Surveillance Of Markers Research Articles

Real-world data from patients with gastric-type mucinous carcinoma of the cervix: a multicenter, retrospective study.

We herein retrospectively analyzed the clinicopathologic features from a large cohort of GAS patients to provide real-world evidence for optimizing the diagnosis and treatment. One hundred and fifty-seven GAS patients from three hospitals were recruited for analysis. We extracted clinical and pathologic information from patient medical records and performed regular follow-up. Logistic regression and Kaplan - Meier analyses were conducted to identify the prognostic factors. 31.2% exhibited stage I tumor, and 11.5%, 33.1%, and 24.2% manifested tumors at stages II, III, and IV, respectively. For the entire group, the median progression-free survival (PFS) and overall survival (OS) were 22 and 33 months, respectively. Multivariate analysis showed tumor stage and ovarian metastasis were predictors for PFS; and that ovarian metastasis and small tumor diameter were independent prognostic factors for OS. We determined an abnormal elevation of tumor abnormal protein (TAP) in 76% GAS patients, which could serve as a sensitive marker for tumor recurrence/metastasis. We demonstrated that ovarian metastasis and FIGO stage (including tumor diameter) were independent prognostic predictors for GAS patients. Moreover, we were the first to report that TAP constituted a potent marker for GAS surveillance, thus warranting further investigation.

Microbial surveillance versus cytokine responsiveness in native and non-native house sparrows.

The success of introduced species often relies on flexible traits, including immune system traits. While theories predict non-natives will have weak defences due to decreased parasite pressure, effective parasite surveillance remains crucial, as infection risk is rarely zero and the evolutionary novelty of infection is elevated in non-native areas. This study examines the relationship between parasite surveillance and cytokine responsiveness in native and non-native house sparrows, hypothesizing that non-natives maintain high pathogen surveillance while avoiding costly inflammation. We made this specific prediction, as this pattern could enable invaders to effectively mitigate pathogen risk in a manner commensurate with the life-history priorities of a colonizing organism (i.e. rapid maturation and high reproductive effort). To test this hypothesis, we measured TLR-2 and TLR-4 expression, markers of pathogen surveillance and cytokine responses (changes in IL-1β and IL-10), regulators of inflammation, to a simulated bacterial infection. In non-native sparrows, we found that as TLR-4 expression increased, IL-1β and IL-10 responses decreased, a relationship not observed in native sparrows. Additionally, higher body condition predicted larger IL-1β and IL-10 responses in all birds. These findings suggest that high TLR-4 surveillance may mitigate strong inflammatory responses in non-native sparrows, with pathological and resource-based costs driving immune variation among and within populations.

Circulating Cell-free Human Papillomavirus DNA as a Tumor Marker in Recurrent or Metastatic Cervical Cancer: A Pilot Study

PURPOSE: Monitoring of circulating human papillomavirus (HPV) cell-free DNA (cfDNA) is a minimally invasive approach for surveillance in HPV-associated cancers, particularly cervical cancer. The aim of this study was to monitor circulating HPV cfDNA levels in patients with recurrent or metastatic cervical cancer during treatment and follow-up to assess the utility of HPV cfDNA as a tumor marker for disease surveillance and in guiding clinical treatment decisions. EXPERIMENTAL DESIGN: In this prospective pilot observational study, levels of HPV cfDNA in serum samples from 28 patients with recurrent or metastatic HPV+ cervical cancer were measured via digital droplet polymerase chain reaction. Results for HPV cfDNA levels were matched to clinical outcomes and to serum levels of squamous cell carcinoma antigen (SCC-Ag) to assess the clinical potential of HPV cfDNA as a tumor marker. RESULTS: HPV cfDNA was detected in all 28 patients (100%). Notably, median baseline HPV cfDNA levels varied according to the metastatic pattern in individual patients (P=0.019). Specifically, patients with a combined multiple-metastasis pattern had higher median baseline HPV cfDNA levels than patients with a single metastasis (P=0.003). All participants exhibited changes in HPV cfDNA levels over a median monitoring period of 2 months (range 0.3-16.9) before evaluations for treatment response or disease progression. Among 26 patients initially diagnosed with squamous cell cervical cancer, the positivity rate was 100% for HPV cfDNA and 69.2% for SCC-Ag (P=0.004, 95% confidence interval, 0-0.391). Among 20 patients longitudinally monitored for squamous cell cervical cancer, the concordance with changes in disease status was 90% for HPV cfDNA and 50% for SCC-Ag (P=0.014, 95% confidence interval, 0.022-0.621). CONCLUSIONS: HPV cfDNA is a promising tumor marker for HPV+ cervical cancer. In the context of precision medicine, HPV cfDNA is poised to play an increasingly pivotal role in monitoring treatment efficacy, providing valuable insights into disease progression, and guiding clinical decisions.

