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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 -
PloS One 2014Anti-EGFR therapy appears to be a potential treatment option for squamous cell anal carcinoma (SCAC). KRAS mutation is a rare event in SCAC, indicating the absence of...
Anti-EGFR therapy appears to be a potential treatment option for squamous cell anal carcinoma (SCAC). KRAS mutation is a rare event in SCAC, indicating the absence of the principal mechanism of resistance to this type of therapy. However, no information is available from the literature regarding the status of BRAF or PIK3CA in this cancer type. We analysed KRAS, BRAF and PIK3CA status in SCAC patients in relation to the clinical-pathological characteristics of patients and to the presence of the human papilloma virus (HPV). One hundred and three patients were treated with the Nigro scheme for anal cancer from March 2001 to August 2012. Fifty patients were considered for the study as there was insufficient paraffin-embedded tumour tissue to perform molecular analysis the remaining 53. DNA was extracted from paraffin-embedded sections. KRAS, BRAF and PIK3CA gene status and HPV genotype were evaluated by pyrosequencing. KRAS and BRAF genes were wild-type in all cases. Conversely, PIK3CA gene was found to be mutated in 11 (22%) cases. In particular, 8 mutations occurred in exon 9 and 3 in exon 20 of the PIK3CA gene. These findings suggest that SCAC could potentially respond to an anti-EGFR drug. PIK3CA mutation may be involved in the process of carcinogenesis in some cases of SCAC.
Topics: Aged; Antineoplastic Agents; Anus Neoplasms; Axons; Carcinoma, Squamous Cell; Class I Phosphatidylinositol 3-Kinases; DNA Mutational Analysis; Female; Fluorouracil; Gamma Rays; Human papillomavirus 16; Humans; Male; Middle Aged; Mitomycin; Mutation; Neoplasm Staging; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Retrospective Studies; ras Proteins
PubMed: 24642661
DOI: 10.1371/journal.pone.0092071 -
Radiographics : a Review Publication of... 2015Although rectal and anal cancers are anatomically close, they are distinct entities with different histologic features, risk factors, staging systems, and treatment... (Review)
Review
Although rectal and anal cancers are anatomically close, they are distinct entities with different histologic features, risk factors, staging systems, and treatment pathways. Imaging is at the core of initial clinical staging of these cancers and most commonly includes magnetic resonance imaging for local-regional staging and computed tomography for evaluation of metastatic disease. The details of the primary tumor and involvement of regional lymph nodes are crucial in determining if and how radiation therapy should be used in treatment of these cancers. Unfortunately, available imaging modalities have been shown to have imperfect accuracy for identification of nodal metastases and imaging features other than size. Staging of nonmetastatic rectal cancers is dependent on the depth of invasion (T stage) and the number of involved regional lymph nodes (N stage). Staging of nonmetastatic anal cancers is determined according to the size of the primary mass and the combination of regional nodal sites involved; the number of positive nodes at each site is not a consideration for staging. Patients with T3 rectal tumors and/or involvement of perirectal, mesenteric, and internal iliac lymph nodes receive radiation therapy. Almost all anal cancers warrant use of radiation therapy, but the extent and dose of the radiation fields is altered on the basis of both the size of the primary lesion and the presence and extent of nodal involvement. The radiologist must recognize and report these critical anatomic and staging distinctions, which affect use of radiation therapy in patients with anal and rectal cancers.
