Epidermoid cancer of the anal canal.
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ABSTRACT:
SUBMITTER: Webb SP
PROVIDER: S-EPMC3311501 | biostudies-other | 2011 Sep
REPOSITORIES: biostudies-other
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Project description:Etiologically linked to HPV infection, malignancies of the anal canal have substantially increased in incidence over the last 20 years. Although most anal squamous cell carcinomas (SCC) respond well to chemoradiotherapy, for undetermined reasons, a subgroup of patients experience a poor outcome. Despite cumulative efforts for discovering independent predictors for overall survival, both nodal status and tumor size are still the only reliable factors predicting patient outcome. In the present study, we correlated both proteomic signatures and clinicopathological features of neoplastic lesions arising from two distinct portions of the anal canal: the lower part (squamous zone) and the more proximal anal transitional zone. Although microdissected cancer cells appeared indistinguishable by morphology (squamous phenotype), unsupervised clustering analysis of the whole proteome significantly highlighted the heterogeneity that exists within anal canal tumors. More importantly, two region-specific subtypes of SCC were revealed. The expression profile (sensitivity/specificity) of several selected biomarkers (keratin filaments) further confirmed the subclassification of anal (pre)cancers based on their cellular origin. Less commonly detected compared to their counterparts located in the squamous mucosa, SCC originating in the transitional zone displayed more frequently a poor or basaloid differentiation and were significantly correlated with reduced disease-free and overall survivals. Taken together, we present for the first time direct evidence that anal canal SCC comprises two distinct entities with different cells of origin, proteomic signatures and survival rates. This study forms the basis for a novel dualistic classification of anal carcinoma with implications for management, outcome expectations and possibly therapeutic approaches.
2016-12-20 | PXD004859 | Pride
Project description:Squamous cell carcinoma of the anus (SCCA) is a rare tumor. However, its incidence has been increasing in men and women over the past 25 years worldwide. Risk factors associated with this cancer are those behaviors that predispose individuals to human papillomavirus (HPV) infection and immunosuppression. Anal cancer is generally preceded by high-grade anal intraepithelial neoplasia (HGAIN), which is most prevalent in human immunodeficiency virus-positive men who have sex with men. High-risk patients may benefit from screening. The most common presentation is rectal bleeding, which is present in nearly 50% of patients. Twenty percent of patients have no symptoms at the time of presentation. Clinical staging of anal cancer requires a digital rectal exam and a positron emission tomography/computed tomography scan of the chest, abdomen, and pelvis. Endorectal/endoanal ultrasound appears to add more-specific staging information when compared with digital rectal examination alone. Treatment of anal cancer prior to the 1970s involved an abdominoperineal resection. However, the current standard of care for localized anal cancer is concurrent chemoradiation therapy, primarily because of its sphincter-saving and colostomy-sparing potential. Studies have addressed alternative chemoradiation regimens to improve the standard protocol of fluorouracil, misogynic, and radiation, but no alternative regimen has proven superior. Surgery is reserved for those patients with residual disease or recurrence.
| S-EPMC3311505 | biostudies-other
Project description:ObjectiveA comparative assessment of treatment alternatives for T1N0 anal canal cancer has never been conducted. We compared the outcomes associated with the treatment alternatives-chemoradiotherapy (CRT), radiotherapy (RT), and surgery or ablation techniques (surgery/ablation)-for T1N0 anal canal cancer.Materials and methodsThis retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) registries linked with Medicare longitudinal data (SEER-Medicare database). Analysis included 190 patients who were treated for T1N0 anal canal cancer using surgery/ablation (n=44), RT (n=50), or CRT (n=96). The outcomes were reported in terms of survival and hazards ratios using Kaplan-Meier and Cox proportional hazards modeling, respectively; lifetime costs; and cost-effectiveness measured in terms of incremental cost-effectiveness ratio, that is, the ratio of the difference in costs between the 2 alternatives to the difference in effectiveness between the same 2 alternatives.ResultsThere was no significant difference in the survival duration between the treatment groups as predicted by the Kaplan-Meier curves. After adjusting for patient characteristics and propensity score, the hazard ratio of death for the patients who received CRT compared with surgery/ablation was 1.742 (95% confidence interval, 0.793-3.829) and RT was 2.170 (95% confidence interval, 0.923-5.101); however, the relationship did not reach statistical significance. Surgery/ablation resulted in lower lifetime cost than RT or CRT. The incremental cost-effectiveness ratio associated with CRT compared with surgery/ablation was $142,883 per life year gained.ConclusionsThere was no statistically significant difference in survival among the treatment alternatives for T1N0 anal canal cancer. Given that surgery/ablation costs less than RT or CRT and might be cost-effective compared with RT and CRT, it is crucial to explore this finding further in this era of limited health care resources.
