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BACKGROUND In patients with suspected deep vein thrombosis (DVT), D-dimer thresholds adjusted to age or clinical pretest probability (CPTP) increase the proportion of patients in whom DVT can be safely excluded compared to a standard approach using a fixed D-dimer threshold. Performance of these diagnostic strategies among cancer patients is uncertain. AIM To compare the performance of age- and CPTP-adjusted D-dimer approaches among cancer outpatients with clinically suspected DVT, and derive a cancer-specific CPTP rule. PATIENTS AND METHODS Consecutive ambulatory patients with active cancer and clinically suspected DVT of the lower extremity underwent CPTP assessment using the Wells rule, D-dimer testing, and whole-leg compression ultrasonography. Patients with normal ultrasonography were followed-up for 3 months for the occurrence of symptomatic venous thromboembolism. RESULTS Upon referral, DVT was diagnosed in 48 of 239 (20.1 %) patients. The age-adjusted approach showed higher specificity and efficiency than the standard approach. Compared to the standard and age-adjusted strategies, the CPTP-adjusted approach had 35 % and 21 % higher specificity, and 34 % and 21 % higher efficiency, respectively. Failure rate, sensitivity, and predictive values were similar across strategies. A simplified CPTP score derived from the Wells rule reduced unnecessary imaging with similar accuracy and efficiency, but higher failure rate. CONCLUSIONS In this prospective cohort of ambulatory cancer patients with clinically suspected DVT, the CPTP-adjusted D-dimer approach held the highest specificity and efficiency, potentially safely reducing unnecessary ultrasonography examinations compared to other approaches. Additional studies are warranted to evaluate the use of a simplified clinical prediction rule in this setting.

This work presents the neoplastic bone changes found in the lower limb of a medieval skeleton from the church of Sant' Agostino in Caravate (Northern Italy). After briefly assessing the individual's overall pathological picture, a differential diagnosis for the neoplastic changes is now proposed. These changes were analysed macroscopically and radiographically and subsequently evaluated considering the paleopathological and clinical literature available. The differential diagnosis allowed us to recognize a tibiofibular osteochondroma and some enchondromas in the medullary cavity of the tibia. The results presented here highlight the importance of radiological analyses in the recognition and study of bone neoplasms in the paleopathological field, further contributing to our knowledge of the presence of neoplasms in Medieval Northern Italy.

Objectives Percutaneous radiofrequency ablation (RFA) is stated as a treatment option for renal cell carcinoma (RCC) smaller than 4 cm (T1a). Microwave ablation (MWA) is a newer technique and is still considered experimental in some guidelines. The objective of this study was to compare the safety and efficacy of RFA and MWA for the treatment of RCC. Methods Patients with T1a RCC treated by RFA or MWA in two referral centers were retrospectively analyzed. Patient records were evaluated to generate mRENAL nephrometry scores. Local tumor progression (LTP) was considered when new (recurrence) or residual tumor enhancement within/adjacent to the ablation zone was objectified. Differences in LTP-free interval (residual + recurrence) between ablation techniques were assessed with Cox proportional hazards models and propensity score (PS) methods. Results In 164 patients, 87 RFAs and 101 MWAs were performed for 188 RCCs. The primary efficacy rate was 92% (80/87) for RFA and 91% (92/101) for MWA. Sixteen patients had residual disease (RFA (n = 7), MWA (n = 9)) and 9 patients developed recurrence (RFA (n = 7), MWA (n = 2)). LTP-free interval was significantly worse for higher mRENAL nephrometry scores. No difference in LTP-free interval was found between RFA and MWA in a model with inverse probability weighting using PS (HR = 0.99, 95% CI 0.35–2.81, p = 0.98) and in a PS-matched dataset with 110 observations (HR = 0.82, 95% CI 0.16–4.31, p = 0.82). Twenty-eight (14.9%) complications (Clavien-Dindo grade I–IVa) occurred (RFA n = 14, MWA n = 14). Conclusion Primary efficacy for ablation of RCC is high for both RFA and MWA. No differences in efficacy and safety were observed between RFA and MWA. Key Points • Both RFA and MWA are safe and effective ablation techniques in the treatment of T1a renal cell carcinomas. • High modified RENAL nephrometry scores are associated with shorter local tumor progression-free interval. • MWA can be used as heat-based ablation technique comparable to RFA for the treatment of T1a renal cell carcinomas.

Castration-resistant prostate cancer (CRPC) is the main driving force of mortality in prostate cancer patients. Among the parameters contributing to the progression of CRPC and treatment failure, elevation of the steroidogenic enzyme AKR1C3 and androgen receptor variant 7 (AR-V7) are frequently reported. The AKR1C3/AR-V7 complex has been recognized as a major driver for drug resistance in advanced prostate cancer. Herein we report that the level of AKR1C3 is reciprocally regulated by the full-length androgen receptor (AR-FL) through binding to the distal enhancer region of the AKR1C3 gene. A novel function of PTUPB in AKR1C3 inhibition was discovered and PTUPB showed more effectiveness than indomethacin and celecoxib in suppressing AKR1C3 activity and CRPC cell growth. PTUPB synergizes with enzalutamide treatment in tumor suppression and gene signature regulation. Combination treatments with PTUPB and enzalutamide provide benefits by blocking AR/AR-V7 signaling, which inhibits the growth of castration relapsed VCaP xenograft tumors and patient derived xenograft organoids. Targeting of the ARK1C3/AR/AR-V7 axis with PTUPB and enzalutamide may overcome drug resistance to AR signaling inhibitors in advanced prostate cancer.

Objectives: To compare four previously published methods for rectal tumor response evaluation after chemoradiotherapy on MRI. Methods: Twenty-two radiologists (5 rectal MRI experts, 17 general/abdominal radiologists) retrospectively reviewed the post-chemoradiotherapy MRIs of 90 patients, scanned at 10 centers (with non-standardized protocols). They applied four response methods; two based on T2W-MRI only (MRI tumor regression grade (mrTRG); split-scar sign), and two based on T2W-MRI+DWI (modified-mrTRG; DWI-patterns). Image quality was graded using a 0–6-point score (including slice thickness and in-plane resolution; sequence angulation; DWI b-values, signal-to-noise, and artefacts); scores < 4 were classified below average. Mixed model linear regression was used to calculate average sensitivity/specificity/accuracy to predict a complete response (versus residual tumor) and assess the impact of reader experience and image quality. Group interobserver agreement (IOA) was calculated using Krippendorff’s alpha. Readers were asked to indicate their preferred scoring method(s). Results: Average sensitivity/specificity/accuracy was 57%/64%/62% (mrTRG), 36%/79%/66% (split-scar), 40%/79%/67% (modified-mrTRG), and 37%/82%/68% (DWI-patterns); mrTRG showed higher sensitivity but lower specificity and accuracy (p < 0.001) compared to the other methods. IOA was lower for the split scar method (0.18 vs. 0.39–0.43). Higher reader experience had a significant positive effect on diagnostic performance and IOA (except for the split scar sign); below-average imaging quality had a significant negative effect on diagnostic performance. DWI pattern was selected as the preferred method by 73% of readers. Conclusions: Methods incorporating DWI showed the most favorable results when combining diagnostic performance, IOA, and reader preference. Reader experience and image quality clearly impacted diagnostic performance emphasizing the need for state-of-the-art imaging and dedicated radiologist training. Key Points: • In a multireader study comparing 4 MRI methods for rectal tumor response evaluation, those incorporating DWI showed the best results when combining diagnostic performance, IOA, and reader preference. • The most preferred method (by 73% of readers) was the “DWI patterns” approach with an accuracy of 68%, high specificity of 82%, and group IOA of 0.43. • Reader experience level and MRI quality had an evident effect on diagnostic performance and IOA.

We discuss an extremely rare case of low-grade Schwann cell leptomeningeal neoplasm with no evident intradural primary, presenting with rapid neurological decline leading to death reflecting the aggressive biological behaviour of this entity despite its low-grade morphology. Notwithstanding extensive investigations, the diagnosis was only established on autopsy as clinical presentation is non-specific making diagnosis challenging. This condition could be considered in patients presenting with leptomeningeal disease if initial workup of more common causes is non-revealing.

Purpose: Sustained minimal residual disease (MRD) negativity is associated with long-term survival in multiple myeloma. The gut microbiome is affected by diet, and in turn can modulate host immunity, for example through production of short-chain fatty acids including butyrate. We hypothesized that dietary factors affect the microbiome (abundance of butyrate-producing bacteria or stool butyrate concentration) and may be associated with multiple myeloma outcomes. Experimental Design: We examined the relationship of dietary factors (via a food frequency questionnaire), stool metabolites (via gas chromatography–mass spectrometry), and the stool microbiome (via 16S sequencing - α-diversity and relative abundance of butyrate-producing bacteria) with sustained MRD negativity (via flow cytometry at two timepoints 1 year apart) in myeloma patients on lenalidomide maintenance. The Healthy Eating Index 2015 score and flavonoid nutrient values were calculated from the food frequency questionnaire. The Wilcoxon rank sum test was used to evaluate associations with two-sided P < 0.05 considered significant. Results: At 3 months, higher stool butyrate concentration (P = 0.037), butyrate producers (P = 0.025), and α-diversity (P = 0.0035) were associated with sustained MRD negativity. Healthier dietary proteins, (from seafood and plants), correlated with butyrate at 3 months (P = 0.009) and sustained MRD negativity (P = 0.05). Consumption of dietary flavonoids, plant nutrients with antioxidant effects, correlated with stool butyrate concentration (anthocyanidins P = 0.01, flavones P = 0.01, and flavanols P = 0.02). Conclusions: This is the first study to demonstrate an association between a plant-based dietary pattern, stool butyrate production, and sustained MRD negativity in multiple myeloma, providing rationale to evaluate a prospective dietary intervention.

