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Abdominal Radiology (New York) Sep 2023The role and method of image-based staging of anal cancer has evolved with the rapid development of newer imaging modalities and the need to address the rising incidence... (Review)
Review
The role and method of image-based staging of anal cancer has evolved with the rapid development of newer imaging modalities and the need to address the rising incidence of this rare cancer. In 2014, the European Society of Medical Oncology mandated pelvic magnetic resonance imaging (MRI) for anal cancer and subsequently other societies such as the National Comprehensive Cancer Network followed suit with similar recommendations. Nevertheless, great variability exists from center to center and even within individual centers. Notably, this is in stark contrast to the imaging of the anatomically nearby rectal cancer. As participating team members for this malignancy, we embarked on a comprehensive literature review of anal cancer imaging to understand the relative merits of these new technologies which developed after computed tomography (CT), e.g., MRI and positron emission tomography/computed tomography (PET/CT). The results of this literature review helped to inform our next stage: questionnaire development regarding the imaging of anal cancer. Next, we distributed the questionnaire to members of the Society of Abdominal Radiology (SAR) Rectal and Anal Disease-Focused Panel, a group of abdominal radiologists with special interest, experience, and expertise in rectal and anal cancer, to provide expert radiologist opinion on the appropriate anal cancer imaging strategy. In our expert opinion survey, experts advocated the use of MRI in general (65% overall and 91-100% for primary staging clinical scenarios) and acknowledged the superiority of PET/CT for nodal assessment (52-56% agreement for using PET/CT in primary staging clinical scenarios compared to 30% for using MRI). We therefore support the use of MRI and PET and suggest further exploration of PET/MRI as an optimal combined evaluation. Our questionnaire responses emphasized the heterogeneity in imaging practice as performed at numerous academic cancer centers across the United States and underscore the need for further reconciliation and establishment of best imaging practice guidelines for optimized patient care in anal cancer.
Topics: Humans; Positron Emission Tomography Computed Tomography; Expert Testimony; Anus Neoplasms; Carcinoma, Squamous Cell; Magnetic Resonance Imaging; Radiology; Neoplasm Staging; Positron-Emission Tomography; Fluorodeoxyglucose F18
PubMed: 36932225
DOI: 10.1007/s00261-023-03863-8 -
Journal of Cancer Research and... Oct 2023Concurrent chemoradiotherapy is considered a standard of care for patients with carcinoma anal canal. Being an unusual malignancy, there is limited Indian data regarding...
CONTEXT
Concurrent chemoradiotherapy is considered a standard of care for patients with carcinoma anal canal. Being an unusual malignancy, there is limited Indian data regarding survival outcomes and prognostic factors.
AIM
To evaluate survival outcomes and associated prognostic factors in patients with carcinoma anal canal treated with radical intent.
METHODS AND MATERIAL
Patients with squamous cell carcinoma of the anal canal, treated with radical intent between 2015 and 2019 were included in the study. Data regarding the baseline characteristics of the patients and treatment outcomes were collected and analyzed. Survival rates were estimated using Kaplan-Meier method. To determine survival difference between the groups, log-rank test was used. Multivariate analyses were performed with Cox proportional hazard models and P value < 0.05 was considered significant.
RESULTS
Forty-two patients were identified after applying suitable eligibility criteria. The median age was 55 years (range: 26-80 years).The median follow-up duration was 23.5 months (range: 1.9-51.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and locoregional (LRC) were 78.5%, 53.1%, and 66.4%, respectively. On multivariate analysis, inferior DFS was significantly affected by lack of concurrent chemotherapy (CT) (hazard ratio [HR], 11.50; 95% confidence interval [CI], 1.92-68.78; P = 0.007) and radiotherapy (RT) dose of 45 Gy or less (HR, 35.96; 95% CI, 6.32-204.56; P = 0.000).
CONCLUSION
For patients of carcinoma anal canal, concurrent CT and RT dose are independent prognostic factors influencing DFS.
Topics: Humans; Middle Aged; Anal Canal; Prognosis; Carcinoma, Squamous Cell; Disease-Free Survival; Progression-Free Survival
PubMed: 38376309
DOI: 10.4103/jcrt.jcrt_357_22 -
Annals of Medicine Dec 2023Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one...