| S-EPMC5393969 | biostudies-literature
Project description:Background & aimsThe anal sphincters and puborectalis are imaged routinely with an endoanal magnetic resonance imaging (MRI) coil, which does not assess co-aptation of the anal canal at rest. By using a MRI torso coil, we identified a patulous anal canal in some patients with anorectal disorders. We aimed to evaluate the relationship between anal sphincter and puborectalis injury, a patulous anal canal, and anal pressures.MethodsWe performed a retrospective analysis of data from 119 patients who underwent MRI and manometry analysis of anal anatomy and pressures, respectively, from February 2011 through March 2013 at the Mayo Clinic. Anal pressures were determined by high-resolution manometry, anal sphincter and puborectalis injury was determined by endoanal MRI, and anal canal integrity was determined by torso MRI. Associations between manometric and anatomic parameters were evaluated with univariate and multivariate analyses.ResultsFecal incontinence (55 patients; 46%) and constipation (36 patients; 30%) were the main indications for testing; 49 patients (41%) had a patulous anal canal, which was associated with injury to more than 1 muscle (all P ≤ .001), and internal sphincter (P < .01), but not puborectalis (P = .09) or external sphincter (P = .06), injury. Internal (P < .01) and external sphincter injury (P = .02) and a patulous canal (P < .001), but not puborectalis injury, predicted anal resting pressure. A patulous anal canal was the only significant predictor (P < .01) of the anal squeeze pressure increment.ConclusionsPatients with anorectal disorders commonly have a patulous anal canal, which is associated with more severe anal injury and independently predicted anal resting pressure and squeeze pressure increment. It therefore is important to identify a patulous anal canal because it appears to be a marker of not only anal sphincter injury but disturbances beyond sphincter injury, such as damage to the anal cushions or anal denervation.
| S-EPMC4575824 | biostudies-literature
Project description:ObjectiveAnal cancer is a common cancer among men who have sex with men (MSM); however, there is no standard screening protocol for anal cancer. We conducted a phase II clinical trial to assess the feasibility of teaching MSM to recognise palpable masses in the anal canal which is a common sign of anal cancer in men.MethodsA clinician skilled in performing digital anorectal examinations (DARE) used a pelvic manikin to train 200 MSM, aged 27-78 years, how to do a self-anal examination (SAE) for singles or a partner anal examination (PAE) for couples. The clinician then performed a DARE without immediately disclosing results, after which the man or couple performed an SAE or PAE, respectively. Percentage agreement with the clinician DARE in addition to sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the SAE, PAE and overall.ResultsMen had a median age of 52 years, 42.5% were African American and 60.5% were HIV positive. DARE detected abnormalities in 12 men while the men's SAE/PAEs detected 9 of these. A total of 93.0% of men classified the health of their anal canal correctly (95% CI 89.5 to 96.5). Overall percentage agreement, sensitivity and specificity were 93.0%, 75.0% and 94.2%, respectively, while PPV and NPV were 45.0% and 98.3%, respectively. The six men who detected the abnormality had nodules/masses ≥3 mm in size. More than half of men (60.5%) reported never checking their anus for an abnormality; however, after performing an SAE/PAE, 93.0% said they would repeat it in the future.ConclusionThese results suggest that tumours of ≥3 mm may be detectable by self or partner palpation among MSM and encourage further investigation given literature suggesting a high cure rate for anal cancer tumours ≤10 mm.
