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Cancer Aug 2023Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers...
BACKGROUND
Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized treatments and improvement of therapeutic outcomes.
METHODS
Forty-six paraffin tumor samples from ASCC patients were analyzed by whole-exome sequencing. Copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied and validated in an independent retrospective cohort of 101 ASCC patients from the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD). GEMCAD cohort proteomics allowed assessing the biological features of these tumors.
RESULTS
On the discovery cohort, the median age was 61 years old, 50% were males, stages I/II/III: 3 (7%)/16 (35%)/27 (58%), respectively, median DFS was 33 months, and overall survival was 45 months. Twenty-nine genes whose duplication was related to DFS were identified. The most representative was duplications of the CYP2D locus, including CYP2D6, CYP2D7P, and CYP2D8P genes. Patients with CYP2D6 CNV had worse DFS at 5 years than those with two CYP2D6 copies (21% vs. 84%; p < .0002, hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.7-24.9). In the GEMCAD validation cohort, patients with CYP2D6 CNV also had worse DFS at 5 years (56% vs. 87%; p = .02, HR = 3.6; 95% CI, 1.1-5.7). Mitochondria and mitochondrial cell-cycle proteins were overexpressed in patients with CYP2D6 CNV.
CONCLUSIONS
Tumor CYP2D6 CNV identified patients with a significantly worse DFS at 5 years among localized ASCC patients treated with 5-fluorouracil, mitomycin C, and radiotherapy. Proteomics pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets for these high-risk patients.
PLAIN LANGUAGE SUMMARY
Anal squamous cell carcinoma is an infrequent tumor whose treatment has not been changed since the 1970s. However, disease-free survival in late staged tumors is between 40% and 70%. The presence of an alteration in the number of copies of CYP2D6 gene is a biomarker of worse disease-free survival. The analysis of the proteins in these high-risk patients pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets. Therefore, the determination of the number of copies of CYP2D6 allows the identification of anal squamous carcinoma patients with a high-risk of relapse that could be redirected to a clinical trial. Additionally, this study may be useful to suggest new treatment strategies to increase current therapy efficacy.
Topics: Female; Humans; Male; Middle Aged; Anus Neoplasms; Biomarkers; Carcinoma, Squamous Cell; Cytochrome P-450 CYP2D6; DNA Copy Number Variations; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies
PubMed: 37096763
DOI: 10.1002/cncr.34797 -
World Journal of Surgical Oncology Jan 2023Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare... (Review)
Review
BACKGROUND
Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare nature of this disease has made it difficult to develop treatment recommendations. This study aims to analyze the clinical and pathological features of perianal Paget's disease (PPD) and to explore rational treatment options and follow-up for this disease.
METHODS
The National Cancer Center Hospital database was searched for all cases of perianal Paget's disease diagnosed between 2006 and 2021. In the 14 patients identified, we reviewed the diagnosis, management, and outcomes of adenocarcinoma with pagetoid spread, including suspected or recurrent cases.
RESULTS
All 14 cases met the inclusion criteria. The median follow-up period after diagnosis was 4.5 (range, 0.1-13.0) years. Pagetoid spread before initial treatment was suspected in 12 cases (85.7%). Underlying rectal cancer was identified in 6 cases, and no primary tumor was detected in the other 6 cases. Seven patients had recurrent disease, with the median time to recurrence of 34.6 (range, 19.2-81.7) months. The time to the first relapse was 3 months, and that to the second relapse was 6 months. The overall 5-year survival rate was 90.0%.
CONCLUSIONS
Endoscopic and radiologic evaluation, as well as immunohistologic examination, should be performed. is to differentiate PPD with and without underlying anorectal carcinoma. The time to first recurrence varies widely, and long-term and regular follow-up for more than 5 years is considered necessary for local recurrence and distant metastasis.
Topics: Humans; Rectal Neoplasms; Anus Neoplasms; Paget Disease, Extramammary; Neoplasm Recurrence, Local; Adenocarcinoma
PubMed: 36658590
DOI: 10.1186/s12957-022-02872-z -
International Journal of Colorectal... Sep 2020In most cases, squamous cell carcinoma of the anus (SCCA) is treated with chemo-radiotherapy preserving sphincter function and offering good long-term survival and low... (Review)
Review
PURPOSE
In most cases, squamous cell carcinoma of the anus (SCCA) is treated with chemo-radiotherapy preserving sphincter function and offering good long-term survival and low recurrence rates. However, chemo-radiotherapy has several side effects: dyspareunia, impotence, fecal incontinence, pain, and skin symptoms. Small/T1 tumors, without metastatic disease, can be treated with local excision alone. We aimed to systematically review the literature regarding outcome following local excision of T1 SCCA.
METHODS
PubMed and Embase databases were searched for studies that investigated outcome following local excision of SCCA.
RESULTS
Twenty-three studies were included. Twenty of the studies were retrospective, and three studies included more than 100 patients. Most of the studies were published before the 1980s. Overall there was great heterogeneity and missing data across the included studies when comparing patient demographics, resection margins, definitions on tumor location, and outcome. Overall 5-year survival was 69% (95% CI 66-72) following local excision. Overall 5-year recurrence was 37% (95% CI 30-45) following local excision. No complications were reported following local excision.