A Proton Pump Inhibitor Independently Elevates Gastrin Levels as a Marker for Metachronous Gastric Cancer After Endoscopic Submucosal Dissection.

Background and Objective: Serum markers such as gastrin and pepsinogen are useful for stratifying gastric cancer risk. However, their utility in predicting metachronous gastric cancer after endoscopic submucosal dissection (ESD) in patients with gastric cancer after Helicobacter pylori eradication (GCAE) is unclear. This study aimed to clarify predictive factors for metachronous gastric cancer after ESD with a focus on serum markers. Methods: A retrospective analysis was conducted on 197 patients with 224 GCAE lesions who underwent ESD at Hiroshima University Hospital between April 2010 and December 2019. In total, 63 patients with 74 differentiated-type lesions were classified into metachronous gastric cancer (MG) and non-metachronous gastric cancer (NMG) groups, excluding proton pump inhibitor (PPI) users, female patients, and undifferentiated-type cases. The predictive value of serum markers was assessed using ROC curve analysis, and their association with carcinogenesis was evaluated using multiple logistic regression. Furthermore, the incidence of MG was compared between long-term PPI users and non-users. Results: ROC analysis revealed that serum gastrin had the highest discriminative ability for MG (AUC 0.77, cut-off 99 pg/mL, sensitivity 61.6%, and specificity 80.0%). Severe mucosal atrophy and high gastrin levels were significantly more common in the MG group and were independent predictors (p < 0.01). Although serum gastrin levels were significantly elevated in PPI users, no increased risk of MG was observed. Conclusions: In addition to severe mucosal atrophy, PPI-independent elevated serum gastrin levels may be associated with an increased risk of MG after ESD. Serum gastrin may serve as a valuable marker for post-ESD cancer surveillance in GCAE patients.

Hsa_circ_0006010 and hsa_circ_0002903 in peripheral blood serve as novel diagnostic, surveillance and prognostic biomarkers for disease progression in chronic myeloid leukemia

BackgroundIn the era of tyrosine kinase inhibitor (TKI) treatment, the progression of chronic myeloid leukemia (CML) remains a significant clinical challenge, and genetic biomarkers for the early identification of CML patients at risk for progression are limited. This study explored whether essential circular RNAs (circRNAs) can be used as biomarkers for diagnosing and monitoring CML disease progression and assessing CML prognosis.MethodsPeripheral blood (PB) samples were collected from 173 CML patients (138 patients with chronic phase CML [CML-CP] and 35 patients with accelerated phase/blast phase CML [CML-AP/BP]) and 63 healthy controls (HCs). High-throughput RNA sequencing (RNA-Seq) was used to screen dysregulated candidate circRNAs for a circRNA signature associated with CML disease progression. Quantitative real-time PCR (qRT-PCR) was used for preliminary verification and screening of candidate dysregulated genes, as well as subsequent exploration of clinical applications. Receiver operating characteristic (ROC) curve analysis, Spearman’s rho correlation test, and the Kaplan-Meier method were used for statistical analysis.ResultsThe aberrant expression of hsa_circ_0006010 and hsa_circ_0002903 during CML progression could serve as valuable biomarkers for differentiating CML-AP/BP patients from CMP-CP patients or HCs. In addition, the expression levels of hsa_circ_0006010 and hsa_circ_0002903 were significantly associated with the clinical features of CML patients but were not directly related to the four scoring systems. Furthermore, survival analysis revealed that high hsa_circ_0006010 expression and low hsa_circ_0002903 expression indicated poor progression-free survival (PFS) in CML patients. Finally, PB hsa_circ_0006010 and hsa_circ_0002903 expression at diagnosis may also serve as disease progression surveillance markers for CML patients but were not correlated with PB BCR-ABL1/ABL1IS.ConclusionsOur study demonstrated that PB levels of hsa_circ_0006010 and hsa_circ_0002903 may serve as novel diagnostic, surveillance, and prognostic biomarkers for CML disease progression and may contribute to assisting in the diagnosis of CML patients at risk for progression and accurate management of advanced CML patients.

