Oncology Education in Angola: Current Status and Recommendations for Improvement.

Angola, a country grappling with prevalent tropical diseases such as malaria, is witnessing an alarming rise in cancer-related deaths. Despite the escalating significance of cancer globally and in Angola, the nation's medical schools lack compulsory oncology disciplines in their curricula. This absence compromises the comprehensive training of medical students, preventing the development of integrated perspectives and skills crucial for addressing the growing cancer burden. This article, authored by the Angolan Oncology Research Group (AORG), proposes an oncology program for undergraduate medical students in Angola, aiming to bridge the educational gap. The program outlines discipline objectives, topics to be covered, class formats, and workload considerations.

Is the incidence rate of colorectal cancer increasing in Mozambique?

Background: Colorectal cancer (CRC) is a significant global health concern, ranking as the third most common cancer and the second leading cause of cancer-related deaths. However, in Africa, CRC is the fifth most common invasive malignancy. Limited data hinder our understanding of the evolving burden of CRC in sub-Saharan Africa. This study explores CRC trends in Mozambique, utilising data from population-based oncological registries. Methods: CRC data were gathered from Beira and Maputo population-based cancer registries, along with supplementary information from pathology-based and hospital-based registries. Comparative analyses were performed across different time periods, focusing on trends and epidemiological characteristics. Results: Incidence rates of CRC in Maputo and Beira were relatively low historically. However, data from recent years showed an increase, especially in age groups above 50. Analyses from pathology-based and hospital-based registries affirmed the rising trend. The age-standardised incidence rate in Maputo (2015-2017) was 3.17 for males and 2.55 for females. Beira exhibited increasing rates between 2009 and 2020, particularly in individuals aged 50 and above. Conclusion: The study reveals an emerging burden of CRC in Mozambique, challenging the perception of low incidence. The rising trend underscores the necessity for tailored interventions, emphasizing early diagnosis, preventive strategies, and investments in healthcare infrastructure to address the increasing CRC burden in the region.

Shaping the future of oral cancer diagnosis: advances in salivary proteomics.

INTRODUCTION: Saliva has gained increasing attention in the quest for disease biomarkers. Because it is a biological fluid that can be collected is an easy, painless, and safe way, it has been increasingly studied for the identification of oral cancer biomarkers. This is particularly important because oral cancer is often diagnosed at late stages with a poor prognosis. AREAS COVERED: The review addresses the evolution of the experimental approaches used in salivary proteomics studies of oral cancer over the years and outlines advantages and pitfalls related to each one. In addition, examines the current landscape of oral cancer biomarker discovery and translation focusing on salivary proteomic studies. This discussion is based on an extensive literature search (PubMed, Scopus and Google Scholar). EXPERT OPINION: The introduction of mass spectrometry has revolutionized the study of salivary proteomics. In the future, the focus will be on refining existing methods and introducing powerful experimental techniques such as mass spectrometry with selected reaction monitoring, which, despite their effectiveness, are still underutilized due to their high cost. In addition, conducting studies with larger cohorts and establishing standardized protocols for salivary proteomics are key challenges that need to be addressed in the coming years.

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

Rehabilitación Respiratoria con cánula nasal de alto flujo en pacientes con enfermedades respiratorias crónicas

Las enfermedades respiratorias crónicas, se incrementan a nivel mundial, destacándose EPOC, fibrosis pulmonar, bronquiectasia y sumándose la condición post COVID-19 asociadas a las vías respiratorias. Objetivo. Determinar los efectos de la rehabilitación respiratoria con cánula nasal de alto flujo en pacientes con enfermedades respiratorias crónicas. Material y método. Estudio realizado en un hospital militar peruano a una muestra constituida por 115 pacientes, quienes ingresaron a un programa de Rehabilitación Respiratoria de 12 semanas con la asistencia de la Cánula de alto flujo durante cada sesión y evaluados al inicio y al final mediante el test de pararse y sentarse en un minuto. El diseño fue pre experimental con pre y post test, corte longitudinal, de tipo aplicada. Se obtuvo la media y desviación estándar y se realizó la prueba de rangos con signo de Wilcoxon, se consideró una significancia del 95% y un valor p<0,05 como estadísticamente significativo. Resultados. La media de la edad fue de 58,30 ± 8,17; el 62,6% fue hombres y 37,4% mujeres; los pacientes con condición Post COVID-19 fueron el 71.30%, seguidos de fibrosis pulmonar con 12,17%; con 7,16±1,24 (p<0,000), en el número de repeticiones mediante pararse y sentarse durante un minuto, lo que mejoró principalmente la fatiga muscular (p<0,003). Conclusiones. Se determina como cambio, que se duplica lo mínimamente significativo mediante la prueba de pararse y sentarse durante un minuto. Además, se evidencia mejor respuesta al ejercicio, con menor disnea y fatiga muscular, por efecto de la presión positiva de la cánula de alto flujo.

