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Simple Summary: Sentinel lymph node (SLN) biopsy is recommended over systematic lymphadenectomy in early-stage endometrial cancer due to its lower morbidity and comparable detection rate. The objective of this study was to identify clinical factors associated with unsuccessful mapping. We conducted a prospective, single-institution study of 120 participants with early-stage uterine cancer. Univariate and multiple linear regressions were performed to identify predictors of unsuccessful mapping. Advanced age, tracer type, and intraoperative detection of enlarged lymph nodes were identified as independent risk factors for unsuccessful mapping in patients undergoing laparoscopic SLN mapping. These factors should be carefully considered during surgical planning and discussions prior to treatment. Additionally, the exploration of relationships between mapping failure and factors such as tumor distance to the serosa, uterine volume, and molecular tumor types, represents a promising area for future research that could complement our findings. Background: Sentinel lymph node (SLN) biopsy is recommended over systematic lymphadenectomy in early-stage endometrial cancer due to its lower morbidity and comparable detection rate. The objective of this study was to identify clinical factors associated with unsuccessful mapping. Methods: Between April 2020 and June 2024, 120 patients over the age of 18 and diagnosed with early-stage endometrial cancer were enrolled in this prospective study at a single institution. Demographic, clinicopathologic, and treatment data were collected and analyzed using descriptive statistics. Univariate and multiple linear regressions were performed to identify predictors of failed mapping. Results: The mean age of the patient cohort was 62.5 years (range 33 to 83), and the mean body mass index (BMI) was 32 kg/m2 (range 18 to 50). Patients underwent intracervical injections with methylene blue (MB), indocyanine green (ICG), or a combination of both tracers, with 40 patients in each group. A total of 108 patients (90.0%) were diagnosed with endometrioid carcinoma and 12 (10.0%) with non-endometrioid cancers. Additionally, 110 patients (91.7%) were diagnosed in early stages of the disease. The overall SLN detection rate was 73.4%, with bilateral detection at 49.2% and unilateral detection at 24.2%. Univariate analysis showed that older age (p < 0.001), menopause (p = 0.001), the use of MB as the sole tracer (p = 0.006), a shorter tumor-to-serosa distance (p = 0.048), and bulky lymph nodes (p = 0.18) were associated with unsuccessful mapping. Multiple linear regression model analysis identified age (p = 0.007), tracer type (p = 0.013), and enlarged lymph nodes (p = 0.013) as independent predictors of SLN mapping failure. Conclusions: Advanced age, tracer type, and intraoperative detection of enlarged lymph nodes were identified as independent risk factors for unsuccessful mapping in patients undergoing laparoscopic SLN mapping. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PCa) is a heterogeneous disease and the second most diagnosticated cancer in men. Epidemiological information is essential to adopt the strategy of early detection. In Mexico there is paucity of epidemiological data. We observed that Mexican men present aggressive disease at diagnosis with metastatic symptoms. Seems the Mexican race is a risk factor for PCa, as African men. "OPUS program " is the actual screening protocol for Mexican men. We describe the concernment of early detection of PCa in the Mexican population to reduce the rate of metastases. Introduction: Epidemiological data are crucial for adopting primary and secondary prevention strategies and to develop screening protocols against prostate cancer (PCa). Despite the comprehensive characterization of PCa across White and Black men, there is a lack of data from the Mexican population. This manuscript presents data from the Can.Prost registry that captures PCa trends over the past two decades in Mexico City; furthermore, we aimed to compare clinical differences and oncological outcomes before and after the promotion of early detection actions through a campaign against PCa that occurred in 2014. Methods: A retrospective observational study on newly diagnosed Mexican PCa patients was carried out at the Instituto Nacional de Cancerología (INCan) in Mexico City. During 2014 and 2015, a project for the early diagnosis of PCa ("OPUS program") was launched in the aforementioned tertiary hospital. Starting at the age of 45 years, all men were invited for a PSA measurement and a specialist urologist consultation. All individuals with clinical or biochemical suspicion of PCa (PSA > 4 ng/mL), in the context of age and prostate volume, underwent ultrasound-guided transrectal prostate biopsy. Then, patients with pathologically confirmed prostate cancer were stratified according to the year of diagnosis: Group A accounted for those diagnosed between 2000 and 2014 and Group B for those patients diagnosed in the timeframe of 2015–2021. Comparisons of PCa characteristics, treatment modalities and oncologic outcomes between Group A and B were performed. Results: Overall, we collected data from 2759 PCa patients from 2000 to 2021. The median PSA at baseline was 32 ng/mL, and 25% had a family history of PCa. Overall, 25.8% were asymptomatic and 46% had a non-metastatic presentation. After the OPUS campaign, PSA at diagnosis was significantly lower across all age groups. The incidence of PCa diagnosis in asymptomatic men was higher (31.4% vs. 19.9%) and a higher proportion of men were diagnosed with organ-confined, palpable disease (46% vs. 28%) (p < 0.001). The rate of patients eligible for active/radical treatment was higher after the OPUS campaign (patients who received surgery increased from 12.78% to 32.41%; patients who underwent radiation increased from 28.38% to 49.61%). The proportion of patients diagnosed with non-clinically significant disease was negligible and remained stable across time. Conclusions: PCa in Mexican patients displays aggressive features at diagnosis, whereas the rate of non-significant disease is negligible. The introduction of early detection strategies may lead to lower symptomatic and metastatic PCa and higher opportunities for radical treatment. This emphasizes the need for public awareness and for adjustment of screening strategies to the peculiarities of the Mexican population. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer-related deaths and early detection is crucial for better outcomes. This study focuses on methylation, a new method for detecting and monitoring NSCLC using a blood test that looks for changes in DNA. These changes can be found in tiny fragments of tumor DNA circulating in the blood. By analyzing existing research, the authors found that this method is accurate and reliable, showing promise for early diagnosis and the better management of NSCLC patients. The findings suggest that this approach could be a valuable tool in clinical practice, potentially leading to improved survival rates by allowing for earlier and more precise treatment. Background: Non-Small Cell Lung Cancer (NSCLC) remains a challenging disease to manage with effectiveness. Early detection and precise monitoring are crucial for improving patient outcomes. Circulating tumor DNA (ctDNA) offers a non-invasive cancer detection and monitoring method. Emerging biomarkers, such as ctDNA methylation, have shown promise in enhancing diagnostic accuracy and prognostic assessment in NSCLC. In this review, we examined the current evidence regarding ctDNA methylation's role in NSCLC detection through a systematic review of the existing literature and meta-analysis. Methods: We systematically searched PubMed, Medline, Embase, and Web of Science databases up to 26 June 2024 for studies on the role of ctDNA methylation analysis in NSCLC patients. We included studies from 2010 to 2024 on NSCLC patients. We excluded case reports, non-English articles, studies on cell lines or artificial samples, those without cfDNA detection, prognostic studies, and studies with non-extractable data or mixed cancer types. Funnel plots were visually examined for potential publication bias, with a p value < 0.05 indicating bias. Meta-analysis was conducted using R packages (meta, forestplot, and mada). Combined sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), positive and negative predictive values, diagnostic odds ratio (DOR), and 95% confidence intervals (95% CI) were calculated. A summary receiver operating characteristic curve (SROC) and area under the curve (AUC) with related Standard Error (SE) were used to evaluate the overall diagnostic performance. Additionally, RASSF1A, APC, SOX17, SEPT9, and RARβ2 were analyzed, since their methylation was assessed in two or more studies. Results: From 38 candidate papers, we finally identified 12 studies, including 472 NSCLC patients. The pooled sensitivity was 0.62 (0.47–0.77) and the specificity was 0.90 (0.85–0.94). The diagnostic odds ratio was 15.6 (95% CI 9.36–26.09) and the area under the curve was 0.249 (SE = 0.138). The positive and negative predictive values were 5.38 (95% CI 3.89–7.44) and 0.34 (95% CI 0.22–0.54), respectively. For single genes, the specificity reached 0.83~0.96, except for RARβ2, but the sensitivity was relatively low for each gene. Significant heterogeneity across the included studies, the potential publication bias for specificity (p = 0.0231), and the need to validate the clinical utility of ctDNA methylation for monitoring treatment response and predicting outcomes in NSCLC patients represent the main limitations of this study. Conclusions: These results provide evidence of the significant potential of ctDNA methylation as a valuable biomarker for improving the diagnosis of NSCLC, advocating for its integration into clinical practice to enhance patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging cancers to diagnose and treat. Despite over 4,300 clinical trials for pancreatic cancer exploring various treatments, progress in developing effective options for PDAC remains slow. This review seeks to offer a detailed and insightful analysis of the current landscape of PDAC-related clinical trials, with the primary goal of identifying ways to expedite drug development and enhance patient outcomes in the battle against this aggressive disease. Despite many decades of research, pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult cancers to diagnose and treat effectively. Although there have been improvements in the 5-year overall survival rate, it is still very low at 12.5%. The limited efficacy of current therapies, even when PDAC is detected early, underscores the aggressive nature of the disease and the urgent need for more effective treatments. Clinical management of PDAC still relies heavily on a limited repertoire of therapeutic interventions, highlighting a significant gap between research efforts and available treatments. Over 4300 clinical trials have been or are currently investigating different treatment modalities and diagnostic strategies for PDAC, including targeted therapies, immunotherapies, and precision medicine approaches. These trials aim to develop more effective treatments and improve early detection methods through advanced imaging techniques and blood-based biomarkers. This review seeks to categorize and analyze PDAC-related clinical trials across various dimensions to understand why so few chemotherapeutic options are available to patients despite the numerous trials being conducted. This review aims to provide a comprehensive and nuanced understanding of the landscape of PDAC-related clinical trials, with the overarching goal of identifying opportunities to accelerate progress in drug development and improve patient outcomes in the fight against this devastating disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolic syndrome (MetS), metabolic dysfunction-associated steatotic liver disease (MASLD), and diabetes are all linked to Cholangiocarcinoma (CCA) in various ways. MASLD may have an increased risk of intrahepatic-CCA, whereas untreated patients with shorter diabetes durations were more likely to develop biliary tract cancer (BTC). More research is needed to understand how reproductive hormones cause BTC. BTC patients may be at increased intrinsic cardiovascular risk of neoplastic/non-neoplastic cardiac complications. Therefore, early detection/prevention of chronic liver disease, as well as intervention studies, will almost certainly be required to determine whether improvements in MetS, weight loss, and diabetes therapy can reduce CCA risk and progression. BTC overall incidence is globally increasing. CCA, including its subtypes, is a form of BTC. MetS, obesity, MASLD, and diabetes are all linked to CCA in interconnected ways. The link between obesity and CCA is less well-defined in Eastern countries as compared to Western. Although more research is needed to determine the relationship between MASLD and extrahepatic CCA (eCCA), MASLD may be a concurrent risk factor for intrahepatic CCA, particularly in populations with established or unidentified underlying liver disease. Interestingly, the risk of biliary tract cancer (BTC) seemed to be higher in patients with shorter diabetes durations who were not treated with insulin. Therefore, early detection and prevention of chronic liver disease, as well as additional intervention studies, will undoubtedly be required to determine whether improvements to MetS, weight loss, and diabetes therapy can reduce the risk and progression of BTC. However, further studies are needed to understand how reproductive hormones are involved in causing BTC and to develop consistent treatment for patients. Finally, it is critical to carefully assess the cardiological risk in BTC patients due to their increased intrinsic cardiovascular risk, putting them at risk for thrombotic complications, cardiovascular death, cardiac metastasis, and nonbacterial thrombotic endocarditis. This review aimed to provide an updated summary of the relation between the abovementioned cardio-metabolic conditions and BTC. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) represents a major global health challenge, ranking as the second leading cause of cancer-related deaths. The high mortality rate is primarily due to late-stage diagnoses, which limit effective treatment options. Recent research emphasizes the development of targeted therapies and radiation immunotherapy as promising alternatives to traditional approaches. The review authors summarize recent advancements in targeted therapies for gastric cancer, focusing on both laboratory and clinical studies. They explore targeted approaches that have shown potential for improving diagnostic accuracy and treatment effectiveness. The findings of this paper may significantly impact the research community by highlighting the importance of personalized medicine in gastric cancer treatment. By identifying specific molecular targets and utilizing nanotechnology for drug delivery, these advancements aim to enhance treatment efficacy while minimizing systemic toxicity. Overall, the review suggests the potential for improved prognosis and treatment strategies through targeted therapies and precision medicine. Gastric cancer (GC) is the second most common cause of cancer-related death worldwide and a serious public health concern. This high death rate is mostly caused by late-stage diagnoses, which lead to poor treatment outcomes. Radiation immunotherapy and targeted therapies are becoming increasingly popular in GC treatment, in addition to surgery and systemic chemotherapy. In this review, we have focused on both in vitro and in vivo research, which presents a summary of recent developments in targeted therapies for gastric cancer. We explore targeted therapy approaches, including integrin receptors, HER2, Claudin 18, and glutathione-responsive systems. For instance, therapies targeting the integrin receptors such as the αvβ3 and αvβ5 integrins have shown promise in enhancing diagnostic precision and treatment efficacy. Furthermore, nanotechnology provides novel approaches to targeted drug delivery and imaging. These include glutathione-responsive nanoplatforms and cyclic RGD peptide-conjugated nanoparticles. These novel strategies seek to reduce systemic toxicity while increasing specificity and efficacy. To sum up, the review addresses the significance of personalized medicine and advancements in gastric cancer-targeted therapies. It explores potential methods for enhancing gastric cancer prognosis and treatment in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PCa) is a major health issue among men, with risk factors such as age, family history, genetics, and race being well known. However, the impact of lifestyle choices has often been overlooked. This study aimed to understand health professionals' perceptions of PCa risk factors to design a questionnaire applicable to the male population. Three focus groups were conducted to discuss topics, such as the impact of diet, physical activity, alcohol consumption, smoking, sexual health, and screening and treatment methods. Although healthy lifestyles can generally improve PCa outcomes, no specific lifestyle change has been identified as a preventive measure, particularly for older adults. Lycopene, present in tomatoes, was highlighted for its antioxidant benefits. This study demonstrates the necessity for additional research on how lifestyle affects PCa and emphasizes the importance of health professionals in encouraging the adoption of healthier habits. It also suggests exploring non-invasive screening through urine and innovative treatment methods to reduce false positives and side effects, respectively. Prostate cancer (PCa) accounts for 20% of new cancer cases and 10.5% of cancer-associated mortality in Portugal. Associated risk factors include advanced age, family history, genetic alterations, and race/ethnicity. However, the role of lifestyle factors is often underestimated. To explore health professionals' perceptions of PCa risk factors, a qualitative study with three focus groups (FG), with a total of twenty-one general practitioners and urologists, was conducted via videoconference between February and April 2023. Seven themes emerged, including general perceptions of PCa; PCa risk factors; nutritional impact; the role of physical activity; alcohol consumption and smoking; sexual activity and sexually transmitted diseases roles in PCa; and screening, diagnosis, and treatment methods. Despite agreeing that healthy lifestyles could promote better PCa outcomes and quality of life, participants did not specify any lifestyle factors that could promote or prevent this disease, posing challenges to lifestyle changes, particularly among older adults. Non-invasive screening methods, such as biomarkers and alternative treatments, are crucial for future research. This study underscores the need for further investigation into the correlation of lifestyle factors with PCa and highlights the necessity of health professionals in encouraging their patients to adopt healthier lifestyles, while offering important insights into awareness, prevention, and alternative screening, diagnosis, and treatment methods, which could help reduce false positives and treatment side effects. [ABSTRACT FROM AUTHOR]

Simple Summary: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive primary liver cancer leading to death in 10–15% of cases. In recent years, the iCCA worldwide incidence has been increasing, and research is currently focused on identifying valuable diagnostic biomarkers and developing specific therapies to counteract the disease despite its high heterogeneity. The use of cutting-edge and broad-spectrum applications like omics represents a successful approach to studying the intricate pathobiology of iCCA. In this review, we discuss how both single- and multi-omics studies can pave the way for identifying potential biomarkers, and more importantly, for stratifying iCCA patients. This stratification aims to enhance the therapeutic intervention through personalized medicine (PM). Intrahepatic cholangiocarcinoma (iCCA) is recognized worldwide as the second leading cause of morbidity and mortality among primary liver cancers, showing a continuously increasing incidence rate in recent years. iCCA aggressiveness is revealed through its rapid and silent intrahepatic expansion and spread through the lymphatic system leading to late diagnosis and poor prognoses. Multi-omics studies have aggregated information derived from single-omics data, providing a more comprehensive understanding of the phenomena being studied. These approaches are gradually becoming powerful tools for investigating the intricate pathobiology of iCCA, facilitating the correlation between molecular signature and phenotypic manifestation. Consequently, preliminary stratifications of iCCA patients have been proposed according to their "omics" features opening the possibility of identifying potential biomarkers for early diagnosis and developing new therapies based on personalized medicine (PM). The focus of this review is to provide new and advanced insight into the molecular pathobiology of the iCCA, starting from single- to the latest multi-omics approaches, paving the way for translating new basic research into therapeutic practices. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is a significant health issue, being the third most common cancer and the second leading cause of cancer deaths worldwide. Most CRC cases are diagnosed at an advanced stage, especially in symptomatic patients, highlighting the need for effective early detection methods. While CRC is more prevalent in developed countries, its impact is felt globally and is influenced by factors such as diet, environment, and genetics. This study aims to review existing research on the effectiveness of various CRC screening methods. Early detection through screening significantly improves survival rates, making it crucial for better health outcomes. The review evaluates different screening tools and their cost-effectiveness and identifies populations that would benefit most from targeted screening. By improving screening strategies, the study aims to enhance early diagnosis and reduce CRC mortality rates, ultimately improving patient prognosis and quality of life. Colorectal cancer (CRC) has the highest mortality rate among men and is the second highest among women under fifty, with incidence and mortality rates rising in younger populations. Studies indicate that up to one-third of patients diagnosed before fifty have a family history or genetic factors, highlighting the need for earlier screening. Contrariwise, diagnosis in healthy subjects through screening strategies enables early-stage detection of the tumor and better clinical outcomes. In recent years, mortality rates of CRC in Western countries have been on a steady decline, which is largely attributed to widespread screening programs and advancements in treatment modalities. Indeed, early detection through screening significantly improves prognosis, with stark differences in survival rates between localized and metastatic disease. This article aims to provide a comprehensive review of the existing literature, delving into the performance and efficacy of various CRC screening strategies. It navigates through available screening tools, evaluating their efficacy and cost-effectiveness. The discussion extends to delineating target populations for screening, emphasizing the importance of tailored approaches for individuals at heightened risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Sarcopenia in cancer patients, understood as the progressive loss of muscle mass and function, reduces physical function, quality of life, and survival, and increases surgical complications and disease progression. Myosteatosis is an excess of fat mass infiltrated into the muscle, which causes a reduction in its functionality. Given the current scientific evidence on its reversibility, it is important to know the implications that its prevention, diagnosis, and early treatment could entail in the evolutionary course of the disease. Therefore, this study aims to make an early diagnosis and evaluate the incidence of sarcopenia and myosteatosis in patients diagnosed with esophageal, stomach, or pancreatic cancer and analyze their clinical evolution. In our sample, 22.2% of the patients had sarcopenia, and 60% had myosteatosis. At 6 months, 60% of the patients with sarcopenia died, compared with 14.3% of the patients who did not have sarcopenia. Therefore, it is important to make a correct early diagnosis to carry out a comprehensive approach that can reverse the patient's situation. Likewise, prevention and care campaigns for muscle health could be carried out at all stages of life. The increase in the global incidence of cancer highlights the need to continue advancing in the techniques of diagnosis and nutritional assessment of cancer patients, given the prognostic and therapeutic impact of nutritional status. In this study, sarcopenia was evaluated as an independent predictor of morbidity and mortality. Data from 45 patients diagnosed with esophagogastric or pancreatic cancer were analyzed. Body composition was determined using computed tomography images, and functionality tests were performed. Sarcopenia was present in 22.2% of the patients, while only 31.1% had correct musculature. A reduction in muscle mass or function was observed in 46.7% of the patients. Likewise, the prevalence of myosteatosis reached 60% of the patients. No significant differences were found with regard to the presence of sarcopenia according to BMI classifications, so it is necessary to evaluate the patient with body composition techniques that include the evaluation of the different muscle and fat compartments. In conclusion, a comprehensive intervention is necessary to improve the detection of sarcopenia/myosteatosis and, in the future, to be able to carry out an approach that improves the quality of life and survival rates of patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper addresses the complex diagnostic challenges of pigmented lesions in the oral mucosa, ranging from benign to potentially malignant conditions. Our study provides a narrative review with a clinical case overview to guide clinicians in differentiating these lesions. By classifying pigmented lesions based on clinical and histological features, we emphasize the need for a structured approach to diagnosis. The study incorporates a retrospective analysis of cases from our oral medicine experience, utilizing clinical pictures and relevant histology. Our findings aim to enhance early and precise diagnosis, improving patient management and outcomes in dental and medical practice. This paper examines the clinical differentiation of pigmented lesions in the oral mucosa, which poses significant diagnostic challenges across dental and medical disciplines due to their spectrum from benign to potentially malignant conditions. Through a literature review and analysis of clinical cases, this study clarifies current diagnostic methodologies, with an emphasis on differential diagnosis, to provide a practical guide for clinicians. The classification of pigmented lesions, such as endogenous, focal melanocytic, and multifocal pigmentation, based on clinical and histological features, highlights the necessity for a structured and informed approach. A retrospective examination of cases from our oral medicine and pathology clinic, coupled with analysis of photographic and histological records, aids in classifying these lesions. This fosters a better understanding and promotes informed discussions among clinicians, ultimately aiming to enhance early and precise diagnosis, thus improving patient management and outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Gonadal teratomas are tumours that can be benign or malignant and affect the gonads, specifically the ovaries in women and the testicles in men. They are predominantly young tumours that affect children and adolescents; therefore, early diagnosis is essential to apply the most suitable therapy to preserve fertility. In this article, based on articles found in the literature, we analysed the past, present and future of gonadal teratomas, starting from the description of the possible causes, the distinction between benign and malignant, and consequent diversification of the diagnostic and, therefore, therapeutic procedure. Furthermore, we concluded on the importance of a team that involves various specialists, including the pathologist, for the correct diagnosis and therapy