Clinical outcome assessment of colistin sulphate in children with carbapenem-resistant organism infections: First data from China

ObjectivesColistin sulphate for injection (CSI) became clinically available in China in July 2019. To date, there is no published data regarding its usage in children. Our research group has been following data on the efficacy and safety of CSI in Chinese paediatric patients with carbapenem-resistant organism infections. The purpose of this short communication is to provide a brief overview of the findings to date. MethodsWe reviewed the electronic medical records of paediatric patients (aged 9–17 y) who were administered CSI during their hospital stay at Tongji Hospital in Wuhan, China, between June 2021 and November 2023. Drug efficacy was evaluated based on clinical and microbiological outcomes, while drug safety was assessed using surveillance markers that reflect adverse reactions. ResultsA total of 20 patients met the inclusion criteria. The predominant pathogens were Klebsiella pneumoniae (8 strains), followed by Acinetobacter baumannii (5 strains) and Pseudomonas aeruginosa (2 strains). The clinical response rate of CSI was 85%, with a bacterial clearance rate of 79%. None of the patients experienced colistin-related nephrotoxicity or neurotoxicity during the treatment. ConclusionsIn this real-world setting, CSI demonstrated a high level of clinical response and was well tolerated for the treatment of carbapenem-resistant organism infections in Chinese children.

Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study

BackgroundPolycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited. ObjectiveTo investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. MethodsThe study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models. ResultsA total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR) = 1.13; 1.02–1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR = 1.19; 1.02–1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk. ConclusionsOur study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.

Key gene modules and hub genes associated with pyrethroid and organophosphate resistance in Anopheles mosquitoes: a systems biology approach

Indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are the main methods used to control mosquito populations for malaria prevention. The efficacy of these strategies is threatened by the spread of insecticide resistance (IR), limiting the success of malaria control. Studies of the genetic evolution leading to insecticide resistance could enable the identification of molecular markers that can be used for IR surveillance and an improved understanding of the molecular mechanisms associated with IR. This study used a weighted gene co-expression network analysis (WGCNA) algorithm, a systems biology approach, to identify genes with similar co-expression patterns (modules) and hub genes that are potential molecular markers for insecticide resistance surveillance in Kenya and Benin. A total of 20 and 26 gene co-expression modules were identified via average linkage hierarchical clustering from Anopheles arabiensis and An. gambiae, respectively, and hub genes (highly connected genes) were identified within each module. Three specific genes stood out: serine protease, E3 ubiquitin-protein ligase, and cuticular proteins, which were top hub genes in both species and could serve as potential markers and targets for monitoring IR in these malaria vectors. In addition to the identified markers, we explored molecular mechanisms using enrichment maps that revealed a complex process involving multiple steps, from odorant binding and neuronal signaling to cellular responses, immune modulation, cellular metabolism, and gene regulation. Incorporation of these dynamics into the development of new insecticides and the tracking of insecticide resistance could improve the sustainable and cost-effective deployment of interventions.

An association between Dasatinib, elevated left atrial pressure and pleural effusion

BackgroundTyrosine kinase inhibitors (TKI), such as Dasatinib, are effective in the treatment of chronic myeloid leukemia (CML) but associated with development of pleural effusions (PE). The relationship between haemodynamic parameters identified on transthoracic echocardiogram (TTE) such as elevated estimated left atrial pressure (LAP), and PE development is unknown. This study aims to describe associations between Dasatinib, elevated LAP and PE. MethodsThis was a retrospective study of 71 CML patients who underwent TTE during treatment with various TKIs. Descriptive analysis was performed to identify associations between TKI use, PE and elevated LAP on TTE. Multivariate logistic regression was performed to identify predictors of elevated LAP. ResultsThere were 36 patients treated with Dasatinib, 15 Nilotinib, and 20 Imatinib. Those treated with Dasatinib had higher rates of elevated LAP (44% vs 7% Nilotinib vs 10% Imatinib, p < 0.01) and PE (39% vs 7% vs 0%, p < 0.01). In the 15 patients who developed PE, 14 (93%) patients were treated with Dasatinib. Patients with PE had higher rates of elevated LAP (67% vs 16%, p < 0.01). Nineteen (26.8%) patients in the entire cohort had elevated LAP. After multivariate adjustment, Dasatinib (OR 33.50, 95% CI = 4.99–224.73, p < 0.01) and age (OR 1.12, 95% CI = 1.04–1.20, p < 0.01) were associated with elevated LAP. ConclusionsAmong patients with CML, there was an association between Dasatinib use, PE and elevated LAP on TTE. These findings are hypothesis generating and further studies are required to evaluate the utility of elevated LAP on TTE as a novel marker for prediction and surveillance of PE.