Chronic respiratory diseases are increasing worldwide, with COPD, pulmonary fibrosis, bronchiectasis and post COVID-19 conditions associated with the respiratory tract standing out. Objective. To determine the effects of respiratory rehabilitation with high-flow nasal cannula in patients with chronic respiratory diseases. Method. Study carried out in a Peruvian military hospital on a sample of 115 patients, who entered a 12-week Respiratory Rehabilitation program with the assistance of the high-flow nasal cannula during each session and evaluated at the beginning and at the end by means of the test of standing up and sitting down in one minute. The design was pre-experimental with pre- and post-test, longitudinal cut, applied type. The mean and standard deviation were obtained and the Wilcoxon signed-rank test was performed, a significance of 95% and a value p<0.05 was considered statistically significant. Results. The mean age was 58.30±8.17; 62.6% were male and 37.4% female; patients with Post COVID-19 condition were 71.30%, followed by pulmonary fibrosis with 12.17%; with 7.16±1.24 (p<0.000), in the number of repetitions by standing and sitting for one minute, which mainly improved muscle fatigue (p<0.003). Conclusions. It is determined as a change, that the minimally significant is duplicated by the test of standing and sitting for one minute. In addition, a better response to exercise is evidenced, with less dyspnea and muscle fatigue, due to the effect of the positive pressure of the high flow cannula.

As doenças respiratórias crónicas estão a aumentar em todo o mundo, com destaque para a DPOC, a fibrose pulmonar, as bronquiectasias e as doenças pós-COVID-19 associadas ao trato respiratório. Objetivo. Determinar os efeitos da reabilitação respiratória com cânula nasal de alto fluxo em doentes com doenças respiratórias crónicas. Método. Estudo realizado num hospital militar peruano com uma amostra de 115 pacientes, que entraram num programa de Reabilitação Respiratória de 12 semanas com a assistência da cânula nasal de alto fluxo durante cada sessão e avaliados no início e no fim através do teste de sentar e levantar de um minuto. O delineamento foi pré-experimental com pré e pós-teste, longitudinal, do tipo aplicado. Obteve-se média e desvio padrão e realizou-se o teste de Wilcoxon signed-rank, com 95% de significância e valor de p < 0,05 foi considerado estatisticamente significativo. Resultados. A média de idade foi de 58,30±8,17; 62,6% eram do sexo masculino e 37,4% do sexo feminino; pacientes com quadro pós COVID-19 foram 71,30%, seguido de fibrose pulmonar com 12,17%; com 7,16±1,24 (p<0,000), no número de repetições em pé e sentado por um minuto, que melhorou principalmente a fadiga muscular (p<0,003). Conclusões. Determina-se como mudança, que o minimamente significativo é duplicado pelo teste de estar de pé e sentado durante um minuto. Além disso, evidencia-se uma melhor resposta ao exercício, com menos dispneia e fadiga muscular, devido ao efeito da pressão positiva da cânula de alto fluxo.

Cisplatin-Resistant Urothelial Bladder Cancer Cells Undergo Metabolic Reprogramming beyond the Warburg Effect.

Advanced urothelial bladder cancer (UBC) patients are tagged by a dismal prognosis and high mortality rates, mostly due to their poor response to standard-of-care platinum-based therapy. Mediators of chemoresistance are not fully elucidated. This work aimed to study the metabolic profile of advanced UBC, in the context of cisplatin resistance. Three isogenic pairs of parental cell lines (T24, HT1376 and KU1919) and the matching cisplatin-resistant (R) sublines were used. A set of functional assays was used to perform a metabolic screening on the cells. In comparison to the parental sublines, a tendency was observed towards an exacerbated glycolytic metabolism in the cisplatin-resistant T24 and HT1376 cells; this glycolytic phenotype was particularly evident for the HT1376/HT1376R pair, for which the cisplatin resistance ratio was higher. HT1376R cells showed decreased basal respiration and oxygen consumption associated with ATP production; in accordance, the extracellular acidification rate was also higher in the resistant subline. Glycolytic rate assay confirmed that these cells presented higher basal glycolysis, with an increase in proton efflux. While the results of real-time metabolomics seem to substantiate the manifestation of the Warburg phenotype in HT1376R cells, a shift towards distinct metabolic pathways involving lactate uptake, lipid biosynthesis and glutamate metabolism occurred with time. On the other hand, KU1919R cells seem to engage in a metabolic rewiring, recovering their preference for oxidative phosphorylation. In conclusion, cisplatin-resistant UBC cells seem to display deep metabolic alterations surpassing the Warburg effect, which likely depend on the molecular signature of each cell line.

