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Journal of the Anus, Rectum and Colon 2023Early-onset colorectal cancer (CRC), which refers to CRC diagnosed in individuals below the age of 50 years, is a growing health concern that presents unique challenges... (Review)
Review
Early-onset colorectal cancer (CRC), which refers to CRC diagnosed in individuals below the age of 50 years, is a growing health concern that presents unique challenges in diagnosis, treatment, and long-term outcomes. Although approximately 70% of early-onset CRC cases are sporadic, with no apparent family history, approximately 25% have a familial component, and up to 20% may be associated with germline mutations, indicating a higher prevalence compared with the general population. Despite the progress in identifying the environmental, molecular, and genetic risk factors of early-onset CRC, the underlying causes for the global increase in its incidence remain unclear. This comprehensive review aims to provide a thorough analysis of early-onset CRC by examining the trends associated with its incidence, clinical and pathological characteristics, risk factors, molecular and genetic profiles, prognosis and screening strategies. By deepening our understanding of early-onset CRC, significant advances related to improving the outcomes and alleviating the burden of this disease on individuals, families, and healthcare systems can be achieved.
PubMed: 37900694
DOI: 10.23922/jarc.2023-032 -
Bioelectronic Medicine Nov 2023Gastrointestinal (GI) disorders, which extend from the esophagus to the anus, are the most common diseases of the GI tract. Among these disorders, pain, encompassing... (Review)
Review
Gastrointestinal (GI) disorders, which extend from the esophagus to the anus, are the most common diseases of the GI tract. Among these disorders, pain, encompassing both abdominal and visceral pain, is a predominant feature, affecting the patients' quality of life and imposing a substantial financial burden on society. Pain signals originating from the gut intricately shape brain dynamics. In response, the brain sends appropriate descending signals to respond to pain through neuronal inhibition. However, due to the heterogeneous nature of the disease and its limited pathophysiological understanding, treatment options are minimal and often controversial. Consequently, many patients with GI disorders use complementary and alternative therapies such as neuromodulation to treat visceral pain. Neuromodulation intervenes in the central, peripheral, or autonomic nervous system by alternating or modulating nerve activity using electrical, electromagnetic, chemical, or optogenetic methodologies. Here, we review a few emerging noninvasive neuromodulation approaches with promising potential for alleviating pain associated with functional dyspepsia, gastroparesis, irritable bowel syndrome, inflammatory bowel disease, and non-cardiac chest pain. Moreover, we address critical aspects, including the efficacy, safety, and feasibility of these noninvasive neuromodulation methods, elucidate their mechanisms of action, and outline future research directions. In conclusion, the emerging field of noninvasive neuromodulation appears as a viable alternative therapeutic avenue for effectively managing visceral pain in GI disorders.
PubMed: 37990288
DOI: 10.1186/s42234-023-00130-5 -
The Oncologist Jun 2024Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these... (Review)
Review
Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these viruses is common and usually cleared within 2 years. Only infections that become persistent are associated with the development of cancer, often occurring several decades later. These cancers mostly arise in 6 different anatomical regions: 5 are anogenital (anus, cervix, penis, vagina, and vulva) and the sixth is the oropharynx. Oncogenic HPVs promote cellular proliferation and genomic instability, but the anatomical niche of the target tissue also plays an important role in the development of cancer. Cells that reside in transitional regions between different types of epithelia, such as in the anus, cervix, and oropharynx, are particularly vulnerable to oncogenesis.
Topics: Humans; Papillomavirus Infections; Female; Male; Papillomaviridae; Neoplasms; Persistent Infection
PubMed: 38630576
DOI: 10.1093/oncolo/oyae071 -
Viruses Apr 2024The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however,... (Review)
Review
The human papillomavirus is the most common sexually transmitted infection in the world. Most HPV infections clear spontaneously within 2 years of infection; however, persistent infection can result in a wide array of diseases, ranging from genital warts to cancer. Most cases of cervical, anal, and oropharyngeal cancers are due to HPV infection, with cervical cancer being one of the leading causes of cancer death in women worldwide. Screening is available for HPV and cervical cancer, but is not available everywhere, particularly in lower-resource settings. HPV infection disproportionally affects individuals living with HIV, resulting in decreased clearance, increased development of cancer, and increased mortality. The development of the HPV vaccine has shown a drastic decrease in HPV-related diseases. The vaccine prevents cervical cancer with near 100% efficacy, if given prior to first sexual activity. Vaccination uptake remains low worldwide due to a lack of access and limited knowledge of HPV. Increasing awareness of HPV and access to vaccination are necessary to decrease cancer and HPV-related morbidity and mortality worldwide.
Topics: Humans; Papillomavirus Infections; Papillomavirus Vaccines; Female; Uterine Cervical Neoplasms; Papillomaviridae; Neoplasms; Vaccination; Anus Neoplasms; HIV Infections; Oropharyngeal Neoplasms; Male; Human Papillomavirus Viruses
PubMed: 38793561
DOI: 10.3390/v16050680 -
Cell Reports Nov 2023Oxidative stress-induced autophagy helps to prevent cellular damage and to maintain homeostasis. However, the regulatory pathway that initiates autophagy remains...