| S-EPMC6173609 | biostudies-literature
Project description:BACKGROUND:Anal cancer is a rare cancer with chemoradiation being the mainstay of treatment for locoregional presentation. In North America, the most common subtype is anal squamous cell carcinoma (epidermoid). A surgical approach is considered for persistent or recurrent anal disease and systemic chemotherapy for metastatic disease. We are presenting a unique case of recurrent anal cancer with isolated peritoneal malignancy, an oligometastatic state which is rare in itself. It was treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. There are currently no clear guidelines for the aforementioned presentation. The discussion drew on the feasibility and safety of this approach. CASE PRESENTATION:A 68-year-old woman diagnosed with an epidermoid anal cancer (stage 3B) was initially treated with chemoradiation therapy (Standard Nigro Protocol) in 2014. At the 5-year mark post-treatment, she was diagnosed with a recurrent anal epidermoid cancer in the form of isolated peritoneal carcinomatosis proven by biopsy. After declining systemic chemotherapy, she underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with Mitomycin-C©. Peritoneal carcinomatosis index was evaluated at 10, and intraoperative frozen sections were positive for carcinoma of epidermoid origin compatible with anal cancer. A completeness of cytoreduction score of 0 was achieved during the cytoreductive surgery, and her hospital course was unremarkable. She remains disease-free 12?months later. CONCLUSIONS:To our knowledge, this is the first case reporting the disease presentation of anal cancer with oligometastatic dissemination to the peritoneum. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were performed. Thus far, this approach seems to be a safe and feasible option for short-term control of the disease.
| S-EPMC7335445 | biostudies-literature
Project description:The first UKCCCR Anal Cancer Trial (1996) demonstrated the benefit of chemoradiation over radiotherapy (RT) alone for treating epidermoid anal cancer, and it became the standard treatment. Patients in this trial have now been followed up for a median of 13 years.A total of 577 patients were randomised to receive RT alone or combined modality therapy using 5-fluorouracil and mitomycin C. All patients were scheduled to receive 45 Gy by external beam irradiation. Patients who responded to treatment were recommended to have boost RT, with either an iridium implant or external beam irradiation. Data on relapse and deaths were obtained until October 2007.Twelve years after treatment, for every 100 patients treated with chemoradiation, there are an expected 25.3 fewer patients with locoregional relapse (95% confidence interval (CI): 17.5-32.0 fewer) and 12.5 fewer anal cancer deaths (95% CI: 4.3-19.7 fewer), compared with 100 patients given RT alone. There was a 9.1% increase in non-anal cancer deaths in the first 5 years of chemoradiation (95% CI +3.6 to +14.6), which disappeared by 10 years.The clear benefit of chemoradiation outweighs an early excess risk of non-anal cancer deaths, and can still be seen 12 years after treatment. Only 11 patients suffered a locoregional relapse as a first event after 5 years, which may influence the choice of end points in future studies.
| S-EPMC2853094 | biostudies-other
Project description:PurposePersistent human papillomavirus infection is associated with squamous cell carcinoma of the anal canal (SCCA). With changing sexual behaviors, SCCA incidence and patient demographics may also have changed in recent years.MethodsThe Surveillance, Epidemiology, and End Results public-use data set from 1973 to 2009 was analyzed to determine incidence trends for and demographic factors characterizing SCCA. Joinpoint analyses identified time points when incidence rates changed. For comparison, similar analyses were conducted for anal adenocarcinoma.ResultsJoinpoint analyses identified 1997 as the single inflection point among 11,231 patients with SCCA, at which the slope of incidence rates statistically increased (1997 to 2009 v 1973 to 1996: risk ratio [RR], 2.2; 95% CI, 2.1 to 2.3). Annual percent change (APC) increased for all SCCA stages and was the greatest for anal carcinoma in situ (CIS; APC, 14.2; 95% CI, 10.2 to 18.4). Demographic changes characterizing later versus earlier time period included younger age at diagnosis and rising incidence rates in all stage, sex, and racial groups. During 1997 to 2009, women were less likely to present with CIS (RR, 0.3; 95% CI, 0.3 to 0.3) but more likely to present with localized (RR, 1.2; 95% CI, 1.1 to 1.3) and regional SCCA (RR, 1.5; 95% CI, 1.4 to 1.7). In contrast, adenocarcinoma APCs among 1,791 patients remained stable during this time period.ConclusionCIS and SCCA incidence increased dramatically after 1997 for men and women, although men were more likely to be diagnosed with CIS. These changes likely resulted from available screening in men and argue for efforts to identify high-risk individuals who may benefit from screening.