CONCLUSION
The current literature on outcome following local excision of T1 anal cancers consists predominantly of smaller, retrospective, and heterogenous studies. Overall 5-year survival is acceptable, but worse than following chemo-radiation therapy. However, local excision seems to have no or only few minor complications. Recurrence rates are high. Therefore, a thorough follow-up program is needed when performing local excision as primary treatment for T1 SCCA. There is an evident need for further studies.
Topics: Anal Canal; Anus Neoplasms; Digestive System Surgical Procedures; Female; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Rectal Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 32671458
DOI: 10.1007/s00384-020-03687-8 -
Journal of Pediatric Surgery Jun 2024Pediatric patients with perianal Crohn's Disease (CD) suffer recalcitrant fistulas, abscesses, and strictures. Fecal diversion is a palliative last resort, but the...
INTRODUCTION
Pediatric patients with perianal Crohn's Disease (CD) suffer recalcitrant fistulas, abscesses, and strictures. Fecal diversion is a palliative last resort, but the expected clinical course and long-term management of the ostomy for this population is unclear. We sought to identify factors predictive of ostomy takedown and establish management recommendations for fistulizing and stenosing disease.
METHODS
We reviewed our institutional registry for patients aged 1-18 years with CD who received perianal surgery from 2011 to 2021. We analyzed medical therapy, examinations under anesthesia (EUA), fistula and stenosis response, and rates of fecal diversion and reversal.
RESULTS
There were 109 patients with fistulizing CD and 21 with stenosing CD. There were 8 diverted for fistula and 4 due to stricture [8/109 (7 %) vs 4/21 (19 %), p = 0.213]. Three patients with fistulizing disease had their ostomy reversed at an average of 1.46 years. Each demonstrated consistent CD control and with no additional perianal flares. The remainder have been diverted 3.15 ± 4.57 years with 2.1 ± 2.8 EUAs. Only one patient with stricture was durably reversed, but they still require serial anal dilation. Two were reversed but required re-diversion due to stricture progression.
CONCLUSION
Reversal rates after fecal diversion for pediatric perianal CD remain disappointingly low and diversion does not obviate the possibility of future EUAs. While reversal was successful for medically responsive patients with fistulizing disease, those with stenosing disease remained dependent on anal dilations and were more likely to fail reversal. Fecal diversion does nothing to reverse an established stricture and such patients will likely need to decide between indefinite dilations or permanent ostomy.
LEVEL OF EVIDENCE
IV.
TYPE OF STUDY
Retrospective review.
Topics: Humans; Crohn Disease; Child; Adolescent; Male; Female; Child, Preschool; Retrospective Studies; Infant; Ostomy; Constriction, Pathologic; Rectal Fistula; Anus Diseases
PubMed: 38104035
DOI: 10.1016/j.jpedsurg.2023.11.009 -
Alimentary Pharmacology & Therapeutics May 2023
Topics: Humans; Crohn Disease; Anus Diseases; Rectal Fistula; Wound Healing
PubMed: 37053478
DOI: 10.1111/apt.17377 -
Canadian Journal of Rural Medicine :... 2021
Topics: Abscess; Anus Diseases; Clinical Competence; Drainage; Humans; Practice Patterns, Physicians'; Rural Health Services; Rural Population
PubMed: 33380604
DOI: 10.4103/CJRM.CJRM_16_20 -
La Clinica Terapeutica 2023Crypts are small anatomical structures situated between the anal papillae, which do not cause any symptoms unless they become inflamed. Cryptitis is a localized...
INTRODUCTION
Crypts are small anatomical structures situated between the anal papillae, which do not cause any symptoms unless they become inflamed. Cryptitis is a localized infection of one or more of the anal crypts.
CASE PRESENTATION
A 42-year-old woman presented to our practice, complaining intermittently of anal pain and pruritus ani over a span of 1 year. She was referred multiple times to various surgeons, and she was treated conservatively for anal fissure without any evident improvement. The referred symptoms were increased often after defecation. Under general anesthesia, a hooked fistula probe was introduced into the inflamed anal crypt and the whole length of the crypt was layed open.
CONCLUSION
Anal cryptitis is a misdiagnosed condition. The un-specific symptomatology of the disease can easily mislead. The clinical suspicion is fundamental for the diagnosis. Patient's history, digital ex-amination, and anoscopy are essential for the diagnosis of anal cryptitis.
Topics: Female; Humans; Adult; Anal Canal; Fissure in Ano; Diagnostic Errors
PubMed: 37199352
DOI: 10.7417/CT.2023.2522 -
Praxis Feb 2022Diagnosis and Therapy of Anal Carcinoma The squamous cell carcinoma of the anorectum is rare and subdivided into perianal, anal canal and combined carcinomas....