Challenging the Dogma: Stage migration or negative lymph nodes, which of them is the main player on gastric cancer prognosis?

Expanding loco-regional nodes harvesting is expected to increase survival. This improvement may be associated to stage migration (SM). However, the great bulk of harvested lymph nodes observed in large dissections is negative. M&M: 830 patients who received R0 gastrectomy for adenocarcinoma were included. pN+ patients with <26 nodes (n = 209) were included for a simulation to "offer 26 nodes" - SM (proportional and exponential based) was simulated and analysed through machine learning algorithms. Overall Survival (OS), in native and simulated stages, were compared. OS of extended lymphadenectomies (pN+, D ≥ 26, n = 273) was compared with the simulated curves. OS of patients in the following dissection intervals of negative nodes were compared: <16 (n = 233), 16-25 (n = 258), ≥26 (n = 339). RESULTS: After simulation to 26 nodes (pN+, D < 26 patients, n = 209), staging was recomputed. OS of native vs simulated early-stages (I-II) and advanced stages (III) were not different (p > 0.05). OS of patients with lymphadenectomy (≥26) was better than simulated for early and advanced stages (p = 0.008; p = 0.005). OS of patients included in distinct intervals of negative lymph nodes were different (p < 0.001). These intervals were an independent prognostic factor (multivariate analysis). CONCLUSIONS: The influence of Stage Migration was null in this set of simulations and Will Rogers phenomenon was not observed. Extended dissection performed better in OS. But the influence of the number of negative nodes, even in large dissections, was highlighted. By emphasizing the role of negative nodes, we aim to facilitate more informed decision-making in management of gastric cancer patients, ultimately leading to improved treatment outcomes and patient care.

Revisiting Multi-Omics Data to Unravel Galectins as Prognostic Factors in Head and Neck Squamous Cell Carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignant cancer with a poor prognosis. Galectins (Gal) have been the subject of intensive research, but the comparative prognostic value of each Gal type is not yet understood. Therefore, a literature search for evaluating galectins as prognostic biomarkers in HNSCC was conducted. The relationship between Gal expression in HNSCC with HPV and TP53 mutational status was assessed using the UALCAN database. The impact of these biomarkers on prognosis was analyzed using ToPP and CPPA web tools. The expression of galectins in the tumor microenvironment and the impact on prognosis depending on the cancer immune subtype were analyzed using single-cell RNA sequencing. Gal-1 and Gal-3BP were shown to be promising biomarkers with a triple function for the prediction of HPV and TP53 mutational status, stratification of the HNSCC prognosis, and prediction of the response to treatment. In addition, these two galectins have been shown to be most influenced by the tumor microenvironment of HNSCC. Gal-1 and Gal-3BP are the most promising galectins in HNSCC. Furthermore, this study highlights the need for further studies to evaluate galectins in HNSCC and clarify the role of individual Gals in the patient's stratification.

The impact of chemotherapy on adipose tissue remodeling: The molecular players involved in this tissue wasting.

The depletion of visceral and subcutaneous adipose tissue (AT) during chemotherapy significantly correlates with diminished overall survival and progression-free survival. Despite its clinical significance, the intricate molecular mechanisms governing this AT loss and its chemotherapy-triggered initiation remain poorly understood. Notably, the evaluation of AT remodeling in most clinical trials has predominantly relied on computerized tomography scans or bioimpedance, with molecular studies often conducted using animal or in vitro models. To address this knowledge gap, a comprehensive narrative review was conducted. The findings underscore that chemotherapy serves as a key factor in inducing AT loss, exacerbating cachexia, a paraneoplastic syndrome that significantly compromises patient quality of life and survival. The mechanism driving AT loss appears intricately linked to alterations in AT metabolic remodeling, marked by heightened lipolysis and fatty acid oxidation, coupled with diminished lipogenesis. However, adipocyte stem cells' lost ability to divide due to chemotherapy also appears to be at the root of the loss of AT. Notably, chemotherapy seems to deactivate the mitochondrial antioxidant system by reducing key regulatory enzymes responsible for neutralizing reactive oxygen species (ROS), thereby impeding lipogenesis. Despite FDG-PET evidence of AT browning, no molecular evidence of thermogenesis was reported. Prospective investigations unraveling the molecular mechanisms modulated in AT by chemotherapy, along with therapeutic strategies aimed at preventing AT loss, promise to refine treatment paradigms and enhance patient outcomes.

Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy.

Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic-co-glycolic acid) (PLGA)-based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties. To achieve this, we synthesized a library of MUC16-Tn glycoepitopes through single-pot enzymatic glycosylation, which were then stably engrafted onto the surface of PLGA nanoparticles, generating multivalent constructs that better represent cancer molecular heterogeneity. These glycoconstructs demonstrated affinity for Macrophage Galactose-type Lectin (MGL) receptor, known to be highly expressed by immature antigen-presenting cells, enabling precise targeting of immune cells. Moreover, the glycopeptide-grafted nanovaccine candidate displayed minimal cytotoxicity and induced the activation of dendritic cells in vitro, even in the absence of an adjuvant. In vivo, the formulated nanovaccine candidate was also nontoxic and elicited the production of IgG specifically targeting MUC16 and MUC16-Tn glycoproteoforms in cancer cells and tumors, offering potential for precise cancer targeting, including targeted immunotherapies.

Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review.

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application.

Aberrantly Glycosylated GLUT1 as a Poor Prognosis Marker in Aggressive Bladder Cancer.

Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O-glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O-glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer.

A multivalent CD44 glycoconjugate vaccine candidate for cancer immunotherapy.

Cancer presents a high mortality rate due to ineffective treatments and tumour relapse with progression. Cancer vaccines hold tremendous potential due to their capability to eradicate tumour and prevent relapse. In this study, we present a novel glycovaccine for precise targeting and immunotherapy of aggressive solid tumours that overexpress CD44 standard isoform (CD44s) carrying immature Tn and sialyl-Tn (sTn) O-glycans. We describe an enzymatic method and an enrichment strategy to generate libraries of well-characterized cancer-specific CD44s-Tn and/or sTn glycoproteoforms, which mimic the heterogeneity found in tumours. We conjugated CD44-Tn-derived glycopeptides with carrier proteins making them more immunogenic, with further demonstration of the importance of this conjugation to overcome the glycopeptides' intrinsic toxicity. We have optimized the glycopeptide-protein maleimide-thiol conjugation chemistry to avoid undesirable cross-linking between carrier proteins and CD44s glycopeptides. The resulting glycovaccines candidates were well-tolerated in vivo, inducing both humoral and cellular immunity, including immunological memory. The generated antibodies exhibited specific reactivity against synthetic CD44s-Tn glycopeptides, CD44s-Tn glycoengineered cells, and human tumours. In summary, we present a promising prototype of a cancer glycovaccine for future therapeutical pre-clinical efficacy validation.

Unexpected pancreatic mixed neuroendocrine-nonneuroendocrine neoplasms (MiNEN)-reflection on a case report.

The authors present a case involving a 51-year-old male who was diagnosed with a 4-cm mass in the body of the pancreas, initially suspected to be a ductal adenocarcinoma due to an elevated Ca 19.9 during routine analysis. Subsequent imaging studies confirmed a resectable disease without suspicious lymph nodes or distant metastasis, leading to the proposal of surgery. The patient underwent a laparoscopic distal splenopancreatectomy, which was uneventful. The histopathological examination revealed a 3.7-cm pancreatic mixed neuroendocrine neoplasia (MiNEN) with a predominant high-grade ductal adenocarcinoma component and a concurrent high-grade neuroendocrine carcinoma, with negative margins. Two lymph node metastases were identified, each representing metastasis of one of the components. The tumor was classified as pT2N1M0. Currently, the patient is undergoing chemotherapy with FOLFIRINOX. This case prompts reflection on the optimal treatment strategy for pancreatic MiNEN and raises the question of how the preoperative diagnosis could influence the patient's outcome.

Minimizing false positives for CTC identification.