BackgroundOver the last decades, a decrease in short-term mortality in cancer patients admitted to the ICU has been described in literature. However, it is unclear whether this decrease also results in a decrease in long-term mortality. Therefore, we examined the 1-year mortality of cancer patients (either haematological or solid) with an unplanned ICU admission.Methods and dataAll adult patients registered in the National Intensive Care Evaluation registry with an unplanned ICU admission in the Netherlands between 2008 and 2017 were included. The primary outcome was 1-year mortality, analysed with a mixed-effects cox-proportional hazard regression. We examined the trend in mortality rates over the inclusion period. Furthermore, we compared the 1-year mortality of cancer patients to that of patients without cancer. ResultsWe included 470,305 patients: 10,401 with haematological cancer, 35,920 with solid tumours, and 423,984 without cancer. The 1-year mortality rates were 60.1%, 46.2%, and 28.3% (pConclusionThe 1-year mortality in cancer patients with an unplanned ICU admission (either haematological or solid) was significantly higher than that of patients without cancer. A visual inspection showed a slight decrease in 1-year mortality in haematological patients, while the 1-year mortality in patients with a solid tumour varied per year. After hospital discharge, a considerable part of the patients with a malignancy died within 1 year. Physicians should discuss the long-term prognosis after an ICU admission with patients and relatives in order to manage treatments and expectations. Future research should focus on identifying cancer patients who will benefit from an ICU admission.

60 p. -- Bibliogr.: p. 22-24 Español El cáncer es una de las de las principales causas de morbi-mortalidad a nivel mundial que provoca un gran impacto, tanto en el paciente como en su entorno. Se trata de una enfermedad estigmatizante, que genera sufrimiento en las personas a todos los niveles. Desde el momento del diagnóstico, y durante sus diferentes fases, el dolor y ansiedad son dos síntomas con una gran incidencia. Cada vez son más los estudios que defienden la necesidad de complementar los tratamientos tradicionales con terapias alternativas que potencien el alivio de los síntomas con el menor número posible de efectos secundarios. Entre esas terapias alternativas se encuentra la musicoterapia. Esta, ha sido diseñada para tratar síntomas, tanto físicos como emocionales, que afectan de manera negativa a la calidad de vida de los pacientes, En el siguiente trabajo se realizó una búsqueda bibliográfica de la que se pudiera extraer la evidencia científica disponible hasta el momento sobre la efectividad de la musicoterapia sobre el dolor y la ansiedad de los pacientes oncológicos.

Background: People living at home with advanced cancer wish to maintain and preserve domestic life, but they experience several barriers in their everyday occupations and thereby occupational performance. There is little knowledge of these barriers experienced by people living alone versus people living with someone. Objective/Aim: To investigate differences in self-perceived occupational performance and the prioritisation of getting self-reported problematic everyday occupations solved among people with advanced cancer, taking living status into consideration. Method: A cross-sectional study using baseline data from an RCT including 174 participants with advanced cancer living at home. Difficulty and priorisation of everyday occupations were assessed using the Individually Prioritised Problem Assessment (IPPA). Results: In total, 731 problematic everyday occupations were reported, mainly related to the categories of housework, self-care and leisure. Conclusions/significance: Overall, no statistically significant difference in self-reported occupational performance was found. However, people living alone perceived statistically significantly more frequently showering/bathing and doing laundry as difficult and therefore important to address. In contrast, people living with someone prioritised social interaction and home maintenance statistically significantly more frequently.

Aim: Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches. Methods: Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipitation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses. Results: We identified IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was significantly associated with resistance to selumetinib, gefitinib, and regorafenib in PDOs and to 5-fluorouracil and oxaliplatin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabilization of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confirmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells. Conclusions: IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mitochondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance.

RESUMO Introdução: A reconstrução da mama imediata pós-mastectomia, com implante de silicone é um método simples, porém, pode evoluir com complicações e remoção do implante. O objetivo do estudo foi analisar as complicações pós-operatórias e buscar relação entre estas e a remoção do implante. Método: No período de 4 anos, foram estudados retrospectivamente 323 casos de reconstrução de mama imediata com implante de silicone após mastectomia total realizados no Institut Gustave-Roussy, França. Resultados: A complicação mais frequente foi a linfocele (34,9%), seguida da necrose cutânea com 22,9%, da infecção com 19,3% e do hematoma, com 13,3% dos casos. A remoção do implante foi mais frequente quando ocorreu algum tipo de complicação cirúrgica e maior quando ocorreu mais de um tipo de complicação. A complicação mais frequente nos casos de remoção do implante foi a infecção (75,0%). O expansor foi o implante que mais teve relação com remoção do implante. O uso de implantes de volume acima de 300 ml teve significativamente mais risco de remoção do implante. Conclusões: 1) A presença de complicação pós-operatória foi fator de risco para a remoção do implante. 2) O risco de remoção foi maior na presença de mais de um tipo de complicação 3) A infecção foi o principal tipo de complicação que se relacionou com a remoção 4) O expansor apresentou maior risco de complicações e de remoção do implante. 5) A utilização de implantes de volume maior do que 300 ml apresentou maior risco de remoção. ABSTRACT Introduction: Immediate breast reconstruction with silicone implants following mastectomy is a simple method, but can develop complications culminating in implant removal. The aim of this study was to analyze postoperative complications and evaluate their correlation with implant removal. Method: In a period of 4 years, 323 cases of immediate breast reconstruction with silicone implants following total mastectomy were retrospectively studied in the Institut Gustave-Roussy, France. Results: The most frequent complication was lymphocele (34.9%), followed by cutaneous necrosis (22.9%), infection (19.3%), and hematoma (13.3%). Implant removal was more frequent when a surgical complication occurred, and even more frequent when there was more than one type of complication. The most frequent complication leading to implant removal was infection (75.0%). The expander was the implant that had the highest correlation with implant removal. The use of implants with a volume greater than 300 ml was associated with a significantly higher risk of implant removal. Conclusions: 1) The presence of postoperative complications was a risk factor for implant removal. 2) The risk of removal was higher when more than one complication was present. 3) Infection was the main type of complication associated with implant removal. 4) The expander presented a higher risk of complications and implant removal. 5) The use of implants with a volume greater than 300 ml had a greater risk of need for removal.

Immunotherapies, such as immune checkpoint inhibitors, cellular therapies, and T-cell engagers, have fundamentally changed our approach to treating cancer. However, successes with cancer vaccines have been more difficult to realize. While vaccines against specific viruses have been widely adopted to prevent the development of cancer, only two vaccines can improve survival in advanced disease: sipuleucel-T and talimogene laherparepvec. These represent the two approaches that have the most traction: vaccinating against cognate antigen and priming responses using tumors in situ. Here, we review the challenges and opportunities researchers face in developing therapeutic vaccines for cancer.

Uvod: Sestrinska skrb usmjerena prema pacijentu i željeni zdravstveni ishodi važni su za kvalitetu zdravstvene skrbi. Istraživači zdravstvenih usluga češće su usmjereni na karakterstike sustava i nepoželjne ishode sestrinske skrbi. Laurel E. Radvin u svojoj teoriji srednjeg opsega opisuje intervencije usmjerene na pacijenta i njihovu povezanost s poželjnim zdravstvenim ishodima. Metode: Teorija Laurel E. Radwin u literaturi predstavlja teoriju srednjeg opsega. Rezultati istraživanja potrebnih za razvoj teorije uglavnom su dobiveni iz Modela kvalitete zdravstvenih ishoda (eng. Quality Health Outcome Model). Rezultati: Teorija prikazuje pozitivnu povezanost između sestrinskih intervencija usmjerenih na pacijenta i željenih zdravstvenih ishoda. Rasprava: Ova teorija sestrinske skrbi usmjerena na onkološkog pacijenta potvrđena je istraživanjem i prikazuje usavršeni Model kvalitete zdravstvenih ishoda. Sve sestrinske intervencije usmjerene na pacijenta zahtijevaju individualiziranost. Pritom se povećavaju mogućnosti poželjnih ishoda sestrinske skrbi. Zaključak: Istraživanjem ove teorije usmjerava se pažnja na važnost planiranja i provođenja intervencija usmjerenih na pacijenta kod onkoloških pacijenata. S obzirom na ispitivane varijable, teoriju je moguće ispitati u različitim klinikama i na različitim odjelima da bi se utvrdila mogućnost primjene u praksi., Uvod: Sestrinska skrb usmjerena prema pacijentu i željeni zdravstveni ishodi važni su za kvalitetu zdravstvene skrbi. Istraživači zdravstvenih usluga češće su usmjereni na karakterstike sustava i nepoželjne ishode sestrinske skrbi. Laurel E. Radvin u svojoj teoriji srednjeg opsega opisuje intervencije usmjerene na pacijenta i njihovu povezanost s poželjnim zdravstvenim ishodima. Metode: Teorija Laurel E. Radwin u literaturi predstavlja teoriju srednjeg opsega. Rezultati istraživanja potrebnih za razvoj teorije uglavnom su dobiveni iz Modela kvalitete zdravstvenih ishoda (eng. Quality Health Outcome Model). Rezultati: Teorija prikazuje pozitivnu povezanost između sestrinskih intervencija usmjerenih na pacijenta i željenih zdravstvenih ishoda. Rasprava: Ova teorija sestrinske skrbi usmjerena na onkološkog pacijenta potvrđena je istraživanjem i prikazuje usavršeni Model kvalitete zdravstvenih ishoda. Sve sestrinske intervencije usmjerene na pacijenta zahtijevaju individualiziranost. Pritom se povećavaju mogućnosti poželjnih ishoda sestrinske skrbi. Uvod: Patient-oriented nursing care and desired health outcomes are important for the quality of health care. Healthcare researchers are more often focused on system characteristics and adverse health care outcomes. In her mid-range theory, Laurel E. Radwin describes patient-centered interventions and their association with desirable health outcomes. Methods: Laurel E. Radwin's theory represents a medium-range theory in the literature. The results of the research necessary for the development of the theory were mainly obtained from the Model on the quality of health outcomes. Results: The theory shows a positive correlation between patient-centered nursing interventions and desired health outcomes. Discussion: This theory of nursing care focused on the oncology patient has been confirmed by research and provides an overview of the improved Model of Health Outcome Quality. All patient-centered nursing interventions require individualization. In doing so, the possibilities of desirable outcomes of nursing care increase. Conclusion: Research on this theory draws attention to the importance of planning and implementing patient-centered interventions in cancer patients. Given the variables examined, the theory can be tested in different clinics and departments to determine the possibility of application in practice.