BACKGROUND
Chemoradiation therapy (CRT) is the standard of care for squamous cell carcinoma of the anus (SCCA), the most common type of anal cancer. However, approximately one fourth of patients still relapse after CRT.
METHODS
We used RNA-sequencing technology to characterize coding and non-coding transcripts in tumor tissues from CRT-treated SCCA patients and compare them between 9 non-recurrent and 3 recurrent cases. RNA was extracted from FFPE tissues. Library preparations for RNA-sequencing were created using SMARTer Stranded Total RNA-Seq Kit. All libraries were pooled and sequenced on a NovaSeq 6000. Function and pathway enrichment analysis was performed with Metascape and enrichment of gene ontology (GO) was performed with Gene Set Enrichment Analysis (GSEA).
RESULTS
There were 449 differentially expressed genes (DEGs) observed (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between the two groups. We identified a core of upregulated genes (, , and in the non-recurrent SCCA tissue enriching to the gene ontology term 'allograft rejection', which suggests a CD4+ T cell driven immune response. Conversely, in the recurrent tissues, keratin () and hedgehog signaling pathway () genes involved in 'Epidermis Development,', were significantly upregulated. We identified miR-4316, that inhibit tumor proliferation and migration by repressing vascular endothelial growth factors, as being upregulated in non-recurrent SCCA. On the contrary, , implicated in the progression of many other cancers, was also found to be more common in our recurrent compared to non-recurrent SCCA.
UNLABELLED
Our study identified key host factors which may drive the recurrence of SCCA and warrants further studies to understand the mechanism and evaluate their potential use in personalized treatment.Key MessageOur study used RNA sequencing (RNA-seq) to identify pivotal factors in coding and non-coding transcripts which differentiate between patients at risk for recurrent anal cancer after treatment. There were 449 differentially expressed genes (390 mRNA, 12 miRNA, 17 lincRNA and 18 snRNA) between 9 non-recurrent and 3 recurrent squamous cell carcinoma of anus (SCCA) tissues. The enrichment of genes related to allograft rejection was observed in the non-recurrent SCCA tissues, while the enrichment of genes related to epidermis development was positively linked with recurrent SCCA tissues.
Topics: Humans; Transcriptome; RNA, Long Noncoding; Hedgehog Proteins; Carcinoma, Squamous Cell; Anus Neoplasms; MicroRNAs; Recurrence; Sequence Analysis, RNA; RNA, Messenger; HIV Infections
PubMed: 37177979
DOI: 10.1080/07853890.2023.2199366 -
Healthcare (Basel, Switzerland) Nov 2023The incidence and mortality of squamous cell carcinoma of the anus (SCCA) is on the rise, which highlights the unmet need for advances in treatment options. The... (Review)
Review
The incidence and mortality of squamous cell carcinoma of the anus (SCCA) is on the rise, which highlights the unmet need for advances in treatment options. The landscape of treatment for this cancer is rapidly evolving with novel combination strategies including immunotherapy, radiation therapy and biomarker-guided therapy. This review article features an overview of recent advancements in both locoregional and metastatic SCCA. The recent focus on locoregional SCCA management is to tailor treatment according to tumor burden and minimize treatment-related toxicities. Mitomycin plus either infusional 5-fluorouracil (5-FU) or capecitabine is used for first-line chemoradiotherapy (CRT), and intensity-modulated radiotherapy (IMRT) is the preferred modality for radiation for locoregional anal cancer. Locally recurrent disease is managed with surgical resection. Systemic treatment is first-line for metastatic SCCA and immunotherapy with nivolumab and pembrolizumab being included as second-line agents. Current and future clinical trials are evaluating treatments for SCCA including immunotherapy alone or in combination regimens, radiotherapies, targeted treatments and novel agents. Another critical aspect of current research in SCCA is the personalization of CRT and immunotherapies based on molecular characterization and biomarkers such as the programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) and circulating tumor DNA.
PubMed: 38063578
DOI: 10.3390/healthcare11233010 -
Journal of the National Cancer Institute Feb 2024In the United States, anal squamous cell carcinoma rates have increased rapidly, particularly among women 50 or older than 66 years of age. As immunosuppression is...