to guarantee the best possible quality of life for the patient. Teratomas are neoplasms arising from germ cells and encompass tissues derived from two or more embryonic germ layers, including ectoderm, mesoderm, and endoderm. These tumours typically localize along the midline or in paramedian positions and can manifest as gonadal (20%) or extragonadal (80%) entities. Although gonadal teratomas are uncommon, they represent the predominant type of gonadal tumour in the paediatric population. They comprise approximately 20–25% of all ovarian tumours in females and about 3–5% of all testicular tumours in males. Ovarian teratomas exhibit a higher incidence in early childhood and adolescence, whereas testicular teratomas are more prevalent during the first three months of life and between the ages of 15 and 19. While the majority of paediatric gonadal teratomas are benign, malignant or mixed variants may also arise, necessitating more aggressive therapeutic interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphedema is a common complication following gynecological cancer treatment, particularly affecting the lower limbs. However, self-reported data on lymphedema detection remain scarce. To address this gap, Yost developed the Lower Extremity Lymphedema Screening Questionnaire (LELSQ) specifically for women. The LELSQ is a straightforward and user-friendly tool designed for the early identification of lower extremity lymphedema (LEL). The validation of the questionnaire in Dutch was crucial for a larger trial called "The Gynolymph", since there were no validated questionnaires in Dutch for the detection of early LEL. This trial aims to enroll four hundred patients who will utilize the screening tool as part of a patient-reported assessment. By doing so, the trial seeks to detect the early development of lymphedema after cancer treatment. To ensure unbiased results, the study team translated and adapted the lymphedema questionnaire to Dutch. The cross-sectional survey conducted during this process demonstrated high internal consistency, test–retest reliability, and validity. Additionally, face and content validity were confirmed, allowing for the implementation of the questionnaire in the early detection of LEL among Dutch-speaking women. Background: Validated questionnaires of self-reported LEL are important in the assessment and diagnosis of LEL. The aim of this study was to validate and translate a Dutch version of the screening questionnaire, the LELSQ developed and validated by Yost et al. Methods: We tested the questionnaire on a group of healthy women and a group of patients diagnosed with LEL. The translation was carried out using the forward and backward method from English to Dutch. Statistical analyses: SPSS (IBM corp, Armonk, New York, NY, USA) version 28.0.1.0 (001) was used for statistical analysis in the process of validation. The internal consistency was assessed by determining Cronbach's alpha. The reliability was tested by test–retest reliability. The validity was determined by ROC analysis, and content and face validity were evaluated. Results: The internal consistency score in both groups had a strong value (0.83 to 0.90). The test–retest reliability was also strong in both groups. Face and content validity showed the LELSQ is an easy, understandable questionnaire that is not too time-consuming in the early detection of LEL. The ROC analysis showed an AUC value of 0.93, indicating strong validity. Conclusions: The validated Dutch translation showed high values for internal consistency, test–retest reliability, and validity, which allows us to implement the questionnaire in the early detection of LEL after gynecological cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer remains a leading cause of cancer-related mortality globally, requiring new diagnostic and therapeutic approaches. This research arises from the need to improve diagnostic accuracy and treatment effectiveness for patients with non-small cell lung cancer. The authors aim to systematically evaluate the potential of emerging biomarkers, including circulating tumor DNA, microRNAs and mutational load of blood tumors and their relationship with different treatments. The findings of this study could have a significant impact on the research community by providing a basis for integrating these biomarkers into clinical practice, thereby improving personalized treatment strategies and patient outcomes in non-small cell lung cancer. Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers—circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood tumor mutational burden (bTMB)—enhanced by next-generation sequencing (NGS) to improve the diagnostic accuracy, prognostic evaluation, and treatment strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients from 2020 to 2024, the review highlights how biomarkers like ctDNA and PD-L1 expression critically inform the selection of personalized therapies, particularly beneficial in the advanced stages of NSCLC. These biomarkers are critical for prognostic assessments and in dynamically adapting treatment plans, where high PD-L1 expression and specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide the use of targeted therapies and immunotherapies. The findings recommend integrating these biomarkers into standardized clinical pathways to maximize their potential in enhancing the treatment precision, ultimately fostering significant advancements in oncology and improving patient outcomes and quality of life. This review substantiates the prognostic and predictive value of these biomarkers and emphasizes the need for ongoing innovation in biomarker research. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates the identification of tumor-specific serological biomarkers for the early diagnosis of glioblastoma multiforme (GBM) recurrence using peripheral whole blood samples in a minimally invasive approach known as "liquid biopsy". Our results indicate that gene expression analysis can detect changes in transcriptional (mRNAs) and post-transcriptional (small RNAs) levels after surgery and upon tumor recurrence. This prospective study aims to develop a diagnostic tool complementary to MRI modalities in the clinical follow-up, helping to track tumor progression/recurrence and to make clinical decisions. GBM WHO CNS Grade 4 represents a major challenge for oncology due to its aggressive behavior. Conventional imaging has restrictions in detecting tumor recurrence. This prospective study aims to identify gene-based biomarkers in whole blood instead of isolating exosomes for the early detection of tumor recurrence. Blood samples (n = 33) were collected from seven GBM patients at time points before and after surgery as well as upon tumor recurrence. Four tumor tissue samples were assessed in parallel. Next-generation sequencing (NGS), including mRNA-seq and small RNA-seq, was used to analyze gene expression profiles in blood samples and tumor tissues. A novel filtering pipeline was invented to narrow down potential candidate genes. In total, between 6–93 mRNA and 1–19 small RNA candidates could be identified among the seven patients. The overlap of genes between the patients was minimal, indicating significant inter-individual variance among GBM patients. In summary, this prospective study supports the applicability of gene expression measurements in whole blood for the detection of tumor recurrence. It might provide an alternative to the challenging workflow of liquid biopsy after laborious exosome isolation from whole blood. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals with atrophic gastritis and gastric intestinal metaplasia, considered gastric precancerous conditions (GPC), are at increased risk of developing gastric adenocarcinoma. The identification and surveillance of these patients are important for the diagnosis of early gastric neoplasia. Non-invasive markers of GPC with good diagnostic performance could allow the implementation of a stepwise screening approach and, with successful personalized endoscopic surveillance, possibly decrease gastric cancer morbidity and mortality. Pepsinogen I and II and their ratio are the most broadly investigated biomarkers with moderate diagnostic performance. Their combination with other markers like Helicobacter pylori antibodies and gastrin-17 (called GastroPanel®) allows for more precise identification of GPC but without significant improvement in overall performance. Other new serum biomarkers could possibly enhance the performance of pepsinogens. Some of them may be considered stand-alone biomarkers; however, until now, no high-quality data support the use of any of them. Gastric cancer (GC) is still one of the most prevalent cancers worldwide, with a high mortality rate, despite improvements in diagnostic and therapeutic strategies. To diminish the GC burden, a modification of the current diagnostic paradigm, and especially endoscopic diagnosis of symptomatic individuals, is necessary. In this review article, we present a broad review and the current knowledge status on serum biomarkers, including pepsinogens, gastrin, Gastropanel®, autoantibodies, and novel biomarkers, allowing us to estimate the risk of gastric precancerous conditions (GPC)—atrophic gastritis and gastric intestinal metaplasia. The aim of the article is to emphasize the role of non-invasive testing in GC prevention. This comprehensive review describes the pathophysiological background of investigated biomarkers, their status and performance based on available data, as well as their clinical applicability. We point out future perspectives of non-invasive testing and possible new biomarkers opportunities. [ABSTRACT FROM AUTHOR]

Simple Summary: Detecting lung cancer early and initiating treatment promptly can greatly enhance patient outcomes. While low-dose computed tomography (LDCT) screening aids in identifying lung cancer at an early stage, there is a risk of diagnostic delays as patients await follow-up scans. To mitigate this challenge, we developed a deep predictive model leveraging generative AI methods to forecast nodule growth patterns in follow-up LDCT scans based on baseline LDCT scans. Our findings illustrated that utilizing the predicted follow-up nodule images generated by our model during baseline screening improved diagnostic accuracy compared to using baseline nodules alone and achieved comparable performance with using real follow-up nodules. This demonstrated the potential of employing deep generative models to forecast nodule appearance in follow-up imaging from baseline LDCT scans, thereby enhancing risk assessment during initial screening. Early diagnosis of lung cancer can significantly improve patient outcomes. We developed a Growth Predictive model based on the Wasserstein Generative Adversarial Network framework (GP-WGAN) to predict the nodule growth patterns in the follow-up LDCT scans. The GP-WGAN was trained with a training set (N = 776) containing 1121 pairs of nodule images with about 1-year intervals and deployed to an independent test set of 450 nodules on baseline LDCT scans to predict nodule images (GP-nodules) in their 1-year follow-up scans. The 450 GP-nodules were finally classified as malignant or benign by a lung cancer risk prediction (LCRP) model, achieving a test AUC of 0.827 ± 0.028, which was comparable to the AUC of 0.862 ± 0.028 achieved by the same LCRP model classifying real follow-up nodule images (p = 0.071). The net reclassification index yielded consistent outcomes (NRI = 0.04; p = 0.62). Other baseline methods, including Lung-RADS and the Brock model, achieved significantly lower performance (p < 0.05). The results demonstrated that the GP-nodules predicted by our GP-WGAN model achieved comparable performance with the nodules in the real follow-up scans for lung cancer diagnosis, indicating the potential to detect lung cancer earlier when coupled with accelerated clinical management versus the current approach of waiting until the next screening exam. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer has been the most fatal female-specific cancer, and in particular, old patients have worse survival compared to young patients. In this study, we test whether the current oncology practice has been able to improve survival, compared to age group-specific past survival. We were able to show that survival in old patients remains poor, and in all patients, the time after year 1 is a critical period for survival. Although survival in ovarian cancer has improved in the Nordic countries over the past 50 years, age-related disparities have remained, or even increased. Survival has not increased for patients older than 60 years after one year of survival. This study calls for more focus on elderly ovarian cancer patients, to aim for early diagnosis and to explore more active therapeutic intervention for which age should not be considered limiting but rather the physical condition. Background: Despite treatment having improved through intensive surgical procedures and chemotherapy—and more recently, targeted therapies—ovarian cancer is the most fatal female cancer. As such, we wanted to analyze age-specific survival trends for ovarian cancer in Denmark, Finland, Norway and Sweden over the past 50 years, with a special aim of comparing survival development between the age groups. Methods: We modelled survival data from the NORDCAN database for 1-, 5- and conditional 5/1-year relative (between years 1 and 5) survival for ovarian cancer from 1972 to 2021. Results: Young patients had a 70% 5-year survival while the survival was only 30% for the oldest patients. Conditional survival showed that survival between years 1 and 5 did not improve for patients older than 60 years throughout the 50-year period, during which time the gaps between the youngest and the oldest patients widened. Conclusions: Improvement in 1-year survival was so large that it masked the modest development between years 1 and 5, resulting in a widening age disparity in 5-year survival. The current treatment practices, which appear increasingly effective for younger patients, have not helped remedy the large age differences in ovarian cancer survival. Early detection methods and therapeutic innovations are urgently needed, and aged patients need a special focus. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent advances in cancer therapy have spotlighted immune checkpoint inhibitors (ICIs) as a breakthrough in treating various cancers. These treatments, however, can lead to immune-related adverse events (irAEs) that mirror the body's heightened immune response, affecting multiple organs. Recognizing and managing these irAEs is critical, and imaging modalities such as 18F-FDG PET/CT have emerged as a potential tool for early detection. This review delves into the capability of 18F-FDG PET/CT to identify irAEs, exploring the patterns of metabolic activation indicative of these events. While highlighting the current utility of PET/CT scans in oncology for tracking therapy response and irAEs, the review also speculates on future directions, suggesting a potential role in refining immunotherapy strategies and enhancing patient care. The insights obtained could transform patient monitoring during ICI therapy, potentially improving outcomes by facilitating prompt management of irAEs. Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized contemporary oncology, presenting efficacy in various solid tumors and lymphomas. However, ICIs may potentially overstimulate the immune system, leading to immune-related adverse events (irAEs). IrAEs may affect multiple organs, such as the colon, stomach, small intestine, kidneys, skin, lungs, joints, liver, lymph nodes, bone marrow, brain, heart, and endocrine glands (e.g., pancreas, thyroid, or adrenal glands), exhibiting autoimmune inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used in oncology for staging and assessment of therapy responses, but it may also serve as a tool for detecting irAEs. This review aims to present various patterns of metabolic activation associated with irAEs due to ICI treatment, identifiable through 18F-FDG PET/CT. It describes the advantages of early detection of irAEs, but also presents the challenges in differentiating them from tumor progression. It also delves into aspects of molecular response assessment within the context of pseudoprogression and hyperprogression, along with typical imaging findings related to these phenomena. Lastly, it summarizes the role of functional PET imaging in oncological immunotherapy, speculating on its future significance and limitations. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates the effects of South Korea's national insurance coverage (NIC) expansion and the inclusion of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. By analyzing data from the Samsung Medical Center, the study reveals a notable increase in testing rates following NIC expansion and the addition of genetic counselors. Particularly noteworthy is the rise in testing rates among triple-negative breast cancer (TNBC) patients under 60. Additionally, the involvement of genetic counselors led to a significant increase in follow-up patients undergoing testing. The NIC expansion also broadened insurance coverage for TNBC patients, thereby enhancing testing accessibility. These findings underscore the positive impact of NIC expansion and genetic counselor involvement on improving patient management. Addressing financial barriers to testing and integrating genetic counseling into healthcare practices present promising strategies for advancing early detection and tailored treatment approaches, thereby contributing to global efforts in cancer care and management. Purpose: This study aims to evaluate the impact of South Korea's national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. Materials and Methods: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. Results: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. Conclusion: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigated a new imaging technique called ex vivo confocal microscopy to examine rare skin conditions. By analyzing tissue samples from different skin disorders, we found that this technique could accurately identify unique microscopic features of both common and rare skin diseases. Importantly, examiners with more experience in interpreting these images achieved higher accuracy in diagnosis. This suggests that ex vivo confocal microscopy has the potential to be a valuable tool alongside traditional methods for diagnosing rare skin conditions early and accurately, leading to better treatment outcomes for patients. While ex vivo confocal laser scanning microscopy has previously demonstrated its utility in most common skin diseases, its use in the assessment of dermatological entities with lower incidence remains unexplored in most cases. We therefore aimed to evaluate the diagnostic efficacy of some rare skin tumors as well as a few inflammatory skin diseases, that have not yet been studied in ex vivo confocal laser scanning microscopy. A total of 50 tissue samples comprising 10 healthy controls, 10 basal cell carcinoma, 10 squamous cell carcinoma, and 20 rare skin conditions were imaged using the newest generation ex vivo confocal microscopy (Vivascope 2500 M-G4, Vivascope GmbH, Munich, Germany). Three blinded investigators were asked to identify characteristic features of rare skin disorders and distinguish them from more common skin diseases in the ex vivo confocal microscopy images. Our findings present the capability of ex vivo confocal microscopy to display distinctive morphologic patterns in common and rare skin diseases. As might be expected, we found a strong correlation between imaging experience and diagnostic accuracy. While the imaging inexperienced dermatohistopathologist reached 60% concordance, the imaging-trained dermatologist obtained 88% agreement with dermatohistopathology. The imaging-trained dermatohistopathologist achieved concordance up to 92% with gold-standard dermatohistopathology. This study highlights the potential of ex vivo confocal laser scanning microscopy as a promising adjunct to conventional dermatohistopathology for the early and precise identification of rare dermatological disorders. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent technological advances, including capsule endoscopy (CE) and balloon-assisted endoscopy (BAE), have revealed that small intestinal disease is more common than previously thought. Early diagnosis of small intestinal tumors is essential for favorable outcomes. For early diagnosis, after examination of the upper and lower gastrointestinal tract, the possibility of small bowel lesions should be considered in patients with unexplained symptoms and signs, including gastrointestinal bleeding, chronic anemia, abdominal pain, obstructive symptoms, body weight loss, palpable abdominal mass, and fever of unknown origin. Recent technological advances, including capsule endoscopy (CE) and balloon-assisted endoscopy (BAE), have revealed that small intestinal disease is more common than previously thought. CE has advantages, including a high diagnostic yield, discomfort-free, outpatient basis, and physiological images. BAE enabled endoscopic diagnosis and treatment in the deep small bowel. Computed tomography (CT) enterography with negative oral contrast can evaluate masses, wall thickening, and narrowing of the small intestine. In addition, enhanced CT can detect abnormalities outside the gastrointestinal tract that endoscopy cannot evaluate. Each modality has its advantages and disadvantages, and a good combination of multiple modalities leads to an accurate diagnosis. As a first-line modality, three-phase enhanced CT is preferred. If CT shows a mass, stenosis, or wall thickening, a BAE should be selected. If there are no abnormal findings on CT and no obstructive symptoms, CE should be selected. If there are significant findings in the CE, determine the indication for BAE and its insertion route based on these findings. Early diagnosis of small intestinal tumors is essential for favorable outcomes. For early diagnosis, the possibility of small bowel lesions should be considered in patients with unexplained symptoms and signs after examination of the upper and lower gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Simple Summary: A prolonged diagnosis of lung cancer can hinder effective treatment processes for cancer patients. Artificial intelligence-based models significantly impact the healthcare system; deep-learning algorithms in the diagnostic process can save time and money and provide high-accuracy results that accelerate and improve the treatment journey. Lung cancer is the leading cause of cancer-related deaths worldwide. Two of the crucial factors contributing to these fatalities are delayed diagnosis and suboptimal prognosis. The rapid advancement of deep learning (DL) approaches provides a significant opportunity for medical imaging techniques to play a pivotal role in the early detection of lung tumors and subsequent monitoring during treatment. This study presents a DL-based model for efficient lung cancer detection using whole-slide images. Our methodology combines convolutional neural networks (CNNs) and separable CNNs with residual blocks, thereby improving classification performance. Our model improves accuracy (96% to 98%) and robustness in distinguishing between cancerous and non-cancerous lung cell images in less than 10 s. Moreover, the model's overall performance surpassed that of active pathologists, with an accuracy of 100% vs. 79%. There was a significant linear correlation between pathologists' accuracy and years of experience (r Pearson = 0.71, 95% CI 0.14 to 0.93, p = 0.022). We conclude that this model enhances the accuracy of cancer detection and can be used to train junior pathologists. [ABSTRACT FROM AUTHOR]

Simple Summary: Accounting for 10% of the new cases in 2020, colorectal cancer (CRC) is one of the most prevalent cancers worldwide. Unfortunately, CRC is frequently identified at a later stage, despite the fact that early detection greatly increases survival rates. Diagnostic endoscopy is the gold standard; however, identifying abnormalities at an early stage is challenging. In particular, convolutional neural networks (CNNs) are being used by researchers to improve detection through deep learning. But prior approaches were primarily concerned with polyp detection. This work provided a novel method for polyp segmentation and endoscopic pathological finding categorization using vision transformers and spatial transformers for the early identification of colorectal cancer (CRC). These approaches perform noticeably better than the current CNN-based algorithms. This work opens up exciting possibilities for improving on early CRC detection beyond just identifying polyps. Endoscopic pathological findings of the gastrointestinal tract are crucial for the early diagnosis of colorectal cancer (CRC). Previous deep learning works, aimed at improving CRC detection performance and reducing subjective analysis errors, are limited to polyp segmentation. Pathological findings were not considered and only convolutional neural networks (CNNs), which are not able to handle global image feature information, were utilized. This work introduces a novel vision transformer (ViT)-based approach for early CRC detection. The core components of the proposed approach are ViTCol, a boosted vision transformer for classifying endoscopic pathological findings, and PUTS, a vision transformer-based model for polyp segmentation. Results demonstrate the superiority of this vision transformer-based CRC detection method over existing CNN and vision transformer models. ViTCol exhibited an outstanding performance in classifying pathological findings, with an area under the receiver operating curve (AUC) value of 0.9999 ± 0.001 on the Kvasir dataset. PUTS provided outstanding results in segmenting polyp images, with mean intersection over union (mIoU) of 0.8673 and 0.9092 on the Kvasir-SEG and CVC-Clinic datasets, respectively. This work underscores the value of spatial transformers in localizing input images, which can seamlessly integrate into the main vision transformer network, enhancing the automated identification of critical image features for early CRC detection. [ABSTRACT FROM AUTHOR]

Simple Summary: The effects of immune checkpoint inhibitor (ICI) therapy on 40 melanoma patients who developed immune-related hypophysitis were examined in this study. These patients were compared to 40 matched ones who did not develop hypophysitis. The onset of hypophysitis varied depending on the type of ICI used. Symptoms commonly included fatigue, headaches, and digestive problems. Patients with hypophysitis had low T4 hormone levels regardless of ICI type. However, low T3 and TSH hormone levels were only observed in patients who developed hypophysitis from ipilimumab. A rapid drop in blood sodium levels was also noted at the time of hypophysitis diagnosis. Additionally, the number of eosinophils and lymphocytes in the blood increased consistently in hypophysitis patients. Early diagnosis of hypophysitis is important because of its potential complications. Monitoring patients for specific symptoms and blood value changes could aid in early detection, allowing for prompt intervention and management. Background: Immune checkpoint inhibitors (ICIs) have shown promising anti-tumor activities and are widely used for the treatment of advanced cancers. However, they may lead to immune-related adverse events (irAEs) and some of them, such as hypophysitis, can be life-threatening. Here, early diagnosis is critical. Methods: We retrospectively analyzed 40 melanoma patients who developed hypophysitis during ICI treatment with either ipilimumab and/or anti-PD1 therapy and compared them to 40 control patients who did not develop hypophysitis during the ICI treatment, matched for age, gender, type of immunotherapy, and stage. Clinical data and blood values such as LDH, CRP, TSH, T3, T4, and absolute immune cell counts were retrieved from the medical records. Patient characteristics, laboratory values, progression-free survival, and overall survival were compared between the two groups. Results: Patients with ir-hypophysitis had a median age of 59 years, and most of them were male. Clinically, frequent symptoms were fatigue, headache, dizziness, and gastrointestinal symptoms such as nausea or abdominal pain. The onset of ir-hypophysitis differed much between ipilimumab- (median 8 weeks) and anti-PD1 (median 40 weeks)-induced hypophysitis (p < 0.001). At baseline, besides a slightly increased CRP level (p = 0.06), no differences were observed in patients who later developed hypophysitis compared to the control. After treatment started, hypophysitis patients showed a constant and significant decline in T4 levels from the start of therapy until diagnosis (p < 0.05), independent of the ICI treatment regime. However, a decline in T3 and TSH was only noted in patients with ipilimumab-induced ir-hypophysitis. Furthermore, serum sodium levels declined rapidly at the diagnosis of hypophysitis (p < 0.001). In addition, there was a constant increase in the absolute counts of eosinophils and lymphocytes from baseline in hypophysitis patients (p < 0.05). Conclusion: Ir-hypophysitis reveals different clinical pictures and onset times depending on the ICI regime used. Whereas a drop in T4 levels was indicative of developing hypophysitis independent of the ICI regime, TSH levels only declined in patients under ipilimumab-based ICI regimes. To best monitor our patients, it is important to recognize these differences. [ABSTRACT FROM AUTHOR]