Emerging trends in antimicrobial resistance in bloodstream infections: multicentric longitudinal study in India (2017–2022)

BackgroundAntimicrobial resistance (AMR) has escalated to pandemic levels, posing a significant global health threat. This study examines the patterns and trends of AMR in Bloodstream Infections (BSIs) across India, aiming to inform better surveillance and intervention strategies. MethodsSix-year data from 21 tertiary care centers in the Indian Council of Medical Research's AMR Surveillance Network (IAMRSN) were retrospectively analyzed to estimate cluster-robust trends in resistance. Time-series analysis was used to discern lead/lag relationships between antibiotic pairs and the directional influence of resistance in community and hospital-acquired BSIs(CA/HA BSIs). A data-driven Bayesian network ensemble averaged over 301 bootstrap samples was modelled to uncover systemic associations between AMR and Sustainable Development Goals (SDGs). FindingsOur findings indicate significant (p<0.001) monthly increases in Imipenem and Meropenem resistance for Klebsiella, E. coli, and Acinetobacter BSIs. Importantly, Carbapenem resistance in HA-BSIs preceded that in CA-BSIs for Klebsiella and Acinetobacter (p<0.05). At a national level, Cefotaxime resistance emerged as a potential early indicator for emerging Carbapenem resistance, proposing a novel surveillance marker. In Klebsiella BSIs, states with higher achievement of SDG3 goals showed lower Imipenem resistance. A model-based AMR scorecard is introduced for focused interventions and continuous monitoring. InterpretationThe identified spatiotemporal trends and drug resistance associations offer critical insights for AMR surveillance aligning with WHO GLASS standards.The escalation of carbapenem resistance in BSIs demands vigilant monitoring and may be crucial for achieving SDGs by 2030. Implementing the proposed framework for data-driven evidence can help nations achieve proactive AMR surveillance. FundingNo specific funding was received for this analysis.

FibroScan as a surveillance marker post-cavopulmonary anastomosis for single-ventricle physiology.

Single-ventricle physiology encompasses a group of congenital cardiac malformations with only one functional ventricle. The Fontan procedure is the final palliation of this pathway and has its complications. One of these is Fontan-associated liver disease (FALD). It is known that all patients with Fontan will have FALD, due to the physiology of the Fontan circuit, and only the severity will vary. The pathophysiology of hepatic damage in FALD is unique and not easily detectable by routine non-invasive investigations. Therefore, this study is aimed to identify if FibroScan can be used as a surveillance marker to detect and assess the progression of FALD. Patients who attended the Cardiothoracic and Vascular Surgery Outpatient Department (OPD) for follow-up post-cavopulmonary anastomosis (bidirectional Glenn and Fontan) were enrolled in this study. They underwent routine examinations and tests, and in addition a FibroScan was performed. FibroScan showed that the liver stiffness measurement (LSM) was increased in all patients who had undergone Fontan and a couple of patients who had undergone bidirectional (BD) Glenn. The LSM was 12.29 (± 3.59) kPa in patients post-Fontan and 6.64 (± 4.24) kPa in patients post-BD Glenn. This raised LSM was not associated with a parallel rise in liver enzymes or other laboratory markers associated with liver function. This emphasizes the suitability of FibroScan as an early and non-invasive surveillance tool for monitoring the progression of hepatic venous congestion and FALD. We have found that LSM via FibroScan can effectively be a surveillance or screening test for FALD. Serial FibroScans can be used to monitor the progress of liver disease. Raised LSM may also have a role in predicting the morbidity for completion of Fontan post-BD Glenn operation. Large-scale studies are needed to validate our findings.