BACKGROUND: Cancer is a leading cause of death worldwide, with metastasis playing a significant role. Circulating Tumour Cells (CTCs) can provide important real-time insights into tumour heterogeneity and clonal evolution, making them an important tool for early diagnosis and patient monitoring. Isolated CTCs are typically identified by immunocytochemistry using positive biomarkers (cytokeratin) and exclusion biomarkers (CD45). However, some white blood cell (WBC) populations can express low levels of CD45 and stain non-specifically for cytokeratin, increasing their risk of misclassification as CTCs. There is a clear need to improve CTC detection and enumeration criteria to unequivocally eliminate interfering WBC populations. RESULTS: This study showed that, indeed, some granulocyte subpopulations expressed low levels of CD45 and stained non-specifically for cytokeratin, misidentifying them as CTCs. These same cells, however, strongly expressed CD15, allowing them to be identified as WBCs and excluded from CTC classification. Flow cytometry confirmed the specificity of the CD15 antibody for the granulocyte subpopulation. False positives were considerably reduced from 25 % to 0.2 % by double exclusion, combining a CD15 antibody with a highly specific CD45 antibody. Furthermore, complete elimination of potential false positives was achieved using double exclusion in combination with improved selection of cytokeratin antibody. The study emphasises the importance of a robust exclusion criteria and high antibody specificity in CTC immuno-assays for accurate identification of CTC candidates and thorough exclusion of interfering WBC subpopulations. SIGNIFICANCE: This study demonstrated how misidentifying a granulocyte subpopulation can lead to inaccurate CTC evaluation. However, sensitivity and specificity of CTC identification may be improved by using high-performing antibodies and by including a second exclusion biomarker, in turn, allowing for a more comprehensive clinical application of CTCs.

Fellowship in surgical oncology: The results of an experience in Portuguese-speaking African countries.

Cancer incidence rates are increasing worldwide including in Portuguese speaking African countries. We present the results of the fellowship in surgical oncology promoted by the Portuguese Institute of Oncology in Porto (IPO), Fernando Pessoa University, Portugal, and the Calouste Gulbenkian Foundation, which involved the training of residents and surgeons from Portuguese-speaking African countries in Portugal. The program's structure and content was the same of UMES/ESSO. The hands-on activity took place at the IPO. After the fellowship, a theoretical and practical assessment was held, and all fellows scored above the threshold to pass. The surgical performance of the fellows was assessed in their workplaces in Africa. The impact of the training was evaluated by a questionnaire completed by all the fellows. It was reported an increase in knowledge, skills and organizational skills that fellows are committed to implement. As the fellowship is certified by a Portuguese University, it may be recognized by the Local Health and University Authorities, impacting on the professional progression of fellows.

Clinical efficacy of endodontic protocols on reducing cultivable bacteria and endotoxin in infected root canal in patients submitted to head and neck radiotherapy: a randomised clinical trial.

OBJECTIVES: Assess the efficacy of biomechanical preparation using a reciprocating system followed by final irrigation protocols, then intracanal medication, on reducing endotoxins and cultivable bacteria of infected teeth in irradiated patients. MATERIALS AND METHODS: Twenty-two infected single-rooted canals in patients submitted to head and neck radiotherapy were prepared by reciprocating motion and 2.5% NaOCl. Patients were randomly divided into two groups of 11 patients before the final irrigation protocol: apical positive pressure (APP) or passive ultrasonic activation (PUA). Both groups were treated in two sessions, using Ca(OH)2 as intracanal medication for 14 days. Root canal content sampling was performed after canal access (S1), after biomechanical preparation plus the irrigation protocol (S2), and after intracanal medication (S3). Chromogenic limulus amoebocyte lysate assay measured endotoxin levels (EU/mL), and bacterial load was determined by culture techniques (CFU/mL). RESULTS: Treatment protocols reduced bacterial counts after S2 in both groups (p = 0.01). S3 differed from S1 (p = 0.01), but not from S2 (p = 0.4). Endotoxin levels were reduced in both groups after S2 (P = 0.03) and were lower in S3 than in S2, with significant differences in the APP group (p = 0.03). CONCLUSIONS: Biomechanical preparation using a reciprocating system and 2.5% NaOCl in irradiated teeth, followed by the irrigation protocol (APP or PUA), demonstrated efficacy in reducing endodontic contaminants. Ca(OH)2 as intracanal medication should be performed in irradiated patients with infected root canals. CLINICAL RELEVANCE: This clinical study demonstrated that endodontic treatment in irradiated patients is efficacious at reducing bacterial load and endotoxin levels.