Simple Summary: An important component in the study of survival in breast cancer patients is how the tumor is detected. This involves examining whether and to what extent survival differs when the tumor is detected, for example, by screening or by symptoms. In such an analysis, it is important to note that survival times are influenced by several biases. One important factor is the bias due to the so-called lead time, i.e., the time by which the diagnosis has been brought forward by screening. Therefore, survival may appear to be longer even if earlier diagnosis did not affect disease progression. We examine whether there is a remaining survival difference after correction for bias that could be attributable to the mode of detection, for example, because of higher quality of care. These results can then be used to further improve the survival of breast cancer patients. (1) Background: Screen-detected breast cancer patients tend to have better survival than patients diagnosed with symptomatic cancer. The main driver of improved survival in screen-detected cancer is detection at earlier stage. An important bias is introduced by lead time, i.e., the time span by which the diagnosis has been advanced by screening. We examine whether there is a remaining survival difference that could be attributable to mode of detection, for example, because of higher quality of care. (2) Methods: Women with a breast cancer (BC) diagnosis in 2000–2022 were included from a population-based cancer registry from Schleswig-Holstein, Germany, which also registers the mode of cancer detection. Mammography screening was available from 2005 onwards. We compared the survival for BC detected by screening with symptomatic BC detection using Kaplan–Meier, unadjusted Cox regressions, and Cox regressions adjusted for age, grading, and UICC stage. Correction for lead time bias was carried out by assuming an exponential distribution of the period during which the tumor is asymptomatic but screen-detectable (sojourn time). We used a common estimate and two recently published estimates of sojourn times. (3) Results: The analysis included 32,169 women. Survival for symptomatic BC was lower than for screen-detected BC (hazard ratio (HR): 0.23, 95% confidence interval (CI): 0.21–0.25). Adjustment for prognostic factors and lead time bias with the commonly used sojourn time resulted in an HR of 0.84 (CI: 0.75–0.94). Using different sojourn times resulted in an HR of 0.73 to 0.90. (4) Conclusions: Survival for symptomatic BC was only one quarter of screen-detected tumors, which is obviously biased. After adjustment for lead-time bias and prognostic variables, including UICC stage, survival was 27% to 10% better for screen-detected BC, which might be attributed to BC screening. Although this result fits quite well with published results for other countries with BC screening, further sources for residual confounding (e.g., self-selection) cannot be ruled out. [ABSTRACT FROM AUTHOR]

Simple Summary: The impact of breast cancer on individuals and in populations can be reduced if the cancer is detected in an early stage of disease as treatments are generally less harsh and more successful. Knowing which factors to modify and by what amount that could shift breast cancer diagnoses to early stages of disease were studied in this project. Factors related to stage at diagnosis in a previous analysis of women diagnosed with breast cancer were assessed using data that mimicked the real data. The proportions of modifiable lifestyle factors in a population were increased or decreased, such as those ever having a mammogram, to see the effect on detecting more cancers in the earliest stages. Similarly, the average amounts of protein eaten per day or calories consumed were also increased and decreased. Increasing the total amount of protein eaten per day by even just 5 grams was the most important factor found in this study to improve early breast cancer diagnoses. The findings from this study could be helpful in breast cancer prevention programs that could target key modifiable factors and by other researchers studying other types of cancer. Background: Breast cancer is the most common cancer in Canadian women; nearly 25% of women diagnosed with cancer have breast cancer. The early detection of breast cancer is a major challenge because tumours often grow without causing symptom. The diagnosis of breast cancer at an early stage (stages I and II) improves survival outcomes because treatments are more effective and better tolerated. To better inform the prevention of and screening for breast cancer, simulations using modifiable rather than non-modifiable risk factors may be helpful in shifting the stage at diagnosis downward. Methods: Breast cancer stages were simulated using the data distributions from Alberta's Tomorrow Project participants who developed breast cancer. Using multivariable partial proportional odds regression models, modifiable lifestyle factors associated with the stage of cancer at diagnosis were evaluated. The proportions or mean levels of these lifestyle factors in the simulated population were systematically changed, then multiplied by their corresponding estimated odds ratios from the real data example. The effects of these changes were evaluated singly as well as cumulatively. Results: Increasing total dietary protein (g/day) intake was the single most important lifestyle factor in shifting the breast cancer stage downwards followed by decreasing total dietary energy intake (kcal/day). Increasing the proportion of women who spend time in the sun between 11 am and 4 pm in the summer months, who have had a mammogram, who have been pregnant or reducing the proportion who are in stressful situations had much smaller effects. The percentage of Stage I diagnoses could be increased by approximately 12% with small modifications of these lifestyle factors. Conclusion: Shifting the breast cancer stage at diagnosis of a population may be achieved through changes to lifestyle factors. This proof of principle study that evaluated multiple factors associated with the stage at diagnosis in a population can be expanded to other cancers as well, providing opportunities for cancer prevention programs to target specific factors and identify populations at higher risk. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is an aggressive brain cancer. Despite progress made in cancer research, patients diagnosed with glioblastomas continue to have a poor rate of survival. Lipidomics is a field of study that seeks to comprehend the structure and function of lipids, otherwise known as fats. Glioblastomas have demonstrated imbalance in lipids, and, therefore, lipidomics shows promise as an avenue to better understand glioblastomas. This paper reviews the literature on lipidomics in glioblastomas and suggests future directions for lipidomic research into the diagnosis, prognosis, and treatment of glioblastomas. Glioblastoma is the most aggressive primary brain malignancy in adults, and has a survival duration of approximately 15 months. First line treatment involves surgical resection, chemotherapy, and radiation, but despite the multi-pronged approach and advances in cancer research, glioblastoma remains devastating with a high mortality rate. Lipidomics is an emerging discipline that studies lipid pathways and characteristics, and is a promising field to understand biochemical mechanisms. In glioblastoma, disrupted lipid homeostasis has been reported in the literature. A thorough understanding of serum lipidomics may offer ways to better understand glioblastoma biomarkers, prognosis, and treatment options. Here, we review the literature, offering future directions for lipidomics research in glioblastomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Significant strides have been made in the understanding and management of breast cancer (BC), yet it remains a pervasive and life-threatening illness globally, necessitating precise diagnostic and therapeutic approaches. Molecular subtyping of BC is crucial for prognostic and predictive purposes due to its diverse clinical behaviors. Disparities in diagnosis and outcomes across different populations, particularly among individuals of African heritage, underscore the importance of localized research efforts. Early detection and treatment are imperative for improving survival rates, prompting the emergence of radiogenomics within precision medicine as a promising avenue. Radiogenomics, which integrates genetic patterns with imaging features, holds potential for enhancing early detection, prognosis, and treatment selection. By eliminating the need for biopsy and sequencing, it streamlines clinical workflows and contributes to advancing individualized patient care. However, challenges such as reproducibility, standardization, and data integration remain, highlighting the need for further research and validation, particularly in prospective multi-institutional settings. Despite limitations, radiogenomics stands as a promising frontier in breast cancer research, with the potential to revolutionize patient care through its non-invasive approach and ability to correlate genomic information with imaging phenotypes. Despite significant progress in the prevention, screening, diagnosis, prognosis, and therapy of breast cancer (BC), it remains a highly prevalent and life-threatening disease affecting millions worldwide. Molecular subtyping of BC is crucial for predictive and prognostic purposes due to the diverse clinical behaviors observed across various types. The molecular heterogeneity of BC poses uncertainties in its impact on diagnosis, prognosis, and treatment. Numerous studies have highlighted genetic and environmental differences between patients from different geographic regions, emphasizing the need for localized research. International studies have revealed that patients with African heritage are often diagnosed at a more advanced stage and exhibit poorer responses to treatment and lower survival rates. Despite these global findings, there is a dearth of in-depth studies focusing on communities in the African region. Early diagnosis and timely treatment are paramount to improving survival rates. In this context, radiogenomics emerges as a promising field within precision medicine. By associating genetic patterns with image attributes or features, radiogenomics has the potential to significantly improve early detection, prognosis, and diagnosis. It can provide valuable insights into potential treatment options and predict the likelihood of survival, progression, and relapse. Radiogenomics allows for visual features and genetic marker linkage that promises to eliminate the need for biopsy and sequencing. The application of radiogenomics not only contributes to advancing precision oncology and individualized patient treatment but also streamlines clinical workflows. This review aims to delve into the theoretical underpinnings of radiogenomics and explore its practical applications in the diagnosis, management, and treatment of BC and to put radiogenomics on a path towards fully integrated diagnostics. [ABSTRACT FROM AUTHOR]

Simple Summary: Endometrial cancer is the fourth most common female malignancy in high socioeconomic index nations and the sixth most common cancer in women worldwide. The disease incidence has increased globally by 132% in the last 30 years, and this trend is set to continue in light of an ageing population and increasing levels of obesity and diabetes. Although more women than ever before are dying of endometrial cancer, the mortality rates are falling due to recent advances in early diagnosis and treatment. Our understanding of the molecular drivers of endometrial cancer has increased substantially, and doctors are now, for the first time, starting to translate this knowledge into the true personalisation of care. This review summarises the recent advances in the field and identifies avenues for future exploration. Endometrial cancer is the sixth commonest cancer in women worldwide, with over 417,000 diagnoses in 2020. The disease incidence has increased by 132% over the last 30 years and is set to continue to rise in response to an ageing population and increasing global rates of obesity and diabetes. A greater understanding of the mechanisms driving endometrial carcinogenesis has led to the identification of potential strategies for primary disease prevention, although prospective evaluation of their efficacy within clinical trials is still awaited. The early diagnosis of endometrial cancer is associated with improved survival, but has historically relied on invasive endometrial sampling. New, minimally invasive tests using protein and DNA biomarkers and cytology have the potential to transform diagnostic pathways and to allow for the surveillance of high-risk populations. The molecular classification of endometrial cancers has been shown to not only have a prognostic impact, but also to have therapeutic value and is increasingly used to guide adjuvant treatment decisions. Advanced and recurrent disease management has also been revolutionised by increasing the use of debulking surgery and targeted treatments, particularly immunotherapy. This review summarises the recent advances in the prevention, diagnosis and treatment of endometrial cancer and seeks to identify areas for future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancers worldwide, with an overall survival rate of <10% at 5 years. For most patients with unresectable or recurrent PDAC, few therapeutic options are available, with limited efficacy. Furthermore, there is an almost complete absence of validated predictive factors. At present, microRNAs represent a promising diagnostic, prognostic, and predictive method for the clinical management of patients, avoiding inappropriate treatments. Pancreatic ductal adenocarcinoma (PDAC), a neoplasm of the gastrointestinal tract, is the most common pancreatic malignancy (90%) and the fourth highest cause of cancer mortality worldwide. Surgery intervention is currently the only strategy able to offer an advantage in terms of overall survival, but prognosis remains poor even for operated patients. Therefore, the development of robust biomarkers for early diagnosis and prognostic stratification in clinical practice is urgently needed. In this work, we investigated deregulated microRNAs (miRNAs) in tissues from PDAC patients with high (G3) or low (G2) histological grade and with (N+) or without (N−) lymph node metastases. miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. The results showed a significant increase in miR-1-3p, miR-31-5p, and miR-205-5p expression in G3 compared to G2 patients (** p < 0.01; *** p < 0.001; *** p < 0.001). miR-518d-3p upregulation and miR-215-5p downregulation were observed in N+ compared to N− patients. A statistical analysis performed using OncomiR program showed the significant involvement (p < 0.05) of two miRNAs (miR-31 and miR-205) in the histological grade of PDAC patients. Also, an expression analysis in PDAC patients showed that miR-31 and miR-205 had the highest expression at grade 3 compared with normal and other tumor grades. Overall, survival plots confirmed that the overexpression of miR-31 and miR-205 was significantly correlated with decreased survival in TCGA PDAC clinical samples. A KEGG pathway analysis showed that all three miRNAs are involved in the regulation of multiple pathways, including the Hippo signaling, adherens junction and microRNAs in cancer, along with several target genes. Based on in silico analysis and experimental validation, our study suggests the potential role of miR-1-3p, miR-31-5p, and miR-205-5p as useful clinical biomarkers and putative therapeutic targets in PDAC, which should be further investigated to determine the specific molecular processes affected by their aberrant expression. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer, a prevalent global concern, continuously motivates the research and development of new technologies for its quick detection and diagnosis. Dielectric spectroscopy is a technique previously used for material characterization but with limitations in accuracy for breast cancer diagnosis due to a lack of control over the material to be characterized. For the first time, and thanks to the assistance of 70 volunteer patients, accurate tissue characterization of breast tumors, benign or malignant (ductal carcinoma, lobular carcinoma, mucinous carcinoma and fibroadenoma), was achieved with dielectric spectroscopy. The results obtained in both relative permittivity and loss tangent show, for the first time, notable differences between the four types of tumors, which can help in making an instantaneous diagnosis of the excised tumor and accelerating subsequent treatment. Early analysis and diagnosis of breast tumors is essential for either quickly launching a treatment or for seeing the evolution of patients who, for instance, have already undergone chemotherapy treatment. Once tissues are excised, histological analysis is the most frequent tool used to characterize benign or malignant tumors. Dielectric microwave spectroscopy makes use of an open-ended coaxial probe in the 1–8 GHz frequency range to quickly identify the type of tumor (ductal carcinoma, lobular carcinoma, mucinous carcinoma and fibroadenoma). The experiment was undertaken with data from 70 patients who had already undergone chemotherapy treatment, which helped to electrically map the histological tissues with their electric permittivity. Thus, the variations in the permittivity of different types of tumors reveal distinctive patterns: benign tumors have permittivity values lower than 35, while malignant ones range between 40 and 60. For example, at a frequency of 2 GHz, the measured permittivity was 45.6 for ductal carcinoma, 33.1 for lobular carcinoma, 59.5 for mucinous carcinoma, and 27.6 for benign tumors. This differentiation remains consistent in a frequency range of 1 to 4.5 GHz. These results highlight the effectiveness of these measurements in the classification of breast tumors, providing a valuable tool for quick and accurate diagnosis and effective treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The purpose of our study was to evaluate the effectiveness of procalcitonin (PCT) as a positive predictive factor for the early identification of post-surgical wound complications, such as cutaneous pharyngeal fistulas, in patients undergoing total laryngectomy. We took into consideration 36 patients who underwent total laryngectomy, dividing them into two groups: a first group made up of 27 patients who had no post-operative complications; a second group made up of 9 patients who had the onset of pharyngeal-cutaneous fistula as a complication. In both groups we evaluated the procalcitonin values at various times in order to evaluate the values found with the onset of the complication. Objectives. The aim of this prospective study was to investigate the role of procalcitonin as an early diagnostic marker of pharyngocutaneous fistula (PCF) in a cohort of head and neck patients treated with total laryngectomy for squamous cell carcinoma. Methods. This prospective study was conducted on a sample of patients enrolled from January 2019 to March 2022. All patients were subjected to a "protocol" of blood chemistry investigations, scheduled as follows: complete blood count with formula, ESR dosage, CPR, and PCT. PCT was also dosed by salivary sampling and a pharyngo-cutaneous swab in patients who presented with PCF. The dosage scheme was systematically repeated: the day before the intervention (t0); the 5th day postoperative (t1); the 20th day postoperative (t2); and at time X, the day of the eventual appearance of the pharyngocutaneous fistula. Results. A total of 36 patients met the inclusion criteria. The patients enrolled in the study were subsequently divided into two groups: 27 patients underwent total laryngectomy (TL) for laryngeal cancer without postoperative complications, and 9 patients were undergoing TL with postoperative PCF. Using the Cochran's Q test, statistical significance was found for PCT among T0, T1, Tx, and T2 (p-value < 0.001) between the PCF and non-PCF groups. The Z test demonstrated that there is a difference in PCT levels at T1 and T2 and that this difference is statistically significant (p < 0.001). Conclusions. PCT could be considered an early marker of complications in open laryngeal surgery. According to our results, it could be useful in the precocious detection of pharyngocutaneous fistulas and in the management of antibiotic therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Actinic keratoses are lesions with a variable potential for malignant transformation, but with a difficult predictability of evolution towards this type of lesions. Non-invasive skin imaging methods represent diagnostic tools that allow a better evaluation of actinic keratoses lesions, as well as the establishment of a diagnosis with greater specificity and sensitivity. This review aims to identify all skin imaging methods that are useful in the diagnosis and monitoring of the treatment of actinic keratoses, as well as to identify those lesions at risk of transforming into squamous cell carcinoma. Non-melanocytic skin cancers represent an important public health problem due to the increasing incidence and the important local destructive potential. Thus, the early diagnosis and treatment of precancerous lesions (actinic keratoses) is a priority for the dermatologist. In recent years, non-invasive skin imaging methods have seen an important development, moving from simple observational methods used in clinical research, to true diagnostic and treatment methods that make the dermatologist's life easier. Given the frequency of these precancerous lesions, their location on photo-exposed areas, as well as the long treatment periods, with variable, imprecise end-points, the need to use non-invasive imaging devices is increasingly evident to complete the clinical observations in the diagnosis and treatment of these lesions, with the aim of increasing accuracy and decreasing the adverse effects due to long treatment duration. This is the first review that brings together all skin imaging methods (dermoscopy, reflectance confocal microscopy, ultrasonography, dermoscopy-guided high frequency ultrasonography, and optical coherence tomography) used in the evaluation of actinic keratoses and their response to different treatment regimens. [ABSTRACT FROM AUTHOR]

Simple Summary: The paper discusses precursor lesions of breast cancer and the subclinical syndrome of multiple organ failure, representing early disease stages with changes occurring before symptoms become clinically detectable. It aims to address why breast cancer patients deteriorate and how their condition progresses from subclinical organ failure to acute multiple organ failure. The review utilized databases like PubMed, Google Scholar, and Scopus, focusing on keywords related to organ failure, breast cancer, and quality of life. It emphasizes the need to identify and prevent the onset of multiple organ failure in cancer patients early on to enhance their quality of life and survival. Despite a subclinical organ failure syndrome undetectable by current diagnostics, the text proposes the increasing importance of AI in aiding physicians in diagnosing this syndrome in the future. This review explores the interconnection between precursor lesions of breast cancer (typical ductal hyperplasia, atypical ductal/lobular hyperplasia) and the subclinical of multiple organ failure syndrome, both representing early stages marked by alterations preceding clinical symptoms, undetectable through conventional diagnostic methods. Addressing the question "Why patients with breast cancer exhibit a tendency to deteriorate", this study investigates the biological progression from a subclinical multiple organ failure syndrome, characterized by insidious but indisputable lesions, to an acute (clinical) state resembling a cascade akin to a waterfall or domino effect, often culminating in the patient's demise. A comprehensive literature search was conducted using PubMed, Google Scholar, and Scopus databases in October 2023, employing keywords such as "MODS", "SIRS", "sepsis", "pathophysiology of MODS", "MODS in cancer patients", "multiple organ failure", "risk factors", "cancer", "ICU", "quality of life", and "breast cancer". Supplementary references were extracted from the retrieved articles. This study emphasizes the importance of early identification and prevention of the multiple organ failure cascade at the inception of the malignant state, aiming to enhance the quality of life and extend survival. This pursuit contributes to a deeper understanding of risk factors and viable therapeutic options. Despite the existence of the subclinical multiple organ failure syndrome, current diagnostic methodologies remain inadequate, prompting consideration of AI as an increasingly crucial tool for early identification in the diagnostic process. [ABSTRACT FROM AUTHOR]

Simple Summary: Unlike NPC, there is little research concerned with the role of EBV in the development of OPSCC. Therefore, it is necessary to search for new markers enabling the early diagnosis and prognosis of this disease. The aim of this study was to evaluate the diagnostic utility of anti-Zta and anti-LMP1 antibodies in EBV positive OPSCC patients. For this purpose, experiments were carried out to determine both the prevalence and level of anti-Zta and anti-LMP1 antibodies in serum patients with OPSCC in relation to grading and TNM classification. The highest level of tested antibodies was observed in more advanced clinical stages. The diagnostic accuracy of anti-Zta antibodies was confirmed using ROC analysis. We showed that the determination of both types of antibodies may be useful in the diagnosis of OPSCC. Moreover, anti-LMP1 antibody may be a diagnostic as well as prognostic biomarker. Background: The role of the Epstein–Barr virus (EBV), the first known human oncogenic virus, in the development of nasopharyngeal cancer (NPC) is already well documented. There are few studies in the available scientific literature on oropharyngeal cancer associated with EBV infection. Due to the lack of an effective vaccine against EBV, it is necessary to search for new markers for the early diagnosis and prognosis of this disease. The aim of current study was to determine the usefulness of anti-Zta and anti-LMP1 antibodies as diagnostic and prognostic markers in EBV positive OPSCC patients. Methods: For this purpose, experiments were carried out to determine both the prevalence and level of EBVCA, EBNA1, EA, Zta, and LMP1 antibodies in serum patients depending on histological differentiation-grading and TNM classification (ELISA assay). Results: Based on the obtained results, we showed that OPSCC EBV positive patients are characterized by a higher level of anti-Zta antibodies than in the EBV negative group. Their level depended on the clinical stage. Moreover, a ROC analysis confirmed the diagnostic accuracy of anti-Zta antibodies. Conclusions: Anti-Zta and anti-LMP1 antibodies may be useful in the diagnosis of OPSCC. It seems that combined antibody testing should be performed to increase diagnostic accuracy. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper aims to highlight the latest advancements in the application of artificial intelligence in the diagnosis of myelodysplastic syndrome. This research focuses on a group of blood disorders called Myelodysplastic Syndrome (MDS), which can potentially develop into a more severe condition called Acute Myeloid Leukemia (AML). Detecting MDS early is crucial, but the current methods are time-consuming and labor-intensive. We aim to explore how artificial intelligence (AI) and machine learning (ML) can make the diagnosis of MDS faster and more accurate. AI involves computer programs that can think like humans, and ML is a part of AI that helps computers learn patterns and make predictions. By using these technologies, doctors can improve how they diagnose MDS, leading to better treatment and outcomes for patients. Myelodysplastic syndrome (MDS) is composed of diverse hematological malignancies caused by dysfunctional stem cells, leading to abnormal hematopoiesis and cytopenia. Approximately 30% of MDS cases progress to acute myeloid leukemia (AML), a more aggressive disease. Early detection is crucial to intervene before MDS progresses to AML. The current diagnostic process for MDS involves analyzing peripheral blood smear (PBS), bone marrow sample (BMS), and flow cytometry (FC) data, along with clinical patient information, which is labor-intensive and time-consuming. Recent advancements in machine learning offer an opportunity for faster, automated, and accurate diagnosis of MDS. In this review, we aim to provide an overview of the current applications of AI in the diagnosis of MDS and highlight their advantages, disadvantages, and performance metrics. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, and immunotherapy could be one of the safest options to control PDAC. Although the p40 family of cytokines has four members comprising IL-12, p40 homodimer (p402), p40 monomer (p40), and IL-23, we found an increase in p402 and p40 and a decrease in IL-12 and IL-23 in serum of pancreatic cancer patients as compared to healthy controls. Similarly, human pancreatic cancer cells also produced greater levels of p402 and p40 and lower levels of IL-12 and IL-23 than normal human pancreatic cells. Accordingly, neutralization of p402 by a3-1d monoclonal antibody (mAb) and p40 by a3-3a mAb separately led to apoptosis of pancreatic cancer cells and tumor shrinkage in a patient-derived xenograft (PDX) mouse model of pancreatic cancer, highlighting the possible therapeutic potential of mAbs against p402 and p40 in pancreatic cancer. Pancreatic cancer is a highly aggressive cancer with a high mortality rate and limited treatment options. It is the fourth leading cause of cancer in the US, and mortality is rising rapidly, with a 12% relative 5-year survival rate. Early diagnosis remains a challenge due to vague symptoms, lack of specific biomarkers, and rapid tumor progression. Interleukin-12 (IL-12) is a central cytokine that regulates innate (natural killer cells) and adaptive (cytokine T-lymphocytes) immunity in cancer. We demonstrated that serum levels of IL-12p40 homodimer (p402) and p40 monomer (p40) were elevated and that of IL-12 and IL-23 were lowered in pancreatic cancer patients compared to healthy controls. Comparably, human PDAC cells produced greater levels of p402 and p40 and lower levels of IL-12 and IL-23 compared to normal pancreatic cells. Notably, neutralization of p402 by mAb a3-1d and p40 by mAb a3-3a induced the death of human PDAC cells, but not normal human pancreatic cells. Furthermore, we demonstrated that treatment of PDX mice with p402 mAb and p40 mAb resulted in apoptosis and tumor shrinkage. This study illustrates a new role of p402 and p40 monomer in pancreatic cancer, highlighting possible approaches against this deadly form of cancer with p402 and p40 monomer immunotherapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Malignant neoplasms are currently one of the main causes of morbidity and mortality worldwide, posing a major public health challenge. However, recent advances in cancer biology and immunity research have led to the development of immunotherapy, which is now used in routine clinical practice in cancer treatment. Along with the increasing number of patients treated with immunotherapy, a wider spectrum of side effects, called immune-related adverse events, have been brought to light. Most of them have a mild or moderate manifestation. However, in rare cases of life-threatening symptoms, proper and rapid management is of utmost importance. In this review, we focus on life-threatening endocrine side effects of immunotherapy to provide information on the symptoms, diagnostics, and management strategies described in the literature to date. Malignant neoplasms are currently one of the leading causes of morbidity and mortality worldwide, posing a major public health challenge. However, recent advances in research in cancer biology and immunity have led to the development of immunotherapy, which is now used on an everyday basis in cancer treatment in addition to surgical treatment, classical cytostatics, and radiotherapy. The efficacy of immunotherapy has promoted the great popularity of this treatment among patients, as well as significant research interest. The increasing number of patients being treated with immunotherapy not only reassures physicians of the efficacy of this technique but also shows the wide spectrum of side effects of this therapy, which has not been considered before. Immune-related adverse events may affect many systems and organs, such as digestive, cardiovascular, respiratory, skin, or endocrine organs. Most complications have a mild or moderate course, but there are life-threatening manifestations that are essential to be aware of because if they are not properly diagnosed and treated on time, they can have fatal consequences. The purpose of this paper was to present the results of a literature review on the current state of knowledge on life-threatening endocrine side effects (such as adrenal crisis, thyroid storm, myxoedema crisis, diabetic ketoacidosis, and severe hypocalcaemia) of immune checkpoint inhibitors to provide information on symptoms, diagnostics, and management strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is a major burden of disease worldwide, with cancer cachexia being a poor prognosis factor which leads to a decreased quality of life and overall survival. There is an increased need for further studies regarding this complex phenomenon of metabolic imbalances, weight loss, inflammatory changes, and other important pathophysiological components that have a drastic impact on the prognosis of cancer patients. The main goal of this paper is to emphasize the importance of the early detection of cancer patients affected by cachexia and to provide a scientific update regarding the main pathophysiological mechanism involved in cancer cachexia pathogenesis and the complex clinical impact that this pathology has. We aim to raise awareness about the importance of identifying potential biomarkers for the early diagnosis of cancer cachexia, as a key factor in improving patients' management and approach. Cancer remains a major health problem and is associated with cachexia in up to 80% of cases, leading to decreased survival and quality of life. Cachexia involves complex metabolic disturbances in both protein and energy balance, muscle wasting phenomena, weight loss, systemic inflammation, overall decreased performance status, and tolerability to treatment. The clinical impact of cancer cachexia is very complex, with early detection of cachectic patients and identification of predictive biomarkers being two key factors for improving survival. Thus, a better understanding of the complexity of cancer cachexia phenomena and its main pathophysiological mechanism is much needed. Our review highlights the most important information about cancer cachexia, aiming to disseminate updated research findings about this highly deadly condition. [ABSTRACT FROM AUTHOR]

Simple Summary: Oesophago-gastric cancers are associated with poor survival due to late diagnosis. By the time patients present to their doctor, there is a high chance the disease has spread around the body. Currently, less than 40% of patients with oesophago-gastric cancer can be treated with potentially curative intent. Non-invasive testing of patients who are at higher risk of oesophago-gastric cancer may help to identify these cancers earlier, before they have spread around the body, potentially increasing chances of cure. Mucins are proteins that are found throughout the digestive system and involved in the development of this disease. In this study, the literature on the role of mucins in the diagnosis of oesophago-gastric cancer has been reviewed. Mucins MUC1, MUC2, MUC5AC and MUC6 were the most frequently implicated in oesophago-gastric cancer. Further study of these mucins in high-risk populations may reveal new markers for non-invasive early diagnostic testing for oesophago-gastric cancer. Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with pre-malignant or benign disease. Following diagnostic confirmation with endoscopic biopsy, early OGC may be treated sooner. Mucins are transmembrane glycoproteins implicated in OGC with potential use as biomarkers of malignant transformation. This systematic review defines the role of mucins in OGC diagnosis. A literature search of MEDLINE, Web of Science, Embase and Cochrane databases was performed following PRISMA protocols for studies published January 1960–December 2022. Demographic data and data on mucin sampling and analysis methods were extracted. The review included 124 studies (n = 11,386 patients). Gastric adenocarcinoma (GAc) was the commonest OG malignancy (n = 101) followed by oesophageal adenocarcinoma (OAc, n = 24) and squamous cell carcinoma (OSqCc, n = 10). Mucins MUC1, MUC2, MUC5AC and MUC6 were the most frequently implicated. High MUC1 expression correlated with poorer prognosis and metastases in OSqCc. MUC2 expression decreases during progression from healthy mucosa to OAc, causing reduced protection from gastric acid. MUC5AC was upregulated, and MUC6 downregulated in GAc. Mucin expression varies in OGC; changes may be epigenetic or mutational. Profiling upper GI mucin expression in OGC, with pre-malignant, benign and healthy controls may identify potential early diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: Early diagnosis of potentially malignant oral disorders (OPMD) is crucial in reducing oral cancer mortality. It is necessary to investigate and identify predictive biomarkers capable of estimating the risk of malignant transformation in potentially malignant oral lesions. In this study, we analyzed a panel of salivary markers, including adenosine deaminase (ADA), ferritin (FRR) and total protein (TP). We found no significant differences in salivary ADA between the OPMD group and controls. However, we did observe statistically significant differences in ferritin and total proteins when compared to the control group. Therefore, ferritin and total proteins may serve as potential salivary biomarkers for diagnosis. Furthermore, saliva tests are a reliable and non-invasive diagnostic tool, offering an intriguing alternative for screening large populations. Nevertheless, validation through extensive clinical studies is required. Introduction: Oral potentially malignant disorders (OPMD) are lesions associated with an increased risk of transformation (MT) into cancer. Objective: A study was made of the salivary levels of adenosine deaminase (ADA), ferritin (FRR) and total proteins (TP) in healthy individuals and in patients with oral potentially malignant disorders (OPMD), assessing the potential role of saliva as a diagnostic tool. Methods: A total of 91 subjects participated in the study, divided into two groups—59 patients with OPMD (oral leukoplakia or oral lichen planus) and 32 healthy controls—with measurements being made of salivary ADA, ferritin (FRR) and total proteins (TP). Results: There were no significant differences in salivary mean ADA between the OPMD group 0.85 ± 2.18 UI/I and the controls 0.71 ± 1.72 UI/I (p = 0.934), though the levels of both FRR mean OPMD, 12.66 ± 10.50 (µg/L), versus control, 7.19 ± 4.44 (p = 0.001), and TP, 23.41 ± 17, versus control, 14.15 ± 15.19, were significantly higher in the OPMD group (p = 0.001). Patients with oral lichen planus showed significant differences in terms of FRR (p = 0.009) and TP (p = 0.003). The ferritin in LPO with a cut-off point of 8.5C showed a sensitivity and specificity of 54.3% and 82.3, respectively. The area under the curve (AUC) was 0.69 (95% confidence interval (95% CI): 0.58–0.82; p = 0.003). Conclusions: Ferritin and total proteins may constitute potential salivary biomarkers for oral lichen planus, though further studies are still needed in this field. In addition, saliva testing is a reliable and noninvasive diagnostic tool and appears to be a reliable strategy offering an interesting alternative for the screening of large populations. [ABSTRACT FROM AUTHOR]

Simple Summary: The research aimed to address the challenges in the early diagnosis of Oral Squamous Cell Carcinoma (OSCC), a critical concern given its high fatality rate and global prevalence. Through the development of hybrid methodologies, the study sought to improve early diagnosis, reduce the burden on pathologists, and enhance the accuracy of OSCC diagnosis. By employing transfer learning, a combination of CNN and SVMs, and a fusion of deep and texture-based features, the research achieved a significant overall accuracy of 97.00%, effectively addressing the critical problem of timely and accurate OSCC diagnosis. Oral cancer is a fatal disease and ranks seventh among the most common cancers throughout the whole globe. Oral cancer is a type of cancer that usually affects the head and neck. The current gold standard for diagnosis is histopathological investigation, however, the conventional approach is time-consuming and requires professional interpretation. Therefore, early diagnosis of Oral Squamous Cell Carcinoma (OSCC) is crucial for successful therapy, reducing the risk of mortality and morbidity, while improving the patient's chances of survival. Thus, we employed several artificial intelligence techniques to aid clinicians or physicians, thereby significantly reducing the workload of pathologists. This study aimed to develop hybrid methodologies based on fused features to generate better results for early diagnosis of OSCC. This study employed three different strategies, each using five distinct models. The first strategy is transfer learning using the Xception, Inceptionv3, InceptionResNetV2, NASNetLarge, and DenseNet201 models. The second strategy involves using a pre-trained art of CNN for feature extraction coupled with a Support Vector Machine (SVM) for classification. In particular, features were extracted using various pre-trained models, namely Xception, Inceptionv3, InceptionResNetV2, NASNetLarge, and DenseNet201, and were subsequently applied to the SVM algorithm to evaluate the classification accuracy. The final strategy employs a cutting-edge hybrid feature fusion technique, utilizing an art-of-CNN model to extract the deep features of the aforementioned models. These deep features underwent dimensionality reduction through principal component analysis (PCA). Subsequently, low-dimensionality features are combined with shape, color, and texture features extracted using a gray-level co-occurrence matrix (GLCM), Histogram of Oriented Gradient (HOG), and Local Binary Pattern (LBP) methods. Hybrid feature fusion was incorporated into the SVM to enhance the classification performance. The proposed system achieved promising results for rapid diagnosis of OSCC using histological images. The accuracy, precision, sensitivity, specificity, F-1 score, and area under the curve (AUC) of the support vector machine (SVM) algorithm based on the hybrid feature fusion of DenseNet201 with GLCM, HOG, and LBP features were 97.00%, 96.77%, 90.90%, 98.92%, 93.74%, and 96.80%, respectively. [ABSTRACT FROM AUTHOR]