Single-cell RNA sequencing highlights epithelial and microenvironmental heterogeneity in malignant progression of pancreatic ductal adenocarcinoma

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Single-cell transcriptomics provides a unique perspective for dissecting the epithelial and microenvironmental heterogeneity that accompanies progression from benign IPMNs to invasive PDAC. Single-cell RNA sequencing was performed through droplet-based sequencing on 35 693 cells from three high-grade IPMNs and two IPMN-derived PDACs (all surgically resected). Analysis of single-cell transcriptomes revealed heterogeneous alterations within the epithelium and the tumor microenvironment during the progression of noninvasive dysplasia to invasive cancer. For epithelial cells, we identified acinar–ductal cells and isthmus–pit cells enriched in IPMN lesions and profiled three types of PDAC-unique ductal cells. Notably, a proinflammatory immune component was distinctly observed in IPMNs, comprising CD4+ T cells, CD8+ T cells, and B cells, whereas M2 macrophages were significantly accumulated in PDAC. Through the analysis of cellular communication, the osteopontin gene (SPP1)–CD44 pathway between macrophages and epithelial cells were particularly strengthened in the PDAC group. Further prognostic analysis revealed that SPP1 is a biomarker of IPMN carcinogenesis for surveillance. This study demonstrates the ability to perform high-resolution profiling of single cellular transcriptomes during the progression of high-grade IPMNs to cancer. Notably, single-cell analysis provides an unparalleled insight into both epithelial and microenvironmental heterogeneity associated with early cancer pathogenesis and provides practical markers for surveillance and targets for cancer interception.

Phenotypic and genetic characterization of daptomycin non-susceptible Staphylococcus aureus strains selected by adaptive laboratory evolution.

Daptomycin non-susceptible Staphylococcus aureus (DNS) strains pose a serious clinical threat, yet their characteristics remain poorly understood. DNS derivatives were generated by exposing S. aureus strains to subinhibitory concentrations of daptomycin. Competition experiment and growth kinetics experiment were used to observe the growth of bacteria. Galleria mellonella larvae and mouse skin abscess models were used to observe the virulence of bacteria. Transmission electron microscopy (TEM), cytochrome C experiment and biofilm formation experiment were used to observe the drug resistance phenotype. And homologous recombination was used to study the role of mutations. Phenotypic profiling of DNS strains revealed impaired growth, increased cell wall thickness, enhanced biofilm formation, reduced negative surface charge, and attenuated virulence compared to their wild-type strains. Whole genome sequencing identified mutations in mprF, cls2, and saeR in DNS strains. Allelic replacement experiments validated the roles of MprF L341F and Cls2 F60S substitutions in augmenting daptomycin non-susceptibility in Newman. Deletion of saeR in the NewmanMprFL341F strain and complementation of saeR in the Newman-DNS strain did not directly alter daptomycin susceptibility. However, the deletion of saeR was found to enhance competitive fitness under daptomycin pressure. This work validates adaptive laboratory evolution (ALE) for modeling clinical DNS strains and uncovers contributions of mprF, cls2, and saeR mutations to the adaptation and resistance mechanisms of S. aureus against daptomycin. These findings enrich our understanding of how S. aureus acquired resistance to daptomycin, thus paving the way for the development of more effective treatment strategies and offering potential molecular markers for resistance surveillance.

Plasma Methylated DNA Markers for Melanoma Surveillance.

Surveillance after primary melanoma treatment aims to detect early signs of low-volume systemic disease. The current standard of care, surveillance imaging, is costly and difficult to access. We therefore sought to develop methylated DNA markers (MDMs) as promising alternatives for disease surveillance. We used reduced representation bisulfite sequencing (RRBS) to identify MDMs in DNA samples obtained from metastatic melanoma, benign nevi, and normal skin tissues. The identified MDMs underwent validation in an independent cohort of tissue and buffy coat DNA samples. Subsequently, we tested the validated MDMs in the plasma DNA of patients with metastatic melanoma undergoing surveillance with total body imaging and compared them with cancer-free controls. To estimate the overall predictive accuracy of the MDMs, we used random forest modeling with bootstrap cross-validation. Forty MDMs demonstrated discrimination between melanoma cases and controls consisting of benign nevi and normal skin. Nine MDMs passing biological validation in tissue were run on 77 plasma samples from individuals with a history of metastatic melanoma, 49 of whom had evidence of disease detected by imaging at the time of blood draw, and 100 cancer-free controls. The cross-validated sensitivity of the panel for imaging-positive disease was 80% with a specificity of 100% in cancer-free controls, resulting in an overall AUC of 0.88 (95% CI, 0.81 to 0.96). The survival estimates for patients with melanoma who tested positive for the panel at 6 months and 1 year were 67% and 56%, respectively, while those who tested negative had survival rates of 100% and 92%. MDMs identified by RRBS demonstrate a high degree of concordance with imaging results in the plasma of patients with metastatic melanoma. Further prospective studies in larger intended use cohorts are needed to confirm these findings.