Textbook Oncological Outcome in European GASTRODATA.

OBJECTIVE: To assess the rate of textbook outcome (TO) and textbook oncological outcome (TOO) in the European population based on the GASTRODATA registry. BACKGROUND: TO is a composite parameter assessing surgical quality and strongly correlates with improved overall survival. Following the standard of treatment for locally advanced gastric cancer, TOO was proposed as a quality and optimal multimodal treatment parameter. METHODS: TO was achieved when all the following criteria were met: no intraoperative complications, radical resection according to the surgeon, pR0 resection, retrieval of at least 15 lymph nodes, no severe postoperative complications, no reintervention, no admission to the intensive care unit, no prolonged length of stay, no postoperative mortality and no hospital readmission. TOO was defined as TO with the addition of perioperative chemotherapy compliance. RESULTS: Of the 2558 patients, 1700 were included in the analysis. TO was achieved in 1164 (68.5%) patients. The use of neoadjuvant chemotherapy [odds ratio (OR) = 1.33, 95% CI: 1.04-1.70] and D2 or D2+ lymphadenectomy (OR = 1.55, 95% CI: 1.15-2.10) had a positive impact on TO achievement. Older age (OR = 0.73, 95% CI: 0.54-0.94), pT3/4 (OR = 0.79, 95% CI: 0.63-0.99), ASA 3/4 (OR = 0.68, 95% CI: 0.54-0.86) and total gastrectomy (OR = 0.56, 95% CI: 0.45-0.70), had a negative impact on TO achievement. TOO was achieved in 388 (22.8%) patients. Older age (OR = 0.37, 95% CI: 0.27-0.53), pT3 or pT4 (OR = 0.52, 95% CI: 0.39-0.69), and ASA 3 or 4 (OR = 0.58, 95% CI: 0.43-0.79) had a negative impact on TOO achievement. CONCLUSIONS: Despite successively improved surgical outcomes, stage-appropriate chemotherapy in adherence to the current guidelines for multimodal treatment of gastric cancer remains poor. Further implementation of oncologic quality metrics should include greater emphasis on perioperative chemotherapy and adequate lymphadenectomy.

MicroRNA Biomarkers as Promising Tools for Early Colorectal Cancer Screening-A Comprehensive Review.

Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Early detection of this neoplasia has proven to improve prognosis, resulting in a 90% increase in survival. However, available CRC screening methods have limitations, requiring the development of new tools. MicroRNA biomarkers have emerged as a powerful screening tool, as they are highly expressed in CRC patients and easily detectable in several biological samples. While microRNAs are extensively studied in blood samples, recent interest has now arisen in other samples, such as stool samples, where they can be combined with existing screening methods. Among the microRNAs described in the literature, microRNA-21-5p and microRNA-92a-3p and their cluster have demonstrated high potential for early CRC screening. Furthermore, the combination of multiple microRNAs has shown improved performance in CRC detection compared to individual microRNAs. This review aims to assess the available data in the literature on microRNAs as promising biomarkers for early CRC screening, explore their advantages and disadvantages, and discuss the optimal study characteristics for analyzing these biomarkers.

Neoadjuvant Gastric Cancer Treatment and Associated Nutritional Critical Domains for the Optimization of Care Pathways: A Systematic Review.

(1) Background: Gastric cancer patients are known to be at a high risk of malnutrition, sarcopenia, and cachexia, and the latter impairs the patient's nutritional status during their clinical course and also treatment response. A clearer identification of nutrition-related critical points during neoadjuvant treatment for gastric cancer is relevant to managing patient care and predicting clinical outcomes. The aim of this systematic review was to identify and describe nutrition-related critical domains associated with clinical outcomes. (2) Methods: We performed a systematic review (PROSPERO ID:CRD42021266760); (3) Results: This review included 14 studies compiled into three critical domains: patient-related, clinical-related (disease and treatment), and healthcare-related. Body composition changes during neoadjuvant chemotherapy (NAC) accounted for the early termination of chemotherapy and reduced overall survival. Sarcopenia was confirmed to have an independent prognostic value. The role of nutritional interventions during NAC has not been fully explored. (4) Conclusions: Understanding critical domain exposures affecting nutritional status will enable better clinical approaches to optimize care plans. It may also provide an opportunity for the mitigation of poor nutritional status and sarcopenia and their deleterious clinical consequences.