BACKGROUND
In the United States, anal squamous cell carcinoma rates have increased rapidly, particularly among women 50 or older than 66 years of age. As immunosuppression is associated with increased risk, autoimmune conditions may be associated with greater risk of anal squamous cell carcinoma.
METHODS
We conducted a population-based, case-control study using Surveillance, Epidemiology, and End Results-Medicare data (2000-2017). Anal squamous cell carcinoma cases (n = 4505) were matched to 200 000 cancer-free controls. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between 47 autoimmune conditions diagnosed before selection, identified using Medicare claims, and anal squamous cell carcinoma. The Bonferroni threshold was used to correct for multiple comparisons. Population attributable fractions were calculated for conditions nominally associated with anal squamous cell carcinoma.
RESULTS
In total, 18% of anal squamous cell carcinoma cases and 15% of cancer-free controls had a diagnosed autoimmune condition. Any autoimmune condition was associated with an increased risk of anal squamous cell carcinoma (OR = 1.11, 95% CI = 1.02 to 1.21; population attributable fraction = 1.8%). Anal squamous cell carcinoma was associated with systemic lupus erythematosus (OR = 1.79, 95% CI = 1.32 to 2.42; population attributable fraction = 0.4%) and nominally associated (P < .05) with sarcoidosis (OR = 2.09, 95% CI = 1.30 to 3.37; population-attributable fraction = 0.2%) and psoriasis (OR = 1.28, 95% CI = 1.06 to 1.56; population attributable fraction = 0.5%). Stratified by sex, only women showed statistically significant associations for systemic lupus erythematosus (OR = 1.97, 95% CI = 1.46 to 2.68). Statistically significant interaction was observed by sex for psoriasis (men vs women: OR = 1.68 [95% CI = 1.03 to 4.28] vs OR = 1.12 [95% CI = 0.88 to 1.43]) and polymyalgia rheumatica (OR = 0.33 [95% CI = 0.12 to 0.89] vs OR = 0.99 [95% CI = 0.75 to 1.30]).
CONCLUSION
Systemic lupus erythematosus, sarcoidosis, and psoriasis were associated with a moderately increased risk of anal squamous cell carcinoma. Given these conditions' rarity and moderate associations with anal squamous cell carcinoma, autoimmune diseases cannot explain the rising trend in this disease.
Topics: Male; Humans; Aged; Female; United States; Case-Control Studies; Medicare; Autoimmune Diseases; Lupus Erythematosus, Systemic; Sarcoidosis; Carcinoma, Squamous Cell; Anus Neoplasms; Psoriasis
PubMed: 37701981
DOI: 10.1093/jnci/djad187 -
European Journal of Cancer Prevention :... Mar 2024Anal cancer is a rare disease, affecting more frequently women than men, mainly related to human papillomavirus infection (HPV). Rising incidence and mortality have been...
OBJECTIVE
Anal cancer is a rare disease, affecting more frequently women than men, mainly related to human papillomavirus infection (HPV). Rising incidence and mortality have been reported over the past four decades in different countries.
METHODS
To provide an up-to-date overview of recent trends in mortality from anal cancer, we analysed death certification data provided by the WHO in selected countries worldwide over the period from 1994 to 2020. We also analysed incidence derived from Cancer Incidence in Five Continents from 1990 to 2012 for all histologies as well as for anal squamous cell carcinoma (SCC).
RESULTS
The highest age-standardised mortality rates around 2020 were registered in Central and Eastern Europe, such as Slovakia (0.9/100 000 men and 0.40/100 000 women), in the UK (0.24/100 000 men and 0.35/100 000 women), and Denmark (0.33/100 000 for both sexes), while the lowest ones were in the Philippines, Mexico, and Japan, with rates below 0.10/100 000 in both sexes. Upwards trends in mortality were reported in most countries for both sexes. Similarly, incidence patterns were upward or stable in most countries considered for both sexes. In 2008-2012, Germany showed the highest incidence rates (1.65/100 000 men and 2.16/100 000 women).
CONCLUSION
Attention towards vaccination against HPV, increased awareness of risk factors, mainly related to sexual behaviours and advancements in early diagnosis and management are required to control anal cancer incidence and mortality.