Oxidative stress-induced autophagy helps to prevent cellular damage and to maintain homeostasis. However, the regulatory pathway that initiates autophagy remains unclear. We previously showed that reactive oxygen species (ROS) function as signaling molecules to activate the ATM-CHK2 pathway and promote autophagy. Here, we find that the E3 ubiquitin ligase TRIM32 functions downstream of ATM-CHK2 to regulate ATG7 ubiquitination. Under metabolic stress, ROS induce ATM phosphorylation at S1981, which in turn phosphorylates CHK2 at T68. We show that CHK2 binds and phosphorylates TRIM32 at the S55 site, which then mediates K63-linked ubiquitination of ATG7 at the K45 site to initiate autophagy. In addition, Chk2 mice show an aggravated infarction phenotype and reduced phosphorylation of TRIM32 and ubiquitination of ATG7 in a stroke model. We propose a molecular mechanism for autophagy initiation by ROS via the ATM-CHK2-TRIM32-ATG7 axis to maintain intracellular homeostasis and to protect cells exposed to pathological conditions from stress-induced tissue damage.
Topics: Animals; Mice; Reactive Oxygen Species; Ubiquitination; Ubiquitin-Protein Ligases; Oxidative Stress; Autophagy
PubMed: 37943659
DOI: 10.1016/j.celrep.2023.113402 -
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 -
Children (Basel, Switzerland) Aug 2023After an initial pull-though, patients with Hirschsprung disease (HD) can present with obstructive symptoms, Hirschsprung-associated enterocolitis (HAEC), failure to... (Review)
Review
After an initial pull-though, patients with Hirschsprung disease (HD) can present with obstructive symptoms, Hirschsprung-associated enterocolitis (HAEC), failure to thrive, or fecal soiling. This current review focuses on algorithms for evaluation and treatment in children with HD as a part of a manuscript series on updates in bowel management. In constipated patients, anatomic causes of obstruction should be excluded. Once anatomy is confirmed to be normal, laxatives, fiber, osmotic laxatives, or mechanical management can be utilized. Botulinum toxin injections are performed in all patients with HD before age five because of the nonrelaxing sphincters that they learn to overcome with increased age. Children with a patulous anus due to iatrogenic damage of the anal sphincters are offered sphincter reconstruction. Hypermotility is managed with antidiarrheals and small-volume enemas. Family education is crucial for the early detection of HAEC and for performing at-home rectal irrigations.
PubMed: 37628417
DOI: 10.3390/children10081418 -
Tomography (Ann Arbor, Mich.) Sep 2023Anal cancer is a rare disease, but its incidence has been increasing steadily. Primary staging and assessment after chemoradiation therapy are commonly performed using... (Review)
Review
UNLABELLED
Anal cancer is a rare disease, but its incidence has been increasing steadily. Primary staging and assessment after chemoradiation therapy are commonly performed using MRI, which is considered to be the preferred imaging modality. CT and PET/CT are useful in evaluating lymph node metastases and distant metastatic disease. Anal squamous-cell carcinoma (ASCC) and rectal adenocarcinoma are typically indistinguishable on MRI, and a biopsy prior to imaging is necessary to accurately stage the tumor and determine the treatment approach. This review discusses the histology, MR technique, diagnosis, staging, and treatment of anal cancer, with a particular focus on the differences in TNM staging between anal and rectal carcinomas.
PURPOSE
This review discusses the histology, MR technique, diagnosis, staging, and treatment of anal cancer, with a particular focus on the differences in TNM staging between anal squamous-cell carcinoma (ASCC) and rectal adenocarcinoma.
METHODS AND MATERIALS
To conduct this updated review, a comprehensive literature search was performed using prominent medical databases, including PubMed and Embase. The search was limited to articles published within the last 10 years (2013-2023) to ensure their relevance to the current state of knowledge.
INCLUSION CRITERIA
(1) articles that provided substantial information on the diagnostic techniques used for ASCC, mainly focusing on imaging, were included; (2) studies reporting on emerging technologies; (3) English-language articles.
EXCLUSION CRITERIA
articles that did not meet the inclusion criteria, case reports, or articles with insufficient data. The primary outcome of this review is to assess the accuracy and efficacy of different diagnostic modalities, including CT, MRI, and PET, in diagnosing ASCC. The secondary outcomes are as follows: (1) to identify any advancements or innovations in diagnostic techniques for ASCC over the past decade; (2) to highlight the challenges and limitations of the diagnostic process.
RESULTS
ASCC is a rare disease; however, its incidence has been steadily increasing. Primary staging and assessment after chemoradiation therapy are commonly performed using MRI, which is considered to be the preferred imaging modality. CT and PET/CT are useful in evaluating lymph node metastases and distant metastatic disease.
CONCLUSION
ASCC and rectal adenocarcinoma are the most common histological subtypes and are typically indistinguishable on MRI; therefore, a biopsy prior to imaging is necessary to stage the tumor accurately and determine the treatment approach.
Topics: Humans; Lymphatic Metastasis; Positron Emission Tomography Computed Tomography; Rare Diseases; Anus Neoplasms; Rectal Neoplasms; Carcinoma, Squamous Cell; Adenocarcinoma
PubMed: 37736988
DOI: 10.3390/tomography9050135 -
CA: a Cancer Journal For Clinicians 2023The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The... (Review)
Review
The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1-T2N1M0 disease, (2) redefined stage IIIA as T3N0-N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether.
Topics: Humans; United States; Neoplasm Staging; Prognosis; Survival Analysis; Anus Neoplasms
PubMed: 37114458
DOI: 10.3322/caac.21780 -
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