The next-generation antiandrogen drugs such as enzalutamide and abiraterone extend survival times and improve quality of life in patients with advanced prostate cancer. However, resistance to both drugs occurs frequently through mechanisms that are incompletely understood. Wnt signaling, particularly through Wnt5a, plays vital roles in promoting prostate cancer progression and induction of resistance to enzalutamide and abiraterone. Development of novel strategies targeting Wnt5a to overcome resistance is an urgent need. In this study, we demonstrated that Wnt5a/FZD2-mediated noncanonical Wnt pathway is overexpressed in enzalutamide-resistant prostate cancer. In patient databases, both the levels of Wnt5a and FZD2 expression are upregulated upon the development of enzalutamide resistance and correlate with higher Gleason score, biochemical recurrence, and metastatic status, and with shortened disease-free survival duration. Blocking Wnt5a/FZD2 signal transduction not only diminished the activation of noncanonical Wnt signaling pathway, but also suppressed the constitutively activated androgen receptor (AR) and AR variants. Furthermore, we developed a novel bioengineered BERA-Wnt5a siRNA construct and demonstrated that inhibition of Wnt5a expression by the BERA-Wnt5a siRNA significantly suppressed tumor growth and enhanced enzalutamide treatment in vivo. These results indicate that Wnt5a/FZD2 signal pathway plays a critical role in promoting enzalutamide resistance, and targeting this pathway by BERA-Wnt5a siRNA can be developed as a potential therapy to treat advanced prostate cancer.

Purpose: To examine the annual hospital volume of surgery in relation to survival in colorectal cancer. Previous studies on hospital volume and survival following colorectal cancer surgery are conflicting. Methods: All 49 032 patients who underwent resection for colorectal cancer in 1987–2016 in Finland were included, with complete follow-up until December 31, 2019. Primary outcome was 5-year mortality. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) for quartiles of annual hospital volume for colorectal surgery, adjusted for calendar period, age, sex, comorbidity, stage, tumor location and oncological therapy. Additionally, colon and rectal cancer surgery were assessed separately. Sensitivity analysis of patients with confirmed curative intent was conducted. Results: Compared to highest quartile (≥108 resections annually), lowest hospital volume (≤37 resections annually) was associated with slightly increased 5-year all-cause mortality (adjusted HR 1.07, 95% CI 1.02–1.12). A pre-planned subgroup-analysis suggested a slightly improved 5-year survival in high-volume institutions for rectal cancer, but not colon cancer surgery. Sensitivity analysis including only those operated with confirmed curative intent suggested no differences between hospital volume groups in colorectal, colon or rectal cancer for 5-year all-cause mortality. Conclusions: Higher hospital volume is associated with slightly improved all-cause 5-year mortality in colorectal cancer surgery, but this effect may be limited to rectal cancer surgery only. Volume-outcome relationship in rectal cancer surgery should be investigated further using large datasets. These results do not support centralization of colon cancer surgery based on hospital volume only.

Background Intestinal microbiota might interact with capecitabine and vice versa. Patients and methods 33 mCRC patients collected faecal samples before, during, and after three cycles capecitabine. Results Intestinal microbiota were not affected by capecitabine and not different between responders and non-responders. Conclusions Our study provides insights into challenges and points of attention for the design of upcoming clinical microbiota studies. Background Previous pre-clinical research has indicated that the intestinal microbiota can potentiate anti-tumour efficacy of capecitabine and that capecitabine treatment impacts intestinal microbiota composition and diversity. Using a longitudinal design, this study explores the associations between the intestinal microbiota and treatment response in patients with metastatic colorectal cancer (mCRC) during capecitabine treatment. Patients and methods Patients with mCRC treated with capecitabine were prospectively enrolled in a multicentre cohort study. Patients collected a faecal sample and completed a questionnaire before, during, and after three cycles of capecitabine. Several clinical characteristics, including tumour response, toxicity and antibiotic use were recorded. Intestinal microbiota were analysed by amplicon sequencing of the 16S rRNA V4 gene-region. Results 33 patients were included. After three cycles of capecitabine, six patients (18%) achieved a partial response, 25 (76%) showed stable disease, and one (3%) experienced progressive disease. 90 faecal samples were collected. Microbial diversity (α-diversity), community structure (β-diversity), and bacterial abundance on phylum and genus level were not significantly different between responders and non-responders and were not significantly affected by three cycles of capecitabine. Conclusions This is the first clinical study with longitudinal intestinal microbiota sampling in mCRC patients that explores the role of the intestinal microbiota during treatment with capecitabine. Intestinal microbiota composition and diversity before, during, and after three cycles of capecitabine were not associated with response in this study population. Capecitabine did not induce significant changes in the microbiota composition and diversity during the treatment period. Individual effects of antibiotics during capecitabine treatment were observed.

Objective Evidence of reduction in colorectal cancer (CRC) mortality following CRC screening based on the faecal immunochemical test (FIT) is insufficient. This study aimed to analyse if CRC mortality was reduced after implementing FIT-based screening. Setting The Danish national CRC screening programme. Methods This nationwide cohort study included residents aged 50–71 years invited to the prevalence round of the screening programme. Invitation order was decided by randomising on birth month; the first two birth months to be invited were classified as invited and the five last were classified as not-yet-invited and given a pseudo invitation data. Follow-up was from (pseudo)invitation date until 31 December 2017, emigration or death. Relative risk (RR) of CRC death was calculated with 95% confidence intervals (CIs). Results A total of 897,812 residents were included (29% invited and 71% not-yet-invited). The median follow-up was 3.3 years. The RR of CRC death at end of follow-up was 0.83 (95% CI 0.66; 1.03) among those invited to screening compared with those not yet invited. For men aged 60–71 years, this RR was 0.68 (95% CI 0.49; 0.94). For those participating in screening compared with a similar group of not-yet-invited residents, the RR was 0.71 (95% CI 0.46–1.08). For male participants aged 60–71 years, this RR was 0.49 (95% CI 0.27−0.89). For women and men aged 50–59 years, RRs were small and statistically non-significant. Conclusion This nationwide study showed that even within a median follow-up of only 3.3 years, implementing FIT-based CRC screening reduced CRC mortality among older men.

Purpose: Paclitaxel (PTX) is one of the most potent and commonly used chemotherapies for breast and pancreatic cancer. Several ongoing clinical trials are investigating means of enhancing delivery of PTX across the blood–brain barrier for glioblastomas. Despite the widespread use of PTX for breast cancer, and the initiative to repurpose this drug for gliomas, there are no predictive biomarkers to inform which patients will likely benefit from this therapy. Experimental Design: To identify predictive biomarkers for susceptibility to PTX, we performed a genome-wide CRISPR knockout (KO) screen using human glioma cells. The genes whose KO was most enriched in the CRISPR screen underwent further selection based on their correlation with survival in the breast cancer patient cohorts treated with PTX and not in patients treated with other chemotherapies, a finding that was validated on a second independent patient cohort using progression-free survival. Results: Combination of CRISPR screen results with outcomes from patients with taxane-treated breast cancer led to the discovery of endoplasmic reticulum (ER) protein SSR3 as a putative predictive biomarker for PTX. SSR3 protein levels showed positive correlation with susceptibility to PTX in breast cancer cells, glioma cells, and in multiple intracranial glioma xenografts models. KO of SSR3 turned the cells resistant to PTX while its overexpression sensitized the cells to PTX. Mechanistically, SSR3 confers susceptibility to PTX through regulation of phosphorylation of ER stress sensor IRE1α. Conclusions: Our hypothesis generating study showed SSR3 as a putative biomarker for susceptibility to PTX, warranting its prospective clinical validation.