Prognostic performance of pretreatment systemic immune-inflammation index in women with epithelial ovarian cancer.

This study investigated the prognostic performance of the systemic immune-inflammation index (SII) in patients with epithelial ovarian cancer (EOC) in Lagos, Nigeria. We performed a secondary analysis of the data of 91 women who had treatment for EOC between 2009 and 2018. The associations between pretreatment SII and survivals were tested. Pretreatment SII more than 610.2 was a significant independent predictor of reduced progression-free survival (HR=2.68; 95% CI, 1.17 to 6.09) while SII greater than 649.0 was a significant independent predictor of reduced 3-year overall survival (HR=2.01; 95% CI, 1.01 to 3.99). These findings suggest that high SII may be a potential prognostic indicator and useful marker for more intensive surveillance and design of personalized treatment in patients with EOC.

The Promise of Epigenetics Research in the Treatment of Appendiceal Neoplasms.

Appendiceal cancers (AC) are a rare and heterogeneous group of malignancies. Historically, appendiceal neoplasms have been grouped with colorectal cancers (CRC), and treatment strategies have been modeled after CRC management guidelines due to their structural similarities and anatomical proximity. However, the two have marked differences in biological behavior and treatment response, and evidence suggests significant discrepancies in their respective genetic profiles. In addition, while the WHO classification for appendiceal cancers is currently based on traditional histopathological criteria, studies have demonstrated that histomorphology does not correlate with survival or treatment response in AC. Due to their rarity, appendiceal cancers have not been studied as extensively as other gastrointestinal cancers. However, their incidence has been increasing steadily over the past decade, making it crucial to identify new and more effective strategies for detection and treatment. Recent efforts to map and understand the molecular landscape of appendiceal cancers have unearthed a wealth of information that has made it evident that appendiceal cancers possess a unique molecular profile, distinct from other gastrointestinal cancers. This review focuses on the epigenetic landscape of epithelial appendiceal cancers and aims to provide a comprehensive overview of the current state of knowledge of epigenetic changes across different appendiceal cancer subtypes, highlighting the challenges as well as the promise of employing epigenetics in the quest for the detection of biomarkers, therapeutic targets, surveillance markers, and predictors of treatment response and survival in epithelial appendiceal neoplasms.

Testing for Human Papillomaviruses in Urine, Blood, and Oral Specimens: an Update for the Laboratory.

Twelve high-risk alpha human papillomavirus (HPV) genotypes cause approximately 690,000 cancer cases annually, with cervical and oropharyngeal cancer being the two most prominent types. HPV testing is performed in laboratory settings for various applications of a clinical, epidemiological, and research nature using a range of clinical specimens collected by clinicians or by individuals (self-collected specimens). Here, we reflect on the importance and justification of using the right test for the right application and provide practical updates for laboratories either participating in or anticipating involvement in HPV testing in three specimen types, namely, urine, blood, and oral specimens, which are considered "alternative" specimens by many. In addition to clinician-collected cervical samples and self-collected cervicovaginal samples, first-void urine is emerging as a credible specimen for HPV-based cervical cancer screening, triage of HPV screen-positive women, monitoring HPV vaccine impact, and HPV testing in groups for which a less invasive sample is preferred. Detection of cell-free DNA (including HPV DNA) in blood has great promise for the early detection of HPV-attributable oropharyngeal cancer (HPV-AOC) and potentially other HPV-driven cancers and as an adjunct prognostic marker in long-term tumor surveillance, including treatment response. The moderate sensitivity of HPV testing in oral rinses or swabs at HPV-AOC diagnosis prevents its use in HPV-AOC secondary prevention but represents a promising prognostic tool in HPV-AOC tertiary prevention, where the HPV persistence in oral rinses throughout treatment may predict early HPV-AOC recurrences and/or the development of secondary HPV-AOC. The increasing sophistication of specific collection devices designed for alternative samples and the enhanced precision of novel molecular technologies are likely to support the evolution of this field and catalyze potential translation into routine practice.