Simple Summary: Current research is exploring the evolving landscape of Myelodysplastic Syndrome (MDS) treatment, a challenging condition often progressing to acute myeloid leukemia. For low-risk MDS, the focus is on personalized care through precise risk assessment and tailored interventions, utilizing means like erythropoiesis-stimulating agents, lenalidomide, and luspatercept. High-risk MDS treatments are shifting towards upfront doublet or triplet therapies and minimal residual disease (MRD) monitoring. A holistic approach integrates treatments like stem cell transplants and post-transplant maintenance, guided by individual patient circumstances. Precision medicine, driven by Next Generation Sequencing (NGS), aids in early diagnosis, prognosis, and customized interventions, allowing for investigations through clinical trials within more homogeneous patient cohorts characterized by similar molecular profiles. Based on these premises, the future of MDS treatment irrefutably moves towards personalized care, leveraging advanced technologies and molecular insights to enhance patient outcomes in the realm of hematological malignancies. This perspective delves into the evolving landscape of Myelodysplastic Syndrome (MDS) treatment. MDS presents a significant clinical challenge, often progressing to acute myeloid leukemia. For low-risk MDS, the emphasis is on personalized care through comprehensive risk assessment, clinical monitoring, and tailored interventions, including promising agents like erythropoiesis-stimulating agents, lenalidomide, and luspatercept, with the anticipation of an expanding therapeutic arsenal and early intervention for improved outcomes. In contrast, high-risk MDS treatment is evolving towards upfront doublet or triplet therapies with a focus on minimal residual disease (MRD) monitoring. A holistic approach integrates various modalities, including stem cell transplant and post-transplant maintenance, all guided by individual patient circumstances. Risk-adapted strategies are crucial for enhancing patient outcomes. Precision medicine for MDS treatment is budding, largely driven by Next Generation Sequencing (NGS). NGS aids in early diagnosis, prognostication, and the targeting of specific mutations, with molecular data increasingly informing treatment responses and allowing for tailored interventions. Clinical trials within homogeneous patient groups with similar molecular profiles are becoming more common, enhancing treatment precision. In conclusion, the future of MDS treatment is moving towards personalized medicine, leveraging advanced technologies like NGS and molecular insights to improve outcomes in the realm of hematological malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor (CAR)-T cells are a novel type of therapy that is becoming more prominent in the treatment of many hematological malignancies. They are associated with serious side effects including hemophagocytic lymphohistiocytosis (HLH), which can be fatal. Diagnosis of HLH can be challenging due to the lack of a uniform diagnostic criteria and the overlap with other frequent toxicities of CAR-T cells. Available treatments have been previously used for HLH but may not be as effective in this setting. The purpose of this literature review was to examine the evolution of the diagnostic criteria and treatment recommendations for HLH specifically in the setting of CAR-T cell therapy in order to facilitate prompt diagnosis and the implementation of suitable treatment to improve patient outcomes. Since CAR-T cell therapy was initially approved in 2017, its use has become more prevalent and so have its side effects. CAR-T-related HLH, also named immune effector cell-associated HLH-like syndrome (IEC-HS), is a rare but fatal toxicity if not recognized promptly. We conducted a review of the literature in order to understand the prevalence of IEC-HS as well as clarify the evolution of the diagnostic criteria and treatment recommendations. IEC-HS occurrence varies between CAR-T cell products and the type of malignancy treated. Diagnosis can be challenging as there are no standardized diagnostic criteria, and its clinical features can overlap with cytokine release syndrome and active hematological disease. Suggested treatment strategies have been extrapolated from prior experience in HLH and include anakinra, corticosteroids and ruxolitinib. IEC-HS is a potentially fatal toxicity associated with CAR-T cell therapy. Early recognition with reliable diagnostic criteria and prompt implementation of treatment specific to IEC-HS is imperative for improving patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to develop a new warning score for cancer patients who are at risk of getting worse in the hospital. Cancer patients can have serious problems due to their treatment or cancer itself. A quick response system is used to find and treat these patients. This study used a deep-learning method to create a warning score based on the changes in vital signs. The warning score, called Can-EWS, was better than the existing score, called MEWS, in predicting and preventing bad outcomes. Can-EWS also had fewer false alarms than MEWS. This study could help improve the safety and care of cancer patients in the hospital. Background: Cancer patients who are admitted to hospitals are at high risk of short-term deterioration due to treatment-related or cancer-specific complications. A rapid response system (RRS) is initiated when patients who are deteriorating or at risk of deteriorating are identified. This study was conducted to develop a deep learning-based early warning score (EWS) for cancer patients (Can-EWS) using delta values in vital signs. Methods: A retrospective cohort study was conducted on all oncology patients who were admitted to the general ward between 2016 and 2020. The data were divided into a training set (January 2016–December 2019) and a held-out test set (January 2020–December 2020). The primary outcome was clinical deterioration, defined as the composite of in-hospital cardiac arrest (IHCA) and unexpected intensive care unit (ICU) transfer. Results: During the study period, 19,739 cancer patients were admitted to the general wards and eligible for this study. Clinical deterioration occurred in 894 cases. IHCA and unexpected ICU transfer prevalence was 1.77 per 1000 admissions and 43.45 per 1000 admissions, respectively. We developed two models: Can-EWS V1, which used input vectors of the original five input variables, and Can-EWS V2, which used input vectors of 10 variables (including an additional five delta variables). The cross-validation performance of the clinical deterioration for Can-EWS V2 (AUROC, 0.946; 95% confidence interval [CI], 0.943–0.948) was higher than that for MEWS of 5 (AUROC, 0.589; 95% CI, 0.587–0.560; p < 0.001) and Can-EWS V1 (AUROC, 0.927; 95% CI, 0.924–0.931). As a virtual prognostic study, additional validation was performed on held-out test data. The AUROC and 95% CI were 0.588 (95% CI, 0.588–0.589), 0.890 (95% CI, 0.888–0.891), and 0.898 (95% CI, 0.897–0.899), for MEWS of 5, Can-EWS V1, and the deployed model Can-EWS V2, respectively. Can-EWS V2 outperformed other approaches for specificities, positive predictive values, negative predictive values, and the number of false alarms per day at the same sensitivity level on the held-out test data. Conclusions: We have developed and validated a deep learning-based EWS for cancer patients using the original values and differences between consecutive measurements of basic vital signs. The Can-EWS has acceptable discriminatory power and sensitivity, with extremely decreased false alarms compared with MEWS. [ABSTRACT FROM AUTHOR]

Simple Summary: The optimal surveillance protocol for patients diagnosed with uveal melanoma is a subject of ongoing debate as the current consensus guidelines make little reference to medical evidence. The objective of this study was to assess whether surveillance with an enhanced protocol (high frequency or enhanced modality) is superior to surveillance using the standard protocol in detecting early metastasis and, more importantly, whether surveillance with the enhanced protocol translates into a survival advantage in uveal melanoma patients with high risk of metastasis. Our study provided that an enhanced protocol with high-frequency or enhanced-modality surveillance detected smaller hepatic metastatic lesions compared to the standard protocol. However, the detection of smaller metastases did not translate into improved overall survival in our study cohort. Purpose: to evaluate the effectiveness of enhanced surveillance protocols (EP) utilizing high frequency (HF) or enhanced modality (EM) compared to the standard protocol (SP) in detecting metastasis and determining their impact on overall survival (OS) in high-risk uveal melanoma (UM) patients. Methods: A total of 87 consecutive patients with Class 2 (high risk) primary UM were enrolled, with negative baseline systemic staging. The patients underwent systemic surveillance with either SP (hepatic ultrasonography [US] every 6 months) or EP (either HF [US every 3 months] or EM [incorporation hepatic computed tomography/magnetic resonance imaging]) following informed discussion. The main outcome measures were largest diameter of largest hepatic metastasis (LDLM), number of hepatic metastatic lesions, time to detection of metastasis (TDM), and OS. Results: This study revealed significant differences in LDLM between surveillance protocols, with the use of EP detecting smaller metastatic lesions (HF, EM, and SP were 1.5 cm, 1.6 cm, and 6.1 cm, respectively). Patients on the EM protocol had a lower 24-month cumulative incidence of >3 cm metastasis (3.5% EM vs. 39% SP; p = 0.021), while those on the HF protocol had a higher 24-month cumulative incidence of ≤3 cm metastasis compared to SP (31% HF vs. 10% SP; p = 0.017). Hazard of death following metastasis was significantly reduced in the EP (HR: 0.25; 95% CI: 0.07, 0.84), HF (HR: 0.23; 95% CI: 0.06, 0.84), and EM (HR: 0.11; 95% CI: 0.02, 0.5) groups compared to SP. However, TDM and OS did not significantly differ between protocols. Conclusions: Enhanced surveillance protocols improved early detection of hepatic metastasis in UM patients but did not translate into a survival advantage in our study cohort. However, early detection of metastasis in patients receiving liver-directed therapies may lead to improved overall survival. [ABSTRACT FROM AUTHOR]

Simple Summary: While a significant number of ECs are successfully treated without recurrence, some cases of EC still result in death even in their early stages. Incorporating molecular classification enhances prognostic accuracy, aiding tailored treatments. This approach has been utilized by the 2021 ESGO/ESTRO/ESP guidelines, the 2022 ESMO guidelines, and the updated 2023 FIGO classification. Our study employed POLE ddPCR, a cost-effective and easy-to-perform test, as an alternative to POLE NGS for molecular classification. This classification was further enriched by the established prognostic marker, L1CAM, resulting in molecular L1CAM classification. The NSMP group was the largest heterogeneous subgroup. Efforts have been made to find additional markers for further subclassification. When we further categorized the NSMP group, which demonstrates an intermediate prognosis between the POLEmut/MMR-D group and the p53abn group, we were able to distinguish the NSMP-L1CAM-positive subgroup, which exhibited a prognosis similar to the p53-mutated subgroup in terms of poorer outcomes. In multivariate analysis, the molecular L1CAM classification showed an independent prognostic factor for recurrence-free survival and overall survival. Aim: In order to enhance risk stratification in early-stage endometrial cancer (EC), we conducted molecular classification using surrogate markers, including the POLE droplet digital polymerase chain reaction (ddPCR) and L1CAM immunohistochemistry (IHC). Method: We analyzed archival tumor tissue from 183 early-stage EC patients. POLE pathogenic mutations of P286R, V411L, S297F, A456P, and S459F within exons 9, 13, and 14 were detected using a ddPCR, while the mismatch repair (MMR) status was determined by MMR protein IHC and MSI tests. Additionally, we conducted IHC for p53 and L1CAM. Results: The 183 ECs were categorized into four subgroups: POLE-mutated (15.9%), MMR-deficient (29.0%), p53-abnormal (8.7%), and non-specific molecular profile (NSMP, 46.4%). We further subcategorized the NSMP subgroup into NSMP-L1CAMneg (41.5%) and NSMP-L1CAMpos (4.9%), which we refer to as the molecular L1CAM classification. The molecular L1CAM classification was an independent prognostic factor for recurrence-free survival (RFS) and overall survival (OS) (p < 0.001, each). Conclusion: Integrating molecular L1CAM classification can enhance risk stratification in early-stage EC, providing valuable prognostic information to guide treatment decisions and improve patient outcomes. POLE ddPCR might be a cost-effective and easy-to-perform test as an alternative to POLE NGS. [ABSTRACT FROM AUTHOR]