| S-EPMC3753461 | biostudies-literature
Project description:Background Squamous cell carcinoma of the anal canal (SCCA) is an uncommon malignancy with limited therapeutic options. Nivolumab and pembrolizumab show promising results in patients with SCCA. Human papillomavirus (HPV)-negative tumors are frequently TP53-mutated (TP53-MT) and often resistant to therapy. Methods We present a large molecularly-profiled cohort of SCCA, exploring the underlying biology of SCCA, differences between TP53-wild type (TP53-WT) and TP53-MT tumors, and differences between local and metastatic tumors. SCCA specimens (n=311) underwent multiplatform testing with immunohistochemistry (IHC), in situ hybridization (ISH) and next-generation sequencing (NGS). Tumor mutational burden (TMB) was calculated using only somatic nonsynonymous missense mutations. Chi-square testing was used for comparative analyses. Results The most frequently mutated genes included PIK3CA (28.1%), KMT2D (19.5%), FBXW7 (12%), TP53 (12%) and PTEN (10.8%). The expression of PD-1 was seen in 68.8% and PD-L1 in 40.5% of tumors. High TMB was present in 6.7% of specimens. HER2 IHC was positive in 0.9%, amplification by chromogenic in situ hybridization (CISH) was seen 1.3%, and mutations in ERBB2 were present in 1.8% of tumors. The latter mutation has not been previously described in SCCA. When compared with TP53-WT tumors, TP53-MT tumors had higher rates of CDKN2A, EWSR1, JAK1, FGFR1 and BRAF mutations. PD-1 and PD-L1 expression were similar, and high TMB did not correlate with PD-1 (P=0.50) or PD-L1 (P=0.52) expression. Conclusions Molecular profiling differences between TP53-MT and TP53-WT SCCA indicate different carcinogenic pathways which may influence response to therapy. Low frequency mutations in several druggable genes may provide therapeutic opportunities for patients with SCCA.
| S-EPMC8576238 | biostudies-literature
Project description:This study is an analysis of the criteria considered when prescribing concomitant chemotherapy and radiotherapy, as a routine treatment for patients with anal canal cancer, and related complications. Between 1990 and 1996, 67 patients were treated at Institut Curie for invasive, nonmetastatic cancer of the anal canal. Median age was 65 years (range, 35-90 years). TNM stage distribution was as follows: seven T1, 17 T2, 27 T3, 16 T4, and 22 N+ patients. A total of 29 patients (i.e., five T1/T2, and 24 T3/T4) received concurrent chemotherapy and radiotherapy. Radiotherapy volumes and dose and prescribed dose for chemotherapy were not statistically different from one group of patients to another. Only 55% of T3/T4 patients underwent standard chemoradiation treatment for anal canal cancer. Age was the one of main factor in determining if the patient would undergo concomitant chemotherapy or not. For the T3/T4 patients, concomitant chemotherapy was prescribed to 69% of patients <55 years, 90% of patients between 56 and 64 years, 45% of patients between 65 and 75 years, and 20% of patients over 75 years (P<0.02). Overall survival at 4 years was 66%. The 4 years overall survival rate of T3/T4 patients, who underwent concomitant chemotherapy, was 72%, and that of T3/T4 patient who did not, was 34% (P<0.04). The patients who did not undergo chemotherapy were significantly older. The difference in cause-specific survival rates (72 vs 48%) was not significant. Relapse-free interval without local recurrence at 4 years was 70%. Relapse-free interval of T3/T4 patients was 78% with chemotherapy and 60% without chemotherapy (p=NS). Rates of treatment discontinuation and early toxicity were not statistically different. Late complications occurred in 33 patients, eight of whom had grade 2/3 tumours. At 2 years, complications occurred in 39% of patients who had undergone concomitant chemotherapy, and in 20% of patients who had not (p<0.02). Differences in grade 2/3 complications were not significant. In conclusion, although radiotherapy with concomitant chemotherapy is considered the current 'gold-standard' treatment for anal canal cancer, in our daily experience, only 55% of our T3/T4 patients have undergone this treatment. The remainder did not undergo chemotherapy mainly because they were deemed too old. In this series, no increase in local control and cause-specific survival was observed in patients who received concomitant chemotherapy; this may be due to the small number of patients included in the series. The increased rate of late complications observed in patients who received the combined treatment, however, provides evidence that this treatment should be restricted to younger patients without comorbidity and therefore justifies our position. Perhaps reduction of doses of chemotherapy must be discussed for older patients.
| S-EPMC2376848 | biostudies-other