Anti-Recem18 Antibody Levels are Associated with Lesion Size and Determine Follow-Up after Resection of Hepatic Alveolar Echinococcosis

Abstract Background Best monitoring practices for patients after resection of hepatic alveolar echinococcosis remain unclear. Aims The current study tested if assessment of anti-recEm18 allows for postsurgical patient surveillance. Methods A retrospective study with patients undergoing liver resection for alveolar echinococcosis at the University Hospital Berne from December 2002 to December 2020 and at the University Hospital and Medical Center Ulm from January 2011 to December 2017 was performed. Analysis was directed to determine a potential association of pre- and postoperative values of anti-recEm18 with clinical outcomes. Results Among 147 patients who underwent liver resection for alveolar echinococcosis in curative intent, perioperative results of recEm18-serology were available in 88 patients. In patients without residual disease, the postoperative anti-recEm18 value after 12 months dropped to a mean of 2 AU/ml (standard deviation: 4 AU/ml). Three trajectories of anti-recEm18 were identified based on a threshold of 10 AU/ml: “Em18-low” (n = 31, 35%) with anti-recEm18 values below 10 AU/ml pre- and postoperatively, “responders” (n = 53, 60%) with preoperative values above 10 AU/ml and a postoperative decrease of more than 80% of the initial anti-recEm18 and “residual disease” (n = 4, 5%) with the postoperative presence of residual disease. The decline of anti-recEm18 in “responders” reached a plateau after 11.4 months at which levels decreased by 80%. The only recurrence in the entire population was identified by a secondary increase of anti-recEm18. Anti-recEm18 levels had a linear correlation to the maximum lesion diameter (R2 = 0.558). Conclusions Anti-recEm18 antibody levels correlate with the lesion size preoperatively and response to surgery postoperatively. Anti-recEm18 allows to be applied as serological surveillance marker during postoperative follow-up in patients with elevated preoperative anti-recEm18 levels.

Breath Volatile Organic Compounds in Surveillance of Gastric Cancer Patients following Radical Surgical Management.

As of today, there is a lack of a perfect non-invasive test for the surveillance of patients for potential relapse following curative treatment. Breath volatile organic compounds (VOCs) have been demonstrated to be an accurate diagnostic tool for gastric cancer (GC) detection; here, we aimed to prove the yield of the markers in surveillance, i.e., following curative surgical management. Patients were sampled in regular intervals before and within 3 years following curative surgery for GC; gas chromatography-mass spectrometry (GC-MS) and nanosensor technologies were used for the VOC assessment. GC-MS measurements revealed a single VOC (14b-Pregnane) that significantly decreased at 12 months, and three VOCs (Isochiapin B, Dotriacontane, Threitol, 2-O-octyl-) that decreased at 18 months following surgery. The nanomaterial-based sensors S9 and S14 revealed changes in the breath VOC content 9 months after surgery. Our study results confirm the cancer origin of the particular VOCs, as well as suggest the value of breath VOC testing for cancer patient surveillance, either during the treatment phase or thereafter, for potential relapse.

Tumor grade as a novel predictor of outcomes in medullary thyroid cancer

The recent development of the International Medullary Thyroid Cancer Grading System (IMTCGS) provided clinicians with a tool to predict for disease outcomes after undergoing resection based on histologic features. However, its impact on the clinical management of patients is still under investigation. Utilizing the IMTCGS, we evaluated the association of grade with postoperative surveillance markers. High-grade tumors, when compared to low-grade, had a significantly more rapid calcitonin doubling time with a vast majority of high-grade patients having doubling times &lt;2 years. While these findings reaffirmed the poor recurrence and mortality outcomes observed in high-grade patients, we found that high-grade patients with rapid calcitonin doubling times were particularly at risk for poor local control and survival outcomes.These findings demonstrate the importance of close clinical follow-up of patients with high-grade disease and further support the determination tumor grade and calcitonin doubling times in MTC patients after resection. In addition, the study supports the use of MTC grading as an important variable for future management of MTC patients. This could lay the foundation for better understanding of neuroendocrine carcinomas of the breast.