Although Tao brush has become one of the most studied and used endometrial cytological samplers, concerns remain about the adequacy of the cytological sample compared with definitive histology. We aimed to assess accuracy of cytological examination from Tao brush sampling in diagnosing endometrial premalignancy and malignancy through a systematic review and meta-analysis. Seven electronic databases were searched from January 2000 to July 2021 for all studies which allowed assessment of accuracy of Tao brush in diagnosing endometrial premalignancy and malignancy. We calculated sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on summary receiver operating characteristic (SROC) curve. Five studies with 774 patients were included. In diagnosing endometrial premalignancy and malignancy, cytological examination from Tao brush endometrial sampling showed pooled sensitivity of 0.95 (95% CI, 0.90-0.98), specificity of 0.92 (95% CI, 0.90-0.94), LR+ of 12.73 (95% CI, 3.94-41.18), LR- of 0.09 (95% CI, 0.05-0.18), DOR of 184.84 (95% CI, 24.37-1401.79), AUC of 0.9757 (standard error: 0.013). In conclusion, cytological examination from Tao brush seems to have a high diagnostic accuracy and might be proposed as both screening and diagnostic tool. However, further studies are necessary to confirm these findings.

Odontogenic keratocysts (OKCs) and orthokeratinized odontogenic Cysts (OOCs) are distinct clinicopathological entities. OKC appears to behave in a way more similar to that of a neoplasm, such as ameloblastoma (AB). The aim of this study is to compare the influence of Ki-67, Cyclin D1 and COX-2 in the diagnosis and pathogenesis of OKC, OOC and AB.A cross-sectional observational study of 41 samples was organized into 3 groups: (1) OKC n=22; (2) AB n=13 and (3) OOC n=6. Paraffin blocks were sectioned and stained with hematoxylin and eosin (HE). Immunohistochemical study using Bond Polymer Refine Red Detection Kit, Leica, Wetzlar, Germany, was performed for the following antibodies: Ki-67, Cyclin D1 and COX-2. Double blind immunostaining was quantified subjectively. Staining: nuclear or cytoplasmic; nuclear (Ki-67 and Cyclin D15% positive) and cytoplasmic (COX-2; 1; 1-30 cytoplasm: 2; 31-60 cytoplasm; 3; 61-100 cytoplasm). Considering positive stained 61-100 cytoplasms.The expression of Ki-67 was higher in the OKC group than in the AB group (p0.05). Cyclin D1 showed a higher expression in OKC vs. OOC and OKC vs. AB (p0.05). Finally, expression of COX-2 was higher in OKC vs AB (p0.05).COX-2, Ki-67 and Cyclin D1 show statistically significant differences between the groups, suggesting that they could be useful tools in the differential diagnosis between OKCs and OOC and a predictive indicator for their biologic behaviour. The higher expressions of these 3 markers of OKC vs AB highlight once more the aggressive behaviour of this now re-considered cystic lesion. These markers could prove useful in the choice of more aggressive surgical treatment in OKCs as their behaviour appears to be similar to that of a neoplasm.

Resumen Introducción: La soledad no deseada es un constructo que se ha relacionado con desenlaces negativos en diferentes aspectos de la salud, incluidos aquellos de los pacientes con cáncer. La escala de soledad de UCLA es un instrumento ampliamente utilizado en el contexto de investigación en salud para medir dicho constructo, y en Colombia la versión 03 de dicho instrumento no se encuentra traducida, ni adaptada transculturalmente. Objetivo: Traducir y adaptar transculturalmente la escala de soledad de UCLA, versión 03 para su uso en pacientes con cáncer en Colombia. Métodos: El proceso de traducción y adaptación transcultural siguió la metodología propuesta por el grupo EORTC, con el objetivo de lograr la equivalencia semántica con la versión original de la escala disponible en inglés. Se realizó una prueba piloto con 20 pacientes colombianos diagnosticados con diferentes tipos de cáncer, que asistieron al Instituto Nacional de Cancerología de Colombia. Resultados: No hubo cambios ni en la traducción de instrucciones ni en las opciones de respuesta. En la versión conciliada se modificó el ítem UC1. En la prueba piloto, dos de 20 pacientes informaron que los ítems UC6, UC7, UC11 y UC19 deberían ser modificados y un paciente mencionó que el ítem UC8 era difícil de entender; sin embargo, no se hicieron cambios dado el bajo número de pacientes que reportaron estos hallazgos, y las sugerencias planteadas podían cambiar el sentido y la equivalencia de los ítems de la escala original. Ninguno de los ítems fue ofensivo para los pacientes. Conclusión: Se generó una versión traducida y adaptada transculturalmente para ser validada en pacientes con cáncer en Colombia. Abstract Introduction: Unwanted loneliness is a construct that has shown relationships with different negative outcomes of health, including those of patients with cancer. In the context of health research, the UCLA loneliness scale is a widely used instrument for measuring this construct. In Colombia, the 03 version of this instrument has still not been neither translated, nor transculturally adapted. Objective: To translate and perform transcultural adaptation of the UCLA loneliness scale, version 03 for its use in patients having cancer in Colombia. Methods: The process of translation and transcultural adaptation followed the methodology proposed by the EORTC group, aimed at achieving semantic equivalence with the original version of the scale. A pilot test has been made with 20 Colombian patients diagnosed with different types of cancer, attending the Instituto Nacional de Cancerología, Colombia. Results: In the reconciliated version, item UC1 has been modified. There has been not changes neither in translation of instructions, nor in response options. In pilot testing two out of 20 patients reported that items UC6, UC7, UC11 y UC19 should be modified and one patient mentioned that item UC8 was difficult to understand; however, no changes were made taking into account the low number of patients describing similar findings, and because these suggestions could change the semantic equivalence of these items. No items were deemed offensive. Conclusion: It is available a transculturally adapted version of the UCLA loneliness scale, version 03 for its validation in patients with cancer in Colombia.

AimsFormal depiction of granulomatous inflammation associated with renal neoplasms has mainly consisted of case reports. Herein, we investigate the clinicopathological features and potential significance of granulomas associated with renal tumours from a large multi-institutional cohort.Methods and resultsOne hundred and eleven study cases were collected from 22 institutions, including 57 partial nephrectomies and 54 radical nephrectomies. Patient ages ranged from 27 to 85 years (average = 60.1 years; male = 61%). Renal neoplasms included clear cell renal cell carcinoma (RCC; 86%), papillary RCC (8%), chromophobe RCC (3%), clear cell papillary RCC (1%), mixed epithelial stromal tumour (1%) and oncocytoma (1%). Granulomas were peritumoral in 36%, intratumoral in 24% and both in 40% of cases. Total granuloma count per case ranged from one to 300 (median = 15) with sizes ranging from 0.15 to 15 mm (mean = 1.9 mm). Necrotising granulomas were seen in 14% of cases. Histochemical stains for organisms were performed on 45% of cases (all negative). Sixteen cases (14%) had a prior biopsy/procedure performed, and eight patients had neoadjuvant immunotherapy or chemotherapy. Eleven patients (10%) had a confirmed diagnosis of sarcoidosis, including five in whom sarcoidosis was diagnosed after nephrectomy.ConclusionBased on this largest case-series to date, peri-/intratumoral granulomas associated with renal neoplasms may be more common than initially perceived. The extent of granulomatous inflammation can vary widely and may or may not have necrosis with possible aetiologies, including prior procedure or immunotherapy/chemotherapy. Although a clinical association with sarcoidosis is infrequent it can still occur, and the presence of granulomas warrants mention in pathology reports.

PURPOSE There is limited evidence on the clinical utility of monitoring measurable residual disease (MRD) in patients with acute myeloid leukemia treated with lower-intensity therapy. Herein, we explored the outcomes of patients treated with venetoclax and azacitidine who achieved composite complete remission (CRc; complete remission + complete remission with incomplete hematologic recovery) and MRD < 10–3 in the VIALE-A trial. METHODS The patients included in this report were treated with venetoclax and azacitidine. Bone marrow aspirate samples for multiparametric flow cytometry assessments were collected for central analysis at baseline, end of cycle 1, and every three cycles thereafter. MRD-negative response was defined as < 1 residual blast per 1,000 leukocytes (< 10–3 or 0.1%) with an estimated analytic sensitivity of 0.0037%-0.0027%. CRc, duration of remission (DoR), event-free survival (EFS), and overall survival (OS) were assessed. A multivariate Cox regression analysis identified prognostic factors associated with OS. RESULTS One hundred sixty-four of one hundred ninety (86%) patients with CRc were evaluable for MRD. MRD < 10–3 was achieved by 67 of 164 (41%), and 97 of 164 (59%) had MRD ≥ 10–3. The median DoR, EFS, and OS were not reached in patients with CRc and MRD < 10–3, and the 12-month estimates for DoR, EFS, and OS in this group were 81.2%, 83.2%, and 94.0%. Among patients with CRc and MRD ≥ 10–3, the median DoR, EFS, and OS were 9.7, 10.6, and 18.7 months. Multivariate analysis showed that CRc with MRD < 10–3 was a strong predictor of OS (adjusted hazard ratio = 0.285; 95% CI, 0.159 to 0.510; P < .001). CONCLUSION Patients who achieved CRc and MRD < 10–3 with venetoclax and azacitidine had longer DoR, EFS, and OS, than responding patients with MRD ≥ 10–3.

Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm.

Background Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. Patients and methods We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). Results Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. Conclusions Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

The final stage of spine neoplasm diagnostics is histological examination. In order to obtain the tissue from neoplasm punction biopsy is used.Objective: to assess the efficacy of punctional biopsy with further pathohistological examination in patients with neoplasm in thoracic and lumbar spine.Methods: we analyzed 259 case histories of patients with pathological spine changes.Results: punction biopsy was made in 238 patients (89 %). In 30 (11 %) patients it was no effective because of the large amount of obtained material, in 27 (10 %) pathohistological diagnosis was not established. Pepeated biopsy was made in these cases. As a result at primary and secondary biopsies the diagnosis was confirmed in 95.5 %.Conclusions: punctional biopsy with pathohystological examination is integral part of diagnostic process at spine neoplasm. It allows to obtain enough material for studying (inspite of the dense of tissues) to decrease the risks of contamination of surrounded tissues. Such minimalinvasive method gives possibility to use it in patients with comorbidities. Most of primary spine cancer is represented by myeloma and malignant lymphoma. Episodic were cases of hondrosarcoma, osteosarcoma and fibrosarcoma, when the lesion was spread on one or two vertebrae. Most frequent non malignant lesions were haemangioma and eosino­philic granuloma. Metastatic disease were revealed in 74 (28 %) of patients and often appeared in cases of low grade cancer and adenocarcinoma., Заключительным этапом диагностики опухолевых заболеваний позвоночника является гистологическое исследование. Для получения ткани из очага поражения используют пункционную биопсию.Цель: оценить эффективность пункционной биопсии (с последующим патогистологическим исследованием) у пациентов с новообразованиями в грудном и поясничном отделах позвоночника.Методы: проанализировано 259 историй болезни пациентов с патологическими изменениями в позвоночнике.Результаты: пункционная биопсия выполнена всем больным. При этом у 30 (11 %) человек она оказалась неэффективной из-за небольшого количества полученного материала, а у 27 (10 %) не установлен патогистологический диагноз. Этим 57 (21 %) пациентам проведена повторная биопсия очага поражения. В результате первичной и вторичной биопсии у 95,5 % обследованных патоморфологически диагноз подтвержден.Выводы: пункционная биопсия с последующим патогистологическим исследованием является неотъемлемым этапом диагностического процесса при новообразованиях позвоночника. Она позволяет получить достаточное количество материала (независимо от плотности ткани) для изучения и уменьшить риск контаминации окружающих тканей. Малоинвазивность метода дает возможность использовать его у пациентов с тяжелыми сопутствующими соматическими патологиями. Большинство злокачествен­ных первичных поражений позвоночника представлены плазмоклеточной миеломой (миеломной болезнью) и злокачественной лимфомой; одиночными были случаи хондросаркомы, остеосаркомы и фибросаркомы, когда очаг поражения распространялся на один или два позвонка. Наиболее часто обнаружены такие доброкачественные поражения позвоночника, как гемангиома и эозинофильная гранулема. Метастатические изменения в позвоночнике выявлены у 74 (28 %) пациентов и чаще всего развивались в случае низкодифференцированного рака и аденокарциномы., Заключним етапом діагностики пухлинних захворювань хребта є гістологічне дослідження. Для отримання тканини з вогнища ураження використовують пункційну біопсію.Мета: оцінити ефективність пункційної біопсії (з подальшим патогістологічним дослідженням) у пацієнтів із новоутвореннями в грудному та поперековому відділах хребта.Методи: проаналізовано 259 історій хвороби пацієнтів із патологічними змінами в хребті.Результати: пункційну біопсію виконано всім хворим. При цьому в 30 (11 %) осіб вона виявилася неефективною через невелику кількість отриманого матеріалу, а у 27 (10 %) не встановлено патогістологічний діагноз. Цим 57 (21 %) пацієнтам проведено повторну біопсію вогнища ураження. У результаті первинної та вторинної біопсії у 95,5 % обстежених патоморфологічно діагноз підтверджений.Висновки: пункційна біопсія з наступним патогістологічним дослідженням є невід’ємним етапом діагностичного процесу в разі новоутворень хребта. Вона дозволяє отримати достатню кількість матеріалу (незалежно від щільності тканини) для вивчення та зменшити ризик контамінації прилеглих тканин. Малоінвазивність методу дає можливість використовувати його в пацієнтів із важкими супутніми соматичними патологіями. Більшість злоякісних первинних уражень хребта представлені плазмоклітинною мієломою (мієломною хворобою) і злоякісною лімфомою; поодинокими були випадки хондросаркоми, остеосаркоми та фібросаркоми, коли вогнище ураження поширювалося на один або два хребця. Найчастіше визначали такі доброякісні ураження хребта, як гемангіома й еозинофільна гранульома. Метастатичні зміни в хребті виявлено в 74 (28 %) пацієнтів і найчастіше розвивалися в разі низькодиференційованого раку й аденокарциноми.

In recent years, new therapies have been developed based on molecules that target molecular mechanisms involved in both the initiation and maintenance of the oncogenic process. Among these molecules are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. PARP1 has emerged as a target with great therapeutic potential for some tumor types, drawing attention to this enzyme and resulting in many small molecule inhibitors of its enzymatic activity. Therefore, many PARP inhibitors are currently in clinical trials for the treatment of homologous recombination (HR)-deficient tumors, BRCA-related cancers, taking advantage of synthetic lethality. In addition, several novel cellular functions unrelated to its role in DNA repair have been described, including post-translational modification of transcription factors, or acting through protein–protein interactions as a co-activator or co-repressor of transcription. Previously, we reported that this enzyme may play a key role as a transcriptional co-activator of an important component of cell cycle regulation, the transcription factor E2F1. Here, we show that PARP inhibitors, which interfere with its activity in cell cycle regulation, perform this without affecting its enzymatic function.

Alternative splicing (AS) is prevalent in cancer, generating an extensive but largely unexplored repertoire of novel immunotherapy targets. We describe I soform peptides from R NA splicing for I mmunotherapy target S creening (IRIS), a computational platform capable of discovering AS-derived tumor antigens (TAs) for T cell receptor (TCR) and chimeric antigen receptor T cell (CAR-T) therapies. IRIS leverages large-scale tumor and normal transcriptome data and incorporates multiple screening approaches to discover AS-derived TAs with tumor-associated or tumor-specific expression. In a proof-of-concept analysis integrating transcriptomics and immunopeptidomics data, we showed that hundreds of IRIS-predicted TCR targets are presented by human leukocyte antigen (HLA) molecules. We applied IRIS to RNA-seq data of neuroendocrine prostate cancer (NEPC). From 2,939 NEPC-associated AS events, IRIS predicted 1,651 epitopes from 808 events as potential TCR targets for two common HLA types (A*02:01 and A*03:01). A more stringent screening test prioritized 48 epitopes from 20 events with “neoantigen-like” NEPC-specific expression. Predicted epitopes are often encoded by microexons of ≤30 nucleotides. To validate the immunogenicity and T cell recognition of IRIS-predicted TCR epitopes, we performed in vitro T cell priming in combination with single-cell TCR sequencing. Seven TCRs transduced into human peripheral blood mononuclear cells (PBMCs) showed high activity against individual IRIS-predicted epitopes, providing strong evidence of isolated TCRs reactive to AS-derived peptides. One selected TCR showed efficient cytotoxicity against target cells expressing the target peptide. Our study illustrates the contribution of AS to the TA repertoire of cancer cells and demonstrates the utility of IRIS for discovering AS-derived TAs and expanding cancer immunotherapies.

Metastasis and failure of present-day therapies represent the most common causes of mortality in patients with cutaneous melanoma. To identify the underlying genetic and transcriptomic landscapes, in this study we analyzed multi-organ metastases and tumor-adjacent tissues from 11 rapid autopsies after treatment with MAPK inhibitor (MAPKi) and/or immune checkpoint blockade (ICB) and death due to acquired resistance. Either treatment elicits shared genetic alterations that suggest immune-evasive, cross-therapy resistance mechanisms. Large, non-clustered deletions, inversions and inter-chromosomal translocations dominate rearrangements. Analyzing data from separate melanoma cohorts including 345 therapy-naive patients and 35 patients with patient-matched pre-treatment and post-acquired resistance tumor samples, we performed cross-cohort analyses to identify MAPKi and ICB as respective contributors to gene amplifications and deletions enriched in autopsy versus therapy-naive tumors. In the autopsy cohort, private/late mutations and structural variants display shifted mutational and rearrangement signatures, with MAPKi specifically selecting for signatures of defective homologous-recombination, mismatch and base-excision repair. Transcriptomic signatures and crosstalks with tumor-adjacent macroenvironments nominated organ-specific adaptive pathways. An immune-desert, CD8+-macrophage-biased archetype, T-cell exhaustion and type-2 immunity characterized the immune contexture. This multi-organ analysis of therapy-resistant melanoma presents preliminary insights with potential to improve therapeutic strategies.