Diagnosis and Therapy of Anal Carcinoma The squamous cell carcinoma of the anorectum is rare and subdivided into perianal, anal canal and combined carcinomas. Persistent infection with a high-risk human papillomavirus (HPV) is believed to be the main cause for the development of anal cancer. Therefore, the incidence in high-risk individuals (e.g. immuno-compromised patients or patients living with HIV) is much higher than in the general population. Nevertheless, a nearly three-fold overall increase was observed within the last three decades. The diagnosis is often made by chance as anal carcinoma presents with unspecific symptoms which could be attributed to many other proctological diseases, especially haemorrhoids. The diagnosis is confirmed by histology using biopsies or excisional biopsies. The subsequent staging requires a detailed documentation of the tumor's location and size as well as an overall examination focusing on palpation of the groin. Sphincter involvement in small lesions can be assessed by endoluminal ultrasound or alternatively by an angulated magnetic resonance imaging of the anal canal/pelvis. A computed tomography scan of the thorax and abdomen is usually performed to rule out a metastatic disease. Positron emission tomography-computed tomography is useful for detection of lymph node (LN) involvement and to accurately define the stage prior to treatment. The therapy of anal carcinoma requires a multidisciplinary approach. In most patients, primary treatment consists of chemoradiotherapy (CRT), which improved 5-year overall survival since its introduction in 1974. A surgical approach is reserved for small perianal lesions without sphincter infiltration, LN or distant metastasis. Furthermore, in recurrent or persistent carcinomas after CRT salvage surgical treatment is recommended. In some cases (obstruction, fistula formation) a deviation colostomy is required. Follow-up clinical and imaging evaluation should follow recommended guidelines and should involve primary physicians in addition to members of the multidisciplinary treatment team. Until now, the impact of HPV immunization on anal carcinoma is still unclear despite having been proven effective in preventing anal intraepithelial neoplasia.
Topics: Anus Neoplasms; Carcinoma in Situ; Carcinoma, Squamous Cell; Humans; Magnetic Resonance Imaging; Neoplasm Recurrence, Local
PubMed: 35105214
DOI: 10.1024/1661-8157/a003804 -
Dermatologic Clinics Apr 2020Evaluation of anogenital dermatitis requires a detailed history, including a sexual history. Men who have sex with men have different risk of certain infectious causes... (Review)
Review
Evaluation of anogenital dermatitis requires a detailed history, including a sexual history. Men who have sex with men have different risk of certain infectious causes compared with men who have sex with women. Infectious causes of balanitis and anal dermatitis are easily treatable once identified. Irritant contact dermatitis is a common cause of balanitis, and avoidance of irritants, including decreased soap washing, helps many patients improve. Detailed histories of the personal products used by the patient and partner(s), including soaps, lotions, perfumes, lubricants, condoms, topical medications, hygiene sprays, personal wipes, and laundry detergent, may reveal possible irritants or contact allergens.
Topics: Anus Diseases; Condoms; Dermatitis; Dermatitis, Allergic Contact; Dermatitis, Irritant; Genital Diseases, Male; Humans; Lubricants; Male; Sexual and Gender Minorities; Sexually Transmitted Diseases; Soaps
PubMed: 32115132
DOI: 10.1016/j.det.2019.10.007 -
Journal of the European Academy of... Aug 2021The incidence of and mortality from anal cancer, predominantly squamous cell carcinoma (SCC), have been increasing since the 1980s, during an era when many common... (Review)
Review
The incidence of and mortality from anal cancer, predominantly squamous cell carcinoma (SCC), have been increasing since the 1980s, during an era when many common malignancies have seen decreases in mortality. Dermatologists may be more likely to see patients at an increased risk for anal SCC, such as those living with HIV, MSM and those presenting for management of anogenital warts, yet there is little guidance in the field on how to manage these patients. We underwent a project to review the evidence surrounding screening and prevention of anal SCC. HPV vaccination, the main preventative measure for anal SCC, is often underutilized and may not be effective for those most at risk. Screening methods currently include high-risk HPV and anal cytology testing, with high-resolution anoscopy (HRA) reserved for biopsy and confirmatory testing. High-risk HPV testing has been associated with high sensitivity for intraepithelial neoplasia, but low specificity in high-risk groups. Recent meta-analyses examining AIN detection using anal cytology estimate a similarly high sensitivity of 74-87%, with a relatively higher specificity (44-66%) for identifying high-grade AIN. HRA is the gold standard for diagnosis, but its accessibility and cost are deterrents from its use as a screening tool. Cervical cancer screening, initially adopted without significant evidence of its impact, has significantly decreased cervical cancer rates. The argument can be made that rates of anal SCC may also benefit from appropriate screening methods, particularly anal cytology. It is prudent for dermatologists to be aware of the methods available to them in the management of at-risk patients, the data supporting them, and the potential benefits of screening in order to counsel patients appropriately and address the increasing burden of disease.
Topics: Anal Canal; Anus Neoplasms; Dermatologists; Early Detection of Cancer; Female; HIV Infections; Homosexuality, Male; Humans; Male; Papillomavirus Infections; Sexual and Gender Minorities; Uterine Cervical Neoplasms
PubMed: 33797819
DOI: 10.1111/jdv.17263