Topics: Adenocarcinoma; Anal Canal; Anus Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Humans; Lymphatic Metastasis; Lymphatic System; Neoplasm Invasiveness; Neoplasm Staging; Neuroendocrine Tumors; Palliative Care; Papillomaviridae; Papillomavirus Infections; Patient Selection; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Adjuvant; Rectal Neoplasms; Rectum; Risk Factors; Tumor Virus Infections
PubMed: 26562239
DOI: 10.1148/rg.2015150037 -
Critical Reviews in Oncology/hematology Mar 2018The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However,... (Review)
Review
The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However, interesting data have recently emerged on the use of anti-epidermal growth factor receptor (EGFR) agents and immunotherapy in advanced disease. Thus, new avenues of research are opening up that will hopefully lead to more effective therapeutic strategies. We provide an overview of the latest studies published on this tumor and discuss the possible future therapeutic options for combination therapy, anti-EGFR treatment and radiotherapy.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Anus Neoplasms; Carcinoma, Squamous Cell; Cetuximab; Combined Modality Therapy; ErbB Receptors; Humans; Immunotherapy; Therapies, Investigational
PubMed: 29482779
DOI: 10.1016/j.critrevonc.2018.01.007 -
Radiation Oncology (London, England) Jan 2014Anal canal carcinoma is a rare gastro-intestinal cancer. Radiochemotherapy is the recommended primary treatment for patients with non-metastatic carcinoma; surgery is... (Review)
Review
Anal canal carcinoma is a rare gastro-intestinal cancer. Radiochemotherapy is the recommended primary treatment for patients with non-metastatic carcinoma; surgery is generally reserved for persistent or recurrent disease. Follow-up and surveillance after primary treatment is paramount to classify patients in those with complete remission, persistent or progressive disease. Locally persistent disease represents a clinically significant problem and its management remains subject of some controversy.The aim of this systematic review is to summarise recommendations for the primary treatment of anal canal carcinoma, to focus on the optimal time to consider residual disease as genuine persistence to proceed with salvage treatment, and to discern how this analysis might inform future clinical trials in management in this class of patients.
Topics: Anus Neoplasms; Combined Modality Therapy; Humans; Neoplasm Recurrence, Local; Neoplasm, Residual; Practice Guidelines as Topic; Radiotherapy; Salvage Therapy; Treatment Failure
PubMed: 24472223
DOI: 10.1186/1748-717X-9-39 -
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 -
ESMO Open Aug 2021Squamous cell carcinoma of the rectum is a rare malignancy (0.3% of all rectal cancers), with no known risk factor. These tumours are assessed as rectal cancer using... (Review)
Review
Squamous cell carcinoma of the rectum is a rare malignancy (0.3% of all rectal cancers), with no known risk factor. These tumours are assessed as rectal cancer using immunohistochemical and radiological tests, and certain criteria (localisation, relationship with neighbouring structures) have to be fulfilled to make the diagnosis. Some clinicians used to stage them with the anal cancer TNM (tumour-node-metastasis), whereas others used the rectal cancer TNM. When localised, the tendency nowadays is to treat those tumours like squamous anal cancers with definitive chemoradiotherapy (5-fluorouracil and mitomycin) and to skip surgery. For metastatic disease there is no clearly validated regimen and treatment should be based on recommendations of squamous anal cancers because of their common histology. Concerning follow-up after a curative approach, techniques should follow those for anal cancer as well, evaluating a delayed response.
Topics: Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Fluorouracil; Humans; Rectal Neoplasms
PubMed: 34111760
DOI: 10.1016/j.esmoop.2021.100180 -
Revista Espanola de Enfermedades... Feb 2018The human papilloma virus is the leading cause of anal squamous cell carcinoma. Cytological screening may reduce the associated morbidity and mortality. The aim of the... (Observational Study)
Observational Study
BACKGROUND AND AIM
The human papilloma virus is the leading cause of anal squamous cell carcinoma. Cytological screening may reduce the associated morbidity and mortality. The aim of the study was to estimate the agreement between anal cytological examination, histopathology and anoscopic visual impression.
METHODS
A prospective study of patients who underwent anal dysplasia screening between 2011 and 2015, in a proctology clinic of a tertiary referral center.
RESULTS
During the study period, 141 patients (91% men, 87% with HIV infection) underwent 175 anal cytology tests. Of these, 33% were negative for intraepithelial lesions or malignancy (NILM), 22% were atypical squamous cells of uncertain significance (ASCUS), 33% were low-grade squamous intraepithelial lesion (LSIL) and 12% were high-grade squamous intraepithelial lesion (HSIL). With regard to anoscopic visual impression, 46% of patients had no lesions and excision/biopsy of the identified lesions was performed in the remaining patients. The weighted kappa-agreement between abnormal cytological results and anoscopic visual impression was moderate (k = 0.48). The weighted kappa-agreement between simultaneous anal cytological examinations and anal histopathologic findings was low (kappa = 0.20). With regard to the histological examination of cases with HSIL or superficially invasive squamous cell carcinoma, 64% of patients had dysplasia of a lower grade according to the cytological analysis (6 ASCUS, 18 LSIL and 4 NILM).