Anal sac neoplasms are common in companion animals, and the epidemiological profile has been extensively described in international studies; however, national data are still lacking. Data on the Brazilian reality of anal sac carcinoma cases’ diagnosis and treatment are also scarce. The purpose of this study was to retrospectively evaluate cases of canine anal sac carcinoma and assess the profile of involvement, tumor size, and lymphatic invasion at the time of diagnosis. Information was obtained from Vetpat laboratory database, from 260 cases spanning a 12-year period (2010-2021). In histopathological evaluation at the time of diagnosis, data on sex, age, and race were described, as well as tumor size and lymphatic invasion. The presence of metastasis was also assessed in cases where lymph nodes were sampled. Simple descriptive statistical analysis was used to evaluate the data. Adult and elderly, female, and mixed-breed animals were more involved, indicating differences from international studies that can be attributed to sociocultural factors. In terms of tumor size, it was observed that 93% of the cases had the largest diameter above 2.5cm. Only 7% of the cases had the largest diameter below 2.5cm, demonstrating the often late diagnosis and the importance of rectal palpation examination during the general physical assessment of canine patients, particularly at an advanced age. Regarding lymphatic invasion and affected lymph nodes, 50% of the cases had lymphatic invasion described in the histopathological examination. However, only 5% of the lymph nodes were sent along with the primary tumor, indicating the disease’s aggressive behavior but with possible metastases underdiagnosed. RESUMO: As neoplasias de saco anal possuem incidência importante nos animais de companhia, tendo o seu perfil epidemiológico de acometimento amplamente descrito em estudos internacionais, entretanto dados nacionais ainda são escassos. De modo semelhante, dados acerca da realidade brasileira, associados ao diagnóstico e conduta desses casos, são inexistentes. O objetivo do presente trabalho foi avaliar, de forma retrospectiva, os casos de carcinoma de saco anal canino, avaliando o perfil de acometimento, o tamanho tumoral e a invasão linfática no momento do diagnóstico. Foi obtido informações de 260 casos, respectivo a um período de 12 anos (2010-2021), proveniente do banco de dados do laboratório Vetpat. Foram descritos os dados acerca do sexo, idade e raça, bem como o tamanho tumoral e presença de invasão linfática em avaliação histopatológica no momento do diagnóstico. Os casos que cursavam com envio dos linfonodos também foram avaliados quanto a presença de metástase. Os dados foram avaliados mediante análise estatística descritiva simples. Foi encontrado um maior acometimento em animais adultos a idosos, do sexo feminino e sem raça definida, evidenciando diferenças em relação a estudos internacionais, que podem ser atribuídas a fatores socioculturais. Em relação ao tamanho tumoral, observou-se que 93% dos casos apresentavam o maior diâmetro acima de 2,5cm e apenas 7% dos casos apresentavam o maior diâmetro abaixo de 2,5cm, evidenciando o diagnostico frequentemente tardio, bem como a importância do exame de palpação retal durante a avaliação física geral de pacientes caninos, principalmente em idade avançada. Quanto a avaliação da invasão linfática e linfonodos acometidos, 50% dos casos cursavam com invasão linfática descrita em exame histopatológico, entretanto em apenas 5% dos casos os linfonodos foram enviados junto ao tumor primário, evidenciando o comportamento agressivo da doença, porém com metástases possivelmente subdiagnosticadas.

Burkitt lymphoma (BL) is a rare, mature, fast-growing and highly aggressive B-cell neoplasm. It has a high-proliferation rate with distinctive genetic changes in the C-MYC oncogene. Treatment usually requires intense and frequent chemotherapy regimens with central nervous system prophylaxis as the usual regimens used for other non-Hodgkin’s lymphoma yield poor survival in BL. This report discusses a patient who was diagnosed with a stage II, high-grade BL who received one cycle of intense chemotherapy and refused further treatment. That patient remained in complete remission in his last follow-up; 7 years from diagnosis without requiring other therapies for his lymphoma.

INTRODUÇÃO:O câncer de mama se caracteriza como uma disfunção celular, em que há uma proliferação exacerbada de determinadas células do nosso corpo, em que sua multiplicação rápida e desordenada caracteriza como uma neoplasia maligna resultando em um tumor, seus fatores para esse comportamento podem estar relacionados à ambientais ou genéticos. Estudos têm mostrado que a obesidade tem ação direta no desenvolvimento de câncer de mama e seu mecanismo de inflamação corporal tem contribuído para que a incidência dessa neoplasia esteja cada vez mais presente na sociedade.OBJETIVO: Analisar e discorrer sobre a prevalência da obesidade nos aspectos de ocorrência do câncer de mama.METODOLOGIA: Trata-se de uma revisão integrativa da literatura, com abordagem qualitativa e descritiva, realizada de janeiro à março de 2023, com a questão norteadora: “Qual a prevalência da obesidade nos aspectos de ocorrência do câncer de mama? ”As bases de dados utilizadas foram Scielo, Lilacs e PubMed, utilizou-se os descritores Decs sob aplicação do operador booleano AND. “Obesidade”, “Câncer de mama”, “Neoplasias”, “Fatores de Prevalência” Artigos na janela temporal de 2019 a 2023.RESULTADOS:Mediante análise dos estudos, constatou-se que a obesidade influencia substancialmente na ocorrência do câncer de mama, com prevalência em mulheres, no entanto, o aumento do sobrepeso em homens têm sido preocupação para o crescimento de desenvolvimento da neoplasia, em uma classe considerada de ocorrência rara. Além disso, as taxas de obesos no Brasil têm crescido com expectativas alarmantes para os próximos anos, atribuindo ainda a relação direta para o crescimento da patologia na mesma proporção, sendo indiscutível ser um problema de saúde pública.CONSIDERAÇÕES FINAIS:Em síntese, nota-se que os dados obtidos demonstram ação direta e preocupante que a obesidade desempenha nos aspectos de ocorrência do câncer de mama, além da larga incidência e crescimento da associação obesidade e neoplasia mamária. Para tanto, acendendo o alerta para mudanças de hábitos e necessidade de políticas públicas na saúde.

Objective: Verify interobserver and intraobserver agreement of malignant compressive vertebral fractures (MCVF) diagnosis using magnetic resonance imaging (MRI). Methods: We retrospectively included a lumbar spine MRI of 63 patients with non-traumatic compressive vertebral fracture diagnoses. Each lumbar vertebra was classified as: without fracture, with fracture of benign characteristics, or with fracture of malignant characteristics. Two medical residents in radiology, one musculoskeletal radiologist fellow, one musculoskeletal radiologist, and two spine surgeons evaluated MRI exams, independently and blindly. Each observer performed two readings, with a 15-day interval between evaluations. A simple Kappa coefficient was used to calculate the intra and interobserver agreement. The reference standard classification was based on bone biopsy or clinical, and imaging follow-up of at least two years, for diagnostic performance analysis. Diagnostic performance was assessed by calculating sensitivity, specificity, accuracy, and positive and negative predictive values with a 95% confidence interval (CI). Results: We observed substantial to perfect intraobserver agreement (kappa: 0.80 to 1.00) and substantial interobserver agreement (kappa 0.64 to 0.77). In general, the sensitivity for the detection of MCVF was moderate, except for the second-year radiology resident that achieved a lower sensitivity. The specificity, accuracy, and negative predictive value were high for all observers. Conclusion: MCVF diagnosis using MRI showed substantial interobserver agreement. The second-year medical resident achieved lower sensitivity but high specificity for MCVF. Regarding the seniors, there was no statistical significance between spine surgeons and the musculoskeletal radiologist. Level of Evidence III; Diagnostic. RESUMO Objetivo: Verificar a concordância interobservador e intraobservador no diagnóstico de fraturas vertebrais compressivas malignas (MCVF) por meio de ressonância magnética (MRI). Métodos: Incluiu-se retrospectivamente a ressonância magnética da coluna lombar de 63 pacientes com diagnóstico de fratura vertebral compressiva não traumática. Cada vértebra lombar foi classificada da seguinte forma: sem fratura, com fratura de características benignas ou com fratura de características malignas. Dois médicos residentes em radiologia, um pesquisador radiologista musculoesquelético, um radiologista musculoesquelético e dois cirurgiões da coluna vertebral avaliaram os exames de ressonância magnética, independentemente e cegamente. Cada observador realizou duas leituras, com um intervalo de 15 dias entre as avaliações. O coeficiente Kappa simples foi utilizado para calcular o acordo intra e interobservador. A classificação padrão de referência foi baseada em biópsia óssea ou clínica, e acompanhamento por imagem de pelo menos dois anos, para análise de desempenho diagnóstico. O desempenho diagnóstico foi avaliado através do cálculo de sensibilidade, especificidade, precisão, valores preditivos positivos e negativos com um intervalo de confiança de 95% (IC). Resultados: Foi observada concordância substancial a perfeita intraobservador (kappa: 0,80 a 1,00) e concordância substancial interobservador (kappa 0,64 a 0,77). Em geral, a sensibilidade para a detecção de MCVF foi moderada, exceto para o segundo ano de residência radiológica que alcançou uma sensibilidade menor. A especificidade, precisão e valor preditivo negativo foram altos para todos os observadores. Conclusão: O diagnóstico de MCVF por ressonância magnética mostrou uma concordância substancial entre observadores. O residente médico do segundo ano alcançou uma sensibilidade menor, mas alta especificidade para MCVF. Com relação aos veteranos, não houve significância estatística entre os cirurgiões da coluna vertebral e o radiologista músculo-esquelético. Nível de Evidencia III; Diagnóstico.