Topics: Male; Humans; Female; Incidence; Papillomavirus Infections; Anus Neoplasms; Carcinoma, Squamous Cell; Risk Factors; Mortality
PubMed: 38047709
DOI: 10.1097/CEJ.0000000000000842 -
Journal of Clinical Virology : the... Jul 2023Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Human papillomavirus associated anogenital cancers are a significant global burden. The detection of biomarkers (circulating tumour DNA; ctDNA or circulating HPV DNA; cHPV DNA) in blood referred to as "liquid biopsy" may support the early diagnosis and monitoring of affected individuals.
METHODS
A systematic review, including meta-analysis of studies available in the literature on the utilization of ctDNA and cHPV DNA as diagnostic, predictive, and monitoring biomarker tests of HPV associated anogenital cancers was performed following the criteria of PRISMA.
RESULTS
A total of 31 studies were eligible for systematic review; 20 used cHPV DNA in cervical cancers; 7 used ctDNA in cervical cancer; 5 used cHPV DNA in anal cancer; no eligible studies on vulva, vaginal or penile cancer were available. The meta-analysis identified low sensitivity (0.36) and high specificity (0.96) of cHPV DNA as diagnostic for cervical cancer. Comparatively, there was high sensitivity (0.95) and specificity (1.0) of cHPV DNA for the diagnosis of anal cancer. cHPV DNA and/or ctDNA in cervical cancer were prognostic markers associated with poor clinical outcomes. Additionally, in anal cancer the post treatment detection of cHPV DNA was informative in the prediction of treatment response or progression-free survival.
CONCLUSION
ctDNA and cHPV DNA are promising diagnostic and prognostic biomarkers for the detection of anogenital disease. Evolution and refinement of molecular tools is likely to improve performance further. Additionally the comparative absence of studies in the vulval, vaginal and penile context warrants further exploration and research.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Human Papillomavirus Viruses; Anus Neoplasms; DNA
PubMed: 37163963
DOI: 10.1016/j.jcv.2023.105469 -
World Journal of Surgical Oncology Oct 2023Colorectal cancer is one of the most common malignant tumors worldwide with high morbidity and mortality. This study aimed to identify different methylation sites as new...
BACKGROUND
Colorectal cancer is one of the most common malignant tumors worldwide with high morbidity and mortality. This study aimed to identify different methylation sites as new methylation markers in CRC and colorectal adenoma through tissue detection.
METHODS
DNA extraction and bisulfite modification as well as Infinium 450K methylation microarray detection were performed in 46 samples of sporadic colorectal cancer tissue, nine samples of colorectal adenoma, and 20 normal samples, and bioinformatic analysis was conducted involving genes enrichments of GO and KEGG. Pyrosequencing methylation detection was further performed in 68 sporadic colorectal cancer tissues, 31 samples of colorectal adenoma, and 49 normal colorectal mucosae adjacent to carcinoma to investigate the differentially methylated genes obtained from methylation microarray.
RESULTS
There were 65,535 differential methylation marker probes, among which 25,464 were hypermethylated markers and 40,071 were hypomethylated markers in the adenoma compared with the normal group, and 395,571 were differentially methylated markers in patients with sporadic colorectal cancer compared with the normal group, including 21,710 hypermethylated markers and 17,861 hypomethylated markers. Five hypermethylated genes including ZNF471, SND1, SPOCK1, FBLIM1, and OTX1 were detected and confirmed in 68 cases of colorectal cancer, 31 cases of adenoma, and 49 cases of normal control group.
CONCLUSIONS
Hypermethylated genes of ZNF471, SND1, SPOCK1, FBLIM1, and OTX1 were obtained from methylation chip detection and further confirm analysis in colorectal cancer and adenoma compared with normal tissue, which may be promising diagnostic markers of colorectal cancer and colorectal adenoma.