CONCLUSION
There was a poor correlation between anal cytology, histopathology and anoscopic visual impression and a high number of histological studies of HGD that were of a lower dysplastic degree according to the cytological examination. Therefore, anal cytology screening should not be used as the sole method of anal dysplasia screening.
Topics: Adult; Anal Canal; Anus Neoplasms; Carcinoma, Squamous Cell; Cohort Studies; Endoscopy; Female; Humans; Male; Mass Screening; Middle Aged; Prospective Studies; Reproducibility of Results; Young Adult
PubMed: 29168646
DOI: 10.17235/reed.2017.4913/2017 -
Annals of Surgery Jul 1978Cloacogenic carcinoma is a rare tumor of the anorectal region originating from a persistant remnant of the cloacal membrane of the embryo. The tumor accounts for 2-3% of...
Cloacogenic carcinoma is a rare tumor of the anorectal region originating from a persistant remnant of the cloacal membrane of the embryo. The tumor accounts for 2-3% of anorectal carcinomas and occurs more than twice as often in women. Most tumors present as fungating or ulcerating lesions, but the tumor may arise in anal ducts and present as a submucosal mass. Wide abdominoperineal resection is the treatment of choice with a five year survival of 50%. Metastases occurs to the inguinal lymph nodes in more than 50% of the patients at sometime during the course of the disease with distant metastases occuring most commonly to liver and lungs.
Topics: Anus Neoplasms; Carcinoma, Transitional Cell; Humans; Male; Middle Aged; Rectal Neoplasms
PubMed: 666378
DOI: 10.1097/00000658-197807000-00009 -
Cancer Medicine May 2023Anal squamous cell cancer (ASCC) incidence in Kentucky is increasing at an alarming rate. In 2009, the incidence surpassed the US national average (2.66 vs. 1.77/100,000...
BACKGROUND
Anal squamous cell cancer (ASCC) incidence in Kentucky is increasing at an alarming rate. In 2009, the incidence surpassed the US national average (2.66 vs. 1.77/100,000 people), and currently, Kentucky ranks second by state per capita. The reasons for this rise are unclear. We hypothesize individuals with ASCC in Kentucky have some unique risk factors associated with worse outcomes.
METHODS
Individuals with ASCC in a population-level state database (1995-2016), as well as those treated at two urban university-affiliated tertiary care centers (2011-2018), were included and analyzed separately. We evaluated patient-level factors including demographics, tobacco use, stage of disease, HIV-status, and HPV-type. We evaluated factors associated with treatment and survival using univariable and multivariable survival analyses.
RESULTS
There were 1698 individuals in state data and 101 in urban center data. In the urban cohort, 77% of patients were ever-smokers. Eighty-four percent of patients had positive HPV testing, and 58% were positive for HPV 16. Seventy-two percent of patients were positive for p16. Neither smoking, HPV, nor p16 status were associated with disease persistence, recurrence-free survival, or overall survival (all p > 0.05). Poorly controlled HIV (CD4 count <500) at time of ASCC diagnosis was associated disease persistence (p = 0.032). Stage III disease (adjusted HR = 5.25, p = 0.025) and local excision (relative to chemoradiation; aHR = 0.19, p = 0.017) were significantly associated with reduced recurrence-free survival.
CONCLUSIONS
The rate of ASCC in Kentucky has doubled over the last 10 years, which is outpacing anal SCC rates in the US with the most dramatic rates seen in Kentucky women. The underlying reasons for this are unclear and require further study. There may be other risk factors unique to Kentucky.
Topics: Humans; Female; Incidence; Papillomavirus Infections; Kentucky; Anus Neoplasms; Carcinoma, Squamous Cell; HIV Infections
PubMed: 36991580
DOI: 10.1002/cam4.5865