Simple Summary The present study investigated the histological characteristics of 35 tumors from 21 lizards, 1 snake, 10 tortoises and 3 turtles that were initially diagnosed as squamous or basal cell carcinoma. Based on in-depth re-evaluation of the tissue characteristics, eight tumors initially diagnosed as squamous cell carcinoma were re-classified as basal cell carcinomas and three squamous cell carcinomas proved to be non-neoplastic lesions. All squamous and basal cell carcinomas were classified into distinct histological variants. To date, basal cell carcinomas have only been described in two reptile species. In the present study, basal cell carcinomas were diagnosed in seven additional species. While immunohistochemical staining with cyclooxygenase-2 and E-cadherin showed significant differences between the examined squamous and basal cell carcinomas, no immunoreactivity was observed for epithelial antigen clone Ber-EP4 and epithelial membrane antigen. The results of this study provide a proposal classification that allows the differentiation of squamous and basal cell carcinoma and their histological variants in squamates and chelonians. In the present study, the histological characteristics of squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs) obtained from 22 squamate and 13 chelonian species were retrospectively evaluated. While the examined tissues were originally diagnosed as 28 SCCs and 7 BCCs based on histological evaluation by a specialty diagnostic service, eight SCCs could be re-classified as BCCs and three SCCs proved to be non-neoplastic lesions. In addition, all SCCs and BCCs were classified into distinct histological variants. The SCCs could be categorized as one SCC in situ, three moderately differentiated SCCs, seven well-differentiated SCCs, and six keratoacanthomas. BCCs were classified as five solid BCCs, four infiltrating BCCs, five keratotic BCCs, and one basosquamous cell carcinoma. In addition, the present study reports the occurrence of BCCs in seven reptile species for the first time. In contrast to what has been documented in humans, IHC staining with the commercially available epithelial membrane antigen and epithelial antigen clone Ber-EP4 does not allow differentiation of SCCs from BCCs in reptiles, while cyclooxygenase-2 and E-cadherin staining seem to have discriminating potential. Although the gross pathological features of the examined SCCs and BCCs were highly similar, each tumor could be unequivocally assigned to a distinct histological variant according to the observed histological characteristics. Based on the results of this study, a histopathological classification for SCCs and BCCs is proposed, allowing accurate identification and differentiation of SCCs and BCCs and their histological variants in the examined reptile species. Presumably, BCCs are severely underdiagnosed in squamates and chelonians.

BackgroundHepatocellular adenoma (HCA) is a rare liver tumour, which can have atypical morphological features such as cytological atypia, pseudoglandular architecture, and altered reticulin framework. Little is known about the genetic and epigenetic alterations of such HCAs and whether they show the alterations classically found in hepatocellular carcinoma (HCC) or in HCA without atypical morphology. MethodsWe analysed five HCAs with atypical morphological features and one HCA with transition to HCC. Every tumour was subtyped by immunohistochemistry, sequenced by a targeted NGS panel, and analysed on a DNA methylation microarray. ResultsSubtyping of the five HCAs with atypical features revealed two beta-catenin mutated HCA (b-HCA), two beta-catenin mutated inflammatory HCA (b-IHCA), and one sonic hedgehog activated HCA (shHCA). None of them showed mutations typically found in HCC, such as, e.g. TERT or TP53 mutations. The epigenomic pattern of HCAs with atypical morphological features clustered with reference data for HCAs without atypical morphological features but not with HCC. Similarly, phyloepigenetic trees using the DNA methylation data reproducibly showed that HCAs with morphological atypia are much more similar to nonmalignant samples than to malignant samples. Finally, atypical HCAs showed no relevant copy number variations (CNV). ConclusionIn our series, mutational, DNA methylation, as well as CNV analyses, supported a relationship of atypical HCAs with nonatypical HCAs rather than with HCC. Therefore, in cases with difficult differential diagnosis between HCC and HCA, it might be advisable to perform targeted sequencing and/or combined methylation/copy number profiling.

Chronic myeloid leukemia (CML) is a blood cancer characterized by dysregulated production of maturing myeloid cells driven by the product of the Philadelphia chromosome, the BCR-ABL1 tyrosine kinase. Tyrosine kinase inhibitors (TKIs) have proved effective in treating CML, but there is still a cohort of patients who do not respond to TKI therapy even in the absence of mutations in the BCR-ABL1 kinase domain that mediate drug resistance. To discover novel strategies to improve TKI therapy in CML, we developed a nonlinear mathematical model of CML hematopoiesis that incorporates feedback control and lineage branching. Cell–cell interactions were constrained using an automated model selection method together with previous observations and new in vivo data from a chimeric BCR-ABL1 transgenic mouse model of CML. The resulting quantitative model captures the dynamics of normal and CML cells at various stages of the disease and exhibits variable responses to TKI treatment, consistent with those of CML patients. The model predicts that an increase in the proportion of CML stem cells in the bone marrow would decrease the tendency of the disease to respond to TKI therapy, in concordance with clinical data and confirmed experimentally in mice. The model further suggests that, under our assumed similarities between normal and leukemic cells, a key predictor of refractory response to TKI treatment is an increased maximum probability of self-renewal of normal hematopoietic stem cells. We use these insights to develop a clinical prognostic criterion to predict the efficacy of TKI treatment and design strategies to improve treatment response. The model predicts that stimulating the differentiation of leukemic stem cells while applying TKI therapy can significantly improve treatment outcomes.

Although widely studied, the association between migraines (M) and breast cancer (BC) risk remains evasive. In this prospective single-center study, 440 early or locally advanced BC patients were enrolled at IRCCS Humanitas Research Hospital. Clinical and demographical data were collected. Those who suffered from headaches were evaluated with the International Classification of Headache Disorders. M was found to be significantly more prevalent in BC patients: 56.1% versus an expected prevalence of 17% in the global population. M patients showed a higher risk of having stage II or III BC than stage I, which was more frequently found in the non-headache population. Interestingly, the frequency of headache attacks was positively correlated with estrogen (r = 0.11, p = 0.05) and progesterone (r = 0.15, p = 0.007) expression, especially in patients with migraine without aura. The higher the expression of hormone receptors in BC, the higher the headache frequency. Moreover, patients suffering from headaches showed an overall earlier onset of BC. Our findings challenge the idea of a net preventive role of M on BC, suggesting a rather complex interaction in which M mostly influences some BC subtypes and vice versa. Further multi-center studies with extended follow-up are needed.

A Organização Mundial da Saúde (OMS) define planta medicinal como sendo todo e qualquer vegetal que possui substâncias que podem ser utilizadas com fins terapêuticos. Como nos casos do câncer, em sua grande maioria, é considerado como um dos problemas mais desafiadores da medicina, sendo uma das alternativas o uso de plantas medicinais, como por exemplo o Pau D’Arco (Handroanthus avellanedae (Lorentz Ex Griseb) Mattos), também muito conhecida como Ipê Roxo. Esta espécie tem como principais constituintes as naftoquinonas lapachol e β-lapachona, com atividade antineoplásica, sendo que nos ensaios de avaliação farmacológica de atividade antitumoral, as preparações feitas com o extrato da planta (complexo fitoterápico) se mostraram mais eficazes do que aquelas feitas com qualquer de seus princípios ativos, isoladamente, indicando a existência de uma ação sinérgica entre seus componentes. Foi realizada revisão de escopo, onde pode verificar que a medicina complementar enfatizando o uso de plantas medicinais são comprovadas cientificamente na sua eficácia contra a neoplasia e na diminuição da sintomatologia do tratamento agressivo, porém é necessário que os pacientes sejam acompanhados para correto uso desses medicamentos fitoterápicos.

Background Breast tumors consist of heterogeneous cellular subpopulations that differ in molecular properties and functional attributes. Cancer stem cells (CSCs) play pivotal roles in cancer therapeutic failure and metastasis. However, it remains indeterminate how CSCs determine the progression of the bulk cancer cell population. Methods Co-culture systems in vitro and co-implantation systems in vivo were designed to characterize the interactions between breast cancer stem cells (BCSCs) and bulk cancer cells. RNA sequencing was performed to study the functional and mechanistic implications of the BCSC secretome on bulk cancer cells. A cytokine antibody array was employed to screen the differentially secreted cytokines in the BCSC secretome. Tail vein injection metastatic models and orthotopic xenograft models were applied to study the therapeutic potential of targeting IL8. Results We identified that the BCSC secretome potentiated estrogen receptor (ER) activity in the bulk cancer cell population. The BCSC secretome rendered the bulk cancer cell population resistant to anti-estrogen and CDK4/6 inhibitor therapy; as well as increased the metastatic burden attributable to bulk cancer cells. Screening of the BCSC secretome identified IL8 as a pivotal factor that potentiated ERα activity, endowed tamoxifen resistance and enhanced metastatic burden by regulation of bulk cancer cell behavior. Pharmacological inhibition of IL8 increased the efficacy of fulvestrant and/or palbociclib by reversing tamoxifen resistance and abrogated metastatic burden. Conclusion Taken together, this study delineates the mechanism by which BCSCs determine the therapeutic response and metastasis of bulk cancer cells; and thereby suggests potential therapeutic strategies to ameliorate breast cancer outcomes.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1–3. Here we developed a clinical-grade approach based on CRISPR–Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRβ). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen–HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial (NCT03970382). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

