The aims of this retrospective study were to assess the overall survival of surgically treated patients affected by lung cancer spinal metastases and identify any factors related to a better survival rate. We recruited 56 consecutive patients (34 male and 22 female) surgically treated for metastatic lung cancer in the spine from 2009 to 2019. Surgical indications were based on a previously published and validated flow chart following a multidisciplinary evaluation. We assessed the localization of vertebral metastases, the presence of other bone or visceral metastases, neurological status according to the Frankel score, ambulatory autonomy, and general status, measured with the Karnofsky performance scale. The expected prognosis was retrospectively assessed according to the revised Tokuhashi score. The median survival was 8.1 months, with over a third of patients surviving more than 1 year. We observed a global improvement in all clinical parameters after surgical treatment. The Tokuhashi predictive score did not correlate with survival after surgery. The results of this study suggest that the surgical treatment of symptomatic spinal metastases from lung cancer can improve quality of life, even in patients with a shorter life expectancy, by controlling pain and improving autonomy

Dideoxynucleoside HIV reverse transcriptase inhibitors and drug-related hepatotoxicity: a case report

This report regards the case of a 43 year-old HIV-positive woman who developed an episode of serious transaminase elevation during stavudine-including antiretroviral therapy. Diagnostic assessment ruled out hepatitis virus co-infection, alcohol abuse besides other possible causes of liver damage. No signs of lactic acidosis were present. Liver biopsy showed portal inflammatory infiltrate, spotty necrosis, vacuoles of macro- and micro-vesicular steatosis, acidophil and foamy hepatocytes degeneration with organelles clumping, poorly formed Mallory bodies and neutrophil granulocytes attraction (satellitosis). A dramatic improvement in liver function tests occurred when stavudine was discontinued and a new antiretroviral regimen with different nucleoside reverse transcriptase inhibitors was used. The importance of considering hepatotoxicity as an adverse event of HAART including stavudine, even in absence of other signs of mitochondrial toxicity should therefore be underlined. Liver biopsy may provide further important information regarding patients with severe transaminase elevation, for a better understanding of the etiology of liver damage

The sacral chordoma margin

[Objective]: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. [Background]: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. [Methods]: A multidisciplinary meeting of the “Chordoma Global Consensus Group” was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. [Results]: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. [Conclusion]: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients

Biological Sample Collection to Advance Research and Treatment: A Fight Osteosarcoma Through European Research and Euro Ewing Consortium Statement

Osteosarcoma and Ewing sarcoma are bone tumors mostly diagnosed in children, adolescents, and young adults. Despite multimodal therapy, morbidity is high and survival rates remain low, especially in the metastatic disease setting. Trials investigating targeted therapies and immunotherapies have not been groundbreaking. Better understanding of biological subgroups, the role of the tumor immune microenvironment, factors that promote metastasis, and clinical biomarkers of prognosis and drug response are required to make progress. A prerequisite to achieve desired success is a thorough, systematic, and clinically linked biological analysis of patient samples, but disease rarity and tissue processing challenges such as logistics and infrastructure have contributed to a lack of relevant samples for clinical care and research. There is a need for a Europe-wide framework to be implemented for the adequate and minimal sampling, processing, storage, and analysis of patient samples. Two international panels of scientists, clinicians, and patient and parent advocates have formed the Fight Osteosarcoma Through European Research consortium and the Euro Ewing Consortium. The consortia shared their expertise and institutional practices to formulate new guidelines. We report new reference standards for adequate and minimally required sampling (time points, diagnostic samples, and liquid biopsy tubes), handling, and bio-banking to enable advanced biological studies in bone sarcoma. We describe standards for analysis and annotation to drive collaboration and data harmonization with practical, legal, and ethical considerations. This position paper provides comprehensive guidelines that should become the new standards of care that will accelerate scientifc progress, promote collaboration, and improve outcomes

Revisiting the Minisci Reaction: New Mild Amidoalkylation of Benzo-Fused N-Heteroaromatic Bases under Metal-Free Conditions

In the last few decades, many efforts have been made to make chemical processes more sustainable and reduce their environmental impact. In this context, for the first time, the α-amidoalkylation of benzo-fused N-heteroaromatic bases has been performed in the presence of sodium persulfate as a free-radical source and terminal oxidant without using acids and transition metals. The desired α-amidoalkylated products have been obtained in high yields in relatively short reaction times compared with those generally reported at 50 and 80 °C. The biggest advantage of this new protocol, which does not require acids and metals, is the higher atom economy due to the reduction of the waste. Regarding the reaction mechanism, an interaction between persulfate and the specific amide seems to play a key role in the overall reaction efficiency