Topics: Humans; DNA Methylation; Biomarkers, Tumor; CpG Islands; Early Detection of Cancer; Colorectal Neoplasms; Adenoma; Cytoskeletal Proteins; Cell Adhesion Molecules; Proteoglycans; Endonucleases; Otx Transcription Factors
PubMed: 37779184
DOI: 10.1186/s12957-023-03189-1 -
Techniques in Coloproctology Jan 2024In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to... (Review)
Review
In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to persistent HPV16 infection. Invasive cancer is preceded by precancerous lesions. In addition to patients with a personal history of precancerous lesions and anal cancer, three groups are at very high risk of anal cancer: (i) men who have sex with men and are living with HIV, (ii) women with a history of high-grade squamous intraepithelial lesions (HSILs) or vulvar HPV cancer, and (iii) women who received a solid organ transplant more than 10 years ago. The purpose of screening is to detect HSILs so that they can be treated, thereby reducing the risk of progression to cancer. All patients with symptoms should undergo a proctological examination including standard anoscopy. For asymptomatic patients at risk, an initial HPV16 test makes it possible to target patients at risk of HSILs likely to progress to cancer. Anal cytology is a sensitive test for HSIL detection. Its sensitivity is greater than 80% and exceeds that of proctological examination with standard anoscopy. It is indicated in the event of a positive HPV16 test. In the presence of cytological abnormalities and/or lesions and a suspicion of dysplasia on clinical examination, high-resolution anoscopy is indicated. Performance is superior to that of proctological examination with standard anoscopy. However, this technique is not widely available, which limits its use. If high-resolution anoscopy is not possible, screening by a standard proctological examination is an alternative. There is a need to develop high-resolution anoscopy and triage tests and to evaluate screening strategies.
Topics: Male; Humans; Female; Human Papillomavirus Viruses; Homosexuality, Male; Sexual and Gender Minorities; Precancerous Conditions; Anus Neoplasms
PubMed: 38198036
DOI: 10.1007/s10151-023-02899-8 -
Frontiers in Immunology 2023Hepatocellular carcinoma (HCC) represents a prominent gastrointestinal malignancy with a grim clinical outlook. In this regard, the discovery of novel early biomarkers...
Unveiling efferocytosis-related signatures through the integration of single-cell analysis and machine learning: a predictive framework for prognosis and immunotherapy response in hepatocellular carcinoma.
BACKGROUND
Hepatocellular carcinoma (HCC) represents a prominent gastrointestinal malignancy with a grim clinical outlook. In this regard, the discovery of novel early biomarkers holds substantial promise for ameliorating HCC-associated mortality. Efferocytosis, a vital immunological process, assumes a central position in the elimination of apoptotic cells. However, comprehensive investigations exploring the role of efferocytosis-related genes (EFRGs) in HCC are sparse, and their regulatory influence on HCC immunotherapy and targeted drug interventions remain poorly understood.
METHODS
RNA sequencing data and clinical characteristics of HCC patients were acquired from the TCGA database. To identify prognostically significant genes in HCC, we performed the limma package and conducted univariate Cox regression analysis. Subsequently, machine learning algorithms were employed to identify hub genes. To assess the immunological landscape of different HCC subtypes, we employed the CIBERSORT algorithm. Furthermore, single-cell RNA sequencing (scRNA-seq) was utilized to investigate the expression levels of ERFGs in immune cells and to explore intercellular communication within HCC tissues. The migratory capacity of HCC cells was evaluated using CCK-8 assays, while drug sensitivity prediction reliability was determined through wound-healing assays.
RESULTS
We have successfully identified a set of nine genes, termed EFRGs, that hold significant potential for the establishment of a hepatocellular carcinoma-specific prognostic model. Furthermore, leveraging the individual risk scores derived from this model, we were able to stratify patients into two distinct risk groups, unveiling notable disparities in terms of immune infiltration patterns and response to immunotherapy. Notably, the model's capacity to accurately predict drug responses was substantiated through comprehensive experimental investigations, encompassing wound-healing assay, and CCK8 experiments conducted on the HepG2 and Huh7 cell lines.
CONCLUSIONS
We constructed an EFRGs model that serves as valuable tools for prognostic assessment and decision-making support in the context of immunotherapy and chemotherapy.
Topics: Humans; Carcinoma, Hepatocellular; Reproducibility of Results; Liver Neoplasms; Prognosis; Single-Cell Analysis
PubMed: 37575252
DOI: 10.3389/fimmu.2023.1237350