Evidence shows that exercise can have a favourable effect in cancer patients. The exercise’s clinical benefits are likely to concern multiple interrelated biological pathways, among which oxidative stress plays a key role. Regular training can induce an adaptive response that strengthens the antioxidative status of the body. To formulate public health recommendations regarding the optimal exercise prescription for cancer patients, a detailed understanding is needed regarding the effect of exercise on variables linked to oxidative stress and antioxidant status of patients. The goal of this systematic review, based on PRISMA, was to explore and critically analyse the evidence regarding the efficacy of exercise on oxidative stress biomarkers among people with cancer. Study search was conducted in the following databases: PubMed, Cochrane, CINAHL, Embase, PEDro, and SPORTDiscus. The studies’ quality was assessed with the Cochrane risk-of-bias tool and STROBE scale. After identification and screening steps, 10 articles were included. The findings provide an encouraging picture of exercise, including resistance training and aerobic activities, in people with cancer. The exercise improved the indicators of the total antioxidant capacity, increased the antioxidant enzymes’ activity, or reduced the biomarkers of oxidative damage in various forms of cancer such as breast, lung, head, and neck. Regarding oxidative DNA damage, the role of exercise intervention has been difficult to assess. The heterogeneity of study design and the plethora of biomarkers measured hampered the comparison of the articles. This limited the possibility of establishing a comprehensive conclusion on the sensitivity of biomarkers to estimate the exercise’s benefits. Further high-quality studies are required to provide data regarding oxidative stress biomarkers responding to exercise. This information will be useful to assess the efficacy of exercise in people with cancer and support the appropriate prescription of exercise in anticancer strategy.

O cistoadenoma seroso pancreático, também chamado de adenoma microcístico, é uma neoplasia de pâncreas relativamente rara. Geralmente benigna, no entanto, pode gerar quadro clínico relevante e ocasionalmente levar à morte, caso haja hemorragia intra-abdominal, obstrução do trato biliar ou gastrointestinal. Por se tratar de um achado pouco frequente, o presente relato visa mostrar as características radiológicas desta neoplasia, a fim de auxiliar o diagnóstico precoce.

Langerhans cell histiocytosis (LCH) is a neoplasm marked by the accumulation of CD1A+CD207+ cells. It is most commonly driven by a somatic, activating mutation in the BRAF serine-threonine kinase (BRAFV600E). Multisystem disease with risk-organ involvement requires myelotoxic chemotherapy, making BRAF-inhibitors an attractive treatment option. Here, we present a comprehensive analysis of the course of an LCH patient treated with the combination of vemurafenib and salvage chemotherapy who achieved sustained clinical and molecular remission. We show that there is no relationship between peripheral blood BRAFV600E levels and clinical presentation during treatment with vemurafenib, but that vemurafenib leads to a fast, efficient, but reversible inhibition of clinical manifestations of systemic inflammation. In line, serum levels of inflammatory cytokines exactly mirror vemurafenib administration. Genotyping analysis identified the BRAFV600E mutation in multiple hematopoietic cell types, including NK cells and granulocytes. Single-cell transcriptome analyses of peripheral blood and bone marrow cells at time of diagnosis and during treatment indicate that RAF-inhibition abrogates the expression of inflammatory cytokines previously implicated in LCH such as IL1B and CXCL8. Together, our data suggest that while the CD1A+CD207+ histiocytes are the hallmark of LCH, other BRAF-mutated cell populations may contribute significantly to morbidity in patients with multisystem LCH.

Background Ear canal and middle ear tumors are rare and exhibit variability in histology and clinical manifestation. Surgical resection remains the treatment of choice, but individualized approach is needed to preserve function when possible. Aims/objectives To review the management and outcome of ear canal and middle ear tumors at an academic referral center. Materials and methods Helsinki University Hospital (HUS) patient files were searched for clinically and histologically confirmed ear canal and middle ear tumors over a 14-year period. The minimum follow-up time was 2 years. Results Eighty-seven patients with 88 tumors were identified. There were 20 (23%) benign external auditory canal (EAC), 36 (41%) benign middle ear space (MES), 29 (33%) malignant EAC, and 3 (3%) malignant MES tumors. Most (92%) tumors were managed with primary resection. Thirty-five percent of the operatively managed patients had a residual or a recurrent tumor. Conclusions and significance EAC and MES tumors show great diagnostic and histologic heterogeneity with need for individualized investigative and treatment approaches. In benign tumors, we advocate aggressive local surgical control without sacrificing vital structures. In malignant tumors, we recommend local surgical control with or without adjunct RT.

International audience; Intensity modulated radiation therapy and brachytherapy are standard techniques of irradiation for the treatment of oral cavity cancers. These techniques are detailed in terms of indication, planning, delineation and selection of the volumes of interest, dosimetry and patients positioning control. This is an update of the guidelines of the French Society of Radiotherapy Correspondence.

Growing bodies of evidence have demonstrated that the identification of prostate cancer (PCa) biomarkers in the patients' blood and urine may remarkably improve PCa diagnosis and progression monitoring. Among diverse cancer-derived circulating materials, extracellular RNA molecules (exRNAs) represent a compelling component to investigate cancer-related alterations. Once outside the intracellular environment, exRNAs circulate in biofluids either in association with protein complexes or encapsulated inside extracellular vesicles (EVs). Notably, EV-associated RNAs (EV-RNAs) were used for the development of several assays (such as the FDA-approved Progensa Prostate Cancer Antigen 3 (PCA3 test) aiming at improving early PCa detection. EV-RNAs encompass a mixture of species, including small non-coding RNAs (e.g. miRNA and circRNA), lncRNAs and mRNAs. Several methods have been proposed to isolate EVs and relevant RNAs, and to perform RNA-Seq studies to identify potential cancer biomarkers. However, EVs in the circulation of a cancer patient include a multitude of diverse populations that are released by both cancer and normal cells from different tissues, thereby leading to a heterogeneous EV-RNA-associated transcriptional signal. Decrypting the complexity of such a composite signal is nowadays the major challenge faced in the identification of specific tumor-associated RNAs. Multiple deconvolution algorithms have been proposed so far to infer the enrichment of cancer-specific signals from gene expression data. However, novel strategies for EVs sorting and sequencing of RNA associated to single EVs populations will remarkably facilitate the identification of cancer-related molecules. Altogether, the studies summarized here demonstrate the high potential of using EV-RNA biomarkers in PCa and highlight the urgent need of improving technologies and computational approaches to characterize specific EVs populations and their relevant RNA cargo.

Objective: To evaluate the effectiveness of exercise for improving bone-related outcomes among cancer survivors. Design: Systematic review and meta-analysis. Methods: An electronic search using the following databases: SPORTDiscus, Science Direct, CINAHL, MEDLINE, Cochrane, Pubmed, Ebscohost, ProQuest Nursing and Allied Health Source. Randomised, controlled, exercise trials involving cancer survivors were eligible. Effect data on bone mineral content (BMC) and density (BMD) outcomes were extracted. Risk of bias was assessed using the Physiotherapy Evidence Database tool. Standardised mean differences (SMD) were calculated to compare differences between exercise and usual care. Subgroup analyses were conducted to assess whether effect differed by exercise mode, intervention length, supervision, treatment, cancer type and risk of bias. Results: Twenty-six trials were included, with intervention durations ranging between 12 weeks and 2 years. Most trials involved breast cancer (n = 13, 50%), and most interventions were supervised (n = 18, 69%) and evaluated mixed-mode (i.e., combined aerobic and resistance) exercise (n = 13, 50%). Significant effects in favour of exercise (aerobic, resistance, mixed-mode and other exercise) were observed for whole body BMD, hip BMD, trochanter BMD and femoral neck BMD (SMD range: 0.19–0.39, all p < 0.05) compared to usual care. Conclusion: Participation in various modes (aerobic, resistance, mixed-mode and other) of supervised and unsupervised exercise is associated with improvements in BMD. The present results provide evidence for clinicians and other health care professionals (e.g., exercise physiologists and physiotherapists) to recommend exercise for cancer survivors to prevent bone loss during and following treatment. Refereed/Peer-reviewed

Uterine adenosarcoma is usually a low-grade neoplasm with a mixed benign epithelial component and malignant stroma, commonly found in postmenopausal women. In the presence of sarcomatous overgrowth, it has been shown to have poor prognosis. Uterine adenosarcoma with sarcomatous overgrowth and rhabdoid features is extremely rare. We report here a case of a 28-year-old female who was found to have adenosarcoma with sarcomatous overgrowth with extensive rhabdoid features. The tumor had metastasized to the pelvis, omentum, iliac, and obturator lymph nodes. She was lost to follow-up for 10 months, after which she presented with recurrent tumor at the hysterectomy site. She was started on palliative chemoradiotherapy, on which she progressed but later experienced drug toxicity, became cachectic, and was unwilling to continue chemotherapy. There are a few cases of adenosarcoma with sarcomatous overgrowth reported in young women and only two cases with rhabdoid features. Based on this report, adenosarcoma with sarcomatous overgrowth and rhabdoid features appears to be an extremely aggressive tumor with poor prognosis.